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Our understanding of the extent of microRNA-based gene regulation has expanded in an impressive pace over the past decade. Now, we are beginning to better appreciate the role of 3'-UTR (untranslated region) cis-elements which harbor not only microRNA but also RNA-binding protein (RBP) binding sites that have significan... | Can untranslated regions (UTRs) regulate gene expression? | Now, we are beginning to better appreciate the role of 3'-UTR (untranslated region) cis-elements which harbor not only microRNA but also RNA-binding protein (RBP) binding sites that have significant effect on the stability and translational rate of mRNAs. |
The presence of homologous nucleic acid sequences can exert profound effects on chromosomal and gene function in a wide range of organisms. These homology effects reveal remarkable forms of regulation as well as suggest possible avenues for the development of new technologies. | What is transvection? | The presence of homologous nucleic acid sequences can exert profound effects on chromosomal and gene function in a wide range of organisms. These homology effects reveal remarkable forms of regulation as well as suggest possible avenues for the development of new technologies |
The aim of this study was to determine the anti-tumour activity of tanshinone IIA in SKOV3 cells. Results suggested that tanshinone IIA could significantly inhibit (IC50 value = 19.6 μM) the proliferation and induce apoptosis of SKOV3 cells as demonstrated by flow cytometry analysis. In addition, tanshinone IIA treat... | What is the function of BAX | pro-apoptotic protein Bax |
Histone H2AX phosphorylation on a C-terminal serine residue to form "γ-H2AX" is a critical early event in the chromatin response to chromosomal DNA double strand breaks in eukaryotes. In mammalian cells, γ-H2AX is formed when H2AX is phosphorylated on serine 139 by ATM or by other DNA damage response kinases. H2AX prev... | What histone variants play a role in the DNA damage reponse? | H2AX phosphorylation on a C-terminal serine residue to form "γ-H2AX" is a critical early event in the chromatin response to chromosomal DNA double strand breaks in eukaryotes |
Iron overload is considered a risk factor for mortality in patients with hematopoietic malignancies. Hepcidin is a key regulator of systemic iron balance. We previously reported dynamic changes of serum hepcidin-25 levels in patients with hematologic malignancies after allogeneic hematopoietic stem cell transplantation... | Hepcidin is a key regulator of what processes? | Hepcidin is a key regulator of systemic iron balance. |
This study suggests most gastrointestinal disease specialists recognize a role for and have used probiotics as part of their therapeutic armamentarium; however, the effective implementation of this practice will benefit from additional supporting studies and the eventual development of clinical practice guidelines supp... | What is the role of probiotics in gastrointestinal disease? | This study suggests most gastrointestinal disease specialists recognize a role for and have used probiotics as part of their therapeutic armamentarium |
The myotonic dystrophies are the commonest cause of adult-onset muscular dystrophy. Phenotypes of DM1 and DM2 are similar, but there are some important differences, including the presence or absence of congenital form, muscles primarily affected (distal vs proximal), involved muscle fiber types (type 1 vs type 2 fibers... | Which are the types of myotonic dystrophy? | For the enormous understanding of the molecular pathogenesis of myotonic dystrophy type 1 and myotonic dystrophy type 2, these diseases are now called "spliceopathies" and are mediated by a primary disorder of RNA rather than proteins. |
RNA polymerases are highly regulated molecular machines. We present a method (global run-on sequencing, GRO-seq) that maps the position, amount, and orientation of transcriptionally engaged RNA polymerases genome-wide. In this method, nuclear run-on RNA molecules are subjected to large-scale parallel sequencing and map... | What is GRO-seq? | We present a method (global run-on sequencing, GRO-seq) that maps the position, amount, and orientation of transcriptionally engaged RNA polymerases genome-wide. In this method, nuclear run-on RNA molecules are subjected to large-scale parallel sequencing and mapped to the genome. |
This study shows both LDR and HDR brachytherapy monotherapy result in low estimated risks of radiation-induced rectal and bladder cancer. LDR resulted in lower bladder cancer risks than HDR, and lower or similar risks of rectal cancer. In absolute terms these differences between techniques were very small. Compared to ... | Does radiotherapy for prostate cancer increase bladder cancer risk? | LDR resulted in lower bladder cancer risks than HDR, and lower or similar risks of rectal cancer. |
Eccrine sweat glands, which are distributed over the whole bodies of primates and humans, have long been regarded mainly to have a function in thermoregulation. However, the discovery of dermcidin-derived antimicrobial peptides in eccrine sweat demonstrated that sweat actively participates in the constitutive innate im... | Where can we find the protein dermcidin? | However, the discovery of dermcidin-derived antimicrobial peptides in eccrine sweat |
Children with autism spectrum disorders (ASD) experience high rates of anxiety, sensory processing problems, and gastrointestinal (GI) problems; however, the associations among these symptoms in children with ASD have not been previously examined. The current study examined bivariate and multivariate relations among an... | Is abdominal pain a common symptom in autism? | The results indicate that anxiety, sensory over-responsivity and GI problems are possibly interrelated phenomenon for children with ASD, and may have common underlying mechanisms. |
Delafloxacin is a broad-spectrum anionic fluoroquinolone under development for the treatment of bacterial pneumonia. The goal of the study was to determine the pharmacokinetic/pharmacodynamic (PK/PD) targets in the murine lung infection model for Staphylococcus aureus, Streptococcus pneumoniae, and Klebsiella pneumonia... | List bacterial families for which delafloxacin has been shown to be effective. | The goal of the study was to determine the pharmacokinetic/pharmacodynamic (PK/PD) targets in the murine lung infection model for Staphylococcus aureus, Streptococcus pneumoniae, and Klebsiella pneumoniae |
Breast carcinoma en cuirasse is a very rare form of cutaneous metastases of breast cancer. The clinical presentation is that of a diffuse indurated carcinomatous infiltration of the skin and subcutaneous tissues of the mammary region and the anterior aspect of the chest. In most cases, breast carcinoma en cuirasse deve... | What is carcinoma en cuirasse? | Breast carcinoma en cuirasse is a very rare form of cutaneous metastases of breast cancer. |
Macrophage actin-associated tyrosine phosphorylated protein (MAYP) belongs to the Pombe Cdc15 homology (PCH) family of proteins involved in the regulation of actin-based functions including cell adhesion and motility. In mouse macrophages, MAYP is tyrosine phosphorylated after activation of the colony-stimulating facto... | Which proteins are involved in actin bundling and filopodia formation and function? | Overexpression of MAYP led to a reduction in total macrophage F-actin content but was associated with increased actin bundling. Consistent with this, purified MAYP bundled F-actin and regulated its turnover in vitro. |
Depression is one of the leading causes of morbidity worldwide and represents a huge burden to society. As with many other psychiatric disorders, a genetic basis for depression has been identified. Evidence for the role of circadian genes in depression is particularly compelling. Circadian gene mutations are also assoc... | What is the genetic basis of the Delayed Sleep-Phase Syndrome (DSPS)? | Polymorphisms in the CLOCK, BMAL1, Per3 and TIMELESS genes have been associated with susceptibility to mood disorder, and single nucleotide polymorphisms and haplotypes in several circadian genes have been observed among those displaying certain circadian phenotypes, including worse mood in the evening, insomnia in man... |
Candida albicans and Candida glabrata are predominant fungi associated with oral candidiasis. Histatin 5 (Hst 5) is a small cationic human salivary peptide with high fungicidal activity against C. albicans, however many strains of C. glabrata are resistant. Since Hst 5 requires fungal binding to cell wall components pr... | How does Hst5 (histatin 5) affect infections by Candida glabrata? | Candida albicans and Candida glabrata are predominant fungi associated with oral candidiasis. |
Anti-IL-5 monoclonal antibody (mepolizumab) reduces baseline bronchial mucosal eosinophils and deposition of extracellular matrix proteins in the reticular basement membrane in mild asthma. Here we report the effect of anti-IL-5, in the same patients, on allergen-induced eosinophil accumulation, tenascin deposition (as... | Which molecule is targeted by a monoclonal antibody Mepolizumab? | Skin biopsies were performed in 24 atopic subjects at allergen- and diluent-injected sites before 6 and 48 h after, three infusions of a humanized, monoclonal antibody against IL-5 (mepolizumab) using a randomized double-blind, placebo-controlled design. |
Hypothyroid heart displays a phenotype of cardioprotection against ischemia and this study investigated whether administration of dronedarone, an amiodarone-like compound that has been shown to preferentially antagonize thyroid hormone binding to thyroid hormone receptor alpha1 (TRalpha1), results in a similar effect. ... | Which genes does thyroid hormone receptor alpha1 regulate in the heart? | lpha-Myosin heavy chain (alpha-MHC) decreased in DRON while beta-myosin heavy chain (beta-MHC) and sarcoplasmic reticulum Ca2+ adenosine triphosphatase (ATPase) expression (SERCA) was similar to CONT. |
5-Formyluracil (fU), a major methyl oxidation product of thymine, forms correct (fU:A) and incorrect (fU:G) base pairs during DNA replication. In the accompanying paper (Masaoka, A., Terato, H., Kobayashi, M., Honsho, A., Ohyama, Y., and Ide, H. (1999) J. Biol. Chem. 274, 25136-25143), it has been shown that fU correct... | What type of DNA repair pathways is initiated by AlkA glycosylase? | These results suggest that fU present in DNA can be restored by two independent repair pathways, i.e. the base excision repair pathway initiated by AlkA and the methyl-directed mismatch repair pathway initiated by MutS. |
Up-regulation of heme oxygenase 1 (HO-1) by ultraviolet A (UVA; 320-380 nm) irradiation of human skin cells protects them against oxidative stress. The role of Nrf2 in up-regulation of HO-1 and other phase II genes is well established. The mechanism underlying Bach1-mediated HO-1 repression is less well understood alth... | Is the transcriptional regulator BACH1 an activator or a repressor? | The mechanism underlying Bach1-mediated HO-1 repression is less well understood |
In ischemic stroke, plasma cytokines and catecholamines were not predictors of neurological outcome at 1 month. In hemorrhagic stroke, high levels of IL-6 in the early phase indicated a poor neurological outcome. | Is there an association between serum interleukin-6 concentrations and outcomes of stroke patients? | In hemorrhagic stroke, high levels of IL-6 in the early phase indicated a poor neurological outcome. |
Histone H3 lysine(27)-to-methionine (H3K27M) gain-of-function mutations occur in highly aggressive pediatric gliomas. We established a Drosophila animal model for the pathogenic histone H3K27M mutation and show that its overexpression resembles polycomb repressive complex 2 (PRC2) loss-of-function phenotypes, causing d... | Which histone mutation is associated with gliomas? | We established a Drosophila animal model for the pathogenic histone H3K27M mutation and show that its overexpression resembles polycomb repressive complex 2 (PRC2) loss-of-function phenotypes, causing derepression of PRC2 target genes and developmental perturbations. |
Autophagy is an essential cellular mechanism that degrades cytoplasmic proteins and organelles to recycle their components. Here we show that autophagy is required for reprogramming of somatic cells to form induced pluripotent stem cells (iPSCs). Our data indicate that mammalian target of rapamycin (mTOR) is downregula... | Does the protein mTOR regulate autophagy? | mTOR remains at a high level and inhibits autophagy. |
Hutchinson-Gilford progeria syndrome (HGPS, OMIM 176670) is a rare multisystem childhood premature aging disorder linked to mutations in the LMNA gene. The most common HGPS mutation is found at position G608G within exon 11 of the LMNA gene. This mutation results in the deletion of 50 amino acids at the carboxyl-termin... | What is the protein that is truncated to produce progerin? | s mutation results in the deletion of 50 amino acids at the carboxyl-terminal tail of prelamin A, and the truncated protein is called progerin. Pr |
Background Calcitonin gene-related peptide plays an important role in migraine pathophysiology. Erenumab, a human monoclonal antibody that inhibits the calcitonin gene-related peptide receptor, is being evaluated for migraine prevention. Methods In this randomized, double-blind, placebo-controlled, phase 3 study, 577 a... | What is the use of erenumab? | Conclusions As a preventive treatment of episodic migraine, erenumab at a dosage of 70 mg monthly significantly reduced migraine frequency and acute migraine-specific medication use. |
Proteolytic processing of the p105 precursor (NF-kappa B1) generates the p50 subunit of NF-kappa B. To address the function of p105 precursor, we have generated embryonic stem (ES) cells which lack the C-terminal inhibiting ankyrin-containing domain of p105 (I kappa B gamma) but contain a functional p50 by homologous r... | Is p100 the precursor protein molecule of the NF-kappaB transcription factor subunit p50? | Proteolytic processing of the p105 precursor (NF-kappa B1) generates the p50 subunit of NF-kappa B |
Enhancers are critical genomic elements that define cellular and functional identity through the spatial and temporal regulation of gene expression. Recent studies suggest that key genes regulating cell type-specific functions reside in enhancer-dense genomic regions (i.e., super enhancers, stretch enhancers). Here we ... | How are super enhancers defined? | Here we report that enhancer RNAs (eRNAs) identified by global nuclear run-on sequencing are extensively transcribed within super enhancers and are dynamically regulated in response to cellular signaling. |
Mutations of the polycystic kidney and hepatic disease 1 (PKHD1) gene have been shown to cause autosomal recessive polycystic kidney disease (ARPKD), but the cellular functions of the gene product (PKHD1) remain uncharacterized. To illuminate its properties, the spatial and temporal expression patterns of PKHD1 were de... | Which is the most common disease attributed to malfunction or absence of primary cilia? | In cultured renal cells, the PKHD1 gene product colocalized with polycystin-2, the gene product of autosomal dominant polycystic disease type 2, at the basal bodies of primary cilia. |
Emery-Dreifuss muscular dystrophy (EDMD) is an X-linked muscular dystrophy in which cardiac involvement can be serious. The disease progresses rapidly and the prognosis is strongly associated with cardiac involvement. We present the case of a 49-year-old man who was admitted with shortness of breath. Echocardiography r... | What is Emery-Dreifuss Muscular Dystrophy (EDMD)? | Emery-Dreifuss muscular dystrophy (EDMD) is an X-linked muscular dystrophy in which cardiac involvement can be serious. |
The probe-to-bone (PTB) test is a commonly used clinical test for osteomyelitis (OM), but its utility has been questioned in clinical settings where the prevalence of OM is low. This article aims to systematically review the accuracy of the PTB test to diagnose diabetic foot OM. We searched Ovid Medline and Scopus data... | Which disease can be diagnosed with the "probe to bone" test? | The probe-to-bone (PTB) test is a commonly used clinical test for osteomyelitis (OM), but its utility has been questioned in clinical settings where the prevalence of OM is low. |
Recent reports have identified defensins as a new type of potassium channel inhibitors; differential binding mechanisms of human β-defensins hBD1 and hBD2 point to complex interactions between human β-defensins and potassium channels. We investigated the inhibitory effects of human defensins hBD3 and hBD4 on potassium ... | List the types of defensins expressed in humans. | the data indicate that the human β-defensin family is a novel group of potassium channel inhibitors with diverse types of human β-defensin-potassium channel interactions. |
Since the discovery of neuromedin U (NmU) from porcine spinal cord in 1985, this neuropeptide has been subsequently identified in many other species with multiple physiological and pathophysiological roles detected, ranging from smooth muscle contraction, feeding, energy balance to tumorigenesis. Intriguingly, NmU is a... | What is Neuromedin U (NmU) | NmU is also emerging to play pro-inflammatory roles involving immune cell activation and cytokine release in a neuron-dependent or neuron-independent manner. |
Non-alcoholic fatty liver disease (NAFLD) has become one of the most prominent forms of chronic liver disease worldwide, reflecting the epidemic of global obesity. Those with the progressive variant of NAFLD, non-alcoholic steatohepatitis (NASH), are at significantly increased risk of multisystem morbidity and mortalit... | Is there any approved treatment for NAFLD? | Although much progress has been made in enhancing our understanding of NAFLD pathogenesis, development of pharmacologic treatments has been hindered by challenges in clinical trial enrollment and complexities in clinical trial design. |
The expanding use of surfactants for proteome sample preparations has prompted the need to systematically optimize the application and removal of these MS-deleterious agents prior to proteome measurements. Here we compare four detergent cleanup methods (trichloroacetic acid (TCA) precipitation, chloroform/methanol/wate... | What is the method FASP used for? | filter-aided sample preparation (FASP) |
As interest in scuba diving is increasing in both sexes, doctors need to be aware of the risks encountered when diving and about gender-related differences in these risks. Individuals prone to panic attacks, claustrophobia or reckless risk-taking should avoid diving. In tolerating cold, muscle mass is more important th... | Is scuba diving safe during pregnancy? | Pregnant women are recommended not to dive, because the risk of birth defects seems to be greater among those who do, and there is a serious risk of fetal decompression disease. |
The gene expression profile seems to be the molecular basis of the diverse immune phenotype of SLE. On the basis of the SLE-related genes found in this study, we suggest that the interferon-related immune pathway is important in the pathogenesis of SLE. IFIT1 is the first gene described as a candidate gene for SLE, and... | Which is the role of the IFIT1 gene in Systemic Lupus Erythematosus (SLE)? | is the first gene described as a candidate gene for SLE, and may function by activating Rho proteins through interaction with Rho/Rac guanine nucleotide exchange factor. IFIT1 |
Gefitinib (Iressa) is a specific and effective epidermal growth factor receptor inhibitor. An understanding of the downstream cellular targets of gefitinib will allow the discovery of biomarkers for predicting outcomes and monitoring anti-epidermal growth factor receptor therapies and provide information for overcoming... | Which is the cellular target of gefitinib? | Gefitinib (Iressa) is a specific and effective epidermal growth factor receptor inhibitor. |
Transforming growth factor-beta (TGF-β) signaling regulates a wide range of biological processes. TGF-β plays an important role in tumorigenesis and contributes to the hallmarks of cancer, including tumor proliferation, invasion and metastasis, inflammation, angiogenesis, and escape of immune surveillance. There are se... | What is mechanism of action of galunisertib? | Galunisertib (LY2157299 monohydrate) is an oral small molecule inhibitor of the TGF-β receptor I kinase that specifically downregulates the phosphorylation of SMAD2, abrogating activation of the canonical pathway. |
Hedgehog (Hh) signaling proteins stimulate cell proliferation, differentiation, and tissue patterning at multiple points in animal development. A single Hh homolog is present in Drosophila, but three Hh homologs, Sonic Hh, Indian Hh, and Desert Hh, are present in mammals. Distribution, movement, and reception of Hh sig... | Which are the different homologs or family members of the hedgehog proteins in mammals? | A single Hh homolog is present in Drosophila, but three Hh homologs, Sonic Hh, Indian Hh, and Desert Hh, are present in mammals. |
Turcot syndrome (TS) is a rare hereditary disorder clinically characterized by the occurrence of primary tumors of the colon and the central nervous system (CNS). Here we present the case of an 11-year-old boy with a synchronous clinical presentation of both glioblastoma multiforme (GBM) and colonic adenocarcinoma. A m... | Is Turcot syndrome associated with glioblastoma? | Based on this case study, the synchronous presentation of glioblastoma multiforme and adenocarcinoma of the colon might suggest a shorter survival rate for patients with Turcot syndrome. |
Cell therapy, in particular liver cell transplantation, holds great therapeutic potential and is partially hindered by the high rate of apoptosis during cell isolation, cryopreservation and engraftment. Apoptosis triggered by cell detachment from the extracellular matrix, which occurs during hepatocyte isolation, is a ... | Which type of cell death is known as anoikis? | Apoptosis triggered by cell detachment from the extracellular matrix, which occurs during hepatocyte isolation, is a phenomenon termed "anoikis". It's importance in the normal physiologic development of the human body, as well as in disease states, has been described. Cancer cells harbor anoikis resistance allowing spr... |
Advances in the understanding of the molecular basis for acute myeloid leukemia (AML) have generated new potential targets for treatment. Fms-like tyrosine kinase 3 (FLT3) is one of the most frequently mutated genes in AML and mutations in this gene are associated with poor overall survival. AXL plays a role in the act... | Which molecules are inhibited by Gilteritinib? | Initial kinase studies showed that gilteritinib, a type I tyrosine kinase inhibitor, was highly selective for both FLT3 and AXL while having weak activity against c-KIT. |
WISP-1 (Wnt-1-induced secreted protein) was identified as an oncogene regulated by the Wnt-1-beta-catenin pathway. WISP-1 belongs to the CCN family of growth factors, which are cysteine-rich, heparin-binding, secreted proteins associated with the extracellular matrix, and can interact with cellular integrins. Expressio... | Is there any cross-talk between the Wnt and the Akt pathways? | Here it is shown that WISP-1 can activate the antiapoptotic Akt/PKB signaling pathway. |
The autoimmune cytopenias are a group of disorders resulting primarily from autoantibody-mediated destruction of blood cells, with variable clinical sequelae depending on the severity and lineage affected. Disease presentation ranges from an asymptomatic finding on a routine full blood count to an acutely unwell patien... | List features of the Thrombotic Thrombocytopenic Purpura pentad. | botic thrombocytopenic purpura (TTP) is a distinct, rare but potentially life-threatening entity that classically but not invariably presents with a pentad of acute onset haemolytic anaemia, thrombocytopenia, neurological symptoms, renal impairment and fevers. Autoimmun |
The number of global clinical trials including Japan is increasing but still much lower than those including the USA and Europe. The regulatory requirements for clinical trials have been harmonized among Japan, USA, and Europe, and the quality of clinical trials is kept high in these regions. Xofluza (baloxavir marboxi... | What is the generic name of the Xofluza? | Xofluza (baloxavir marboxil) for influenza approved in Japan under the SAKIGAKE Designation System is a good example of clinical trials including Japan. |
We investigated the expression of Na(+)/Ca(2+) exchanger (NCX) and the functional role of NCX in retinal damage by using NCX1-heterozygous deficient mice (NCX1(+/-)) and SEA0400 (2-[4-[(2,5-difluorophenyl)methoxy] phenoxy]-5-ethoxyaniline), a selective NCX inhibitor in vivo. We also examined the role of NCX in oxygen-g... | The small molecule SEA0400 is an inhibitor of which ion antiporter/exchanger? | We investigated the expression of Na(+)/Ca(2+) exchanger (NCX) and the functional role of NCX in retinal damage by using NCX1-heterozygous deficient mice (NCX1(+/-)) and SEA0400 (2-[4-[(2,5-difluorophenyl)methoxy] phenoxy]-5-ethoxyaniline), a selective NCX inhibitor in vivo. |
The histidine-rich calcium binding protein (HRC) Ser96Ala polymorphism was shown to correlate with ventricular arrhythmias and sudden death only in dilated cardiomyopathy patients but not in healthy human carriers. In the present study, we assessed the molecular and cellular mechanisms underlying human arrhythmias by a... | Is the Histidine-Rich Calcium Binding protein (HRC) related to arrhythmias and cardiac disease? | These findings indicate that the HRC Ser96Ala variant increases the propensity of arrhythmogenic Ca(2+) waves in the stressed failing heart, suggesting a link between this genetic variant and life-threatening ventricular arrhythmias in human carriers. |
We report the case of a patient in whom the diagnosis of Ewing sarcoma arising from a soft tissue was made after successful treatment of diffuse large B-cell lymphoma. A 65-year-old woman presented with a rapidly growing mass in her left scapular region 8 years after successful chemotherapy with the cyclophosphamide, h... | Which technique is used for detection of EWS/FLI1 fusion transcripts? | Reverse transcriptase-polymerase chain reaction confirmed the expression of EWS-FLI1 fusion transcripts |
Kabuki syndrome (KS) is a rare congenital disorder characterized by distinctive facies, postnatal growth deficiency, cardiac defects and skeletal anomalies. Studies have determined that pathogenic variants of the lysine-specific methyltransferase 2D (KMT2D) and lysine-specific demethylase 6A (KDM6A) genes are the major... | What syndrome is associated with mutations in lysine methyltransferase 2D KMT2D? | Kabuki syndrome (KS) is a rare congenital disorder characterized by distinctive facies, postnatal growth deficiency, cardiac defects and skeletal anomalies. Studies have determined that pathogenic variants of the lysine-specific methyltransferase 2D (KMT2D) and lysine-specific demethylase 6A (KDM6A) genes are the major... |
Acquired resistance to proteasome inhibitors represents a considerable impediment to their effective clinical application. Carfilzomib and its orally bioavailable structural analog oprozomib are second-generation, highly-selective, proteasome inhibitors. However, the mechanisms of acquired resistance to carfilzomib and... | What is oprozomib? | Carfilzomib and its orally bioavailable structural analog oprozomib are second-generation, highly-selective, proteasome inhibitors. |
Alu elements are the most abundant repetitive elements in the human genome; they have amplified by retrotransposition to reach the present number of more than one million copies. Alu elements can be transcribed in two different ways, by two independent polymerases. 'Free Alu RNAs' are transcribed by Pol III from their ... | Are Alu elements transcribed? | Recent studies have demonstrated that both free and embedded Alu RNAs play a major role in post transcriptional regulation of gene expression |
DTaP(5)-IPV-Hib combination vaccine was shown to be immunogenic and well tolerated. No clinically important differences in the safety or immunologic profiles were noted for DTaP(5)-IPV-Hib versus the separately administered, US-licensed equivalent vaccines. DTaP(5)-IPV-Hib is a suitable replacement for separately admin... | Can Daptacel be used instead of IPOL? | DTaP(5)-IPV-Hib is a suitable replacement for separately administered DTaP, IPV, and Hib vaccines. |
Myelin - the multilayer membrane that envelops axons - is a facilitator of rapid nerve conduction. Oligodendrocytes form CNS myelin; the prevailing hypothesis being that they do it by extending a process that circumnavigates the axon. It is pertinent to ask how myelin is built because oligodendrocyte plasma membrane an... | What is myelin? | Myelin - the multilayer membrane that envelops axons - is a facilitator of rapid nerve conduction. |
We previously estimated that 42% of patients with severe developmental disorders carry pathogenic de novo mutations in coding sequences. The role of de novo mutations in regulatory elements affecting genes associated with developmental disorders, or other genes, has been essentially unexplored. We identified de novo mu... | Are de novo mutations in regulatory elements responsible for neurodevelopmental disorders? | Here we show that de novo mutations in highly evolutionarily conserved fetal brain-active elements are significantly and specifically enriched in neurodevelopmental disorders. |
DNA damage that blocks the transcription of genes is prioritized for repair by transcription-coupled DNA repair pathways. RNA polymerases stalled at DNA lesions obstruct repair enzymes, but this situation is turned to the advantage of the cell by transcription-repair coupling factors that remove the stalled RNA polymer... | Which proteins act as factors that promote transcription-coupled repair in bacteria? | Recent structural studies of the bacterial transcription-repair coupling factor, Mfd, have revealed a modular architecture in which an ATP-dependent DNA-based motor is coupled to protein-protein interaction domains that can attach the motor to RNA polymerase and the DNA repair protein UvrA |
The antibody-drug conjugate trastuzumab deruxtecan might become a promising new treatment option for patients with metastatic HER2-positive breast cancer whose disease has progressed after multiple therapies. In a phase II trial, the drug was associated with a high objective response rate and long median progression-fr... | Which molecules are targeted by Trastuzumab Deruxtecan? | The antibody-drug conjugate trastuzumab deruxtecan might become a promising new treatment option for patients with metastatic HER2-positive breast cancer whose disease has progressed after multiple therapies. |
Bilirubin, a breakdown product of heme, is normally glucuronidated and excreted by the liver into bile. Failure of this system can lead to a buildup of conjugated bilirubin in the blood, resulting in jaundice. The mechanistic basis of bilirubin excretion and hyperbilirubinemia syndromes is largely understood, but that ... | Which syndrome is associated with OATP1B1 and OATP1B3 deficiency? | Here, we analyzed 8 Rotor-syndrome families and found that Rotor syndrome was linked to mutations predicted to cause complete and simultaneous deficiencies of the organic anion transporting polypeptides OATP1B1 and OATP1B3. |
Our results indicate that mutant-FUS alters the dynamic properties of stress granules, which is consistent with a gain-of-toxic mechanism for mutant-FUS in stress granule assembly and cellular stress response. | Which components of the stress granules are known to be related to motor neuron degeneration in Amyotrophic Lateral Sclerosis? | Our results indicate that mutant-FUS alters the dynamic properties of stress granules, which is consistent with a gain-of-toxic mechanism for mutant-FUS in stress granule assembly and cellular stress response. |
It is well established that eukaryotic genomes are pervasively transcribed producing cryptic unstable transcripts (CUTs). However, the mechanisms regulating pervasive transcription are not well understood. Here, we report that the fission yeast CENP-B homolog Abp1 plays an important role in preventing pervasive transcr... | How are cryptic unstable transcripts (CUTs) defined? | It is well established that eukaryotic genomes are pervasively transcribed producing cryptic unstable transcripts (CUTs). |
We present a patient who suffered from sleep attacks after starting entacapone in addition to levodopa. Entacapone, a catechol-O-methyl transferase inhibitor, alters the pharmacokinetics of levodopa, leading to increase of levodopa concentration in plasma and brain. This mechanism is suspected to be involved in the pat... | Which two catechol-O-methyl transferase (COMT) inhibitors can be used for treatment of Parkinson disease? | We present a patient who suffered from sleep attacks after starting entacapone in addition to levodopa. Entacapone, a catechol-O-methyl transferase inhibitor, alters the pharmacokinetics of levodopa, leading to increase of levodopa concentration in plasma and brain. |
Post-translational modifications, such as ubiquitylation, need to be tightly controlled to guarantee the accurate localization and activity of proteins. Ubiquitylation is a dynamic process primarily responsible for proteasome-mediated degradation of substrate proteins and crucial for both normal homeostasis and disease... | What is a PROTAC? | PROteolysis-TArgeting Chimera (PROTAC) is an innovative strategy that takes advantage by the cell's own Ubiquitin-Proteasome System (UPS). |
Clinical teaching dictates that isolated unicoronal synostosis is sporadic in occurrence and is possibly related to intrauterine constraint. Despite this, isolated reports document a familial occurrence. It has previously been recognized that there may be a familial pattern of inheritance. Recently, mutations in fibrob... | Is there an association between FGFR3 mutation and plagiocephaly? | The occurrence of the FGFR3 mutation among patients with unicoronal synostosis provides evidence for a genetic basis of certain forms of plagiocephaly |
Practical relevance: Feline coronavirus (FCoV) infection is very common in cats, usually causing only mild intestinal signs such as diarrhoea. Up to 10% of FCoV infections, however, result in the fatal disease feline infectious peritonitis (FIP). Clinical challenges: Obtaining a definitive diagnosis of FIP based on non... | The virus that causes FIP, Feline Infectious Peritonitis belongs to what family? | Feline coronavirus (FCoV) infection is very common in cats, usually causing only mild intestinal signs such as diarrhoea. Up to 10% of FCoV infections, however, result in the fatal disease feline infectious peritonitis (FIP). |
Although the textbook view of the Pendred syndrome is that of an autosomal recessive condition characterised by deafness and goitre, it is increasingly clear that not all patients present this classical clinical description. Malform-ations of the inner ear, specifically, enlargement of the vestibular aqueduct, are comm... | Do patients with Pendred syndrome present congenital deafness? | Although the textbook view of the Pendred syndrome is that of an autosomal recessive condition characterised by deafness and goitre, it is increasingly clear that not all patients present this classical clinical description. |
Cerliponase alfa (Brineura™) is a recombinant human tripeptidyl peptidase-1 (TPP1) being developed by BioMarin Pharmaceutical Inc. for use in patients with neuronal ceroid lipofuscinosis type 2 (CLN2), a paediatric neurodegenerative disease caused by a deficiency in TPP1. CLN2 is characterised by progressive impairment... | Cerliponase alfa is apprived for treatment of which disease? | This article summarizes the milestones in the development of cerliponase alfa leading to its first global approval in the USA for the treatment of motor function loss in paediatric patients ≥3 years of age with CLN2, and subsequent approval in the EU for CLN2 in all ages. |
Circular RNAs (circRNA) have been reported as regulators involved in hepatocellular carcinoma (HCC), but their mechanism of activity remains unknown. This study performed quantitative reverse-transcription polymerase chain reaction to determine if circNFATC3 was downregulated in 46 paired HCC tissues and cell lines. 3-... | What is the function of Circular RNA (circRNA)? | Circular RNAs (circRNA) have been reported as regulators involved in hepatocellular carcinoma (HCC), but their mechanism of activity remains unknown. |
The protein Vezf1 plays multiple roles important for embryonic development. In Vezf1(-/-) mouse embryonic stem (mES) cells, our earlier data showed widespread changes in gene-expression profiles, including decreased expression of the full-length active isoform of Dnmt3b methyltransferase and concomitant genome-wide red... | What histone trimethylation has been associated to RNA splicing? | Vezf1 interacts with Mrg15/Mrgbp, a protein that recognizes H3K36 trimethylation, consistent with the role of histone modifications at alternatively spliced sites |
Intra-abdominal thrombosis is a complication of paroxysmal nocturnal hemoglobinuria (PNH). There is scarcity of data on cases presenting with thrombosis in whom PNH is the predisposing factor. We assessed the role of PNH defect in 81 patients with intra-abdominal thrombosis, 44 patients of Budd Chiari syndrome and 37 p... | Can CD55 deficiency cause thrombosis? | Data of this study indicate that the PNH defect as detected with CD55, CD59, and CD16 is not an important cause of intra-abdominal thrombosis in northwestern India. |
Psoriasis is a chronic immune-mediated inflammatory disorder with epidermal hyperplasia. There is some evidence that the cytokine interleukin-17A (often known as IL-17), which is mainly produced by Th17 cells, has a role in the pathogenesis of psoriasis. "IL-17" is a pro-inflammatory cytokine mainly important in the ho... | What molecule is targeted by brodalumab? | The three new therapies with biologic drugs - brodalumab, secukinumab, and ixekizumab - all target the IL-17 signaling pathway. Secukinumab and ixekizumab neutralize IL-17A, while brodalumab blocks its receptor. |
A phase II trial shows that a chemotherapy-free regimen of dasatinib and blinatumomab produces molecular responses in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia. The study found that 60% of patients had molecular responses after two cycles of blinatumomab and 71% had molecular responses... | Dasatinib and Blinatumomab are used for treatment of which disease? | A phase II trial shows that a chemotherapy-free regimen of dasatinib and blinatumomab produces molecular responses in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia. |
Increasing flow rates of HHHFNC therapy are associated with linear increases in NP pressures in bronchiolitis patients. Larger studies are needed to assess the clinical efficacy of HHHFNC therapy in bronchiolitis. | Are high-flow nasal cannulae effective for treatment of preterm infants? | Increasing flow rates of HHHFNC therapy are associated with linear increases in NP pressures in bronchiolitis patients. |
EEM syndrome is a rare condition characterised by ectodermal dysplasia, ectrodactyly and macular dystrophy. Additional abnormalities such as alopecia, cataract, absent eyebrows, and oligodontia may occur. We report two brothers and a sister born to consanguineous parents with EEM syndrome. EEM syndrome differs from oth... | List clinical features of EEM syndrome. | EEM syndrome is a rare condition characterised by ectodermal dysplasia, ectrodactyly and macular dystrophy. |
Anemia is one of the most common extraintestinal symptoms of inflammatory bowel disease (IBD). The pathophysiology of anemia in IBD is complex. It may be developed in the course of inflammation, intestinal bleeding or disorders of iron absorption. Hepcidin, discovered in the year 2000, is an endogenous peptide responsi... | Hepcidin is a key regulator of what processes? | Recent data suggests that hepcidin is a major mediator of anemia and plays a central role in iron homeostasis and metabolism |
The role of promoter methylation in the process of cancer cell metastasis has, however, not yet been studied. Recently, methylation of the TPEF (transmembrane protein containing epidermal growth factor and follistatin domain) gene was reported in human colon, gastric, and bladder cancer cells. Using the Methylight assa... | Which genes were found to be methylated in bladder cancer cells? | Recently, methylation of the TPEF (transmembrane protein containing epidermal growth factor and follistatin domain) gene was reported in human colon, gastric, and bladder cancer cells. |
The objective of this study is to identify the contribution that selected demographic characteristics, health behaviors, physical health outcomes, and workplace environmental factors have on presenteeism (on-the-job productivity loss attributed to poor health and other personal issues). Analyses are based on a cross-se... | Is there an association between presenteeism and depression? | Factors with less contribution to presenteeism included physical limitations, depression or anxiety, inadequate job training, and problems with supervisors and coworkers. |
The B cell adaptor protein with ankyrin repeats (BANK1) and the B lymphoid tyrosine kinase (BLK) have been genetically associated with autoimmunity. The proteins of these genes interact physically and work in concert during B-cell signaling. Little is know about their interactions with other B-cell signaling molecules ... | Which is the primary interacting protein of BLK? | The B cell adaptor protein with ankyrin repeats (BANK1) and the B lymphoid tyrosine kinase (BLK) have been genetically associated with autoimmunity. The proteins of these genes interact physically and work in concert during B-cell signaling. |
Portal vein involvement is considered one of the most fearful complications of hepatocellular carcinoma (HCC). Portal vein tumor thrombosis (PVTT) is associated with aggressive tumor biology (high grade), high tumor burden (number and size of lesions), high levels of serum markers (AFP), poor liver function (deranged L... | A combination of which two drugs was tested in the IMbrave150 trial? | nt Phase III (IMbrave150) trial favor the combination of atezolizumab and bevacizumab over sorafenib as a standard of care in advanced unresectable HCC. While only lenvatinib |
Lysine methylation of histones is associated with both transcriptionally active chromatin and with silent chromatin, depending on what residue is modified. Histone methyltransferases and demethylases ensure that histone methylations are dynamic and can vary depending on cell cycle- or developmental stage. KDM4A demethy... | How do histone methyltransferases cause histone modification? | Lysine methylation of histones is associated with both transcriptionally active chromatin and with silent chromatin, depending on what residue is modified. Histone methyltransferases and demethylases ensure that histone methylations are dynamic and can vary depending on cell cycle- or developmental stage. |
Primary chemotherapy for locally advanced breast cancer, usually an anthracycline-containing regimen, improves local disease control allowing for an initially inoperable tumour to be resected. The feasibility and efficacy of a regimen containing vinorelbine (V), cisplatin (P) and 5-fluorouracil (5-Fu) as continuous inf... | Which drugs are included in the VIFUP regimen for breast cancer? | e feasibility and efficacy of a regimen containing vinorelbine (V), cisplatin (P) and 5-fluorouracil (5-Fu) as continuous infusion (ViFuP regimen) for patients with locally advanced breast cancer were evaluated. Twenty-s |
Correct and bias-free interpretation of the deep sequencing data is inevitably dependent on the complete mapping of all mappable reads to the reference sequence, especially for quantitative RNA-seq applications. Seed-based algorithms are generally slow but robust, while Burrows-Wheeler Transform (BWT) based algorithms ... | Which NGS alignment software implement the Burrows-Wheeler Transform? | Seed-based algorithms are generally slow but robust, while Burrows-Wheeler Transform (BWT) based algorithms are fast but less robust. To have both advantages, we developed an algorithm FANSe2 with iterative mapping strategy based on the statistics of real-world sequencing error distribution to substantially accelerate ... |
Circular RNAs (circRNAs) are a novel class of non-coding RNA that assumes a covalently closed continuous conformation. CircRNAs were previously thought to be the byproducts of splicing errors caused by low abundance and the technological limitations. With the recent development of high-throughput sequencing technology,... | Can a circRNA be translated into protein? | Circular RNAs (circRNAs) are a novel class of non-coding RNA that assumes a covalently closed continuous conformation. |
Dendritic cells (DC) and macrophages phagocytose pathogens and degrade them in their phagosomes to allow for proper presentation of foreign antigens to other cells of the immune system. The Plasmodium parasite, causative agent of malaria, infects RBC that are phagocytosed by DC and macrophages during the course of infe... | Which is the causative agent of malaria? | The Plasmodium parasite, causative agent of malaria, infects RBC that are phagocytosed by DC and macrophages during the course of infection. |
The canonical action of the p85α regulatory subunit of phosphatidylinositol 3-kinase (PI3K) is to associate with the p110α catalytic subunit to allow stimuli-dependent activation of the PI3K pathway. We elucidate a p110α-independent role of homodimerized p85α in the positive regulation of PTEN stability and activity. p... | Does p85α homodimerize? | homodimeric but not monomeric p85α |
Cohesin-mediated sister chromatid cohesion is essential for chromosome segregation and post-replicative DNA repair. In addition, evidence from model organisms and from human genetics suggests that cohesin is involved in the control of gene expression. This non-canonical role has recently been rationalized by the findin... | What is the role of cohesins at the IFNG locus? | Here we show that cohesin forms the topological and mechanistic basis for cell-type-specific long-range chromosomal interactions in cis at the developmentally regulated cytokine locus IFNG. |
The treatment of primary gastric lymphoma is controversial. The role of surgery has come to be questioned with increasing knowledge about the pathogenesis of gastric lymphoma and with new therapeutic approaches such as eradication of Helicobacter pylori. We review published clinical trials of primary gastric lymphoma, ... | What is the treatment of choice for gastric lymphoma? | The treatment of primary gastric lymphoma is controversial. The role of surgery has come to be questioned with increasing knowledge about the pathogenesis of gastric lymphoma and with new therapeutic approaches such as eradication of Helicobacter pylori. |
The "GI Cocktail" is a mixture of medications often given in the Emergency Department (ED) for dyspepsia symptoms. Several combinations are used, but the most effective has not yet been determined. This study compared three combinations commonly given for dyspepsia. The study was a prospective, randomized, double-blind... | Which drugs are included in GI cocktail? | This study compared three combinations commonly given for dyspepsia. The study was a prospective, randomized, double-blinded trial comparing antacid (group 1); antacid + Donnatal (group 2); antacid + Donnatal + viscous lidocaine (group 3) for acute treatment of dyspepsia in the ED. |
Skeletal muscle satellite cells are quiescent mononucleated myogenic cells, located between the sarcolemma and basement membrane of terminally-differentiated muscle fibres. These are normally quiescent in adult muscle, but act as a reserve population of cells, able to proliferate in response to injury and give rise to ... | What are the skeletal muscle satellite cells? | Satellite cell-derived muscle precursor cells may be used to repair and regenerate damaged or myopathic skeletal muscle, or to act as vectors for gene therapy. |
Cilia and flagella play multiple essential roles in animal development and cell physiology. Defective cilium assembly or motility represents the etiological basis for a growing number of human diseases. Therefore, how cilia and flagella assemble and the processes that drive motility are essential for understanding thes... | Where in the cell do we find the protein Cep135? | Drosophila Bld10, the ortholog of Chlamydomonas reinhardtii Bld10p and human Cep135, is a ubiquitous centriolar protein that also localizes to the spermatid basal body. M |
McKusick-Kaufman syndrome is a rare, autosomal, recessive disorder characterized by hydrometrocolpos, post-axial polydactyly, and congenital heart disease. Less than one hundred cases have been reported in the English literature to date, mainly in the Amish population; sporadic cases have also been described. We presen... | What 3 disorders are commonly associated with Kaufman-McKusick syndrome? | McKusick-Kaufman syndrome is a rare, autosomal, recessive disorder characterized by hydrometrocolpos, post-axial polydactyly, and congenital heart disease. |
Biogenesis of mitochondria involves the expression of genes located on nuclear chromosomes as well as on mitochondrial DNA. We studied the coordination of the two genomes by measuring transcript levels for nuclear (IV, Va, and VIc) and mitochondrial (II and III) subunits of cytochrome-c oxidase after altering the mitoc... | Which mitochondrial genes are regulated by thyroid hormone? | We studied the coordination of the two genomes by measuring transcript levels for nuclear (IV, Va, and VIc) and mitochondrial (II and III) subunits of cytochrome-c oxidase after altering the mitochondrial content of rat muscle and liver by altering the thyroid state of the animals. Tissue levels of these mRNAs were gen... |
Though Deflazacort and prednisone improve clinical endpoints in Duchenne muscular dystrophy (DMD) patients, Deflazacort produces fewer side effects. As mechanisms of improvement and side effect differences remain unknown, we evaluated effects of corticosteroid administration on gene expression in blood of DMD patients.... | Does deflazacort have more side effects than prednisone? | Though Deflazacort and prednisone improve clinical endpoints in Duchenne muscular dystrophy (DMD) patients, Deflazacort produces fewer side effects. |
One of the key issues pertaining to the control of memory is to respond to a consistently changing environment or microbial niche present in it. Human cyclic AMP response element binding protein (CREB) transcription factor which plays a crucial role in memory has a homolog in C. elegans, crh-1. crh-1 appears to influen... | Is CREB a key memory protein? | Human cyclic AMP response element binding protein (CREB) transcription factor which plays a crucial role in memory |
FCM prevents recurrence of anemia in patients with IBD, compared with placebo. Nevertheless, the high rate of anemia recurrence warrants optimization of the frequency and requirements for FCM treatment. | Can ferric carboxymaltose be used to treat anemia in inflammatory bowel disease patients? | FCM prevents recurrence of anemia in patients with IBD, compared with placebo. |
Psychologists, quality of life and well-being researchers have grown increasingly interested in understanding the factors that are associated with human happiness. Although twin studies estimate that genetic factors account for 35-50% of the variance in human happiness, knowledge of specific genes is limited. However, ... | Is there a genetic component for happiness? | Although twin studies estimate that genetic factors account for 35-50% of the variance in human happiness, knowledge of specific genes is limited. |
5-Lipoxygenase (5-Lox), an enzyme involved in the metabolism of arachidonic acid participates in the modulation of the proliferation and differentiation of neural stem cells and cerebellar granule cell (CGC) precursors. Since epigenetic mechanisms including DNA methylation regulate 5-LOX expression and have been sugges... | Which enzyme is involved in the maintenance of DNA (cytosine-5-)-methylation? | The 5-LOX DNA methylation increased with the age of the cells. |
The four major flavivirus clades are transmitted by mosquitoes, ticks, directly between vertebrates or directly between arthropods, respectively, but the molecular determinants of mode of transmission in flaviviruses are unknown. To assess the role of the UTRs in transmission, we generated chimeric genomes in which the... | How Flaviviridae family of viruses infects vertebrates? | four major flavivirus clades are transmitted by mosquitoes, ticks, directly between vertebrates or directly between arthropods, respectively, but the molecular determinants of mode of transmission in flaviviruses are unknown. |
The use of predictive models is becoming widespread. However, these models should be developed appropriately (CHecklist for critical Appraisal and data extraction for systematic Reviews of prediction Modeling Studies [CHARMS] and Prediction model Risk Of Bias ASsessment Tool [PROBAST] statements). Concerning mortality/... | What is CHARMS with respect to medical review of predictive modeling? | However, these models should be developed appropriately (CHecklist for critical Appraisal and data extraction for systematic Reviews of prediction Modeling Studies [CHARMS] and Prediction model Risk Of Bias ASsessment Tool [PROBAST] statements). |
The Drosophila JIL-1 kinase is known to phosphorylate histone H3 at Ser10 (H3S10) during interphase. This modification is associated with transcriptional activation, but its function is not well understood. Here we present evidence suggesting that JIl-1-mediated H3S10 phosphorylation is dependent on chromatin remodelin... | Which factors play a role in promoter proximal pausing of RNA polymerase II? | pausing factor DSIF (DRB sensitivity-inducing factor) |
Dominant mutations in PIEZO2, which codes for the principal mechanotransduction channel for proprioception and touch sensation, have been found to cause different forms of distal arthrogryposis. Some observations suggest that these dominant mutations induce a gain-of-function effect on the channel. Here, we report a co... | Please list 3 diseases associated with the PIEZO2 gene. | Dominant mutations in PIEZO2, which codes for the principal mechanotransduction channel for proprioception and touch sensation, have been found to cause different forms of distal arthrogryposi |
Farnesoid X receptor (FXR, Nr1h4) is a ligand-activated transcription factor belonging to the nuclear receptor superfamily. FXR is essential in maintaining bile acid (BA) homeostasis, and FXR(-/-) mice develop cholestasis, inflammation, and spontaneous liver tumors. The signal transducer and activator of transcription ... | Is farnesoid X receptor (FXR) a nuclear receptor? | Farnesoid X receptor (FXR, Nr1h4) is a ligand-activated transcription factor belonging to the nuclear receptor superfamily. |
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