bluuebunny/crossref_metadata_2025_split huggingface dataset:
A new Defective Helper RNA to produce recombinant Sindbis virus that infects neurons but does not propagate
Authors: Kebschull Justus M , Garcia da Silva Pedro , Zador Anthony M 
Published: December 2015

AbstractRecombinant Sindbis viruses are important tools in neuroscience because they combine rapid and high transgene expression with a capacity to carry large transgenes. Currently, two packaging systems based on the DH(26S)5’SIN and the DH-BB(tRNA;TE12) Defective Helper (DH) RNAs are available for making recombinant Sindbis virus that is neurotropic (able to infect neurons and potentially other cells). Both systems produce a fraction of viral particles that can propagate beyond the primary infected neuron. When injected into mouse brains, viruses produced using these DH RNAs label neurons at the injection site, but also elsewhere in the brain. Such ectopic labeling caused recombinant Sindbis viruses to be classified as anterograde viruses with limited retrograde spread, and can complicate the interpretation of neuroanatomical and other experiments.Here we describe a new DH RNA, DH-BB(5’SIN;TE12ORF), that can be used to produce virus that is both neurotropic and propagation-incompetent. We show in mice that DH-BB(5’SIN;TE12ORF)- packaged virus eliminates infection of cells outside the injection site. We also provide evidence that ectopically labeled cells observed in previous experiments with recombinant Sindbis virus resulted from secondary infection by propagation-competent virus, rather than from inefficient retrograde spread.Virus produced with our new packaging system retains all the advantages of previous recombinant Sindbis viruses, but minimizes the risks of confounding results with unwanted ectopic labeling. It should therefore be considered in future studies in which a neurotropic, recombinant Sindbis virus is needed.
Measuring and modeling diffuse scattering in protein X-ray crystallography
Authors: Van Benschoten Andrew H. , Liu Lin , Gonzalez Ana , Brewster Aaron S. , Sauter Nicholas K. , Fraser James S. , Wall Michael E. 
Published: December 2015

AbstractX-ray diffraction has the potential to provide rich information about the structural dynamics of macromolecules. To realize this potential, both Bragg scattering, which is currently used to derive macromolecular structures, and diffuse scattering, which reports on correlations in charge density variations must be measured. Until now measurement of diffuse scattering from protein crystals has been scarce, due to the extra effort of collecting diffuse data. Here, we present three-dimensional measurements of diffuse intensity collected from crystals of the enzymes cyclophilin A and trypsin. The measurements were obtained from the same X-ray diffraction images as the Bragg data, using best practices for standard data collection. To model the underlying dynamics in a practical way that could be used during structure refinement, we tested Translation-Libration-Screw (TLS), Liquid-Like Motions (LLM), and coarse-grained Normal Modes (NM) models of protein motions. The LLM model provides a global picture of motions and were refined against the diffuse data, while the TLS and NM models provide more detailed and distinct descriptions of atom displacements, and only used information from the Bragg data. Whereas different TLS groupings yielded similar Bragg intensities, they yielded different diffuse intensities, none of which agreed well with the data. In contrast, both the LLM and NM models agreed substantially with the diffuse data. These results demonstrate a realistic path to increase the number of diffuse datasets available to the wider biosciences community and indicate that NM-based refinement can generate dynamics-inspired structural models that simultaneously agree with both Bragg and diffuse scattering.SignificanceThe structural details of protein motions are critical to understanding many biological processes, but they are often hidden to conventional biophysical techniques. Diffuse X-ray scattering can reveal details of the correlated movements between atoms; however, the data collection historically has required extra effort and dedicated experimental protocols. We have measured three-dimensional diffuse intensities in X-ray diffraction from CypA and trypsin crystals using standard crystallographic data collection techniques. Analysis of the resulting data is consistent with the protein motions resembling diffusion in a liquid or vibrations of a soft solid. Our results show that using diffuse scattering to model protein motions can become a component of routine crystallographic analysis through the extension of commonplace methods.
Competition between binding sites determines gene expression at low transcription factor concentrations
Authors: van Dijk David , Sharon Eilon , Lotan-Pompan Maya , Weinberger Adina , Segal Eran , Carey Lucas B. 
Published: December 2015

AbstractThe response of gene expression to intra-and extra-cellular cues is largely mediated through changes in the activity of transcription factors (TFs), whose sequence specificities are largely known. However, the rules by which promoters decode the amount of active TF into gene expression are not well understood. Here, we measure the activity of 6500 designed promoters at six different levels of TF activity in budding yeast. We observe that maximum promoter activity is determined by TF activity and not by the number of sites. Surprisingly, the addition of an activator-binding site often reduces expression. A thermodynamic model that incorporates competition between neighboring binding sites for a local pool of TF molecules explains this behavior and accurately predicts both absolute expression and the amount by which addition of a site increases or reduces expression. Taken together, our findings support a model in which neighboring binding sites interact competitively when TF is limiting but otherwise act additivelySignificance StatementIn response to intracellular and extracellular signals organisms alter the concentration and activity of transcription factors (TFs), proteins that regulate gene expression. However, the molecular mechanisms that determine the response of a target promoter to changes in the number of active TF molecules are not well understood. By combining mathematical modeling with measurements of TF dose-response curves for thousands of designed promoters, we show that competition for active TF molecules is a major factor in determining gene expression. At low TF concentrations additional activator-binding sites within a promoter can actually reduce expression. Thermodynamic modeling suggests that steric hindrance between neighboring binding sites cannot explain this behavior, but that competition for limiting TF molecules can.
Across-cohort QC analyses of genome-wide association study summary statistics from complex traits
Authors: Chen Guo-Bo , Lee Sang Hong , Robinson Matthew R , Trzaskowski Maciej , Zhu Zhi-Xiang , Winkler Thomas W , Day Felix R , Croteau-Chonka Damien C , Wood Andrew R , Locke Adam E , Kutalik Zoltán , Loos Ruth J F , Frayling Timothy M , Hirschhorn Joel N , Yang Jian , Wray Naomi R ,   The Genetic Investigation of Anthropometric Traits (GIANT) Consortium, Visscher Peter M 
Published: December 2015

AbstractGenome-wide association studies (GWASs) have been successful in discovering replicable SNP-trait associations for many quantitative traits and common diseases in humans. Typically the effect sizes of SNP alleles are very small and this has led to large genome-wide association meta-analyses (GWAMA) to maximize statistical power. A trend towards ever-larger GWAMA is likely to continue, yet dealing with summary statistics from hundreds of cohorts increases logistical and quality control problems, including unknown sample overlap, and these can lead to both false positive and false negative findings. In this study we propose a new set of metrics and visualization tools for GWAMA, using summary statistics from cohort-level GWASs. We proposed a pair of methods in examining the concordance between demographic information and summary statistics. In method I, we use the population geneticsFststatistic to verify the genetic origin of each cohort and their geographic location, and demonstrate using GWAMA data from the GIANT Consortium that geographic locations of cohorts can be recovered and outlier cohorts can be detected. In method II, we conduct principal component analysis based on reported allele frequencies, and is able to recover the ancestral information for each cohort. In addition, we propose a new statistic that uses the reported allelic effect sizes and their standard errors to identify significant sample overlap or heterogeneity between pairs of cohorts. Finally, to quantify unknown sample overlap across all pairs of cohorts we propose a method that uses randomly generated genetic predictors that does not require the sharing of individual-level genotype data and does not breach individual privacy.
Habitat variability does not generally promote metabolic network modularity in flies and mammals
Authors: Takemoto Kazuhiro 
Published: December 2015

AbstractThe evolution of species habitat range is an important topic over a wide range of research fields. In higher organisms, habitat range evolution is generally associated with genetic events such as gene duplication. However, the specific factors that determine habitat variability remain unclear at higher levels of biological organization (e.g., biochemical networks). One widely accepted hypothesis developed from both theoretical and empirical analyses is that habitat variability promotes network modularity; however, this relationship has not yet been directly tested in higher organisms. Therefore, I investigated the relationship between habitat variability and metabolic network modularity using compound and enzymatic networks in flies and mammals. Contrary to expectation, there was no clear positive correlation between habitat variability and network modularity. As an exception, the network modularity increased with habitat variability in the enzymatic networks of flies. However, the observed association was likely an artifact, and the frequency of gene duplication appears to be the main factor contributing to network modularity. These findings raise the question of whether or not there is a general mechanism for habitat range expansion at a higher level (i.e., above the gene scale). This study suggests that the currently widely accepted hypothesis for habitat variability should be reconsidered.
The reported healthy ageing gene expression score: lack of association in two cohorts
Authors: Pilling Luke C. , Harries Lorna W , Hernandez Dena G , Singleton Andrew B , Kuchel George A. , Ferrucci Luigi , Melzer David 
Published: December 2015

AbstractSoodet al. report a multi-tissue RNA signature “predictive of human health, using only peripheral blood samples”. We tested this score in blood in two independent, larger cohorts and found no associations with age or related phenotypes, including muscle strength, interleukin-6 or mortality.
Effect of Poli I:C in murine model of autoimmune thyroiditis
Authors: Vera C , Barria M. 
Published: December 2015

ABSTRACTHashimoto’s thyroiditis is one of the most common autoimmune diseases in humans and, similar to other autoimmune diseases, is multifactorial in nature. Moreover, the expression of TLRs has been implicated in the pathogenesis of autoimmune and inflammatory diseases, such as diabetes and insulinitis. The TLRs are a family of at least 10 receptors associated with innate immunity that are present in monocytes, macrophages, and dendritic cells, which recognize highly conserved patterns of the surface of microorganisms, such as LPS, peptidoglycan, and dsRNA and CpG sequences.The aim of this study was to evaluate mRNA of the TLR3, TLR9 and cytokines (IFN-beta, TNF and IL-1) in thyroid follicular cells obtained of mice with autoimmune experimental thyroiditis (EAT). For that C57BL/6 mice were immunized with Tg plus complete Freund’s adyuvant and treated or not with Poli I:C. Anti-thyroglobulin autoantibodies level was determined by indirect ELISA. Also isolated thyroid follicles were treatedin vitrowith Poli IC. The results show that TLR3 receptors and some cytokines (IFN-beta, TNF and IL-10) are more highly expressed in thyroid follicular cells treated with Poli I:C. and in the animals with TAE, which present humoral autoimmune response. Taken together, these results suggest that TLR3 expression in thyroid follicular cells induces signaling mechanisms to enhanced IL-1, TNF and IFN-β levels during pathogen infections and that could trigger of autoimmune thyroiditis.
Cultural and Organisational Diversity Evaluation (CODE)
Authors: Siakas Kerstin , Siakas Dimitrios 
Published: December 2015

Purpose– This paper aims to present the Cultural and Organisational Diversity Evaluation (CODE) model and its subsequent electronic tool, aiming to assess the cultural fit of global partners.Design/methodology/approach– The study is a longitudinal study for gaining profound insights into cultural differences and for increasing understanding of human dynamics influencing the success of global relationships. A multi-method including overlapping qualitative and quantitative research methodology was used comprising interviews, observations and questionnaires.Findings– Incorporating cultural knowledge and understanding of the specific context of the partners in global transactions was found to bring added value to global partners. The results of the pilot studies suggest that increased appreciation and awareness of cultural diversity in global transactions are important factors for achieving harmonised distributed collaboration. Such awareness, also called cultural intelligence, can be reached by using a customised assessment tool that evaluates the particularities of the partners.Research limitations/implications– The conceptual CODE model has so far only been piloted in a few cases in a longitudinal study and is not a commercial tool.Practical implications– Raising awareness of cultural concerns is important for organisations that are involved in global transactions to improve communication, mutual understanding and effectivity. The CODE assesses the cultural fit of partners in a global context.Social implications– Organisations involved in global transactions would benefit from understanding the culture of partners for improved effectiveness.Originality/value– The CODE model, an instrument for assessing the fit between organisational and national culture, is a novel model developed by the authors.
Resolving patterns of population genetic and phylogeographic structure to inform control and eradication initiatives for brown rats Rattus norvegicus on South Georgia
Authors: Piertney Stuart B. , Black Andy , Watt Laura , Christie Darren , Poncet Sally , Collins Martin A. 
Published: December 2015

Summary

The control and eradication of invasive species is a common management strategy to protect or restore native biodiversity. On South Georgia in the Southern Ocean, the brown rat Rattus norvegicus was brought onto the island with the onset of whaling and sealing activity in the 1800s and has had a significant detrimental impact on key bird species of conservation concern. Efforts to eradicate rats from South Georgia using poisoned bait are ongoing.

Despite the South Georgia rat eradication programme being the geographically largest and most ambitious eradication initiative to date, its success is facilitated by the potential that rat populations are effectively isolated by glacial barriers. This allows for localized eradication effort at manageable scales, leading to sequential eradication of individual populations with minimal risk of incursion from neighbouring areas.

Here, we use the levels of population genetic divergence estimated from 299 single nucleotide polymorphism (SNP) loci and DNA sequence variation across 993 base pairs of the mitochondrial DNA cytochrome B locus to examine whether rat populations from nine glacially isolated areas on South Georgia are genetically distinct and so can be treated as independent eradication units.

Bayesian clustering of individuals based on SNP similarity identified seven different genetic groups, which were confirmed using analyses based on pairwise genetic distance estimates and ordination of individuals using principal coordinate analysis. From a management perspective, these seven groups represent individual targets in baiting operations.

Two mtDNA haplotypes were resolved across South Georgia, with a distinct geographical separation between the north‐western and south‐eastern populations. Approximate Bayesian computation (ABC) was used to identify that this divergence was a consequence of two separate historical colonization events.

Synthesis and applications. We illustrate that molecular markers are a valuable tool in species management and pest eradication given that the spatial distribution of genetic diversity can: (i) identify demographically and genetically independent populations on which local eradication effort can be focussed, (ii) distinguish between incomplete eradication and immigration in situations where individuals remain after eradication has been attempted and (iii) identify the source of migrants when dispersal occurs over large spatial scales.
Which landscape size best predicts the influence of forest cover on restoration success? A global meta‐analysis on the scale of effect
Authors: Crouzeilles Renato , Curran Michael 
Published: December 2015

Summary

Landscape context is a strong predictor of species persistence, abundance and distribution, yet its influence on the success of ecological restoration remains unclear. Thus, a primary question arises: which landscape size best predicts the effects of forest cover on restoration success?

To answer this question, we conducted a global meta‐analysis for biodiversity (mammals, birds, invertebrates, herpetofauna and plants) and measures of vegetation structure (cover, density, height, biomass and litter). Response ratios were calculated for comparisons between reference (e.g. old‐growth forest) and disturbed sites (degraded or restored). Using an information‐theoretic approach, mean response ratio (restoration success) and response ratio variance (restoration predictability) within each study landscape were regressed against the percentage of overall (summed forest cover) and contiguous (summed pixels of ≥60% forest cover) forest within eight different buffer sizes of radius 5–200 km (at 1‐km resolution).

We included 247 studies encompassing 196 study landscapes and 4360 quantitative comparisons. The best buffer (landscape) size varied for the following: (i) overall and contiguous forest cover, (ii) biodiversity and vegetation structure and (iii) mean response ratio and response ratio variance. Only plant biodiversity was influenced by overall forest cover (buffer size of 5, 10 and 200 km radii), while plants (10 and 200 km radii), mammals (5, 10 and 50–200 km radii), invertebrates (5 and 10 km radii), cover (5 km radii), height (5 km radii) and litter (100 km radii) were influenced by contiguous forest cover. Overall, mean response ratio and response ratio variance were positively and negatively nonlinearly related with both overall and contiguous forest cover, respectively.

We reveal for the first time a clear pattern of increasing restoration success and decreasing uncertainty as contiguous forest cover increases. We also indicate preliminary recommended buffer sizes for investigating landscape restoration effects on biodiversity and vegetation structure. However, the coarse grain and variability in the data mean the optimal landscape size may not have been detected; thus, further research is needed.

Synthesis and applications. When setting targets for ecological restoration, policymakers and restoration practitioners should account for the following: (i) the landscape context, particularly the amount of contiguous habitat up to 10 km around a disturbed site, and (ii) the uncertainty in restoration success, as it increases when contiguous forest cover falls below about 50%.
Relationship between malnutrition and selected risk factors in two hospitals in Vietnam
Authors: Hanna Katherine L. , Glen Kate D. , Lau Bonnie T. , Tran Cuong Q. , Truong Nam T. , Gallegos Danielle 
Published: December 2015

AbstractAimThe purpose of the present study was to determine the percentage of patients assessed as malnourished using the Subjective Global Assessment in two hospitals in Ho Chi Minh City and Can Tho across multiple wards; and to investigate the association with factors including gender, age, days since admission, medical diagnosis and number of medications used.MethodsThis cross‐sectional study involved 205 inpatients from a hospital in Ho Chi Minh City and 78 inpatients and 89 outpatients from a hospital in Can Tho. Malnutrition status was assessed using Subjective Global Assessment. Ward, gender, age, medical diagnosis, time since admission and medication number were extracted from medical records.ResultsUp to 36% of inpatients and 9.0% of outpatients were malnourished. Multivariate analysis revealed factors predicting malnutrition status within inpatients (OR (95% CI)) were: age (OR = 1.03 (1.01–1.06)); cancer diagnosis (OR = 34.25 (3.16–370.89)); respiratory ward (11.49 (1.05–125.92)); or general medicine ward (20.34 (2.10–196.88)).ConclusionsResults indicate that malnutrition is a common problem in hospitals in Vietnam. Further research is needed to confirm this finding across a wider range of hospitals and to investigate the feasibility and efficacy of implementation of nutrition interventions in hospital settings.
Advances in genomics, transcriptomics and proteomics of toxin‐producing cyanobacteria
Authors: D'Agostino Paul M. , Woodhouse Jason N. , Makower A. Katharina , Yeung Anna C. Y. , Ongley Sarah E. , Micallef Melinda L. , Moffitt Michelle C. , Neilan Brett A. 
Published: December 2015

SummaryA common misconception persists that the genomes of toxic and non‐toxic cyanobacterial strains are largely conserved with the exception of the presence or absence of the genes responsible for toxin production. Implementation of ‐omics era technologies has challenged this paradigm, with comparative analyses providing increased insight into the differences between strains of the same species. The implementation of genomic, transcriptomic and proteomic approaches has revealed distinct profiles between toxin‐producing and non‐toxic strains. Further, metagenomics and metaproteomics highlight the genomic potential and functional state of toxic bloom events over time. In this review, we highlight how these technologies have shaped our understanding of the complex relationship between these molecules, their producers and the environment at large within which they persist.