Biology subjects

Browse preprints

Search indexed bioRxiv preprints in genomics, neuroscience, cell biology and bioinformatics. Read source abstracts and check manuscript versions; preprints are not peer reviewed.

At least 1,261 records · Page 70Linked to original sources

bioRxiv2018

Effect of light intensity and nutritional value of food resources on flight response of adult parasitoid, Cotesia plutellae (Kurdjumov) (Hymenoptera: Braconidae)

Cotesia plutellae (Kurdjumov) (Hymenoptera: Braconidae) is the major larval parasitoid of Plutella xylostella (L) (Lepidoptera: Plutellidae), which is a serious pest of cruciferous plants throughout the world. We evaluated the influence of light intensities and feeding conditions on the vertical angle of flight in freshly emerged wasps in a cylinder having diameter 15cm and height 30cm. Light intensity was found to directly affects the flight activity. Increase in light intensity causes increase in vertical flight of the female wasps. However, Increase in light intensity did not influence the inclination of vertical flight in males. Feeding condition was also found to affect the vertical flight of the wasps. Honey odour, from below the flight chamber, arrested the flight of unfed or sucrose fed wasps. However, flight of honey fed wasps was not affected by honey odour. Male flight response was also influenced by feeding condition and light intensity but the response was not as higher as shown by females. The present study is useful for selecting suitable food prior to inundative release of parasitoid in the field at suitable time period of the day.

animal behavior and cognition↗

bioRxiv2018

Human neurons from Christianson syndrome iPSCs reveal allele-specific responses to rescue strategies

Human genetic disorders provide a powerful lens to understanding the human brain. Induced pluripotent stem cells (iPSC) represent an important, new resource for mechanistic studies and therapeutic development. Christianson syndrome (CS), an X-linked neurological disorder with attenuation of brain growth postnatally (postnatal microcephaly), is caused by mutations in SLC9A6, the gene encoding endosomal Na+/H+ exchanger 6 (NHE6). We developed CS iPSC lines from patients with a mutational spectrum, as well as robust biologically-related and isogenic controls. We demonstrate that mutations in CS lead to loss of protein function by a variety of mechanisms. Regardless of mutation, all patient-derived neurons demonstrate reduced neurite growth and arborization, likely underlying diminished postnatal brain growth in patients. Additionally, phenotype rescue strategies show allele-specific responses: a gene replacement strategy shows efficacy in nonsense mutations but not in a missense mutation, whereas application of exogenous trophic factors (BDNF or IGF-1) rescues arborization phenotypes across all mutations. Our data emphasize the important principle of personalized medicine whereby success of some therapeutic strategies may be more linked to patient genotype than others.

neuroscience↗

bioRxiv2018

Quantitative reconstruction of time-varying 3D cell forces with traction force optical coherence microscopy

Cellular traction forces (CTFs) play an integral role in both physiological processes and disease, and are a topic of interest in mechanobiology. Traction force microscopy (TFM) is a family of methods used to quantify CTFs in a variety of settings. State-of-the-art 3D TFM methods typically rely on confocal fluorescence microscopy, which can impose limitations on acquisition speed, volumetric coverage, and temporal sampling or coverage. In this report, we present the first quantitative implementation of a new TFM technique: traction force optical coherence microscopy (TF-OCM). TF-OCM leverages the capabilities of optical coherence microscopy and computational adaptive optics (CAO) to enable the quantitative reconstruction of 3D CTFs in scattering media with minute-scale temporal resolution. We applied TF-OCM to quantify CTFs exerted by isolated NIH-3T3 fibroblasts embedded in Matrigel, with five-minute temporal sampling, using images which spanned a 500x500x500 m3 field-of-view. Due to the reliance of TF-OCM on computational imaging methods, we have provided extensive discussion of the underlying equations, assumptions, and failure modes of these methods. TF-OCM has the potential to advance studies of biomechanical behavior in scattering media, and may be especially well-suited to the study of cell collectives such as spheroids, a prevalent model in mechanobiology research.

bioengineering↗

bioRxiv2018

Individual differences in visual salience vary along semantic dimensions

What determines where we look? Theories of attentional guidance hold that image features and task demands govern fixation behaviour, while differences between observers are noise. Here, we investigated the fixations of > 100 human adults freely viewing a large set of complex scenes. We found systematic individual differences in fixation frequencies along six semantic stimulus dimensions. These differences were large (> twofold) and highly stable across images and time. Surprisingly, they also held for first fixations directed towards each image, commonly interpreted as bottom-up visual salience. Their perceptual relevance was documented by a correlation between individual face salience and recognition skills. The dimensions of individual salience and their covariance pattern replicated across samples from three different countries, suggesting they reflect fundamental biological mechanisms of attention. Our findings show stable individual salience differences along semantic dimensions, with meaningful perceptual implications. Salience reflects features of the observer as well as the image.

neuroscience↗

bioRxiv2018

Electron Microscopy Analysis of hAPP-Induced Neurodegeneration in the Glomerular Network

Loss of smell is an early indicator of Alzheimers disease (AD), making the olfactory system an accessible model to study the effect of AD related proteins such as Amyloid Precursor Protein (APP). The regenerative capacity of the system further enables studies of circuit recovery after APP-induced degeneration. While the cellular effects of APP are well documented, little is known about its effects on brain circuits at the ultrastructural level. To study circuitry changes, we overexpressed humanized APP with familial AD mutations (hAPP) in olfactory sensory neurons and performed serial electron microscopy on olfactory bulb glomeruli from both control and hAPP expressing mice. We found that hAPP-expressing mice showed a striking decrease in glomerular connectivity along with widespread changes of subcellular structures. By then turning off hAPP expression for 6 weeks we tested the capacity of glomerular circuits to recover and found clear restoration of both connectivity and subcellular features, including an increase in post-synaptic density to above the control level. These data provide an important ultrastructural view of olfactory regions associated with AD and suggest that circuit recovery is possible in brain tissue that has experienced APP-induced neurodegeneration.

neuroscience↗

bioRxiv2018

The influence of fluctuating population densities on evolutionary dynamics

The causes and consequences of fluctuating population densities are an important topic in ecological literature. Yet, the effects of such fluctuations on maintenance of variation in spatially structured populations have received little analytic treatment. We analyze what happens when two habitats coupled by migration not only differ in their trade-offs in selection but also in their demographic stability - and show that equilibrium allele frequencies can change significantly due to ecological feedback arising from locally fluctuating population sizes. When an ecological niche exhibits such fluctuations, these drive an asymmetry in the relative impact of gene flow, and therefore, the equilibrium frequency of the locally adapted type decreases. Our results extend the classic conditions on maintenance of diversity under selection and migration by including the effect of fluctuating population densities. We find simple analytic conditions in terms of the strength of selection, immigration, and the extent of fluctuations between generations in a continent-island model. Whereas weak fluctuations hardly affect coexistence, strong recurrent fluctuations lead to extinction of the type better adapted to the fluctuating niche - even if the invader is locally maladapted. There is a disadvantage to specialization to an unstable habitat, as it makes the population vulnerable to swamping from more stable habitats.

evolutionary biology↗

bioRxiv2018

EEG signal diversity reflects capability for behavioral responsiveness during propofol sedation

Transitions between wakefulness and anesthesia are accompanied by profound changes in brain functioning. A key challenge is thus to disentangle neuronal mechanisms specific to loss and recovery of consciousness, from more general effects that are not directly related to the capacity for conscious experience. Measures of neuronal diversity have been recently proposed to constitute a robust correlate of the global states of consciousness. In the present study we investigated whether EEG signal diversity is indeed related to behavioral responsiveness during propofol sedation, or rather to the general drug-related effects. To this end, we reanalyzed data collected from 20 subjects sedated with propofol. Based on the responsiveness to auditory stimuli all subjects were subdivided into two subgroups - responsive (n = 13), who remains awake throughout the experiment, and drowsy (n = 7), who becomes unresponsive during moderate sedation. Resting state EEG recorded during wakefulness and sedation was characterized by the Mean Information Gain (MIG) and Fluctuation complexity (FC) - information-theory measures estimating signal diversity or complexity, respectively. The main finding is that the drowsy group exhibited a decrease in diversity during sedation but, unexpectedly, the responsive group exhibited a robust increase in diversity (ANOVA group x state interaction: F(3) = 7.81, p < 0.001; BF10 > 197). However, signal complexity neither differentiated the subgroups, nor decreased reliably during sedation (t-test wake vs. moderate sedation: t(19) = 2.57, p = 0.092; BF10 = 3.08). Further, we show that a change in signal diversity is negatively correlated with a delta power change (r = -0.62, p = 0.002), and positively correlated with a beta power change (r = 0.84, p < 0.001). Finally, we show that MIG behaves in a qualitatively similar manner to Lempel-Ziv - another diversity measures used in several recent studies. Overall, we revealed that propofol sedation is initially related to an increase in EEG signal diversity, and that only upon loss of responsiveness EEG diversity decreases. The qualitatively different pattern of changes in the responsive and drowsy groups makes EEG diversity a robust indirect index of responsiveness and, presumably, consciousness.

neuroscience↗

bioRxiv2018

Maximum Caliber can build and infer models of oscillation in a three-gene feedback network

Single-cell protein expression time trajectories provide rich temporal data quantifying cellular variability and its role in dictating fitness. However, theoretical models to analyze and fully extract information from these measurements remain limited for three reasons: i) gene expression profiles are noisy, rendering models of averages inapplicable, ii) experiments typically measure only a few protein species while leaving other molecular actors - necessary to build traditional bottom-up models - unnoticed, and iii) measured data is in fluorescence, not particle number. We have recently addressed these challenges in an alternate top-down approach using the principle of Maximum Caliber (MaxCal) to model genetic switches with one and two protein species. In the present work we address scalability and broader applicability of MaxCal by extending to a three-gene (A, B, C) feedback network that exhibits oscillation, commonly known as the repressilator. We test MaxCals inferential power by using synthetic data of noisy protein number time traces - serving as a proxy for experimental data - generated from a known underlying model. We notice that the minimal MaxCal model - accounting for production, degradation, and only one type of symmetric coupling between all three species - reasonably infers several underlying features of the circuit such as the effective production rate, degradation rate, frequency of oscillation, and protein number distribution. Next, we build models of higher complexity including different levels of coupling between A, B, and C and rigorously assess their relative performance. While the minimal model (with four parameters) performs remarkably well, we note that the most complex model (with six parameters) allowing all possible forms of crosstalk between A, B, and C slightly improves prediction of rates, but avoids ad-hoc assumption of all the other models. It is also the model of choice based on Bayesian Information Criteria. We further analyzed time trajectories in arbitrary fluorescence (using synthetic trajectories) to mimic realistic data. We conclude that even with a three-protein system including both fluorescence noise and intrinsic gene expression fluctuations, MaxCal can faithfully infer underlying details of the network, opening up future directions to model other network motifs with many species.

synthetic biology↗

bioRxiv2018

Biology and Bias in Cell Type-Specific RNAseq of Nucleus Accumbens Medium Spiny Neurons

Isolation of cell populations is untangling complex biological interactions, but studies comparing methodologies lack in vivo complexity and draw limited conclusions about the types of transcripts identified by each technique. Furthermore, few studies compare FACS-based techniques to ribosomal affinity purification, and none do so genome-wide. We addressed this gap by systematically comparing nuclear-FACS, whole cell-FACS, and RiboTag affinity purification in the context of D1 or D2 dopamine receptor-expressing medium spiny neuron (MSN) subtypes of the nucleus accumbens (NAc), a key brain reward region. We find that nuclear-FACS-seq generates a substantially longer list of differentially expressed genes between these cell types, and a significantly larger number of neuropsychiatric GWAS hits than the other two methods. RiboTag-seq has much lower coverage of the transcriptome than the other methods, but very efficiently distinguishes D1- and D2-MSNs. We also demonstrate differences between D1- and D2-MSNs with respect to RNA localization, suggesting fundamental cell type differences in mechanisms of transcriptional regulation and subcellular transport of RNAs. Together, these findings guide the field in selecting the RNAseq method that best suits the scientific questions under investigation.

neuroscience↗

bioRxiv2018

Longitudinal Visual Analytics for Unpacking the Cancer Journey

Retrospective cancer research requires identification of patients matching both categorical and temporal inclusion criteria, often based on factors exclusively available in clinical notes. Although natural language processing approaches for inferring higher-level concepts have shown promise for bringing structure to clinical texts, interpreting results is often challenging, involving the need to move between abstracted representations and constituent text elements. We discuss qualitative inquiry into user tasks and goals, data elements and models resulting in an innovative natural language processing pipeline and a visual analytics tool designed to facilitate interpretation of patient summaries and identification of cohorts for retrospective research.

cancer biology↗

bioRxiv2018

Programmed DNA elimination of germline development genes in songbirds

Genomes can vary within individual organisms. Programmed DNA elimination leads to dramatic changes in genome organisation during the germline-soma differentiation of ciliates1, lampreys2, nematodes3,4, and various other eukaryotes5. A particularly remarkable example of tissue-specific genome differentiation is the germline-restricted chromosome (GRC) in the zebra finch which is consistently absent from somatic cells6. Although the zebra finch is an important animal model system7, molecular evidence from its large GRC (>150 megabases) is limited to a short intergenic region8 and a single mRNA9. Here, we combined cytogenetic, genomic, transcriptomic, and proteomic evidence to resolve the evolutionary origin and functional significance of the GRC. First, by generating tissue-specific de-novo linked-read genome assemblies and re-sequencing two additional germline and soma samples, we found that the GRC contains at least 115 genes which are paralogous to single-copy genes on 18 autosomes and the Z chromosome. We detected an amplification of [≥]38 GRC-linked genes into high copy numbers (up to 308 copies) but, surprisingly, no enrichment of transposable elements on the GRC. Second, transcriptome and proteome data provided evidence for functional expression of GRC genes at the RNA and protein levels in testes and ovaries. Interestingly, the GRC is enriched for genes with highly expressed orthologs in chicken gonads and gene ontologies involved in female gonad development. Third, we detected evolutionary strata of GRC-linked genes. Developmental genes such as bicc1 and trim71 have resided on the GRC for tens of millions of years, whereas dozens have become GRC-linked very recently. The GRC is thus likely widespread in songbirds (half of all bird species) and its rapid evolution may have contributed to their diversification. Together, our results demonstrate a highly dynamic evolutionary history of the songbird GRC leading to dramatic germline-soma genome differences as a novel mechanism to minimise genetic conflict between germline and soma.

evolutionary biology↗

bioRxiv2018

Genetic networks underlying natural variation in basal and induced activity levels in Drosophila melanogaster

Exercise is recommended by health professionals across the globe as part of a healthy lifestyle to prevent and/or treat the consequences of obesity. While overall, the health benefits of exercise and an active lifestyle are well understood, very little is known about how genetics impacts an individuals inclination for and response to exercise. To address this knowledge gap, we investigated the genetic architecture underlying natural variation in activity levels in the model system Drosophila melanogaster. Activity levels were assayed in the Drosophila Genetics Reference Panel 2 fly strains at baseline and in response to a gentle exercise treatment using the Rotational Exercise Quantification System. We found significant, sex-dependent variation in both activity measures and identified over 100 genes that contribute to basal and induced exercise activity levels. This gene set was enriched for genes with functions in the central nervous system and in neuromuscular junctions and included several candidate genes with known activity phenotypes such as flightlessness or uncoordinated movement. Interestingly, there were also several chromatin proteins among the candidate genes, two of which were validated and shown to impact activity levels. Thus, the study described here reveals the complex genetic architecture controlling basal and exercise-induced activity levels in D. melanogaster and provides a resource for exercise biologists.

genetics↗

bioRxiv2018

CoCoScore: Context-aware co-occurrence scoring for text mining applications using distant supervision

Information extraction by mining the scientific literature is key to uncovering relations between biomedical entities. Most existing approaches based on natural language processing extract relations from single sentence-level co-mentions, ignoring co-occurrence statistics over the whole corpus. Existing approaches counting entity co-occurrences ignore the textual context of each co-occurrence. We propose a novel corpus-wide co-occurrence scoring approach to relation extraction that takes the textual context of each co-mention into account. Our method, called CoCoScore, scores the certainty of stating an association for each sentence that co-mentions two entities. CoCoScore is trained using distant supervision based on a gold-standard set of associations between entities of interest. Instead of requiring a manually annotated training corpus, co-mentions are labeled as positives/negatives according to their presence/absence in the gold standard. We show that CoCoScore outperforms previous approaches in identifying human disease-gene and tissue-gene associations as well as in identifying physical and functional protein-protein associations in different species. CoCoScore is a versatile text-mining tool to uncover pairwise associations via co-occurrence mining, within and beyond biomedical applications. CoCoScore is available at: https://github.com/JungeAlexander/cocoscore

bioinformatics↗

bioRxiv2018

Tightly-orchestrated rearrangements govern catalytic center assembly of the ribosome

The catalytic activity of the ribosome is mediated by RNA, yet proteins are essential for the function of the peptidyl transferase center (PTC). In eukaryotes, final assembly of the PTC occurs in the cytoplasm by insertion of the ribosomal protein Rpl10. We determine structures of six intermediates in late nuclear and cytoplasmic maturation of the large subunit that reveal a tightly-choreographed sequence of protein and RNA rearrangements controlling the insertion of Rpl10. We also determine the structure of the biogenesis factor Yvh1 and show how it promotes assembly of the P stalk, a critical element for recruitment of GTPases that drive translation. Together, our structures provide a blueprint for final assembly of a functional ribosome.\n\nOne Sentence SummaryCryo-EM structures of six novel intermediates in the assembly of the large ribosomal subunit reveal mechanism of creating the catalytic center.

biochemistry↗

bioRxiv2018

Contribution of sensory encoding to measured bias

Perceptual decision-making is a complex process that involves sensory integration followed by application of a cognitive threshold. Signal detection theory (SDT) provides a mathematical framework for attributing the underlying neurobiological processes to these distinct phases of perceptual decision-making. In particular, SDT reveals the sensitivity (d) of the neuronal response distributions and the bias (c) of the decision criterion, which are commonly thought to reflect sensory and cognitive processes, respectively. However, neuronal representations of bias have been observed in sensory areas, suggesting that some changes in bias are due to effects on sensory encoding. To directly test whether sensory encoding can influence bias, we optogenetically manipulated neuronal excitability in primary visual cortex (V1) during a detection task. Increasing excitability in V1 significantly decreased behavioral bias, while decreasing excitability had the opposite effect. To determine whether this change in bias is consistent with the effects on sensory encoding, we made extracellular recordings from V1 neurons in passively viewing mice. Indeed, we found that optogenetic manipulation of excitability shifted the neuronal bias in the same direction as the behavioral bias, despite using a fixed artificial decision criterion to predict hit and false alarm rates from the neuronal firing rates. To test the generality these effects, we also manipulated the quality of V1 encoding by changing stimulus contrast or inter-stimulus interval. These stimulus manipulations also resulted in consistent changes in bias measured both behaviorally and neuronally. Thus, changes in sensory encoding are sufficient to drive changes in bias measured using SDT.

neuroscience↗

bioRxiv2018

Microbiota-dependent elevation of Alcohol Dehydrogenase in Drosophila is associated with changes in alcohol-induced hyperactivity and alcohol preference

The gut microbiota impacts diverse aspects of host biology including metabolism, immunity, and behavior, but the scope of those effects and their underlying molecular mechanisms are poorly understood. To address these gaps, we used Two-dimensional Difference Gel Electrophoresis (2D-DIGE) to identify proteomic differences in male and female Drosophila heads raised with a conventional microbiota and those raised in a sterile environment (axenic). We discovered 22 microbiota-dependent protein differences, and identified a specific elevation in Alcohol Dehydrogenase (ADH) in axenic male flies. Because ADH is a key enzyme in alcohol metabolism, we asked whether physiological and behavioral responses to alcohol were altered in axenic males. Here we show that alcohol induced hyperactivity, the first response to alcohol exposure, is significantly increased in axenic males, requires ADH activity, and is modified by genetic background. While ADH activity is required, we did not detect significant microbe-dependent differences in systemic ADH activity or ethanol level. Like other animals, Drosophila exhibit a preference for ethanol consumption, and here we show significant microbiota-dependent differences in ethanol preference specifically in males. This work demonstrates that male Drosophilas association with their microbiota affects their physiological and behavioral responses to ethanol.

microbiology↗

bioRxiv2018

Geometric principles of second messenger dynamics in dendritic spines.

Dendritic spines are small, bulbous protrusions along dendrites in neurons and play a critical role in synaptic transmission. Dendritic spines come in a variety of shapes that depend on their developmental state. Additionally, roughly 14-19% of mature spines have a specialized endoplasmic reticulum called the spine apparatus. How does the shape of a postsynaptic spine and its internal organization affect the spatio-temporal dynamics of short timescale signaling? Answers to this question are central to our understanding the initiation of synaptic transmission, learning, and memory formation. In this work, we investigated the effect of spine and spine apparatus size and shape on the spatio-temporal dynamics of second messengers using mathematical modeling using reaction-diffusion equations in idealized geometries (ellipsoids, spheres, and mushroom-shaped). Our analyses and simulations showed that in the short timescale, spine size and shape coupled with the spine apparatus geometries govern the spatiotemporal dynamics of second messengers. We show that the curvature of the geometries gives rise to pseudo-harmonic functions, which predict the locations of maximum and minimum concentrations along the spine head. Furthermore, we showed that the lifetime of the concentration gradient can be fine-tuned by localization of fluxes on the spine head and varying the relative curvatures and distances between the spine apparatus and the spine head. Thus, we have identified several key geometric determinants of how the spine head and spine apparatus may regulate the short timescale chemical dynamics of small molecules that control synaptic plasticity.

biophysics↗

bioRxiv2018

Association study of long-term kidney transplant rejection using whole-exome sequencing

Long-term renal allograft rejection is the most common outcome in kidney transplantation. Continuing the crusade to extend allograft function after the first year post-transplantation, we attempted to associate genetic factors that might contribute to long-term allograft outcomes by sequencing the exomes of patients diagnosed with chronic allograft nephropathy/interstitial fibrosis and tubular atrophy. A variety of association analyses were employed, but these analyses failed to identify statistically significant associations. The study was underpowered to detect the association of rare genomic variants with small effect sizes. However, it confirmed previous reports of the absence of large effects from common variants. We have made both the study data and analysis workflow available for public use, and we hope that these resources will help to power future meta-analyses that may detect smaller effects.

genetics↗