bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of SERINC5-001 as the Predominant Spliced Isoform for HIV-1 Restriction
Authors: Zhang Xianfeng , Zhou Tao , Yang Jie , Lin Yumei , Shi Jing , Zhang Xihe , Frabutt Dylan A. , Zeng Xiangwei , Li Sunan , Venta Patrick J. , Zheng Yong-Hui 
Published: March 2017

ABSTRACT

Among the five serine incorporator (SERINC) family members, SERINC5 (Ser5) was reported to strongly inhibit HIV-1 replication, which is counteracted by Nef.
Ser5
produces 5 alternatively spliced isoforms: Ser5-001 has 10 putative transmembrane domains, whereas Ser5-004, -005, -008a, and -008b do not have the last one. Here, we confirmed the strong Ser5 anti-HIV-1 activity and investigated its isoforms' expression and antiviral activities. It was found that
Ser5-001
transcripts were detected at least 10-fold more than the other isoforms by real-time quantitative PCR. When Ser5-001 and its two isoforms Ser5-005 and Ser5-008a were expressed from the same mammalian expression vector, only Ser5-001 was stably expressed, whereas the others were poorly expressed due to rapid degradation. In addition, unlike the other isoforms, which are located mainly in the cytoplasm, Ser5-001 is localized primarily to the plasma membrane. To map the critical determinant, Ser5 mutants bearing C-terminal deletions were created. It was found that the 10th transmembrane domain is required for Ser5 stable expression and plasma membrane localization. As expected, only Ser5-001 strongly inhibits HIV-1 infectivity, whereas the other Ser5 isoforms and mutants that do not have the 10th transmembrane domain show very poor activity. It was also observed that the Nef counteractive activity could be easily saturated by Ser5 overexpression. Thus, we conclude that Ser5-001 is the predominant antiviral isoform that restricts HIV-1, and the 10th transmembrane domain plays a critical role in this process by regulating its protein stability and plasma membrane targeting.

IMPORTANCE
Human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) express a small protein, Nef, to enhance viral pathogenesis
in vivo
. Nef has an important
in vitro
function, which is to make virus particles more infectious, but the mechanism has been unclear. Recently, Nef was reported to counteract a novel anti-HIV host protein, SERINC5 (Ser5). Ser5 has five alternatively spliced isoforms, Ser5-001, -004, -005, -008a, and -008b, and only Ser5-001 has an extra C-terminal transmembrane domain. We now show that the Ser5-001 transcripts are produced at least 10-fold more than the others, and only Ser5-001 produces stable proteins that are targeted to the plasma membrane. Importantly, only Ser5-001 shows strong anti-HIV-1 activity. We further demonstrate that the extra transmembrane domain is required for Ser5 stable expression and plasma membrane localization. These results suggest that plasma membrane localization is required for Ser5 antiviral activity, and Ser5-001 is the predominant isoform that contributes to the activity.
Viruses in the Oceanic Basement
Authors: Nigro Olivia D. , Jungbluth Sean P. , Lin Huei-Ting , Hsieh Chih-Chiang , Miranda Jaclyn A. , Schvarcz Christopher R. , Rappé Michael S. , Steward Grieg F. 
Published: March 2017

ABSTRACT

Microbial life has been detected well into the igneous crust of the seafloor (i.e., the oceanic basement), but there have been no reports confirming the presence of viruses in this habitat. To detect and characterize an ocean basement virome, geothermally heated fluid samples (ca. 60 to 65°C) were collected from 117 to 292 m deep into the ocean basement using seafloor observatories installed in two boreholes (Integrated Ocean Drilling Program [IODP] U1362A and U1362B) drilled in the eastern sediment-covered flank of the Juan de Fuca Ridge. Concentrations of virus-like particles in the fluid samples were on the order of 0.2 × 10
5
to 2 × 10
5
ml
−1
(
n
= 8), higher than prokaryote-like cells in the same samples by a factor of 9 on average (range, 1.5 to 27). Electron microscopy revealed diverse viral morphotypes similar to those of viruses known to infect bacteria and thermophilic archaea. An analysis of virus-like sequences in basement microbial metagenomes suggests that those from archaeon-infecting viruses were the most common (63 to 80%). Complete genomes of a putative archaeon-infecting virus and a prophage within an archaeal scaffold were identified among the assembled sequences, and sequence analysis suggests that they represent lineages divergent from known thermophilic viruses. Of the clustered regularly interspaced short palindromic repeat (CRISPR)-containing scaffolds in the metagenomes for which a taxonomy could be inferred (163 out of 737), 51 to 55% appeared to be archaeal and 45 to 49% appeared to be bacterial. These results imply that the warmed, highly altered fluids in deeply buried ocean basement harbor a distinct assemblage of novel viruses, including many that infect archaea, and that these viruses are active participants in the ecology of the basement microbiome.

IMPORTANCE
The hydrothermally active ocean basement is voluminous and likely provided conditions critical to the origins of life, but the microbiology of this vast habitat is not well understood. Viruses in particular, although integral to the origins, evolution, and ecology of all life on earth, have never been documented in basement fluids. This report provides the first estimate of free virus particles (virions) within fluids circulating through the extrusive basalt of the seafloor and describes the morphological and genetic signatures of basement viruses. These data push the known geographical limits of the virosphere deep into the ocean basement and point to a wealth of novel viral diversity, exploration of which could shed light on the early evolution of viruses.
A preconsultation web-based tool to generate an agenda for discussion in diabetes outpatient clinics to improve patient outcomes (DIAT): a feasibility study
Authors: Ukoumunne Obioha C , Vaidya Bijay , Frost Julia , Anderson Rob , Argyle Catherine , Daly Mark , Harris-Golesworthy Faith , Harris Jim , Gibson Andy , Ingram Wendy , Pinkney Jon , Vickery Jane , Britten Nicky 
Published: March 2017

ObjectiveTo test the feasibility of running a randomised controlled trial of a preconsultation web-based intervention (Presenting Asking Checking Expressing (PACE-D)) to improve the quality of care and clinical outcomes in patients with diabetes.Design and settingA feasibility study (with randomisation) conducted at outpatient diabetes clinics at two secondary care hospitals in Devon, UK.ParticipantsPeople with diabetes (type 1 and type 2) attending secondary care general diabetes outpatient clinics.InterventionThe PACE-D, a web-based tool adapted for patients with diabetes to use before their consultation to generate an agenda of topics to discuss with their diabetologist.OutcomesThe percentage of eligible patients who were recruited and the percentage of participants for whom routine glycosylated haemoglobin (HbA1c) data (the putative primary outcome) could be extracted from medical notes and who completed secondary outcome assessments via questionnaire at follow-up were reported.ResultsIn contrast with the planned recruitment of 120 participants, only 71 participants were randomised during the 7-month recruitment period. This comprised 18.7% (95% CI 14.9% to 23.0%) of those who were eligible. Mean (SD) age of the participants was 56.5 (12.4) years and 66.2% had type 1 diabetes. Thirty-eight patients were randomised to the intervention arm and 33 to the control arm. HbA1c data were available for only 73% (95% CI 61% to 83%) of participants at the 6 months follow-up. The questionnaire-based data were collected for 66% (95% CI 54% to 77%) of the participants at 6 months follow-up. Participants reported that the PACE-D tool was easy to use.ConclusionsA randomised controlled trial of the preconsultation web-based intervention as set out in our current protocol is not feasible without significant modification to improve recruitment and follow-up of participants. The study also provides insights into the feasibility and challenges of conducting complex intervention trials in everyday clinical practice.Trial registrationISRCTN75070242.
Association between perceived weight discrimination and physical activity: a population-based study among English middle-aged and older adults
Authors: Jackson Sarah E , Steptoe Andrew 
Published: March 2017

ObjectiveTo examine the association between perceived weight discrimination and physical activity in a large population-based sample.DesignData were from 2423 men and 3057 women aged ≥50 years participating in Wave 5 (2010/11) of the English Longitudinal Study of Ageing. Participants reported experiences of weight discrimination in everyday life and frequency of light, moderate and vigorous physical activities. We used logistic regression to test associations between perceived weight discrimination and physical activity, controlling for age, sex, socioeconomic status and body mass index (BMI).ResultsPerceived weight discrimination was associated with almost 60% higher odds of being inactive (OR 1.59, 95% CI 1.05 to 2.40, p=.028) and 30% lower odds of engaging in moderate or vigorous activity at least once a week (OR 0.70, 95% CI 0.53 to 0.94, p=.017).ConclusionsIndependent of BMI, individuals who perceive unfair treatment on the basis of their weight are less physically active than those who do not perceive discrimination. This has important implications for the health and well-being of individuals who experience weight-based discrimination, and may also contribute to a cycle of weight gain and further mistreatment.
Qualitative analysis of young adult ENDS users' expectations and experiences
Authors: Hoek Janet , Thrul Johannes , Ling Pamela 
Published: March 2017

ObjectivesDespite extensive research into the determinants of electronic nicotine delivery system (ENDS) uptake, few studies have examined the psychosocial benefits ENDS users seek and experience. Using a consumer ritual framework, we explored how ENDS users recreated or replaced smoking practices, and considered implications for smoking cessation.DesignIn-depth interviews; data analysed using thematic analysis.SettingDunedin, New Zealand.Participants16 young adult ENDS users (age M=21.4, SD=1.9; 44% female).ResultsParticipants reported using different ENDS to achieve varying outcomes. Some used ‘cigalikes’ to recreate a physically and visually similar experience to smoking; they privileged device appearance over nicotine delivery. In contrast, others used personally crafted mods to develop new rituals that differentiated them from smokers and showcased their technical expertise. Irrespective of the device they used, several former smokers and dual users of cigarettes and ENDS experienced strong nostalgia for smoking attributes, particularly the elemental appeal of fire and the finiteness of a cigarette. Non-smoking participants used ENDS to maintain social connections with their peers.ConclusionsParticipants used ENDS to construct rituals that recreated or replaced smoking attributes, and that varied in the emphasis given to device appearance, nicotine delivery, and social performance. Identifying how ENDS users create new rituals and the components they privilege within these could help promote full transition from smoking to ENDS and identify those at greatest risk of dual use or relapse to cigarette smoking.
Epidemiology of injuries in the Spanish national futsal male team: a five-season retrospective study
Authors: Martinez-Riaza Luis , Herrero-Gonzalez Helena , Lopez-Alcorocho Juan M , Guillen-Garcia Pedro , Fernandez-Jaen Tomas F 
Published: March 2017

BackgroundFutsal started being played in 1930 and the number of futsal players has increased all over the world ever since. Nonetheless, despite the fact that Spain is one of the most relevant national teams worldwide, information on the incidence of injuries and their anthropometric characteristics is sparse in this country.AimTo analyse medical assistance provided to players in their prematch concentration camps with the Spanish national team over five seasons, from 2010–2011 to 2014–2015, and also to collect data regarding anthropometric characteristics.Materials and methodsThis is a retrospective and detailed study of injuries players suffered over these five seasons. All variables were registered on an Excel spreadsheet and later analysed statistically.Results411 injuries were studied in total. The dominant somatotype was mesomorph and the injured pivots were both the most endomorphic and the most mesomorphic. The most injured body structure was the hamstring muscles, occurring due to training and intrinsic mechanisms, where fatigue was the most frequent diagnosis. Only a few complementary examinations were carried out and prematch withdrawal was rare.DiscussionThe skinfold test total sum was lower than that of the Spanish 11-a-side players or than that in the lower category futsal Spanish players. In various research studies analysing exclusively injuries occurring in matches, the most frequent injury is ligament injury by extrinsic mechanism. The body mass index was not a useful parameter when assessing players’ appropriate weight. Most injuries occurred in training sessions, mostly by intrinsic mechanism; the highest percentage of traumatic injuries occurred in official matches.
Injuries during the international floorball tournaments from 2012 to 2015
Authors: Pasanen Kati , Bruun Merita , Vasankari Tommi , Nurminen Minna , Frey Walter O 
Published: March 2017

BackgroundFloorball is a running indoor team sport that has growing popularity worldwide. Some prospective studies have investigated injuries in national floorball leagues, but such studies at the international level are lacking.ObjectiveTo investigate the incidence and characteristics of injuries during 12 International Floorball Federation (IFF) events.MethodsAll top-level IFF events from 2012 to 2015 were included in the study. The IFF events were divided into the following groups: Men’s World Floorball Championships (2012 and 2014), Women’s World Floorball Championships (2013 and 2015), Men’s Champions Cup (2012, 2013, 2014 and 2015) and Women’s Champions Cup (2012, 2013, 2014 and 2015). The team medical personnel prospectively recorded the injuries that occurred in games and practices. The time of exposure was calculated for entire teams based on the IFF statistics.ResultsSixty-eight injuries were registered among 67 players. Sixty-five of the injuries occurred in games, resulting in an injury incidence of 21.24 per 1000 game hours (95% CI 16.13 to 26.35). There was no significant difference in the incidence of game injuries between females and males (incidence rate ratio 0.68, 95% CI 0.41 to 1.11). The ankle was the most common site of injury (24%), followed by the head (18%) and the knee (18%). Almost half of the injuries (46%) involved joints or ligaments.ConclusionsRisk of injury during IFF tournaments was lower than in many other team sports at the highest level of play. Preventive actions should focus on acute ankle and knee injuries as well as head and face injuries.
Leaky pipeline, gender bias, self-selection or all three? A quantitative analysis of gender balance at an international palliative care research conference
Authors: Sleeman Katherine E , Koffman Jonathan , Higginson Irene J 
Published: March 2017

ObjectivesThe ‘leaky pipeline’ in academia is a clearly described phenomenon, but has not been examined in palliative care. We analysed the gender balance of speakers at the 9th World Research Congress of the European Association of Palliative Care (EAPC) to test the null hypothesis that there is no difference in the proportion of women and men with senior academic visibility in palliative care conference programmes.MethodsThe final programme of the 2016 EAPC World Congress was examined, and the gender of each speaker was recorded. Presentations were assessed using a three-tier hierarchy of senior academic visibility: Free Communication sessions, Themed sessions and invited Plenaries (low to high). As there was only one Invited Plenary at EAPC 2016, we examined the gender balance at EAPC Plenaries from 2012 to 2016.ResultsOverall, the majority of speakers at EAPC 2016 (96/130, 73.8%) were women. The proportion of women was highest in the Free Communication sessions (84/107, 78.5%). In the Themed sessions, women made up just over half of speakers (12/22, 54.5%). In 2016, there was 1 invited Plenary speaker, a man. From 2012 to 2016, just 6 of 23 invited Plenary speakers at EAPC conferences have been women (26.1%) (χ2=25.4, p<0.001).ConclusionsThese data reject our null hypothesis and suggest that there is attrition of women along the academic pipeline in palliative care. Other factors such as self-selection (that women decline invitations to give talks) and unconscious gender bias need further exploration, as well as actions to address the imbalance.
Patients expectations and fulfilment of expectations before and after treatment for suspected coronary artery disease assessed with a newly developed questionnaire in combination with established health-related quality of life questionnaires
Authors: Odell Annika , Bång Angela , Andréll Paulin , Widell Charlotte , Fryklund Henrik , Kallryd Anders , Tygesen Hans , Grip Lars 
Published: March 2017

BackgroundClinical decision-making is often based on evidence of outcome after a specific treatment. Healthcare providers and patients may, however, have different perceptions and expectations of what to achieve from a certain healthcare measure.AimsTo evaluate patients’ expectations, perceptions and health related quality of life (HRQoL) before a care process including coronary angiography for suspected coronary artery disease and to evaluate the fulfilment of these expectations in relation to established patient reported outcome measures (PROMs) 6 months later. Furthermore, an aim was to try to define meaningful patient reported experience measures (PREMs) in this population.Methods544 patients planned for coronary angiography completed a newly developed questionnaire to assess expectations and perceptions of treatment, the expectation questionnaire (ExpQ) and two established HRQoL questionnaires together with the established generic Short-Form 36 (SF36) and the disease specific Seattle Angina Questionnaire (SAQ).ResultsPatients had before the intervention, in general, high expectations of improvement after investigation and treatment and there was a positive attitude towards life style changes, medication and participation in decision-making regarding their own treatment. Only, 56.4% of the patients, however, reported fulfilment of treatment expectations. Fulfilment of treatment expectations correlated strongly with improvement in HRQoL after the care process.ConclusionsTo measure patients ́ expectations and fulfilments of these may offer simple and meaningful outcomes to evaluate a healthcare process from a patient ́s perspective. To approach patients’ expectations may also strengthen patient involvement in the care process with the possibilities of both higher patient satisfaction and medical results of the treatment.
Activity-dependent increases in [Ca2+]i contribute to digital-analog plasticity at a molluscan synapse
Authors: Ludwar Bjoern Ch. , Evans Colin G. , Cambi Monica , Cropper Elizabeth C. 
Published: March 2017

In a type of short-term plasticity that is observed in a number of systems, synaptic transmission is potentiated by depolarizing changes in the membrane potential of the presynaptic neuron before spike initiation. This digital-analog form of plasticity is graded. The more depolarized the neuron, the greater the increase in the efficacy of synaptic transmission. In a number of systems, including the system presently under investigation, this type of modulation is calcium dependent, and its graded nature is presumably a consequence of a direct relationship between the intracellular calcium concentration ([Ca2+]i) and the effect on synaptic transmission. It is therefore of interest to identify factors that determine the magnitude of this type of calcium signal. We studied a synapse in Aplysia and demonstrate that there can be a contribution from currents activated during spiking. When neurons spike, there are localized increases in [Ca2+]i that directly trigger neurotransmitter release. Additionally, spiking can lead to global increases in [Ca2+]i that are reminiscent of those induced by subthreshold depolarization. We demonstrate that these spike-induced increases in [Ca2+]i result from the activation of a current not activated by subthreshold depolarization. Importantly, they decay with a relatively slow time constant. Consequently, with repeated spiking, even at a low frequency, they readily summate to become larger than increases in [Ca2+]i induced by subthreshold depolarization alone. When this occurs, global increases in [Ca2+]i induced by spiking play the predominant role in determining the efficacy of synaptic transmission. NEW & NOTEWORTHY We demonstrate that spiking can induce global increases in the intracellular calcium concentration ([Ca2+]i) that decay with a relatively long time constant. Consequently, summation of the calcium signal occurs even at low firing frequencies. As a result there is significant, persistent potentiation of synaptic transmission.
The Checkpoint Kinase 1 Inhibitor Prexasertib Induces Regression of Preclinical Models of Human Neuroblastoma
Authors: Lowery Caitlin D. , VanWye Alle B. , Dowless Michele , Blosser Wayne , Falcon Beverly L. , Stewart Julie , Stephens Jennifer , Beckmann Richard P. , Bence Lin Aimee , Stancato Louis F. 
Published: March 2017

Abstract
Purpose: Checkpoint kinase 1 (CHK1) is a key regulator of the DNA damage response and a mediator of replication stress through modulation of replication fork licensing and activation of S and G2–M cell-cycle checkpoints. We evaluated prexasertib (LY2606368), a small-molecule CHK1 inhibitor currently in clinical testing, in multiple preclinical models of pediatric cancer. Following an initial assessment of prexasertib activity, this study focused on the preclinical models of neuroblastoma.
Experimental Design: We evaluated the antiproliferative activity of prexasertib in a panel of cancer cell lines; neuroblastoma cell lines were among the most sensitive. Subsequent Western blot and immunofluorescence analyses measured DNA damage and DNA repair protein activation. Prexasertib was investigated in several cell line–derived xenograft mouse models of neuroblastoma.
Results: Within 24 hours, single-agent prexasertib promoted γH2AX–positive double-strand DNA breaks and phosphorylation of DNA damage sensors ATM and DNA–PKcs, leading to neuroblastoma cell death. Knockdown of CHK1 and/or CHK2 by siRNA verified that the double-strand DNA breaks and cell death elicited by prexasertib were due to specific CHK1 inhibition. Neuroblastoma xenografts rapidly regressed following prexasertib administration, independent of starting tumor volume. Decreased Ki67 and increased immunostaining of endothelial and pericyte markers were observed in xenografts after only 6 days of exposure to prexasertib, potentially indicating a swift reduction in tumor volume and/or a direct effect on tumor vasculature.
Conclusions: Overall, these data demonstrate that prexasertib is a specific inhibitor of CHK1 in neuroblastoma and leads to DNA damage and cell death in preclinical models of this devastating pediatric malignancy. Clin Cancer Res; 23(15); 4354–63. ©2017 AACR.