bluuebunny/crossref_metadata_2025_split huggingface dataset:
Road and landscape-context impacts on bird pollination in a Mediterranean-type shrubland of the southeastern Cape Floristic Region
Authors: Grobler B. Adriaan , Campbell Eileen. E. 
Published: October 2019

AbstractRoad verges can provide important habitats for plants, especially in transformed landscapes. However, roads and their associated traffic have several adverse impacts on ecosystems that can disrupt vital ecological processes, including pollination. In transformed landscapes, road effects on pollination might be complemented by impacts of large-scale habitat modification. In these landscapes, road verge populations of plants that rely on pollinators for pollen transfer could thus be at risk of pollination failure. This study investigates the pollination of a reseeding, bird-pollinated shrub,Erica glandulosa, in road verges of a fragmented and transformed rural landscape in the southeastern Cape Floristic Region. We test for road impacts on pollination by comparing number of ruptured anther rings—a proxy for pollination—in fynbos vegetation fragments at different distances from the road (0–10, 20–30 and 40–50 m). We also test whether different land-cover types (intact fynbos, alien thickets and rangelands/pastures) next to road verges influence the number of ruptured anther rings. After controlling for robbing rate and plant density, fewer flowers were pollinated near the road than farther away, and fewer flowers were pollinated where road verges occurred next to alien thickets or pastures/rangelands compared to intact fynbos. However, bird pollination was not excluded in road verges: on average, ca. 20–30% of flowers were still visited by birds near the road. These findings potentially call into question the suitability of road verges as refugia for seed-dependent, bird-pollinated plant species in transformed landscapes.
Blood-brain barrier transport using a high-affinity, brain-selective VNAR (Variable Domain of New Antigen Receptor) antibody targeting transferrin receptor 1
Authors: Stocki Pawel , Szary Jaroslaw , Rasmussen Charlotte LM , Demydchuk Mykhaylo , Northall Leandra , Logan Diana Bahu , Gauhar Aziz , Thei Laura , Moos Torben , Walsh Frank S , Rutkowski J Lynn 
Published: October 2019

ABSTRACTTransfer across the blood-brain barrier (BBB) remains a significant hurdle for the development of biopharmaceuticals with therapeutic effects within the central nervous system. We established a functional selection method to identify high-affinity single domain antibodies to the transferrin receptor 1 (TfR1) with efficient biotherapeutic delivery across the BBB.MethodsA synthetic phage display library based on the variable domain of new antigen receptor (VNAR) was used forin vitroselection against recombinant human TfR1 ectodomain (rh-TfR1-ECD) followed byin vivoselection in mouse for brain parenchyma penetrating antibodies. Phage formatted VNARs cross-reactive to recombinant human and mouse TfR1-ECD were fused to Fc domain of human IgG1 (hFc) and tested for TfR1-ECD binding by ELISA and surface plasmon resonance. The pharmacokinetics and biodistribution of VNAR-hFcs were studied in mice by ELISA and immunolabeling following intravenous (IV) injection and cardiac perfusion. Functional activity was measured by body temperature reduction following the IV injection of neurotensin fused to a TXB2-hFc (TXB2-hFc-NT).ResultsTXB2 was identified as a high-affinity, species cross-reactive VNAR antibody against TfR1-ECD, that does not to compete with transferrin or ferritin for receptor binding. IV dosing of TXB2-hFc at 25 nmol/kg (1.875 mg/kg) in mice resulted in rapid binding to brain capillaries with subsequent transport into the brain parenchyma and specific uptake into TfR1-positive neurons. Likewise, IV dosing of TXB2-hFc-NT at 25 nmol/kg resulted in a rapid and reversible pharmacological response as measured by body temperature reduction. TXB2-hFc did not elicit any acute adverse reactions, bind or deplete circulating reticulocytes or reduce BBB-expressed endogenous TfR1 in mice. There was no evidence of target-mediated clearance or accumulation in peripheral organs except lung.ConclusionsA species cross-reactive and brain-selective VNAR antibody to TfR1 was identified by a combination ofin vitroandin vivophage selection. As a high-affinity, bivalent Fc fusion protein, TXB2 rapidly crossed the BBB and exhibited a favorable pharmacokinetic and safety profile and can be readily adapted to carry a wide variety of biotherapeutics from blood to brain.
The effects of sex on extinction dynamics and evolutionary rescue ofChlamydomonas reinhardtiidepend on the rate of environmental change
Authors: Petkovic Nikola , Colegrave Nick 
Published: October 2019

AbstractThe continued existence of sex despite many costs it entails still lacks an adequate explanation. Previous experimental studies demonstrated that sex enhances the rate of adaptation in changing environments. To the best of our knowledge, no experimental study that investigated the effects of sex on adaptation has manipulated the rate of environmental change, which is negatively correlated with the probability of population survival. Since the patterns of adaptation (adaptive walk) depend on the rate of environmental change, the overall effects of sex may also be altered by this factor.To investigate the interplay of sex and the rate of environmental deterioration, we carried out a long-term selection experiment with a unicellular alga (Chlamydomonas reinhardtii), by manipulating mode of reproduction (asexual or sexual populations) and the rate of environmental deterioration (an increase of salt concentration). We monitored both the population size and extinction dynamics and estimated the probability of evolutionary rescue.We detected a faster decline of population size in the asexual group relative to both the obligate sexual and facultative sexual group, irrespective of the rate of environmental deterioration. The results revealed significant interaction between mode of reproduction and the rate of environmental deterioration on extinction rate of experimental populations. Obligate sexual reproduction was advantageous under the intermediate rate of environmental deterioration, while facultative sexuality was favoured under the high rate of environmental deterioration. The populations within the obligate sexual group were most likely to adapt to grow in conditions lethal for the ancestral populations, irrespective of the rate of environmental deterioration.To the best of our knowledge, this is the first study which indicates that different modes of sexual reproduction will be beneficial (slower extinction rate) at different rates of environmental deterioration and that obligate sexuality maximizes the probability of adaptation irrespective of the rate of environmental deterioration.
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

ABSTRACTThe 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

AbstractBlood-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

ABSTRACTHeterochromatin 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.
Application of the Hierarchical Bootstrap to Multi-Level Data in Neuroscience
Authors: Saravanan Varun , Berman Gordon J. , Sober Samuel J. 
Published: October 2019

AbstractA 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

AbstractShoot 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

AbstractViruses 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

AbstractMethyl-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

AbstractPooled 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

ABSTRACTThe 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

ABSTRACTIntroductionEvidence 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.MethodsSummary 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.ResultsGenetically 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).DiscussionThe 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

SummaryRetinal 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.