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Rxivist combines biology preprints from bioRxiv and medRxiv with data from Twitter to help you find the papers being discussed in your field. Currently indexing 140,607 papers from 597,880 authors.

Most downloaded biology preprints, since beginning of last month

135,599 results found. For more information, click each entry to expand.

127421: A-to-I RNA editing uncovers hidden signals of adaptive genome evolution in animals
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Posted 04 Dec 2017

A-to-I RNA editing uncovers hidden signals of adaptive genome evolution in animals
2 downloads bioRxiv evolutionary biology

Niko Popitsch, Christian D Huber, Ilana Buchumenski, Eli Eisenberg, Michael Jantsch, Arndt von Haeseler, Miguel Gallach

In animals, the most common type of RNA editing is the deamination of adenosines (A) into inosines (I). Because inosines base-pair with cytosines (C), they are interpreted as guanosines (G) by the cellular machinery and genomically encoded G alleles at edited sites mimic the function of edited RNAs. The contribution of this hardwiring effect on genome evolution remains obscure. We looked for population genomics signatures of adaptive evolution associated with A-to-I RNA edited sites in humans and Drosophila melanogaster. We found that single nucleotide polymorphisms at edited sites occur 3 (humans) to 15 times (Drosophila) more often than at unedited sites, the nucleotide G is virtually the unique alternative allele at edited sites and G alleles segregate at higher frequency at edited sites than at unedited sites. Our study reveals that coding synonymous and nonsynonymous as well as silent and intergenic A-to-I RNA editing sites are likely adaptive in the distantly related human and Drosophila lineages.

127422: Complete genome sequence of Bacillus velezensis JT3-1, a microbial germicide isolated from yak feces
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Posted 19 Feb 2019

Complete genome sequence of Bacillus velezensis JT3-1, a microbial germicide isolated from yak feces
2 downloads bioRxiv genomics

Youquan Li, Xuan Li, Dan Jia, Junlong Liu, Jinming Wang, Aihong Liu, Zhijie Liu, Guiquan Guan, Guangyuan Liu, Jianxun Luo, Hong Yin

Bacillus velezensis JT3-1 is a probiotic strain isolated from feces of the domestic yak (Bos grunniens) in the Gansu province of China. It has strong antagonistic activity against Listeria monocytogenes, Staphylococcus aureus, Escherichia coli, Salmonella Typhimurium, Mannheimia haemolytica, Staphylococcus hominis, Clostridium perfringens, and Mycoplasma bovis. These properties have made the JT3-1 strain the focus of commercial interest. In this study, we describe the complete genome sequence of JT3-1, with a genome size of 3,929,799 bp, 3761 encoded genes and an average GC content of 46.50%. Whole genome sequencing of Bacillus velezensis JT3-1 will lay a good foundation for elucidation of the mechanisms of its antimicrobial activity, and for its future application.

127423: XPO1 gene therapy restores cardiac function in rats with chronic induced myocardial infarction
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Posted 12 Mar 2019

XPO1 gene therapy restores cardiac function in rats with chronic induced myocardial infarction
2 downloads bioRxiv molecular biology

María García-Manzanares, Carolina Gil-Cayuela, Luis Martínez-Dolz, José Ramón González-Juanatey, Francisca Lago, Manuel Portolés, Esther Roselló-Lletí, Miguel Rivera

Background: In previous studies, we showed that several nuclear-cytoplasmic transport molecules were closely related to ventricular dysfunction in human heart failure. Particularly, the transcriptomic signature of XPO1 was highly expressed and inversely related to left ventricular function in heart failure patients of ischemic etiology. Therefore, we hypothesized that in a rat model of myocardial infarction treated with AAV9-shXPO1, an improvement in the ventricular function after a follow-up period may be observed. Methods: We induced myocardial infarction by coronary ligation in Sprague-Dawley rats (n=10), five of them received AAV9-shXPO1 treatment after four months and the other five infarcted rats did not receive any treatment. For non-failing controls, healthy Sham rats (n=5) received the placebo AAV9-scramble. Serial echocardiographic assessment was performed before, as well as, two and five months after intravenous injection. Results: AAV9-shXPO1-treated rats showed improved fractional shortening (16.8 +/- 2.8 vs 24.6 +/- 4.1%, P<0.05) and LV systolic (5.10 +/- 0.79 vs 3.52 +/- 0.88mm, P<0.05) and diastolic (6.17 +/- 0.95 vs 4.70 +/- 0.93mm, P<0.05) diameters when comparing measurements obtained before and five months after AAV9 injection. We did not observe this improvement in untreated infarcted rats. Furthermore, EXP-1 levels in rats heart, brain, skeletal muscle, and liver were determined by western-blot and compared to controls in AAV9-shXPO1-treated rats. Lower levels of EXP-1 in cardiac tissue were observed (P<0.05). Discussion: At five months follow-up, ischemic AAV9-shXPO1-treated rats showed partial recovery of LV myocardial function. No secondary symptoms attributable to AAV9-shXPO1 were observed in skeletal muscle, liver and brain.

127424: Differences in the temporal processing between identification and categorization of durations: a behavioral and ERP study
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Posted 07 May 2018

Differences in the temporal processing between identification and categorization of durations: a behavioral and ERP study
2 downloads bioRxiv neuroscience

Dorian Bannier, J. Wearden, Christophe C. Le Dantec, Mohamed Rebaï

This study examined how different forms of decision-making modulate time perception. Participants performed temporal bisection and generalization tasks, requiring them to either categorize a stimulus duration as more similar to short or long standards (bisection), or identify whether or not a duration was the same as a previously presented standard (generalization). They responded faster in the bisection task than in the generalization one for long durations. This behavioral effect was accompanied by modulation of event-related potentials (ERPs). More specifically, between 500 ms and 600 ms after stimulus offset, a late positive component (LPC), appearing in the centro-parietal region, showed lower amplitude in the bisection task than in the generalization one, for long durations, mirroring the behavioral result. Before (200-500 ms) and after (600-800 ms) this window, the amplitude of the LPC was globally larger in the generalization paradigm, independently of the presented duration. Finally, the latency of the LPC peak was earlier for long durations than for the short ones, indicating that the decision about the former stimuli was made earlier than for the latter ones. Taken together, these results indicate that the categorization of durations engages fewer cognitive resources than their identification.

127425: A First-principles Approach to Large-scale Nuclear Architecture
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Posted 07 May 2018

A First-principles Approach to Large-scale Nuclear Architecture
2 downloads bioRxiv biophysics

Ankit Agrawal, Nirmalendu Ganai, Surajit Sengupta, Gautam I. Menon

Model approaches to nuclear architecture have traditionally ignored the biophysical consequences of ATP-fueled active processes acting on chromatin. However, transcription-coupled activity is a source of stochastic forces that are substantially larger than the Brownian forces present at physiological temperatures. Here, we describe a first-principles approach to large-scale nuclear architecture in metazoans that incorporates cell-type-specific active processes. The model predicts the statistics of positional distributions, shapes and overlaps of each chromosome. Our simulations reproduce common organising principles underlying large-scale nuclear architecture across human cell nuclei in interphase. These include the differential positioning of euchromatin and heterochromatin, the territorial organisation of chromosomes including both gene-density-based and size-based chromosome radial positioning schemes, the non-random locations of chromosome territories and the shape statistics of individual chromosomes. We propose that the biophysical consequences of the distribution of transcriptional activity across chromosomes should be central to any chromosome positioning code.

127426: Unravelling intra- and intersegmental neuronal connectivity between central pattern generating networks in a multi-legged locomotor system
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Posted 25 Oct 2018

Unravelling intra- and intersegmental neuronal connectivity between central pattern generating networks in a multi-legged locomotor system
2 downloads bioRxiv neuroscience

Silvia Daun, Charalampos Mantziaris, Tibor I. Tóth, Ansgar Büschges, Nils Rosjat

Animal walking results from a complex interplay of central pattern generating networks (CPGs), local sensory signals expressing position, velocity and forces generated in the legs, and coordinating signals between neighboring ones. In the stick insect intra- and intersegmental coordination is conveyed by these sensory signals. The CPGs control the activity of motoneuron pools and are thereby responsible for the generation of rhythmic leg movements. The rhythmic activity of the CPGs can be modified by the aforementioned sensory signals. However, the precise nature of the interaction between the CPGs and these sensory signals has remained largely unknown. Experimental methods aiming at finding out details of these interactions often apply the muscarinic acetylcholine receptor agonist, pilocarpine in order to induce rhythmic activity in the CPGs. Using this general approach, we removed the influence of sensory signals and investigated the putative connections between CPGs associated with the coxa-trochanter (CTr)-joint in the different segments (legs) in more detail. The experimental data underwent connectivity analysis using Dynamic Causal Modelling (DCM). This method can uncover the underlying coupling structure and strength between pairs of segmental ganglia (CPGs). For the analysis we set up different coupling schemes (models) for DCM and compared them using Bayesian Model Selection (BMS). Models with contralateral connections in each segment and ipsilateral connections on both sides, as well as the coupling from the meta-to the ipsilateral prothoracic ganglion were preferred by BMS to all other types of models tested. Moreover, the intrasegmental coupling strength in the mesothoracic ganglion was the strongest and most stable in all three ganglia.

127427: Towards accurate high-throughput ligand affinity prediction by exploiting structural ensembles, docking metrics and ligand similarity
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Posted 12 Mar 2019

Towards accurate high-throughput ligand affinity prediction by exploiting structural ensembles, docking metrics and ligand similarity
2 downloads bioRxiv bioinformatics

Melanie Schneider, Jean-Luc Pons, William Bourguet, Gilles Labesse

Motivation: Nowadays, virtual screening (VS) plays a major role in the process of drug development. Nonetheless, an accurate estimation of binding affinities, which is crucial at all stages, is not trivial and may require target-specific fine-tuning. Furthermore, drug design also requires improved predictions for putative secondary targets among which is Estrogen Receptor alpha (ERα). Results: VS based on combinations of Structure-Based VS (SBVS) and Ligand-Based VS (LBVS) is gaining momentum to help characterizing secondary targets of xenobiotics (including drugs and pollutants). In this study, we propose an integrated approach using ligand docking based on multiple structural ensembles to reflect the conformational flexibility of the receptor. Then, we investigate the impact of the two different types of features (structure-based docking descriptors and ligand-based molecular descriptors) for affinity predictions based on a random forest algorithm. We find that ligand-based features have limited predictive power (rP=0.69, R2=0.47), compared to structure-based features (rP=0.78, R2=0.60) while their combination maintains the overall accuracy (rP=0.77, R2=0.56). Extending the training dataset to include xenobiotics, leads to a novel high-throughput affinity prediction method for ERα ligands (rP=0.85, R2=0.71). Method's robustness is tested on several ligand databases and performances are compared with existing rescoring procedures. The presented prediction tool is provided to the community as a dedicated satellite of the @TOME server.

127428: Performance in a novel environment subject to ghost competition
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Posted 09 Jan 2019

Performance in a novel environment subject to ghost competition
2 downloads bioRxiv evolutionary biology

Karen Bisschop, Frederik Mortier, Dries Bonte, Rampal S. Etienne

Background A central tenet of the evolutionary theory of communities is that competition impacts evolutionary processes such as local adaptation. Species in a community exert a selection pressure on other species and may drive them to extinction. We know, however, very little about the influence of unsuccessful or ghost species on the evolutionary dynamics within the community. Methods Here, we studied the long-term influence of a ghost competitor on the performance of a more successful species using experimental evolution. We transferred the spider mite Tetranychus urticae onto a novel host plant under initial presence or absence of a competing species, the congeneric mite T. ludeni . Results The latter species unintentionally went extinct soon after the start of the experiment, but we nevertheless completed the experiment and found that the initial density of this ghost competitor positively affected the performance (i.e. fecundity) of the more successful species. This effect on T. urticae even lasted for at least 25 generations. Discussion Our study supports the hypothesis that early experienced selection pressures can exert a persistent evolutionary signal on species’ performance in novel environments.

127429: Using Structural Equation Modeling to Jointly Estimate Maternal and Foetal Effects on Birthweight in the UK Biobank
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Posted 06 Jul 2017

Using Structural Equation Modeling to Jointly Estimate Maternal and Foetal Effects on Birthweight in the UK Biobank
2 downloads bioRxiv genetics

Nicole M. Warrington, Rachel Freathy, Michael C. Neale, David M Evans

Background: To date, 60 genetic variants have been robustly associated with birthweight. It is unclear whether these associations represent the effect of an individual's own genotype on their birthweight, their mother's genotype, or both. Methods: We demonstrate how structural equation modelling (SEM) can be used to estimate both maternal and foetal effects when phenotype information is present for individuals in two generations and genotype information is available on the older individual. We conduct an extensive simulation study to assess the bias, power and type 1 error rates of the SEM and also apply the SEM to birthweight data in the UK Biobank study. Results: Unlike simple regression models, our approach is unbiased when there is both a maternal and foetal effect. The method can be used when either the individual's own phenotype or the phenotype of their offspring is not available, and allows the inclusion of summary statistics from additional cohorts where raw data cannot be shared. We show that the type 1 error rate of the method is appropriate, there is substantial statistical power to detect a genetic variant that has a moderate effect on the phenotype, and reasonable power to detect whether it is a foetal and/or maternal effect. We also identify a subset of birth weight associated SNPs that have opposing maternal and foetal effects in the UK Biobank. Conclusions: Our results show that SEM can be used to estimate parameters that would be difficult to quantify using simple statistical methods alone.

127430: Voltage-gating of mechanosensitive PIEZO channels
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Posted 27 Jun 2017

Voltage-gating of mechanosensitive PIEZO channels
2 downloads bioRxiv neuroscience

Mirko Moroni, Martha Rocio Servin-Vences, Raluca Fleischer, Gary R. Lewin

Mechanosensitive PIEZO ion channels are evolutionarily conserved proteins whose presence is critical for normal physiology in multicellular organisms. Here we show that, in addition to mechanical stimuli, PIEZO channels are also powerfully modulated by voltage and can even switch to a purely voltage gated mode. Mutations that cause human diseases such as Xerocytosis profoundly shift voltage sensitivity of PIEZO1 channels towards the resting membrane potential and strongly promote pure voltage gating. Our data may be explained by the presence of an inactivation gate in the pore, the opening of which is promoted by outward permeation. Invertebrate (fly) and vertebrate (fish) PIEZO proteins are also voltage sensitive but voltage gating is a much more prominent feature of these older channels. We propose that the voltage sensitivity of PIEZO channels is a deep property co-opted to add a regulatory mechanism for PIEZO activation in widely different cellular contexts.

127431: A Stu2-mediated intrinsic tension-sensing pathway promotes chromosome biorientation in vivo
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Posted 25 Oct 2018

A Stu2-mediated intrinsic tension-sensing pathway promotes chromosome biorientation in vivo
2 downloads bioRxiv cell biology

Matthew P Miller, Rena K. Evans, Alex Zelter, Elisabeth A Geyer, Michael J. MacCoss, Luke Rice, Trisha N. Davis, Charles L Asbury, Sue Biggins

Accurate segregation of chromosomes to daughter cells is a critical aspect of cell division. It requires the kinetochores on duplicated chromosomes to biorient, attaching to microtubules from opposite poles of the cell. Bioriented attachments come under tension, while incorrect attachments lack tension and must be destabilized. A well-studied error correction pathway is mediated by the Aurora B kinase, which destabilizes low tension-bearing attachments. We recently discovered that in vitro, kinetochores display an additional intrinsic tension-sensing pathway that utilizes Stu2. This pathway's contribution to error correction in cells, however, was unknown. Here, we identify a Stu2 mutant that abolishes its kinetochore function and show that it causes error correction defects in vivo. We also show that this intrinsic tension-sensing pathway functions in concert with the Aurora B-mediated pathway. Together, our work indicates that cells employ at least two pathways to ensure biorientation and the accuracy of chromosome segregation.

127432: High Frequency Haplotypes are Expected Events, not Historical Figures
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Posted 07 Jul 2015

High Frequency Haplotypes are Expected Events, not Historical Figures
2 downloads bioRxiv genetics

Elsa G. Guillot, Murray P. Cox

Cultural transmission of reproductive success states that successful men have more children and pass this raised fecundity to their offspring. Balaresque and colleagues found high frequency haplotypes in a Central Asian Y chromosome dataset, which they attribute to cultural transmission of reproductive success by prominent historical men, including Genghis Khan. Using coalescent simulation, we show that these high frequency haplotypes are consistent with a neutral model, where they commonly appear simply by chance. Hence, explanations invoking cultural transmission of reproductive success are statistically unnecessary.

127433: The impact of host metapopulation structure on the population genetics of colonizing bacteria
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Posted 25 Sep 2015

The impact of host metapopulation structure on the population genetics of colonizing bacteria
2 downloads bioRxiv genetics

Elina Numminen, Michael Gutmann, Mikhail Shubin, Pekka Marttinen, Guillaume Méric, Willem van Schaik, Teresa M Coque, Fernando Baquero, Rob J.L. Willems, Samuel K Sheppard, Edward J. Feil, William P. Hanage, Jukka Corander

Many key bacterial pathogens are frequently carried asymptomatically, and the emergence and spread of these opportunistic pathogens can be driven, or mitigated, via demographic changes within the host population. These inter-host transmission dynamics combine with basic evolutionary parameters such as rates of mutation and recombination, population size and selection, to shape the genetic diversity within bacterial populations. Whilst many studies have focused on how molecular processes underpin bacterial population structure, the impact of host migration and the connectivity of the local populations has received far less attention. A stochastic neutral model incorporating heightened local transmission has been previously shown to fit closely with genetic data for several bacterial species. However, this model did not incorporate transmission limiting population stratification, nor the possibility of migration of strains between subpopulations, which we address here by presenting an extended model. The model captures the observed population patterns for the common nosocomial pathogens Staphylococcus epidermidis and Enterococcus faecalis, while Staphylococcus aureus and Enterococcus faecium display deviations attributable to adaptation. It is demonstrated analytically and numerically that expected strain relatedness may either increase or decrease as a function of increasing migration rate between subpopulations, being a complex function of the rate at which microepidemics occur in the metapopulation. Moreover, it is shown that in a structured population markedly different rates of evolution may lead to indistinguishable patterns of relatedness among bacterial strains; caution is thus required when drawing evolution inference in these cases.

127434: CX3CL1 and CX3CR1 Expressing Tendon Cells – A novel Immune Cell Population in the Tendon Core
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Posted 04 Jul 2019

CX3CL1 and CX3CR1 Expressing Tendon Cells – A novel Immune Cell Population in the Tendon Core
2 downloads bioRxiv cell biology

Christine Lehner, Gabriel Spitzer, Renate Gehwolf, Andrea Wagner, Nadja Weissenbacher, Christian Deininger, Katja Emmanuel, Florian Wichlas, Herbert Tempfer, Andreas Traweger

Tendon disorders frequently occur and recent evidence has clearly implicated the presence of immune cells and inflammatory events during early tendinopathy. However, the origin and properties of these cells remain poorly defined. Therefore, the aim of this study was to determine the presence of myleoid cells in healthy rodent and human tendon tissue and to characterize them. Using various transgenic reporter mouse models, we demonstrate the presence of tendon cells in the dense matrix of the tendon core expressing the fractalkine (Fkn) receptor CX3CR1 and its cognate ligand CX3CL1/Fkn. Pro-inflammatory stimulation of 3D tendon-like constructs in vitro resulted in a significant increase in the expression of IL-1beta, IL-6, Mmp3, Mmp9, Cx3cl1, and epiregulin which has been reported to contribute to inflammation, wound healing, and tissue repair. Furthermore, we demonstrate that inhibition of the fractalkine receptor blocked tendon cell migration in vitro and show the presence of CX3CR1/CX3CL1/EREG expressing cells in healthy human tendons. Taken together, we demonstrate the presence of CX3CL1+/CX3CR1+ 'tenophages' within the healthy tendon proper potentially fulfilling surveillance functions in tendons.

127435: Somatic nicotinic acetylcholine receptors control the activity of dopamine neurons and reward-related behaviors.
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Posted 15 Feb 2018

Somatic nicotinic acetylcholine receptors control the activity of dopamine neurons and reward-related behaviors.
2 downloads bioRxiv neuroscience

Romain Durand-de Cuttoli, Sarah Mondoloni, Fabio Marti, Damien Lemoine, Jeremie Naude, Thibaut d’Izarny-Gargas, Stéphanie Pons, Uwe Maskos, Dirk Trauner, Richard H Kramer, Philippe Faure, Alexandre Mourot

Dopamine (DA) neurons of the ventral tegmental area (VTA) integrate cholinergic inputs to regulate key functions such as motivation and goal-directed behaviors. Yet the temporal dynamic range and mechanism of action of acetylcholine (ACh) on the modulation of VTA circuits and reward-related behaviors are not known. Here we used a chemical-genetic approach for rapid and precise optical manipulation of nicotinic neurotransmission in VTA neurons in vivo. We provide direct evidence that the ACh tone fine-tunes the firing properties of VTA DA neurons through somatic β2-containing (β2*) nicotinic ACh receptors (nAChRs). Furthermore, locally photo-antagonizing these receptors in the VTA was sufficient to reversibly switch nicotine reinforcement on and off. By enabling control of nicotinic transmission in targeted brain circuits, this technology will help unravel the various physiological functions of nAChRs and may assist in the design of novel therapies relevant to neuropsychiatric disorders.

127436: Biochemical reconstitution of branching microtubule nucleation
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Posted 11 Jul 2019

Biochemical reconstitution of branching microtubule nucleation
2 downloads bioRxiv cell biology

Raymundo Alfaro-Aco, Akanksha Thawani, Sabine Petry

Microtubules are nucleated from specific locations at precise times in the cell cycle. However, the factors that constitute these microtubule nucleation pathways still need to be identified along with their mode of action. Here, using purified Xenopus laevis proteins we biochemically reconstitute branching microtubule nucleation, a nucleation pathway where microtubules originate from pre-existing microtubules, which is essential for spindle assembly and chromosome segregation. We found that besides the microtubule nucleator gamma-tubulin ring complex (g-TuRC), the two branching effectors augmin and TPX2 are required to efficiently nucleate branched microtubules. Specifically, TPX2 generates regularly-spaced patches that recruit augmin and g-TuRC to microtubules, which then nucleate new microtubules at preferred branching angles of less than 90 degrees. Our work demonstrates how g-TuRC is brought to its nucleation site for branching microtubule nucleation. It provides a blueprint for other microtubule nucleation pathways and for generating a particular microtubule architecture by regulating microtubule nucleation.

127437: Lack of evidence for cross-frequency phase-phase coupling between theta and gamma oscillations in the hippocampus
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Posted 28 Mar 2016

Lack of evidence for cross-frequency phase-phase coupling between theta and gamma oscillations in the hippocampus
2 downloads bioRxiv neuroscience

Robson Scheffer-Teixeira, Adriano BL Tort

Phase-amplitude coupling between theta and multiple gamma sub-bands hallmarks hippocampal activity and is believed to take part in information routing. More recently, theta and gamma oscillations were also reported to exhibit reliable phase-phase coupling, or n:m phase-locking. The existence of n:m phase-locking suggests an important mechanism of neuronal coding that has long received theoretical support. However, here we show that n:m phase-locking (1) is much lower than previously reported, (2) highly depends on epoch length, (3) does not statistically differ from chance (when employing proper surrogate methods), and that (4) filtered white noise has similar n:m scores as actual data. Moreover, (5) the diagonal stripes in theta-gamma phase-phase histograms of actual data can be explained by theta harmonics. These results point to lack of theta-gamma phase-phase coupling in the hippocampus, and suggest that studies investigating n:m phase-locking should rely on appropriate statistical controls, otherwise they could easily fall into analysis pitfalls.

127438: Effects of the Salinity under Soilless Culture Systems on Gamma Linolenic Acid Levels in Borage Seed Oil
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Posted 26 Oct 2018

Effects of the Salinity under Soilless Culture Systems on Gamma Linolenic Acid Levels in Borage Seed Oil
2 downloads bioRxiv plant biology

Miguel Urrestarazu, Victor Manuel Gallegos-Cedillo, Francisca Ferrón-Carrillo, José Luis Guil-Guerrero, Teresa Lao, Juan Eugenio Álvaro

Borage is a well-known plant of great importance in human nutrition and health. Expanding knowledge of particular plants that have anti-cancer products is a global concern. There is substantial information regarding the benefits, presence and extraction of gamma linolenic acid (GLA) in different plants around the world, especially in borage seeds. However, there is little information concerning the effects of the salinity of the nutrient solution on the growth and presence of GLA in borage seeds. The objective of this work was to determine the optimal salinity of the nutrient solution for obtaining GLA in soilless cultivation systems. Borage plants were grown in coconut fibre and provided three treatments of nutrient solution of 2.20, 3.35 and 4.50 dS m-1, increasing solution salinity with the standard nutrient solution of concentrated macronutrients as a reference. Vegetative growth, seed production and GLA ratio were measured. The results of vegetative development and GLA production doubled and tripled with the increase in salinity of the nutrient solution, respectively.

127439: Population imaging at subcellular resolution supports specific and local inhibition by granule cells in the olfactory bulb
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Posted 29 Mar 2016

Population imaging at subcellular resolution supports specific and local inhibition by granule cells in the olfactory bulb
2 downloads bioRxiv neuroscience

Martin Wienisch, Venkatesh N Murthy

Information processing in early sensory regions is modulated by a diverse range of inhibitory interneurons. We sought to elucidate the role of olfactory bulb interneurons called granule cells (GCs) in odor processing by imaging the activity of hundreds of these cells simultaneously in mice. Odor responses in GCs were temporally diverse and spatially disperse, with some degree of non-random, modular organization. The overall sparseness of activation of GCs was highly correlated with the extent of glomerular activation by odor stimuli. Increasing concentrations of single odorants led to proportionately larger population activity, but some individual GCs had non-monotonic relation to concentration due to local inhibitory interactions. Individual dendritic segments could sometimes respond independently to odors, revealing their capacity for compartmentalized signaling in vivo. Collectively, the response properties of GCs point to their role in specific and local processing, rather than global operations such as response normalization proposed for other interneurons.

127440: Heterozygous RFX6 protein truncating variants cause Maturity-Onset Diabetes of the Young (MODY) with reduced penetrance
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Posted 22 Jan 2017

Heterozygous RFX6 protein truncating variants cause Maturity-Onset Diabetes of the Young (MODY) with reduced penetrance
2 downloads bioRxiv genetics

Kashyap A. Patel, Jarno Kettunen, Markku Laakso, Alena Stančáková, Thomas W Laver, Kevin Colclough, Matthew B Johnson, Marc Abramowicz, Leif Groop, Päivi J. Miettinen, Maggie H. Shepherd, Sarah E Flanagan, Sian Ellard, Nobuya Inagaki, Andrew T Hattersley, Tiinamaija Tuomi, Miriam Cnop, Michael N Weedon

Finding new genetic causes of monogenic diabetes can help to understand development and function of the human pancreas. We aimed to find novel protein-truncating variants causing Maturity-Onset Diabetes of the Young (MODY), a subtype of monogenic diabetes. We used a combination of next-generation sequencing of MODY cases with unknown aetiology along with comparisons to the ExAC database to identify new MODY genes. In the discovery cohort of 36 European patients, we identified two probands with novel RFX6 heterozygous nonsense variants. RFX6 protein truncating variants were enriched in the MODY discovery cohort compared to the European control population within ExAC (odds ratio, OR=131, P=1x10-4). We found similar results in non-Finnish European (n=348, OR=43, P=5x10-5) and Finnish (n=80, OR=22, P=1x10-6) replication cohorts. The overall meta-analysis OR was 34 (P=1x10-16). RFX6 heterozygotes had reduced penetrance of diabetes compared to common HNF1A and HNF4A-MODY mutations (27%, 70% and 55% at 25 years of age, respectively). The hyperglycaemia resulted from beta-cell dysfunction and was associated with lower fasting and stimulated gastric inhibitory polypeptide (GIP) levels. Our study demonstrates that heterozygous RFX6 protein truncating variants are associated with MODY with reduced penetrance.

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