bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alternative transcription start site selection in Mr-OPY2 controls lifestyle transitions in the fungus Metarhizium robertsii
Authors: Guo Na , Qian Ying , Zhang Qiangqiang , Chen Xiaoxuan , Zeng Guohong , Zhang Xing , Mi Wubing , Xu Chuan , St. Leger Raymond J. , Fang Weiguo 
Published: November 2017

AbstractMetarhizium robertsiiis a versatile fungus with saprophytic, plant symbiotic and insect pathogenic lifestyle options. Here we show thatM. robertsiimediates the saprophyte-to-insect pathogen transition through modulation of the expression of a membrane protein, Mr-OPY2. Abundant Mr-OPY2 protein initiates appressorium formation, a prerequisite for infection, whereas reduced production of Mr-OPY2 elicits saprophytic growth and conidiation. The precise regulation of Mr-OPY2 protein production is achieved via alternative transcription start sites. During saprophytic growth, a single long transcript is produced with small upstream open reading frames in its 5′ untranslated region. Increased production of Mr-OPY2 protein on host cuticle is achieved by expression of a transcript variant lacking a small upstream open reading frame that would otherwise inhibit translation of Mr-OPY2. RNA-seq and qRT-PCR analyses show that Mr-OPY2 is a negative regulator of a transcription factor that we demonstrate is necessary for appressorial formation. These findings provide insights into the mechanisms regulating fungal lifestyle transitions.
Therapeutic effects of hepatocyte growth factor-overexpressing dental pulp stem cells on liver cirrhosis in a rat model
Authors: Cao Xiao-fang , Jin Shi-zhu , Sun Liang , Zhan Yuan-bo , Lin Feng , Li Ying , Zhou Ying-lian , Wang Xiu-mei , Gao Li , Zhang Bin 
Published: November 2017

AbstractCirrhosis is the terminal stage of hepatic diseases and is prone to develop into hepatocyte carcinoma. Increasing evidence suggests that the transplantation of dental pulp stem cells (DPSCs) may promote recovery from cirrhosis, but the key regulatory mechanisms involved remain to be determined. In this study, we overexpressed human hepatocyte growth factor (hHGF) in primary rat DPSCs and evaluated the effects of HGF overexpression on the biological behaviors and therapeutic efficacy of grafted DPSCs in cirrhosis. Liver cirrhosis was induced via the intraperitoneal injection of CCl4 twice weekly for 12 weeks and was verified through histopathological and serological assays. HGF was overexpressed in DPSCs via transduction with a hHGF-lentiviral vector and confirmed based on the elevated expression and secretion of HGF. The HGF-overexpressing DPSCs were transplanted into rats intravenously. The HGF-overexpressing DPSCs showed increased survival and hepatogenic differentiation in host liver tissue at 6 weeks after grafting. They also exhibited a significantly greater repair potential in relation to cirrhosis pathology and impaired liver function than did DPSCs expressing HGF at physiological levels. Our study may provide an experimental basis for the development of novel methods for the treatment of liver cirrhosis in clinical practice.
Repurposing of the anti-malaria drug chloroquine for Zika Virus treatment and prophylaxis
Authors: Shiryaev Sergey A. , Mesci Pinar , Pinto Antonella , Fernandes Isabella , Sheets Nicholas , Shresta Sujan , Farhy Chen , Huang Chun-Teng , Strongin Alex Y. , Muotri Alysson R. , Terskikh Alexey V. 
Published: November 2017

AbstractOne of the major challenges of the current Zika virus (ZIKV) epidemic is to prevent congenital foetal abnormalities, including microcephaly, following ZIKV infection of pregnant women. Given the urgent need for ZIKV prophylaxis and treatment, repurposing of approved drugs appears to be a viable and immediate solution. We demonstrate that the common anti-malaria drug chloroquine (CQ) extends the lifespan of ZIKV-infected interferon signalling-deficient AG129 mice. However, the severity of ZIKV infection in these mice precludes the study of foetal (vertical) viral transmission. Here, we show that interferon signalling-competent SJL mice support chronic ZIKV infection. Infected dams and sires are both able to transmit ZIKV to the offspring, making this an ideal model for in vivo validation of compounds shown to suppress ZIKV in cell culture. Administration of CQ to ZIKV-infected pregnant SJL mice during mid-late gestation significantly attenuated vertical transmission, reducing the ZIKV load in the foetal brain more than 20-fold. Given the limited side effects of CQ, its lack of contraindications in pregnant women, and its worldwide availability and low cost, we suggest that CQ could be considered for the treatment and prophylaxis of ZIKV.
In Vitro Maturation and In Vivo Integration and Function of an Engineered Cell-Seeded Disc-like Angle Ply Structure (DAPS) for Total Disc Arthroplasty
Authors: Martin J. T. , Gullbrand S. E. , Kim D. H. , Ikuta K. , Pfeifer C. G. , Ashinsky B. G. , Smith L. J. , Elliott D. M. , Smith H. E. , Mauck R. L. 
Published: November 2017

AbstractTotal disc replacement with an engineered substitute is a promising avenue for treating advanced intervertebral disc disease. Toward this goal, we developed cell-seeded disc-like angle ply structures (DAPS) and showed through in vitro studies that these constructs mature to match native disc composition, structure, and function with long-term culture. We then evaluated DAPS performance in an in vivo rat model of total disc replacement; over 5 weeks in vivo, DAPS maintained their structure, prevented intervertebral bony fusion, and matched native disc mechanical function at physiologic loads in situ. However, DAPS rapidly lost proteoglycan post-implantation and did not integrate into adjacent vertebrae. To address this, we modified the design to include polymer endplates to interface the DAPS with adjacent vertebrae, and showed that this modification mitigated in vivo proteoglycan loss while maintaining mechanical function and promoting integration. Together, these data demonstrate that cell-seeded engineered discs can replicate many characteristics of the native disc and are a viable option for total disc arthroplasty.
Differential regulation of synaptic AP-2/clathrin vesicle uncoating in synaptic plasticity
Authors: Candiello Ermes , Mishra Ratnakar , Schmidt Bernhard , Jahn Olaf , Schu Peter 
Published: November 2017

AbstractAP-1/σ1B-deficiency causes X-linked intellectual disability. AP-1/σ1B −/− mice have impaired synaptic vesicle recycling, fewer synaptic vesicles and enhanced endosome maturation mediated by AP-1/σ1A. Despite defects in synaptic vesicle recycling synapses contain two times more endocytic AP-2 clathrin-coated vesicles. We demonstrate increased formation of two classes of AP-2/clathrin coated vesicles. One which uncoats readily and a second with a stabilised clathrin coat. Coat stabilisation is mediated by three molecular mechanisms: reduced recruitment of Hsc70 and synaptojanin1 and enhanced μ2/AP-2 phosphorylation and activation. Stabilised AP-2 vesicles are enriched in the structural active zone proteins Git1 and stonin2 and synapses contain more Git1. Endocytosis of the synaptic vesicle exocytosis regulating Munc13 isoforms are differentially effected. Regulation of synaptic protein endocytosis by the differential stability of AP-2/clathrin coats is a novel molecular mechanism of synaptic plasticity.
Constructing Genetic Networks using Biomedical Literature and Rare Event Classification
Authors: Al-Aamri Amira , Taha Kamal , Al-Hammadi Yousof , Maalouf Maher , Homouz Dirar 
Published: November 2017

AbstractText mining has become an important tool in bioinformatics research with the massive growth in the biomedical literature over the past decade. Mining the biomedical literature has resulted in an incredible number of computational algorithms that assist many bioinformatics researchers. In this paper, we present a text mining system called Gene Interaction Rare Event Miner (GIREM) that constructs gene-gene-interaction networks for human genome using information extracted from biomedical literature. GIREM identifies functionally related genes based on their co-occurrences in the abstracts of biomedical literature. For a given gene g, GIREM first extracts the set of genes found within the abstracts of biomedical literature associated with g. GIREM aims at enhancing biological text mining approaches by identifying the semantic relationship between each co-occurrence of a pair of genes in abstracts using the syntactic structures of sentences and linguistics theories. It uses a supervised learning algorithm, weighted logistic regression to label pairs of genes to related or un-related classes, and to reflect the population proportion using smaller samples. We evaluated GIREM by comparing it experimentally with other well-known approaches and a protein-protein interactions database. Results showed marked improvement.
Contact morphology and revisited photocurrent dynamics in monolayer MoS2
Authors: Parzinger Eric , Hetzl Martin , Wurstbauer Ursula , Holleitner Alexander W. 
Published: November 2017

AbstractTwo-dimensional (2D) layered transition metal dichalcogenides (TMDs) have emerged as promising materials for electronic, optoelectronic, and valleytronic applications. Recent work suggests drastic changes of the band gap and exciton binding energies of photo-excited TMDs with ultrafast non-radiative relaxation processes effectively heating the crystal lattice. Such phenomena have not been considered in the context of optoelectronic devices yet. We resolve corresponding ultrafast photoconductance dynamics within monolayer MoS2. The data suggest that a bolometric contribution as well as a defect-related conductance dominate the overall photoconductance. We further reveal that a focused laser illumination, as is used in many standard optoelectronic measurements of MoS2, can modify and anneal the morphology of metal contacts. We show that a junction evolves with lateral built-in electric fields, although Raman spectra and photoluminescence spectra indicate no significant changes, such as a crystal phase transition. We highlight how such optimized devices can drive ultrafast electromagnetic signals in on-chip high-frequency and THz circuits.
Defining the Role of Free Flaps in Partial Breast Reconstruction
Authors: Molina Bianca , Dayan Erez , Jablonka Eric , Okwali Michelle , Kim Julie , Dayan Joseph , Smith Mark 
Published: November 2017

Background Free flaps have a well-established role in breast reconstruction after mastectomy; however, their role in partial breast reconstruction remains poorly defined. We reviewed our experience with partial breast reconstruction to better understand indications for free tissue transfer.
Methods A retrospective review was performed of all patients undergoing partial breast reconstruction at our center between February 2009 and October 2015. We evaluated the characteristics of patients who underwent volume displacement procedures versus volume replacement procedures and free versus pedicled flap reconstruction.
Results There were 78 partial breast reconstructions, with 52 reductions/tissue rearrangements (displacement group) and 26 flaps (replacement group). Bra cup size and body mass index (BMI) were significantly smaller in the replacement group. Fifteen pedicled and 11 free flaps were performed. Most pedicled flaps (80.0%) were used for lateral or upper pole defects. Most free flaps (72.7%) were used for medial and inferior defects or when there was inadequate donor tissue for a pedicled flap. Complications included hematoma, cellulitis, and one aborted pedicled flap.
Conclusion Free and pedicled flaps are useful for partial breast reconstruction, particularly in breast cancer patients with small breasts undergoing breast-conserving treatment (BCT). Flap selection depends on defect size, location, and donor tissue availability. Medial defects are difficult to reconstruct using pedicled flaps due to arc of rotation and intervening breast tissue. Free tissue transfer can overcome these obstacles. Confirming negative margins before flap reconstruction ensures harvest of adequate volume and avoids later re-operation. Judicious use of free flaps for oncoplastic reconstruction expands the possibility for breast conservation.
Posterior Nutcracker Phenomenon in a Patient with Left Atrial Isomerism
Authors: Tsvelodub Stanislav , Putman Léon , Gieselmann Andrea , Sievers Hans-Hinrich 
Published: November 2017

Background Nutcracker phenomenon (NCP) can occur due to various anatomical anomalies. Anterior and posterior NCP are defined in the literature. Posterior NCP combined with left atrial isomerism is a rare condition.
Case description We present a rare case of an asymptomatic posterior NCP involving the azygos vein in a patient with a complex cardiovascular pathology with left atrial isomerism, left ventricular outflow tract obstruction, interrupted inferior vena cava, and azygos continuation.
Conclusion Detection of the NCP especially involving such a rare anatomical anomaly as an azygos continuation has a crucial importance for diagnostic and surgical procedures.
Gap junctional coupling between retinal amacrine and ganglion cells underlies coherent activity integral to global object perception
Authors: Roy Kaushambi , Kumar Sandeep , Bloomfield Stewart A. 
Published: November 2017

Significance
Neuron ensembles in the brain visual system often show correlated responses, but the sensory information encoded by this activity remains unclear. Here, we show that widely separated ganglion cells in the mouse retina show correlated activity when presented with a large, contiguous object, but not when the object is disjointed. We show that these long-range correlations are produced by electrical coupling via gap junctions made with polyaxonal amacrine cells, which can span distances greater than a millimeter. Blockade or ablation of these gap junctions eliminates correlations between distant ganglion cells and, moreover, diminishes an animal’s ability to discriminate large, solid objects from disjointed ones. Our findings indicate that long-range correlated activity in the retina encodes visual information critical for global object perception.
Insights into functions of the H channel of cytochrome
c
oxidase from atomistic molecular dynamics simulations
Authors: Sharma Vivek , Jambrina Pablo G. , Kaukonen Markus , Rosta Edina , Rich Peter R. 
Published: November 2017

Significance
Cytochrome oxidase is a widespread respiratory enzyme that conserves energy released when oxygen is reduced by pumping protons across the membrane in which it is located. Here, we use atomistic simulations of the whole bovine enzyme to investigate properties of the H channel, a structure that has been proposed to provide the pathway for pumped protons in mammalian forms of the enzyme. These studies show that although parts of the structure could function in this manner, a gap persists. This gap could be bridged only if a buried histidine becomes protonated. Based on these simulations, we propose that the H channel acts as a dielectric well, modulating effects of buried charge changes.
RNA stem structure governs coupling of dicing and gene silencing in RNA interference
Authors: Koh Hye Ran , Ghanbariniaki Amirhossein , Myong Sua 
Published: November 2017

Significance
RNAi is an RNA-induced gene-silencing pathway that is shared among various organisms. Better understanding of RNAi is urgently needed to improve our knowledge of RNA-mediated gene regulation and to advance the field of functional genomics and its application to gene therapy. We counted with high precision the number of transcripts in each cell’s nucleus and cytoplasm as a function of silencing time to investigate the role of small RNA secondary structures such as loop length and stem mismatches. We screened various structural features of small RNAs and discovered a distinct role of each structural element that contributes to gene-silencing kinetics. We provide a helpful guideline for designing small RNAs for more efficient gene silencing.
Resident macrophages of pancreatic islets have a seminal role in the initiation of autoimmune diabetes of NOD mice
Authors: Carrero Javier A. , McCarthy Derrick P. , Ferris Stephen T. , Wan Xiaoxiao , Hu Hao , Zinselmeyer Bernd H. , Vomund Anthony N. , Unanue Emil R. 
Published: November 2017

Significance
Our studies indicate that the resident macrophages of the pancreatic islets of Langerhans have a seminal role in the initiation and progression of autoimmune diabetes in NOD mice. In this study, islet macrophages were depleted by administration of a monoclonal antibody to the CSF-1 receptor. Macrophage depletion, either at the start of the autoimmune process or when diabetogenesis is active, leads to a significant reduction in diabetes incidence. Depletion of the islet macrophages reduces the entrance of T cells into islets and results in the absence of antigen presentation. Concordantly, a regulatory pathway develops that controls diabetes progression. We conclude that treatments that target the islet macrophages may have important clinical relevance for the control of autoimmune type 1 diabetes.
A review of riverine ecosystem service quantification: Research gaps and recommendations
Authors: Hanna Dalal E. L. , Tomscha Stephanie A. , Ouellet Dallaire Camille , Bennett Elena M. 
Published: November 2017

Abstract

Increasing demand for benefits provided by riverine ecosystems threatens their sustainable provision. The ecosystem service concept is a promising avenue to inform riverine ecosystem management, but several challenges have prevented the application of this concept.

We quantitatively assess the field of riverine ecosystem services’ progress in meeting these challenges. We highlight conceptual and methodological gaps, which have impeded integration of the ecosystem service concept into management.

Across 89 relevant studies, 33 unique riverine ecosystem services were evaluated, for a total of 404 ecosystem service quantifications. Studies quantified between 1 and 23 ecosystem services, although the majority (55%) evaluated three or less. Among studies that quantified more than one service, 58% assessed interactions between services. Most studies (71%) did not include stakeholders in their quantification protocols, and 34% developed future scenarios of ecosystem service provision. Almost half (45%) conducted monetary valuation, using 16 methods. Only 9% did not quantify or discuss uncertainties associated with service quantification. The indicators and methods used to quantify the same type of ecosystem service varied. Only 3% of services used indicators of capacity, flow and demand in concert.

Our results suggest indicators, data sources and methods for quantifying riverine ecosystem services should be more clearly defined and accurately represent the service they intend to quantify. Furthermore, more assessments of multiple services across diverse spatial extents and of riverine service interactions are needed, with better inclusion of stakeholders. Addressing these challenges will help riverine ecosystem service science inform river management.

Synthesis and applications. The ecosystem service concept has great potential to inform riverine ecosystem management and decision‐making processes. However, this review of riverine ecosystem service quantification uncovers several remaining research gaps, impeding effective use of this tool to manage riverine ecosystems. We highlight these gaps and point to studies showcasing methods that can be used to address them.
Demonstrating multiple benefits from periodically harvested fisheries closures
Authors: Goetze Jordan S. , Claudet Joachim , Januchowski‐Hartley Fraser , Langlois Timothy J. , Wilson Shaun K. , White Crow , Weeks Rebecca , Jupiter Stacy D. 
Published: November 2017

AbstractPeriodically harvested closures (PHCs) are one of the most common forms of fisheries management in Melanesia, demonstrating multiple objectives, including sustaining fish stocks and increasing catch efficiency to support small‐scale fisheries. No studies have comprehensively assessed their ability to provide short‐term fisheries benefits across the entire harvest regime.We present a novel analytical framework to guide a meta‐analysis and assist future research in conceptualizing and assessing the potential ofPHCs to deliver benefits for multiple fisheries‐related objectives.TenPHCs met our selection criteria and on average, they provided a 48% greater abundance and 92% greater biomass of targeted fishes compared with areas open to fishing prior to being harvested.This translated into tangible harvest benefits, with fishers removing 21% of the abundance and 49% of the biomass withinPHCs, resulting in few post‐harvest protection benefits.WhenPHCs are larger, closed for longer periods or well enforced, short‐term fisheries benefits are improved. However, an increased availability of fish withinPHCs leads to greater removal during harvests.Synthesis and applications. Periodically harvested closures (PHCs) can provide short‐term fisheries benefits. Use of the analytical framework presented here will assist in determining long‐term fisheries and conservation benefits. We recommendPHCs be closed to fishing for as long as possible, be as large as possible, that compliance be encouraged via community engagement and enforcement, and strict deadlines/goals for harvesting set to prevent overfishing.
Drug interactions between rifamycin antibiotics and hormonal contraception: a systematic review
Authors: Simmons KB , Haddad LB , Nanda K , Curtis KM 
Published: November 2017

BackgroundRifamycin antibiotics are commonly used for treatment of tuberculosis, but may reduce the effectiveness of hormonal contraception (HC).ObjectivesTo determine whether interactions between rifamycins and HC result in decreased effectiveness or increased toxicity of either therapy.Search strategyWe searched MEDLINE, Embase, Cochrane and clinicaltrials.gov through May 2017.Selection criteriaWe included trials, cohort, and case‐control studies addressing pregnancy rates, pharmacodynamics or pharmacokinetic (PK) outcomes when HC and rifamycins were administered together versus apart. Of 7291 original records identified, 11 met inclusion criteria after independent review by two authors.Data collection and analysisTwo authors independently abstracted study details and assessed study quality using the United States Preventive Services Task Force grading system. Findings are reported descriptively.Main resultsStudies only addressed combined oral contraceptives (COCs) and none reported pregnancy rates. Quality ranged from good to poor. Rifampin increased the frequency of ovulation in two of four studies, and reduced estrogen and/or progestin exposure in five studies. Rifabutin led to smaller PK changes than rifampin in two studies. In one study each, rifaximin and rifalazil did not alter hormone PK.ConclusionsNo studies evaluated pregnancy risk or non‐oral HCs. PK and ovulation outcomes support a clinically concerning drug interaction between COCs and rifampin, and to a lesser extent rifabutin. Data are limited for other rifamycins.Tweetable abstractRifampin and rifabutin reduce systemic exposure of oral contraceptives, but no studies have evaluated pregnancy risk.