bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vitrified canine testicular cells allow the formation of spermatogonial stem cells and seminiferous tubules following their xenotransplantation into nude mice
Authors: Lee Kyung Hoon , Lee Won Young , Kim Dong Hoon , Lee Seung Hoon , Do Jung Tae , Park Chankyu , Kim Jae Hwan , Choi Young Suk , Song Hyuk 
Published: February 2016

AbstractBelgian Malinois (BM), one of the excellent military dog breeds in South Korea, is usually castrated before sexual maturation. Therefore, the transfer of their genetic features to the next generation is difficult. To overcome this, testicular cells from 4-month-old BMs were frozen. Testicular cells were thawed after 3 months and cultured in StemPro-34 medium. Spermatogonial stem cell (SSC) characteristics were determined by the transplantation of the cultured germ cell-derived colonies (GDCs) into empty testes, containing only several endogenous SSCs and Sertoli cells, of immunodeficient mice, 4 weeks after busulfan treatment. Following the implantation, the transplanted cells localized in the basement membrane of the seminiferous tubules, and ultimately colonized the recipient testes. Xenotransplantation of GDCs together with testicular somatic cells conjugated with extracellular matrix (ECM), led to the formation ofde novoseminiferous tubules. These seminiferous tubules were mostly composed of Sertoli cells. Some germ cells were localized in the basement membrane of seminiferous tubules. This study revealed that BM-derived SSCs, obtained from the castrated testes, might be a valuable tool for the transfer of BM genetic features to the next generation.
Period-independent novel circadian oscillators revealed by timed exercise and palatable meals
Authors: Flôres Danilo E. F. L. , Bettilyon Crystal N. , Yamazaki Shin 
Published: February 2016

AbstractThe mammalian circadian system is a hierarchical network of oscillators organized to optimally coordinate behavior and physiology with daily environmental cycles. The suprachiasmatic nucleus (SCN) of the hypothalamus is at the top of this hierarchy, synchronizing to the environmental light-dark cycle and coordinates the phases of peripheral clocks. The Period genes are critical components of the molecular timekeeping mechanism of these clocks. Circadian clocks are disabled in Period1/2/3 triple mutant mice, resulting in arrhythmic behavior in constant conditions. We uncovered rhythmic behavior in this mutant by simply exposing the mice to timed access to a palatable meal or running wheel. The emergent circadian behavior rhythms free-ran for many cycles under constant conditions without cyclic environmental cues. Together, these data demonstrate that the palatable meal-inducible circadian oscillator (PICO) and wheel-inducible circadian oscillator (WICO) are generated by non-canonical circadian clocks. Entrainment of these novel oscillators by palatable snacks and timed exercise could become novel therapeutics for human conditions caused by disruptions of the circadian clocks.
Antithrombotic and antiplatelet activities of small-molecule alkaloids from Scolopendra subspinipes mutilans
Authors: Lee Wonhwa , Lee JungIn , Kulkarni Roshan , Kim Mi-Ae , Hwang Jae Sam , Na MinKyun , Bae Jong-Sup 
Published: February 2016

AbstractThe aim of this study was to discover small-molecule anticoagulants from Scolopendra subspinipes mutilans (SSM). A new acylated polyamine (1) and a new sulfated quinoline alkaloid (2) were isolated from SSM. Treatment with the new alkaloids 1, 2, and indole acetic acid 4 prolonged the activated partial thromboplastin time and prothrombin time and inhibited the activity and production of thrombin and activated factor X. Furthermore, compounds 1, 2, and 4 inhibited thrombin-catalyzed fibrin polymerization and platelet aggregation. In accordance with these potential in vitro antiplatelet activities, compounds 1, 2, and 4 showed enhanced antithrombotic effects in an in vivo pulmonary embolism and arterial thrombosis model. Compounds 1, 2, and 4 also elicited anticoagulant effects in mice. Collectively, this study may serve as the groundwork for commercializing SSM or compounds 1, 2, and 4 as functional food components for the prevention and treatment of pathogenic conditions and serve as new scaffolds for the development of anticoagulants.
Pyruvate Carboxylase Activates the RIG-I-like Receptor-Mediated Antiviral Immune Response by Targeting the MAVS signalosome
Authors: Cao Zhongying , Zhou Yaqin , Zhu Shengli , Feng Jian , Chen Xueyuan , Liu Shi , Peng Nanfang , Yang Xiaodan , Xu Gang , Zhu Ying 
Published: February 2016

AbstractWhen retinoic acid-inducible gene 1 protein (RIG-I)-like receptors sense viral dsRNA in the cytosol, RIG-I and melanoma differentiation-associated gene 5 (MDA5) are recruited to the mitochondria to interact with mitochondrial antiviral signaling protein (MAVS) and initiate antiviral immune responses. In this study, we demonstrate that the biotin-containing enzyme pyruvate carboxylase (PC) plays an essential role in the virus-triggered activation of nuclear factor kappa B (NF-κB) signaling mediated by MAVS. PC contributes to the enhanced production of type I interferons (IFNs) and pro-inflammatory cytokines and PC knockdown inhibits the virus-triggered innate immune response. In addition, PC shows extensive antiviral activity against RNA viruses, including influenza A virus (IAV), human enterovirus 71 (EV71) and vesicular stomatitis virus (VSV). Furthermore, PC mediates antiviral action by targeting the MAVS signalosome and induces IFNs and pro-inflammatory cytokines by promoting phosphorylation of NF-κB inhibitor-α (IκBα) and the IκB kinase (IKK) complex, as well as NF-κB nuclear translocation, which leads to activation of interferon-stimulated genes (ISGs), including double-stranded RNA-dependent protein kinase (PKR) and myxovirus resistance protein 1 (Mx1). Our findings suggest that PC is an important player in host antiviral signaling.
Using Multi-objective Optimization to Identify Dynamical Network Biomarkers as Early-warning Signals of Complex Diseases
Authors: Vafaee Fatemeh 
Published: February 2016

AbstractBiomarkers have gained immense scientific interest and clinical value in the practice of medicine. With unprecedented advances in high-throughput technologies, research interest in identifying novel and customized disease biomarkers for early detection, diagnosis, or drug responses is rapidly growing. Biomarkers can be identified in different levels of molecular biomarkers, networks biomarkers and dynamical network biomarkers (DNBs). The latter is a recently developed concept which relies on the idea that a cell is a complex system whose behavior is emerged from interplay of various molecules and this network of molecules dynamically changes over time. A DNB can serve as an early-warning signal of disease progression, or as a leading network that drives the system into the disease state and thus unravels mechanisms of disease initiation and progression. It is therefore of great importance to identify DNBs efficiently and reliably. In this work, the problem of DNB identification is defined as a multi-objective optimization problem and a framework to identify DNBs out of time-course high-throughput data is proposed. Temporal gene expression data of a lung injury with carbonyl chloride inhalation exposure has been used as a case study and the functional role of the discovered biomarker in the pathogenesis of lung injury has been thoroughly analyzed.
Local Maps of the Polarization and Depolarization in Organic Ferroelectric Field-Effect Transistors
Authors: Cai Ronggang , Jonas Alain M. 
Published: February 2016

AbstractWe study the local ferroelectric polarization and depolarization of poly(vinylidene fluoride-co-trifluoroethylene) (P(VDF-TrFE)) in p-type ferroelectric field-effect transistors (FeFETs). Piezoresponse force microscopy (PFM) is used to obtain local maps of the polarization on model metal-semiconductor-ferroelectric stacks and on FeFETs stripped from their top-gate electrode; transfer curves are measured on complete FeFETs. The influence of the semiconductor layer thickness and of the polarity and amplitude of the poling voltage are investigated. In accumulation, the stable “on” state consists of a uniform upward-polarized ferroelectric layer, with compensation holes accumulating at the ferroelectric/semiconducting interface. In depletion, the stable “off” state consists of a depolarized region in the center of the transistor channel, surrounded by partially downward-polarized regions over the source and drain electrodes and neighboring regions. The partial depolarization of these regions is due to the incomplete screening of polarization charges by the charges of the remote electrodes. Therefore, thinner semiconducting layers provide higher downward polarizations, which result in a more depleted transistor channel and a higher charge injection barrier between the electrodes and the semiconductor, leading to lower threshold voltages and higher on/off current values at zero gate bias. Clues for optimization of the devices are finally provided.
Probing the Effects and Mechanisms of Electroacupuncture at Ipsilateral or Contralateral ST36–ST37 Acupoints on CFA-induced Inflammatory Pain
Authors: Lu Kung-Wen , Hsu Chao-Kuei , Hsieh Ching-Liang , Yang Jun , Lin Yi-Wen 
Published: February 2016

AbstractTransient receptor potential vanilloid 1 (TRPV1) and associated signaling pathways have been reported to be increased in inflammatory pain signaling. There are accumulating evidences surrounding the therapeutic effect of electroacupuncture (EA). EA can reliably attenuate the increase of TRPV1 in mouse inflammatory pain models with unclear signaling mechanisms. Moreover, the difference in the clinical therapeutic effects between using the contralateral and ipsilateral acupoints has been rarely studied. We found that inflammatory pain, which was induced by injecting the complete Freund’s adjuvant (CFA), (2.14 ± 0.1, p < 0.05, n = 8) can be alleviated after EA treatment at either ipsilateral (3.91 ± 0.21, p < 0.05, n = 8) or contralateral acupoints (3.79 ± 0.25, p < 0.05, n = 8). EA may also reduce nociceptive Nav sodium currents in dorsal root ganglion (DRG) neurons. The expression of TRPV1 and associated signaling pathways notably increased after the CFA injection; this expression can be further attenuated significantly in EA treatment. TRPV1 and associated signaling pathways can be prevented in TRPV1 knockout mice, suggesting that TRPV1 knockout mice are resistant to inflammatory pain. Through this study, we have increased the understanding of the mechanism that both ipsilateral and contralateral EA might alter TRPV1 and associated signaling pathways to reduce inflammatory pain.
Deep-sea whale fall fauna from the Atlantic resembles that of the Pacific Ocean
Authors: Sumida Paulo Y. G. , Alfaro-Lucas Joan M. , Shimabukuro Mauricio , Kitazato Hiroshi , Perez Jose A. A. , Soares-Gomes Abilio , Toyofuku Takashi , Lima Andre O. S. , Ara Koichi , Fujiwara Yoshihiro 
Published: February 2016

AbstractWhale carcasses create remarkable habitats in the deep-sea by producing concentrated sources of organic matter for a food-deprived biota as well as places of evolutionary novelty and biodiversity. Although many of the faunal patterns on whale falls have already been described, the biogeography of these communities is still poorly known especially from basins other than the NE Pacific Ocean. The present work describes the community composition of the deepest natural whale carcass described to date found at 4204 m depth on Southwest Atlantic Ocean with manned submersible Shinkai 6500. This is the first record of a natural whale fall in the deep Atlantic Ocean. The skeleton belonged to an Antarctic Minke whale composed of only nine caudal vertebrae, whose degradation state suggests it was on the bottom for 5–10 years. The fauna consisted mainly of galatheid crabs, a new species of the snail Rubyspira and polychaete worms, including a new Osedax species. Most of the 41 species found in the carcass are new to science, with several genera shared with NE Pacific whale falls and vent and seep ecosystems. This similarity suggests the whale-fall fauna is widespread and has dispersed in a stepping stone fashion, deeply influencing its evolutionary history.
Bacterial diversity in saliva and oral health-related conditions: the Hisayama Study
Authors: Takeshita Toru , Kageyama Shinya , Furuta Michiko , Tsuboi Hidenori , Takeuchi Kenji , Shibata Yukie , Shimazaki Yoshihiro , Akifusa Sumio , Ninomiya Toshiharu , Kiyohara Yutaka , Yamashita Yoshihisa 
Published: February 2016

AbstractThis population-based study determined the salivary microbiota composition of 2,343 adult residents of Hisayama town, Japan, using 16S rRNA gene next-generation high-throughput sequencing. Of 550 identified species-level operational taxonomic units (OTUs), 72 were common, in ≥75% of all individuals, as well as in ≥75% of the individuals in the lowest quintile of phylogenetic diversity (PD). These “core” OTUs constituted 90.9 ± 6.1% of each microbiome. The relative abundance profiles of 22 of the core OTUs with mean relative abundances ≥1% were stratified into community type I and community type II by partitioning around medoids clustering. Multiple regression analysis revealed that a lower PD was associated with better conditions for oral health, including a lower plaque index, absence of decayed teeth, less gingival bleeding, shallower periodontal pockets and not smoking, and was also associated with tooth loss. By contrast, multiple Poisson regression analysis demonstrated that community type II, as characterized by a higher ratio of the nine dominant core OTUs, including Neisseria flavescens, was implicated in younger age, lower body mass index, fewer teeth with caries experience, and not smoking. Our large-scale data analyses reveal variation in the salivary microbiome among Japanese adults and oral health-related conditions associated with the salivary microbiome.
Anodal transcranial direct current stimulation boosts synaptic plasticity and memory in mice via epigenetic regulation of Bdnf expression
Authors: Podda Maria Vittoria , Cocco Sara , Mastrodonato Alessia , Fusco Salvatore , Leone Lucia , Barbati Saviana Antonella , Colussi Claudia , Ripoli Cristian , Grassi Claudio 
Published: February 2016

AbstractThe effects of transcranial direct current stimulation (tDCS) on brain functions and the underlying molecular mechanisms are yet largely unknown. Here we report that mice subjected to 20-min anodal tDCS exhibited one-week lasting increases in hippocampal LTP, learning and memory. These effects were associated with enhanced: i) acetylation of brain-derived neurotrophic factor (Bdnf) promoter I; ii) expression of Bdnf exons I and IX; iii) Bdnf protein levels. The hippocampi of stimulated mice also exhibited enhanced CREB phosphorylation, pCREB binding to Bdnf promoter I and recruitment of CBP on the same regulatory sequence. Inhibition of acetylation and blockade of TrkB receptors hindered tDCS effects at molecular, electrophysiological and behavioral levels. Collectively, our findings suggest that anodal tDCS increases hippocampal LTP and memory via chromatin remodeling of Bdnf regulatory sequences leading to increased expression of this gene and support the therapeutic potential of tDCS for brain diseases associated with impaired neuroplasticity.
A curative regimen would decrease HIV prevalence but not HIV incidence unless targeted to an ART-naïve population
Authors: Dimitrov Dobromir T. , Kiem Hans-Peter , Jerome Keith R. , Johnston Christine , Schiffer Joshua T. 
Published: February 2016

AbstractHIV curative strategies currently under development aim to eradicate latent provirus, or prevent viral replication, progression to AIDS and transmission. The impact of implementing curative programs on HIV epidemics has not been considered. We developed a mathematical model of heterosexual HIV transmission to evaluate the independent and synergistic impact of ART, HIV prevention interventions and cure on HIV prevalence and incidence. The basic reproduction number was calculated to study the potential for the epidemic to be eliminated. We explored scenarios with and without the assumption that patients enrolled into HIV cure programs need to be on antiretroviral treatment (ART). In our simulations, curative regimes had limited impact on HIV incidence if only ART patients were eligible for cure. Cure implementation had a significant impact on HIV incidence if ART-untreated patients were enrolled directly into cure programs. Concurrent HIV prevention programs moderately decreased the percent of ART treated or cured patients needed to achieve elimination. We project that widespread implementation of HIV cure would decrease HIV prevalence under all scenarios but would only lower rate of new infections if ART-untreated patients were targeted. Current efforts to identify untreated HIV patients will gain even further relevance upon availability of an HIV cure.
Phosphorylation and calcium antagonistically tune myosin-binding protein C’s structure and function
Authors: Previs Michael J. , Mun Ji Young , Michalek Arthur J. , Previs Samantha Beck , Gulick James , Robbins Jeffrey , Warshaw David M. , Craig Roger 
Published: February 2016

Significance
Mutations in cardiac myosin-binding protein C (cMyBP-C) are the leading cause of inherited hypertrophic cardiomyopathy, demonstrating the key role that cMyBP-C plays in the heart’s contractile machinery. Since its discovery >40 years ago, cardiovascular biologists have wondered how cMyBP C’s structure regulates its function. Using atomic force spectroscopy, electron microscopy, in vitro model systems of contractility, and mutant protein expression, we show how phosphorylation affects cMyBP-C’s structure to tune its functions within the contractile apparatus. We also identify a novel molecular mechanism by which calcium ions that trigger each muscle contraction override phosphorylation’s structural and functional impact. This intersection of posttranslational modification and calcium signaling may occur in other biological systems that rely on these pathways to control cellular processes.
Determining optimal cadence for an individual road cyclist from field data
Authors: Reed Robert , Scarf Philip , Jobson Simon Adrian , Passfield Louis 
Published: February 2016

AbstractThe cadence that maximises power output developed at the crank by an individual cyclist is conventionally determined using a laboratory test. The purpose of this study was two‐fold: (i) to show that such a cadence, which we call the optimal cadence, can be determined using power output, heart‐rate, and cadence measured in the field and (ii) to describe methodology to do so. For an individual cyclist's sessions, power output is related to cadence and the elicited heart‐rate using a non‐linear regression model. Optimal cadences are found for two riders (83 and 70 revolutions per minute, respectively); these cadences are similar to the riders’ preferred cadences (82–92 rpm and 65–75 rpm). Power output reduces by approximately 6% for cadences 20 rpm above or below optimum. Our methodology can be used by a rider to determine an optimal cadence without laboratory testing intervention: the rider will need to collect power output, heart‐rate, and cadence measurements from training and racing sessions over an extended period (>6 months); ride at a range of cadences within those sessions; and calculate his/her optimal cadence using the methodology described or a software tool that implements it.
Transcript structure and domain display: a customizable transcript visualization tool
Authors: Watanabe Kenneth A. , Ma Kaiwang , Homayouni Arielle , Rushton Paul J. , Shen Qingxi J. 
Published: February 2016

Abstract
Summary: Transcript Structure and Domain Display (TSDD) is a publicly available, web-based program that provides publication quality images of transcript structures and domains. TSDD is capable of producing transcript structures from GFF/GFF3 and BED files. Alternatively, the GFF files of several model organisms have been pre-loaded so that users only needs to enter the locus IDs of the transcripts to be displayed. Visualization of transcripts provides many benefits to researchers, ranging from evolutionary analysis of DNA-binding domains to predictive function modeling.
Availability and implementation: TSDD is freely available for non-commercial users at http://shenlab.sols.unlv.edu/shenlab/software/TSD/transcript_display.html.
Contact: jeffery.shen@unlv.nevada.edu
Beyond Continuing Medical Education: Clinical Coaching as a Tool for Ongoing Professional Development
Authors: Iyasere Christiana A. , Baggett Meridale , Romano Jordan , Jena Anupam , Mills Gabrielle , Hunt Daniel P. 
Published: February 2016

Problem
For most physicians, the period of official apprenticeship ends with the completion of residency or fellowship, yet the acquisition of expertise requires ongoing opportunities to practice a given skill and obtain structured feedback on one’s performance.

Approach
In July 2013, the authors developed a clinical coaching pilot program to provide early-career hospitalists with feedback from a senior clinical advisor (SCA) at Massachusetts General Hospital. A Hospital Medicine Unit–wide retreat was held to help design the SCA role and obtain faculty buy-in. Twelve SCAs were recruited from hospitalists with more than five years of experience; each served as a clinical coach to 28 early-career hospitalists during the pilot. Clinical narratives and programmatic surveys were collected from SCAs and early-career hospitalists.

Outcomes
Of 25 responding early-career hospitalists, 23 (92%) rated the SCA role as useful to very useful, 20 (80%) reported interactions with the SCA led to at least one change in their diagnostic approach, and 13 (52%) reported calling fewer subspecialty consults as a result of guidance from the SCA. In response to questions about professional development, 18 (72%) felt more comfortable as an independent physician following their interactions with the SCA, and 19 (76%) thought the interactions improved the quality of care they delivered.

Next Steps
To better understand the impact and generalizability of clinical coaching, a larger, longitudinal study is required to look at patient and provider outcomes in detail. Further refinement of the SCA role to meet faculty needs is needed and could include faculty development.