bluuebunny/crossref_metadata_2025_split huggingface dataset:
Virus infection is controlled by cell type-specific sensing of murine cytomegalovirus through MyD88 and STING
Authors: Piersma Sytse J. , Poursine-Laurent Jennifer , Yang Liping , Barber Glen N. , Parikh Bijal A. , Yokoyama Wayne M. 
Published: March 2020

AbstractRecognition of DNA viruses, such as cytomegaloviruses (CMVs), through patternrecognition receptor (PRR) pathways involving MyD88 or STING constitute a first-line defense against infections mainly through production of type I interferon (IFN-I). However, the role of these pathways in different tissues is incompletely understood, an issue particularly relevant to the CMVs which have broad tissue tropisms. Herein, we investigated anti-viral effects of MyD88 and STING in distinct cell types that are infected with murine CMV (MCMV). Bone marrow chimeras revealed STING-mediated MCMV control in hematological cells, similar to MyD88. However, unlike MyD88, STING also contributed to viral control in non-hematological, stromal cells. Infected splenic stromal cells produced IFN-I in a cGAS-STING-dependent and MyD88-independent manner, while plasmacytoid dendritic cell IFN-I had inverse requirements. MCMV-induced natural killer (NK) cytotoxicity was dependent on MyD88 and STING. Thus, MyD88 and STING contribute to MCMV control in distinct cell types that initiate downstream immune responses.
Holistic assessment of large old trees: a framework and its application for Romania
Authors: Arghius Viorel , Malos Cristian , Macicasan Vlad , Hartel Tibor 
Published: March 2020

AbstractLarge old trees are keystone ecological structures and have exceptional sociocultural values. Still, holistic approaches to national assessments of large old trees are scarse in the scientific literature. Here we propose and apply a holistic framework to understand the distribution of large old trees, the formal regulations targeting the conservation of large old trees and the ways large old trees are present in the popular news in Romania. There were 4032 large old tree records in Romania most of the records being concentrated in the Central and North-Western part of Romania. The number of tree records decreases with the decreasing terrain accessibility. Almost 50% of the large old tree records are in areas not covered by nature conservation regulations and 2/3 of the terrestrial protected areas have no open access large old tree records, so far. We identified five formal regulations which could be relevant for large old tree conservation in Romania, however, only two of these explicitly targets large old trees. The lack of knowledge and interest, the lack of expertize, institutional capacity, vested interests (corruption) and inconsistencies within the regulations are the major barriers in the formal protection of large old trees. We also identified several opportunities for the local initiatives to protect large old trees, based on the current legislative frameworks. We identified 259 internet news targeting large old trees in Romania which reveals a wide range of values and concerns associated to large old trees at the level of the local communities. While discussing our results we highlight the benefits of a wider adoption of our approach for science, decision making and local initiatives to save large old trees.
Persistence of aWolbachia-driven sex ratio bias in an island population ofEuremabutterflies
Authors: Kageyama Daisuke , Narita Satoko , Konagaya Tatsuro , Miyata Mai N. , Abe Jun , Mitsuhashi Wataru , Nomura Masashi 
Published: March 2020

AbstractIt is generally believed that when maternally inherited sex ratio distorters become predominant, either the host population goes extinct or nuclear suppressors evolve in the host. Here, we show an empirical case where all-female-producingWolbachiais likely to be stably maintained at a high frequency. On an island population of the butterflyEurema mandarina, aWolbachiastrainwFem, which makes female hosts produce all-female offspring without sibling lethality (female drive), is highly prevalent. We found that, with some fluctuations,wFem appeared to be stably maintained for at least 12 years at a high frequency, resulting in the existence of an abnormally high number of virgin females. Interestingly, comparison between sex ratios of captive individuals and sex ratios deduced fromwFem frequencies suggested a plastic behavioral change of males and females in response to the shift of sex ratios.wFem presence does not affect brood size but has a slightly negative effect on body size. Stable coexistence ofwFem-positive and -negative females in the population may be explained via mate choice by males, which keepswFem in check. Taken together, this butterfly population is an attractive model for future studies on the population dynamics of sex ratios and mating behavior.
Prevalence and trend of malaria with anaemia among under-five children in Jasikan District, Ghana
Authors: Domechele William , Wak George Pokoanti , Zotor Francis Bruno 
Published: March 2020

AbstractBackgroundMalaria still remains a major killer of children under-five, claiming the life of one child every two minutes globally. More than 78% of deaths among children under-five in Africa are as a result of malaria infection. Despite the several interventions to reduce malaria and anaemia, the disease remains a global public concern as more children continue to die. This study assessed the prevalence and trend of malaria and anaemia in children under-five years from 2012 to 2016.MethodsWe conducted a descriptive cross-sectional study among children under-five with malaria and anaemia who received care at the hospital in Jasikan town, Ghana from 2012 to 2016. Data were extracted from the children’s ward admission and discharge registers. We computed descriptive statistics to describe the data. STATA version 14 was used to carry out the analyses.ResultsOut of 30082 malaria cases, 835 were with anaemia from 2012 to 2016. This study demonstrated an overall proportion of malaria with anaemia as 0.028 (28 per 1000 malaria cases). Year 2014 recorded the highest proportion (38 per 1,000 malaria cases) of malaria with anaemia cases in the district. Overall, prevalence rate of malaria and anaemia cases separately was found as 61.5% and 4.4% respectively from 2012-2016. Children within 24-35 months’ age group contributed the highest (28.3%) and 0-11 months accounted for the lowest (12.9%) malaria with anaemia cases. Majority of malaria with anaemia cases 531 (63.6%) occurred in the rainy season from June to July.ConclusionThere is a high prevalence of malaria with anaemia cases among children under-five from 2012-2016. Age and seasonal variation were found to be predictors of an increase in the prevalence of malaria with anaemia.
A unifying structural and functional model of the coronavirus replication organelle: tracking down RNA synthesis
Authors: Snijder Eric J. , Limpens Ronald W.A.L. , de Wilde Adriaan H. , de Jong Anja W. M. , Zevenhoven-Dobbe Jessika C. , Maier Helena J. , Faas Frank F.G.A. , Koster Abraham J. , Bárcena Montserrat 
Published: March 2020

AbstractZoonotic coronavirus (CoV) infections, like those responsible for the current SARS-CoV-2 epidemic, cause grave international public health concern. In infected cells, the CoV RNA-synthesizing machinery associates with modified endoplasmic reticulum membranes that are transformed into the viral replication organelle (RO). While double-membrane vesicles (DMVs) appear to be apan-coronavirus RO element, studies to date describe an assortment of additional coronavirus-induced membrane structures. Despite much speculation, it remains unclear which RO element(s) accommodate viral RNA synthesis. Here we provide detailed 2D and 3D analyses of CoV ROs and show that diverse CoVs essentially induce the same membrane modifications, including the small open double-membrane spherules (DMSs) previously thought to be restricted to gamma- and delta-CoV infections and proposed as sites of replication. Metabolic labelling of newly-synthesized viral RNA followed by quantitative EM autoradiography revealed abundant viral RNA synthesis associated with DMVs in cells infected with the beta-CoVs MERS-CoV and SARS-CoV, and the gamma-CoV infectious bronchitis virus. RNA synthesis could not be linked to DMSs or any other cellular or virus-induced structure. Our results provide a unifying model of the CoV RO and clearly establish DMVs as the central hub for viral RNA synthesis and a potential drug target in coronavirus infection.
De NovoPhosphoinositide Synthesis in Zebrafish Is Required for Triad Formation but Not Essential for Myogenesis
Authors: Smith Lindsay , Fabian Lacramioara , Al-Maawali Almundher , Noche Ramil R. , Dowling James J. 
Published: March 2020

AbstractPhosphoinositides (PIPs) and their regulatory enzymes are key players in many cellular processes and are required for aspects of vertebrate development. Dysregulated PIP metabolism has been implicated in several human diseases, including a subset of skeletal myopathies that feature structural defects in the triad. The role of PIPs in skeletal muscle formation, and particularly triad biogenesis, has yet to be determined. CDP-diacylglycerol-inositol 3-phosphatidyltransferase (CDIPT) catalyzes the formation of phosphatidylinositol, which is the base of all PIP species. Loss of CDIPT should, in theory, result in the failure to produce PIPs, and thus provide a strategy for establishing the requirement for PIPs during embryogenesis. In this study, we generatedcdiptmutant zebrafish and determined the impact on skeletal myogenesis. Analysis ofcdiptmutant muscle revealed no apparent global effect on early muscle development. However, small but significant defects were observed in triad size, with T-tubule area, inter terminal cisternae distance and gap width being smaller incdiptmutants. This was associated with a decrease in motor performance. Overall, these data suggest that myogenesis in zebrafish does not requirede novoPIP synthesis but does implicate a role for CDIPT in triad formation.
Unilateral vocal nerve resection alters neurogenesis in the avian song system in a region-specific manner
Authors: Aronowitz Jake V. , Perez Alice , O’Brien Christopher , Aziz Siaresh , Rodriguez Erica , Wasner Kobi , Ribeiro Sissi , Green Dovounnae , Faruk Farhana , Pytte Carolyn L. 
Published: March 2020

AbstractNew neurons undergo a critical period soon after migration during which the behavior of the animal may result in the survival or culling of these cells. In the songbird song system, new neurons may be maintained in the song motor pathway with respect to motor progression toward a target song--during juvenile song learning, seasonal song restructuring, and experimentally manipulated song variability. However, it is not known whether the quality of song per se, without progressive improvement, may also influence new neuron survival. To test this idea, we experimentally altered song acoustic structure by unilateral denervation of the syrinx. We found no effect of aberrant song on numbers of new neurons in the HVC of the song motor pathway, a loss of left-side dominance in new neurons in the auditory region caudomedial nidopallium (NCM), and a bilateral decrease in new neurons in the basal ganglia nucleus Area X. We propose new neuron survival may be determined in response to behavioral feedback in accordance with the function of new neurons within a given brain region. Studying the effects of singing behaviors on new neurons across multiple brain regions that subserve singing may give rise to general rules underlying the regulation of new neuron survival across taxa and brain regions more broadly.
From a biological template model to gait assistance with an exosuit
Authors: Firouzi Vahid , Davoodi Ayoob , Bahrami Fariba , Sharbafi Maziar A. 
Published: March 2020

AbstractBy invention of soft wearable assistive devices, known as exosuits, a new aspect in assisting unimpaired subjects is introduced. In this study, we designed and developed an exosuit with compliant biarticular thigh actuators, called BAExo. Unlike common method of using rigid actuators in exosuits, the BAExo is made of serial elastic actuators (SEA) resembling artificial muscles (AM). This bioinsipred design is complemented by the novel control concept of using the ground reaction force to adjust these AMs’ stiffness in the stance phase. By locking the motors in the swing phase the SEAs will be simplified to passive biarticular springs, which is sufficient for leg swinging. The key concept in our design and control approach is synthesizing human locomotion to develop assistive device, instead of copying the outputs of human motor control. Analysing human walking assistance using an experiment-based OpenSim model demonstrates the advantages of the proposed design and control of BAExo, regarding metabolic cost reduction and efficiency of the system. In addition, pilot experiments with the recently developed BAExo hardware support the applicability of the introduced method.Author summaryAging and mobility of elderly people are of crucial concern in developed countries. The U.S. Census Bureau reports that by the middle of the 21st century, about 80 million Americans will be 65 or older. According to the group’s research, medical costs resulting from falls by the elderly are expected to approach $32.4 billion by 2020. Therefore, assistance of elderly people and making the assistive devices more intelligent is a need in near future. However, this is not the only application of assistive devices. Exosuits, as soft wearable robots, introduced a new aspect in assisting a large range of population, even healthy young people. We introduce a novel design and control method for a new exosuit. As the research in the field of wearable assistive devices is growing in recent years and its application in daily life becomes more evident for the society, such studies with a unique view in design and control could have a significant impact. Our proposed biologically inspired approach could be potentially applied to other exosuits.
Genomic basis of parallel adaptation varies with divergence inArabidopsisand its relatives
Authors: Bohutínská Magdalena , Vlček Jakub , Yair Sivan , Laenen Benjamin , Konečná Veronika , Fracassetti Marco , Slotte Tanja , Kolář Filip 
Published: March 2020

AbstractParallel adaptation provides valuable insight into the predictability of evolutionary change through replicated natural experiments. A steadily increasing number of studies have demonstrated genomic parallelism, yet the magnitude of this parallelism varies depending on whether populations, species or genera are compared. This led us to hypothesize that the magnitude of genomic parallelism scales with genetic divergence between lineages, but whether this is the case and the underlying evolutionary processes remain unknown. Here, we resequenced seven parallel lineages of twoArabidopsisspecies which repeatedly adapted to challenging alpine environments. By combining genome-wide divergence scans with model-based approaches we detected a suite of 151 genes that show parallel signatures of positive selection associated with alpine colonization, involved in response to cold, high radiation, short season, herbivores and pathogens. We complemented these parallel candidates with published gene lists from five additional alpine Brassicaceae and tested our hypothesis on a broad scale spanning ~ 0.02 to 18 million years of divergence. Indeed, we found quantitatively variable genomic parallelism whose extent significantly decreased with increasing divergence between the compared lineages. We further modeled parallel evolution over theArabidopsiscandidate genes and showed that a decreasing probability of repeated selection of the same standing or introgressed alleles drives the observed pattern of divergence-dependent parallelism. We therefore conclude that genetic divergence between populations, species and genera, affecting the pool of shared variants, is an important factor in the predictability of genome evolution.Significance statementRepeated evolution tends to be more predictable. The impressive spectrum of recent reports on genomic parallelism, however, revealed that the fraction of the genome that evolves in parallel largely varies, possibly reflecting different evolutionary scales investigated. Here, we demonstrate divergence-dependent parallelism using a comprehensive genome-wide dataset comprising 12 cases of parallel alpine adaptation and identify decreasing probability of adaptive re-use of genetic variation as the major underlying cause. This finding empirically demonstrates that evolutionary predictability is scale dependent and suggests that availability of pre-existing variation drives parallelism within and among populations and species. Altogether, our results inform the ongoing discussion about the (un)predictability of evolution, relevant for applications in pest control, nature conservation, or the evolution of pathogen resistance.
Harvestman: A framework for hierarchical feature learning and selection from whole genome sequencing data
Authors: Frisby Trevor S. , Baker Shawn James , Marçais Guillaume , Hoang Quang Minh , Kingsford Carl , Langmead Christopher James 
Published: March 2020

AbstractWe present Harvestman, a method that takes advantage of hierarchical relationships among the possible biological interpretations and representations of genomic variants to perform automatic feature learning, feature selection, and model building. We demonstrate that Harvestmanscales to thousands of genomes comprising more than 84 million variants by processing phase 3 data from the 1000 Genomes Project, the largest publicly available collection of whole genome sequences. Next, using breast cancer data from The Cancer Genome Atlas, we show that Harvestmanselects a rich combination of representations that are adapted to the learning task, and performs better than a binary representation of SNPs alone. Finally, we compare Harvestmanto existing feature selection methods and demonstrate that our method selects smaller and less redundant feature subsets, while maintaining accuracy of the resulting classifier. The data used is available through either the 1000 Genomes Project or The Cancer Genome Atlas. Access to TCGA data requires the completion of a Data Access Request through the Database of Genotypes and Phenotypes (dbGaP). Binary releases of Harvestmancompatible with Linux, Windows, and Mac are available for download athttps://github.com/cmlh-gp/Harvestman-public/releases
Profiling anti-apoptotic protein BCL-xL expression in U-87 MG glioblastoma cells and patient-derived tumorspheres
Authors: Fanfone D. , Gabut M. , Ichim G. 
Published: March 2020

AbstractGlioblastoma is one of the cancers with the worst prognosis, despite huge efforts to understand its unusual heterogeneity and aggressiveness. These are mainly attributable to glioblastoma stem cells, which are also responsible for the frequent tumour recurrence following surgery or chemo/radiotherapy. We report here that tumorspheres derived from the U-87 MG glioblastoma cells have an increased expression of the anti-apoptotic protein BCL-xL. Modulation of this expression in tumorspheres enlightened us on the potential role of apoptosis and BCL-2 proteins might play in the survival of glioblastoma stem cells. Moreover, increased BCL-xL expression appears to sensitise glioblastoma cells to the newly developed BH3 mimetics, opening new therapeutic perspectives for treating glioblastoma patients.
Towards CNN Representations for Small Mass Spectrometry Data Classification: From Transfer Learning to Cumulative Learning
Authors: Seddiki Khawla , Saudemont Philippe , Precioso Frédéric , Ogrinc Nina , Wisztorski Maxence , Salzet Michel , Fournier Isabelle , Droit Arnaud 
Published: March 2020

AbstractRapid and accurate clinical diagnosis of pathological conditions remains highly challenging. A very important component of diagnosis tool development is the design of effective classification models with Mass spectrometry (MS) data. Some popular Machine Learning (ML) approaches have been investigated for this purpose but these ML models require time-consuming preprocessing steps such as baseline correction, denoising, and spectrum alignment to remove non-sample-related data artifacts. They also depend on the tedious extraction of handcrafted features, making them unsuitable for rapid analysis. Convolutional Neural Networks (CNNs) have been found to perform well under such circumstances since they can learn efficient representations from raw data without the need for costly preprocessing. However, their effectiveness drastically decreases when the number of available training samples is small, which is a common situation in medical applications. Transfer learning strategies extend an accurate representation model learnt usually on a large dataset containing many categories, to a smaller dataset with far fewer categories. In this study, we first investigate transfer learning on a 1D-CNN we have designed to classify MS data, then we develop a new representation learning method when transfer learning is not powerful enough, as in cases of low-resolution or data heterogeneity. What we propose is to train the same model through several classification tasks over various small datasets in order to accumulate generic knowledge of what MS data are, in the resulting representation. By using rat brain data as the initial training dataset, a representation learning approach can have a classification accuracy exceeding 98% for canine sarcoma cancer cells, human ovarian cancer serums, and pathogenic microorganism biotypes in 1D clinical datasets. We show for the first time the use of cumulative representation learning using datasets generated in different biological contexts, on different organisms, in different mass ranges, with different MS ionization sources, and acquired by different instruments at different resolutions. Our approach thus proposes a promising strategy for improving MS data classification accuracy when only small numbers of samples are available as a prospective cohort. The principles demonstrated in this work could even be beneficial to other domains (astronomy, archaeology…) where training samples are scarce.