bluuebunny/crossref_metadata_2025_split huggingface dataset:
Zyxin stabilizes RIG-I and MAVS interactions and promotes type I interferon response
Authors: Kouwaki Takahisa , Okamoto Masaaki , Tsukamoto Hirotake , Fukushima Yoshimi , Matsumoto Misako , Seya Tsukasa , Oshiumi Hiroyuki 
Published: September 2017

AbstractRIG-I and MDA5 are cytoplasmic viral RNA sensors that belong to the RIG-I-like receptors (RLRs), which induce antiviral innate immune responses, including the production of type I interferon and other pro-inflammatory cytokines. After recognition of viral RNA, the N-terminal caspase activation and recruitment domains (CARDs) of RIG-I and MDA5 bind to a CARD in the MAVS adaptor molecule, resulting in MAVS oligomerization and downstream signaling. To reveal the molecular mechanism of MAVS-dependent signaling, we performed a yeast two-hybrid screening and identified zyxin as a protein that binds to MAVS. Zyxin co-immunoprecipitated with MAVS in human cells. A proximity ligation assay showed that zyxin and MAVS partly co-localized on mitochondria. Ectopic expression of zyxin augmented MAVS-mediated IFN-β promoter activation, and knockdown of zyxin (ZYX) attenuated the IFN-β promoter activation. Moreover, ZYX knockdown reduced the expression of type I IFN and an interferon-inducible gene after stimulation with polyI:C or influenza A virus RNA. Interestingly, physical interactions between RLRs and MAVS were abrogated by ZYX knockdown. These observations indicate that zyxin serves as a scaffold for the interactions between RLRs and MAVS.
Allele Age Under Non-Classical Assumptions is Clarified by an Exact Computational Markov Chain Approach
Authors: De Sanctis Bianca , Krukov Ivan , de Koning A. P. Jason 
Published: September 2017

AbstractDetermination of the age of an allele based on its population frequency is a well-studied problem in population genetics, for which a variety of approximations have been proposed. We present a new result that, surprisingly, allows the expectation and variance of allele age to be computed exactly (within machine precision) for any finite absorbing Markov chain model in a matter of seconds. This approach makes none of the classical assumptions (e.g., weak selection, reversibility, infinite sites), exploits modern sparse linear algebra techniques, integrates over all sample paths, and is rapidly computable for Wright-Fisher populations up toNe = 100,000. With this approach, we study the joint effect of recurrent mutation, dominance, and selection, and demonstrate new examples of “selective strolls” where the classical symmetry of allele age with respect to selection is violated by weakly selected alleles that are older than neutral alleles at the same frequency. We also show evidence for a strong age imbalance, where rare deleterious alleles are expected to be substantially older than advantageous alleles observed at the same frequency when population-scaled mutation rates are large. These results highlight the under-appreciated utility of computational methods for the direct analysis of Markov chain models in population genetics.
Cyanobacterial Sfp-type phosphopantetheinyl transferases functionalize carrier proteins of diverse biosynthetic pathways
Authors: Yang Guang , Zhang Yi , Lee Nicholas K. , Cozad Monica A. , Kearney Sara E. , Luesch Hendrik , Ding Yousong 
Published: September 2017

AbstractCyanobacteria produce structurally and functionally diverse polyketides, nonribosomal peptides and their hybrids. Sfp-type phosphopantetheinyl transferases (PPTases) are essential to the production of these compounds via functionalizing carrier proteins (CPs) of biosynthetic megaenzymes. However, cyanobacterial Sfp-type PPTases remain poorly characterized, posing a significant barrier to the exploitation of cyanobacteria for biotechnological and biomedical applications. Herein, we describe the detailed characterization of multiple cyanobacterial Sfp-type PPTases that were rationally selected. Biochemical characterization of these enzymes along with the prototypic enzyme Sfp from Bacillus subtilis demonstrated their varying specificities toward 11 recombinant CPs of different types of biosynthetic pathways from cyanobacterial and Streptomyces strains. Kinetic analysis further indicated that PPTases possess the higher binding affinity and catalytic efficiency toward their cognate CPs in comparison with noncognate substrates. Moreover, when chromosomally replacing the native PPTase gene of Synechocystis sp. PCC6803, two selected cyanobacterial PPTases and Sfp supported the growth of resulted mutants. Cell lysates of the cyanobacterial mutants further functionalized recombinant CP substrates. Collectively, these studies reveal the versatile catalysis of selected cyanobacterial PPTases and provide new tools to synthesize cyanobacterial natural products using in vitro and in vivo synthetic biology approaches.
Ylehd, an epoxide hydrolase with promiscuous haloalkane dehalogenase activity from tropical marine yeast Yarrowia lipolytica is induced upon xenobiotic stress
Authors: Bendigiri Chandrika , Zinjarde Smita , RaviKumar Ameeta 
Published: September 2017

AbstractRecalcitrant environmental pollutants, like bromoorganics and epoxides are hydrolysed with limited substrate specificities by microbial oxygenases, reductases, hydrolases and dehalogenases. Here, we report the identification and characterisation of a protein (XP_504164) from the tropical marine yeast Yarrowia lipolytica NCIM 3589, known to degrade bromoorganics and epoxides. Multiple sequence alignment suggests it belongs to α/β superfamily with conservation of catalytic triad and oxyanion hole motifs. The corresponding gene cloned and protein (Ylehd) expressed in E. coli BL21AI exhibited epoxide hydrolase activity (24 ± 0.7 nmol s−1 mg−1 protein) at pH 8.0 and promiscuous haloalkane dehalogenase (1.5 ± 0.2 nmol s−1 mg−1 protein) at pH 4.5. Recombinant Ylehd catalyses structurally diverse epoxides and bromoorganics with maximum catalytic efficiency (kcat/Km) of 96.56 and 10.1 mM−1 s−1 towards 1,2-Epoxyoctane (EO) and 1-Bromodecane (BD). The expression of Ylehd was highly induced in presence of BD and EO but not in glucose grown cells as studied by immunoblot analyses, q-PCR and activity levels. Immunoelectron microscopy confirmed higher expression in presence of xenobiotics and located it to cytosol. Such inducible nature of Ylehd suggests its physiological role in xenobiotic stress mitigation. This study represents the first functional characterisation of a bifunctional EH/HLD in eukaryotic microbes with broad substrate specificity making it a potential biocatalyst for bioremediation/biosensing of mixed pollutants.
Highly sensitive fiber-optic accelerometer by grating inscription in specific core dip fiber
Authors: Rong Qiangzhou , Guo Tuan , Bao Weijia , Shao Zhihua , Peng Gang-Ding , Qiao Xueguang 
Published: September 2017

AbstractA highly sensitive fiber-optic accelerometer based on detecting the power output of resonances from the core dip is demonstrated. The sensing probe comprises a compact structure, hereby a short section of specific core (with a significant core dip) fiber stub containing a straight fiber Bragg grating is spliced to another single-mode fiber via a core self-alignment process. The femtosecond laser side-illumination technique was utilized to ensure that the grating inscription region is precisely positioned and compact in size. Two well-defined core resonances were achieved in reflection: one originates from the core dip and the other originates from fiber core. The key point is that only one of these two reflective resonances exhibits a high sensitivity to fiber bend (and vibration), whereas the other is immune to it. For low frequency (<10 Hz) and weak vibration excitation (<0.3 m/s2) measurement, the proposed sensor shows a much higher resolution (1.7 × 10−3 m/s2) by simply monitoring the total power output of the high-order core mode reflection. Moreover, the sensor simultaneously provides an inherent power reference to eliminate unwanted power fluctuations from the light source and transmission lines, thus providing a means of evaluating weak seismic wave at low frequency.
An efficient Co3S4/CoP hybrid catalyst for electrocatalytic hydrogen evolution
Authors: Wang Tingting , Wu Liqian , Xu Xiaobing , Sun Yuan , Wang Yuanqi , Zhong Wei , Du Youwei 
Published: September 2017

AbstractThe development of efficient, universal and inexpensive electrocatalysts for hydrogen evolution reaction (HER) is central to the area of sustainable energy conversion. Considering the Co-based sulfides/phosphides have the same catalytic mechanism with the hydrogenases occurring in nature. Here, a new catalyst based on Co3S4/CoP hybrid that is comprised entirely cheap and earthabundant elements, was first synthesized via a two-step method, the Co(CO3)0.5(OH)·0.11H2O precursor was prepared by a hydrothermal method, followed by phosphidation and sulphidation under Ar atmosphere simultaneously. The resulting Co3S4/CoP hybrid material possessed porous core-shell structure with a homogeneous element distribution and large electroactive surface area (~21.04 mF cm−2). More importantly, the nanostructured Co3S4/CoP electrode exhibits excellent HER properties in acid medium with a low onset overpotential of 34 mV, a small Tafel slope of 45 mV dec−1, as well as a large exchange current density of 150 μA cm−2. These results obtained in this study indicate that the Co3S4/CoP hybrid nanorod is promising replacement to the Pt-based catalysts for H2 production. Moreover, the synthetic method presented in this work can provide an efficient way to synthesis other nanocomposites.
Mapping diffuse interstellar bands in the local ISM on small scales via MUSE 3D spectroscopy
Authors: Wendt Martin , Husser Tim-Oliver , Kamann Sebastian , Monreal-Ibero Ana , Richter Philipp , Brinchmann Jarle , Dreizler Stefan , Weilbacher Peter M. , Wisotzki Lutz 
Published: September 2017

Context. We map the interstellar medium (ISM) including the diffuse interstellar bands (DIBs) in absorption toward the globular cluster NGC 6397 using VLT/MUSE. Assuming the absorbers are located at the rim of the Local Bubble we trace structures on the order of mpc (milliparsec, a few thousand AU).
Aims. We aimed to demonstrate the feasibility to map variations of DIBs on small scales with MUSE. The sightlines defined by binned stellar spectra are separated by only a few arcseconds and we probe the absorption within a physically connected region.
Methods. This analysis utilized the fitting residuals of individual stellar spectra of NGC 6397 member stars and analyzed lines from neutral species and several DIBs in Voronoi-binned composite spectra with high signal-to-noise ratio (S/N).
Results. This pilot study demonstrates the power of MUSE for mapping the local ISM on very small scales which provides a new window for ISM observations. We detect small scale variations in Na I and K I as well as in several DIBs within few arcseconds, or mpc with regard to the Local Bubble. We verify the suitability of the MUSE 3D spectrograph for such measurements and gain new insights by probing a single physical absorber with multiple sight lines.
Umsetzung der Nationalen VersorgungsLeitlinie (NVL) zur Therapie des Diabetes mellitus Typ 2 in diabetologischen Schwerpunktpraxen
Authors: Marahrens Lydia , Röck Daniel , Ziemssen Tjalf , Kern Raimar , Ziemssen Focke , Fritsche Andreas 
Published: September 2017

Zusammenfassung
Hintergrund Die Nationale VersorgungsLeitlinie (NVL) zur Therapie des Diabetes mellitus Typ 2 sieht eine Therapieintensivierung zur Blutzuckersenkung in vier Therapiestufen vor. Bisher gibt es kaum Daten, wie die NVL Patienten-individuell implementiert wird.
Methodik In der DiabCheckOCTplus-Studie wurden 810 Patienten in diabetologischen Schwerpunktpraxen untersucht. Im internistischen Teil des Studienprotokolls wurden die Angaben der elektronischen Patientenkartei von unabhängiger Seite analysiert und eine Klassifizierung in die Stufenleiter des NVL-Therapiealgorithmus für jeden einzelnen Patienten mit Typ 2 Diabetes vorgenommen (NCT02 311 504).
Ergebnisse 81 % der Patienten in Therapiestufe 2 erhielten Metformin, 48 % in Therapiestufe 3 die Pharmaka-Zweifachkombination Metformin plus DPP4-Inhibitor und 41 % in Therapiestufe 4 die intensivierte Insulintherapie mit Metformin.Der Gesamtanteil lag 2014 für Metformin bei 67 %, für DPP4-Inhibitoren bei 21 % und für Sulfonylharnstoffe bei nur 10 %. Die Diabetesdauer stieg mit den NVL-Stufen deutlich an. Nach 3 Jahren Diabetesdauer erhielten 55 % mehr als 1 Antidiabetikum. Nach 9 Jahren wurde die Hälfte aller Patienten in Stufe 4 mit komplexen Insulinstrategien behandelt, nach 25 Jahren nahezu alle Patienten.
Schlussfolgerung Die Therapie der diabetischen Sekundärversorgung entsprach in einem hohen Maß den nationalen und internationalen Leitlinien. Entsprechende Daten aus der hausärztlichen Versorgung wären von Interesse. Die Therapiestufe korrelierte bei den untersuchten Patienten eng mit der Diabetesdauer; der Parameter könnte sich daher zur Kommunikation des Risikoprofils eignen.
Bupleurum chinense Roots: a Bioactivity-Guided Approach toward Saponin-Type NF-κB Inhibitors
Authors: Liu Xin , Latkolik Simone , Atanasov Atanas , Kunert Olaf , Pferschy-Wenzig Eva-Maria , Heiss Elke , Malainer Clemens , Schinkovitz Andreas , Kollroser Manfred , Dirsch Verena , Bauer Rudolf 
Published: September 2017

AbstractThe roots of Bupleurum chinense have a long history in traditional medicine to treat infectious diseases and inflammatory disorders. Two major compounds, saikosaponins A and D, were reported to exert potent anti-inflammatory activity by inhibiting NF-κB. In the present study, we isolated new saikosaponin analogues from the roots of B. chinese interfering with NF-κB activity in vitro. The methanol-soluble fraction of the dichloromethane extract of Radix Bupleuri was subjected to activity-guided isolation yielding 18 compounds, including triterpenoids and polyacetylenes. Their structures were determined by spectroscopic methods as saikogenin D (1), prosaikogenin D (2), saikosaponins B2 (3), W (4), B1 (5), Y (6), D (7), A (8), E (9), B4 (10), B3 (11), and T (12), saikodiyne A (13), D (14), E (15) and F (16), falcarindiol (17), and 1-linoleoyl-sn-glycero-3-phosphorylcholine (18). Among them, 4, 15, and 16 are new compounds, whereas 6, previously described as a semi-synthetic compound, is isolated from a natural source for the first time, and 13–17 are the first reports of polyacetylenes from this plant. Nine saponins/triterpenoids were tested for inhibition of NF-κB signaling in a cell-based NF-κB-dependent luciferase reporter gene model in vitro. Five of them (1, 2, 4, 6, and 8) showed strong (> 50%, at 30 µM) NF-κB inhibition, but also varying degrees of cytotoxicity, with compounds 1 and 4 (showing no significant cytotoxicity) presenting IC50 values of 14.0 µM and 14.1 µM in the cell-based assay, respectively.
Network of microbial and antibiotic interactions drive colonization and infection with multidrug-resistant organisms
Authors: Wang Joyce , Foxman Betsy , Mody Lona , Snitkin Evan S. 
Published: September 2017

Significance
The proliferation of multidrug-resistant organisms (MDROs) is one of the world’s most pressing public health problems. Despite great efforts to prevent MDRO spread in healthcare facilities, antibiotic-resistant infections remain a significant threat. We hypothesized that current infection prevention initiatives are hindered by their targeting of individual MDROs; neglecting the fact that healthcare institutions have multiple circulating MDRO species whose propagation is driven by competing risk factors. We tested this hypothesis by identifying risk factors for the spread of multiple MDROs among nursing home residents and unraveled a complex network of interactions between antibiotic exposure and microbial factors. Our results indicate that interactions among MDROs and underlying drivers must be considered simultaneously to design optimal strategies to reduce MDRO propagation.
Modeling Parkinson’s disease pathology by combination of fibril seeds and α-synuclein overexpression in the rat brain
Authors: Thakur Poonam , Breger Ludivine S. , Lundblad Martin , Wan Oi Wan , Mattsson Bengt , Luk Kelvin C. , Lee Virginia M. Y. , Trojanowski John Q. , Björklund Anders 
Published: September 2017

Significance
Parkinson’s disease is the most common neurodegenerative movement disorder, but its faithful modeling in animals has been challenging. Animal models based on overexpression of the disease-causing protein, α-synuclein (α-syn), are useful for studies of disease pathogenesis but rely on unphysiologically high levels of α-syn. Here, we present a model that combines preformed human α-syn fibrils and adenoassociated virus (AAV)-mediated overexpression of human α-syn, given in doses that, by themselves, do not cause any acute neurodegeneration. This combined approach reproduces several cardinal features of the human disease, including Lewy-like synucleinopathy, neuroinflammation, and progressive dopaminergic cell loss. The short time span and distinct sequence of pathological and degenerative changes make it attractive as an experimental model for studies aimed at neuroprotection and disease modification.
The social space, the symbolic space and masculine domination: the gendered correspondence between class and lifestyles in the UK
Authors: Atkinson Will 
Published: September 2017

ABSTRACT
There have been countless efforts to test and ‘update’ Pierre Bourdieu's thesis that there is a correspondence between the space of social positions and the space of lifestyles. The best known of these targeting the UK are the Cultural Capital and Social Exclusion project and, more recently, the Great British Class Survey, but their conceptual and methodological limitations mean their findings are questionable and hinder closer investigation of an oft-sidelined piece of the puzzle one of the projects specifically highlighted: the significance of gender in structuring taste. Drawing on the 2012 wave of the British Cohort Study, which included a battery of questions on cultural consumption, and deploying a logic and measure of class closer to Bourdieu's own, I thus seek to offer an alternative examination of not only the nature and degree of correspondence between the social space and lifestyles but its entwinement with masculinity and femininity.
Secure detection in quantum key distribution by real-time calibration of receiver
Authors: Marøy Øystein , Makarov Vadim , Skaar Johannes 
Published: September 2017

Abstract
The single-photon detectionefficiency of the detector unit is crucial for the security of common quantum key distribution protocols like Bennett-Brassard 1984 (BB84). A low value for the efficiency indicates a possible eavesdropping attack that exploits the photon receiver’s imperfections. We present a method for estimating the detection efficiency, and calculate the corresponding secure key generation rate. The estimation is done by testing gated detectors using a randomly activated photon source inside the receiver unit. This estimate gives a secure rate for any detector with non-unity single-photon detection efficiency, both inherit or due to blinding. By adding extra optical components to the receiver, we make sure that the key is extracted from photon states for which our estimate is valid. The result is a quantum key distribution scheme that is secure against any attack that exploits detector imperfections.
Identification and visualization of differential isoform expression in RNA-seq time series
Authors: Nueda María José , Martorell-Marugan Jordi , Martí Cristina , Tarazona Sonia , Conesa Ana 
Published: September 2017

Abstract

Motivation
As sequencing technologies improve their capacity to detect distinct transcripts of the same gene and to address complex experimental designs such as longitudinal studies, there is a need to develop statistical methods for the analysis of isoform expression changes in time series data.

Results
Iso-maSigPro is a new functionality of the R package maSigPro for transcriptomics time series data analysis. Iso-maSigPro identifies genes with a differential isoform usage across time. The package also includes new clustering and visualization functions that allow grouping of genes with similar expression patterns at the isoform level, as well as those genes with a shift in major expressed isoform.

Availability and implementation
The package is freely available under the LGPL license from the Bioconductor web site.

Supplementary information
Supplementary data are available at Bioinformatics online.
Update: Topical Antimicrobial Agents for Chronic Wounds
Authors: Sibbald R. Gary , Elliott James A. , Verma Luvneed , Brandon Alisa , Persaud Reneeka , Ayello Elizabeth A. 
Published: September 2017

GENERAL PURPOSE:
To provide information on the use of topical antimicrobial agents for the treatment of chronic wounds.

TARGET AUDIENCE:
This continuing education activity is intended for physicians, physician assistants, nurse practitioners, and nurses with an interest in skin and wound care.

LEARNING OBJECTIVES/OUTCOMES:
After participating in this educational activity, the participant should be better able to:
1. Examine features of wounds and wound healing as well as the purpose of specific antimicrobial agents.
2. Identify potential therapeutic and adverse effects of specific topical antimicrobial agents for the treatment of chronic wounds.

ABSTRACT
Bacteria can delay or prevent healing in the surface compartment of a chronic wound or invade the deep and surrounding structures. This article focuses on the superficial compartment and the appropriate use of topical antimicrobial therapies. The authors have reviewed the published evidence for the last 5 years (2012–2017) and extrapolated findings to clinical practice with critical appraisal and synthesis of the recent literature with expert opinion, patient-centered concerns, and healthcare systems perspectives. Summary evidence tables for commonly used topical antimicrobials are included.
Physicians’ Decision-making When Implementing Buprenorphine With New Patients: Conjoint Analyses of Data From a Cohort of Current Prescribers
Authors: Knudsen Hannah K. , Lofwall Michelle R. , Walsh Sharon L. , Havens Jennifer R. , Studts Jamie L. 
Published: September 2017

Objectives:
Few studies have considered how providers make decisions to prescribe buprenorphine to new patients with opioid use disorder. This study examined the relative importance of patients’ clinical, financial, and social characteristics on physicians’ decision-making related to willingness to prescribe buprenorphine to new patients and the number of weeks of medication that they are willing to initially prescribe after induction.

Methods:
A national sample of 1174 current prescribers was surveyed. Respondents rated willingness to prescribe on a 0 to 10 scale and indicated the number of weeks of medication (ranging from none to >4 weeks) for 20 hypothetical patients. Conjoint analysis estimated relative importance scores and part-worth utilities for these 2 outcome ratings.

Results:
The mean rating for willingness to prescribe was 5.52 (SD 2.47), indicating a moderate willingness to implement buprenorphine treatment. The mean prescription length was 2.06 (SD 1.34), which corresponds to 1 week of medication. For both ratings, the largest importance scores were for other risky substance use, method of payment, and spousal involvement in treatment. Illicit benzodiazepine use, having Medicaid insurance to pay for the office visit, and having an opioid-using spouse were negatively associated with these outcome ratings, whereas a history of no risky alcohol or benzodiazepine use, cash payment, and having an abstinent spouse were positively associated with both ratings.

Conclusions:
Reticence to prescribe to individuals using an illicit benzodiazepine and individuals with a drug-using spouse aligns with practice guidelines. However, reluctance to prescribe to patients with Medicaid may hamper efforts to expand access to treatment.