bluuebunny/crossref_metadata_2025_split huggingface dataset:
Probiotics in Human Immunodeficiency Virus Infection: A Systematic Review and Evidence Synthesis of Benefits and Risks
Authors: Carter George M. , Esmaeili Aryan , Shah Hardikkumar , Indyk Debbie , Johnson Matthew , Andreae Michael , Sacks Henry S. 
Published: July 2016

AbstractPeople living with human immunodeficiency virus frequently use dietary supplements, including probiotics, but concern exists about ingesting live organisms. We performed a systematic review of the benefits of probiotics and a meta-analysis of sepsis risk. We undertook a protocol-driven, comprehensive review to identify all relevant studies, assess their quality, and summarize the evidence. Of 2068 references, 27 were analyzed. The data suggest possible benefits for CD4 count, recurrence or management of bacterial vaginosis, and diarrhea management. We examined randomized, controlled studies explicitly assessing sepsis in any patient population, and we found zero cases of supplement-associated bacteremia or fungemia in 39 randomized controlled trials comprising 9402 subjects. The estimated number needed to harm is 7369 in Bayesian approach (95% credible interval: 1689, ∞), which should reassure clinicians. No or mild adverse effects were reported. Longer duration studies investigating different individual and mixed strains for plausible indications are needed to establish best practices.
A multi-line ammonia survey of the Galactic center region with the Tsukuba 32 m telescope. I. Observations and data
Authors: Arai Hitoshi , Nagai Makoto , Fujita Shinji , Nakai Naomasa , Seta Masumichi , Yamauchi Aya , Kaneko Hiroyuki , Hagiwara Kenzaburo , Mamyoda Koh-ichi , Miyamoto Yusuke , Horie Masa-aki , Ishii Shun , Koide Yusuke , Ogino Mitsutoshi , Maruyama Masaki , Hirai Katsuaki , Oshiro Wataru , Nagai Satoshi , Akiyama Daiki , Konakawa Keita , Nonogawa Hiroaki , Salak Dragan , Terabe Yuki , Nihonmatsu Yoshiki , Funahashi Fumiyoshi 
Published: July 2016

Abstract
We present survey data of six NH3 (J, K) = (1, 1), (2, 2), (3, 3), (4, 4), (5, 5), and (6, 6) lines, simultaneously observed with the Tsukuba 32 m telescope, in the main part of the central molecular zone of the Galaxy. The total number of on-source positions was 2655. The three lower transitions were detected with S/N &gt; 3 at 2323 positions (93% of all the on-source positions). Among 2323, the S/N 's of (J, K) = (4, 4), (5, 5), and (6, 6) exceeded 3.0 at 1426(54%), 1150(43%), and 1359(51%) positions, respectively. Simultaneous observations of the lines enabled us to accurately derive intensity ratios with less systematic errors. Boltzmann plots indicate that there are two temperature components: cold (∼20 K) and warm (∼100 K). Typical intensity ratios of Tmb(2, 2)/Tmb(1, 1), Tmb(4, 4)/Tmb(2, 2), Tmb(5, 5)/Tmb(4, 4), and Tmb(6, 6)/Tmb(3, 3) were 0.71, 0.45, 0.65, and 0.17, respectively. These line ratios correspond to the diversity of the rotational temperature, which results from mixing of the two temperature components.
Negative selection in humans and fruit flies involves synergistic epistasis
Authors: Sohail Mashaal , Vakhrusheva Olga A. , Sul Jae Hoon , Pulit Sara , Francioli Laurent ,   GoNL Consortium, Alzheimer’s Disease Neuroimaging Initiative, van den Berg Leonard H. , Veldink Jan H. , de Bakker Paul , Bazykin Georgii A. , Kondrashov Alexey S. , Sunyaev Shamil R. 
Published: July 2016

AbstractNegative selection against deleterious alleles produced by mutation is the most common form of natural selection, which strongly influences within-population variation and interspecific divergence. However, some fundamental properties of negative selection remain obscure. In particular, it is still not known whether deleterious alleles affect fitness independently, so that cumulative fitness loss depends exponentially on the number of deleterious alleles, or synergistically, so that each additional deleterious allele results in a larger decrease in relative fitness. Negative selection with synergistic epistasis must produce negative linkage disequilibrium between deleterious alleles, and therefore, underdispersed distribution of the number of deleterious alleles in the genome. Indeed, we detected underdispersion of the number of rare loss-of-function (LoF) alleles in eight independent datasets from modern human andDrosophila melanogasterpopulations. Thus, ongoing selection against deleterious alleles is characterized by synergistic epistasis, which can explain how human and fly populations persist despite very high genomic deleterious mutation rates.
Receptive field formation by interacting excitatory and inhibitory synaptic plasticity
Authors: Clopath Claudia , Vogels Tim P. , Froemke Robert C. , Sprekeler Henning 
Published: July 2016

AbstractThe stimulus selectivity of synaptic currents in cortical neurons often shows a co-tuning of excitation and inhibition, but the mechanisms that underlie the emergence and plasticity of this co-tuning are not fully understood. Using a computational model, we show that an interaction of excitatory and inhibitory synaptic plasticity reproduces both the developmental and – when combined with a disinhibitory gate – the adult plasticity of excitatory and inhibitory receptive fields in auditory cortex. The co-tuning arises from inhibitory plasticity that balances excitation and inhibition, while excitatory stimulus selectivity can result from two different mechanisms. Inhibitory inputs with a broad stimulus tuning introduce a sliding threshold as in Bienenstock-Cooper-Munro rules, introducing an excitatory stimulus selectivity at the cost of a broader inhibitory receptive field. Alternatively, input asymmetries can be amplified by synaptic competition. The latter leaves any receptive field plasticity transient, a prediction we verify in recordings in auditory cortex.
Posterior parietal cortex guides visual decisions in rats
Authors: Licata Angela M. , Kaufman Matthew T. , Raposo David , Ryan Michael B. , Sheppard John P. , Churchland Anne K. 
Published: July 2016

AbstractNeurons in putative decision-making structures can reflect both sensory and decision signals, making their causal role in decisions unclear. Here, we tested whether rat posterior parietal cortex (PPC) is causal for processing visual sensory signals or instead for accumulating evidence for decision alternatives. We optogenetically disrupted PPC activity during decision-making and compared effects on decisions guided by auditory vs. visual evidence. Deficits were largely restricted to visual decisions. To further test for visual dominance in PPC, we evaluated electrophysiological responses following individual sensory events and observed much larger responses following visual stimuli than auditory stimuli. Finally, we measured spike count variability during stimulus presentation and decision formation. This sharply decreased, suggesting the network is stabilized by inputs, unlike what would be expected if sensory signals were locally accumulated. Our findings argue that PPC plays a causal role in discriminating visual signals that are accumulated elsewhere.
The effect of crack cocaine addiction and age on the microstructure and morphology of the human striatum and thalamus using shape analysis and fast diffusion kurtosis imaging
Authors: Garza-Villarreal Eduardo A , Mallar Chakravarty M , Hansen Brian , Eskildsen Simon F , Devenyi Gabriel A. , Castillo-Padilla Diana , Balducci Thania , Reyes-Zamorano Ernesto , Jespersen Sune N , Perez-Palacios Pamela , Patel Raihaan , Gonzalez-Olvera Jorge J 
Published: July 2016

AbstractThe striatum and thalamus are subcortical structures intimately involved in addiction. The morphology and microstructure of these have been studied in murine models of cocaine addiction, showing an effect of drug use, but also chronological age in morphology. Human studies using non-invasive MRI have shown inconsistencies in volume changes, and have also shown an age effect. In this exploratory study, we used MRI-based volumetric and novel shape analysis, as well as a novel fast diffusion kurtosis imaging sequence to study the morphology and microstructure of striatum and thalamus in crack cocaine addiction (CA) compared to matched healthy controls (HC), while investigating the effect of age and years of cocaine consumption. We did not find significant differences in volume and mean kurtosis (MKT) between groups. However, we found significant contraction of nucleus accumbens in CA compared to HC. We also found significant age related changes in volume and MKT of CA in striatum and thalamus that are different to those seen in normal aging. Interestingly, we found different effects and contributions of age and years of consumption in volume, displacement and MKT changes, suggesting each measure provides different but complementing information about morphological brain changes and that not all changes are related to the toxicity or the addiction to the drug. Our findings suggest that the use of finer methods and sequences provide complementing information about morphological and microstructural changes in cocaine addiction, and that brain alterations in cocaine addiction are related cocaine use and age differently.
Examining the occupancy-density relationship for a low density carnivore
Authors: Linden Daniel W. , Fuller Angela K. , Royle J. Andrew , Hare Matthew P. 
Published: July 2016

AbstractThe challenges associated with monitoring low-density carnivores across large landscapes have limited the ability to implement and evaluate conservation and management strategies for such species. Noninvasive sampling techniques and advanced statistical approaches have alleviated some of these challenges and can even allow for spatially explicit estimates of density, arguably the most valuable wildlife monitoring tool.For some species, individual identification comes at no cost when unique attributes (e.g., pelage patterns) can be discerned with remote cameras, while other species require viable genetic material and expensive lab processing for individual assignment. Prohibitive costs may still force monitoring efforts to use species distribution or occupancy as a surrogate for density, which may not be appropriate under many conditions.Here, we used a large-scale monitoring study of fisherPekania pennantito evaluate the effectiveness of occupancy as an approximation to density, particularly for informing harvest management decisions. We used a combination of remote cameras and baited hair snares during 2013–2015 to sample across a 70,096 km2region of western New York, USA. We fit occupancy and Royle-Nichols models to species detection-nondetection data collected by cameras, and spatial capture-recapture models to individual encounter data obtained by genotyped hair samples.We found a close relationship between grid-cell estimates of fisher state variables from the models using detection-nondetection data and those from the SCR model, likely due to informative spatial covariates across a large landscape extent and a grid cell resolution that worked well with the movement ecology of the species. Spatially-explicit management recommendations for fisher were similar across models. We discuss design-based approaches to occupancy studies that can improve approximations to density.
Cross-scale dynamics and the evolutionary emergence of infectious diseases
Authors: Schreiber Sebastian J. , Ke Ruian , Loverdo Claude , Park Miran , Ahsan Prianna , Lloyd-Smith James O. 
Published: July 2016

AbstractWhen emerging pathogens encounter new host species for which they are poorly adapted, they must evolve to escape extinction. Pathogens experience selection on traits at multiple scales, including replication rates within host individuals and transmissibility between hosts. We analyze a stochastic model linking pathogen growth and competition within individuals to transmission between individuals. Our analysis reveals a new factor, the cross-scale reproductive number of a mutant virion, that quantifies how quickly mutant strains increase in frequency when they initially appear in the infected host population. This cross-scale reproductive number combines with viral mutation rates, single-strain reproductive numbers, and transmission bottleneck width to determine the likelihood of evolutionary emergence, and whether evolution occurs swiftly or gradually within chains of transmission. We find that wider transmission bottlenecks facilitate emergence of pathogens with short-term infections, but hinder emergence of pathogens exhibiting cross-scale selective conflict and long-term infections. Our results provide a framework to advance the integration of laboratory, clinical and field data in the context of evolutionary theory, laying the foundation for a new generation of evidence-based risk assessment of emergence threats.
Quantifying climate change impacts emphasises the importance of managing regional threats in the endangered Yellow-eyed penguin
Authors: Mattern Thomas , Meyer Stefan , Ellenberg Ursula , Houston David M. , Darby John T. , Young Melanie , van Heezik Yolanda , Seddon Philip J. 
Published: July 2016

AbstractClimate change is a global issue with effects that are difficult to manage at a regional scale. Yet more often than not climate factors are just some of multiple stressors affecting species on a population level. Non-climatic factors - especially those of anthropogenic origins - may play equally important roles with regard to impacts on species and are often more feasible to address. Here we assess the influence of climate change on population trends of the endangered Yellow-eyed penguin (Megadyptes antipodes) over the last 30 years, using a Bayesian model. Sea surface temperature (SST) proved to be the dominating factor influencing survival of both adult birds and fledglings. Increasing SST since the mid-1990s was accompanied by a reduction in survival rates and population decline. The population model showed that 33% of the variation in population numbers could be explained by SST alone, significantly increasing pressure on the penguin population. Consequently, the population becomes less resilient to non-climate related impacts, such as fisheries interactions, habitat degradation and human disturbance. However, the extent of the contribution of these factors to declining population trends is extremely difficult to assess principally due to the absence of quantifiable data, creating a discussion bias towards climate variables, and effectively distracting from non-climate factors that can be managed on a regional scale to ensure the viability of the population.
Cohort Specific Effects of Cereal-bar Supplementation in Overweight Patients With or Without Type 2 Diabetes Mellitus
Authors: Jason Chou Chieh , Lauber Chris , Chakrabarti Anirikh , Siddharth Jay , Chalut-Carpentier Anne , Pataky Zoltan , Golay Alain , Parkinson Scott 
Published: July 2016

AbstractThe importance of gut microbes to metabolic health is becoming more evident and nutrition-based therapies to alter the composition of bacterial communities to manage metabolic disease are an attractive avenue to ameliorate some effects of Western diets. While the composition of gut microbial communities can vary significantly across disease states, it is not well known if these communities have common responses to nutritional interventions. To better understand fiber-bacterial community interactions, we collected biological parameters and fecal samples of overweight non-diabetic (OND) and diabetic (OD) individuals before and after daily supplementation of 2.8 g β-glucan on their habitual diet for 30 days. Fecal bacterial communities in an age-matched cohort were measured by sequencing partial 16S rRNA genes and imputed metagenomic content. Unexpectedly, we observed disconnected responses of biological measurements and the bacterial community. Based on average effect size, biological measurements were greater in the OND group while effects on the bacterial community were greatest on the OD cohort, and we suspect these observations are due to the significantly lower alpha diversity in the OD cohort. Our data indicate that responses to fiber supplementation are cohort specific and this should be considered when manipulating the microbiome via fiber supplementation.
Genetic diagnosis of Mendelian disorders via RNA sequencing
Authors: Kremer Laura S , Bader Daniel M , Mertes Christian , Kopajtich Robert , Pichler Garwin , Iuso Arcangela , Haack Tobias B , Graf Elisabeth , Schwarzmayr Thomas , Terrile Caterina , Koňařiková Eliška , Repp Birgit , Kastenmüller Gabi , Adamski Jerzy , Lichtner Peter , Leonhardt Christoph , Funalot Benoit , Donati Alice , Tiranti Valeria , Lombes Anne , Jardel Claude , Gläser Dieter , Taylor Robert W. , Ghezzi Daniele , Mayr Johannes A , Rötig Agnes , Freisinger Peter , Distelmaier Felix , Strom Tim M , Meitinger Thomas , Gagneur Julien , Prokisch Holger 
Published: July 2016

AbstractAcross a large variety of Mendelian disorders, ~50-75% of patients do not receive a genetic diagnosis by whole exome sequencing indicative of underlying disease-causing variants in non-coding regions. In contrast, whole genome sequencing facilitates the discovery of all genetic variants, but their sizeable number, coupled with a poor understanding of the non-coding genome, makes their prioritization challenging. Here, we demonstrate the power of transcriptome sequencing to provide a confirmed genetic diagnosis for 10% (5 of 48) of undiagnosed mitochondrial disease patients and identify strong candidate genes for patients remaining without diagnosis. We found a median of 1 aberrantly expressed gene, 5 aberrant splicing events, and 6 mono-allelically expressed rare variants in patient-derived fibroblasts and established disease-causing roles for each kind. Private exons often arose from sites that are weakly spliced in other individuals, providing an important clue for future variant prioritization. One such intronic exon-creating variant was found in three unrelated families in the complex I assembly factor TIMMDC1, which we consequently established as a novel disease-associated gene. In conclusion, our study expands the diagnostic tools for detecting non-exonic variants of Mendelian disorders and provides examples of intronic loss-of-function variants with pathological relevance.
Independent modes of ganglion cell translocation ensure correct lamination of the zebrafish retina
Authors: Icha Jaroslav , Grunert Christiane , Rocha-Martins Mauricio , Norden Caren 
Published: July 2016

AbstractThe arrangement of neurons into distinct layers is critical for neuronal connectivity and function of the nervous system. During development, most neurons move from their birthplace to the appropriate layer, where they polarize. However, kinetics and modes of many neuronal translocation events still await exploration. Here, we investigate ganglion cell (RGC) translocation across the embryonic zebrafish retina. After completing their translocation, RGCs establish the most basal retinal layer where they form the optic nerve. Usingin totolight sheet microscopy, we show that somal translocation of RGCs is a fast and directed event. It depends on basal process attachment and stabilized microtubules. Interestingly, interference with somal translocation induces a switch to multipolar migration. This multipolar mode is less efficient but still leads to successful RGC layer formation. When both modes are inhibited, RGCs that fail to translocate induce lamination defects, indicating that correct RGC translocation is crucial for subsequent retinal lamination.
Bright photoactivatable fluorophores for single-molecule imaging
Authors: Grimm Jonathan B. , English Brian P. , Muthusamy Anand K. , Mehl Brian P. , Dong Peng , Brown Timothy A. , Liu Zhe , Lionnet Timothée , Lavis Luke D. 
Published: July 2016

ABSTRACTSmall molecule fluorophores are important tools for advanced imaging experiments. The development of self-labeling protein tags such as the HaloTag and SNAP-tag has expanded the utility of chemical dyes in live-cell microscopy. We recently described a general method for improving the brightness and photostability of small, cell-permeable fluorophores, resulting in the azetidine-containing “Janelia Fluor” (JF) dyes. Here, we refine and extend the utility of the JF dyes by synthesizing photoactivatable derivatives that are compatible with established live-cell labeling strategies. These compounds retain the superior brightness of the JF dyes but their facile photoactivation enables improved single-particle tracking and localization microscopy experiments.
Inconsistencies inC. elegansbehavioural annotation
Authors: Szigeti Balázs , Stone Thomas , Webb Barbara 
Published: July 2016

AbstractHigh quality behavioural annotation is a key component to link genes to behaviour, yet relatively little attention has been paid to check the consistency of various automated methods and expert judgement. In this paper we investigate the consistency of annotation for the ‘Omega turn’ ofC. elegans, which is a frequently used behavioural assay for this animal. First the output of four Omega detection algorithms are examined for the same data set, and shown to have relative low consistency, with F-scores around 0.5. Consistency of expert annotation is then analysed, based on an online survey combining two methods: participants judged a fixed set of predetermined clips; and an adaptive psychophysical procedure was used to estimate individual’s threshold for Omega turn detection. This survey also revealed a substantial lack of consistency in decisions and thresholds. Such inconsistency makes cross-publication comparison difficult and raises issues of reproducibility.
A statistical definition for reproducibility and replicability
Authors: Patil Prasad , Peng Roger D. , Leek Jeffrey T. 
Published: July 2016

AbstractEveryone agrees that reproducibility and replicability are fundamental characteristics of scientific studies. These topics are attracting increasing attention, scrutiny, and debate both in the popular press and the scientific literature. But there are no formal statistical definitions for these concepts, which leads to confusion since the same words are used for different concepts by different people in different fields. We provide formal and informal definitions of scientific studies, reproducibility, and replicability that can be used to clarify discussions around these concepts in the scientific and popular press.
Temporal Stability and Molecular Persistence of the Bone Marrow Plasma Cell Antibody Repertoire
Authors: Wu Gabriel C. , Cheung Nai-Kong V. , Georgiou George , Marcotte Edward M. , Ippolito Gregory C. 
Published: July 2016

ABSTRACTPlasma cells in human bone marrow (BM PCs) are thought to be intrinsically long-lived and to be responsible for sustaining lifelong immunity through the constitutive secretion of antibody—but the underlying basis for this serological memory remains controversial. Here, we analyzed the molecular persistence of serological immunity by an examination of BM PC immunoglobulin heavy-chain (IGH) transcripts derived from serial bone marrow specimens obtained during a span of several years. Using high-throughput sequence analysis of the same individual for 6.5 years, we show that the BM PC repertoire is remarkably stable over time. We find that the bias in IGH V, D, and J individual gene usage and also the combinatorial V–D, V–J, D–J, and V-D-J usage across time to be nearly static. When compared to a second donor with time points 2 years apart, these overall patterns are preserved, and surprisingly, we find high correlation of gene usage between the two donors. Lastly, we report the persistence of numerous BM PC clonal clusters (~2%) identifiable across 6.5 years at all time points assayed, supporting a model of serological memory based, at least in part, upon intrinsic longevity of human PCs. We anticipate that this longitudinal study will facilitate the ability to differentiate between healthy and diseased antibody repertoire states, by serving as a point of comparison with future deep-sequencing studies involving immune intervention.