Miracle-dz/UniFAR-FTUs huggingface dataset:
Presence of a Shared 5′-Leader Sequence in Ancestral Human and Mammalian Retroviruses and Its Transduction into Feline Leukemia Virus

ABSTRACT Recombination events induce significant genetic changes, and this process can result in virus genetic diversity or in the generation of novel pathogenicity. We discovered a new recombinant feline leukemia virus (FeLV) gag gene harboring an unrelated insertion, termed the X region, which was derived from Felis catus endogenous gammaretrovirus 4 (FcERV-gamma4). The identified FcERV-gamma4 proviruses have lost their coding capabilities, but some can express their viral RNA in feline tissues. Although the X-region-carrying recombinant FeLVs appeared to be replication-defective viruses, they were detected in 6.4% of tested FeLV-infected cats. All isolated recombinant FeLV clones commonly incorporated a middle part of the FcERV-gamma4 5′-leader region as an X region. Surprisingly, a sequence corresponding to the portion contained in all X regions is also present in at least 13 endogenous retroviruses (ERVs) observed in the cat, human, primate, and pig genomes. We termed this shared genetic feature the commonly shared (CS) sequence. Despite our phylogenetic analysis indicating that all CS-sequence-carrying ERVs are classified as gammaretroviruses, no obvious closeness was revealed among these ERVs. However, the Shannon entropy in the CS sequence was lower than that in other parts of the provirus genome. Notably, the CS sequence of human endogenous retrovirus T had 73.8% similarity with that of FcERV-gamma4, and specific signals were detected in the human genome by Southern blot analysis using a probe for the FcERV-gamma4 CS sequence. Our results provide an interesting evolutionary history for CS-sequence circulation among several distinct ancestral viruses and a novel recombined virus over a prolonged period. IMPORTANCE Recombination among ERVs or modern viral genomes causes a rapid evolution of retroviruses, and this phenomenon can result in the serious situation of viral disease reemergence. We identified a novel recombinant FeLV gag gene that contains an unrelated sequence, termed the X region. This region originated from the 5′ leader of FcERV-gamma4, a replication-incompetent feline ERV. Surprisingly, a sequence corresponding to the X region is also present in the 5′ portion of other ERVs, including human endogenous retroviruses. Scattered copies of the ERVs carrying the unique genetic feature, here named the commonly shared (CS) sequence, were found in each host genome, suggesting that ancestral viruses may have captured and maintained the CS sequence. More recently, a novel recombinant FeLV hijacked the CS sequence from inactivated FcERV-gamma4 as the X region. Therefore, tracing the CS sequences can provide unique models for not only the modern reservoir of new recombinant viruses but also the genetic features shared among ancient retroviruses.
Rv2074 is a novel F420H2‐dependent biliverdin reductase in Mycobacterium tuberculosis

Bilirubin is a potent antioxidant that is produced from the reduction of the heme degradation product biliverdin. In mammalian cells and Cyanobacteria, NADH/NADPH‐dependent biliverdin reductases (BVRs) of the Rossmann‐fold have been shown to catalyze this reaction. Here, we describe the characterization of Rv2074 from Mycobacterium tuberculosis, which belongs to a structurally and mechanistically distinct family of F420H2‐dependent BVRs (F‐BVRs) that are exclusively found in Actinobacteria. We have solved the crystal structure of Rv2074 bound to its cofactor, F420, and used this alongside molecular dynamics simulations, site‐directed mutagenesis and NMR spectroscopy to elucidate its catalytic mechanism. The production of bilirubin by Rv2074 could exploit the anti‐oxidative properties of bilirubin and contribute to the range of immuno‐evasive mechanisms that have evolved in M. tuberculosis to allow persistent infection.
Genotype-Specific Measles Transmissibility: A Branching Process Analysis

Background Substantial heterogeneity in measles outbreak sizes may be due to genotype-specific transmissibility. Using a branching process analysis, we characterize differences in measles transmission by estimating the association between genotype and the reproduction number R among postelimination California measles cases during 2000-2015 (400 cases, 165 outbreaks). Methods Assuming a negative binomial secondary case distribution, we fit a branching process model to the distribution of outbreak sizes using maximum likelihood and estimated the reproduction number R for a multigenotype model. Results Genotype B3 is found to be significantly more transmissible than other genotypes (P = .01) with an R of 0.64 (95% confidence interval [CI], .48-.71), while the R for all other genotypes combined is 0.43 (95% CI, .28-.54). This result is robust to excluding the 2014-2015 outbreak linked to Disneyland theme parks (referred to as "outbreak A" for conciseness and clarity) (P = .04) and modeling genotype as a random effect (P = .004 including outbreak A and P = .02 excluding outbreak A). This result was not accounted for by season of introduction, age of index case, or vaccination of the index case. The R for outbreaks with a school-aged index case is 0.69 (95% CI, .52-.78), while the R for outbreaks with a non-school-aged index case is 0.28 (95% CI, .19-.35), but this cannot account for differences between genotypes. Conclusions Variability in measles transmissibility may have important implications for measles control; the vaccination threshold required for elimination may not be the same for all genotypes or age groups.
ADAM17 is required for EGF-R–induced intestinal tumors via IL-6 trans-signaling

Colorectal cancer is treated with antibodies blocking epidermal growth factor receptor (EGF-R), but therapeutic success is limited. EGF-R is stimulated by soluble ligands, which are derived from transmembrane precursors by ADAM17-mediated proteolytic cleavage. In mouse intestinal cancer models in the absence of ADAM17, tumorigenesis was almost completely inhibited, and the few remaining tumors were of low-grade dysplasia. RNA sequencing analysis demonstrated down-regulation of STAT3 and Wnt pathway components. Because EGF-R on myeloid cells, but not on intestinal epithelial cells, is required for intestinal cancer and because IL-6 is induced via EGF-R stimulation, we analyzed the role of IL-6 signaling. Tumor formation was equally impaired in IL-6−/− mice and sgp130Fc transgenic mice, in which only trans-signaling via soluble IL-6R is abrogated. ADAM17 is needed for EGF-R–mediated induction of IL-6 synthesis, which via IL-6 trans-signaling induces &bgr;-catenin–dependent tumorigenesis. Our data reveal the possibility of a novel strategy for treatment of colorectal cancer that could circumvent intrinsic and acquired resistance to EGF-R blockade.
The Association between Detected drug Resistance Mutations and CD4+ T-Cell Decline in HIV-Positive Individuals Maintained on a Failing Treatment Regimen

Background To analyse the effect of drug resistance mutations (DRM) on CD4+ T-cell (CD4) trends in HIV-positive people maintained on virologically failing anti-retroviral therapy (ART). Methods Individuals from two large cohorts experiencing virological failure (VF) while maintained on ART with ≥1 CD4 count and ≥1 resistance test were included. CD4 slopes were estimated using linear mixed models. Principal component analysis (PCA) was used to assess the effect of clusters of mutations, defined using extracted component based scores from the PCA, on CD4 decline. Results 5,357 individuals contributing 7,661 VF episodes were included: any DRM were detected in 88.8% of episodes. After adjustment, CD4 counts declined less steeply during episodes where DRM were detected compared to episodes with no DRM (difference =28 cells/mm3/year, 95% CI =18, 39; P<0.001). Among individuals with at least one DRM, we found evidence that any nucleoside/ nucleotide reverse transcriptase inhibitor (NRTI) resistance, the reverse transcriptase (RT) mutations M184V, D67N and T215Y as well as the protease mutations V82A and I54V were associated with reduced CD4 declines. The detection of any non-nucleoside reverse transcriptase inhibitor resistance, the RT mutations V179D and L74V were associated with steeper CD4 declines. The presence of some mutation patterns similar to the clusters identified by the PCA also affected the CD4 decline. Conclusions Detection of resistance and of certain DRM during VF of ART has a small but significant favourable effect on CD4 decline.
The Role of Gender in Suicidal Ideation among Long-term Opioid Users

Objective: This study aims to examine factors associated with suicidal ideation among people with opioid dependence and to explore whether these factors are gender-specific. Methods: Cross-sectional data were collected among long-term opioid-dependent individuals (n = 176; 46.0% women). Lifetime histories of suicidal ideation were measured using the Composite International Diagnostic Interview, and additional data were collected regarding sociodemographic characteristics, drug use, health, and adverse life events. Multivariable logistic regression was used to determine the relationships between these variables and suicidal ideation for the full study sample and separately for women and men to explore the potential role of gender. Results: A total of 43.8% (n = 77) of participants reported a lifetime history of suicidal ideation. Among those with suicidal ideation, 49.3% were women and the overall average age of first ideation was 19.82 years (SD, 11.66 years). Results from multivariable analyses showed that a history of depression, anxiety, and childhood emotional neglect and the number of lifetime traumatic events were significantly associated with higher odds of suicidal ideation. The gender-based analysis suggested that histories of depression and anxiety remained independently associated with lifetime suicidal ideation among women, whereas for men, childhood emotional neglect and the number of lifetime potentially traumatic events were independently associated with lifetime suicidal ideation. Conclusions: This study offers a critical first step to understanding factors associated with suicidal ideation among long-term opioid-dependent men and women and the potential importance of gender-sensitive approaches for suicidal behavior interventions. These data inform further research and clinical opportunities aiming to better respond to the psychological health needs of this population.
Mycobacterium tuberculosis multistage antigens confer comprehensive protection against pre- and post-exposure infections by driving Th1-type T cell immunity

There is an urgent need for a vaccine against tuberculosis (TB) that is more effective than the current sole licensed option. However, target antigens of Mycobacterium tuberculosis with the vaccine potential remain elusive. Five immunodominant antigens with characteristic expressions at the stages of primary infection (Ag85A), the regulation of nutrition and metabolism when transferring from rapid growth to latency (PhoY2 and Rv3407), latency (Rv2626c), and reactivation (RpfB) were selected to construct the fusion polyprotein WH121, which has better immunogenicity and protection than each multistage antigen. DMT adjuvanted WH121 vaccinated C57BL/6 mice could confer persistent and significant protection against the respiratory challenge with 80 CFU of virulent M. tuberculosis H37Rv at 9 and 18 weeks after immunization, as the BCG vaccine did. Moreover, WH121/DMT could boost the BCG primed mice against post-exposure infection, and more significantly inhibit the growth of M. tuberculosis in the spleen than BCG repeat vaccination. The protection elicited by WH121/DMT is attributed to the WH121-specific Th1-type biased immune responses, characterized by increased antigen-specific IgG2a/IgG1 ratio and high levels of IFN-γ secreted by the splenocytes of vaccinated mice. In particular, high levels of IFN-γ+ TEM cells in the spleen are an effective biomarker for the vaccine-induced early protection, and the persistent protection mainly depends on the increasing IL-2+IFN-γ+CD4+ and CD8+ T cells, especially IL-2+ TCM cells. These findings demonstrate that multistage-specific antigens might be promising targets for the next generation TB vaccine, and a combination of these antigens such as WH121/DMT is required for further preclinical evaluation.
Spatial Arrangement Overrules Environmental Factors to Structure Native and Non-Native Assemblages of Synanthropic Harvestmen

Understanding how space affects the occurrence of native and non-native species is essential for inferring processes that shape communities. However, studies considering spatial and environmental variables for the entire community - as well as for the native and non-native assemblages in a single study - are scarce for animals. Harvestmen communities in central Europe have undergone drastic turnovers during the past decades, with several newly immigrated species, and thus provide a unique system to study such questions. We studied the wall-dwelling harvestmen communities from 52 human settlements in Luxembourg and found the assemblages to be largely dominated by non-native species (64% of specimens). Community structure was analysed using Moran's eigenvector maps as spatial variables, and landcover variables at different radii (500 m, 1000 m, 2000 m) in combination with climatic parameters as environmental variables. A surprisingly high portion of pure spatial variation (15.7% of total variance) exceeded the environmental (10.6%) and shared (4%) components of variation, but we found only minor differences between native and non-native assemblages. This could result from the ecological flexibility of both, native and non-native harvestmen that are not restricted to urban habitats but also inhabit surrounding semi-natural landscapes. Nevertheless, urban landcover variables explained more variation in the non-native community, whereas coverage of semi-natural habitats (forests, rivers) at broader radii better explained the native assemblage. This indicates that some urban characteristics apparently facilitate the establishment of non-native species. We found no evidence for competitive replacement of native by invasive species, but a community with novel combination of native and non-native species.
Attributed Community Analysis: Global and Ego-centric Views

The proliferation of rich information available for real world entities and their relationships gives rise to a type of graph, namely attributed graph, where graph vertices are associated with a number of attributes. The set of an attribute can be formed by a series of keywords. In attributed graphs, it is practically useful to discover communities of densely connected components with homogeneous attribute values. In terms of different aspects, the community analysis tasks can be categorized into global network-wide and ego-centric personalized. The global network-wide community analysis considers the entire network, such that community detection, which is to ﬁnd all communities in a network. On the other hand, the ego-centric personalized community analysis focuses on the local neighborhood sub-graph of given query nodes, such that community search. Given a set of query nodes and attributes, community search in attributed graphs is to locally detect meaningful community containing query-related nodes in the online manner. In this work, we brieﬂy survey several state-of-the-art community models based on various dense subgraphs, meanwhile also investigate social circles, that one special kind of communities are formed by friends in 1-hop neighborhood network for a particular user.
Fabrication and Compressive Behavior of Corrugated Aramid-Epoxy Cellular Solids

Author: Jeffrey Arthur Schneider Title: Fabrication and Compressive Behavior of Corrugated Aramid-Epoxy Cellular Solids Institution: Embry-Riddle Aeronautical University Degree: Master of Science in Aerospace Engineering Year: 2007 Cellular solids are materials whose base material does not always occupy the entire solid fraction available. A number of cellular solids can provide blast protection and absorb impact energy, but few perform well resisting blunt object (ballistic) penetration. In this thesis, a method is proposed for fabricating cellular solids from aramid-epoxy composites that can absorb impact energy and resist blunt object penetration. The aramid-epoxy samples were fabricated using wetlayup techniques, with two different styles of Kevlar 49 woven fabric in a variety of orientations. Test sample density ranged from 0.08 0.23 g/cm. Different lamination orientations, assembly techniques, and bonding adhesives were investigated and assessed for their effect on quasi-static and dynamic crushing. A maximum plateau stress of 1.5 MPa was recorded with corresponding energy absorption of 4.2 J/g; values comparable to commercially produced metal foams. Methods for prediction of mechanical properties are presented/assessed along with suggestions for further improvements.
Physical Activity and Adiposity-related Inflammation: The MESA

Purpose Physical activity is associated with decreased adiposity-related inflammation in adults. Whether this association is independent of central obesity is unknown but important for understanding the mechanisms associated with reducing cardiometabolic disease risk through physical activity. This study examined whether associations of physical activity and obesity-related inflammatory markers were independent of central adiposity. Methods Between 2002 and 2005, 1970 participants from the Multi-Ethnic Study of Atherosclerosis completed detailed health history and physical activity questionnaires, underwent physical measurements including computed tomography to quantify abdominal visceral and subcutaneous fat, and measurements of adiponectin, leptin, interleukin-6, tumor necrosis factor-alpha, and resistin. Statistical analyses included analysis of covariance and multivariable-adjusted regression. Results The mean (range) age of participants was 64.7 (55–84) yr and 50% were women. After adjustment for age and sex, and compared with the lowest quartile, inflammatory markers in the highest quartile of moderate-to-vigorous physical activity were 16% higher for adiponectin and 30%, 26%, and 9% lower for leptin, interleukin-6, and resistin, respectively (P < 0.05 for all). In linear regression adjusted for demographics, dyslipidemia, hypertension, diabetes, smoking, glomerular filtration rate, renin, and aldosterone, each standard deviation increment of moderate-to-vigorous physical activity was associated with significantly higher levels of adiponectin (&bgr; = 0.04) and lower levels of leptin (&bgr; = −0.06), interleukin-6 (&bgr; = −0.08), and resistin (&bgr; = −0.05, P < 0.05 for all). The associations with leptin, interleukin-6, and resistin were independent of total and central adiposity (P < 0.05), whereas the association between moderate-to-vigorous physical activity and adiponectin was attenuated by central adiposity (P > 0.05). There were no significant interactions by race/ethnicity or sex. Conclusions Moderate-to-vigorous physical activity was associated with a more favorable profile of inflammatory markers, independent of relevant cardiometabolic disease risk factors including central obesity.
Deployment and Preterm Birth Among US Army Soldiers

With increasing integration of women into combat roles in the US military, it is critical to determine whether deployment, which entails unique stressors and exposures, is associated with adverse reproductive outcomes. Few studies have examined whether deployment increases the risk of preterm birth; no studies (to our knowledge) have examined a recent cohort of servicewomen. We therefore used linked medical and administrative data from the Stanford Military Data Repository for all US Army soldiers with deliveries between 2011 and 2014 to estimate the associations of prior deployment, recency of deployment, and posttraumatic stress disorder with spontaneous preterm birth (SPB), adjusting for sociodemographic, military-service, and health-related factors. Of 12,877 deliveries, 6.1% were SPBs. The prevalence was doubled (11.7%) among soldiers who delivered within 6 months of their return from deployment. Multivariable discrete-time logistic regression models indicated that delivering within 6 months of return from deployment was strongly associated with SPB (adjusted odds ratio = 2.1, 95% confidence interval: 1.5, 2.9). Neither multiple past deployments nor posttraumatic stress disorder was significantly associated with SPB. Within this cohort, timing of pregnancy in relation to deployment was identified as a novel risk factor for SPB. Increased focus on servicewomen's pregnancy timing and predeployment access to reproductive counseling and effective contraception is warranted.
An Interactive Exploration of the Virtual Stronghold Dillenburg

This paper presents the results of an interdisciplinary project aiming at the virtual three-dimensional reconstruction of the stronghold Dillenburg, which has been completely destroyed in 1768. For an interactive virtual exploration, a high-quality 3D model was generated in close cooperation between local historians and scientists from the field of Computer Graphics based on a collection of ancient text documents, drawings and floor plans. Computer animations were generated and assembled in a DVD product for comfortable access to the virtual fortress. For the exhibition in the museum Dillenburg, a real-time application was developed for on site virtual exploration. Provided with a touch screen for interaction and a wide-screen display system, visitors can intuitively explore the virtual reconstruction and access supplemental historical background material on demand. With the multimedia installation we present a new experience which empowers visitors of the museum to explore an historical site freely at their own preferences and encourages younger audience to show more interest in cultural heritage.
Prenatal, perinatal and neonatal risk factors for perinatal arterial ischaemic stroke: a systematic review and meta‐analysis

The aim of the present study was to perform a meta‐analysis of published data to determine the significance of clinical factors and exposures to the risk of perinatal arterial ischaemic stroke (PAIS) and provide guidance for clinical diagnosis and treatment. A comprehensive literature search of the PubMed, Embase, MEDLINE and Cochrane Library databases for relevant observational studies (cohort/case−control) from March 1984 to March 2016 was undertaken. Two review authors independently examined the full text records to determine which studies met the inclusion criteria and evaluated risk factors for PAIS. Risk ratios, odds ratios and 95% confidence intervals were estimated. A total of 11 studies were included in the analyses. Intrapartum fever >38°C, pre‐eclampsia, oligohydramnios, primiparity, forceps delivery, vacuum delivery, fetal heart rate abnormalities, abnormal cardiotocography tracing, cord abnormalities, birth asphyxia, emergency caesarean section, tight nuchal cord, meconium‐stained amniotic fluid, umbilical arterial pH <7.10, Apgar score at 5 min <7, resuscitation at birth, hypoglycaemia, male gender and small for gestational age were identified as risk factors for PAIS. This systemic review and meta‐analysis provides a preliminary evidence‐based assessment of the risk factors for PAIS. Patients with any of the risk factors identified in this analysis should be given careful consideration to ensure the prevention of PAIS. Future studies focusing on the combined effects of multiple prenatal, perinatal and neonatal risk factors for PAIS are warranted.