bluuebunny/crossref_metadata_2025_split huggingface dataset:
Robust summarization and inference in proteome-wide label-free quantification
Authors: Sticker Adriaan , Goeminne Ludger , Martens Lennart , Clement Lieven 
Published: June 2019

AbstractLabel-Free Quantitative mass spectrometry based workflows for differential expression (DE) analysis of proteins impose important challenges on the data analysis due to peptide-specific effects and context dependent missingness of peptide intensities. Peptide-based workflows, like MSqRob, test for DE directly from peptide intensities and outper-form summarization methods which first aggregate MS1 peptide intensities to protein intensities before DE analysis. However, these methods are computationally expensive, often hard to understand for the non-specialised end-user, and do not provide protein summaries, which are important for visualisation or downstream processing. In this work, we therefore evaluate state-of-the-art summarization strategies using a benchmark spike-in dataset and discuss why and when these fail compared to the state-of-the-art peptide based model, MSqRob. Based on this evaluation, we propose a novel summarization strategy, MSqRob-Sum, which estimates MSqRob’s model parameters in a two-stage procedure circumventing the drawbacks of peptide-based workflows. MSqRobSum maintains MSqRob’s superior performance, while providing useful protein expression summaries for plotting and downstream analysis. Summarising peptide to protein intensities considerably reduces the computational complexity, the memory footprint and the model complexity, and makes it easier to disseminate DE inferred on protein summaries. Moreover, MSqRobSum provides a highly modular analysis framework, which provides researchers with full flexibility to develop data analysis workflows tailored towards their specific applications.
Monosynaptic tracing maps brain-wide afferent oligodendrocyte precursor cell connectivity
Authors: Mount Christopher W , Yalçın Belgin , Cunliffe-Koehler Kennedy , Monje Michelle 
Published: June 2019

AbstractNeurons form bona fide synapses with oligodendrocyte precursor cells (OPCs), but the circuit context of these neuron to OPC synapses remains incompletely understood. Using monosynaptically-restricted rabies virus tracing of OPC afferents, we identified extensive afferent synaptic inputs to OPCs residing in secondary motor cortex, corpus callosum, and primary somatosensory cortex of adult mice. These inputs primarily arise from functionally-interconnecting cortical areas and thalamic nuclei, demonstrating that OPCs have strikingly comprehensive synaptic access to brain-wide functionally-related projection networks. Quantification of these inputs revealed excitatory and inhibitory components that are consistent in number across brain regions and stable in barrel cortex despite whisker trimming-induced sensory deprivation.
One year prevalence of psychotic disorders among first treatment contact patients at Butabika National Psychiatric Referral Hospital in Uganda
Authors: Mwesiga Emmanuel Kiiza , Nakasujja Noeline , Nakku Juliet , Nanyonga Annet , Gumikiriza Joy Louise , Bangirana Paul , Akena Dickens , Musisi Seggane 
Published: June 2019

ABSTRACTIntroductionHospital based studies for psychotic disorders are scarce in low and middle income countries. This may impact on development of intervention programs.ObjectiveWe aimed to determine the burden of psychotic disorders among first treatment contact patients at the national psychiatric referral hospital in Uganda.MethodsA retrospective patient chart-file review was carried out in March 2019 for all patients presenting to the hospital for the first time in the previous year. Patients were categorised into those with and without psychotic disorders. We collected sociodemographic data on age, gender, occupation, level of education, ethnicity, religion and home district. We determined the one year prevalence of psychotic disorders among first treatment contact patients. Using logistic regression models, we also determined the association between psychotic disorders and various exposure variables among first treatment contact patients.ResultsIn 2018, 63% (95% CI: 60.2 – 65.1) of all first time contact patients had a psychosis related diagnosis. Among the patients with psychotic disorders, the median age was 29 years (IQR 24 – 36). Most of the patients were male (62.8%) and unemployed (63.1%). After adjusting for patients’ residence, psychotic disorders were found to be more prevalent among the female gender [OR 1.58 (CI1.46-1.72)] and those of Pentecostal faith [OR 1.25 (CI 1.10-1.42)].ConclusionAmong first treatment contact patients in Uganda, there is a large burden of psychotic disorders. The burden was more prevalent among females as well as people of Pentecostal faith who seemed to use their church for faith-based healing. Incidence studies are warranted to determine if this phenomenon is replicated at illness onset.
Transcriptome analysis of Xanthomonas oryzae pv. oryzicola exposed to H2O2 reveals horizontal gene transfer contributes to its oxidative stress response
Authors: Fang Yuan , Wang Haoye , Liu Xia , Rao Yuchun , Dedong Xin , Zhu Bo 
Published: June 2019

AbstractXanthomonas oryzae pv. oryzicola (Xoc) is the causal agent of bacterial leaf streak in rice. It is known as one of the most severe seed-born bacterial diseases of rice, molecular role governing its interaction with rice is mostly still unexplored. To successfully invade rice, the survival of the Xoc is mandotarory following generating a specific response to its host’s oxidative stress condition. However, the response network of Xoc is still unknown. To address this question, we performed a time-series RNA-seq analysis on the Xoc response to H2O2. Overall, our RNA sequence analysis of Xoc revealed a significant global gene expression profile when it exposed to H2O2. The response of key genes was also noted that soxR triggers and regulates the Xoc oxidative stress response in the early stage of infection, gene expression kinetics among the time-series samples, namely for TonB-dependent receptors and the suf and pst operons. Moreover, a hypothetical protein (XOC_2868) showed significant differential expression following its mutant endorsed RNA-seq findings by clearly displaying a greater H2O2 sensitivity and decreased pathogenicity than the wild-type. Gene location and phylogeny analysis strongly suggests that this gene may have been horizontally transferred from a Burkholderiaceae ancestor. Our study not only provides a first glance of Xoc’s global response against oxidative stress, but it also reveals the impact of horizontal gene transfer in the evolutionary history of Xoc.
Disentangling group specific QTL allele effects from genetic background epistasis using admixed individuals in GWAS: an application to maize flowering
Authors: Simon Rio , Tristan Mary-Huard , Laurence Moreau , Cyril Bauland , Carine Palaffre , Delphine Madur , Valérie Combes , Alain Charcosset 
Published: June 2019

AbstractWhen handling a structured population in association mapping, group-specific allele effects may be observed at quantitative trait loci (QTLs) for several reasons: (i) a different linkage disequilibrium (LD) between SNPs and QTLs across groups, (ii) group-specific genetic mutations in QTL regions, and/or (iii) epistatic interactions between QTLs and other loci that have differentiated allele frequencies between groups. We present here a new genome-wide association (GWAS) approach to identify QTLs exhibiting such group-specific allele effects. We developed genetic materials including admixed progeny from different genetic groups with known genome-wide ancestries (local admixture). A dedicated statistical methodology was developed to analyze pure and admixed individuals jointly, allowing one to disentangle the factors causing the heterogeneity of allele effects across groups. This approach was applied to maize by developing an inbred “Flint-Dent” panel including admixed individuals that was evaluated for flowering time. Several associations were detected revealing a wide range of configurations of allele effects, both at known flowering QTLs (Vgt1, Vgt2 and Vgt3) and new loci. We found several QTLs whose effect depended on the group ancestry of alleles while others interacted with the genetic background. The existence of directional epistasis was highlighted by comparing admixed with pure individuals and was consistent with epistatic interactions identified at the level of QTLs. Our GWAS approach provides useful information on the stability of QTL effects across genetic groups and can be applied to a wide range of species.Author summaryIdentification of genomic regions involved in genetic architecture of traits has become commonplace in quantitative genetics studies. Genetic structure is a common feature in human, animal and plant species and most current methods target genomic regions whose effects on traits are conserved between genetic groups. However, a heterogeneity of allele effects may be observed due to different factors: a group-specific correlation between the alleles of the tagged marker and those of the causal variant, a group-specific mutation at the causal variant or an epistatic interaction between the causal variant and the genetic background. We propose a new method adapted to structured populations including admixed individuals, which aims to identify these genomic regions and to unravel the previous factors. method was applied to a maize inbred diversity panel including lines from the dent and the flint genetic groups, as well as admixed lines, evaluated for flowering time. Several genomic regions were detected with various configurations of allele effects, with evidence of epistatic interactions between some of the loci and the genetic background.
On the use of inhibitors of 4-hydroxyphenylpyruvate dioxygenase as a vector-selective insecticide in the control of mosquitoes
Authors: Ramirez Marlon A. V. , Sterkel Marcos , de Jesus Martins Ademir , Lima José Bento Pereira , Oliveira Pedro L. 
Published: June 2019

AbstractBlood-sucking insects incorporate many times their body weight of blood in a single meal. As proteins are the major component of vertebrate blood, its digestion in the gut of hematophagous insects generates extremely high concentrations of free amino acids. Previous reports showed that the tyrosine degradation pathway plays an essential role in adapting these animals to blood feeding. Inhibiting 4-hydroxyphenylpyruvate dioxygenase (HPPD), the rate-limiting step of tyrosine degradation, results in the death of insects after a blood meal. Therefore, it was suggested that compounds that block the catabolism of tyrosine could act selectively on blood-feeding insects. Here we have evaluated the toxicity against mosquitoes of three HPPD inhibitors currently used as herbicides and in human health. Among the compounds tested, nitisinone (NTBC) proved to be more potent than mesotrione (MES) and isoxaflutole (IFT) in Aedes aegypti. NTBC was lethal to Ae. aegypti in artificial feeding assays (LD50: 4.36 µM), as well as in topical application (LD50: 0.0033 nmol/mosquito). NTBC was also lethal to Ae. aegypti populations that were resistant to neurotoxic insecticides, and it was lethal to other mosquito species (Anopheles and Culex). Therefore, HPPD inhibitors, particularly NTBC, represent promising new drugs for mosquito control. Since they only affect blood-feeding organisms, they would represent a safer and more environmentally friendly alternative to conventional neurotoxic insecticides.Author SummaryThe control of mosquitoes has been pursued in the last decades by the use of neurotoxic insecticides to prevent the spreading of dengue, zika and malaria, among other diseases. However, the selection and propagation of different mechanisms of resistance hinder the success of these compounds. New methodologies are needed for their control. Hematophagous arthropods, including mosquitoes, ingest quantities of blood that represent many times their body weight in a single meal, releasing huge amounts of amino acids during digestion. Recent studies showed that inhibition of the tyrosine catabolism pathway could be a new selective target for vector control. Thus we tested three different inhibitors of the second enzyme in the tyrosine degradation pathway as tools for mosquito control. Results showed that Nitisinone (NTBC), an inhibitor used in medicine, was the most potent of them. NTBC was lethal to Aedes aegypti when it was administered together with the blood meal and when it was topically applied. It also caused the death of Anopheles aquasalis and Culex quinquefasciatus mosquitoes, as well as field-collected Aedes populations resistant to neurotoxic insecticides, indicating that there is no cross-resistance. We discuss the possible use of NTBC as a new insecticide.
The RNA Binding Protein FMRP Promotes Myelin Sheath Growth
Authors: Doll Caleb A. , Yergert Katie M. , Appel Bruce H. 
Published: June 2019

SummaryDuring development, oligodendrocytes in the central nervous system extend a multitude of processes that wrap axons with myelin. The highly polarized oligodendrocytes generate myelin sheaths on many different axons, which are far removed from the cell body. Neurons use RNA binding proteins to transport, stabilize, and locally translate mRNA in distal domains of neurons. Local synthesis of synaptic proteins during neurodevelopment facilitates the rapid structural and functional changes underlying neural plasticity and avoids extensive protein transport. We hypothesize that RNA binding proteins also regulate local mRNA regulation in oligodendrocytes to promote myelin sheath growth. Fragile X mental retardation protein (FMRP), an RNA binding protein that plays essential roles in the growth and maturation of neurons, is also expressed in oligodendrocytes. To determine whether oligodendrocytes require FMRP for myelin sheath development, we examinedfmr1-/-mutant zebrafish and droveFMR1expression specifically in oligodendrocytes. We found oligodendrocytes infmr1-/-mutants developed myelin sheaths of diminished length, a phenotype that can be autonomously rescued in oligodendrocytes withFMR1expression. Myelin basic protein (Mbp), an essential myelin protein, was reduced in myelin tracts offmr1-/-mutants, but loss of FMRP function did not impact the localization ofmbpatranscript in myelin. Finally, expression of FMR1-I304N, a missense allele that abrogates FMRP association with ribosomes, failed to rescuefmr1-/-mutant sheath growth and induced short myelin sheaths in oligodendrocytes of wild-type larvae. Taken together, these data suggest that FMRP promotes sheath growth through local regulation of translation.
Natural variants in C. elegans atg-5 3’UTR uncover divergent effects of autophagy on polyglutamine aggregation in different tissues
Authors: Alexander-Floyd J , Haroon S , Ying M , Entezari AA , Jaeger C , Vermulst M , Gidalevitz T 
Published: June 2019

AbstractDiseases caused by protein misfolding and aggregation, in addition to cell selectivity, often exhibit variation among individuals in the age of onset, progression, and severity of disease. Genetic variation has been shown to contribute to such clinical variation. We have previously found that protein aggregation-related phenotypes in a model organism, C. elegans, can be modified by destabilizing polymorphisms in the genetic background and by natural genetic variation. Here, we identified a large modifier locus in a Californian wild strain of C. elegans, DR1350, that alters the susceptibility of the head muscle cells to polyglutamine (polyQ) aggregation, and causes an increase in overall aggregation, without changing the basal activity of the muscle proteostasis pathways known to affect polyQ aggregation. We found that the two phenotypes were genetically separable, and identified regulatory variants in a gene encoding a conserved autophagy protein ATG-5 (ATG5 in humans) as being responsible for the overall increase in aggregation. The atg-5 gene conferred a dosage-dependent enhancement of polyQ aggregation, with DR1350-derived atg-5 allele behaving as a hypermorph. Examination of autophagy in animals bearing the modifier locus indicated enhanced response to an autophagy-activating treatment. Because autophagy is known to be required for the clearance of polyQ aggregates, this result was surprising. Thus, we tested whether directly activating autophagy, either pharmacologically or genetically, affected the polyQ aggregation in our model. Strikingly, we found that the effect of autophagy on polyQ aggregation was tissue-dependent, such that activation of autophagy decreased polyQ aggregation in the intestine, but increased it in the muscle cells. Our data show that cryptic genetic variants in genes encoding proteostasis components, although not causing visible phenotypes under normal conditions, can have profound effects on the behavior of aggregation-prone proteins, and suggest that activation of autophagy may have divergent effects on the clearance of such proteins in different cell types.
Shared dynamic functional connectivity across schizophrenia, bipolar disorder and major depressive disorder
Authors: Li Chao , Xu Ke , Dong Mengshi , Wei Yange , Duan Jia , Han Shaoqiang , Feng Ruiqi , Zhang Luheng , Zhao Pengfei , Chen Yifan , Jiang Xiaowei , Wei Shengnan , Yin Zhiyang , Zhang Yifan , Chen Huafu , Tang Yanqing , Wang Fei 
Published: June 2019

AbstractDynamic functional connectivity (DFC) analysis can capture time-varying properties of connectivity and may provide further information about transdiagnostic psychopathology across major psychiatric disorders. In this study, we used resting state functional MRI and a sliding-window method to study DFC in 150 schizophrenia (SZ), 100 bipolar disorder(BD), 150 major depressive disorder (MDD), and 210 healthy controls (HC). DFC were clustered into two functional connectivity states. Significant 4-group differences in DFC were found only in state 2. Post hoc analyses showed that transdiagnostic dysconnectivity among there disorders featured decreased connectivity within visual, somatomotor, salience and frontoparietal networks. Our results suggest that decreased connectivity within both lower-order (visual and somatomotor) and higher-order (salience and frontoparietal) networks may serve as transdiagnostic marker of these disorders, and that these dysconnectivity is state-dependent. Targeting these dysconnectivity may improve assessment and treatment for patients that having more than one of these disorders at the same time.
Patch-Clamp Recording of K+ Current from Lacrimal Gland Duct Cells
Authors: Haarsma Loren D. , Ubels John L. 
Published: June 2019

AbstractElectrophysiologic studies have characterized ion channels in lacrimal gland acinar cells, but due to relative paucity and inaccessibility, such studies on lacrimal gland duct cells are challenging. The duct cells are believed to secrete the high level of K+ that is present in tears. The goal of this project was to develop a method for isolation of viable, single duct cells, demonstrate their utility for patch-clamp recording and characterize the K+ channels expressed by duct cells. Exorbital lacrimal gland slices from Sprague-Dawley rats were incubated with collagenase. Under a microscope, the ducts were microdissected from the glands and then incubated with elastase and collagenase. Dispersed duct cells were plated on a cover slip coated with BD Cell-Tak. Duct cells were distinguished from acinar cells by their smaller size and lack of granularity. Whole-cell K+ currents were recorded from duct cells using the perforated-patch technique and pipettes with resistances of less than 10 MΩ. EGTA and CaCl2 in the pipette solution were adjusted to give 1 uM free Ca++. When held at −80 mV, duct cells showed K+ currents that activated at command voltages near 0 mV and reached amplitudes near 1 nA at +100 mV. Currents reached peak amplitude less than 20 ms after depolarization and did not inactivate. These currents were inactivated by holding the cells at 0 mV. Currents were blocked reversibly by TEA in the presence of Ca2+, but were not blocked by TEA in the absence of Ca2+. Currents were not affected by clotrimazole (10 uM) or Ba2+ (5 mM). A method has been established for isolation and dissociation lacrimal gland duct cells for electrophysiologic studies. These cells express a voltage-activated K+ channel that is dependent on the presence of intracellular Ca2+ and may correspond to the IKCa1 channel expressed on the apical membranes of lacrimal gland ducts.
Microplastic ingestion by a herring Opisthonema sp., in the Pacific coast of Costa Rica
Authors: Bermúdez-Guzmán Luis , Alpízar-Villalobos Crista , Gatgens-García Johan , Jiménez-Huezo Gabriel , Rodríguez-Arias Marco , Molina-Ureña Helena , Villalobos Javier , Paniagua Sergio A. , Vega-Baudrit José R. , Rojas-Jimenez Keilor 
Published: June 2019

AbstractDespite there is a growing interest in studying the presence and effects of microplastics (MP) in fishes and other aquatic species, knowledge is still limited in tropical areas. In this study, we examined the presence of MP in the gastrointestinal content of 30 filter feeders of thread herring, Opisthonema complex (Clupeiformes: Clupeidae) from the Central Pacific coast of Costa Rica. We detected the presence of MP in 100% of the individuals with an average of 36.7 pieces per fish, of which 79.5% were fibers and 20.5% particles. To our knowledge, this is the first study in Costa Rica that demonstrates the presence of MP in planktivorous fishes. The effects of microplastics ingestion by O. libertate and its transit through aquatic food webs should be studied in greater detail, with greater number of sampling points at different times of the year. However, our work confirms that contamination by microplastics is having direct effects on the marine life of Costa Rica.CapsuleThis is the first multidisciplinary study in Costa Rica demonstrating the presence and nature of microplastics in the digestive tract of planktivorous fish.
All thresholds of maternal hyperglycaemia from the WHO 2013 criteria for gestational diabetes identify women with a higher genetic risk for type 2 diabetes
Authors: Hughes Alice E , Hayes M. Geoffrey , Egan Aoife M , Patel Kashyap A , Scholtens Denise M , Lowe Lynn P , Lowe William L , Dunne Fidelma P , Hattersley Andrew T , Freathy Rachel M 
Published: June 2019

ABSTRACTBackgroundUsing genetic scores for fasting plasma glucose (FPG GS) and type 2 diabetes (T2D GS), we investigated whether the fasting, 1-hour and 2-hour glucose thresholds from the WHO 2013 criteria for gestational diabetes (GDM) have different implications for genetic susceptibility to raised fasting glucose and type 2 diabetes in women from the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) and Atlantic Diabetes in Pregnancy (DIP) studies.MethodsCases were divided into three subgroups: (i) FPG ≥5.1 mmol/L only, n=222; (ii) 1-hour glucose post 75 g oral glucose load ≥10 mmol/L only, n=154 (iii) 2-hour glucose ≥8.5 mmol/L only, n=73); and (iv) both FPG ≥5.1 mmol/L and either of a 1-hour glucose ≥10 mmol/L or 2-hour glucose ≥8.5 mmol/L, n=172. We compared the FPG and T2D GS of these groups with controls (n=3,091) in HAPO and DIP separately.ResultsIn HAPO and DIP, the mean FPG GS in women with a FPG ≥5.1 mmol/L, either on its own or with 1-hour glucose ≥10 mmol/L or 2-hour glucose ≥8.5 mmol/L, was higher than controls (all P <0.01). Mean T2D GS in women with a raised FPG alone or with either a raised 1-hour or 2-hour glucose was higher than controls (all P <0.05). GDM defined by 1-hour or 2-hour hyperglycaemia only was also associated with a higher T2D GS than controls (all P <0.05).ConclusionsThe different diagnostic categories that are part of the WHO 2013 criteria for GDM identify women with a genetic predisposition to type 2 diabetes as well as a risk for adverse pregnancy outcomes.