bluuebunny/crossref_metadata_2025_split huggingface dataset:
High-throughput isolation and culture of human gut bacteria with droplet microfluidics
Authors: Villa Max M , Bloom Rachael J , Silverman Justin D , Durand Heather K , Jiang Sharon , Wu Anchi , Huang Shuqiang , You Lingchong , David Lawrence A 
Published: May 2019

AbstractIsolation and culture of gut bacteria enable testing for microbial roles in disease and may also lead to novel therapeutics. However, the diversity of human gut microbial communities (microbiota) impedes comprehensive experimental studies of individual bacterial taxa. Here, we combine advances in droplet microfluidics and high-throughput DNA sequencing to develop a platform for isolating and assaying microbiota members in picoliter droplets (MicDrop). MicDrop can be used to create millions of distinct bacterial colonies in a single experiment while using off-the-shelf parts compact enough to fit in an anaerobic chamber. In proof-of-concept experiments, we used the platform to characterize inter-individual metabolic variation among hundreds of polysaccharide-degrading gut bacteria from nine stool donors. We also used MicDrop to test the hypothesis that growth kinetics of individual gut bacterial taxa are associated with longterm community dynamics in an artificial gut. These demonstrations suggest the MicDrop platform could support future diagnostic efforts to personalize microbiota-directed therapies, as well as to provide comprehensive new insights into the ecology of human gut microbiota.
Superloser: a plasmid shuffling vector forSaccharomyces cerevisiaewith exceedingly low background
Authors: Haase Max A. B. , Truong David M. , Boeke Jef D. 
Published: May 2019

AbstractHere we report a new plasmid shuffle vector for forcing budding yeast (Saccharomyces cerevisiae) to incorporate a new genetic pathway in place of a native pathway – even essential ones – while maintaining low false positive rates (less than 1 in 108per cell). This plasmid, dubbed “Superloser”, was designed with reduced sequence similarity to commonly used yeast plasmids (i.e. pRS400 series) to limit recombination, a process that in our experience leads to retention of the yeast gene(s) instead of the desired gene(s). In addition, Superloser utilizes two orthogonal copies of the counter-selectable markerURA3to reduce spontaneous 5-fluoroorotic acid resistance. Finally, the CEN/ARS sequence is fused to theGAL1-10promoter, which disrupts plasmid segregation in the presence of the sugar galactose, causing Superloser to rapidly be removed from a population of cells. We show one proof of concept shuffling experiment: swapping yeast’s core histones out for their human counterparts. Superloser is especially useful for forcing yeast to use highly unfavorable genes, such as human histones, as it enables plating a large number of cells (1.4×109) on a single 10 cm petri dish while maintaining a very low background. Therefore, Superloser is a useful tool for yeast geneticists to effectively shuffle low viability genes and/or pathways in yeast that may arise in as low as 1 in 108cells.
Loss of dominant caterpillar genera in a protected tropical forest
Authors: Salcido Danielle M. , Forister Matthew L. , Lopez Humberto Garcia , Dyer Lee A. 
Published: May 2019

ABSTRACTReports of biodiversity loss have increasingly focused on the abundance and diversity of insects, but it is still unclear if substantive insect diversity losses are occurring in intact low-latitude forests. We collected 22 years of plant-caterpillar-parasitoid data in a protected tropical forest and found reductions in diversity and density of these insects that appear to be partly driven by a changing climate and weather anomalies. The decline in parasitism represents a reduction in an important ecosystem service: enemy control of primary consumers. The consequences of these changes are in many cases irreversible and are likely to be mirrored in nearby forests; overall declines in the region will have negative consequences for surrounding agriculture. The decline of important tropical taxa and associated ecosystem function illuminates the consequences of numerous threats to global insect diversity and provides additional impetus for research on tropical diversity.
Postpartum breast cancer progression is driven by semaphorin 7a mediated invasion and survival
Authors: Tarullo Sarah E , Hill Ryan C , Hansen Kirk , Behbod Fariba , Borges Virginia F , Nelson Andrew C , Lyons Traci R 
Published: May 2019

ABSTRACTYoung women diagnosed with breast cancer (BC) have poor prognosis due to increased rates of metastasis. Additionally, women within 10 years of most recent childbirth at diagnosis are ∼3 times more likely to develop metastasis than age and stage matched nulliparous women. We define these cases as postpartum BC (PPBC) and propose that the unique biology of the postpartum mammary gland drives tumor progression. Our published results revealed roles for SEMA7A in breast tumor cell growth, motility, invasion, and tumor associated-lymphangiogenesis, all of which are also increased in pre-clinical models of PPBC. However, whether SEMA7A drives progression in PPBC remains largely unexplored. Our results presented herein show that silencing of SEMA7A decreases tumor growth in a model of PPBC while overexpression is sufficient to increase growth in nulliparous hosts. Further, we show that SEMA7A promotes multiple known drivers of PPBC progression including tumor associated COX-2 expression and fibroblast-mediated collagen deposition in the tumor microenvironment. Additionally, we show for the first time that SEMA7A expressing cells deposit fibronectin to promote tumor cell survival. Finally, we show that co-expression of SEMA7A/COX-2/FN predicts for poor prognosis in breast cancer patient cohorts. These studies suggest SEMA7A as a key mediator of BC progression and that targeting SEMA7A may open avenues for novel therapeutic strategies.
Nearly unbiased estimator of contemporary effective population size using within-cohort sibling pairs incorporating parental and non-parental reproductive variations
Authors: Akita Tetsuya 
Published: May 2019

AbstractIn this study, we developed a nearly unbiased estimator of contemporary effective mother size in a population, which is based on a known maternal half-sibling relationship found within the same cohort. Our method allows for variance of the average number of offspring per mother (i.e., parental variation, such as age-specific fecundity) and variance of the number of offspring among mothers with identical reproductive potential (i.e., non-parental variation, such as family-correlated survivorship). We also developed estimators of the variance and coefficient variation of contemporary effective mother size and qualitatively evaluated the performance of the estimators by running an individual-based model. Our results provide guidance for (i) a sample size to ensure the required accuracy and precision when the order of effective mother size is available and (ii) a degree of uncertainty regarding the estimated effective mother size when information about the size is unavailable. To the best of our knowledge, this is the first report to demonstrate the derivation of a nearly unbiased estimator of effective population size; however, its current application is limited to effective mother size and situations in which the sample size is not particularly small and maternal half-sibling relationships can be detected without error. The results of this study demonstrate the usefulness of a sibship assignment method for estimating effective population size; in addition, they have the potential to greatly widen the scope of genetic monitoring.
Bagremycin Antibiotics and Ferroverdin iron-chelators are synthetized by the Same Gene Cluster
Authors: Martinet Loïc , Naômé Aymeric , Deflandre Benoit , Maciejewska Marta , Tellatin Déborah , Tenconi Elodie , Smargiasso Nicolas , de Pauw Edwin , van Wezel Gilles P. , Rigali Sébastien 
Published: May 2019

AbstractBiosynthetic gene clusters (BGCs) are organized groups of genes involved in the production of specialized metabolites. Typically, one BGC is responsible for the production of one or several similar compounds with bioactivities that usually only vary in terms of strength and/or specificity. Here we show that the previously described ferroverdins and bagremycins, which are families of metabolites with different bioactivities, are produced from the same BGC, whereby the fate of the biosynthetic pathway depends on iron availability. Under conditions of iron depletion, the monomeric bagremycins are formed, which are amino-aromatic antibiotics resulting from the condensation of 3-amino-4-hydroxybenzoic acid with p-vinylphenol. Conversely, when iron is abundantly available, the biosynthetic pathway additionally produces a molecule based on p-vinylphenyl-3-nitroso-4-hydroxybenzoate, which complexes iron to form the trimeric ferroverdins that have anticholesterol activity. Thus our work challenges the concept that BGCs should produce a single family of molecules with one type of bioactivity, the occurrence of the different metabolites being triggered by the environmental conditions.
Galacto-oligosaccharides modulate the juvenile gut microbiome and innate immunity to improve broiler chicken performance
Authors: Richards Philip J. , Flaujac Lafontaine Geraldine M. , Connerton Phillippa L. , Liang Lu , Asiani Karishma , Fish Neville M. , Connerton Ian F. 
Published: May 2019

ABSTRACTImprovements in growth performance and health are key goals in broiler chicken production. Inclusion of prebiotic galacto-oligosaccharides in broiler feed enhanced the growth rate and feed conversion of chickens relative to a calorie-matched control diet. Comparison of the cecal microbiota identified key differences in abundance ofLactobacillusspp. Increased levels ofL. johnsoniiin GOS-fed juvenile birds at the expense ofL. crispatuswas linked to improved performance (growth rate and market weight). Investigation of the innate immune responses highlighted increases of ileal and cecal IL-17A gene expression counterposed to a decrease in IL-10 and IL-17F. Quantification of the autochthonousLactobacillusssp. revealed a correlation between bird performance andL. johnsoniiabundance. Shifts in the cecal populations of keyLactobacillusspp. of juvenile birds primed intestinal innate immunity without harmful pathogen challenge.IMPORTANCEImprovements in the growth rate of broiler chickens can be achieved through dietary manipulation of the naturally occurring bacterial populations whilst mitigating the withdrawal of antibiotic growth promoters. Prebiotic galacto-oligosaccharides (GOS) are manufactured as a by-product of dairy cheese production, which can be incorporated in the diets of juvenile chickens to improve their health and performance. This study investigates the key mechanisms behind this progression and pin pointsL. johnsoniias a key species that facilitates the enhancements in growth rate and gut health. It also relates the role of the innate immune system in the response to the GOS diet.
Cyclic di-GMP Increases Catalase Production and Hydrogen Peroxide Tolerance inVibrio cholerae
Authors: Fernandez Nicolas L. , Waters Christopher M. 
Published: May 2019

AbstractVibrio choleraeis a Gram-negative bacterial pathogen that causes the disease cholera, which affects nearly 1 million people each year. In between outbreaks,V. choleraeresides in fresh and salt water environments where it is able to persist through changes in temperature, oxygen, and salinity. One key characteristic that promotes environmental persistence ofV. choleraeis the ability to form multicellular communities, called biofilms, that often adhere to biotic and abiotic sources. Biofilm formation inV. choleraeis positively regulated by the dinucleotide second messenger cyclic dimeric guanosine monophosphate (c-di-GMP). While most research on the c-di-GMP regulon has focused on biofilm formation or motility, we hypothesized the c-di-GMP signaling network encompassed a larger set of effector functions than reported. We found that high intracellular c-di-GMP increased catalase activity approximately 4-fold relative to strains with unaltered c-di-GMP. Genetic studies demonstrated that c-di-GMP mediated catalase activity was due to increased expression of the catalase encoding genekatB. Moreover, c-di-GMP mediated regulation of catalase activity andkatBexpression required the c-di-GMP dependent transcription factors VpsT and VpsR. Lastly, we found that high c-di-GMP increased survival after H2O2challenge in akatB, vpsR, andvpsTdependent manner. Our results indicate antioxidant production is regulated by c-di-GMP inV. choleraeuncovering a new node in the growing VpsT and VpsR c-di-GMP signaling network.ImportanceAs a result of infection withV. cholerae, patients become dehydrated leading to death if not properly treated. The marine environment is the natural reservoir forV. choleraewhere it can survive alterations in temperature, salinity, and oxygen. The second messenger molecule c-di-GMP is an important signal regulating host and marine environmental persistence because it controls whetherV. choleraewill form a biofilm or disperse through flagellar motility. In this work, we demonstrate another function of c-di-GMP inV. choleraebiology: promoting tolerance to the reactive oxygen species H2O2through differential regulation of catalase expression. Our results suggest a mechanism where c-di-GMP simultaneously controls biofilm formation and antioxidant production, which could promote persistence in human and marine environments.
Directional DBS Leads Show Large Deviations from their Intended Implantation Orientation
Authors: Dembek TA , Hoevels M , Hellerbach A , Horn A , Petry-Schmelzer JN , Borggrefe J , Wirths J , Dafsari HS , Barbe MT , Visser-Vandewalle V , Treuer H 
Published: May 2019

AbstractObjectiveLead orientation is a new degree of freedom with directional deep brain stimulation (DBS) leads. We investigated how prevalent deviations from the intended implantation direction are in a large patient cohort.MethodsThe Directional Orientation Detection (DiODe) algorithm to determine lead orientation from postoperative CT scans was implemented into the open-source Lead-DBS toolbox. Lead orientation was analysed in 100 consecutive patients (198 leads). Different anatomical targets and intraoperative setups were compared.ResultsDeviations of up to 90° from the intended implantation direction were observed. Deviations of more than 30° were seen in 42 % of the leads and deviations of more than 60° in about 11 % of the leads. Deviations were independent from the neuroanatomical target and the stereotactic frame but increased depending on which microdrive was used.DiscussionOur results indicate that large deviations from the intended implantation direction are a common phenomenon in directional leads. Postoperative determination of lead orientation is thus mandatory for investigating directional DBS.Full DisclosuresTill A. Dembek reports speaker honoraria from Medtronic and Boston Scientific.Mauritius Hoevels has nothing to disclose.Alexandra Hellerbach has nothing to disclose.Andreas Horn reports speaker honoraria from Medtronic.Jan Niklas Petry-Schmelzer reports travel grants from Boston Scientific.Jan Borggrefe has nothing to disclose.Jochen Wirths reports travel grants from Boston Scientific.Haidar Salimi-Dafsari reports honoraria from Medtronic and Boston Scientific.Michael T. Barbe reports grants from Medtronic and Boston Scientific.Veerle Visser-Vandewalle is a member of the advisory boards and reports consultancies for Medtronic, Boston Scientific and St Jude Medical. She received a grant from SAPIENS Steering Brain Stimulation. Harald Treuer has nothing to disclose.
Systems-wide analysis unravels the new roles of CCM signal complex (CSC)
Authors: Abou-Fadel Johnathan , Vasquez Mariana , Grajeda Brian , Ellis Cameron , Zhang Jun 
Published: May 2019

AbstractCerebral cavernous malformations (CCMs) are characterized by abnormally dilated intracranial capillaries that result in increased susceptibility to stroke. Three genes have been identified as causes of CCMs; KRIT1 (CCM1), MGC4607 (CCM2) and PDCD10 (CCM3); one of them is disrupted in most CCM cases. It was demonstrated that both CCM1 and CCM3 bind to CCM2 to form a CCM signaling complex (CSC) to modulate angiogenesis. In this report, we deployed both RNA-seq and proteomic analysis of perturbed CSC after depletion of one of three CCM genes to generate interactomes for system-wide studies. Our results demonstrated a unique portrait detailing alterations in angiogenesis and vascular integrity. Interestingly, only in-direct overlapped alterations between RNA and protein levels were detected, supporting the existence of multiple layers of regulation in CSC cascades. Notably, this is the first report identifying that both β4 integrin and CAV1 signaling are downstream of CSC, conveying the angiogenic signaling. Our results provide a global view of signal transduction modulated by the CSC, identifies novel regulatory signaling networks and key cellular factors associated with CSC.
Spatial Confidence Sets for Raw Effect Size Images
Authors: Bowring Alexander , Telschow Fabian , Schwartzman Armin , Nichols Thomas E. 
Published: May 2019

AbstractThe mass-univariate approach for functional magnetic resonance imagery (fMRI) analysis remains a widely used and fundamental statistical tool within neuroimaging. However, this method suffers from at least two fundamental limitations: First, with sample sizes growing to 4, 5 or even 6 digits, the entire approach is undermined by the null hypothesis fallacy, i.e. with sufficient sample size, there is high enough statistical power to reject the null hypothesis everywhere, making it difficult if not impossible to localize effects of interest. Second, with any sample size, when cluster-size inference is used a significantp-value only indicates that a cluster is larger than chance, and no notion of spatial uncertainty is provided. Therefore, no perception of confidence is available to express the size or location of a cluster that could be expected with repeated sampling from the population.In this work, we address these issues by extending on a method proposed bySommerfeld, Sain, and Schwartzman (2018)to develop spatial Confidence Sets (CSs) on clusters found in thresholded raw effect size maps. While hypothesis testing indicates where the null, i.e. a raw effect size of zero, can be rejected, the CSs give statements on the locations where raw effect sizes exceed, and fall short of, anon-zerothreshold, providing both an upper and lower CS.While the method can be applied to any parameter in a mass-univariate General Linear Model, we motivate the method in the context of BOLD fMRI contrast maps for inference on percentage BOLD change raw effects. We propose several theoretical and practical implementation advancements to the original method in order to deliver an improved performance in small-sample settings. We validate the method with 3D Monte Carlo simulations that resemble fMRI data. Finally, we compute CSs for the Human Connectome Project working memory task contrast images, illustrating the brain regions that show a reliable %BOLD change for a given %BOLD threshold.
Comparative profiling of the synaptic proteome from Alzheimer’s disease patients with focus on the APOE genotype
Authors: Hesse Raphael , Hurtado Maica Llavero , Jackson Rosemary J. , Eaton Samantha L. , Herrmann Abigail G , Colom-Cadena Marti , King Declan , Rose Jamie , Tulloch Jane , McKenzie Chris-Anne , Smith Colin , Henstridge Christopher , Lamont Douglas , Wishart Thomas M. , Spires-Jones Tara L. 
Published: May 2019

AbstractDegeneration of synapses in Alzheimer’s disease (AD) strongly correlates with cognitive decline, and synaptic pathology contributes to disease pathophysiology. We recently discovered that the strongest genetic risk factor for sporadic AD, apolipoprotein E epsilon 4 (APOE4), exacerbates synapse loss and synaptic accumulation of oligomeric amyloid beta in human AD brain. To begin to understand the molecular cascades involved in synapse loss in AD and how this is mediated byAPOE, and to generate a resource of knowledge of changes in the synaptic proteome in AD, we conducted a proteomic screen and systematicin-silicoanalysis of synaptoneurosome preparations from temporal and occipital cortices of human AD and control subjects with knownAPOEgene status. Our analysis identified over 5,500 proteins in human synaptoneurosomes and highlighted disease, brain region, and APOE-associated changes in multiple molecular pathways including a decreased abundance in AD of proteins important for synaptic and mitochondrial function and an increased abundance of proteins involved in neuroimmune interactions and intracellular signaling.HighlightsProteomic analysis of synapses isolated from Alzheimer’s disease and control subject brains identifies over 5,500 proteins in human synapses.In silico analysis reveals region-specific decreases in proteins involved in synaptic and mitochondrial function and increases in proteins involved in neuroimmune signaling and intracellular signaling in AD.The apolipoprotein E4 risk gene is associated with exacerbated changes in synaptic proteins in AD.
Bi-Alignments as Models of Incongruent Evolution of RNA Sequence and Structure
Authors: Waldl Maria , Will Sebastian , Wolfinger Michael T. , Hofacker Ivo L. , Stadler Peter F. 
Published: May 2019

AbstractRNA molecules may experience independent selection pressures on their sequence and (secondary) structure. Structural features then may be preserved without maintaining their exact position along the sequence. In such cases, corresponding base pairs are no longer formed by homologous bases, leading to the incongruent evolutionary conservation of sequence and structure. In order to model this phenomenon, we introduce bi-alignments as a superposition of two alignments: one modeling sequence homology; the other, structural homology. We show that under natural assumptions on the scoring functions, bi-alignments form a special case of 4-way alignments, in which the incongruencies are measured as indels in the pairwise alignment of the two alignment copies. A preliminary survey of the Rfam database suggests that incongruent evolution of RNAs is not a very rare phenomenon.AvailabilityOur software is freely available at https://github.com/s-will/BiAlign