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These data suggest that low FT3 levels are not predictive for mortality in a subgroup of stable HD patients who could survive more than 12 months. | Is low T3 syndrome a prognostic marker in patients with renal insufficiency? | These data suggest that low FT3 levels are not predictive for mortality in a subgroup of stable HD patients who could survive more than 12 months. |
Fusobacterium necrophorum is a gram-negative anaerobic bacterium that is the causative agent of the invasive disease Lemierre's syndrome. In addition, it is also associated with peritonsillar abscess formation and otitis media in small children. Recent research has shown that F. necrophorum may be involved in pharyngot... | Is fusobacterium associated with Lemierre's syndrome? | Fusobacterium necrophorum is a gram-negative anaerobic bacterium that is the causative agent of the invasive disease Lemierre's syndrome. |
Cryptic unstable transcripts (CUTs) are rapidly degraded by the nuclear exosome. However, the mechanism by which they are recognized and targeted to the exosome is not fully understood. Here we report that the MTREC complex, which has recently been shown to promote degradation of meiotic mRNAs and regulatory ncRNAs, is... | Which proteins control the degradation of cryptic unstable transcripts (CUTs) in yeast? | The MTREC complex specifically binds to CUTs, meiotic mRNAs and unspliced pre-mRNA transcripts and targets these RNAs for degradation by the nuclear exosome, while the TRAMP complex has only a minor role in this process |
Low efficiency of gene transfer is the main obstacle for a clinically effective gene therapy at the level of the pluripotent hematopoietic stem cell. Another important aspect of stem cell gene therapy, the actual expression of the transduced genes, has only been investigated adequately in very few studies, mainly for g... | Why are insulators necessary in gene therapy vectors? | We propose the incorporation of chromatin insulators in the design of gene therapy vectors to overcome the problem of position effects. Chromatin insulators are protein-binding DNA elements that lack intrinsic promoter/enhancer activity but shelter genes from transcriptional influence of surrounding chromatin. |
Glucocorticoids (GCs) are widely used to treat acute graft-versus-host disease (aGvHD) due to their immunosuppressive activity, but they also reduce the beneficial graft-versus-leukemia (GvL) effect of the allogeneic T cells contained in the graft. Here, we tested whether aGvHD therapy could be improved by delivering G... | What is the mode of action of dexamethasone? | Glucocorticoids (GCs) are widely used to treat acute graft-versus-host disease (aGvHD) due to their immunosuppressive activity, but they also reduce the beneficial graft-versus-leukemia (GvL) effect of the allogeneic T cells contained in the graft. |
Circadian clock genes regulate 10-15% of the transcriptome, and might function as tumor suppressor genes. Relatively little is known about the circadian clock in tumors and its effect on surrounding healthy tissues. Therefore, we compared the 24-hr expression levels of key circadian clock genes in liver and kidney of h... | List core circadian clock genes. | Expression levels of five clock genes (Rev-Erbα, Per1, Per2, Bmal1 and Cry1) |
Sox proteins are transcriptional regulators with a high-mobility-group domain as sequence-specific DNA-binding domain. For function, they generally require other transcription factors as partner proteins. Sox proteins furthermore affect DNA topology and may shape the conformation of enhancer-bound multiprotein complexe... | Which transcription factors are essential for the melanocyte lineage? | In melanocytes, studies have so far focused on the Sox10 protein which functions both during melanocyte specification and at later times in the melanocyte lineage. |
Use of gene therapy for heart failure is gaining momentum as a result of the recent successful completion of phase II of the Calcium Upregulation by Percutaneous Administration of Gene Therapy in Cardiac Disease (CUPID) trial, which showed clinical safety and efficacy of an adeno-associated viral vector expressing sarc... | Which genes have been proposed as potential candidates for gene therapy of heart failure? | Use of gene therapy for heart failure is gaining momentum as a result of the recent successful completion of phase II of the Calcium Upregulation by Percutaneous Administration of Gene Therapy in Cardiac Disease (CUPID) trial, which showed clinical safety and efficacy of an adeno-associated viral vector expressing sarc... |
Given the limited efficacy and potential disadvantages of erythropoiesis-stimulating agents (ESAs) in treating anemia of chronic kidney disease (CKD), the development of better alternative therapies has become a priority. The primary purpose of this study is to investigate the effects of polysaccharide (ASP) and its u... | Is the TFR1 gene dispensable for erythropoiesis? | The restoration of EPO production and EPOR mRNA expression with ASP treatment activated EPOR downstream JAK2/STAT5 and PI3K/Akt signaling, induced their target genes, such as Bcl-xL, Fam132b and Tfrc, and increased Bcl-2/Bax ratio in bone marrow-derived mononuclear cells of CKD rats. |
Peginesatide, a polyethylene glycol (PEG)ylated peptide-based erythropoiesis-stimulating agent, stimulates the erythropoietin receptor dimer that governs erythropoiesis. Studies were designed to determine the erythropoietic response, pharmacokinetics (PK), tissue distribution, metabolism, and excretion of peginesatide ... | What is the mechanism of action of peginesatide? | Peginesatide, a polyethylene glycol (PEG)ylated peptide-based erythropoiesis-stimulating agent, stimulates the erythropoietin receptor dimer that governs erythropoiesis. |
Epithelial-mesenchymal transition (EMT) has recently been studied to elucidate mechanisms of the liver metastatic process. We investigated EMT in the process of liver metastasis and the effects of chemotherapy on EMT cells as therapeutic strategy for colorectal liver metastasis. We used the CT26 murine colorectal carci... | Is c-met involved in the activation of the Akt pathway? | HGF mediated both ERK and Akt phosphorylation. |
We propose that DMT1 deficiency negatively affects metabolism and life span of mature erythrocytes; two other aspects of defective erythropoiesis which contribute to the pathophysiology of the disease. | Could divalent metal transporter 1 deficiency lead to anemia? | We propose that DMT1 deficiency negatively affects metabolism and life span of mature erythrocytes; two other aspects of defective erythropoiesis which contribute to the pathophysiology of the disease. |
Fanconi anemia (FA), an autosomal recessive disorder characterized by a progressive pancytopenia associated with congenital anomalies and high predisposition to malignancies, is a genetically and clinically heterogeneous disease. At least eight complementation groups (FA-A to FA-H) have been identified. Previously, we ... | Is Fanconi anemia presented as a genetically and clinically heterogeneous disease entity? | Fanconi anemia (FA), an autosomal recessive disorder characterized by a progressive pancytopenia associated with congenital anomalies and high predisposition to malignancies, is a genetically and clinically heterogeneous disease. |
Uterine leiomyomas represent the most common form of benign gynecological tumors affecting 20-40% of women during their life. Several therapeutic options are available for treating these patients. The use of medical treatment for myomas has largely grown in the last years, in particular for women who would refuse, post... | Which disease can be treated with Relugolix. | Relugolix is an orally active nonpeptide GnRH-ant, recently licensed for marketing in Japan for the treatment of symptoms related to uterine myomas. |
Epithelial ovarian cancer (EOC) is one of the leading causes of cancer deaths in women worldwide. Ubiquitin-conjugating enzyme 9 (Ubc9), the sole conjugating enzyme for sumoylation, regulates protein function and plays an important role in sumoylation-mediated cellular pathways. Although sumoylation plays a key role in... | What is the role of the UBC9 enzyme in the protein sumoylation pathway? | Ubiquitin-conjugating enzyme 9 (Ubc9), the sole conjugating enzyme for sumoylation, regulates protein function and plays an important role in sumoylation-mediated cellular pathways. |
Asbestos exposure causes asbestosis and malignant mesothelioma, disorders which remain difficult to cure. We focused on alveolar macrophages (AM) and natural killer (NK) cells in asbestosis and mesothelioma, respectively, and examined their functions upon exposure to asbestos or in patients with mesothelioma. Exposure ... | Is mesothelioma caused by asbestos exposure? | Asbestos exposure causes asbestosis and malignant mesothelioma, disorders which remain difficult to cure. |
Drug and alcohol abuse continue to be commonly encountered problems in most patient populations. To deal effectively with these problems, the primary care physician must have a thorough knowledge of the pharmacology of commonly abused drugs and the adjunctive agents used in treatment. Management of alcoholism may invol... | Which medication should be administered when managing patients with suspected acute opioid overdose? | Management of opioid overdose, whether illicit or iatrogenic, requires the prompt and skillful use of opioid overdose, whether illicit or iatrogenic, requires the prompt and skillful use of opioid antagonists. |
In vitro selection of nucleic acid binding species (aptamers) is superficially similar to the immune response. Both processes produce biopolymers that can recognize targets with high affinity and specificity. While antibodies are known to recognize the sequence and conformation of protein surface features (epitopes), v... | What is the role of peptide aptamers? | Moreover, the aptamers appeared to be able to bind peptides with different solution conformations, implying an induced fit mechanism for binding. |
Background Exploding head syndrome (EHS) is characterized by loud noises or a sense of explosion in the head during sleep transitions. Though relatively common, little is known about its characteristic symptoms or associated features. Methods A cross-sectional study of 49 undergraduates with EHS was performed. A clinic... | Is there a disease or condition called Exploding Head Syndrome? | Exploding head syndrome (EHS) is characterized by loud noises or a sense of explosion in the head during sleep transitions. |
Signaling photoreceptors mediate diverse organismal adaptations in response to light. As light-gated protein switches, signaling photoreceptors provide the basis for optogenetics, a term that refers to the control of organismal physiology and behavior by light. We establish as novel optogenetic tools the plasmids pDusk... | Optogenetics refers to the study of gene expression optimization | As light-gated protein switches, signaling photoreceptors provide the basis for optogenetics, a term that refers to the control of organismal physiology and behavior by light. |
Expression of the programmed death-1 (PD-1) ligand 1 (PD-L1) is used to select patients and analyze responses to anti-PD-1/L1 antibodies. The expression of PD-L1 is regulated in different ways, which leads to a different significance of its presence or absence. PD-L1 positivity may be a result of genetic events leading... | What is the difference between PD-1 and PD-L1? | Expression of the programmed death-1 (PD-1) ligand 1 (PD-L1) is used to select patients and analyze responses to anti-PD-1/L1 antibodies. |
The protein of the gustavus (gus) gene has a typical SOCS box domain and repeats in the splA and RyR (SPRY) domains. GUS can interact with Vasa and is necessary for the specification of germ cells. We cloned two zebrafish genes, SSB-1 and SSB-4 (SPRY domain SOCS box proteins). Phylogenetic analysis shows that zebrafish... | What are the biological roles proposed for proteins containing the SPRY domain? | We hypothesize that SSB-4 plays a role in the early development of germ cells |
Hakaru Hashimoto described 4 patients with a hitherto unknown cause for goitre, struma lymphomatosa, a century ago. He was careful to distinguish this from Riedel thyroiditis but it has become clear that fibrosis and atrophy of the thyroid are indeed components of Hashimoto thyroiditis, and in rare cases IgG4-related s... | Which antibodies cause Riedel thyroiditis? | He was careful to distinguish this from Riedel thyroiditis but it has become clear that fibrosis and atrophy of the thyroid are indeed components of Hashimoto thyroiditis, and in rare cases IgG4-related sclerosing disease may be an outcome. |
Hutchinson-Gilford progeria syndrome (HGPS) is a rare but well known entity characterized by extreme short stature, low body weight, early loss of hair, lipodystrophy, scleroderma, decreased joint mobility, osteolysis, and facial features that resemble aged persons. Cardiovascular compromise leads to early demise. Cogn... | Is progeria caused by an autosomal recessive gene? | Pattern of inheritance of non-classical progeria is most probably autosomal recessive. |
In a double-blind placebo-controlled prospective clinical trial we studied the efficacy and safety of the benzodiazepine antagonist, flumazenil. In 23 patients admitted to the Intensive Care Unit with coma due to overdose with benzodiazepines or other sedatives, flumazenil i.v. (up to 2 mg or placebo) was given. In 13 ... | Which drug should be used as an antidote in benzodiazepine overdose? | In 23 patients admitted to the Intensive Care Unit with coma due to overdose with benzodiazepines or other sedatives, flumazenil i.v. (up to 2 mg or placebo) was given. In 13 patients given flumazenil the Glasgow Coma Scale (GCS) increased significantly from 4.9 to 7.8 (p less than 0.05). Six of these 13 patients, incl... |
Mammalian target of rapamycin (mTOR) complex 1 (mTORC1) is an important, highly conserved, regulator of cell growth. Ancient among the signals that regulate mTORC1 are nutrients. Amino acids direct mTORC1 to the surface of the late endosome/lysosome, where mTORC1 becomes receptive to other inputs. However, the interpla... | Which transcription factor is considered as a master regulator of lysosomal genes? | These data uncover a regulatory network linking an oncogenic transcription factor that is a master regulator of lysosomal biogenesis, TFEB, to mTORC1 and endocytosis. |
Septins are guanosine-5'-triphosphate-binding proteins involved in wide-ranging cellular processes including cytokinesis, vesicle trafficking, membrane remodelling and scaffolds, and with diverse binding partners. Precise roles for these structural proteins in most processes often remain elusive. Identification of smal... | What are Septins? | Septins are guanosine-5'-triphosphate-binding proteins involved in wide-ranging cellular processes including cytokinesis, vesicle trafficking, membrane remodelling and scaffolds, and with diverse binding partners |
Alpha-synuclein (a-syn) can aggregate and form toxic oligomers and insoluble fibrils which are the main component of Lewy bodies. Intra-neuronal Lewy bodies are a major pathological characteristic of Parkinson's disease (PD). These fibrillar structures can act as seeds and accelerate the aggregation of monomeric a-syn.... | Please summarize the relationship between a-syn and cell death. | Alpha-synuclein (a-syn) can aggregate and form toxic oligomers and insoluble fibrils which are the main component of Lewy bodies. Intra-neuronal Lewy bodies are a major pathological characteristic of Parkinson's disease (PD). These fibrillar structures can act as seeds and accelerate the aggregation of monomeric a-syn.... |
Chronic wasting disease (CWD) is a fatal, emerging disease of cervids associated with transmissible protease-resistant prion proteins. The potential for CWD to cause dramatic declines in deer and elk populations and perceived human health risks associated with consuming CWD-contaminated venison have led wildlife agenci... | What is Chronic Wasting Disease (CWD) in deer? | Chronic wasting disease (CWD) is a fatal, emerging disease of cervids associated with transmissible protease-resistant prion proteins. |
The sarcoplasmic reticulum calcium pump (SERCA) and its regulator, phospholamban, are essential components of cardiac contractility. Phospholamban modulates contractility by inhibiting SERCA, and this process is dynamically regulated by β-adrenergic stimulation and phosphorylation of phospholamban. Herein we reveal mec... | Which protein kinases have been found to phosphorylate Phospholamban and affect its biological activity? | Deletion of Arg(14) disrupts the protein kinase A recognition motif, which abrogates phospholamban phosphorylation and results in constitutive SERCA inhibition. |
AMPK is a highly conserved sensor of cellular energy status that is activated under conditions of low intracellular ATP. AMPK responds to energy stress by suppressing cell growth and biosynthetic processes, in part through its inhibition of the rapamycin-sensitive mTOR (mTORC1) pathway. AMPK phosphorylation of the TSC2... | Under which conditions does AMPK phosphorylate TSC2? | AMPK phosphorylation of the TSC2 tumor suppressor contributes to suppression of mTORC1; however, TSC2-deficient cells remain responsive to energy stress. |
Several neurodegenerative diseases such as transmissible spongiform encephalopathies, Alzheimer's and Parkinson's diseases are caused by the conversion of cellular proteins to a pathogenic conformer. Despite differences in the primary structure and subcellular localization of these proteins, which include the prion pro... | What are prions? | Several neurodegenerative diseases such as transmissible spongiform encephalopathies, Alzheimer's and Parkinson's diseases are caused by the conversion of cellular proteins to a pathogenic conformer. |
To date, there have been a limited number of useful biomarkers for the screening and monitoring of B-cell non-Hodgkin's lymphoma (B-NHL), which leads to the impetus to discover novel biomarkers for the disease. In the present study, gas chromatography-mass spectrometry (GC-MS) combined with head-space solid-phase micro... | List blood marker for Non-Hodgkin lymphoma. | To date, there have been a limited number of useful biomarkers for the screening and monitoring of B-cell non-Hodgkin's lymphoma (B-NHL), which leads to the impetus to discover novel biomarkers for the disease. |
Factor V Leiden is a well-recognized etiology of venous thrombosis, but reports of stroke in patients with this mutation are few. Marijuana smoking has rarely been associated with thrombosis of cerebral and renal arteries and may be due to a direct toxic effect on the endothelium. Reported here is the case of a previou... | Is marijuana use associated with increased risk for stroke? | Reported here is the case of a previously healthy young man who smoked marijuana on a daily basis and had an occipital lobe stroke; he was found to be heterozygous for factor V Leiden. |
Interleukin-1β (IL-1β) is a key orchestrator in inflammatory and several immune responses. IL-1β exerts its effects through interleukin-1 receptor type I (IL-1RI) and interleukin-1 receptor accessory protein (IL-1RAcP), which together form a heterotrimeric signaling-competent complex. Canakinumab and gevokizumab are hi... | Which molecule is targeted by the drug Gevokizumab? | Canakinumab and gevokizumab are highly specific IL-1β monoclonal antibodies |
Angiogenesis is regulated by the highly coordinated function of various proteins with pro- and antiangiogenic functions. Proangiogenic factors include vascular endothelial growth factor (VEGF), fibroblast growth factor, platelet-derived growth factor, insulin-like growth factor, transforming growth factor, angiopoietin... | Is endostatin a proangiogenic factor? | antiangiogenic factors include thrombospondin-1, angiostatin, and endostatin |
This study evaluated the correlation and agreement between the Bispectral Index (BIS) or A-line Autoregressive Index (AAI) and a clinical scoring system, the Ramsay Sedation Scale (RSS), in 40 patients after elective cardiac surgery and admission to the intensive care unit. All patients received sedation with propofol ... | Is Propofol used for short-term sedation? | All patients received sedation with propofol according to the study protocol. |
Scoring functions are a critically important component of computer-aided screening methods for the identification of lead compounds during early stages of drug discovery. Here, we present a new multigrid implementation of the footprint similarity (FPS) scoring function that was recently developed in our laboratory whic... | List programs suitable for protein docking | the method yields improved success over the standard DOCK energy function for pose identification across a large test set of experimental co-crystal structures, for crossdocking, and for database enrichment |
The postnatal functions of the Dlx1&2 transcription factors in cortical interneurons (CINs) are unknown. Here, using conditional Dlx1, Dlx2, and Dlx1&2 knockouts (CKOs), we defined their roles in specific CINs. The CKOs had dendritic, synaptic, and survival defects, affecting even PV+ CINs. We provide evidence that DLX... | Is there any role of Dlx1 and Dlx2 transcription factors in cortical interneurons? | Furthermore, Dlx1/2 CKO had hypoplastic dendrites, fewer excitatory synapses, and reduced excitatory input. |
Unlike the Peyer's patches of rats and mice, which are considered to be secondary lymphoid organs, the ileal Peyer's patch of sheep is thought to be responsible for the primary generation of B cells, like the bursa of Fabricius of birds. The ileal Peyer's patch of sheep shows prenatal maturation, antigen-independent ly... | Where is the body would the Peyer's patches be found | The jejunal Peyer's patches are devoid of CAP, persist in the adult animal, contain M cells with clusters of B cells in the follicle-associated epithelium, and have many CD4+ lymphocytes in the follicles and in the interfollicular areas. |
The clinical significance of tumor-infiltrating immune cells has been reported in a variety of human carcinomas including breast cancer. However, molecular signature of tumor-infiltrating immune cells and their prognostic value in breast cancer patients remain elusive. We hypothesized that a distinct network of immune ... | Which diseases can Oncotype DX be used for? | We hypothesized that a distinct network of immune function genes at the tumor site can predict a low risk versus high risk of distant relapse in breast cancer patients regardless of the status of ER, PR, or HER-2/neu in their tumors. |
Staphylococcus epidermidis is a frequent pathogen in infections associated with orthopedic implants. We studied 123 S. epidermidis strains from infections related to orthopedic implants, as regards their ability to express a factor of virulence, namely the slime, an extracellular polysaccharide, which mediates adherenc... | What is Congo red agar plates used for? | by culture on Congo red agar plates in which slime-producing strains form black colonies, while nonslime-forming ones develop red colonies. |
A substantial proportion of Ashkenazi Jewish (AJ) breast and ovarian cancer families carry one of three founder mutations in BRCA1 (185delAG, 5382InsC) and BRCA2 (6174delT). Non-founder mutations are identified in another 2-4% of such families. The extent to which major genomic rearrangements in BRCA contribute to brea... | Could BRCA gene test used for breast and ovarian cancer risk? | We identified AJ individuals with breast and/or ovarian cancer undergoing hereditary breast/ovarian cancer risk assessment since 2006 without evidence of a deleterious mutation on BRCA gene sequencing who were screened for major gene rearrangements in BRCA1 and BRCA2. |
Studies of coat color mutants have greatly contributed to the discovery of genes that regulate melanocyte development and function. Here, we generated Yy1 conditional knockout mice in the melanocyte-lineage and observed profound melanocyte deficiency and premature gray hair, similar to the loss of melanocytes in human ... | What is the function of the YY1 transcriptional regulator? | Although YY1 is a ubiquitous transcription factor, YY1 interacts with M-MITF, the Waardenburg Syndrome IIA gene and a master transcriptional regulator of melanocytes. |
Hypertrophic cardiomyopathy (HCM) is a clinically heterogeneous autosomal dominant heart disease characterised by left ventricular hypertrophy in the absence of another cardiac or systemic disease that is capable of producing significant wall thickening. Microscopically it is characterised by cardiomyocyte hypertrophy,... | Which pathological condition of the heart is known as hypertrophic cardiomyopathy (HCM)? | Hypertrophic cardiomyopathy (HCM) is a clinically heterogeneous autosomal dominant heart disease characterised by left ventricular hypertrophy in the absence of another cardiac or systemic disease that is capable of producing significant wall thickening. |
Selective estrogen receptor modulators (SERMs) are compounds that exhibit tissue-specific estrogen receptor (ER) agonist or antagonist activity, and are used for various indications, including treatment of breast cancer, osteoporosis, and menopausal symptoms. Endometrial safety has been a key differentiator between SER... | What is a SERM? | Selective estrogen receptor modulators (SERMs) |
Urea breath testing may provide a useful diagnostic and biomarker assay for tuberculosis and for treatment response. Future work will test specificity for M. tuberculosis using lung-targeted dry powder inhalation formulations, combined with co-administering oral urease inhibitors together with a saturating oral dose of... | What are the breath test biomarkers of pulmonary tuberculosis | Urea breath testing may provide a useful diagnostic and biomarker assay for tuberculosis and for treatment response |
Insights into the circular RNA (circRNA) exploration have revealed that they are abundant in eukaryotic transcriptomes. Diverse genomic regions can generate different types of RNA circles, implying their diversity. Covalently closed loop structures elevate the stability of this new type of noncoding RNA. High-throughpu... | Can a circRNA be translated into protein? | Covalently closed loop structures elevate the stability of this new type of noncoding RNA. |
We have previously shown that mutations in the GGAA core motif of the Ets1 binding site, EBSI, or deletion of EBSI, reduced basal and Tax1 transactivation of the PTHrP P2 promoter. Here we demonstrate that, in addition to EBSI, a CACCC-like motif located between -53 and -58 is required for full basal activity of this p... | Which is the binding site motif of Sp1? | Gel shift competition studies and DNase I footprinting analyses revealed that Sp1 specifically interacts with the CACCC motif |
Members of the 2-aminobenzamide class of histone deacetylase (HDAC) inhibitors show promise as therapeutics for the neurodegenerative diseases Friedreich's ataxia (FRDA) and Huntington's disease (HD). While it is clear that HDAC3 is one of the important targets of the 2-aminobenzamide HDAC inhibitors, inhibition of oth... | For which diseases members of the 2-aminobenzamide class of histone deacetylase (HDAC) inhibitors show promise as therapeutics? | While it is clear that HDAC3 is one of the important targets of the 2-aminobenzamide HDAC inhibitors, inhibition of other class I HDACs (HDACs 1 and 2) may also be involved in the beneficial effects of these compounds in FRDA and HD, and other HDAC interacting proteins may be impacted by the compound. |
Hypertrophic cardiomyopathy (HCM) is a disease that typically has heterogeneous hypertrophy and dysfunction of the myocardium. Cardiac magnetic resonance imaging (CMR) can be used to accurately assess ventricular wall thickness and regional fibrosis. We investigated the effects of hypertrophy and fibrosis on the hetero... | Which is the clinical meaning of the presence of delayed enhancement in patients with hypertrophic cardiomyopathy? | The extent of regional myocardial fibrosis is associated with regional myocardial function independently of morphological changes of the myocardium, and the correlation extended to global LV function. |
Among a large collection of nonsense (termination) suppressors of Saccharomyces cerevisiae, a few remained obscure for their molecular nature. Of those, a group of weak and recessive suppressors, sup111, sup112 and sup113, is of particular interest because of their dependency on [PSI+], a yeast prion. From the facts th... | Which are the main NMD factors in Saccharomyces cerevisiae? | From these results, we conclude that sup111, sup112 and sup113 are mutant alleles of UPF2, UPF3 and UPF1, respectively, and thus attribute suppressor activity of these mutations to defects in the NMD (nonsense-mediated mRNA decay) machinery. |
A chemical screen designed to identify novel inducers of autophagy led to the discovery that signal transducer and activator of transcription 3 (STAT3) inhibitors can potently stimulate the autophagic flux. Although STAT3 is best known as a pro-inflammatory and oncogenic transcription factor, mechanistic analyses revea... | Is STAT3 involved in EIF2AK2-dependent suppression of autophagy? | A further screen designed to identify EIF2AK2-dependent autophagy inducers revealed that several fatty acids including palmitate trigger autophagy via a pathway that involves the disruption of the STAT3-EIF2AK2 complex |
Forty years after the publication of a landmark paper by the Ad Hoc Committee of the Harvard Medical School, the general concept of brain death has achieved widespread acceptance. In the United States, irreversible dysfunction of the brain and brainstem are required for the diagnosis of brain death. Although primarily ... | What are the main clinical components of the brain death exam? | Nonetheless, on occasion patients clinically diagnosed with brain death will exhibit persistent intracranial blood flow or electrical activity. |
JAK2, CALR, and MPL are myeloproliferative neoplasm (MPN)-driver mutations, whereas SF3B1 is strongly associated with ring sideroblasts (RS) in myelodysplastic syndrome (MDS). Concomitant mutations of SF3B1 and MPN-driver mutations out of the context of MDS/MPN with RS and thrombocytosis (MDS/MPN-RS-T) are not well-stu... | Which disease is caused by mutations in the gene CALR? | JAK2, CALR, and MPL are myeloproliferative neoplasm (MPN)-driver mutations, |
The use of several translation initiation codons in a single mRNA, by expressing several proteins from a single gene, contributes to the generation of protein diversity. A small, yet growing, number of mammalian mRNAs initiate translation from a non-AUG codon, in addition to initiating at a downstream in-frame AUG codo... | Do all proteins start with methionine? | The use of several translation initiation codons in a single mRNA, by expressing several proteins from a single gene, contributes to the generation of protein diversity. A small, yet growing, number of mammalian mRNAs initiate translation from a non-AUG codon, in addition to initiating at a downstream in-frame AUG codo... |
Amblyopia is defined as the reduction of best-corrected visual acuity of one or both eyes caused by conditions that affect normal visual development. The basic strategy to treat amblyopia is to obtain a clear retinal image in each eye and correct ocular dominance through forced use of the amblyopic eye. Treatment modal... | Does Amblyopia affect the eye? | Amblyopia is defined as the reduction of best-corrected visual acuity of one or both eyes caused by conditions that affect normal visual development |
Early developmental conditions, including prenatal testosterone seem to play a role on the malignant transformation of gastric lesions. The 2D:4D pattern found for gastric cancer parallels that earlier described for breast cancer. The findings suggest that 2D:4D could add to the list of etiological factors and be a put... | What is known about the Digit Ratio (2D:4D) cancer? | The 2D:4D pattern found for gastric cancer parallels that earlier described for breast cancer. |
In the developing central nervous system (CNS), Notch signaling preserves progenitor pools and inhibits neurogenesis and oligodendroglial differentiation. It has recently been postulated that Notch instructively drives astrocyte differentiation. Whether the role of Notch signaling in promoting astroglial differentiatio... | Which proteins participate in the formation of the Notch transcriptional activation complex? | We report here that the astrogliogenic role of Notch is in part mediated by direct binding of the Notch intracellular domain to the CSL DNA binding protein, forming a transcriptional activation complex onto the astrocyte marker gene, glial fibrillary acidic protein (GFAP). |
Coal workers' pneumoconiosis is a preventable occupational disorder of the respiratory system resulting from exposure to and retention of respirable coal dust. It exists in two distinguishable forms: simple, which is seldom if ever disabling, and complicated, also known as progressive massive fibrosis (PMF), which is s... | What causes Black Lung? | Coal workers' pneumoconiosis is a preventable occupational disorder of the respiratory system resulting from exposure to and retention of respirable coal dust. |
Human coronavirus (HCoV) infection causes respiratory diseases with mild to severe outcomes. In the last 15 years, we have witnessed the emergence of two zoonotic, highly pathogenic HCoVs: severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). Replication o... | Please list 2 human diseases caused by a coronavirus. | In the last 15 years, we have witnessed the emergence of two zoonotic, highly pathogenic HCoVs: severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). |
Sequence logos have been widely used as graphical representations of conserved nucleic acid and protein motifs. Due to the complexity of the amino acid (AA) alphabet, rich post-translational modification, and diverse subcellular localization of proteins, few versatile tools are available for effective identification an... | Which R/Bioconductor package has been developed for visualizing differential amino acid group usage in proteomics? | Sequence logos have been widely used as graphical representations of conserved nucleic acid and protein motifs. Due to the complexity of the amino acid (AA) alphabet, rich post-translational modification, and diverse subcellular localization of proteins, few versatile tools are available for effective identification an... |
We report on an Italian boy with the Meier-Gorlin syndrome (ear-patella-short stature syndrome). This rare autosomal recessive disorder comprises the triad of microtia, absent patellae, and growth retardation with prenatal onset. The patient had also an acute torsion of his left spermatic cord, a condition related to a... | Which are the characteristics of the Meier-Gorlin syndrome? | We report on an Italian boy with the Meier-Gorlin syndrome (ear-patella-short stature syndrome). |
The results of cerebrospinal fluid agarose gel electrophoresis in 300 consecutive patients were correlated with neurological examinations and diagnoses, other cerebrospinal fluid studies, and the results of evoked potential examinations. The presence of oligoclonal bands was the most sensitive test for multiple scleros... | What is the most sensitive test for the diagnosis of multiple sclerosis? | These results indicate that the presence of oligoclonal bands provides sensitive supporting evidence for the diagnosis of MS but that bands may be present in other disorders, including those not directly related to infection or abnormal immune response. The data suggest that oligoclonal bands may represent an immune re... |
Use of oral corticosteroids in patients on long-term warfarin therapy may result in a clinically significant interaction, which requires close INR monitoring and possible warfarin dose reduction. | Please list 7 classes of drugs that interact with Warfarin. | Use of oral corticosteroids in patients on long-term warfarin therapy may result in a clinically significant interaction, which requires close INR monitoring and possible warfarin dose reduction. |
Mitochondrial (mt)DNA mutations contribute to various disease states characterized by low ATP production. In contrast, thyroid hormone [3,3',5-triiodothyronine (T(3))] induces mitochondrial biogenesis and enhances ATP generation within cells. To evaluate the role of T(3)-mediated mitochondrial biogenesis in patients wi... | How does thyroid hormone regulate mitochondrial biogenesis in the myocardium? | T(3) acts to reduce cellular oxidative stress, which may help attenuate ROS-mediated damage, along with improving mitochondrial function and energy status in cells with mtDNA defects. |
MicroRNAs (miRNAs) are a family of 19-24 nucleotide noncoding RNAs (ncRNAs) with posttranscriptional regulatory functions. Increasing evidences from the literature show that miRNAs play a pivotal role in human tumorigenesis. Many studies have addressed the role of miRNAs in normal hematopoiesis, giving an interpretativ... | Are transcribed ultraconserved regions involved in cancer? | Moreover, the recent demonstration that other ncRNAs, the ultraconserved genes (UCGs) or transcribed ultraconserved regions (T-UCRs), are involved in human cancerogenesis, suggests that the wider family of ncRNAs (including both miRNAs and UCGs) could contribute to the development of the malignant phenotype. |
Dengue and West Nile viruses are enveloped RNA viruses that belong to genus Flavivirus (family Flaviviridae) and are considered important mosquito-borne viral pathogenic agents worldwide. A potential target for intervention strategies is the virus cell entry mechanism. Previous studies of flavivirus entry have focused ... | How Flaviviridae family of viruses infects vertebrates? | West Nile viruses are enveloped RNA viruses that belong to genus Flavivirus (family Flaviviridae) and are considered important mosquito-borne viral pathogenic agents worldwide |
Mitochondria play a key role in adaptation during stressing situations. Cardiolipin, the main anionic phospholipid in mitochondrial membranes, is expected to be a determinant in this adaptive mechanism since it modulates the activity of most membrane proteins. Here, we used Saccharomyces cerevisiae subjected to conditi... | Is diphosphatidylglycerol (cardiolipin) a phospholipid of the mitochondrial membranes? | Cardiolipin, the main anionic phospholipid in mitochondrial membranes, is expected to be a determinant in this adaptive mechanism since it modulates the activity of most membrane proteins |
The basic-helix-loop-helix-leucine zipper (bHLHZip) protein MITF (microphthalmia-associated transcription factor) is a master regulator of melanocyte development. Mutations in the MITF have been found in patients with the dominantly inherited hypopigmentation and deafness syndromes Waardenburg syndrome type 2A (WS2A) a... | Which mutated gene is associated with Waardenburg and Tietz syndromes? | Mutations in the MITF have been found in patients with the dominantly inherited hypopigmentation and deafness syndromes Waardenburg syndrome type 2A (WS2A) and Tietz syndrome (TS). |
Chemotherapeutic regimens in present use for recurrent glioma have substantial toxicity. Activity against recurrent gliomas has been reported for both tamoxifen and interferon alpha, agents that have more acceptable toxicity profiles and that can be administered in an outpatient setting. We tested the efficacy and toxi... | Was tamoxifen tested for treatment of glioma patients? | We tested the efficacy and toxicity of the combination of high-dose tamoxifen and interferon alpha in adults with recurrent glioma in a phase II trial. Eligible patients had radiographically measurable recurrent gliomas of any grade after initial radiation therapy. |
The cohesin complex holds sister chromatids together and is essential for chromosome segregation. Recently, cohesins have been implicated in transcriptional regulation and insulation through genome-wide colocalization with the insulator protein CTCF, including involvement at the imprinted H19/Igf2 locus. CTCF binds to ... | Where does CTCF colocalize with cohesin? | Results of these experiments demonstrate an unappreciated role for CTCF and cohesins in the repression of imprinted genes in somatic cells. |
Mediator is a highly conserved transcriptional coactivator organized into four modules, namely Tail, Middle, Head, and Kinase (CKM). Previous work suggests regulatory roles for Tail and CKM, but an integrated model for these activities is lacking. Here, we analyzed the genome-wide distribution of Mediator subunits in w... | Which is the role of mediator in genome organization? | Collectively, our data suggest that the essential function of Mediator is mediated by Head and Middle at core promoters, while Tail and CKM play regulatory roles. |
During neurogenesis, neural patterning is a critical step during which neural progenitor cells differentiate into neurons with distinct functions. However, the molecular determinants that regulate neural patterning remain poorly understood. Here we optimized the "dual SMAD inhibition" method to specifically promote dif... | Which is the main difference in the roles of Otx2 and Nanog during development? | Our findings have uncovered a mutual antagonism between NANOG and OTX2 underlying cell fate decisions during neural patterning, critical for the regulation of early neural development in humans. |
Delayed hypersensitivity disorders and food allergies are often challenging for the clinician and patient alike. A recent discovery of an IgE antibody specific to galactose-α-1,3-galactose, which is a carbohydrate abundantly expressed on cells and tissues of beef, pork, and lamb, adds one more tool to aid the clinician... | A bite from the Lone Star Tick Amblyomma americanum, can cause the victim to become allergic to red meat, yes or no? | A recent discovery of an IgE antibody specific to galactose-α-1,3-galactose, which is a carbohydrate abundantly expressed on cells and tissues of beef, pork, and lamb, adds one more tool to aid the clinician in making the appropriate diagnosis. A link has been discovered between the bite of the Lone Star Tick (Amblyomm... |
Discovered in 2003 at the Royal Veterinary College, London, canine respiratory coronavirus (CRCoV) is a betacoronavirus of dogs and major cause of canine infectious respiratory disease complex. Generally causing mild clinical signs of persistent cough and nasal discharge, the virus is highly infectious and is most prev... | Covid-19 is though to have arisen from what species? | o other betacoronaviruses, SARS-CoV-2 appears to have crossed the species barrier, most likely from bats, clearly reinforcing the One Health concept. Veterinary |
Secondary brain tumors rarely arise after cranial irradiation; among them, meningiomas and glioblastomas are the most common and secondary oligodendroglial tumors the most rare. We present a 48-year-old man who developed an oligodendroglial tumor 38 years after receiving 50 Gy of cranial irradiation to a pineal tumor. ... | Can secondary glioblastoma be caused by brain irradiation? | Secondary brain tumors rarely arise after cranial irradiation; among them, meningiomas and glioblastomas are the most common and secondary oligodendroglial tumors the most rare. |
mTOR complex 2 (mTORC2) signaling is upregulated in multiple types of human cancer, but the molecular mechanisms underlying its activation and regulation remain elusive. Here, we show that microRNA-mediated upregulation of Rictor, an mTORC2-specific component, contributes to tumor progression. Rictor is upregulated via... | List the components of mTOR Complex 2 (mTORC2). | Rictor, an mTORC2-specific component |
Burning mouth syndrome (BMS) is a chronic oral pain or burning sensation affecting the oral mucosa, often unaccompanied by mucosal lesions or other evident clinical signs. It is observed principally in middle-aged patients and postmenopausal women and may be accompanied by xerostomia and altered taste. Burning mouth sy... | What is Burning Mouth Syndrome(BMS)? | Burning mouth syndrome (BMS) is a chronic oral pain or burning sensation affecting the oral mucosa, often unaccompanied by mucosal lesions or other evident clinical signs. |
This phase II study provides clear evidence of the safety and efficacy of oxaliplatin monotherapy at this dose and schedule in patients with previously untreated metastatic colorectal carcinoma. | What is the efficacy of oxaliplatin monotherapy in the management of colorectal cancer? | This phase II study provides clear evidence of the safety and efficacy of oxaliplatin monotherapy at this dose and schedule in patients with previously untreated metastatic colorectal carcinoma |
There have been extensive observations that RNA containing repetitive elements accumulates in transformed cells and tumor tissues. In the present study, we first obtained result consistent with previous observations by in situ hybridization. Then we used primer extension analysis to determine the level of polymerase II... | Are Alu elements transcribed? | Then we used primer extension analysis to determine the level of polymerase III directed Alu RNA and found an increased expression of Alu RNA in hepatocellular carcinoma |
The single cell-based 3D organoid system may serve as a highly efficient platform to explore cancer therapeutics and therapy resistance mechanisms in conjunction with morphological and functional assays with implications for translation in personalized medicine. | What is an organoid? | The single cell-based 3D organoid system may serve as a highly efficient platform to explore cancer therapeutics and therapy resistance mechanisms in conjunction with morphological and functional assays with implications for translation in personalized medicine. |
In CKD patients with proteinuria, low T3 concentration predicted all-cause mortality and cardiovascular event independently of the severity of proteinuria. | Is low T3 syndrome a prognostic marker in patients with renal insufficiency? | In CKD patients with proteinuria, low T3 concentration predicted all-cause mortality and cardiovascular event independently of the severity of proteinuria. |
While there have been numerous advances in the field of non-Hodgkin lymphoma (NHL) over the last decade, relapsed and/or refractory (R/R) NHL remains a challenge and an area with unmet needs. T-cell redirecting immunotherapeutic approaches including chimeric antigen receptor (CAR) T-cells and bispecific antibodies (BsA... | What are the targets of Mosunetuzumab? | However, several CD20 × CD3 BsAbs including odronextamab, mosunetuzumab, glofitamab, and epcoritamab emerged recently. |
Although more than 100 different types of RNA modifications have been characterized across all living organisms, surprisingly little is known about the modified positions and their functions. Recently, various high-throughput modification sequencing methods have been developed to identify diverse post-transcriptional m... | List RNA modifications databases | we developed a novel resource, RMBase (RNA Modification Base, http://mirlab.sysu.edu.cn/rmbase/), to decode the genome-wide landscape of RNA modifications identified from high-throughput modification data generated by 18 independent studies. |
Epigenetics is defined as mitotically and meiotically heritable changes in gene expression that do not involve a change in the DNA sequence. Two major areas of epigenetics-DNA methylation and histone modifications-are known to have profound effects on controlling gene expression. DNA methylation is involved in normal c... | Are epigenetic changes heritable? | Epigenetics is defined as heritable changes in gene expression that do not involve a change in DNA sequence. |
X-linked myotubular myopathy (XLMTM) is a congenital muscular disease characterized by severe hypotonia and generalized muscle weakness, leading in most cases to early postnatal death. The gene responsible for the disease, MTM1, encodes a dual specificity phosphatase, named myotubularin, which is highly conserved throu... | Which gene test can be used for the X-linked myotubular myopathy? | X-linked myotubular myopathy (XLMTM) is a congenital muscular disease characterized by severe hypotonia and generalized muscle weakness, leading in most cases to early postnatal death. The gene responsible for the disease, MTM1, encodes a dual specificity phosphatase, named myotubularin, which is highly conserved throu... |
Internationally adopted children often present diseases contracted in the country of origin. Skin diseases are common in new arrivals, and diagnosis may prove challenging for GPs or even dermatologists if they are inexperienced in the extensive geographic and ethnic diversity of international adoptees. To analyse the f... | What disease is tinea ? | The most frequent diseases observed at arrival were dermatological conditions. Of the adoptees, 70% presented at least one skin disease, of which 57.5% were infectious; Tinea capitis being the most frequent (n = 42). The recovery rate of Tinea capitis was 89% (n = 32/36). |
Fanconi anemia (FA) is a heterogeneous disease characterized by spontaneous chromosomal breaks and abnormal DNA repair. Major clinical problems in FA include congenital abnormalities, endocrinopathies, early onset bone marrow failure and increased risk of myelodysplastic syndrome, acute leukemia and solid tumors. To da... | Is Fanconi anemia presented as a genetically and clinically heterogeneous disease entity? | Fanconi anemia (FA) is a heterogeneous disease characterized by spontaneous chromosomal breaks and abnormal DNA repair |
The monocarboxylate transporter 8 (MCT8) plays a critical role in mediating the uptake of thyroid hormones (THs) into the brain. In patients, inactivating mutations in the MCT8 gene are associated with a severe form of psychomotor retardation and abnormal serum TH levels. Here, we evaluate the therapeutic potential of ... | Which are the thyroid hormone analogs utilized in human studies? | Here, we evaluate the therapeutic potential of the TH analog 3,5,3',5'-tetraiodothyroacetic acid (tetrac) as a replacement for T(4) in brain development. |
The Disease Activity Score (DAS) is integral in tailoring the clinical management of rheumatoid arthritis (RA) patients and is an important measure in clinical research. Different versions have been developed over the years to improve reliability and ease of use. Combining the original DAS and the newer DAS28 data in b... | What does "28" stand for in the Disease Activity Score DAS28? | DAS were transformed to DAS28 using an existing formula quoted in the literature, and the newly developed formulas. Bland and Altman plots were used to compare the transformed DAS with the recorded DAS28 to ascertain levels of agreement. |
Glutamate transport is coupled to the co-transport of 3Na(+) and 1H(+) and the countertransport of 1 K(+). However, the mechanism of how this process occurs is not well understood. The crystal structure of an archaeal homolog of the human glutamate transporters, Glt(Ph), has provided the framework to begin to understan... | Which are the human glutamate transporters? | First, Li(+) cannot support transport by EAAT2, whereas it can support transport by the other excitatory amino acid transporters, and second, EAAT2 is sensitive to a wider range of blockers than other subtypes. |
Circular RNAs (circRNAs) are involved in the development of various diseases, but there is little knowledge of circRNAs in osteoarthritis (OA). The aim of study was to identify circRNA expression in articular cartilage and to explore the function of chondrocyte extracellular matrix (ECM)-related circRNAs (circRNA-CER) ... | Do circRNAs remain untranslated? | The aim of study was to identify circRNA expression in articular cartilage and to explore the function of chondrocyte extracellular matrix (ECM)-related circRNAs (circRNA-CER) in cartilage. |
Phase III trials showed that bapineuzumab failed to improve cognitive and functional performances in AD patients, and was associated with a high incidence of amyloid-related imaging abnormalities (ARIA). Solanezumab's two Phase III trials in AD patients failed to meet endpoints when analyzed independently. However, ana... | Is bapineuzumab effective for treatment of patients with Alzheimer's disease? | Phase III trials showed that bapineuzumab failed to improve cognitive and functional performances in AD patients, and was associated with a high incidence of amyloid-related imaging abnormalities (ARIA). |
Mechanistic insights into aggrephagy, a selective basal autophagy process to clear misfolded protein aggregates, are lacking. Here, we report and describe the role of Estrogen Related Receptor α (ERRα, HUGO Gene Nomenclature ESRRA), new molecular player of aggrephagy, in keeping autophagy flux in check by inhibiting au... | Is aggrephagy a variant of autophagy? | Mechanistic insights into aggrephagy, a selective basal autophagy process to clear misfolded protein aggregates, |
The mammalian constitutive photomorphogenesis 9 (COP9) signalosome (CSN), a protein complex involved in embryonic development, is implicated in cell cycle regulation and the DNA damage response. Its role in tumor development, however, remains unclear. Here, we have shown that the COP9 subunit 6 (CSN6) gene is amplified... | What is the role of the constitutive photomorphogenesis 9 signalosome (CSN)? | The mammalian constitutive photomorphogenesis 9 (COP9) signalosome (CSN), a protein complex involved in embryonic development, is implicated in cell cycle regulation and the DNA damage response |
The exoribonuclease Xrn1 is widely recognised as a key component in the 5'-3' RNA degradation pathway. This enzyme is highly conserved between yeast and humans and is known to be involved in RNA interference and degradation of microRNAs as well as RNA turnover. In yeast and human tissue culture cells, Xrn1 has been sho... | Is exonuclease Xrn1 a component of the P-bodies? | In this paper we show for the first time that Pacman, the Drosophila homologue of Xrn1, is localized in cytoplasmic particles in Drosophila testis cells. |
Even after adjusting for contact pattern, vaccination status, and waning of vaccine effectiveness, the Omicron variant of SARS-CoV-2 tends to propagate more easily among children than the pre-Omicron strains. | Is COVID-19 caused by the Omicron variant less severe than infection caused by other variants? | Even after adjusting for contact pattern, vaccination status, and waning of vaccine effectiveness, the Omicron variant of SARS-CoV-2 tends to propagate more easily among children than the pre-Omicron strains. |
Tuberous Sclerosis Complex (TSC) is a multisystem genetic disorder caused by mutation in either Tsc1 or Tsc2 genes that leads to the hyper activation of the mTOR pathway, a key signalling pathway for synaptic plasticity. TSC is characterized by benign tumors arising in different organs and severe neuropsychiatric sympt... | Which signalling pathway is involved in Tuberous Sclerosis? | Tuberous Sclerosis Complex (TSC) is a multisystem genetic disorder caused by mutation in either Tsc1 or Tsc2 genes that leads to the hyper activation of the mTOR pathway, a key signalling pathway for synaptic plasticity. |
The highly specific induction of RNA interference-mediated gene knockdown, based on the direct application of small interfering RNAs (siRNAs), opens novel avenues towards innovative therapies. Two decades after the discovery of the RNA interference mechanism, the first siRNA drugs received approval for clinical use by ... | What is the reason for N-acetylgalactosamine (GalNAc) conjugation of siRNAs? | Two decades after the discovery of the RNA interference mechanism, the first siRNA drugs received approval for clinical use by the US Food and Drug Administration and the European Medicines Agency between 2018 and 2022. These are mainly based on an siRNA conjugation with a targeting moiety for liver hepatocytes, |
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