bluuebunny/crossref_metadata_2025_split huggingface dataset:
Retrospective serological analysis reveals presence of the emerging lagovirus RHDV2 in Australian wild rabbits at least six months prior to its first detection
Authors: Strive Tanja , Piper Melissa , Huang Nina , Mourant Roslyn , Kovaliski John , Capucci Lorenzo , Cox Tarnya E , Smith Ina 
Published: April 2019

SummaryThe lagovirus Rabbit Haemorrhagic Disease Virus (RHDV) has been circulating in Australia since the mid-1990s when it was deliberately released to control overabundant rabbit populations. In recent years, the viral diversity of different RHDVs in Australia has increased, and currently four different types of RHDV are known to be circulating. To allow for ongoing epidemiological studies and impact assessments of these viruses on Australian wild rabbit populations, it is essential that serological tools are updated. To this end, Reference sera were produced against all four virulent RHDVs (including RHDV2) known to be present in Australia and tested in a series of available immunological assays originally developed for the prototype RHDV, to assess patterns of cross reactivity and the usefulness of these assays to detect lagovirus antibodies, either in a generic or specific manner. Enzyme Linked Immuno Sorbent Assays (ELISAs) developed to detect antibody isotypes IgM, IgA and IgG were sufficiently cross reactive to detect antibodies raised against all four virulent lagoviruses. For the more specific detection of antibodies to the antigenically more different RHDV2, a competition ELISA was adapted using RHDV2 specific monoclonal antibodies in combination with Australian viral antigen. Archival serum banks from a long term rabbit monitoring site where rabbits were sampled quarterly over a period of six years were re-screened using this assay, and revealed serological evidence for the arrival of RHDV2 in this population at least six months prior to its initial detection in Australia in a deceased rabbit in May 2015. The serological methods and reference reagents described here will provide valuable tools to study presence, prevalence and impact of RHDV2 on Australian rabbit populations; however the discrimination of different antigenic variants of RHDVs as well as mixed infections at the serological level remains challenging.
Vinculin anchors contractile actin to the cardiomyocyte adherens junction
Authors: Merkel Chelsea D. , Li Yang , Raza Qanber , Stolz Donna B. , Kwiatkowski Adam V. 
Published: April 2019

AbstractThe adherens junction (AJ) couples the actin cytoskeletons of neighboring cells to allow mechanical integration and tissue organization. The physiological demands of intercellular adhesion require that the AJ be responsive to dynamic changes in force while maintaining mechanical load. These demands are tested in the heart, where cardiomyocyte AJs must withstand repeated cycles of actomyosin-mediated contractile force. Here we show that force-responsive cardiomyocyte AJs recruit actin-binding ligands to selectively couple actin networks and promote contact maturation. We employed a panel of N-cadherin-αE-catenin fusion proteins to rebuild AJs with specific actin linkages in N-cadherin-null cardiomyocytes. In this system, vinculin recruitment was required to rescue myofibril integration and desmosome assembly at nascent contacts. In contrast, loss of vinculin disrupted junction morphology and blocked myofibril integration. Our results identify vinculin as a critical link to contractile actomyosin and offer insight to how actin integration at the AJ is regulated to provide mechanical stability and cellular organization.
Direct observation of branching MT nucleation in living animal cells
Authors: Verma Vikash , Maresca Thomas J. 
Published: April 2019

ABSTRACTCentrosome-mediated microtubule (MT) nucleation has been well-characterized; however, numerous non-centrosomal MT nucleation mechanisms exist. The branching MT nucleation pathway envisages that the γ-tubulin ring complex (γ-TuRC) is recruited to MTs by the augmin complex to initiate nucleation of new MTs. While the pathway is well-conserved at a molecular and functional level, branching MT nucleation by core constituents has never been directly observed in animal cells. Here, multi-color TIRF microscopy was applied to visualize and quantitatively define the entire process of branching MT nucleation in dividingDrosophilacells. The stereotypical branching nucleation event entailed augmin first binding to a “mother” MT, recruitment of γ-TuRC after 16s, followed by nucleation 15s later of a “daughter” MT at a 36° branch angle. Daughters typically remained attached throughout their ~40s lifetime unless the mother depolymerized past the branch point. Assembly of branched MT arrays, which did not require D-TPX2 (Drosophila TPX2) or evident regulation by a RanGTP gradient, enhanced localized RhoA activation during cytokinesis.
Biologically plausible learning in a deep recurrent spiking network
Authors: Rotermund David , Pawelzik Klaus R. 
Published: April 2019

AbstractArtificial deep convolutional networks (DCNs) meanwhile beat even human performance in challenging tasks. Recently DCNs were shown to also predict real neuronal responses. Their relevance for understanding the neuronal networks in the brain, however, remains questionable. In contrast to the unidirectional architecture of DCNs neurons in cortex are recurrently connected and exchange signals by short pulses, the action potentials. Furthermore, learning in the brain is based on local synaptic mechanisms, in stark contrast to the global optimization methods used in technical deep networks. What is missing is a similarly powerful approach with spiking neurons that employs local synaptic learning mechanisms for optimizing global network performance. Here, we present a framework consisting of mutually coupled local circuits of spiking neurons. The dynamics of the circuits is derived from first principles to optimally encode their respective inputs. From the same global objective function a local learning rule is derived that corresponds to spike-timing dependent plasticity of the excitatory inter-circuit synapses. For deep networks built from these circuits self-organization is based on the ensemble of inputs while for supervised learning the desired outputs are applied in parallel as additional inputs to output layers.Generality of the approach is shown with Boolean functions and its functionality is demonstrated with an image classification task, where networks of spiking neurons approach the performance of their artificial cousins. Since the local circuits operate independently and in parallel, the novel framework not only meets a fundamental property of the brain but also allows for the construction of special hardware. We expect that this will in future enable investigations of very large network architectures far beyond current DCNs, including also large scale models of cortex where areas consisting of many local circuits form a complex cyclic network.
Cohort Profile: HealthWise Wales. A research register and data collection and analysis platform with linkage to NHS datasets in Wales
Authors: Hurt Lisa , Ashfield-Watt Pauline , Townson Julia , Heslop Luke , Copeland Lauren , Atkinson Mark , Horton Jeffrey , Paranjothy Shantini 
Published: April 2019

AbstractPurposeRecruitment and follow-up in epidemiological studies is challenging, time-consuming and expensive. Combining online data collection with a register of individuals who agree to be contacted with information on research opportunities provides an efficient, cost-effective platform for population-based research. HealthWise Wales (HWW) aims to support researchers by recruiting a cohort of “research-ready” individuals; advertising relevant studies to these participants; providing access to cohort data for secondary analyses; and supporting data collection on specific topics that can be linked with healthcare data.ParticipantsAdults (aged 16 and above) living or receiving their healthcare in Wales are eligible for inclusion. Participants consent to be followed-up every 6 months; for their details to be used to access their routinely-collected NHS records for research purposes; to be contacted about research projects in which they could participate; and to be informed about involvement or engagement opportunities. Data are collected using a web-based application, with new questionnaires added every six months. Data collection on socio-demographic and lifestyle factors is repeated at two-to-three year intervals. Recruitment is ongoing, with 21,779 active participants (alive and currently registered).Findings to date99% of participants have complete information on age and sex, and 64% have completed questionnaires on socio-demographic and lifestyle factors. These data can be linked with national health databases within the Secure Anonymised Information Linkage (SAIL) databank, with 93% of participants matching a record in SAIL. HWW has facilitated recruitment of 43,826 participants to 15 different studies.Future plansThe medium-term goal for the project is to enrol at least 50,000 adults. Recruitment strategies are being devised to achieve a study sample that closely models the population of Wales, with sufficient numbers in socio-demographic subgroups to allow for the selection of populations for research from those groups. Potential bio-sampling methods are also currently being explored.
Meningeal Worm Infection in Central Iowa Goat Herds II: Individual Cases and Treatment Using a Camelid Therapeutic Protocol
Authors: Smith Joe , Kreuder Amanda , Breuer Ryan , Still-Brooks Kelly 
Published: April 2019

Summary and ImplicationsMeningeal worm (Paralaphostrongylus tenuis) infection, also known as cerebrospinal nematodiasis, is a common parasitic infection in New World Camelids in the United States. There is also a considerable risk for this disease in the Boer goat population. Despite the rapidly increasing size of the national goat herd, there are no treatment protocols reported in the literature for goats with this disease. This study describes a successful clinical approach and treatment of 3 Boer goat cases with therapy previously reported for use in New World Camelids. The clinical presentation, diagnosis, and long-term outcome of P. tenuis infections in these goats presented to ISU Food Animal and Camelid Hospital (FACH) is reported here within. Practitioners should be aware that clinical presentation and diagnosis are similar for goats as reported for camelids with cerebrospinal nematodiasis. Additionally, the described treatment protocols for camelids appear to demonstrate a comparative efficacy in goats.
Status of Soil-transmitted helminthiasis among pregnant women attending antenatal clinic in Kilifi county hospital, Kenya
Authors: Njeru Albert , Mutuku Francis , Muriu Simon 
Published: April 2019

AbstractSoil-transmitted helminthes (STH) refers to parasites whose life cycle depends on a period of development outside the human host typically in a moist or warm soil. The most important geohelminths are; roundworms (Ascaris lumbricoides), whipworms (Trichuris trichiura) and hookworms (Necator americanusandAncylostoma duodenale). The study aimed at investigating the current epidemiological status of soil-transmitted helminth infections among pregnant women in Kilifi County hospital (KCH) following the intervention of preventive chemotherapy.Data collection and analysis involved evaluation of transmission trends of geohelminths from the previous surveys/ hospital records, use of direct fecal smears and Kato-Katz smears in estimation of prevalence and infection intensity and the use of structured questionnaires for the assessment of the predisposing factors associated with STH infections. Logistic regression analysis was employed to determine the risk factors associated with STH infections.A total of 191 stool samples were collected and analyzed. Three species of soil-transmitted helminths (STHs) were identified with the overall prevalence of any STH infection being 16.75%.Trichuris trichiurawas predominant (8.38 %), followed byA. lumbricoides(7.85%) then hookworms (6.29 %). About 10.99% of the participants had a single worm infection, 5.76 % had double co-infections and none of the participants had triple infection.Preventive chemotherapy appears to give maximal returns in terms of reducing significantly the number of geohelminths reported since 2001. The study recommended the routine stool analysis in the antenatal profile, provision of alternative sources of iron to the pregnant women in order to reduce the tendency for soil consumption and the associated risk of STH infections, provision of safe water for domestic use, improved sanitation and proper personal hygiene (WASH).
Hippocampal network reorganization underlies the formation of a temporal association memory
Authors: Ahmed Mohsin S. , Priestley James B. , Castro Angel , Stefanini Fabio , Balough Elizabeth M. , Lavoie Erin , Mazzucato Luca , Fusi Stefano , Losonczy Attila 
Published: April 2019

AbstractEpisodic memory requires linking events in time, a function dependent on the hippocampus. In “trace” fear conditioning, animals learn to associate a neutral cue with an aversive stimulus despite their separation in time by a delay period on the order of tens of seconds. But how this temporal association forms remains unclear. Here we use 2-photon calcium imaging to track neural population dynamics over the complete time-course of learning and show that, in contrast to previous theories, the hippocampus does not generate persistent activity to bridge the time delay. Instead, learning is concomitant with broad changes in the active neural population in CA1. While neural responses were highly stochastic in time, cue identity could be reliably read out from population activity rates over longer timescales after learning. These results question the ubiquity of neural sequences during temporal association learning, and suggest that trace fear conditioning relies on mechanisms that differ from persistent activity accounts of working memory.
Lapses in perceptual decisions reflect exploration
Authors: Pisupati Sashank , Chartarifsky-Lynn Lital , Khanal Anup , Churchland Anne K. 
Published: April 2019

ABSTRACTPerceptual decision-makers often display a constant rate of errors independent of evidence strength. These “lapses” are treated as a nuisance arising from noise tangential to the decision, e.g. inattention or motor errors. Here, we use a multisensory decision task in rats to demonstrate that these explanations cannot account for lapses’ stimulus dependence. We propose a novel explanation: lapses reflect a strategic trade-off between exploiting known rewarding actions and exploring uncertain ones. We tested the model’s predictions by selectively manipulating one action’s reward magnitude or probability. As uniquely predicted by this model, changes were restricted to lapses associated with that action. Finally, we show that lapses are a powerful tool for assigning decision-related computations to neural structures based on disruption experiments (here, posterior striatum and secondary motor cortex). These results suggest that lapses reflect an integral component of decision-making and are informative about action values in normal and disrupted brain states.
Characteristics of respiratory measures in young adults scanned at rest, including systematic changes and “missed” respiratory events
Authors: Power Jonathan D. , Silver Benjamin M. , Martin Alex , Jones Rebecca M. 
Published: April 2019

AbstractBreathing rate and depth influence the concentration of carbon dioxide in the blood, altering cerebral blood flow and thus functional magnetic resonance imaging (fMRI) signals. Such respiratory fluctuations can have substantial influence in studies of fMRI signal covariance in subjects at rest, the so-called “resting state functional connectivity” technique. If respiration is monitored during fMRI scanning, it is typically done using a belt about the subject’s abdomen to record abdominal circumference. Several measures have been derived from these belt records, including the windowed envelope of the waveform (ENV), the windowed variance in the waveform (respiration variation, RV), and a measure of the amplitude of each breath divided by the cycle time of the breath (respiration volume per time, RVT). Any attempt to gauge respiratory contributions to fMRI signals requires a respiratory measure, but little is known about how these measures compare to each other, or how they perform beyond the small studies in which they were initially proposed. In this paper, we examine the properties of these measures in hundreds of healthy young adults scanned for an hour each at rest, a subset of the Human Connectome Project chosen for having high-quality physiological records. We find: 1) ENV, RV, and RVT are all similar, though ENV and RV are more similar to each other than to RVT; 2) respiratory events like deep breaths exhibit characteristic fMRI signal changes, head motions, and image quality abnormalities time-locked to deep breaths evident in the belt traces; 3) all measures can “miss” respiratory events evident in the belt traces; 4) RVT “misses” deep breaths (i.e., yawns and sighs) more than ENV or RV; 5) all respiratory measures change systematically over the course of a 14.4-minute scan, decreasing in mean value. We discuss the implication of these findings for the literature, and ways to move forward in modeling respiratory influences on fMRI scans.Highlights- Examines 3 respiratory measures in resting state fMRI scans of healthy young adults- All respiratory measures “miss” respiratory events, some more than others- Respiration volume per time (RVT) frequently “misses” deep breaths- All respiratory measures decrease systematically over 14.4 minute scans- Systematic decreases are due to decreased breathing depth and rate
Towards Quantitative Imaging Biomarkers of Tumor Dissemination: a Multi-scale Parametric Modeling of Multiple Myeloma
Authors: Piraud Marie , Wennmann Markus , Kintzelé Laurent , Hillengass Jens , Keller Ulrich , Langs Georg , Weber Marc-André , Menze Björn H. 
Published: April 2019

AbstractThe advent of medical imaging and automatic image analysis is bringing the full quantitative assessment of lesions and tumor burden at every clinical examination within reach. This opens avenues for the development and testing of functional disease models, as well as their use in the clinical practice for personalized medicine. In this paper, we introduce a Bayesian statistical framework, based on mixed-effects models, to quantitatively test and learn functional disease models at different scales, on population longitudinal data. We also derive an effective mathematical model for the crossover between initially detected lesions and tumor dissemination, based on the Iwata-Kawasaki-Shigesada model. We finally propose to leverage this descriptive disease progression model into model-aware biomarkers for personalized risk-assessment, taking all available examinations and relevant covariates into account. As a use case, we study Multiple Myeloma, a disseminated plasma cell cancer, in which proper diagnostics is essential, to differentiate frequent precursor state without end-organ damage from the rapidly developing disease requiring therapy. After learning the best biological models for local lesion growth and global tumor burden evolution on clinical data, and computing corresponding population priors, we use individual model parameters as biomarkers, and can study them systematically for correlation with external covariates, such as sex or location of the lesion. On our cohort of 63 patients with smoldering Multiple Myeloma, we show that they perform substantially better than other radiological criteria, to predict progression into symptomatic Multiple Myeloma. Our study paves the way for modeling disease progression patterns for Multiple Myeloma, but also for other metastatic and disseminated tumor growth processes, and for analyzing large longitudinal image data sets acquired in oncological imaging. It shows the unprecedented potential of model-based biomarkers for better and more personalized treatment decisions and deserves being validated on larger cohorts to establish its role in clinical decision making.
Automated analysis of large-scale NMR data generates metabolomic signatures and links them to candidate metabolites
Authors: Khalili Bita , Tomasoni Mattia , Mattei Mirjam , Parera Roger Mallol , Sonmez Reyhan , Krefl Daniel , Rueedi Rico , Bergmann Sven 
Published: April 2019

AbstractIdentification of metabolites in large-scale 1H NMR data from human biofluids remains challenging due to the complexity of the spectra and their sensitivity to pH and ionic concentrations. In this work, we test the capacity of three analysis tools to extract metabolite signatures from 968 NMR profiles of human urine samples. Specifically, we studied sets of co-varying features derived from Principal Component Analysis (PCA), the Iterative Signature Algorithm (ISA) and Averaged Correlation Profiles (ACP), a new method we devised inspired by the STOCSY approach. We used our previously developed metabomatching method to match the sets generated by these algorithms to NMR spectra of individual metabolites available in public databases. Based on the number and quality of the matches we concluded that both ISA and ACP can robustly identify about a dozen metabolites, half of which were shared, while PCA did not produce any signatures with robust matches.
Nerve Excitability Differences in Slow and Fast Motor Axons of the Rat: more than just Ih
Authors: Bell James M. , Lorenz Chad , Jones Kelvin E. 
Published: April 2019

AbstractObjectiveThe objective was to determine if choice of anaesthetic confounded previous conclusions about the differences in nerve excitability indices between fast and slow motor axons.MethodologyNerve excitability of the rat sciatic nerve was tested while measuring responses of motor axons innervating the slow-twitch soleus (SOL) and fast-twitch tibialis anterior (TA) muscles. The experiments were conducted with sodium pentobarbital (SP) anaesthetic and compared to previous results that used ketamine-xylazine (KX).Results and ConclusionsPrevious conclusions about the differences in nerve excitability indices between TA and SOL motor axons using KX were corroborated and extended when experiments were done with SP. Nerve excitability indices sensitive to changes in hyperpolarization-activated inwardly rectifying cation current (Ih) indicated an increase in Ih in SOL axons compared to TA axons (e.g. S3 (−100 %), t=7.949 (df=10), p < 0.0001; TEh (90–100 ms), t=2.659 (df=20), p = 0.0145; hyperpolarizing I/V slope, t=4.308 (df=19), p = 0.0004). SOL axons also had a longer strength-duration time constant (t=3.35 (df=20), p = 0.0032) and a longer and larger magnitude relative refractory period (RRP (ms) t=3.53 (df=12), p = 0.0041; Refractoriness at 2 ms t=0.0055 (df=9), p = 0.0055).Anaesthetic choice affected many measures of peripheral nerve excitability with differences most apparent in tests of threshold electrotonus and recovery cycle. For example, recovery cycle with KX lacked a clear superexcitable and late subexcitable period. We conclude that KX had a confounding effect on nerve excitability results consistent with ischaemic depolarization. Results using SP revealed the full extent of differences in nerve excitability measures between putative slow and fast motor axons of the rat. These differences have important implications for the use of nerve excitability measures during processes such as ageing where it is believed that there is a selective loss of fast axons.New & NoteworthyNerve excitability testing is a tool used to provide insight into the properties of ion channels in peripheral nerves. It is used clinically to assess pathophysiology of motor axons. Researchers customarily think of motor axons as homogeneous; however, we demonstrate there are clear differences between fast and slow axons in the rat. This is important for interpreting results with selective motor neuronopathy, like aging where fast axons are at high risk of degeneration.