bluuebunny/crossref_metadata_2025_split huggingface dataset:
Two White Spot Syndrome Virus MicroRNAs Target the
Dorsal
Gene To Promote Virus Infection in Marsupenaeus japonicus Shrimp
Authors: Ren Qian , Huang Xin , Cui Yalei , Sun Jiejie , Wang Wen , Zhang Xiaobo 
Published: February 2017

ABSTRACT

In eukaryotes, microRNAs (miRNAs) serve as regulators of many biological processes, including virus infection. An miRNA can generally target diverse genes during virus-host interactions. However, the regulation of gene expression by multiple miRNAs has not yet been extensively explored during virus infection. This study found that the Spaztle (Spz)-Toll-Dorsal-antilipopolysaccharide factor (ALF) signaling pathway plays a very important role in antiviral immunity against invasion of white spot syndrome virus (WSSV) in shrimp (
Marsupenaeus japonicus
).
Dorsal
, the central gene in the Toll pathway, was targeted by two viral miRNAs (WSSV-miR-N13 and WSSV-miR-N23) during WSSV infection. The regulation of
Dorsal
expression by viral miRNAs suppressed the Spz-Toll-Dorsal-ALF signaling pathway in shrimp
in vivo
, leading to virus infection. Our study contributes novel insights into the viral miRNA-mediated Toll signaling pathway during the virus-host interaction.

IMPORTANCE
An miRNA can target diverse genes during virus-host interactions. However, the regulation of gene expression by multiple miRNAs during virus infection has not yet been extensively explored. The results of this study indicated that the shrimp
Dorsal
gene, the central gene in the Toll pathway, was targeted by two viral miRNAs during infection with white spot syndrome virus. Regulation of
Dorsal
expression by viral miRNAs suppressed the Spz-Toll-Dorsal-ALF signaling pathway in shrimp
in vivo
, leading to virus infection. Our study provides new insight into the viral miRNA-mediated Toll signaling pathway in virus-host interactions.
A Sequence-Independent, Unstructured Internal Ribosome Entry Site Is Responsible for Internal Expression of the Coat Protein of Turnip Crinkle Virus
Authors: May Jared , Johnson Philip , Saleem Huma , Simon Anne E. 
Published: February 2017

ABSTRACT

To maximize the coding potential of viral genomes, internal ribosome entry sites (IRES) can be used to bypass the traditional requirement of a 5′ cap and some/all of the associated translation initiation factors. Although viral IRES typically contain higher-order RNA structure, an unstructured sequence of about 84 nucleotides (nt) immediately upstream of the
Turnip crinkle virus
(TCV) coat protein (CP) open reading frame (ORF) has been found to promote internal expression of the CP from the genomic RNA (gRNA) both
in vitro
and
in vivo
. An absence of extensive RNA structure was predicted using RNA folding algorithms and confirmed by selective 2′-hydroxyl acylation analyzed by primer extension (SHAPE) RNA structure probing. Analysis of the IRES region
in vitro
by use of both the TCV gRNA and reporter constructs did not reveal any sequence-specific elements but rather suggested that an overall lack of structure was an important feature for IRES activity. The CP IRES is A-rich, independent of orientation, and strongly conserved among viruses in the same genus. The IRES was dependent on eIF4G, but not eIF4E, for activity. Low levels of CP accumulated
in vivo
in the absence of detectable TCV subgenomic RNAs, strongly suggesting that the IRES was active in the gRNA
in
vivo
. Since the TCV CP also serves as the viral silencing suppressor, early translation of the CP from the viral gRNA is likely important for countering host defenses. Cellular mRNA IRES also lack extensive RNA structures or sequence conservation, suggesting that this viral IRES and cellular IRES may have similar strategies for internal translation initiation.

IMPORTANCE
Cap-independent translation is a common strategy among positive-sense, single-stranded RNA viruses for bypassing the host cell requirement of a 5′ cap structure. Viral IRES, in general, contain extensive secondary structure that is critical for activity. In contrast, we demonstrate that a region of viral RNA devoid of extensive secondary structure has IRES activity and produces low levels of viral coat protein
in vitro
and
in vivo
. Our findings may be applicable to cellular mRNA IRES that also have little or no sequences/structures in common.
High-intensity interval training improves obstructive sleep apnoea
Authors: Karlsen Trine , Nes Bjarne Martens , Tjønna Arnt Erik , Engstrøm Morten , Støylen Asbjørn , Steinshamn Sigurd 
Published: February 2017

BackgroundThree hours per week of vigorous physical activity is found to be associated with reduced odds of sleep-disordered breathing.AimTo investigate whether 12 weeks of high-intensity interval training (HIIT) reduced the apnoea–hypopnea index (AHI) in obese subjects with moderate-to-severe obstructive sleep apnoea.MethodsIn a prospective randomised controlled exercise study, 30 (body mass index 37±6 kg/m2, age 51±9 years) patients with sleep apnoea (AHI 41.5±25.3 events/hour) were randomised 1:1 to control or 12 weeks of supervised HIIT (4×4 min of treadmill running or walking at 90%–95% of maximal heart rate two times per week).ResultsIn the HIIT group, the AHI was reduced by 7.5±11.6 events/hour (within-group p<0.05), self-reported sleepiness (Epworth scale) improved from 10.0±3.6 to 7.3±3.7 (between-group p<0.05) and maximal oxygen uptake improved from 28.2±7.4 to 30.2±7.7 mL/kg/min (between-group p<0.05) from baseline to 12 weeks. The AHI, self-reported sleepiness and VO2maxwere unchanged from baseline to 12 weeks in controls (baseline AHI 50.3±25.5 events/hour, Epworth score 5.9±4.3, maximal oxygen uptake 27.0±6.8 mL/kg/min). Body weight remained unchanged in both groups.ConclusionTwelve weeks of HIIT improved the AHI and self-reported daytime sleepiness in subjects with obese sleep apnoea without any change in the desaturation index and body weight.
Modelling the Functional Comorbidity Index as a predictor of health-related quality of life in patients with glenoid labrum disorders
Authors: Zughaib Marc , Gagnier Joel J 
Published: February 2017

Background/aimHealth-related quality of life (HRQoL) is increasingly assessed within orthopaedic research. For those patients presenting with glenoid labral pathologies, there is little information on how baseline comorbidities affect long-term outcomes and HRQoL. This study aimed to investigate a model, including baseline comorbidities and demographics, to predict change in 2-year HRQoL scores in adult patients with glenoid labral tears or degenerations.MethodsParticipants provided Functional Comorbidity Index (FCI) scores and self-completed the Western Ontario Rotator Cuff (WORC) index at 6, 12 and 24 months. Univariable and multivariable linear regressions were performed to assess predictive quality of baseline comorbidities and demographics on the primary outcome measure of interest (change in WORC score).ResultsMultivariate regression with a continuous scaled FCI (β=617.8, p=0.042), age (by decade) (β=297, p<0.01), surgical group (β=−476.69, p<0.01) and an interaction term between FCI and age (β=−103.65, p=0.03) were significant predictors of change in WORC scores at 2-year follow-up (r2=0.293858). Multivariate regression with FCI scaled categorically reported only patients with three comorbidities (β=−454.06, p=0.057) and age (by decade) (β=156.87, p=0.04) as the only significant predictors of change in WORC scores at 2-year follow-up (r2=0.1279).ConclusionThe continuous FCI model is better suited to predict future WORC and HRQoL scores among this patient population. Patients reporting with higher numbers of baseline comorbidities improved significantly more than patients with fewer comorbidities. This information on expected change in HRQoL scores among patients with a wide range of FCI scores at baseline may help guide treatment decisions based on these criteria.
Implications of heavy neutralino dark matter: The underlying structure in the hidden sector
Authors: Yoshimatsu Nobuki 
Published: February 2017

The possibility of heavy neutralino dark matter (DM) in the gravity-mediation mechanism is explored. The appearance of the heavy lightest supersymmetric particle is seemingly suggested by Large Hadron Collider runs, which have not provided evidence of superparticles around the TeV region. On the basis of the so-called WIMPZILLA scenario, it is understood that the nonthermally produced DM has the larger mass than the reheating temperature. Hence, the expected DM mass should be more than 109 GeV so that thermal leptogenesis successfully occurs. In this paper, we first examine the generation of the Higgsino mass parameter [Formula: see text] in the context of gravity mediation, postulating that the resolution of the strong CP problem should be the criterion for arriving at a valid hypothesis for heavy neutralino DM. Accordingly, we address how the Peccei–Quinn (PQ) symmetry could influence dynamical supersymmetry breaking (DSB) models. It is found that as long as [Formula: see text] (the SUSY-breaking scale) approximately coincides with [Formula: see text] (the PQ-breaking scale), no DSB models can naturally account for the existence of the heavy neutralino DM, based upon the supersymmetric Dine–Fischler–Srednicki–Zhitinitski (DFSZ)-like mechanism. Thus, we attempt to construct a new model wherein hierarchical SUSY breakings occur. For this purpose, we propose gauge coupling unification in the hidden-sector dynamics at some high-energy scale, and we show that such a class of models can achieve [Formula: see text] through renormalization flow. As a consequence, the nonthermal neutralino, practically the wino-like one in our model, is shown to be a rather natural and viable DM candidate. Moreover, we argue that on the basis of Kac–Moody algebra, multiple breakdowns of supersymmetry may entail unified gauge dynamics. We also present a possible unified model. Finally, the heavy wino-like neutralino may be a DM candidate that will favor future direct DM detection experiments, mainly because its scattering on nuclei well conserves isospin symmetry.
Structural inheritance and difference between Ti2AlC, Ti3AlC2 and Ti5Al2C3 under pressure from first principles
Authors: Gao Qing-He , Du An , Yang Ze-Jin 
Published: February 2017

The structural inheritance and difference between Ti2AlC, Ti3AlC2 and Ti5Al2C3 under pressure from first principles are studied. The results indicate that the lattice parameter a are almost the same within Ti2AlC, Ti3AlC2 and Ti5Al2C3, and the value of c in Ti5Al2C3 is the sum of Ti2AlC and Ti3AlC2 which is revealed by the covalently bonded chain in the electron density difference: Al–Ti–C–Ti–Al for Ti2AlC, Al–Ti2–C–Ti1–C–Ti2–Al for Ti3AlC2 and Al–Ti3–C2–Ti3–Al–Ti2–C1–Ti1–C1–Ti2–Al for Ti5Al2C3. The calculated axial compressibilities, volumetric shrinkage, elastic constant [Formula: see text], [Formula: see text] ratio, bulk modulus, shear modulus, and Young’s modulus of Ti5Al2C3 are within the range of the end members (Ti2AlC and Ti3AlC2) in a wide pressure range of 0–100 GPa. Only Ti2AlC is isotropic crystal at about 50 GPa within the Ti–Al–C compounds. All of the Ti 3d density of states curves of the three compounds move from lower energy to higher energy level with pressure increasing. The similarities of respective bond length, bond overlap population (Ti–C, Ti–Al and Ti–Ti), atom Mulliken charges under pressure as well as the electron density difference for the three compounds are discovered. Among the Ti–Al–C ternary compounds, Ti–Ti bond behaves least compressibility, whereas the Ti–Al bond is softer than that of Ti–C bonds, which can also been confirmed by the density of states and electron density difference. Bond overlap populations of Ti–Ti, Ti–C and Ti–Al indicate that the ionicity interaction becomes more and more stronger in the three structures as the pressure increasing. Mulliken charges of Ti1, Ti2, Ti3, C and Al are 0.65, 0.42, 0.39, −0.73, −0.04 at 0 GPa, respectively, which are consistent with the Pauling scale.
A high-resolution tunneling magneto-resistance sensor interface circuit
Authors: Li Xiangyu , Yin Liang , Chen Weiping , Gao Zhiqiang , Liu Xiaowei 
Published: February 2017

In this paper, a chopper instrumentation amplifier and a high-precision and low-noise CMOS band gap reference in a standard 0.5 [Formula: see text] CMOS technology for a tunneling magneto-resistance (TMR) sensor is presented. The noise characteristic of TMR sensor is an important factor in determining the performance of the sensor. In order to obtain a larger signal to noise ratio (SNR), the analog front-end chip ASIC weak signal readout circuit of the sensor includes the chopper instrumentation amplifier; the high-precision and low-noise CMOS band gap reference. In order to achieve the low noise, the chopping technique is applied in the first stage amplifier. The low-frequency flicker noise is modulated to high-frequency by chopping switch, so that the modulator has a better noise suppression performance at the low frequency. The test results of interface circuit are shown as below: At a single 5 V supply, the power dissipation is 40 mW; the equivalent offset voltage is less than 10 uV; the equivalent input noise spectral density 30 nV/Hz[Formula: see text](@10 Hz), the equivalent input noise density of magnetic is 0.03 nTHz[Formula: see text](@10 Hz); the scale factor temperature coefficient is less than 10 ppm/[Formula: see text]C, the equivalent input offset temperature coefficient is less than 70 nV/[Formula: see text]C; the gain error is less than 0.05%, the common mode rejection ratio is greater than 120 dB, the power supply rejection ratio is greater than 115 dB; the nonlinear is 0.1% FS.
Perceptual precision of passive body tilt is consistent with statistically optimal cue integration
Authors: Lim Koeun , Karmali Faisal , Nicoucar Keyvan , Merfeld Daniel M. 
Published: February 2017

When making perceptual decisions, humans have been shown to optimally integrate independent noisy multisensory information, matching maximum-likelihood (ML) limits. Such ML estimators provide a theoretic limit to perceptual precision (i.e., minimal thresholds). However, how the brain combines two interacting (i.e., not independent) sensory cues remains an open question. To study the precision achieved when combining interacting sensory signals, we measured perceptual roll tilt and roll rotation thresholds between 0 and 5 Hz in six normal human subjects. Primary results show that roll tilt thresholds between 0.2 and 0.5 Hz were significantly lower than predicted by a ML estimator that includes only vestibular contributions that do not interact. In this paper, we show how other cues (e.g., somatosensation) and an internal representation of sensory and body dynamics might independently contribute to the observed performance enhancement. In short, a Kalman filter was combined with an ML estimator to match human performance, whereas the potential contribution of nonvestibular cues was assessed using published bilateral loss patient data. Our results show that a Kalman filter model including previously proven canal-otolith interactions alone (without nonvestibular cues) can explain the observed performance enhancements as can a model that includes nonvestibular contributions.NEW & NOTEWORTHY We found that human whole body self-motion direction-recognition thresholds measured during dynamic roll tilts were significantly lower than those predicted by a conventional maximum-likelihood weighting of the roll angular velocity and quasistatic roll tilt cues. Here, we show that two models can each match this “apparent” better-than-optimal performance: 1) inclusion of a somatosensory contribution and 2) inclusion of a dynamic sensory interaction between canal and otolith cues via a Kalman filter model.
Abnormal vaginal bleeding in women with venous thromboembolism treated with apixaban or warfarin
Authors: Bleker Suzanne , Hutten Barbara , Timmermans Anne , Büller Harry , Middeldorp Saskia , Brekelmans Marjolein , Scheres Luuk 
Published: February 2017

SummaryAbnormal vaginal bleeding can complicate direct oral anticoagulant (DOAC) treatment. We aimed to investigate the characteristics of abnormal vaginal bleeding in patients with venous thromboembolism (VTE) receiving apixaban or enoxaparin/warfarin. Data were derived from the AMPLIFY trial. We compared the incidence of abnormal vaginal bleeding between patients in both treatment arms and collected information on clinical presentation, diagnostic procedures, management and outcomes. In the AMPLIFY trial, 1122 women were treated with apixaban and 1106 received enoxaparin/warfarin. A clinically relevant non-major (CRNM) vaginal bleeding occurred in 28 (2.5 %) apixaban and 24 (2.1 %) enoxaparin/warfarin recipients (odds ratio [OR] 1.2, 95 % confidence interval [CI] 0.7–2.0). Of all CRNM bleeds, 28 of 62 (45 %) and 24 of 120 (20 %) were of vaginal origin in the apixaban and enoxaparin/warfarin group, respectively (OR 3.4; 95 % CI 1.8–6.7). Premenopausal vaginal bleeds on apixaban were characterised by more prolonged bleeding (OR 2.3; 95 %CI 0.5–11). In both pre- and postmenopausal vaginal bleeds, diagnostic tests were performed in six (21 %) and in seven (29 %) apixaban and enoxaparin/ warfarin treated patients, respectively. Medical treatment was deemed not necessary in 16 (57 %) apixaban and 16 (67 %) enoxaparin/warfarin recipients. The severity of clinical presentation and course of the bleeds was mild in 75 % of the cases in both groups. In conclusion, although the absolute number of vaginal bleeding events is comparable between apixaban and enoxaparin/warfarin recipients, the relative occurrence of vaginal bleeds is higher in apixaban-treated women. The characteristics and severity of bleeding episodes were comparable in both treatment arms.
Dipeptidyl Peptidase-4 Induces Aortic Valve Calcification by Inhibiting Insulin-Like Growth Factor-1 Signaling in Valvular Interstitial Cells
Authors: Choi Bongkun , Lee Sahmin , Kim Sang-Min , Lee Eun-Jin , Lee Sun Ro , Kim Dae-Hee , Jang Jeong Yoon , Kang Sang-Wook , Lee Ki-Up , Chang Eun-Ju , Song Jae-Kwan 
Published: February 2017

Background:
Calcification of the aortic valve leads to increased leaflet stiffness and consequently to the development of calcific aortic valve disease. However, the underlying molecular and cellular mechanisms of calcification remain unclear. Here, we identified that dipeptidyl peptidase-4 (DPP-4, also known as CD26) increases valvular calcification and promotes calcific aortic valve disease progression.

Methods:
We obtained the aortic valve tissues from humans and murine models (wild-type and endothelial nitric oxide synthase-deficient-mice) and cultured the valvular interstitial cells (VICs) and valvular endothelial cells from the cusps. We induced osteogenic differentiation in the primary cultured VICs and examined the effects of the DPP-4 inhibitor on the osteogenic changes in vitro and aortic valve calcification in endothelial nitric oxide synthase-deficient-mice. We also induced calcific aortic stenosis in male New Zealand rabbits (weight, 2.5–3.0 kg) by a cholesterol-enriched diet+vitamin D2 (25 000 IU, daily). Echocardiography was performed to assess the aortic valve area and the maximal and mean transaortic pressure gradients at baseline and 3-week intervals thereafter. After 12 weeks, we harvested the heart and evaluated the aortic valve tissue using immunohistochemistry.

Results:
We found that nitric oxide depletion in human valvular endothelial cells activates NF-κB in human VICs. Consequently, the NF-κB promotes DPP-4 expression, which then induces the osteogenic differentiation of VICs by limiting autocrine insulin-like growth factor-1 signaling. The inhibition of DPP-4 enzymatic activity blocked the osteogenic changes in VICs in vitro and reduced the aortic valve calcification in vivo in a mouse model. Sitagliptin administration in a rabbit calcific aortic valve disease model led to significant improvements in the rate of change in aortic valve area, transaortic peak velocity, and maximal and mean pressure gradients over 12 weeks. Immunohistochemistry staining confirmed the therapeutic effect of Sitagliptin in terms of reducing the calcium deposits in the rabbit aortic valve cusps. In rabbits receiving Sitagliptin, the plasma insulin-like growth factor-1 levels were significantly increased, in line with DPP-4 inhibition.

Conclusions:
DPP-4-dependent insulin-like growth factor-1 inhibition in VICs contributes to aortic valve calcification, suggesting that DPP-4 could serve as a potential therapeutic target to inhibit calcific aortic valve disease progression.
Medical Therapy for Secondary Prevention and Long-Term Outcome in Patients With Myocardial Infarction With Nonobstructive Coronary Artery Disease
Authors: Lindahl Bertil , Baron Tomasz , Erlinge David , Hadziosmanovic Nermin , Nordenskjöld Anna , Gard Anton , Jernberg Tomas 
Published: February 2017

Background:
Myocardial infarction with nonobstructive coronary arteries (MINOCA) occurs in 5% to 10% of all patients with myocardial infarction. Clinical trials of secondary prevention treatment in MINOCA patients are lacking. Therefore, the aim of this study was to examine the associations between treatment with statins, renin-angiotensin system blockers, β-blockers, dual antiplatelet therapy, and long-term cardiovascular events.

Methods:
This is an observational study of MINOCA patients recorded in the SWEDEHEART registry (the Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapy) between July 2003 and June 2013 and followed until December 2013 for outcome events in the Swedish Cause of Death Register and National Patient Register. Of 199 162 myocardial infarction admissions, 9466 consecutive unique patients with MINOCA were identified. Among those, the 9136 patients surviving the first 30 days after discharge constituted the study population. Mean age was 65.3 years, and 61% were women. No patient was lost to follow-up. A stratified propensity score analysis was performed to match treated and untreated groups. The association between treatment and outcome was estimated by comparing between treated and untreated groups by using Cox proportional hazards models. The exposures were treatment at discharge with statins, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, β-blockers, and dual antiplatelet therapy. The primary end point was major adverse cardiac events defined as all-cause mortality, hospitalization for myocardial infarction, ischemic stroke, and heart failure.

Results:
At discharge, 84.5%, 64.1%, 83.4%, and 66.4% of the patients were on statins, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, β-blockers, and dual antiplatelet therapy, respectively. During the follow-up of a mean of 4.1 years, 2183 (23.9%) patients experienced a major adverse cardiac event. The hazard ratios (95% confidence intervals) for major adverse cardiac events were 0.77 (0.68–0.87), 0.82 (0.73–0.93), and 0.86 (0.74–1.01) in patients on statins, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, and β-blockers, respectively. For patients on dual antiplatelet therapy followed for 1 year, the hazard ratio was 0.90 (0.74–1.08).

Conclusions:
The results indicate long-term beneficial effects of treatment with statins and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers on outcome in patients with MINOCA, a trend toward a positive effect of β-blocker treatment, and a neutral effect of dual antiplatelet therapy. Properly powered randomized clinical trials to confirm these results are warranted.