bluuebunny/crossref_metadata_2025_split huggingface dataset:
Non-Linear Realignment Improves Hippocampus Subfield Segmentation
Authors: Shaw Thomas B , Bollmann Steffen , Atcheson Nicole T , Guo Christine , Fripp Jurgen , Salvado Olivier , Barth Markus 
Published: April 2019

AbstractParticipant movement can deleteriously affect MR image quality. Further, for the visualization and segmentation of small anatomical structures, there is a need to improve image quality, specifically signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR), by acquiring multiple anatomical scans consecutively. We aimed to ameliorate movement artefacts and increase SNR in a high-resolution turbo spin-echo (TSE) sequence acquired thrice using non-linear realignment in order to improve segmentation consistency of the hippocampus subfields. We assessed the method in young healthy participants, Motor Neurone Disease patients, and age matched controls. Results show improved image segmentation of the hippocampus subfields when comparing template-based segmentations with individual segmentations with Dice overlaps N=51;ps< 0.001 (Friedman’s test) and higher sharpnessps< 0.001 in non-linearly realigned scans as compared to linearly, and arithmetically averaged scans.
Transmission of West Nile and other temperate mosquito-borne viruses peaks at intermediate environmental temperatures
Authors: Shocket Marta S. , Verwillow Anna B. , Numazu Mailo G. , Slamani Hani , Cohen Jeremy M. , El Moustaid Fadoua , Rohr Jason , Johnson Leah R. , Mordecai Erin A. 
Published: April 2019

ABSTRACTThe temperature-dependence of many important mosquito-borne diseases has never been quantified. These relationships are critical for understanding current distributions and predicting future shifts from climate change. We used trait-based models to characterize temperature-dependent transmission of 10 vector–pathogen pairs of mosquitoes (Culex pipiens, Cx. quinquefascsiatus, Cx. tarsalis, and others) and viruses (West Nile, Eastern and Western Equine Encephalitis, St. Louis Encephalitis, Sindbis, and Rift Valley Fever viruses), most with substantial transmission in temperate regions. Transmission is optimized at intermediate temperatures (23–26°C) and often has wider thermal breadths (due to cooler lower thermal limits) compared to pathogens with predominately tropical distributions (in previous studies). The incidence of human West Nile virus cases across US counties responded unimodally to average summer temperature and peaked at 24°C, matching model-predicted optima (24–25°C). Climate warming will likely shift transmission of these diseases, increasing it in cooler locations while decreasing it in warmer locations.
Transcriptome profile of Carrizo citrange roots in response toPhytophthora parasiticainfection
Authors: Naveed Zunaira Afzal , Huguet-Tapia Jose C. , Ali Gul Shad 
Published: April 2019

AbstractPhytophthora parasiticais one of the most widespreadPhytophthoraspecies, which is known to cause root rot, foot rot/gummosis and brown rot of fruits in citrus. In this study, we have analyzed the transcriptome of a commonly used citrus rootstock Carrizo citrange in response toP. parasiticainfection using the RNA-seq technology. In total, we have identified 6692 differentially expressed transcripts (DETs) amongP. parasitica-inoculated and mock-treated roots. Of these, 3960 genes were differentially expressed at 24 hours post inoculation and 5521 genes were differentially expressed at 48 hours post inoculation. Gene ontology analysis of DETs suggested substantial transcriptional reprogramming of diverse cellular processes particularly the biotic stress response pathways in Carrizo citrange roots. ManyRgenes, transcription factors, and several other genes putatively involved in plant immunity were differentially modulated in citrus roots in response toP. parasiticainfection. Analysis reported here lays out a strong foundation for future studies aimed at improving resistance of citrus rootstocks toP. parasitica.
The effect of stress on the balance between goal-directed and habit networks in obsessive-compulsive disorder
Authors: van der Straten Anouk , van Leeuwen Wieke , Denys Damiaan , van Marle Hein , van Wingen Guido 
Published: April 2019

AbstractThe classical cognitive-behavioral theory of obsessive-compulsive disorder (OCD) holds that compulsions are performed to reduce distress that is evoked by obsessions, whereas a recent neuroscience-inspired theory suggests that compulsivity results from a disbalance between goal-directed and habit-related neural networks. To bridge these theories, we investigated whether the balance between goal-directed and habit networks in patients with OCD was affected in the late aftermath of stress. Twenty-three OCD patients and twenty-three healthy controls participated in a controlled stress induction paradigm using the socially evaluated cold-pressor test in a crossover design. Stress responses were evaluated through cortisol levels, blood pressure, and anxiety ratings. Functional connectivity of the caudate nucleus and posterior putamen was assessed using seed region analysis of resting-state functional magnetic resonance imaging data, which are hubs of the goal-directed and habit network, respectively. Stress induction increased blood pressure and psychological stress measures across groups and resulted in blunted cortisol responses in patients. Furthermore, patients showed a blunted reduction in connectivity between the caudate nucleus and precuneus in the aftermath of stress, which was positively correlated with compulsivity but not obsession severity. The posterior putamen showed no significant group differences in stress-induced connectivity. These results suggest that compulsivity in OCD in the aftermath of stress is associated with altered connectivity between the goal-directed and default mode networks.
Ageing in house sparrows is insensitive to environmental effects
Authors: Simons Mirre J. P. , Winney Isabel , Girndt Antje , Rees Mark , Nakagawa Shinichi , Schroeder Julia , Burke Terry 
Published: April 2019

AbstractVariation in individual life histories, and physiology, determines the rates at which new life is generated (reproduction) and lost (death) in a population. Studying the demography of deaths thus reveals fundamental aspects of the biology of individuals within a population. We studied mortality senescence – the increase in mortality rate with age – in wild and captive house sparrows (Passer domesticus), and demonstrate highly similar mortality senescence in both, but markedly lower vulnerability to death (frailty) in captivity. This suggests that house sparrows have a species-specific rate of ageing that is insensitive to environmental effects. Unexpectedly, juvenile and adult mortality co-varied positively across years in the wild, indicating that mortality is not strongly density-dependent. Mortality also varied widely among years, suggesting a strong environmental effect, and we explain the observed patterns using temperature data and predation by birds of prey. We discuss how stochastic environmental effects can affect the evolution of ageing.
The ELIXIR Core Data Resources: fundamental infrastructure for the life sciences
Authors: Drysdale Rachel , Cook Charles E. , Petryszak Robert , Baillie-Gerritsen Vivienne , Barlow Mary , Gasteiger Elisabeth , Gruhl Franziska , Haas Jürgen , Lanfear Jerry , Lopez Rodrigo , Redaschi Nicole , Stockinger Heinz , Teixeira Daniel , Venkatesan Aravind , Blomberg Niklas , Durinx Christine , McEntyre Johanna ,   ELIXIR Core Data Resource Forum
Published: April 2019

AbstractMotivationLife science research in academia, industry, agriculture, and the health sector depends critically on free and open data resources. ELIXIR (www.elixir-europe.org), the European Research Infrastructure for life sciences data, has identified a set of Core Data Resources within Europe that are of most fundamental importance for the long-term preservation of biological data. We explore characteristics of their usage, impact and assured funding horizon to assess their value and importance as an infrastructure, to understand sustainability of the infrastructure, and to demonstrate a model for assessing Core Data Resources worldwide.ResultsThe nineteen resources currently designated ELIXIR Core Data Resources form a data infrastructure in Europe which is a subset of the worldwide open life science data infrastructure. We show that, from 2014 to 2018, data managed by the Core Data Resources more than tripled while staff numbers increased by less than a tenth. Additionally, support for the Core Data Resources is precarious: together they have assured funding for less than a third of current staff after four years.Our findings demonstrate the importance of the ELIXIR Core Data Resources as repositories for research data and knowledge, while also demonstrating the uncertain nature of the funding environment for this infrastructure. ELIXIR is working towards longer-term support for the Core Data Resources and, through the Global Biodata Coalition, aims to ensure support for the worldwide life science data resource infrastructure of which the ELIXIR Core Data Resources are a subset.Contactrachel.drysdale@elixir-europe.orgSupplementary informationSupplementary data are available at Bioinformatics online.
Steric Regulation of Tandem Calponin Homology Domain Actin-Binding Affinity
Authors: Harris Andrew R , Belardi Brian , Jreij Pamela , Wei Kathy , Shams Hengameh , Bausch Andreas , Fletcher Daniel A 
Published: April 2019

ABSTRACTTandem calponin homology (CH1-CH2) domains are common actin-binding domains in proteins that interact with and organize the actin cytoskeleton. Despite regions of high sequence similarity, CH1-CH2 domains can have remarkably different actin-binding properties, with disease-associated point mutants known to increase as well as decrease affinity for f-actin. To investigate features that affect CH1-CH2 affinity for f-actin in cells and in vitro, we perturbed the utrophin actin-binding domain by making point mutations at the CH1-CH2 interface, replacing the linker domain, and adding a PEG polymer to CH2. Consistent with a previous model describing CH2 as a steric negative regulator of actin binding, we find that utrophin CH1-CH2 affinity is both increased and decreased by modifications that change the effective ‘openness’ of CH1 and CH2 in solution. We also identified interface mutations that caused a large increase in affinity without changing solution ‘openness’, suggesting additional influences on affinity. Interestingly, we also observe non-uniform sub-cellular localization of utrophin CH1-CH2 that depends on the N-terminal flanking region but not on bulk affinity. These observations provide new insights into how small sequence changes, such as those found in diseases, can affect CH1-CH2 binding properties.
A simplified transposon mutagenesis method to perform phenotypic forward genetic screens in cultured cells
Authors: Feddersen Charlotte R. , Wadsworth Lexy S. , Zhu Eliot Y. , Vaughn Hayley R. , Voigt Andrew P. , Riordan Jesse D. , Dupuy Adam J. 
Published: April 2019

AbstractThe introduction of genome-wide shRNA and CRISPR libraries has facilitated cell-based screens to identify loss-of-function mutations associated with a phenotype of interest. Approaches to perform analogous gain-of-function screens are less common, although some reports have utilized arrayed viral expression libraries or the CRISPR activation system. However, a variety of technical and logistical challenges make these approaches difficult for many labs to execute. In addition, genome-wide shRNA or CRISPR libraries typically contain of hundreds of thousands of individual engineered elements, and the associated complexity creates issues with replication and reproducibility for these methods. Here we describe a simple, reproducible approach using the Sleeping Beauty transposon system to perform phenotypic cell-based genetic screens. This approach employs only three plasmids to perform unbiased, whole-genome transposon mutagenesis. We also describe a ligation-mediated PCR method that can be used in conjunction with the included software tools to map raw sequence data, identify candidate genes associated with phenotypes of interest, and predict the impact of recurrent transposon insertions on candidate gene function. Finally, we demonstrate the high reproducibility of our approach by having three individuals perform independent replicates of a mutagenesis screen to identify drivers of vemurafenib resistance in cultured melanoma cells. Collectively, our work establishes a facile, adaptable method that can be performed by labs of any size to perform robust, genome-wide screens to identify genes that influence phenotypes of interest.
Misfolded amyloid β-42 induced impairment of the endosomal-lysosomal pathway revealed by real-time optical monitoring
Authors: Marshall Karen E , Vadukul Devkee , Staras Kevin , Serpell Louise C 
Published: April 2019

ABSTRACTMisfolding and aggregation of proteins is strongly linked to several neurodegenerative diseases but how such species bring about their cytotoxic actions remains poorly understood. Here we used specifically-designed optical reporter probes and live fluorescence imaging in primary hippocampal neurons to characterise the mechanism by which prefibrillar, oligomeric forms of the Alzheimer’s-associated peptide, Aβ42, exert their detrimental effects. We used a pH-sensitive reporter, Aβ42-CypHer, to track Aβ internalisation in real time, demonstrating that oligomers are rapidly taken up into cells in a dynamin-dependent manner, and trafficked via the endo-lysosomal pathway resulting in accumulation in lysosomes. In contrast, a non-assembling variant of Aβ42 (vAβ42) assayed in the same way is not internalised. Tracking ovalbumin uptake into cells using CypHer or Alexa Fluor tags shows that preincubation with Aβ42 significantly disrupts protein uptake. Our results identify a potential mechanism by which amyloidogenic aggregates directly impair cellular function through disruption of the endosomal-lysosomal pathway.
APOL1-G0protects podocytes in a mouse model of HIV-associated nephropathy
Authors: Bruggeman Leslie A. , Wu Zhenzhen , Luo Liping , Madhavan Sethu , Drawz Paul E. , Thomas David B. , Barisoni Laura , O’Toole John F. , Sedor John R. 
Published: April 2019

ABSTRACTBackgroundAfrican polymorphisms in the gene for Apolipoprotein L1 (APOL1) confer a survival advantage against lethal trypanosomiasis but also an increased risk for several chronic kidney diseases (CKD) including HIV-associated nephropathy (HIVAN). APOL1 is expressed in renal cells, however, the pathogenic events that lead to renal cell damage and kidney disease are not fully understood.MethodsThe podocyte function ofAPOL1-G0versusAPOL1-G2in the setting of a known disease stressor was assessed using transgenic mouse models. Survival, renal pathology and function, and podocyte density were assessed in an intercross of a mouse model of HIVAN (Tg26) with two mouse models that express eitherAPOL1-G0orAPOL1-G2in podocytes.ResultsMice that expressed HIV genes developed heavy proteinuria and glomerulosclerosis, and had significant losses in podocyte numbers and reductions in podocyte densities. Mice that co-expressedAPOL1-G0and HIV had preserved podocyte numbers and densities, with fewer morphologic manifestations typical of HIVAN pathology. Podocyte losses and pathology in mice co-expressingAPOL1-G2and HIV were not significantly different from mice expressing only HIV. Podocyte hypertrophy, a known compensatory event to stress, was increased in the mice co-expressing HIV andAPOL1-G0, but absent in the mice co-expressing HIV andAPOL1-G2. Mortality and renal function tests were not significantly different between groups.ConclusionsAPOL1-G0expressed in podocytes may have a protective function against podocyte loss or injury when exposed to an environmental stressor. This function appears to be absent withAPOL1-G2expression, suggestingAPOL1-G2is a loss-of-function variant.
RUNX1 safeguards the identity of the fetal ovary through an interplay with FOXL2
Authors: Nicol Barbara , Grimm Sara A. , Chalmel Frederic , Lecluze Estelle , Pannetier Maëlle , Pailhoux Eric , Dupin-De-Beyssat Elodie , Guiguen Yann , Capel Blanche , Yao Humphrey H.-C. 
Published: April 2019

AbstractSex determination of the gonads begins with fate specification of gonadal supporting cells into either ovarian granulosa cells or testicular Sertoli cells. This process of fate specification hinges on a balance of transcriptional control. We discovered that expression of the transcription factor RUNX1 is enriched in the fetal ovary in rainbow trout, turtle, mouse, goat and human. In the mouse, RUNX1 marks the supporting cell lineage and becomes granulosa cell-specific as the gonads differentiate. RUNX1 plays complementary/redundant roles with FOXL2 to maintain fetal granulosa cell identity, and combined loss of RUNX1 and FOXL2 results in masculinization of the fetal ovaries. At the chromatin level, RUNX1 occupancy overlaps partially with FOXL2 occupancy in the fetal ovary, suggesting that RUNX1 and FOXL2 target a common set of genes. These findings identify RUNX1, with an ovary-biased pattern conserved across species, as a novel regulator in securing the identity of ovarian supporting cells and the ovary.
Budgerigars adopt robust, but idiosyncratic flight paths
Authors: Karmaker Debajyoti , Schiffner Ingo , Srinivasan Mandyam V. 
Published: April 2019

AbstractWe have investigated the paths taken by Budgerigars while flying in a tunnel. The preferred flight trajectories of nine Budgerigars (Melopsittacus undulatus) were reconstructed in 3D from high speed stereo videography of their flights in an obstacle-free tunnel. Individual birds displayed highly idiosyncratic flight trajectories that were consistent from flight to flight over the course of several months. We then investigated the robustness of each bird’s trajectory by interposing a disk-shaped obstacle in its preferred flight path. We found that each bird continued to fly along its preferred trajectory up to a point very close to the obstacle before veering away rapidly, making a minimal deviation to avoid a collision, and subsequently returning to its original path. Thus, Budgerigars show a high propensity to stick to their individual, preferred flight paths even when confronted with a clearly visible obstacle, and do not adopt a substantially different, safer route. Detailed analysis of the last-minute avoidance manoeuvre suggests that a collision is avoided by restricting the magnitude of the optic flow generated by the obstacle to a maximum value of about 700 deg/sec. The robust preference for idiosyncratic flight paths, and the tendency to pass obstacles by flying above them, provide new insights into the strategies that underpin obstacle avoidance in birds. It could also have wide-ranging implications for conservation efforts to mitigate collisions of birds with man-made obstacles – especially obstacles that are poorly visible, such as wind turbines or buildings with glass facades. Our findings indicate that care needs to be exercised to ensure that newly planned structures are not located near major bird flyways, wherever possible, and to ensure that the positioning takes into consideration the cues and behaviours that birds use to avoid such obstacles.
Dendritic spines on GABAergic neurons respond to cholinergic signaling in theCaenorhabditis elegansmotor circuit
Authors: Cuentas-Condori Andrea , Mulcahy Ben , He Siwei , Palumbos Sierra , Zhen Mei , Miller David M. 
Published: April 2019

SUMMARYDendritic spines are specialized postsynaptic structures that detect and integrate presynaptic signals. The shape and number of dendritic spines are regulated by neural activity and correlated with learning and memory. Most studies of spine function have focused on the mammalian nervous system. However, spine-like protrusions have been previously reported in invertebrates, suggesting that the experimental advantages of smaller model organisms could be exploited to study the biology of dendritic spines. Here, we document the presence of dendritic spines inCaenorhabditis elegansmotor neurons. We used super-resolution microscopy, electron microscopy, live-cell imaging and genetic manipulation to show that GABAergic motor neurons display functional dendritic spines. Our analysis revealed salient features of dendritic spines: (1) A key role for the actin cytoskeleton in spine morphogenesis; (2) Postsynaptic receptor complexes at the tips of spines in close proximity to presynaptic active zones; (3) Localized postsynaptic calcium transients evoked by presynaptic activity; (4) The presence of endoplasmic reticulum and ribosomes; (5) The regulation of spine density by presynaptic activity. These studies provide a solid foundation for a new experimental paradigm that exploits the power ofC. elegansgenetics and live-cell imaging for fundamental studies of dendritic spine morphogenesis and function.HIGHLIGHTS-Spines inC. elegansGABAergic motor neurons are enriched in actin cytoskeleton.-Spines are dynamic structures.-Spines display Ca++transients coupled with presynaptic activation.-Spine density is regulated during development and is modulated by actin dynamics and cholinergic signaling.
Developmental and cell-specific expression ofCacna1dsplice variants
Authors: Brianna LaCarubba , Alexandra Bunda , Kitty Savage , Hannah Sargent , Marie Akiki , Thomas Foxall , Arturo Andrade 
Published: April 2019

ABSTRACTCaV1.3 is an L-type voltage-gated calcium channel implicated in several functions including gene expression, pacemaking activity, and neurotransmitter release. The gene that encodes the CaVα1-pore forming subunit of CaV1.3 (Cacna1d) is a multi-exon gene that undergoes extensive alternative splicing, which provides functional versatility to this gene across tissues and cell-types. The function and expression of severalCacna1dsplice variants within the C-terminus have been previously characterized. These splice variants differ in their voltage-dependence of activation, Ca2+-dependent inactivation, and their sensitivity to dihydropyridines. However, less is known about alternatively spliced exons inCacna1dlocated downstream of domain I and upstream of the C-terminus (e11, e22a/e22, e31a/e31b/e32). Here, we performed a systematic study to determine the developmental and cell-specific expression of severalCacna1dsplice variants. We found that the cassette e11 is upregulated during brain development, and in adult cortical tissue is more abundant in excitatory neurons relative to inhibitory interneurons. This exon is also upregulated upon nerve growth factor (NGF) induced differentiation of pheochromocytoma cells, PC12. At the functional level, the splice variants resulting from e11 alternative splicing (+e11-Cacna1dand Δe11-Cacna1d) form functional CaV1.3 channels with similar biophysical properties in expression mammalian systems. Of the pair of mutually exclusive exons, e22a and e22, the later dominates at all stages. However, we observed a slight upregulation of e22 from embryonic to adult human brain. A second pair of mutually exclusive exons, e31a and e31b, was also studied. We found that e31a increases during brain development. Finally, the cassette exon 32 is repressed in adult brain tissue.