Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification of a novel HIV-1-neutralizing antibody from a CRF07_BC-infected Chinese donor

The identification of human monoclonal antibodies (mAbs) able to neutralize a broad spectrum of primary HIV-1 isolates is highly important for understanding the immune response of HIV-1 infection and developing vaccines and therapeutics. In this study, we isolated a novel human mAb termed Y498 from a phage display antibody library constructed with the PBMC samples of a CRF07_BC-infected Chinese donor whose sera exhibited broadly neutralizing activity. Y498 cross-reacted with diverse Env antigens and neutralized 30% of 70 tested HIV-1 isolates. It efficiently blocked the binding of soluble CD4 to gp120 and competed with the CD4-binding site (CD4bs)-specific mAbs. By combining molecular docking and site-directed mutagenesis, the epitope of Y498 was characterized to contain three antigenic sites on gp120, including the CD4 binding loop in C3, the β23 in C4 and the β24-α5 in C5, which overlap the binding sites of CD4 and CD4bs-directed mAbs (b12, VRC01, A16). Therefore, Y498 is a novel neutralizing human mAb targeting a conformation-dependent CD4bs-based epitope, and its isolation and characterization could provide helpful information for elucidating human immune response to HIV-1 infection and designing effective vaccines and immunotherapeutics.
Health and Quality of Life Outcomes

Background: Little is known about longitudinal associations between post-traumatic stress disorder (PTSD) and quality of life (QoL) after exposure to violence. The aims of the current study were to examine quality of life (QoL) and the predictive value of post-traumatic stress disorder (PTSD) for QoL in victims of non-domestic violence over a period of 12 months. Methods: A single-group (n = 70) longitudinal design with three repeated measures over a period of 12 months were used. Posttraumatic psychological symptoms were assessed by using the Impact of Event Scale, a 15-item self-rating questionnaire comprising two subscales (intrusion and avoidance) as a screening instrument for PTSD. The questionnaire WHOQOL-Bref was used to assess QoL. The WHOQOL-BREF instrument comprises 26 items, which measure the following broad domains: physical health, psychological health, social relationships, and environment. Results of the analysis were summarized by fitting Structural Equation Modelling (SEM). Results: For each category of PTSD (probable cases, risk level cases and no cases), the mean levels of the WHOQOL-Bref subscales (the four domains and the two single items) were stable across time of assessment. Individuals who scored as probable PTSD or as risk level cases had significantly lower scores on the QoL domains such as physical health, psychological health, social relationships and environmental than those without PTSD symptoms. In addition, the two items examining perception of overall quality of life and perception of overall health in WHOQOL showed the same results according to PTSD symptoms such as QoL domains. PTSD symptoms predicted lower QoL at all three assessments. Similarly PTSD symptoms at T1 predicted lower QoL at T2 and PTSD symptoms at T2 predicted lower QoL at T3. Conclusion: The presence of PTSD symptoms predicted lower QoL, both from an acute and prolonged perspective, in victims of non-domestic violence. Focusing on the individual's perception of his/her QoL in addition to the illness may increase the treatment priorities and efforts. Published: 21 May 2007 Health and Quality of Life Outcomes 2007, 5:26 doi:10.1186/1477-7525-5-26 Received: 28 March 2007 Accepted: 21 May 2007 This article is available from: http://www.hqlo. com/content/5/1/26 © 2007 Johansen et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
SOX2 in cancer stemness: tumor malignancy and therapeutic potentials

Abstract Cancer stem cells (CSCs), a minor subpopulation of tumor bulks with self-renewal and seeding capacity to generate new tumors, posit a significant challenge to develop effective and long-lasting anti-cancer therapies. The emergence of drug resistance appears upon failure of chemo-/radiation therapy to eradicate the CSCs, thereby leading to CSC-mediated clinical relapse. Accumulating evidence suggests that transcription factor SOX2, a master regulator of embryonic and induced pluripotent stem cells, drives cancer stemness, fuels tumor initiation, and contributes to tumor aggressiveness through major drug resistance mechanisms like epithelial-to-mesenchymal transition, ATP-binding cassette drug transporters, anti-apoptotic and/or pro-survival signaling, lineage plasticity, and evasion of immune surveillance. Gaining a better insight and comprehensive interrogation into the mechanistic basis of SOX2-mediated generation of CSCs and treatment failure might therefore lead to new therapeutic targets involving CSC-specific anti-cancer strategies.
DNA sequence encodes the position of DNA supercoils

The three-dimensional structure of DNA is increasingly understood to play a decisive role in gene regulation and other vital cellular processes, which has triggered an explosive growth of research on the spatial architecture of the genome. Many studies focus on the role of various DNA-packaging proteins, crowding, and confinement in organizing chromatin, but structural information might also be directly encoded in bare DNA itself. Here, using a high-throughput single-molecule technique, we visualize plectonemes, the extended intertwined DNA loops that form upon twisting DNA. We discover that the underlying DNA sequence directly encodes the structure of supercoiled DNA by pinning plectonemes at specific positions. To explain this sequence-structure relationship, we develop a physical model that predicts the level of plectoneme pinning, in excellent agreement with the data. Intrinsic curvature is found to be the key property governing the supercoiled structure of DNA. By examining sequenced genomes, we show that plectonemes are likely to localize directly upstream of transcription start sites in Escherichia coli – a prediction that is experimentally verified in our measurements on such sequences. Our results reveal that DNA directly encodes for sequences that help to spatially organize the genome.
Bad Boys and Mean Girls: Callous-Unemotional Traits, Management of Disruptive Behavior in School, the Teacher-Student Relationship and Academic Motivation

Callous-unemotional (CU) traits comprise a temperament dimension characterised by low empathy, interpersonal callousness, restricted affect and a lack of concern for performance. CU traits are the hallmark feature of psychopathy in youth and are associated with more varied, severe and stable antisocial behaviour. However, little is known about the presentation, impact and correlates of CU traits in schools. We conducted a mixed methods study investigating the relationships between CU traits, student disruptive behaviour, responses to classroom management strategies, teacher-student relationship quality and academic motivation. Participants comprised 437 children aged 11 to 14 years (M = 12.5 years, 51% female) and 12 teachers recruited from a state school in England. Teacher participants consisted of 8 women and 4 men aged 23 to 51 (M = 35.27 years, SD = 10.43). Children completed the Inventory of Callous-Unemotional Traits (ICU; Frick, 2004). Teachers then completed an interview and questionnaires for a randomly selected subsample of students who i) scored in the top 25% on student report of CU traits (n = 24), and ii) scored below the median (n = 23). Thematic analysis of teacher interviews revealed that high CU children display more frequent, severe antisocial behaviour in school. Teachers reported that high CU students were resistant to teacher discipline strategies, often showing intense displays of anger in response to their attempts to set limits. High CU students appeared to be less responsive to social rewards (e.g., praise). Encouragingly, some teachers reported a good relationship with a child identified as high in CU traits, despite recognizing that this student’s behaviour made it difficult for other teachers to maintain a harmonious classroom environment. Teachers attributed the poor academic performance of children high in CU traits to a lack of motivation, reporting the need for intense monitoring and feedback to ensure that these students completed schoolwork. Findings suggest that risk pathways for poor school outcomes may differ for antisocial children high and low in CU traits, and emphasize the need to modify existing school-based interventions to promote academic engagement and prosocial behaviour in this high-risk subgroup of antisocial children.
SITES OF FORMATION OF IMMUNE GLOBULINS AND OF A COMPONENT OF C'3

Human, and monkey tissues were cultured in the presence of labeled amino acid. The culture fluids were then examined for labeled serum proteins by means of autoradiography of immunoelectrophoretic patterns prepared from mixtures of the fluids and carrier sera. Gamma globulin, β2A-globulin, β2Mglobulin, and β1C-globulin were found to be formed in human lymph node, bone marrow, and ileum. Gamma globulin, β2M-globulin, and β1C-globulin were found to be formed in monkey spleen, lymph node, and bone marrow. Formation of several other serum proteins was observed in the monkey liver.
Narrative review of therapies for chronic enteropathies in dogs and cats

Background The optimal medical treatment for chronic enteropathy (CE) in dogs and cats is controversial. Sequential treatment using diet, antimicrobials, and immunosuppressive drugs is the most common strategy used by clinicians. Objectives To review the evidence for the effectiveness of dietary, drug, and alternative health interventions for inducing clinical remission in dogs and cats with CE. Animals Retrospective study of dogs and cats with a diagnosis of chronic enteropathy. Methods MEDLINE and Centre for Agriculture and Bioscience International (CABI) databases (1950 to March 2017) were searched for randomized controlled trials (RCTs), observational studies, and case series. The primary outcome was induction of clinical remission. All studies were evaluated using the quality of evidence grading guidelines (I‐IV), which assign a score defining the strength and quality of the evidence. Results Twenty‐two studies (11 RCTs in dogs and 2 in cats and 9 cohort studies or case series) met the inclusion criteria for inducing remission of gastrointestinal (GI) signs. Of the 13 RCTs achieving grade I scores, 10 studies (totaling 218 dogs and 65 cats) compared single treatment: diet (n = 3), immunosuppressives (n = 3), antimicrobials (n = 2), anti‐inflammatory drugs (n = 1), and probiotics (n = 1). Three case series (grade III) reported clinical remission using an elimination diet fed to 55 cats and use of enrofloxacin to induce remission in dogs with granulomatous colitis (2 studies totaling 16 dogs). Conclusions and Clinical Importance The current evidence for treatment of CE is much greater in dogs than in cats. There is sufficient strong evidence to recommend the use of therapeutic GI diets, glucocorticoids, enrofloxacin, or some combination of these in dogs with CE. Therapeutic GI diets and glucocorticoids are most useful in cats with CE.
Comparison of Commonly Used Questionnaires to Identify Obstructive Sleep Apnea in a High-Risk Population.

STUDY OBJECTIVES Sleep apnea is associated with adverse health outcomes. Despite being an important comorbidity in obesity, type 2 diabetes, heart failure, and resistant hypertension, it is underdiagnosed in these patient groups. An inexpensive and readily accessible sleep apnea screening tool would help address this problem. We sought to compare three commonly used screening tools. METHODS We recruited 812 patients who had not previously been investigated for sleep apnea from our institution's diabetes (n = 512), obesity (n = 129), resistant hypertension (n = 74) and heart failure (n = 43) clinics. Patients completed three frequently used sleep apnea screening questionnaires (STOP-BANG, Berlin, and OSA50). A total of 758 patients had a valid (> 4 hours' duration) level 3 home sleep study. Studies were reported by a sleep physician and were deemed positive if they recorded a respiratory event index (REI) ≥ 15 events/h. RESULTS The 758 patients with valid sleep studies were age 59 ± 11 years and 63% were male. A total of 38% of patients had a positive test. The respective sensitivities and specificities of the screening questionnaires at the recommended screening thresholds (REI ≥ 15 events/h) were STOP-BANG ≥ 3 (95% and 19%), STOP-BANG ≥ 5 (60% and 69%), Berlin (75% and 38%), and OSA50 (88% and 21%). We identified six independent predictors (age, sex, body mass index, neck circumference, snoring ≥ 3 days per week, observed apnea ≥ 3 days per week). However, combining these factors was no better than the STOP-BANG in predicting sleep apnea. All patients with a STOP-BANG < 3 had an REI < 30 events/h. CONCLUSIONS There is a high prevalence of undiagnosed symptomatic sleep apnea in high-risk patient groups. The STOP-BANG questionnaire appeared superior, though all questionnaires had significant limitations. Incorporation of STOP-BANG ≥ 3 in this high-risk population might reduce the need for sleep testing in a resource-constrained setting.
Neural systems for landmark-based wayfinding in humans

Humans and animals use landmarks during wayfinding to determine where they are in the world and to guide their way to their destination. To implement this strategy, known as landmark-based piloting, a navigator must be able to: (i) identify individual landmarks, (ii) use these landmarks to determine their current position and heading, (iii) access long-term knowledge about the spatial relationships between locations and (iv) use this knowledge to plan a route to their navigational goal. Here, we review neuroimaging, neuropsychological and neurophysiological data that link the first three of these abilities to specific neural systems in the human brain. This evidence suggests that the parahippocampal place area is critical for landmark recognition, the retrosplenial/medial parietal region is centrally involved in localization and orientation, and both medial temporal lobe and retrosplenial/medial parietal lobe regions support long-term spatial knowledge.
Source-apportioned coarse particulate matter exacerbates allergic airway responses in mice

Abstract Exposure to coarse particulate matter (PM) is associated with lung inflammation and exacerbation of respiratory symptoms in sensitive populations, but the degree to which specific emission sources contribute to these effects is unclear. We examined whether coarse PM samples enriched with diverse sources differentially exacerbate allergic airway responses. Coarse PM was collected weekly (7/2009–6/2010) from urban (G.T. Craig [GTC]) and rural (Chippewa Lake Monitor [CLM]) sites in the Cleveland, Ohio area. Source apportionment results were used to pool GTC filter PM extracts into five samples dominated by traffic, coal, steel (two samples), or road salt sources. Five CLM samples were prepared from corresponding weeks. Control non-allergic and house dust mite (HDM)-allergic Balb/cJ mice were exposed by oropharyngeal aspiration to 100 μg coarse GTC or CLM, control filter extract, or saline only, and responses were examined 2 d after PM exposures. In allergic mice, CLM traffic, CLM road salt and all GTC samples except steel-1 significantly increased airway responsiveness to methacholine (MCh) compared with control treatments. In non-allergic mice, CLM traffic, CLM steel-2 and all GTC samples except coal significantly increased bronchoalveolar lavage fluid (BALF) neutrophils, while only CLM traffic PM increased eosinophils in allergic mice. In non-allergic mice, CLM coal PM increased BALF interleukin (IL)-13 and GTC steel-1 PM increased TNF-α levels. These results demonstrate that equal masses of GTC and CLM coarse PM enriched with a variety of sources exacerbate allergic airway disease. Greater PM concentrations at the urban GTC site signify a greater potential for human health effects.
Na+ and K+ transport at basolateral membranes of epithelial cells. I. Stoichiometry of the Na,K-ATPase

The stoichiometry of pump-mediated Na/K exchange was studied in isolated epithelial sheets of frog skin. 42K influx across basolateral membranes was measured with tissues in a steady state and incubated in either beakers or in chambers. The short-circuit current provided estimates of Na+ influx at the apical membranes of the cells. 42K influx of tissues bathed in Cl- or SO4-Ringer solution averaged approximately 8 microA/cm2. Ouabain inhibited 94% of the 42K influx. Furosemide was without effect on pre-ouabain-treated tissues but inhibited a ouabain-induced and Cl--dependent component of 42K influx. After taking into account the contribution of the Na+ load to the pump by way of basolateral membrane recycling of Na+, the stoichiometry was found to increase from approximately 2 to 6 as the pump-mediated Na+ transport rate increased from 10 to 70 microA/cm2. Extrapolation of the data to low rates of Na+ transport (less than 10 microA/cm2) indicated that the stoichiometry would be in the vicinity of 3:2. As pump- mediated K+ influx saturates with increasing rates of Na+ transport, Na+ efflux cannot be obligatorily coupled to K+ influx at all rates of transepithelial Na+ transport. These results are similar to those of Mullins and Brinley (1969. Journal of General Physiology. 53:504-740) in studies of the squid axon.
CD40 Activation Rescues Antiviral CD8+ T Cells from PD-1-Mediated Exhaustion

The intrahepatic immune environment is normally biased towards tolerance. Nonetheless, effective antiviral immune responses can be induced against hepatotropic pathogens. To examine the immunological basis of this paradox we studied the ability of hepatocellularly expressed hepatitis B virus (HBV) to activate immunologically naïve HBV-specific CD8+ T cell receptor (TCR) transgenic T cells after adoptive transfer to HBV transgenic mice. Intrahepatic priming triggered vigorous in situ T cell proliferation but failed to induce interferon gamma production or cytolytic effector function. In contrast, the same T cells differentiated into cytolytic effector T cells in HBV transgenic mice if Programmed Death 1 (PD-1) expression was genetically ablated, suggesting that intrahepatic antigen presentation per se triggers negative regulatory signals that prevent the functional differentiation of naïve CD8+ T cells. Surprisingly, coadministration of an agonistic anti-CD40 antibody (αCD40) inhibited PD-1 induction and restored T cell effector function, thereby inhibiting viral gene expression and causing a necroinflammatory liver disease. Importantly, the depletion of myeloid dendritic cells (mDCs) strongly diminished the αCD40 mediated functional differentiation of HBV-specific CD8+ T cells, suggesting that activation of mDCs was responsible for the functional differentiation of HBV-specific CD8+ T cells in αCD40 treated animals. These results demonstrate that antigen-specific, PD-1-mediated CD8+ T cell exhaustion can be rescued by CD40-mediated mDC-activation.
Cross-lingual Linking of Multi-word Entities and language-dependent learning of Multi-word Entity Patterns

We address large-scale multilingual multi-word entity (MWEntity) recognition and variant matching. Firstly, we recognise MWEntities in 22 different languages, identify monolingual variant spellings and link equivalent groups of variants across all languages. We then use the previously recognised MWEntities to learn new recognition rules based on distributional patterns. Not requiring any linguistic tools, the method is suitable for our highly multilingual environment. When adding the new rules to the original rule-based NER system, F1 performance for Spanish increases from 42.4% to 50% (18% increase) and for English from 43.4% to 44.5% (2.5% increase). Besides aiming at turning free text into semi-structured data for search and for machine-processing purposes, we use the system to link related news over time and across languages, as well as to detect trends.
Cost-effectiveness of a Genetic Test for Breast Cancer Risk

Genetic testing of seven single-nucleotide polymorphisms (7SNP) can improve estimates of risk of breast cancer relative to the Gail risk test alone, for the purpose of recommending MRI screening for women at high risk. A simulation of breast cancer and health care processes was used to conduct a virtual trial comparing the use of the 7SNP test with the Gail risk test to categorize patients by risk. Average-risk patients received annual mammogram, whereas high-risk patients received annual MRI. Cancer incidence was based on Surveillance, Epidemiology, and End Results data and validated to Cancer Prevention Study II Nutrition Cohort data. Risk factor values were drawn from National Health and Nutrition Examination Survey (NHANES-4) and Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial data. Mammogram characteristics were derived from Breast Cancer Surveillance Consortium data. The test was most cost-effective when given to patients at an intermediate lifetime risk of breast cancer. For patients with a risk of 16% to 28%, it resulted in a 1.91% reduction in cancer deaths, saving 0.005 quality-adjusted life years per person at a cost of $163,264 per QALY. These results were sensitive to the age at which the test is given, the discount rate, and the costs of the genetic test and MRI. The cost effectiveness of using the 7SNP test for patients with intermediate Gail risk is similar to that of other recommended strategies, including annual MRI for patients with a lifetime risk greater than 20% or BRCA1/2 mutations. Cancer Prev Res; 6(12); 1328–36. ©2013 AACR.
Lack of NWC protein (c11orf74 homolog) in murine spermatogenesis results in reduced sperm competitiveness and impaired ability to fertilize egg cells in vitro

NWC is an uncharacterised protein containing three strongly conserved domains not found in any other known protein. Previously, we reported that the NWC protein is detected in cells in the germinal layer in murine testes (strain: C57BL/6), and its knockout results in no obvious phenotype. We determined the NWC expression pattern during spermatogenesis, and found this protein in spermatocytes and round spermatids, but not in epididymal sperm. Although NWC knockout males are fertile, we further characterised their reproductive potential employing non-standard mating that better simulates the natural conditions by including sperm competition. Such an approach revealed that the sperm of knockout males fail to successfully compete with control sperm. After analysing selected characteristics of the male reproductive system, we found that NWC knockout sperm had a reduced ability to fertilize cumulus-intact eggs during IVF. This is the first report describing a subtle phenotype of NWC knockout mice that could be detected under non-standard mating conditions. Our results indicate that NWC plays an important role in spermatogenesis and its deficiency results in the production of functionally impaired sperm.