bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantitative trait loci (QTL) underlying phenotypic variation in bioethanol-related processes in Neurospora crassa
Authors: Waters Joshua C. , Jhaveri Deval , Biffinger Justin C. , Lee Kwangwon 
Published: August 2019

AbstractBioethanol production from lignocellulosic biomass has received increasing attention over the past decade. Many attempts have been made to reduce the cost of bioethanol production by combining the separate steps of the process into a single-step process known as consolidated bioprocessing. This requires identification of organisms that can efficiently decompose lignocellulose to simple sugars and ferment the pentose and hexose sugars liberated to ethanol. There have been many attempts in engineering laboratory strains by adding new genes or modifying genes to expand the capacity of an industrial microorganism. There has been less attention in improving bioethanol-related processes utilizing natural variation existing in the natural ecotypes. In this study, we sought to identify genomic loci contributing to variation in saccharification of cellulose and fermentation of glucose in the fermenting cellulolytic fungus Neurospora crassa through quantitative trait loci (QTL) analysis. We identified one major QTL contributing to fermentation of glucose and multiple putative QTL’s underlying saccharification. Understanding the natural variation of the major QTL gene would provide new insights in developing industrial microbes for bioethanol production.
State of pedestrian road safety in Uganda: are interventions failing or absent?
Authors: Osuret Jimmy , Namatovu Stella , Biribawa Claire , Balugaba Bonny E , Zziwa Esther Bayiga , Muni Kennedy , Ningwa Albert , Oporia Frederick , Mutto Milton , Kyamanywa Patrick , Guwatudde David , Kobusingye Olive 
Published: August 2019

AbstractIntroductionIn Uganda, pedestrians are the most frequently injured category of road users, accounting for 40% of road traffic fatalities and 25% of serious injuries every year. There is paucity of information on existing pedestrian interventions and challenges that affect their implementation in Uganda. In this paper, we ascertain the state of pedestrian road safety interventions in Uganda and explore the challenges in the process of design, implementation, monitoring and evaluation of existing interventions.MethodsWe conducted a qualitative study that started with a desk review of existing policy documents, police statistics, media reports, non-governmental organization reports, and published research. We supplemented the review with 14 key informant interviews and 4 focus group discussions. Participants were drawn from various agencies and stakeholders responsible for road safety. In total, we collected and synthesized data on the design, implementation, and evaluation of pedestrian safety interventions from 25 documents. Data were analyzed using qualitative thematic content analysis.ResultsThe National Road Safety Council within the Ministry of Works and Transport is the lead agency tasked with coordinating all road safety efforts, while the Uganda Police is largely engaged in enforcing pedestrian safety. We identified several existing policies and regulations for pedestrian safety like the Non-Motorized Transport policy whose implementation has been inadequate. Implementation is constrained by weak institutional capacity and limited resources. Moreover, road safety stakeholders operated in silos and this hindered efforts to coordinate pedestrian safety activities. Interventions like road designs were implemented with limited reference to any supporting data and therefore did not cater for pedestrian needs.ConclusionThere are interventions targeting pedestrian safety in Uganda, but effective implementation is lacking or failing due to constraints related to weak institutional capacity. This necessitates strategies to mobilize resources to strengthen the capacity of the lead agency to effectively coordinate road safety interventions.
Evaluating and improving heritability models using summary statistics
Authors: Speed Doug , Holmes John , Balding David J 
Published: August 2019

AbstractThere is currently much debate regarding the best way to model how heritability varies across the genome. The authors of GCTA recommend the GCTA-LDMS-I Model, the authors of LD Score Regression recommend the Baseline LD Model, while we have instead recommended the LDAK Model. Here we provide a statistical framework for assessing heritability models using summary statistics from genome-wide association studies. Using data from studies of 31 complex human traits (average sample size 136,000), we show that the Baseline LD Model is the most realistic of the existing heritability models, but that it can be improved by incorporating features from the LDAK Model. Our framework also provides a method for estimating the selection-related parameter α from summary statistics. We find strong evidence (P<1e-6) of negative genome-wide selection for traits including height, systolic blood pressure and college education, and that the impact of selection is stronger inside functional categories such as coding SNPs and promoter regions.
Prediction of a cell-type specific mouse mesoconnectome using gene expression data
Authors: Timonidis Nestor , Bakker Rembrandt , Tiesinga Paul 
Published: August 2019

AbstractReconstructing brain connectivity at sufficient resolution for computational models designed to study the biophysical mechanisms underlying cognitive processes is extremely challenging. For such a purpose, a mesoconnectome that includes laminar and cell-type specificity would be a major step forward. We analysed the ability of gene expression patterns to predict cell-type and laminar specific projection patterns and analyzed the biological context of the most predictive groups of genes. To achieve our goal, we used publicly available volumetric gene expression and connectivity data and pre-processed it for prediction by averaging across brain regions, imputing missing values and rescaling. Afterwards, we predicted the strength of axonal projections and their binary form using expression patterns of individual genes and co-expression patterns of spatial gene modules.For predicting projection strength, we found that ridge (L2-regularized) regression had the highest cross-validated accuracy with a median r2 score of 0.54 which corresponded for binarized predictions to a median area under the ROC value of 0.89. Next, we identified 200 spatial gene modules using the dictionary learning and sparse coding approach. We found that these modules yielded predictions of comparable accuracy, with a median r2 score of 0.51. Finally, a gene ontology enrichment analysis of the most predictive gene groups resulted in significant annotations related to postsynaptic function.Taken together, we have demonstrated a prediction pipeline that can be used to perform multimodal data integration to improve the accuracy of the predicted mesoconnectome and support other neuroscience use cases.
Implicit perceptual memory can increase or decrease with ageing
Authors: Zhivago KA , Shashidhara Sneha , Garani Ranjini , Purokayastha Simran , Rao Naren P. , Murthy Aditya , Arun SP 
Published: August 2019

ABSTRACTA decline in declarative or explicit memory has been extensively characterized in cognitive ageing and is a hallmark of cognitive impairments. However, whether and how implicit perceptual memory varies with ageing or cognitive impairment is unclear. Here, we compared implicit perceptual memory and explicit memory measures in three groups of subjects: (1) 59 healthy young volunteers (20-30 years); (2) 238 healthy old volunteers (50-90 years) and (3) 21 patients with mild cognitive impairment MCI (50-90 years). To measure explicit memory, subjects were tested on standard recognition and recall tasks. To measure implicit perceptual memory, we used a classic perceptual priming paradigm. Subjects had to report the shape of a visual search pop-out target. Implicit priming was measured as the speedup in response time for targets with the same vs different color/position on consecutive trials.Our main findings are as follows: (1) Explicit memory was weaker in old compared to young subjects, and in MCI compared to age-matched controls; (2) Surprisingly, implicit perceptual memory did not always decline with age: color priming was smaller in older subjects but position priming was larger; (3) Position priming was less frequent in the MCI group compared to age-matched controls; (4) Implicit and explicit memory measures were uncorrelated in all three groups. Thus, implicit memory can increase or decrease with age or cognitive impairment, but this decline does not covary with explicit memory. We propose that incorporating explicit and implicit measures can yield a richer characterization of memory.
Fish larvae tackle the complex fluid-structure interactions of undulatory swimming with simple actuation
Authors: Voesenek Cees J. , Li Gen , Muijres Florian T. , van Leeuwen Johan L. 
Published: August 2019

AbstractMost fish swim with body undulations that result from fluid-structure interactions between the fish’s internal tissues and the surrounding water. As just-hatched larvae can swim effectively without a fully-developed brain, we hypothesise that fish larvae tackle the underlying complex physics with simple actuation patterns. To address this hypothesis, we developed a dedicated experimental-numerical approach to calculate the lateral bending moment distributions, which represent the system’s net actuation. The bending moment varies over time and along the fish’s central axis due to muscle actions, passive tissues, inertia, and fluid dynamics. Our 3D analysis of a large dataset of swimming events of larvae from 3 to 12 days after fertilisation shows that these bending moment patterns are not only relatively simple but also strikingly similar throughout early development, and from fast starts to periodic swimming. This suggests also similar muscle activation patterns, allowing fish larvae to produce swimming movements relatively simply, yet effectively, while restructuring their neuromuscular control system.
Regulation of amino acid and nucleotide metabolism by crustacean hyperglycemic hormone in the muscle and hepatopancreas of the crayfishProcambarus clarkii
Authors: Li Wenfeng , Chiu Kuo-Hsun , Lee Chi-Ying 
Published: August 2019

AbstractTo comprehensively characterize the metabolic roles of crustacean hyperglycemic hormone (CHH), metabolites in two CHH target tissues of the crayfishProcambarus clarkii, whose levels were significantly different between CHH-silenced and saline-treated control animals, were analyzed using bioinformatics tools provided by an on-line analysis suite (MetaboAnalyst). Analysis with Metabolic Pathway Analysis (MetPA) indicated that in the muscle Glyoxylate and dicarboxylate metabolism, Nicotinate and nicotinamide metabolism, Alanine, aspartate and glutamate metabolism, Pyruvate metabolism, and Nitrogen metabolism were significantly affected by silencing of CHH gene expression at 24 hours post injection (hpi), while only Nicotinate and nicotinamide metabolism remained significantly affected at 48 hpi. In the hepatopancreas, silencing of CHH gene expression significantly impacted, at 24 hpi, Pyruvate metabolism and Glycolysis or gluconeogenesis, and at 48 hpi, Glycine, serine and threonine metabolism. Moreover, analysis using Metabolite Set Enrichment Analysis (MSEA) showed that many metabolite sets were significantly affected in the muscle at 24hpi, including Ammonia recycling, Nicotinate and nicotinamide metabolism, Pyruvate metabolism, Purine metabolism, Warburg effect, Citric acid cycle, and metabolism of several amino acids, and at 48 hpi only Nicotinate and nicotinamide metabolism, Glycine and serine metabolism, and Ammonia recycling remained significantly affected. In the hepatopancreas, MSEA analysis showed that Fatty acid biosynthesis was significantly impacted at 24 hpi. Finally, in the muscle, levels of several amino acids decreased significantly, while those of 5 other amino acids or related compounds significantly increased in response to CHH gene silencing. Levels of metabolites related to nucleotide metabolism significantly decreased across the board at both time points. In the hepatopancreas, the effects were comparatively minor with only levels of thymine and urea being significantly decreased at 24 hpi. The combined results showed that the metabolic effects of silencing CHH gene expression were far more diverse than suggested by previous studies that emphasized on carbohydrate and energy metabolism. Based on the results, metabolic roles of CHH on the muscle and hepatopancreas were summarized and discussed.
Tritrophic interactions involving a dioecious fig tree, its fig pollinating wasp and fig nematodes
Authors: Jauharlina J. , Oktarina Hartati , Sriwati Rina , Kanzaki Natsumi , Quinnell Rupert J. , Compton Stephen G. 
Published: August 2019

AbstractMany species of fig trees (Ficus spp., Moraceae) have nematodes that develop inside their inflorescences (figs). Nematodes are carried into young figs by females of the trees’ host-specific pollinating fig wasps (Agaonidae) that enter the figs to lay their eggs. The majority of Asian fig trees are functionally dioecious. Pollinators that enter figs on female trees cannot reproduce and offspring of any nematodes they carry will also be trapped inside. The biology of the nematodes is diverse, but poorly understood. We contrasted the development of nematodes carried by the pollinating fig wasp Ceratosolen solmsi marchali into figs on male and female trees of Ficus hispida in Sumatra, Indonesia. Figs were sampled from both male and female trees over a six-month period, with the nematodes extracted to record their development of their populations inside the figs. Populations of three species of nematodes developed routinely inside figs of both sexes: Caenorhabditis sp. (Rhabditidae), Ficophagus cf. centerae and Martininema baculum (both Aphelenchoididae). This is the first record of a Caenorhabditis sp. associated with F. hispida. Mean numbers of nematodes reached around 120-140 in both male and female figs. These peak population sizes coincided with the emergence of the new generation of adult fig wasps in male fig trees. We conclude that figs on female trees can support development and reproduction of some nematode species, but the absence of vectors means that their populations cannot persist beyond the lifetime of a single fig. Just like their fig wasp vectors, the nematodes cannot avoid this routine source of mortality.
Post-translational epigenetics: PRMT7 regulates RNA-binding capacity and protein stability to controlLeishmaniaparasite virulence
Authors: Ferreira Tiago R. , Dowle Adam A. , Parry Ewan , Alves-Ferreira Eliza V. C. , Kolokousi Foteini , Larson Tony R. , Plevin Michael J. , Cruz Angela K. , Walrad Pegine B. 
Published: August 2019

ABSTRACTRNA binding proteins (RBPs) are the primary gene regulators in kinetoplastids as transcriptional control is nearly absent, makingLeishmaniaan exceptional model for investigating methylation of non-histone substrates. Arginine methylation is an evolutionarily conserved protein modification catalyzed by Protein aRginine MethylTransferases (PRMTs). The chromatin modifier PRMT7 is the only Type III PRMT found in higher eukaryotes and a restricted number of unicellular eukaryotes. InLeishmania major, PRMT7 is a cytoplasmic protein implicit in pathogenesis with unknown substrates. Using comparative methyl-SILAC proteomics for the first time in protozoa, we identified 40 putative targets, including 17 RBPs hypomethylated upon PRMT7 knockout. PRMT7 can modify Alba3 and RBP16trans-regulators (mammalian RPP25 and YBX2 homologs, respectively) as direct substratesin vitro. The absence of PRMT7 levelsin vivoselectively reduces Alba3 mRNA-binding capacity to specific target transcripts and can impact the relative stability of RBP16 in the cytoplasm. RNA immunoprecipitation analyses demonstrate PRMT7-dependent methylation promotes Alba3 association with select target transcripts and stability ofδ-amastinsurface antigen. These results highlight a novel role for PRMT7-mediated arginine methylation upon RBP substrates, suggesting a regulatory pathway controlling gene expression and virulence inLeishmania. This work introducesLeishmaniaPRMTs as epigenetic regulators of mRNA metabolism with mechanistic insight into the functional manipulation of RBPs by methylation.
Evaluation of 20 enset (Ensete ventricosum) landraces for response to Xanthomonas vasicola pv. musacearum infection
Authors: Muzemil Sadik , Chala Alemayehu , Tesfaye Bezuayehu , Studholme David J. , Grant Murray , Yemataw Zerihun , Olango Temesgen Magule 
Published: August 2019

AbstractBacterial wilt, caused by Xanthomonas vasicola pv. musacearum (Xvm), formerly X. campestris pv. musacearum, is the most threatening and economically important disease of enset (Ensete ventricosum), the multipurpose food security crop orphan to south and southwestern Ethiopia. Xvm has also had a major impact on banana and plantain production in East Africa following its detection in Uganda in 2001 and subsequent spread. Effective control of this disease currently relies on integrated disease management (IDM) strategies including minimization of field pathogen inoculum and deployment of wilt resistant enset landraces. Identifying landraces with stable and durable Xvm resistance will greatly accelerate breeding of varieties that can be included as a component of IDM. In this study, 20 enset landraces previously reported to exhibit lower susceptibility to Xvm were grown in pots under open field conditions and inoculated with an aggressive Xvm inoculum isolated from a disease hotspot area. Longitudinal and survival analyses were applied to each landrace, based on disease units representing a combination of area-under-disease progress stairs, disease index and apparent infection rate. Considerable variation was observed among the 20 landraces; however, none exhibited full immunity to Xvm infection. Three landraces, viz. Hae’la, Mazia and Lemat (HML), showed lowest susceptibility to Xvm as evidenced by lower disease units and higher survival rates. Landraces Kuro, Gezewet, Bededet, and Alagena showed similar levels of Xvm infection as did HML, but with lower survival rates. By contrast, landrace Arkia showed the highest infection level and lowest survival rate, suggesting a high degree of susceptibility to Xvm. This study identifies new material that can be used in future breeding programmes to develop Xvm-resistant enset varieties.
Flotillin mediated membrane fluidity controls peptidoglycan synthesis and MreB movement
Authors: Zielińska Aleksandra , Savietto Abigail , de Sousa Borges Anabela , Martinez Denis , Berbon Melanie , Roelofsen Joël R. , Hartman Alwin M. , de Boer Rinse , van der Klei Ida J. , Hirsch Anna K. H. , Habenstein Birgit , Bramkamp Marc , Scheffers Dirk-Jan 
Published: August 2019

AbstractThe bacterial plasma membrane is an important cellular compartment. In recent years it has become obvious that protein complexes and lipids are not uniformly distributed within membranes. Current hypotheses suggest that flotillin proteins are required for the formation of complexes of membrane proteins including cell-wall synthetic proteins. We show here that bacterial flotillins are important factors for membrane fluidity homeostasis. Loss of flotillins leads to a decrease in membrane fluidity that in turn leads to alterations in MreB dynamics and, as a consequence, in peptidoglycan synthesis. These alterations are reverted when membrane fluidity is restored by a chemical fluidizer. In vitro, the addition of a flotillin increases membrane fluidity of liposomes. Our data support a model in which flotillins are required for direct control of membrane fluidity rather than for the formation of protein complexes via direct protein-protein interactions.
Parallel changes in gut microbiome composition and function in parallel local adaptation and speciation
Authors: Rennison Diana J. , Rudman Seth M. , Schluter Dolph 
Published: August 2019

AbstractThe processes of local adaptation and ecological speciation are often strongly shaped by biotic interactions such as competition and predation. One of the strongest lines of evidence that biotic interactions drive evolution comes from repeated divergence of lineages in association with repeated changes in the community of interacting species. Yet, relatively little is known about the repeatability of changes in gut microbial communities and their role in adaptation and divergence of host populations in nature. Here we utilize three cases of rapid, parallel adaptation and speciation in freshwater threespine stickleback to test for parallel changes in associated gut microbiomes. We find that features of the gut microbial communities have shifted repeatedly in the same direction in association with parallel divergence and speciation of stickleback hosts. These results suggest that changes to gut microbiomes can occur rapidly and predictably in conjunction with host evolution, and that host-microbe interactions might play an important role in host adaptation and diversification.
Investigating dual Ca2+modulation of the ryanodine receptor 1 by molecular dynamics simulation
Authors: Zheng Wenjun , Wen Han 
Published: August 2019

AbstractThe ryanodine receptors (RyR) are essential to calcium signaling in striated muscles. A deep understanding of the complex Ca2+-activation/inhibition mechanism of RyRs requires detailed structural and dynamic information for RyRs in different functional states (e.g., with Ca2+bound to activating or inhibitory sites). Recently, high-resolution structures of the RyR isoform 1 (RyR1) were solved by cryo-electron microscopy, revealing the location of a Ca2+binding site for activation. Toward elucidating the Ca2+-modulation mechanism of RyR1, we performed extensive molecular dynamics simulation of the core RyR1 structure in the presence and absence of bound and solvent Ca2+(total simulation time is > 5 microseconds). In the presence of solvent Ca2+, Ca2+binding to the activating site enhanced dynamics of RyR1 with higher inter-subunit flexibility, asymmetric inter-subunit motions, outward domain motions and partial pore dilation, which may prime RyR1 for subsequent channel opening. In contrast, the solvent Ca2+alone reduced dynamics of RyR1 and led to inward domain motions and pore contraction, which may cause inhibition. Combining our simulation with the map of disease mutation sites in RyR1, we constructed a wiring diagram of key domains coupled via specific hydrogen bonds involving the mutation sites, some of which were modulated by Ca2+binding. The rich structural and dynamic information gained from this study will guide future mutational and functional studies of RyR1 activation and inhibition by Ca2+.Statement of SignificanceThe ryanodine receptors (RyR) are key players in calcium signaling, and make prominent targets for drug design owning to their association with many diseases of cardiac and skeletal muscles. However, the molecular mechanism of their activation and inhibition by Ca2+remains elusive for the lack of high-resolution structural and dynamic information. Recent solutions of RyR1 structures by cryo-EM have paved the way for structure-based investigation of this important receptor by atomistic molecular simulation. This study presented, to our knowledge, the most extensive MD simulation of RyR1 core structure. Our simulation has offered new insights to the dual modulation mechanism of Ca2+, in which Ca2+binding to the activating site primes RyR1 activation by elevating its dynamics while solvent Ca2+inhibits RyR1 by reducing its dynamics. Additionally, our simulation has yielded a new wiring diagram of the allosterically coupled RyR1 domains informed by disease mutations.