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Rxivist combines preprints from bioRxiv with data from Twitter to help you find the papers being discussed in your field. Currently indexing 62,292 bioRxiv papers from 276,522 authors.

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49,489 results found. For more information, click each entry to expand.

49001: Fractone bulbs derive from ependymal cells and their laminin composition influence the stem cell niche in the subventricular zone
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Posted to bioRxiv 14 Dec 2016

Fractone bulbs derive from ependymal cells and their laminin composition influence the stem cell niche in the subventricular zone
1 download neuroscience

Marcos Assis Nascimento, Lydia Sorokin, Tatiana Coelho-Sampaio

Fractones are extracellular matrix structures in the neural stem cell niche of the subventricular zone (SVZ), where they appear as round deposits named bulbs or thin branching lines called stems. Their cellular origin and what determines their localization at this site is poorly studied and it remains unclear whether they influence neural stem and progenitor cells formation, proliferation and/or maintenance. To address these questions, we analyzed whole mount preparations of the lateral ventricle by confocal microscopy using different extracellular matrix and cell markers. We found that bulbs are rarely connected to stems and that they contain laminin α5 and α2 chains, respectively. Fractone bulbs were profusely distributed throughout the SVZ and appeared associated with the center of pinwheels, a critical site for adult neurogenesis. We demonstrate that bulbs appear at the apical membrane of ependymal cells at the end of the first week after birth. The use of transgenic mice lacking laminin α5 gene expression (Lama5) in endothelium and in FoxJ1-expressing ependymal cells, revealed ependymal cells as the source of laminin α5-containing fractone bulbs. Loss of laminin α5 from bulbs correlated with a 60% increase in cell proliferation, as determined by PH3 staining, and with a selective reduction in the number of quiescent neural stem cells in the SVZ. These results indicate that fractones are a key component of the SVZ and suggest that laminin α5 modulates the physiology of the neural stem cell niche.

49002: Biogeographic study of human gut-associated crAssphage suggests impacts from industrialization and recent expansion
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Posted to bioRxiv 07 Aug 2018

Biogeographic study of human gut-associated crAssphage suggests impacts from industrialization and recent expansion
1 download evolutionary biology

Tanvi P Honap, Krithivasan Sankaranarayanan, Stephanie L Schnorr, Andrew T Ozga, Christina Warinner, Cecil M Lewis

CrAssphage (cross-assembly phage) is a bacteriophage that was first discovered in human gut metagenomic data. CrAssphage belongs to a diverse family of crAss-like bacteriophages thought to infect gut commensal bacteria belonging to Bacteroides species. However, not much is known about the biogeography of crAssphage and whether certain strains are associated with specific human populations. In this study, we screened publicly available human gut metagenomic data from 3,341 samples for the presence of crAssphage sensu stricto (NC_024711.1). We found that crAssphage prevalence is low in traditional, hunter-gatherer populations, such as the Hadza from Tanzania and Matses from Peru, as compared to industrialized, urban populations. Statistical comparisons showed no association of crAssphage prevalence with variables such as age, sex, body mass index, and health status of individuals. Phylogenetic analyses show that crAssphage strains reconstructed from the same individual over multiple time-points, cluster together. CrAssphage strains from individuals from the same study population do not always cluster together. Some evidence of clustering is seen at the level of broadly defined geographic regions, however, the relative positions of these clusters within the crAssphage phylogeny are not well-supported. We hypothesize that this lack of strong biogeographic structuring is suggestive of a recent expansion event within crAssphage. Using a Bayesian dating approach, we estimate this expansion has occurred within the past 200 years. Overall, we determine that crAssphage presence is associated with an industrialized lifestyle. The absence of strong biogeographic structuring within global crAssphage strains is likely due to a recent population expansion within this bacteriophage.

49003: A simple centrifugation protocol increases mitochondrial DNA yield 140-fold and facilitates mitogenomic studies
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Posted to bioRxiv 07 Feb 2017

A simple centrifugation protocol increases mitochondrial DNA yield 140-fold and facilitates mitogenomic studies
1 download molecular biology

Jan Niklas Macher, Vera Zizka, Alexander Martin Weigand, Florian Leese

DNA (meta)barcoding is used to study biodiversity and is available for standardised assessments. However, it suffers from PCR bias, which can lead to the loss of specific taxa. PCR-free techniques such as shotgun metagenomics are therefore thought to be more suited for biodiversity assessments, but are currently limited by incomplete reference libraries. The technique of "mitogenome-skimming" or "mitogenomics", in which complete mitochondrial genomes are sequenced, is ideal to bridge the techniques of (meta)barcoding and metagenomics. However, without the enrichment of mitochondria, roughly 99 % of all sequencing reads are of non-mitochondrial origin and mostly useless for common applications, e.g. species identification. Here, we present a simple centrifugation protocol that leads to an average 140-fold enrichment of mitochondrial DNA. By sequencing six "mock"- communities - comprising the freshwater taxa Corbicula fluminea, Gammarus roeselii and Hydropsyche exocellata each - we recovered whole mitochondrial genomes of these species and the acanthocephalan endoparasite Pomphorhynchus laevis. The presented protocol will greatly speed up building reference libraries for whole mitochondrial genomes, as dozens of species could be sequenced on a single MiSeq run. Subsequently, it will also allow biodiversity assessments using mitogenomics at greatly reduced costs in comparison to mitogenomic approaches without prior enrichment for mitochondria.

49004: Drug repurposing: omeprazole increases the efficacy of acyclovir against herpes simplex virus type 1 and 2
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Posted to bioRxiv 02 May 2018

Drug repurposing: omeprazole increases the efficacy of acyclovir against herpes simplex virus type 1 and 2
1 download pharmacology and toxicology

Martin Michaelis, Malte Christian Kleinschmidt, Mark N Wass, Jindrich Cinatl

Objectives: Omeprazole was shown to improve the anti-cancer effect of the nucleoside-analogue 5-fluorouracil. Here, we investigated the effects of omeprazole on the activities of the antiviral nucleoside analogues ribavirin and acyclovir. Methods: West Nile virus-infected Vero cells and influenza A H1N1-infected MDCK cells were treated with omeprazole and/or ribavirin. Herpes simplex virus 1 (HSV-1)- or HSV-2-infected Vero or HaCat cells were treated with omeprazole and/or acyclovir. Antiviral effects were determined by examination of cytopathogenic effects (CPE), immune staining, and virus yield assay. Cell viability was investigated by MTT assay. Results: Omeprazole concentrations up to 80 microg/mL did not affect the antiviral effects of ribavirin. In contrast, omeprazole increased the acyclovir-mediated effects on HSV-1- and HSV-2-induced CPE formation in a dose-dependent manner in Vero and HaCat cells. Addition of omeprazole 80 microg/mL resulted in a 10.8-fold reduction of the acyclovir concentration that reduces CPE formation by 50% (IC50) in HSV-1-infected Vero cells and in a 47.7-fold acyclovir IC50 reduction in HSV-1-infected HaCat cells. In HSV-2-infected cells, omeprazole reduced the acyclovir IC50 by 7.3-fold (Vero cells) or by 12.9-fold (HaCat cells). Omeprazole also enhanced the acyclovir-mediated effects on viral antigen expression and virus replication in HSV-1- and HSV-2-infected cells. In HSV-1-infected HaCat cells, omeprazole 80 microg/mL reduced the virus titre in the presence of acyclovir 1 microg/mL by 1.6x10(5)-fold. In HSV-2-infected HaCat cells omeprazole 80 microg/mL reduced the virus titre in the presence of acyclovir 2 microg/mL by 9.2x10(3)-fold. The investigated drug concentrations did not affect cell viability, neither alone nor in combination. Conclusions: Omeprazole increases the anti-HSV activity of acyclovir. As clinically well-established and tolerated drug, it is a candidate drug for antiviral therapies in combination with acyclovir.

49005: Domain-invariant features for mechanism of action prediction in a multi-cell-line drug screen
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Posted to bioRxiv 03 Jun 2019

Domain-invariant features for mechanism of action prediction in a multi-cell-line drug screen
1 download bioinformatics

Joseph C Boyd, Alice Pinheiro, Elaine Del Nery, Fabien Reyal, Thomas Walter

High Content Screening is an important tool in drug discovery and characterisation. Often, high content drug screens are performed on one single cell line. Yet, a single cell line cannot be thought of as a perfect disease model. Many diseases feature an important molecular heterogeneity. Consequently, a drug may be effective against one molecular subtype of a disease, but less so against another. To characterise drugs with respect to their effect not only on one cell line but on a panel of cell lines is therefore a promising strategy to streamline the drug discovery process. The contribution of this paper is twofold. First, we investigate whether we can predict drug mechanism of action (MOA) at the molecular level without optimisation of the MOA classes to the screen specificities. To this end, we benchmark a set of algorithms within a conventional pipeline, and evaluate their MOA prediction performance according to a statistically rigorous framework. Second, we extend this conventional pipeline to the simultaneous analysis of multiple cell lines, each manifesting potentially different morphological baselines. For this, we propose multitask autoencoders, including a domain-adaptive model used to construct domain-invariant feature representations across cell lines. We apply these methods to a pilot screen of two triple negative breast cancer cell lines as models for two different molecular subtypes of the disease.

49006: Disease-causing mutations in subunits of OXPHOS complex I affect their physical interactions
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Posted to bioRxiv 22 Jan 2019

Disease-causing mutations in subunits of OXPHOS complex I affect their physical interactions
1 download genomics

Gilad Barshad, Nicol Zlotinkov-Poznianski, Lihi Gal, Maya Schuldiner, Dan Mishmar

Mitochondrial complex I (C1) is the largest multi-subunit oxidative phosphorylation (OXPHOS) protein complex. Recent availability of a high-resolution human C1 structure, and from two non-human mammals, enabled predicting the impact of mutations on interactions involving each of the 44 C1 subunits. However, experimentally assessing the impact of the predicted interactions requires an easy and high-throughput method. Here, we created such a platform by cloning all 37 nuclear DNA (nDNA) and 7 mitochondrial DNA (mtDNA)-encoded human C1 subunits into yeast expression vectors to serve as both 'prey' and 'bait' in the split murine dihydrofolate reductase (mDHFR) protein complementation assay (PCA). We first demonstrated the capacity of this approach and then used it to examine reported pathological OXPHOS C1 mutations that occur at subunit interaction interfaces. Our results indicate that a pathological frame-shift mutation in the MT-ND2 gene, causing the replacement of 126 C-terminal residues by a stretch of only 30 amino acids, resulted in loss of specificity in ND2-based interactions involving these residues. Hence, the split mDHFR PCA is a powerful assay for assessing the impact of disease-causing mutations on pairwise protein-protein interactions in the context of a large protein complex, thus revealing the mechanism underlying any associated pathogenicity.

49007: Pooled CRISPR screening with single-cell transcriptome read-out
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Posted to bioRxiv 27 Oct 2016

Pooled CRISPR screening with single-cell transcriptome read-out
1 download genomics

Paul Datlinger, Christian Schmidl, André F Rendeiro, Peter Traxler, Johanna Klughammer, Linda Schuster, Christoph Bock

CRISPR-based genetic screens have revolutionized the search for new gene functions and biological mechanisms. However, widely used pooled screens are limited to simple read-outs of cell proliferation or the production of a selectable marker protein. Arrayed screens allow for more complex molecular read-outs such as transcriptome profiling, but they provide much lower throughput. Here we demonstrate CRISPR genome editing together with single-cell RNA sequencing as a new screening paradigm that combines key advantages of pooled and arrayed screens. This approach allowed us to link guide-RNA expression to the associated transcriptome responses in thousands of single cells using a straightforward and broadly applicable screening workflow.

49008: Chronic ethanol ingestion impairs Drosophila melanogaster health in a microbiome-dependent manner
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Posted to bioRxiv 09 Nov 2017

Chronic ethanol ingestion impairs Drosophila melanogaster health in a microbiome-dependent manner
1 download microbiology

James Angus Chandler, Lina Victoria Innocent, Isaac L Huang, Jane L Yang, Michael B. Eisen, William B Ludington

The microbiome can modulate the interaction between animals and their environment. In particular, intestinal microbes play a strong role in shaping how animals respond to their diets, and especially dietary toxins. In this study, we investigated how the microbiome affects the interaction between the fruit fly Drosophila melanogaster and ingested ethanol. D. melanogaster naturally feeds on fermenting fruits and therefore commonly ingests ethanol. This dietary ethanol is generally considered to be a toxin, but its effect on adult fly fitness has yet to be shown. We found that the reproductive output of bacterially-colonized flies remains high with low amounts of dietary ethanol, while that of bacteria-free flies decreases precipitously after ethanol ingestion. This shows that bacteria protect D. melanogaster from the damaging effects of ingested ethanol, which has important implications for fitness under natural conditions. We also observed that bacterial colonization and ethanol both negatively affect fly lifespan. In particular, bacteria play a dominant role on fly lifespan and therefore the negative effects of ethanol are only observed in bacteria-free flies. We next asked how the bacterial microbiota changes in response to dietary ethanol. Contrary to our expectations, we found that total bacterial abundance stays relatively constant with increasing ethanol. In vivo survival of bacteria was well above the in vitro toxic dose of ethanol, demonstrating that the host is shielding the microbiome from the negative effects of ethanol. Next, we investigated several aspects of host physiology that may underlie bacterially-modulated fitness changes. We found that regardless of bacterial colonization, ethanol ingestion decreases the prevalence of intestinal barrier failure and increases fly body fat content, suggesting these mechanisms are not directly responsible for bacteria-dependent fitness differences. Finally, measurements of dietary ethanol content suggest that bacterial metabolism can only partially explain the observed fitness effects. Overall, we found significant bacteria-by-ethanol interactions on D. melanogaster and that bacteria ameliorate the negative effects of ethanol on host fecundity. Because of the central role of ethanol in the ecology of D. melanogaster, these results have important implications for our understanding of fruit fly natural history. More generally, they underscore the importance of the microbiome in shaping an animal's interaction with its environment.

49009: Fixing the stimulus-as-fixed-effect fallacy in task fMRI
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Posted to bioRxiv 25 Sep 2016

Fixing the stimulus-as-fixed-effect fallacy in task fMRI
1 download neuroscience

Jacob Westfall, Thomas E Nichols, Tal Yarkoni

Most fMRI experiments record the brain's responses to samples of stimulus materials (e.g., faces or words). Yet the statistical modeling approaches used in fMRI research universally fail to model stimulus variability in a manner that affords population generalization--meaning that researchers' conclusions technically apply only to the precise stimuli used in each study, and cannot be generalized to new stimuli. A direct consequence of this stimulus-as-fixed-effect fallacy is that the majority of published fMRI studies have likely overstated the strength of the statistical evidence they report. Here we develop a Bayesian mixed model (the random stimulus model; RSM) that addresses this problem, and apply it to a range of fMRI datasets. Results demonstrate considerable inflation (50-200% in most of the studied datasets) of test statistics obtained from standard "summary statistics"-based approaches relative to the corresponding RSM models. We demonstrate how RSMs can be used to improve parameter estimates, properly control false positive rates, and test novel research hypotheses about stimulus-level variability in human brain responses.

49010: A parametric interpretation of Bayesian Nonparametric Inference from Gene Genealogies: linking ecological, population genetics and evolutionary processes
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Posted to bioRxiv 09 Oct 2017

A parametric interpretation of Bayesian Nonparametric Inference from Gene Genealogies: linking ecological, population genetics and evolutionary processes
1 download genetics

Jose Miguel Ponciano

Using a nonparametric Bayesian approach Palacios and Minin (2013) dramatically improved the accuracy, precision of Bayesian inference of population size trajectories from gene genealogies. These authors proposed an extension of a Gaussian Process (GP) nonparametric inferential method for the intensity function of non-homogeneous Poisson processes. They found that not only the statistical properties of the estimators were improved with their method, but also, that key aspects of the demographic histories were recovered. The authors' work represents the first Bayesian nonparametric solution to this inferential problem because they specify a convenient prior belief without a particular functional form on the population trajectory. Their approach works so well and provides such a profound understanding of the biological process, that the question arises as to how truly "biology-free" their approach really is. Using well-known concepts of stochastic population dynamics, here I demonstrate that in fact, Palacios and Minin's GP model can be cast as a parametric population growth model with density dependence and environmental stochasticity. Making this link between population genetics and stochastic population dynamics modeling provides novel insights into eliciting biologically meaningful priors for the trajectory of the effective population size. The results presented here also bring novel understanding of GP as models for the evolution of a trait. Thus, the ecological principles foundation of Palacios and Minin (2013)'s prior adds to the conceptual and scientific value of these authors' inferential approach. I conclude this note by listing a series of insights brought about by this connection with Ecology.

49011: Environmental Assessment of Cytotoxic Drugs in the Oncology Center of Cyprus
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Posted to bioRxiv 16 Apr 2019

Environmental Assessment of Cytotoxic Drugs in the Oncology Center of Cyprus
1 download pharmacology and toxicology

Elpidoforos S. Soteriades, Sofia C Economidou, Artemis Tsivitanidou, Petros Polyviou, Amanda Lorimer, Nikos Katodritis, Stavroula Theophanous-Kitiri

Background Cytotoxic drugs constitute an important workplace hazard in the hospital environment. Our aim was to conduct an environmental assessment of hazardous drugs in the Oncology center of Cyprus. Methods Wipe samples were obtained from 42 workplace areas of the Oncology Center including two pairs of gloves in an initial assessment, while 10 samples were obtained at follow-up 3 years later. Potential contamination with cyclophosphamide (CP), ifosphamide (IF) and 5-fluorouracil (5-FU) and other cytotoxic medications was examined using the GC-MSMS system (CP, IF) and the HPLC system with UV detection (5-FU) method, respectively. Results Wipe sample contamination was detected at 11.9% and 15% in the initial and follow-up assessment, respectively. Both pairs of gloves assessed were free from contamination. The results showed contamination with cyclophosphamide on the work space inside the isolator, on a day-care office phone and on the central pharmacy bench. Ifosphamide was only detected on the floor of a patient’s room. Contamination with 5-fluorouracil was found only on the surface of a prepared IV infusion bag. The levels of contamination in the positive samples ranged from 0.05 to 10.12 ng/cm2. Conclusions The overall percentage of sample contamination at the Oncology Center was very low compared to other centers around the world. In addition, the detected levels of contamination with cytotoxic drugs were relatively low with the exception of the workspace inside the biological safety cabinet. These results in both assessments may reflect the implementation of comprehensive control measures including employee training, technological equipment and effective cleaning procedures.

49012: Arabidopsis JASMONATE-INDUCED OXYGENASES down-regulate plant immunity by hydroxylation and inactivation of the hormone jasmonic acid
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Posted to bioRxiv 29 Jan 2017

Arabidopsis JASMONATE-INDUCED OXYGENASES down-regulate plant immunity by hydroxylation and inactivation of the hormone jasmonic acid
1 download plant biology

Lotte Caarls, Joyce Elberse, Mo Awwanah, Nora R. Ludwig, Michel de Vries, Tieme Zeilmaker, Saskia C.M. Van Wees, Robert C. Schuurink, Guido Van den Ackerveken

The phytohormone jasmonic acid (JA) is vital in plant defense and development. Although biosynthesis of JA and activation of JA-responsive gene expression by the bioactive form JA-isoleucine (JA-Ile) have been well-studied, knowledge on JA metabolism is incomplete. In particular, the enzyme that hydroxylates JA to 12-OH-JA, an inactive form of JA that accumulates after wounding and pathogen attack, is unknown. Here, we report the identification of four paralogous 2-oxoglutarate/Fe(II)-dependent oxygenases in Arabidopsis thaliana as JA hydroxylases and show that they down-regulate JA-dependent responses. As they are induced by JA we named them JASMONATE-INDUCED OXYGENASEs (JOXs). Concurrent mutation of the four genes in a quadruple Arabidopsis mutant resulted in increased defense gene expression and increased resistance to the necrotrophic fungus Botrytis cinerea and the caterpillar Mamestra brassicae. In addition, root and shoot growth of the plants was inhibited. Metabolite analysis of leaves showed that loss of function of the four JOX enzymes resulted in over-accumulation of JA and in reduced turnover of JA into 12-OH-JA. Transformation of the quadruple mutant with each JOX gene strongly reduced JA levels, demonstrating that all four JOXs inactivate JA in plants. The in vitro catalysis of 12-OH-JA from JA by recombinant enzyme could be confirmed for three JOXs. The identification of the enzymes responsible for hydroxylation of JA reveals a missing step in JA metabolism, which is important for the inactivation of the hormone and subsequent down-regulation of JA-dependent defenses.

49013: Overexpression of the vascular brassinosteroid receptor BRL3 confers drought resistance without penalizing plant growth
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Posted to bioRxiv 09 May 2018

Overexpression of the vascular brassinosteroid receptor BRL3 confers drought resistance without penalizing plant growth
1 download plant biology

Norma Fàbregas, Fidel Lozano-Elena, David Blasco-Escámez, Takayuki Tohge, Cristina Martínez-Andújar, Alfonso Albacete, Sonia Osorio, Mariana Bustamante, José Luis Riechmann, Takahito Nomura, Takao Yokota, Ana Conesa, Francisco Pérez Alfocea, Alisdair R Fernie, Ana I Caño-Delgado

Drought is the primary cause of global agricultural losses and represents a major threat to worldwide food security. Currently, plant biotechnology stands as the most promising strategy to increase crop growth in rain-fed conditions. The main mechanisms underlying drought resistance have been uncovered from the study of plant physiology and by engineering drought resistance genes into crops. However, plants with enhanced drought resistance usually display lower growth, necessitating the search for novel strategies to uncouple drought resistance from growth. Here, we show that the brassinosteroid family of receptors, in addition to promoting growth, guides the phenotypic adaptation responses to a great variety of drought stress traits herein analyzed. Whilst mutations in the ubiquitously localized BRI1 receptor pathway show an enhanced drought resistance at the expense of growth, we found that vascular-localized BRL3 receptors confer drought tolerance without penalizing overall plant growth. Systematic analyses reveal that upon drought stress the vascular BRL3 receptor pathway triggers the synthesis and mobilization of osmoprotectant metabolites, mainly proline and sugars, preferentially in the roots favoring overall plant growth. Altogether, our results uncover a new role for the spatial control of BR signaling in drought tolerance, while offer a novel strategy to address food security issues in an increasingly water limited climate.

49014: Quadriceps and hamstrings coactivation in exercises used in prevention and rehabilitation of hamstring strain injury in young soccer players
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Posted to bioRxiv 11 Mar 2019

Quadriceps and hamstrings coactivation in exercises used in prevention and rehabilitation of hamstring strain injury in young soccer players
1 download scientific communication and education

Gonzalo Torres, David Chorro, Archit Navandar, Javier Rueda, Luís Fernández, Enrique Navarro

This study aimed to study the co-activation of hamstring-quadriceps muscles during submaximal strength exercises without the use of maximum voluntary isometric contraction testing and compare (i) the inter-limb differences in muscle activation, (ii) the intra-muscular group activation pattern, and (iii) the activation during different phases of the exercise. Muscle activation was recorded by surface electromyography of 19 elite male youth players. Participants performed five repetitions of the Bulgarian squat, lunge and the squat with an external load of 10 kg. Electrical activity was recorded for the rectus femoris, vastus medialis, vastus lateralis, biceps femoris and semitendinosus. No significant inter-limb differences were found (F1, 13=619; p=0.82; partial η2=0.045). Significant differences were found in the muscle activation between different muscles within the muscle group (quadriceps and hamstrings) for each of the exercises : Bulgarian squat (F1,18=331: p<0.001; partial η2=0.80), lunge (F4,72=114.5; p<0.001; partial η2=0.86) and squat (F1,16=247.31; p<0.001; partial η2=0.93).Differences were found between the concentric, isometric and eccentric phases of each of the exercises (F2, 26=52.27; p=0.02; partial η2=0.80). The existence of an activation pattern of each of the muscles in the three proposed exercises could be used for muscle assessment and as a tool for injury recovery.

49015: Fast, multicolor 3-D imaging of brain organoids with a new single-objective two-photon virtual light-sheet microscope
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Posted to bioRxiv 03 Nov 2018

Fast, multicolor 3-D imaging of brain organoids with a new single-objective two-photon virtual light-sheet microscope
1 download biophysics

Irina Rakotoson, Brigitte Delhomme, Philippe Djian, Andreas Deeg, Maia Brunstein, Christian Seebacher, Rainer Uhl, Clément Ricard, Martin Oheim

Human inducible pluripotent stem cells (hiPSCs) hold a large potential for disease modeling. hiPSC-derived human astrocyte and neuronal cultures permit investigations of neural signaling pathways with subcellular resolution. Combinatorial cultures, and three-dimensional (3-D) embryonic bodies enlarge the scope of investigations to multi-cellular phenomena. A the highest level of complexity, brain organoids that - in many aspects - recapitulate anatomical and functional features of the developing brain permit the study of developmental and morphological aspects of human disease. An ideal microscope for 3-D tissue imaging at these different scales would combine features from both confocal laser-scanning and light-sheet microscopes: a micrometric optical sectioning capacity and sub-micrometric spatial resolution, a large field of view and high frame rate, and a low degree of invasiveness, i.e., ideally, a better photon efficiency than that of a confocal microscope. In the present work, we describe such an instrument that belongs to the class of two-photon (2P) light-sheet microsocpes. Its particularity is that - unlike existing two- or three-lens designs - it is using a single, low-magnification, high-numerical aperture objective for the generation and scanning of a virtual light sheet. The microscope builds on a modified Nipkow-Petran spinning-disk scheme for achieving wide-field excitation. However, unlike the common Yokogawa design that uses a tandem disk, our concept combines micro lenses, dichroic mirrors and detection pinholes on a single disk. This design, advantageous for 2P excitation circumvents problems arising with the tandem disk from the large wavelength-difference between the infrared excitation light and visible fluorescence. 2P fluorescence excited in by the light sheet is collected by the same objective and imaged onto a fast sCMOS camera. We demonstrate three-dimensional imaging of TO-PRO3-stained embryonic bodies and of brain organoids, under control conditions and after rapid (partial) transparisation with triethanolamine and formamide (RTF) and compare the performance of our instrument to that of a confocal microscope having a similar numerical aperture. 2P-virtual light-sheet microscopy permits one order of magnitude faster imaging, affords less photobleaching and permits better depth penetration than a confocal microscope with similar spatial resolution.

49016: Spatial gene-by-environment mapping for schizophrenia reveals locale of upbringing effects beyond urban-rural differences
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Posted to bioRxiv 11 May 2018

Spatial gene-by-environment mapping for schizophrenia reveals locale of upbringing effects beyond urban-rural differences
1 download epidemiology

Chun Chieh Fan, John J. McGrath, Vivek Appadurai, Alfonso Buil, Michael J. Gandal, Andrew J Schork, Preben Bo Mortensen, Esben Agerbo, Sandy A. Geschwind, Daniel Geschwind, Thomas Werge, Wesley K Thompson, Carsten Bøcker Pedersen

Identification of mechanisms underlying the incidence of psychiatric disorders has been hampered by the difficulty in discovering highly-predictive environmental risk factors. For example, prior efforts have failed to establish environmental effects predicting geospatial clustering of schizophrenia incidence beyond urban-rural differences. Here, we employ a novel statistical framework for decomposing the geospatial risk for schizophrenia based on locale of upbringing (place of residence, ages 0-7 years) and its synergistic effects with genetic liabilities (polygenic risk for schizophrenia). We use this statistical framework to analyze unprecedented geolocation and genotyping data in a case-cohort study of n=24,028 subjects, drawn from the 1.47 million Danish persons born between 1981 and 2005. Using this framework we estimate the effects of upbringing locale (E) and gene-by-locale interactions (GxE). After controlling for potential confounding variables, upbringing at high-risk locales increases the risk for schizophrenia on average by 122%, while GxE modulates genetic risk for schizophrenia on average by 78%. Within the boundaries of Copenhagen (the largest and most densely populated city of Denmark) specific locales vary substantially in their E and GxE effects, with hazard ratios ranging from 0.26 to 9.26 for E and from 0.20 to 5.95 for GxE. This study provides insight into the degree of geospatial clustering of schizophrenia risk, and our novel analytic procedure provides a framework for decomposing variation in geospatial risk into G, E, and GxE components.

49017: Genetic population variation and phylogeny of Sinomenium acutum (Menispermaceae) in subtropical China through chloroplast marker
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Posted to bioRxiv 22 Oct 2018

Genetic population variation and phylogeny of Sinomenium acutum (Menispermaceae) in subtropical China through chloroplast marker
1 download molecular biology

Ying He, Chun Guo, Xiyao Zeng, Hua Yang, Xingyao Xiong, Ping Qiu

Sinomenium acutum (Menispermaceae) is a traditional Chinese medicine. In recent years, extensive harvesting for medicinal purposes has resulted in a sharp decline in its population. Genetic information is crucial for the proper exploitation and conservation of Sinomenium acutum, but little is known about it at present. In this study, we analyzed 77 samples from 4 populations using four non-coding regions (atpI-atpH, trnQ-5’rps16, trnH-psbA, and trnL-trnF) of chloroplast DNA and 14 haplotypes (from C1 to C14) were identified. C1 and C3 were common haplotypes, which were shared by all populations, and C3 was an ancestral haplotype, the rest were rare haplotypes. Obvious phylogeographic structure was not existed inferred by GST / NST test. Mismatch distribution, Tajima’s D and Fu’s FS tests failed to support a rapid demographic expansion in Sinomenium acutum. AMOVA highlighted that the high level of genetic differentiation within population. Low genetic variation among populations illustrated gene flow was not restricted. Genetic diversity analyses demonstrated that the populations of Xuefeng, Dalou, and Daba Mountains were possible refugia localities of Sinomenium acutum. Based on this study, we proposed a preliminary protection strategy for it that C1, C3, C11 and C12 must be collected. These results offer an valuable and useful information for this species of population genetic study as well as further conservation.

49018: Transcranial Alternating Current Stimulation (tACS) Entrains Alpha Oscillations by Preferential Phase Synchronization of Fast-Spiking Cortical Neurons to Stimulation Waveform
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Posted to bioRxiv 28 Feb 2019

Transcranial Alternating Current Stimulation (tACS) Entrains Alpha Oscillations by Preferential Phase Synchronization of Fast-Spiking Cortical Neurons to Stimulation Waveform
1 download neuroscience

Ehsan Negahbani, Iain M. Stitt, Marshall Davey, Thien T. Doan, Moritz Dannhauer, Anna C. Hoover, Angel Peterchev, Susanne Radtke-Schuller, Flavio Frohlich

Modeling studies predict that transcranial alternating current stimulation (tACS) entrains brain oscillations, yet direct examination has been lacking or potentially contaminated by stimulation artefact. Here we first demonstrate how the posterior parietal cortex drives primary visual cortex and thalamic LP in the alpha-band in head-fixed awake ferrets. The spike-field synchrony is maximum within alpha frequency, and more prominent for narrow-spiking neurons than broad-spiking ones. Guided by a validated model of electric field distribution, we produced electric fields comparable to those in humans and primates (< 0.5 mV/mm). We found evidence to support the model-driven predictions of how tACS entrains neural oscillations as explained by the triangular Arnold tongue pattern. In agreement with the stronger spike-field coupling of narrow-spiking cells, tACS more strongly entrained this cell population. Our findings provide the first in vivo evidence of how tACS with electric field amplitudes used in human studies entrains neuronal oscillators.

49019: Assessment of knowledge, attitudes and practices about antibiotic resistance among medical students in India
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Posted to bioRxiv 11 Feb 2019

Assessment of knowledge, attitudes and practices about antibiotic resistance among medical students in India
1 download scientific communication and education

Manoj Kumar Gupta, Chirag Vohra, Pankaja Raghav

Background To reduce the magnitude of antimicrobial resistance, there is a need to change the knowledge and behavior of future prescribers regarding use and prescription of antibiotics. This can be ensured through the appropriate training of next generation doctors and medical students. But, before planning or strengthening any teaching or training program for any group, it is required to have a conclusive evidence about knowledge, attitude and practices of that group. With this background this study was conducted to assess the knowledge, attitudes and the practices of medical students in India with respect to antibiotic resistance and usage Methods It was a cross-sectional study which was done online through google forms. A semi-structured questionnaire containing a five point Likert scale was used for the data collection. The questionnaire was sent to medical students across India by sharing link through contacts of Medical Students Association of India. Respondent-driven sampling technique was also adopted for the study. Data was analyzed using SPSS v.25 and Microsoft Excel 2016. Results The overall mean score of awareness for the students was 4.36 + 0.39. As compared to first year students, mean score of awareness was significantly higher among students of all the years. A significantly better awareness was also observed among pre final year students as compared to other years. Variable practices have been observed regarding use of antibiotics among medical students. Conclusion The awareness level of medical students regarding antibiotics and its resistance was quite satisfactory. As far as attitude and practices are concerned, there is a significant need for improvements.

49020: The Molecular Link Between Auxin And ROS-Mediated Polar Growth
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Posted to bioRxiv 14 Mar 2017

The Molecular Link Between Auxin And ROS-Mediated Polar Growth
1 download plant biology

Silvina Mangano, Silvina Paola Denita-Juarez, Hee-Seung Choi, Eliana Marzol, Youra Hwang, Philippe Ranocha, Silvia Melina Velasquez, Cecilia Borassi, María Laura Barberini, Ariel Alejandro Aptekmann, Jorge Prometeo Muschietti, Alejandro Daniel Nadra, Christophe Dunand, Hyung-Taeg Cho, José Manuel Estevez

Root hair polar growth is endogenously controlled by auxin and sustained by oscillating levels of reactive oxygen species (ROS). These cells extend several hundred-fold their original size toward signals important for plant survival. Although their final cell size is of fundamental importance, the molecular mechanisms that control it remain largely unknown. Here, we show that ROS production is controlled by the transcription factors RSL4, which in turn is transcriptionally regulated by auxin through several Auxin Responsive Factors (ARFs). In this manner, auxin controls ROS-mediated polar growth by activating RSL4, which then upregulates the expression of genes encoding NADPH oxidases (also known as RBOHs, RESPIRATORY BURST OXIDASE HOMOLOG proteins) and Class-III Peroxidases (PER), which catalyse ROS production. Chemical or genetic interference with the ROS balance or peroxidase activity affect root hair final cell size. Overall, our findings establish a molecular link between auxin regulated ARFs-RSL4 and ROS-mediated polar root hair growth.

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