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Production of a red blood cell's hemoglobin depends on mitochondrial heme synthesis. However, mature red blood cells are devoid of mitochondria and rely on glycolysis for ATP production. The molecular basis for the selective elimination of mitochondria from mature red blood cells remains controversial. Recent evidence ... | Is macroautophagy a selective degradation process? | However, in contrast to the core autophagy genes such as atg5 and atg7, expression of ulk1 is not essential for induction of macroautophagy in response to nutrient deprivation or for survival of newborn mice. Together, these data suggest that the ATG1 homologue, Ulk1, is a component of the selective autophagy machinery... |
Mitogen-activated protein kinase (MAPK) cascades are involved in the regulation of cellular proliferation, differentiation, survival, apoptosis, as well as in inflammatory responses. Signal intensity and duration have been recognized as crucial parameters determining MAPK signaling output. Phosphatases play a particula... | Is protein M3/6 a dual specificity phosphatase? | M3/6 (DUSP8) is a dual-specificity phosphatase implicated in the dephosphorylation and inactivation of JNK |
Lurasidone (Latuda(®)), a benzisothiazole derivative antipsychotic, is approved in the USA and Canada for the treatment of adults with major depressive episodes (MDE) associated with bipolar I disorder; this article reviews studies of lurasidone in this indication. In two 6-week, placebo-controlled trials in adults wit... | What is the first indication for lurasidone? | Lurasidone (Latuda(®)), a benzisothiazole derivative antipsychotic, is approved in the USA and Canada for the treatment of adults with major depressive episodes (MDE) associated with bipolar I disorder; this article reviews studies of lurasidone in this indication. |
Atogepant (Qulipta™) is an orally administered, small-molecule, calcitonin gene-related peptide (CGRP) receptor antagonist being developed by AbbVie for the prophylaxis of migraine. In September 2021, atogepant was approved in the USA for the preventive treatment of episodic migraine in adults. The drug is also in phas... | What is the use of Atogepant? | Atogepant (Qulipta™) is an orally administered, small-molecule, calcitonin gene-related peptide (CGRP) receptor antagonist being developed by AbbVie for the prophylaxis of migraine. In September 2021, atogepant was approved in the USA for the preventive treatment of episodic migraine in adults. The drug is also in phas... |
Depressive pseudodementia is a major depressive disorder in which the cognitive deficits secondary to the affective disorder is so significant that clinicians are obliged to consider dementia as a differential diagnosis. The relationship between depression and dementia is complex and intricate. Even after depressive ps... | What is pseudodementia? | Depressive pseudodementia is a major depressive disorder in which the cognitive deficits secondary to the affective disorder is so significant that clinicians are obliged to consider dementia as a differential diagnosis. |
The number of patients taking new oral anticoagulants is rising, so is the number of serious bleeding events. In severe bleeding, the decision to start a procoagulant therapy is difficult to take. With Idarucizumab and Andexanet Alfa, specific antidotes have been developed against both, direct thrombin inhibitors as we... | Andexanet Alfa is an antidote of which clotting factor inhibitors? | With Idarucizumab and Andexanet Alfa, specific antidotes have been developed against both, direct thrombin inhibitors as well as direct Factor Xa inhibitors. |
An essentially full-length cDNA clone for the human enzyme monoamine oxidase type A (MAO-A) has been used to determine the chromosomal location of a gene encoding it. This enzyme is important in the degradative metabolism of biogenic amines throughout the body and is located in the outer mitochondrial membrane of many ... | Which is the chromosomal location of the gene MAOA? | Using rodent-human somatic cell hybrids containing all or part of the human X chromosome, we have mapped these fragments to the region Xp21-p11. |
Submicroscopic deletions of chromosome 22q11 have been reported in a multiple anomaly syndrome variously labelled as velocardiofacial syndrome, conotruncal anomaly face syndrome, and Di George syndrome. Most 22q11 microdeletions occur sporadically, although in some cases the deletion may be transmitted. We describe two... | Velocardial facial syndrome, otherwise known as Di George syndrome is caused by a deletion in chromosome 21, yes or no? | Submicroscopic deletions of chromosome 22q11 have been reported in a multiple anomaly syndrome variously labelled as velocardiofacial syndrome, conotruncal anomaly face syndrome, and Di George syndrome |
Several studies have shown that the current prevalence of food allergy in Western Europe is about 4% and will further increase. Because of missing therapeutic alternatives, food allergy patients are required to identify individual allergens in the daily food by carefully reading the product's ingredient lists. Experien... | In which diseases have electronic patient diaries been applied ? | Instead of measuring physiological parameters, a Smartphone based Personal Allergy Assistant (PAA) allows patients to keep an electronic patient diary by scanning the barcode of the consumed food products. |
Hepatocyte growth factor modulates activation and antigen-presenting cell function of dendritic cells. However, the molecular basis for immunoregulation of dendritic cells by hepatocyte growth factor is undefined. In the current study, we demonstrate that hepatocyte growth factor exhibits inhibitory effect on dendritic... | Is c-met involved in the activation of the Akt pathway? | Notably, hepatocyte growth factor-stimulated c-Src activation results in induction of phosphatidylinositol 3-kinase complexes p85α/p110α and p85α/p110δ, which is required for activation of mammalian target of rapamycin, and consequent inhibition of IκB kinase and nuclear factor-κB activation. |
Dermatillomania or skin picking disorder (SPD) is a chronic, recurrent, and treatment resistant neuropsychiatric disorder with an underestimated prevalence that has a concerning negative impact on an individual's health and quality of life. The current treatment strategies focus on behavioral and pharmacological therap... | What is the difference between dermatillomania and skin picking disorder? | Dermatillomania or skin picking disorder (SPD) is a chronic, recurrent, and treatment resistant neuropsychiatric disorder with an underestimated prevalence that has a concerning negative impact on an individual's health and quality of life. |
In the epidermal growth factor receptor (EGFR) pathway, polymorphisms in EGFR and its ligand EGF have been studied as biomarkers for anti-EGFR treatment. However, the potential pharmacogenetic role of other EGFR ligands such as amphiregulin (AREG) and epiregulin (EREG) has not been elucidated. We studied 74 KRAS and BR... | List signaling molecules (ligands) that interact with the receptor EGFR? | EGFR and its ligand EGF |
Novel protein kinase C isoforms (PKC δ and ε) mediate early events in acute pancreatitis. Protein kinase D (PKD/PKD1) is a convergent point of PKC δ and ε in the signaling pathways triggered through CCK or cholinergic receptors and has been shown to activate the transcription factor NF-κB in acute pancreatitis. For the... | What is the mechanism of the drug CRT0066101? | For the present study we hypothesized that a newly developed PKD/PKD1 inhibitor, CRT0066101, would prevent the initial events leading to pancreatitis. |
Upon exposure to various environmental stresses such as arsenite, hypoxia, and heat shock, cells inhibit their translation and apoptosis and then repair stress-induced alterations, such as DNA damage and the accumulation of misfolded proteins. These types of stresses induce the formation of cytoplasmic RNA granules cal... | Which are the main functions of G3BP1 and G3BP2 proteins? | like G3BP1, the overexpression of G3BP2 induced SGs even without stress stimuli |
Alzheimer's disease (AD) is the most common age related neurodegenerative disease. Currently, there are no disease modifying drugs, existing therapies only offer short-term symptomatic relief. Two of the pathognomonic indicators of AD are the presence of extracellular protein aggregates consisting primarily of the Aβ p... | PBT2 has been tested for which disorder? | The most advanced of these strategies is the so-called 'metal protein attenuating compound' approach, with the lead molecule PBT2 having successfully completed early phase clinical trials. |
The mammalian genome contains numerous regions known as facultative heterochromatin, which contribute to transcriptional silencing during development and cell differentiation. We have analyzed the pattern of histone modifications associated with facultative heterochromatin within the mouse imprinted Snurf-Snrpn cluster... | Which histone modifications are associated with constitutive heterochromatin? | This result indicates that H3K36me3 is associated with both facultative and constitutive heterochromatin |
Warfarin and heparin are the traditional mainstay anticoagulant therapies for treating thromboembolic disease. These drugs, with a documented history of utility, also have inherent difficulties in usage; in particular, the complicated monitoring and numerous drug-drug interactions of warfarin, and the need for parenter... | Are there any specific antidotes for rivaroxaban? | Rivaroxaban, which inhibits activated factor X (Xa), is currently in clinical trials and is the most advanced factor Xa inhibitor. The drug offers once-daily oral dosing, with no need for injections, dose titration, or frequent blood tests to monitor the international normalised ratio. It has a rapid onset of action an... |
The use of medicinal plants concomitantly with conventional drugs can result in herb-drug interactions that cause fluctuations in drug bioavailability and consequent therapeutic failure and/or toxic effects. The CYP superfamily of enzymes plays an important role in herb-drug interactions. Among CYP enzymes, CYP3A4 and ... | What percentage of currently available drugs are metabolized by CYP3A4? | Among CYP enzymes, CYP3A4 and CYP2D6 are the most relevant since they metabolize about 50% and 30% of the drugs on the market, respectively. |
Cystathionine-β-synthase (CBS) gene encodes L-serine hydrolyase which catalyzes β-reaction to condense serine with homocysteine (Hcy) by pyridoxal-5'-phosphate helps to form cystathionine which in turn is converted to cysteine. CBS resides at the intersection of transmethylation, transsulfuration, and remethylation pat... | Are circular RNAs implicated in diseases of the eye? | Although circular RNAs (circRNAs) are dominant players regulating their parental genes' expression dynamics, their importance in ocular biology has not been appreciated. |
Autistic behavior is often accompanied by numerous disturbing symptoms on the part of gastrointestinal system, such as abdominal pain, constipation or diarrhea. These problems are often connected with deregulation of physiological microflora in intestine. The aim of this study was to determine differences in intestinal... | Is abdominal pain a common symptom in autism? | Autistic behavior is often accompanied by numerous disturbing symptoms on the part of gastrointestinal system, such as abdominal pain, constipation or diarrhea. |
The Melkersson-Rosenthal syndrome (MRS) is a rare condition characterized by the triad of familial relapsing peripheral facial palsy, facial edema, and lingua plicata. Within a well-documented family aggregate of MRS, an index case simultaneously demonstrated all the elements of the triad, as well as gingival changes s... | What is the triad of Melkersson-Rosenthal syndrome? | The Melkersson-Rosenthal syndrome (MRS) is a rare condition characterized by the triad of familial relapsing peripheral facial palsy, facial edema, and lingua plicata. |
Patients with systemic lupus erythematosus (SLE) have a markedly increased risk to develop cardiovascular disease, and traditional cardiovascular risk factors fail to account for this increased risk. We used microarray to probe the platelet transcriptome in patients with SLE and healthy controls, and the gene and prote... | Which is the main gene signature in Systemic Lupus Erythematosus (SLE)? | Real-time PCR was used to confirm a type I interferon (IFN) gene signature in patients with SLE, and the IFN-regulated proteins PRKRA, IFITM1 and CD69 (P < .0001) were found to be up-regulated in platelets from SLE patients compared with healthy volunteers. |
PI3K plays a key role in cellular metabolism and cancer. Using a mass spectrometry-based metabolomics platform, we discovered that plasma concentrations of 26 metabolites, including amino acids, acylcarnitines, and phosphatidylcholines, were decreased in mice bearing PTEN-deficient tumors compared with non-tumor-bearin... | What is the mechanism of action of Pictilisib? | Using a mass spectrometry-based metabolomics platform, we discovered that plasma concentrations of 26 metabolites, including amino acids, acylcarnitines, and phosphatidylcholines, were decreased in mice bearing PTEN-deficient tumors compared with non-tumor-bearing controls and in addition were increased following dosin... |
Dravet syndrome is an epileptic encephalopathy characterized by multiple types of seizures. We report the first case of musicogenic reflex seizures in a 7-year-old male with a mutation in the SCN1A gene causing Dravet syndrome. Reflex seizures have been reported in patients with Dravet syndrome provoked by body tempera... | What is Dravet syndrome? | Dravet syndrome is an epileptic encephalopathy characterized by multiple types of seizures. |
Subclinical hypothyroidism (SH), defined by elevated serum levels of thyroid stimulating hormone (TSH) with normal levels of free thyroid hormones, is common in adults, especially in women over 60 years of age. Among individuals with this condition, up to two-thirds have serum TSH levels between 5-10 mU/L and thyroid a... | At which kind of individuals is pharmacological treatment of subclinical hypothyroidism effective in reducing cardiovascular events? | Restoration of euthyroidism by levothyroxine (LT4) treatment may correct the lipid profile and cardiac abnormalities, especially in patients with an initially higher deviation from normality and higher serum TSH levels. Importantly, a strong association between SH and atherosclerotic cardiovascular disease, independent... |
Fusarium wilt is one of the most prevalent and damaging diseases of tomato. Among various toxins secreted by the Fusarium oxysporum f. sp. lycopersici (causal agent of Fusarium wilt of tomato), fusaric acid (FA) is suspected to be a potent pathogenicity factor in tomato wilt disease development. With this rationale the... | Fusarium oxysporum f. sp lycopersici. is a plant pathogen in plants producing what common food? | Fusarium wilt is one of the most prevalent and damaging diseases of tomato. Among various toxins secreted by the Fusarium oxysporum f. sp. lycopersici (causal agent of Fusarium wilt of tomato) |
Atopic Dermatitis (AD) is a common inflammatory skin disease with increasing prevalence in industrialized countries. Up to one-third of adults with AD have moderate-to-severe disease, leading to a large, unmet need for effective treatments. While current therapeutics focus mainly on symptom control, major advances have... | Signaling of which pathways is inhibited by Dupilumab? | An IL-4R antagonist, dupilumab, is the first drug that shows great promise in phase II trials. |
Epigenetic changes are defined as inherited modifications that are not present in DNA sequence. Gene expression is regulated at various levels and not only in response to DNA modifications. Examples of epigenetic control are DNA methylation, histone deacetylation and mi-RNA expression. Methylation of several tumor supp... | What are some examples of epigenetic modifications? | Examples of epigenetic control are DNA methylation, histone deacetylation and mi-RNA expression. |
Prediction of membrane spanning segments in beta-barrel outer membrane proteins (OMP) and their topology is an important problem in structural and functional genomics. In this work, we propose a method based on radial basis networks for predicting the number of beta-strands in OMPs and identifying their membrane spanni... | What are the computational methods for the prediction of beta-barrel transmembrane proteins? | We have developed a web server, TMBETAPRED-RBF for predicting the transmembrane beta-strands from amino acid sequence and it is available at http://rbf.bioinfo.tw/~sachen/tmrbf.html |
Cudratricusxanthone G (CTXG), a natural bioactive cudratricusxanthone extracted from C. tricuspidata, has shown anti-cancer properties. However, the function and mechanism of CTXG in tumor invasion have not been elucidated to date. In this study, we investigated the inhibitory effect of CTXG on the proliferation, migra... | Is Rac1 involved in cancer cell invasion? | The suppression of MMP-2 expression by CTXG led to an inhibition of SW620 cells invasion and migration by inactivating Rac1 and Cdc42 but not RhoA GTPase. |
The prevalence of anxiety symptoms and the prevalence of depression symptoms are high among patients suffering psoriatic arthritis in the studied population. | What is the link between psoriatic arthritis and depression | The prevalence of anxiety symptoms and the prevalence of depression symptoms are high among patients suffering psoriatic arthritis in the studied population. |
Clinical uses of doxorubicin (DOX), a highly active anticancer agent, are limited by its severe cardiotoxic side effects associated with increased oxidative stress and apoptosis. In this study we investigated whether aged garlic has protective effects against doxorubicin-induced free radical production and cardiotoxici... | Is Doxorubicin cardiotoxic? | Clinical uses of doxorubicin (DOX), a highly active anticancer agent, are limited by its severe cardiotoxic side effects associated with increased oxidative stress and apoptosis |
Rigel Pharmaceuticals Inc is developing fostamatinib, a prodrug of the spleen tyrosine kinase (Syk) inhibitor R-406, for the potential treatment of autoimmune diseases such as rheumatoid arthritis (RA), idiopathic thrombocytopenic purpura (ITP) and B-cell lymphomas. Syk is a key mediator of Fc and B-cell receptor signa... | Which enzyme is inhibited by a drug fostamatinib? | Rigel Pharmaceuticals Inc is developing fostamatinib, a prodrug of the spleen tyrosine kinase (Syk) inhibitor R-406, for the potential treatment of autoimmune diseases such as rheumatoid arthritis (RA), idiopathic thrombocytopenic purpura (ITP) and B-cell lymphomas. |
The organelle genome database GOBASE is now in its twelfth release, and includes 350,000 mitochondrial sequences and 118,000 chloroplast sequences, roughly a 3-fold expansion since previously documented. GOBASE also includes a fully reannotated genome sequence of Rickettsia prowazekii, one of the closest bacterial rela... | Which species of bacteria did the mitochondria originate from? | GOBASE also includes a fully reannotated genome sequence of Rickettsia prowazekii, one of the closest bacterial relatives of mitochondria, and will shortly expand to contain more data from bacteria from which organelles originated. |
Epigenetic regulation involves changes in gene expression independent of DNA sequence variation that are inherited through cell division. In addition to a fundamental role in cell differentiation, some epigenetic changes can also be transmitted transgenerationally through meiosis. Epigenetic alterations (epimutations) ... | Can epigenetic modifications be heritable? | Epigenetic alterations (epimutations) could thus contribute to heritable variation within populations and be subject to evolutionary processes such as natural selection and drift. |
We present two patients with inflammatory bowel disease who, despite negative tuberculosis screening, developed a de novo tuberculosis infection after the start of anti tumor necrosis factor alpha treatment. We discuss current screening methods and their limitations, the approach after positive screening and the timing... | What is the link between TB (Turbeculosis) infection and TNFa inhibition? | We present two patients with inflammatory bowel disease who, despite negative tuberculosis screening, developed a de novo tuberculosis infection after the start of anti tumor necrosis factor alpha treatment. |
NF-κB essential modulator (NEMO) and cylindromatosis protein (CYLD) are intracellular proteins that regulate the NF-κB signaling pathway. Although mice with either CYLD deficiency or an alteration in the zinc finger domain of NEMO (K392R) are born healthy, we found that the combination of these two gene defects in doub... | Is NEMO a zinc finger protein? | an alteration in the zinc finger domain of NEMO (K392R) |
We introduce a novel hash-based method for constructing the string graph. We use incremental hashing, and specifically a modification of the Karp-Rabin fingerprint, and Bloom filters. Using these probabilistic methods might create false-positive and false-negative edges during the algorithm's execution, but these are a... | In which fields of DNA sequencing are Bloom filters applied? | We introduce a novel hash-based method for constructing the string graph. We use incremental hashing, and specifically a modification of the Karp-Rabin fingerprint, and Bloom filters |
Fanconi anemia (FA) is a genetic disorder that predisposes to hematopoietic failure, birth defects and cancer. We identified an interaction between the FA protein, FANCA and brm-related gene 1 (BRG1) product. BRG1 is a subunit of the SWI/SNF complex, which remodels chromatin structure through a DNA-dependent ATPase act... | Which SWI/SNF protein complex subunit has been demonstrated to interact with the FANCA gene product? | We identified an interaction between the FA protein, FANCA and brm-related gene 1 (BRG1) product |
A central issue in stem cell biology is to understand the mechanisms that regulate the self-renewal of haematopoietic stem cells (HSCs), which are required for haematopoiesis to persist for the lifetime of the animal. We found that adult and fetal mouse and adult human HSCs express the proto-oncogene Bmi-1. The number ... | Which cyclin- dependent kinase inhibitor is regulated by Bmi-1? | A gene expression analysis revealed that the expression of stem cell associated genes, cell survival genes, transcription factors, and genes modulating proliferation including p16Ink4a and p19Arf was altered in bone marrow cells of the Bmi-1-/- mice |
Duchenne muscular dystrophy (DMD) is an X-linked genetic disease, caused by the absence of the dystrophin protein. Although many novel therapies are under development for DMD, there is currently no cure and affected individuals are often confined to a wheelchair by their teens and die in their twenties/thirties. DMD is... | Elaborate on the TREAT-NMD initiative for DMD patients | TREAT-NMD is a worldwide network for neuromuscular diseases that provides an infrastructure to support the delivery of promising new therapies for patients. |
We reviewed the natural history and differential diagnosis of ornithine transcarbamylase deficiency (an X-linked inborn error of urea synthesis) in 13 symptomatic female heterozygotes. The patients presented as early as the first week of life or as late as the sixth year. The most common symptoms before diagnosis were ... | What are the clinical symptoms of an ornithine transcarbamylase deficiency? | extreme irritability (100 percent), episodic vomiting and lethargy (100 percent), protein avoidance (92 percent), ataxia (77 percent), Stage II coma (46 percent), delayed physical growth (38 percent), developmental delay (38 percent), and seizures |
The independent mitochondrial genetic information is organized in so-called mitochondrial nucleoids that, in vertebrates, typically contain 5-7 genetic units. The total number of nucleoids per cell is several hundred in cultured cells. Mitochondrial nucleoids, similarly to the whole mitochondrial network, have recently... | What is a mitochondrial nucleoid? | The independent mitochondrial genetic information is organized in so-called mitochondrial nucleoids |
These data indicate that aberrant proteolytic activity in the NOD SMG results in increased fractalkine cleavage and generation of a unique fractalkine fragment. This specific cleavage may contribute to autoimmunity. | What is known about aberrant proteolytic activity in disease? | These data indicate that aberrant proteolytic activity in the NOD SMG results in increased fractalkine cleavage and generation of a unique fractalkine fragment. This specific cleavage may contribute to autoimmunity. |
Estrogens and progesterones are major drivers of breast development but also promote carcinogenesis in this organ. Yet, their respective roles and the mechanisms underlying their action in the human breast are unclear. Receptor activator of nuclear factor κB ligand (RANKL) has been identified as a pivotal paracrine med... | To the ligand of which receptors does Denosumab (Prolia) bind? | Whether the factor has the same role in humans is of clinical interest because an inhibitor for RANKL, denosumab, is already used for the treatment of bone disease and might benefit breast cancer patients. |
Ctf4p (chromosome transmission fidelity) has been reported to function in DNA metabolism and sister chromatid cohesion in Saccharomyces cerevisiae. In this study, a ctf4(S143F) mutant was isolated from a yeast genetic screen to identify replication-initiation proteins. The ctf4(S143F) mutant exhibits plasmid maintenanc... | What is the main role of Ctf4 in dna replication? | These data indicate that Ctf4p facilitates Mcm10p to promote the DNA replication |
Allgrove syndrome (or triple A syndrome) is a rare autosomal recessive disorder characterized by alacrima, achalasia, ACTH-resistant adrenal insufficiency and autonomic/neurological abnormalities. It is caused by mutations in the AAAS gene, located on chromosome 12q13. We describe a 42-year-old patient who presented wi... | List symptoms of Allgrove syndrome. | Allgrove syndrome should be suspected in patients with neurological impairment associated with two or more of the main symptoms (alacrima, achalasia or adrenal insufficiency). |
Glutamate is the major neurotransmitter of the brain, whose extracellular levels are tightly controlled by glutamate transporters. Five glutamate transporters in the human brain (EAAT1-5) are present on both astroglia and neurons. We characterize the profile of three different human astroglial progenitors in vitro: hum... | Which are the human glutamate transporters? | Five glutamate transporters in the human brain (EAAT1-5) are present on both astroglia and neurons. We characterize the profile of three different human astroglial progenitors in vitro: human glial restricted precursors (HGRP), human astrocyte precursors (HAPC), and early-differentiated astrocytes. |
Conversion of the soluble, nontoxic amyloid β-protein (Aβ) into an aggregated, toxic form rich in β-sheets is a key step in the onset of Alzheimer's disease (AD). It has been suggested that Aβ induces changes in neuronal membrane fluidity as a result of its interactions with membrane components such as cholesterol, pho... | As of Feb 2019, are major brain gangliosides a target for the treatment of Alzheimer's disease? | An understanding of the mechanism on the interaction of GM1 and Aβs in AD may contribute to the development of new neuroregenerative therapies for this disorder. |
Peripheral neuropathy (PN) has been reported in idiopathic and hereditary forms of parkinsonism, but the pathogenic mechanisms are unclear and likely heterogeneous. Levodopa-induced vitamin B12 deficiency has been discussed as a causal factor of PN in idiopathic Parkinson's disease, but peripheral nervous system involv... | Which syndrome is associated with mutations in the LYST gene? | Rarely, an association of parkinsonism with PN may be encountered in other neurodegenerative diseases such as fragile X-associated tremor and ataxia syndrome related to premutation CGG repeat expansion in the fragile X mental retardation (FMR1) gene, Machado-Joseph disease related to an abnormal CAG repeat expansion in... |
Beside the digestion of the extracellular matrix during tumor invasion and metastasis, more recently, new functions for matrix metalloproteinases (MMPs) have been proposed. We studied the expression and function of these enzymes in pituitary cells. We observed the activities of MMP-2 and MMP-9 together with expression ... | Is there association of matrix metalloproteinases with behaviour of pituitary adenomas? | We found surprisingly high levels of MMP activity and low levels of tissue inhibitor of metalloproteinases, indicating a high level of extracellular matrix-degrading activity in pituitary adenomas. |
The ATP-dependent chromatin-remodelling enzyme Chd1 is a 168-kDa protein consisting of a double chromodomain, Snf2-related ATPase domain, and a C-terminal DNA-binding domain. Here, we show the DNA-binding domain is required for Saccharomyces cerevisiae Chd1 to bind and remodel nucleosomes. The crystal structure of this... | What is the molecular function of the Chd1 protein? | Through inclusion of Chd1 sequences in homology searches SLIDE domains were identified in CHD6-9 proteins. |
Gastric cancer (GC) is currently the second leading cause of cancer death worldwide; unfortunately, most patients will present with locally advanced or metastatic disease. Despite recent progress in diagnosis, surgery, chemotherapy, and radiotherapy, prognosis remains poor. A better understanding of GC biology and sign... | Matuzumab has been tested for treatment of which cancers? | This article focuses on anti-Her-2 therapy, specifically trastuzumab, as well as other epidermal growth factor receptor antagonists such as cetuximab, panitumub, matuzumab, nimotzumab, gefitinib, and erlotinib. |
Conjugation of small interfering RNA (siRNA) to an asialoglycoprotein receptor ligand derived from N-acetylgalactosamine (GalNAc) facilitates targeted delivery of the siRNA to hepatocytes in vitro and in vivo. The ligands derived from GalNAc are compatible with solid-phase oligonucleotide synthesis and deprotection con... | What is the reason for N-acetylgalactosamine (GalNAc) conjugation of siRNAs? | Conjugation of small interfering RNA (siRNA) to an asialoglycoprotein receptor ligand derived from N-acetylgalactosamine (GalNAc) facilitates targeted delivery of the siRNA to hepatocytes in vitro and in vivo. |
Upc2p, a transcription factor of the zinc cluster family, is an important regulator of sterol biosynthesis and azole drug resistance in Candida albicans. To better understand Upc2p function in C. albicans, we used genomewide location profiling to identify the transcriptional targets of Upc2p in vivo. A triple hemagglut... | Which proteins are controlling sterol metabolism in S. cerevisiae? | Northern blot analysis showed that increased binding correlates with increased expression for the analyzed Upc2p targets (ERG11, MDR1, CDR1, YOR1, SUT1, SMF12, and CBP1). |
Whole genome sequencing is a useful diagnostic test in patients with suspected mitochondrial disorders, yielding a diagnosis in a further 31% after exclusion of common causes. Most diagnoses were non-mitochondrial disorders and included developmental disorders with intellectual disability, epileptic encephalopathies, o... | Can whole genome sequencing be used for diagnosis of mitochondrial disease? | Whole genome sequencing is a useful diagnostic test in patients with suspected mitochondrial disorders, yielding a diagnosis in a further 31% after exclusion of common causes. Most diagnoses were non-mitochondrial disorders and included developmental disorders with intellectual disability, epileptic encephalopathies, o... |
Traumatic brain injury (TBI) is one of the leading causes of neurological disability in young adults. Edaravone, a novel synthetic small-molecule free-radical scavenger, has been shown to have a neuroprotective effect in both animal models of cerebral ischemia and stroke patients; however, the underlying mechanism is p... | What is the role of edaravone in traumatic brain injury? | Edaravone treatment significantly decreased hippocampal CA3 neuron loss, reduced oxidative stress, and decreased neuronal programmed cell death compared to vehicle treatment. |
Toll-like receptors (TLRs) and the nucleotide-binding domain, leucine rich repeat containing family (or Nod-like receptors, NLRs) are two important families of microbial sensors that are membrane-associated and cytosolic molecules, respectively. The Nod proteins Nod1 and Nod2 are two NLR family members that trigger imm... | Is NOD1 activated in inflammation? | Nod1 is also critically implicated in shaping adaptive immune responses towards bacterial-derived constituents. |
Glucocorticoids have been shown repeatedly to inhibit the release of prolactin (PRL) in the rat but their site and mode of action is unknown. In the present study, we used an in vitro model to examine the requirement for protein synthesis for dexamethasone to suppress the release of immunoreactive (ir)-PRL release from... | What is the mode of action of dexamethasone? | Glucocorticoids have been shown repeatedly to inhibit the release of prolactin (PRL) in the rat but their site and mode of action is unknown. |
We describe the neurologic findings in a patient with alpha-N-acetylgalactosaminidase deficiency (Kanzaki disease). Clinical and electrophysiologic studies revealed sensory-motor polyneuropathy, and sural nerve pathology showed decreased density of myelinated fibers with axonal degeneration. The patient had mildly impa... | Is Kanzaki disease associated with deficiency in alpha-N-acetylgalactosaminidase? | We describe the neurologic findings in a patient with alpha-N-acetylgalactosaminidase deficiency (Kanzaki disease). |
Ameloblastoma (AM) is a slow growing and aggressive benign tumor with an odontogenic epithelial origin arising from the mandible or maxilla. The odontogenic neoplasm invades local tissues asymptomatically and accounts for 1% of oral tumors and over 10% of odontogenic tumors. A 64-year-old man with a history of allergic... | Is Ameloblastoma (AB) a common benign tumor occurring in the brain? | Ameloblastoma (AM) is a slow growing and aggressive benign tumor with an odontogenic epithelial origin arising from the mandible or maxilla. |
Bertolotti's syndrome refers to the association of back pain with lumbosacral transitional vertebrae. Such vertebrae were observed in 140 of 2,000 adults with back pain over a 4-year period of study. Each patient had radiographic evaluation of the lumbar spine by plain films as well as a sectional imaging modality (mag... | Abnormality in which vertebral region is important in the Bertolotti's syndrome? | Bertolotti's syndrome refers to the association of back pain with lumbosacral transitional vertebrae. |
Escherichia coli rnhA mutants devoid of RNase HI exhibit constitutive stable DNA replication, cSDR, which is thought to be initiated from R-loops stabilized in the absence of RNase HI. We found that a combination of an rnhA and a recG mutation is lethal to the cell. recG mutations that inactivate the helicase activity ... | Do R-loops tend to form at sites of DNA replication? | Escherichia coli rnhA mutants devoid of RNase HI exhibit constitutive stable DNA replication, cSDR, which is thought to be initiated from R-loops stabilized in the absence of RNase HI. |
Recent studies on yeast transcriptome have revealed the presence of a large set of RNA polymerase II transcripts mapping to intergenic and antisense regions or overlapping canonical genes. Most of these ncRNAs (ncRNAs) are subject to termination by the Nrd1-dependent pathway and rapid degradation by the nuclear exosome... | How are cryptic unstable transcripts (CUTs) defined? | Most of these ncRNAs (ncRNAs) are subject to termination by the Nrd1-dependent pathway and rapid degradation by the nuclear exosome and have been dubbed cryptic unstable transcripts (CUTs). |
Sudden cardiac death (SCD) is an uncommon but devastating potential consequence of participation in competitive sport. It is seen in adolescent and young adult athletes. The most common cause of this, hypertrophic cardiomyopathy (HCM), is a genetic disorder responsible for more than a third of cases and is manageable. ... | Which is the most common cause of sudden cardiac death in young athletes? | The most common cause of this, hypertrophic cardiomyopathy (HCM), is a genetic disorder responsible for more than a third of cases and is manageable. |
Published studies show that among identical twins, lower birthweight is associated with lower adult intelligence. However, no such relation between birthweight and adult IQ exists among fraternal twins. A likely explanation for the association between birthweight and intelligence among identical twins is the identical ... | In twin-twin transfusion syndrome, are the twins identical? | A likely explanation for the association between birthweight and intelligence among identical twins is the identical twin transfusion syndrome which occurs only between some monochorionic identical twin pairs. |
Hepatocellular carcinoma (HCC) is one of the common malignancy and lacks effective therapeutic targets. Here, we demonstrated that ectopic expression of trophinin-associated protein (TROAP) dramatically drove HCC cell growth assessed by foci formation in monolayer culture, colony formation in soft agar and orthotopic l... | Please summarize the function of Trophinin-associated protein (TROAP) | ctopic expression of trophinin-associated protein (TROAP) dramatically drove HCC cell growth assessed by foci formation in monolayer culture, colony f |
We present a review of 60 cases of cluster headache. Most patients were males, ranging from 19 to 65 years of age at the time of the first visit. Headaches consisted of short-lasting (from 15 to 210 minutes), intense, unilateral pain attacks, most frequently in the periorbital area, with ipsilateral autonomic signs (rh... | What pharmacological and non-pharmacological interventions can be considered as prophylactic therapies in Cluster Headache patients? | Prophylactic therapy in most cases consisted of verapamil, also with a good response. |
Telomerase is mainly active in human tumor cells, which provides an opportunity for a therapeutic window on telomerase targeting. We sought to evaluate the potential of the thio-phosphoramidate oligonucleotide inhibitor of telomerase, imetelstat, as a drug candidate for treatment of esophageal cancer. Our results showe... | Which enzyme is targeted by the drug Imetelstat? | We sought to evaluate the potential of the thio-phosphoramidate oligonucleotide inhibitor of telomerase, imetelstat, as a drug candidate for treatment of esophageal cancer. Our results showed that imetelstat inhibited telomerase activity in a dose-dependent manner in esophageal cancer cells |
Cutaneous lesions of sarcoidosis present with various manifestations including specific and non-specific cutaneous lesions. Ichthyosiform sarcoidosis is a rare form of cutaneous sarcoidosis, presenting with asymptomatic, adherent, polygonal scales, mainly appearing on the lower limbs. Ichthyosiform sarcoidosis has a p... | List symptoms of Heerfordt syndrome. | Case 3 showed Heerfordt syndrome with facial nerve paralysis. |
Harlequin sign and harlequin syndrome, which are used interchangeably in the literature, are characterized by sudden onset of hemifacial sweating and flushing, induced by exercise and heat. Hemifacial sweating and flushing with normal ocular sympathetic innervation, known as harlequin syndrome, is rarely associated wit... | Describe clinical manifestation of the Harlequin syndrome. | Harlequin sign and harlequin syndrome, which are used interchangeably in the literature, are characterized by sudden onset of hemifacial sweating and flushing, induced by exercise and heat. |
Zika virus has rapidly spread through the World Health Organization's Region of the Americas since being identified in Brazil in early 2015. Transmitted primarily through the bite of infected Aedes species mosquitoes, Zika virus infection during pregnancy can cause spontaneous abortion and birth defects, including micr... | What are some of the effects of Zika Virus in infected individuals? | Zika virus infection during pregnancy can cause spontaneous abortion and birth defects, including microcephaly |
In this article, we give hands-on instructions to obtain translatome data from different Arabidopsis thaliana root cell types via the translating ribosome affinity purification (TRAP) method and consecutive optimized low-input library preparation. As starting material, we employ plant lines that express GFP-tagged ribo... | What is the aim of the TRAP method? | In this article, we give hands-on instructions to obtain translatome data from different Arabidopsis thaliana root cell types via the translating ribosome affinity purification (TRAP) method |
IL-18 is a proinflammatory and immune regulatory cytokine, member of the IL-1 family. IL-18 was initially identified as an IFN-γ-inducing factor in T and NK cells, involved in Th1 responses. IL-18 is produced as an inactive precursor (pro-IL-18) that is enzymatically processed into a mature form by Casp1. Different cel... | What is the role of IL-18BP? | The natural inhibitor IL-18BP , whose production is enhanced by IFN-γ and IL-27, further regulates IL-18 activity in the extracellular environment. |
First isolated in 1947 from a monkey in the Zika forest in Uganda, and from mosquitoes in the same forest the following year, Zika virus has gained international attention due to concerns for infection in pregnant women potentially causing fetal microcephaly. More than one million people have been infected since the ap... | What are some of the effects of Zika Virus in infected individuals? | Zika virus has gained international attention due to concerns for infection in pregnant women potentially causing fetal microcephaly. |
RNA interference has tremendous yet unrealized potential to treat a wide range of illnesses. Innovative solutions are needed to protect and selectively deliver small interfering RNA (siRNA) cargo to and within a target cell to fully exploit siRNA as a therapeutic tool in vivo. Herein, we describe ammonium-functionalize... | Are there RNAi approaches considered for the treatment of kidney injury? | Herein, we describe ammonium-functionalized carbon nanotube (fCNT)-mediated transport of siRNA selectively and with high efficiency to renal proximal tubule cells in animal models of acute kidney injury (AKI). |
A 36-year-old female patient was treated with PUVA for dyshidrotic eczema that had not shown sufficient response to topical therapy over the previous months. PUVA therapy caused acute aggravation of the eczema. Patch testing demonstrated Type IV sensitization to 8-methoxypsoralen in Meladinine solution. | Is PUVA therapy indicated for eczema treatment? | A 36-year-old female patient was treated with PUVA for dyshidrotic eczema that had not shown sufficient response to topical therapy over the previous months. |
A novel coronavirus (SARS-CoV-2) has been identified as the causative pathogen of an ongoing outbreak of respiratory disease, now named COVID-19. Most cases and sustained transmission occurred in China, but travel-associated cases have been reported in other countries, including Europe and Italy. Since the symptoms are... | Is there a way to distinguish COVID-19 clinically from other respiratory illnesses, such as influenza? | Since the symptoms are similar to other respiratory infections, differential diagnosis in travellers arriving from countries with wide-spread COVID-19 must include other more common infections such as influenza and other respiratory tract diseases. |
Autologous, patient-specific chimeric antigen receptor T-cell (CART) therapy has emerged as a powerful and potentially curative therapy for cancer, especially for CD19-positive hematological malignancies. Indeed, on August 30, 2017, the University of Pennsylvania-designed CD19-directed CART (CART-19) cell therapy (CTL0... | What is the mechanism of action of Tisagenlecleucel? | Indeed, on August 30, 2017, the University of Pennsylvania-designed CD19-directed CART (CART-19) cell therapy (CTL019, tisagenlecleucel-t, Kymriah - Novartis) became the first CART therapy approved by the Food and Drug Administration (FDA) for acute lymphoblastic leukemia. |
Background. A common research goal in transcriptome projects is to find genes that are differentially expressed in different phenotype classes. Biologists might wish to validate such gene candidates experimentally, or use them for downstream systems biology analysis. Producing a coherent differential gene expression an... | Which type of analysis does DeSeq2 perform? | When triplicates or more are available, GFOLD is a sharp tool for identifying high confidence differentially expressed genes for targeted qPCR validation; for downstream systems level analysis, combined results from DESeq2 and edgeR are useful. |
Zika fever, considered as an emerging disease of arboviral origin, because of its expanding geographic area, is known as a benign infection usually presenting as an influenza-like illness with cutaneous rash. So far, Zika virus infection has never led to hospitalisation. We describe the first case of Guillain-Barré syn... | What are some of the effects of Zika Virus in infected individuals? | We describe the first case of Guillain-Barré syndrome (GBS) occurring immediately after a Zika virus infection, during the current Zika and type 1 and 3 dengue fever co-epidemics in French Polynesia. |
The enhancer landscape of pluripotent stem cells undergoes extensive reorganization during early mammalian development. The functions and mechanisms behind such reorganization, however, are unclear. Here, we show that the transcription factor GRHL2 is necessary and sufficient to activate an epithelial subset of enhance... | What is formative pluripotency? | Here, we show that the transcription factor GRHL2 is necessary and sufficient to activate an epithelial subset of enhancers as naive embryonic stem cells (ESCs) transition into formative epiblast-like cells (EpiLCs). |
Erythropoiesis requires large amounts of iron for hemoglobin synthesis, which is mainly provided by macrophages and the intestines in a transferrin (Tf)-bound form. Bone marrow erythroblasts incorporate Tf through endocytosis, which is mediated by transferrin receptor 1 (TFR1). Recently, human TFR1, aside from its role... | Is the TFR1 gene dispensable for erythropoiesis? | Erythropoiesis requires large amounts of iron for hemoglobin synthesis, which is mainly provided by macrophages and the intestines in a transferrin (Tf)-bound form. |
The proteasome inhibitor bortezomib is emerging as a potent anti-cancer agent. Still, recent clinical trials have revealed a significant secondary toxicity of bortezomib. Consequently, there is much interest in dissecting the mechanism of action of this compound to rationally improve its therapeutic index. The cytotoxi... | Is bortezomib a Proteasome inhibitor? | The proteasome inhibitor bortezomib is emerging as a potent anti-cancer agent. |
IMGT/3Dstructure-DB is the three-dimensional (3D) structure database of IMGT, the international ImMunoGenetics information system that is acknowledged as the global reference in immunogenetics and immunoinformatics. IMGT/3Dstructure-DB contains 3D structures of immunoglobulins (IG) or antibodies, T cell receptors (TR),... | What systems have been developed for the numbering of antibody residues? | amino acid positions according to the IMGT unique numbering (NUMEROTATION) that are used in IMGT/3Dstructure-DB cards, results of contact analysis and renumbered flat files. |
In approximately 10-20% of all sudden deaths, no structural cardiac abnormalities can be identified. Important potential causes of sudden cardiac deaths in the absence of heart disease are primary electrical diseases such as Brugada syndrome, long QT syndrome (LQTS), short QT syndrome (SQTS), and catecholaminergic poly... | Could Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) | null |
NADPH:protochlorophyllide (Pchlide) oxidoreductase (POR) is the key enzyme in the light-induced greening of higher plants. A unique light-harvesting POR:Pchlide complexes (LHPP) has been found in barley etioplasts, but not in other plant species. Why PORs from barley, but not from other plants, can form LHPP? And its f... | In what type(s) of plant organelles we can detect prolamellar bodies? | POR complex assembly (including LHPP and POR dimers) did not affect the formation of prolamellar bodies (PLBs) that function for efficient capture of light energy for photo conversion in etioplasts. |
Expression of transposable elements in the germline is controlled by Piwi-interacting (pi) RNAs produced by genomic loci termed piRNA clusters and associated with Rhino, a heterochromatin protein 1 (HP1) homolog. Previously, we have shown that transgenes containing a fragment of the retrotransposon form de novo piRNA ... | What is the function of HP1a in the nucleus? | Expression of transposable elements in the germline is controlled by Piwi-interacting (pi) RNAs produced by genomic loci termed piRNA clusters and associated with Rhino, a heterochromatin protein 1 (HP1) homolog. Pre |
Immunoelectron microscopy was performed to study the biosynthesis of lysosomal beta-galactosidase (beta-gal) in normal and mutant human fibroblasts. Using polyclonal and monoclonal antibodies we show in normal cells precursor forms of beta-gal in the rough endoplasmic reticulum (RER) and in the Golgi apparatus througho... | Which enzyme deficiency can cause GM1 gangliosidoses? | In the autosomal recessive disease GM1-gangliosidosis caused by a beta-gal deficiency and in galactosialidosis, associated with a combined deficiency of lysosomal neuraminidase and beta-gal, precursor forms of the latter enzyme are found in RER, Golgi and some labeling is present at the cell surface. The lysosomes rema... |
Treatment for myasthenia gravis should be individualized to each patient based on the clinical characteristics of myasthenia including the distribution, duration, and severity of weakness and resulting functional impairment; the risks for treatment complications related to age, gender, and medical comorbidities; and th... | Which acetylcholinesterase inhibitors are used for treatment of myasthenia gravis? | Acetylcholinesterase inhibitors provide temporary, symptomatic treatment for all forms of myasthenia gravis. |
Translocations involving ETS-transcription factors, most commonly leading to the EWSR1-FLI1 fusion protein, are the hallmark of Ewing sarcoma. Despite knowledge of this driving molecular event, an effective therapeutic strategy is lacking. To test potential treatment regimes, we established a novel Ewing sarcoma zebraf... | Which translocation is the hallmark of Ewing sarcoma? | Translocations involving ETS-transcription factors, most commonly leading to the EWSR1-FLI1 fusion protein, are the hallmark of Ewing sarcoma |
Neutrophil elastase gene (ELANE) mutations are responsible for the majority of cases of severe congenital neutropenia (CN) and cyclic neutropenia (CyN). We screened CN (n = 395) or CyN (n = 92) patients for ELANE mutations and investigated the impact of mutations on mRNA expression, protein expression, and activity. We... | Which gene is most commonly associated with severe congenital and cyclic neutropenia? | Neutrophil elastase gene (ELANE) mutations are responsible for the majority of cases of severe congenital neutropenia (CN) and cyclic neutropenia (CyN) |
Many debilitating diseases, including neurodegenerative diseases, involve apoptosis. Several methods have been developed for visualizing apoptotic cells in vitro or in fixed tissues, but few tools are available for visualizing apoptotic cells in live animals. Here we describe a genetically encoded fluorescent reporter ... | List fluorescent reporter proteins. | yellow fluorescent protein |
Given the increasing prevalence of atrial fibrillation, the need for safe and effective stroke prophylaxis will continue to rise. Warfarin has been around for many years and has proven efficacy in preventing stroke, but it has major limitations due to its variable dosing, food and drug interactions, and requirement for... | Which two drugs were compared in the ARISTOTLE Trial? | The ARISTOTLE trial showed apixaban was superior to warfarin for stroke prevention, significantly reduced all major bleeding, and resulted in a significant reduction in all-cause mortality. |
MiR-223 is intensely expressed in RA synovium, and overexpression of miR-223 suppresses osteoclastogenesis in vitro. This study demonstrates the possibility of gene therapy with miR-223 to treat bone destruction in RA patients. | Which micro-RNAs have been associated in the pathogenesis of Rheumatoid Arthritis? | MiR-223 is intensely expressed in RA synovium, and overexpression of miR-223 suppresses osteoclastogenesis in vitro |
Apolipoprotein E (apo E) plays a role in the regulation of the lipid metabolism of humans. Apo E, 229 amino acid polypeptide, is classified into three major isoform (E2, E3, E4) according to the differences of amino acid in position 112 and 158. In the normal population apo E3 isoform is most prevalent and apo E2 or E4... | Which ApoE isoform is associated with hyperlipoproteinemia? | From the data of a high association of apo E4 allele and cardiovascular disease with hypercholesterolemia, apo E isoform may be one of the determinants of hyperlipoproteinemia. |
Although molecular tools for controlling neuronal activity by light have vastly expanded, there are still unmet needs which require development and refinement. For example, light delivery into the brain is still a major practical challenge that hinders potential translation of optogenetics in human patients. In additio... | Are Luminopsins a fusion proteins of luminol and Rhodopsin ? | luminopsins by fusing light-sensing opsins with light-emitting luciferases. |
Background Findings from clinical trials of proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors have led to concern that these drugs or the low levels of low-density lipoprotein (LDL) cholesterol that result from their use are associated with cognitive deficits. Methods In a subgroup of patients from a ran... | Does Evolocumab improve cognitive function? | Conclusions In a randomized trial involving patients who received either evolocumab or placebo in addition to statin therapy, no significant between-group difference in cognitive function was observed over a median of 19 months. |
Nusinersen (ISIS-SMNRx or ISIS 396443) is an antisense oligonucleotide drug administered intrathecally to treat spinal muscular atrophy. We summarize lumbar puncture experience in children with spinal muscular atrophy during a phase 1 open-label study of nusinersen and its extension. During the studies, 73 lumbar punct... | Which disease is treated with Nusinersen? | Nusinersen (ISIS-SMNRx or ISIS 396443) is an antisense oligonucleotide drug administered intrathecally to treat spinal muscular atrophy. We summarize lumbar puncture experience in children with spinal muscular atrophy during a phase 1 open-label study of nusinersen and its extension. |
Ubiquitination is best known for its role in targeting proteins for degradation by the proteasome, but evidence of the nonproteolytic functions of ubiquitin is also rapidly accumulating. One example of the regulatory, rather than proteolytic, function of ubiquitin is provided by study of the tumor necrosis factor (TNF)... | What is the biological role of K-48 linked protein ubiquitination? | Indeed, the TRAF2-interacting protein RIP can mediate IKK activation when it is modified by K(63) polyubiquitin chains, but is targeted to degradation by the proteasome when it is K(48)-polyubiquitinted by the NF-kappaB inhibitor A20. |
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