bluuebunny/crossref_metadata_2025_split huggingface dataset:
A catalogue of omics biological ageing clocks reveals substantial commonality and associations with disease risk
Authors: Macdonald-Dunlop Erin , Taba Nele , Klaric Lucija , Frkatovic Azra , Walker Rosie , Hayward Caroline , Esko Tonu , Haley Chris , Fischer Krista , Wilson James F , Joshi Peter K 
Published: February 2021

AbstractBiological age (BA), a measure of functional capacity and prognostic of health outcomes that discriminates between individuals of the same chronological age (chronAge), has been estimated using a variety of biomarkers. Previous comparative studies have mainly used epigenetic models (clocks), we use ~1000 participants to create eleven omics ageing clocks, with correlations of 0.45-0.97 with chronAge, even with substantial sub-setting of biomarkers. These clocks track common aspects of ageing with 94% of the variance in chronAge being shared among clocks. The difference between BA and chronAge - omics clock age acceleration (OCAA) - often associates with health measures. One year’s OCAA typically has the same effect on risk factors/10-year disease incidence as 0.46/0.45 years of chronAge. Epigenetic and IgG glycomics clocks appeared to track generalised ageing while others capture specific risks. We conclude BA is measurable and prognostic and that future work should prioritise health outcomes over chronAge.
The beta component of gamma-band auditory steady-state responses in patients with schizophrenia
Authors: Metzner Christoph , Steuber Volker 
Published: February 2021

AbstractThe mechanisms underlying circuit dysfunctions in schizophrenia (SCZ) remain poorly understood. Auditory steady-state responses (ASSRs), especially in the gamma and beta band, have been suggested as a potential biomarker for SCZ. While the reduction of 40Hz power for 40Hz drive has been well established and replicated in SCZ patients, studies are inconclusive when it comes to an increase in 20Hz power during 40Hz drive. There might be several factors explaining the inconsistencies, including differences in the sensitivity of the recording modality (EEG vs MEG), differences in stimuli (click-trains vs amplitude-modulated tones) and large differences in the amplitude of the stimuli. Here, we used a computational model of ASSR deficits in SCZ and explored the effect of three SCZ-associated microcircuit alterations: reduced GABA activity, increased GABA decay times and NMDA receptor hypofunction. We investigated the effect of input strength on gamma (40 Hz) and beta (20 Hz) band power during gamma ASSR stimulation and saw that the pronounced increase in beta power during gamma stimulation seen experimentally could only be reproduced in the model when GABA decay times were increased and only for a specific range of input strengths. More specifically, when the input was in this specific range, the rhythmic drive at 40Hz produced a strong 40Hz rhythm in the control network; however, in the ‘SCZ-like’ network, the prolonged inhibition led to a so-called ‘beat-skipping’, where the network would only strongly respond to every other input. This mechanism was responsible for the emergence of the pronounced 20Hz beta peak in the power spectrum. The other two microcircuit alterations were not able to produce a substantial 20 Hz component but they further narrowed the input strength range for which the network produced a beta component when combined with increased GABAergic decay times. Our finding that the beta component only existed for a specific range of input strengths might explain the seemingly inconsistent reporting in experimental studies and suggests that future ASSR studies should systematically explore different amplitudes of their stimuli. Furthermore, we provide a mechanistic link between a microcircuit alterations and an electrophysiological marker in schizophrenia and argue that more complex ASSR stimuli are needed to disentangle the nonlinear interactions of microcircuit alterations. The computational modelling approach put forward here is ideally suited to facilitate the development of such stimuli in a theory-based fashion.
Preparatory activity links frontal eye field activity with small amplitude motor unit recruitment of neck muscles during gaze planning
Authors: Rungta Satya P. , Basu Debaleena , Sendhilnathan Naveen , Murthy Aditya 
Published: February 2021

AbstractA hallmark of intelligent behavior is that we can separate intention from action. To understand the mechanism that gates the flow of information between motor planning and execution, we compared the activity of frontal eye field neurons with motor unit activity from neck muscles in the presence of an intervening delay period in which spatial information regarding the target was available to plan a response. Whereas we could infer spatially-specific delayed period activity from the activity of frontal eye field neurons, neck motor unit activity during the delay period could not be used to infer the direction of an upcoming movement, Nonetheless, motor unit activity was correlated with the time it took to initiate saccades. Interestingly, we observed a heterogeneity of responses amongst motor units, such that only units with smaller amplitudes showed a clear modulation during the delay period. These small amplitude motor units also had higher spontaneous activity compared to the units which showed modulation only during the movement epoch. Taken together, our results suggest that the temporal information is visible in the periphery amongst smaller motor units during eye movement planning and explains how the delay period primes muscle activity leading to faster reaction times.Significance statementThis study shows that the temporal aspects of a motor plan in the oculomotor circuitry can be accessed by peripheral neck muscles hundreds of milliseconds prior to the instruction to initiate a saccadic eye movement. The coupling between central and peripheral processes during the delay time is mediated by the recruitment pattern of motor units with smaller amplitude in the periphery. Besides giving insight into how information processed in cortical areas is read out by the muscles, these findings could be useful to decode intentional signals from the periphery to control brain machine interface devices.
Development and validation of a cellular host response test as an early diagnostic for sepsis
Authors: Guillou Lionel , Sheybani Roya , Jensen Anne E. , Di Carlo Dino , Caffery Terrell , Thomas Christopher , Shah Ajay M. , Tse Henry T. K. , O’Neal Hollis R. 
Published: February 2021

AbstractSepsis must be diagnosed quickly to avoid morbidity and mortality. However, the clinical manifestations of sepsis are highly variable and emergency department (ED) clinicians often must make rapid, impactful decisions before laboratory results are known. We previously developed a technique that allows the measurement of the biophysical properties of white blood cells as they are stretched through a microfluidic channel. In this study we describe and validate the resultant output as a model and score – the IntelliSep Index (ISI) – that aids in the diagnosis of sepsis in patients with suspected or confirmed infection from a single blood draw performed at the time of ED presentation. By applying this technique to a high acuity cohort with a 23.5% sepsis incidence (n=307), we defined specific metrics – the aspect ratio and visco-elastic inertial response – that are more sensitive than cell size or cell count in predicting disease severity. The final model was trained and cross-validated on the high acuity cohort, and the performance and generalizability of the model was evaluated on a separate low acuity cohort with a 6.4% sepsis incidence (n=94) and healthy donors (n=72). For easier clinical interpretation, the ISI is divided into three interpretation bands of Green, Yellow, and Red that correspond to increasing disease severity. The ISI agreed with the diagnosis established by retrospective physician adjudication, and accurately identified subjects with severe illness as measured by SOFA, APACHE-II, hospital-free days, and intensive care unit admission. Measured using routinely collected blood samples, with a short run-time and no requirement for patient or laboratory information, the ISI is well suited to aid ED clinicians in rapidly diagnosing sepsis.
Sablefish (Anoplopoma fimbraPallas, 1814) plasma biochemistry and hematology reference intervals including blood cell morphology
Authors: Schubiger Carla B. , Gorman M. Elena , Johns Jennifer L. , Arkoosh Mary R. , Dietrich Joseph P. 
Published: February 2021

AbstractPlasma biochemistry and hematology reference intervals are integral health assessment tools in all medical fields, including aquatic animal health. As sablefish (Anoplopoma fimbria) are becoming aquaculturally and economically more important, this manuscript provides essential reference intervals (RI) for their plasma biochemistry and hematology along with reference photomicrographs of blood cells in healthy, fasted sablefish. Blood cell morphology can differ between fish species. In addition, blood cell counts and blood chemistry can vary between fish species, demographics, water conditions, seasons, diets, and culture systems, which precludes the use of RI’s from other fish species. For this study, blood was collected for plasma biochemistry and hematology analysis between June 20 and July 18, 2019, from healthy, yearling sablefish, hatched and reared in captivity on a commercial diet. Overnight fast of 16-18 hours did not sufficiently reduce lipids in the blood, which led to visible lipemia and frequent rupture of blood cells during analysis. Therefore, sablefish should be fasted for 24 to 36 hours before blood is collected to reduce hematology artifacts or possible reagent interference in plasma biochemistry analysis. Lymphocytes were the most dominant leukocytes (98%), while eosinophils were rare, and basophils were not detected in sablefish. Neutrophils were very large cells with Döhle bodies. In mammals and avian species, Döhle bodies are usually signs of toxic change from inflammation, but no such association was found in these fish. In conclusion, lipemia can interfere with sablefish blood analysis, and available removal methods should be evaluated as fasting for up to 36 h might not always be feasible. Also, more studies are required to establish RI for different developmental stages and rearing conditions.
How animals endure by bending environmental space: Redefining the fundamental niche
Authors: Matthiopoulos Jason 
Published: February 2021

ABSTRACTFor 70 years, the fundamental niche, the complete set of environments that allow an individual, population, or species to persist, has shaped ecological thinking. Yet, its properties have eluded quantification, particularly for mobile, cognitively complex organisms. Here, I derive a concise mathematical equation for the fundamental niche and fit it to population growth and distribution data. I find that, within traditionally defined environmental spaces, habitat heterogeneity and behavioural plasticity make the fundamental niche more complex and malleable, but also more predictable, than previously envisaged. This important re-evaluation restores the fundamental niche as a cornerstone of ecological theory and promotes it as a central tool for applied ecology. It quantifies how organisms buffer themselves from change by bending the boundaries of viable environmental space, and offers a framework for designing optimal habitat interventions to protect biodiversity or obstruct invasive species.ONE-SENTENCE SUMMARYThe fundemental niche of animal species
Selfish migrants: How a meiotic driver is selected to increase dispersal
Authors: Runge Jan-Niklas , Kokko Hanna , Lindholm Anna K. 
Published: February 2021

AbstractMeiotic drivers are selfish genetic elements that manipulate meiosis to increase their transmission to the next generation to the detriment of the rest of the genome. One example is thethaplotype in house mice, which is a naturally occurring meiotic driver with deleterious traits—poor fitness in polyandrous matings and homozygote inviability or infertility—that prevent its fixation. Recently, we discovered and validated a novel effect oftin a long-term field study on free-living wild house mice and with experiments:t-carriers are more likely to disperse. Here, we ask what known traits of thethaplotype can select for a difference in dispersal betweent-carriers and wildtype mice. To that end, we built individual-based models with dispersal loci on thetand the homologous wildtype chromosomes. We also allow for density-dependent expression of these loci. Thethaplotype consistently evolves to increase the dispersal propensity of its carriers, particularly at high densities. By examining variants of the model that modify different costs caused byt, we show that the increase in dispersal is driven by the deleterious traits oft, disadvantage in polyandrous matings and lethal homozygosity or male sterility. Finally, we show that an increase in driver-carrier dispersal can evolve across a range of values in driver strength and disadvantages.
SCOPE: Flexible targeting and stringent CARF activation enables type III CRISPR-Cas diagnostics
Authors: Steens Jurre A. , Zhu Yifan , Taylor David W. , Bravo Jack P.K. , Prinsen Stijn H.P , Schoen Cor D. , Keijser Bart J.F , Ossendrijver Michel , Hofstra L. Marije , Brouns Stan J.J. , Shinkai Akeo , van der Oost John , Staals Raymond H.J. 
Published: February 2021

SummaryCharacteristic properties of type III CRISPR-Cas systems include recognition of target RNA (rather than DNA) and the subsequent induction of a multifaceted immune response. This involves sequence-specific cleavage of a target RNA and production of cyclic oligoadenylate (cOA) second messenger molecules that may trigger dormancy or cell death. In this study, we discovered that a largely exposed seed region at the 3’ end of the crRNA is essential for target RNA binding and cleavage, whereas base pairing at a unique region at the 5’ end of the guide is required to trigger cOA production. Moreover, we uncovered that the natural variation in the composition of type III complexes within a single host results in different guide lengths, and hence variable seed regions. This shifting seed may prevent escape by invading genetic elements, while controlling cOA production very tightly to prevent unnecessary damage to the host. Lastly, we used these findings to develop a new diagnostic tool, named SCOPE, which was used for the specific detection of SARS-CoV-2 from human nasal swab samples, showing sensitivities in the atto-molar range.
Agricultural fertilization with poultry manure results in persistent environmental contamination with the pathogenClostridioides difficile
Authors: Frentrup Martinique , Thiel Nadine , Junker Vera , Behrens Wiebke , Münch Steffen , Siller Paul , Kabelitz Tina , Faust Matthias , Indra Alexander , Baumgartner Stefanie , Schepanski Kerstin , Amon Thomas , Roesler Uwe , Funk Roger , Nübel Ulrich 
Published: February 2021

SummaryDuring a field experiment applying broiler manure for fertilization of agricultural land, we detected viableClostridioides(formerly,Clostridium)difficilein broiler feces, manure, dust, and fertilized soil. A large diversity of toxigenicC. difficileisolates was recovered, including PCR ribotypes common from human disease. Genomic relatedness ofC. difficileisolates from dust and from soil, recovered more than two years after fertilization, traced their origins to the specific chicken farm that had delivered the manure. We present evidence of long-term contamination of agricultural soil with manure-derivedC. difficileand demonstrate the potential for airborne dispersal ofC. difficilethrough dust emissions during manure application.Clostridioidesgenome sequences virtually identical to those from manure had been recovered from chicken meat and from human infections in previous studies, suggesting broiler-associatedC. difficileare capable of zoonotic transmission.
Phase Gradients and Anisotropy of the Suprachiasmatic Network
Authors: Yoshikawa Tomoko , Pauls Scott , Foley Nicholas , Taub Alana , LeSauter Joseph , Foley Duncan , Honma Ken-Ichi , Honma Sato , Silver Rae 
Published: February 2021

AbstractBiological neural networks operate at several levels of granularity, from the individual neuron to local neural circuits to networks of thousands of cells. The daily oscillation of the brain’s master clock in the suprachiasmatic nucleus (SCN) rests on a yet to be identified network of connectivity among its ~20,000 neurons. The SCN provides an accessible model to explore neural organization at several levels of organization. To relate cellular to local and global network behaviors, we explore network topology by examining SCN slices in three orientations using immunochemistry, light and confocal microscopy, real-time imaging, and mathematical modeling. Importantly, the results reveal small local groupings of neurons that form intermediate structures, here termed “phaseomes” which can be identified through stable local phase differences of varying magnitude among neighboring cells. These local differences in phase are distinct from the global phase relationship – that between individual cells and the mean oscillation of the overall SCN. The magnitude of the phaseomes’ local phase differences are associated with a global phase gradient observed in the SCN’s rostral-caudal extent. Modeling results show that a gradient in connectivity strength can explain the observed gradient of phaseome strength, an extremely parsimonious explanation for the heterogeneous oscillatory structure of the SCN.Significance statementOscillation is a fundamental property of information sensing and encoding in the brain. Using real time imaging and modeling, we explore encoding of time by examining circadian oscillation in single neurons, small groups of neurons, and the entire nucleus, in the brain’s master: the suprachiasmatic nucleus (SCN). New insights into the network organization underlying circadian rhythmicity include the discovery of intermediate structures, termed ‘phaseomes’, characterized by neurons which are stably out of phase with their neighbors. Modeling indicates that the pattern of phaseomes across the tissue encompasses a gradient in connectivity strength from the rostral to caudal aspects of the nucleus. Anisotropy in network organization emerges from comparisons of phaseomes and connectivity gradients in sagittal, horizontal and coronal slices.
Itaconate and fumarate derivatives exert a dual inhibitory effect on canonical NLRP3 activation in macrophages and microglia
Authors: Hoyle Christopher , Green Jack P , Allan Stuart M , Brough David , Lemarchand Eloise 
Published: February 2021

AbstractThe NLRP3 inflammasome is a multi-protein complex that regulates the protease caspase-1 and subsequent interleukin (IL)-1β release from cells of the innate immune system, or microglia in the brain, in response to infection or injury. Derivatives of the metabolites itaconate and fumarate, dimethyl itaconate (DMI), 4-octyl itaconate (4OI) and dimethyl fumarate (DMF), limit both expression of IL-1β, and IL-1β release following NLRP3 inflammasome activation. However, the direct effects of these metabolite derivatives on NLRP3 inflammasome responses in macrophages and microglia require further investigation. Using murine bone marrow-derived macrophages, mixed glia and organotypic hippocampal slice cultures (OHSCs), we demonstrate that DMI and 4OI pre-treatment limited IL-1β, IL-6 and tumor necrosis factor production in response to lipopolysaccharide (LPS) priming, as well as inhibiting subsequent NLRP3 inflammasome activation. DMI, 4OI, DMF and monomethyl fumarate (MMF), another fumarate derivative, also directly inhibited biochemical markers of NLRP3 activation in LPS-primed macrophages, mixed glia and OHSCs, including ASC speck formation, caspase-1 activation, gasdermin D cleavage and IL-1β release. Finally, DMF, an approved treatment for multiple sclerosis, as well as DMI, 4OI and MMF, inhibited NLRP3 activation in macrophages in response to the phospholipid lysophosphatidylcholine, which is used to induce demyelination, suggesting a possible mechanism of action for DMF in multiple sclerosis through NLRP3 inhibition. Together, these findings reveal the importance of immunometabolic regulation for both the priming and activation steps of NLRP3 activation in macrophages and microglia. Furthermore, we highlight itaconate and fumarate derivatives as a potential therapeutic option in NLRP3-driven diseases, including in the brain.Summary statementWe show that itaconate and fumarate derivatives inhibit both the priming and activation steps of NLRP3 inflammasome responses in macrophages and microglia, revealing the importance of immunometabolic NLRP3 regulation.
Risk assessment for the establishment of the Asian giant hornet (Vespa mandarinia) in the Pacific Northwest
Authors: Norderud Erik D. , Powell Scott L. , Peterson Robert K. D. 
Published: February 2021

AbstractThe recent introduction of the Asian giant hornet (Vespa mandariniaSmith) in the United States in late 2019 has raised concerns about its establishment in the Pacific Northwest and its potential deleterious effects on honey bees and their pollination services in the region. Therefore, we conducted a risk assessment of the establishment ofV. mandariniain Washington and Oregon on a county-by-county basis. Our tier-1 qualitative and semi-quantitative risk assessment relied on the biological requirements and ecological relationships ofV. mandariniain the environments of the Pacific Northwest. We based the risk characterization on climate and habitat suitability estimates forV. mandariniaqueens to overwinter and colonize nests, density and distribution of apiaries, and locations of major human-mediated introduction pathways that may increase establishment of the hornet in the counties of Washington and Oregon. Our results suggest that 5 counties in the region could be at low risk, 48 at medium risk, and 22 at high risk of establishment. For Washington, counties at high risk included Clallam, Clark, Cowlitz, Grays Harbor, King, Pierce, Skagit, Snohomish, and Whatcom. The high risk Oregon counties included Benton, Clackamas, Clatsop, Coos, Douglas, Hood River, Lane, Lincoln, Linn, Marion, Multnomah, Polk, and Yamhill. Many of the western counties of both Washington and Oregon were estimated to be at the highest risk of establishment mainly due to their suitable climate for queens to overwinter, dense forest biomass for nest colonization, and proximity to major port and freight hubs in the region. Considering its negative effects, these counties should be prioritized in ongoing monitoring and eradication efforts ofV. mandarinia.