bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adiponectin promotes muscle regeneration through binding to T-cadherin
Authors: Tanaka Yoshimitsu , Kita Shunbun , Nishizawa Hitoshi , Fukuda Shiro , Fujishima Yuya , Obata Yoshinari , Nagao Hirofumi , Masuda Shigeki , Nakamura Yuto , Shimizu Yuri , Mineo Ryohei , Natsukawa Tomoaki , Funahashi Tohru , Ranscht Barbara , Fukada So-ichiro , Maeda Norikazu , Shimomura Iichiro 
Published: January 2019

AbstractSkeletal muscle has remarkable regenerative potential and its decline with aging is suggested to be one of the important causes of loss of muscle mass and quality of life in elderly adults. Metabolic abnormalities such as obesity were linked with decline of muscle regeneration. On the other hand, plasma levels of adiponectin are decreased in such metabolic conditions. However, plasma levels of adiponectin have been shown to inversely correlate with muscle mass and strength in elderly people especially with chronic heart failure (CHF). Here we have addressed whether adiponectin has some impact on muscle regeneration after cardiotoxin-induced muscle injury in mice. Muscle regeneration was delayed by angiotensin II infusion, mimicking aging and CHF as reported. Adiponectin overexpression in vivo decreased necrotic region and increased regenerating myofibers. Such enhanced regeneration by excess adiponectin was also observed in adiponectin null mice, but not in T-cadherin null mice. Mechanistically, adiponectin accumulated on plasma membrane of myofibers both in mice and human, and intracellularly colocalized with endosomes positive for a multivesicular bodies/exosomes marker CD63 in regenerating myofibers. Purified high-molecular multimeric adiponectin similarly accumulated intracellularly and colocalized with CD63-positive endosomes and enhanced exosome secretion in differentiating C2C12 myotubes but not in undifferentiated myoblasts. Knockdown of T-cadherin in differentiating C2C12 myotubes attenuated both adiponectin-accumulation and adiponectin-mediated exosome production. Collectively, our studies have firstly demonstrated that adiponectin stimulates muscle regeneration through T-cadherin, where intracellular accumulation and exosome-mediated process of adiponectin may have some roles.
Repositioning salicylanilide anthelmintic drugs to treat adenovirus infections
Authors: Marrugal-Lorenzo José A. , Serna-Gallego Ana , Berastegui-Cabrera Judith , Pachón Jerónimo , Sánchez-Céspedes Javier 
Published: January 2019

AbstractThe repositioning of drugs already approved by regulatory agencies for other indications is an emerging alternative for the development of new antimicrobial therapies. The repositioning process involves lower risks and costs than the de novo development of novel antimicrobial drugs. Currently, infections by adenovirus show a steady increment with a high clinical impact in immunosuppressed and immunocompetent patients. The lack of a safe and efficacious drug to treat these infections supports the search for new antiviral drugs. Here we evaluated the anti-adenovirus activity of niclosanide, oxyclozanide, and rafoxanide, three salicylanilide anthelmintic drugs. Also, we carried out the cytotoxicity evaluation and partial characterization of the mechanism of action of these drugs. The salicylanilide anthelmintic drugs showed significant anti-adenovirus activity at low micromolar concentrations with little cytotoxicity. Moreover, our mechanistic assays suggest differences in the way the drugs exert anti-adenovirus activity. Niclosamide and rafoxanide target transport of the HAdV particle from the endosome to the nuclear envelope, whilst oxyclozanide specifically targets adenovirus immediately early gene E1A transcription. Data suggests that the studied salicylanilide anthelmintic drugs could be suitable for further clinical evaluation for the development of new antiviral drugs to treat infections by adenovirus in immunosuppressed patients and in immunocompetent individuals with community-acquired pneumonia.
Wavefunction Engineering of Type-I/Type-II Excitons of CdSe/CdS Core-Shell Quantum Dots
Authors: Nandan Yashaswi , Mehata Mohan Singh 
Published: January 2019

AbstractNanostructured semiconductors have the unique shape/size-dependent band gap tunability, which has various applications. The quantum confinement effect allows controlling the spatial distribution of the charge carriers in the core-shell quantum dots (QDs). Upon increasing shell thickness (e.g., from 0.25–3.25 nm) of core-shell QDs, the radial distribution function (RDF) of hole shifts towards the shell suggesting the confinement region switched from Type-I to Type-II excitons. As a result, there is a jump in the transition energy towards the higher side (blue shift). However, an intermediate state appeared as pseudo Type II excitons, in which holes are co-localized in the shell as well core whereas electrons are confined in core only, resulting in a dual absorption band (excitation energy), carried out by the analysis of the overlap percentage using the Hartree-Fock method. The findings are a close approximation to the experimental evidences. Thus, the understanding of the motion of e-h in core-shell QDs is essential for photovoltaic, LEDs, etc.
Heterochromatin suppresses gross chromosomal rearrangements at centromeres by repressing Tfs1/TFIIS-dependent transcription
Authors: Okita Akiko K. , Zafar Faria , Su Jie , Weerasekara Dayalini , Kajitani Takuya , Takahashi Tatsuro S. , Kimura Hiroshi , Murakami Yota , Masukata Hisao , Nakagawa Takuro 
Published: January 2019

AbstractHeterochromatin, characterized by histone H3 lysine 9 (H3K9) methylation, assembles on repetitive regions including centromeres. Although centromeric heterochromatin is important for correct segregation of chromosomes, its exact role in maintaining centromere integrity remains elusive. Here, we found in fission yeast that heterochromatin suppresses gross chromosomal rearrangements (GCRs) at centromeres. Mutations in Clr4/Suv39 methyltransferase increased the formation of isochromosomes, whose breakpoints were located in centromere repeats. H3K9A and H3K9R mutations also increased GCRs, suggesting that Clr4 suppresses centromeric GCRs via H3K9 methylation. HP1 homologs Swi6 and Chp2 and the RNAi component Chp1 were the chromodomain proteins essential for full suppression of GCRs. Remarkably, mutations in RNA polymerase II (RNAPII) or Tfs1/TFIIS, the transcription factor that facilitates restart of RNAPII after backtracking, specifically bypassed the requirement of Clr4 for suppressing GCRs. These results demonstrate that heterochromatin suppresses GCRs by repressing Tfs1-dependent transcription of centromere repeats.
Altered expression of long non-coding RNA GAS5 in digestive tumors
Authors: Lu Shounan , Su Zhilei , Fu Wen , Cui Zhankun , Jiang Xingming , Tai Sheng 
Published: January 2019

Abstract
Cancer has become one of the most important diseases that affect human health and life. The effects of cancer in the digestive system are particularly prominent. Recently, long non-coding RNA (lncRNA) has attracted the attention of more and more researchers and has become an emerging field of gene research. The lncRNA growth arrest-specific 5 (GAS5) is a novel lncRNA that has attracted the attention of researchers in recent years and plays an important role in the development of tumors, especially in digestive system tumors. GAS5 was first identified in a mouse cDNA library. It was generally considered that it has the role of tumor suppressor genes, but there are still studies that have a certain ability to promote cancer. Furthermore, the 5-bp indel polymorphism (rs145204276) in the GAS5 promoter region also has a carcinogenic effect. The discovery of GAS5 and in-depth study of single nucleotide polymorphism (SNP) mechanism can provide a new way for the prevention and treatment of digestive system tumors.
Seismic performance
Authors: Mosser B. , Michel E. , Samadi R. , Miglio A. , Davies G. R. , Girardi L. , Goupil M. J. 
Published: January 2019

Context. Asteroseismology is a unique tool that can be used to study the interior of stars and hence deliver unique information for the studiy of stellar physics, stellar evolution, and Galactic archaeology.
Aims. We aim to develop a simple model of the information content of asteroseismology and to characterize the ability and precision with which fundamental properties of stars can be estimated for different space missions.
Methods. We defined and calibrated metrics of the seismic performance. The metrics, expressed by a seismic index ℰ defined by simple scaling relations, are calculated for an ensemble of stars. We studied the relations between the properties of mission observations, fundamental stellar properties, and the performance index. We also defined thresholds for asteroseismic detection and measurement of different stellar properties.
Results. We find two regimes of asteroseismic performance: the first where the signal strength is dominated by stellar properties and not by observational noise; and the second where observational properties dominate. Typically, for evolved stars, stellar properties provide the dominant terms in estimating the information content, while main sequence stars fall in the regime where the observational properties, especially stellar magnitude, dominate. We estimate scaling relations to predict ℰ with an intrinsic scatter of around 21%. Incidentally, the metrics allow us to distinguish stars burning either hydrogen or helium.
Conclusions. Our predictions will help identify the nature of the cohort of existing and future asteroseismic observations. In addition, the predicted performance for PLATO will help define optimal observing strategies for defined scientific goals.
HIV peptidome-wide association study reveals patient-specific epitope repertoires associated with HIV control
Authors: Arora Jatin , McLaren Paul J. , Chaturvedi Nimisha , Carrington Mary , Fellay Jacques , Lenz Tobias L. 
Published: January 2019

Significance
Individual differences in HIV-1 control and progression to AIDS have been pinpointed to genetic variation in the HLA, coding for antigen-presenting molecules. However, our understanding of the corresponding antigens is still incomplete. Here we developed an approach that combines HLA genotypes and viral load data of HIV-infected individuals to screen the entire HIV-1 proteome for disease-relevant peptides. Our PepWAS approach identified a limited manageable core set of peptides, accounting for the entire variation in viral load previously associated with genetic variation in the HLA. This core set of disease-relevant antigens thus provides a functional link between HLA genetic variation and HIV-1 control, confirming several known antigens, but also prioritizing previously undescribed antigens as potential therapeutic targets.
Nanoscale infrared imaging analysis of carbonaceous chondrites to understand organic-mineral interactions during aqueous alteration
Authors: Kebukawa Yoko , Kobayashi Hanae , Urayama Norio , Baden Naoki , Kondo Masashi , Zolensky Michael E. , Kobayashi Kensei 
Published: January 2019

Significance
Spatial relationships between organic matter and minerals are necessary for understanding the formation and evolution of organic matter during aqueous and thermal alteration in their parent bodies, as well as preaccretional history. Infrared spectroscopy is a powerful tool to analyze the molecular structures of organic matter and identification of minerals. However, its spatial resolution is limited due to the diffraction limit. Recently, the atomic force microscopy (AFM) based IR nanospectroscopy was developed and applied in various scientific fields to overcome the diffraction limit of IR. We applied the AFM-based IR nanospectroscopy to carbonaceous chondrites and studied organic-mineral associations at the ∼30 nm spatial resolution.
Systematic Review and Meta-analysis: Optimal Salvage Therapy in Acute Severe Ulcerative Colitis
Authors: Choy Matthew C , Seah Dean , Faleck David M , Shah Shailja C , Chao Che-Yung , An Yoon-Kyo , Radford-Smith Graham , Bessissow Talat , Dubinsky Marla C , Ford Alexander C , Churilov Leonid , Yeomans Neville D , De Cruz Peter P 
Published: January 2019

AbstractBackgroundInfliximab is an effective salvage therapy in acute severe ulcerative colitis; however, the optimal dosing strategy is unknown. We performed a systematic review and meta-analysis to examine the impact of infliximab dosage and intensification on colectomy-free survival in acute severe ulcerative colitis.MethodsStudies reporting outcomes of hospitalized steroid-refractory acute severe ulcerative colitis treated with infliximab salvage were identified. Infliximab use was categorized by dose, dose number, and schedule. The primary outcome was colectomy-free survival at 3 months. Pooled proportions and odds ratios with 95% confidence intervals were reported.ResultsForty-one cohorts (n = 2158 cases) were included. Overall colectomy-free survival with infliximab salvage was 79.7% (95% confidence interval [CI], 75.48% to 83.6%) at 3 months and 69.8% (95% CI, 65.7% to 73.7%) at 12 months. Colectomy-free survival at 3 months was superior with 5-mg/kg multiple (≥2) doses compared with single-dose induction (odds ratio [OR], 4.24; 95% CI, 2.44 to 7.36; P < 0.001). However, dose intensification with either high-dose or accelerated strategies was not significantly different to 5-mg/kg standard induction at 3 months (OR, 0.70; 95% CI, 0.39 to 1.27; P = 0.24) despite being utilized in patients with a significantly higher mean C-reactive protein and lower albumin levels.ConclusionsIn acute severe ulcerative colitis, multiple 5-mg/kg infliximab doses are superior to single-dose salvage. Dose-intensified induction outcomes were not significantly different compared to standard induction and were more often used in patients with increased disease severity, which may have confounded the results. This meta-analysis highlights the marked variability in the management of infliximab salvage therapy and the need for further studies to determine the optimal dose strategy.
Reimagining the research-practice relationship: policy recommendations for informatics-enabled evidence-generation across the US health system
Authors: Embi Peter J , Richesson Rachel , Tenenbaum Jessica , Kannry Joseph , Friedman Charles , Sarkar Indra Neil , Smith Jeff ,   The members of 2016 AMIA Policy Invitational Planning Committee
Published: January 2019

Abstract
The widespread adoption and use of electronic health records and their use to enable learning health systems (LHS) holds great promise to accelerate both evidence-generating medicine (EGM) and evidence-based medicine (EBM), thereby enabling a LHS. In 2016, AMIA convened its 10th annual Policy Invitational to discuss issues key to facilitating the EGM-EBM paradigm at points-of-care (nodes), across organizations (networks), and to ensure viability of this model at scale (sustainability). In this article, we synthesize discussions from the conference and supplements those deliberations with relevant context to inform ongoing policy development. Specifically, we explore and suggest public policies needed to facilitate EGM-EBM activities on a national scale, particularly those policies that can enable and improve clinical and health services research at the point-of-care, accelerate biomedical discovery, and facilitate translation of findings to improve the health of individuals and populations.
Discovery of new mycoviral genomes within publicly available fungal transcriptomic datasets
Authors: Gilbert Kerrigan B. , Holcomb Emily E. , Allscheid Robyn L. , Carrington James C. 
Published: January 2019

AbstractThe distribution and diversity of RNA viruses in fungi is incompletely understood due to the often cryptic nature of mycoviral infections and the focused study of primarily pathogenic and/or economically important fungi. As most viruses that are known to infect fungi possess either single-stranded or double-stranded RNA genomes, transcriptomic data provides the opportunity to query for viruses in diverse fungal samples without any a priori knowledge of virus infection. Here we describe a systematic survey of all transcriptomic datasets from fungi belonging to the subphylum Pezizomycotina. Using a simple but effective computational pipeline that uses reads discarded during normal RNA-seq analyses, followed by identification of a viral RNA-dependent RNA polymerase (RdRP) motif in de novo assembled contigs, 59 viruses from 44 different fungi were identified. Among the viruses identified, 89% were determined to be new species and 68% are, to our knowledge, the first virus described from the fungal species. Comprehensive analyses of both nucleotide and inferred protein sequences characterize the phylogenetic relationships between these viruses and the known set of mycoviral sequences and support the classification of up to four new families and two new genera. Thus the results provide a deeper understanding of the scope of mycoviral diversity while also increasing the distribution of fungal hosts. Further, this study demonstrates the suitability of analyzing RNA-seq data to facilitate rapid discovery of new viruses.
Overexpression of long noncoding RNA GAS5 suppresses tumorigenesis and development of gastric cancer by sponging miR-106a-5p through the Akt/mToR pathway
Authors: Dong Shuaijun , Zhang Xiefu , Liu Dechun 
Published: January 2019

AbstractLong non-coding RNAs (lncRNAs) have emerged as important regulators of human cancers. LncRNA GAS5 (GAS5) is identified tumor suppressor involved in several cancers. However, the roles of GAS5 and the mechanisms responsible for its functions in gastric cancer (GC) have not been well undocumented. Herein, the decreased GAS5 and increased miRNA-106a-5p levels were observed in GC and cell lines. GAS5 expression level was significantly inversely correlated with miRNA-106a-5p level in GC tissues. Moreover, luciferase reporter and qRT-PCR assays showed that GAS5 bound to miRNA-106a-5p and negatively regulated its expression in GC cells. Functional experiments showed that GAS5 overexpression suppressed GC cell proliferation, migration, and invasion capabilities and promoted apoptosis, while miRNA-106a-5p overexpression inversed the functional effects induced by GAS5 overexpression. In vivo, GAS5 overexpression inhibited tumor growth by negatively regulating miRNA-106a-5p expression. Mechanistic investigations revealed that GAS5 overexpression inactivating the Akt/mToR pathway by suppressing miRNA-106a-5p expression in vitro and in vivo. Taken together, our findings conclude the GAS5 overexpression suppresses tumorigenesis and development of gastric cancer by sponging miR-106a-5p through the Akt/mToR pathway.
Ephrin receptor A4 (EphA4) is a new Kaposi’s sarcoma-associated herpesvirus virus entry receptor
Authors: Chen Jia , Zhang Xianming , Schaller Samantha , Jardetzky Theodore S. , Longnecker Richard 
Published: January 2019

AbstractKaposi’s sarcoma-associated herpesvirus (KSHV) is a human γ-herpesvirus associated with the development of Kaposi’s sarcoma (KS). KSHV target cells include endothelial cells, B cells, monocytes, epithelial cells, dendritic cells, macrophages, and fibroblasts. KSHV entry into target cells is a complex multistep process and is initiated by the binding and interaction of viral envelope glycoproteins with the cellular receptors. In our current studies, we have found that EphA4 promotes KSHV gH/gL-mediated fusion and infection better than EphA2 in HEK293T cells indicating that EphA4 is a new KSHV entry receptor. To confirm that epithelial cells express EphA2 and EphA4, we analyzed the expression of EphA2 and EphA4 in epithelial cells, endothelial cells, B cells, monocytes, fibroblasts using RNA-seq data analysis of existing data sets. We found these cell types broadly express both EphA2 and EphA4 with the exception of monocytes and B cells. To confirm EphA4 is important for KSHV fusion and infection, we generated EphA2 and EphA4 single and double knockout cells. We found that both EphA2 and EphA4 play a role in KSHV fusion and infection, since EphA2/EphA4 double knockout cells had the greatest decrease in fusion activity and infection compared to single knockout cells. Fusion and infection of KSHV was rescued in the EphA2/EphA4 double knock cells upon overexpression of EphA2 and/or EphA4. EphA2 binds to both EBV and KSHV gH/gL; however, EphA4 binds only to KSHV gH/gL. Taken together, our results identify EphA4 as a new entry receptor for KSHV.ImportanceThe overall entry mechanism for herpesviruses is not completely known including that for the human γ-herpesviruses Kaposi’s sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV). To fully understand the herpesvirus entry process, functional receptors need to be identified. In our current study, we found that EphA4 can also function for a KSHV entry receptor along with EphA2. Interestingly, we found that EphA4 does not function as an entry receptor for EBV whereas EphA2 does. The discovery of EphA4 as KSHV entry receptor has important implications for KSHV pathogenesis in humans and may prove useful in understanding the unique pathogenesis of KSHV infection in humans and may uncover new potential targets that can be used for the development of novel interventional strategies.
Integrated high-resolution phenotyping, chlorophyll fluorescence induction kinetics and photosystem II dynamics under water stress and heat in Wheat (Triticum aestivum)
Authors: Shanker Arun K. , Coe Robert , Sirault Xavier 
Published: January 2019

AbstractAn experiment was conducted in controlled conditions in three varieties of wheat under water stress, heat and heat +water stress treatments with the objective of studying Chlorophyll a fluorescence, chlorophyll fluorescence induction kinetics and the function of Photosystem II by plant phenotyping as affected by stress. We hypothesised that during stress, specific adaptive strategies are employed by plants, such as structural and functional changes in PS II by which they acquire new homeostasis which may be protective adaptations. Water stress stress treatment was imposed on Water stress and Heat +Water stress treatments at 43 DAS. Heat treatment was imposed on 48 DAS. Maximum quantum yield of primary photochemistry was measured with PAM 2500 and OJIP was measured with FluorPen FP 100 after the onset of stress at four observation times on two days viz., pre-dawn and afternoon during stress. In addition continuous monitoring of photosynthetic efficiency was done with Monitoring PAM. Heat +Water stress stress was more detrimental as compared to Heat or Water stress alone in terms of maximum quantum yield of photochemistry. This could have been due to higher decrease in connectivity between PSII and its antennae resulting in lower photosynthetic efficiency resulting in the impairment and disruption of the electron transport. K step was observed in heat stress and heat +Water stress stress which may be because of damage to Oxygen Evolving Complex indicating that low thermostability of the complex. The stress treatments had a reduction in the plastoquinone pool size as indicated by the reduced area above the OJIP curve. Our study indicated that the instrument PAM 2500 sensed both stresses separately and combined earlier than the other instruments, so in terms of sensitivity PAM 2500 was more effective than FluorPen FP 100 and MultispeQ. Rapid screening of stress was more effectively with FluorPen FP 100 and MultispeQ than by PAM 2500.