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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 57,648 bioRxiv papers from 265,372 authors.

Most downloaded bioRxiv papers, since beginning of last month

56,291 results found. For more information, click each entry to expand.

55301: Sexual transmission causes a marked increase in the incidence of Zika in women in Rio de Janeiro, Brazil.
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Posted to bioRxiv 26 May 2016

Sexual transmission causes a marked increase in the incidence of Zika in women in Rio de Janeiro, Brazil.
6 downloads epidemiology

Flávio Codeço Coelho, Betina Durovni, Valeria Saraceni, Cristina Lemos, Claudia Torres Codeço, Sabrina Camargo, Luiz Max de Carvalho, Leonardo Bastos, Denise Arduini, Daniel A.M. Villela, Margaret Armstrong

The recent emergence of Zika in Brazil and its association with increased congenital malformation rates has raised concerns over its impact on the birth rates in the country. Using data on the incidence of Zika in 2015-2016 and dengue in 2013 and 2015-16 for the city of Rio de Janeiro (pop: 6.4 million), we document a massive increase of Zika in women compared to men. Even after correcting for the bias due to the systematic testing of pregnant women for Zika, there are 90% more registered cases per 100,000 women in the sexually active age group (15-65 years) than for men but not before 15 or after 65. Assuming that infected men transmit the disease to women in their semen but that the converse is not true, some extra incidence in women is to be expected. An alternate hypothesis would be that women visit doctors more often than men. To test this, we compared the incidence of dengue fever in men and women in 2015 and in 2013 (before Zika reached Rio de Janeiro): in both years, women are 30% more likely to be reported with dengue. Summing up, women in the sexually active age bracket are far more likely to get Zika than men (+90% increase); sexual transmission is the most probable cause. Women in the 15-65 age group are also 30% more likely to be reported with dengue than men, which is probably due to women being more careful with their health.

55302: A Computational Framework To Assess Genome-Wide Distribution Of Polymorphic Human Endogenous Retrovirus-K In Human Populations
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Posted to bioRxiv 15 Oct 2018

A Computational Framework To Assess Genome-Wide Distribution Of Polymorphic Human Endogenous Retrovirus-K In Human Populations
6 downloads genomics

Lin Lin

Human Endogenous Retrovirus type K (HERV-K) is the only HERV known to be insertionally polymorphic. It is possible that HERV-Ks contribute to human disease because people differ in both number and genomic location of these retroviruses. Indeed viral transcripts, proteins, and antibody against HERV-K are detected in cancers, auto-immune, and neurodegenerative diseases. However, attempts to link a polymorphic HERV-K with any disease have been frustrated in part because population frequency of HERV-K provirus at each site is lacking and it is challenging to identify closely related elements such as HERV-K from short read sequence data. We present an integrated and computationally robust approach that uses whole genome short read data to determine the occupation status at all sites reported to contain a HERV-K provirus. Our method estimates the proportion of fixed length genomic sequence (k-mers) from whole genome sequence data matching a reference set of k-mers unique to each HERV-K loci and applies mixture model-based clustering to account for low depth sequence data. Our analysis of 1000 Genomes Project Data (KGP) reveals numerous differences among the five KGP super-populations in the frequency of individual and co-occurring HERV-K proviruses; we provide a visualization tool to easily depict the prevalence of any combination of HERV-K among KGP populations. Further, the genome burden of polymorphic HERV-K is variable in humans, with East Asian (EAS) individuals having the fewest integration sites. Our study identifies population-specific sequence variation for several HERV-K proviruses. We expect these resources will advance research on HERV-K contributions to human diseases.

55303: Impact of Direct Acting Antivirals on Survival in Patients with Chronic Hepatitis C and Hepatocellular Carcinoma
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Posted to bioRxiv 12 Mar 2019

Impact of Direct Acting Antivirals on Survival in Patients with Chronic Hepatitis C and Hepatocellular Carcinoma
6 downloads immunology

William M Kamp, Cortlandt M Sellers, Stacey M Stein, Joseph K Lim, Hyun S. Kim

Background: To investigate the impact of direct-acting antivirals (DAA) and 12-week sustained viral response (SVR12) in patients with hepatocellular carcinoma (HCC) and chronic hepatitis C virus (HCV) infection. Methods: Retrospective analysis of HCC patients diagnosed from 2005 to 2016 at an urban tertiary-care hospital. Kaplan-Meier curves and multivariable Cox proportional hazards models were used to assess survival. Results: 969 patients met inclusion criteria. 478 patients received interventional oncology treatment (catheter-based therapies, ablation or combination locoregional therapies), 141 received supportive care (palliative or no treatment), 125 underwent liver transplantation, 112 had tumor resection and 94 received chemotherapy or radiation as their primary treatment. Median overall survival of the cohort was 24.2 months (95% CI: 20.9-27.9). 470 patients had HCV (56%). 123 patients received DAA therapies for HCV (26.2%), 83 of whom achieved SVR12 (68%). HCV-positive and HCV-negative patients had similar survival (20.7 months vs 17.4 months, p=0.22). Patients receiving DAA therapy had an overall survival of 71.8 months (CI: 39.5-not reached) vs 11.6 months (CI: 9.8-14.5) for patients without DAA therapy (p<0.0001). DAA patients who achieved SVR12 had an overall survival of 75.6 months (CI: 49.2-not reached) vs the non-SVR12 group (26.7 months, CI: 13.7-31.1, p<0.0001). Multivariable analysis revealed AJCC, Child-Pugh Score, MELD, tumor size, tumor location and treatment type had independent influence on survival (p<0.05). In HCV-positive patients, AJCC, MELD, tumor location, treatment allocation and DAA were significant (p<0.05). In patients receiving DAA therapy, only MELD and SVR12 were predictive of overall survival (p<0.05). Conclusions: DAA therapy and achieving SVR12 is associated with increased overall survival in HCV patients with HCC.

55304: Waving goodbye to contrast: Self-generated hand movements attenuate visual sensitivity
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Posted to bioRxiv 21 Nov 2018

Waving goodbye to contrast: Self-generated hand movements attenuate visual sensitivity
6 downloads neuroscience

Madis Vasser, Laurène Vuillaume, Axel Cleeremans, Jaan Aru

It is well known that the human brain continuously predicts the sensory consequences of its own body movements, which typically results in sensory attenuation. Yet, the extent and exact mechanisms underlying sensory attenuation are still debated. To explore this issue, we asked participants to decide which of two visual stimuli was of higher contrast in a virtual reality situation where one of the stimuli could appear behind the participants' invisible moving hand or not. Over two experiments, we measured the effects of such "virtual occlusion" on first-order sensitivity and on metacognitive monitoring. Our findings show that self-generated hand movements reduced the apparent contrast of the stimulus. This result can be explained by the active inference theory. Moreover, sensory attenuation seemed to affect only first-order sensitivity and not (second-order) metacognitive judgments of confidence.

55305: Genetic distance between complex repeats
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Posted to bioRxiv 26 Oct 2018

Genetic distance between complex repeats
6 downloads bioinformatics

Luca Ferretti, Aurora Ruiz-Herrera, Alice Ledda

Complex nucleotide or amino acid repeats with long units play an important role in proteins. The evolutionary analysis of these variants is challenging due to genetic diversity within repeat units as well as variability in the arrangement of different units along the repeat sequence. Here we present a new approach for the computation of genetic distances between complex repeats. This method takes into account evolutionary processes including point mutations, insertions and deletions of repeat units, as well as duplication of single units. We provide an algorithm for the computation of these distances along with the corresponding global pairwise alignment of repeats. As an example, we apply our approach to the evolution of repeat units in the highly polymorphic zinc-finger repeat domain of the PRDM9 protein across wild populations of house mice. This approach opens the way for new insights into the evolutionary history of polymorphic repeats.

55306: Glucosinolates promote initial population establishment of feral oilseed rape
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Posted to bioRxiv 27 Sep 2018

Glucosinolates promote initial population establishment of feral oilseed rape
6 downloads ecology

Elze Hesse, Dave Hodgson, Tom de Jong

Crops are often selected for traits that confer a selective disadvantage in the wild. A key trait that has been greatly altered by domestication is investment in herbivore defence. It remains unclear, however, whether variation in chemical defence affects a crops ability to colonize semi-natural habitats where it typically has to compete with a resident community. Here, we investigate how breeding efforts aimed at reducing glucosinolate levels in seeds (canonical herbivore deterrents) influence initial establishment of Brassica populations spanning a wild-feral-domesticated gradient. We followed the dynamics of twenty-nine Brassica accessions in two experimental fields by recording life table parameters and vegetation cover biannually over a two-year period. Accessions were selected to vary in their glucosinolate content, and included lines of wild turnip (B. rapa), feral B. napus as well as modern canola and historical oilseed rape cultivars. Populations were established by sowing seeds on bare soil after which the natural vegetation was allowed to regenerate, providing a temporal gradient in the degree of interspecific competition. Populations flourished in the first year, but many perished during a second year of growth, in particular those of oilseed rape. Declines coincided with an increase in vegetation cover, but were slower in populations harbouring more glucosinolates. These compounds had opposing effects on different life cycle stages: seedling establishment was greater in high-glucosinolate lines, which traded off with reduced post-recruitment survival. Crucially, the effect of glucosinolates on persistence was lost when focussing on oilseed rape only, but the underlying demographic trade-off remained. Our study illustrates that initial establishment of feral oilseed rape is governed by glucosinolate-mediated trade-offs between seedling recruitment and subsequent survival, with low-glucosinolate lines (modern canola) being most successful when post-recruitment conditions are relatively benign. Such demographic trade-offs likely extend to other species, and must be considered when managing escaped crops and invasive plants.

55307: Variations in neonatal age segments mortality in Kenya’s malaria epidemiological zones by community uptake of iron-supplements and anti-malaria drugs during pregnancy: Analysis based on 2014 Kenya demographic and health survey
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Posted to bioRxiv 09 Aug 2018

Variations in neonatal age segments mortality in Kenya’s malaria epidemiological zones by community uptake of iron-supplements and anti-malaria drugs during pregnancy: Analysis based on 2014 Kenya demographic and health survey
6 downloads epidemiology

Boniface Omuga K'Oyugi

Introduction Although past studies have established that iron-supplements and anti-malaria drugs taken by mothers during pregnancy reduce the risk of neonatal deaths in high prone malaria areas, little is known about their impact on mortality risks in neonatal age segments in Kenya. The study objective was to analyse variations in neonatal age segments mortality rates by uptake of these two antenatal care services and determine their effects on the age segments mortality in Kenya’s malaria zones. Data and methods This study used data from the 2014 Kenya Demographic and Health Survey (KDHS). Survival status information for 20,794 children born less than 60 months prior to interview date and reported mothers’ uptake of iron-supplements and anti-malaria drugs during last pregnancy was analysed. Life table method was used to estimate mortality rates and Poisson multivariate regression models were fitted to determine relative risks of death for the study variables. Results The results show that variations in neonatal age segments mortality in Kenya’s malaria zones are statistically insignificant. The contributions of early neonatal (0 to 7 days) to neonatal mortality rate are 80% and 100% in low and high malaria zones, respectively. Combined high community uptake of iron-supplements and anti-malaria drugs during pregnancy reduce significantly mortality risk in late neonatal (8 days to less than one month) in all malaria zones when effects of other risk factors are controlled for. Conclusions The findings suggest that future decline in neonatal mortality in all Kenya’s malaria zones depend mainly on reduction of early neonatal mortality. High community uptake of iron-supplements and anti-malaria drugs during pregnancy has significant reduction effect on late neonatal mortality in all malaria zones. This study recommends improvement of future KDHS data quality, especially on care for small and sick neonates.

55308: A single test approach for accurate and sensitive detection and taxonomic characterization of Trypanosomes by comprehensive analysis of ITS1 amplicons
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Posted to bioRxiv 14 Sep 2018

A single test approach for accurate and sensitive detection and taxonomic characterization of Trypanosomes by comprehensive analysis of ITS1 amplicons
6 downloads epidemiology

Alex Kiarie Gaithuma, Junya Yamagishi, Axel Martinelli, Kyoko Hayashida, Naoko Kawai, Megasari Marsela, Chihiro Sugimoto

The World Health Organization has targeted stopping the transmission of Human African Trypanosomiasis by 2030. To achieve this, better tools are urgently required to identify and monitor Trypanosome infections in human, animals, and tsetse fly vectors. This study presents a single test approach for detection and identification of Trypanosomes and their comprehensive characterization at species and sub-group level. Our method uses newly designed ITS1 PCR primers (a widely used method for detection of African Trypanosomes, amplifying the ITS1 region of ribosomal RNA genes) coupled to Illumina sequencing of the amplicon. The protocol is based on the widely used Illumina’s 16s bacterial metagenomic analysis procedure that makes use of multiplex PCR and dual indexing. We analyzed wild tsetse flies collected from Zambia and Zimbabwe. Our results show that the traditional method for Trypanosome species detection based on band size comparisons on a gel is unable to distinguish between T. vivax and T. godfreyi accurately. Additionally, this approach shows increased sensitivity of detection at species level. Through phylogenetic analysis, we identified Trypanosomes at species and sub-group level without the need for any additional tests. Our results show T. congolense Kilifi sub-group is more closely related to T. simiae than to other T. congolense sub-groups. This agrees with previous studies using satellite DNA and 18s RNA analysis. While current classification does not list any sub-groups for T. vivax and T. godfreyi, we observed distinct subgroups for these species. Interestingly, sequences matching T. congolense Tsavo (now classified as T. simiae Tsavo) clusters distinctly from the rest of the T. simiae Tsavo sequences suggesting that the Nannomonas group is more divergent than currently thought thus the need for a better classification criteria. This approach has the potential for refining classification of Trypanosomes and provide detailed molecular epidemiology information useful for surveillance and transmission control efforts.

55309: Genome-wide identification and analysis of A-to-I RNA editing events in the malignantly transformed cell lines from BEP2D induced by α-particles radiation
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Posted to bioRxiv 15 Feb 2019

Genome-wide identification and analysis of A-to-I RNA editing events in the malignantly transformed cell lines from BEP2D induced by α-particles radiation
6 downloads genetics

Qiaowei Liu, Hao Li, Lukuan You, Tao Li, Lingling Li, Pingkun Zhou, Xiaochen Bo, Hebing Chen, Xiaohua Chen, Yi Hu

Adenosine (A) to inosine (I) RNA editing is the most prevalent RNA editing mechanism in humans and play critical roles in tumorigenesis. However, the effects of radiation on RNA editing and the mechanisms of radiation-induced cancer were poorly understood. Here, we analyzed human bronchial epithelial BEP2D cells and radiation-induced malignantly transformed cells with next generation sequencing. By performing an integrated analysis of A-to-I RNA editing, we found that genome-encoded single-nucleotide polymorphisms (SNPs) might induce the downregulation of ADAR2 enzymes, and further caused the abnormal occurrence of RNA editing in malignantly transformed cells. These editing events were significantly enriched in differentially expressed genes between normal cells and cancer cells. In addition, oncogenes CTNNB1 and FN1 were highly edited and significantly overexpressed in cancer cells, thus may be responsible for the lung cancer progression. Our work provides a systematic analysis of RNA editing from lung tumor specimens with high-throughput RNA sequencing and DNA sequencing. Moreover, these results demonstrate further evidence for RNA editing as an important tumorigenesis mechanism.

55310: The effect of carnitine on preservation of renal cold ischemia in rats
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Posted to bioRxiv 13 Dec 2018

The effect of carnitine on preservation of renal cold ischemia in rats
6 downloads pharmacology and toxicology

Arif Aslaner, Omer Gunal, Hamdi Taner Turgut, Umran Yildirim

Background: Although, University of Wisconsin (UW) solution is referred to as the gold standard for the preservation from cold ischemia, studies that aiming to protract the cold ischemia time still goes on. This study was planned to evaluate the effectiveness of carnitine that is added to UW solution on renal cold ischemia time. Methods: Thirty two male Wistar Albino rats were divided into four groups of 8 each; Control, UW, carnitine with Ringer Lactate (RL) and UW groups. Retrieved renal grafts were preserved in solutions at +4C after perfusion. At the same time tissue samples of 72th hour was assessed to measure Malondialdehyde (MDA) levels. Preservation solution samples were assessed at 0th, 24th, 48th, and 72th hours to measure Lactate Dehydrogenase (LDH) activity. Tissue injury was histologically scored by evaluating the hematoxilen-eosin stained paraffin sections. Results: Administration of carnitine to preservation solutions decreased the mean tissue MDA levels in groups 2 and 4. Carnitine administration slowed the increase of LDH levels in preservation solutions as well as the histopathological total tissue injury scores. Discussion: We conclude that the addition of carnitine to UW solution increased the preventive effect of preservative solution on cold ischemia injury of kidney. Keywords: Kidney; Cold Preservation; University of Wisconsin; Ringer Lactate

55311: Asparagine availability is an essential limiting factor for poxvirus protein synthesis
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Posted to bioRxiv 27 Sep 2018

Asparagine availability is an essential limiting factor for poxvirus protein synthesis
6 downloads microbiology

Anil Pant, Shuai Cao, Zhilong Yang

Virus actively interfaces with host metabolism because viral replication relies on host cells to provide nutrients and energy. For efficient viral replication in culture, vaccinia virus (VACV; the prototype poxvirus) prefers glutamine to glucose, to the extent that in glutamine-free medium, VACV replication is inefficient. Remarkably, VACV replication can be fully rescued from glutamine depletion by asparagine supplementation. By global metabolic profiling, genetic and chemical intervening of asparagine supply, we provide evidence demonstrating that the requirement of asparagine for efficient viral replication accounts for VACV's preference of glutamine to glucose, rather than because glutamine is superior to glucose in feeding the tricarboxylic acid (TCA) cycle. Further, we show that asparagine availability is a critical factor for efficient viral protein synthesis. Our study highlights that the asparagine metabolism, whose regulation has been evolutionarily tailored in mammalian cells, presents a critical barrier to poxvirus replication, suggesting new directions of anti-viral strategy development.

55312: Single-molecule imaging of DNA gyrase activity in living Escherichia coli
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Posted to bioRxiv 01 Nov 2018

Single-molecule imaging of DNA gyrase activity in living Escherichia coli
6 downloads biophysics

Mathew Stracy, Adam JM Wollman, Elzbieta Kaja, Jacek Gapinski, Ji-Eun Lee, Victoria A. Leek, Shannon J. McKie, Lesley A. Mitchenall, Anthony Maxwell, David J. Sherratt, Mark C. Leake, Pawel Zawadzki

Bacterial DNA gyrase introduces negative supercoils into chromosomal DNA and relaxes positive supercoils introduced by replication and transiently by transcription. Removal of these positive supercoils is essential for replication fork progression and for the overall unlinking of the two duplex DNA strands, as well as for ongoing transcription. To address how gyrase copes with these topological challenges, we used high-speed single-molecule fluorescence imaging in live Escherichia coli cells. We demonstrate that at least 300 gyrase molecules are stably bound to the chromosome at any time, with ~12 enzymes enriched near each replication fork. Trapping of reaction intermediates with ciprofloxacin revealed complexes undergoing catalysis. Dwell times of ~2 s were observed for the dispersed gyrase molecules, which we propose maintain steady-state levels of negative supercoiling of the chromosome. In contrast, the dwell time of replisome-proximal molecules was ~8 s, consistent with these catalyzing processive positive supercoil relaxation in front of the progressing replisome.

55313: Role of ethnicity and socio-economic status (SES) in the presentation of retinoblastoma: findings from the UK
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Posted to bioRxiv 01 May 2019

Role of ethnicity and socio-economic status (SES) in the presentation of retinoblastoma: findings from the UK
6 downloads epidemiology

Rabia Bourkiza, Phillippa Cumberland, Hiranya Abeysekera, Manoj Parulekar, Mandeep S Sagoo, Jugnoo Rahi, Ashwin Reddy

Purpose: The aim of this study was to investigate if there was a relationship between ethnicity or socioeconomic status and the presentation of advanced non-familial retinoblastoma in the UK. Methods: A cross sectional study based at the two centres providing retinoblastoma care in the UK. Non-familial cases of retinoblastoma (Rb) presenting between January 2006 and December 2011 were included. Data collected included: age at diagnosis , gender, child's ethnicity, International Intraocular Retinoblastoma Classification (IIRC) stage with Groups D and E being considered advanced, laterality, treatment, and postcodes. Individual postcode (ZIP code) data was used to obtain the Index of Multiple Deprivation (IMD) score. A postal questionnaire was sent to participants' parents to collect further, person-level, information on languages spoken and household socioeconomic position. Measures of severity of retinoblastoma also included: requirement for primary enucleation; the use of adjuvant chemotherapy; and mortality. Results: 189 cases were analyzed. 98 (52%) male and 91 (48%) female. Median age at diagnosis was 16 months [IQR 8 – 34 months]. 153/189 (81%) of cases presented with advanced retinoblastoma; 75 (40%) group E, 78 (41%) group D. 134 (72%) of cases were treated with enucleation. Multivariable analysis showed that older age at presentation was associated with enucleation and bilateral disease was associated with adjuvant chemotherapy. There was some indication that South Asian ethnicity and being in the most deprived IMD quintile were associated with a higher likelihood of presentation with advanced disease, but these estimates did not reach statistical significance. Conclusions: In this first national UK study of patients with non-familial retinoblastoma, there was no evidence of an association of ethnicity or socio-economic status and the risk of presenting with advanced disease. This may reflect equality in access of health care in the UK. As a result, awareness campaigns should continue.

55314: Population Structure of Leishmania using POPSICLE reveals extensive dichotomy in zygosity and discloses the role of sex in diversity of the parasite
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Posted to bioRxiv 18 Sep 2018

Population Structure of Leishmania using POPSICLE reveals extensive dichotomy in zygosity and discloses the role of sex in diversity of the parasite
6 downloads bioinformatics

Jahangheer Shaik

Mosaic aneuploidy prevalent in organisms such as Leishmania and Fungi and in genomes of some neurological disorders and cancers manifest as non-integer haplotypes due to heterogeneity in somy across a population of cells. Thus, the tools designed for strictly haploid or diploid genomes are insufficient to study them. We addressed this issue by upgrading our population genetics tool POPSICLE for aneuploid genomes and studied the population structure of 50 strains of Leishmania to understand genetic diversity and the sexual strategies that predispose to that diversity. Leishmania showed enormous diversity but a dichotomic nature of extreme zygosities. To understand this dichotomy, we specifically studied two species, L. tropica that contained strains with both hetero and homozygosities and L. major that were mainly homozygous. The homozygosity in L. tropica was a consequence of extreme inbreeding while heterozygosity was due to recent hybridizations involving two different genotypes. In contrast, L. major also contained two different genotypes and products of extreme inbreeding but no recent hybridizations. The heterozygous strains of L. tropica that were geographically isolated from the homozygous strains were F1 hybrids that appeared sterile to each other while those in proximity to the homozygous strains were outcrosses involving multiple cycles of hybridization indicating their mating preference with homozygous strains. Development of POPSICLE for aneuploid genomes offers a unique tool for determining the shared ancestries and in reinforcing sex as one of the driving mechanisms for speciation as demonstrated for Leishmania. POPSICLE is a Java based utility available for free download at https://popsicle-admixture.sourceforge.io/

55315: Microsatellite primer development for invasive perennial herb, Gypsophila paniculata (Caryophyllaceae)
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Posted to bioRxiv 27 Aug 2018

Microsatellite primer development for invasive perennial herb, Gypsophila paniculata (Caryophyllaceae)
6 downloads plant biology

Hailee B Leimbach-Maus, Syndell R Parks, Charlyn G Partridge

Premise of the study: Gypsophila paniculata L. (babys breath) is an herbaceous perennial that has invaded much of northern and western United States and Canada, outcompeting and crowding out native and endemic species. Microsatellite primers were developed to analyze the genetic structure of invasive populations. Methods and Results: We have identified 16 polymorphic nuclear microsatellite loci for G. paniculata out of 73 loci that successfully amplified from a primer library created using Illumina sequencing technology. The developed primers amplified microsatellite loci in 3 invasive populations in Michigan. Primers amplified di-, tri-, and tetra-nucleotide repeats. Conclusions: These markers will be useful in characterizing the genetic structure of invasive populations throughout North America to aid targeted management efforts, and in native Eurasian populations to better understand invasion history. Five of these developed primers also amplified in G. elegans.

55316: Revealing unobserved factors underlying cortical activity using a rectified latent variable model applied to neural population recordings
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Posted to bioRxiv 29 Aug 2016

Revealing unobserved factors underlying cortical activity using a rectified latent variable model applied to neural population recordings
6 downloads neuroscience

Matthew R Whiteway, Daniel A Butts

The activity of sensory cortical neurons is not only driven by external stimuli, but is also shaped by other sources of input to the cortex. Unlike external stimuli these other sources of input are challenging to experimentally control or even observe, and as a result contribute to variability of neuronal responses to sensory stimuli. However, such sources of input are likely not “noise”, and likely play an integral role in sensory cortex function. Here, we introduce the rectified latent variable model (RLVM) in order to identify these sources of input using simultaneously recorded cortical neuron populations. The RLVM is novel in that it employs non-negative (rectified) latent variables, and is able to be much less restrictive in the mathematical constraints on solutions due to the use an autoencoder neural network to initialize model parameters. We show the RLVM outperforms principal component analysis, factor analysis and independent component analysis across a variety of measures using simulated data. We then apply this model to the 2-photon imaging of hundreds of simultaneously recorded neurons in mouse primary somatosensory cortex during a tactile discrimination task. Across many experiments, the RLVM identifies latent variables related to both the tactile stimulation as well as non-stimulus aspects of the behavioral task, with a majority of activity explained by the latter. These results suggest that properly identifying such latent variables is necessary for a full understanding of sensory cortical function, and demonstrates novel methods for leveraging large population recordings to this end.

55317: Optic disc centered imaging versus quadrant imaging in retinal oximetry
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Posted to bioRxiv 19 Nov 2018

Optic disc centered imaging versus quadrant imaging in retinal oximetry
6 downloads physiology

Ashwin Mohan, Rohit Shetty, Padmamalini Mahendradas, Carroll AB Webers, Tos Berendschot

We aimed to compare intra eye quadrant variation in retinal vessel oxygen saturation in optic disc centered versus quadrant imaging. Forty two consecutive healthy subjects were included in the study. Fifty degree optic disc centered images and images of 4 quadrants (supero-temporal - ST, supero-nasal - SN, infero-nasal - IN and infero-temporal - IT) were taken. The thickest arteriole and venule were chosen in each quadrant in the optic disc centered images. For quadrant images averaged values of 3 segments of thickest arterioles and venules, each above 100µm were chosen. The intra-eye variation between quadrants for arteriolar and venous saturation (%) was compared between optic disc centered and quadrant images. Smaller vessels (70 – 100 µm) in the quadrant images were selected to study the effect of vessel calibre on oxygen saturation. Optic disc centered images gave average arteriolar saturation (%) of 90, 94, 93 and 89 and venous saturation of 58, 60, 60 and 52 in the ST, SN, IN and IT respectively. For quadrant images the average arteriolar saturation was 94, 95, 94 and 91 and the venous saturation was 62, 60, 61 and 60 in the ST, SN, IN and IT respectively. Temporally, the saturation values were significantly different (p<0.001) between optic disc centered and quadrant images. We found no differences nasally. The average intra eye range for arterioles was 11.9 in optic disc centered versus 7.1 in quadrant images (p<0.001) and for venules was 11.6 in optic disc centered versus 7.5 in quadrant images (p<0.001). We found a positive correlation of r=0.18 between saturation and vessel calibre for arteries (p=0.001) and a negative correlation of r=-0.52 for venes (p<0.001). Quadrant imaging significantly reduced intra eye variation between quadrant measurements indicating that maybe the larger variation observed in optic disc centered images are artefactual. Differences in saturation between optic disc centered and quadrant imaging were only seen temporally. We also see physiologically reducing saturation from large arterioles to small arterioles to small venules to large venules.

55318: Population-specific effect of Wolbachia on the cost of fungal infection in spider mites
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Posted to bioRxiv 26 Apr 2019

Population-specific effect of Wolbachia on the cost of fungal infection in spider mites
6 downloads ecology

Flore Zele, Mustafa Altintas, Ines Filipa Lopes dos Santos, Ibrahim Cakmak, Sara Magalhaes

Many studies have revealed the ability of the endosymbiotic bacteria Wolbachia to protect its arthropod hosts against diverse pathogens. However, as Wolbachia may also increase the susceptibility of its host to infection, predicting the outcome of a particular Wolbachia-host-pathogen interaction remains elusive. Yet, understanding such interactions is crucial for disease and pest control strategies. Tetranychus urticae spider mites are herbivorous crop pests, causing severe damage on numerous economically important crops. Due to the rapid evolution of pesticide resistance, biological control strategies using generalist entomopathogenic are being developed. However, although spider mites are infected with various Wolbachia strains worldwide, whether this endosymbiont protects them from fungi is as yet unknown. Here, we compared the survival of two populations, treated with antibiotics or harbouring different Wolbachia strains, after exposure to the fungal biocontrol agents Metarhizium brunneum and Beauveria bassiana. In one population, Wolbachia affected survival in absence of fungi but not in their presence, whereas in the other population Wolbachia increased the mortality induced by B. bassiana. To control for potential effects of the bacterial community of spider mites, we also compared the susceptibility of two populations naturally uninfected by Wolbachia, treated with antibiotics or not. The antibiotic treatment increased the susceptibility of spider mites to M. brunneum in one naturally Wolbachia-uninfected population, but it had no effect in the other treatments. These results highlight the complexity of within-host pathogens interactions, and the importance of considering the whole bacterial community of arthropods when assessing the effect of Wolbachia in a particular system.

55319: The accuracy and bias of single-step genomic prediction for populations under selection
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Posted to bioRxiv 28 Nov 2016

The accuracy and bias of single-step genomic prediction for populations under selection
6 downloads genomics

Wan-Ling Hsu, Dorian J Garrick, Rohan L Fernando

ABSTRACT In single-step analyses, missing genotypes are explicitly or implicitly imputed, and this requires centering the observed genotypes, ideally using the mean of the unselected founders. If genotypes are only available on selected individuals, centering on the unselected founder mean is impossible. Here, computer simulation is used to study an alternative analysis that does not require centering genotypes but fits the mean μg of unselected individuals as a fixed effect. To improve numerical properties of the analysis, centering the entire matrix of observed and imputed genotypes, using their sample means can be done in addition to fitting μg. Starting with observed diplotypes from 721 cattle, a 5 generation population was simulated with sire selection to produce 40,000 individuals with phenotypes of which the 1,000 sires had genotypes. The next generation of 8,000 genotyped individuals was used for validation. Evaluations were undertaken: with (J) or without (N) μg when marker covariates were not centered; and with (JC) or without (C) μg when all marker covariates were centered. A pedigree based evaluation was less accurate than genomic analyses. Centering did not influence accuracy of genomic prediction, but fitting μg did. Accuracies were improved when the panel comprised only QTL, models JC and J had accuracies of 99.2%; and models C and N had accuracies of 85.6%. When only markers were in the panel, the 4 models had accuracies of 63.9%. In panels that included causal variants, fitting μg in the model improved accuracy, but had little impact when the panel contained only markers.

55320: gEVAL - A web based browser for evaluating genome assemblies
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Posted to bioRxiv 02 Feb 2016

gEVAL - A web based browser for evaluating genome assemblies
6 downloads genomics

William Chow, Kim Brugger, Mario Caccamo, Ian Sealy, James Torrance, Kerstin Howe

For most research approaches, genome analyses are dependent on the existence of a high quality genome reference assembly. However, the local accuracy of an assembly remains difficult to assess and improve. The gEVAL browser allows the user to interrogate an assembly in any region of the genome by comparing it to different datasets and evaluating the concordance. These analyses include: a wide variety of sequence alignments, comparative analyses of multiple genome assemblies, and consistency with optical and other physical maps. gEVAL highlights allelic variations, regions of low complexity, abnormal coverage, and potential sequence and assembly errors, and offers strategies for improvement. While gEVAL focuses primarily on sequence integrity, it can also display arbitrary annotation including Ensembl or TrackHub sources. We provide gEVAL web sites for many human, mouse, zebrafish and chicken assemblies to support the Genome Reference Consortium, and gEVAL is also downloadable to enable its use for any organism and assembly.

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