bluuebunny/crossref_metadata_2025_split huggingface dataset:
Obesity/ Type II Diabetes Promotes Function-limiting Changes in Flexor Tendon Extracellular Matrix that are not Reversed by Restoring Normal Metabolic Function
Authors: Studentsova Valentina , Mora Keshia M. , Glasner Melissa F. , Buckley Mark R. , Loiselle Alayna E. 
Published: May 2017

AbstractType II Diabetes (T2DM) negatively alters baseline tendon function, including decreased range of motion and mechanical properties; however, the biological mechanisms that promote diabetic tendinopathy are unknown. To facilitate identification of therapeutic targets we developed a novel murine model of diabetic tendinopathy. Mice fed a High Fat Diet (HFD) developed diet induced obesity and T2DM. Obesity/ T2DM resulted in progressive impairments in tendon gliding function and mechanical properties, relative to mice fed a Low Fat Diet (LFD), as well as a decrease in collagen fibril diameter by transmission electron microscopy. We then determined if restoration of normal metabolic function, by switching mice from HFD to LFD, is sufficient to halt the pathological changes in tendon due to obesity/T2DM. However, switching from a HFD to LFD resulted in greater impairments in tendon gliding function than mice maintained on a HFD. Mechanistically, IRβ signaling is decreased in obese/T2DM murine tendons, suggesting altered IRβ signaling as a driver of diabetic tendinopathy. However, knock-down of IRβ expression in S100a4-lineage cells (IRcKOS100a4) was not sufficient to induce diabetic tendinopathy as no impairments in tendon gliding function or mechanical properties were observed in IRcKOS100a4relative to WT. Collectively, these data define a murine model of diabetic tendinopathy, and demonstrate that tendon-specific, rather than systemic treatment approaches are needed.
Functional preference for object sounds but not for voices in the occipito-temporal cortex of early blind individuals
Authors: Dormal Giulia , Pelland Maxime , Rezk Mohamed , Yakobov Esther , Lepore Franco , Collignon Olivier 
Published: May 2017

AbstractSounds activate occipital regions in early blind individuals. How different sound categories map onto specific regions of the occipital cortex remains however debated. We used fMRI to characterize brain responses of early blind and sighted individuals to familiar object sounds, human voices and their respective low-level control sounds. Sighted participants were additionally tested when viewing pictures of faces, objects and phase-scrambled control pictures. In both early blind and sighted, a double dissociation was evidenced in bilateral auditory cortices between responses to voices and object sounds: voices elicited categorical responses in bilateral superior temporal sulci while object sounds elicited categorical responses along the lateral fissure bilaterally, including the primary auditory cortex and planum temporale. Outside of the auditory regions, object sounds additionally elicited categorical responses in left lateral and ventral occipito-temporal regions in both groups. These regions also showed response preference for images of objects in the sighted, thus suggesting a functional specialization in these regions that is independent of sensory input and visual experience. Between-group comparisons revealed that only in the blind group, categorical responses to object sounds extended more posteriorly into the occipital cortex. Functional connectivity analyses evidenced a selective increase in the functional coupling between these reorganized regions and regions of the ventral occipito-temporal cortex in the early blind. In contrast, vocal sounds did not elicit preferential responses in the occipital cortex in either group. Nevertheless, enhanced voice-selective connectivity between the left temporal voice area and the right fusiform gyrus were found in the blind. Altogether, these findings suggest that separate auditory categories are not equipotent in driving selective auditory recruitment of occipito-temporal regions in the absence of developmental vision, highlighting domain-region constraints on the expression of crossmodal plasticity.
High-throughput laboratory evolution ofEscherichia coliunder multiple stress environments
Authors: Horinouchi Takaaki , Suzuki Shingo , Kotani Hazuki , Tanabe Kumi , Sakata Natsue , Shimizu Hiroshi , Furusawa Chikara 
Published: May 2017

AbstractBacterial cells have a remarkable capacity to adapt and to evolve to environmental changes. Although many mutations contributing to adaptive evolution have been identified, the relationship between the mutations and the phenotypic changes responsible for fitness gain has yet to be fully elucidated. For a better understanding of phenotype-genotype relationship in evolutionary dynamics, we performed high-throughput laboratory evolution ofEscherichia coliunder various stress conditions using an automated culture system. One measure of phenotype, transcriptome analysis, revealed that the expression changes which occurred during the evolution were generally similar among the strains evolved in the same stress environment. We also found several genes and gene functions for which mutations were commonly fixed in the strains resistant to the same stress, and whose effects on resistance were verified experimentally. We demonstrated that the integration of transcriptome and genome data enables us to extract the mechanisms for stress resistance.Author summaryUnderstanding the relationship between phenotypic and genetic changes is a fundamental goal in evolutionary biology, which can provide insights into the past and future evolutionary trajectories. Evolution of microorganisms in a laboratory has been the primary approach to clarify the mappings of phenotypic and genotypic changes. Here, we performed high-throughput laboratory evolution with bacteria using an automated culture system, to quantify phenotypic and genotypic changes occurred under various stress conditions. We identified various stress-specific gene expression changes and mutations, and contributions of them to fitness gain were validated. These results demonstrated that the integration of phenotypic and genotypic changes makes it possible to extract the mechanisms for stress resistance evolution, which will contribute to bioengineering applications.
Genome-wide comparison of toxigenic and non-toxigenicCorynebacterium diphtheriaeisolates identifies differences in the pan genomes between respiratory and cutaneous strains
Authors: Timms Verlaine J , Nguyen Trang , Crighton Taryn , Yuen Marion , Sintchenko Vitali 
Published: May 2017

AbstractObjectivesCorynebacterium diphtheriaeis the main etiological agent of diphtheria, a global disease causing life-threatening infections, particularly in infants and children. Vaccination with diphtheria toxoid protects against infection with potent toxin producing strains. However a growing number of apparently non-toxigenic but potentially invasiveC. diphtheriaestrains are identified in countries with low prevalence of diphtheria, raising key questions about genomic structures and population dynamics of the species.MethodsThis study examined genomic diversity among 47C. diphtheriaeisolates collected in Australia over a 10-year period using whole genome sequencing. Phylogeny was determined using SNP-based mapping and genome wide analysis.ResultsC. diphtheriaesequence type (ST) 32, a non-toxigenic ST with evidence of enhanced virulence that is also circulating in Europe, appears to be endemic in Australia. Isolates from temporospatially related patients displayed the same ST and similarity in their core genomes. The genome-wide analysis highlighted a role of pilins, adhesion factors and iron utilization in infections caused by toxigenic as well as non-toxigenic strains.ConclusionsThe genomic diversity of toxigenic and non-toxigenic strains ofC. diphtheriaein Australia suggests multiple local and overseas sources of infection and colonisation. Our findings suggest that regular genomic surveillance of co-circulating toxigenic and non-toxigenicC. diphtheriaecan deliver highly nuanced data in order to inform targeted public health actions and policy for predicting the future impact of this highly successful pathogen.
Lamellar junctions in the endolymphatic sac act as a relief valve to regulate inner ear pressure
Authors: Swinburne Ian A. , Mosaliganti Kishore R. , Upadhyayula Srigokul , Liu Tsung-Li , Hildebrand David G. C. , Tsai Tony Y.-C. , Chen Anzhi , Al-Obeidi Ebaa , Fass Anna K. , Malhotra Samir , Engert Florian , Lichtman Jeff W. , Kirchhausen Tom , Betzig Eric , Megason Sean G. 
Published: May 2017

AbstractThe inner ear is a fluid-filled closed-epithelial structure whose normal function requires maintenance of an internal hydrostatic pressure and fluid composition by unknown mechanisms. The endolymphatic sac (ES) is a dead-end epithelial tube connected to the inner ear. ES defects can cause distended ear tissue, a pathology often seen in hearing and balance disorders. Using live imaging of zebrafish larvae, we reveal that the ES undergoes cycles of slow pressure-driven inflation followed by rapid deflation every 1-3 hours. Using serial-section electron microscopy and adaptive optics lattice light-sheet microscopy, we find a pressure relief valve in the ES comprised of thin overlapping basal lamellae that dynamically extend over neighboring cells before rupturing under pressure leading to ES collapse. The unexpected discovery of a physical relief valve in the ear emphasizes the need for further study into how organs control fluid pressure, volume, flow, and ion homeostasis in development and disease.
Both lipopolysaccharide and lipoteichoic acids potently induce anomalous fibrin amyloid formation: assessment with novel Amytracker™stains
Authors: Pretorius Etheresia , Page Martin J , Hendricks Lisa , Nkosi Nondumiso B , Benson Sven R , Kell Douglas B 
Published: May 2017

AbstractIn recent work, we discovered that the presence of highly substoichiometric amounts (10−8molar ratio) of lipopolysaccharide (LPS) from Gram-negative bacteria caused fibrinogen clotting to lead to the formation of an amyloid form of fibrin. We here show that the broadly equivalent lipoteichoic acids (LTAs) from two species of Gram-positive bacteria have similarly (if not more) potent effects. Using thioflavin T fluorescence to detect amyloid as before, the addition of low concentrations of free ferric ion is found to have similar effects. Luminescent conjugated oligothiophene dyes (LCOs), marketed under the trade name AmytrackerTM, also stain classical amyloid structures. We here show that they too give very large fluorescence enhancements when clotting is initiated in the presence of the four amyloidogens (LPS, ferric ions and two LTA types). The staining patterns differ significantly as a function of both the amyloidogens and the dyes used to assess them, indicating clearly that the nature of the clots formed is different. This is also the case when clotting is measured viscometrically using thromboelastography. Overall, the data provide further evidence for an important role of bacterial cell wall products in the various coagulopathies that are observable in chronic, inflammatory diseases. The assays may have potential in both diagnostics and therapeutics.
Global gene repression by Dicer-independent tRNA Fragments
Authors: Kuscu Canan , Kumar Pankaj , Kiran Manjari , Su Zhangli , Malik Asrar , Dutta Anindya 
Published: May 2017

AbstracttRNA derived RNA fragments (tRFs) is an emerging group of small RNAs as abundant as miRNAs, and yet their roles are not well understood. Here, we focus on endogenous tRFs (18-22 bases) derived from 3’ end of human mature tRNAs (tRF-3) and their functions in gene repression. tRF-3 levels increase upon parental tRNA over-expression or tRNA induction by c-Myc oncogene activation. Elevated tRF-3 levels lead to repression of target genes with a sequence complementary to the tRF-3 in the 3’ UTR. The tRF-3-mediated repression is Dicer-independent, Argonaute-dependent and the targets are recognized by 5’ seed sequence rules similar to miRNAs. Furthermore, tRF-3s associate with GW proteins in P-bodies. RNA-seq identifies the endogenous target genes of tRF-3s that are specifically repressed upon tRF-3 induction. Overall, our analysis shows Dicer-independent tRF-3s, generated upon tRNA upregulation such as c-Myc overexpression, regulate gene expression globally through Argounate via seed sequence matches.
Monocyte-lymphocyte cross-communication via soluble CD163 directly links innate immune system activation and adaptive immune system suppression following ischemic stroke
Authors: O’Connell Grant C. , Tennant Connie S. , Lucke-Wold Noelle , Kabbani Yasser , Tarabishy Abdul R. , Chantler Paul D. , Barr Taura L. 
Published: May 2017

AbstractCD163 is a scavenger receptor expressed on innate immune cell populations which can be shed from the plasma membrane via the metalloprotease ADAM17 to generate a soluble peptide with lympho-inhibitory properties. The purpose of this study was to investigate CD163 as a possible effector of stroke-induced adaptive immune system suppression. Liquid biopsies were collected from ischemic stroke patients (n=39), neurologically asymptomatic controls (n=20), and stroke mimics (n=20) within 24 hours of symptom onset. Peripheral blood ADAM17 activity and soluble CD163 levels were elevated in stroke patients relative to non-stroke control groups, and negatively associated with post-stroke lymphocyte counts. Subsequentin vitroexperiments suggested that this stroke-induced elevation in circulating soluble CD163 likely originates from activated monocytic cells, as serum from stroke patients stimulated ADAM17-dependant CD163 shedding from healthy donor-derived monocytes. Additionalin vitroexperiments demonstrated that stroke-induced elevations in circulating soluble CD163 can elicit direct suppressive effects on the adaptive immune system, as serum from stroke patients inhibited the proliferation of healthy donor-derived lymphocytes, an effect which was attenuated following serum CD163 depletion. Collectively, these observations provide novel evidence that the innate immune system employs protective mechanisms aimed at mitigating the risk of post-stroke autoimmune complications driven by adaptive immune system overactivation, and that CD163 is key mediator of this phenomenon.
Cooperative Contributions of Structural and Functional Connectivity to Successful Memory and Aging
Authors: Davis Simon W , Szymanski Amanda , Boms Homa , Fink Thomas , Cabeza Roberto 
Published: May 2017

AbstractUnderstanding the precise relation between functional connectivity and structural (white-matter) connectivity and how these relationships account for cognitive changes in older adults are major challenges for neuroscience. We investigate these issues using a new approach in which structural equation modeling (SEM) is employed to integrate functional and structural connectivity data analyzed with a common framework based on regions connected by canonical tract groups (CTGs). CTGs (e.g., uncinate fasciculus, cingulum, etc.) serve as a common currency between functional and structural connectivity matrices, and ensures that the same amount of data contributing to brain-behavior relationships. We used this approach to investigate the neural mechanisms supporting memory for items and memory for associations, and how they are affected by healthy aging. Our results are threefold. Firstly, structural and functional CTGs made independent contributions to associative memory performance, suggesting that both forms of connectivity underlie age-related changes in associative memory. Secondly, distinct groups of CTGs supported associative versus item memory. Lastly, the relationship between functional and structural connectivity was best explained by the relationship between latent variables describing functional and structural CTGs based on a constrained set of tracts—but no one specific CTG group—suggesting that age effects in connectivity are constrained to specific pathways. These results provide further insights into the interplay between structural and functional connectivity patterns, and help to elucidate their relative contribution to age-related changes in associative memory performance.
R2s for Correlated Data: Phylogenetic Models, LMMs, and GLMMs
Authors: Ives Anthony R. 
Published: May 2017

AbstractMany researchers want to report anR2to measure the variance explained by a model. When the model includes correlation among data, such as phylogenetic models and mixed models, defining anR2faces two conceptual problems. (i) It is unclear how to measure the variance explained by predictor (independent) variables when the model contains covariances. (ii) Researchers may want theR2to include the variance explained by the covariances by asking questions such as “How much of the variance is explained by phylogeny?” Here, I investigate threeR2s for phylogenetic and mixed models. A least-squaresR2lsis an extension of the ordinary least-squaresR2that weights residuals by variances and covariances estimated by the model; it is closely related toR2glmmproposed by Nakagawa & Schielzeth (2013). The conditional expectationR2ceis based on “predicting” each residual from the remaining residuals of the fitted model. The likelihood ratioR2lrwas first used by Cragg & Uhler (1970) for logistic regression, and here is used with the standardization proposed by Nagelkerke (1991). These threeR2s are formulated as partialR2s, making it possible to compare the contributions of mean components (regression coefficients in phylogenetic models and fixed effects in mixed models) and variance components (phylogenetic correlations and random effects) to the fit of models. The properties of theR2s for phylogenetic models were assessed using simulations for continuous and binary response data (phylogenetic generalized least squares and phylogenetic logistic regression). Because theR2s are designed broadly for any model for correlated data, theR2s were also compared for LMMs and GLMMs.R2ls,R2ce, andR2lrall have good performance, and each has advantages and disadvantages for different applications. TheseR2s are computed in the R package rr2 (https://github.com/arives/rr2). [Binomial regression, coefficient of determination, non-independent residuals, phylogenetic model, pseudo-likelihood]
Determinants of celebrity-owned brands leveraging price premium
Authors: Singh Gaganpreet , Pandey Neeraj 
Published: May 2017

Purpose
The purpose of this paper is to investigate the celebrity-brand association from a different perspective.

Design/methodology/approach
This study uses exploratory factor analysis, confirmatory factor analysis, and binary logistic regression.

Findings
This study conceptualizes celebrity-owned brands (COBs). It statistically validates the complimentary and synergistic effects of six inter-related but distinct factors that are likely to influence a buyer’s willingness to pay price premium for COBs.

Originality/value
This study makes a novel attempt by analysing the celebrity-brand relationship from a different perspective. The paper deviates from the traditional and widely researched linkage of a celebrity with a brand through endorsement.
Genetic fusion protein 3×STa‐ovalbumin is an effective coating antigen in ELISA to titrate anti‐STa antibodies
Authors: Duan Qiangde , Zhang Weiping 
Published: May 2017

ABSTRACTHeat‐stable toxin type I (STa)‐ovalbumin chemical conjugates are currently used as the only coating antigen in ELISA to titrate anti‐STa antibodies for ETEC vaccine candidates. STa‐ovalbumin chemical conjugation requires STa toxin purification, a process that can be carried out by only a couple of laboratories and often with a low yield. Alternative ELISA coating antigens are needed for anti‐STa antibody titration for ETEC vaccine development. In the present study, we genetically fused STa toxin gene (three copies) to a modified chicken ovalbumin gene for genetic fusion 3×STa‐ovalbumin, and examined application of this fusion protein as an alternative coating antigen of anti‐STa antibody titration ELISA. Data showed fusion protein 3×STa‐ovalbumin was effectively expressed and extracted, and anti‐STa antibody titration ELISA using this recombinant protein (25 ng per well) or STa‐ovalbumin chemical conjugates (10 ng/well) showed the same levels of sensitivity and specificity. Furthermore, mice immunized with this fusion protein developed anti‐STa antibodies; induced antibodies showedin vitroneutralization activity against STa toxin. These results indicate that recombinant fusion protein 3×STa‐ovalbumin is an effective ELISA coating antigen for anti‐STa antibody titration, enabling a reliable reagent supply to make standardization of STa antibody titration assay feasible and to accelerate ETEC vaccine development.
Reviewing the quality of discourse information measures in aphasia
Authors: Pritchard Madeleine , Hilari Katerina , Cocks Naomi , Dipper Lucy 
Published: May 2017

AbstractBackgroundDiscourse is fundamental to everyday communication, and is an increasing focus of clinical assessment, intervention and research. Aphasia can affect the information a speaker communicates in discourse. Little is known about the psychometrics of the tools for measuring information in discourse, which means it is unclear whether these measures are of sufficient quality to be used as clinical outcome measures or diagnostic tools.AimsTo profile the measures used to describe information in aphasic discourse, and to assess the quality of these measures against standard psychometric criteria.Methods & ProceduresA scoping review method was employed. Studies were identified using a systematic search of Scopus, Medline and Embase databases. Standard psychometric criteria were used to evaluate the measures’ psychometric properties.Main contributionThe current review summarizes and collates the information measures used to describe aphasic discourse, and evaluates their quality in terms of the psychometric properties of acceptability, reliability and validity. Seventy‐six studies described 58 discourse information measures, with a mean of 2.28 measures used per study (SD = 1.29, range = 1–7). Measures were classified as ‘functional’ measures (n = 33), which focused on discourse macrostructure, and ‘functional and structural’ measures (n = 25), which focused on micro‐linguistic and macro‐structural approaches to discourse. There were no reports of the acceptability of data generated by the measures (distribution of scores, missing data). Test–retest reliability was reported for just 8/58 measures with 3/8 > 0.80. Intra‐rater reliability was reported for 9/58 measures and in all cases percentage agreement was reported rather than reliability. Per cent agreement was also frequently reported for inter‐rater reliability, with only 4/76 studies reporting reliability statistics for 12/58 measures; this was generally high (>.80 for 11/12 measures). The majority of measures related clearly to the discourse production model indicating content validity. A total of 36/58 measures were used to make 41 comparisons between participants with aphasia (PWA) and neurologically healthy participants (NHP), with 31/41 comparisons showing a difference between the groups. Four comparisons were made between discourse genres, with two measures showing a difference between genres, and two measures showing no difference.ConclusionsThere is currently insufficient information available to justify the use of discourse information measures as sole diagnostic or outcome measurement tools. Yet the majority of measures are rooted in relevant theory, and there is emerging evidence regarding their psychometric properties. There is significant scope for further psychometric strengthening of discourse information measurement tools.