bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improved read/write cost tradeoff in DNA-based data storage using LDPC codes
Authors: Chandak Shubham , Tatwawadi Kedar , Lau Billy , Mardia Jay , Kubit Matthew , Neu Joachim , Griffin Peter , Wootters Mary , Weissman Tsachy , Ji Hanlee 
Published: September 2019

AbstractWith the amount of data being stored increasing rapidly, there is significant interest in exploring alternative storage technologies. In this context, DNA-based storage systems can offer significantly higher storage densities (petabytes/gram) and durability (thousands of years) than current technologies. Specifically, DNA has been found to be stable over extended periods of time which has been demonstrated in the analysis of organisms long since extinct. Recent advances in DNA sequencing and synthesis pipelines have made DNA-based storage a promising candidate for the storage technology of the future.Recently, there have been multiple efforts in this direction, focusing on aspects such as error correction for synthesis/sequencing errors and erasure correction for handling missing sequences. The typical approach is to use separate codes for handling errors and erasures, but there is limited understanding of the efficiency of this framework. Furthermore, the existing techniques use short block-length codes and heavily rely on read consensus, both of which are known to be suboptimal in coding theory.In this work, we study the tradeoff between the writing and reading costs involved in DNA-based storage and propose a practical scheme to achieve an improved tradeoff between these quantities. Our scheme breaks with the traditional separation framework and instead uses a single large block-length LDPC code for both erasure and error correction. We also introduce novel techniques to handle insertion and deletion errors introduced by the synthesis process. For a range of writing costs, the proposed scheme achieves 30-40% lower reading costs than state-of-the-art techniques on experimental data obtained using array synthesis and Illumina sequencing.The code, data, and Supplementary Material is available athttps://github.com/shubhamchandak94/LDPC_DNA_storage.
Multi-omics data analysis implicating epigenetic inheritance in evolution and disease
Authors: Sharma Abhay 
Published: September 2019

AbstractRecent evidence surprisingly suggests existence of germline mediated epigenetic inheritance in diverse species including mammals. The evolutionary and health implications as well as the mechanistic plausibility of epigenetic inheritance are subjects of immense current interest and controversy, with integrative analysis expected to provide valuable insights. Here, an unbiased gene set enrichment analysis of existing multi-omics data is presented that readily supports a role of sperm DNA methylome in evolution and disease, as also in developmental mechanisms. In mice, differentially methylated sperm genes in cold induced inheritance specifically overrepresent genes associated with cold adaptation. Similarly, in humans, differentially methylated sperm genes associate with disease and adaptation in general, with specific disease association supported by prior evidence. Further, the sperm genes, like disease and adaptation genes, overrepresent genes known to exhibit higher mutability, loss-of-function intolerance, and haploinsufficiency. Finally, both mouse and human sperm genes show enrichment for genes that retain sperm methylation during development and are developmentally expressed. Together, the present analysis provides one-stop evidence to suggest that sperm DNA methylome acts as a melting pot of gene-environment interaction, inheritance, evolution, and health and disease.
Understanding the evolution of interspecies interactions in microbial communities
Authors: Gorter Florien A. , Manhart Michael , Ackermann Martin 
Published: September 2019

AbstractMicrobial communities are complex multi-species assemblages that are characterized by a multitude of interspecies interactions, which can range from mutualism to competition. The overall sign and strength of interspecies interactions have important consequences for emergent community-level properties such as productivity and stability. It is not well understood whether and how interspecies interactions change over evolutionary timescales. Here, we review the empirical evidence that evolution is an important driver of microbial community properties and dynamics on timescales that have traditionally been regarded as purely ecological. Next, we briefly discuss different modelling approaches to study evolution of communities, emphasizing the similarities and differences between evolutionary and ecological perspectives. We then propose a simple conceptual model for the evolution of communities. Specifically, we propose that the evolution of interspecies interactions depends crucially on the spatial structure of the environment. We predict that in well-mixed environments, traits will be selected exclusively for their direct fitness effects, while in spatially structured environments, traits may also be selected for their indirect fitness effects. Selection of indirectly beneficial traits should result in an increase in interaction strength over time, while selection of directly beneficial traits should not have such a systematic effect. We tested our intuitions using a simple quantitative model and found support for our hypotheses. The next step will be to test these hypotheses experimentally and provide input for a more refined version of the model in turn, thus closing the scientific cycle of models and experiments.
The effects of resource subsidy duration on detritus-based stream ecosystem: a stream mesocosm experiment
Authors: Sato Takuya , Ueda Rui , Takimoto Gaku 
Published: September 2019

SummaryMost of the resource subsidies are temporally variable, and studies have revealed that ecological processes can be mediated by the temporal attributes of subsidies, such as timing and frequency. Less studies have, however, examined the effects of the subsidy duration, an another major temporal attribute, on consumer populations, communities and ecosystem functions. Using an outdoor mesocosm experiment, we demonstrated that, even with the same total amounts, the prolonged subsidy let large-stage fish effectively monopolize the subsidy over small-stage fish, while the pulsed subsidy allowed small-stage fish to increase the ingestion rate of the subsidy. This effect resulted in causing weaker indirect positive effects on in-situ benthic prey and a leaf breakdown rate with the prolonged subsidy than with the pulsed-subsidy although it depended on dominant benthic prey species having different edibility. Increasing evidences have shown that global warming would not only advance, but also prolong the growing seasons, which may, in turn, make subsidies more prolonged. The ecological significance of the subsidy duration might be common in nature, and should be incorporated to better understand ecological processes in spatially and temporally coupled ecosystems.
Performance of Turquoise killifish, model organism in aging, on commercial pelleted diet: a step towards husbandry standardization
Authors: Žák Jakub , Dyková Iva , Reichard Marin 
Published: September 2019

SUMMARYDietary alteration is one of the most universally effective aging interventions, making its standardization a fundamental need for model organisms in aging. Here we address the current lack of standardized formulated diet for Turquoise KillifishNothobranchius furzeri– a promising model organism. We first demonstrated thatN. furzerican be fully weaned onto a standardized commercially available pelleted diet as the sole nutrition when kept in social tanks. We then compared nine somatic and six reproductive parameters between fish fed a typical laboratory diet - frozen chironomid larvae (bloodworms) and fish fed solely on BioMar pellets. Killifish readily consumed the pellets. Although fish consumed 7.5 times less food mass in the form of pellets than bloodworms, they had comparable somatic and reproductive performance. There was no difference between diet groups in body size, specific growth rate, condition or extent of hepatocellular vacuolation. Fish fed a pelleted diet had higher juvenile body mass and more visceral fat. Pellet-fed males had lower liver mass and possessed a lipid type of hepatocellular vacuolation instead of the prevailing glycogen-like vacuolation in the bloodworm-fed group. No significant effect was found on reproductive parameters. The negligible differences between dietary groups and good acceptance of pellets indicates their suitability as a useful starting point for diet standardization (and potential manipulation) inNothobranchius furzeri.
Practical Speedup of Bayesian Inference of Species Phylogenies by Restricting the Space of Gene Trees
Authors: Wang Yaxuan , Ogilvie Huw A. , Nakhleh Luay 
Published: September 2019

AbstractSpecies tree inference from multi-locus data has emerged as a powerful paradigm in the post-genomic era, both in terms of the accuracy of the species tree it produces as well as in terms of elucidating the processes that shaped the evolutionary history. Bayesian methods for species tree inference are desirable in this area as they have been shown to yield accurate estimates, but also to naturally provide measures of confidence in those estimates. However, the heavy computational requirements of Bayesian inference have limited the applicability of such methods to very small data sets.In this paper, we show that the computational efficiency of Bayesian inference under the multispecies coalescent can be improved in practice by restricting the space of the gene trees explored during the random walk, without sacrificing accuracy as measured by various metrics. The idea is to first infer constraints on the trees of the individual loci in the form of unresolved gene trees, and then to restrict the sampler to consider only resolutions of the constrained trees. We demonstrate the improvements gained by such an approach on both simulated and biological data.
A deeper understanding of intestinal organoid metabolism revealed by combining fluorescence lifetime imaging microscopy (FLIM) and extracellular flux analyses
Authors: Okkelman Irina A. , Neto Nuno , Papkovsky Dmitri B. , Monaghan Michael , Dmitriev Ruslan I. 
Published: September 2019

AbstractStem cells and the niche in which they reside feature a complex microenvironment with tightly regulated homeostasis, cell-cell interactions and dynamic regulation of metabolism. A significant number of organoid models has been described over the last decade, yet few methodologies can enable single cell level resolution analysis of the stem cell niche metabolic demands, in real-time and without perturbing integrity. Here, we studied the redox metabolism of Lgr5-GFP intestinal organoids by two emerging microscopy approaches based on luminescence lifetime measurement – fluorescence-based FLIM for NAD(P)H, and phosphorescence-based PLIM for real-time oxygenation. We found that exposure of stem (Lgr5-GFP) and differentiated (no GFP) cells to high and low glucose concentrations resulted in measurable shifts in oxygenation and redox status. NAD(P)H-FLIM and O2-PLIM both indicated that at high ‘basal’ glucose conditions, Lgr5-GFP cells had lower activity of oxidative phosphorylation when compared with cells lacking Lgr5. However, when exposed to low (0.5 mM) glucose, stem cells utilized oxidative metabolism more dynamically than non-stem cells. The high heterogeneity of complex 3D architecture and energy production pathways of Lgr5-GFP organoids were also confirmed by the extracellular flux (XF) analysis. Our data reveals that combined analysis of NAD(P)H-FLIM and organoid oxygenation by PLIM represents promising approach for studying stem cell niche metabolism in a live readout.
Predicting suitability of regions for Zika outbreaks with zero-inflated models trained using climate data
Authors: Roth Samantha , Teboh-Ewungkem Miranda , Li Ming 
Published: September 2019

AbstractIn recent years, Zika spread through the Americas. This virus has been linked to Guillain-Barré syndrome, which can lead to paralysis, and microcephaly, a severe birth defect. Zika is primarily transmitted by Aedes (Ae.) aegypti, a mosquito whose geographic range has expanded and is anticipated to continue shifting as the climate changes.We used statistical models to predict regional suitability for autochthonous Zika transmission using climatic variables. By suitability for Zika, we mean the potential for an outbreak to occur based on the climate’s habitability for Ae. aegypti. We trained zero-inflated Poisson (ZIP) and zero-inflated negative binomial (ZINB) regression models to predict Zika outbreak suitability using 20 subsets of climate variables for 102 regions. Variable subsets were selected for the final models based on importance to Ae. aegypti survival and their performance in aiding prediction of Zika-suitable regions. We determined the two best models to both be ZINB models. The best model’s regressors were winter mean temperature, yearly minimum temperature, and population, and the second-best model’s regressors were winter mean temperature and population.These two models were then run on bias-corrected climate projections to predict future climate suitability for Zika, and they generated reasonable predictions. The predictions find that most of the sampled regions are expected to become more suitable for Zika outbreaks. The regions with the greatest risk have increasingly mild winters and high human populations. These predictions are based on the most extreme scenario for climate change, which we are currently on track for.Author Summary:In recent years, Zika spread through the Americas. This virus has been linked to Guillain-Barré syndrome, which can lead to paralysis, and microcephaly, a severe birth defect. Zika is primarily transmitted by Aedes (Ae.) aegypti, a mosquito whose geographic range has expanded and is anticipated to continue shifting as the climate changes. We used statistical models to predict regional suitability for locally-acquired Zika cases using climatic variables. By suitability for Zika, we mean the potential for an outbreak to occur based on the climate’s habitability for Ae. aegypti. We trained statistical models to predict Zika outbreak suitability using 20 subsets of climate variables for 102 regions. Variable subsets were selected for the final two models based on importance to Ae. aegypti survival and their performance in aiding prediction of Zika-suitable regions. These two models were then run on climate projections to predict future climate suitability for Zika, and they generated reasonable predictions. The predictions find that most of the sampled regions are expected to become more suitable for Zika outbreaks. The regions with the greatest risk have high human populations and increasingly mild winters.
%svy_freqs: A generic SAS macro for cross-tabulation between a factor and a by-group variable given a third variable and creating publication-quality tables using data from complex surveys
Authors: Muthusi Jacques , Mwalili Samuel , Young Peter 
Published: September 2019

AbstractIntroductionIn epidemiological studies, cross-tabulations are a simple but important tool for understanding the distribution of socio-demographic characteristics among study participants. They become more useful when comparisons are presented using a by-group variable such as key demographic characteristic or an outcome status; for instance, sex or the presence or absence of a disease status. Most available statistical analysis software can easily perform cross-tabulations, however, output from these must be processed further to make it readily available for review and use in a publication. In addition, performing three-way cross-tabulations of complex survey data such as those required to show the distribution of disease prevalence across multiple factors and a by-group variable is not easily implemented directly using available standard procedures of commonly used statistical software.MethodsWe developed a generic SAS macro, %svy_freqs, to create quality publication-ready tables from cross-tabulations between a factor and a by-group variable given a third variable using survey or non-survey data. The SAS macro also performs classical two-way cross-tabulations and refines output into publication-quality tables. It provides extra features not available in existing procedures such as ability to incorporate parameters for survey design and replication-based variance estimation methods, performing validation checks for input parameters, transparently formatting character variable values into numeric ones and allowing for generalizability.ResultsWe demonstrate the application of the SAS macro in the analysis of data from the 2013-2014 National Health and Nutrition Examination Survey (NHANES), a complex survey designed to assess the health and nutritional status of adults and children in the United States (U.S.).ConclusionThe SAS code use to develop the macro is simple yet comprehensive, easy to follow, straightforward for the end user and simple for a SAS programmer to extend. The SAS macro has shown to shorten turn-around time for statistical analysis, eliminate errors when preparing output, and support reproducible research.
Distribution of Human T-Lymphotropic Virus (HTLV) and Hepatitis C Co-infection in Bahia, Brazil
Authors: Pereira Felicidade Mota , Almeida Maria da Conceição Chagas de , Santos Fred Luciano Neves , Carreiro Roberto Perez , Galvão-Castro Bernardo , Grassi Maria Fernanda Rios 
Published: September 2019

AbstractBoth Human T-lymphotropic virus type 1 (HTLV-1) and hepatitis C virus (HCV) are endemic in Brazil. In Salvador, the capital of the state of Bahia, 2% and 1.5% of the general population is infected with HTLV-1 or HCV. This study aimed to estimate the prevalence and the distribution of HTLV/HCV coinfection in Bahia. This cross-sectional study was conducted at the Central Laboratory of Public Health for the state of Bahia (LACEN-BA). All samples in the LACEN database submitted to serological testing for anti-HCV (chemiluminescence) and anti-HTLV-1/2 (chemiluminescence/ELISA and Western blot) from 2004 to 2013 were included. Infection rate was expressed as the number of infected individuals per 100,000 inhabitants in a given municipality; municipalities were grouped by microregion for further analysis. A total of 120,192 samples originating from 358 of the 417 municipalities in Bahia (85.8%) were evaluated. The overall HCV coinfection rate in HTLV-positive was 14.31% [2.8 (ranging from 0.4 to 8.0) per 100,000 inhabitants.] Twenty-one (5%) of the municipalities reported at least one case of HTLV/HCV coinfection. Most cases (87%) were concentrated in three microregions (Salvador: 79%, Ilhéus/Itabuna: 5%, Porto Seguro: 3%). Coinfection occurred more frequently in males (51%) with a mean age of 59 [(IQR): 46 – 59] years. HTLV/HCV coinfection in the state of Bahia was more frequently found among males living in the microregions of Salvador, Ilhéus/Itabuna and Porto Seguro, all of which are known to be endemic for HTLV infection. Keywords: HTLV; HCV; Coinfection; Bahia; Prevalence
Nuclear gene proximity and protein interactions shape transcript covariances in mammalian single cells
Authors: Tarbier Marcel , Mackowiak Sebastian D. , Frade João , Catuara-Solarz Silvina , Biryukova Inna , Gelali Eleni , Menéndez Diego Bárcena , Zapata Luis , Ossowski Stephan , Bienko Magda , Gallant Caroline J. , Friedländer Marc R. 
Published: September 2019

AbstractSingle-cell RNA sequencing studies into gene co-expression patterns could yield important new regulatory and functional insights, but have so far been limited by the confounding effects of cell differentiation and the cell cycle. We apply a tailored experimental design that eliminates these confounders, and report >80,000 intrinsically covarying gene pairs in mouse embryonic stem cells. These covariances form a network with biological properties, outlining known and novel gene interactions. We provide the first evidence that miRNAs naturally induce transcriptome-wide covariances, and compare the relative importance of nuclear organization, transcriptional and post-transcriptional regulation in defining covariances. We find that nuclear organization has the greatest impact, and that genes encoding for physically interacting proteins specifically tend to covary, suggesting importance for protein complex stoichiometry. Our results lend support to the concept of post-transcriptional ‘RNA operons’, but we further present evidence that nuclear proximity of genes on the same or even distinct chromosomes also provides substantial functional regulation in mammalian single cells.
A novel antibody targeting ICOS increases intratumoural cytotoxic to regulatory T cell ratio and induces tumour regression
Authors: Sainson Richard C.A. , Thotakura Anil K. , Kosmac Miha , Borhis Gwenoline , Parveen Nahida , Kimber Rachael , Carvalho Joana , Henderson Simon , Pryke Kerstin , Okell Tracey , O’Leary Siobhan , Ball Stuart , Gamand Lauriane , Taggart Emma , Pring Eleanor , Ali Hanif , Craig Hannah , Wong Vivian W. Y. , Liang Qi , Rowlands Robert J. , Lecointre Morgane , Campbell Jamie , Kirby Ian , Melvin David , Germaschewski Volker , Oelmann Elisabeth , Quaratino Sonia , McCourt Matthew 
Published: September 2019

AbstractThe immunosuppressive tumour microenvironment constitutes a significant hurdle to the response to immune checkpoint inhibitors. Both soluble factors and specialised immune cells such as regulatory T cells (TReg) are key components of active intratumoural immunosuppression. Previous studies have shown that Inducible Co-Stimulatory receptor (ICOS) is highly expressed in the tumour microenvironment, especially on TReg, suggesting that it represents a relevant target for preferential depletion of these cells. Here, we used immune profiling of samples from tumour bearing mice and cancer patients to characterise the expression of ICOS in different tissues and solid tumours. By immunizing anIcosknockout transgenic mouse line expressing antibodies with human variable domains, we selected a fully human IgG1 antibody called KY1044 that binds ICOS from different species. Using KY1044, we demonstrated that we can exploit the differential expression of ICOS on T cell subtypes to modify the tumour microenvironment and thereby improve the anti-tumour immune response. We showed that KY1044 induces sustained depletion of ICOShighTRegcells in mouse tumours and depletion of ICOShighT cells in the blood of non-human primates, but was also associated with secretion of pro-inflammatory cytokines from ICOSlowTEFFcells. Altogether, KY1044 improved the intratumoural TEFF:TRegratio and increased activation of TEFFcells, resulting in monotherapy efficacy or in synergistic combinatorial efficacy when administered with the immune checkpoint blocker anti-PD-L1. In summary, our data demonstrate that targeting ICOS with KY1044 can favourably alter the intratumoural immune contexture, promoting an anti-tumour response.