Biology subjects

Huang, Y.

Publications and source records attributed to Huang, Y..

At least 1,009 records · Page 56Linked to original sources

bioRxiv2018

A Convenient Non-harm Cervical Spondylosis Intelligent Identity method based on Machine Learning

Cervical spondylosis(CS), a most common orthopedic diseases, is mainly identified by the doctors judgment from the clinical symptoms and cervical change provided by expensive instruments in hospital. Owing to the development of the surface electromyography(sEMG) technique and artificial intelligence, we proposed a convenient non-harm CS intelligent identify method EasiCNCSII, including the sEMG data acquisition and the CS identification. For the convenience and efficiency of data acquisition with the limited testable muscles provided by the sEMG technology, we proposed a data acquisition method based on the relationship between muscle activity pattern, the tendons theory and CS etiology. It is easily performed in less than 20 minutes, even outside the hospital. Faced with the challenge of high-dimension and the weak availability, the 3-tier model EasiAI is developed to intelligently identify CS. The common features and new features are extracted from raw sEMG data in first tier. The EasiRF is proposed in second tier to further reduce the data dimension and improve the performance. With the limited and weakly available data, the gradient boosted regression tree is developed in third tier to effectively identify CS. The EasiAI achieve the best performance with 91.02% in accuracy, 97.14% in sensitivity, and 81.43% in specificity compared with 4 common machine learning classification model, validating the EasiCNCSII effectiveness.

bioinformatics↗

bioRxiv2018

Heat shock induces the depletion of Oct4 in mouse blastocysts and stem cells

Temperature is an important microenvironmental factor that functions epigenetically in normal embryonic development. However, the effect of heat shock in the stem cells is not fully understood. Oct4 is a tightly regulated master regulator of pluripotency maintenance in stem cells and during early embryonic development. We report here that Oct4 protein level was significantly reduced under heat shock in mouse blastocysts and embryonic stem cells. The reduction in Oct4 in the mouse embryonic stem cells under heat shock was mediated by a ubiquitin-proteasome pathway that was dependent on the activity of death- associated protein kinase 1 (Dapk1) to phosphorylate its substrate, Pin1. Our results imply that the depletion of Oct4 via brief heat shock, such as a high fever, during early pregnancy might severely impair the growth of the mammalian embryo or even cause its death.

molecular biology↗

bioRxiv2018

Base-pair resolution detection of transcription factor binding site by deep deconvolutional network

MotivationTranscription factor (TF) binds to the promoter region of a gene to control gene expression. Identifying precise transcription factor binding sites (TFBS) is essential for understanding the detailed mechanisms of TF mediated gene regulation. However, there is a shortage of computational approach that can deliver single base pair (bp) resolution prediction of TFBS.\n\nResultsIn this paper, we propose DeepSNR, a Deep Learning algorithm for predicting transcription factor binding location at Single Nucleotide Resolution de novo from DNA sequence. DeepSNR adopts a novel deconvolutional network (deconvNet) model and is inspired by the similarity to image segmentation by deconvNet. The proposed deconvNet architecture is constructed on top of Deep-Bind and we trained the entire model using TF specific data from ChIP-exonuclease (ChIP-exo) experiments. DeepSNR has been shown to outperform motif search based methods for several evaluation metrics. We have also demonstrated the usefulness of DeepSNR in the regulatory analysis of TFBS as well as in improving the TFBS prediction specificity using ChIP-seq data.\n\nAvailabilityDeepSNR is available open source in the GitHub repository (https://github.com/sirajulsalekin/DeepSNR)\n\nContactyufei.huang@utsa.edu

genomics↗

bioRxiv2017

WSL5, a pentatricopeptide repeat protein, is essential for chloroplast biogenesis in rice under cold stress

AbstactChloroplasts play an essential role in plant growth and development, and cold has a great effect on chloroplast development. Although many genes or regulators involved in chloroplast biogenesis and development have been isolated and characterized, identification of novel components associated with cold is still lacking. In this study, we reported the functional characterization of white stripe leaf 5 (wsl5) mutant in rice. The mutant developed white-striped leaves during early leaf development and was albinic when planted under cold stress. Genetic and molecular analysis revealed that WSL5 encodes a novel chloroplast-targeted pentatricopeptide repeat protein. RNA-seq analysis showed that expression of nuclear-encoded photosynthetic genes in the mutant was significantly repressed, and expression of many chloroplast-encoded genes was also significantly changed. Notably, the WSL5 mutation caused defects in editing of rpl2 and atpA, and in splicing of rpl2 and rps12. Chloroplast ribosome biogenesis was impaired under cold stress. We propose that WSL5 is required for normal chloroplast development in rice under cold stress.

genetics↗

bioRxiv2017

Quantitative morphological variation in the developing Drosophila wing

Quantitative variation in morphology is pervasive in all species and is the basis for the evolution of differences among species. The developmental causes of such variation are a relatively neglected research topic. Quantitative comparisons of variation arising at different developmental stages with the variation in the final structure enable us to determine when variation arises, and to generate hypotheses about the causes of that variation. We measured shape and size variation in the wing of Drosophila melanogaster at three developmental stages: late third instar, post-pupariation and in the adult fly. Flies of a wild-type and two mutants (shf and ds) with effects on the adult wing shape and size were studied. Despite experimental noise related to the difficulty of comparing developing structures, we found consistent differences in wing shape and size at each developmental stage between genotypes. In addition we provide linear rules allowing to link late disc morphology with early wings. Our approach provides a framework to analyze quantitative morphological variation in the developing fly wing. This framework should help to characterize the natural variation of the larval and pupal wing shape, and to measure the contribution of the processes occurring during these developmental stages to the natural variation in adult wing morphology.

genetics↗

bioRxiv2017

Optogenetics reprogramming of planktonic cells for biofilm formation

Single-cell behaviors play essential roles during early-stage biofilms formation. In this study, we evaluated whether biofilm formation could be guided by precisely manipulating single cells behaviors. Thus, we established an illumination method to precisely manipulate the type IV pili (TFP) mediated motility and microcolony formation of Pseudomonas aeruginosa by using a combination of a high-throughput bacterial tracking algorithm, optogenetic manipulation and adaptive microscopy. We termed this method as Adaptive Tracking Illumination (ATI). We reported that ATI enables the precise manipulation of TFP mediated motility and microcolony formation during biofilm formation by manipulating bis-(3'-5')-cyclic dimeric guanosine monophosphate (c-di-GMP) levels in single cells. Moreover, we showed that the spatial organization of single cells in mature biofilms can be controlled using ATI. Thus, the established method (i.e., ATI) can markedly promote ongoing studies of biofilms.

microbiology↗

bioRxiv2017

Realistic vOlumetric-Approach to Simulate Transcranial Electric Stimulation -- ROAST -- a fully automated open-source pipeline

Research in the area of transcranial electrical stimulation (TES) often relies on computational models of current flow in the brain. Models are built based on the magnetic resonance images (MRI) of the human head to capture detailed individual anatomy. To simulate current flow on an individual, the subjects MRI is segmented, virtual electrodes are placed on this anatomical model, the volume is tessellated into a mesh, and a finite element model (FEM) is solved numerically to estimate the current flow. Various software tools are available for each step, as well as processing pipelines that connect these tools for automated or semi-automated processing. The goal of the present tool - ROAST - is to provide an end-to-end pipeline that can automatically process individual heads with realistic volumetric anatomy leveraging open-source software and custom scripts to improve segmentation and execute electrode placement. The electric field estimated with the open-source tools used by ROAST differ little from the results obtained with commercial meshing and FEM solving software. We also do not find large differences between the various automated segmentation methods used by ROAST and SimNIBS, a well-established open-source modeling pipeline. However, we do find large differences when volumetric segmentation are converted into surfaces that are used in SimNIBS to generate volumetric meshes. Evaluation on intracranial recordings from human subjects suggests that ROAST outperforms newer versions of SimNIBS in predicting field distribution and magnitudes, but that an older version of SimNIBS performs similarly. We hope that the detailed comparisons presented here of various choices in this modeling pipeline can provide guidance for future tool development. We release ROAST as an open-source, easy-to-install and fully-automated pipeline for individualized TES modeling at https://www.parralab.org/roast/.

biophysics↗

bioRxiv2017

Strong positive biodiversity-productivity relationships in a subtropical forest experiment

Forest ecosystems contribute substantially to global terrestrial primary productivity and climate regulation, but, in contrast to grasslands, experimental evidence for a positive biodiversity-productivity relationship in highly diverse forests is still lacking1. Here, we provide such evidence from a large forest biodiversity experiment with a novel design2 in subtropical China. Productivity (stand-level tree basal area, aboveground volume and carbon and their annual increment) increased linearly with the logarithm of tree species richness. Additive partitioning3 showed that increasing positive complementarity effects combined with weakening negative selection effects caused a strengthening of the relationship over time. In 2-species mixed stands, complementary effects increased with functional distance and selection effects with vertical crown dissimilarity between species. Understorey shrubs reduced stand-level tree productivity, but this effect of competition was attenuated by shrub species richness, indicating that a diverse understorey may facilitate overall ecosystem functioning. Identical biodiversity-productivity relationships were found in plots of different size, suggesting that extrapolation to larger scales is possible. Our results highlight the potential of multi-species afforestation strategies to simultaneously contribute to mitigation of climate change and biodiversity restoration.

ecology↗

bioRxiv2017

Effect of vertical slit turbulence on metabolism and swimming behavior of juvenile grass carp (ctenopharyngodon idella)

Baffles were incorporated into the swim chamber of a flume-type swimming respirometer, and the effect of vertical slit turbulence on the swimming behavior and metabolism of juvenile grass carp were investigated. Results showed a significant lower TBF in turbulent flow than in laminar flow (p< 0.05). However, differences in TBF at different inlet velocities were not significant (p> 0.05), whether the fish passed through the baffles or not. In turbulent flow, the residence time ratios of test fish at different flow zone were low water velocity > medium velocity > high velocity. Oxygen consumption rate (MO2) increased with flow velocity and was higher in turbulent flow than in laminar flow. Further, the speed exponent c, in turbulent flow, was significantly higher than in laminar flow, indicated a decrease swimming efficiency. This study of fish swimming in turbulent flow extends knowledge of fish ecology and provides data for guiding the design of hydrokinetic turbulent where needed, so preventing ecological impacts.

animal behavior and cognition↗

bioRxiv2017

Fishing for New Bt Receptors in Diamondback Moth

Bt toxins bind to receptors in the brush border membrane of the insect gut and create pores, leading to insect death. Bt-resistant insects demonstrate reduced binding of the Bt toxins to gut membranes. However, our understanding of the gut receptors involved in Bt toxin binding, and which receptors confer resistance to these toxins is incomplete, especially in diamondback moth (Plutella xylostella), a major agricultural pest. Identifying receptors has remained challenging because we lack sufficiently sensitive methods to detect Bt receptor interactions. Here, we report a modified far-immunoblotting technique, which revealed a broad spectrum of binding targets for the Bt toxins Cry1Ac, Cry1Ab, and Cry1Bd in diamondback moth. We confirm the role of the glucosinolate sulfatases GSS1 and GSS2 in Cry1Bd toxicity. GSS1 and GSS2 bind directly to Cry1Bd, and their expression is crucial for Cry1Bd toxicity. These results improve our understanding of the molecular mechanisms of Bt toxicity.\n\nAUTHOR SUMMARYThe Bt toxins, from the soil bacterium Bacillus thuringiensis, have wide applications in agriculture as insecticides applied to plants or expressed in genetically modified crops. Bt toxins bind to receptors in the brush border membrane of the insect gut and create pores leading to insect death. The success of the Bt toxins in controlling insect pests has been hindered by the emergence of resistant insects, which show reduced binding of Bt to their gut membranes. Although ongoing research has identified a few receptors, many remain unknown and the mechanisms by which these receptors cause resistance remain unclear. Here, we used a modified far-immunoblotting technique to identify proteins that bind to the toxins Cry1Ac, Cry1Ab, and Cry1Bd in the diamondback moth. This identified two glucosinolate sulfatases that bind directly to Cry1Bd; also, the toxicity of Cry1Bd requires expression of these glucosinolate sulfatases. Therefore, identification of these candidate receptors improves our understanding of Bt function and resistance.

biochemistry↗

bioRxiv2017

Low Perfusion Compartments in Glioblastoma Quantified by Advanced Magnetic Resonance Imaging: Correlation with Patient Survival

BackgroundGlioblastoma exhibits profound intratumoral heterogeneity in blood perfusion, which may cause inconsistent therapy response. Particularly, low perfusion may create hypoxic microenvironment and induce resistant clones. Thus, developing validated imaging approaches that define low perfusion compartments is crucial for clinical management.\n\nMethodsA total of 112 newly-diagnosed supratentorial glioblastoma patients were prospectively recruited for maximal safe resection. Preoperative MRI included anatomical, dynamic susceptibility contrast (DSC), diffusion tensor imaging (DTI) and chemical shift imaging (CSI). The apparent diffusion coefficient (ADC) and relative cerebral blood volume (rCBV) were calculated from DTI and DSC respectively. Using thresholding methods, two low perfusion compartments (ADCH-rCBVL and ADCL-rCBVL) were identified. Volumetric analysis was performed. Lactate and macromolecule/lipid levels were determined from multivoxel spectroscopy. Progression-free survival (PFS) and overall survival (OS) were analysed using Kaplan-Meier and multivariate Cox regression analyses.\n\nResultsTwo compartments displayed higher lactate and macromolecule/lipid levels than normal controls (each P < 0.001), suggesting hypoxic and pro-inflammatory microenvironment. The proportional volume of ADCL-rCBVL compartment was associated with a larger infiltration area (P < 0.001, rho = 0.42). Lower lactate in this compartment was associated with a less invasive phenotype visualized on DTI. Multivariate Cox regression showed higher lactate level in the ADCL-rCBVL compartment was associated with a worse survival (PFS: HR 2.995, P = 0.047; OS: HR 4.974, P = 0.005).\n\nConclusionsThe ADCL-rCBVL compartment represent a treatment resistant sub-region associated with glioblastoma invasiveness. This approach was based on clinically available imaging modalities and could thus provide crucial pretreatment information for clinical decision making.

cancer biology↗

bioRxiv2017

Nonparametric Bayesian inference of transcriptional branching and recombination identifies regulators of early human germ cell development

During embryonic development, cells undertake a series of fate decisions to form a complete organism comprised of various cell types, epitomising a branching process. A striking example of branching occurs in humans around the time of implantation, when primordial germ cells (PGCs), precursors of sperm and eggs, and somatic lineages are specified. Due to inaccessibility of human embryos at this stage of development, understanding the mechanisms of PGC specification remains difficult. The integrative modelling of single cell transcriptomics data from embryos and appropriate in vitro models should prove to be a useful resource for investigating this system, provided that the cells can be suitably ordered over a developmental axis. Unfortunately, most methods for inferring cell ordering were not designed with structured (time series) data in mind. Although some probabilistic approaches address these limitations by incorporating prior information about the developmental stage (capture time) of the cell, they do not allow the ordering of cells over processes with more than one terminal cell fate. To investigate the mechanisms of PGC specification, we develop a probabilistic pseudotime approach, branch-recombinant Gaussian process latent variable models (B-RGPLVMs), that use an explicit model of transcriptional branching in individual marker genes, allowing the ordering of cells over developmental trajectories with arbitrary numbers of branches. We use first demonstrate the advantage of our approach over existing pseudotime algorithms and subsequently use it to investigate early human development, as primordial germ cells (PGCs) and somatic cells diverge. We identify known master regulators of human PGCs, and predict roles for a variety of signalling pathways, transcription factors, and epigenetic modifiers. By concentrating on the earliest branched signalling events, we identified an antagonistic role for FGF receptor (FGFR) signalling pathway in the acquisition of competence for human PGC fate, and identify putative roles for PRC1 and PRC2 in PGC specification. We experimentally validate our predictions using pharmacological blocking of FGFR or its downstream effectors (MEK, PI3K and JAK), and demonstrate enhanced competency for PGC fate in vitro, whilst small molecule inhibition of the enzymatic component of PRC1/PRC2 reveals reduced capacity of cells to form PGCs in vitro. Thus, B-RGPLVMs represent a powerful and flexible data-driven approach for dissecting the temporal dynamics of cell fate decisions, providing unique insights into the mechanisms of early embryogenesis. Scripts relating to this analysis are available from: https://github.com/cap76/PGCPseudotime

developmental biology↗

bioRxiv2017

Inherited chromosomally integrated human herpesvirus 6 genomes are ancient, intact and potentially able to reactivate from telomeres

Human herpesviruses 6A and 6B (HHV6-A and HHV-6B; species Human herpesvirus 6A and Human herpesvirus 6B) have the capacity to integrate into telomeres, the essential capping structures of chromosomes that play roles in cancer and ageing. About 1% of people worldwide are carriers of chromosomally integrated HHV-6 (ciHHV-6), which is inherited as a genetic trait. Understanding the consequences of integration for the evolution of the viral genome, for the telomere and for the risk of disease associated with carrier status is hampered by a lack of knowledge about ciHHV-6 genomes. Here, we report an analysis of 28 ciHHV-6 genomes and show that they are significantly divergent from the few modern non-integrated HHV-6 strains for which complete sequences are currently available. In addition ciHHV-6B genomes in Europeans are more closely related to each other than to ciHHV-6B genomes from China and Pakistan, suggesting regional variation of the trait. Remarkably, at least one group of European ciHHV-6B carriers has inherited the same ciHHV-6B genome, integrated in the same telomere allele, from a common ancestor estimated to have existed 24,500 {+/-}10,600 years ago. Despite the antiquity of some, and possibly most, germline HHV-6 integrations, the majority of ciHHV-6B (95%) and ciHHV-6A (72%) genomes contain a full set of intact viral genes and therefore appear to have the capacity for viral gene expression and full reactivation.\n\nIMPORTANCEInheritance of HHV-6A or HHV-6B integrated into a telomere occurs at a low frequency in most populations studied to date but its characteristics are poorly understood. However, stratification of ciHHV-6 carriers in modern populations due to common ancestry is an important consideration for genome-wide association studies that aim to identify disease risks for these people. Here we present full sequence analysis of 28 ciHHV-6 genomes and show that ciHHV-6B in many carriers with European ancestry most likely originated from ancient integration events in a small number of ancestors. We propose that ancient ancestral origins for ciHHV-6A and ciHHV-6B are also likely in other populations. Moreover, despite their antiquity, all of the ciHHV-6 genomes appear to retain the capacity to express viral genes and most are predicted to be capable of full viral reactivation. These discoveries represent potentially important considerations in immune-compromised patients, in particular in organ transplantation and in stem cell therapy.

evolutionary biology↗

bioRxiv2017

Diabetes and dementia incidence in Latin America; a 10/66 population-based cohort study

BackgroundDiabetes prevalence is already high in middle income countries, particularly among older people. Current evidence on diabetes as a risk factor for dementia is limited to cohort studies in high income countries. Few studies carried out fasting glucose assessments to identify undiagnosed cases, and assess diabetes control. We aimed to determine the association between both diagnosed diabetes and total diabetes (including undiagnosed cases) and incident dementia, examining also the impact of glycaemic control on dementia risk.\n\nMethodsPopulation-based cohort studies of those aged 65 years and over in sites in Cuba, Dominican Republic, Puerto Rico, Peru, Venezuela, and Mexico. Diagnosed diabetes was assessed through self-reported diagnosis, and undiagnosed diabetes through fasting blood samples (glucose >= 7mmol/L). Blood pressure, smoking, underactivity and waist circumference were assessed from questionnaires and physical examination. Incident 10/66 dementia (and subtypes), and mortality, were ascertained three to five years later.\n\nResults12,297 interviews were completed at baseline, with 80-95% responding by site. The at risk cohort comprised 10,945 dementia-free individuals, of whom 8,171 (75%) provided blood samples. Mean age varied from 72.0 to 75.1 years by site. Total diabetes prevalence was 43.5% in Puerto Rico, ranging from 11.5% to 27.0% in other sites. Most diabetes cases (50.2% to 68.4%) were not controlled (fasting glucose >7.0 mmol/L). 7,000 participants were followed up for 26,423 person-years with 659 incident dementia cases, and 905 dementia free deaths. Total diabetes was associated with incident 10/66 dementia (pooled meta-analysed adjusted sub-hazard ratio [pASHR] 1.25, 95% CI, 1.05-1.49, I2=48.6%), with a stronger association for uncontrolled (pASHR 1.47, 95% CI 1.19-1.81, I2=49.6%) than controlled cases (pASHR 1.29, 95% CI 0.95-1.74, I2=13.3%). Total diabetes was strongly associated with the incidence of vascular dementia (pASHR 2.25, 95% CI 1.24-4.08, I2=23.7%), but not Alzheimers Disease (pASHR 0.99, 95% CI 0.70-1.42, I2=49.0%).\n\nConclusionsDiabetes, particularly when poorly controlled, may increase dementia risk. There is considerable scope for improved detection and control of diabetes among older people in these settings, and hence an opportunity to carry out proof of concept prevention trials. Overlapping epidemics of these age dependent disorders will challenge poorly-resourced health systems in the future.

epidemiology↗

bioRxiv2017

Leg Length, Skull Circumference, And The Incidence Of Dementia In Latin America And China; A 10/66 Population-Based Cohort Study

BackgroundAdult leg length is influenced by nutrition in the first few years of life. Adult head circumference is an indicator of brain growth. Cross-sectional studies indicate inverse associations with dementia risk, but there have been few prospective studies.\n\nMethodsPopulation-based cohort studies in urban sites in Cuba, Dominican Republic Puerto Rico and Venezuela, and rural and urban sites in Peru, Mexico and China. Sociodemographic and risk factor questionnaires were administered to all participants, and anthropometric measures taken, with ascertainment of incident 10/66 dementia, and mortality, three to five years later.\n\nResultsOf the original at risk cohort of 13,587 persons aged 65 years and over, 2,443 (18.0%) were lost to follow-up; 10,540 persons with skull circumference assessments were followed up for 40,466 person years, and 10,400 with leg length assessments were followed up for 39,954 person years. There were 1,009 cases of incident dementia, and 1,605 dementia free deaths. The fixed effect pooled meta-analysed adjusted subhazard ratio (ASHR) for leg length (highest vs. lowest quarter) was 0.80 (95% CI, 0.66-0.97) and for skull circumference was 1.02 (95% CI, 0.84-1.25), with no heterogeneity of effect between sites (I2=0%). Leg length measurements tended to be shorter at follow-up, particularly for those with baseline cognitive impairment and dementia. However, leg length change was not associated with dementia incidence (ASHR, per cm 1.006, 95% CI 0.992-1.020), and the effect of leg length was little altered after adjusting for baseline frailty (ASHT 0.82, 95% CI 0.67-0.99). A priori hypotheses regarding effect modification by gender or educational level were not supported.\n\nConclusionsConsistent findings across settings provide quite strong support for an association between adult leg length and dementia incidence in late-life. Leg length is a relatively stable marker of early life nutritional programming, which may confer brain reserve and protect against neurodegeneration in later life through mitigation of cardiometabolic risk. Further clarification of these associations could inform predictive models for future dementia incidence in the context of secular trends in adult height, and invigorate global efforts to improve childhood nutrition, growth and development.

epidemiology↗

bioRxiv2017

Reproductive Period, Endogenous Estrogen Exposure And Dementia Incidence Among Women In Latin America And China; A 10/66 Population-Based Cohort Study

BackgroundExposure to endogenous estrogen may protect against dementia, but evidence remains equivocal. Such effects may be assessed more precisely in settings where exogenous estrogen administration is rare. We aimed to determine whether reproductive period (menarche to menopause), and other indicators of endogenous estrogen exposure are inversely associated with dementia incidence\n\nMethodsPopulation-based cohort studies, of women aged 65 years and over in urban sites in Cuba, Dominican Republic Puerto Rico and Venezuela, and rural and urban sites in Peru, Mexico and China. Sociodemographic and risk factor questionnaires were administered to all participants, including ages at menarche, birth of first child, and menopause, and parity, with ascertainment of incident 10/66 dementia, and mortality, three to five years later.\n\nResults9,428 women participated in the baseline phase, with response rates of 72-98% by site. The at risk cohort comprised 8,466 dementia-free women. Mean age at baseline varied from 72.0 to 75.4 years, lower in rural than urban sites and in China than in Latin America. Mean parity was 4.1, generally higher in rural than urban sites and ranging from 2.4-7.2 by site. 6,854 women with baseline reproductive period data were followed up for 26,463 person years. There were 692 cases of incident dementia, and 895 dementia free deaths. Pooled meta-analysed fixed effects, per year, for reproductive period (Adjusted Sub-Hazard Ratio [ASHR] 1.001, 95% CI 0.988-1.015) did not support any association with dementia incidence, with no evidence also for any interaction between APOE genotype and reproductive period (ASHR 0.993, 95% CI 0.947-1.041, I2=39.3%). Similarly no association was observed between incident dementia and; ages at menarche, birth of first child, and menopause: nulliparity; or index of cumulative endogenous estrogen exposure. Greater parity was positively associated with incident dementia (ASHR 1.030, 95% CI 1.002-1.059, I2=0.0%).\n\nConclusionsWe found no evidence to support the theory that natural variation in cumulative exposure to endogenous oestrogens across the reproductive period influences the incidence of dementia in late life.

epidemiology↗

bioRxiv2017

Imp/Syp Temporal Gradients Govern Decommissioning Of Drosophila Neural Stem Cells

Timing of Drosophila neuroblast decommissioning is controlled in a lineage-specific manner. Following a prepupal ecdysone pulse, the ecdysone receptor and mediator complex cause neuroblasts to shrink. Shrinking is followed by nuclear accumulation of Prospero and cell cycle exit. Only mushroom body (MB) neuroblasts escape early pupal termination. Here, we demonstrate that the opposing temporal gradients of Imp and Syp RNA-binding proteins that govern temporal fate also regulate neuroblast decommissioning. The Imp gradient declines slower in MB neuroblasts so they still express Imp when it is absent from others. The presence of Imp in MB neuroblasts prevents decommissioning partly through inhibiting the mediator complex. Moreover, a timely induction of Imp can protect many non-MB neuroblasts from aging. We also show that the increasing Syp gradient permits Prospero accumulation and neuroblast termination. Together our results reveal that progeny temporal fate and progenitor decommissioning are co-regulated in protracted neuronal lineages.

developmental biology↗

bioRxiv2017

A heuristic method to identify runs of homozygosity associated with reduced performance in livestock.

While for the most part genome-wide metrics are currently employed in managing livestock inbreeding, genomic data offer, in principle, the ability to identify functional inbreeding. Here we present a heuristic method to identify haplotypes contained within a run of homozygosity (ROH) associated with reduced performance. Results are presented for simulated and swine data. The algorithm comprises 3 steps. Step 1 scans the genome based on marker windows of decreasing size and identifies ROH genotypes associated with an unfavorable phenotype. Within this stage, multiple aggregation steps reduce the haplotype to the smallest possible length. In step 2, the resulting regions are formally tested for significance with the use of a linear mixed model. Lastly, step 3 removes nested windows. The effect of the unfavorable haplotypes identified and their associated haplotype probabilities for a progeny of a given mating pair or an individual can be used to generate an inbreeding load matrix (ILM). Diagonals of ILM characterize the functional inbreeding load of individual (IIL). We estimated the accuracy of predicting the phenotype based on ILL. We further compared the significance of the regression coefficient for IIL on phenotypes to genome-wide inbreeding metrics. We tested the algorithm using simulated scenarios (n =12) combining different levels of linkage disequilibrium (LD) and number of loci impacting a quantitative trait. Additionally, we investigated 9 traits from two maternal purebred swine lines. In simulated data, as the LD in the population increased the algorithm identified a greater proportion of the true unfavorable ROH effects. For example, the proportion of highly unfavorable true ROH effects identified raised from 32 to 41 % for the low to the high LD scenario. In both simulated and real data the haplotypes identified were contained within a much larger ROH (9.12-12.1 Mb). The IIL prediction accuracy was greater than zero across all scenarios for simulated data (high LD scenario mean (95% confidence interval): 0.49 (0.47-0.52)) and for nearly all swine traits (mean {+/-} SD: 0.17{+/-}0.10). On average across simulated and swine datasets the IIL regression coefficient was more closely related to progeny performance than any genome-wide inbreeding metric. A heuristic method was developed that identified ROH genotypes with reduced performance and characterized the combined effects of ROH genotypes within and across individuals.

genomics↗