Miracle-dz/UniFAR-FTUs huggingface dataset:
Rv3615c is a highly immunodominant RD1 (Region of Difference 1)-dependent secreted antigen specific for Mycobacterium tuberculosis infection

The 6-kDa early secretory antigenic target of Mycobacterium tuberculosis (ESAT-6) and the 10-kDa culture filtrate antigen (CFP-10), encoded in region of difference 1 (RD1) and secreted by the ESAT-6 system 1 (Esx-1) secretion system, are the most immunodominant and highly M. tuberculosis (MTB)-specific antigens. These attributes are responsible for their primary importance in tuberculosis (TB) immunodiagnosis and vaccine development. Rv3615c [Esx-1 substrate protein C (EspC)], encoded outside RD1, is similar in size and sequence homology to CFP-10 and ESAT-6, suggesting it might be a target of cellular immunity in TB. Using ex vivo enzyme-linked immunospot- and flow cytometry-based cytokine-secretion assay, we comprehensively assessed cellular immune responses to EspC in patients with active TB, latently infected persons, and uninfected bacillus Calmette–Guérin (BCG)-vaccinated controls. EspC was at least as immunodominant as ESAT-6 and CFP-10 in both active and latent TB infection. EspC contained broadly recognized CD4+ and CD8+ epitopes, inducing a predominantly CD4+ T-cell response that comprised functional T-cell subsets secreting both IFN-γ and IL-2 as well as functional T-cell subsets secreting only IFN-γ. Surprisingly, T-cell responses to EspC were as highly specific (93%) for MTB infection as responses to ESAT-6 and CFP-10, with only 2 of 27 BCG-vaccinated controls responding to each antigen. Using quantitative proteomics and metabolically labeled mutant and genetically complemented MTB strains, we identified the mechanism of the specificity of anti-EspC immunity as the Esx-1 dependence of EspC secretion. The high immunodominance of EspC, equivalent to that of ESAT-6 and CFP-10, makes it a TB vaccine candidate, and its high specificity confers strong potential for T-cell–based immunodiagnosis.
South Asia - Maternal and reproductive health at a glance

The South Asia Region (SAR) includes Afghanistan, Bangladesh, Bhutan, India, Maldives, Nepal, Pakistan, and Sri Lanka. With over 1.6 billion people, it is the most densely populated region in the world. The populations vary from 400,000 in the Maldives to 1.2 billion in India. The economies range from fragile and low-income to middle-income countries. SAR experienced 20 years of robust economic growth, averaging 6 percent a year. Growth resulted in declining poverty and impressive improvements in human development. More than 42 percent of the developing worlds poor live in SAR, where about 500 million people survive on less than $1.25 a day.
Effect of propofol on hypoxia re‐oxygenation induced neuronal cell damage in vitro *

Propofol may protect neuronal cells from hypoxia re‐oxygenation injury, possibly via an antioxidant actions under hypoxic conditions. This study investigated the molecular effects of propofol on hypoxia‐induced cell damage using a neuronal cell line. Cultured human IMR‐32 cells were exposed to propofol (30 μm) and biochemical and molecular approaches were used to assess cellular effects. Propofol significantly reduced hypoxia‐mediated increases in lactate dehydrogenase, a marker of cell damage (mean (SD) for normoxia: 0.39 (0.07) a.u. ; hypoxia: 0.78 (0.21) a.u. ; hypoxia + propofol: 0.44 (0.17) a.u. ; normoxia vs hypoxia, p < 0.05; hypoxia vs hypoxia + propofol, p < 0.05), reactive oxygen species and hydrogen peroxide. Propofol also diminished the morphological signs of cell damage. Increased amounts of catalase, which degrades hydrogen peroxide, were detected under hypoxic conditions. Propofol decreased the amount of catalase produced, but increased its enzymatic activity. Propofol protects neuronal cells from hypoxia re‐oxygenation injury, possibly via a combined direct antioxidant effect along with induced cellular antioxidant mechanisms.
Patients with medically unexplained physical symptoms experience of receiving treatment in a primary-care psychological therapies service: a qualitative study

Abstract As a pilot site under the primary-care Increasing Access to Psychological Therapies (IAPT) Long Term Condition/Medically Unexplained Physical Symptoms (MUPS) project, patients with MUPS were offered cognitive behaviour therapy (CBT)-based treatments or attendance at a mindfulness-based stress reduction (MBSR) programme. This study aimed to gain an understanding of the views and experiences of MUPS patients that received CBT-based therapy or MBSR within an IAPT service and to investigate the relationship between their experiences and health outcomes measured on self-report questionnaires. Thematic analysis was used to analyse data gathered via semi-structured interviews with 11 patients. Data collected from three self-report measures were considered in relation to key features of participants’ reported experiences and patterns identified. Four main themes emerged: (1) something needs to change; (2) making connections between physical symptoms and mood, thoughts or activities; (3) sharing experiences and feeling understood; and (4) reflections on treatment experience. Participants generally reported a positive experience of treatment and felt better able to cope with their symptoms, although treatment did not necessarily result in reliable change in symptoms as measured by the Patient Health Questionnaire (PHQ-9), Generalized Anxiety Disorder Scale (GAD-7) and Work and Social Adjustment Scale (WSAS). This novel model of treatment appears to be acceptable for this patient group although evaluation of the pilot should consider the ability of routinely used measures to capture the value of treatment to patients, including improved coping with symptoms.
A Flexible and Highly Pressure‐Sensitive Graphene–Polyurethane Sponge Based on Fractured Microstructure Design

A fractured microstructure design: A new type of piezoresistive sensor with ultra-high-pressure sensitivity (0.26 kPa(-1) ) in low pressure range (<2 kPa) and minimum detectable pressure of 9 Pa has been fabricated using a fractured microstructure design in a graphene-nanosheet-wrapped polyurethane (PU) sponge. This low-cost and easily scalable graphene-wrapped PU sponge pressure sensor has potential application in high-spatial-resolution, artificial skin without complex nanostructure design.
Peroxisome proliferator-activated receptor-γ coactivator 1-α (PGC1α) is a metabolic regulator of intestinal epithelial cell fate

Peroxisome proliferator-activated receptor-γ coactivator 1-α (PGC1α) is a transcriptional coactivator able to up-regulate mitochondrial biogenesis, respiratory capacity, oxidative phosphorylation, and fatty acid β-oxidation with the final aim of providing a more efficient pathway for aerobic energy production. In the continuously renewed intestinal epithelium, proliferative cells in the crypts migrate along the villus axis and differentiate into mature enterocytes, increasing their respiratory capacity and finally undergoing apoptosis. Here we show that in the intestinal epithelial surface, PGC1α drives mitochondrial biogenesis and respiration in the presence of reduced antioxidant enzyme activities, thus determining the accumulation of reactive oxygen species and fostering the fate of enterocytes toward apoptosis. Combining gain- and loss-of-function genetic approaches in human cells and mouse models of intestinal cancer, we present an intriguing scenario whereby PGC1α regulates enterocyte cell fate and protects against tumorigenesis.
Towards a map of cis-regulatory sequences in the human genome

Abstract Accumulating evidence indicates that transcription factor (TF) binding sites, or cis-regulatory elements (CREs), and their clusters termed cis-regulatory modules (CRMs) play a more important role than do gene-coding sequences in specifying complex traits in humans, including the susceptibility to common complex diseases. To fully characterize their roles in deriving the complex traits/diseases, it is necessary to annotate all CREs and CRMs encoded in the human genome. However, the current annotations of CREs and CRMs in the human genome are still very limited and mostly coarse-grained, as they often lack the detailed information of CREs in CRMs. Here, we integrated 620 TF ChIP-seq datasets produced by the ENCODE project for 168 TFs in 79 different cell/tissue types and predicted an unprecedentedly completely map of CREs in CRMs in the human genome at single nucleotide resolution. The map includes 305 912 CRMs containing a total of 1 178 913 CREs belonging to 736 unique TF binding motifs. The predicted CREs and CRMs tend to be subject to either purifying selection or positive selection, thus are likely to be functional. Based on the results, we also examined the status of available ChIP-seq datasets for predicting the entire regulatory genome of humans.
Blockade of class IB phosphoinositide-3 kinase ameliorates obesity-induced inflammation and insulin resistance

Obesity and insulin resistance, the key features of metabolic syndrome, are closely associated with a state of chronic, low-grade inflammation characterized by abnormal macrophage infiltration into adipose tissues. Although it has been reported that chemokines promote leukocyte migration by activating class IB phosphoinositide-3 kinase (PI3Kγ) in inflammatory states, little is known about the role of PI3Kγ in obesity-induced macrophage infiltration into tissues, systemic inflammation, and the development of insulin resistance. In the present study, we used murine models of both diet-induced and genetically induced obesity to examine the role of PI3Kγ in the accumulation of tissue macrophages and the development of obesity-induced insulin resistance. Mice lacking p110γ (Pik3cg−/−), the catalytic subunit of PI3Kγ, exhibited improved systemic insulin sensitivity with enhanced insulin signaling in the tissues of obese animals. In adipose tissues and livers of obese Pik3cg−/− mice, the numbers of infiltrated proinflammatory macrophages were markedly reduced, leading to suppression of inflammatory reactions in these tissues. Furthermore, bone marrow-specific deletion and pharmacological blockade of PI3Kγ also ameliorated obesity-induced macrophage infiltration and insulin resistance. These data suggest that PI3Kγ plays a crucial role in the development of both obesity-induced inflammation and systemic insulin resistance and that PI3Kγ can be a therapeutic target for type 2 diabetes.
Dioxygenases in Burkholderia ambifaria and Yersinia pestis that hydroxylate the outer Kdo unit of lipopolysaccharide

Several Gram-negative pathogens, including Yersinia pestis, Burkholderia cepacia, and Acinetobacter haemolyticus, synthesize an isosteric analog of 3-deoxy-d-manno-oct-2-ulosonic acid (Kdo), known as d-glycero-d-talo-oct-2-ulosonic acid (Ko), in which the axial hydrogen atom at the Kdo 3-position is replaced with OH. Here we report a unique Kdo 3-hydroxylase (KdoO) from Burkholderia ambifaria and Yersinia pestis, encoded by the bamb_0774 (BakdoO) and the y1812 (YpkdoO) genes, respectively. When expressed in heptosyl transferase-deficient Escherichia coli, these genes result in conversion of the outer Kdo unit of Kdo2-lipid A to Ko in an O2-dependent manner. KdoO contains the putative iron-binding motif, HXDXn>40H. Reconstitution of KdoO activity in vitro with Kdo2-lipid A as the substrate required addition of Fe2+, α-ketoglutarate, and ascorbic acid, confirming that KdoO is a Fe2+/α-ketoglutarate/O2-dependent dioxygenase. Conversion of Kdo to Ko in Kdo2-lipid A conferred reduced susceptibility to mild acid hydrolysis. Although two enzymes that catalyze Fe2+/α-ketoglutarate/O2-dependent hydroxylation of deoxyuridine in fungal extracts have been reported previously, kdoO is the first example of a gene encoding a deoxy-sugar hydroxylase. Homologues of KdoO are found exclusively in Gram-negative bacteria, including the human pathogens Burkholderia mallei, Yersinia pestis, Klebsiella pneumoniae, Legionella longbeachae, and Coxiella burnetii, as well as the plant pathogen Ralstonia solanacearum.
Chemical generation of bispecific antibodies

Bispecific antibodies (BsAbs) are regarded as promising therapeutic agents due to their ability to simultaneously bind two different antigens. Several bispecific modalities have been developed, but their utility is limited due to problems with stability and manufacturing complexity. Here we report a versatile technology, based on a scaffold antibody and pharmacophore peptide heterodimers, that enables rapid generation and chemical optimization of bispecific antibodies, which are termed bispecific CovX-Bodies. Two different peptides are joined together using a branched azetidinone linker and fused to the scaffold antibody under mild conditions in a site-specific manner. Whereas the pharmacophores are responsible for functional activities, the antibody scaffold imparts long half-life and Ig-like distribution. The pharmacophores can be chemically optimized or replaced with other pharmacophores to generate optimized or unique bispecific antibodies. As a prototype, we developed a bispecific antibody that binds both vascular endothelial growth factor (VEGF) and angiopoietin-2 (Ang2) simultaneously, inhibits their function, shows efficacy in tumor xenograft studies, and greatly augments the antitumor effects of standard chemotherapy. This unique antiangiogenic bispecific antibody is in phase-1 clinical trials.
High‐Performance Sensors Based on Molybdenum Disulfide Thin Films

High-performance sensors based on molybdenum disulfide (MoS2 ) grown by sulfurization of sputtered molybdenum layers are presented. Using a simple integration scheme, it is found that the electrical conductivity of MoS2 films is highly sensitive to NH3 adsorption, consistent with n-type semiconducting behavior. A sensitivity of 300 ppb at room temperature is achieved, showing the high potential of 2D transition metal-dichalcogenides for sensing.
T-cell factor 3 (Tcf3) deletion increases somatic cell reprogramming by inducing epigenome modifications

The heterochromatin barrier must be overcome to generate induced pluripotent stem cells and cell fusion-mediated reprogrammed hybrids. Here, we show that the absence of T-cell factor 3 (Tcf3), a repressor of β-catenin target genes, strikingly and rapidly enhances the efficiency of neural precursor cell (NPC) reprogramming. Remarkably, Tcf3−/− ES cells showed a genome-wide increase in AcH3 and decrease in H3K9me3 and can reprogram NPCs after fusion greatly. In addition, during reprogramming of NPCs into induced pluripotent stem cells, the silencing of Tcf3 increased AcH3 and decreased the number of H3K9me3-positive heterochromatin foci early and long before reactivation of the endogenous stem cell genes. In conclusion, our data suggest that Tcf3 functions as a repressor of the reprogramming potential of somatic cells.
Redox-dependent control of i-Motif DNA structure using copper cations

Abstract Previous computational studies have shown that Cu+ can act as a substitute for H+ to support formation of cytosine (C) dimers with similar conformation to the hemi-protonated base pair found in i-motif DNA. Through a range of biophysical methods, we provide experimental evidence to support the hypothesis that Cu+ can mediate C–C base pairing in i-motif DNA and preserve i-motif structure. These effects can be reversed using a metal chelator, or exposure to ambient oxygen in the air that drives oxidation of Cu+ to Cu2+, a comparatively weak ligand. Herein, we present a dynamic and redox-sensitive system for conformational control of an i-motif forming DNA sequence in response to copper cations.
The impact of managed care on psychologists' ability to accurately diagnose, treat and perceive their clients

It has been demonstrated psychologists are more likely to over-diagnose clients to obtain reimbursement if clients are using insurance (Pomerantz & Segrist, 2006). Although diagnoses are helpful in providing direction for treatment plans, incorrect diagnoses may be stigmatizing and result in flawed care (Wahl, 1999). Using an experimental design with video vignettes simulating therapy sessions, this paper will explore whether psychologists tend to excessively believe in false diagnoses when forced to provide them, as well as whether those labels negatively affect psychologists' opinions of clients. Hierarchical multiple regression will be used to determine if those in the group forced to diagnose a client tend to over-diagnose and have a more negative opinion of the client.
Ultra-deep sequencing of foraminiferal microbarcodes unveils hidden richness of early monothalamous lineages in deep-sea sediments

Deep-sea floors represent one of the largest and most complex ecosystems on Earth but remain essentially unexplored. The vastness and remoteness of this ecosystem make deep-sea sampling difficult, hampering traditional taxonomic observations and diversity assessment. This problem is particularly true in the case of the deep-sea meiofauna, which largely comprises small-sized, fragile, and difficult-to-identify metazoans and protists. Here, we introduce an ultra-deep sequencing-based metagenetic approach to examine the richness of benthic foraminifera, a principal component of deep-sea meiofauna. We used Illumina sequencing technology to assess foraminiferal richness in 31 unsieved deep-sea sediment samples from five distinct oceanic regions. We sequenced an extremely short fragment (36 bases) of the small subunit ribosomal DNA hypervariable region 37f, which has been shown to accurately distinguish foraminiferal species. In total, we obtained 495,978 unique sequences that were grouped into 1,643 operational taxonomic units, of which about half (841) could be reliably assigned to foraminifera. The vast majority of the operational taxonomic units (nearly 90%) were either assigned to early (ancient) lineages of soft-walled, single-chambered (monothalamous) foraminifera or remained undetermined and yet possibly belong to unknown early lineages. Contrasting with the classical view of multichambered taxa dominating foraminiferal assemblages, our work reflects an unexpected diversity of monothalamous lineages that are as yet unknown using conventional micropaleontological observations. Although we can only speculate about their morphology, the immense richness of deep-sea phylotypes revealed by this study suggests that ultra-deep sequencing can improve understanding of deep-sea benthic diversity considered until now as unknowable based on a traditional taxonomic approach.
Steric‐Repulsion‐Based Magnetically Responsive Photonic Crystals

The first steric-repulsion-based magnetically responsive photonic crystals (MRPCs) is constructed by synthesizing uniform superparamagnetic polyvinylpyrrolidone-coated Fe3 O4 colloidal nanocrystal clusters. The color tunable range of the MRPCs can not only cover almost the entire visible specztrum in solvents of diverse polarities, but also is insusceptible to ionic strength or pH values, facilitating the practical applications of MRPCs.
CD83-stimulated monocytes suppress T-cell immune responses through production of prostaglandin E2

CD83 is commonly known as a specific marker for mature dendritic cells. It has been shown to be important for CD4+ T-cell development in the thymus. However, its function in the peripheral immune system remains enigmatic. Here, we show that CD83 inhibits proliferation and production of IL-2 and IFN-γ by T cells, and the inhibitory effect of CD83 is mediated by monocytes. Prostaglandin E2 (PGE2), but not IL-10 or TGF-β, was up-regulated specifically by CD83 in monocytes. Consistent with high levels of PGE2, expression of COX-2 also was increased upon CD83 treatment. NF-κB activation also is required for induction of PGE2 by CD83. Finally, application of the COX-2–selective inhibitor NS-398 fully prevented CD83-triggered inhibition of T-cell responses. Our study establishes an immune-regulatory mechanism by CD83 via stimulation of PGE2 production in monocytes.
Autoregulation of an RNA polymerase II promoter by the RNA polymerase III transcription factor III C (TFIIIC) complex

Extra TFIIIC (ETC) sites are chromosomal locations bound in vivo by the RNA polymerase III (Pol III) transcription factor III C (TFIIIC) complex, but are not necessarily associated with Pol III transcription. Although the location of ETC sequences are conserved in budding yeast, and similar sites are found in other organisms, their functions are largely unstudied. One such site, ETC6 in Saccharomyces cerevisiae, lies upstream of TFC6, a gene encoding a subunit of the TFIIIC complex itself. Promoter analysis shows that the ETC6 B-box sequence is involved in autoregulation of the TFC6 promoter. Mutation of ETC6 increases TFC6 mRNA levels, whereas mutation immediately upstream severely weakens promoter activity. A temperature-sensitive mutation in TFC3 that weakens DNA binding of TFIIIC also results in increased TFC6 mRNA levels; however, no increase is observed in mutants of TFIIIB or Pol III subunits, demonstrating a specific role for the TFIIIC complex in TFC6 promoter regulation. Chromatin immunoprecipitation shows an inverse relationship of TFIIIC occupancy at ETC6 versus TFC6 mRNA levels. Overexpression of TFC6 increases association of TFIIIC at ETC6 (and other loci) and results in reduced expression of a TFC6 promoter-URA3 reporter gene. Both of these effects are dependent on the ETC6 B-box. These results demonstrate that the TFC6 promoter is directly regulated by the TFIIIC complex, a demonstration of an RNA polymerase II promoter being directly responsive to a core Pol III transcription factor complex. This regulation could have implications in controlling global tRNA expression levels.
Chemical storage of hydrogen in few-layer graphene

Birch reduction of few-layer graphene samples gives rise to hydrogenated samples containing up to 5 wt % of hydrogen. Spectroscopic studies reveal the presence of sp3 C-H bonds in the hydrogenated graphenes. They, however, decompose readily on heating to 500 °C or on irradiation with UV or laser radiation releasing all the hydrogen, thereby demonstrating the possible use of few-layer graphene for chemical storage of hydrogen. First-principles calculations throw light on the mechanism of dehydrogenation that appears to involve a significant reconstruction and relaxation of the lattice.
In vivo demonstration that α-synuclein oligomers are toxic

The aggregation of proteins into oligomers and amyloid fibrils is characteristic of several neurodegenerative diseases, including Parkinson disease (PD). In PD, the process of aggregation of α-synuclein (α-syn) from monomers, via oligomeric intermediates, into amyloid fibrils is considered the disease-causative toxic mechanism. We developed α-syn mutants that promote oligomer or fibril formation and tested the toxicity of these mutants by using a rat lentivirus system to investigate loss of dopaminergic neurons in the substantia nigra. The most severe dopaminergic loss in the substantia nigra is observed in animals with the α-syn variants that form oligomers (i.e., E57K and E35K), whereas the α-syn variants that form fibrils very quickly are less toxic. We show that α-syn oligomers are toxic in vivo and that α-syn oligomers might interact with and potentially disrupt membranes.
Flexible Supercapacitor Made of Carbon Nanotube Yarn with Internal Pores

Electrochemical deposition of MnO2 onto carbon nanotube (CNT) yarn gives a high-performance, flexible yarn supercapacitor. The hybrid yarn's blended structure, resulting from trapping of MnO2 in its internal pores, effectively enlarges electrochemical area and reduces charge diffusion length. Accordingly, the yarn supercapacitor exhibits high values of capacitance, energy density, and average power density. Applications in wearable electronics can be envisaged.