bluuebunny/crossref_metadata_2025 huggingface dataset:
Parallel and scalable workflow for the analysis of Oxford Nanopore direct RNA sequencing datasets
Authors: Cozzuto Luca , Liu Huanle , Pryszcz Leszek P. , Pulido Toni Hermoso , Ponomarenko Julia , Novoa Eva Maria
Published: October 2019

The direct RNA sequencing platform offered by Oxford Nanopore Technologies allows for direct measurement of RNA molecules without the need of conversion to complementary DNA, fragmentation or amplification. As such, it is virtually capable of detecting any given RNA modification present in the molecule that is being sequenced, as well as provide polyA tail length estimations at the level of individual RNA molecules. Although this technology has been publicly available since 2017, the complexity of the raw Nanopore data, together with the lack of systematic and reproducible pipelines, have greatly hindered the access of this technology to the general user. Here we address this problem by providing a fully benchmarked workflow for the analysis of direct RNA sequencing reads, termed MasterOfPores. The pipeline converts raw current intensities into multiple types of processed data, providing metrics of the quality of the run, quality-filtering, base-calling and mapping. The output of the pipeline can in turn be used to compute per-gene counts, RNA modifications, and prediction of polyA tail length and RNA isoforms. The software is written using the NextFlow framework for parallelization and portability, and relies on Linux containers such as Docker and Singularity for achieving better reproducibility. The MasterOfPores workflow can be executed on any Unix-compatible OS on a computer, cluster or cloud without the need of installing any additional software or dependencies, and is freely available in Github (https://github.com/biocorecrg/master_of_pores). This workflow will significantly simplify the analysis of nanopore direct RNA sequencing data by non-bioinformatics experts, thus boosting the understanding of the (epi)transcriptome with single molecule resolution.
20-hydroxyecdysone (20E) primes innate immune responses that limit bacteria and malaria parasite survival in Anopheles gambiae
Authors: Reynolds Rebekah A. , Kwon Hyeogsun , Smith Ryan C.
Published: October 2019

Blood-feeding is an integral behavior of mosquitoes to acquire nutritional resources needed for reproduction. This requirement also enables mosquitoes to serve as efficient vectors to acquire and potentially transmit a multitude of mosquito-borne diseases, most notably malaria. Recent studies suggest that mosquito immunity is stimulated following a blood meal, independent of infection status. Since blood-feeding results in the increased production of the hormone 20-hydroxyecdysone (20E), we hypothesized that 20E may play an important role in priming the immune response for pathogen challenge. Herein, we examine the immunological effects of priming in Anopheles gambiae with 20E prior to pathogen infection, demonstrating a significant reduction in bacteria and Plasmodium berghei survival in the mosquito host. RNA-seq analysis following 20E treatment identifies several known 20E-regulated genes, as well as several immune genes with previously reported function in anti-pathogen defense. This includes the anti-microbial peptide cecropin 3, which we demonstrate its role as an antagonist of bacteria and Plasmodium in Anopheles gambiae and provide support that these responses are under temporal regulation. Together, these data demonstrate that 20E influences cellular immune function and anti-pathogen immunity following mosquito blood-feeding, arguing the importance of hormones in the regulation of mosquito innate immune function.
Imaging the response to DNA damage in heterochromatin domains reveals core principles of heterochromatin maintenance
Authors: Fortuny Anna , Chansard Audrey , Caron Pierre , Chevallier Odile , Leroy Olivier , Renaud Olivier , Polo Sophie E.
Published: October 2019

Heterochromatin is a critical chromatin compartment, whose integrity governs genome stability and cell fate transitions. How heterochromatin features, including higher-order chromatin folding and histone modifications associated with transcriptional silencing, are maintained following a genotoxic stress challenge is unknown. Here, we establish a system for targeting UV damage to pericentric heterochromatin in mammalian cells and for tracking the heterochromatin response to UV in real time. We uncover profound heterochromatin compaction changes during repair, orchestrated by the UV damage sensor DDB2, which stimulates linker histone displacement from chromatin. Despite massive heterochromatin unfolding, heterochromatin-specific histone modifications and transcriptional silencing are maintained. We unveil a central role for the methyltransferase SETDB1 in the maintenance of heterochromatic histone marks after UV, SETDB1 coordinating histone methylation with new histone deposition in damaged heterochromatin, thus protecting cells from genome instability. Our data shed light on fundamental molecular mechanisms safeguarding higher-order chromatin integrity following DNA damage.
Genomic duplications shaped current retrotransposon position distribution in human
Authors: Riba Andrea , Fumagalli Maria Rita , Caselle Michele , Osella Matteo
Published: October 2019

Retrotransposons, DNA sequences capable of creating copies of themselves, compose about half of the human genome and played a central role in the evolution of mammals. Their current position in the host genome is the result of the retrotranscription process and of the following host genome evolution. We apply a model from statistical physics to show that the genomic distribution of the two most populated classes of retrotransposons in human deviates from random placement, and that this deviation increases with time. The time dependence suggests a major role of the host genome dynamics in shaping the current retrotransposon distributions. In fact, these distributions can be explained by a stochastic process of random placement due to retrotranscription followed by genome expansion and sequence duplications. Besides the inherent interest in understanding the origin of current retrotransposon distributions, this work sets a general analytical framework to analyze quantitatively the effects of genome evolutionary dynamics on the distribution of genomic elements.
Application of the Hierarchical Bootstrap to Multi-Level Data in Neuroscience
Authors: Saravanan Varun , Berman Gordon J. , Sober Samuel J.
Published: October 2019

Abstract

A common feature in many neuroscience datasets is the presence of hierarchical data structures, most commonly recording the activity of multiple neurons in multiple animals across multiple trials. Accordingly, the measurements constituting the dataset are not independent, even though the traditional statistical analyses often applied in such cases (e.g. Student’s t-test) treat them as such. The hierarchical bootstrap has been shown to be an effective tool to accurately analyze such data and while it has been used extensively in the statistical literature, its use is not widespread in neuroscience - despite the ubiquity of hierarchical datasets. In this paper, we illustrate the intuitiveness and utility of this approach to analyze hierarchically nested datasets. We use simulated neural data to show that traditional statistical tests can result in a false positive rate of over 45%, even if the Type-I error rate is set at 5%. While summarizing data across non-independent points (or lower levels) can potentially fix this problem, this approach greatly reduces the statistical power of the analysis. The hierarchical bootstrap, when applied sequentially over the levels of the hierarchical structure, keeps the Type-I error rate within the intended bound and retains more statistical power than summarizing methods. We conclude by demonstrating the effectiveness of the method in two real-world examples, first analyzing singing data in male Bengalese finches (Lonchura striatavar.domestica) and second quantifying changes in behavior under optogenetic control in flies (Drosophila melanogaster).
Local auxin biosynthesis promotes shoot patterning and stem cell differentiation in Arabidopsis shoot apex
Authors: Yadav Shalini , Kumar Harish , Yadav Ram Kishor
Published: October 2019

Shoot apical meristem (SAM) of higher plants is comprises of three distinct functional zones. Central zone (CZ) is placed at the meristem summit and harbors pluripotent stem cells. Stem cells undergoes cell division within the CZ and give rise descendants which enters into the surrounding peripheral zone (PZ), where they get recruited into organs. Stem cell daughters that get pushed underneath the CZ form rib meristem (RM). RM cells differentiate into stem tissue and vascular bundles. Understanding how stem cell daughters differentiate into PZ and RM cell types is essential to unravel the mechanism of meristem development in higher plants. Here, we show that meristem patterning and lateral organ primordia formation, besides intercellular transport, are also regulated by auxin biosynthesis mediated by two closely related genes belonging toTRYPTOPHAN AMINOTRANSFERASEfamily. In Arabidopsis SAM,TAA1andTAR2are required to maintain auxin responses and identity of PZ cell types. Furthermore, our genetic analysis shows that in the absence of local auxin production and transport differentiation of stem cells into PZ and RM cell types is stalled causing a complete arrest of shoot growth and development. Our study revealed that auxin biosynthesis and transport together control the patterning of SAM into PZ and RM cell types.
Infectious bronchitis virus regulates cellular stress granule signaling
Authors: Brownsword Matthew J. , Doyle Nicole , Brocard Michèle , Locker Nicolas , Maier Helena J.
Published: October 2019

Viruses must hijack cellular translation machinery to efficiently express viral genes. In many cases, this is impeded by cellular stress responses. These stress responses swiftly relocate and repurpose translation machinery, resulting in global inhibition of translation and the aggregation of stalled 48S mRNPs into cytoplasmic foci called stress granules. This results in translational silencing of all mRNAs excluding those beneficial for the cell to resolve the specific stress. For example, expression of antiviral factors is maintained during viral infection. Here we investigated stress granule regulation by Gammacoronavirus infectious bronchitis virus (IBV), which causes the economically important poultry disease, infectious bronchitis. Interestingly, we found that IBV is able to inhibit multiple cellular stress granule signaling pathways whilst at the same time IBV replication also results in induction of seemingly canonical stress granules in a proportion of infected cells. Moreover, IBV infection uncouples translational repression and stress granule formation and both processes are independent of eIF2α phosphorylation. These results provide novel insights into how IBV modulates cellular translation and antiviral stress signaling.
Methyl-CpG2-binding protein 2 mediates overlapping mechanisms across brain disorders
Authors: Bach Snow , Ryan Niamh M. , Guasoni Paolo , Corvin Aiden , Tropea Daniela
Published: October 2019

Methyl-CpG binding protein 2 (MeCP2) is a chromatin-binding protein and a modulator of gene expression. Initially identified as an oncogene, MECP2 is now mostly associated to Rett Syndrome, a neurodevelopmental condition, though there is evidence of its influence in other brain disorders.

We design a procedure that considers several binding properties of MeCP2 and we screen for potential targets across neurological and neuropsychiatric conditions.

We find MeCP2 target genes associated to a range of disorders, including - among others-Alzheimer Disease, Autism, Attention Deficit Hyperactivity Disorder and Multiple Sclerosis. The analysis of biological mechanisms and pathways modulated by MeCP2’s target genes shows that such mechanisms are involved in three main processes: neuronal transmission, immuno-reactivity and development.

These results suggest that similar symptoms present in different pathologies have a common molecular basis, and that treatments for one condition have potential applications to related disorders.
MAUDE: Inferring expression changes in sorting-based CRISPR screens
Authors: de Boer Carl G. , Ray John P. , Hacohen Nir , Regev Aviv
Published: October 2019

Pooled CRISPR screens allow high-throughput interrogation of genetic elements that alter expression of a reporter gene readout. New computational methods are needed to model these data. We created MAUDE (Mean Alterations Using Discrete Expression) for quantifying the impact of guide RNAs on a target gene’s expression in a pooled, sorting-based expression screen. MAUDE quantifies guide-level effects by modeling the distribution of cells across sorting expression bins. It then combines guides to estimate the statistical significance and effect size of targeted genetic elements. We show that MAUDE significantly improves over previous approaches and provide experimental design guidelines to best leverage MAUDE.
The N-terminal domain of Eukaryotic Initiation Factor 4B Drives Yeast Translational Control in Response to Urea
Authors: Liu Xiaozhuo , Moshiri Houtan , He Qian , Sahoo Ansuman , Walker Sarah
Published: October 2019

The yeast eukaryotic initiation factor 4B binds the 40S subunit in translation preinitiation complexes (PICs), promoting mRNA binding. Recent evidence suggests mRNAs have variable dependence on eIF4B, suggesting this factor could promote changes in mRNA selection for translation, in order to adapt to stressors. However, the importance of eIF4B and its constituent domains for mRNA selection under diverse cellular and environmental conditions remain undefined. Here we compared the effects of disrupting eIF4B RNA- and ribosome-binding motifs under ~1400 growth conditions. The RNA-Recognition Motif (RRM) was dispensable for stress responses, but the 40S-binding N-terminal Domain (NTD) promoted growth in response to various stressors. In particular, the NTD conferred a strong growth advantage in the presence of urea. Ribosome profiling revealed that the NTD promoted translation of mRNAs with long and highly structured 5-prime untranslated regions, both with and without urea exposure. Our results suggest eIF4B controls mRNA loading and scanning as a part of the PIC, rather than by activating mRNPs prior to ribosome binding. Furthermore, our data indicate the yeast response to urea includes a translational component, driven by production of proteins associated with the cellular periphery. Together our analyses suggest general eIFs can promote diverse cellular responses.
Physical activity and risk of Alzheimer’s disease: a two-sample Mendelian randomization study
Authors: Baumeister Sebastian E , Karch André , Bahls Martin , Teumer Alexander , Leitzmann Michael F , Baurecht Hansjörg
Published: October 2019

Introduction

Evidence from observational studies for the effect of physical activity on the risk of Alzheimer’s disease (AD) is inconclusive. We performed Mendelian randomization analysis to examine whether physical activity is a protective factor for AD.

Methods

Summary data of genome-wide association studies on physical activity and AD were identified using PubMed and the GWAS catalog. The study population included 21,982 AD cases and 41,944 cognitively normal controls. Eight single nucleotide polymorphisms (SNP) known at P < 5×10−8 to be associated with accelerometer-assessed physical activity served as instrumental variables.

Results

Genetically predicted accelerometer-assessed physical activity had no effect on the risk of AD (inverse variance weighted odds ratio [OR] per standard deviation (SD) increment: 1.03, 95% confidence interval: 0.97-1.10, P=0.332).

Discussion

The present study does not support a relationship between physical activity and risk of AD, and suggests that previous observational studies might have been biased.
Retinal ganglion cells harboring the OPTN(E50K) mutation exhibit neurodegenerative phenotypes when derived from hPSC-derived three dimensional retinal organoids
Authors: VanderWall KB , Huang KC , Pan Y , Lavekar SS , Fligor CM , Allsop A , Lentsch K , Dang P , Zhang C , Tseng HC , Cummins TR , Meyer JS
Published: October 2019

Retinal ganglion cells (RGCs) serve as the primary connection between the eye and the brain, with this connection disrupted in glaucoma. Numerous cellular mechanisms have been associated with glaucomatous neurodegeneration, and useful models of glaucoma allow for the precise analysis of degenerative phenotypes. Human pluripotent stem cells (hPSCs) serve as powerful tools for studying human neurodegenerative diseases, particularly cellular mechanisms underlying degeneration. Thus, efforts were initially focused upon the use of hPSCs with an E50K mutation in the Optineurin (OPTN) gene. CRISPR/Cas9 gene editing was used to introduce the OPTN(E50K) mutation into existing lines of hPSCs, as well as the generation of isogenic control lines from OPTN(E50K) patient-derived hPSC lines. OPTN(E50K) RGCs exhibited numerous neurodegenerative deficits, including neurite retraction, autophagy dysfunction, apoptosis, and increased excitability. The results of this study provide an extensive analysis of the OPTN(E50K) mutation in hPSC-derived RGCs, with the opportunity to develop novel treatments for glaucoma.
Staufen 1 amplifies pro-apoptotic activation of the unfolded protein response
Authors: Gandelman Mandi , Dansithong Warunee , Figueroa Karla P , Paul Sharan , Scoles Daniel R , Pulst Stefan M
Published: October 2019

Staufen-1 (STAU1) is an RNA binding protein that becomes highly overabundant in numerous neurodegenerative disease models, including those carrying mutations in presenilin1 (PSEN1), microtubule associated protein tau (MAPT), huntingtin (HTT), TAR DNA-binding protein-43 gene (TARDBP) or C9orf72. We previously reported that elevations in STAU1 determine autophagy defects. Additional functional consequences of STAU1 overabundance, however, have not been investigated. We studied the role of STAU1 in the chronic activation of the Unfolded Protein Response (UPR), a common feature among the neurodegenerative diseases where STAU1 is increased, and is directly associated with neuronal death. Here we report that STAU1 is a novel modulator of the UPR, and is required for apoptosis induced by activation of the PERK-CHOP pathway. STAU1 levels increased in response to multiple ER stressors and exogenous expression of STAU1 was sufficient to cause apoptosis through the PERK-CHOP pathway of the UPR. Cortical neurons and skin fibroblasts derived from Stau1−/− mice showed reduced UPR and apoptosis when challenged with thapsigargin. In fibroblasts from SCA2 patients or with ALS-causing TDP-43 and C9ORF72 mutations we found highly increased STAU1 and CHOP levels in basal conditions. STAU1 knockdown restored CHOP levels to normal. Taken together, these results show STAU1 overabundance reduces cellular resistance to ER stress and precipitates apoptosis.
On the heterozygosity of an admixed population
Authors: Boca Simina M. , Huang Lucy , Rosenberg Noah A.
Published: October 2019

A population is termedadmixedif its members possess recent ancestry from two or more separate sources. As a result of the fusion of source populations with different genetic variants, admixed populations can exhibit high levels of genetic variation, reflecting contributions of their multiple ancestral groups. For a model of an admixed population derived fromKsource groups, we obtain a relationship between its level of genetic variation, as measured by heterozygosity, and its proportions of admixture from the various source populations. We show that the heterozygosity of the admixed population is at least as great as that of the least heterozygous source population, and that it potentially exceeds the heterozygosities ofallof the source populations. The admixture proportions that maximize the heterozygosity possible for an admixed population formed from a specified set of source populations are also obtained under specific conditions. We examine the special case ofK= 2 source populations in detail, characterizing the maximal admixture in terms of the heterozygosities of the two source populations and the value ofFSTbetween them. In this case, the heterozygosity of the admixed population exceeds the maximal heterozygosity of the source groups if the divergence between them, measured byFST, is large enough, namely above a certain bound that is a function of the heterozygosities of the source groups. We present applications to simulated data as well as to data from human admixture scenarios, providing results useful for interpreting the properties of genetic variability in admixed populations.
C-terminal binding proteins 1 and 2 in traumatic brain injury-induced inflammation and their inhibition as an approach for anti-inflammatory treatment
Authors: Li Hong , Zhang Caiguo , Yang Chunxia , Blevins Melanie , Norris David , Zhao Rui , Huang Mingxia
Published: October 2019

Traumatic brain injury (TBI) induces an acute inflammatory response in the central nervous system that involves both resident and peripheral immune cells. The ensuing chronic neuroinflammation causes cell death and tissue damage and may contribute to neurodegeneration. The molecular mechanisms involved in the maintenance of this chronic inflammation state remain underexplored. C-terminal binding protein (CtBP) 1 and 2 are transcriptional coregulators that repress diverse cellular processes. Unexpectedly, we find that the CtBPs can transactivate a common set of proinflammatory genes both in lipopolysaccharide-activated microglia, astrocytes and macrophages, and in a mouse model of the mild form of TBI. We also find that the expression of these genes is markedly enhanced by a single mild injury in both brain and peripheral blood leukocytes in a severity- and time-dependent manner. Moreover, we were able to demonstrate that specific inhibitors of the CtBPs effectively suppress the expression of the CtBP target genes and thus improve neurological outcome in mice receiving single and repeated mild TBIs. This discovery suggests new avenues for therapeutic modulation of the inflammatory response to brain injury.
Integration of ethnobotany and population genetics uncovers the agrobiodiversity of date palms of Siwa Oasis (Egypt) and their importance to the evolutionary history of the species
Authors: Gros-Balthazard Muriel , Battesti Vincent , Ivorra Sarah , Paradis Laure , Aberlenc Frédérique , Zango Oumarou , Zehdi Salwa , Moussouni Souhila , Naqvi Summar Abbas , Newton Claire , Terral Jean-Frédéric
Published: October 2019

Crop diversity is shaped by biological and social processes interacting at different spatiotemporal scales. Here we combined population genetics and ethnobotany to investigate date palm (Phoenix dactyliferaL.) diversity in Siwa Oasis, Egypt. Based on interviews with farmers and observation of practices in the field, we collected 149 date palms from Siwa Oasis and 27 uncultivated date palms from abandoned oases in the surrounding desert. Using genotyping data from 18 nuclear and plastid microsatellite loci, we confirmed that some named types each constitute a clonal line, i.e. a true-to-type cultivar. We also found that others are collections of clonal lines, i.e. ethnovarieties, or even unrelated samples, i.e. local categories. This alters current assessments of agrobiodiversity, which are visibly underestimated, and uncovers the impact of low-intensity, but highly effective, farming practices on biodiversity. These hardly observable practices, hypothesized by ethnographic survey and confirmed by genetic analysis, are enabled by the way Isiwans conceive and classify living beings in their oasis, which do not quite match the way biologists do: a classic disparity ofeticvs.emiccategorizations. In addition, we established that Siwa date palms represent a unique and highly diverse genetic cluster, rather than a subset of North African and Middle Eastern palm diversity. As previously shown, North African date palms display evidence of introgression by the wild relativePhoenix theophrasti, and we found that the uncultivated date palms from the abandoned oases share even more alleles with this species than cultivated palms in this region. The study of Siwa date palms could hence be a key to the understanding of date palm diversification in North Africa. Integration of ethnography and population genetics promoted the understanding of the interplay between diversity management in the oasis (short-time scale), and the origins and dynamic of diversity through domestication and diversification (long-time scale).
annonex2embl: automatic preparation of annotated DNA sequences for bulk submissions to ENA
Authors: Gruenstaeudl Michael
Published: October 2019

Motivation

The submission of annotated sequence data to public sequence databases constitutes a central pillar in biological research. The surge of novel DNA sequences awaiting database submission due to the application of next-generation sequencing has increased the need for software tools that facilitate bulk submissions. This need has yet to be met with a concurrent development of tools to automate the preparatory work preceding such submissions.

Results

I introduceannonex2embl, a Python package that automates the preparation of complete sequence flatfiles for large-scale sequence submissions to the European Nucleotide Archive. The tool enables the conversion of DNA sequence alignments that are co-supplied with sequence annotations and metadata to submission-ready flatfiles. Among other features, the software automatically accounts for length differences among the input sequences while maintaining correct annotations, automatically interlaces metadata to each record, and displays a design suitable for easy integration into bioinformatic workflows. As proof of its utility,annonex2emblis employed in preparing a dataset of more than 1,500 fungal DNA sequences for database submission.
Low atmospheric CO2 levels induce nocturnal carbon accumulation in the lycophyte genus Isoëtes
Authors: Suissa Jacob S. , Green Walton A.
Published: October 2019

Background and Aims

Crassulacean Acid Metabolism (CAM) is an adaptation to increase water use efficiency in dry environments. Oddly, similar biochemical patterns occur in the submerged aquatic lycophyte genus Isoëtes. It has long been assumed that CAM-like nocturnal carbon accumulation in aquatic plants is an adaptation to low daytime carbon levels in aquatic ecosystems, but this has never been directly tested.

Methods

To test this hypothesis, populations of terrestrial Isoëtes engelmannii and I. tuckermanii were grown in climate-controlled chambers and starved of atmospheric CO2 during the day while pH was measured for 24-hours.

Key results

We demonstrate that terrestrial plants exposed to low atmospheric CO2 display diel acidity cycles similar to those in both xerophytic CAM plants and submerged Isoëtes.

Conclusions

CO2 starvation induces CAM-like nocturnal carbon accumulation in terrestrial Isoëtes, substantiating the hypothesis that carbon starvation is a selective pressure for nocturnal carbon accumulation in Isoëtes. Furthermore, while aquatic carbon levels undoubtedly promote nocturnal carbon accumulation in extant Isoëtes, the induction of this behavior in terrestrial plants suggests a possible earlier terrestrial evolution of this metabolism in Isoetalean ancestors in response to low atmospheric CO2 levels. We both provide support for a long-standing assumption about nocturnal carbon accumulation Isoëtes as well as suggest an earlier evolution of this behavior.
High-resolution in vivo identification of miRNA targets by Halo-Enhanced Ago2 Pulldown
Authors: Li Xiaoyi , Pritykin Yuri , Concepcion Carla P. , Lu Yuheng , Rocca Gaspare La , Zhang Minsi , Cook Peter J. , Au Yu Wah , Popow Olesja , Paulo Joao A. , Otis Hannah G. , Mastroleo Chiara , Ogrodowski Paul , Schreiner Ryan , Haigis Kevin M. , Betel Doron , Leslie Christina S. , Ventura Andrea
Published: October 2019

The identification of miRNA targets by Ago2 crosslinking-immunoprecipitation (CLIP) methods has provided major insights into the biology of this important class of non-coding RNAs. However, these methods are technically challenging and not easily translated to an in vivo setting. To overcome these limitations and to facilitate the investigation of miRNA functions in mice, we have developed a method (HEAP: for Halo-Enhanced Ago2 Pulldown) to map miRNA-mRNA binding sites. This method is based on a novel genetically engineered mouse harboring a conditional, Cre-regulated, Halo-Ago2 allele expressed from the endogenous Ago2 locus. By using a resin conjugated to the HaloTag ligand, Ago2-miRNA-mRNA complexes can be efficiently purified from cells and tissues expressing the endogenous Halo-Ago2 allele. We demonstrate the reproducibility and sensitivity of this method in mouse embryonic stem cells, in developing embryos, in adult tissues and in autochthonous mouse models of human brain and lung cancers.

The tools and the datasets we have generated will serve as a valuable resource to the scientific community and will facilitate the characterization of miRNA functions under physiological and pathological conditions.
Adaptive Spike-Artifact Removal from Local Field Potentials Uncovers Prominent Beta and Gamma Band Neuronal Synchronization
Authors: Boroujeni Kianoush Banaie , Tiesinga Paul , Womelsdorf Thilo
Published: October 2019

Background

Many neurons synchronize their action potentials to the phase of local field potential (LFP) fluctuations in one or more frequency bands. Analyzing this spike-to-LFP synchronization is challenging, however, when neural spikes and LFP are generated in the same local circuit, because the spike’s action potential waveform leak into the LFP and distort phase synchrony estimates. Existing approaches to address this spike bleed-through artifact relied on removing the average action potential waveforms of neurons, but this leaves artifacts in the LFP and distorts synchrony estimates.

New Method

We describe a spike-removal method that surpasses these limitations by decomposing individual action potentials into their frequency components before their removal from the LFP. The adaptively estimated frequency components allow for variable spread, strength and temporal variation of the spike artifact.

Results

This adaptive approach effectively removes spike bleed-through artifacts in synthetic data with known ground truth, and in single neuron and LFP recordings in nonhuman primate striatum. For a large population of neurons with both narrow and broad action potential waveforms, the use of adaptive artifact removal uncovered 20-35 Hz beta and 35-45 Hz gamma band spike-LFP synchronization that would have remained contaminated otherwise.

Comparison with Existing Methods

We demonstrate that adaptive spike-artifact removal cleans LFP data that remained contaminated when applying existing Bayesian and non-Bayesian methods of average spike-artifact removal.

Conclusions

Applying adaptive spike-removal from field potentials allows to estimate the phase at which neurons synchronize and the consistency of their phase-locked firing for both beta and low gamma frequencies. These metrics may prove essential to understand cell-to-circuit neuronal interactions in multiple brain systems.
A comprehensive conceptual and computational dynamics framework for Autonomous Regeneration Systems
Authors: Minh-Thai Tran Nguyen , Samarasinghe Sandhya , Levin Michael
Published: October 2019

This paper presents a new conceptual and computational dynamics framework for damage detection and regeneration in multicellular structures similar to living animals. The model uniquely achieves complete and accurate regeneration from any damage anywhere in the system. We demonstrated the efficacy of the proposed framework on an artificial organism consisting of three tissue structures corresponding to the head, body and tail of a worm. Each structure consists of a stem cell surrounded by a tissue of differentiated cells. We represent a tissue as an Auto-Associative Neural Network (AANN) with local interactions and stem cells as a self-repair network with long-range interactions. We also propose another new concept, Information Field which is a mathematical abstraction over traditional components of tissues, to keep minimum pattern information of the tissue structures to be accessed by stem cells in extreme cases of damage. Through entropy, a measure of communication between a stem cell and differentiated cells, stem cells monitor the tissue pattern integrity, violation of which triggers damage detection and tissue repair. Stem cell network monitors its state and invokes stem cell repair in the case of stem cell damage. The model accomplishes regeneration at two levels: In the first level, damaged tissues with intact stem cells regenerate themselves. Here, stem cell identifies entropy change and finds the damage and regenerates the tissue in collaboration with the AANN. In the second level, involving missing whole tissues and stem cells, the remaining stem cell(s) access the information field to restore the stem cell network and regenerate missing tissues. In the case of partial tissue damage with missing stem cells, the two levels collaborate to accurately restore the stem cell network and tissues. This comprehensive hypothetical framework offers a new way to conceptualise regeneration for better understanding the regeneration processes in living systems. It could also be useful in biology for regenerative medicine and in engineering for building self-repairing biobots.
Sea foams are ephemeral hotspots for distinctive bacterial communities contrasting sea-surface microlayer and underlying surface water
Authors: Rahlff Janina , Stolle Christian , Giebel Helge-Ansgar , Mustaffa Nur Ili Hamizah , Wurl Oliver , Herlemann Daniel P. R.
Published: October 2019

The occurrence of foams at oceans’ surfaces is patchy and generally short-lived but a detailed understanding of bacterial communities inhabiting sea foams is lacking. Here we investigated how marine foams differ from the sea-surface microlayer (SML), a <1 mm thick layer at the air-sea interface and underlying water from 1 m depth. Samples of sea foams, SML and underlying water collected from the North Sea and Timor Sea indicated that foams were often characterized by a high abundance of small eukaryotic phototrophic and prokaryotic cells as well as a high concentration of surface-active substances (SAS). Amplicon sequencing of 16S rRNA (gene) revealed a distinctive foam bacterial community compared to SML and underlying water, with high abundance of Gammaproteobacteria. Especially Pseudoalteromonas and Vibrio, typical SML dwellers, were highly abundant, active foam inhabitants and thus might enhance foam formation and stability by producing SAS. Despite a clear difference in the overall bacterial community composition between foam and SML, the presence of SML bacteria in foams supports previous assumptions that foam is strongly influenced by the SML. We conclude that active and abundant bacteria from interfacial habitats potentially contribute to foam formation and stability, carbon cycling and air-sea exchange processes in the ocean.

One-sentence summary

Floating foams at the oceans’ surface have a unique bacterial community signature in contrast to sea-surface microlayer and underlying water but receive and select for bacterial inhabitants from surface habitats.
Heliconiusbutterflies host characteristic and phylogenetically structured adult-stage microbiomes
Authors: Hammer Tobin J. , Dickerson Jacob C. , McMillan W. Owen , Fierer Noah
Published: October 2019

Lepidoptera (butterflies and moths) are diverse and ecologically important, yet we know little about how they interact with microbes as adults. Due to metamorphosis, the form and function of their adult-stage microbiomes might be very different from microbiomes in the larval stage (caterpillars). We studied adult-stage microbiomes ofHeliconiusand closely related passion-vine butterflies (Heliconiini), which are an important model system in evolutionary biology. To characterize the structure and dynamics of heliconiine microbiomes, we used field collections of wild butterflies, 16S rRNA gene sequencing, quantitative PCR, and shotgun metagenomics. We found thatHeliconiusharbor simple and abundant bacterial communities that are moderately consistent among conspecific individuals and over time. Heliconiine microbiomes also exhibited a strong signal of host phylogeny, with a major distinction betweenHeliconiusand other butterflies. These patterns were largely driven by differing relative abundances of bacterial phylotypes shared among host species and genera, as opposed to the presence or absence of host-specific phylotypes. We suggest that phylogenetic structure in heliconiine microbiomes arises from conserved host traits that differentially filter microbes from the environment. While the relative importance of different traits remains unclear, our data indicate that pollen-feeding (unique toHeliconius) is not a primary driver. Using shotgun metagenomics, we also discovered trypanosomatids and microsporidia to be prevalent in butterfly guts, raising the possibility of antagonistic interactions between eukaryotic parasites and co-localized gut bacteria. Our discovery of characteristic and phylogenetically structured microbiomes provides a foundation for tests of adult-stage microbiome function, a poorly understood aspect of lepidopteran biology.

Importance

Many insects host microbiomes with important ecological functions. However, the prevalence of this phenomenon is unclear, because in many insect taxa microbiomes have only been studied in part of the life cycle, if at all. A prominent example is the butterflies and moths, in which the composition and functional role of adult-stage microbiomes are largely unknown. We comprehensively characterized microbiomes in adult passion-vine butterflies. Butterfly-associated bacterial communities are generally abundant in guts, consistent within populations, and composed of taxa widely shared among hosts. More closely related butterflies harbor more similar microbiomes, with the most dramatic shift in microbiome composition occurring in tandem with a suite of ecological and life history traits unique to the genusHeliconius. Butterflies are also frequently infected with previously undescribed eukaryotic parasites, which may interact with bacteria in important ways. These findings advance our understanding of butterfly biology and of insect-microbe interactions generally.
N-linked surface glycan biosynthesis, composition, inhibition, and function in cnidarian-dinoflagellate symbiosis
Authors: Tivey Trevor R. , Parkinson John Everett , Mandelare Paige E. , Adpressa Donovon A. , Peng Wenjing , Dong Xue , Mechref Yehia , Weis Virginia M. , Loesgen Sandra
Published: October 2019

The success of symbioses between cnidarian hosts (e.g. corals and sea anemones) and micro-algal symbionts hinges on the molecular interactions that govern the establishment and maintenance of intracellular mutualisms. As a fundamental component of innate immunity, glycan-lectin interactions impact the onset of marine endosymbioses, but our understanding of the effects of cell surface glycome composition on symbiosis establishment remains limited. In this study, we examined the canonical N-glycan biosynthesis pathway in the genome of the dinoflagellate symbiontBreviolum minutum(family Symbiodiniaceae) and found it to be conserved with the exception of the transferase GlcNAc-TII (MGAT2). Using coupled liquid chromatography-mass spectrometry (LC-MS/MS), we characterized the cell surface N-glycan content ofB. minutum, providing the first insight into the molecular composition of surface glycans in dinoflagellates. We then used the biosynthesis inhibitors kifunensine and swainsonine to alter the glycan composition ofB. minutum. Successful high-mannose enrichment via kifunensine treatment resulted in a significant decrease in colonization of the model sea anemone Aiptasia (Exaiptasia pallida) byB. minutum. Hybrid glycan enrichment via swainsonine treatment, however, could not be confirmed and did not impact colonization. We conclude that functional Golgi processing of N-glycans is critical for maintaining appropriate cell surface glycan composition and for ensuring colonization success byB. minutum.
Genome wide association study reveals novel candidate genes associated with productivity and disease resistance to Moniliophthora spp. in cacao (Theobroma cacao L.)
Authors: Osorio-Guarín Jaime A. , Berdugo-Cely Jhon A. , Coronado-Silva Roberto A. , Baez Eliana , Jaimes Yeirme , Yockteng Roxana
Published: October 2019

Cacao (Theobroma cacao L.), the source of chocolate, is one the most important commodity products for farmers to improve their economic benefits. However, diseases such as frosty pod rot (FPRD) caused by Moniliophthora roreri and witches’ broom (WBD) caused by Moniliophthora perniciosa, limits the increase in yields. Molecular tools can help to develop more rapidly cacao varieties with disease resistance. In the present study, we sequenced by genotyping-by-sequencing (GBS), 229 cacao accessions to examine their genetic diversity and population structure. From those accessions, 102 have been evaluated for disease resistance and productivity to conduct a genome-wide association study (GWAS) based on 9,003 and 8,131 SNPs recovered by mapping against to the annotated cacao genomes (Criollo and Matina). Three promissory accessions for productivity and 10 accessions showing good tolerance to the evaluated diseases were found in the phenotypic evaluation. The work presented herein provides the first association mapping study in cacao using SNP markers based on GBS data. The GWAS identified two genes associated to productivity and seven to disease resistance. The results enriched the knowledge of the genetic regions associated to important traits in cacao that can have significant implications for conservation and breeding strategies such as marker-assisted selection (MAS).
Meta-analytic activation maps can help identify affective processes captured by contrast-based task fMRI: the case of threat-related facial expressions
Authors: Kim M. Justin , Knodt Annchen R. , Hariri Ahmad R.
Published: October 2019

Meta-analysis of functional magnetic resonance imaging (fMRI) data is an effective method for capturing the distributed patterns of brain activity supporting discrete cognitive and affective processes. One opportunity presented by the resulting meta-analysis maps (MAMs) is as a reference for better understanding the nature of individual contrast maps (ICMs) derived from specific task fMRI data. Here, we compared MAMs from 148 neuroimaging studies representing the broad emotion categories of fear, anger, disgust, happiness, and sadness with ICMs from fearful > neutral and angry > neutral facial expressions from an independent dataset of task fMRI (n = 1263). Analyses revealed that both fear and anger ICMs exhibited the greatest pattern similarity to fear MAMs. As the number of voxels included for the computation of pattern similarity became more selective, the specificity of MAM-ICM correspondence decreased. Notably, amygdala activity long considered critical for processing threat-related facial expressions was neither sufficient nor necessary for detecting MAM-ICM pattern similarity effects. Our analyses suggest that both fearful and angry facial expressions are best captured by distributed patterns of brain activity associated with fear. More generally, our analyses demonstrate how MAMs can be leveraged to better understand affective processes captured by ICMs in task fMRI data.
The genome of the butternut canker pathogen, Ophiognomonia clavigignenti-juglandacearum shows an elevated number of genes associated with secondary metabolism and protection from host resistance responses in comparison with other members of the Diaporthales
Authors: Wu Guangxi , Schuelke Taruna A. , Broders Kirk
Published: October 2019

Ophiognomonia clavigignentijuglandacearum (Oc-j) is a plant pathogenic fungus that causes canker and branch dieback diseases in the hardwood tree butternut, Juglans cinerea. Oc-j is a member of the order of Diaporthales, which includes many other plant pathogenic species, several of which also infect hardwood tree species. In this study, we sequenced the genome of Oc-j and achieved a high-quality assembly and delineated the phylogeny of Oc-j within the Diaporthales order using a genome-wide multi-gene approach. We also further examined multiple gene families that might be involved in plant pathogenicity and degradation of complex biomass, which are relevant to a pathogenic life-style in a tree host. We found that the Oc-j genome contains a greater number of genes in these gene families compared to other species in Diaporthales. These gene families include secreted CAZymes, kinases, cytochrome P450, efflux pumps, and secondary metabolism gene clusters. The large numbers of these genes provide Oc-j with an arsenal to cope with the specific ecological niche as a pathogen of the butternut tree.
Subthreshold psychosis symptoms associated with molecular genetic risk in a population-based cohort: Findings from Generation Scotland
Authors: Docherty A.R. , Shabalin Andrey A. , Adkins Daniel E. , Mann Frank , Krueger Robert F. , Campbell Archie , Hayward Caroline , Porteous David J. , McIntosh Andrew M. , Kendler Kenneth S.
Published: October 2019

Importance

Subthreshold psychosis symptoms in the general population may be associated with genetic risk for schizophrenia. In this analysis, empirically-derived symptom factor scores led to a detection of significant and robust polygenic signal.

Objective

This study sought to optimize genetic association with data-driven symptom factor scores, accounting for cohort factor structure and sex differences.

Design

EFA-derived symptom factor scores were regressed onto PRS for schizophrenia in models accounting for age and genetic ancestry principal components. Follow-up examination of symptom factor score associations with other related genetic risks included ADHD, autism, bipolar disorder, major depression, and neuroticism.

Participants

This study examined the newly expanded symptom dataset from the Northern European ancestry cohort, Generation Scotland: Scottish Family Health Study (N = 9,105 individuals 18-65 years of age) comprising common variant and subthreshold psychosis symptom data. A total of 5,391 females and 3,713 males with age M[SD] = 45.2 [13] were included in the final analyses.

Main Outcome and Measure

Subthreshold psychosis symptoms were measured using the Schizotypal Personality Questionnaire-Brief (SPQ-B). Primary phenotypic factor scores and genome-wide polygenic risk scores (PRS) reflected weighted sum scores and were examined as continuous measures. Polygenic risk scores were calculated from genome-wide association summary statistics using 7,358,674 imputed common genetic variants passing quality control.

Results

In males, symptom factor scores were positively associated with polygenic risk for schizophrenia alone and implicated primarily interpersonal/negative symptoms. In females, symptom factor scores were positively associated with polygenic risks for ADHD and autism but not schizophrenia. Scores were robustly associated with genetic risk for neuroticism across both males and females.

Conclusions and Relevance

This study detected a significant association of subthreshold psychosis symptoms with genetic risk for schizophrenia and neuroticism in a population-based sample. Furthermore, important sex differences suggest a need for better understanding of schizophrenia risk assessment in females.

Key Points

Question

What molecular genetic risks are associated with subthreshold psychosis symptoms in the general population?

Findings

In a large population-based cohort (N = 9,084), significant associations of polygenic risks with symptoms were observed. Symptoms were associated with genetic risk for schizophrenia in males, for ADHD and autism spectrum disorder in females, and for neuroticism across both males and females.

Meaning

Associations of genetic risk with symptoms in the general population are highly significant and suggest important sex differences.