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Iron is an essential metal for cell survival that is regulated by the peptide hormone hepcidin. However, its influence on certain diseases is directly related to iron metabolism or secondary to underlying diseases. Genetic alterations influence the serum hepcidin concentration, which can lead to an iron overload in tis... | Hepcidin is a key regulator of what processes? | Iron is an essential metal for cell survival that is regulated by the peptide hormone hepcidin. However, its influence on certain diseases is directly related to iron metabolism or secondary to underlying diseases. |
Acute cytokine release syndromes are associated with some therapeutic antibodies in man, leading to a spectrum of clinical signs from nausea, chills and fever to more serious dose limiting hypotension and tachycardia. When anticipated this syndrome is typically manageable, however this adverse reaction recently became ... | Describe a cytokine release syndrome. | Acute cytokine release syndromes are associated with some therapeutic antibodies in man, leading to a spectrum of clinical signs from nausea, chills and fever to more serious dose limiting hypotension and tachycardia. |
Triad of Hakim--Adams is well known for normal pressure hydrocephalus (NPH): dementia, gait disturbances and urinary incontinence. Variability of intensity of these symptoms is obvious. However in clinical practice all classic signs are present. We describe a case of posttraumatic NPH producing only gait impairment wit... | List symptoms of the Hakim Triad? | Triad of Hakim--Adams is well known for normal pressure hydrocephalus (NPH): dementia, gait disturbances and urinary incontinence. |
X-inactive specific transcript (Xist) is a long noncoding RNA that is essential for initiating and maintaining epigenetic silencing of one copy of the X chromosome in mammalian females. But the mechanism by which Xist localizes and spreads on the X chromosome and facilitates transcriptional silencing remains largely un... | The X-inactive specific transcript (Xist) gene is responsible for mediating the X-chromosome inactivation in females, where one X-chromosome is silenced and transcriptionally inactivated. What does Xist encode? | X-inactive specific transcript (Xist) is a long noncoding RNA that is essential for initiating and maintaining epigenetic silencing of one copy of the X chromosome in mammalian females. |
Noncoding DNA regions have central roles in human biology, evolution, and disease. ChromHMM helps to annotate the noncoding genome using epigenomic information across one or multiple cell types. It combines multiple genome-wide epigenomic maps, and uses combinatorial and spatial mark patterns to infer a complete annota... | What is the function of the chromHMM software? | ChromHMM helps to annotate the noncoding genome using epigenomic information across one or multiple cell types. It combines multiple genome-wide epigenomic maps, and uses combinatorial and spatial mark patterns to infer a complete annotation for each cell type |
Hypothalamic hormones as well as anterior pituitary hormones were detected in the peripheral plasma after the diagnosis of brain death. It is possible that residual hypothalamic tissue was functioning after satisfying the usual criteria of total brain death. To examine this possibility, endocrinological and morphologic... | What is the role of Thyrotropin Releasing Hormone in the treatment of comatose patients? | The direct TRH (thyrotropin releasing hormone) stimulation to the anterior lobe was responded to well. |
During the autumn of 1992, Western Australia experienced a large viral meningitis outbreak of dual aetiology. Of the 161 cases, 64% were children under 15 years of age, with the highest notification rate being in children less than 5 years of age. Echovirus 9 caused 41% of cases and occurred mainly in the metropolitan ... | Which are the types of viral meningitis? | Echovirus 9 caused 41% of cases and occurred mainly in the metropolitan areas of Western Australia whereas echovirus 6, which caused 37% of cases, was more widespread. |
With specialized care, patients with myasthenia gravis can have very good outcomes. The mainstays of treatment are acetylcholinesterase inhibitors, and immunosuppressive and immunomodulatory therapies. There is good evidence thymectomy is beneficial in thymomatous and nonthymomatous disease. Nearly all of the drugs use... | Is eculizumab used for treatment of myasthenia gravis? | The 2 exceptions are acetylcholinesterase inhibitors and complement inhibition with eculizumab, which was recently approved by the US Food and Drug Administration for myasthenia gravis. |
This study reports on molecular analysis of a Measles virus (MV) isolate from a patient who was infected in Japan but showed symptoms after arriving to Brazil. This patient had typical clinical measles infection symptoms: fever, rash, cough and coryza. After isolating the virus in B95a cells, a fragment of the nucleopr... | Please list symptoms of measles. | This patient had typical clinical measles infection symptoms: fever, rash, cough and coryza. |
The cause of familial isolated pituitary adenomas (FIPA) remains unknown in a high percentage of cases, but the AIP gene plays an important role in the etiology. The aim of the study is to describe a family with FIPA syndrome and the results of genomic studies. A 16-year-old man had a giant prolactinoma resistant tomed... | Mutation of which gene is implicated in the familial isolated pituitary adenoma? | The cause of familial isolated pituitary adenomas (FIPA) remains unknown in a high percentage of cases, but the AIP gene plays an important role in the etiology. |
BOS172722 (CCT289346) is a highly potent, selective, and orally bioavailable inhibitor of spindle assembly checkpoint kinase MPS1. BOS172722 treatment alone induces significant sensitization to death, particularly in highly proliferative triple-negative breast cancer (TNBC) cell lines with compromised spindle assembly ... | List orally bioavailable MPS1 kinase inhibitors | BOS172722 (CCT289346) is a highly potent, selective, and orally bioavailable inhibitor of spindle assembly checkpoint kinase MPS1. BOS172722 treatment alone induces significant sensitization to death, particularly in highly proliferative triple-negative breast cancer (TNBC) cell lines with compromised spindle assembly ... |
Various neurodegenerative diseases are associated with aberrant gene expression. We recently identified a novel class of pimelic o-aminobenzamide histone deacetylase (HDAC) inhibitors that show promise as therapeutics in the neurodegenerative diseases Friedreich's ataxia (FRDA) and Huntington's disease (HD). Here, we d... | For which diseases members of the 2-aminobenzamide class of histone deacetylase (HDAC) inhibitors show promise as therapeutics? | We recently identified a novel class of pimelic o-aminobenzamide histone deacetylase (HDAC) inhibitors that show promise as therapeutics in the neurodegenerative diseases Friedreich's ataxia (FRDA) and Huntington's disease (HD). |
The mechanistic target of rapamycin (mTOR) functions as a component of two large complexes, mTORC1 and mTORC2, which play crucial roles in regulating cell growth and homeostasis. However, the molecular mechanisms by which mTOR controls cell proliferation remain elusive. Here we show that the FoxO3a transcription factor... | Which protein pathway is regulating SGK1-mediated phosphorylation of FOXO3a to control cell proliferation? | the FoxO3a transcription factor is coordinately regulated by mTORC1 and mTORC2, and plays a crucial role in controlling cell proliferation |
The diverse cellular contributions to the skeletal elements of the vertebrate shoulder and pelvic girdles during embryonic development complicate the study of their patterning. Research in avian embryos has recently clarified part of the embryological basis of shoulder formation. Although dermomyotomal cells provide th... | Which disease has been associated to a disruptive ALX1 protein? | Scapular truncation in triple mutants of Tbx15, Alx4 and Cart1 indicates essential functions for Alx4 and Cart1 in the anterior part of the scapula |
On September 1, 2017, the FDA granted approval for gemtuzumab ozogamicin (Mylotarg; Pfizer Inc.) in combination with daunorubicin and cytarabine and as a monotherapy for the treatment of adult patients with newly diagnosed CD33-positive acute myeloid leukemia (AML). Gemtuzumab ozogamicin is a CD33-targeted antibody-dru... | Where does gemtuzumab ozogamicin bind? | Gemtuzumab ozogamicin is a CD33-targeted antibody-drug conjugate joined to calicheamicin. |
Drug-induced interstitial lung disease (D-ILD) can be caused by various drugs, including antibiotics, amiodarone, antitumor, rheumatological and non-steroidal anti-inflammatory drugs. D-ILD includes hypersensitivity reactions, organizing and non-specific interstitial pneumonia, eosinophilic lung diseases, diffuse alveo... | What class of drugs is commonly associated with Drug-induced interstitial lung disease (DIILD)? | Drug-induced interstitial lung disease (D-ILD) can be caused by various drugs, including antibiotics, amiodarone, antitumor, rheumatological and non-steroidal anti-inflammatory drugs. |
Some antibiotics are suggested to exert neuroprotective effects via regulation of glial responses. Attenuation of microglial activation by minocycline prevents neuronal death in a variety of experimental models for neurological diseases, such as cerebral ischemia, Parkinson's and Huntington's disease. Ceftriaxone delay... | What is known about clinical efficacy of ceftriaxone for treatment of amyotrophic lateral sclerosis? | Ceftriaxone delays loss of neurons in genetic animal models of amyotrophic lateral sclerosis through upregulation of astrocytic glutamate transporter expression (GLT-1). |
COVID-19 vaccines are effective and important to control the ongoing pandemic, but vaccine reactogenicity may contribute to poor uptake. Analgesics or antipyretic medications are often used to alleviate vaccine side effects, but their effect on immunogenicity remains uncertain. Few studies have assessed the effect of a... | Can analgesics or antipyretics be taken for side effects following COVID-19 vaccination? | Specific data on the impact of analgesic/antipyretic medications on immunogenicity of COVID-19 vaccines are limited. |
Although thalidomide was withdrawn in the 1960s after its teratogenic property was recognized, it was subsequently found that this drug possesses immunomodulatory and anti-inflammatory effects. Recent studies have also demonstrated that thalidomide has antineoplastic activity via an antiangiogenic mechanism. Observatio... | Is thalidomide used as an immunomodulatory drug nowadays? | Although thalidomide was withdrawn in the 1960s after its teratogenic property was recognized, it was subsequently found that this drug possesses immunomodulatory and anti-inflammatory effects. |
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? | 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... |
The pathogenesis of stroke involves inflammation, apoptosis, and excitotoxicity, which is mediated in part by neuronal NO synthase (nNOS) activation. Ghrelin, an endogenous 28-amino acid peptide, is shown to exert antiapoptotic and anti-inflammatory properties. However, the effect of ghrelin in permanent focal cerebral... | Does ghrelin play a role in ischemic stroke? | Human ghrelin treatment in vagus nerve-intact rats significantly decreased the above measurements. Human ghrelin treatment also improved 7-day survival and significantly decreased neurological deficit over the entire 7 days after MCAO in vagus nerve-intact rats compared with vehicle. |
Stem cell transplantation is currently generating a significant interest for use in the future treatment of cardiovascular diseases. Stem cell populations are rapidly increasing, and we are still in the search of optimal cell types to use in clinical trials as bone marrow stem cells did not show significant improvement... | Are there clinical trials using stem cells for the treatment of cardiac disease? | Stem cell populations are rapidly increasing, and we are still in the search of optimal cell types to use in clinical trials as bone marrow stem cells did not show significant improvement in cardiac function following transplantation. |
Cri-du-chat syndrome is a chromosomal disorder caused by a deletion of the short arm of chromosome 5. The disease severity, levels of intellectual and developmental delay, and patient prognosis have been related to the size and position of the deletion. Aiming to establish genotype-phenotype correlations, we applied ar... | Is Cri Du Chat associated with an expansion of a repeat with in the gene found on chromosome 5? | Cri-du-chat syndrome is a chromosomal disorder caused by a deletion of the short arm of chromosome 5 |
Intramural hematoma of the aorta is a condition increasingly observed in clinical practice. Uncertainty exists whether such lesions represent a different pathology or simply the precursors of classic dissecting aneurysm. The patient was a 76-year-old woman with intramural hematoma of the ascending aorta. Clinical cours... | What is the most frequent evolution (next stage) when Aortic intramural hematoma (IMH) is not treated? | We stress that intramural hematoma of the ascending aorta has to be managed as an aortic type A dissection and that aggressive treatment is advisable. |
AtxA, a unique regulatory protein of unknown molecular function, positively controls expression of the major virulence genes of Bacillus anthracis. The 475 amino acid sequence of AtxA reveals DNA binding motifs and regions similar to proteins associated with the phosphoenolpyruvate: carbohydrate phosphotransferase syst... | What is the function of the AtxA pleiotropic regulator? | AtxA, a unique regulatory protein of unknown molecular function, positively controls expression of the major virulence genes of Bacillus anthracis. |
Activating transcription factor 4 (ATF4) belongs to the ATF/CREB (activating transcription factor/cyclic AMP response element binding protein) family of basic region-leucine zipper (bZip) transcription factors, which have the consensus binding site cAMP responsive element (CRE). ATF4 has numerous dimerization partners.... | Has ATF4 transcription factor been linked to cancer and neoplastic transformation? | ATF4 expression is upregulated in cancer. |
Kearns-Sayre syndrome (KSS) is a disease with severe clinical symptoms that often arises from a mitochondrial DNA deletion of 4977 bp. Quantification of defective mitochondrial DNA is important since the severity of symptoms in KSS is thought to be related to increased content of abnormal mitochondrial DNA. We develope... | What is Kearns-Sayre syndrome (KSS)? | Kearns-Sayre syndrome (KSS) is a disease with severe clinical symptoms that often arises from a mitochondrial DNA deletion of 4977 bp. |
Alemtuzumab (previously known as Campath(®)) is a humanized monoclonal antibody directed against the CD52 antigen on mature lymphocytes that results in lymphopenia and subsequent modification of the immune repertoire. Here we explore evidence for its efficacy and safety in relapsing-remitting multiple sclerosis. One Ph... | What are the names of anti-CD52 monoclonal antibody that is used for treatment of multiple sclerosis patients? | Compared to interferon beta-1a, alemtuzumab reduced the relapse rate by 49%-74% (P < 0.0001), and in two studies it reduced the risk of sustained disability accumulation by 42%-71% (P < 0.01). In one study (Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis; CARE-MS1), there was no significant differenc... |
Telomerase plays an important role in cell proliferation and carcinogenesis and is believed to be a good target for anti-cancer drugs. Elimination of template function of telomerase RNA may repress the telomerase activity. A hammer-headed ribozyme (telomerase ribozyme, teloRZ) directed against the RNA component of huma... | What makes telomerase a good drug target? | Telomerase plays an important role in cell proliferation and carcinogenesis and is believed to be a good target for anti-cancer drugs. |
Thyroid hormone analogs with selective actions through specific thyroid hormone receptor (TR) subtypes are of great interest. They might offer the possibility of mimicking physiological actions of thyroid hormone with receptor subtype or tissue specificity with therapeutic aims. They are also pharmacological tools to d... | Which compounds exist that are thyroid hormone analogs? | two thyroid hormone agonists, the TRβ-selective GC-24 and the TRα-selective CO23 |
Leptin, an adipocyte-released hormone, modifies food intake and energy expenditure regulating hypothalamic-pituitary-thyroid axis function. We previously reported that thyrotropin-releasing hormone (TRH) precursor gene overexpression induces hypertension in the normal rat and that spontaneously hypertensive rats have c... | What is the role of TRH in hypertension? | We propose that because leptin produces central TRH synthesis and release, obesity may induce hypertension through TRH system activation and that the TRH-leptin interaction may thus contribute to the strong association between hypertension and obesity. |
Titin, the largest protein identified to date (over 1 micron long, almost 3 million daltons in mass) is the third most abundant component of the sarcomere. In the mature myofibril, titin molecules span from M line to Z line, forming a third filament system which provides sarcomeric alignment and elastic recoil. In the ... | Is Titin the largest single protein molecule found in Nature? | Titin, the largest protein identified to date (over 1 micron long, almost 3 million daltons in mass) is the third most abundant component of the sarcomere. |
In this report, we investigated the hexopyranose chemical modification Altriol Nucleic Acid (ANA) within small interfering RNA (siRNA) duplexes that were otherwise fully modified with the 2'-deoxy-2'-fluoro and 2'-O-methyl pentofuranose chemical modifications. The siRNAs were designed to silence the transthyretin (Ttr)... | What is the reason for N-acetylgalactosamine (GalNAc) conjugation of siRNAs? | d to a trivalent N-acetylgalactosamine (GalNAc) ligand for targeted delivery to hepatocytes. Sense and antisense strands of the parent duplex were syn |
While nuclear compartmentalization is an essential feature of three-dimensional genome organization, no genomic method exists for measuring chromosome distances to defined nuclear structures. In this study, we describe TSA-Seq, a new mapping method capable of providing a "cytological ruler" for estimating mean chromoso... | What is TSA-Seq used for? | this study, we describe TSA-Seq, a new mapping method capable of providing a "cytological ruler" for estimating mean chromosomal distances from nuclear speckles genome-wide and for predicting several Mbp chromosome trajectories between nuclear compartments without sophisticated computational modeling. Ense |
Active improvised music therapy may offer an adjuvant from of treatment in the early rehabilitation of severe brain-injured patients. Active music therapy consists of musical improvisation between patient and therapist by singing or by playing different musical instruments, according to the vital functions, the neurolo... | What is the role of music therapy in coma patients. | Our preliminary results show a significant improvement of the collaboration of the severe brain-injured patients and a reduction of undesired behaviours such as inertia (reduced psychomotor initiative) or psychomotor agitation. |
Pimavanserin is the first FDA-approved atypical antipsychotic drug indicated for the treatment of hallucinations and delusions associated with Parkinson's disease psychosis (PDP). Areas covered: This review focuses on the preclinical discovery of pimavanserin. It analyzes the pharmacological, behavioral and molecular m... | Is pimavanserin a typical antipsychotic? | Pimavanserin is the first FDA-approved atypical antipsychotic drug indicated for the treatment of hallucinations and delusions associated with Parkinson's disease psychosis (PDP). |
null | Therefore, SCG-Pred can serve as an alternative gene-finding tool for newly sequenced eukaryotic genomes. The program is freely available at http://bio.scu.edu.cn/SCGPred/. | null |
One-and-a-half syndrome is a clinical disorder featuring extraocular movements characterized by horizontal conjugate gaze palsy with internuclear ophthalmoplegia. It usually results from a unilateral lesion of the midbrain, and the most common cause of this syndrome in young women is multiple sclerosis. We report the c... | List symptoms of the One-and-a-half syndrome. | One-and-a-half syndrome is a clinical disorder featuring extraocular movements characterized by horizontal conjugate gaze palsy with internuclear ophthalmoplegia. |
Thyroid hormones are essential for normal development and metabolism. Their synthesis requires transport of iodide into thyroid follicles. The mechanisms involving the apical efflux of iodide into the follicular lumen are poorly elucidated. The discovery of mutations in the SLC26A4 gene in patients with Pendred syndrom... | Do patients with Pendred syndrome present congenital deafness? | The discovery of mutations in the SLC26A4 gene in patients with Pendred syndrome (congenital deafness, goiter, and defective iodide organification) suggested a possible role for the encoded protein, pendrin, as an apical iodide transporter. |
Cells of Aspergillus terreus, free and immobilized in polyurethane foam, were employed in itaconic acid fermentation processes on glycerol-based media. The purpose was to assess their suitability for animal bone char solubilization and the development of a biotechnological alternative to P fertilizers chemically produc... | Which species may be used for the biotechnological production of itaconic acid? | Cells of Aspergillus terreus, free and immobilized in polyurethane foam, were employed in itaconic acid fermentation processes on glycerol-based media. |
Brown adipose tissue (BAT) non-shivering thermogenesis impacts energy homeostasis in rodents and humans. Mitochondrial uncoupling protein 1 in brown fat cells produces heat by dissipating the energy generated by fatty acid and glucose oxidation. In addition to thermogenesis and despite its small relative size, sympathe... | Do brown fat cells produce heat? | Mitochondrial uncoupling protein 1 in brown fat cells produces heat by dissipating the energy generated by fatty acid and glucose oxidation. |
Efficient tagging methodologies are an integral aspect of protein complex characterization by proteomic approaches. Owing to the very high affinity of biotin for avidin and streptavidin, biotinylation tagging offers an attractive approach for the efficient purification of protein complexes. The very high affinity of th... | Describe the isolation of transcription factor complexes by in vivo biotinylation tagging and direct binding to streptavidin beads, as applied for the case of the essential hematopoietic transcription factor GATA-1. | A short sequence tag fused N-terminally to the transcription factor of interest is very efficiently biotinylated by BirA coexpressed in the same cells, as was demonstrated by the tagging of the essential hematopoietic transcription factor GATA-1. |
The universality of secure base construct, which suggests that one's use of an attachment figure as a secure base from which to explore the environment is an evolutionary outcome, is one of the core ideas of attachment theory. However, this universality idea has been critiqued because exploration is not as valued in Ja... | What is Hikikomori syndrome? | However, a low ASA score was related to a psychological dysfunction in the Japanese cultural context; hikikomori symptoms, which are defined as a desire to remain in his or her own room and his or her understanding of this behavior in other people. |
Conventional lipid lowering strategies do not efficiently lower plasma TG levels, leaving a residual CVD and pancreatitis risk. Both apolipoprotein C-III (apoC-III) and angiopoietin-like 3 (ANGPTL3) are important regulators in TG-rich lipoprotein (TRL) metabolism. Several novel agents targeting these linchpins have end... | What is the target of Volanesorsen? | Volanesorsen targeting apoC-III has shown reductions in plasma TG levels up to 90%. |
Flow through the sphincter of Oddi was studied by a constant-pressure perfusion apparatus, and by using a constant rate of infusion and measuring pressure changes just proximal to the sphincter. Pressure changes from balloons placed in the gastric antrum and duodenum were recorded. Despite considerable variation in act... | What 3 organs are the sphincter of Oddi associated with? | The sphincter of Oddi appears to be partially autonomous but is readily affected by changes in duodenal tone.2. |
Prevalence data for tick-borne pathogens are used to assess the risk for human health. In this study the presence and identity of Borrelia burgdorferi sensu lato, Ehrlichia, Anaplasma, and Rickettsia species in Bulgarian Ixodes ricinus ticks and in non- Ixodes ticks from Turkey and Albania was determined by polymerase ... | Is Ixodes a species of tick? | Rickettsia conorii was found in virtually all non- Ixodes tick species from Albania and Turkey. |
Li-Fraumeni syndrome (LFS) is an inherited, autosomal-dominant condition that predisposes individuals to a wide-spectrum of tumors at an early age. Approximately 70% of families with classic LFS have pathogenic variants in the tumor suppressor gene that disrupt protein function or stability. While more than 70% of pat... | Is Li–Fraumeni syndrome a rare, autosomal recessive, hereditary disorder that predisposes carriers to cancer development? | Li-Fraumeni syndrome (LFS) is an inherited, autosomal-dominant condition that predisposes individuals to a wide-spectrum of tumors at an early age. |
TNF-α is a major cytokine implicated in rheumatoid arthritis. Its expression is regulated both at the transcriptional and posttranscriptional levels and recent data demonstrated that miRNAs are implicated in TNF-α response in macrophages. LPS-activated FLS isolated from RA patients express TNF-α mRNA but not the mature... | Which micro-RNAs have been associated in the pathogenesis of Rheumatoid Arthritis? | Using a microarray, we found two miRNAs, miR-125b and miR-939 predicted to target the 3'-UTR of TNF-α mRNA, to be up-regulated in RA FLS in response to LPS, but their repression did not restore mature TNF-α expression in FLS |
4'-Thio-2'-deoxycytidine was synthesized as a 5'- protected phosphoramidite compatible with solid phase DNA synthesis. When incorporated as the target cytosine (C*) in the GC*GC recognition sequence for the DNA methyltransferase M. HhaI, methyl transfer was strongly inhibited. In contrast, these same oligonucleotides w... | Which are the DNA (cytosine-5-)-methyltransferases inhibitors? | The inhibitory effect of the 4'sulfur atom on enzymatic activity may be traced to perturbation of a step in the methylation reaction after DNA binding but prior to methyl transfer. |
Titin is the largest protein known, and is essential for organising muscle sarcomeres. It has many domains with a variety of functions, and stretches from the Z-line to the M-line in the muscle sarcomere. Close to the M-line, titin contains a kinase domain, which is known to phosphorylate the Z-line protein telethonin ... | Is Titin the largest single protein molecule found in Nature? | Titin is the largest protein known, and is essential for organising muscle sarcomeres. |
Activation of a large multisubunit protein kinase, called the inhibitor kappaB kinase (IKK) complex, is central to the induction of the family of transcription factors nuclear factor kappaB. IKK is comprised of two catalytic subunits, IKKalpha and IKKbeta, and a regulatory IKKgamma subunit. It is known that the catalyt... | Which are the subunits of the IkB protein kinase (IKK)? | Activation of a large multisubunit protein kinase, called the inhibitor kappaB kinase (IKK) complex, is central to the induction of the family of transcription factors nuclear factor kappaB. IKK is comprised of two catalytic subunits, IKKalpha and IKKbeta, and a regulatory IKKgamma subunit. |
Recurrent mutations in the promoter region of telomerase reverse transcriptase (TERT) have been found in various cancers including diffuse gliomas. Mutations lead to TERT upregulation and are associated with aggressive clinical behavior in glioblastomas. However, the clinical significance of TERT promoter mutations in ... | Is there an association between TERT promoter mutation and survival of glioma patients? | Mutations lead to TERT upregulation and are associated with aggressive clinical behavior in glioblastomas. |
The European Medicines Agency has approved a multicomponent serogroup B meningococcal vaccine (Bexsero®) for use in individuals of 2 months of age and older. A cost-effectiveness analysis (CEA) from the societal and Italian National Health Service perspectives was performed in order to evaluate the impact of vaccinatin... | What is Bexsero? | The European Medicines Agency has approved a multicomponent serogroup B meningococcal vaccine (Bexsero®) for use in individuals of 2 months of age and older. |
All mutations in the human gene for CuZn superoxide dismutase (CuZnSOD) reported to date are associated with the disease amyotrophic lateral sclerosis (ALS). These mutations, mostly of a familial nature (ALS 1, MIM 105400), span all of the coding region of this enzyme except for a highly conserved centrally located dom... | Can Amyotrophic Lateral Sclerosis (ALS) be associated with a mutation of the Super Oxide Dismutase 1 (SOD) gene? | All mutations in the human gene for CuZn superoxide dismutase (CuZnSOD) reported to date are associated with the disease amyotrophic lateral sclerosis (ALS). |
Emapalumab-Izsg (hereafter referred to as emapalumab) [Gamifant] is a monoclonal antibody directed against interferon gamma that is available as an intravenous infusion. Emapalumab is being developed by Novimmune and Swedish Orphan Biovitrum for the treatment of haemophagocytic lymphohistiocytosis (HLH). In November 20... | Which disease is treated with Emapalumab? | ember 2018, emapalumab received its first global approval in the USA, for the treatment of paediatric (newborn and older) and adult patients with primary HLH, who have refractory, recurrent or progressive disease or intolerance to conventional HLH therapy. Emapalumab |
Chronic myeloproliferative neoplasms (MPN) comprise a spectrum of clonal neoplastic disorders characterized by overproduction of terminally differentiated cells of the myeloid lineage. A common genetic basis for the BCR-ABL-negative MPN disorders was elucidated in 2005 with the identification of the JAK2V617F mutation ... | Has ruxolitinib received FDA approval? | Testing for JAK2 mutations is now included in the World Health Organization (WHO) criteria for the diagnosis of MPN, and in 2011 the oral JAK2 kinase inhibitor ruxolitinib became the first Food and Drug Administration (FDA)-approved drug for the treatment of myelofibrosis. |
Protein aggregation is a pathological hallmark of and may play a central role in the neurotoxicity in age-associated neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease. Accordingly, inhibiting aggregation of amyloidogenic proteins, including amyloid β and α-synuclein, has been a main therap... | Is Solanezumab effective for Alzheimer's Disease? | Notably, a recent study of solanezumab, an amyloid β monoclonal antibody, raises hope for the further therapeutic potential of immunotherapy, not only in Alzheimer's disease, but also for other neurodegenerative disorders, including Parkinson's disease. |
Mitochondria are dynamic cellular organelles that balance fission and fusion to regulate organelle morphology, distribution, and activity, and Opa1 is one of three GTPases known to regulate mitochondrial fusion. In humans, loss of a single Opa1 allele causes dominant optic atrophy, a degenerative condition that leads t... | Which is the cellular localization of the protein Opa1? | Our results define, for the first time, a function of the middle domain of the Opa1 protein and demonstrate that mitochondrial retention of Opa1 protein is essential for normal embryogenesis. |
Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant incurable skeletal muscle disease. FSHD1 constitutes 95% of cases and is linked to truncation of the D4Z4 macrosatellite at 4q35. In most cases the condition initially presents with facial and proximal weakness of the upper limbs, but over the cours... | Which are some symptoms of FSHD? | A classical presentation (74%) and 3 facial sparing phenotypes: a mild presentation (5%) with later facial and periscapular involvement, an early shoulder presentation (10%) with accelerated periscapular weakness and an early foot presentation (9%) with accelerated foot dorsiflexor weakness. |
Progressive bone marrow failure starting in the first decade of life is one of the main characteristics of Fanconi anemia. Along with the bone marrow failure, this pathology is characterized by congenital malformations, endocrine dysfunction and an extraordinary predisposition to develop cancer. The fact that hematopoi... | Which are the main clinical features of Fanconi anemia? | Progressive bone marrow failure starting in the first decade of life is one of the main characteristics of Fanconi anemia |
Our aim for this narrative review was to undertake a search of studies into exercise for people living with Idiopathic Inflammatory myopathies (IIM). We explored the strength of existing evidence with a particular consideration for the implications for people living with IIM and what is important to them. The search st... | Which are the known inflammatory myopathies? | The search strategy from the 2021 Cochrane Physical Activity review in neuromuscular disease was used, and we selected articles that included people with IIM, including Dermatomyositis (DM), Inclusion Body Myositis (IBM), Immune Mediated Necrotising Myopathy (IMNM) [also known as necrotizing autoimmune myopathy (NAM)],... |
Acid alpha-glucosidase (GAA) deficiency causes Pompe disease, a lethal lysosomal glycogen storage disease for which no effective treatment currently exists. We investigated the endocytic process in deficient cells of human recombinant GAA produced in Chinese hamster ovary cells, and the potential of GAA-deficient Japan... | Is acid alpha-glucosidase the enzyme that causes Pompe disease when mutant? | Acid alpha-glucosidase (GAA) deficiency causes Pompe disease, a lethal lysosomal glycogen storage disease for which no effective treatment currently exists. |
Background: Roflumilast cream (ARQ-151) is a highly potent, selective phosphodiesterase-4 inhibitor in development for once-daily topical treatment of chronic plaque psoriasis. Objectives: To assess the safety and efficacy of once-daily roflumilast cream 0.5% and 0.15% in patients with chronic plaque psoriasis. Methods... | Roflumilast Cream is effective for which disease? | Background: Roflumilast cream (ARQ-151) is a highly potent, selective phosphodiesterase-4 inhibitor in development for once-daily topical treatment of chronic plaque psoriasis. |
Conserved noncoding elements (CNEs) in vertebrate genomes often act as developmental enhancers, but a critical issue is how well orthologous CNE sequences retain the same activity in their respective species, a characteristic important for generalization of model organism studies. To quantify how well CNE enhancer acti... | Do Conserved noncoding elements act as enhancers? | Conserved noncoding elements (CNEs) in vertebrate genomes often act as developmental enhancers, |
The trace element selenium is an essential micronutrient that is required for the biosynthesis of selenocysteine-containing selenoproteins. Most of the known selenoproteins are expressed in the thyroid gland, including some with still unknown functions. Among the well-characterized selenoproteins are the iodothyronine ... | Is selenium deficiency involved in autoimmune thyroid disease? | Selenium deficiency is likely to constitute a risk factor for a feedforward derangement of the immune system-thyroid interaction, while selenium supplementation appears to dampen the self-amplifying nature of this derailed interaction |
CD38, a type II transmembrane glycoprotein highly expressed in hematological malignancies including multiple myeloma (MM), represents a promising target for mAb-based immunotherapy. In this study, we describe the cytotoxic mechanisms of action of daratumumab, a novel, high-affinity, therapeutic human mAb against a uniq... | What is the target of daratumumab? | In this study, we describe the cytotoxic mechanisms of action of daratumumab, a novel, high-affinity, therapeutic human mAb against a unique CD38 epitope. |
Restless legs syndrome (RLS) is a common condition that is frequently unrecognized, misdiagnosed and poorly managed. It is characterized by uncomfortable sensations deep in the legs developing at rest that compel the person to move; symptoms are worst at night and sleep disturbance is common. RLS occurs in 7%-11% of th... | Which deficiency is the cause of restless leg syndrome? | RLS may also be secondary to a number of conditions including iron deficiency, pregnancy and end-stage renal failure and, perhaps, neuropathy. |
The Ewing family of tumors harbors chromosomal translocations that join the N-terminal region of the EWS gene with the C-terminal region of several transcription factors of the ETS family, mainly FLI1, resulting in chimeric transcription factors that play a pivotal role in the pathogenesis of Ewing tumors. To identify ... | Which fusion protein is involved in the development of Ewing sarcoma? | The high levels of DAX1 found in Ewing tumors and its potent transcriptional repressor activity suggest that the oncogenic effect of EWS/FLI1 may be mediated, at least in part, by the up-regulation of DAX1 expression |
The SWR1 complex (SWR1C) in yeast catalyzes the replacement of nucleosomal H2A with the H2AZ variant, which ensures full activation of underlying genes. We compared the phenotype of mutants in the homologs of SWR1C components in Arabidopsis thaliana. Mutations in Arabidopsis SWC6 (AtSWC6), SUPPRESSOR OF FRIGIDA 3 (SUF3... | Which protein mediates the replacement of H2A by H2A.Z in the yeast Saccharomyces cerevisiae? | In addition, H2AZ, a substrate of SWR1C, interacts with both PIE1 and AtSWC2. |
Heme oxygenase (HO)-1 is an inducible cytoprotective enzyme that degrades heme to iron, carbon monoxide (CO), and biliverdin, the latter two of which are thought to mediate the anti-inflammatory and antioxidant actions of HO-1. Bach1 is a transcriptional repressor of the HO-1 gene (Hmox-1). Previous reports have demons... | What is the function of BACH1 | Bach1 is a transcriptional repressor of the HO-1 gene (Hmox-1). |
Vanishing lung syndrome (VLS) is a rare radiological syndrome in which the lungs appear to be disappearing on X-ray. It is a chronic, progressive condition usually affecting young male smokers and is characterised by giant emphysematous bullae, which commonly develop in the upper lobes. We describe here a rare case of ... | Describe Vanishing lung syndrome. | Eventually, his CT chest revealed the diagnosis of giant bullous disease/vanishing lung syndrome. |
Transcriptionally active and inactive chromatin domains tend to segregate into separate sub-nuclear compartments to maintain stable expression patterns. However, here we uncovered an inter-chromosomal network connecting active loci enriched in circadian genes to repressed lamina-associated domains (LADs). The interacto... | Does the association of PARP1 and CTCF follow a circadian rhythm? | PARP1- and CTCF-regulated contacts between circadian loci and the repressive chromatin environment at the lamina therefore mediate circadian transcriptional plasticity. |
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? | Although single knockdown of either G3BP1 or G3BP2 in 293T cells partially reduced the number of SG-positive cells induced by arsenite, the knockdowns of both genes significantly reduced the number |
The identical PLN mutation can be associated with both mild and severe forms of dilated cardiomyopathy. Additionally, PLN mutations should be considered in late onset cardiomyopathy. (Genetics of Cardiovascular and Neuromuscular Disease; http://www.clinicaltrials.gov/ct/show/NCT00138931?order=1; NCT00138931) | Can PLN mutations lead to dilated cardiomyopathy? | The identical PLN mutation can be associated with both mild and severe forms of dilated cardiomyopathy. Additionally, PLN mutations should be considered in late onset cardiomyopathy |
Glaucoma is an ocular disease characterized by distinctive changes in the optic nerve head (ONH) and visual field. Glaucoma can strike without symptoms and causes blindness if it remains without treatment. Therefore, early disease detection is important so that treatment can be initiated and blindness prevented. In thi... | What is the 3D tomography imaging technique for diagnosis of eye disease? | In this paper, we present a new framework for detection of glaucoma progression using 3D SD-OCT images. |
Targeting the renin-angiotensin system is proposed to affect mortality due to coronavirus disease 2019 (COVID-19). We aimed to compare the mortality rates in COVID-19 patients who received angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ACEIs/ARBs) and those who did not. In this retrospective... | Do angiotensin-converting-enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) increase the likelihood of severe COVID-19? | ACEIs/ARBs are protective factors against mortality in COVID-19 patients with HTN, and these agents can be considered potential therapeutic options in this disease. |
The target of rapamycin complex 1 (TORC1) is a central kinase that coordinates nutrient availability with eukaryotic cell growth. Although TORC1 signaling is repressed by various stresses in yeast, the underlying mechanisms remain elusive. Here we report that TORC1 signaling upon heat stress is regulated by stress gran... | Where does TORC1 sequester during heat stress? | Here we report that TORC1 signaling upon heat stress is regulated by stress granules (SGs), which are cytoplasmic foci formed under certain stresses. Ectopic formation of SGs achieved by Pbp1 overexpression in unstressed cells sequesters TORC1 in this compartment, thereby blunting TORC1 signaling |
Deregulation of the c-Myc transcription factor is involved in many types of cancer, making this oncoprotein an attractive target for drug discovery. One approach to its inhibition has been to disrupt the dimeric complex formed between its basic helix-loop-helix leucine zipper (bHLHZip) domain and a similar domain on it... | Which small molecules inhibit the c-Myc/Max dimerization? | One approach to its inhibition has been to disrupt the dimeric complex formed between its basic helix-loop-helix leucine zipper (bHLHZip) domain and a similar domain on its dimerization partner, Max. As monomers, bHLHZip proteins are intrinsically disordered (ID). Previously we showed that two c-Myc-Max inhibitors, 100... |
Athletes consuming these supplements could train with higher exercise intensity. The antioxidant effect of the two proteins is based on different mechanisms of action. | Which are the supplemental antioxidant in athletes? | The antioxidant effect of the two proteins is based on different mechanisms of action. |
Women with hormone receptor-positive, human epidermal growth factor receptor 2- negative breast cancer-the most common subtype-have new options as palbociclib and similar drugs debut. This article outlines the rationale and evidence for their use. | In which breast cancer patients can palbociclib be used? | Women with hormone receptor-positive, human epidermal growth factor receptor 2- negative breast cancer-the most common subtype-have new options as palbociclib and similar drugs debut. |
One of the most important achievement of contemporary epileptology has been a concept of epileptic syndromes. According to the Commission on Classification and Terminology of the International League Against Epilepsy there are many epileptic syndromes which differ from each other not only by prognosis but also by react... | Which is the major symptom of the Doose syndrome? | His refractory epilepsy which started 7 years ago shares symptoms and signs of both epilepsy with myoclonic-astatic seizures (Doose Syndrome) and Lennox-Gastaut Syndrome |
Multidrug resistance-associated protein 4 (MRP4/ABCC4) makes a vital contribution to the bodily distribution of drugs and endogenous compounds because of its cellular efflux abilities. However, little is known about the mechanism regulating its cell surface expression. MRP4 has a PDZ-binding motif, which is a potential... | What are the functions of sorting nexin 27? | Knockdown of SNX27 by siRNA in HEK293 cells raised MRP4 expression on the plasma membrane, increased the extrusion of 6-[(14)C]mercaptopurine, an MRP4 substrate, and conferred resistance against 6-[(14)C]mercaptopurine. |
Burning mouth syndrome is characterized by a burning sensation in the tongue or other oral sites, usually in the absence of clinical and laboratory findings. Affected patients often present with multiple oral complaints, including burning, dryness and taste alterations. Burning mouth complaints are reported more often ... | What is Burning Mouth Syndrome(BMS)? | Burning mouth syndrome is characterized by a burning sensation in the tongue or other oral sites, usually in the absence of clinical and laboratory findings. |
Recent studies have revealed that, in addition to hormones and other protein factors, noncoding RNA molecules play an important regulatory role in milk protein synthesis. Circular RNAs (circRNAs) are universally expressed noncoding RNA species that have been proposed recently to regulate the expression of their parenta... | Do circRNAs remain untranslated? | A total of 4,804 and 4,048 circRNAs were identified in the cow mammary gland on d 90 and 250 postpartum, respectively, of which only 2,231 circRNAs were co-expressed at both lactation stages, suggesting high stage specificity in the circRNAs. |
A prospective case-control study was undertaken to assess respiratory disability in 133 former coal miners who were claimants for "black lung" benefits. Consecutive assignment was made to either case or control group based on their chest radiograph having shown coal workers' pneumoconiosis or no coal workers' pneumocon... | What causes Black Lung? | A prospective case-control study was undertaken to assess respiratory disability in 133 former coal miners who were claimants for "black lung" benefits. Consecutive assignment was made to either case or control group based on their chest radiograph having shown coal workers' pneumoconiosis or no coal workers' pneumocon... |
A hallmark of mitosis is the appearance of high levels of histone phosphorylation, yet the roles of these modifications remain largely unknown. Here, we demonstrate that histone H3 phosphorylated at threonine 3 is directly recognized by an evolutionarily conserved binding pocket in the BIR domain of Survivin, which is ... | Which is the substrate of the haspin kinase during mitosis? | kinase activity of Haspin, which phosphorylates H3T3, |
Bone events related to bariatric surgery remain controversial. Denosumab, used in osteoporosis treatment, is safe and efficient. Romosozumab, an antibody raised against sclerostin, is a promising bone anabolic agent. Odanacatib, a cathepsin-K inhibitor, decreases bone resorption and reduces osteoporotic fracture risk. ... | What is the mechanism of action of Romosozumab? | Romosozumab, an antibody raised against sclerostin, is a promising bone anabolic agent. |
The DNA helicase Rrm3 promotes replication fork progression through >1000 discrete genomic regions and represses the cDNA-mediated mobility of the Ty1 retrotransposon. We explored the connection between DNA replication and Ty1 retromobility by investigating the basis of increased retromobility in an rrm3 mutant. Even t... | What is the effect of the absence of Saccharomyces cerevisiae Rrm3p? | The DNA helicase Rrm3 promotes replication fork progression through >1000 discrete genomic regions and represses the cDNA-mediated mobility of the Ty1 retrotransposon. We explored the connection between DNA replication and Ty1 retromobility by investigating the basis of increased retromobility in an rrm3 mutant. Even t... |
Recent results from genetic and treatment studies have shed new light on chronic inflammatory and autoimmune diseases such as rheumatoid arthritis (RA). In particular, genome-wide association studies (GWAS) have provided supportive evidence that RA is a disease with a strong genetic background. Interestingly, a series ... | How many genes outside of the MHC locus have been genetically associated to Rheumatoid Arthritis through GWAS? | Among these genes, PTPN22 plays an outstanding role. CD40, STAT4, PRM1, and TNFAIP3 also seem to be of relevance |
Pediatric high-grade gliomas (HGGs)--including glioblastoma multiforme, anaplastic astrocytoma, and diffuse intrinsic pontine glioma--are difficult to treat and are associated with an extremely poor prognosis. There are no effective chemotherapeutic regimens for the treatment of pediatric HGG, but many new treatment op... | What is the role of nimotuzumab in treatment of pontine glioma? | . Studies are also ongoing in pediatric HGG with 2 EGFR inhibitors: cetuximab and nimotuzumab. |
It is widely recognized that smelling food results in a mouth-watering feeling and influences appetite. However, besides changes in volume, little is known about the effects that food odours have on the composition of saliva. The aim of the present study was to access the effects that smelling bread has on saliva prote... | List the main proteins found in human saliva. | several protein spots of immunoglobulin chains |
DNA double-strand breaks (DSBs) are major DNA lesions that are constantly formed during physiological processes such as DNA replication, transcription, and recombination, or as a result of exogenous agents such as ionizing radiation, radiomimetic drugs, and genome editing nucleases. Unrepaired DSBs threaten genomic sta... | What is the basis of the BLISS technique? | Recently, we have further expanded the quantitative nature, applicability, and scalability of BLESS by developing Breaks Labeling In Situ and Sequencing (BLISS) |
GPR151 is a G-protein coupled receptor for which the endogenous ligand remains unknown. In the nervous system of vertebrates, its expression is enriched in specific diencephalic structures, where the highest levels are observed in the habenular area. The habenula has been implicated in a range of different functions in... | What is known about the orphan receptor GPR151? | GPR151 is a G-protein coupled receptor for which the endogenous ligand remains unknown. In the nervous system of vertebrates, its expression is enriched in specific diencephalic structures, where the highest levels are observed in the habenular area. |
Bidirectional (anterograde and retrograde) motor-based intraflagellar transport (IFT) governs cargo transport and delivery processes that are essential for primary cilia growth and maintenance and for hedgehog signaling functions. The IFT dynein-2 motor complex that regulates ciliary retrograde protein transport contai... | Which intraflagellar transport (IFT) motor protein has been linked to human skeletal ciliopathies? | The IFT dynein-2 motor complex that regulates ciliary retrograde protein transport contains a heavy chain dynein ATPase/motor subunit, DYNC2H1, along with other less well functionally defined subunits. Deficiency of IFT proteins, including DYNC2H1, underlies a spectrum of skeletal ciliopathies. |
A new class of lipid-lowering drugs, inhibitors of PCSK9 has been generating impressive clinical trial data over the last several years, and alirocumab (Praluent) has become the first to be approved by the US FDA. Alirocumab has been shown to lower low density lipoprotein cholesterol by 45-62% with a safety profile gen... | Which are the Proprotein Convertase Subtilisin Kexin 9 (PCSK9) inhibitors that are FDA approved? | A new class of lipid-lowering drugs, inhibitors of PCSK9 has been generating impressive clinical trial data over the last several years, and alirocumab (Praluent) has become the first to be approved by the US FDA. |
Oncotype DX, PAM50, and MammaPrint are multigene tests that are being used clinically for early-stage breast cancer to predict recurrence risk and guide adjuvant chemotherapy decisions. These tests have been validated in multiple retrospective studies, and prospective clinical trials are in progress. The TAILORx trial ... | What is the use of MammaPrint and Oncotype DX? | Oncotype DX, PAM50, and MammaPrint are multigene tests that are being used clinically for early-stage breast cancer to predict recurrence risk and guide adjuvant chemotherapy decisions. |
The regulative capability of single cells to give rise to all primary embryonic lineages is termed pluripotency. Observations of fluctuating gene expression and phenotypic heterogeneity in vitro have fostered a conception of pluripotency as an intrinsically metastable and precarious state. However, in the embryo and in... | What is formative pluripotency? | Two phases of pluripotency, called naïve and primed, have previously been described. In this Hypothesis article, a third phase, called formative pluripotency, is proposed to exist as part of a developmental continuum between the naïve and primed phases. |
DEAD-box proteins, a large class of RNA-dependent ATPases, regulate all aspects of gene expression and RNA metabolism. They can facilitate dissociation of RNA duplexes and remodeling of RNA-protein complexes, serve as ATP-dependent RNA-binding proteins, or even anneal duplexes. These proteins have highly conserved sequ... | What is the function of a DEAD box protein? | DEAD-box proteins, a large class of RNA-dependent ATPases, regulate all aspects of gene expression and RNA metabolism. |
Despite vast efforts and expenditures in the past few decades, malaria continues to kill millions of persons every year, and new approaches for disease control are urgently needed. To complete its life cycle in the mosquito, Plasmodium, the causative agent of malaria, has to traverse the epithelia of the midgut and sal... | Which is the causative agent of malaria? | To complete its life cycle in the mosquito, Plasmodium, the causative agent of malaria, has to traverse the epithelia of the midgut and salivary glands. |
We present a case of Brooke-Spiegler syndrome with a germline deep intronic mutation in the CYLD gene leading to intronic exonization. Additionally, diverse somatic mutations were identified, namely loss of heterozygosity, a recurrent nonsense mutation, and a sequence mutation causing exon skipping. These somatic aberr... | Which pathological conditions are caused by mutations in the CYLD gene? | A deep intronic mutation resulting in exonization and a somatic sequence mutations causing exon skipping are hitherto unreported genetic mechanisms involving the CYLD gene in patients with Brooke-Spiegler syndrome |
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