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Blocking apoptosis proteins with birinapant increases tumor cell death in ovarian cancer
Inhibitors of apoptosis proteins (IAPs) are key regulators of apoptosis and are frequently dysregulated in ovarian cancer. It was hypothesized that blocking IAPs with birinapant would increase tumor cell death and result in objective responses for women with platinum-refractory and -resistant ovarian cancer.
[ "The inhibitor-of-apoptosis proteins (IAPs) regulate programmed cell death by inhibiting members of the caspase family of enzymes. Recently, a mammalian protein called Smac (also named DIABLO) was identified that binds to the IAPs and promotes caspase activation. Although undefined in the X-ray structure, the amino...
miRLocator: a novel algorithm for locating mature miRNAs within plant pre-miRNAs
MicroRNAs (miRNAs) are a class of short, non-coding RNA that play regulatory roles in a wide variety of biological processes, such as plant growth and abiotic stress responses. Although several computational tools have been developed to identify primary miRNAs and precursor miRNAs (pre-miRNAs), very few provide the fun...
[ "MicroRNAs (miRNAs) are a family of non-coding RNAs approximately 21 nucleotides in length that play pivotal roles at the post-transcriptional level in animals, plants and viruses. These molecules silence their target genes by degrading transcription or suppressing translation. Studies have shown that miRNAs are in...
Pharmacokinetics of vancomycin in neonatal patients with late-onset staphylococcal sepsis
To develop a vancomycin population pharmacokinetic model and assess the probability of attaining a pharmacodynamic target associated with clinical and microbiological success, a ratio of the 24-hour area under the concentration-time curve to the minimum inhibitory concentration (MIC) ≥ 400, in a 5-year clinical cohort ...
[ "Immature renal function in neonates requires antibiotic dosage adjustment. Population pharmacokinetic studies were performed to determine the optimal dosage regimens for three types of antibiotics: an aminoglycoside, arbekacin; a glycopeptide, vancomycin; and a carbapenem, panipenem. Eighty-three neonates received...
Tenofovir disoproxil fumarate and kidney function in HIV-infected women
Tenofovir disoproxil fumarate is a commonly used antiretroviral drug, but risk factors for tenofovir (TFV)-associated kidney disease are not fully understood. We used intensive pharmacokinetic studies in a cohort of HIV-infected women on TFV-based therapy to study the relationship between TFV exposure and subsequent ki...
[ "Women, particularly women of color, remain underrepresented in antiretroviral (ARV) clinical trials. To evaluate sex-based differences in darunavir/ritonavir-based therapy, the Gender, Race And Clinical Experience (GRACE) study was designed to enroll and retain a high proportion of women representative of the raci...
Cytotoxic T cell and NK cell subpopulations in epithelial ovarian cancer
A number of observations have indicated that the immune system plays a significant role in patients with epithelial ovarian cancer (EOC). In cases of EOC, the prognostic significance of tumour infiltrating lymphocytes has not been clearly explained yet. The aim is to determine the phenotype and activation molecules of ...
[ "Tumor-infiltrating lymphocytes (TIL), in particular CD8(+) T cells and CD20(+) B cells, are strongly associated with survival in ovarian cancer and other carcinomas. Although CD8(+) TIL can mediate direct cytolytic activity against tumors, the role of CD20(+) TIL is poorly understood. Here, we investigate the poss...
AKT1 expression induces lung and brain metastases in non-metastatic BRAF(V600E)/Cdkn2a(Null) mouse melanomas
Metastases are the major cause of melanoma-related mortality. Previous studies implicating aberrant AKT signaling in human melanoma metastases led us to evaluate the effect of activated AKT1 expression in non-metastatic BRAF(V600E)/Cdkn2a(Null) mouse melanomas in vivo. Expression of activated AKT1 resulted in highly me...
[ "The serine/threonine kinase Akt has been implicated in the control of cell survival and metabolism. Here we report the disruption of the most ubiquitously expressed member of the akt family of genes, akt1, in the mouse. Akt1(-/-) mice are viable but smaller when compared to wild-type littermates. In addition, the ...
Engaging Young Adults in a Social Media Intervention for Smoking Cessation
Social media offer a great opportunity to deliver smoking cessation treatment to young adults, but previous online and social media interventions targeting health behavior change have struggled with low participant engagement. We examined engagement generated by content based on the Transtheoretical Model of Behavior C...
[ "The purpose of the study is to evaluate the performance of theoretically-derived mediators of health behavior change. Participants were university seniors (184 females; 154 males) randomly assigned to an intervention course designed to promote physical activity or to a control course. Five physical activity outcom...
Does Japanese culture have become more individualistic by investigating the practice of naming babies
We examined whether Japanese culture has become more individualistic by investigating how the practice of naming babies has changed over time. Cultural psychology has revealed substantial cultural variation in human psychology and behavior, emphasizing the mutual construction of socio-cultural environment and mind. How...
[ "Today, countries around the world are caught in the tide of change toward Gesellshaft, or individualistic socio-demographic condition. Recent investigations in Japan have suggested negative impacts of change on emotional and motivational aspects of the Japanese self (Norasakkunkit et al., 2012; Ogihara and Uchida,...
Reverse Transcriptase Multiplex Ligation-Dependent Probe Amplification (RT-MLPA) for Single Cell Analysis of Breast Cancer
Single cell analysis techniques have great potential in the cancer genomics field. The detection and characterization of circulating tumour cells are important for identifying metastatic disease at an early stage and monitoring it. This protocol is based on transcript profiling using Reverse Transcriptase Multiplex Lig...
[ "At present, sampling of the lymph nodes or bone marrow for the detection of regions of metastatic disease in patients with breast cancer can only be undertaken at the time of initial diagnosis and surgery. However, the sampling of these tissues and the methods used are inaccurate, time consuming, and cannot be use...
Genome-wide association analysis of Hirschsprung disease
Hirschsprung disease (HSCR; OMIM 142623) is a developmental disorder characterized by aganglionosis along variable lengths of the distal gastrointestinal tract, which results in intestinal obstruction. Interactions among known HSCR genes and/or unknown disease susceptibility loci lead to variable severity of phenotype....
[ "Hirschsprung disease (HSCR) is the most frequent genetic cause of congenital intestinal obstruction with an incidence of 1:5000 live births. In a pathway-based epistasis analysis of data generated by genome-wide association study on HSCR, specific genotype of Patched 1 (PTCH1) has been linked to an increased risk ...
Pediatric Intramedullary Spinal Cord Lesions
Pediatric intramedullary spinal cord lesions are not only rare but also different from adults in a number of aspects. We aimed to study the incidence and the frequencies of various pediatric intramedullary mass lesions, their outcome to treatment and the factors determining their outcome of treatment.
[ "Between March 9, 1984 and January 29, 1992, 42 children with newly diagnosed symptomatic or previously diagnosed progressive low-grade gliomas received outpatient chemotherapy as their primary treatment. This study was a single arm, phase II trial designed to estimate the time to tumor progression and toxicity of ...
Validation of genetic profiles for cancer treatment
Personalized cancer treatments depend on the determination of a patient's genetic status according to known genetic profiles for which targeted treatments exist. Such genetic profiles must be scientifically validated before they is applied to general patient population. Reproducibility of findings that support such gen...
[ "UV-damaged DNA-binding activity (UV-DDB) is deficient in some xeroderma pigmentosum group E individuals due to mutation of the p48 gene, but its role in DNA repair has been obscure. We found that UV-DDB is also deficient in cell lines and primary tissues from rodents. Transfection of p48 conferred UV-DDB to hamste...
The jasmonate defense signal pathway is a major defense signaling pathway of Asian corn borer's defense against insect herbivory
Corn defense systems against insect herbivory involve activation of genes that lead to metabolic reconfigurations to produce toxic compounds, proteinase inhibitors, oxidative enzymes, and behavior-modifying volatiles. Similar responses occur when the plant is exposed to methyl jasmonate (MeJA). To compare the defense r...
[ "Ultra-deep RNA sequencing has become a powerful approach for genome-wide analysis of pre-mRNA alternative splicing. We develop MATS (multivariate analysis of transcript splicing), a bayesian statistical framework for flexible hypothesis testing of differential alternative splicing patterns on RNA-Seq data. MATS us...
Open-label safety study with vemurafenib in patients with metastatic melanoma
The BRAF inhibitor vemurafenib has improved progression-free survival and overall survival in patients with BRAFV600-mutation-positive metastatic melanoma. Here we present the results of an open-label safety study with vemurafenib in patients with metastatic melanoma enrolled in Polish oncological centres.
[ "Microscopic satellitosis in melanoma is uncommon. The role of regional basin staging/therapy in patients with this high-risk feature has not been well defined. Patients presenting from 1996 to 2005 with clinically localized melanoma containing microscopic satellitosis were identified from a prospective, single-ins...
The Fourth Law of Behavior Genetics
Behavior genetics is the study of the relationship between genetic variation and psychological traits. Turkheimer (2000) proposed "Three Laws of Behavior Genetics" based on empirical regularities observed in studies of twins and other kinships. On the basis of molecular studies that have measured DNA variation directly...
[ "Recent discoveries of hundreds of common susceptibility SNPs from genome-wide association studies provide a unique opportunity to examine population genetic models for complex traits. In this report, we investigate distributions of various population genetic parameters and their interrelationships using estimates ...
Sedation and Cognitive Function in Critically Ill Patients on Mechanical Ventilation in the Intensive Care Unit
The practice of sedation dosing strategy in mechanically ventilated patient has a profound effect on cognitive function. We conducted a comprehensive review of outcome of sedation on mental health function in critically ill patients on mechanical ventilation in the intensive care unit (ICU). We specifically evaluated c...
[ "Aims: This study aimed to estimate the prevalence of severe Posttraumatic Stress Disorder (PTSD) symptoms and to identify factors associated with PTSD in survivors of intensive care unit (ICU) treatment following traumatic injury. Methods: Fifty-two patients who were admitted to an ICU through the emergency ward f...
Preparation of mouth dissolving films of Amlodipine Besylate
The present investigation was undertaken with an objective of formulating mouth dissolving films (MDFs) of Amlodipine Besylate (AMLO) to enhance convenience and compliance of the elderly and pediatric patients for better therapeutic efficacy. Film formers like hydroxy propyl methyl cellulose (HPMC) and methyl cellulose...
[ "The objectives of this work were to apply several profile comparison approaches to dissolution data of four different but bioequivalent metoprolol tartrate tablet formulations to (1) identify the advantages and disadvantages of each approach, (2) quantify the metric for comparing dissolution profiles of each metho...
Age-Dependent Neuroimmune Effects of Alcohol
The role of neuroimmune activation in withdrawal from chronic alcohol (ethanol) has been established in both adolescent and adult models, but direct comparisons across age are sparse. Studies need to elucidate age-dependent neuroimmune effects of alcohol and to focus research attention on age-dependent mechanisms and o...
[ "The relative anticonvulsant potential of the gamma-aminobutyric acid (GABA) agonist, muscimol, was compared after microinjection into either the inferior colliculus, substantia nigra or medial septum of ethanol-dependent rats. Bilateral microinjection of muscimol (10-30 ng) into the inferior colliculus 15 to 60 mi...
C-type lectin receptor Clec4d is inducible myeloid-expressed CTLR in mice
The C-type lectin receptor (CTLR), Clec4d (MCL, CLECSF8), is a member of the Dectin-2 cluster of CTLRs, which also includes the related receptors Mincle and Dectin-2. Like Mincle, Clec4d recognizes mycobacterial cord factor, trehalose dimycolate, and we recently demonstrated its key role in anti-mycobacterial immunity ...
[ "The interaction of microbes with pattern recognition receptors (PRRs) is essential for protective immunity. While many PRRs that recognize mycobacteria have been identified, none is essentially required for host defense in vivo. Here, we have identified the C-type lectin receptor CLECSF8 (CLEC4D, MCL) as a key mol...
Endocrine Fibroblast Growth Factors and Their Therapeutic Potential
The endocrine fibroblast growth factors (FGFs), FGF19, FGF21 and FGF23, are critical for maintaining whole-body homeostasis, with roles in bile acid, glucose and lipid metabolism, modulation of vitamin D and phosphate homeostasis and metabolic adaptation during fasting. Given these functions, the endocrine FGFs have th...
[ "Intestinal FGF19 has emerged as a novel endocrine regulator of hepatic bile salt and lipid metabolism. In patients with nonalcoholic fatty liver disease (NAFLD) hepatic lipid metabolism is deranged. A possible role of FGF19 in NAFLD has not been reported yet. In this study, we assessed intestinal FGF19 production ...
Epstein-Barr virus tegument protein BGLF2 activates AP-1 and NF-B promoter activity
Epstein-Barr virus (EBV) is a ubiquitous gammaherpesvirus associated with both B cell and epithelial cell malignancies. EBV infection of B cells triggers activation of several signaling pathways that are critical for cell survival, virus latency, and growth transformation. To identify EBV proteins important for regulat...
[ "Latent membrane protein 1 (LMP1) of Epstein-Barr virus (EBV) is an integral membrane protein which has transforming potential and is necessary but not sufficient for B-cell immortalization by EBV. LMP1 molecules aggregate in the plasma membrane and recruit tumour necrosis factor receptor (TNF-R) -associated factor...
Rapid Inactivation of Human Coronavirus 229E on Copper Alloys
The evolution of new and reemerging historic virulent strains of respiratory viruses from animal reservoirs is a significant threat to human health. Inefficient human-to-human transmission of zoonotic strains may initially limit the spread of transmission, but an infection may be contracted by touching contaminated sur...
[ "The environment may act as a reservoir for pathogens that cause healthcare-associated infections (HCAIs). Approaches to reducing environmental microbial contamination in addition to cleaning are thus worthy of consideration. Copper is well recognised as having antimicrobial activity but this property has not been ...
Endoplasmic reticulum-resident glycoprotein in human cytomegalovirus
The viral glycoproteins that decorate enveloped viruses play crucial roles in cell entry and in large part dictate the spectrum of cell types that a virus can infect. The identification in human cytomegalovirus (HCMV) of a viral endoplasmic reticulum (ER)-resident glycoprotein that regulates the composition of alternat...
[ "Fusion of herpesviruses with their target cells requires a minimum of three glycoproteins, namely, gB and a complex of gH and gL. Epstein-Barr virus (EBV) fusion with an epithelial cell requires no additional virus glycoproteins, and we have shown previously that it can be initiated by an interaction between integ...
Transanal Total Mesorectal Excision: Current Experience and Future Prospects
Low anterior resection can be a challenging operation, especially in obese male patients and in particular after radiotherapy. Transanal total mesorectal excision (TaTME) might offer technical advantages over laparoscopic or open approaches particularly for tumors in the distal third of the rectum. The aim of this arti...
[ "The TME trial investigated the value of preoperative short-term radiotherapy in combination with total mesorectal excision (TME). Long-term results are reported after a median follow-up of 12 years. Between Jan 12, 1996, and Dec 31, 1999, 1861 patients with resectable rectal cancer without evidence of distant dise...
A low resolution structure of the catalytic domain of CESA1 from Arabidopsis
A cellulose synthesis complex with a "rosette" shape is responsible for synthesis of cellulose chains and their assembly into microfibrils within the cell walls of land plants and their charophyte algal progenitors. The number of cellulose synthase proteins in this large multisubunit transmembrane protein complex and t...
[ "The cytoplasmic domain of the rosette terminal complex has been imaged in situ in patches of plasma membrane isolated from tobacco BY-2 protoplasts. By partially extracting the plasma membrane lipids, cellulose microfibrils were observed through the plasma membrane. Rosette terminal complexes were identified on th...
The effects of sleep loss on the homeostatic regulation of sleep
The nuclear receptor REV-ERBα is a potent, constitutive transcriptional repressor critical for the regulation of key circadian and metabolic genes. Recently, REV-ERBα's involvement in learning, neurogenesis, mood, and dopamine turnover was demonstrated suggesting a specific role in central nervous system functioning. W...
[ "Peroxisome proliferator-activated receptors (PPARs) are a group of nuclear receptors that function as transcription factors regulating the expression of numerous target genes. PPARs play an essential role in various physiological and pathological processes, especially in energy metabolism. It has long been known t...
Increased filamin C levels in frontotemporal dementia patients and a murine model
TAR DNA-binding protein 43 (TDP-43) inclusions are pathological hallmarks of patients with frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). Loss of TDP-43 in zebrafish engenders a severe muscle and vascular phenotype with a concomitant elevation of filamin C (FLNC) levels, an observatio...
[ "Ligands possessing different physico-chemical structures productively interact with G protein-coupled receptors generating distinct downstream signaling events due to their abilities to activate/select idiosyncratic receptor entities ('receptorsomes') from the full spectrum of potential receptor partners. We have ...
The HTR2A T102C polymorphism is a predictor of individual differences in empathic and autistic-like traits
Previous studies have indicated that empathic traits, such as perspective taking, are associated with the levels of serotonin in the brain and with autism spectrum conditions. Inspired by the finding that the serotonin receptor 2A gene (HTR2A) modulates the availability of serotonin, this study investigated to what ext...
[ "The ability to \"read the mind\" of other individuals, that is, to infer their mental state by interpreting subtle social cues, is indispensable in human social interaction. The neuropeptide oxytocin plays a central role in social approach behavior in nonhuman mammals. In a double-blind, placebo-controlled, within...
Klotho is essential for cell survival in triple negative breast cancer
Over the last decade, breast cancer mortality has declined. However, triple negative breast cancer (TNBC) remains a challenging problem mostly due to early recurrence and lack of molecularly driven treatments. There is a critical need to identify subgroups of TNBC with common molecular features that can be therapeutica...
[ "Normal human colonic epithelial cells (HCECs) are not immortalized by telomerase alone but also require CDK4. Some human cell types growth-arrest due to stress- or aberrant signaling-induced senescence (stasis). Stasis represents the consequences of growth conditions culture that are inadequate to maintain long-te...
Potency and Selectivity of PLK-1-Targeted Inhibitors
Mitotic kinases are the key components of the cell cycle machinery and play vital roles in cell cycle progression. PLK-1 (Polo-like kinase-1) is a crucial mitotic protein kinase that plays an essential role in both the onset of G2/M transition and cytokinesis. The overexpression of PLK-1 is strongly correlated with a w...
[ "Polo-like kinase 1 (Plk1) is a conserved serine/threonine kinase that plays an essential role in regulating the many processes involved in mitotic entry and progression. In humans, Plk1 is expressed primarily during late G(2) and M phases and, in conjunction with Cdk1/cyclin B1, acts as master regulatory kinases f...
Bayesian Dose-Finding in Two Treatment Cycles
This paper is motivated by a phase I-II clinical trial of a targeted agent for advanced solid tumors. We study a stylized version of this trial with the goal to determine optimal actions in each of two cycles of therapy. A design is presented that generalizes the decision-theoretic two-cycle design of Lee and others (2...
[ "The continual reassessment method (CRM) is an adaptive model-based design used to estimate the maximum tolerated dose in phase I clinical trials. Asymptotically, the method has been shown to select the correct dose given that certain conditions are satisfied. When sample size is small, specifying a reasonable mode...
RNA-binding proteins regulate protrusion stability and mesenchymal-like morphology
Polarization of cells into a protrusive front and a retracting cell body is the hallmark of mesenchymal-like cell migration. Many mRNAs are localized to protrusions, but it is unclear to what degree mRNA localization contributes toward protrusion formation. We performed global quantitative analysis of the distributions...
[ "The 5' and 3' untranslated regions of eukaryotic mRNAs (UTRs) play crucial roles in the post-transcriptional regulation of gene expression through the modulation of nucleo-cytoplasmic mRNA transport, translation efficiency, subcellular localization and message stability. UTRdb is a curated database of 5' and 3' un...
Single Molecule Microscopy with TIRF Illumination
In the course of a single decade single molecule microscopy has changed from being a secluded domain shared merely by physicists with a strong background in optics and laser physics to a discipline that is now enjoying vivid attention by life-scientists of all venues (1). This is because single molecule imaging has the...
[ "Monomeric (m)Eos2 is an engineered photoactivatable fluorescent protein widely used for super-resolution microscopy. We show that mEos2 forms oligomers at high concentrations and forms aggregates when labeling membrane proteins, limiting its application as a fusion partner. We solved the crystal structure of tetra...
Frequency of small intestinal bacterial overgrowth in patients with refractory functional gastrointestinal disorders
Small intestinal bacterial overgrowth (SIBO) is considered to be involved in the pathogenesis of functional gastrointestinal disorders (FGID). However, the prevalence and clinical conditions of SIBO in patients with FGID remain to be fully elucidated. Here, we examined the frequency of SIBO in patients with refractory ...
[ "Small intestinal bacterial overgrowth (SIBO), defined as excessive bacteria in the small intestine, remains a poorly understood disease. Initially thought to occur in only a small number of patients, it is now apparent that this disorder is more prevalent than previously thought. Patients with SIBO vary in present...
A federated logistic regression algorithm for vertically partitioned distributed data sets
To develop an accurate logistic regression (LR) algorithm to support federated data analysis of vertically partitioned distributed data sets.
[ "We sought to develop an intensive care unit research database applying automated techniques to aggregate high-resolution diagnostic and therapeutic data from a large, diverse population of adult intensive care unit patients. This freely available database is intended to support epidemiologic research in critical c...
MHC class I and KIR gene systems in the rhesus macaque AIDS model
Natural killer lymphocytes are essentially involved as the first line of defense against agents such as viruses and malignant cells. The activity of these cells is regulated via interaction of specific and diverse killer cell immunoglobulin-like receptors (KIR) with the highly polymorphic cognate MHC class I proteins o...
[ "The use of Chinese-origin rhesus macaques (Macaca mulatta) for infectious disease immunity research is increasing despite the relative lack of major histocompatibility complex (MHC) class I immunogenetics information available for this population. We determined transcript-based MHC class I haplotypes for 385 Chine...
Heme-induced apoptosis and toll-like receptor activation mediates endothelial progenitor cell depletion during malaria pathogenesis
Plasmodium falciparum infection can cause microvascular dysfunction, cerebral encephalopathy and death if untreated. We have previously shown that high concentrations of free heme, and C-X-C motif chemokine 10 (CXCL10) in sera of malaria patients induce apoptosis in microvascular endothelial and neuronal cells contribu...
[ "Transplantation of bone marrow cells as well as circulating endothelial progenitor cells (EPC) enhances neovascularization after ischemia. The chemokine receptor CXCR4 is essential for migration and homing of hematopoietic stem cells. Therefore, we investigated the role of CXCR4 and its downstream signaling cascad...
Identification of a gene encoding dihydroflavonol 4-reductase for the W3 locus in soybean
The wide range of flower colors in soybean is controlled by six independent loci (W1, W2, W3, W4, Wm, and Wp). Among these loci, mutations in the W3 locus under the w4 allelic background (i.e., w3w4) produce near-white flowers, while the W3w4 genotype produces purple throat flowers. Although a gene encoding dihydroflav...
[ "Genetic analyses have demonstrated that together with TTG1, a WD-repeat (WDR) protein, TT2 (MYB), and TT8 (bHLH) are necessary for the correct expression of BANYULS (BAN). This gene codes for the core enzyme of proanthocyanidin biosynthesis in Arabidopsis thaliana seed coat. The interplays of TT2, TT8, and their c...
Upregulation of caspases 1 and 11 by SJL/J mouse brain astrocytes infected with the BeAn strain of Theiler's murine encephalomyelitis virus
In this study, we demonstrate the upregulation in the expression of caspases 1 and 11 by SJL/J mouse brain astrocytes infected with the BeAn strain of Theiler's murine encephalomyelitis virus (TMEV). The upregulation of both proteases hints at protection of astrocytic cells from apoptotic death. We therefore looked for...
[ "The ASC (apoptosis speck-like protein) is a key component of multimeric protein complexes that mediate inflammation and host defence. Comprising a PYD (Pyrin) domain and a CARD (caspase activation and recruitment domain), ASC functions downstream of NLRs (nucleotide-binding domain, leucine-rich repeat-containing r...
Pegvisomant (PEG) in the Spanish cohort of ACROSTUDY
To evaluate the long-term safety of Pegvisomant (PEG) in the Spanish cohort of ACROSTUDY.
[ "Basal and recombinant human growth hormone (rhGH)-stimulated insulin-like growth factor (IGF-I) levels were studied in 19 insulin-dependent diabetic patients and 4 healthy subjects. Diabetic patients were divided according to glucagon test result into CpN (10 patients without residual beta cell activity) and CpP (...
Genome-wide association mapping of natural selection in indigenous goats and sheep
Goats and sheep are versatile domesticates that have been integrated into diverse environments and production systems. Natural and artificial selection have shaped the variation in the two species, but natural selection has played the major role among indigenous flocks. To investigate signals of natural selection, we a...
[ "We report the ∼2.66-Gb genome sequence of a female Yunnan black goat. The sequence was obtained by combining short-read sequencing data and optical mapping data from a high-throughput whole-genome mapping instrument. The whole-genome mapping data facilitated the assembly of super-scaffolds >5× longer by the N50 me...
Nitric oxide-induced autophagy is a survival mechanism in MC3T3-E1 cells
Nitric oxide (NO) is important in the regulation of bone remodeling, whereas high concentration of NO promotes cell death of osteoblast. However, it is not clear yet whether NO-induced autophagy is implicated in cell death or survival of osteoblast. The present study is aimed to examine the role of NO-induced autophagy...
[ "AMP-activated protein kinase (AMPK) is an evolutionarily conserved energy sensor important for cell growth, proliferation, survival, and metabolic regulation. Active AMPK inhibits biosynthetic enzymes like mTOR and acetyl CoA carboxylase (required for protein and lipid synthesis, respectively) to ensure that cells...
Generate retinal progenitor cells from rat embryonic stem cells
Degenerative retinal diseases like age-related macular degeneration (AMD) are the leading cause of blindness. Cell transplantation showed promising therapeutic effect for such diseases, and embryonic stem cell (ESC) is one of the sources of such donor cells. Here, we aimed to generate retinal progenitor cells (RPCs) fr...
[ "There is currently no real treatment for blinding disorders that stem from the degeneration of cells in the retina and affect at least 50 million individuals worldwide. The excitement that accompanied the first studies showing the potential of retinal cell transplantation to alleviate the progress of blindness in ...
Severe hyperlactatemia in critically ill patients
Hyperlactatemia may occur for a variety of reasons and is a predictor of poor clinical outcome. However, only limited data are available on the underlying causes of hyperlactatemia and the mortality rates associated with severe hyperlactatemia in critically ill patients. We therefore aimed to evaluate the etiology of s...
[ "To analyze the prognostic value of tissue oxygen saturation (StO(2)) in septic shock patients with restored mean arterial pressure (MAP). This was a prospective observational study of patients admitted to the ICU in the early phase of septic shock, after restoration of MAP. Demographic data, severity score, hemody...
Simultaneous, quantitative determination of intracellular nucleoside triphosphates and other polar metabolites using liquid chromatography with electrospray ionization tandem mass spectrometry
Simultaneous, quantitative determination of intracellular nucleoside triphosphates and other polar metabolites using liquid chromatography with electrospray ionization tandem mass spectrometry (LC-MS/MS) represents a bioanalytic challenge because of charged, highly hydrophilic analytes presented at a large concentratio...
[ "An ion-pairing high-performance liquid chromatographic method for the direct and simultaneous determination of nucleotides, deoxynucleotides, cAMP, nicotinic coenzymes, oxypurines, nucleosides, and bases in perchloric acid cell extracts is presented. By using an Alltima C-18, 250 x 4.6-mm, 5-microns particle size ...
Molecular model for the regulation of the Down's syndrome cell adhesion molecule (Dscam) gene
Mutually exclusive splicing is an important means of increasing the protein repertoire, by which the Down's syndrome cell adhesion molecule (Dscam) gene potentially generates 38,016 different isoforms in Drosophila melanogaster. However, the regulatory mechanisms remain obscure due to the complexity of the Dscam exon c...
[ "The Drosophila gene Dscam, encoding Down syndrome cell-adhesion molecule, is required for the development of neural circuits. Alternative splicing of Dscam mRNA potentially generates 38016 isoforms of a cell-surface recognition protein of the immunoglobulin superfamily. These isoforms include 19008 different ectod...
is corticotropin releasing factor in alzheimer's
Stress and corticotropin-releasing factor (CRF) have been implicated as mechanistically involved in Alzheimer's disease (AD), but agents that impact CRF signaling have not been carefully tested for therapeutic efficacy or long-term safety in animal models.
[ "Corticotropin-releasing factor (CRF) is the principal neuroregulator of the hypothalamic-pituitary-adrenocortical axis and plays an important role in coordinating the endocrine, autonomic, and behavioral responses to stress and immune challenge. We report here the cloning of a cDNA coding for a CRF receptor from a...
Cell topographies and biomechanical properties of temporomandibular joint discs from goats
This study is performed to investigate the cell topographies and biomechanical properties of two different types of temporomandibular joint (TMJ) discs from goats by using JPK Nano Wizard 3 biological atomic force microscopy (AFM). This process provides a guideline for selecting seed cells for TMJ disc tissue engineeri...
[ "As articular cartilage has very limited self-repair capability, the repair and regeneration of damaged cartilage is a major challenge. This review aims to outline the past, present, and future of cell therapies for articular cartilage defect repair. Autologous chondrocyte implantation (ACI) has been used clinicall...
Epigenetic Regulation of Keratinocyte Differentiation
The epidermal differentiation program is regulated at several levels including signaling pathways, lineage-specific transcription factors, and epigenetic regulators that establish well-coordinated process of terminal differentiation resulting in formation of the epidermal barrier. The epigenetic regulatory machinery op...
[ "p63 is a p53 homologue required for cutaneous development that is expressed in immature squamous epithelium and reserve cells of the cervix. Humans with p63 mutations exhibit defects in limb, accessory organ (skin appendage, breast, prostate), and genitourinary development. Because p63 expression patterns imply a ...
Computational analysis of viral transmembrane proteins
Viruses are the most abundant and genetically diverse biological entities on earth, yet the repertoire of viral proteins remains poorly explored. As the number of sequenced virus genomes grows into the thousands, and the number of viral proteins into the hundreds of thousands, we report a systematic computational analy...
[ "A global classification of all currently known protein sequences is performed. Every protein sequence is partitioned into segments of 50 amino acid residues and a dynamic programming distance is calculated between each pair of segments. This space of segments is initially embedded into Euclidean space. The algorit...
Diapeptidyl peptidase-4 inhibitors and new-onset diabetes after transplantation.
Despite strict pre- and post-transplantation screening, the incidence of new-onset diabetes after transplantation (NODAT) remains as high as 60%. This complication affects the risk of cardiovascular events and patient and graft survival rates. Thus, reducing the impact of NODAT could improve overall transplant success....
[ "Chemokines mediate the recruitment of leukocytes to the sites of inflammation. N-terminal truncation of chemokines by the protease dipeptidyl peptidase IV (DPPIV) potentially restricts their activity during inflammatory processes such as allergic reactions, but direct evidence in vivo is very rare. After demonstra...
Parallel visual coding in OFF bipolar cells
Using whole-cell clamp methods, we characterized the temporal coding in each type of OFF bipolar cell. We found that type 2 and 3a cells are transient, type 1 and 4 cells are sustained, and type 3b cells are intermediate. The light-evoked excitatory postsynaptic potentials in some types were rectified, suggesting that ...
[ "The receptive field of the Y-ganglion cell comprises two excitatory mechanisms: one integrates linearly over a narrow field, and the other integrates nonlinearly over a wide field. The linear mechanism has been attributed to input from bipolar cells, and the nonlinear mechanism has been attributed to input from a ...
can bronchopulmonary dysplasia be caused by prenatal inflammation?
Prenatal or postnatal systemic inflammation can contribute to the development of bronchopulmonary dysplasia (BPD). We investigated whether prenatal intra-amniotic (i.a.) inflammation or early postnatal systemic inflammation can induce BPD in a rat model.
[ "We tested whether rosiglitazone (RGZ), a peroxisome proliferator-activated receptor-γ agonist, can restore alveolar development and vascular growth in a rat model of bronchopulmonary dysplasia (BPD). A rat model of BPD was induced through intra-amniotic delivery of lipopolysaccharide (LPS) and postnatal hyperoxia ...
Transmembrane topologies of Arabidopsis MCA1 and MCA2
Sensing mechanical stresses, including touch, stretch, compression, and gravity, is crucial for growth and development in plants. A good mechanosensor candidate is the Ca(2+)-permeable mechanosensitive (MS) channel, the pore of which opens to permeate Ca(2+) in response to mechanical stresses. However, the structure-fu...
[ "Extracellular Ca(2+) (Ca(2+)(o)) is required for various physiological and developmental processes in animals and plants. In response to varied Ca(2+)(o) levels, plants maintain relatively constant internal Ca(2+) content, suggesting a precise regulatory mechanism for Ca(2+) homeostasis. However, little is known a...
miR-17-19b fine-tunes c-MYC-driven lymphomas
The synergism between c-MYC and miR-17-19b, a truncated version of the miR-17-92 cluster, is well-documented during tumor initiation. However, little is known about miR-17-19b function in established cancers. Here we investigate the role of miR-17-19b in c-MYC-driven lymphomas by integrating SILAC-based quantitative pr...
[ "Activation of Myc (c-Myc) causes epidermal cells to exit the stem cell compartment and differentiate into sebocytes and interfollicular epidermis at the expense of the hair lineages. To investigate how Myc exerts these effects we analysed the transcription of more than 10000 genes following Myc activation in the b...
Effect of flow cytometry status on outcomes of reduced-intensity conditioning allogeneic hematopoietic cell transplantation for acute myeloid leukemia.
Stringent complete remission (CR) in acute myeloid leukemia (AML) requires the absence of both morphologic and flow cytometric evidence of disease. We have previously shown that persistent AML detected by flow cytometry (FC+) before reduced-intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (all...
[ "Although reduced-intensity conditioning (RIC) and non-myeloablative (NMA)-conditioning regimens have been used for over a decade, their relative efficacy vs myeloablative (MA) approaches to allogeneic hematopoietic cell transplantation in patients with AML and myelodysplasia (MDS) is unknown. We compared disease s...
Milky spots in peritoneal adipose promote ovarian cancer cell metastatic colonization
High-grade serous ovarian cancer (HGSC), the cause of widespread peritoneal metastases, continues to have an extremely poor prognosis; fewer than 30% of women are alive 5 years after diagnosis. The omentum is a preferred site of HGSC metastasis formation. Despite the clinical importance of this microenvironment, the co...
[ "The molecular determinants of survival in ovarian cancer are poorly understood. Using expression microarrays, we recently found that high expression of the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) gene is associated with prolonged survival in advanced ovarian cancer. TRAIL has also been show...
Coevolved Residue Interactions in Bacterial Flagellar Rotation
Switching of bacterial flagellar rotation is caused by large domain movements of the FliG protein triggered by binding of the signal protein CheY to FliM. FliG and FliM form adjacent multi-subunit arrays within the basal body C-ring. The movements alter the interaction of the FliG C-terminal (FliGC) "torque" helix with...
[ "In contrast to the situation in enteric bacteria, chemotaxis in Rhodobacter sphaeroides requires transport and partial metabolism of chemoattractants. A chemotaxis operon has been identified containing homologues of the enteric cheA, cheW, cheR genes and two homologues of the cheY gene. However, mutations in these...
Cell-Cycle Quiescence Alters the Genetic Requirements for Stem Cell Maintenance
Many types of adult stem cells exist in a state of cell-cycle quiescence, yet it has remained unclear whether quiescence plays a role in maintaining the stem cell fate. Here we establish the adult germline of Caenorhabditis elegans as a model for facultative stem cell quiescence. We find that mitotically dividing germ ...
[ "Hematopoietic stem cells (HSCs) give rise to all lineages of blood cells. Because HSCs must persist for a lifetime, the balance between their proliferation and quiescence is carefully regulated to ensure blood homeostasis while limiting cellular damage. Cell cycle regulation therefore plays a critical role in cont...
Pancreatic Intraepithelial Neoplasia and Invasive Carcinoma of the Pancreas
International experts met to discuss recent advances and to revise the 2004 recommendations for assessing and reporting precursor lesions to invasive carcinomas of the pancreas, including pancreatic intraepithelial neoplasia (PanIN), intraductal papillary mucinous neoplasm (IPMN), mucinous cystic neoplasm, and other le...
[ "The aim of this study was to determine recurrence and long-term survival after resection of pancreatic intraductal papillary mucinous neoplasm and to correlate recurrence and survival with histology, extent of resection, and duration of follow-up. A single pathologist, without knowledge of previous interpretations...
Acid ceramidase-regulated sphingolipid signaling in human melanoma.
Acid ceramidase (AC) is a lysosomal cysteine amidase that controls sphingolipid signaling by lowering the levels of ceramides and concomitantly increasing those of sphingosine and its bioactive metabolite, sphingosine 1-phosphate. In the present study, we evaluated the role of AC-regulated sphingolipid signaling in mel...
[ "Activation-induced cell death (AICD), a process mediated by CD95 and CD95 ligand (CD95L), plays a critical role in regulating homeostasis of the immune system. Although the role of sphingolipids such as ceramides has been suggested to participate in CD95-mediated apoptosis, the exact role of these molecules in thi...
Angiogenic and antiangiogenic isoforms of vascular endothelial growth factor A regulate spermatogonial stem cell homeostasis
Despite being well-known for regulating angiogenesis in both normal and tumorigenic environments, vascular endothelial growth factor A (VEGFA) has been recently implicated in male fertility, namely in the maintenance of spermatogonial stem cells (SSC). The VEGFA gene can be spliced into multiple distinct isoforms that ...
[ "We hypothesized that vascular endothelial growth factor A (VEGFA) angiogenic isoforms and their receptors, FLT1 and KDR, regulate follicular progression in the perinatal rat ovary. Each VEGFA angiogenic isoform has unique functions (based on its exons) that affect diffusibility, cell migration, branching, and deve...
CD8+ non-cytolytic antiviral response in rhesus macaques.
The ability of long term non progressors to maintain very low levels of HIV/SIV and a healthy state, involves various host genetic and immunological factors. CD8+ non-cytolytic antiviral response (CNAR) most likely plays an important role in this regard. In order to gain a deeper insight into this unique phenomenon, th...
[ "Here, we report on the expression of programmed death (PD)-1 on human virus-specific CD8(+) T cells and the effect of manipulating signaling through PD-1 on the survival, proliferation, and cytokine function of these cells. PD-1 expression was found to be low on naive CD8(+) T cells and increased on memory CD8(+) ...
Effects of medical ozone preconditioning and treatment on methotrexate acute induced hepatotoxicity in rats
The aim of this study is to determine the effects of medical ozone preconditioning and treatment on the methotrexate acute induced hepatotoxicity in rats that has not reports elsewhere. Eighteen rats were randomly assigned into three equal groups; control, Mtx and Mtx with ozone. Hepatotoxicity was performed with a sin...
[ "The acceptance of any complementary medical approach is conditioned by the results obtained after the same scientific scrutiny applied in orthodox medicine. Otherwise any claim of efficacy remains in the realm of fiction. In the case of ozone therapy, the mechanisms of action have remained nebulous and in a series...
Targeted proteomics of oral squamous cell carcinoma biomarkers in saliva
Head and neck cancers, including oral squamous cell carcinoma (OSCC), are the sixth most common malignancy in the world and are characterized by poor prognosis and a low survival rate. Saliva is oral fluid with intimate contact with OSCC. Besides non-invasive, simple, and rapid to collect, saliva is a potential source ...
[ "New biomarkers that replace or are used in conjunction with the current ovarian cancer diagnostic antigen, CA125, are needed for detection of ovarian cancer in the presurgical setting, as well as for detection of disease recurrence. We previously demonstrated the upregulation of leucine-rich alpha-2-glycoprotein-1...
Effects of fluorescent superparamagnetic iron oxide particles on bioactivities and osteogenetic differentiation of rat bone marrow mesenchymal stem cells
The aim of this study was to investigate the impacts of fluorescent superparamagnetic iron oxide particles (Molday ION Rhodamine B, MIRB) on bioactivities and osteogenetic differentiation of rat bone marrow mesenchymal stem cells (BMSCs). The Cell Counting Kit-8 (CCK-8) method was used to detect the proliferation of su...
[ "Mononuclear phagocyte system is the first target for injected nanomaterials. Monocytes/macrophages are the central actors for trafficking and clearance of magnetic nanoparticles in vivo. However the fate of nanosized magnetic label is an ongoing issue. Here we demonstrate that the monocyte/macrophage system shows ...
Reproducible chromatin-immunoprecipitation-based deep sequencing of hematopoietic stem cells
Understanding how chromatin modification regulates development and disease can be limited by available material. Despite recent progress, balancing high-quality and reliable mapping using chromatin-immunoprecipitation-based deep sequencing (ChIP-seq) remains a challenge. We report two techniques, recovery via protectio...
[ "We report the application of single-molecule-based sequencing technology for high-throughput profiling of histone modifications in mammalian cells. By obtaining over four billion bases of sequence from chromatin immunoprecipitated DNA, we generated genome-wide chromatin-state maps of mouse embryonic stem cells, ne...
G9a-mediated histone H3 lysine 9 dimethylation is essential for postimplantation development
Early mouse development is accompanied by dynamic changes in chromatin modifications, including G9a-mediated histone H3 lysine 9 dimethylation (H3K9me2), which is essential for embryonic development. Here we show that genome-wide accumulation of H3K9me2 is crucial for postimplantation development, and coincides with re...
[ "DNA methylation is extensively reprogrammed during the early phases of mammalian development, yet genomic targets of this process are largely unknown. We optimized methylated DNA immunoprecipitation for low numbers of cells and profiled DNA methylation during early development of the mouse embryonic lineage in viv...
Instanton droplet excitations in a localized spin-polarized current
The interfacial Dzyaloshinskii-Moriya Interaction can modify the topology of droplets excited by a localized spin-polarized current. Here, we show that, in addition to the stationary droplet excitations with skyrmion number either one (topological) or zero (non-topological), there exists, for a fixed current, an excite...
[ "Topologically nontrivial spin textures have recently been investigated for spintronic applications. Here, we report on an ultrathin magnetic film in which individual skyrmions can be written and deleted in a controlled fashion with local spin-polarized currents from a scanning tunneling microscope. An external mag...
DNAM-1 promotes NK cell-mediated cytotoxicity and cytokine production via an immunoreceptor tyrosine tail-like motif.
DNAM-1 (CD226) is an activating receptor expressed on natural killer (NK) cells, CD8(+) T cells, and other immune cells. Upon recognition of its ligands, CD155 and CD112, DNAM-1 promotes NK cell-mediated elimination of transformed and virus-infected cells. It also has a key role in expansion and maintenance of virus-sp...
[ "Natural killer (NK) cells are innate lymphocytes that are crucial for the control of infections and malignancies. NK cells express a variety of inhibitory and activating receptors that facilitate fine discrimination between damaged and healthy cells. Among them, a family of molecules that bind nectin and nectin-li...
Attractiveness of animal baits to necrophagous Diptera (Calliphoridae, Fanniidae, Muscidae, Phoridae and Sarcophagidae) in a rainforest fragment in Brazil
Insects associated with carrion can have parasitological importance as vectors of several pathogens and causal agents of myiasis to men and to domestic and wild animals. We tested the attractiveness of animal baits (chicken liver) at different stages of decomposition to necrophagous species of Diptera (Calliphoridae, F...
[ "The aim of this note was to record for the first time the finding of Hemilucilia segmentaria acting as biological vector of Dermatobia hominis, during a study of the diversity of Calliphoridae at Reserva Biol gica do Tinguá, Rio de Janeiro, Brazil. The insects were captured using traps baited with chicken vicera, ...
Proteomics and cancer research
Systematic studies of the cancer genome have generated a wealth of knowledge in recent years. These studies have uncovered a number of new cancer genes not previously known to be causal targets in cancer. Genetic markers can be used to determine predisposition to tumor development, but molecularly targeted treatment st...
[ "The emergence of MS-based proteomic platforms as a prominent technology utilized in biochemical and biomedical research has increased the need for high-quality MS measurements. To address this need, National Institute of Standards and Technology (NIST) reference material (RM) 8323 yeast protein extract is introduc...
Workplace-based interventions for preventing and managing upper extremity musculoskeletal disorders
The burden of disabling musculoskeletal pain and injuries (musculoskeletal disorders, MSDs) arising from work-related causes in many workplaces remains substantial. There is little consensus on the most appropriate interventions for MSDs. Our objective was to update a systematic review of workplace-based interventions ...
[ "Upper extremity musculoskeletal disorders (MSD) are very common in regular computer users and leading cause of work related illness. The objective of the present study is to evaluate effectiveness of yogic exercises in the improvement of symptoms of MSDs of upper limbs. 60 study participants were randomly divided ...
Direct and Efficient Generation of Neural Stem Cells from Mouse Embryo Neuroepithelium
Neural stem cells (NSCs) are multi-potent stem cells able to self-renew and generate immature and differentiated cell populations by asymmetric division. The NSCs are of considerable interest for cell replacement in neuro-degenerative diseases. NSCs are usually identified and expanded by their ability to generate free-...
[ "The pathogenesis of neurological diseases and disorders remains mostly unknown. Neuroinflammation has been proposed as a causative factor for neurological diseases. The confirmation that neurogenesis occurs in the adult brain and neural stem cells (NSCs) reside in the adult central nervous system (CNS) of mammals ...
Serotonin Reuptake Inhibitors and Osteoporosis
Osteoporosis is a chronic skeletal disease marked by microarchitectural deterioration of the bone matrix and depletion of bone mineral density (BMD), with a consequent increased risk for fragility fractures. It has been frequently associated with depression, which is also a chronic and debilitating disorder with high p...
[ "Disruption of serotonin synthesis in neurons and the periphery by knockout (KO) of mouse genes for tryptophan hydroxylases (peripheral Tph1 and neuronal Tph2) has been claimed to decrease (Tph2 KO) and increase (Tph1 KO) bone mass. In this report, adult male and female Tph2 KO mice were observed to have elevated s...
Circadian regulation of lipid-associated genes in the liver
Disruption of the body clock has been recognized as a risk factor for cardiovascular disease. How the circadian pacemaker interacts with the genetic factors associated with plasma lipid traits remains poorly understood. Recent genome-wide association studies have identified an expanding list of genetic variants that in...
[ "The mammalian circadian clock involves a transcriptional feed back loop in which CLOCK and BMAL1 activate the Period and Cryptochrome genes, which then feedback and repress their own transcription. We have interrogated the transcriptional architecture of the circadian transcriptional regulatory loop on a genome sc...
where did early modern humans come from
Anthropological and genetic data agree in indicating the African continent as the main place of origin for anatomically modern humans. However, it is unclear whether early modern humans left Africa through a single, major process, dispersing simultaneously over Asia and Europe, or in two main waves, first through the A...
[ "It has recently been shown that ancestors of New Guineans and Bougainville Islanders have inherited a proportion of their ancestry from Denisovans, an archaic hominin group from Siberia. However, only a sparse sampling of populations from Southeast Asia and Oceania were analyzed. Here, we quantify Denisova admixtu...
Lipid and glucose metabolism in Alzheimer disease
Diabetes is a risk factor for Alzheimer disease (AD). Apolipoprotein E (ApoE) and several genes related to AD have recently been identified by genome-wide association studies (GWAS) as being closely linked to lipid metabolism. Lipid metabolism and glucose-energy metabolism are closely related. Here, we review the emerg...
[ "Apolipoprotein (apo) E is an exchangeable apolipoprotein that plays an integral role in cholesterol transport in the plasma and the brain. It is also associated with protein misfolding or amyloid proteopathy of the beta amyloid peptide (Abeta) in Alzheimer's disease (AD) and cerebral amyloid angiopathy. The C-term...
Differential role of myeloid differentiation factor 88 on graft-versus-host disease and graft-versus-leukemia effect after allogeneic stem cell transplantation
Despite the presence of toll like receptor (TLR) expression in conventional TCRαβ T cells, the direct role of TLR signaling via myeloid differentiation factor 88 (MyD88) within T lymphocytes on graft-versus-host disease (GVHD) and graft-versus-leukemia (GVL) effect after allogeneic stem cell transplantation (allo-SCT) ...
[ "In allogeneic bone marrow transplantation (BMT) donor T cells are primarily responsible for antihost activity, resulting in graft-versus-host disease (GVHD), and for antileukemia activity, resulting in the graft-versus-leukemia (GVL) effect. The relative contributions of the Fas ligand (FasL) and perforin cytotoxi...
Malaria control in Kenya: a national survey
Since 2004, Kenya's national malaria treatment guidelines have stipulated artemisinin-based combination therapy (ACT) as first-line treatment for uncomplicated malaria, and since 2014, confirmatory diagnosis of malaria in all cases before treatment has been recommended. A number of strategies to support national guidel...
[ "Despite the benefits of malaria diagnosis, most presumed malaria episodes are never tested. A primary reason is the absence of diagnostic tests in retail establishments, where many patients seek care. Malaria rapid diagnostic tests (RDTs) in drug shops hold promise for guiding appropriate treatment. However, retai...
Thyroid hormone and anacardic acid enhance embryoid body formation in mouse embryonic stem cells
The epigenetics of early commitment to embryonal cardiomyocyte is poorly understood. In this work, we compared the effect of thyroid hormone and that of anacardic acid, a naturally occurring histone acetylase inhibitor, or both in combination, on mouse embryonic stem cells (mES) differentiating into embryonal cardiomyo...
[ "Chromosome 1p36 deletion syndrome is one of the most common terminal deletions observed in humans and is related to congenital heart disease (CHD). However, the 1p36 genes that contribute to heart disease have not been clearly delineated. Human CASZ1 gene localizes to 1p36 and encodes a zinc finger transcription f...
Mitochondrial quality control induced by proteasome impairment
Mitochondria are vital and highly dynamic organelles that continuously fuse and divide to maintain mitochondrial quality. Mitochondrial dysfunction impairs cellular integrity and is known to be associated with various human diseases. However, the mechanism by which the quality of mitochondria is maintained remains larg...
[ "Dysfunction of mitochondria has severe cellular consequences and is linked to ageing and neurodegeneration in human. Several surveillance strategies have evolved that limit mitochondrial damage and ensure cellular integrity. Intraorganellar proteases conduct protein quality control and exert regulatory functions, ...
Apolipoprotein E-enriched proteinaceous aggregates in pantothenate kinase-associated neurodegeneration
Pantothenate kinase-associated neurodegeneration (PKAN) is a progressive movement disorder that is due to mutations in PANK2. Pathologically, it is a member of a class of diseases known as neurodegeneration with brain iron accumulation (NBIA) and features increased tissue iron and ubiquitinated proteinaceous aggregates...
[ "Pyruvate dehydrogenase deficiency is a major cause of primary lactic acidosis and neurological dysfunction in infancy and early childhood. Most cases are caused by mutations in the X-linked gene for the E1alpha subunit of the complex. Mutations in DLAT, the gene encoding dihydrolipoamide acetyltransferase, the E2 ...
Molecular regulation by the miR-290 family in mouse embryonic stem cells
Members of the miR-290 family are the most abundantly expressed microRNAs (miRNAs) in mouse embryonic stem cells (ESCs). They regulate aspects of differentiation, pluripotency, and proliferation of ESCs, but the molecular program that they control has not been fully delineated. In the absence of Dicer, ESCs fail to exp...
[ "Polycomb group proteins are essential for early development in metazoans, but their contributions to human development are not well understood. We have mapped the Polycomb Repressive Complex 2 (PRC2) subunit SUZ12 across the entire nonrepeat portion of the genome in human embryonic stem (ES) cells. We found that S...
S119, a novel inhibitor of influenza virus replication
S119 was a top hit from an ultrahigh throughput screen performed to identify novel inhibitors of influenza virus replication. It showed a potent antiviral effect (50% inhibitory concentration, IC
[ "Influenza nucleoprotein (NP) plays multiple roles in the virus life cycle, including an essential function in viral replication as an integral component of the ribonucleoprotein complex, associating with viral RNA and polymerase within the viral core. The multifunctional nature of NP makes it an attractive target ...
Reconstruction of the dorsum of the hand with bilateral rotation flap
In some cases, keratoacanthomas can be indistinguishable from squamous cell carcinoma, making the gold standard treatment surgical excision with histopathological evaluation. The surgical defects created on the back of the hand can be challenging to repair. We describe the use of bilateral rotation flap as an option in...
[ "After injection of stained latex at the brachial artery, the arterial supply of the dorsal aspect of the thumb was studied by light microscopy in 25 cadavers. An artery, located on the dorsoulnar side and connecting the head of the first metacarpal with the dorsal arcade of the proximal nail fold, was found in all...
Using electronic health records to improve the quality of medication allergy data
Antimicrobial resistance is a growing, global public health crisis, due in large part to the overuse and misuse of antibiotics. Understanding medication allergy data and allergy reactions that are documented in electronic health records (EHRs) can help to identify opportunities to improve the quality of documentation o...
[ "Dangerous, antibiotic resistant bacteria have been observed with increasing frequency over the past several decades. In this review the factors that have been linked to this phenomenon are addressed. Profiles of bacterial species that are deemed to be particularly concerning at the present time are illustrated. Fa...
The EXS domain of the Arabidopsis phosphate exporter is essential for signaling and homeostasis
The response of shoots to phosphate (Pi) deficiency implicates long-distance communication between roots and shoots, but the participating components are poorly understood. We have studied the topology of the Arabidopsis (Arabidopsis thaliana) PHOSPHATE1 (PHO1) Pi exporter and defined the functions of its different dom...
[ "Phosphorus, one of the essential elements for plants, is often a limiting nutrient because of its low availability and mobility in soils. Significant changes in plant morphology and biochemical processes are associated with phosphate (Pi) deficiency. However, the molecular bases of these responses to Pi deficiency...
Bone marrow based coculture of human primary myeloma cells
Human primary myeloma (MM) cells do not survive in culture; current in vitro and in vivo systems for growing these cells are limited to coculture with a specific bone marrow (BM) cell type or growth in an immunodeficient animal model. The purpose of the study is to establish an interactive healthy donor whole BM based ...
[ "Advances in multiple myeloma support the notion that the associated bone disease, characterized by increased osteoclastogenesis and suppressed osteoblastogenesis, is both a consequence and necessity of tumour progression. Osteoblastogenesis is suppressed by secreted inhibitors and dysregulation of cell-surface 'co...
Correlations between articulation disorders in PD patients and sociodemographic factors
Evaluation of speech disorders in PD taking into account sociodemographic conditions is not frequent. This paper aims to establish correlations between articulation disorders in PD patients and factors such as the patients' sex, age, education and residence.
[ "The purpose of this study was to examine the relationship between scaled speech intelligibility and selected acoustic variables in persons with dysarthria. Control speakers and speakers with amyotrophic lateral sclerosis (ALS) and Parkinson's disease (PD) produced sentences which were analyzed acoustically and per...
Elastography as a diagnostic tool in breast cancer screening.
Elastography (ES) is a technique that, when associated with traditional B mode ultrasound (US), allows the degree of elasticity of tissue to be evaluated according to a color scale system. The aims of the study were to compare the diagnostic characteristics of two widely used techniques adopted in breast cancer screeni...
[ "The aim of the breast team is to obtain a definitive, nonoperative diagnosis of all potential breast abnormalities in a timely and cost-effective way. Percutaneous needle biopsy with its high sensitivity and specificity should now be standard practice, removing the need for open surgical biopsy or frozen section. ...
Structural Indistinguishability of Nanolipoprotein Particles Produced by Cell-Free Expression of Membrane Scaffold Protein
Nanolipoprotein particles (NLPs), composed of membrane scaffold proteins and lipids, have been used to support membrane proteins in a native-like bilayer environment for biochemical and structural studies. Traditionally, these NLPs have been prepared by the controlled removal of detergent from a detergent-solubilized p...
[ "We systematically examined the mechanism of the solvent polarity dependence of the fluorescence ON/OFF threshold of the BODIPY (boron dipyrromethene) fluorophore and the role of photoinduced electron transfer (PeT). In a series of BODIPY derivatives with variously substituted benzene moieties at the 8-position, th...
Human Toll-Like Receptor 8 Activates Human Peripheral Blood Mononuclear Cells
Toll-like receptor (TLR) 13 and TLR2 are the major sensors of Gram-positive bacteria in mice. TLR13 recognizes Sa19, a specific 23S ribosomal (r) RNA-derived fragment and bacterial modification of Sa19 ablates binding to TLR13, and to antibiotics such as erythromycin. Similarly, RNase A-treated Staphylococcus aureus ac...
[ "Bacterial RNA (bRNA) can induce cytokine production in macrophages and dendritic cells (DCs) through a previously unidentified receptor. Gene expression analysis of murine DCs showed that bRNA induced gene regulation similar to that induced by stimulation of TLR7 with R848. Although TLR7 was dispensable for cytoki...
Generate query for cysteine dioxygenase type 1
Cysteine dioxygenase type 1 (
[ "ROC curves are a popular method for displaying sensitivity and specificity of a continuous diagnostic marker, X, for a binary disease variable, D. However, many disease outcomes are time dependent, D(t), and ROC curves that vary as a function of time may be more appropriate. A common example of a time-dependent va...
Iron deficiency and iron deficiency anemia in children
Iron is a key nutrient and is essential for the developing fetus, neonate, infant, and child. Iron requirements are high during early stages of life because it is critically important for the production of new red blood cells and muscle cells as well as brain development. Neonates, infants, and children obtain iron fro...
[ "To assess associations between breastfeeding and iron status at 9 months of age in 2 samples of Chinese infants. Associations between feeding at 9 months of age (breastfed as sole milk source, mixed fed, or formula fed) and iron deficiency anemia (IDA), iron deficiency, and iron sufficiency were determined in infa...
Effects of drought on the defense and nutrition allocation of pea aphids in Medicago truncatula
The activation of the abscisic acid (ABA) signaling pathway reduces water loss from plants challenged by drought stress. The effect of drought-induced ABA signaling on the defense and nutrition allocation of plants is largely unknown. We postulated that these changes can affect herbivorous insects. We studied the effec...
[ "There is a long-standing controversy as to whether drought limits photosynthetic CO2 assimilation through stomatal closure or by metabolic impairment in C3 plants. Comparing results from different studies is difficult due to interspecific differences in the response of photosynthesis to leaf water potential and/or...
Quorum sensing in the human pathogen Vibrio cholerae
Quorum sensing (QS) is a microbial signaling process for monitoring population density and complexity. Communication among bacterial cells via QS relies on the production, secretion, and detection of small molecules called autoinducers. Many bacteria have evolved their QS systems with different network architectures to...
[ "The growing threat of antibiotic resistance necessitates the development of novel antimicrobial therapies. Antivirulence agents that target group-beneficial traits in microorganisms (i.e., phenotypes that help the cells surrounding the producer cell instead of selfishly benefiting only the producer cell) represent...
Long-term effects of maternal separation on behavior, HPA axis activity and voluntary alcohol intake in female rats
Environmental factors during the early-life period are known to have long-term consequences for the adult phenotype. An intimate interplay between genes and environment shape the individual and may affect vulnerability for psychopathology in a sex-dependent manner. A rodent maternal separation model was here used to st...
[ "Defensive and vocal behaviors of 18 female Long-Evans rats (Rattus norvegicus) in encounters with aggressive, lactating conspecifics were examined in order to determine if female rats emit ultrasounds during agonistic interactions and to characterize any such calls. The subjects, selected during estrus or diestrus...
Multicriteria Decision Analysis for Rare Diseases
The multiplicity of issues, including uncertainty and ethical dilemmas, and policies involved in appraising interventions for rare diseases suggests that multicriteria decision analysis (MCDA) based on a holistic definition of value is uniquely suited for this purpose. The objective of this study was to analyze and fur...
[ "Zoonoses are a growing international threat interacting at the human-animal-environment interface and call for transdisciplinary and multi-sectoral approaches in order to achieve effective disease management. The recent emergence of Lyme disease in Quebec, Canada is a good example of a complex health issue for whi...
Palbociclib in combination with an anti-androgen enzalutamide in triple negative breast cancer
Triple negative breast cancer (TNBC) lacks specific drug targets and remains challenging. Palbociclib, a cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitor is approved for metastatic estrogen receptor (ER)-positive and human epithermal growth factor 2 (HER2)-negative breast cancer. The nature of cell cycle inhibition ...
[ "High-grade serous ovarian cancers (HGSOC) are genomically complex, heterogeneous cancers with a high mortality rate, due to acquired chemoresistance and lack of targeted therapy options. Cyclin-dependent kinase inhibitors (CDKi) target the retinoblastoma (RB) signaling network, and have been successfully incorpora...