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The wiring of the nervous system is established through a progressive refinement of the choices made by a growing axon. The growth cone is a highly motile structure at the tip of the axon that integrates the multitude of signals present in its environment and translates these signals into structural changes of the cyto... | Is Mical an oxidoreductase? | the oxidoreductase MICAL |
In the last few weeks, the FDA approved three new therapies for multiple myeloma: ixazomib, the first oral proteasome inhibitor; and daratumumab and elotuzumab, two monoclonal antibodies that target CD38 and SLAMF7, respectively. | What is the target of daratumumab? | In the last few weeks, the FDA approved three new therapies for multiple myeloma: ixazomib, the first oral proteasome inhibitor; and daratumumab and elotuzumab, two monoclonal antibodies that target CD38 and SLAMF7, respectively. |
Miller Fisher syndrome is an acute inflammatory polyradiculoneuropathy that is generally considered a variant of Guillain-Barré syndrome and is characterized by the clinical triad of ataxia, areflexia, and ophthalmoplegia. Several reports of familial Guillain-Barré syndrome have been reported, indicating a possible und... | Is the Miller-Fisher syndrome considered to be a variant of Guillain-Barré? | Miller Fisher syndrome is an acute inflammatory polyradiculoneuropathy that is generally considered a variant of Guillain-Barré syndrome and is characterized by the clinical triad of ataxia, |
Primary neuronal cultures are a useful tool for measuring pharmacological- and transgene-regulated gene expression; however, accurate measurements can be confounded by heterogeneous cell types and inconsistent transfection efficiency. Here we describe our adaptation of a ribosomal capture strategy that was designed to ... | What is RiboTag profiling? | Here we describe our adaptation of a ribosomal capture strategy that was designed to be used in transgenic mice expressing tagged ribosomal subunits (RiboTag) in specific cell types, thereby allowing measurement of translating RNAs from desired cell types within complex tissues. Using this strategy we were able to isol... |
Alcohol-based hand sanitizer is a liquid, gel, or foam that contains ethanol or isopropanol used to disinfect hands. Hand hygiene is an important component of the U.S. response to the emergence of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19). If soap and water are not readily available, CDC rec... | What is the active ingredient in the most common hand sanitizer? | Clinicians should maintain a high index of suspicion for methanol poisoning when evaluating adult or pediatric patients with reported swallowing of an alcohol-based hand sanitizer product or with symptoms, signs, and laboratory findings (e.g., elevated anion-gap metabolic acidosis) compatible with methanol poisoning. |
Weevils (Curculionoidea) comprise one of the most diverse groups of organisms on earth. There is hardly a vascular plant or plant part without its own species of weevil feeding on it and weevil species diversity is greater than the number of fishes, birds, reptiles, amphibians and mammals combined. Here, we employ ultr... | What is the contribution of ultraconserved elements in Australasian smurf-weevils? | Here, we employ ultraconserved elements (UCEs) designed for beetles and a novel partitioning strategy of loci to help resolve phylogenetic relationships within the radiation of Australasian smurf-weevils (Eupholini). Despite being emblematic of the New Guinea fauna, no previous phylogenetic studies have been conducted ... |
A quantitative trait locus (QTL) affecting milk fat percentage has been mapped to the centromeric end of the bovine chromosome 14 (BTA14). This genomic area includes the DGAT1 gene, which encodes acyl-CoA:diacylglycerol acyltransferase 1, the key enzyme of triglyceride biosynthesis. Genetic and biochemical studies led ... | What is the function of the DGAT1 gene product? | This genomic area includes the DGAT1 gene, which encodes acyl-CoA:diacylglycerol acyltransferase 1, the key enzyme of triglyceride biosynthesis. |
The optimal surgical procedure for patients with calcified and organized chronic subdural haematoma (CSDH), or "armoured brain", has not been established because it is difficult to obtain good re-expansion of the brain after surgery. We present herein the case of a 32-year-old woman with huge calcified CSDH manifesting... | Describe armoured brain syndrome. | The optimal surgical procedure for patients with calcified and organized chronic subdural haematoma (CSDH), or "armoured brain", has not been established because it is difficult to obtain good re-expansion of the brain after surgery |
In the nucleus HuR binds to mRNAs containing adenylate-uridylate rich elements in the 3'-untranslated region. HuR may influence expression of its ligand mRNA through regulation of polyadenylation, translocation of the message to the cytosol, stabilization of the mRNA and/or altering its translational efficiency. Suppre... | Which are the main functions of the human HuR (ELAVL1) protein in fibroblasts? | Suppression of HuR using siRNA resulted in an attenuation of the 3T3-L1 differentiation program, consistent with HuR control of the expression of mRNA ligand(s) critical to the differentiation process. |
Transcription-coupled DNA repair is a mechanism by which bulky DNA lesions that block transcription by RNA polymerase are prioritised for removal by the nucleotide excision repair apparatus. The trigger is thought to be the presence of an irreversibly blocked transcription complex, which is recognised by a transcriptio... | Which proteins act as factors that promote transcription-coupled repair in bacteria? | The effect of the bacterial transcription-repair coupling factor, Mfd, at such lesions is not known: it has been suggested that Mfd may promote mutagenesis by increasing the efficiency with which RNA polymerase bypasses non-bulky lesions, but it has also been reported that 8-oxoguanine, a major product of oxidative DNA... |
Mutations in genes known to be responsible for most of the recognizable syndromes associated with bilateral coronal synostosis can be detected by molecular testing. The genetic alterations that could cause unilateral coronal synostosis are more elusive. It is recognized that FGFR and TWIST mutations can give rise to ei... | Is there an association between FGFR3 mutation and plagiocephaly? | Other abnormalities in the craniofacial region and extremities were clues to a particular mutation in FGFR2, FGFR3, TWIST, or the X-linked mutation. |
The production performance of pigs has been significantly improved due to long-term artificial selection, and the specific variation characterizations (selection signatures) emerged from the selected genome regions. Different types of breeds are subjected to different selection intensities and had different selection s... | Which software are used for the detection of selective sweeps? | Using gPLINK software to set quality control standards, a total of 34 304 SNPs were selected for statistical analysis. Fst values between two breeds were estimated with Genepop package and the average Fst value was 0.3209. |
Recent studies have disclosed the function of enhancer RNAs (eRNAs), which are long non-coding RNAs transcribed from gene enhancer regions, in transcriptional regulation. However, it remains unclear whether eRNAs are involved in the regulation of human heme oxygenase-1 gene (HO-1) induction. Here, we report that multip... | Are there enhancer RNAs (eRNAs)? | Recent studies have disclosed the function of enhancer RNAs (eRNAs), which are long non-coding RNAs transcribed from gene enhancer regions, in transcriptional regulation. |
The prevalence of metabolic disorders (MDs), especially diabetes, is rapidly increasing worldwide, leading to an increasing risk of cardiovascular and other socially relevant complications. To boost MD biomarker discovery, advanced proteomics can harmonize metabolomics. Indeed, the rapid development of mass spectrometr... | What is the main application of SWATH-MS in proteomics? | ew strategies, such as SWATH™ MS, which allows us to systematically characterize and quantify query sample sets of 'any protein of interest' in complex biological samples, |
Obstructive sleep apnea (OSA) is a highly prevalent sleep disorder; however, it remains underdiagnosed and undertreated. Although screening tools such as the Berlin questionnaire (BQ), STOP-BANG questionnaire (SBQ), STOP questionnaire (STOP), and Epworth sleepiness scale (ESS) are widely used for OSA, the findings rega... | Which disease risk can be estimated with the Stop-Bang questionnaire? | Compared with the BQ, STOP, and ESS, the SBQ is a more accurate tool for detecting mild, moderate, and severe OSA. Sleep specialists should use the SBQ to conduct patient interviews for the early diagnosis of OSA in clinical settings, particularly in resource-poor countries and sleep clinics where PSG is unavailable. |
Diabetes induces cardiomyocyte apoptosis and suppresses cardiac autophagy, indicating that the interplay between autophagy and apoptotic cell death pathways is important in the pathogenesis of diabetic cardiomyopathy. The potential mechanism, however, remains unknown. We recently reported that diabetes depresses AMP-ac... | What is the role of AMPK in diabetic cardiomyopathy? | Activation of AMPK directly phosphorylates MAPK8, which mediates BCL2 phosphorylation and subsequent BECN1-BCL2 dissociation, leading to restoration of cardiac autophagy, protection against cardiac apoptosis, and ultimately improvement in cardiac structure and function. |
In an animal model of AMI relevant to the human disease, intracoronary administration of IGF-1/HGF is a practical and effective strategy to reduce pathological cardiac remodeling, induce myocardial regeneration, and improve ventricular function. | what is the role of IGF-1 in cardiac regeneration after myocardial infarction? | In an animal model of AMI relevant to the human disease, intracoronary administration of IGF-1/HGF is a practical and effective strategy to reduce pathological cardiac remodeling, induce myocardial regeneration, and improve ventricular function. |
Ivosidenib (Tibsovo) is a small molecule, orally available inhibitor of mutated cytosolic isocitrate dehydrogenase 1 (IDH1) that is being developed by Agios Pharmaceuticals for the treatment of cancer in patients with IDH1 mutations. The mutated form of the IDH1 enzyme produces a metabolite, 2-hydroxyglutarate (2-HG), ... | Which molecule is inhibited by ivosidenib? | Ivosidenib targets the IDH1 metabolic pathway to prevent a build-up of the oncometabolite 2-HG. |
Background We evaluated the effect of erenumab, a fully human monoclonal antibody that inhibits the canonical calcitonin gene-related peptide receptor, on migraine-related disability, impact, and health-related quality of life among patients with episodic migraine. Methods Patients enrolled in a phase 3, 6-month, doubl... | Which receptor is targeted by Erenumab? | Background We evaluated the effect of erenumab, a fully human monoclonal antibody that inhibits the canonical calcitonin gene-related peptide receptor, on migraine-related disability, impact, and health-related quality of life among patients with episodic migraine. |
CENP-A is a centromere-specific histone H3 variant that is required for kinetochore assembly and accurate chromosome segregation. For it to function properly, CENP-A must be specifically localized to centromeres. In fission yeast, Scm3sp and the Mis18 complex, composed of Mis16, Eic1, and Mis18, function as a CENP-A(Cn... | What is the function of the Mis18 protein? | In fission yeast, Scm3sp and the Mis18 complex, composed of Mis16, Eic1, and Mis18, function as a CENP-A(Cnp1)-specific chaperone and a recruiting factor, respectively, and together ensure accurate delivery of CENP-A(Cnp1) to centromeres. |
Metabotropic glutamate receptor 5 (mGluR5) has been implicated in Alzheimer's disease (AD) pathology. We sought to understand whether mGluR5's role in AD requires glutamate signaling. We used a potent mGluR5 silent allosteric modulator (SAM, BMS-984923) to separate its well-known physiological role in glutamate signali... | Silent Allosteric Modulation of mGluR5 is a form of treatment for what disease? | silent allosteric modulation of mGluR5 has promise as a disease-modifying AD intervention with a broad therapeutic window. |
Monoamine Oxidase A (MAOA) is a critical enzyme in the catabolism of monoaminergic neurotransmitters. MAOA transcriptional activity is thought to be regulated by a well characterized 30 base pair (bp) variable nucleotide repeat (VNTR) that lies approximately ∼1000 bp upstream of the transcriptional start site (TSS). Ho... | With which personality traits has the human monoamine oxidase A (MAOA) gene been associated? | However, clinical associations between this VNTR genotype and behavioral states have been inconsistent. |
A recently described protein, metaxin 1, serves as a component of a preprotein import complex in the outer membrane of the mammalian mitochondrion. A yeast two-hybrid screen with metaxin 1 as bait has now identified a novel protein, which we have termed metaxin 2, as a metaxin 1-binding protein. Metaxin 2 shares 29% id... | Where is the metaxin complex localized? | In subcellular fractions of mouse liver, a 29 kD immunoreactive protein, consistent in size with the predicted translation product of metaxin 2 cDNA, was found solely in mitochondria. |
Acute akinesia is a life-threatening complication of Parkinson disease (PD). It is unlike the "wearing-off" phenomenon that occurs when dopaminergic drug levels decline and responds to dopaminergic rescue drugs. Acute akinesia may be a clinical entity distinct from the previously described PD motor fluctuations. | What is the "wearing-off" phenomenon in levodopa-treated patients with Parkinson's Disease? | It is unlike the "wearing-off" phenomenon that occurs when dopaminergic drug levels decline and responds to dopaminergic rescue drugs. |
No standard chemotherapy regimens have been defined yet for extranodal natural killer/T cell lymphoma (ENKTL), and the prognosis of patients with advanced or relapsed disease is very poor. Daratumumab, an investigated anti-cancer drug targeting CD38, has been of great interest in the treatment of CD38-expressing malign... | Which molecule is targeted by Daratumumab? | Daratumumab, an investigated anti-cancer drug targeting CD38, has been of great interest in the treatment of CD38-expressing malignancies, especially multiple myeloma. |
C3G (Crk SH3 domain binding guanine nucleotide releasing factor) (Rap guanine nucleotide exchange factor 1), essential for mammalian embryonic development, is ubiquitously expressed and undergoes regulated nucleocytoplasmic exchange. Here we show that C3G localizes to SC35-positive nuclear speckles and regulates splici... | Which biological process takes place in nuclear speckles? | Here we show that C3G localizes to SC35-positive nuclear speckles and regulates splicing activity. |
Progranulin, a secreted glycoprotein, is encoded in humans by the single GRN gene. Progranulin consists of seven and a half, tandemly repeated, non-identical copies of the 12 cysteine granulin motif. Many cellular processes and diseases are associated with this unique pleiotropic factor that include, but are not limite... | What protein is encoded by the GRN gene? | Progranulin, a secreted glycoprotein, is encoded in humans by the single GRN gene. |
Mammalian interphase chromosomes fold into a multitude of loops to fit the confines of cell nuclei, and looping is tightly linked to regulated function. Chromosome conformation capture (3C) technology has significantly advanced our understanding of this structure-to-function relationship. However, all 3C-based methods ... | What is the TALE-iD method used for? | Using different cell types and loci, computational modeling, and a methylation-based orthogonal validation method, "TALE-iD", we show that native interactions resemble cross-linked ones, but display improved signal-to-noise ratios and are more focal on regulatory elements and CTCF sites, while strictly abiding to topol... |
The large size of spectrin, the flexible protein promoting reversible deformation of red cells, has been an obstacle to elucidating the molecular mechanism of its function. By studying cloned fragments of the repeating unit domain, we have found a correspondence between positions of selected spectrin repeats in a tetra... | Alpha-spectrin and beta-spectrin subunits form parallel or antiparallel heterodimers? | Two of the less stably folded fragments, human erythroid alpha-spectrin repeats 13 and 14 (HEalpha13,14) and human erythroid beta-spectrin repeats 8 and 9 (HEbeta8,9), are located opposite each other on antiparallel spectrin dimers. |
We have determined the nucleotide sequence of the murine immunoglobulin gamma 2a membrane 3' untranslated region (1413 nucleotides) and approximately 679 nucleotides of downstream sequence. Two AATAAA hexanucleotide sequences are present in the 2092 nucleotide interval. The first one functions as the major polyA signal... | What is the most prominent sequence consensus for the polyadenylation site? | Two AATAAA hexanucleotide sequences are present in the 2092 nucleotide interval. The first one functions as the major polyA signal |
The anti programmed cell death-1 (PD-1) antibodies pembrolizumab and nivolumab have been recently licensed by the Food and Drug Administration for the treatment of advanced melanoma. Immune checkpoint inhibitors such as these can induce endocrine adverse events but autoimmune diabetes has not been described to date. Ho... | What is targeted by monoclonal antibody Pembrolizumab? | We describe for the first time the case of an adult patient who developed autoimmune diabetes likely as a consequence of PD-1 inhibition with pembrolizumab. |
Drug interactions involving protease inhibitors are common. Protease inhibitors are well known inhibitors of the 3A4 isozyme of cytochrome P450. Select protease inhibitors, including co-formulated lopinavir/ritonavir, may induce glucuronidation or the activity of other CYP450 isozymes. We describe the case of a patient... | Please list 7 classes of drugs that interact with Warfarin. | We review the possible mechanisms of this interaction and the reported interactions between warfarin and other protease inhibitors. |
Different classes of non-coding RNAs, including microRNAs, have recently been implicated in the process of tumourigenesis. In this study, we examined the expression and putative functions of a novel class of non-coding RNAs known as transcribed ultraconserved regions (T-UCRs) in neuroblastoma. Genome-wide expression pr... | Are transcribed ultraconserved regions involved in cancer? | Different classes of non-coding RNAs, including microRNAs, have recently been implicated in the process of tumourigenesis. In this study, we examined the expression and putative functions of a novel class of non-coding RNAs known as transcribed ultraconserved regions (T-UCRs) in neuroblastoma |
Biological systems are hierarchically self-organized complex structures characterized by nonlinear interactions. Biochemical energy is transformed into work of physical forces required for various biological functions. We postulate that energy transduction depends on endogenous electrodynamic fields generated by microt... | Which is the primary distinction between the Reverse Warburg effect and the conventional Warburg effect? | The metabolic energy transduction pathways are strongly affected in cancers. Mitochondrial dysfunction in cancer cells (Warburg effect) or in fibroblasts associated with cancer cells (reverse Warburg effect) results in decreased or increased power of the generated electromagnetic field, respectively |
Septins are an evolutionarily conserved family of GTP-binding proteins. They are involved in diverse processes including cytokinesis, apoptosis, infection, neurodegeneration and neoplasia. In this study, through thorough data mining of existed channel catfish genomic resources, we identified a complete set of 15 septin... | What are Septins? | Septins are an evolutionarily conserved family of GTP-binding proteins. They are involved in diverse processes including cytokinesis, apoptosis, infection, neurodegeneration and neoplasia. |
Angiogenin (ANG) promotes cell growth and survival. Under growth conditions, ANG undergoes nuclear translocation and accumulates in the nucleolus where it stimulates rRNA transcription. When cells are stressed, ANG mediates the production of tRNA-derived stress-induced small RNA (tiRNA), which reprograms protein transl... | Which is the subcellular localization of the protein angiogenin? | Under growth conditions, ANG undergoes nuclear translocation and accumulates in the nucleolus where it stimulates rRNA transcription |
The methylation state of lysine 20 on histone H4 (H4K20) has been linked to chromatin compaction, transcription, DNA repair and DNA replication. Monomethylation of H4K20 (H4K20me1) is mediated by the cell cycle-regulated histone methyltransferase PR-Set7. PR-Set7 depletion in mammalian cells results in defective S phas... | Is H4K20 methylation associated with DNA replication? | The methylation state of lysine 20 on histone H4 (H4K20) has been linked to chromatin compaction, transcription, DNA repair and DNA replication. |
At the beginning of this century the compulsory vaccination and revaccination which was legally founded after the introduction of the vaccination by Jenner (1796) led to the removal of the smallpox in Europe and Northern America. However, up to the sixties in the developing countries of Asia, Africa as well as of South... | Has small pox been eradicated from the world? | In May 1980 the World Health Assembly in Geneva announced in solemn form the world-wide eradication of the small-pox and gave recommendations to the member countries for concluding measures concerning the small-pox vaccination, the foundation of vaccine reserves and the control of the epidemiological situation in the w... |
Duchenne and Becker types of muscular dystrophy are usually differentiated according to age of onset and rate of progression criteria which are not sufficient. The aim of this paper was to re-establish the clues for distinguishing Duchenne from Becker types of muscular dystrophy. According to the onset and progression ... | What is the difference between Duchenne muscular Dystrophy and Becker muscular dystrophy? | Clinical data confirm some well known differences between Duchenne and Becker muscular dystrophy concerning the age of onset, severity of disease and rate of progression. |
We describe a case of a 42-year-old man, with a previous episode of angina and a normal ECG and serum cardiac markers, and a two months later finding of biphasic T wave in leads V2-V3 and deeply inverted T wave in V4-V5 at a asymptomatic occupational evaluation. This is a typical ECG pattern of Wellens' syndrome. A sub... | Describe Wellens' Syndrome. | We describe a case of a 42-year-old man, with a previous episode of angina and a normal ECG and serum cardiac markers, and a two months later finding of biphasic T wave in leads V2-V3 and deeply inverted T wave in V4-V5 at a asymptomatic occupational evaluation. This is a typical ECG pattern of Wellens' syndrome. |
The contribution of human subtelomeric DNA and chromatin organization to telomere integrity and chromosome end protection is not yet understood in molecular detail. Here, we show by ChIP-Seq that most human subtelomeres contain a CTCF- and cohesin-binding site within ∼1-2 kb of the TTAGGG repeat tract and adjacent to a... | Does the CTCF protein co-localize with cohesin? | These findings indicate that CTCF and cohesin are integral components of most human subtelomeres, and important for the regulation of TERRA transcription and telomere end protection |
Phospholamban (PLB) is a major target of the beta-adrenergic cascade in the heart, functioning to modulate contractile force by altering the rate of calcium re-sequestration by the Ca-ATPase. Functionally, inhibition by PLB binding is manifested by shifts in the calcium dependence of Ca-ATPase activation toward higher ... | Is phospholamban phosphorylated by Protein kinase A? | Phospholamban (PLB) is a major target of the beta-adrenergic cascade in the heart, functioning to modulate contractile force by altering the rate of calcium re-sequestration by the Ca-ATPase. Functionally, inhibition by PLB binding is manifested by shifts in the calcium dependence of Ca-ATPase activation toward higher ... |
Evolutionary innovation relies partially on changes in gene regulation. While a growing body of evidence demonstrates that such innovation is generated by functional changes or translocation of regulatory elements via mobile genetic elements, the de novo generation of enhancers from non-regulatory/non-mobile sequences ... | Is there evidence for de novo genesis of enhancers in vertebrates? | Here we show evidence for the de novo genesis of enhancers in vertebrates. |
Modified nucleotides in messenger RNA (mRNA) have been discovered over 40 years ago, but until recently little was known about which transcripts contain them and what their function is. High-throughput sequencing approaches revealed a dynamic landscape of the 'Epitranscriptome' for many mRNA modifications in various or... | What is "Epitranscriptome analysis"? | Modified nucleotides in messenger RNA (mRNA) have been discovered over 40 years ago, but until recently little was known about which transcripts contain them and what their function is. High-throughput sequencing approaches revealed a dynamic landscape of the 'Epitranscriptome' for many mRNA modifications in various or... |
Extracellular ATP is an important signaling molecule throughout the inflammatory cascade, serving as a danger signal that causes activation of the inflammasome, enhancement of immune cell infiltration, and fine-tuning of several signaling cascades including those important for the resolution of inflammation. Recent stu... | Where is the protein Pannexin1 located? | Recent studies demonstrated that ATP can be released from cells in a controlled manner through pannexin (Panx) channels. |
Breast cancer is a very heterogeneous disease, encompassing several intrinsic subtypes with various morphological and molecular features, natural history and response to therapy. Currently, molecular targeted therapies are available for estrogen receptor (ER)(-) and human epidermal growth factor receptor 2 (Her2)-posit... | Proteomic analyses have revealed proteins associated with the triple-negative breast cancers. List some proposed proteins. | We present here our results, including a large cumulative database of proteins based on the analysis of 78 TNBCs, and the identification and validation of one specific protein, Mage-A4, which was expressed in a significant fraction of TNBC and Her2-positive/ER negative lesions. |
Protein phosphorylation-dephosphorylation events play a primary role in regulation of almost all aspects of cell function including signal transduction, cell cycle, or apoptosis. Thus far, T cell phosphoproteomics have focused on analysis of phosphotyrosine residues, and little is known about the role of serine/threoni... | Global quantitative phosphoproteomic analyses are emerging. List the preferred technologies for the enrichment for phosphorylated peptides? | Combining immunoprecipitation with an antiphosphotyrosine antibody, titanium dioxide phosphopeptide enrichment, isobaric tag for the relative and absolute quantitation methodology, and strong cation exchange separation, we were able to identify 2814 phosphopeptides. |
The muscular dystrophy is a group of inherited disorders characterized in the most of cases by progressive muscle weakness. The best known are X-linked disorder Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD). BMD is a milder form of the disease with a later age of onset and a slower clinical prog... | Where is the DMD gene located? | The DMD gene, located on Xp21, is the largest human gene in the human genome (2. |
Numerous abnormalities of thyroid hormones in end-stage renal disease (ESRD) have been described. Our aim was to analyze the impact of these abnormalities on survival. In 167 hemodialyzed ESRD patients, TSH and thyroid hormone levels (T4, fT4, T3, fT3, rT3) were determined. The patients were then prospectively followed... | Is low T3 syndrome a prognostic marker in patients with renal insufficiency? | Increased rT3 may be more common in ESRD patients than previously described, and together with decreased T3 it may serve as an indicator of poor prognosis in subsequent months. |
Hepcidin is encoded as an 84 amino acid prepropeptide containing a typical N-terminal 24 amino acid endoplasmic reticulum targeting signal sequence, and a 35 amino acid proregion (pro) with a consensus furin cleavage site immediately followed by the C-terminal 25 amino acid bioactive iron-regulatory hormone (mature pep... | What is the connection between furin and hepcidin? | In conclusion, the hepatic prohormone convertase furin mediates the posttranslational processing of hepcidin. |
The dopaminergic stabilizer pridopidine demonstrates state-dependent effects on locomotor activity, counteracting both hypo- and hyperactivity in rats. Pridopidine has been shown to display both functional dopamine D2 receptor antagonist properties and increase in biomarkers associated with NMDA-mediated glutamate tran... | Pridopidine has been tested for treatment of which disorder? | These effects of pridopidine may serve to strengthen the cortico-striatal communication and to improve motor control in Huntington's disease for which pridopidine is currently in development. |
The amyloid hypothesis has long been the central dogma in drug discovery for Alzheimer's disease (AD), leading to many small-molecule and biological drug candidates. One major target has been the β-site amyloid-precursor-protein-cleaving enzyme 1 (BACE-1), with many big pharma companies expending great resources in the... | Is Verubecestat effective for Alzheimer's Disease? | The lack of efficacy of verubecestat in mild-to-moderate AD raises important questions about the timing of intervention with BACE-1 inhibitors, and anti-amyloid therapies in general, in AD treatment. |
Small deletions and duplications frequently occur in the pericentromeric region of chromosomes and many of these are associated with developmental abnormalities. These developmental syndromes are conventionally attributed to abnormal expression of protein-coding genes in the affected region. A hypothesis has recently b... | Which is the definition of pyknons in DNA? | The new GSCKs are produced by evolutionary consolidation of retro-transcripts into pyknons that collect and evolve at the end of the pericentromeric heterochromatin and are eventually incorporated into the MDP |
During adult homeostasis and regeneration, the freshwater planarian must accomplish a constant balance between cell proliferation and cell death, while also maintaining proper tissue and organ size and patterning. How these ordered processes are precisely modulated remains relatively unknown. Here we show that planaria... | Is the Wnt protein modified by notum? | the WNT-inhibitor notum. |
Radiation-induced sarcomas are recognized complications of radiation therapy and are associated with poor prognosis. Radiation-induced osteosarcoma is one of the rare types of radiation-induced sarcomas, with the risk of radiation-induced osteosarcomas being only 0.01%-0.03% among all patients treated with radiotherapy... | Can radiotherapy cause radiation induced osteosarcoma? | Here, we report a unique case of radiation-induced osteosarcomas arising on the skull and extending to the skin, with a short latent period. |
In metazoans, enhancers of gene transcription must often exert their effects over tens of kilobases of DNA. Over the past decade it has become clear that to do this, enhancers come into close proximity with target promoters with the looping away of intervening sequences. In a few cases proteins that are involved in the... | Do enhancers have to be close to their gene targets? | In metazoans, enhancers of gene transcription must often exert their effects over tens of kilobases of DNA. Over the past decade it has become clear that to do this, enhancers come into close proximity with target promoters with the looping away of intervening sequences. |
Lacosamide (LCM) is a newer antiepileptic drug with a dual mode of action. It selectively enhances slow inactivation of voltage-gated sodium channels without affecting fast inactivation, and modulates collapsing response mediator protein 2 (CRMP-2). It has a high oral bioavailability of approximately 100%. It has shown... | What are the main indications of lacosamide? | Lacosamide (LCM) is a newer antiepileptic drug with a dual mode of action. |
Hemophilic pseudotumor is a rare, but well-known, complication of hemophilia. We describe a 50-year-old man with mild hemophilia A, but with no previous need for Factor VIII supplementation, who presented with a pathologic fracture of the right femoral neck and shaft caused by a large hemophilic pseudotumor. Initial no... | What is Hemophilic Pseudotumor? | Although pseudotumor formation is a well-recognized complication of hemophilia, the pseudotumor in our study is one of the largest yet described. |
Fluorescent reporter proteins based on flavin-binding photosensors were recently developed as a new class of genetically encoded probes characterized by small size and oxygen-independent maturation of fluorescence. Flavin-based fluorescent proteins (FbFPs) address two major limitations associated with existing fluoresc... | List fluorescent reporter proteins. | Flavin-based fluorescent proteins (FbFPs) |
Proper development of the immune system is an intricate process dependent on many factors, including an intact DNA damage response. The DNA double-strand break signaling kinase ATM and its cofactor NBS1 are required during T cell development and for the maintenance of genomic stability. The role of a second ATM cofacto... | What is the role of DNA Repair Cofactors ATMIN and NBS1? | Our findings reveal a novel model for an intestinal bowel disease phenotype that occurs upon combined loss of the DNA repair cofactors ATMIN and NBS1. |
The establishment of cell fates involves alterations of transcription factor repertoires and repurposing of transcription factors by post-translational modifications. In embryonic stem cells (ESCs), the chromatin organizers SATB2 and SATB1 balance pluripotency and differentiation by activating and repressing pluripoten... | Is Satb1 a transcription factor? | chromatin organizers SATB2 and SATB1 |
The interaction between the (epi)genetic makeup of an individual and his/her environmental exposure record (exposome) is accepted as a determinant factor for a significant proportion of human malignancies. Recent evidence has highlighted the key role of epigenetic mechanisms in mediating gene-environment interactions a... | What is a exposome? | The interaction between the (epi)genetic makeup of an individual and his/her environmental exposure record (exposome) is accepted as a determinant factor for a significant proportion of human malignancies. |
Focal cortical dysplasias are a well-recognized cause of medically intractable seizures. The clinical relevance of certain subgroups of the International League Against Epilepsy (ILAE) classification scheme remains to be determined. The aim of the present work is to assess the effect of the focal cortical dysplasia typ... | Which disorder is rated by Palmini classification? | Crude analysis revealed no significant difference between patients with subtypes of ILAE focal cortical dysplasia type I or Palmini et al focal cortical dysplasia type I concerning postoperative outcome according to the Engel and ILAE scoring systems on seizure frequency. |
Proteins on the surface of parasite-infected erythrocytes (PIESPs) have been one of the major focuses of malaria research due to their role in pathogenesis and their potential as targets for immunity and drug intervention. Despite intense scrutiny, only a few surface proteins have been identified and characterized. We ... | Which is the localization of the RIFIN family of proteins? | In contrast to other known PIESPs, such as PfEMP1 and Rifin, |
We live in an age of access to more information than ever before. This can be a double-edged sword. Increased access to information allows for more informed and empowered researchers, while information overload becomes an increasingly serious risk. Thus, there is a need for intelligent information retrieval systems tha... | List available biomedical question answering systems. | We present a review and comparison of three biomedical question answering systems: askHERMES (http://www. |
Late gadolinium enhancement is the technique of choice for detecting myocardial fibrosis. Although this technique is used in a wide range of cardiovascular pathologies, ischemic cardiomyopathy and the workup for myocarditis and other cardiomyopathies make up a significant proportion of the total indications. Multiple s... | What is the clinical indication of cardiac T1 mapping magnetic resonance? | Recent T1 mapping techniques aim to overcome the limitations of late gadolinium enhancement to assess diffuse fibrosis. |
The tafazzin gene encodes a phospholipid-lysophospholipid transacylase involved in cardiolipin metabolism, but it is not known why it forms multiple transcripts as a result of alternative splicing. Here we studied the intracellular localization, enzymatic activity, and metabolic function of four isoforms of human tafaz... | What is the function of the protein tafazzin? | Among the human isoforms, only full-length tafazzin (FL) and tafazzin lacking exon 5 (Delta5) had transacylase activity, and only these two isoforms were able to restore a normal cardiolipin pattern, normal respiratory activity of mitochondria, and male fertility in tafazzin-deficient flies. |
The ability of bicuculline, a GABA antagonist, to enhance dopamine (DA) synthesis in retinas of rats 1, 4, 7, 15 and 60 days after eye opening was assessed and compared to the time course of postnatal development of the light-induced increase in DA synthesis. The accumulation of dihydroxyphenylalanine (DOPA) following ... | Is NSD-1015 an inhibitor of Aromatic L-Amino Acid Decarboxylase? | The accumulation of dihydroxyphenylalanine (DOPA) following administration of the L-aromatic amino acid decarboxylase inhibitor, NSD 1015, was used to estimate DA synthesis. |
Pheochromocytomas synthesize and release catecholamines, which subsequently are related to various clinical manifestations of the disease. However, pheochromocytomas are not innervated and the catecholamine release and synthesis are not initiated by neural impulses. It is still unknown how catecholamine synthesis is re... | Which enzymes synthesize catecholamines in adrenal glands? | As a first step toward understanding the molecular mechanisms by which catecholamine synthesis is controlled in the tumor, we measured the levels of mRNA coding for the catecholamine synthesizing enzyme, tyrosine hydroxylase (TH) and catecholamines in 6 pheochromocytomas and 2 normal adrenal glands |
A human genetic defect associated with 'long Q-T syndrome', an abnormality of cardiac rhythm involving the repolarization of the action potential, was recently found to lie in the HERG gene, which codes for a potassium channel. The HERG K+ channel is unusual in that it seems to have the architectural plan of the depola... | Does the hERG gene code for a protein which is part of a sodium channel? | A human genetic defect associated with 'long Q-T syndrome', an abnormality of cardiac rhythm involving the repolarization of the action potential, was recently found to lie in the HERG gene, which codes for a potassium channel. |
The social impairments of autism spectrum disorder (ASD) have a major impact on quality of life, yet there are no medications that effectively treat these core social behavior deficits. Preclinical research suggests that arginine vasopressin (AVP), a neuropeptide involved in promoting mammalian social behaviors, may be... | Is autism thought to be related to the Arginine Vasopressin Peptide (AVP)? | Preclinical research suggests that arginine vasopressin (AVP), a neuropeptide involved in promoting mammalian social behaviors, may be a possible treatment for ASD. |
Mulibrey nanism (muscle-liver-brain-eye nanism; MUL) is an autosomal recessively transmitted disease characterized by severe growth delays of prenatal onset caused by mutations in the TRIM37 gene. Recent studies on the subcellular localization revealed that the TRIM37 (KIAA0898) protein is located in peroxisomes. There... | Does TRIM37 gene mutation causes Mulibrey nanism? | Mulibrey nanism (muscle-liver-brain-eye nanism; MUL) is an autosomal recessively transmitted disease characterized by severe growth delays of prenatal onset caused by mutations in the TRIM37 gene. |
In recent years, the introduction and Federal Drug Administration approval of immune checkpoint inhibitor antibodies has dramatically improved the clinical outcomes for patients with advanced melanoma. These antagonist monoclonal antibodies are capable of unleashing dormant or exhausted antitumor immunity, which has le... | What are PD-1 inhibitors? | Nivolumab and pembrolizumab target programmed cell death protein 1 (PD-1) receptors and have proven to be superior to ipilimumab alone. T |
Awareness of the risk of airborne transmission of SARS-CoV-2 makes patients hesitant about using inhaled medications that are considered as a potential source of viral transmission and immunosuppression. However, patients with asthma or COPD should continue all prescribed inhaled medications. Apparently, inhalers, incl... | Should patients using inhaled glucocorticoids for asthma or COPD be advised to stop these medications to prevent COVID-19? | However, patients with asthma or COPD should continue all prescribed inhaled medications. |
In growing cells, apurinic/apyrimidinic (AP) sites generated spontaneously or resulting from the enzymatic elimination of oxidized bases must be processed by AP endonucleases before they compromise cell integrity. Here, we investigated how AP sites and the processing of these noncoding lesions by the AP endonucleases N... | Which mechanisms underlie adaptive mutagenesis (stationary-phase mutagenesis) in Bacillus subtilis? | subtilis can be generated through a novel mechanism mediated by error-prone processing of AP sites accumulated in the stationary phase by the PolX DNA polymerase |
Several second-generation active β-amyloid (Aβ) vaccines and passive Aβ immunotherapies are under clinical investigation with the aim of boosting Aβ clearance from the brain of the Alzheimer's disease (AD) patients. However, the preliminary cognitive efficacy of bapineuzumab, a humanized anti-Aβ monoclonal antibody, ap... | Is bapineuzumab effective for treatment of patients with Alzheimer's disease? | However, the preliminary equivocal cognitive results obtained with bapineuzumab as well as the detrimental cognitive effects observed with semagacestat, a potent γ-secretase inhibitor, raise the possibility that targeting Aβ may not be clinically efficacious in AD. |
Super-enhancers are characterized by high levels of Mediator binding and are major contributors to the expression of their associated genes. They exhibit high levels of local chromatin interactions and a higher order of local chromatin organization. On the other hand, lncRNAs can localize to specific DNA sites by formi... | Is Mediator present at super enhancers? | Super-enhancers are characterized by high levels of Mediator binding and are major contributors to the expression of their associated genes. |
Epigenetic changes are defined as inherited modifications that are not present in DNA sequence. Gene expression is regulated at various levels and not only in response to DNA modifications. Examples of epigenetic control are DNA methylation, histone deacetylation and mi-RNA expression. Methylation of several tumor supp... | What are some examples of epigenetic modifications? | Epigenetic changes are defined as inherited modifications that are not present in DNA sequence. |
cause sudden cardiac death? | Patients diagnosed with an electrical cardiomyopathy have an increased risk of syncope and sudden cardiac death (SCD). | null |
The pathology of drug-induced pulmonary toxicity in children is poorly understood and probably under-estimated, in the absence of any prospective studies evaluating in a systematic fashion the side effect of medication on the respiratory apparatus. The pulmonary toxicity of thoracic irradiation has markedly receded wit... | What class of drugs is commonly associated with Drug-induced interstitial lung disease (DIILD)? | Cytotoxic drugs are the most common cause of toxic lung disease. |
Mgm1 is a member of the dynamin family of GTP-binding proteins. Mgm1 was first identified in yeast, where it affects mitochondrial morphology. The human homologue of Mgm1 is called OPA1. Mutations in the OPA1 gene are the prevailing cause of dominant optic atrophy, a hereditary disease in which progressive degeneration... | Which is the cellular localization of the protein Opa1? | We find that Mgm1/OPA1 is localized to the mitochondrial intermembrane space, |
Macrophage actin-associated tyrosine phosphorylated protein (MAYP) belongs to the Pombe Cdc15 homology (PCH) family of proteins involved in the regulation of actin-based functions including cell adhesion and motility. In mouse macrophages, MAYP is tyrosine phosphorylated after activation of the colony-stimulating facto... | Which proteins are involved in actin bundling and filopodia formation and function? | Overexpression of MAYP decreased CSF-1-induced membrane ruffling and increased filopodia formation, motility and CSF-1-mediated chemotaxis. |
The septins are filament-forming, GTP-binding proteins that are conserved from yeast to humans. Septins assemble into higher-order structures such as rings, bars, and gauzes with diverse functions including serving as membrane diffusion barriers and scaffolds for cell signaling. The basis for septin filament polymeriza... | What are Septins? | The septins are filament-forming, GTP-binding proteins that are conserved from yeast to humans. Septins assemble into higher-order structures such as rings, bars, and gauzes with diverse functions including serving as membrane diffusion barriers and scaffolds for cell signaling. |
The members of the NOX family of enzymes are expressed in a variety of tissues and serve a number of functions. There is a high level of conservation of primary protein sequence, as well as functional features, although specialized responses are beginning to emerge. In this context, our data demonstrate that the NOX1 c... | Which NADPH oxidase family member requires interaction with NOXO1 for function? | Studies of cytosolic co-factors showed that the C-terminal cytoplasmic domain of NOX1 was absolutely required for activation with NOXO1 and NOXA1 and that this activity required interaction of the putative NADPH-binding region of this domain with NOXA1. |
Fanconi anemia (FA) is a genetically heterogeneous autosomal recessive syndrome associated with chromosomal instability, hypersensitivity to DNA cross-linking agents, and predisposition to malignancy. The gene for FA complementation group G (FANCG) was the third FA gene to be cloned, and was found to be identical with ... | Is Fanconi anemia presented as a genetically and clinically heterogeneous disease entity? | Fanconi anemia (FA) is a genetically heterogeneous autosomal recessive syndrome associated with chromosomal instability, hypersensitivity to DNA cross-linking agents, and predisposition to malignancy |
The CHEK2-1100delC mutation is recurrent in the population and is a moderate risk factor for breast cancer. To identify additional CHEK2 mutations potentially contributing to breast cancer susceptibility, we sequenced 248 cases with early-onset disease; functionally characterized new variants and conducted a population... | Which is the main CHEK2 genetic variant, thought to be involved in familial breast cancer? | The CHEK2-1100delC mutation is recurrent in the population and is a moderate risk factor for breast cancer |
Patients with Sjögren syndrome are at increased risk of lymphoma development. Because most lymphomas initially involve the neck organs, including the lymph nodes, meticulous imaging studies mainly focused on the cervical regions are recommended in the follow-up of patients with Sjögren syndrome. | Are patients with Sjogren syndrome at increased risk for lymphoma? | Patients with Sjögren syndrome are at increased risk of lymphoma development. |
Teprotumumab (teprotumumab-trbw; TEPEZZA™ - Horizon Therapeutics) is a monoclonal antibody insulin-like growth factor-I receptor (IGF-IR) antagonist developed for the treatment of thyroid eye disease (Graves ophthalmopathy/orbitopathy, thyroid-associated ophthalmopathy). Based on positive results from two multinational... | Which molecule is targeted by Teprotumumab? | Teprotumumab (teprotumumab-trbw; TEPEZZA™ - Horizon Therapeutics) is a monoclonal antibody insulin-like growth factor-I receptor (IGF-IR) antagonist developed for the treatment of thyroid eye disease (Graves ophthalmopathy/orbitopathy, thyroid-associated ophthalmopathy). |
The leucine rich repeat kinase 2 (LRRK2/dardarin) is implicated in autosomal dominant familial and sporadic Parkinson's disease (PD); mutations in LRRK2 account for up to 40% of PD cases in some populations. LRRK2 is a large protein with a kinase domain, a GTPase domain, and multiple potential protein interaction domai... | What is the dardarin protein? | The leucine rich repeat kinase 2 (LRRK2/dardarin) is implicated in autosomal dominant familial and sporadic Parkinson's disease (PD); |
Invasion of the subendothelial space by vascular smooth muscle cells (VSMCs) contributes to the development and progression of diverse cardiovascular diseases. In this report we show that the expression of activated versions of Src, Cdc42 and Rac1, or a kinase-dead but open form of the p21-activated kinase (PAK1), indu... | In which process Src, Cortactin and MT1-MMP are playing an essential role? | In this report we show that the expression of activated versions of Src, Cdc42 and Rac1, or a kinase-dead but open form of the p21-activated kinase (PAK1), induces primary rat aorta VSMCs to form extracellular matrix-degrading actin-rich protrusions that are morphologically similar to the invadopodia formed by highly i... |
Surgical or pharmacologic methods to control gonadal androgen biosynthesis are effective approaches in the treatment of a variety of non-neoplastic and neoplastic diseases. For example, androgen ablation and its consequent reduction in circulating levels of testosterone is an effective therapy for advanced prostate can... | Which enzyme is inhibited by Orteronel? | Orteronel (TAK-700), a novel, selective, and potent inhibitor of 17,20-lyase is under development as a drug to inhibit androgen synthesis |
Delayed cerebral ischemia following aneurysmal subarachnoid hemorrhage is a cause of considerable morbidity and mortality. Magnesium sulfate has been proposed as a prophylactic intervention for angiographic vasospasm and to improve clinical outcomes. A systematic review was conducted to determine the evidence for the p... | Does magnesium sulfate improve outcomes of subarachnoid hemorrhage patients? | Current evidence does not support the prophylactic use of magnesium sulfate in aneurysmal subarachnoid hemorrhage |
Most radiation-induced osteosarcomas of the skull are reported to arise in the facial bone or paranasal sinus after radiotherapy for retinoblastoma and/or pituitary adenoma. Here we report two cases of radiation-induced osteosarcoma in the paranasal sinus after treatment for frontal glioma. Case 1 was a 56-year-old wom... | Can radiotherapy cause radiation induced osteosarcoma? | As the prognosis of radiation-induced osteosarcoma is poorer than that of primary osteo-sarcoma, careful attention is required for consideration of the long-term survival of patients with glioma. |
We sought to evaluate the efficacy and safety data of a combination regimen using weekly irinotecan in combination with capecitabine and concurrent radiotherapy (CapIri-RT) as neoadjuvant treatment in rectal cancer in a phase-II trial. Patients with rectal cancer clinical stages T3/4 Nx or N+ were recruited to receive ... | Which drugs are included in the CAPIRI regimen? | We sought to evaluate the efficacy and safety data of a combination regimen using weekly irinotecan in combination with capecitabine and concurrent radiotherapy (CapIri-RT) as neoadjuvant treatment in rectal cancer in a phase-II trial. |
Ras/Raf-prototypic oncogenes induce cellular senescence, a terminal cell-cycle arrest, as a default cellular safeguard program, while oncogenic Myc is known to rather promote apoptosis as the prime failsafe mechanism. We review and discuss here evidence for Myc-induced senescence - which is detectable to a limited degr... | Which oncogenes are able to induce cellular senescence? | Ras/Raf-prototypic oncogenes induce cellular senescence, a terminal cell-cycle arrest, as a default cellular safeguard program |
Miller Fisher syndrome is a variant of Guillain-Barre syndrome characterized by the classic triad of ophthalmoplegia, ataxia, and areflexia. Pupillary involvement is common in MFS and has been reported in 35-42% of MFS patients. Although case reports have discussed isolated ophthalmoplegia as a presentation of MFS, ani... | Is the Miller-Fisher syndrome considered to be a variant of Guillain-Barré? | Miller Fisher syndrome is a variant of Guillain-Barre syndrome characterized by the classic triad of ophthalmoplegia, ataxia, and areflexia |
Pulmonary hypertension (PH) is a progressive disease that is accompanied by a poor prognosis. Pulmonary vasoconstriction is facilitated through multiple pathways and results in increased pulmonary vascular pressure leading to cell proliferation, vascular remodeling, right ventricular hypertrophy/failure, and ultimately... | What is generic name of drug Adempas? | On October 8, 2013, riociguat (Adempas®) became the first medication approved for multiple etiologies of PH. |
An unexpectedly large fraction of genes in metazoans (human, mouse, zebrafish, worm, fruit fly) express high levels of circularized RNAs containing canonical exons. Here we report that circular RNA isoforms are found in diverse species whose most recent common ancestor existed more than one billion years ago: fungi (Sc... | What is the function of circular RNA? | Circular RNA may be an ancient, conserved feature of eukaryotic gene expression programs. |
This research paper examines the challenges in the development and adoption of an electronic patient diary within the Pathways Home for Respiratory Illness Project. This project supported community-based patients suffering from chronic obstructive pulmonary disease (COPD) to achieve increased levels of self-management ... | In which diseases have electronic patient diaries been applied ? | This project supported community-based patients suffering from chronic obstructive pulmonary disease (COPD) to achieve increased levels of self-management and self-efficacy using electronic-monitoring techniques and mentoring by community health nurses. |
Coronavirus disease 2019 (COVID-19) has become a global pandemic. Previous studies showed that comorbidities in patients with COVID-19 are risk factors for adverse outcomes. This study aimed to clarify the association between nervous system diseases and severity or mortality in patients with COVID-19. We performed a sy... | What factors are associated with severe COVID-19? | This study aimed to clarify the association between nervous system diseases and severity or mortality in patients with COVID-19. |
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