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Classically, temporally precise excitation of membrane potential in neurons within intact tissue can be achieved by direct electrical stimulation or indirect electrical stimulation induced by changing magnetic fields. Both of these approaches have a predetermined selectivity based on the biophysical properties of the n...	What are viral vectors used for in optogenetics?	To express ChR in neurons, the common expression systems include viral vectors, in utero electroporation, and transgenic animals, each with their advantages and limitations regarding the cost, expression pattern, and the required effort.
McKusick-Kaufman syndrome is a human developmental anomaly syndrome comprising mesoaxial or postaxial polydactyly, congenital heart disease and hydrometrocolpos. This syndrome is diagnosed most frequently in the Old Order Amish population and is inherited in an autosomal recessive pattern with reduced penetrance and va...	What 3 disorders are commonly associated with Kaufman-McKusick syndrome?	McKusick-Kaufman syndrome is a human developmental anomaly syndrome comprising mesoaxial or postaxial polydactyly, congenital heart disease and hydrometrocolpos.
Septo-optic dysplasia, also known as de Morsier syndrome, is a rare congenital entity almost always characterized by hypoplasia/dysplasia of the optical nerve, chiasma or optic radiations and the complete or partial absence of the septum pellucidum. It may also be accompanied by other malformations, including multiple ...	What are clinical features of the de Morsier syndrome?	Septo-optic dysplasia, also known as de Morsier syndrome, is a rare congenital entity almost always characterized by hypoplasia/dysplasia of the optical nerve, chiasma or optic radiations and the complete or partial absence of the septum pellucidum.
Pendred syndrome is an autosomal recessive disorder characterized by congenital deafness and thyroid goiter. The thyroid disease typically develops around puberty and is associated with a mild organification defect, characterized by an inappropriate discharge of iodide upon perchlorate stimulation (a positive perchlora...	Which hormone abnormalities are characteristic to Pendred syndrome?	Pendred syndrome is an autosomal recessive disorder characterized by congenital deafness and thyroid goiter.
In the nervous system, voltage-gated Ca2+ channels regulate numerous processes critical to neuronal function including secretion of neurotransmitters, initiation of action potentials in dendritic regions of some neurons, growth cone elongation, and gene expression. Because of the critical role which Ca2+ channels play ...	Which type of lung cancer is the most strongly associated with Lambert-Eaton syndrome?	LEMS has a high degree of coincidence (approximately 60%) with small cell lung cancer; the remaining 40% of patients with LEMS have no detectable tumor.
Inositol 1,4,5-trisphosphate (IP(3)) receptors (IP(3)Rs) are large, ubiquitously expressed, endoplasmic reticulum membrane proteins that form tetrameric IP(3) and Ca(2+)-gated Ca(2+) channels. Endogenous IP(3)Rs provide very appealing tools for studying the ubiquitin-proteasome pathway in intact mammalian cells because...	Is K-63 linked protein ubiquitination related to proteasomal degradation?	Importantly, although Lys-48-linked ubiquitin chains appear to trigger proteasomal degradation, the presence of Lys-63-linked ubiquitin chains suggests that ubiquitination of IP(3)Rs may have physiological consequences beyond signaling for degradation.
Th2 cells produce Th2 cytokines such as IL-4, IL-5 and IL-13, but repress Th1 cytokine IFNγ. Recent studies have revealed various distinct memory-type Th2 cell subsets, one of which produces a substantial amount of IFNγ in addition to Th2 cytokines, however it remains unclear precisely how these Th2 cells produce IFNγ....	What is the role of Gata3 in Th2 cells?	posttranslational modifications of Gata3 that control the regulation of IFNγ expression in memory Th2 cells.
Therapeutic plasma exchange (TPE) has been mainly used in the treatment of autoimmune diseases. The main mechanisms of action of TPE include the removal of circulating autoantibodies, immune complexes, complement components, cytokines and adhesion molecules, along with sensitization of antibody-producing cells to immun...	Treatment with plasma exchange (TPE) is used for what diseases	Therapeutic plasma exchange (TPE) has been mainly used in the treatment of autoimmune diseases.
MutT-related proteins degrade 8-oxo-7,8-dihydrodeoxyguanosine triphosphate (8-oxo-dGTP), a mutagenic substrate for DNA synthesis, in the nucleotide pool, thereby preventing DNA replication errors. During a search of GenBank EST database, we found a new member of MutT-related protein, MTH2, which possesses the 23-amino ...	By which mechanism MutT proteins act against DNA lesions in bacteria?	MutT-related proteins degrade 8-oxo-7,8-dihydrodeoxyguanosine triphosphate (8-oxo-dGTP), a mutagenic substrate for DNA synthesis, in the nucleotide pool, thereby preventing DNA replication errors.
The Signs of Depression Scale is easily completed by clinical staff, although we found the sensitivity when completed by nurses to be low. Information from carers shows potential to improve screening and it is important for nurses to value the knowledge and skills of carers in detecting depression following a stroke. F...	Which depression rating scales were shown to have acceptable psychometric properties for screening of poststroke depression?	The Signs of Depression Scale is easily completed by clinical staff, although we found the sensitivity when completed by nurses to be low. Information from carers shows potential to improve screening and it is important for nurses to value the knowledge and skills of carers in detecting depression following a stroke. F...
Deficiency of ornithine transcarbamylase, an enzyme in the urea cycle, results in hyperammonemia. The X-linked recessive inheritance results in neonatal death of affected males but a variable symptomatic pattern in females, with onset of symptoms in childhood. We report the cases of two heterozygous women with onset of...	What are the clinical symptoms of an ornithine transcarbamylase deficiency?	Deficiency of ornithine transcarbamylase, an enzyme in the urea cycle, results in hyperammonemia
The incidence of reporting and diagnosis of coeliac disease (CD) in children is increasing with the improvement in sensitivity and specificity of screening markers. This in turn has led to an increasing awareness of gluten-sensitive enteropathy and associated disorders. We report the unusual case of an 8-month-old chil...	What is the typical rash associated with gluten ?	We report the unusual case of an 8-month-old child presenting to his general practitioner with pruritic skin lesions, subsequently proven to be dermatitis herpetiformis (DH) as the first sign of gluten-sensitive disease.
Dyslipidaemia is a critical risk factor for the development of cardiovascular complications such as ischemic heart disease and stroke. Although statins are effective anti-dyslipidemic drugs, their usage is fraught with issues such as failure of adequate lipid control in 30% of cases and intolerance in select patients. ...	Which enzyme is targeted by Evolocumab?	Some of the anti-dyslipidemic drugs which work by PCSK9 inhibition include evolocumab, alirocumab and ALN-PCS.
Aliskiren is a novel molecule which blocks the renin-angiotensin-aldosterone system in its rate limiting step by renin inhibition. Aliskiren is validated as an antihypertensive drug in many countries based on its efficacy data. Although some surrogate endpoint trials suggest that its potential advantages based on its m...	Describe the mechanism of action of aliskiren.	Aliskiren is a novel molecule which blocks the renin-angiotensin-aldosterone system in its rate limiting step by renin inhibition.
BTK is a cytoplasmic protein-tyrosine kinase, whose corresponding gene was isolated in the early 1990s. BTK was initially identified by positional cloning of the gene causing X-linked agammaglobulinemia and independently in a search for new kinases. Given the phenotype of affected patients, namely lack of B-lymphocytes...	Is the tyrosine kinase BTK implicated in autoimmunity?	Given the phenotype of affected patients, namely lack of B-lymphocytes and plasma cells with the ensuing inability to mount humoral immune responses, BTK inhibitors were anticipated to have beneficial effects on antibody-mediated pathologies, such as autoimmunity
During chromatin replication and nucleosome assembly, newly synthesized histone H4 is acetylated before it is deposited onto DNA, then deacetylated as assembly proceeds. In a previous study (Perry and Annunziato, Nucleic Acids Res. 17, 4275 [1989]) it was shown that when replication occurs in the presence of sodium but...	What is the main difference between nascent and mature chromatin?	In a previous study (Perry and Annunziato, Nucleic Acids Res. 17, 4275 [1989]) it was shown that when replication occurs in the presence of sodium butyrate (thereby inhibiting histone deacetylation), nascent chromatin fails to mature fully and instead remains preferentially sensitive to DNaseI, more soluble in magnesiu...
Subjective Wellbeing (SWB) can be assessed with distinct measures that have been hypothesized to represent different domains of SWB. The current study assessed SWB with four different measures in a genetically informative sample of adolescent twins and their siblings aged 13-28 years (N = 5,024 subjects from 2,157 fami...	Is there a genetic component for happiness?	The clustering of the four different measures (quality of life in general, satisfaction with life, quality of life at present, and subjective happiness) was explained by an underlying additive genetic factor and an underlying non-additive genetic factor.
Stress-promoted mutations that occur in nondividing cells (adaptive mutations) have been implicated strongly in causing genetic variability as well as in species survival and evolutionary processes. Oxidative stress-induced DNA damage has been associated with generation of adaptive His(+) and Met(+) but not Leu(+) reve...	Which mechanisms underlie adaptive mutagenesis (stationary-phase mutagenesis) in Bacillus subtilis?	MMR regulation of the mutagenic/antimutagenic properties of MutY promotes stationary-phase mutagenesis in B. subtilis cells.
In APCs, the protein tyrosine kinase Syk is required for signaling of several immunoreceptors, including the BCR and FcR. We show that conditional ablation of the syk gene in dendritic cells (DCs) abrogates FcgammaR-mediated cross priming of diabetogenic T cells in RIP-mOVA mice, a situation phenocopied in wild-type RI...	Which enzyme is inhibited by a drug fostamatinib?	We show that conditional ablation of the syk gene in dendritic cells (DCs) abrogates FcgammaR-mediated cross priming of diabetogenic T cells in RIP-mOVA mice, a situation phenocopied in wild-type RIP-mOVA mice treated with the selective Syk inhibitor R788.
The molecular basis of sarcoma remains poorly understood. However, recent studies have begun to uncover some of the molecular pathways involved in sarcomagenesis. The chemokine receptor CXCR4 has been implicated in sarcoma development and has been found to be a prognostic marker for poor clinical outcome. There is grow...	Is protein CXCR4 used as a prognostic marker of cancer?	The chemokine receptor CXCR4 has been implicated in sarcoma development and has been found to be a prognostic marker for poor clinical outcome.
The coordinated replication and transcription of pericentromeric repeats enable RNA interference (RNAi)-mediated transmission of pericentromeric heterochromatin in fission yeast, which is essential for the proper function of centromeres. Rad3/ATR kinase phosphorylates histone H2A on serine-128/-129 to create γH2A in pe...	What genes are related to breast cancer?	coordinated replication and transcription of pericentromeric repeats enable RNA interference (RNAi)-mediated transmission of pericentromeric heterochromatin in fission yeast, which is essential for the proper function of centromeres. Rad3/ATR kinase phosphorylates histone H2A on serine-128/-129 to create γH2A in perice...
Dermatitis herpetiformis (DH) is an autoimmune blistering skin disorder that is associated with gluten sensitivity. It presents as a papulovesicular rash and is often associated with enteropathy. The rash resolves when the patient is placed on a gluten-free diet and/or dapsone. DH, as well as celiac disease, is tightly...	What is the typical rash associated with gluten ?	Dermatitis herpetiformis (DH) is an autoimmune blistering skin disorder that is associated with gluten sensitivity
Pendred syndrome is a recessive inherited disorder that consists of developmental abnormalities of the cochlea, sensorineural hearing loss, and diffuse thyroid enlargement (goiter). This disorder may account for up to 10% of cases of hereditary deafness. The disease gene (PDS) has been mapped to chromosome 7q22-q31, an...	Which hormone abnormalities are characteristic to Pendred syndrome?	Pendred syndrome is a recessive inherited disorder that consists of developmental abnormalities of the cochlea, sensorineural hearing loss, and diffuse thyroid enlargement (goiter).
Manipulation of the cellular stress response offers strategies to protect brain cells from damage induced by ischemia and neurodegenerative diseases. Overexpression of Hsp70 reduced ischemic injury in the mammalian brain. Investigation of the domains within Hsp70 that confers ischemic neuroprotection revealed the impor...	Is arimoclomol a co-inducer of the heat shock response?	Arimoclomol, a coinducer of heat shock proteins, delayed progression of amyotrophic lateral sclerosis (ALS) in a mouse model in which motor neurons in the spinal cord and motor cortex degenerate.
Despite the recent major advancement in therapy for multiple myeloma, it remains an incurable disease. There remains an unmet need for novel therapies that target different mechanisms of action. Immunotherapy with monoclonal antibodies is a promising area of development and will expand our therapeutic armamentarium in ...	Which molecule is targeted by Daratumumab?	This review focuses on the CD38 antigen and its targeting with daratumumab and provides an update on the results of recent clinical studies involving daratumumab.
Transcription stimulates the genetic instability of trinucleotide repeat sequences. However, the mechanisms leading to transcription-dependent repeat length variation are unclear. We demonstrate, using biochemical and genetic approaches, that the formation of stable RNA.DNA hybrids enhances the instability of CTG.CAG r...	Which DNA sequences are more prone for the formation of R-loops?	We demonstrate, using biochemical and genetic approaches, that the formation of stable RNA.DNA hybrids enhances the instability of CTG.CAG repeat tracts.
Mycobacterium tuberculosis develops spontaneous resistance mutants to virtually every drug in use. Courses of therapy select for these mutants and drug-resistant organisms emerge. The development of drug-resistant organisms has reached the point that drug resistance now threatens to undermine global success against tub...	What is the mode of action of bedaquiline?	Bedaquiline has an entirely novel mechanism of action and so should be active against otherwise highly resistant organisms. It acts on the transmembrane component of adenosine triphosphate synthase and acts by preventing electron transport.
This report describes creation of a bone-anchored sling with the InVance™ system (American Medical Systems, Minnetonka, MN, USA) for the treatment of 2 patients with incontinence after radical prostatectomy. The InVance™ system uses a silicon-coated polyester sling positioned under the bulbar urethra via a perineal inc...	Has silicon been used in treatment of incontinence ?	The InVance™ system uses a silicon-coated polyester sling positioned under the bulbar urethra via a perineal incision.
The methyltransferase-like 3 (Mettl3) is a key component of the large N6-adenosine-methyltransferase complex in mammalian responsible for RNA N6-methyladenosine (m6A) modification, which plays an important role in gene post-transcription modulation. Although RNA m6A is enriched in mammalian neurons, its regulatory func...	Is adenosine methylation an epigenetic modification?	The methyltransferase-like 3 (Mettl3) is a key component of the large N6-adenosine-methyltransferase complex in mammalian responsible for RNA N6-methyladenosine (m6A) modification, which plays an important role in gene post-transcription modulation.
Accumulated evidence implies that mutations in the gene coding for Cu/Zn superoxide dismutase (SOD) are associated with the pathogenesis of the familial form of amyotrophic lateral sclerosis (ALS). The clinical and pathological similarities of the familial and the sporadic forms of the disease may suggest that abnormal...	Can Amyotrophic Lateral Sclerosis (ALS) be associated with a mutation of the Super Oxide Dismutase 1 (SOD) gene?	Accumulated evidence implies that mutations in the gene coding for Cu/Zn superoxide dismutase (SOD) are associated with the pathogenesis of the familial form of amyotrophic lateral sclerosis (ALS).
Avapritinib (AYVAKIT™) is a potent and selective tyrosine kinase inhibitor of platelet-derived growth factor receptor alpha (PDGFRA) and KIT activation loop mutants. It is being developed by Blueprint Medicines for the treatment of gastrointestinal stromal tumours (GIST), solid tumours and systemic mastocytosis. Avapri...	What are the targets of avapritinib?	Avapritinib (AYVAKIT™) is a potent and selective tyrosine kinase inhibitor of platelet-derived growth factor receptor alpha (PDGFRA) and KIT activation loop mutants.
Insulin/IGF-I-dependent signals play important roles for the regulation of proliferation, differentiation, metabolism, and autophagy in various cells, including hematopoietic cells. Although the early protein kinase activation cascade has been intensively studied, the whole picture of intracellular signaling events has...	Where is the protein CLIC1 localized?	CLIC1, an intracellular chloride ion channel,
Growth differentiation factor 10 (Gdf10), also known as Bmp3b, is a member of the transforming growth factor (TGF)-ß superfamily. Gdf10 is expressed in Bergmann glial cells, which was investigated by single-cell transcriptional profiling (Koirala and Corfas, (2010) PLoS ONE 5: e9198). Here we provide a detailed charact...	What is GDF10?	Growth differentiation factor 10 (Gdf10), also known as Bmp3b, is a member of the transforming growth factor (TGF)-ß superfamily
In early 1992, U.S. troops returning from the Gulf War began reporting a variety of nonspecific symptoms such as fatigue, skin rash, headache, muscle and joint pain, and loss of memory. These reports marked the beginning of what was to be identified as the Gulf War Syndrome (GWS). In the years since the war, as many as...	What memory problems are reported in the " Gulf war syndrome"?	In early 1992, U.S. troops returning from the Gulf War began reporting a variety of nonspecific symptoms such as fatigue, skin rash, headache, muscle and joint pain, and loss of memory. These reports marked the beginning of what was to be identified as the Gulf War Syndrome (GWS).
The Bacillus anthracis toxin genes, cya, lef, and pag, can be viewed as a regulon, in which transcription of all three genes is activated in trans by the same regulatory gene, atxA, in response to the same signal, CO2. In atxA+ strains, toxin gene expression is increased 5- to 20-fold in cells grown in 5% CO2 relative ...	Which metabolite activates AtxA?	Comparison of the resulting protein patterns indicated that synthesis of non-toxin proteins is influenced by growth in elevated CO2 and the toxin gene regulator, atxA.
Surgical therapy for occult breast cancer has traditionally centered on mastectomy; however, breast conservation with whole breast radiotherapy followed by axillary lymph node dissection has shown equivalent results. Patients with breast cancer in pregnancy can be safely and effectively treated; given a patient's pregn...	Is there an association between Klinefelter syndrome and breast cancer?	Male breast cancer risk factors show strong association with BRCA2 mutations, as well as Klinefelter syndrome.
We herein describe the case of a 65-year-old male patient who presented with Osler's triad, which is the combination of endocarditis, pneumonia, and meningitis. This report is even more unusual since the pathogen isolated was the invasive and virulent strain of Streptococcus pneumoniae serotype 3. The clinical entity d...	Austrian syndrome is a rare entity characterized by Osler's triad. Please list the 3 components of Osler's triad.	We herein describe the case of a 65-year-old male patient who presented with Osler's triad, which is the combination of endocarditis, pneumonia, and meningitis
Automated melanoma recognition in dermoscopy images is a very challenging task due to the low contrast of skin lesions, the huge intraclass variation of melanomas, the high degree of visual similarity between melanoma and non-melanoma lesions, and the existence of many artifacts in the image. In order to meet these cha...	Briefly describe a deep learning system that is more accurate than human experts at detecting melanoma.	In order to meet these challenges, we propose a novel method for melanoma recognition by leveraging very deep convolutional neural networks (CNNs).
Pseudotumor cerebri is a central nervous disorder with elevated intracranial pressure that is most common among young obese women. It presents with headache, transient visual obscurations and loss of central vision. Papilledema and visual field defects are frequent. Acetazolamid can be used for treatment. If medical tr...	Define pseudotumor cerebri. How is it treated?	Pseudotumor cerebri is a central nervous disorder with elevated intracranial pressure that is most common among young obese women.
The International Conference on Bioprinting and Biofabrication in Bordeaux (3B'09) demonstrated that the field of bioprinting and biofabrication continues to evolve. The increasing number and broadening geography of participants, the emergence of new exciting bioprinting technologies, and the attraction of young invest...	Can bioprinting use human cells?	Bioprinting can be defined as the use of computer-aided transfer processes for patterning and assembling living and non-living materials with a prescribed 2D or 3D organization in order to produce bio-engineered structures serving in regenerative medicine, pharmacokinetic and basic cell biology studies.