bluuebunny/crossref_metadata_2025_split huggingface dataset:
OsNLA1, a RING‐type ubiquitin ligase, maintains phosphate homeostasis in Oryza sativa via degradation of phosphate transporters
Authors: Yue Wenhao , Ying Yinghui , Wang Chuang , Zhao Yang , Dong Changhe , Whelan James , Shou Huixia 
Published: February 2017

SummaryInorganic phosphate (Pi) transporters (PTs) play vital roles in Pi uptake and translocation in plants. Under Pi sufficient conditions, PTs are degraded to prevent excess Pi accumulation. The mechanisms targeting PTs for degradation are not fully elucidated. In this study, we found that the Oryza sativa (rice) ortholog of Arabidopsis thaliana nitrogen limitation adaptation (NLA), OsNLA1 protein, a RING‐type E3 ubiquitin‐ligase, was predominantly localized in the plasma membrane, and could interact with rice phosphate transporters OsPT2 and OsPT8. Mutation of the 265th cysteine residue in OsNLA1 that was required for ubiquitination prevented breakdown of OsPT2/PT8, suggesting OsNLA1 targeted OsPT2/PT8 for degradation. Mutation in OsNLA1 (osnla1) led to a significant increase of Pi concentration in leaves in a nitrate‐independent manner. Overexpression of OsNLA1 or repression of OsPT2/PT8 restored the high leaf Pi concentration in osnla1 mutants to a level similar to that of wild‐type plants. In contrast to what has been observed in Arabidopsis, the transcript abundance of OsNLA1 did not decrease under Pi limited conditions or in OsmiR827 (microRNA827)‐ or OsPHR2 (PHOSPHATE STARVATION RESPONSE 2)‐overexpressing transgenic lines. Moreover, there was no interaction of OsNLA1 and OsPHO2, an E2 ubiquitin‐conjugase, suggesting that OsPHO2 was not the partner of OsNLA1 involved in ubiquitin‐mediated PT degradation. Our results show that OsNLA1 is involved in maintaining phosphate homeostasis in rice by mediating the degradation of OsPT2 and OsPT8, and OsNLA1 differs from the ortholog in Arabidopsis in several aspects.
First cases of Zika virus–infected US blood donors outside states with areas of active transmission
Authors: Williamson Phillip C. , Linnen Jeffrey M. , Kessler Debra A. , Shaz Beth H. , Kamel Hany , Vassallo Ralph R. , Winkelman Valerie , Gao Kui , Ziermann Rainer , Menezes Juscilene , Thomas Stephen , Holmberg Jerry A. , Bakkour Sonia , Stone Mars , Lu Kai , Simmons Graham , Busch Michael P. 
Published: February 2017

BACKGROUNDZika virus (ZIKV) is transmitted by Aedes mosquitos and can result in severe congenital and adult neurologic abnormalities. ZIKV has rapidly spread northward through Central America and the Caribbean and autochthonous cases have been identified in the continental United States. High rates of ZIKA RNA positivity were detected in blood donors during previous epidemics. ZIKV transmission by transfused blood from healthy donor components has been a growing concern.STUDY DESIGN AND METHODSIndividual‐donation aliquots of plasma from volunteer blood donors were tested individually with an investigational Procleix ZIKV assay. Initially reactive samples were tested for ZIKV RNA in plasma and red blood cells (RBCs) and for ZIKV‐specific antibodies in serum. A confirmed positive classification required confirmation of RNA and/or detection of ZIKV antibodies in index and/or follow‐up samples.RESULTSBetween September 19 and November 30, 2016, a total of 466,834 donations were screened for ZIKV RNA. Five donors (one in approx. 93,000) were reactive for ZIKV RNA by both the Procleix ZIKV assay and supplemental testing. The donations were collected outside areas considered as having active transmission, and all five donors had travel exposures. A lookback case demonstrated no infection despite transfusion of a Zika IgG–positive platelet (PLT) component with probable low levels of ZIKV RNA.CONCLUSIONSThis report describes the first ZIKV‐positive donors detected outside areas with active transmission. These donors most likely represent travel‐acquired “tail‐end infections” with prolonged RBC‐associated ZIKV RNA. The lack of transmission to the recipient of an apheresis PLT may suggest that these units are not infectious.
Differential serotonergic modulation across the main and accessory olfactory bulbs
Authors: Huang Zhenbo , Thiebaud Nicolas , Fadool Debra Ann 
Published: February 2017

Key points
There are serotonergic projections to both the main (MOB) and the accessory olfactory bulb (AOB).
Current‐clamp experiments demonstrate that serotonergic afferents are largely excitatory for mitral cells (MCs) in the MOB where 5‐HT2A receptors mediate a direct excitatory action.
Serotonergic afferents are predominately inhibitory for MCs in the AOB. There are two types of inhibition: indirect inhibition mediated through the 5‐HT2 receptors on GABAergic interneurons and direct inhibition via the 5‐HT1 receptors on MCs.
Differential 5‐HT neuromodulation of MCs across the MOB and AOB could contribute to select behaviours such as olfactory learning or aggression.
AbstractMitral cells (MCs) contained in the main (MOB) and accessory (AOB) olfactory bulb have distinct intrinsic membrane properties but the extent of neuromodulation across the two systems has not been widely explored. Herein, we investigated a widely distributed CNS modulator, serotonin (5‐HT), for its ability to modulate the biophysical properties of MCs across the MOB and AOB, using an in vitro, brain slice approach in postnatal 15–30 day mice. In the MOB, 5‐HT elicited three types of responses in 93% of 180 cells tested. Cells were either directly excited (70%), inhibited (10%) or showed a mixed response (13%)– first inhibition followed by excitation. In the AOB, 82% of 148 cells were inhibited with 18% of cells showing no response. Albeit located in parallel partitions of the olfactory system, 5‐HT largely elicited MC excitation in the MOB while it evoked two different kinetic rates of MC inhibition in the AOB. Using a combination of pharmacological agents, we found that the MC excitatory responses in the MOB were mediated by 5‐HT2A receptors through a direct activation. In comparison, 5‐HT‐evoked inhibitory responses in the AOB arose due to a polysynaptic, slow‐onset inhibition attributed to 5‐HT2 receptor activation exciting GABAergic interneurons. The second type of inhibition had a rapid onset as a result of direct inhibition mediated by the 5‐HT1 class of receptors. The distinct serotonergic modulation of MCs between the MOB and AOB could provide a molecular basis for differential chemosensory behaviours driven by the brainstem raphe nuclei into these parallel systems.
Hepatitis C Virus-Specific T Cell Receptor mRNA-Engineered Human T Cells: Impact of Antigen Specificity on Functional Properties
Authors: Balasiddaiah Anangi , Davanian Haleh , Aleman Soo , Pasetto Anna , Frelin Lars , Sällberg Matti , Lohmann Volker , Koh Sarene , Bertoletti Antonio , Chen Margaret 
Published: February 2017

ABSTRACT
Therapy with genetically modified autologous T cells has shown great promise in cancer therapy. For an efficient control of hepatitis C virus (HCV) infection, cytotoxic T cells (CTL) are pivotal, but persistence of activated T cells may lead to liver toxicity. Here, anti-HCV T cell receptors (TCRs) recognizing the HCV nonstructural (NS) NS3 or NS5 viral peptide target were examined by mRNA transfection of human peripheral blood lymphocytes (PBLs) derived from healthy donors as well as chronically infected HCV patients. Immunological analysis shows that while the CTLs expressing the NS5-specific TCR reduced HCV RNA replication by a noncytotoxic mechanism, the NS3-specific TCR-redirected CTLs were polyfunctional and inhibited HCV RNA replication through antigen-specific cytotoxicity. Transcriptome signatures from these two types of CTL responses revealed uniquely expressed gene clusters upon encountering hepatoma target cells presenting endogenously expressed HCV proteins. The NS3 TCR induced a rapid expression of apoptotic signaling pathways and formation of embryonic gene clusters, whereas the NS5A TCR activation induced extended proliferative and metabolic pathways as the HCV target cells survived. Our results provide detailed insights into basic HCV T cell immunology and have clinical relevance for redirecting T cells to target virally infected hepatoma cells.

IMPORTANCE
Due to the protective ability of HCV-specific T cells and the hepatotoxic potential that they possess, there is a great need for the understanding of the functional aspects of HCV-specific T cells. To circumvent the low level of precursor frequency in patients, we engineered primary CD8
+
T cells by mRNA TCR vectors to confer HCV specificity to new T cells. HCV TCRs that differ in antigen specificity and polyfunctionality were examined. mRNA TCR engineering of peripheral blood lymphocytes from healthy donors or chronically infected HCV patients resulted in strikingly high levels of HCV TCR expression and HCV-specific responses. While a cytotoxicity response from a polyfunctional T cell activation caused hepatotoxicity and the rapid induction of apoptotic signaling pathways, the noncytotoxic T cell activation showed extended proliferative, metabolic pathways and persistence of HCV target cells. Our results provide detailed insights into basic HCV T cell immunology and have clinical relevance for immune protection of HCV-associated diseases.
Childhood academic ability in relation to cigarette, alcohol and cannabis use from adolescence into early adulthood: Longitudinal Study of Young People in England (LSYPE)
Authors: Williams James , Hagger-Johnson Gareth 
Published: February 2017

ObjectivesOur aim was to determine the association between childhood academic ability and the onset and persistence of tobacco, alcohol and cannabis use across adolescence in a representative sample of English schools pupils. Previous research has produced conflicting findings.DesignData from 7 years of the Longitudinal Study of Young People in England (LSYPE), 2004–2010 (age 13/14–19/20).SettingSelf-completion questionnaires during home visits, face-to-face interviews and web-based questionnaires.ParticipantsData from 6059 participants (3093 females) with information on academic ability around age 11 and health behaviours from age 13/14 to 16/17 (early adolescence) and from age 18/19 to 19/20 (late adolescence).Outcome measuresRegularity of cigarette smoking, alcohol drinking and cannabis use from early to late adolescence.ResultsIn multinomial logistic regression models adjusting for a range of covariates, the high (vs low) academic ability reduced the risk of persistent cigarette smoking (RR=0.62; CI 95% 0.48 to 0.81) in early adolescence. High (vs low) academic ability increased the risk of occasional (RR=1.25; CI 95% 1.04 to 1.51) and persistent (RR=1.83; CI 95% 1.50 to 2.23) regular alcohol drinking in early adolescence and persistent (RR=2.28; CI 95% 1.84 to 2.82) but not occasional regular alcohol drinking in late adolescence. High academic ability was also positively associated with occasional (RR=1.83; CI 95% 1.50 to 2.23) and persistent (RR=1.83; CI 95% 1.50 to 2.23) cannabis use in late adolescence.ConclusionsIn a sample of over 6000 young people in England, high childhood academic at age 11 is associated with a reduced risk of cigarette smoking but an increased risk of drinking alcohol regularly and cannabis use. These associations persist into early adulthood, providing evidence against the hypothesis that high academic ability is associated with temporary ‘experimentation’ with substance use.
Descriptive analysis of objectively assessed physical activity among talented soccer players: a study of three Norwegian professional football clubs
Authors: Sæther Stig Arve , Aspvik Nils Petter 
Published: February 2017

BackgroundTalented football players are expected to overcome large training and match loads, indicating a high weekly level of physical activity (PA).AimsWith the use of accelerometers, the aim of this study was to objectively describe the players’ total time spent in moderate-to-vigorous PA (MVPA), vigorous PA (VPA) and very vigorous PA (VVPA) per day in 1 week. Since high-intensity PA has been highlighted as important in terms of overall PA load, we also included 2 and 4 min bouts of VPA.MethodsData were collected in three junior teams in professional football clubs in March (club 1: 2014, club 2: 2012 and club 3: 2011). A one-way analysis of variance was applied to analyse differences between the three respective clubs.ResultsThe players averaged 77.2–86.2 min in MVPA, 14.9–18.5 min in VPA and 1.0–3.1 in VVPA per day. While there were no differences in total time spent in MVPA and VPA per day, VVPA was significantly higher in club 1 (p<0.01) compared with clubs 2 and 3. Moreover, when using the VPA bouts, club 3 (p<0.01) achieved significantly more time in this intensity compared with clubs 1 and 2.ConclusionThis study acknowledges the importance of including both club-related and non-club-related PA when analysing talented football players’ PA level. We suggest that future studies examining players’ PA with accelerometers should emphasise time spent in high-intensity PA and how this is associated with physical overload, psychological burnout and risk of injury.
Food responsiveness regulates episodic behavioral states inCaenorhabditis elegans
Authors: McCloskey Richard J. , Fouad Anthony D. , Churgin Matthew A. , Fang-Yen Christopher 
Published: February 2017

Animals optimize survival and reproduction in part through control of behavioral states, which depend on an organism’s internal and external environments. In the nematode Caenorhabditis elegans a variety of behavioral states have been described, including roaming, dwelling, quiescence, and episodic swimming. These states have been considered in isolation under varied experimental conditions, making it difficult to establish a unified picture of how they are regulated. Using long-term imaging, we examined C. elegans episodic behavioral states under varied mechanical and nutritional environments. We found that animals alternate between high-activity (active) and low-activity (sedentary) episodes in any mechanical environment, while the incidence of episodes and their behavioral composition depend on food levels. During active episodes, worms primarily roam, as characterized by continuous whole body movement. During sedentary episodes, animals exhibit dwelling (slower movements confined to the anterior half of the body) and quiescence (a complete lack of movement). Roaming, dwelling, and quiescent states are manifest not only through locomotory characteristics but also in pharyngeal pumping (feeding) and in egg-laying behaviors. Next, we analyzed the genetic basis of behavioral states. We found that modulation of behavioral states depends on neuropeptides and insulin-like signaling in the nervous system. Sensory neurons and the Foraging homolog EGL-4 regulate behavior through control of active/sedentary episodes. Optogenetic stimulation of dopaminergic and serotonergic neurons induced dwelling, implicating dopamine as a dwell-promoting neurotransmitter. Our findings provide a more unified description of behavioral states and suggest that perception of nutrition is a conserved mechanism for regulating animal behavior.NEW & NOTEWORTHY One strategy by which animals adapt to their internal states and external environments is by adopting behavioral states. The roundworm Caenorhabditis elegans is an attractive model for investigating how behavioral states are genetically and neuronally controlled. Here we describe the hierarchical organization of behavioral states characterized by locomotory activity, feeding, and egg-laying. We show that decisions to engage in these behaviors are controlled by the nervous system through insulin-like signaling and the perception of food.
Are cardiovascular risk factors also associated with the incidence of atrial fibrillation?
Authors: Allan Victoria , Honarbakhsh Shohreh , Casas Juan-Pablo , Wallace Joshua , Hunter Ross , Schilling Richard , Perel Pablo , Morley Katherine , Banerjee Amitava , Hemingway Harry 
Published: February 2017

SummaryEstablished primary prevention strategies of cardiovascular diseases are based on understanding of risk factors, but whether the same risk factors are associated with atrial fibrillation (AF) remains unclear. We conducted a systematic review and field synopsis of the associations of 23 cardiovascular risk factors and incident AF, which included 84 reports based on 28 consented and four electronic health record cohorts of 20,420,175 participants and 576,602 AF events. We identified 3-19 reports per risk factor and heterogeneity in AF definition, quality of reporting, and adjustment. We extracted relative risks (RR) and 95 % confidence intervals [CI] and visualised the number of reports with inverse (RR [CI]<1.00), or direct (RR [CI]>1.00) associations. For hypertension (13/17 reports) and obesity (19/19 reports), there were direct associations with incident AF, as there are for coronary heart disease (CHD). There were inverse associations for non-White ethnicity (5/5 reports, with RR from 0.35 to 0.84 [0.82–0.85]), total cholesterol (4/13 reports from 0.76 [0.59–0.98] to 0.94 [0.90–0.97]; 8/13 reports with non-significant inverse associations), and diastolic blood pressure (2/11 reports from 0.87 [0.78–0.96] to 0.92 [0.85–0.99]; 5/11 reports with non-significant inverse associations), and direct associations for taller height (7/10 reports from 1.03 [1.02–1.05] to 1.92 [1.38–2.67]), which are in the opposite direction of known associations with CHD. A systematic evaluation of the available evidence suggests similarities as well as important differences in the risk factors for incidence of AF as compared with other cardiovascular diseases, which has implications for the primary prevention strategies for atrial fibrillation.
Does the Use of a Decision Aid Improve Decision Making in Prosthetic Heart Valve Selection?
Authors: Korteland Nelleke M. , Ahmed Yunus , Koolbergen David R. , Brouwer Marjan , de Heer Frederiek , Kluin Jolanda , Bruggemans Eline F. , Klautz Robert J.M. , Stiggelbout Anne M. , Bucx Jeroen J.J. , Roos-Hesselink Jolien W. , Polak Peter , Markou Thanasie , van den Broek Inge , Ligthart Rene , Bogers Ad J.J.C. , Takkenberg Johanna J.M. 
Published: February 2017

Background—
A Dutch online patient decision aid to support prosthetic heart valve selection was recently developed. A multicenter randomized controlled trial was conducted to assess whether use of the patient decision aid results in optimization of shared decision making in prosthetic heart valve selection.

Methods and Results—

In a 5-center randomized controlled trial, patients were allocated to receive either standard preoperative care (control group) or additional access to the patient decision aid (intervention group). Legally capable adult patients accepted for elective isolated or combined aortic and mitral valve replacement were included. Primary outcome was preoperative decisional conflict (Decisional Conflict Scale); secondary outcomes included patient knowledge, involvement in valve selection, anxiety and depression, (valve-specific) quality of life, and regret. Out of 306 eligible patients, 155 were randomized (78 control and 77 intervention). Preoperative decisional conflict did not differ between the groups (34% versus 33%;
P
=0.834). Intervention patients felt better informed (median Decisional Conflict Scale informed subscore: 8 versus 17;
P
=0.046) and had a better knowledge of prosthetic valves (85% versus 68%;
P
=0.004). Intervention patients experienced less anxiety and depression (median Hospital Anxiety and Depression Scale score: 6 versus 9;
P
=0.015) and better mental well-being (mean Short Form Health Survey score: 54 versus 50;
P
=0.032). Three months postoperatively, valve-specific quality of life and regret did not differ between the groups.

Conclusions—
A patient decision aid to support shared decision making in prosthetic heart valve selection does not lower decisional conflict. It does result in more knowledgeable, better informed, and less anxious and depressed patients, with a better mental well-being.

Clinical Trial Registration—

http://www.trialregister.nl
. Unique identifier: NTR4350.
Myocardial Infarction Risk After Discontinuation of Thienopyridine Therapy in the Randomized DAPT Study (Dual Antiplatelet Therapy)
Authors: Stefanescu Schmidt Ada C. , Kereiakes Dean J. , Cutlip Donald E. , Yeh Robert W. , D’Agostino Ralph B. , Massaro Joseph M. , Hsieh Wen-Hua , Mauri Laura 
Published: February 2017

Background:
Thienopyridine plus aspirin beyond 1 year after coronary stenting reduces myocardial infarction (MI) risk and increases bleeding risk in comparison with aspirin alone. The hazard associated with late thienopyridine discontinuation and risk factors for MI after discontinuation are poorly defined.

Methods:
In the DAPT Study (Dual Antiplatelet Therapy), after percutaneous coronary intervention and 12 months of thienopyridine (clopidogrel or prasugrel) plus aspirin, eligible patients remained on aspirin and were randomly assigned to continued thienopyridine versus placebo for 18 months. At 30 months, patients stopped the study drug and were observed for 3 months. Cumulative incidence of MI was assessed over 3 months after randomization (months 12–15) and 3 months after study drug discontinuation (months 30–33). The MI hazard for each of these periods was assessed across randomized treatment arms and by DAPT score values <2 or ≥2.

Results:

Among the 11 648 randomly assigned patients, the monthly cumulative incidence of MI was lower with continued thienopyridine versus placebo at 12 to 15 months (0.12% versus 0.37%,
P
<0.001, in all patients; 0.13% versus 0.27%,
P
=0.02, in patients not treated with paclitaxel-eluting stents), and higher at 30 to 33 months (0.30% versus 0.15%,
P
=0.013, in all patients; in patients without paclitaxel-eluting stents, 0.18% versus 0.17%,
P
=0.91). The majority of MIs in both time periods (74% and 76%) were not related to stent thrombosis. After multivariable adjustment, treatment arm independently predicted MI at months 12 to 15 (
P
<0.001) and 30 to 33 (
P
=0.011). During months 12 to 15, patients with DAPT scores <2 or ≥2 both had lower rates of MI with continued thienopyridine (MI monthly incidence 0.16% versus 0.51%,
P
<0.001, for scores ≥2; 0.08% versus 0.24%,
P
=0.012, for scores<2, interaction
P
=0.064).

Conclusions:
Discontinuing thienopyridine after either 12 or 30 months is associated with an early increase in MI risk, mainly unrelated to stent thrombosis; the magnitude of risk is highest in the earlier time frame, and lower in patients not treated with paclitaxel-eluting stents. Although higher DAPT scores identify patients with greater absolute ischemic benefit (relative to bleeding harm) with continued thienopyridine therapy, discontinuation at 12 months increases MI hazard regardless of DAPT score group.

Clinical Trial Registration:

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00977938.