bluuebunny/crossref_metadata_2025_split huggingface dataset:
Presynaptic Gαo(GOA-1) signals to depress command neuron excitability and allow stretch-dependent modulation of egg laying inCaenorhabditis elegans
Authors: Ravi Bhavya , Zhao Jian , Chaudhry Sana , Bartole Mattingly , Kopchock Richard J. , Guijarro Christian , Kang Lijun , Collins Kevin M. 
Published: July 2019

AbstractEgg laying in the nematode wormCaenorhabditis elegansis a two-state behavior modulated by internal and external sensory input. We have previously shown that homeostatic feedback of embryo accumulation in the uterus regulates bursting activity of the serotonergic HSN command neurons that sustains the egg-laying active state. How sensory feedback of egg release signals to terminate the egg-laying active state is less understood. We find that Gαo, a conserved Pertussis Toxin-sensitive G protein, signals within HSN to inhibit egg-laying circuit activity and prevent entry into the active state. Gαosignaling hyperpolarizes HSN, reducing HSN Ca2+activity and input onto the postsynaptic vulval muscles. Loss of inhibitory Gαosignaling uncouples presynaptic HSN activity from a postsynaptic, stretch-dependent homeostat, causing precocious entry into the egg-laying active state when only a few eggs are present in the uterus. Feedback of vulval opening and egg release activates the uv1 neuroendocrine cells which release NLP-7 neuropeptides which signal to inhibit egg laying through Gαo-independent mechanisms in the HSNs and Gαo-dependent mechanisms in cells other than the HSNs. Thus, neuropeptide and inhibitory Gαosignaling maintains a bi-stable state of electrical excitability that dynamically controls circuit activity in response to both external and internal sensory input to drive a two-state behavior output.
Individual variation in dispersal and fecundity increases rates of spatial spread
Authors: Schreiber Sebastian J. , Beckman Noelle G. 
Published: July 2019

AbstractDispersal and fecundity are two fundamental traits underlying the spread of populations. Using integral difference equation models, we examine how individual variation in these fundamental traits and the heritability of these traits influence rates of spatial spread of populations along a one-dimensional transect. Using a mixture of analytic and numerical methods, we show that individual variation in dispersal rates increases spread rates and the more heritable this variation, the greater the increase. In contrast, individual variation in lifetime fecundity only increases spread rates when some of this variation is heritable. The highest increases in spread rates occurs when variation in dispersal positively covaries with fecundity. Our results highlight the importance of estimating individual variation in dispersal rates, dispersal syndromes in which fecundity and dispersal co-vary positively, and heritability of these traits to predict population rates of spatial spread.
FINE GRAINED LONGITUDINAL ANALYSIS OF COCOA BEAN FERMENTATION PROVIDES INSIGHTS INTO THE DYNAMICS OF MICROBIAL POPULATIONS
Authors: Pacheco-Montealegre M. E. , Dávila-Mora L. L. , Botero-Rute L. M. , Reyes A. , Caro-Quintero A. 
Published: July 2019

ABSTRACTCocoa bean fermentation is an important microbial driven process where metabolites that affect chocolate quality and aroma are produced. Although considerable research has been devoted to the yeast and bacteria species involved in this process, less attention has been paid to the role of populations and strains, which hinders its selection, monitoring and use. Here we present a study that evaluates the microbial diversity associated to the tools and bean mass during spontaneous cocoa fermentation and in two distinct agro-ecological zones in Colombia. Using high-throughput sequencing of molecular markers for bacteria and yeast, we established the dynamics at the species-level (OTUs) and strains-level (oligotypes). Our results show that cocoa bean fermentation is catalyzed by a composite of strains within each OTU and not by one single strain. Eventhough we found only a few bacterial OTUs, one Enterobacter, three of Lactic Acid Bacteria and two of Acetic Acid Bacteria, these could be further split into 6, 23 and 19 oligotypes, respectively. Only two fungal OTUs were found. Comparison between fermentations suggest that local protocols generated a specific footprint in the dynamics of the microbial communities and that tools are reservoirs of some of those groups. The population analysis shows that the oligotypes that become most dominant are the same in the two locations, coupling co-abundance and dominance analysis we suggest that a combination of Enterobacter and Acetobacter oligotypes seem more optimal for the starter cultures. In conclusion, the results presented here show that exploring the fine level dynamics of microbial fermentation is necessary to understand the patterns of the dominance of specific populations and can be used as a valuable approach to select and monitor specific bacteria for the design of starter cultures in the food industry.IMPORTANCEIn Colombia, the lack of tools to validate and standardize fermentation protocols are one of the principal reasons why Colombian cocoa beans are not recognized as “fine-flavor” and widely marketed. Because of the large influence of the microbial fermentation in cocoa quality, the present study explores the microbial dynamics using high-throughput sequencing of molecular markers in two of the most important producer regions in Colombia. The results show that the identification of dominant and transitive strains can be used to select, design and monitor starter cultures and/or the effect of adjustments in the fermentation protocols.
Planar polarization of cilia in the zebrafish floor-plate involves Par3-mediated posterior localization of highly motile basal bodies
Authors: Donati Antoine , Schneider-Maunoury Sylvie , Vesque Christine 
Published: July 2019

ABSTRACTTo produce a directional flow, ciliated epithelia display a uniform orientation of ciliary beating. Oriented beating requires planar cell polarity (PCP), which leads to planar orientation and asymmetric positioning of the ciliary basal body (BB) along the polarity axis. We took advantage of the polarized mono-ciliated epithelium of the embryonic zebrafish floor plate to investigate by live-imaging the dynamics and mechanisms of BB polarization. We showed that BBs, although bearing a cilium, were highly motile along the antero-posterior axis. BBs contacted both the anterior and the posterior membranes, with a bias towards posterior contacts from early somitogenesis on. Contacts exclusively occurred at junctional Par3 local enrichments or “patches” and were often preceded by transient membrane digitations extending towards the BB, suggesting focused cortical pulling forces. Accordingly, BBs and Par3 patches were linked by dynamic microtubules. We showed that Par3 became posteriorly enriched prior to BB posterior positioning and that floor plate polarization was impaired upon Par3 patches disruption triggered by Par3 or aPKC overexpression. In the PCP mutant Vangl2, where floor plate cells fail to polarize, we observed that BB were still motile but presented behavioral defects, such as ectopic contacts with lateral membranes that correlated with Par3 patch fragmentation and spreading to lateral membranes. Our data lead us to propose an unexpected function for posterior local Par3 enrichment in controlling BB asymmetric positioning downstream of the PCP pathway via a microtubule capture/shrinkage mechanism.
Hemibiotrophic fungal pathogen induces systemic susceptibility and systemic shifts in wheat metabolome and microbiome composition
Authors: Seybold Heike , Demetrowitsch Tobias , Hassani M. Amine , Szymczak Silke , Reim Ekaterina , Haueisen Janine , Rühlemann Malte , Franke Andre , Schwarz Karin , Stukenbrock Eva H. 
Published: July 2019

AbstractYield losses caused by fungal pathogens represent a major threat to global food production. One of the most devastating fungal wheat pathogens is Zymoseptoria tritici. Despite the importance of this fungus and wheat as main staple food crop the underlying mechanisms of plant-pathogen interactions are poorly understood. Here we present a conceptual framework based on coinfection assays, comparative metabolomics, and microbiome profiling to study the interaction of Z. tritici in susceptible and resistant wheat. We demonstrate that Z. tritici suppresses the production of immune-related metabolites in a susceptible cultivar. Remarkably, this fungus-induced immune suppression spreads within the leaf and even to other leaves, a previously undescribed phenomenon that we term “systemic induced susceptibility”. Using a comparative metabolomics approach, we identified defense-related biosynthetic pathways that are suppressed and induced in susceptible and resistant cultivars, respectively. We show that these fungus-induced changes also dramatically affect the wheat leaf microbiome. Our findings emphasize that immune suppression by this hemibiotrophic pathogen impacts specialized plant metabolism, alters its associated microbial communities, and renders wheat vulnerable to further infections.
Systematic assessment of commercially available low-input miRNA library preparation kits
Authors: Heinicke Fatima , Zhong Xiangfu , Zucknick Manuela , Breidenbach Johannes , Sundaram Arvind , Flåm Siri T. , Leithaug Magnus , Dalland Marianne , Farmer Andrew , Henderson Jordana M. , Hussong Melanie A. , Moll Pamela , Nguyen Loan , McNulty Amanda , Shaffer Jonathan M. , Shore Sabrina , Yip HoiChong Karen , Vitkovska Jana , Rayner Simon , Lie Benedicte A , Gilfillan Gregor D. 
Published: July 2019

AbstractHigh-throughput sequencing is increasingly favoured to assay the presence and abundance of micro RNAs (miRNAs) in biological samples, even from low RNA amounts, and a number of commercial vendors now offer kits that allow miRNA sequencing from sub-nanogram (ng) inputs. However, although biases introduced during library preparation have been documented, the relative performance of current reagent kits has not been investigated in detail. Here, six commercial kits capable of handling <100ng total RNA input were used for library preparation, performed by kit manufactures, on synthetic miRNAs of known quantities and human biological total RNA samples. We compared the performance of miRNA detection sensitivity, reliability, titration response and the ability to detect differentially expressed miRNAs. In addition, we assessed the use of unique molecular identifiers sequence (UMI) tags in one kit. We observed differences in detection sensitivity and ability to identify differentially expressed miRNAs between the kits, but none were able to detect the full repertoire of expected miRNAs. The reliability within the replicates of all kits was good, while larger differences were observed between the kits, although none could accurately quantify the majority of miRNAs. UMI tags, at least within the input ranges tested, offered little advantage to improve data utility. In conclusion, biases in miRNA abundance are heavily influenced by the kit used for library preparation, suggesting that comparisons of datasets prepared by different procedures should be made with caution. This article is intended to assist researchers select the most appropriate kit for their experimental conditions.
Modulation of Actin network and Tau phosphorylation by HDAC6 ZnF UBP domain
Authors: Balmik Abhishek Ankur , Sonawane Shweta Kishor , Chinnathambi Subashchandrabose 
Published: July 2019

AbstractMicrotubule-associated protein Tau undergoes aggregation in Alzheimer’s disease and a group of other related diseases collectively known as Tauopathies. In AD, Tau forms aggregates, which are deposited intracellularly as neurofibrillary tangles. HDAC6 plays an important role in aggresome formation where it recruits polyubiquitinated aggregates to the motor protein dynein. Here, we have studied the effect of HDAC6 ZnF UBP on Tau phosphorylation, ApoE localization, GSK-3β regulation and cytoskeletal organization in neuronal cells by immunocytochemistry. Immunocytochemistry reveals that HDAC6 ZnF UBP can modulate Tau phosphorylation and actin cytoskeleton organization when the cells are exposed to the domain. HDAC6 ZnF UBP treatment to cells does not affect their viability and resulted in enhanced neurite extension and formation of structures similar to podosomes, lamellipodia and podonuts suggesting its role in actin re-organization. Also, HDAC6 treatment showed increased nuclear localization of ApoE and tubulin localization in microtubule organizing centre. Our studies suggest the regulatory role of this domain in different aspects of neurodegenerative diseases.
Defining the emergence of myeloid-derived suppressor cells in breast cancer using single-cell transcriptomics
Authors: Alshetaiwi Hamad , Pervolarakis Nicholas , McIntyre Laura Lynn , Ma Dennis , Nguyen Quy , Rath Jan Akara , Nee Kevin , Hernandez Grace , Evans Katrina , Torosian Leona , Silva Anushka , Walsh Craig , Kessenbrock Kai 
Published: July 2019

AbstractMyeloid-derived suppressor cells (MDSCs) are innate immune cells that acquire the capacity to suppress adaptive immune responses during cancer. It remains elusive how MDSCs differ from their normal myeloid counterparts, which limits our ability to specifically detect and therapeutically target MDSCs during cancer. Here, we used single-cell RNAseq to compare MDSC-containing splenic myeloid cells from breast tumor-bearing mice to wildtype controls. Our computational analysis of 14,646 single-cell transcriptomes reveals that MDSCs emerge through a previously unrealized aberrant neutrophil maturation trajectory in the spleen giving rise to a unique chemokine-responsive, immunosuppressive cell state that strongly differs from normal myeloid cells. We establish the first MDSC-specific gene signature and identify novel surface markers for improved detection and enrichment of MDSCs in murine and human samples. Our study provides the first single-cell transcriptional map defining the development of MDSCs, which will ultimately enable us to specifically target these cells in cancer patients.One Sentence SummaryWe used single cell transcriptomics to identify the unique molecular features distinguishing myeloid-derived suppressor cells (MDSCs) from their normal, myeloid counterparts, which enabled us to reveal distinct transitory gene expression changes during their maturation in the spleen, and to identify novel cell surface markers for improved detection and isolation of MDSCs.
A custom genotyping array reveals population-level heterogeneity for the genetic risks of prostate cancer and other cancers in Africa
Authors: Harlemon Maxine , Ajayi Olabode , Kachambwa Paidamoyo , Kim Michelle S. , Simonti Corinne N. , Quiver Melanie H. , Petersen Desiree C. , Mittal Anuradha , Fernandez Pedro , Hsing Ann W. , Baichoo Shakuntala , Agalliu Ilir , Jalloh Mohamed , Gueye Serigne M. , Snyper Nana Yaa , Adusei Ben , Mensah James E. , Abrahams Afua O.D. , Adebiyi Akindele O. , Orunmuyi Akin , Aisuodionoe-Shadrach Oseremen I. , Nwegbu Maxwell M. , Joffe Maureen , Chen Wenlong C. , Irusen Hayley , Neugut Alfred I. , Quintana Yuri , Seutloali Moleboheng , Fadipe Mayowa , Warren Christopher , Woehrmann Marcos H. , Zhang Peng , Ongaco Chrissie , Mawhinney Michelle , McBride Jo , Andrews Caroline , Adams Marcia , Pugh Elizabeth , Rebbeck Timothy R. , Petersen Lindsay , Lachance Joseph 
Published: July 2019

AbstractAlthough prostate cancer is the leading cause of cancer mortality for African men, the vast majority of known disease associations have been detected in European study cohorts. Furthermore, most genome-wide association studies have used genotyping arrays that are hindered by SNP ascertainment bias. To overcome these disparities in genomic medicine, the Men of African Descent and Carcinoma of the Prostate (MADCaP) Network has developed a genotyping array that is optimized for African populations. The MADCaP Array contains more than 1.5 million markers and an imputation backbone that successfully tags over 94% of common genetic variants in African populations. This array also has a high density of markers in genomic regions associated with cancer susceptibility, including 8q24. We assessed the effectiveness of the MADCaP Array by genotyping 399 prostate cancer cases and 403 controls from seven urban study sites in sub-Saharan Africa. We find that samples from Ghana and Nigeria cluster together, while samples from Senegal and South Africa yield distinct ancestry clusters. Using the MADCaP array, we identified cancer-associated loci that have large allele frequency differences across African populations. Polygenic risk scores were also generated for each genome in the MADCaP pilot dataset, and we found that predicted risks of CaP are lower in Senegal and higher in Nigeria.SignificanceWe have developed an Africa-specific genotyping array which enables investigators to identify novel disease associations and to fine-map genetic loci that are associated with prostate and other cancers.
Quantitative real-time PCR assay for the rapid identification of the multidrug-resistant bacterial pathogen Stenotrophomonas maltophilia
Authors: Fraser Tamieka A. , Bell Mikaela G. , Harris Patrick N.A. , Bell Scott C. , Bergh Haakon , Nguyen Thuy-Khanh , Kidd Timothy J. , Nimmo Graeme R. , Sarovich Derek S. , Price Erin P. 
Published: July 2019

AbstractStenotrophomonas maltophilia is emerging as an important cause of disease in nosocomial and community-acquired settings, including bloodstream, wound and catheter-associated infections. Cystic fibrosis airways also provide optimal growth conditions for various opportunistic pathogens with high antibiotic tolerance, including S. maltophilia. Currently, there is no rapid, cost-effective, and accurate molecular method for detecting this potentially life-threatening pathogen, particularly in polymicrobial specimens, suggesting that its true prevalence may be underestimated. Here, we used large-scale comparative genomics to identify a specific genetic target for S. maltophilia, with subsequent development and validation of a real-time PCR assay for its detection. Analysis of 165 Stenotrophomonas spp. genomes identified a 4kb region specific to S. maltophilia, which was targeted for Black Hole Quencher assay design. Our assay yielded the positive detection of 89 of 89 (100%) clinical S. maltophilia strains, and no amplification of 23 non-S. maltophilia clinical isolates. S. maltophilia was detected in 10/16 CF sputa, demonstrating the utility for direct detection in respiratory specimens. The assay demonstrated good sensitivity, with limits of detection and quantitation on pure culture of ~10 and ~100 genome equivalents, respectively. Our assay provides a highly specific, sensitive, and cost-effective method for the accurate identification of S. maltophilia, and will improve the diagnosis and treatment of this under-recognized pathogen by enabling its accurate and rapid detection from polymicrobial clinical and environmental samples.
Frontoparietal network dynamics impairments in juvenile myoclonic epilepsy revealed by MEG energy landscape
Authors: Krzemiński Dominik , Masuda Naoki , Hamandi Khalid , Singh Krish D , Routley Bethany , Zhang Jiaxiang 
Published: July 2019

AbstractJuvenile myoclonic epilepsy (JME) is a form of idiopathic generalized epilepsy affecting brain activity. It is unclear to what extent JME leads to abnormal network dynamics across functional networks. Here, we proposed a method to characterise network dynamics in MEG resting-state data, combining a pairwise maximum entropy model (pMEM) and the associated energy landscape analysis. Fifty-two JME patients and healthy controls underwent a resting-state MEG recording session. We fitted the pMEM to the oscillatory power envelopes in theta (4-7 Hz), alpha (8-13 Hz), beta (15-25 Hz) and gamma (30-60 Hz) bands in three source-localised resting-state networks: the frontoparietal network (FPN), the default mode network (DMN), and the sensorimotor network (SMN). The pMEM provided an accurate fit to the MEG oscillatory activity in both patient and control groups, and allowed estimation of the occurrence probability of each network state, with its regional activity and pairwise regional co-activation constrained by empirical data. We used energy values derived from the pMEM to depict an energy landscape of each network, with a higher energy state corresponding to a lower occurrence probability. When comparing the energy landscapes between groups, JME patients showed fewer local energy minima than controls and had elevated energy values for the FPN within the theta, beta and gamma-bands. Furthermore, numerical simulation of the fitted pMEM showed that the proportion of time the FPN was occupied within the basins of characteristic energy minima was shortened in JME patients. These network alterations were confirmed by a significant leave-one-out classification of individual participants based on a support vector machine employing the energy values of pMEM as features. Our findings suggested that JME patients had altered multi-stability in selective functional networks and frequency bands in the frontoparietal cortices.HighlightsAn energy landscape analysis characterises the dynamics of MEG oscillatory activityPatients with JME exhibit fewer local minima of the energy in their energy landscapesJME affects the network dynamics in the frontoparietal network.Energy landscape measures allow good single-patient classification.
Depressive disorder and its associated factors among prisoners in Debre Berhan Town, North Showa, Ethiopia
Authors: Reta Yared , Getachew Ruth , Bahiru Melese , Kale Bethelhem , Workie Keralem , G/Egziabher Yohannes 
Published: July 2019

AbstractBackgroundDepression is a commonest mental disorder among prisoners characterized by an intense mood involving a feeling of sadness, lack of interest or hopelessness that lasts for weeks, months, or even longer. In addition to imprisonment, depression is the primary factor leading to suicidal attempt. Therefore, this study revealed the magnitude of depressive disorder and its associated factors among prisoners of Debre Berhan Town.MethodsWe conducted an institution based cross-sectional quantitative study. We collected the data from 336 randomly selected prisoners by using interviewer-administered Patient Health Questioner-9 (PHQ-9). Multiple logistic regression was performed to identify independent predictors.ResultOut of the total of 336 prisoners 330 (98%) were males. Using PHQ-9 at the cut of point >5 for caseness, the prevalence of depression found to be 44% (n=148). Widowed (AOR=6.30 CI: 1.09-36.67), those who are educated at college or university level (AOR=5.34 CI:1.59-17.94), a history of suicidal attempt (AOR=2.76 CI: 1.04-7.31), Previously facing severe stressful life event (AOR=2.57 CI: 1.41-4.67), 5-10 years of sentence (AOR=2.51 CI:1.32-4.79) and having chronic medical illness (AOR= 3.32 CI: 1.26-8.75) are found to be independently associated with depression.ConclusionIn general, there is a high prevalence of depression among prisoners in of Debre Berhan town. Therefore, designing strategies for early screening and treatment of depression at prisons is very crucial.