bluuebunny/crossref_metadata_2025_split huggingface dataset:
Population mobility and dengue fever transmission in a major city in Southeastern Brazil, 2007-2015
Authors: Johansen Igor C. , Castro Marcia C. , Alves Luciana C. , Carmo Roberto L. 
Published: October 2019

AbstractBackgroundAround 14% of world dengue virus (DENV) cases occur in the Americas, the majority of them in Brazil. Although socioeconomic, environmental and behavioral correlates of dengue have been analyzed for different contexts, the role played by population mobility on DENV epidemics, especially at the local level, remains scant. This study assesses whether the daily pattern of population mobility is associated with DENV transmission in Campinas, a Brazilian major city with over 1.2 million inhabitants in São Paulo state.Methodology/Principal FindingsDENV notifications from 2007 to 2015 were geocoded at street level (n=114,884) and combined with sociodemographic and environmental data from the 2010 Population Census. Population mobility was extracted from the Origin-Destination Survey (ODS), carried out in 2011, and daily precipitation was obtained from satellite imagery. Zero-Inflated Negative Binomial (ZINB) regression models controlled by demographic and environmental factors revealed that high population mobility had a substantial positive effect on higher risk for DENV transmission. High income and residence in apartments were found to be protective against the disease, while unpaved streets, number of strategic points (such as scrapyards and tire repair shops), and precipitation were consistently risk factors for DENV infection.Conclusions/SignificanceThe use of fine-scale geographical data can unravel transmission idiosyncrasies not evident from a coarse spatial analysis. Even in a major city like Campinas, the vast majority of population daily mobility occurs at short distances. Based on our results, public policies on DENV transmission control should dedicate special attention to local hubs of population mobility, especially during high transmission weeks and in high dengue incidence areas.Author SummaryCurrently, about half of the world population is at risk of a dengue infection. Numerous studies have addressed the socioeconomic and environmental determinants of the disease. However, little is known about the role played by population mobility on dengue transmission, particularly at the local scale. This study aims at investigating this issue. Our hypothesis was that population movements are a prominent driving force for dengue diffusion locally. We investigated the case of Campinas, a municipality with over 1.2 million inhabitants in Brazil that recorded dengue epidemics in 2007, 2014 and 2015. Our study focused on the years 2007 to 2015, comprising more than 114 thousand cases, geocoded to the household address, and combined with socioeconomic, environmental and daily population mobility data. Our results showed that even controlling for demographic and environmental factors, population mobility was the most important predictor for dengue fever incidence.
Intracellular localization and gene expression analysis provide new insights on LEA proteins’ diversity in anhydrobiotic midge
Authors: Kondratyeva Sabina A. , Nesmelov Alexander A. , Cherkasov Alexander V. , Miyata Yugo , Tokumoto Shoko , Kikawada Takahiro , Gusev Oleg A. , Shagimardanova Elena I. 
Published: October 2019

AbstractAnhydrobiosis, an adaptive ability to withstand complete desiccation, is in insects limited to a single species: the nonbiting midge Polypedilum vanderplanki (the sleeping chironomid). Evolution of anhydrobiosis in a single representative of a large genus is associated with drastic changes in genome structure, including the emergence of new multimember gene families directly involved in desiccation tolerance. Among them, Late Embryogenesis Abundant (LEA) proteins, which protect other proteins from aggregation caused by desiccation, are believed to originate via horizontal gene transfer from a bacterial donor. To obtain new insights on the biological background of the expanded 27-member LEA protein group in P. vanderplanki, we investigated the expression of corresponding genes in a P. vanderplanki-derived cell line, capable of anhydrobiosis, in a normal state and during induction of desiccation tolerance. We found that all LEA proteins genes identified in P. vanderplanki’s genome except PvLea16 and PvLea17 are also expressed in Pv11 cells. Their expression was elevated in response to anhydrobiosis-inducing trehalose treatment. Expression patterns of PvLea genes were well preserved in Pv11 cells in comparison to P. vanderplanki’s larvae both in the control group and during the anhydrobiosis cycle. We also investigated localization of LEA proteins in Pv11 cells and Sf9 cells and found a different level of conservation in intracellular localization of the protein expressed in mammalian and insect cells.
Genetic diversity and population structure of indigenous chicken in Rwanda using microsatellite markers
Authors: Habimana R. , Okeno T.O. , Ngeno K. , Mboumba S. , Assami P. , Gbotto A. , Keambou C.T. , Nishimwe K. , Mahoro J. , Yao N. 
Published: October 2019

AbstractRwanda has about 4.5 million of indigenous chicken (IC) that are very low in productivity. To initiate any genetic improvement programme, IC needs to be accurately characterized. The key purpose of this study was to ascertain the genetic diversity of IC in Rwanda using microsatellite markers. Blood samples of IC sampled from 5 agro-ecological zones were collected from which DNA was extracted, amplified by PCR and genotyped using 28 microsatellite markers. A total of 325 (313 indigenous and 12 exotic) chicken were genotyped and revealed a total number of 305 alleles varying between 2 and 22 with a mean of 10.89 per locus. 186 distinct alleles and 60 private alleles were also observed. The frequency of private alleles was highest in samples from the Eastern region, whereas those from the North West had the lowest. The influx of genes was lower in the Eastern agro-ecological zone than the North West. The mean observed heterozygosity was 0.6155, whereas the average expected heterozygosity was 0.688. The overall inbreeding coefficient among the population was 0.040. Divergence from the Hardy-Weinberg equilibrium was significant in 90% of loci in all the populations. The analysis of molecular variance revealed that about 92% of the total variation originated from variation within populations. Additionally, the study demonstrated that IC in Rwanda could be clustered into four gene groups. In conclusion, there was considerable genetic diversity in IC in Rwanda, which represents a crucial genetic resource that can be conserved or optimized through genetic improvement.
Discrete populations of isotype-switched memory B lymphocytes are maintained in murine spleen and bone marrow
Authors: Riedel René , Addo Richard , Ferreira-Gomes Marta , Heinz Gitta Anne , Heinrich Frederik , Kummer Jannis , Greiff Victor , Schulz Daniel , Klaeden Cora , Cornelis Rebecca , Menzel Ulrike , Kröger Stefan , Stervbo Ulrik , Köhler Ralf , Haftmann Claudia , Kühnel Silvia , Lehmann Katrin , Maschmeyer Patrick , McGrath Mairi , Naundorf Sandra , Hahne Stefanie , Sercan-Alp Özen , Siracusa Francesco , Stefanowski Jonathan , Weber Melanie , Westendorf Kerstin , Zimmermann Jakob , Hauser Anja E. , Reddy Sai T. , Durek Pawel , Chang Hyun-Dong , Mashreghi Mir-Farzin , Radbruch Andreas 
Published: October 2019

AbstractHere we describe tissue-resident memory B lymphocytes of spleen and bone marrow. Single cell transcriptomes and B cell receptor repertoires identify several exclusive populations of isotype-switched memory B cells (Bsm) in murine spleen and bone marrow, and one interconnected population of 10-20%. A population of marginal zone-like Bsm is located exclusively in the spleen while a novel population of quiescent Bsm is located exclusively in the bone marrow. Cells of two further populations, present in both, spleen and bone marrow, differ in repertoire between the two organs, i.e. are resident as well. Finally, another interconnected population of Bsm of the B1 lineage is present in spleen and bone marrow. In the bone marrow, all Bsm individually dock onto VCAM1+ stromal cells, resting in terms of activation, proliferation and mobility. The discrete B cell memory of bone marrow may be key to rapid secondary humoral responses to systemic antigens.
Amplitude effects allow short jetlags and large seasonal phase shifts in minimal clock models
Authors: Ananthasubramaniam Bharath , Schmal Christoph , Herzel Hanspeter 
Published: October 2019

AbstractMathematical models of varying complexity have helped shed light on different aspects of circadian clock function. In this work, we question whether minimal clock models (Goodwin models) are sufficient to reproduce essential phenotypes of the clock: a small phase response curve (PRC), fast jetlag and seasonal phase shifts. Instead of building a single best model, we take an approach where we study the properties of a set of models satisfying certain constraints; here a one-hour pulse PRC with a range of three hours and clock periods between 22h and 26h. Surprisingly, almost all these randomly parameterized models showed a four hour change in phase of entrainment between long and short days and jetlag durations of three to seven days in advance and delay. Moreover, intrinsic clock period influenced jetlag duration and entrainment amplitude and phase. Fast jetlag was realized in this model by means of an interesting amplitude effect: the association between clock amplitude and clock period termed ‘twist’. This twist allows amplitude changes to speed up and slow down clocks enabling faster shifts. These findings were robust to the addition of positive feedback to the model. In summary, the known design principles of rhythm generation – negative feedback, long delay and switch-like inhibition (we review these in detail) – are sufficient to reproduce the essential clock phenotypes. Furthermore, amplitudes play a role in determining clock properties and must be always considered, although they are difficult to measure.
Whole genome re-sequencing reveals recent signatures of selection in three strains of farmed Nile tilapia (Oreochromis niloticus)
Authors: Cádiz María I. , López María E. , Díaz-Domínguez Diego , Cáceres Giovanna , Yoshida Grazyella M. , Gomez-Uchida Daniel , Yáñez José M. 
Published: October 2019

AbstractNile tilapia (Oreochromis niloticusLinnaeus, 1758) belong to the second most cultivated group of fish in the world, mainly because of its favorable characteristics for production. Genetic improvement programs in this species began in the late 1980s to enhance some traits of commercial interest. The resulting domestication process of Nile tilapia may have modified the genome through selective pressure, leaving signals that can be detected at the molecular level. In this work, signatures of selection were identified using genome-wide SNP data, using two complementary methods based in extended haplotype homozygosity (EHH)._Whole-genome sequencing of 326 individuals from three strains (A, B and C) of farmed tilapia from two countries (Brazil and Costa Rica) was carried out using Illumina HiSeq 2500 technology. After applying conventional SNP-calling and quality-control pipelines, a total of ~1.3M high-quality SNPs were inferred and used as input for the Integrated Haplotype Score (|iHS|) and standardized log-ratio of integrated EHH between pairs of populations (Rsb) methods. We detected 16, 174 and 96 candidate genes subjected to selection in strain A, B, and C, respectively. These candidate genes represent putative genomic landmarks that could contain functions of biological and commercial interest.
A Synthetic Biology Approach to Sequential Stripe Patterning and Somitogenesis
Authors: Wu Fuqing , He Changhan , Fang Xin , Baez Javier , Ohnmacht Thai , Zhang Qi , Chen Xingwen , Allison Kyle R. , Kuang Yang , Wang Xiao 
Published: October 2019

AbstractReaction-diffusion (RD) based clock and wavefront model has long been proposed as the mechanism underlying biological pattern formation of repeated and segmented structures including somitogenesis. However, systematic molecular level understanding of the mechanism remains elusive, largely due to the lack of suitable experimental systems to probe RD quantitatively in vivo. Here we design a synthetic gene circuit that couples gene expression regulation (reaction) with quorum sensing (diffusion) to guide bacterial cells self-organizing into stripe patterns at both microscopic and colony scales. An experimentally verified mathematical model confirms that these periodic spatial structures are emerged from the integration of oscillatory gene expression as the molecular clock and the outward expanding diffusions as the propagating wavefront. Furthermore, our paired model-experiment data illustrate that the RD-based patterning is sensitive to initial conditions and can be modulated by external inducers to generate diverse patterns, including multiple-stripe pattern, target-like pattern and ring patterns with reversed fluorescence. Powered by our synthetic biology setup, we also test different topologies of gene networks and show that network motifs enabling robust oscillations are foundations of sequential stripe pattern formation. These results verified close connections between gene network topology and resulting RD driven pattern formation, offering an engineering approach to help understand biological development.
ECMarker: Interpretable machine learning model identifies gene expression biomarkers predicting clinical outcomes and reveals molecular mechanisms of human disease in early stages
Authors: Jin Ting , Nguyen Nam D. , Talos Flaminia , Wang Daifeng 
Published: October 2019

AbstractGene expression and regulation, a key molecular mechanism driving human disease development, remains elusive, especially at early stages. Integrating the increasing amount of population-level genomic data and understanding gene regulatory mechanisms in disease development are still challenging. Machine learning has emerged to solve this, but many machine learning methods were typically limited to building an accurate prediction model as a “black box”, barely providing biological and clinical interpretability from the box. To address these challenges, we developed an interpretable and scalable machine learning model, ECMarker, to predict gene expression biomarkers for disease phenotypes and simultaneously reveal underlying regulatory mechanisms. Particularly, ECMarker is built on the integration of semi- and discriminative- restricted Boltzmann machines, a neural network model for classification allowing lateral connections at the input gene layer. This interpretable model is scalable without needing any prior feature selection and enables directly modeling and prioritizing genes and revealing potential gene networks (from lateral connections) for the phenotypes. With application to the gene expression data of non-small cell lung cancer (NSCLC) patients, we found that ECMarker not only achieved a relatively high accuracy for predicting cancer stages but also identified the biomarker genes and gene networks implying the regulatory mechanisms in the lung cancer development. Additionally, ECMarker demonstrates clinical interpretability as its prioritized biomarker genes can predict survival rates of early lung cancer patients (p-value < 0.005). Finally, we identified a number of drugs currently in clinical use for late stages or other cancers with effects on these early lung cancer biomarkers, suggesting potential novel candidates on early cancer medicine. ECMarker is open source as a general-purpose tool at https://github.com/daifengwanglab/ECMarker.
Silicon Nanowires for Intracellular Optical Interrogation with Sub-Cellular Resolution
Authors: Rotenberg Menahem Y. , Elbaz Benayahu , Nair Vishnu , Schaumann Erik , Yamamoto Naomi , Matino Laura , Santoro Francesca , Tian Bozhi 
Published: October 2019

ABSTRACTCurrent techniques for intracellular electrical interrogation are substrate bound and are technically demanding, or lack high spatial resolution. In this work, we use silicon nanowires, which are spontaneously internalized by many cell types, to achieve photo-stimulation with sub-cellular resolution. Myofibroblasts loaded with silicon nanowires remain viable and can undergo cell division. Stimulation of silicon nanowires at separate intracellular locations results in local calcium fluxes. We also show that nanowire-containing myofibroblasts can electrically couple to cardiomyocytes in co-culture and that photo-stimulation of the nanowires increases the spontaneous activation rate in neighboring cardiomyocytes. Finally, we demonstrate that this methodology can be extended to the interrogation of signaling in neuron–glia interactions using nanowire-containing oligodendrocytes.
Transcriptome profiles in brains of mice heterozygous for a DYT1 dystonia-associated mutation in the endogenous Tor1a gene
Authors: Mitchell Sara B. , Chimenti Michael S. , Kawano Hiroyuki , Tom Yuen Tsun Ming , Sjurson Ashley E. , Iwabuchi Sadahiro , Knudtson Kevin L , Bair Thomas B , Kolbe Diana , Harata N. Charles 
Published: October 2019

ABSTRACTIn patients with the brain disorder dystonia, body movement is severely affected – with involuntary muscle contractions and abnormal postures, causing extensive deterioration of the patient’s quality of life. The most common inherited form of this disorder is DYT1 dystonia, which is caused by a mutation in TOR1A gene and autosomal dominant. The molecular mechanisms that underlie the effects of the TOR1A mutation on brain function remain unclear. To understand these, we examined the gene expression profiles (transcriptome) in four brain regions (cerebral cortex, hippocampus, striatum and cerebellum) in a mouse model, the heterozygous ΔE-torsinA knock-in mice which genetically reproduce the mutation in DYT1 dystonia. The samples were obtained at 2 to 3 weeks of age, a period during which synaptic abnormalities have been reported. Pairwise comparisons of brain regions revealed differential gene expression irrespective of genotype. A comparison of heterozygous to wild-type mice failed to reveal genotype-dependent differences in gene expression in any of the four brain regions when examined individually. However, genotype-dependent differences became apparent when the information for all brain regions was combined. These results suggest that any changes in the transcriptome within a brain region were subtle at this developmental stage, but that statistically significant changes occur across all brain regions. Such changes in the transcriptome, although subtle in degree, could underlie the processes that give rise to DYT1 dystonia.
Found in Transcription: Gene fusions arise through defects in RNA processing in the absence of chromosomal rearrangements
Authors: Jiang Yue , Apostolides Michael J. , Husić Mia , Siddaway Robert , Yu Man , Mark Stephanie , Ramani Arun K. , Hawkins Cynthia , Brudno Michael 
Published: October 2019

AbstractRecent advancements in high throughput sequencing analysis have enabled the characterization of cancer-driving fusions, improving our understanding of cancer development. Most fusion calling methods, however, examine either RNA or DNA information alone and are limited to a rigid definition of what constitutes a fusion. For this study we developed a pipeline that incorporates several fusion calling methods and considers both RNA and DNA to capture a more complete representation of the tumour fusion landscape. Interestingly, most of the fusions we identified were specific to RNA, with no evidence of corresponding genomic restructuring. Further, while the average total number of fusions in tumour and normal brain tissue samples is comparable, their overall fusion profiles vary significantly. Tumours have an over-representation of fusions occurring between coding genes, whereas fusions involving intergenic or non-coding regions comprised the vast majority of those in normals. Tumours were also more abundant in unique, sample-specific fusions compared to normals, though several fusions exhibited strong recurrence in the tumour type examined (diffuse intrinsic pontine glioma; DIPG) and were absent from both normal tissues and other cancers. Intriguingly, tumours also show broad up- or down-regulation of spliceosomal gene expression, which significantly correlates with fusion number (p=0.007). Our results show that RNA-specific fusions are abundant in both tumour and normal tissue and are associated with spliceosomal gene dysregulation. RNA-specific fusions should be considered as a potential mechanism that may contribute to cancer formation initiation and maintenance alongside more traditional structural events.
Antagonism of PP2A is an independent and conserved function of HIV-1 Vif and causes cell cycle arrest
Authors: Marelli Sara , Williamson James C , Protasio Anna V , Naamati Adi , Greenwood Edward JD , Deane Janet E , Lehner Paul J , Matheson Nicholas J 
Published: October 2019

AbstractThe seminal description of cellular restriction factor APOBEC3G and its antagonism by HIV-1 Vif has underpinned two decades of research on the host-virus interaction. As well as APOBEC3G and its homologues, however, we have recently discovered that Vif is also able to degrade the PPP2R5 family of regulatory subunits of key cellular phosphatase PP2A (PPP2R5A-E) (Greenwood et al., 2016; Naamati et al., 2019). We now identify amino acid polymorphisms at positions 31 and 128 of HIV-1 Vif which selectively regulate the degradation of PPP2R5 family proteins. These residues covary across HIV-1 virusesin vivo, favouring depletion of PPP2R5A-E. Through analysis of point mutants and naturally occurring Vif variants, we further show that degradation of PPP2R5 family subunits is both necessary and sufficient for Vif-dependent G2/M cell cycle arrest. Antagonism of PP2A by HIV-1 Vif is therefore independent of APOBEC3 family proteins, and regulates cell cycle progression in HIV-infected cells.
Minutes-timescale 3D isotropic imaging of entire organs at subcellular resolution by content-aware compressed-sensing light-sheet microscopy
Authors: Fang Chunyu , Chu Tingting , Yu Tingting , Huang Yujie , Li Yusha , Wan Peng , Feng Wenyang , Wang Xuechun , Mei Wei , Zhu Dan , Fei Peng 
Published: October 2019

AbstractInstant 3D imaging of entire organs and organisms at cellular resolution is a recurring challenge in life science. Here we report on a computational light-sheet microscopy able to achieve minute-timescale mapping of entire macro-scale organs at high spatial resolution, thereby overcoming the throughput limit of current 3D microscopy implementations. Through combining a dual-side confocally-scanned Bessel light-sheet illumination which provides thinner-and-wider optical sectioning of deep tissues, with a content-aware compressed sensing (CACS) computation pipeline which further improves the contrast and resolution based on a single acquisition, our method yields 3D images with high, isotropic spatial resolution and rapid acquisition improved by two-orders of magnitude. We demonstrate the imaging of whole brain (∼400 mm3), entire gastrocnemius and tibialis muscles (∼200 mm3) of mouse at subcellular resolution (0.5-μm isovoxel) and ultra-high throughput of 5∼10 minutes per sample. Various system-level cellular analyses, such as mapping cell populations at different brain sub-regions, tracing long-distance projection neurons over the entire brain, and calculating neuromuscular junction occupancy across whole muscle, were also readily enabled by our method.