bluuebunny/crossref_metadata_2025_split huggingface dataset:
Removal of the C6 vaccinia virus interferon-β inhibitor in the hepatitis C vaccine candidate MVA-HCV elicited in mice high immunogenicity in spite of reduced host gene expression
Authors: Marín María Q. , Pérez Patricia , Gómez Carmen E. , Sorzano Carlos Óscar S. , Esteban Mariano , García-Arriaza Juan 
Published: May 2018

ABSTRACTHepatitis C virus (HCV) represents a major global health problem for which a vaccine is not available. MVA-HCV is a unique HCV vaccine candidate based in the modified vaccinia virus Ankara (MVA) vector expressing the nearly full-length genome of HCV genotype 1a that elicits broad and polyfunctional CD8+T-cell responses in mice. With the aim to improve the immune response of MVA-HCV and due to the importance of interferon (IFN) in HCV infection, we deleted in MVA-HCV the vaccinia virus (VACV)C6Lgene, encoding an inhibitor of IFN-β that prevents activation of the transcription factors IRF3 and IRF7. The resulting vaccine candidate (MVA-HCV ΔC6L) expresses all HCV antigens and deletion ofC6Lhad no effect on viral growth in permissive chicken cells. In human monocyte-derived dendritic cells, infection with MVA-HCV ΔC6L triggered severe down-regulation of IFN-β, IFN-β-induced genes and cytokines similarly to MVA-HCV, as defined by real-time PCR and microarray analysis. In infected mice both vectors had a similar profile of recruited immune cells and induced comparable levels of adaptive and memory HCV-specific CD8+T-cells, mainly against p7+NS2 and NS3 HCV proteins, with a T cell effector memory (TEM) phenotype. Furthermore, antibodies against E2 were also induced. Overall, our findings showed that while these vectors had a profound inhibitory effect on gene expression of the host, they strongly elicited CD8+T cell and humoral responses against HCV antigens. These observations add support to the consideration of these vectors as potential vaccine candidates against HCV.IMPORTANCEHepatitis C virus represents a global health problem with 71 million of people infected worldwide. While direct-acting antivirals agents can cure hepatitis C virus infection in most of patients, their high cost and the emergence of drug resistant variants make them not a feasible and affordable strategy to eradicate the virus. Therefore, a vaccine is an urgent goal that requires efforts in understanding the correlates of protection for hepatitis C virus clearance. Poxvirus vectors, in particular the attenuated modified vaccinia virus Ankara, are ideal as vaccine candidates due to their ability to induce both T and B cell immune responses against heterologous antigens and protection against a wide spectrum of pathogens. Here we describe the generation, genetics and immunogenicity elicited by MVA-HCV ΔC6L, a novel vaccine candidate for hepatitis C virus that expresses nearly all of hepatitis C proteins but lacks an IFN-β inhibitor, the C6 vaccinia virus protein.
Outbreak of Glomerulonephritis byStreptococcus zooepidemicusSzPHV5 type, in Monte Santo de Minas, Minas Gerais, Brazil
Authors: Torres Rosângela S.L.A. , Santos Talita Z. , Bernardes Andre F. L. , Soares Patricia A. , Soares Ana C. C. , Dias Ricardo S. 
Published: May 2018

ABSTRACTStreptococcus zooepidemicusis an emerging and opportunistic zoonotic pathogen, which playsan important role in the development of severe and life-threatening diseases and potentially capable of triggering large glomerulonephritis outbreaks. Between December 2012 and February 2013, 175 cases of glomerulonephritis were confirmed in the town of Monte Santo de Minas / MG / Brazil. During the outbreak, 19 isolates ofS. zooepidemicuswere recovered: one from ice cream, two from the oropharynx of food handlers and 16 from patients affected by acute post streptococcal glomerulonephritis (APSGN). AllS. zooepidemicusinvolved in the outbreak amplified the same sequence of the hypervariable region of the SzP protein (SzPHV5) and presented indistinguishable banding patterns with high similarity (> 99%) by rep-PCR technique. Inspection programs on the milk supply chain should be strengthened and continuously encouraged so that consumers’ health is preserved.
Reactive Initiation Training is more effective than Shuttle Run to improve the on-court agility of novice badminton players
Authors: Dong Minkai , Lyu Jidong , Hart Thomas , Zhu Qin 
Published: May 2018

AbstractPurposeDespite its well-known importance in sports, agility is ambiguously defined and lack of research. Shuttle Run (SR) is commonly used to improve the on-court agility of badminton players. Reactive Initiation Training (RIT) contrasts SR in that it only demands rapid generation of initiation step toward the direction of shuttlecock. The current study compared SR with RIT to determine which one is more effective for improving on-court agility of novice badminton players.Method20 novice badminton players were split in half to receive either RIT or SR on court for five days. Before and after training, participants were assessed on their ability to intercept the shuttlecocks randomly thrown by a coach to six corners of the court with and without visual occlusion of the coach. All trials of interception were recorded for video analysis of initiation time, running time and total time.ResultsThe mean total times were greater with visual occlusion and varied systematically with the position of interception. Both training methods shortened the mean running time, however, only RIT additionally reduced the initiation time and its proportion on those time-consuming positions in the occluded condition.ConclusionRIT is more effective than SR to improve the on-court agility of novice badminton players.
Cofilin-actin rod formation in neuronal processes after brain ischemia
Authors: Won Seok Joon , Minnella Angela M. , Wu Long , Eun Claire H. , Rome Eric , Shaw Alisa E. , Herson Paco S. , Bamburg James R. , Swanson Raymond A. 
Published: May 2018

AbstractFunctional impairment after brain ischemia results in part from loss of neuronal spines and dendrites, independent of neuronal death. Cofilin-actin rods are covalently linked aggregates of colfilin-1 and actin that form in neuronal processes (neurites) under conditions of ATP depletion and oxidative stress, and which cause neurite degeneration if not disassembled. ATP depletion and oxidative stress occur with differing severity, duration, and time course in different ischemic conditions. Here we evaluated four mouse models of brain ischemia to define the conditions that drive formation of cofilin-actin rods. Three of the models provide early reperfusion: transient middle cerebral artery occlusion (MCAo), transient bilateral common carotid occlusion (CCAo), and cardiac arrest / cardiopulmonary resuscitation (CA/CPR). Early reperfusion restores ATP generating capacity, but also induces oxidative stress. The fourth model, photothrombotic cortical infarction, does not provide reperfusion. Cofilin-actin rods were formed in each of these models, but with differing patterns. Where acute reperfusion occurred, rod formation was maximal within 4 hours after reperfusion. Where infarction occurred, rods continued to form for at least 24 hours after ischemic onset, and extended into the adjacent non-ischemic tissue. Interventions that limit cofilin-actin rod formation may help to preserve integrity of neuronal processes in permanent ischemia.
Animal models with group-specific additive genetic variances: extending genetic group models
Authors: Muff Stefanie , Niskanen Alina K. , Saatoglu Dilan , Keller Lukas F. , Jensen Henrik 
Published: May 2018

Abstract1.Theanimal modelis a key tool in quantitative genetics and has been used extensively to estimate fundamental parameters, such as additive genetic variance, heritability, or inbreeding effects. An implicit assumption of animal models is that all founder individuals derive from a single population. This assumption is commonly violated, for instance in cross-bred livestock breeds, when an observed population receive immigrants, or when a meta-population is split into genetically differentiated subpopulations. Ignoring genetic differences among different source populations of founders may lead to biased parameter estimates, in particular for the additive genetic variance.2.To avoid such biases, genetic group models, extensions to the animal model that account for the presence of more than one genetic group, have been proposed. As a key limitation, the method to date only allows that the breeding values differ in their means, but not in their variances among the groups. Methodology previously proposed to account for group-specific variances included terms for segregation variance, which rendered the models infeasibly complex for application to most real study systems.3.Here we explain why segregation variances are often negligible when analyzing the complex polygenic traits that are frequently the focus of evolutionary ecologists and animal breeders. Based on this we suggest an extension of the animal model that permits estimation of group-specific additive genetic variances. This is achieved by employing group-specific relatedness matrices for the breeding value components attributable to different genetic groups. We derive these matrices by decomposing the full relatedness matrix via the generalized Cholesky decomposition, and by scaling the respective matrix components for each group. To this end, we propose a computationally convenient approximation for the matrix component that encodes for the Mendelian sampling variance. Although convenient, this approximation is not critical.4.Simulations and an example from an insular meta-population of house sparrows in Norway with three genetic groups illustrate that the method is successful in estimating group-specific additive genetic variances and that segregation variances are indeed negligible in the empirical example.5.Quantifying differences in additive genetic variance within and among populations is of major biological interest in ecology, evolution, and animal and plant breeding. The proposed method allows to estimate such differences for subpopulations that form a connected meta-population, which may also be useful to study temporal or spatial variation of additive genetic variance.
Targeting light-gated chloride channels to neuronal somatodendritic domain reduces their excitatory effect in the axon
Authors: Messier Jessica E. , Chen Hongmei , Cai Zhao-Lin , Xue Mingshan 
Published: May 2018

AbstractLight-gated chloride channels are emerging as promising optogenetic tools for inhibition of neural activity. However, their effects depend on the transmembrane chloride electrochemical gradient and may be complex due to the heterogeneity of this gradient in different developmental stages, neuronal types, and subcellular compartments. Here we characterized a light-gated chloride channel, GtACR2, in mouse cortical neurons. We found that GtACR2 activation inhibited the soma, but unexpectedly depolarized the presynaptic terminals resulting in neurotransmitter release. Other light-gated chloride channels had similar effects. Reducing the chloride concentrations in the axon and presynaptic terminals diminished the GtACR2-induced neurotransmitter release, indicating an excitatory effect of chloride channels in these compartments. A novel hybrid somatodendritic targeting motif reduced the GtACR2-induced neurotransmitter release while enhancing the somatic photocurrents. Our results highlight the necessity of precisely determining the effects of light-gated chloride channels under specific experimental conditions and provide a much-improved light-gated chloride channel for optogenetic inhibition.
GoFish: A Streamlined Environmental DNA Presence/Absence Assay for Marine Vertebrates
Authors: Stoeckle Mark Y. , Mishu Mithun Das , Charlop-Powers Zachary 
Published: May 2018

AbstractHere we describe GoFish, a streamlined environmental DNA (eDNA) presence/absence assay. The assay amplifies a 12S segment with broad-range vertebrate primers, followed by nested PCR with M13-tailed, species-specific primers. Sanger sequencing confirms positives detected by gel electrophoresis. We first obtained 12S sequences from 77 fish specimens representing 36 northwestern Atlantic taxa not well documented in GenBank. Using the newly obtained and published 12S records, we designed GoFish assays for 11 bony fish species common in the lower Hudson River estuary and tested seasonal abundance and habitat preference at two sites. Additional assays detected nine cartilaginous fish species and a marine mammal, bottlenose dolphin, in southern New York Bight. GoFish sensitivity was equivalent to Illumina MiSeq metabarcoding. Unlike quantitative PCR (qPCR), GoFish does not require tissues of target and related species for assay development and a basic thermal cycler is sufficient. Unlike Illumina metabarcoding, indexing and batching samples are unnecessary and advanced bioinformatics expertise is not needed. The assay can be carried out from water collection to result in three days. The main limitations so far are species with shared target sequences and inconsistent amplification of rarer eDNAs. We think this approach will be a useful addition to current eDNA methods when analyzing presence/absence of known species, when turnaround time is important, and in educational settings.
Grape polyphenols reduce gut-localized reactive oxygen species associated with the development of metabolic syndrome in mice
Authors: Kuhn Peter , Kalariya Hetalben M. , Poulev Alexander , Ribnicky David M. , Jaja-Chimedza Asha , Roopchand Diana E. , Raskin Ilya 
Published: May 2018

AbstractHigh-fat diet (HFD)-induced leaky gut syndrome combined with low-grade inflammation increase reactive oxygen species (ROS) in the intestine and may contribute to dysbiosis and metabolic syndrome (MetS). Poorly bioavailable and only partially metabolizable dietary polyphenols, such as proanthocyanidins (PACs), may exert their beneficial effects on metabolic health by scavenging intestinal ROS. To test this hypothesis, we developed and validated a novel, noninvasive, in situ method for visualizing intestinal ROS using orally administered ROS-sensitive indocyanine green (ICG) dye. C57BL/6J mice fed HFD for 10 weeks accumulated high levels of intestinal ROS compared to mice fed low-fat diet (LFD). Oral administration of poorly bioavailable grape polyphenol extract (GPE) and β-carotene decreased HFD-induced ROS in the gut to levels comparable to LFD-fed mice, while administration of more bioavailable dietary antioxidants (α- lipoic acid, vitamin C, vitamin E) did not. Forty percent of administered GPE antioxidant activity was measured in feces collected over 24 h, confirming poor bioavailability and persistence in the gut. The bloom of beneficial anaerobic gut bacteria, such asAkkermansia muciniphila, associated with improved metabolic status in rodents and humans may be directly linked to protective antioxidant activity of some dietary components. These findings suggest a possible mechanistic explanation for the beneficial effects of poorly bioavailable polyphenols on metabolic health.
Shorter telomere length is associated with a more recent diagnosis of coeliac disease
Authors: Goorkiz Pierre , Hearn Nerissa L , van der Kooi Saskia , Chiu Christine L , Lind Joanne M 
Published: May 2018

AbstractBackgroundCoeliac disease (CD) is an autoimmune disease that causes an inappropriate inflammatory immune response to dietary gluten. Telomere length is a marker of biological ageing and is reduced in several autoimmune conditions. This observational study measured salivary telomere length (TL) in gluten-free diet (GFD) treated CD individuals to determine if CD, and length of time on a GFD, is associated with salivary TL.MethodsClinical and demographic information was collected from CD individuals currently treated with a GFD and healthy non-affected controls. Only participants aged under 35 years at recruitment were included. Relative telomere length was measured using quantitative PCR in oral mucosa collected from saliva. Linear regression was used to determine whether salivary TL was associated with CD, or length of time on a GFD, adjusting for age and sex.ResultsThis study included 79 participants, 52 GFD-treated CD and 27 non-affected controls. No significant difference in salivary TL between individuals with treated CD and controls was found. Within CD individuals, salivary TL was associated with length of time on a GFD, with individuals who started a GFD ≤3 years ago having shorter salivary TL compared to those who started a GFD > 3 years ago (0.37±0.05 vs 0.50±0.04; p=0.002).ConclusionOur findings indicate that salivary TL shorten while CD is untreated, however following treatment on a GFD, they appear to recover to those seen in unaffected controls. This highlights the importance of early diagnosis and initiation of GFD to minimise mucosal damage and telomere shortening, to enable TL to recover.
MMOD-induced structural changes of hydroxylase in soluble methane monooxygenase
Authors: Kim Hanseong , An Sojin , Park Yeo Reum , Jang Hara , Park Sang Ho , Lee Seung Jae , Cho Uhn-Soo 
Published: May 2018

SummarySoluble methane monooxygenase in methanotrophs converts methane to methanol under ambient conditions1-3. The maximum catalytic activity of hydroxylase (MMOH) is achieved via interplay of its regulatory protein (MMOB) and reductase4-6. An additional auxiliary protein, MMOD, is believed to function as an inhibitor of the catalytic activity of MMOH; however, the mechanism of its action remains unknown7,8. Herein, we report the crystal structure of MMOH–MMOD complex fromMethylosinus sporiumstrain 5 (2.6 Å), which illustrates that two molecules of MMOD associate symmetrically with the canyon region of MMOH in a manner similar to MMOB, indicating that MMOD competes with MMOB for MMOH recognition. Further, MMOD binding disrupts the geometry of the di-iron centre and opens the substrate access channel. Notably, the electron density of 1,6-hexanediol at the substrate access channel mimics products of sMMO in hydrocarbon oxidation. The crystal structure of MMOH–MMOD unravels the inhibitory mechanism by which MMOD suppresses the MMOH catalytic activity, and reveals how hydrocarbon substrates/products access to the di-iron centre.
High Precision Detection of Rare Splice Isoforms Using Multiplexed Primer Extension Sequencing
Authors: Xu Hansen , Fair Benjamin J. , Dwyer Zach , Gildea Michael , Pleiss Jeffrey A. 
Published: May 2018

ABSTRACTTargeted RNA-sequencing aims to focus coverage on areas of interest that are inadequately sampled in standard RNA-sequencing experiments. Here we present a novel approach for targeted RNA-sequencing that uses complex pools of reverse transcription primers to enable sequencing enrichment at user-selected locations across the genome. We demonstrate this approach by targeting hundreds to thousands of pre-mRNA splice junctions, revealing high-precision detection of splice isoforms, including rare pre-mRNA splicing intermediates.
Ancestral resurrection reveals mechanisms of kinase regulatory evolution
Authors: Sang Dajun , Pinglay Sudarshan , Vatansever Sezen , Lou Hua Jane , Turk Benjamin , Gümüş Zeynep H. , Holt Liam J. 
Published: May 2018

AbstractProtein kinases are crucial to coordinate cellular decisions and therefore their activities are strictly regulated. We used ancestral resurrection to uncover a mechanism underlying the evolution of kinase control within the ERK family of Mitogen Activated Protein Kinases (MAPKs). Kinase activities switched from high to low intrinsic autophosphorylation at the transition from the ancestors of ERKs1-5 and ERKs1-2. A shortening of the loop between β3-αC and a mutation in the gatekeeper residue drove this transition. Molecular dynamics simulations suggested that the change in the β3-αC loop length affected kinase cis-autophosphorylation by altering the positioning of catalytic residues and by allowing greater flexibility in the L16 kinase loop. This latter effect likely synergizes with the known role of gatekeeper mutations in facilitating domain closure and thus kinase activation, providing a rationale for the synergy between the two evolutionary mutations. Our results shed light on the evolutionary mechanisms that led to tight regulation of a central kinase in development and disease.
Identifying Parkinson’s disease and parkinsonism cases using routinely-collected healthcare data: a systematic review
Authors: Harding Zoe , Wilkinson Tim , Stevenson Anna , Horrocks Sophie , Ly Amanda , Schnier Christian , Breen David P , Rannikmäe Kristiina , Sudlow Cathie LM ,   on behalf of Dementias Platform UK
Published: May 2018

AbstractBackgroundPopulation-based, prospective studies can provide important insights into Parkinson’s disease (PD) and other parkinsonian disorders. Participant follow-up in such studies is often achieved through linkage to routinely-collected healthcare datasets. We systematically reviewed the published literature on the accuracy of these datasets for this purpose.MethodsWe searched four electronic databases for published studies that compared PD and parkinsonism cases identified using routinely-collected data to a reference standard. We extracted study characteristics and two accuracy measures: positive predictive value (PPV) and/or sensitivity.ResultsWe identified 18 articles, resulting in 27 measures of PPV and 14 of sensitivity. For PD, PPVs ranged from 56-90% in hospital datasets, 53-87% in prescription datasets, 81-90% in primary care datasets and was 67% in mortality datasets. Combining diagnostic and medication codes increased PPV. For parkinsonism, PPVs ranged from 36-88% in hospital datasets, 40-74% in prescription datasets, and was 94% in mortality datasets. Sensitivities ranged from 15-73% in single datasets for PD and 43-63% in single datasets for parkinsonism.ConclusionsIn many settings, routinely-collected datasets generate good PPVs and reasonable sensitivities for identifying PD and parkinsonism cases. Further research is warranted to investigate primary care and medication datasets, and to develop algorithms that balance a high PPV with acceptable sensitivity.
Experimental and theoretical study ofMatricaria recutitachamomile extract as corrosion inhibitor for steel in neutral chloride media
Authors: Nasr Khaoula , Fedel Michele , Essalah Khaled , Deflorian Flavio , Souissi Nebil 
Published: May 2018

PurposeThis study aims to investigate the inhibition performance of an aqueous extract ofMatricaria recutitachamomile on the corrosion of S235JR steel in 0.5 M NaCl by using electrochemical impedance spectroscopy (EIS) and polarization measurements.Design/methodology/approachThe inhibition performance was investigated using EIS and polarization measurements. Surface analysis demonstrates the presence of a protective layer on the steel surface in the presence of the extract. Quantum chemical parameters calculated for the molecules contained in the aqueous extract are interpreted to predict the corrosion inhibition efficiency of the considered extract.FindingsThe inhibition efficiency of chamomile aqueous extract for S235JR steel increases with increasing amounts of plant concentration and with an increase in the immersion time. The optimal inhibition efficiency of chamomile extract, 98.90 per cent, was achieved for S235JR steel when immersed in 15 per cent v/v of extract concentration for 2 h. The surface analysis in the absence and presence of the chamomile extract confirmed the formation of a protective layer on steel surface. The quantum chemical calculations allowed to explain the great inhibition efficiency values by interpreting the calculated quantum parameters.Originality/valueThis is the first study carrying out an experimental and theoretical investigation onM. recutitachamomile as a green corrosion inhibitor, with interesting potential industrial applications.