title stringlengths 0 1.13k | abstract stringlengths 1 15.7k | PMID int64 22 36.5M |
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Kinesin-1 (uKHC/KIF5B) is required for bidirectional motility of ER exit sites and efficient ER-to-Golgi transport. | Transport of proteins and lipids between intracellular compartments is fundamental to the organization and function of eukaryotic cells. The efficiency of this process is greatly enhanced through coupling of membranes to microtubules. This serves two functions, organelle positioning and vesicular transport. In this study, we show that in addition to the well-known role for the minus-end motor dynein in endoplasmic reticulum (ER)-to-Golgi transport, the plus-end-directed motor kinesin-1 is involved in positioning coat protein II-coated ER exit sites (ERES) in cells as well as the formation of transport carriers and their movement to the Golgi. Using two-dimensional Gaussian fitting to determine their location at high spatial resolution, we show that ERES undergo short-range bidirectional movements. Bidirectionality depends on both kinesin-1 and dynein. Suppression of kinesin-1 (KIF5B) also inhibits ER-to-Golgi transport and affects the morphology of ER-to-Golgi transport carriers. Furthermore, we show that suppression of dynein heavy chain expression increases the range of movement of ERES, suggesting that dynein might anchor ERES, or the ER itself, to microtubules. These data implicate kinesin-1 in the spatial organization of the ER/Golgi interface as well as in traffic outside the ER. | 18,817,524 |
The ESCRT-I subunit TSG101 controls endosome-to-cytosol release of viral RNA. | Like other enveloped viruses, vesicular stomatitis virus infects cells through endosomes. There, the viral envelope undergoes fusion with endosomal membranes, thereby releasing the nucleocapsid into the cytoplasm and allowing infection to proceed. Previously, we reported that the viral envelope fuses preferentially with the membrane of vesicles present within multivesicular endosomes. Then, these intra-endosomal vesicles (containing nucleocapsids) are transported to late endosomes, where back-fusion with the endosome limiting membrane delivers the nucleocapsid into the cytoplasm. In this study, we show that the tumor susceptibility gene 101 (Tsg101) subunit of the endosomal sorting complexes required for transport (ESCRT)-I complex, which mediates receptor sorting into multivesicular endosomes, is dispensable for viral envelope fusion with endosomal membranes and viral RNA transport to late endosomes but is necessary for infection. Our data indicate that Tsg101, in contrast to the ESCRT-0 component Hrs, plays a direct role in nucleocapsid release from within multivesicular endosomes to the cytoplasm, presumably by controlling the back-fusion process. We conclude that Tsg101, through selective interactions with its partners including Hrs and Alix, may link receptor sorting and lysosome targeting to the back-fusion process involved in viral capsid release. | 18,817,529 |
The signature of long-standing balancing selection at the human defensin beta-1 promoter. | Defensins, small endogenous peptides with antimicrobial activity, are pivotal components of the innate immune response. A large cluster of defensin genes is located on human chromosome 8p; among them the beta defensin 1 (DEFB1) promoterhas been extensively studied since discovery that specific polymorphisms and haplotypes associate with asthma and atopy, susceptibility to severe sepsis, as well as HIV and Candida infection predisposition. Here, we characterize the sequence variation and haplotype structure of the DEFB1 promoter region in six human populations. In all of them, we observed high levels of nucleotide variation, an excess of intermediate-frequency alleles, reduced population differentiation and a genealogy with common haplotypes separated by deep branches. Indeed, a significant departure from the expectation of evolutionary neutrality was observed in all populations and the possibility that this is due to demographic history alone was ruled out. Also, we verified that the selection signature is restricted to the promoter region and not due to a linked balanced polymorphism. A phylogeny-based estimation indicated that the two major haplotype clades separated around 4.5 million years ago, approximately the time when the human and chimpanzee lineages split. Altogether, these features represent strong molecular signatures of long-term balancing selection, a process that is thought to be extremely rare outside major histocompatibility complex genes. Our data indicate that the DEFB1 promoter region carries functional variants and support previous hypotheses whereby alleles predisposing to atopic disorders are widespread in modern societies because they conferred resistance to pathogens in ancient settings. | 18,817,538 |
Persisting atypical and cystic forms of Borrelia burgdorferi and local inflammation in Lyme neuroborreliosis. | The long latent stage seen in syphilis, followed by chronic central nervous system infection and inflammation, can be explained by the persistence of atypical cystic and granular forms of Treponema pallidum. We investigated whether a similar situation may occur in Lyme neuroborreliosis. Atypical forms of Borrelia burgdorferi spirochetes were induced exposing cultures of Borrelia burgdorferi (strains B31 and ADB1) to such unfavorable conditions as osmotic and heat shock, and exposure to the binding agents Thioflavin S and Congo red. We also analyzed whether these forms may be induced in vitro, following infection of primary chicken and rat neurons, as well as rat and human astrocytes. We further analyzed whether atypical forms similar to those induced in vitro may also occur in vivo, in brains of three patients with Lyme neuroborreliosis. We used immunohistochemical methods to detect evidence of neuroinflammation in the form of reactive microglia and astrocytes. Under these conditions we observed atypical cystic, rolled and granular forms of these spirochetes. We characterized these abnormal forms by histochemical, immunohistochemical, dark field and atomic force microscopy (AFM) methods. The atypical and cystic forms found in the brains of three patients with neuropathologically confirmed Lyme neuroborreliosis were identical to those induced in vitro. We also observed nuclear fragmentation of the infected astrocytes using the TUNEL method. Abundant HLA-DR positive microglia and GFAP positive reactive astrocytes were present in the cerebral cortex. The results indicate that atypical extra- and intracellular pleomorphic and cystic forms of Borrelia burgdorferi and local neuroinflammation occur in the brain in chronic Lyme neuroborreliosis. The persistence of these more resistant spirochete forms, and their intracellular location in neurons and glial cells, may explain the long latent stage and persistence of Borrelia infection. The results also suggest that Borrelia burgdorferi may induce cellular dysfunction and apoptosis. The detection and recognition of atypical, cystic and granular forms in infected tissues is essential for the diagnosis and the treatment as they can occur in the absence of the typical spiral Borrelia form. | 18,817,547 |
Abbreviation definition identification based on automatic precision estimates. | The rapid growth of biomedical literature presents challenges for automatic text processing, and one of the challenges is abbreviation identification. The presence of unrecognized abbreviations in text hinders indexing algorithms and adversely affects information retrieval and extraction. Automatic abbreviation definition identification can help resolve these issues. However, abbreviations and their definitions identified by an automatic process are of uncertain validity. Due to the size of databases such as MEDLINE only a small fraction of abbreviation-definition pairs can be examined manually. An automatic way to estimate the accuracy of abbreviation-definition pairs extracted from text is needed. In this paper we propose an abbreviation definition identification algorithm that employs a variety of strategies to identify the most probable abbreviation definition. In addition our algorithm produces an accuracy estimate, pseudo-precision, for each strategy without using a human-judged gold standard. The pseudo-precisions determine the order in which the algorithm applies the strategies in seeking to identify the definition of an abbreviation. On the Medstract corpus our algorithm produced 97% precision and 85% recall which is higher than previously reported results. We also annotated 1250 randomly selected MEDLINE records as a gold standard. On this set we achieved 96.5% precision and 83.2% recall. This compares favourably with the well known Schwartz and Hearst algorithm. We developed an algorithm for abbreviation identification that uses a variety of strategies to identify the most probable definition for an abbreviation and also produces an estimated accuracy of the result. This process is purely automatic. | 18,817,555 |
An ontology for Xenopus anatomy and development. | The frogs Xenopus laevis and Xenopus (Silurana) tropicalis are model systems that have produced a wealth of genetic, genomic, and developmental information. Xenbase is a model organism database that provides centralized access to this information, including gene function data from high-throughput screens and the scientific literature. A controlled, structured vocabulary for Xenopus anatomy and development is essential for organizing these data. We have constructed a Xenopus anatomical ontology that represents the lineage of tissues and the timing of their development. We have classified many anatomical features in a common framework that has been adopted by several model organism database communities. The ontology is available for download at the Open Biomedical Ontologies Foundry http://obofoundry.org. The Xenopus Anatomical Ontology will be used to annotate Xenopus gene expression patterns and mutant and morphant phenotypes. Its robust developmental map will enable powerful database searches and data analyses. We encourage community recommendations for updates and improvements to the ontology. | 18,817,563 |
Apigenin and luteolin modulate microglial activation via inhibition of STAT1-induced CD40 expression. | It is well known that most neurodegenerative diseases are associated with microglia-mediated inflammation. Our previous research demonstrates that the CD40 signaling is critically involved in microglia-related immune responses in the brain. For example, it is well known that the activation of the signal transducer and activator of transcription (STAT) signaling pathway plays a central role in interferon-gamma (IFN-gamma)-induced microglial CD40 expression. We and others have previously reported that microglial CD40 expression is significantly induced by IFN-gamma and amyloid-beta (A beta) peptide. Recent studies have shown that certain flavonoids possess anti-inflammatory and neuroprotective properties distinct from their well-known anti-oxidant effects. In particular, flavonoids, apigenin and luteolin have been found to be effective CD40 immunomodulators. Cultured microglia, both N9 and primary derived lines, were treated with flavonoids in the presence of IFN-gamma and/or CD40 ligation to assess any anti-inflammatory effects and/or mechanisms. CD40 expression on microglia was analyzed by fluorescence activated cell sorting (FACS). Anti-inflammatory effects and mechanisms were confirmed by ELISA for interleukin-6 (IL-6) and TNF-alpha, lactate dehydrogenase (LDH) assay, and STAT1 Western blotting. Apigenin and luteolin concentration-dependently suppressed IFN-gamma-induced CD40 expression. Apigenin and luteolin also suppressed microglial TNF-alpha and IL-6 production stimulated by IFN-gamma challenge in the presence of CD40 ligation. In addition, apigenin and luteolin markedly inhibited IFN-gamma-induced phosphorylation of STAT1 with little impact on cell survival. Our findings provide further support for apigenin and luteolin's anti-inflammatory effects and suggest that these flavonoids may have neuroprotective/disease-modifying properties in various neurodegenerative disorders, including Alzheimer's disease (AD). | 18,817,573 |
Low wintertime vitamin D levels in a sample of healthy young adults of diverse ancestry living in the Toronto area: associations with vitamin D intake and skin pigmentation. | Vitamin D plays a critical role in bone metabolism and many cellular and immunological processes. Recent research indicates that concentrations of serum 25-hydroxyvitamin D [25(OH)D], the main indicator of vitamin D status, should be in excess of 75 nmol/L. Low levels of 25(OH)D have been associated with several chronic and infectious diseases. Previous studies have reported that many otherwise healthy adults of European ancestry living in Canada have low vitamin D concentrations during the wintertime. However, those of non-European ancestry are at a higher risk of having low vitamin D levels. The main goal of this study was to examine the vitamin D status and vitamin D intake of young Canadian adults of diverse ancestry during the winter months. One hundred and seven (107) healthy young adults self-reporting their ancestry were recruited for this study. Each participant was tested for serum 25(OH)D concentrations and related biochemistry, skin pigmentation indices and basic anthropometric measures. A seven-day food diary was used to assess their vitamin D intake. An ANOVA was used to test for significant differences in the variables among groups of different ancestry. Linear regression was employed to assess the impact of relevant variables on serum 25(OH)D concentrations. More than 93% of the total sample had concentrations below 75 nmol/L. Almost three-quarters of the subjects had concentrations below 50 nmol/L. There were significant differences in serum 25(OH)D levels (p < 0.001) and vitamin D intake (p = 0.034) between population groups. Only the European group had a mean vitamin D intake exceeding the current Recommended Adequate Intake (RAI = 200 IU/day). Total vitamin D intake (from diet and supplements) was significantly associated with 25(OH)D levels (p < 0.001). Skin pigmentation, assessed by measuring skin melanin content, showed an inverse relationship with serum 25(OH)D (p = 0.033). We observe that low vitamin D levels are more prevalent in our sample of young healthy adults than previously reported, particularly amongst those of non-European ancestry. Major factors influencing 25(OH)D levels were vitamin D intake and skin pigmentation. These data suggest a need to increase vitamin D intake either through improved fortification and/or supplementation. | 18,817,578 |
A retrospective analysis of human cystic echinococcosis in Hamedan province, an endemic region of Iran. | In a retrospective investigation, the medical files of the patients who, between 1992 and 2006, underwent surgery for the treatment of cystic echinococcosis (CE) in one of the three university hospitals in Hamedan province, in western Iran, were explored. Of the 179 patients involved, 44.1% were male and 55.9% female, giving a male/ female ratio of 0.79. The mean annual surgical incidence of CE in the catchment areas of the study hospitals was estimated to be 1.33 cases/100,000. Although most of Hamedan's population is urban (53.02% at the last census, in 1997), most (57.5%) of the patients lived in rural areas (P<0.05). Among the CE cases, housewives (47.3%), farmers (16.6%) and labourers (16.0%) were over-represented compared with the frequencies of these occupations in the general population of the region (P<0.05 for each). Most of the CE cases were aged 20-39 years (35.8%) or 40-59 years (29.0%) and most had liver cysts, either alone (60.9%) or with cysts in other sites (9.5%), although 19.6% of the cases appeared only to have lung cysts. Overall, 90.5% of the cases showed single-organ involvement. Liver involvement was 3.3-fold more common than lung involvement, the ratio between cases with liver cysts and those with lung cysts generally increasing with age (from 1.6 for the cases aged <20 years to 5.6 among the cases aged 40-59 years). The most common clinical symptoms were abdominal pain and/or a sensation of abdominal mass in those with hepatic CE, and chest pain, cough, dyspnoea and/or haemoptysis in those with pulmonary CE. Although 72% of the cases each had a single cyst, 19.6% had two cysts each and 8.4% each had at least three cysts. Only three (1.7%) of the cases had had previous surgery for CE. Diagnosis of CE in Hamedan province is largely dependent on ultrasonography and computed tomography. Together, these results confirm that CE is endemic in the province and indicate that certain occupations (housewife, farmer and labourer) and/or rural life are risk factors. | 18,817,601 |
Stimulation of Na+-Ca2+ exchange by purified antibody against alpha-2 repeat of Na+-Ca2+ exchanger in rat cardiomyocytes. | The aim of the present study was to investigate the effect of the antibody against alpha-2 repeat on Na+-Ca2+ exchanger (NCX) current (I(Na/Ca)). To evaluate the functional specificity of this antibody, its effects on L-type Ca2+ current (I(Ca,L)), voltage-gated Na+ current (I(Na)) and delayed rectifier K+ current (I(K)) were also observed. The whole-cell patch-clamp technique was used in this study. The antibody against alpha-2 repeat augmented both the outward and inward Na+-Ca2+ exchanger current concentration-dependently, with EC(50) values of 27.9 nmol/L and 24.7 nmol/L, respectively. Meanwhile, the antibody could also increase I(Ca,L) in a concentration-dependent manner with the EC(50) of 33.6 nmol/L. Effects of the antibody on I(Na) and I(K) were not observed in the present study. The present results suggest that antibody against alpha-2 repeat is a stimulating antibody to NCX and could also increase I(Ca,L) in a concentration-dependent manner, but did not have an obvious effect on I(Na) and I(K). | 18,817,621 |
Discrimination analysis of mass spectrometry proteomics for ovarian cancer detection. | A discrimination analysis has been explored for the probabilistic classification of healthy versus ovarian cancer serum samples using proteomics data from mass spectrometry (MS). The method employs data normalization, clustering, and a linear discriminant analysis on surface-enhanced laser desorption ionization (SELDI) time-of-flight MS data. The probabilistic classification method computes the optimal linear discriminant using the complex human blood serum SELDI spectra. Cross-validation and training/testing data-split experiments are conducted to verify the optimal discriminant and demonstrate the accuracy and robustness of the method. The cluster discrimination method achieves excellent performance. The sensitivity, specificity, and positive predictive values are above 97% on ovarian cancer. The protein fraction peaks, which significantly contribute to the classification, can be available from the analysis process. The discrimination analysis helps the molecular identities of differentially expressed proteins and peptides between the healthy and ovarian patients. | 18,817,630 |
Ventricular arrhythmia onset during diagnostic coronary angiography with a 5F or 4F universal catheter. | Of 18,365 patients who underwent coronary angiography with a 4F or 5F universal catheter between April 2004 and May 2007, 24 (0.131%) experienced sustained ventricular tachycardia or ventricular fibrillation during the procedure. There was no significant difference in any clinical or angiographic characteristic between patients who had a ventricular arrhythmia and those who did not. Of the 24 episodes of ventricular arrhythmia, 14 were related to catheter manipulation, 8 to ischemia, and 2 to the contrast medium, while the cause could not be clearly established in 4. The incidence of ventricular arrhythmia with a universal catheter was 0.131%, and with a preformed catheter, 0.054% (P=.72). The study shows that serious ventricular arrhythmia occurs only rarely as a complication when coronary angiography is carried out using modern techniques and that imperfect manipulation of the catheter explains most episodes. | 18,817,686 |
[Static posturography versus clinical tests in elderly people with vestibular pathology]. | Balance can be quantified by clinical tests and through instrumental studies. The objective of this paper is to determine the correlation between static posturography and 4 clinical tests of balance in elderly people with vestibular disorders and to identify its capability to discriminate the groups studied. 60 patients with vestibular disorders and 60 healthy subjects performed 4 clinical tests (one leg standing with opened eyes, Timed Up and Go, Tinetti and Berg tests) and a static posturography analysis (NedSVE/IBV system) under 4 conditions: Romberg Test, Eyes Open (REO), Romberg Test, Eyes Closed (REC), Romberg Test on Foam with Eyes Open (RFEO), and Romberg Test on Foam with Eyes Closed (RFEC). RFEO correlated best with the clinical tests and RFEC was the worst. RFEO distinguished between healthy individuals and decompensated patients. RFEO gave the best information about postural balance in the elderly. RFEC was not useful. Static posturography can be useful to distinguish vestibular compensation status. | 18,817,715 |
Potential associations between fecal shedding of Salmonella in feedlot cattle treated for apparent respiratory disease and subsequent adverse health outcomes. | A prospective cohort study was used to assess whether Salmonella fecal shedding in commercial feedlot cattle treated with antimicrobials for respiratory disease was associated with subsequent adverse health outcomes. Feces were collected per rectum from cattle that were examined for apparent respiratory disease, had a rectal temperature > or = 40 degrees C, and subsequently received antimicrobial treatment. Salmonella were recovered from 918 (73.7%) of 1 245 fecal samples and weekly prevalence estimates ranged from 49 to 100% over the 3-month study. Genotypic and phenotypic characteristics of Salmonella strains in the population were determined. Serogroup E Salmonella were most common (73.3%), followed by C1 (11.0%), C3 (8.6%), and B (1.1%). Predominant serotypes were Orion (46.5%), Anatum (19.8%), Kentucky (8.7%), Montevideo (7.5%), and Senftenberg (4.9%). Few isolates (36/918) were positive for antimicrobial resistance-associated integron gene intI1. Phenotypic susceptibility was associated with isolate intI1 status. Crude re-pull, re-treatment and case fatality risks were higher for cattle that were Salmonella-positive versus -negative at initial treatment, but not statistically different on multivariable analysis. However, case fatality risk was higher for cattle shedding Group B Salmonella than for cattle shedding other serogroups. Lots (groups) with a higher Salmonella prevalence at first treatment had a higher proportion of mortalities occur in a hospital pen, higher overall re-treatment risks, and were more likely to be sampled later in the study. Results indicate a high prevalence of Salmonella in this population of cattle treated for apparent respiratory disease, but that effects associated with clinical outcomes may depend on the Salmonella strain. | 18,817,722 |
Multiple roles of calcium ions in the regulation of neurotransmitter release. | The intracellular calcium concentration ([Ca(2+)]) has important roles in the triggering of neurotransmitter release and the regulation of short-term plasticity (STP). Transmitter release is initiated by quite high concentrations within microdomains, while short-term facilitation is strongly influenced by the global buildup of "residual calcium." A global rise in [Ca(2+)] also accelerates the recruitment of release-ready vesicles, thereby controlling the degree of short-term depression (STD) during sustained activity, as well as the recovery of the vesicle pool in periods of rest. We survey data that lead us to propose two distinct roles of [Ca(2+)] in vesicle recruitment: one accelerating "molecular priming" (vesicle docking and the buildup of a release machinery), the other promoting the tight coupling between releasable vesicles and Ca(2+) channels. Such coupling is essential for rendering vesicles sensitive to short [Ca(2+)] transients, generated during action potentials. | 18,817,727 |
Calcium channel regulation and presynaptic plasticity. | Voltage-gated calcium (Ca(2+)) channels initiate release of neurotransmitters at synapses, and regulation of presynaptic Ca(2+) channels has a powerful influence on synaptic strength. Presynaptic Ca(2+) channels form a large signaling complex, which targets synaptic vesicles to Ca(2+) channels for efficient release and mediates Ca(2+) channel regulation. Presynaptic plasticity regulates synaptic function on the timescale of milliseconds to minutes in response to neurotransmitters and the frequency of action potentials. This article reviews the regulation of presynaptic Ca(2+) channels by effectors and regulators of Ca(2+) signaling and describes the emerging evidence for a critical role of Ca(2+) channel regulation in control of neurotransmission and in presynaptic plasticity. Failure of function and regulation of presynaptic Ca(2+) channels leads to migraine, ataxia, and potentially other forms of neurological disease. We propose that presynaptic Ca(2+) channels serve as the regulatory node in a dynamic, multilayered signaling network that exerts short-term control of neurotransmission in response to synaptic activity. | 18,817,729 |
3,4-Dihydroxyphenylalanine gel diffusion assay for polyphenol oxidase quantification. | We have developed a simple, inexpensive plate assay to detect and quantify polyphenol oxidase (PPO) activity from different origins. The logarithm of enzyme activity is linearly correlated with the diameter of the dark, l-3,4-dihydroxyphenylalanine (l-DOPA) oxidized circles produced in the gel, thereby allowing quantification of PPO. Moreover, precision and high reproducibility of the assay were confirmed by statistical analysis. | 18,817,742 |
Control of the blue fluorescent protein with advanced evolutionary pulse shaping. | We demonstrate optical coherent control of the two-photon fluorescence of the blue fluorescent protein (BFP), which is of interest in investigations of protein-protein interactions. In addition to biological relevance, BFP represents an interesting target for coherent control from a chemical perspective due to its many components of highly nonexponential fluorescence decay and low quantum yield resulting from excited state isomerization. Using a genetic algorithm with a multiplicative (rather than ratiometric) fitness parameter, we are able to control the ratio of BFP fluorescence to second-harmonic generation without a considerable drop in the maximized signal. The importance of linear chirp and power-scaling on the discrimination process is investigated in detail. | 18,817,751 |
The aryl hydrocarbon receptor cross-talks with multiple signal transduction pathways. | Exposure to toxic polycyclic aromatic hydrocarbons raises a number of toxic and carcinogenic responses in experimental animals and humans mediated for the most part by the aryl hydrocarbon -- or dioxin -- receptor (AHR). The AHR is a ligand-activated transcription factor whose central role in the induction of drug-metabolizing enzymes has long been recognized. For quite some time now, it has become clear that the AHR also functions in pathways outside of its role in detoxification and that perturbation of these pathways by xenobiotic ligands may be an important part of the toxicity of these compounds. AHR activation by some of its ligands participates among others in pathways critical to cell cycle regulation, mitogen-activated protein kinase cascades, immediate-early gene induction, cross-talk within the RB/E2F axis and mobilization of crucial calcium stores. Ultimately, the effect of a particular AHR ligand may depend as much on the adaptive interactions that it established with pathways and proteins expressed in a specific cell or tissue as on the toxic responses that it raises. | 18,817,753 |
Similar behaviour and primate-like properties of adult canine Schwann cells and olfactory ensheathing cells in long-term culture. | Adult canine Schwann cells and olfactory ensheathing cells (OECs) have been shown to promote neural regeneration in vivo. Since the majority of studies have been performed in rodents, it is not yet clear in how far OECs from large animals and humans share the reported properties. Moreover, due to the lack of comparative studies, it remains to be established whether Schwann cells and OECs display cell type-specific characteristics. In the present study, adult canine Schwann cells and OECs were comparatively analyzed regarding long-term growth, morphology, growth factor responsiveness, and antigenic expression. Adult canine Schwann cells and OECs displayed the same typical spindle-shaped morphology and expressed the cell type-specific marker p75(NTR). Moreover, the proliferation of both cell types was promoted by the same mitogens, including fibroblast growth factor-2 (FGF-2) and heregulin-1beta (HRG-1beta). Several observations indicate that canine OECs differ from the well characterized rodent OECs and display properties reminiscent on primate cells. Both cell types (i) proliferated through multiple passages in the absence of growth factors and did not enter a senescent state until 3 months in culture, (ii) were not responsive to the cAMP-elevating agent forskolin, and (iii) stably expressed p75(NTR) in long-term culture. Taken together, this is the first report demonstrating that adult canine Schwann cells and OECs in long-term culture share the same in vitro characteristics and display primate-like properties. This underscores the relevance of the dog as a translational species between rodents and humans. | 18,817,757 |
D-Glucose sensing by a plasma membrane regulator of G signaling protein, AtRGS1. | Plants use sugars as signaling molecules and possess mechanisms to detect and respond to changes in sugar availability, ranging from the level of secondary signaling molecules to altered gene transcription. G-protein-coupled pathways are involved in sugar signaling in plants. The Arabidopsis thaliana regulator of G-protein signaling protein 1 (AtRGS1) combines a receptor-like seven transmembrane domain with an RGS domain, interacts with the Arabidopsis Galpha subunit (AtGPA1) in a d-glucose-regulated manner, and stimulates AtGPA1 GTPase activity. We determined that AtRGS1 interacts with additional components, genetically defined here, to serve as a plasma membrane sensor for d-glucose. This interaction between AtRGS1 and AtGPA1 involves, in part, the seven-transmembrane domain of AtRGS1. | 18,817,773 |
Effects of the nicotinic receptor partial agonists varenicline and cytisine on the discriminative stimulus effects of nicotine in rats. | The nicotinic partial agonist varenicline (VCL) is a recently approved medication for the treatment of tobacco dependence, yet very little preclinical research on this drug has been published. The present experiment examined the nicotinic partial agonist properties of VCL and its parent compound, cytisine (CYT), in a nicotine discrimination assay. Rats were trained to discriminate nicotine (0.4 mg/kg, s.c.) from saline using a two-lever discrimination procedure, followed by generalization and antagonism tests with VCL and CYT. Antagonism was examined across a range of nicotine doses. In generalization tests, VCL produced a maximum of 63% responding on the nicotine-appropriate lever, indicating partial generalization. In antagonism tests, VCL decreased the % responding on the nicotine-appropriate lever at 0.2 and 0.4 mg/kg nicotine, indicating antagonism of nicotine's discriminative stimulus effects. No dose of VCL produced significant effects on response rate. The two highest doses of CYT weakly substituted for nicotine, producing a maximum of 23% nicotine-appropriate responding. CYT produced a weak antagonism of the discrimination of moderate nicotine doses, but not of the training dose. These results demonstrate that VCL and CYT partially generalize to and partially antagonize nicotine's discriminative stimulus effects, consistent with a partial agonist mechanism of action. | 18,817,808 |
Fourier transform infrared study of protein secondary structural changes in the muscle of Labeo rohita due to arsenic intoxication. | Protein is one of the most important nutrients in human diets and fish has become an increasingly important source of protein in most of the developing countries. Among the various fish tissues, muscle is the major contributor of proteins and the whole mass of the body. The goal of this study is to assess the changes in the biochemical compositions in general, and the protein structural changes in particular, in the muscle of Labeo rohita fingerlings due to arsenic intoxication using Fourier transform infrared (FT-IR) spectroscopy. The results of the present study indicate that arsenic intoxication induces significant alteration in the major biochemical compositions such as proteins, lipids and nucleic acids of Labeo rohita. Further, the results clearly indicate considerable change in the composition of muscle proteins due to arsenic intoxication. It is therefore concluded that FT-IR spectroscopy can be a successful detection tool in toxicological research. | 18,817,838 |
Reduced NGF level and TrkA protein and TrkA gene expression in the optic nerve of rats with experimentally induced glaucoma. | Glaucoma (GL) is an optic neuropathy characterized by progressive loss of visual field due to retinal cell death and optic nerve (ON) degeneration, usually in response to abnormal elevated intraocular pressure (EIOP). It has previously demonstrated that cells of the ON express nerve growth factor (NGF) and NGF-receptors. Relatively little is known, however, about their role on the ON of the glaucomatous eye. The aim of the study was to elucidate this aspect. Using a rat model of GL we investigated the response of NGF and NGF-receptors in the ON of subjects with experimentally induced EIOP. Our results show that EIOP significantly impairs the presence of NGF and NGF-receptor proteins and TrkA gene expression in the ON of glaucomatous eye. These findings suggest that NGF and NGF-receptor might be important signals for the ON response in the EIOP. | 18,817,846 |
Timed restricted feeding restores the rhythms of expression of the clock protein, Period2, in the oval nucleus of the bed nucleus of the stria terminalis and central nucleus of the amygdala in adrenalectomized rats. | Feeding schedules that limit food availability to a set time of day are powerful synchronizers of the rhythms of expression of the circadian clock protein Period 2 (PER2) in the limbic forebrain in rats. Little is known, however, about the mechanisms that mediate the effect of such timed restricted feeding (TRF) schedules on the expression of PER2. Adrenal glucocorticoids have been implicated in the circadian regulation of clock genes expression in peripheral tissues as well as in the control of the rhythms of expression of PER2 in certain limbic forebrain regions, such as the oval nucleus of the bed nucleus of the stria terminalis (BNSTov) and central nucleus of the amygdala (CEA) in rats. To study the possible involvement of glucocorticoids in the regulation of PER2 expression by TRF, we assessed the effect of adrenalectomy on TRF-entrained PER2 rhythms in the limbic forebrain in rats. Adrenalectomy selectively abolished the rhythms of PER2 in the BNSTov and CEA in normally fed rats, as previously shown, but had no effect on TRF-entrained PER2 rhythms in the same structures. These findings show that the effect of TRF on PER2 rhythms in the limbic forebrain is independent of adrenal glucocorticoids and demonstrate that the involvement of glucocorticoids in the regulation PER2 rhythms in the limbic forebrain is not only region specific, as previously shown, but also state dependent. | 18,817,849 |
Bmi1 promotes prostate tumorigenesis via inhibiting p16(INK4A) and p14(ARF) expression. | We report here that the polycomb group protein Bmi1 promotes prostate tumorigenesis. Bmi1 is detected at higher levels in androgen-independent PC3 and DU145 than in androgen-dependent LNCaP prostate cancer (CaP) cells. Ectopic Bmi1 enhanced the expression of human telomerase reverse transcriptase (hTERT) and suppressed the exression of p16(INK4A) and p14(ARF) in CaP cells. Consistent with these observations, immunohistochemical staining of 51 cases of primary CaP specimens revealed 1.4 fold (p=0.014) and 1.3 fold (p=0.051) higher levels of Bmi1-positive cells in carcinoma compared to normal prostatic epithelial cells and PIN, respectively. In primary CaPs, Bmi1 expression was associated with a reduction in p16(INK4A) and p14(ARF). Furthermore, in comparison to empty vector-transfected cells, Bmi1-expressing DU145 cells formed significantly larger tumors in NOD/SCID mice. Taken together, we demonstrate that Bmi1 promotes prostate tumorigenesis. | 18,817,867 |
High-level expression of active recombinant ubiquitin carboxyl-terminal hydrolase of Drosophila melanogaster in Pichia pastoris. | Ubiquitin carboxyl-terminal hydrolases (UCHs) are implicated in the proteolytic processing of polymeric ubiquitin. The high specificity for the recognition site makes UCHs useful enzymes for in vitro cleavage of ubiquitin fusion proteins. In this work, an active C-terminal His-tagged UCH from Drosophila melanogaster (DmUCH) was produced as a secretory form in a recombinant strain of the methylotrophic yeast Pichia pastoris. The production of recombinant DmUCH by Mut(s) strain was much higher than that by Mut(+) strain, which was confirmed by Western blot analysis. When expression was induced at pH 6.0 in a BMMY/methanol medium, the concentration of recombinant DmUCH reached 210 mg l(-1). With the (His)(6)-tag, the recombinant DmUCH was easily purified by Ni-NTA chromatography and 18 mg pure active DmUCH were obtained from 100ml culture broth supernatant. Ubiquitin-magainin fusion protein was efficiently cleaved by DmUCH, yielding recombinant magainin with high antimicrobial activity. After removing the contaminants by Ni-NTA chromatography, recombinant magainin was purified to homogeneity easily by reversed-phase HPLC. Analysis of the recombinant magainin by ESI-MS showed that the molecular weight of the purified recombinant magainin was 2465 Da, which perfectly matches the mass calculated from the amino acid sequence. The result of mass spectrometry confirmed that the purified His-tagged DmUCH can recognize the ubiquitin-magainin fusion protein and cleave it at the carboxyl terminus of ubiquitin precisely. Our results showed that P. pastoris is a robust system to express the secreted form of DmUCH. | 18,817,875 |
Classical crosses of common carp (Cyprinus carpio L.) show co-segregation of antibody response with major histocompatibility class II B genes. | In cyprinids, two paralogous groups of major histocompatibility (MH) class II B genes, DAB1 and DAB3, have been reported but have not been studied in detail. In our study on MH association with immune responsiveness in common carp (Cyprinus carpio L.) we have taken a long-term approach using divergent selection for antibody production. We report the co-segregation of Cyca-DAB1-like and Cyca-DAB3-like genes with antibody response, in backcrosses to high- and low-responsive parental carp lines. We show that the presence of Cyca-DAB1-like, but not Cyca-DAB3-like genes, preferentially leads to a high DNP-specific antibody response in carp. Background genes other than Cyca-DAB genes also influenced the level of antibody response. Our data support the hypothesis of a genetic control by Cyca-DAB genes on the antibody response measured. We could not detect an association of the Cyca-DAB genes with disease resistance to the parasite Trypanoplasma borreli. Sequence information, constitutive transcription levels and our co-segregation data indicate that both paralogous Cyca-DAB1-like and Cyca-DAB3-like groups represent functional MH class II B genes. Previously defined differences in allelic diversity between Cyca-DAB1-like genes, especially, identify Cyca-DAB1 as the most interesting DAB gene for further study in common carp. | 18,817,879 |
Go no-go performance under psychosocial stress: beneficial effects of implementation intentions. | Acute stress has been found to have negative and implementation intentions (IIs) to have positive effects on cognitive performance. This study was the first to examine the effects of IIs on executive action control under acute psychosocial stress. Forty-two male subjects aged 21-39 years were randomly assigned to the Trier Social Stress Test (TSST) versus a rest condition. In addition, the instruction to the executive task (a go no-go task) was manipulated (IIs versus standard instruction). After the stress test, a dual-task procedure including a go no-go task was conducted. The TSST resulted in increases in cortisol response, heart rate and state anxiety compared to the rest condition. Acute stress significantly impaired go no-go performance, but only in the group without IIs. We conclude that under acute stress conditions executive functioning is reduced, but the use of IIs can be an effective strategy to overcome this negative effect. | 18,817,886 |
Effectiveness, safety, and acceptability of cryotherapy by midwives for cervical intraepithelial neoplasia in Maharashtra, India. | To evaluate the effectiveness, safety, and acceptability of cryotherapy for cervical intraepithelial neoplasia (CIN) when provided by trained midwives in rural India. Women with colposcopic findings of CIN lesions suitable for ablative treatment received cryotherapy from trained midwives before the biopsy results were known. Cure rates, adverse effects, and complications were assessed and factors influencing cure rates were evaluated by chi(2) tests. Cure was defined as no clinical or histologic evidence of CIN lesions 6 or more months after treatment. Of 1068 women treated with cryotherapy, 728 had histologically proven CIN in their pretreatment biopsy specimens; of the 574 reporting for follow-up, 538 (93.7%) were cured (95% confidence interval [CI], 92.1%-96.3%). Cure rates were 96.4% (95% CI, 94.6%-98.1%) for CIN 1 and 82.1% (95% CI, 74.7%-89.4%) for CIN 2 and CIN 3 lesions combined. Minor adverse effects were documented in 5.2% of the women. Cryotherapy provided by midwives was found to be safe, effective, and acceptable by the women. | 18,817,909 |
Gastric neuroendocrine carcinoma associated with atrophic gastritis in the norwegian lundehund. | In humans and rodents the association between atrophic gastritis, hypergastrinemia and gastric neoplasia is well-documented. Gastric tumours are rare in dogs, but the Norwegian Lundehund (puffin dog) appears predisposed to the development of gastric neoplasia associated with chronic atrophic gastritis. The present study describes 8 Lundehunds with gastric neoplasia. Seven of these animals had concurrent chronic atrophic gastritis characterized by reduction in parietal cells and hyperplasia of neuroendocrine cells. Four of the tumours displayed neuroendocrine (enterochromaffin-like cell; ECL) differentiation, suggesting that hypergastrinemia secondary to fundic atrophy may be important in carcinogenesis. The Norwegian Lundehund may therefore represent a further animal model for the study of the role of gastrin in the induction of gastric neoplasia. | 18,817,920 |
Study of surface electrocardiogram spectrum before and after pulmonary vein ablation in patients with persistent atrial fibrillation. | Atrial fibrillation (AF) is the most common clinical cardiac arrhythmia and is usually treated with the electrical isolation of the pulmonary veins from the atria. However, it is estimated that about 30% of the patients undergoing this therapy will develop AF again. The purpose of this study was to test the dynamic changes of the spectra calculated in surface electrocardiograms (ECGs) before and after the ablation of the pulmonary veins. Surface ECGs of 14 patients with persistent AF undergoing this intervention were considered for this study. The QRS-T waves were subtracted from the ECGs using common spatial pattern, isolating the electrical activity of the atrium. The spectrum was then calculated and the main frequency peaks were identified. The smaller peaks with amplitude below 50% of the maximum were discarded. Eleven of the patients were followed up after the intervention for 1 to 6 months. Two of the patients developed AF again; the other 9 remained in sinus rhythm. For most of the patients, the spectrum showed more order after the intervention. However, the main frequency did not experience a significant decrease in average (5.1 Hz [+/-1.3] to 4.9 Hz [+/-1.0]). Interestingly, the increment or decrease of the main frequency did not correlate with the recurrence of AF or not. | 18,817,922 |
Biomarkers of environmental toxicity and susceptibility in autism. | Autism spectrum disorders (ASDs) may result from a combination of genetic/biochemical susceptibilities in the form of a reduced ability to excrete mercury and/or increased environmental exposure at key developmental times. Urinary porphyrins and transsulfuration metabolites in participants diagnosed with an ASD were examined. A prospective, blinded study was undertaken to evaluate a cohort of 28 participants with an ASD diagnosis for Childhood Autism Rating Scale (CARS) scores, urinary porphyrins, and transsulfuration metabolites. Testing was conducted using Vitamin Diagnostics, Inc. (CLIA-approved) and Laboratoire Philippe Auguste (ISO-approved). Participants with severe ASDs had significantly increased mercury intoxication-associated urinary porphyrins (pentacarboxyporphyrin, precoproporphyrin, and coproporphyrin) in comparison to participants with mild ASDs, whereas other urinary porphyrins were similar in both groups. Significantly decreased plasma levels of reduced glutathione (GSH), cysteine, and sulfate were observed among study participants relative to controls. In contrast, study participants had significantly increased plasma oxidized glutathione (GSSG) relative to controls. Mercury intoxication-associated urinary porphyrins were significantly correlated with increasing CARS scores and GSSG levels, whereas other urinary porphyrins did not show these relationships. The urinary porphyrin and CARS score correlations observed among study participants suggest that mercury intoxication is significantly associated with autistic symptoms. The transsulfuration abnormalities observed among study participants indicate that mercury intoxication was associated with increased oxidative stress and decreased detoxification capacity. | 18,817,931 |
Bilateral extravesical ureteral reimplantation in toilet-trained children: short-stay procedure without urinary retention. | We have previously reported on the ability of toilet-trained children to undergo bilateral extravesical ureteral reimplantation with a 1-day hospitalization and without urinary retention using a critical pathway and modification of the surgical technique. The objective of this study was to determine whether additional refinement of the critical pathway and surgical technique could continue to result in 1-day hospitalization and possibly an outpatient procedure, without urinary retention, in toilet-trained children. We evaluated all toilet-trained children undergoing bilateral extravesical ureteroneocystostomy, with a critical pathway for preoperative education, operative management, and postoperative care. A modified technique was used that limits ureteral dissection, ureteral mobilization, and detrusor dissection to as distally as possible such that a 5:1 ratio of tunnel length to ureteral diameter can be accomplished. Patients followed a strict postoperative critical pathway, and parents received extensive preoperative and postoperative education. A child was required to fulfill 5 strict criteria to be discharged from the hospital. A total of 84 patients underwent bilateral extravesical ureteral reimplantation. Of the 84 patients, 64 were girls and 20 were boys. The age range was 1.9-12.8 years (mean 4.6). The first 78 patients were discharged on the first postoperative day as planned. The next 6 patients in this series were discharged the same day as surgery as planned, using the modification of the critical pathway. All patients were able to spontaneously void postoperatively without any instances of acute or chronic urinary retention, acute urinary tract infection, or rehospitalization. The results of this study further support our initial findings that bilateral extravesical ureteral reimplantation can be performed in toilet-trained children after a 1-day hospitalization without postoperative urinary retention. In the present study, this was also accomplished as an outpatient procedure. | 18,817,956 |
Psychomotor functioning in chronic fatigue syndrome and major depressive disorder: a comparative study. | Studies comparing chronic fatigue syndrome (CFS) and major depressive disorder (MDD) reported similarities as well as differences between the two disorders. However, whereas psychomotor symptoms have been studied extensively in MDD, such research in CFS is more limited. Moreover, the few studies that compared cognitive and motor performance in MDD and CFS yielded inconsistent results. This study hence directly compares fine psychomotor functioning in both syndromes. Thirty-eight patients diagnosed with CFS without a current major depressive episode (MDE), 32 MDD patients with a current MDE and 38 healthy controls performed two computerized copying tasks differing in complexity: a line-copying task that mainly requires motor effort and a figure-copying task requiring additional cognitive efforts. All participants were female. A multivariate general linear model was used to compute group differences. Overall, both patient groups performed more slowly than the controls. Compared to CFS patients, patients with MDD needed significantly more time to copy the single lines but no such between-group performance difference was observed for the figure reproductions. In this latter copying task, the increasing complexity of the figures resulted in prolonged reaction times for all three participant groups with the effect being larger and the magnitude similar for the two patient groups. All patients were female and most were on psychotropic medication. Both the MDD and CFS patients tested demonstrated an overall fine motor slowing, with the motor component being more affected in the MDD patients than in the CFS patients while both patient groups showed similar cognitive impairments. | 18,817,977 |
Development and validation of the Combined Emotional and Affective Temperament Scale (CEATS): towards a brief self-rated instrument. | Temperament relates to both emotional dimensions and prevailing mood, but these different views are rarely integrated. Based on a model where temperament works as a system with activation, inhibition and control (inspired in Cloninger's and Rothbart's models), which produce the affective tone (inspired by Akiskal's and Kraepelin's model), we developed and validated the Combined Emotional and Affective Temperament Scale (CEATS). 1007 subjects (28% males) from the general population and university students filled in the instrument either in the Internet or in a pen and paper version. The CEATS has an emotional section (dimensional only), an Affective section (both dimensional and categorical) and an evaluation of problems and benefits related to temperament. The data was analyzed with standard psychometric batteries and different sections were compared. In the emotional section, 4 factors with Eingenvalue >1 explained 46% of the variation. These factors were interpreted as drive, control, disinhibition-fear and anger, had a normal distribution and had satisfactory Chronbach's alphas (0.70-0.82). Anger was particularly associated with problems and drive with benefits. In the Affective section, all 10 categorical affective temperaments were selected, being euthymic and hyperthymic the most prevalent (18-23%), followed by cyclothymic and irritable (11-13%), anxious and depressive (8-9%) and dysphoric, disinhibited, labile and apathetic temperaments (3-7%). The dimensional evaluation of affective temperaments showed 95% of the sample was able to ascribe to at least one affective temperament. Only the euthymic and hyperthymic temperaments were clearly associated with a favorable problem/benefit profile. The comparison between the emotional and affective sections revealed that each affective temperament had a particular emotional configuration. Both computerized and pen and paper versions were used. The sample was not evaluated for psychiatric symptoms. Quantification of the dimensional assessment of affective temperament is limited. The CEATS is a brief and adequate instrument to evaluate emotional and affective aspects of temperament simultaneously. | 18,817,978 |
Sulphurous water inhalations in the prophylaxis of recurrent upper respiratory tract infections. | The aim of this study was to evaluate the efficacy and the effect of sulphurous thermal water inhalations in the treatment of the recurrent upper respiratory tract (RURT) infections in children. A total of 100 children with RURT infections were included. All children underwent a 12-day course warm vapour inhalations. For the inhalations, we used sulphurous thermal water in the group A, while physiological solution in the group B. At the beginning, at the end and 3 months after start, all children underwent medical history, ENT examination, plasma levels of immunoglobulins class E, G, A, M (IgE, IgG, IgA, IgM), subjective assessment of symptoms (VAS), nasal mucociliar transport time (NMTT) determination, and evaluation of frequency, duration, severity and social impact of RURT episodes. Compared with group B, after the treatment and at the end of the study, in children treated with sulphurous thermal water, the serum concentration of IgE was significantly (p<0.05) lower (75.13+/-27.1mg/dl vs 96.87+/-41.3mg/dl; 74.23+/-26.2mg/dl vs 98.24+/-42.7 mg/dl), IgA titers were higher (238.14+/-122.1mg/dl vs 218.62+/-115.8 mg/dl; 239.72+/-119.7 mg/dl vs 210.46+/-107.3mg/dl), serum concentrations of IgG and IgM unchanged, VAS scores presented a significant (p<0.05) improvement (1.8+/-0.19 vs 6.8+/-0.54; 1.9+/-0.21 vs 6.9+/-0.61), NMTT was normal (11.15+/-1.59 min vs 17.63+/-2.17; 11.25+/-2.10 min vs 17.77+/-2.19 min) and frequency, duration, severity and social impact of RURT episodes were significantly (p<0.05) lower. Our findings indicate that, in addition to their known effects, the sulphurous water also have an immunomodulant activity that contributes to their therapeutic effects. | 18,817,987 |
Long-term effects of the antifouling booster biocide Irgarol 1051 on periphyton, plankton and ecosystem function in freshwater pond mesocosms. | Irgarol is a highly effective biocide used in antifouling coatings to prevent the growth of periphyton. Environmental concentrations of Irgarol in marine and freshwater have often exceeded the effect concentrations of autotrophic organisms tested in the laboratory and give reason for concern that natural periphyton communities may be endangered. A 150 days freshwater mesocosm study in 8 indoor ponds was conducted at nominal concentrations between 0.04 and 5 microgL(-1) in order to investigate the effects of Irgarol on periphyton and plankton. The results demonstrated that periphyton communities were strongly affected after single applications of 1 and 5 microgL(-1) Irgarol. For these concentrations no recovery was observed in the course of the study. For chlorophytes, the EC(50) (nominal, 135 days) was 0.34 microgL(-1). Phytoplankton also decreased in abundance directly after Irgarol application but recovered after a few weeks, as Irgarol concentrations rapidly decreased in the water body and nutrient levels increased due to lack of competition with periphyton and macrophytes. Zooplankton was indirectly affected by Irgarol. Principle response curve analysis revealed a species shift from macrophyte associated zooplankton species to free-swimming species. For species of cyclopoid copepods and ostracods the EC(50) was, respectively, 0.09 and 0.11 microgL(-1). The study simulated a best-case scenario since the mesocosms were dosed only once. Under field conditions, however, permanent exposure of organisms to Irgarol is more likely due to permanent leaching from painted ship hulls. Therefore, the effects presented in this study most likely underestimate the effects under natural conditions. | 18,817,992 |
Pioglitazone induces regression of coronary atherosclerotic plaques in patients with type 2 diabetes mellitus or impaired glucose tolerance: a randomized prospective study using intravascular ultrasound. | A large clinical trial clarified that pioglitazone reduces cardiovascular events in diabetic patients. However, effects of pioglitazone on structure of coronary atherosclerotic plaques have not been demonstrated. We examined whether pioglitazone reduces volumes of coronary atherosclerotic plaques using intravascular ultrasound (IVUS). Twenty-six consecutive patients with type 2 diabetes mellitus (DM) or impaired glucose tolerance (IGT) undergoing percutaneous coronary intervention (PCI) were enrolled. Echolucent plaques without significant stenosis were selected in IVUS video images at non-PCI-influenced coronary segments and volumetric analysis of the targeted plaques was performed. The patients were randomly assigned into 2 groups: pioglitazone group consisted of 13 patients taking pioglitazone 15 mg/day for initial 14 days after PCI and subsequent 30 mg/day during 6-month follow-up, and control group with 13 patients as control. The plaque volumes and some parameters such as plasma lipid profiles and high-sensitive C-reacting protein (hs-CRP) levels were compared between baseline and the follow-up in those groups. In the pioglitazone group after 6 months, the plaque volume was significantly reduced (101.3+/-32.1 to 94.6+/-33.6 mm(3), -7.2%; p=0.0023), plasma triglyceride was significantly decreased (- 14.9%) and high density lipoprotein cholesterol was substantially increased (+20.0%) without any significant change in low density lipoprotein cholesterol (LDL-C). Also, hs-CRP level tended to be decreased. However, no significant change in plaque volumes and those parameters was observed in the control group. Pioglitazone may induce regression of coronary atherosclerotic plaques without LDL-C reduction in patients with DM and IGT. | 18,817,993 |
[A rare splenic lesion, the splenoma or splenic hamartoma]. | We report a new case of splenoma in a previously healthy adult. A 52-year-old man was admitted for a splenomegaly with thrombocytopenia. The computed tomographic scan showed a tumor which measured 56 mm in diameter. A splenectomy was performed. Histologic examination of the splenectomy specimen revealed a splenoma. Splenoma or splenic hamartoma is a rare primary splenic tumor most often incidentally discovered, radiologically. It can also meet in a particular pathological context, evoking more a coexistence rather than an association or a complication, underlying the role of the pathologist in its diagnosis. | 18,818,001 |
Quality of life in climacteric Chilean women treated with low-dose estrogen. | To evaluate the impact of low-dose oral estrogen therapy on the health-related quality of life (HRQoL) in 45-64-year-old women from the East Metropolitan Health Service (SSMO) in Santiago, Chile. We conducted an observational cross-sectional study. A random population sample of women between 45 and 64 years of age was obtained through an invitation to contact one of 15 primary health care centers of the SSMO of Santiago, Chile. Out of the 927 women who were originally contacted, 844 women were able to complete the Menopausal Rating Scale (MRS) questionnaire. Information about demographic parameters, health issues, and modality of hormonal therapy (HT) were registered. Three groups were compared: group 1 (n=647; non-users of HT), group 2 (n=82; users of low-dose oral estrogen HT), and group 3 (n=115; users of non low-dose estrogens HT). There were no differences among groups in terms of demographic and health issue parameters. The results of the MRS scores (total score and somatic, psychological and urogenital domain scores) showed significant differences across the 3 study groups, with more favorable results for HRQoL in groups 2 and 3 (p<0.01 for total, somatic, and psychological scores; p=0.05 for urogenital score). Climacteric women in the 45-64 age range using HT were shown to have a more favorable impact on HRQoL than non-HT users. Women using low-dose oral estrogen HT had a positive effect on HRQoL, similar to that obtained using non low-dose estrogen regimens. | 18,818,032 |
Rupture of the pectoralis major: a case report and review. | Rupture of the pectoralis major muscle is a rare clinical entity that is becoming more common due to the increasing popularity of weightlifting and recreational sports. Due to the rarity of this condition, it may be missed at initial presentation and inappropriately treated, potentially leading to increased disability. This case highlights the mechanism of injury, clinical features, diagnosis, and treatment of rupture of the pectoralis major. The patient was a 31-year-old male bodybuilder who presented to the Emergency Department with acute pain and swelling in the left axilla after performing a bench press with a 400-pound barbell. The diagnosis of pectoralis major rupture was suspected and confirmed by magnetic resonance imaging, and early surgical repair was performed. The most common mechanism of injury is excessive tension on a maximally contracted pectoralis major muscle. Weightlifting, specifically bench pressing, is a common cause. The diagnosis can usually be made based on a patient's history and physical examination, but shortly after injury, the diagnosis may be obscured by severe pain and swelling. Magnetic resonance imaging is the imaging modality of choice when the diagnosis remains unclear, and can avoid surgical delays. Early diagnosis and treatment within 3 to 8 weeks after the injury has the advantage of avoiding adhesions and muscle atrophy, and can prevent a delayed return to normal activities. Given the trend toward improved results with early surgical repair of complete rupture, it is important to raise awareness about pectoralis major muscle injury among Emergency Physicians to prevent missed or delayed diagnosis and repair. | 18,818,044 |
Dopaminergic and serotonergic activity in neostriatum and nucleus accumbens enhanced by intranasal administration of testosterone. | Testosterone was administered intranasally in anesthetized male rats, and its effects on the activity of dopaminergic and serotonergic neurons in the neostriatum and nucleus accumbens were assessed by means of microdialysis and HPLC. The treatment (0.5, 1.0 or 2.0 mg/kg of testosterone or vehicle, 10 microl volume) was applied in both nostrils, half (5 microl) into each. Subcutaneous injections of testosterone (2.0, 4.0 or 8.0 mg/kg) or vehicle were tested in other subjects. Samples were collected for 5 h. In the neostriatum, an increase of dopamine occurred after 2.0 mg/kg. Serotonin levels increased after 1.0 mg/kg dose. In the nucleus accumbens, dopamine and serotonin increased after 1.0 mg/kg and 2.0 mg/kg doses. Subcutaneous administration of 8.0 mg/kg testosterone increased dopamine and serotonin in the neostriatum only. We conclude that intranasal administration of testosterone is a more efficacious way for targeting the brain than the subcutaneous route, and may be considered as a means to activate central dopaminergic and serotonergic systems. | 18,818,056 |
Synthesis and in vitro biological evaluation of ring B abeo-sterols as novel inhibitors of Mycobacterium tuberculosis. | A series of 3beta-hydroxy steroid analogues possessing a contracted cyclopentane B-ring were prepared based on the initial activity screening of a recently reported naturally occurring marine 5(6-->7)abeo-sterol against Mycobacterium tuberculosis. All of the novel ring B abeo-sterols synthesized showed good inhibitory activity, whereas none of the starting steroids based on the common 3beta-hydroxy-Delta(5)-cholestane nucleus, proved to be active. Therefore, the 5(6-->7)abeo-sterol nucleus present in compounds 3, 5, 7, 9, and 11 represents a novel scaffold for the development of new antitubercular agents. | 18,818,073 |
Study of efficacy of miltefosine and allopurinol in dogs with leishmaniosis. | Visceral leishmaniosis is a life-threatening disease of medical, social and economic importance in endemic areas. It is an opportunistic infection in immunocompromised patients, including human immunodeficiency virus-positive subjects. Dogs are the main reservoir of Leishmania infantum. The aim of this study was to evaluate the efficacy of miltefosine and allopurinol for the control of human leishmaniosis using the dog as a model. The study included 28 sick dogs treated with miltefosine (2 mg/kg/day PO) administered concurrently with allopurinol (10 mg/kg/day, PO) for 30 days, and then with allopurinol alone, at the same dosage, for 1 year. Eight dogs (four of which relapsed) received a second cycle of miltefosine within 6 months of the first cycle. Efficacy was measured by real-time polymerase chain reaction assay on whole blood samples and lymph node aspirates, collected at baseline and every 3 months for 12 months. Of the total number of animals (28), two showed renal insufficiency and died after the start of therapy with miltefosine. Two other dogs presented some side effects to treatment, such as nausea, vomiting and reduction in white and red blood cell counts, and these animals were excluded from the follow-up. The results showed that the first cycle of therapy with miltefosine and allopurinol induced a drastic and progressive reduction of L. infantum load in lymph node aspirates but the second cycle did not eliminate the parasite. | 18,818,112 |
[Axillary nerve schwannoma (case report)]. | The schwannoma is a benign tumour that can be eradicated; it usually occurs in the peripheral nerves of the upper limb. We report an exceptional localization in the axillary nerve. The diagnosis is based on the typical MRI appearance: in addition, confirmation of the diagnosis has to be made by histological examination. The surgical treatment by resection, taking care to preserve adjacent nerve fibres. This allows recovery without any after-effects since the recurrence rate as well as the potential for malignant transformation of this type of tumour is low. | 18,818,115 |
[Double simultaneous fingertip metastasis of an epidermoid carcinoma. A case report]. | Fingertip metastases are rare. The authors report the case of a patient with an epidermoid carcinoma of the larynx who presented with two separate finger pulp metastases in each hand. According to the literature this seems a very unusual occurrence. This diagnosis must be considered in the differential diagnosis of every suspicious fingertip lesion. | 18,818,116 |
Mechanisms of proteasome inhibitor action and resistance in cancer. | Proteasome inhibitors (PIs), such as bortezomib, carfilzomib or NPI-0052, have excellent clinical activity in patients with multiple myeloma and mantle cell lymphoma, and they are currently being evaluated in combination with other agents in patients with solid tumors. Although they exert broad effects on cancer cells, their ability to (1) stabilize pro-apoptotic members of the BCL-2 family, (2) inhibit the two major pathways leading to NFkappaB activation, and (3) cause the build-up of misfolded proteins appear to be particularly important. In addition, PIs may disrupt tumor-stromal interactions that drive NFkappaB activation and angiogenesis and in such a way sensitize cancer cells to other agents. Still, drug resistance ultimately emerges in all tumors that initially respond to PIs. This review provides an overview of the current thinking about how PIs may kill cancer cells exemplified for pancreatic cancer and the possible mechanisms involved in resistance to PIs. | 18,818,117 |
Changes in tissue-Doppler echocardiographic assessment of left ventricular filling during NT-proBNP guided heart failure treatment titration: a pilot study. | Although brain natriuretic peptide (BNP) and E/Ea are closely related in heart failure (HF) patients and may be helpful to guide HF therapy, the response of E/Ea to changes in BNP over several weeks of intensive HF treatment optimisation is unknown. This study was designed to investigate this relationship. In 17 patients with decompensated HF, treatment was titrated to reduce the NT-proBNP level to <200pg/mL over 10 weeks. Paired NT-proBNP measurements and echocardiograms were performed at two weekly intervals during the study. Treatment titration was associated with a reduction in E/Ea (17.6+/-6.8S.D. to 13.7+/-5.0S.D., p=0.018) in keeping with the reduction in NT-proBNP (median 603 [S.E. 561] to 311 [S.E. 235], p=0.045). This relationship remained in those who responded to titration (reduction in NT-proBNP of >or=50%), and those who did not. The overall change in E/Ea was similar to the changes observed in NT-proBNP in each group however there appeared to be temporal differences in the changes in E/Ea and NT-proBNP. This pilot study demonstrates that the E/Ea decreases after NT-proBNP guided HF therapy. E/Ea may be a complementary target for HF therapy optimisation; this hypothesis should be further evaluated in larger scale randomised trials. | 18,818,124 |
The development of perioperative practices for liver transplantation: advances and current trends. | Transplantation is a young medical specialty that has grown rapidly over the past 50 years. Anesthesiologists, surgeons and hepatologists are all essential partners in the process of determining patient outcome. Each specialty has made landmark improvements in patient outcome. However, there is still variability in practice patterns in each of the 3 major specialties. This review will use a historic perspective to explore the unique forces that shaped specific transplant practices and those that gave rise to differences in perioperative practices. Anesthesiologists and surgeons have made significant improvements in the management of blood loss, and coagulation monitoring and intervention. This has improved operative survival and early patient outcome. Perioperative survival has improved despite a worldwide shortage of donor organs and a trend to transplant sicker patients. A smaller pool of donor organs is required to meet the needs of an expanding waiting list. The innovations to reduce deaths on the transplant wait list are reviewed along with their impact on overall patient outcome. The evolving organ shortage is the pinnacle point in shaping future transplant practices. Currently, institutional-specific practices may be reinforced by the informal "tutorship" that is used to train physicians and by the resources available at each site of practice. However, there is evidence that specific intraoperative practices such as the use of a low central venous pressure, selection of vasopressors and certain surgical techniques can modify patient outcome. Further investigation is needed to determine whether the good or the bad associated with each practice prevails and in what unique circumstance. | 18,818,135 |
Pyogenic liver abscess associated with septic pulmonary embolism. | Septic pulmonary embolism (SPE) is one of the metastatic foci of pyogenic liver abscess. The purpose of this study was to investigate the clinical presentations of, and management options for patients with pyogenic liver abscess complicated with SPE. A retrospective chart review was conducted from January 1, 1999 to December 31, 2005 inclusively, in a medical center in northern Taiwan. We collected and analyzed the clinical presentations, diagnostic modalities, treatment programs and prognoses for all pyogenic liver abscess patients with SPE. The association between liver abscess affected with the complication of SPE and diabetes mellitus was significant. There were 9 patients who had pyogenic liver abscess with SPE. Abnormal chest radiograph (CXR) findings with multiple ill-defined peripheral round densities were noted in all patients. Seven patients were diabetic, fever occurred in 5 patients, respiratory symptoms were noted in 6 patients, and abdominal pain occurred in 3 patients. Endophthalmitis coexisted in 3 patients, meningitis in 1 patient, and necrotizing fasciitis in 2 patients. Microbiological studies revealed Klebsiella pneumoniae in 9 patients. Computed tomography (CT) demonstrated metastatic nodules in both lung lobes, some of which featured cavitation, in all 9 patients. Three patients soon advanced to acute respiratory failure, and later died due to acute respiratory distress syndrome and/or septic shock. The remaining 6 patients survived without complication during their hospital course. There is diagnostic value in performing a chest CT scan in diabetic patients who have liver abscess plus abnormal CXR findings with multiple ill-defined peripheral round densities, in order to detect SPE, which has a relatively poor outcome in patients with liver abscess. | 18,818,136 |
Determination of trans fatty acid levels by FTIR in processed foods in Australia. | Health authorities around the world advise 'limiting consumption of trans fatty acid', however in Australia the trans fatty acid (TFA) content is not required to be listed in the nutrition information panel unless a declaration or nutrient claim is made about fatty acids or cholesterol. Since there is limited knowledge about trans fatty acid levels in processed foods available in Australia, this study aimed to determine the levels of TFA in selected food items known to be sources of TFA from previously published studies. Food items (n=92) that contain vegetable oil and a total fat content greater than 5% were included. This criterion was used in conjunction with a review of similar studies where food items were found to contain high levels of trans fatty acids. Lipids were extracted using solvents. Gravimetric methods were used to determine total fat content and trans fatty acid levels were quantified by Attenuated Total Reflectance Fourier Transform Infrared spectroscopy. High levels of trans fatty acids were found in certain items in the Australian food supply, with a high degree of variability. Of the samples analysed, 13 contained greater than 1 g of trans fatty acids per serving size, the highest value was 8.1 g/serving. Apart from when the nutrition information panel states that the content is less than a designated low level, food labels sold in Australia do not indicate trans fatty acid levels. We suggested that health authorities seek ways to assist consumers to limit their intakes of trans fatty acids. | 18,818,158 |
Multiple micronutrient deficiencies persist during early childhood in Mongolia. | Data on the prevalence of micronutrient deficiencies in children in Mongolia is limited. We therefore determined the prevalence of anaemia, iron deficiency anaemia (IDA), and deficiencies of iron, folate, vitamin A, zinc, selenium, and vitamin D among young Mongolian children. Anthropometry and non-fasting morning blood samples were collected from 243 children aged 6-36 months from 4 districts in Ulaanbaatar and 4 rural capitols for haemoglobin (Hb), serum ferritin, folate, retinol, zinc, selenium, and 25-hydroxyvitamin D (25-OHD) assays. Children with alpha-1-glycoprotein >1.2mg/L (n=27) indicative of chronic infection were excluded, except for folate, selenium, and 25-hydroxyvitamin D assays. Of the children 14.5% were stunted and none were wasted. Zn deficiency (serum Zn <9.9 micromol/L) had the highest prevalence (74%), followed by vitamin D deficiency 61% (serum 25-OHD<25 nmol/L). The prevalence of anaemia (24%) and iron deficiency anaemia (IDA) (16%) was lower, with the oldest children (24-36 mos) at lowest risk. Twenty one percent of the children had low iron stores, and 33% had vitamin A deficiencies (serum retinol < 0.70 micromol/L), even though two thirds had received vitamin A supplements. Serum selenium values were low, perhaps associated with low soil selenium concentrations. In contrast, no children in Ulaanbaatar and only 4% in the provincial capitols had low serum folate values (<6.8 nmol/L). Regional differences (p<0.05) existed for anaemia, deficiencies of vitamin A, folate, and selenium, but not for zinc or IDA. Of the children, 78% were at risk of > or = two coexisting micronutrient deficiencies emphasizing the need for multimicronutrient interventions in Mongolia. | 18,818,163 |
High fish consumption in French Polynesia and prenatal exposure to metals and nutrients. | French Polynesians consume high quantities of fish and are therefore exposed to seafood-related contaminants such as mercury (Hg) or lead (Pb) and nutrients such as iodine, selenium and long chain polyunsaturated fatty acids (LC-PUFAs). As the developing foetus is sensitive to contaminants and nutrients, a cross-sectional study was conducted in French Polynesia in 2005-2006 to assess prenatal exposure to contaminants and nutrients through fish consumption. Two hundred and forty one (241) delivering women originating from all islands of French Polynesia were recruited and agreed to answer questions on fish consumption and gave permission to collect umbilical cord blood for metals and nutrients analyses. All parameters were found in high concentrations in cord blood samples except for lead. Mercury concentrations averaged 64.6 nmol/L (or 13 microg/L) with values ranging from 0.25 to 240 nmol/L. Of the sample, 82.5% had Hg concentrations above the US-EPA blood guide-line of 5.8 microg/L. Tuna was the fish species which contributed the most to Hg exposure. High selenium and LC-PUFAs may counterbalance the potential risk of prenatal exposure to Hg in French Polynesia. Due to the high fish consumption of mothers, Polynesian newborns are prenatally exposed to high doses of mercury. Although selenium and omega-3 fatty acids may counteract mercury toxicity, informing pregnant women on both the mercury and nutrient content of local fish species is important. | 18,818,168 |
The 2nd International Conference on East-West Perspectives on Functional Foods: Science, Innovations and Claims. | The 2nd International Conference on East-West Perspective on Functional Foods held in Kuala Lumpur, Malaysia, on November, 2007, discussed the current work on some traditional Asian foods and new technologies that offer both challenges and opportunities for functional foods. The highlight of the conference was on the current regulatory status of nutrition and health claims related to functional foods and the experiences in some countries on the substantiation of claims. Attention was also given to strategies for effective communication of functional foods to consumers. The conference concluded with recommendations to strengthen R and D efforts and harmonization of protocols and methodologies on functional foods within the region. | 18,818,176 |
Early-onset liver mtDNA depletion and late-onset proteinuric nephropathy in Mpv17 knockout mice. | In humans, MPV17 mutations are responsible for severe mitochondrial depletion syndrome, mainly affecting the liver and the nervous system. To gain insight into physiopathology of MPV17-related disease, we investigated an available Mpv17 knockout animal model. We found severe mtDNA depletion in liver and, albeit to a lesser extent, in skeletal muscle, whereas hardly any depletion was detected in brain and kidney, up to 1 year after birth. Mouse embryonic fibroblasts did show mtDNA depletion, but only after several culturing passages, or in a serumless culturing medium. In spite of severe mtDNA depletion, only moderate decrease in respiratory chain enzymatic activities, and mild cytoarchitectural alterations, were observed in the Mpv17(-/-) livers, but neither cirrhosis nor failure ever occurred in this organ at any age. The mtDNA transcription rate was markedly increased in liver, which could contribute to compensate the severe mtDNA depletion. This phenomenon was associated with specific downregulation of Mterf1, a negative modulator of mtDNA transcription. The most relevant clinical features involved skin, inner ear and kidney. The coat of the Mpv17(-/-) mice turned gray early in adulthood, and 18-month or older mice developed focal segmental glomerulosclerosis (FSGS) with massive proteinuria. Concomitant degeneration of cochlear sensory epithelia was reported as well. These symptoms were associated with significantly shorter lifespan. Coincidental with the onset of FSGS, there was hardly any mtDNA left in the glomerular tufts. These results demonstrate that Mpv17 controls mtDNA copy number by a highly tissue- and possibly cytotype-specific mechanism. | 18,818,194 |
A functional Ser(413)/Ser(413) PAI-2 polymorphism is associated with susceptibility and damage index score in systemic lupus erythematosus. | Systemic lupus erythematosus in some cases is characterized for development of thrombotic events with a significantly increased risk of mortality. The frequencies and clinical associations of Ser(413)/Cys(413) PAI-2 polymorphism in 40 systemic lupus erythematosus, 50 rheumatoid arthritis patients, and 100 healthy subjects were investigated. The Ser(413)/Ser(413) genotype frequency was 53% (lupus), 36% (rheumatoid arthritis), and 35% (healthy subjects). The Ser(413) allele was associated with systemic lupus erythematosus (P = .04, odds ratio = 1.76, 95% confidence interval = 1.01-3.06). In all, 4 patient carriers of Ser(413)/Ser(413) genotype, developed thrombotic events. The lupus patients identified with Ser( 413)/Ser(413) genotype showed an increased damage (57%), compared with Ser(413)/Cys(413) and Cys(413)/Cys(413) genotypes, with significant difference (P = .03). These findings suggest an association of Ser( 413) /Ser( 413) genotype with greater damage index score and Ser( 413) allele with systemic lupus erythematosus. Besides, PAI-2 polymorphism could be related with thrombotic phenomena in systemic lupus erythematosus. | 18,818,228 |
A review of the trials comparing carotid endarterectomy and carotid angioplasty and stenting. | In the last decade, carotid artery angioplasty and stenting (CAS) has gained popularity as an alternative to carotid endarterectomy (CEA) for the treatment of carotid stenosis, particularly in patients who are at high operative risk. CAS offers the advantage of being a less invasive procedure, potentially minimizing the risks of wound complications and cranial nerve injury, which may translate into shorter length of hospitalization and less resource utilization. Since the advent of CAS, several randomized controlled trials and carotid stent registry trials have been conducted comparing the outcomes of CEA with those of CAS for the treatment of carotid stenosis in both symptomatic and asymptomatic patients. This review will summarize the results of randomized controlled trials (CAVATAS, WALLSTENT, SAPPHIRE, EVA-3S, SPACE, and CaRESS) as well as pivotal carotid registry studies (ARCHeR, BEACH, CAPTURE, CASES-PMS, CREATE, and CABernET) intended to evaluate the safety and efficacy of CEA and CAS in treatment of carotid stenosis. In addition, it will provide a preview of the current ongoing and future trials examining the safety, applicability, and indications of CAS and CEA (CREST, CAVATAS-2, ACT 1, and TACIT). | 18,818,232 |
Predictors of long-term major adverse cardiac events and clinical restenosis following elective percutaneous coronary stenting. | Limited data exist regarding the predictors of long-term clinical outcomes following elective percutaneous coronary intervention (PCI) in the current era of stenting. The authors investigated the predictors of major adverse cardiac events (MACE) and clinical restenosis in 740 consecutive patients who underwent successful elective PCI with bare metal stents (BMSs) or drug-eluting stents (DESs). At 30-month follow-up, compared with BMS recipients, DES recipients had a significantly lower rate of MACE, which was mainly driven by a decreased repeat target vessel PCI. The rate of 30-month clinical restenosis was significantly lower in DES recipients. The authors conclude that baseline clinical, angiographic, and procedural characteristics determine long-term MACE and clinical restenosis after elective PCI, with DES being the independent predictor for both. | 18,818,239 |
Benefits of low-intensity pain-free treadmill exercise on functional capacity of individuals presenting with intermittent claudication due to peripheral arterial disease. | Patients with intermittent claudication due to peripheral arterial disease (PAD) experience muscle aching during walking secondary to ischemia. The purpose of this study was to examine the effects of low-intensity pain-free exercise (LIPFE) on functional capacity of individuals with PAD. A total of 12 participants with PAD underwent training on treadmill for 6 weeks, twice a week, for about 45 minutes. Outcome measures included walking distance (WDI), walking duration (WDU), mean walking rate (WR), estimated oxygen consumption (EVO(2)), metabolic equivalent (MET), estimated total energy expenditure (ETEE), and estimated rate of energy expenditure (EREE). Mean improvement of WDI, WDU, and MWR were 104% (an addition of 1.0 km), 55% (an addition of 13.3 minutes), and 41% (0.9 km/h faster), respectively. Mean improvement of EVO(2), MET, ETEE, and EREE, were 20%, 20%, 80%, and 20%, respectively. In conclusion, it appears that LIPFE training is an effective intervention for individuals presenting with PAD. | 18,818,240 |
A select combination of clinically relevant phytoestrogens enhances estrogen receptor beta-binding selectivity and neuroprotective activities in vitro and in vivo. | We have previously shown that a number of naturally occurring phytoestrogens and derivatives were effective to induce some measures of neuroprotective responses but at a much lower magnitude than those induced by the female gonadal estrogen 17beta-estradiol. In the present study, we sought to investigate whether a combination of select phytoestrogens could enhance neural responses without affecting the reproductive system. We performed a range of comparative analyses of the estrogen receptor (ER) alpha/beta binding profile, and in vitro to in vivo estrogenic activities in neural and uterine tissues induced by clinically relevant phytoestrogens: genistein, daidzein, equol, and IBSO03569, when used alone or in combination. Our analyses revealed that both the ERalpha/beta binding profile and neural activities associated with individual phytoestrogens are modifiable when used in combination. Specifically, the combination of genistein plus daidzein plus equol resulted in the greatest binding selectivity for ERbeta and an overall improved efficacy/safety profile when compared with single or other combined formulations, including: 1) an approximate 30% increase in ERbeta-binding selectivity (83-fold over ERalpha); 2) a greater effect on neuronal survival against toxic insults in primary neurons; 3) an enhanced activity in promoting neural proactive defense mechanisms against neurodegeneration, including mitochondrial function and beta-amyloid degradation; and 4) no effect on uterine growth. These observations suggest that select phytoestrogens in combination have the therapeutic potential of an alternative approach to conventional estrogen therapy for long-term safe use to reduce the increased risk of cognitive decline and neurodegenerative disease associated with menopause in women. | 18,818,291 |
S4-based voltage sensors have three major conformations. | Voltage sensors containing the charged S4 membrane segment display a gating charge vs. voltage (Q-V) curve that depends on the initial voltage. The voltage-dependent phosphatase (Ci-VSP), which does not have a conducting pore, shows the same phenomenon and the Q-V recorded with a depolarized initial voltage is more stable by at least 3RT. The leftward shift of the Q-V curve under prolonged depolarization was studied in the Ci-VSP by using electrophysiological and site-directed fluorescence measurements. The fluorescence shows two components: one that traces the time course of the charge movement between the resting and active states and a slower component that traces the transition between the active state and a more stable state we call the relaxed state. Temperature dependence shows a large negative enthalpic change when going from the active to the relaxed state that is almost compensated by a large negative entropic change. The Q-V curve midpoint measured for pulses that move the sensor between the resting and active states, but not long enough to evolve into the relaxed states, show a periodicity of 120 degrees, indicating a 3(10) secondary structure of the S4 segment when determined under histidine scanning. We hypothesize that the S4 segment moves as a 3(10) helix between the resting and active states and that it converts to an alpha-helix when evolving into the relaxed state, which is most likely to be the state captured in the crystal structures. | 18,818,307 |
Assembling materials with DNA as the guide. | DNA's remarkable molecular recognition properties and structural features make it one of the most promising templates to pattern materials with nanoscale precision. The emerging field of DNA nanotechnology strips this molecule from any preconceived biological role and exploits its simple code to generate addressable nanostructures in one, two, and three dimensions. These structures have been used to precisely position proteins, nanoparticles, transition metals, and other functional components into deliberately designed patterns. They can also act as templates for the growth of nanowires, aid in the structural determination of proteins, and provide new platforms for genomics applications. The field of DNA nanotechnology is growing in a number of directions, carrying with it the promise to substantially affect materials science and biology. | 18,818,351 |
The coevolution of cultural groups and ingroup favoritism. | Cultural boundaries have often been the basis for discrimination, nationalism, religious wars, and genocide. Little is known, however, about how cultural groups form or the evolutionary forces behind group affiliation and ingroup favoritism. Hence, we examine these forces experimentally and show that arbitrary symbolic markers, though initially meaningless, evolve to play a key role in cultural group formation and ingroup favoritism because they enable a population of heterogeneous individuals to solve important coordination problems. This process requires that individuals differ in some critical but unobservable way and that their markers be freely and flexibly chosen. If these conditions are met, markers become accurate predictors of behavior. The resulting social environment includes strong incentives to bias interactions toward others with the same marker, and subjects accordingly show strong ingroup favoritism. When markers do not acquire meaning as accurate predictors of behavior, players show a markedly reduced taste for ingroup favoritism. Our results support the prominent evolutionary hypothesis that cultural processes can reshape the selective pressures facing individuals and so favor the evolution of behavioral traits not previously advantaged. | 18,818,361 |
Hyaluronan-mediated leukocyte adhesion and dextran sulfate sodium-induced colitis are attenuated in the absence of signal transducer and activator of transcription 1. | Inflammatory bowel disease is a chronic inflammatory condition of the intestinal mucosa whose etiology is unclear but is likely to be multifactorial. We have shown previously that an increased amount of hyaluronan (HA) is present both in the inflamed mucosa of inflammatory bowel disease patients and in isolated human cells after polyI:C treatment. The signal transducer and activator of transcription (STAT)1 protein plays an important role in many signaling pathways that are associated with inflammation. We therefore investigated the role of STAT1 in adhesive interactions that occur between leukocytes and polyI:C-induced mucosal smooth muscle cells (M-SMCs). Activation of STAT1 was observed after the polyI:C treatment of M-SMCs. Specific phosphorylation of tyrosine and serine residues of STAT1 was observed in polyI:C-treated, but not untreated, M-SMC cultures. To evaluate further the role of STAT1, a corresponding STAT-1-null mouse was used. PolyI:C-induced, HA-mediated leukocyte adhesion to colon SMCs from STAT1-null mice was significantly decreased compared with that from wild-type control mice. In vivo, using the dextran sulfate sodium-induced model of colon inflammation, both tissue damage and HA deposition were attenuated in STAT1-null mice compared with that in wild-type control mice. Additionally, the inter-alpha-trypsin inhibitor (IalphaI), a proteoglycan essential for facilitating leukocyte binding to the HA matrix, was reduced in STAT1-null mice. Together, these results demonstrate that STAT1 plays an important role in HA-mediated inflammatory processes. | 18,818,378 |
Pioglitazone inhibits the expression of inflammatory cytokines from both monocytes and lymphocytes in patients with impaired glucose tolerance. | The current study determines whether pioglitazone (PIO) therapy reduces both monocyte and lymphocyte inflammatory activity and their ability to induce inflammation in other tissues. Monocyte and lymphocyte cytokine gene and protein expression of interleukin (IL)-6 were first shown to be greater in subjects with impaired glucose tolerance (IGT) than in subjects with normal glucose tolerance. Sixty-six IGT subjects were then randomized to 4,5 months of placebo or PIO therapy. After receiving PIO, subjects had lower triglycerides and higher HDL cholesterol (P<0.05) than did subjects receiving placebo. Monocyte gene and protein expression of IL-1 beta, IL-6, and IL-8 (and IL-2, IL-6 and IL-8 from lymphocytes) was significantly lower after PIO therapy in the resting state, as well as after lipopolysaccharide (LPS) stimulation (P<0.05 for all). Moreover, IL-6, IL-8, and MCP-1 gene expression were decreased by nearly 50% in human adipocytes exposed to conditioned media from monocytes or lymphocytes from PIO treated subjects. These results demonstrate that PIO therapy in IGT can reduce proinflammatory gene and protein expression from both monocytes and lymphocytes. This intervention also reduces the inflammatory cross-talk between these immune cells and adipose tissue, which could in turn contribute to the metabolic improvements resulting from PIO therapy. | 18,818,415 |
Deficiency and inhibition of cathepsin K reduce body weight gain and increase glucose metabolism in mice. | Previous studies demonstrated increased levels of cysteine proteases cathepsins in serum and adipose tissues from obese patients. We now provide evidence from a mouse model of obesity to suggest a direct participation of cathepsin K (CatK) in mouse body weight gain and glucose metabolism. Using real-time polymerase chain reaction, we detected 12-fold increase in CatK transcripts after adipogenesis of human preadipocytes. Using an immunohistology analysis, we consistently observed high levels of CatK expression in adipose tissues from obese humans and mice. Selective inhibition of CatK activity blocked the lipid accumulation in human and mouse preadipocytes. In mice, CatK deficiency reduced significantly diet-induced body weight gain and serum glucose and insulin levels. Similar results were obtained in diet-induced and genetically created (ob/ob) obese mice after animals were treated with a CatK-selective inhibitor. Mechanistic study demonstrated a role for CatK in degrading fibronectin, a matrix protein that controls adipogenesis. Deficiency or inhibition of CatK leads to fibronectin accumulation in muscle and adipose tissues. This study demonstrates an essential role of CatK in adipogenesis and mouse body weight gain, possibly via degradation of fibronectin, thus suggesting a novel therapeutic strategy for the control of obesity by regulating CatK activity. | 18,818,416 |
Bone morphogenetic proteins 2 and 4 are selectively expressed by late outgrowth endothelial progenitor cells and promote neoangiogenesis. | Endothelial progenitor cells are currently identified either by their surface antigen expression or by their generation of early colonies in culture (CFU-Hill). Another population, endothelial colony-forming cells (ECFCs), has strong vessel-forming capacity but is less well characterized. Given the potential usefulness of CFU-Hill and ECFCs as cell therapy products, their thorough characterization is of major importance. CFU-Hill and ECFCs were expanded from human cord and adult blood. Bone morphogenetic proteins 2 and 4 (BMP2/4) were selectively expressed by ECFCs but not by CFU-Hill. The BMP pathway was involved in ECFC commitment and angiogenic potential in vitro. In vivo, BMP inhibition strongly reduced plug vascularization in bFGF-containing Matrigel plugs implanted in C57/Bl6 mice. Moreover, ECFC exposure to BMP increased their therapeutic potential in a nude mouse model of hindlimb ischemia. In amputation specimens from patients with critical leg ischemia who had received a local therapeutic injection of bone marrow mononuclear cells, newly formed vessels were strongly positive for BMP2/4, suggesting that endothelial cells involved in neovascularization have an ECFC-like phenotype. BMP2/4 are a marker of ECFCs and play a key role in ECFC commitment and outgrowth during neovascularization. | 18,818,419 |
Chemokines in vascular dysfunction and remodeling. | Vascular remodeling stands for structural changes of the vessel wall in response to various noxious stimuli, which results in reorganization of the vessel wall architecture. Luminal narrowing because of neointima formation and constrictive remodeling leading to hypoperfusion is the most relevant clinical effect. Smooth muscle cell (SMC) accumulation, inflammatory cell recruitment, and endothelial regeneration are the critical parts in obstructive vascular remodeling. Chemokines and chemokine receptors have a great impact on initiating and progressing neointimal formation by controlling each step of the remodeling process. SDF-1alpha regulates vascular repair by CXCR4-dependent smooth muscle progenitor cell recruitment, which contributes to the maladaptive response to injury. The three distinct chemokine-chemokine receptor pairs MCP-1/CCR2, RANTES/CCR5, and Fractalkine/CX(3)CR1 direct lesional leukocyte infiltration. In addition MCP-1/CCR2 and Fractalkine/CX(3)CR1 increase neointimal SMC expansion. In contrast, KC/Gro-alpha supports endothelial recovery through CXCR2, which attenuates neointima formation. These findings highlight the importance to characterize specific functions of the chemokine network to enable therapeutic intervention. | 18,818,421 |
Semitendinosus tendon graft versus a modified Weaver-Dunn procedure for acromioclavicular joint reconstruction in chronic cases: a prospective comparative study. | Biomechanical studies comparing various surgical techniques for acromioclavicular joint reconstruction have reported that semitendinosus tendon graft for coracoclavicular ligament reconstruction provides a substantial improvement in initial stability and a load-to-failure equivalent to the intact coracoclavicular ligaments. Although it represents a biomechanical improvement compared with coracoacromial ligament transfer, there is still a lack of prospective comparative studies confirming the clinical relevance of these biomechanical findings. Semitendinosus tendon graft for coracoclavicular ligament reconstruction is associated with superior clinical results compared with a modified Weaver-Dunn procedure in chronic complete acromioclavicular joint dislocation. Cohort study; Level of evidence, 2. Twenty-four patients (mean age, 42 years) with painful, chronic Rockwood type III through V acromioclavicular joint dislocations were subjected to surgical reconstruction. In 12 patients, a modified Weaver-Dunn procedure was performed; in the other 12 patients, autogenous semitendinosus tendon graft was used. Clinical evaluation was performed using the American Shoulder and Elbow Surgeons shoulder score and the Constant score after a mean follow-up time of 37 months. Preoperative and postoperative radiographs were compared. The mean American Shoulder and Elbow Surgeons shoulder score improved from 74 +/- 7 points preoperatively to 86 +/- 8 points postoperatively in the Weaver-Dunn group, and from 74 +/- 4 points to 96 +/- 5 points in the semitendinosus tendon group (P < .001 for both techniques). The mean Constant score improved from 70 +/- 8 points to 81 +/- 8 points in the Weaver-Dunn group, and from 71 +/- 5 points to 93 +/- 7 points in the semitendinosus tendon group (P < .001). The results in the semitendinosus tendon group were significantly better than in the Weaver-Dunn group (P < .001). The radiologic measurements showed a mean coracoclavicular distance of 12.3 +/- 4 mm in the Weaver-Dunn group increasing to 14.9 +/- 6 mm under stress loading, compared with 11.4 +/- 3 mm increasing to 11.8 +/- 3 mm under stress in the semitendinosus tendon group. The difference during stress loading was statistically significant (P = .027). In the semitendinosus tendon group, horizontal displacement of the lateral clavicle end could be reduced in all cases with type IV dislocation. Semitendinosus tendon graft for coracoclavicular ligament reconstruction resulted in significantly superior clinical and radiologic outcomes compared to the modified Weaver-Dunn procedure. | 18,818,433 |
Death, dropout, and longitudinal measurements of cognitive change in old age. | During a 20-year longitudinal study of cognitive change in old age 2,342 of 5,842 participants died and 3,204 dropped out. To study cognitive change as death approaches, we grouped participants by survival, death, dropout, or dropout followed by death. Linear mixed-effects pattern-mixture models compared rates of cognitive change before death and dropout from four quadrennial administrations of tests of fluid intelligence, vocabulary, and verbal learning. After we took into account the significant effects of age, gender, demographics, and recruitment cohorts, we found that approach to death and dropout caused strikingly similar reductions in mean test scores and amounts of practice gains between successive quadrennial testing sessions. Participants who neither dropped out nor died showed significant but slight cognitive declines. These analyses illustrate how neglect of dropout miscalculates effects of death, of worsening health, and of all other factors affecting rates of cognitive change. | 18,818,441 |
Effects of sensorimotor adaptation training on functional mobility in older adults. | The goal of this study was to determine if prolonged exposure to perceptual-motor mismatch increased adaptability and retention of balance in older adults. Sixteen adults, aged 66 to 81 years, were randomized to one of two groups: either the control group (n=8) or the experimental group (n=8). Both groups first completed six trials of walking an obstacle course. Participants then trained twice a week for 4 weeks. In the training, the control group walked on a treadmill for 20 minutes while viewing a static visual scene and the experimental group walked on a treadmill for 20 minutes while viewing a rotating visual scene that provided a perceptual-motor mismatch. Following training, both groups were post-tested on the obstacle course. The experimental group moved faster through the obstacle course with fewer penalties. This training effect was retained for 4 weeks. Exposure to perceptual-motor mismatch induced an adaptive training effect that improved balance and locomotor control in older adults. | 18,818,444 |
Dental education in Peru. | This paper provides information about Peru's dental history and dental school system, including the curriculum and dental licensure. With the increase in the number of dental schools in Peru, the number of dentists is also increasing. Until 1965, Peru had only three dental schools; currently, there are 14. Four of these dental schools are public, and ten are private. A five- or six-year dental program leads to the B.D.S. degree. After successful completion of a thesis defense or competency examination, the D.D.S. degree is awarded. The D.D.S. is mandatory for practicing dentistry in Peru. Currently, there are approximately 14,000 active dentists, with a dentist-patient ratio of approximately 1:2,000. | 18,818,472 |
Use of mineral trioxide aggregate in the open apex of a maxillary first premolar. | Mineral trioxide aggregate (MTA) has shown potential as a root-end filling material. This clinical case describes the successful treatment of a premolar with an open apex using MTA and the warm gutta-percha technique. The results suggested that MTA may be used as an apical filling material in permanent teeth with multiple canals. | 18,818,475 |
Pentadecapeptide BPC 157, in clinical trials as a therapy for inflammatory bowel disease (PL14736), is effective in the healing of colocutaneous fistulas in rats: role of the nitric oxide-system. | We focused on the therapeutic effect of the stable gastric pentadecapeptide BPC 157 and how its action is related to nitric oxide (NO) in persistent colocutaneous fistula in rats (at 5 cm from anus, colon defect of 5 mm, skin defect of 5 mm); this peptide has been shown to be safe in clinical trials for inflammatory bowel disease (PL14736) and safe for intestinal anstomosis therapy. BPC 157 (10 microg/kg, 10 ng/kg) was applied i) in drinking water until the animals were sacrificed at post-operative day 1, 3, 5, 7, 14, 21, and 28; or ii) once daily intraperitoneally (first application 30 min following surgery, last 24 h before sacrifice) alone or with N(G)-nitro-L-arginine methyl ester (L-NAME) (5 mg/kg), L-arginine (200 mg/kg), and their combinations. Sulphasalazine (50 mg/kg) and 6-alpha-methylprednisolone (1 mg/kg) were given once daily intraperitoneally. BPC 157 accelerated parenterally or perorally the healing of colonic and skin defect, leading to the suitable closure of the fistula, macro/microscopically, biomechanically, and functionally (larger water volume sustained without fistula leaking). L-NAME aggravated the healing failure of colocutaneous fistulas, skin, and colon wounds (L-NAME groups). L-Arginine was effective only with blunted NO generation (L-NAME + L-arginine groups) but not without (L-arginine groups). All of the BPC 157 beneficial effects remained unchanged with blunted NO-generation (L-NAME + BPC 157 groups) and with NO substrate (L-arginine + BPC 157 groups) as well as L-NAME and L-arginine co-administration (L-NAME + L-arginine + BPC 157 groups). Sulphasalazine was only moderately effective, and corticosteroid even had an aggravating effect. | 18,818,478 |
Kidney transplantation improves sleep-related breathing in hemodialysis patients. | To assess whether kidney transplantation improves sleep-related breathing disorders associated with hemodialysis. A prospective study was carried out using full-night polysomnography. Nine hemodialysis patients (7 men and 2 women, aged 42 +/- 16.2 years, BMI 26 +/- 3.7) who later received a successful kidney transplantation were evaluated. Main sleep quality and respiratory variables were recorded: number of dips in oxygen saturation (SaO(2)) > or =3% per hour of sleep; percentage of sleep time with SaO(2) <90%; percentage of sleep time in apnea and hypopnea, and sleep apnea/hypopnea index (AHI). After kidney transplantation, the AHI improved in 8 of the 9 patients (10 +/- 10.7 vs. 4.9 +/- 6.1, p = 0.029). A decrease in the percentage of sleep time in apnea/hypopnea (5 +/- 6.8 vs. 0.7 +/- 1.1%, p = 0.008) and a reduction in the number of desaturations (25 +/- 26 vs. 12 +/- 11.2%, p = 0.010) were observed. Kidney transplantation improved respiratory events and nocturnal SaO(2) in hemodialysis patients. | 18,818,490 |
X-ray structure of the complex of regulatory subunits of human DNA polymerase delta. | The eukaryotic DNA polymerase delta (Pol delta) participates in genome replication, homologous recombination, DNA repair and damage tolerance. Regulation of the plethora of Pol delta functions depends on the interaction between the second (p50) and third (p66) non-catalytic subunits. We report the crystal structure of p50*p66(N) complex featuring oligonucleotide binding and phosphodiesterase domains in p50 and winged helix-turn-helix N-terminal domain in p66. Disruption of the interaction between the yeast orthologs of p50 and p66 by strategic amino acid changes leads to cold-sensitivity, sensitivity to hydroxyurea and to reduced UV mutagenesis, mimicking the phenotypes of strains where the third subunit of Pol delta is absent. The second subunits of all B family replicative DNA polymerases in archaea and eukaryotes, except Pol delta, share a three-domain structure similar to p50*p66(N), raising the possibility that a portion of the gene encoding p66 was derived from the second subunit gene relatively late in evolution. | 18,818,516 |
The let-7 microRNA interfaces extensively with the translation machinery to regulate cell differentiation. | MicroRNAs (miRNAs) are noncoding RNAs that regulate numerous target genes through a posttranscriptional mechanism and thus control major developmental pathways. The phylogenetically conserved let-7 miRNA regulates cell proliferation and differentiation, thus functioning as a key regulator of developmental timing in C. elegans and a tumor suppressor gene in humans. Using a reverse genetic screen, we have identified genetic interaction partners of C. elegans let-7, including known and novel potential target genes. Initial identification of several translation initiation factors as suppressors of a let-7 mutation led us to systematically examine genetic interaction between let-7 and the translational machinery, which we found to be widespread. In the presence of wild-type let-7, depletion of the translation initiation factor eIF3 resulted in precocious cell differentiation, suggesting that developmental timing is translationally regulated, possibly by let-7. As overexpression of eIF3 in humans promotes translation of mRNAs that are also targets of let-7-mediated repression, we suggest that eIF3 may directly or indirectly oppose let-7 activity. This might provide an explanation for the opposite functions of let-7 and eIF3 in regulating tumorigenesis. | 18,818,519 |
Dihydrocapsaicin (DHC), a saturated structural analog of capsaicin, induces autophagy in human cancer cells in a catalase-regulated manner. | Although capsaicin, a pungent component of red pepper, is known to induce apoptosis in several types of cancer cells, the mechanisms underlying capsaicin-induced cytotoxicity are unclear. Here, we showed that dihydrocapsaicin (DHC), an analog of capsaicin, is a potential inducer of autophagy. DHC was more cytotoxic than capsaicin in HCT116, MCF-7 and WI38 cell lines. Capsaicin and DHC did not affect the sub-G(1) apoptotic peak, but induced G(0)/G(1) arrest in HCT116 and MCF-7 cells. DHC caused the artificial autophagosome marker GFP-LC3 to redistribute and upregulated expression of autophagy-related proteins. Blocking of autophagy by 3-methyladenine (3MA) as well as siRNA Atg5 induced a high level of caspase-3 activation. Although pretreatment with zVAD completely inhibited caspase-3 activation by 3MA, it did not prevent cell death. DHC-induced autophagy was enhanced by zVAD pretreatment, as shown by increased accumulation of LC3-II protein. DHC attenuated basal ROS levels through catalase induction; this effect was enhanced by antioxidants, which increased both LC3-II expression and caspase-3 activation. The catalase inhibitor 3-amino-1,2,4-triazole (3AT) abrogated DHC-induced expression of LC3-II, overexpression of the catalase gene increased expression of LC3-II protein, and knockdown decreased it. Additionally, DHC-induced autophagy was independent of p53 status. Collectively, DHC activates autophagy in a p53-independent manner and that may contribute to cytotoxicity of DHC. | 18,818,525 |
Influenza activity--United States and worldwide, May 18-September 19, 2008. | During May 18-September 19, 2008, influenza A (H1), influenza A (H3), and influenza B viruses were detected worldwide and were identified sporadically in the United States. This report summarizes influenza activity in the United States and worldwide since the last update and reviews the new influenza vaccine recommendations for the upcoming season. Influenza viruses circulating this summer appear antigenically similar to the strains included in the 2008-09 influenza vaccine. Recent antiviral resistance data are limited, but oseltamivir resistance among influenza A (H1N1) viruses might persist during the 2008-09 influenza season. | 18,818,585 |
Structural insights into microneme protein assembly reveal a new mode of EGF domain recognition. | The obligate intracellular parasite Toxoplasma gondii, a member of the phylum Apicomplexa that includes Plasmodium spp., is one of the most widespread parasites and the causative agent of toxoplasmosis. Adhesive complexes composed of microneme proteins (MICs) are secreted onto the parasite surface from intracellular stores and fulfil crucial roles in host-cell recognition, attachment and penetration. Here, we report the high-resolution solution structure of a complex between two crucial MICs, TgMIC6 and TgMIC1. Furthermore, we identify two analogous interaction sites within separate epidermal growth factor-like (EGF) domains of TgMIC6-EGF2 and EGF3-and confirm that both interactions are functional for the recognition of host cell receptor in the parasite, using immunofluorescence and invasion assays. The nature of this new mode of recognition of the EGF domain and its abundance in apicomplexan surface proteins suggest a more generalized means of constructing functional assemblies by using EGF domains with highly specific receptor-binding properties. | 18,818,666 |
Complexity of VEGF responses in skin carcinogenesis revealed through ex vivo assays based on a VEGF-A null mouse keratinocyte cell line. | Vascular endothelial growth factor (VEGF-A) is a critical player in cutaneous angiogenesis. However, the relative contribution of VEGF-A from different sources including epithelial and mesenchymal cells has not been fully characterized during skin repair and tumorigenesis. Moreover, the actual involvement of other vascular-specific acting molecules has remained elusive in part due to the masking and/or overlapping effects of VEGF-A. To shed light on these uncertainties we generated and characterized a clonal VEGF-null mouse keratinocyte cell line, through in vitro adenoviral gene transfer of Cre recombinase to VEGF-LoxP primary keratinocytes followed by repeated cell passaging under controlled conditions and cloning. In vitro and in vivo assays demonstrated that VEGF-null keratinocytes were nontumorigenic and expressed normal differentiation markers after calcium switch. Hras-induced tumorigenesis of immortalized VEGF-null keratinocytes upon subcutaneous injection was markedly reduced but not fully suppressed. However, the metastatic ability of Hras-transformed VEGF-null keratinocytes was abolished. These ex vivo approaches suggest the existence of VEGF-dependent and independent angiogenic stimuli in skin carcinogenesis. The VEGF-null mouse keratinocyte cell line arises as an important tool to assess the actual contribution of keratinocyte-derived VEGF with respect to other angiogenic factors in skin homeostasis and malignancy. | 18,818,673 |
Irf4 is a positional and functional candidate gene for the control of serum IgM levels in the mouse. | Natural IgM are involved in numerous immunological functions but the genetic factors that control the homeostasis of its secretion and upholding remain unknown. Prompted by the finding that C57BL/6 mice had significantly lower serum levels of IgM when compared with BALB/c mice, we performed a genome-wide screen and found that the level of serum IgM was controlled by a QTL on chromosome 13 reaching the highest level of association at marker D13Mit266 (LOD score=3.54). This locus was named IgMSC1 and covered a region encompassing the interferon-regulatory factor 4 gene (Irf4). The number of splenic mature B cells in C57BL/6 did not differ from BALB/c mice but we found that low serum levels of IgM in C57BL/6 mice correlated with lower frequency of IgM-secreting cells in the spleen and in the peritoneal cavity. These results suggested that C57BL/6 mice have lower efficiency in late B-cell maturation, a process that is highly impaired in Irf4 knockout mice. In fact, we also found reduced Irf4 gene expression in B cells of C57BL/6 mice. Thus, we propose Irf4 as a candidate for the IgMSC1 locus, which controls IgM homeostatic levels at the level of B-cell terminal differentiation. | 18,818,690 |
Adaptation and selective information transmission in the cricket auditory neuron AN2. | Sensory systems adapt their neural code to changes in the sensory environment, often on multiple time scales. Here, we report a new form of adaptation in a first-order auditory interneuron (AN2) of crickets. We characterize the response of the AN2 neuron to amplitude-modulated sound stimuli and find that adaptation shifts the stimulus-response curves toward higher stimulus intensities, with a time constant of 1.5 s for adaptation and recovery. The spike responses were thus reduced for low-intensity sounds. We then address the question whether adaptation leads to an improvement of the signal's representation and compare the experimental results with the predictions of two competing hypotheses: infomax, which predicts that information conveyed about the entire signal range should be maximized, and selective coding, which predicts that "foreground" signals should be enhanced while "background" signals should be selectively suppressed. We test how adaptation changes the input-response curve when presenting signals with two or three peaks in their amplitude distributions, for which selective coding and infomax predict conflicting changes. By means of Bayesian data analysis, we quantify the shifts of the measured response curves and also find a slight reduction of their slopes. These decreases in slopes are smaller, and the absolute response thresholds are higher than those predicted by infomax. Most remarkably, and in contrast to the infomax principle, adaptation actually reduces the amount of encoded information when considering the whole range of input signals. The response curve changes are also not consistent with the selective coding hypothesis, because the amount of information conveyed about the loudest part of the signal does not increase as predicted but remains nearly constant. Less information is transmitted about signals with lower intensity. | 18,818,723 |
Evolutionary dynamics and emergence of panzootic H5N1 influenza viruses. | The highly pathogenic avian influenza (HPAI) H5N1 virus lineage has undergone extensive genetic reassortment with viruses from different sources to produce numerous H5N1 genotypes, and also developed into multiple genetically distinct sublineages in China. From there, the virus has spread to over 60 countries. The ecological success of this virus in diverse species of both poultry and wild birds with frequent introduction to humans suggests that it is a likely source of the next human pandemic. Therefore, the evolutionary and ecological characteristics of its emergence from wild birds into poultry are of considerable interest. Here, we apply the latest analytical techniques to infer the early evolutionary dynamics of H5N1 virus in the population from which it emerged (wild birds and domestic poultry). By estimating the time of most recent common ancestors of each gene segment, we show that the H5N1 prototype virus was likely introduced from wild birds into poultry as a non-reassortant low pathogenic avian influenza H5N1 virus and was not generated by reassortment in poultry. In contrast, more recent H5N1 genotypes were generated locally in aquatic poultry after the prototype virus (A/goose/Guangdong/1/96) introduction occurred, i.e., they were not a result of additional emergence from wild birds. We show that the H5N1 virus was introduced into Indonesia and Vietnam 3-6 months prior to detection of the first outbreaks in those countries. Population dynamics analyses revealed a rapid increase in the genetic diversity of A/goose/Guangdong/1/96 lineage viruses from mid-1999 to early 2000. Our results suggest that the transmission of reassortant viruses through the mixed poultry population in farms and markets in China has selected HPAI H5N1 viruses that are well adapted to multiple hosts and reduced the interspecies transmission barrier of those viruses. | 18,818,732 |
Successful inhibition of tumor development by specific class-3 semaphorins is associated with expression of appropriate semaphorin receptors by tumor cells. | The class-3 semaphorins (sema3s) include seven family members. Six of them bind to neuropilin-1 (np1) or neuropilin-2 (np2) receptors or to both, while the seventh, sema3E, binds to the plexin-D1 receptor. Sema3B and sema3F were previously characterized as tumor suppressors and as inhibitors of tumor angiogenesis. To determine if additional class-3 semaphorins such as sema3A, sema3D, sema3E and sema3G possess anti-angiogenic and anti-tumorigenic properties, we expressed the recombinant full length semaphorins in four different tumorigenic cell lines expressing different combinations of class-3 semaphorin receptors. We show for the first time that sema3A, sema3D, sema3E and sema3G can function as potent anti-tumorigenic agents. All the semaphorins we examined were also able to reduce the concentration of tumor associated blood vessels although the potencies of the anti-angiogenic effects varied depending on the tumor cell type. Surprisingly, there was little correlation between the ability to inhibit tumor angiogenesis and their anti-tumorigenic activity. None of the semaphorins inhibited the adhesion of the tumor cells to plastic or fibronectin nor did they modulate the proliferation of tumor cells cultured in cell culture dishes. However, various semaphorins were able to inhibit the formation of soft agar colonies from tumor cells expressing appropriate semaphorin receptors, although in this case too the inhibitory effect was not always correlated with the anti-tumorigenic effect. In contrast, the anti-tumorigenic effect of each of the semaphorins correlated very well with tumor cell expression of specific signal transducing receptors for particular semaphorins. This correlation was not broken even in cases in which the tumor cells expressed significant concentrations of endogenous semaphorins. Our results suggest that combinations of different class-3 semaphorins may be more effective than single semaphorins in cases in which tumor cells express more than one type of semaphorin receptors. | 18,818,766 |
Incidental colorectal computed tomography abnormalities: would you send every patient for a colonoscopy? | The clinical significance of colorectal wall thickening (CRWT) in patients undergoing abdominal computed tomography (CT) has not yet been definitively established. To compare alleged findings on abdominal CT with those of a follow-up colonoscopy. Ninety-four consecutive patients found to have large-bowel abnormalities on abdominal CT were referred for colonoscopy. Of these patients, 48 were referred for a suspected colorectal tumour and 46 for CRWT. Colonoscopy was performed and findings were compared. Of the 48 suspected colorectal tumours, 34 were determined to be neoplastic lesions on colonoscopy. Of these, 26 were malignant and eight were benign. Colonoscopy revealed no abnormality in 30 of 46 patients with CRWT as a solitary finding, and revealed some abnormality in 16 patients (12 had diverticular disease, four had benign neoplastic lesions). CRWT as an incidental and solitary finding on CT should not be regarded as a pathology prompting a colonoscopy. Approximately two-thirds of the patients had a normal colonoscopy and the remaining patients had benign lesions (12 had diverticular disease and four had benign neoplastic lesions). However, many of these patients seem to warrant colonoscopy regardless of CT findings, particularly patients who have a family history of colorectal cancer, have positive fecal occult blood test results or who are older than 50 years of age. | 18,818,789 |
Latent lymphocytic enterocolitis associated with celiac disease manifesting after resection for colon cancer: case report and review of the literature. | Lymphocytic colitis, a cause of chronic watery diarrhea, is histologically characterized by increased intraepithelial lymphocytosis. Studies have associated this disorder with celiac disease, although there are no reports of patients with both lymphocytic colitis and colon cancer. The present case report describes a patient with lymphocytic colitis, which manifested five years after he presented with a cecal adenocarcinoma, and three years following a diagnosis of celiac disease. Pathological review of his initial resection specimen demonstrated lymphocytic enterocolitis, indicating a five-year latency in the presentation of this disease. | 18,818,792 |
Droplet-based microfluidic system for individual Caenorhabditis elegans assay. | A droplet-based microfluidic system integrating a droplet generator and a droplet trap array is described for encapsulating individual Caenorhabditis elegans into a parallel series of droplets, enabling characterization of the worm behavior in response to neurotoxin at single-animal resolution. | 18,818,795 |
Open micro-fluidic system for atomic force microscopy-guided in situ electrochemical probing of a single cell. | Ultra-sharp nano-probes and customized atomic force microscopy (AFM) have previously been developed in our laboratory for in situ sub-cellular probing of electrochemical phenomena in living plant cells during their photosynthesis. However, this AFM-based electrochemical probing still has numerous engineering challenges such as immobilization of the live cells, compatibility of the immobilization procedure with AFM manipulation of the probe, maintenance of biological activity of the cells for an extended time while performing the measurements, and minimization of electrochemical noise. Thus, we have developed an open micro-fluidic channel system (OMFC) in which individual cells can be immobilized in micro-traps by capillary flow. This system affords easy AFM access and allows for maintenance of the cells in a well-defined chemical environment, which sustains their biological activity. The use of micro-channels for making the electrochemical measurements significantly reduces parasitic electrical capacitances and allows for current detection in the sub-pico-ampere range at high signal bandwidths. The OMFC was further studied using simulation packages for optimal design conditions. This system was successfully used to measure light-dependent oxidation currents of a few pico-amperes from the green alga Chlamydomonas reinhardtii. | 18,818,800 |
Scanning tunneling microscopy as a tool to study catalytically relevant model systems. | The surface science approach to catalysis, pioneered by 2007 Nobel Laureate in chemistry Gerhard Ertl, has helped revolutionize our understanding of heterogeneous catalysis at the atomic level. In this tutorial review we show how the scanning tunnelling microscope (STM), in combination with this surface science approach, is a very important tool for the study of catalytically relevant model systems. We illustrate how the high spatial and temporal resolution of the STM can be used to obtain quantitative information on elementary processes involved in surface catalyzed reactions. Furthermore, we show that the STM is an outstanding surface science tool to bridge the materials gap and the pressure gap between surface science experiments and real catalysis. Finally, we show that we are approaching an era where the atomic-scale insight gained from fundamental STM surface science studies can be used for the rational design of new catalysts from first principles. | 18,818,822 |
Oxide ultra-thin films on metals: new materials for the design of supported metal catalysts. | Ultrathin oxide films on metals offer new opportunities for the design of supported nanoclusters with potential use in catalysis. This requires a characterization at the atomistic level of the structure and composition of the thin film, of its morphology and defect structure. A proper selection of metal/oxide interface, film thickness, lattice mismatch, etc. makes it possible to prepare collections of supported metal particles with novel properties. This critical review describes some illustrative examples, emphasizes the role of the interplay between theory and experiment, and relates some recent findings related to the possibility to control the charge state of a supported nanoparticle on an ultrathin oxide film (211 references). | 18,818,825 |
Microkinetic simulations of the oxidation of CO on Pd based nanocatalysis: a model including co-dependent support interactions. | The catalysed oxidation of CO using mass-selected Pd(13) clusters supported on thin MgO films was modelled using a microkinetic simulation of the reaction. The model of the system includes reverse spill-over calculations which were intrinsically incorporated into the formulation of the kinetics. The spill-over model is based on a capture-zone approach including a co-dependence on the variables of the kinetic equations. The experimental values were determined using dual pulsed-molecular beam measurements and recorded at a range of temperatures. The experiment allowed the turn-over frequency and reaction probability to be determined as a function of mole fraction. Comparison of the kinetic model with the experimental data gives excellent agreement and strongly highlights the importance of substrate effects. In particular, the origin of the low temperature catalysis of the Pd clusters is elucidated. The model allows the mole fraction and temperature dependent values such as the sticking coefficients for these clusters to be predicted. | 18,818,841 |
Dissociations of copper(II)-containing complexes of aromatic amino acids: radical cations of tryptophan, tyrosine, and phenylalanine. | The dissociations of two types of copper(II)-containing complexes of tryptophan (Trp), tyrosine (Tyr), or phenylalanine (Phe) are described. The first type is the bis-amino acid complex, [Cu(II)(M)(2)].(2+), where M = Trp, Tyr, or Phe; the second [Cu(II)(4Cl-tpy)(M)].(2+), where 4Cl-tpy is the tridendate ligand 4'-chloro-2,2':6',2''-terpyridine. Dissociations of the Cu(ii) bis-amino acid complexes produce abundant radical cation of the amino acid, M.(+), and/or its secondary products. By contrast, dissociations of the 4Cl-tpy-bearing ternary complexes give abundant M.(+) only for Trp. Density functional theory (DFT) calculations show that for Tyr and Phe, amino-acid displacement reactions by H(2)O and CH(3)OH (giving [Cu(II)(4Cl-tpy)(H(2)O)].(2+) and [Cu(II)(4Cl-tpy)(CH(3)OH)].(2+)) are energetically more favorable than dissociative electron transfer (giving M.(+) and [Cu(I)(4Cl-tpy)](+)). The fragmentation pathway common to all these [Cu(II)(4Cl-tpy)(M)].(2+) ions is the loss of NH(3). DFT calculations show that the loss of NH(3) proceeds via a "phenonium-type" intermediate. Dissociative electron transfer in [Cu(II)(4Cl-tpy)(M-NH(3))].(2+) results in [M-NH(3)].(+). The [Phe-NH(3)] (+) ion dissociates facilely by eliminating CO(2) and giving a metastable phenonium-type ion that rearranges readily into the styrene radical cation. | 18,818,845 |
Microbiological assessment of the ultraviolet screening effect of sunscreen preparations. | The purpose of this study was the development of a microbiological method for the assessment of the ultraviolet (UV) screening effect of sunscreen preparations and determination of their sun protection factor. The method is based on the lethal effect of UV radiation on Escherichia coli (E. coli ) and the protective ability of sunscreens. The time of UV exposure required for the reduction of the E. coli viable count by 90% (decimal reduction time, DRT) was used as the photoprotection assessment parameter. The method was tested by assessing the effect of selected experimental variables on the DRT. The suitability of the method as a quality control tool for sunscreen preparations was then checked by assessing the influence of selected formulation variables on the photoprotective effect of a series of o/w emulsion formulations with different compositions. The method proved valid for detecting changes in the photoprotective effect of a market sunscreen product as a result of modifying experimental conditions. It also proved valid for ranking market sunscreen products according to their UV screening effect. Equally important, the method could successfully detect changes in the photoprotective effect of sunscreen test formulations as a function of the concentration and type of the sunscreen agents. | 18,818,849 |
Bone marrow transplantation for severe aplastic anemia secondary to temozolomide. | Radiotherapy (RT) and concomitant/adjuvant therapy with temozolomide (Temodar) is a common treatment regimen for children and adults with glioma. Although temozolomide is generally well tolerated with temporary myelosuppression as the primary dose-limiting toxicity, irreversible bone-marrow aplasia after treatment with temozolomide has been reported. We report the case of an adolescent patient with a high-grade glioma who, after >2 years of event-free survival, underwent successful bone marrow transplantation for treatment of temozolomide-induced severe aplastic anemia (SAA). | 18,818,880 |
Innate immunity in the pathogenesis of polytropic retrovirus infection in the central nervous system. | Neuroinflammation, including astrogliosis, microgliosis, and the production of proinflammatory cytokines and chemokines is a common response in the central nervous system (CNS) to virus infection, including retrovirus infection. However, the contribution of this innate immune response in disease pathogenesis remains unresolved. Analysis of the neuroinflammatory response to polytropic retrovirus infection in the mouse has provided insight into the potential contribution of the innate immune response to retrovirus-induced neurologic disease. In this model, retroviral pathogenesis correlates with the induction of neuroinflammatory responses including the activation of astrocytes and microglia, as well as the production of proinflammatory cytokines and chemokines. Studies of the neurovirulent determinants of the polytropic envelope protein as well as studies with knockout mice suggest that retroviral pathogenesis in the brain is multifaceted and that cytokine and chemokine production may be only one mechanism of disease pathogenesis. Analysis of the activation of the innate immune response to retrovirus infection in the CNS indicates that toll-like receptor 7 (TLR7) is a contributing factor to retrovirus-induced neuroinflammation, but that other factors can compensate for the lack of TLR7 in inducing both neuroinflammation and neurologic disease. | 18,818,884 |
Perioperative use of recombinant factor VII to prevent intraoperative aneurysm rupture in high risk patients: a preliminary safety evaluation. | The authors present a safety evaluation of the perioperative use of recombinant activated factor VII (rFVIIa) in a series of subarachnoid hemorrhage patients undergoing microsurgical aneurysm clipping. We performed a retrospective chart review of the records of 18 consecutive subarachnoid hemorrhage patients who underwent craniotomy for aneurysm clipping and received an intraoperative dose of rFVIIa. In each case, the aneurysm was felt to be a "high risk" lesion for intraoperative rupture either because it had bled multiple times prior to surgery or based on anatomical considerations. All complications were recorded whether or not they were attributed to the use of rFVIIa. Eighteen patients, 7 men and 11 women, ranging in age from 42 to 85 years were included in this review. Nine patients (50%) were either Hunt/Hess Grades IV or V. Six patients developed clinically significant cerebral vasospasm. Fifteen patients required ventricular drainage on admission, and seven patients ultimately required a ventriculoperitoneal shunt. One lower extremity deep venous thrombosis and seven upper extremity venous thromboses in association with peripherally inserted central catheter (PICC) lines were identified on screening Doppler evaluations. There were no associated pulmonary emboli. No aneurysm ruptured intraoperatively. We describe our experience with the use of a single dose of rFVIIa administered perioperatively in an attempt to decrease the rate of intraoperative aneurysm rupture in patients undergoing microsurgical aneurysm clipping. There were no significant immediate or long-term adverse effects attributable to the use of rFVIIa in this group, and we encountered no intraoperative ruptures in this relatively small series. | 18,818,887 |
Magnetic resonance imagination of the peroneus longus tendon after anterior cruciate ligament reconstruction. | Several studies report that tendons can regenerate after harvesting. These studies have been performed especially in patellar and hamstring tendons. At our institution, 10 cm length of full thickness peroneus longus tendon has been harvested to reconstruct torn anterior cruciate ligament since 1997 as a different graft source. The aim of this study was to investigate whether the peroneus longus tendon used the anterior cruciate ligament reconstruction has a regeneration potential or not. Twelve patients, who had originally undergone harvesting of the peroneus longus tendon for the primary surgery of the anterior cruciate ligament reconstruction, underwent magnetic resonance imaging (MRI). Images of both legs were acquired simultaneously with the use of the scanner's extremity coil, as we aimed to compare harvested peroneus longus tendon with the other leg's peroneus longus tendon (healthy side) for evaluation of the regeneration potential. The average age of the patients was 31 years. There were eight right and four left legs. The average time interval was 52 months between ligament surgery and MRI. In all patients, a varying amount of the regeneration of the peroneus longus tendon was seen on the MRI images. Although the extent of PLT regeneration in proximal sections seemed better than in mid- and distal sections, there was no statistical difference between sections (P = 0.130). These data show that the peroneus longus tendon has a regeneration potential after harvesting for anterior cruciate ligament reconstruction. | 18,818,901 |
Positional and directional preponderances in vection. | We examined the biases in vection strength caused by motion direction (temporonasal vs. nasotemporal motion) and position of stimulus presentation (nasal and temporal semi-retinas) to investigate a subcortical contribution to vection. These biases have been identified for optokinetic nystagmus (OKN) and are acknowledged as evidence for a subcortical origin of OKN. In experiments, subjects monocularly observed hemi-field motion stimuli and made magnitude estimations. The results indicated significant directional and positional biases when luminance modulated gratings were used as stimuli. Vection was stronger with nasotemporal motions and nasal retina presentations, but there were no interactions between the two factors. However, these biases disappeared for second-order motion stimuli (contrast modulation), which are presumably processed by the cortex. In addition, when subjects were asked to make subjective ratings of motion impression, there was no significant difference in subjective strength between the stimuli that induced the strongest vection and weakest vection. These results, together, suggest the involvement of the subcortical pathway in vection induction. | 18,818,907 |
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