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In this study the authors sought to determine the prevalence and long-term prognostic value of low triiodothyronine levels in elderly patients with heart failure and no thyroid disease. Lower levels of triiodothyronine are more prevalent in patients with advanced heart failure without thyroid disease, and this may have... | What is the prognostic role of thyroid hormone in patients with heart failure? | The authors conclude that among elderly patients with heart failure, lower triiodothyronine concentrations are more prevalent and are associated with a worse prognosis. |
Recursive splicing is a process in which large introns are removed in multiple steps by re-splicing at ratchet points--5' splice sites recreated after splicing. Recursive splicing was first identified in the Drosophila Ultrabithorax (Ubx) gene and only three additional Drosophila genes have since been experimentally sh... | Is recursive splicing more common in short introns? | Recursive splicing is a process in which large introns are removed in multiple steps by re-splicing at ratchet points--5' splice sites recreated after splicing. |
Flumazenil is used infrequently in the management of BZD OD in the UK. It was effective and associated with a low incidence of seizure. These results compare favourably with the results of published randomised controlled trials and cohort studies, although previous studies have not reported the use of flumazenil in suc... | Which drug should be used as an antidote in benzodiazepine overdose? | Flumazenil is used infrequently in the management of BZD OD in the UK. |
Cardiovascular disease is the most common cause of death worldwide and is mainly due to atherosclerosis. Elevated levels of low-density lipoprotein cholesterol (LDL-C) are the main risk factor for atherosclerosis. Treatment with existing therapies for dyslipidemia and life-style changes are often sufficient to reach th... | What is the mechanism of action of Evinacumab? | Evinacumab is a human monoclonal antibody which binds and inhibits angiopoietin-like protein 3 (ANGPTL3). |
Replicative DNA helicases expose the two strands of the double helix to the replication apparatus, but accessory helicases are often needed to help forks move past naturally occurring hard-to-replicate sites, such as tightly bound proteins, RNA/DNA hybrids, and DNA secondary structures. Although the Schizosaccharomyces... | Is Pfh1 a component of the replisome? | Consistent with this interpretation, Pfh1 co-purified with many key replisome components, including the hexameric MCM helicase, replicative DNA polymerases, RPA, and the processivity clamp PCNA in an S phase dependent manner. |
The muscle LIM protein (MLP) and cofilin 2 (CFL2) are important regulators of striated myocyte function. Mutations in the corresponding genes have been directly associated with severe human cardiac and skeletal myopathies, and aberrant expression patterns have often been observed in affected muscles. Herein, we have in... | Through which protein interaction does MLP regulate F-actin dynamics? | This interaction has direct implications in actin cytoskeleton dynamics in regulating CFL2-dependent F-actin depolymerization, with maximal depolymerization enhancement at an MLP/CFL2 molecular ratio of 2:1. Deregulation of this interaction by intracellular pH variations, CFL2 phosphorylation, MLP or CFL2 gene mutation... |
Numerous sense-antisense gene pairs have been discovered in various organisms. Antisense genes play important roles in establishing parentally imprinted gene expression patterns in mammals. Typically, protein-coding sense genes are reciprocally regulated by their non-coding antisense partners. One example for antisense... | Which is the transcript responsible for X-chromosome inactivation? | Xist (X-inactive specific transcript) and Tsix gene pair, which is pivotal in X-inactivation. |
Sarcolipin (SLN) is a 3 kD membrane protein found in sarcoplasmic reticulum (SR). It has 31 amino acid residues; SLN and phopholamban (PLB) are belong to the same protein family, so they have similar physiological functions. SLN inhibits sarcoplasmic reticulum Ca(2+) ATPase (SERCA) activity and reduces its affinity of ... | Is Sarcolipin a regulatory/inhibitory protein of the Calcium ATPase SERCA? | Sarcolipin (SLN) is a 3 kD membrane protein found in sarcoplasmic reticulum (SR). It has 31 amino acid residues; SLN and phopholamban (PLB) are belong to the same protein family, so they have similar physiological functions. SLN inhibits sarcoplasmic reticulum Ca(2+) ATPase (SERCA) activity and reduces its affinity of ... |
A single dose of RV3-BB rotavirus vaccine was well tolerated in adults, children and infants. Most infants (8/9) who received RV3-BB demonstrated vaccine take following a single dose. These data support progression of RV3-BB to Phase II immunogenicity and efficacy trials. | RV3-BB vaccine is used for prevention of which viral infection? | A single dose of RV3-BB rotavirus vaccine was well tolerated in adults, children and infants. |
Ascorbate (ascorbic acid, vitamin C) is one of the early, unorthodox treatments for cancer. The evidence upon which people base the use of ascorbate in cancer treatment falls into two categories: clinical data on dose concentration relationships, and laboratory data describing potential cell toxicity with high concentr... | What is known about efficacy of the high dose intravenous ascorbate in the treatment of cancer patients? | Ascorbate (ascorbic acid, vitamin C) is one of the early, unorthodox treatments for cancer. The evidence upon which people base the use of ascorbate in cancer treatment falls into two categories: clinical data on dose concentration relationships, and laboratory data describing potential cell toxicity with high concentr... |
Children with uncorrected cyanotic congenital heart diseases can present for non cardiac surgeries. They pose several challenges to the Anaesthesiologist, especially when they are posted for emergency surgery, due to the complex haemodynamic changes secondary to the heart disease. Pentalogy of Fallot (POF) is a rare fo... | List Pentalogy of Fallot. | Pentalogy of Fallot (POF) is a rare form of congenital heart disease characterized by the association of Tetralogy of Fallot (TOF) with an atrial septal defect (ASD). |
Targeted genetic engineering of human pluripotent cells is a prerequisite for exploiting their full potential. Such genetic manipulations can be achieved using site-specific nucleases. Here we engineered transcription activator-like effector nucleases (TALENs) for five distinct genomic loci. At all loci tested we obtai... | Is TALEN being used on stem cells? | At all loci tested we obtained human embryonic stem cell (ESC) and induced pluripotent stem cell (iPSC) clones carrying transgenic cassettes solely at the TALEN-specified location. Our data suggest that TALENs employing the specific architectures described here mediate site-specific genome modification in human pluripo... |
Squamous cell lung carcinoma (SCC) accounts for 30% of patients with NSCLC and to date, no molecular targeted agents are approved for this type of tumor. However, recent studies have revealed several oncogenic mutations in SCC patients, including an alteration of the PI3K/AKT pathway, i.e. PI3K point mutations and ampl... | Which molecules are targeted by defactinib? | Prompted by our observation of a correlation between PTEN loss and FAK phosphorylation in a cohort of patients with stage IV SCC, we evaluated the relevance of PTEN loss in cancer progression as well as the efficacy of a new combined treatment with the pan PI3K inhibitor buparlisip and the FAK inhibitor defactinib. |
Standard CD44 (CD44s) and variant isoforms (CD44v) are expressed on different malignant cells and tissues. Their upregulation has been implicated, in the progression and metastasis of malignomas. In this work we addressed the question of whether these molecules are also expressed on xenografted human breast carcinomas ... | Are CD44 variants (CD44v) associated with poor prognosis of metastasis? | variant isoforms (CD44v) are expressed on different malignant cells and tissues. Their upregulation has been implicated, in the progression and metastasis of malignomas. |
DNA replication initiates at defined sites called origins, which serve as binding sites for initiator proteins that recruit the replicative machinery. Origins differ in number and structure across the three domains of life and their properties determine the dynamics of chromosome replication. Bacteria and some archaea ... | Do all archaea possess multiple origins of DNA replication? | Bacteria and some archaea replicate from single origins, whereas most archaea and all eukaryotes replicate using multiple origins |
High-grade gliomas (HGG) are a devastating group of cancers, and represent the leading cause of brain tumour-related death in both children and adults. Therapies aimed at mechanisms intrinsic to glioma cells have translated to only limited success; effective therapeutic strategies will need also to target elements of t... | Which brain tumors does neuroligin-3 promote? | This work defines a promising strategy for targeting NLGN3 secretion, which could prove transformative for HGG therapy. |
The two major virulence factors of Bacillus anthracis are the tripartite toxin and the polyglutamate capsule, which are encoded by genes on the large plasmids, pXO1 and pXO2, respectively. The genes atxA, located on pXO1, and acpA, located on pXO2, encode positive trans-acting proteins that are involved in bicarbonate-... | Which metabolite activates AtxA? | We identified two major apparent transcriptional start sites, designated P1 and P2, located at positions 731 bp and 625 bp, respectively, upstream of the translation-initiation codon of capB. Transcription initiated from P1 and P2 was activated by both atxA and acpA, and activation appeared to be stimulated by bicarbon... |
The firing of eukaryotic origins of DNA replication requires CDK and DDK kinase activities. DDK, in particular, is involved in setting the temporal program of origin activation, a conserved feature of eukaryotes. Rif1, originally identified as a telomeric protein, was recently implicated in specifying replication timin... | How does Rif1 regulate DNA replication? | Rif1, originally identified as a telomeric protein, was recently implicated in specifying replication timing in yeast and mammals. We show that this function of Rif1 depends on its interaction with PP1 phosphatases |
Exercise training improves the aging-induced downregulation of myosin heavy chain (MHC) and sarcoplasmic reticulum (SR) Ca(2+)-ATPase, which participate in the regulation of cardiac contraction and relaxation. Thyroid hormone receptor (TR), a transcriptional activator, affected the regulation of gene expression of MHC ... | How does exercise affect thyroid hormone receptors expression in the heart? | Expression of TR-alpha1 and TR-beta1 proteins in the heart were significantly lower in sedentary aged rats than in sedentary young rats and were significantly higher in trained aged rats than in sedentary aged rats. |
Despite the recent major advancement in therapy for multiple myeloma, it remains an incurable disease. There remains an unmet need for novel therapies that target different mechanisms of action. Immunotherapy with monoclonal antibodies is a promising area of development and will expand our therapeutic armamentarium in ... | Which molecule is targeted by Daratumumab? | Daratumumab is a novel, high-affinity, therapeutic human monoclonal antibody against unique CD38 epitope with broad-spectrum killing activity. |
Sequence variations of the KCNQ2 and KCNQ3 genes may contribute to the etiology of common idiopathic epilepsy syndromes. | Is the protein KCNQ2 associated with idiopathic epilepsy? | Sequence variations of the KCNQ2 and KCNQ3 genes may contribute to the etiology of common idiopathic epilepsy syndromes. |
Romano-Ward syndrome (RWS), the autosomal dominant form of the congenital long QT syndrome, is characterised by prolongation of the cardiac repolarisation process associated with ventricular tachyarrhythmias of the torsades de pointes type. Genetic studies have identified mutations in six ion channel genes, KCNQ1, KCNH... | Which genes are affected in ROMANO-WARD syndrome? | Genetic studies have identified mutations in six ion channel genes, KCNQ1, KCNH2, SCN5A, KCNE1 and KCNE2 and the accessory protein Ankyrin-B gene, to be responsible for this disorder. |
: A radiation-attenuated (Pf) sporozoite (SPZ) malaria vaccine, PfSPZ Vaccine, protected 6 of 6 subjects (100%) against homologous Pf (same strain as in the vaccine) controlled human malaria infection (CHMI) 3 weeks after 5 doses administered intravenously. The next step was to assess protective efficacy against heter... | Which disease can be prevented with PfSPZ Vaccine? | have demonstrated for the first time to our knowledge that PfSPZ Vaccine can protect against a 3-week heterologous CHMI in a limited group of malaria-naive adult subjects. |
Transcription factor binding sites (TFBSs) are most commonly characterized by the nucleotide preferences at each position of the DNA target. Whereas these sequence motifs are quite accurate descriptions of DNA binding specificities of transcription factors (TFs), proteins recognize DNA as a three-dimensional object. DN... | What is TFBSshape? | Existing motif databases contain extensive nucleotide sequences identified in binding experiments based on their selection by a TF. To utilize DNA shape information when analysing the DNA binding specificities of TFs, we developed a new tool, the TFBSshape database (available at http://rohslab.cmb.usc.edu/TFBSshape/), ... |
Cyclic guanosine monophosphate (cGMP) specific phosphodiesterase type-5 (PDE5), a clinically proven target to treat erectile dysfunction and diseases associated with lower cGMP levels in humans, is present in corpus cavernosum, heart, lung, platelets, prostate, urethra, bladder, liver, brain, and stomach. Sildenafil, v... | Is avanafil indicated for treatment of erectile dysfunction? | Sildenafil, vardenafil, tadalafil and avanafil are FDA approved drugs in market as PDE5 inhibitors for treating erectile dysfunction. |
Neutrophils are a key cell type of the innate immune system. They are short-lived and need to be continuously generated in steady-state conditions from haematopoietic stem and progenitor cells in the bone marrow to ensure their immediate availability for the containment of invading pathogens. However, if microbial infe... | What is the function of emergency granulopoiesis? | This involves the markedly increased de novo production of neutrophils, which results from enhanced myeloid precursor cell proliferation in the bone marrow |
Developmental and epileptic encephalopathy (DEE) is a group of conditions characterized by the co-occurrence of epilepsy and intellectual disability (ID), typically with developmental plateauing or regression associated with frequent epileptiform activity. The cause of DEE remains unknown in the majority of cases. We p... | List characteristics of Developmental and Epileptic Encephalopathies (DEEs). | Developmental and epileptic encephalopathy (DEE) is a group of conditions characterized by the co-occurrence of epilepsy and intellectual disability (ID), typically with developmental plateauing or regression associated with frequent epileptiform activity. Th |
The skeletal and immune systems have a complex relationship. Both systems are intimately coupled, with osteoclastogenesis and hematopoiesis occurring in the bone marrow. Bone and immune cells also share common hematopoietic precursors. Furthermore, the skeletal and immune systems share various cytokines, receptors, and... | To the ligand of which receptors does Denosumab (Prolia) bind? | Denosumab, an anti-RANKL monoclonal antibody with proven antiosteoclast activity, may suppress immune responses. |
DNA methylation is an epigenetic regulatory mechanism commonly associated with transcriptional silencing. DNA methyltransferases (DNMTs) are a family of related proteins that both catalyze the de novo formation of 5-methylcytosine and maintain these methylation marks in cell-specific patterns in virtually all mitotic c... | Which are the families of mammalian DNA-(cytosine-5)-methyltransferases? | Of the DNMTs, DNMT1 and DNMT3a are most highly expressed in postmitotic neurons. |
The detrimental effects of ultraviolet B (UVB) irradiation have been connected with the enhanced generation of reactive oxygen species (ROS) by UVB. However, the exact source of ROS produced by UVB has not been clearly revealed yet. In this study, we determined the source of ROS production and its role in the UVB-induc... | Can NADPH oxidase be inhibited by apocynin and diphenylene iodonium? | UVB irradiation generated ROS in a dose-dependent manner, and this was significantly inhibited by diphenylene iodonium (DPI), apocynin (Apo) and neopterine (Neo), inhibitors of the NADPH oxidase, and indomethacin (Indo), a cyclooxygenase (COX) inhibitor, but not by the mitochondrial electron transport inhibitors and ot... |
We investigate how DNA sequence, ATP-dependent chromatin remodeling and nucleosome-depleted 'barriers' co-operate to determine the kinetics of nucleosome organization, in a stochastic model of nucleosome positioning and dynamics. We find that 'statistical' positioning of nucleosomes against 'barriers', hypothesized to ... | Is nucleosome eviction ATP-dependent? | ATP-dependent chromatin remodeling and nucleosome-depleted 'barriers' co-operate to determine the kinetics of nucleosome organization |
Newborns and infants are often exposed to painful procedures during hospitalization. Several different scales have been validated to assess pain in specific populations of pediatric patients, but no single scale can easily and accurately assess pain in all newborns and infants regardless of gestational age and disease ... | What are the most common pain scales used to measure pain in neonates? | Pain was assessed using indicators from three previously established scales (CRIES, the Premature Infant Pain Profile, and the Neonatal Infant Pain Scale), as well as the COVERS Scale, depending upon gestational age. |
Andexanet alfa is a specific reversal agent for Factor Xa inhibitors. The molecule is a recombinant protein analog of factor Xa that binds to Factor Xa inhibitors and antithrombin:LMWH complex but does not trigger prothrombotic activity. In ex vivo, animal, and volunteer human studies, andexanet alfa (AnXa) was able to... | Andexanet Alfa is an antidote of which clotting factor inhibitors? | Andexanet alfa is a specific reversal agent for Factor Xa inhibitors. |
Matjes River Rock Shelter is a large shell midden on the southern coast of South Africa. Stable nitrogen (delta(15)N) and carbon (delta(13)C) isotope ratios were measured in bone collagen and dentine from human skeletons excavated from this site in order to establish a weaning curve in mid-Holocene hunter-gatherers. de... | Which bone protein is used in archaelogy for dating and species identification? | Stable nitrogen (delta(15)N) and carbon (delta(13)C) isotope ratios were measured in bone collagen and dentine from human skeletons excavated from this site in order to establish a weaning curve in mid-Holocene hunter-gatherers. |
Afterglow or persistent luminescence eliminates the need for light excitation and thus circumvents the issue of autofluorescence, holding promise for molecular imaging. However, current persistent luminescence agents are rare and limited to inorganic nanoparticles. This study reports the design principle, synthesis, an... | Can nanoparticles be used for afterglow imaging? | Afterglow or persistent luminescence eliminates the need for light excitation and thus circumvents the issue of autofluorescence, holding promise for molecular imaging. However, current persistent luminescence agents are rare and limited to inorganic nanoparticles. This study reports the design principle, synthesis, an... |
Lipid lowering drugs, such as statins, are commonly used to treat approximately 10 million Canadians affected by hypercholesterolemia. The most commonly experienced side-effect of statin medication is muscle pain. Statin induced myopathy consists of a spectrum of myopathic disorders ranging from mild myalgia to fatal r... | What class of drugs frequently has muscle pain and other muscle toxicities such as mysositis and rhabdomyolysis as a side effect? | Lipid lowering drugs, such as statins, are commonly used to treat approximately 10 million Canadians affected by hypercholesterolemia. The most commonly experienced side-effect of statin medication is muscle pain |
Dupuytren's contracture is a common hand problem that affects the palmar fascia. Several treatment options exist, but none are curative and recurrence is common. Bacterial collagenase has recently been proven beneficial for treating Dupuytren's disease, cleaving the collagen fibers at different sites, with weakening an... | What is Dupuytren's contracture? | Dupuytren's contracture is a common hand problem that affects the palmar fascia. |
These results show that siltuximab effectively block the IL-6 signaling pathways and IL-6-induced gene expression. Blockage of IL-6 signaling may provide benefits for the treatment of ovarian cancer. | Which interleukin is blocked by Siltuximab? | These results show that siltuximab effectively block the IL-6 signaling pathways and IL-6-induced gene expression. |
Drosophila larval neurogenesis is an excellent system for studying the balance between self-renewal and differentiation of a somatic stem cell (neuroblast). Neuroblasts (NBs) give rise to differentiated neurons and glia via intermediate precursors called GMCs or INPs. We show that E(spl)mγ, E(spl)mβ, E(spl)m8 and Deadp... | What is the difference between ganglion mother cells (GMC) and intermediate neural precursor cells (INP) in Drosophila? | Neuroblasts (NBs) give rise to differentiated neurons and glia via intermediate precursors called GMCs or INPs. |
Thyroid hormones [predominantly 3, 5, 3 -I- iodothyronine (T3)] regulate cholesterol and lipoprotein metabolism but cardiac effects restrict their use as hypolipidemic drugs. New molecules have been developped which target specifically the thyroid hormone receptor ss, predominant isoform in liver. The first thyroid hor... | Which compounds exist that are thyroid hormone analogs? | thyroid hormone agonist, called GC1 |
The Braf(V600E) mutation has been detected in patients with metastatic melanoma, colon, thyroid, and other cancers. Studies suggested that tumors with this mutation are especially sensitive to BRAF inhibitors-hence the need to reliably determine the BRAF status of tumor specimens. The present technologies used to scree... | Are BRAF mutations common in melanoma? | The Braf(V600E) mutation has been detected in patients with metastatic melanoma, colon, thyroid, and other cancers. |
Chronic myelogenous leukemia (CML) is genetically characterized by the reciprocal translocation of chromosome 9 and 22, t(9;22)(q34;q11) which results in the fusion of BCR/ABL gene observed on the derivative chromosome 22 called Philadelphia (Ph') chromosome. About 5-8% of Philadelphia positive patients with CML show v... | Which gene fusion is the result of the "philadelphia translocation" or the "philadelphia chromosome" mutation? | Chronic myelogenous leukemia (CML) is genetically characterized by the reciprocal translocation of chromosome 9 and 22, t(9;22)(q34;q11) which results in the fusion of BCR/ABL gene observed on the derivative chromosome 22 called Philadelphia (Ph') chromosome |
Vaccination of pregnant women against influenza A (H1N1) by Russian subunit formulation (MonoGrippol plus) showed reactogenicity comparable to control group by the level of influence on general metabolic and immunologic homeostasis and on the course of pregnancy, which is an evidence of its safety. | Is pregnancy an additional risk during during H1N1 infection? | Vaccination of pregnant women against influenza A (H1N1) by Russian subunit formulation (MonoGrippol plus) showed reactogenicity comparable to control group by the level of influence on general metabolic and immunologic homeostasis and on the course of pregnancy, which is an evidence of its safety |
Thirty-two female patients with clinical and urodynamic findings of genuine stress urinary incontinence were evaluated before and 6 months after surgery for stress urinary incontinence. Twenty-nine control patients had identical evaluations before and 6 months after surgery which did not involve the urethrovesical junc... | Which type of urinary incontinence is diagnosed with the Q tip test? | Simple clinical tests for support of the urethrovesical junction, such as the Q tip test, are non-specific in patients with stress urinary incontinence. |
These results support a role for maternal smoking during pregnancy in the etiology of childhood brain tumors. Our findings should be confirmed in other prospective studies. | What is known about maternal smoking and brain tumor risk? | These results support a role for maternal smoking during pregnancy in the etiology of childhood brain tumors. |
Recurrences develop in up to 20-50% of patients with acute pericarditis. Although different causes of recurrent pericarditis have been identified, the etiology remains obscure in most cases which are therefore labelled as idiopathic. Autoinflammatory syndromes include familial Mediterranean fever (FMF), due to mutation... | What is the treatment of acute pericarditis? | A poor response to colchicine treatment and/or a steroid-dependence may be the clue to investigate TNFRSF1A mutations in patients with idiopathic recurrent pericarditis. |
Hemophilic pseudotumor is a rare complication of hemophilia, occurring in 1 to 2 percent of individuals with severe factor VIII or factor IX deficiency. A 35-year-old male presented with a swelling in the right lower abdomen for 3 months. There was no history of trauma. Examination revealed a swelling over the right il... | What is Hemophilic Pseudotumor? | Hemophilic pseudotumor is a rare complication of hemophilia, occurring in 1 to 2 percent of individuals with severe factor VIII or factor IX deficiency. A |
Mutations in MECP2 cause the neurodevelopmental disorder Rett syndrome (RTT). The RTT missense MECP2 mutation prevents MeCP2 from interacting with the NCoR/histone deacetylase 3 (HDAC3) complex; however, the neuronal function of HDAC3 is incompletely understood. We found that neuronal deletion of Hdac3 in mice elicited... | What disease is associated with mutations in the MECP2 transcription factor? | Mutations in MECP2 cause the neurodevelopmental disorder Rett syndrome (RTT). |
Fanconi anemia (FA) is a heterogeneous disease associated with a bone marrow failure, cancer predisposition and hypersensitivity to DNA crosslinking agents. To date, 15 different genes have been shown to cause FA, all of which have some role in repair of defective DNA interstrand crosslinks. On a biochemical level, man... | Is Fanconi anemia presented as a genetically and clinically heterogeneous disease entity? | Fanconi anemia (FA) is a heterogeneous disease associated with a bone marrow failure, cancer predisposition and hypersensitivity to DNA crosslinking agents. |
Microexons are small sized (≤51 bp) exons which undergo extensive alternative splicing in neurons, microglia, embryonic stem cells, and cancer cells, giving rise to cell type specific protein isoforms. Due to their small sizes, microexons provide a unique challenge for the splicing machinery. They frequently lack exon ... | Does microexon alternative splicing of small GTPase regulators have implication in central nervous system diseases? | We further discuss the emerging evidence for dysregulation of the Rho GTPase pathway in CNS diseases and the consequences contributed by the mis-splicing of microexons. |
Thyroid-associated ophthalmopathy (TAO), a localized periocular manifestation of the autoimmune syndrome known as Graves' disease, remains incompletely understood. Discussions of its pathogenesis are generally focused on the thyrotropin receptor, the proposed role for which is supported by substantial evidence. Conside... | Which molecule is targeted by Teprotumumab? | Results from a very recently published clinical trial assessing the safety and efficacy of teprotumumab, an inhibitory human anti-IGF-IR monoclonal antibody, in active, moderate to severe TAO are extremely encouraging. |
Iodothyronine deiodinase in vitro activity studies in the chicken showed the presence of type I and type III iodothyronine deiodinase activity in both liver and kidney. Due to the lack of a specific antiserum the cellular localization of the deiodinase proteins could not be revealed until now. In the present study, spe... | Which deiodinase is known to be present in liver? | Iodothyronine deiodinase in vitro activity studies in the chicken showed the presence of type I and type III iodothyronine deiodinase activity in both liver and kidney. |
Until now, sex determination in equine embryos has been performed by detection of Y-chromosome-specific sequences only. In the present study, expression of a Barr-body-specific marker, the X-inactivated-specific transcript (Xist) gene, whose gene product consists of RNA which coats and thereby inactivates one of the X ... | In which tissues is the lincRNA Xist expressed? | Preattachment embryos at different times after ovulation (Day 8: n = 9; Day 10: n = 12; Day 12: n = 15) were analyzed for Xist RNA expression using quantitative and qualitative reverse transcription-polymerase chain reaction (RT-PCR). |
The telomerase complex is responsible for telomere maintenance and represents a promising neoplasia therapeutic target. In order to determine whether G-quadruplex-interactive telomerase inhibitor, telomestatin (SOT-095), might have effects on telomere dynamics and to evaluate the clinical utility, we assessed the effec... | Is telomestatin, a novel statin drug used to treat high cholesterol? | We found that treatment with telomestatin reproducibly inhibited telomerase activity in the BCR-ABL-positive leukemic cell lines |
A wide range of adipokines identified over the past years has allowed considering the white adipose tissue as a secretory organ closely integrated into overall physiological and metabolic control. Apelin, a ubiquitously expressed peptide was known to exert different physiological effects mainly on the cardiovascular sy... | Is Apelin usually decreased in diabetes? | Moreover, different studies in both animals and humans have shown that plasma apelin concentrations are usually increased during obesity and type 2 diabetes. |
Although it is still debated whether chronic cerebro-spinal venous insufficiency (CCSVI) plays a role in multiple sclerosis (MS) development, many patients underwent endovascular treatment (ET) of CCSVI. The objective of the study is to evaluate the outcome and safety of ET in Italian MS patients. Italian MS centers th... | What is the lay name of the treatment for CCSVI (chronic cerebro-spinal venous insufficiency) in multiple sclerosis. | Although it is still debated whether chronic cerebro-spinal venous insufficiency (CCSVI) plays a role in multiple sclerosis (MS) development, many patients underwent endovascular treatment (ET) of CCSVI. |
Nemaline myopathy is a heterogenous form of congenital myopathy characterised by a variable spectrum of clinical features, predominated in the severe form by profound muscle hypotonia and weakness accompanied by respiratory insufficiency. The clinical variability, with differing age of onset and severity of symptoms ma... | Are ACTA1 (alpha actin) and NEB (nebulin) genes related to nemaline myopathy? | Severe forms of nemaline myopathy may be caused by mutation of a number of different genes: skeletal muscle actin (ACTA1), nebulin (NEB) and alpha-tropomyosin (TPM3), all of which encode components of the sarcomeric thin filaments of skeletal muscle |
In this study, two novel FIPs have been identified and characterized. The first is FIP-nha, identified in the ascomycete Nectria haematococca, and as such, FIP-nha would be the first FIP to be identified outside the order of Basidiomycota. The second is LZ-9, an LZ-8 like protein identified in Ganoderma lucidum. Recomb... | Magnetic beads has been used in numerous applications. List some coatings used. | His-affinity magnetic beads |
Charcot-Marie-Tooth (CMT) disease is the most-common form of inherited motor and sensory neuropathy. The autosomal dominant axonal form of the disease (CMT2) is currently subdivided into seven types based on genetic localization. These are CMT2A (1p35-p36), CMT2B (3q13-q22), CMT2C (unknown), CMT2D (7p14), CMT2E (8p21),... | Which genes are associated with autosomal dominant Charcot-Marie-Tooth? | We identified a novel neurofilament-light missense mutation (C64T) that causes the disease in a large Slovenian CMT2 family. This novel mutation shows complete co-segregation with the dominantly inherited CMT2 phenotype in our family |
Gonadal development in vertebrates depends on the early determination of primordial germ cells (PGCs) and their correct migration to the sites where the gonads develop. Several genes have been implicated in PGC specification and migration in vertebrates. Additionally, some of the genes associated with pluripotency, suc... | Which cellular processes are regulated by Nanog? | Nanog mediates PGC migration by regulating Cxcr4b expression |
Recent research using chromatin conformation capture technologies, such as Hi-C, has demonstrated the importance of topologically associated domains (TADs) and smaller chromatin loops, collectively referred hereafter as "interacting domains." Many such domains change during development or disease, and exhibit cell- and... | Which R packages have been developed for studying TADs? | TADCompare is based on a spectral clustering-derived measure called the eigenvector gap, which enables a loci-by-loci comparison of boundary differences. |
Human induced pluripotent stem cells (hiPSC) hold great promise for providing various differentiated cell models for in vitro toxigenicity testing. For Clostridium botulinum neurotoxin (BoNT) detection and mechanistic studies, several cell models currently exist, but none examine toxin function with species-specific re... | How is active neurotoxin of Clostridium botulinum detected? | A direct comparison of BoNT detection using primary rat spinal cord cells and hiPSC-derived neurons showed equal or increased sensitivity |
Reversible phosphorylation is a key event in many biological processes and is therefore a much studied phenomenon. The mass spectrometric (MS) analysis of phosphorylation is challenged by the substoichiometric levels of phosphorylation and the lability of the phosphate group in collision-induced dissociation (CID). Her... | What is the advantage of neutral loss detection in phosphoproteomics? | CID of phosphopeptides typically results in spectra dominated by a neutral loss of the phosphate group. |
Neuromedin U (NMU) is a brain-gut peptide, which peripherally stimulates smooth muscle, increases of blood pressure, alters ion transport in the gut, controls local blood flow, and regulates adrenocortical function. Although intracerebroventricular (i.c.v.) administration of NMU is known to decrease food intake and bod... | What is Neuromedin U (NmU) | Neuromedin U (NMU) is a brain-gut peptide, which peripherally stimulates smooth muscle, increases of blood pressure, alters ion transport in the gut, controls local blood flow, and regulates adrenocortical function. |
Epithelial-mesenchymal transition (EMT), a crucial event in cancer progression and embryonic development, is induced by transforming growth factor (TGF)-beta in mouse mammary NMuMG epithelial cells. Id proteins have previously been reported to inhibit major features of TGF-beta-induced EMT. In this study, we show that ... | Which transcription factors are involved in E-cadherin repression during EMT? | SIP1 and deltaEF1 each dramatically down-regulated the transcription of E-cadherin in NMuMG cells through direct binding to the E-cadherin promoter. |
Deletion mutants of CHL1 or CTF4, which are required for sister chromatid cohesion, showed higher sensitivity to the DNA damaging agents methyl methanesulfonate (MMS), hydroxyurea (HU), phleomycin, and camptothecin, similar to the phenotype of mutants of RAD52, which is essential for recombination repair. The levels of... | Is Ctf4 involved in sister chromatid cohesion establishment? | Our results suggest that Chl1 and Ctf4 are directly involved in homologous recombination repair rather than acting indirectly via the establishment of sister chromatid cohesion. |
The transcribed-ultraconserved regions (T-UCRs) are a novel class of non-coding RNAs, which are absolutely conserved (100%) between the orthologous regions of the human, rat and mouse genomes. Previous studies have described that several T-UCRs show differential expressions in cancers and might be involved in cancer de... | Which T-UCRs have been implicated in gastric cancer? | We investigated the transcriptional levels of representative 26 T-UCRs and determined the regions that were differently expressed in prostate cancer (PCa) and gastric cancer (GC). A quantitative reverse transcription-polymerase chain reaction analysis revealed the downregulation of Uc.158+A expression by a DNA methylat... |
More than 20.8 million people are infected with HIV in sub-Saharan Africa, with South Africa having one of the fastest growing HIV-1 epidemics, where an estimated 2.4 million people were infected. Thirty-two sera from 25 patients were tested for their ability to neutralize HTLV-IIIB (IIIB) and four primary isolates rep... | How is the sequence variability defined in antibodies? | The V3 region of the isolates used in the neutralization assay was amplified by PCR, directly sequenced, and analyzed to reveal variability between the consensus HIV-1 sequences and the isolates. |
Sidekick-1, a cell adhesion molecule of the immunoglobulin superfamily, is up-regulated in glomerular podocytes in the collapsing glomerulopathy of HIV-associated nephropathy (HIVAN). Sidekick-1 and its ortholog sidekick-2 have also been shown to function as neuronal targeting molecules, guiding developing neurons to s... | Are Sidekick proteins members of the immunoglobulin superfamily? | Sidekick-1, a cell adhesion molecule of the immunoglobulin superfamily, is up-regulated in glomerular podocytes in the collapsing glomerulopathy of HIV-associated nephropathy (HIVAN). |
Respiratory syncytial virus (RSV) infection is ubiquitous with almost all infants having been infected by 2 years of age and lifelong repeated infections common. It is the second largest cause of mortality, after malaria, in infants outside the neonatal period and causes up to 200,000 deaths per year worldwide. RSV res... | List indications for palivizumab for treatment of RSV-induced bronchiolitis. | There is currently no licensed vaccine to prevent RSV infection but passive immunoprophylaxis using a monoclonal antibody, palivizumab, reduces the risk of hospitalization due to RSV infection by 39-78% in various high-risk infants predisposed to developing severe RSV disease. |
The purpose of the RAZOR (randomized open vs robotic cystectomy) study is to compare open radical cystectomy (ORC) vs robot-assisted RC (RARC), pelvic lymph node dissection (PLND) and urinary diversion for oncological outcomes, complications and health-related quality of life (HRQL) measures with a primary endpoint of ... | Which two surgical methods were compared in the RAZOR trial? | AZOR is a multi-institutional, non-inferiority trial evaluating cancer outcomes, surgical complications and HRQL measures of ORC vs RARC with a primary endpoint of 2-year PFS. Full data from the RAZOR trial are not expected until 2016-2017. |
N‑acetylcysteine (NAC) is a thiol‑containing antioxidant that modulates the intracellular redox state. NAC can scavenge reactive oxygen species (ROS) and maintain reduced glutathione (GSH) levels, in order to protect cardiomyocytes from oxidative stress. The present study aimed to determine whether NAC protects cardiom... | List five proteins with antioxidant properties? | Non‑reducing redox western blotting was performed to detect the redox status of intracellular antioxidant proteins, including thioredoxin 1 (Trx1), peroxiredoxin 1 (Prx1), GSH reductase (GSR), and phosphatase and tensin homolog (PTEN). |
The AP-1 transcription factor c-Jun is a master regulator of the axonal response in neurons. c-Jun also functions as a negative regulator of myelination in Schwann cells (SCs) and is strongly reactivated in SCs upon axonal injury. We demonstrate here that, after injury, the absence of c-Jun specifically in SCs caused i... | Which proteins have been identified as RET ligands? | We demonstrate here that, after injury, the absence of c-Jun specifically in SCs caused impaired axonal regeneration and severely increased neuronal cell death. c-Jun deficiency resulted in decreased expression of several neurotrophic factors, and GDNF and Artemin, both of which encode ligands for the Ret receptor tyro... |
Our findings show that CTCF and possibly chromatin insulation are present in basal nematodes. We suggest that the insulator protein CTCF has been secondarily lost in derived nematodes like C. elegans. We propose a switch in the regulation of gene expression during nematode evolution, from the common vertebrate and inse... | Do nematodes contain architectural proteins like CTCF? | suggest that the insulator protein CTCF has been secondarily lost in derived nematodes like C. elegans. W |
The eukaryotic cytosolic chaperonin containing TCP-1 (CCT) has an important function in maintaining cellular homoeostasis by assisting the folding of many proteins, including the cytoskeletal components actin and tubulin. Yet the nature of the proteins and cellular pathways dependent on CCT function has not been establ... | What is the function of a chaperonin? | The eukaryotic cytosolic chaperonin containing TCP-1 (CCT) has an important function in maintaining cellular homoeostasis by assisting the folding of many proteins, including the cytoskeletal components actin and tubulin. Y |
Evidence on the optimum choice of prosthesis for hemiarthroplasty of the hip is lacking. National guidance is currently based on expert opinion rather than empirical evidence. The incidence of hip fracture is likely to continue to increase and providing high quality evidence on the optimumCite this article: A. L. Sims.... | What disease was the topic of the World Hip Trauma Evaluation (WHiTE) trial? | The World Hip Trauma Evaluation Study 3: Hemiarthroplasty Evaluation by Multicentre Investigation - WHITE 3: HEMI - An Abridged Protocol. |
Humans are genetically incapable of producing the mammalian sialic acid N-glycolylneuraminic acid (Neu5Gc), due to an inactivating mutation in the enzyme synthesizing it. Despite this, human cells and tissues appear capable of metabolically incorporating Neu5Gc from exogenous sources, including dietary red meat and dai... | Why can't humans synthesize Neu5Gc (N-Glycolylneuraminic acid)? | Humans are genetically incapable of producing the mammalian sialic acid N-glycolylneuraminic acid (Neu5Gc), due to an inactivating mutation in the enzyme synthesizing it. |
ToppGene Suite (http://toppgene.cchmc.org; this web site is free and open to all users and does not require a login to access) is a one-stop portal for (i) gene list functional enrichment, (ii) candidate gene prioritization using either functional annotations or network analysis and (iii) identification and prioritizat... | Which are the most common methods for gene prioritization analysis? | The protein-protein interaction network (PPIN)-based disease candidate gene prioritization uses social and Web networks analysis algorithms (extended versions of the PageRank and HITS algorithms, and the K-Step Markov method) |
Sclerostin regulates bone formation by inhibiting Wnt pathway signaling. Low circulating sclerostin levels cause high bone mass. We hypothesized that postmenopausal women with increased sclerostin levels have a greater risk for osteoporosis-related fractures. We examined the association between circulating sclerostin t... | Sclerostin regulates what process? | Sclerostin regulates bone formation by inhibiting Wnt pathway signaling. |
Idiopathic toe walking is a relatively common developmental condition often leading to secondary problems such as pain and muscle contractures in the lower extremities. The cause of idiopathic toe walking is unknown, which hinders the development of treatment strategies. To test whether children with idiopathic toe wal... | What is Idiopathic toe walking? | Idiopathic toe walking is a relatively common developmental condition often leading to secondary problems such as pain and muscle contractures in the lower extremities. |
Tumor infiltrating leukocytes (TILs) are an integral component of the tumor microenvironment and have been found to correlate with prognosis and response to therapy. Methods to enumerate immune subsets such as immunohistochemistry or flow cytometry suffer from limitations in phenotypic markers and can be challenging to... | What is CIBERSORT used for? | We recently described CIBERSORT, a versatile computational method for quantifying cell fractions from bulk tissue gene expression profiles (GEPs). |
Primary intestinal lymphangiectasia (PIL) is a rare disorder of unknown etiology characterized by diffuse or localized dilation and eventual rupture of the enteric lymphatic vessels in mucosa, submucosa, and/or subserosa. Lymph, rich in all kinds of proteins and lymphocytes, leaks into the gastrointestinal tract via th... | How is primary intestinal lymphangiectasia (PIL) caused? | PIL, effusions, and lymphedema can be the features of multisegmental generalized lymphatic dysplasia. |
The early Caenorhabditis elegans embryo is an attractive model to investigate evolutionarily conserved cellular mechanisms. However, there is a paucity of automated methods to gather quantitative information with subcellular precision in this system. We developed ASSET (Algorithm for the Segmentation and the Standardiz... | What is the application of the ASSET algorithm in C.elegans? | In summary, we establish ASSET as a novel tool for the efficient quantification and standardization of images from early C. elegans embryos. |
The hepatocellular carcinoma (HCC) treatment landscape changed a decade ago, with sorafenib demonstrating survival benefit in the first-line setting and becoming the first systemic therapy to be approved for HCC. More recently, regorafenib and nivolumab have received approval in the second-line setting after sorafenib,... | Is cabozantinib effective for Hepatocellular Carcinoma? | More recently, regorafenib and nivolumab have received approval in the second-line setting after sorafenib, with further positive phase 3 studies emerging in the first line (lenvatinib non-inferior to sorafenib) and second line versus placebo (cabozantinib and ramucirumab). |
Craniosynostosis, the premature closure of cranial suture, is a pathologic condition that affects 1/2000 live births. Saethre-Chotzen syndrome is a genetic condition characterized by craniosynostosis. The Saethre-Chotzen syndrome, which is defined by loss-of-function mutations in the TWIST gene, is the second most prev... | What is craniosynostosis? | Craniosynostosis, the premature closure of cranial suture, is a pathologic condition that affects 1/2000 live births |
To investigate the effects of arsenite on cell proliferation and the signal transduction in hapatocytes in vivo, rats received a single injection of sodium arsenite immediately after partial hepatectomy. Characteristic DNA fragmentation was observed at 4h after the arsenite-injection in partially hepatectomized liver, ... | Is the JNK pathway activated during liver regeneration? | arsenite induced apoptosis in the hepatocytes in vivo, through the enhancement of the activation of JNK and p38 MAPK caused by partial hepatectomy |
The formation of reactive metabolites through biotransformation is the suspected cause of many adverse drug reactions. Testing for the propensity of a drug to form reactive metabolites has increasingly become an integral part of lead-optimization strategy in drug discovery. DNA reactivity is one undesirable facet of a ... | What are reactive metabolites? | The formation of reactive metabolites through biotransformation is the suspected cause of many adverse drug reactions. |
During spermiogenesis, haploid spermatids undergo extensive chromatin remodeling events in which histones are successively replaced by more basic protamines to generate highly compacted chromatin. Here we show for the first time that H3K79 methylation is a conserved feature preceding the histone-to-protamine transition... | What is the general function of H3K79 methylation? | In rat, H3K79 methylation also correlates with H4 hyperacetylation but not with active RNA polymerase II, which might point towards a conserved function in chromatin remodeling during the histone-to-protamine transition in both Drosophila and rat |
Dynamic changes of the lengths of mRNA poly(A) tails are catalysed by diverse deadenylase enzymes. Modulating the length of the poly(A) tail of an mRNA is a widespread means of controlling protein production and mRNA stability. Recent insights illuminate the specialized activities, biological functions and regulation o... | What is the role of deadenylases in the cell? | Dynamic changes of the lengths of mRNA poly(A) tails are catalysed by diverse deadenylase enzymes. |
In a 3-year prospective study, all cases of disseminated Fusobacterium necrophorum infections found in Denmark from 1998 to 2001 were analysed, with the aim of describing the epidemiology and clinical features of the variants of Lemierre's syndrome and disseminated non-head-and-neck-associated F. necrophorum infections... | Is fusobacterium associated with Lemierre's syndrome? | In a 3-year prospective study, all cases of disseminated Fusobacterium necrophorum infections found in Denmark from 1998 to 2001 were analysed, with the aim of describing the epidemiology and clinical features of the variants of Lemierre's syndrome and disseminated non-head-and-neck-associated F. necrophorum infections... |
Epithelial Cell Adhesion Molecule (EpCAM) has been discovered as one of the first tumor-specific antigens overexpressed in epithelial cancer. The present review focuses on the role of EpCAM in physiology and homeostasis of epithelia. Recent research pointed to a close interaction of EpCAM with other cell-cell contact m... | Where is the EpCam protein mainly located? | Tumor cells display increased EpCAM expression that often correlates with the loss of strict basolateral localization. |
Immune-regulatory mechanisms are used by cancer to hide from the immune system. Advances and in-depth understanding of the biology of melanoma and its interaction with the immune system have led to the development of some of antagonistic antibodies to the programmed death 1 pathway (PD-1) and one of its ligands, progra... | What is the target of a drug pidilizumab? | , pembrolizumab (formerly known as MK-3475 and lambrolizumab), and pidilizumab are anti-PD-1 antibodies in clinical development for melanoma, non-small cell lung cancer, renal cell carcinoma, head and neck cancers, lymphoma, and several other cancers. Long-term survi |
Extraction and purification of an acid β-glucosidase from human placenta (alglucerase) for the treatment of Gaucher disease, replaced a few years later by a recombinant enzyme (imiglucérase, Cerezyme(®)), has paved the way to the development of enzyme replacement therapies (ERT) for the treatment of lysosomal storage d... | Is Migalastat used for treatment of Fabry Disease? | Molecular chaperones (e.g. migalastat for Fabry disease) and inhibitors of glucosylceramide synthesis (e.g. eliglustat tartrate for Gaucher disease) are currently under investigation in various clinical trials. |
The prevalence, the prognostic effect, and interaction with other molecular markers of DNMT3A mutations was studied in 415 patients with acute myeloid leukemia (AML) younger than 60 years. We show mutations in DNMT3A in 96 of 415 patients with newly diagnosed AML (23.1%). Univariate Cox regression analysis showed that ... | Could DNA (cytosine-5-)-methyltransferases serve as tumour markers? | The prevalence, the prognostic effect, and interaction with other molecular markers of DNMT3A mutations was studied in 415 patients with acute myeloid leukemia (AML) younger than 60 years. |
Communicating the current knowledge of medical outcomes after live kidney donation necessary to support donor candidates in well informed decision-making requires grounding in perspectives of comparison. Baseline risk (without donating), risk attributable to donation, and absolute risk (after donating) need to be consi... | What is the association between kidney donation risk of gestational complications? | Pregnancies in donors may incur attributable risk of gestational hypertension or preeclampsia (11% versus 5% incidence in one study). |
Empagliflozin (Jardiance): a novel SGLT2 inhibitor for the treatment of type-2 diabetes. | Which protein does empagliflozin inhibit? | Empagliflozin (Jardiance): a novel SGLT2 inhibitor for the treatment of type-2 diabetes. |
An ulcer area larger than 2 cm2, a positive probe-to-bone test result, an erythrocyte sedimentation rate of more than 70 mm/h, and an abnormal plain radiograph result are helpful in diagnosing the presence of lower extremity osteomyelitis in patients with diabetes. A negative MRI result makes the diagnosis much less li... | Which disease can be diagnosed with the "probe to bone" test? | An ulcer area larger than 2 cm2, a positive probe-to-bone test result, an erythrocyte sedimentation rate of more than 70 mm/h, and an abnormal plain radiograph result are helpful in diagnosing the presence of lower extremity osteomyelitis in patients with diabetes. |
Hereditary hemochromatosis (HH) is one of the most common genetically transmitted conditions in individuals of Northern European ancestry. The disease is characterized by excessive intestinal absorption of dietary iron, resulting in pathologically high iron storage in tissues and organs. If left untreated, HH can damag... | What is Hemochromatosis? | Hereditary hemochromatosis (HH) is one of the most common genetically transmitted conditions in individuals of Northern European ancestry. The disease is characterized by excessive intestinal absorption of dietary iron, resulting in pathologically high iron storage in tissues and organs |
Oligodendrogliomas are primary human brain tumors with a characteristic 1p/19q co-deletion of important prognostic relevance, but little is known about the pathology of this chromosomal mutation. We developed a network-based approach to identify novel cancer gene candidates in the region of the 1p/19q co-deletion. Gene... | The 1p19q co-deletion is associated with what types of tumors? | Oligodendrogliomas are primary human brain tumors with a characteristic 1p/19q co-deletion of important prognostic relevance, but little is known about the pathology of this chromosomal mutation. |
Sorting nexin 27 (SNX27) is a 62-kDa protein localized to early endosomes and known to regulate the intracellular trafficking of ion channels and receptors. In addition to a PX domain, SNX27 is the only sorting family member that contains a PDZ domain. To identify novel SNX27-PDZ binding partners, we performed a proteo... | What are the functions of sorting nexin 27? | Sorting nexin 27 (SNX27) is a 62-kDa protein localized to early endosomes and known to regulate the intracellular trafficking of ion channels and receptors. |
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