bluuebunny/crossref_metadata_2025_split huggingface dataset:
The cellular basis of protease activated receptor type 2 (PAR2) evoked mechanical and affective pain
Authors: Hassler Shayne N , Kume Moeno , Mwirigi Juliet M. , Ahmad Ayesha , Shiers Stephanie , Wangzhou Andi , Ray Pradipta R , Belugin Serge N , Naik Dhananjay K. , Burton Michael D. , Vagner Josef , Boitano Scott , Akopian Armen N , Dussor Gregory , Price Theodore J 
Published: February 2020

ABSTRACTProtease-activated receptor type-2 (PAR2) has long been implicated in inflammatory and visceral pain, but the cellular basis of PAR2-evoked pain has not been delineated. While many studies have attributed PAR2-evoked pain to sensory neuron expression, RNA-sequencing experiments are ambiguous on detection ofF2rl1mRNA. Moreover, many pharmacological tools for PAR2 have been shown to be non-specific as they also act on the Mas-related (Mrg) family of g-protein coupled receptors (GPCRs) that are highly enriched in sensory neurons. We sought to bring clarity to the cellular basis of PAR2 pain. We developed a PAR2 conditional mutant mouse by loxp targeting of exon 2 of theF2rl1gene and specifically deleted PAR2 in all sensory neurons using thePirtCremouse line. Our behavioral findings show that PAR2 agonist-evoked mechanical hyperalgesia and facial grimacing, but not thermal hyperalgesia, is completely dependent on PAR2 expression in sensory neurons that project to the hindpaw in male and female mice.F2rl1mRNA is expressed in a discrete population (~4%) of sensory neurons that also express theNppbandIL31ragenes. This cell population has previously been implicated in itch, but our work shows that PAR2 activation in these cells causes clear pain-related behaviors from the skin. Our findings clarify the mechanism through which proteases, like tryptase and elastase, cause pain via PAR2 activation in a small subset of nociceptors.
The context dependent effects of host competence, competition, and the pathogen transmission mode on disease prevalence
Authors: Cortez Michael H. , Duffy Meghan A. 
Published: February 2020

ABSTRACTBiodiversity in communities is changing globally, including the gain and loss of host species in host-pathogen communities. Increased host diversity can cause infection prevalence in a focal host to increase (amplification) or decrease (dilution). However, it is unclear what general rules govern the context dependent effects, in part because theories for pathogens with different transmission modes have developed largely independently. Using a two-host model, we explore how the pathogen transmission mode and characteristics of a second host (disease competence and competitive ability) influence disease prevalence in a focal host. Our work shows how the theories for pathogens with environmental transmission, density-dependent direct transmission, and frequency-dependent direct transmission can be unified. Our work also identifies general rules about how host and pathogen characteristics affect amplification/dilution. For example, higher competence hosts promote amplification, unless they are strong interspecific competitors; strong interspecific competitors promote dilution, unless they are large sources of new infections; and dilution occurs under frequency-dependent direct transmission more than density-dependent direct transmission, unless interspecific host competition is sufficiently strong. Our work helps explain how the characteristics of the pathogen and a second host affect disease prevalence in a focal host.
The architecture of metabolism maximizes biosynthetic diversity in the largest class of fungi
Authors: Gluck-Thaler Emile , Haridas Sajeet , Binder Manfred , Grigoriev Igor V. , Crous Pedro W. , Spatafora Joseph W. , Bushley Kathryn , Slot Jason C. 
Published: February 2020

Abstract:BackgroundEcological diversity in fungi is largely defined by metabolic traits, including the ability to produce secondary or “specialized” metabolites (SMs) that mediate interactions with other organisms. Fungal SM pathways are frequently encoded in biosynthetic gene clusters (BGCs), which facilitate the identification and characterization of metabolic pathways. Variation in BGC composition reflects the diversity of their SM products. Recent studies have documented surprising diversity of BGC repertoires among isolates of the same fungal species, yet little is known about how this population-level variation is inherited across macroevolutionary timescales.ResultsHere, we applied a novel linkage-based algorithm to reveal previously unexplored dimensions of diversity in BGC composition, distribution, and repertoire across 101 species of Dothideomycetes, which are considered to be the most phylogenetically diverse class of fungi and are known to produce many SMs. We predicted both complementary and overlapping sets of clustered genes compared with existing methods and identified novel gene pairs that associate with known secondary metabolite genes. We found that variation in BGC repertoires is due to non-overlapping BGC combinations and that several BGCs have biased ecological distributions, consistent with niche-specific selection. We observed that total BGC diversity scales linearly with increasing repertoire size, suggesting that secondary metabolites have little structural redundancy in individual fungi.ConclusionsWe project that there is substantial unsampled BGC diversity across specific families of Dothideomycetes, which will provide a roadmap for future sampling efforts. Our approach and findings lend new insight into how BGC diversity is generated and maintained across an entire fungal taxonomic class.
Effects of dopamine agonist treatment on resting-state network connectivity in Parkinson’s disease
Authors: Cole David M. , Mohammadi Bahram , Milenkova Maria , Kollewe Katja , Schrader Christoph , Samii Amir , Dengler Reinhard , Münte Thomas F. , Beckmann Christian F. 
Published: February 2020

ABSTRACTDopamine agonist (DA) medications commonly used to treat, or ‘normalise’, motor symptoms of Parkinson’s disease (PD) may lead to cognitive-neuropsychiatric side effects, such as increased impulsivity in decision-making. Subject-dependent variation in the neural response to dopamine modulation within cortico-basal ganglia circuitry is thought to play a key role in these latter, non-motor DA effects. This neuroimaging study combined resting-state functional magnetic resonance imaging (fMRI) with DA modification in patients with idiopathic PD, investigating whether brain ‘resting-state network’ (RSN) functional connectivity metrics identify disease-relevant effects of dopamine on systems-level neural processing. By comparing patients both ‘On’ and ‘Off’ their DA medications with age-matched, un-medicated healthy control subjects (HCs), we identified multiple non-normalising DA effects on frontal and basal ganglia RSN cortico-subcortical connectivity patterns in PD. Only a single isolated, potentially ‘normalising’, DA effect on RSN connectivity in sensori-motor systems was observed, within cerebro-cerebellar neurocircuitry. Impulsivity in reward-based decision-making was positively correlated with ventral striatal connectivity within basal ganglia circuitry in HCs, but not in PD patients. Overall, we provide brain systems-level evidence for anomalous DA effects in PD on large-scale networks supporting cognition and motivated behaviour. Moreover, findings suggest that dysfunctional striatal and basal ganglia signalling patterns in PD are compensated for by increased recruitment of other cortico-subcortical and cerebro-cerebellar systems.
Cytoprotection by a naturally occurring variant of ATP5G1 in Arctic ground squirrels
Authors: Singhal Neel S. , Bai Meirong , Lee Evan M. , Luo Shuo , Cook Kayleigh R. , Ma Dengke K. 
Published: February 2020

AbstractMany organisms, from anaerobic bacteria to hibernating ground squirrels, have evolved mechanisms to tolerate severe hypoxia or ischemia. In particular, the arctic ground squirrel (AGS) has been shown to be highly resilient to ischemic and reperfusion injuries, demonstrating an ability to withstand metabolic stress under hibernation conditions. Although physiological adaptations are critical to ischemic tolerance in AGS, little is known about cellular mechanisms underlying intrinsic AGS cell tolerance to metabolic stressors. Through cell survival-based cDNA expression screens and comparative genomics, we have discovered that in AGS, a cytoprotective variant of ATP5G1 helps confer improved mitochondrial metabolism and cell resilience to metabolic stress.ATP5G1encodes a proton-transporting subunit of the mitochondrial ATP synthase complex. Ectopic expression in mouse cells and CRISPR/Cas9 base editing of the endogenous AGS locus revealed causal roles of one AGS-specific amino acid substitution (leucine-32) in mediating the cytoprotective effects of AGS ATP5G1. We provide evidence that AGS ATP5G1 promotes cell resilience to stress by modulating mitochondrial morphological change and metabolic functions. Thus, our results identify a naturally occurring variant of ATP5G1 from a mammalian hibernator that causally contributes to intrinsic cytoprotection against metabolic stresses.
The novel coronavirus 2019 (2019-nCoV) uses the SARS-coronavirus receptor ACE2 and the cellular protease TMPRSS2 for entry into target cells
Authors: Hoffmann Markus , Kleine-Weber Hannah , Krüger Nadine , Müller Marcel , Drosten Christian , Pöhlmann Stefan 
Published: February 2020

AbstractThe emergence of a novel, highly pathogenic coronavirus, 2019-nCoV, in China, and its rapid national and international spread pose a global health emergency. Coronaviruses use their spike proteins to select and enter target cells and insights into nCoV-2019 spike (S)-driven entry might facilitate assessment of pandemic potential and reveal therapeutic targets. Here, we demonstrate that 2019-nCoV-S uses the SARS-coronavirus receptor, ACE2, for entry and the cellular protease TMPRSS2 for 2019-nCoV-S priming. A TMPRSS2 inhibitor blocked entry and might constitute a treatment option. Finally, we show that the serum form a convalescent SARS patient neutralized 2019-nCoV-S-driven entry. Our results reveal important commonalities between 2019-nCoV and SARS-coronavirus infection, which might translate into similar transmissibility and disease pathogenesis. Moreover, they identify a target for antiviral intervention.One sentence summaryThe novel 2019 coronavirus and the SARS-coronavirus share central biological properties which can guide risk assessment and intervention.
Online analysis of microendoscopic 1-photon calcium imaging data streams
Authors: Friedrich Johannes , Giovannucci Andrea , Pnevmatikakis Eftychios A. 
Published: February 2020

AbstractIn-vivo calcium imaging through microendoscopic lenses enables imaging of neuronal populations deep within the brains of freely moving animals. Previously, a constrained matrix factorization approach (CNMF-E) has been suggested to extract single-neuronal activity from microendoscopic data. However, this approach relies on offline batch processing of the entire video data and is demanding both in terms of computing and memory requirements. These drawbacks prevent its applicability to the analysis of large datasets and closed-loop experimental settings. Here we address both issues by introducing two different online algorithms for extracting neuronal activity from streaming microendoscopic data. Our first algorithm presents an online adaptation of the CNMF-E algorithm, which dramatically reduces its memory and computation requirements. Our second algorithm proposes a convolution-based background model for microendoscopic data that enables even faster (real time) processing on GPU hardware. Our approach is modular and can be combined with existing online motion artifact correction and activity deconvolution methods to provide a highly scalable pipeline for microendoscopic data analysis. We apply our algorithms on two previously published typical experimental datasets and show that they yield similar high-quality results as the popular offline approach, but outperform it with regard to computing time and memory requirements.Author summaryCalcium imaging methods enable researchers to measure the activity of genetically-targeted large-scale neuronal subpopulations. Whereas previous methods required the specimen to be stable, e.g. anesthetized or head-fixed, new brain imaging techniques using microendoscopic lenses and miniaturized microscopes have enabled deep brain imaging in freely moving mice.However, the very large background fluctuations, the inevitable movements and distortions of imaging field, and the extensive spatial overlaps of fluorescent signals complicate the goal of efficiently extracting accurate estimates of neural activity from the observed video data. Further, current activity extraction methods are computationally expensive due to the complex background model and are typically applied to imaging data after the experiment is complete. Moreover, in some scenarios it is necessary to perform experiments in real-time and closed-loop – analyzing data on-the-fly to guide the next experimental steps or to control feedback –, and this calls for new methods for accurate real-time processing. Here we address both issues by adapting a popular extraction method to operate online and extend it to utilize GPU hardware that enables real time processing. Our algorithms yield similar high-quality results as the original offline approach, but outperform it with regard to computing time and memory requirements. Our results enable faster and scalable analysis, and open the door to new closed-loop experiments in deep brain areas and on freely-moving preparations.
Axonal ER Ca2+Release Enhances Miniature, but Reduces Activity-Dependent Glutamate Release in a Huntington Disease Model
Authors: Mackay James P. , Smith-Dijak Amy I. , Koch Ellen T. , Zhang Peng , Fung Evan , Nassrallah Wissam B. , Buren Caodu , Schmidt Mandi , Hayden Michael R. , Raymond Lynn A. 
Published: February 2020

AbstractAction potential-independent (miniature) neurotransmission occurs at all chemical synapses, but remains poorly understood, particularly in pathological contexts. Spontaneous release of Ca2+from the axonal endoplasmic reticulum (ER) is thought to facilitated miniature neurotransmission, and aberrant ER Ca2+handling is notably implicated in the progression of Huntington’s disease (HD) and other neurodegenerative diseases. Here, we report elevated glutamate-mediated miniature synaptic event frequencies in YAC128 (HD-model) cortical neurons, which pharmacological experiments suggest is mediated by enhanced spontaneous ER Ca2+release. Calcium imaging using an axon-localized sensor revealed slow action potential (AP)-independent axonal Ca2+waves, which were more common in YAC128 cortical neurons. Conversely, spontaneous axonal ER Ca2+release was associated with reduced AP-dependent axonal Ca2+events and consequent glutamate release. Together, our results suggest spontaneous release of axonal ER Ca2+stores oppositely regulates activity-dependent and -independent neurotransmitter release in HD, with potential implications for the fidelity and plasticity of cortical excitatory signaling.
Haplotype Diversity and Sequence Heterogeneity of Human Telomeres
Authors: Grigorev Kirill , Foox Jonathan , Bezdan Daniela , Butler Daniel , Luxton Jared J. , Reed Jake , Meydan Cem , Bailey Susan M. , Mason Christopher E. 
Published: February 2020

AbstractTelomeres are regions of repetitive nucleotide sequences capping the ends of eukaryotic chromosomes that protect against deterioration, whose lengths can be correlated with age and disease risk factors. Given their length and repetitive nature, telomeric regions are not easily reconstructed from short read sequencing, making telomere sequence resolution a very costly and generally intractable problem. Recently, long-read sequencing, with read lengths measuring in hundreds of Kbp, has made it possible to routinely read into telomeric regions and inspect their structure. Here, we describe a framework for extracting telomeric reads from single-molecule sequencing experiments, describing their sequence variation and motifs, and for haplotype inference. We find that long telomeric stretches can be accurately captured with long-read sequencing, observe extensive sequence heterogeneity of human telomeres, discover and localize non-canonical motifs (both previously reported as well as novel), and report the first motif composition maps of human telomeric diplotypes on a multi-Kbp scale.
Evaluation of Professional Ballet Dancers Body Posture During Barre Movements
Authors: Patterson R. M. , Hershberger N. , Balyakina E. , Capell W. , Mirochnitchenko A. , Surve S. 
Published: February 2020

AbstractBallet dancers have finite careers due to the demands placed upon their bodies throughout years of training, study, and performance. The average age a dancer retires is 34 due to persistent stress on their joints and injuries due to mechanical overload or overuse. Proper form is crucial to prevent injury. The aim of this study was to establish benchmarks for normal movement patterns among professional dancers. Ten professional ballerinas were studied. Reflective markers were placed on the pelvis, left and right anterior superior iliac spine (ASIS), and posterior iliac spine (PSIS) to evaluate motion during Barre movements: plié, grand battement, and développé. Pelvis flexion/extension, mediolateral rotation, and torsion were analyzed. These motions test different skills. The plié is a controlled coordinated motion using both legs. The grand battement and développé both require leg extension, one with a quick motion that creates momentum and one using controlled motion that requires strength. Each requires core and pelvis stability to perform accurately and with less injury. Dancers' motions were consistent. Maximum pelvis range of motion for the plié, grand battement, and développé were 8.0, 42, and 50 deg, respectively. This represents usable benchmarks with which other dancers may be compared, for example, those who are at different levels of training, injured, predisposed to injury, or recovering from injury. Early recognition of pathologic movement patterns could benefit professional and amateur dancers by helping to prevent injuries, and potentially improve the quality and length of their careers.
Acoustic Cell Separation Based on Density and Mechanical Properties
Authors: Xie Yuliang , Mao Zhangming , Bachman Hunter , Li Peng , Zhang Peiran , Ren Liqiang , Wu Mengxi , Huang Tony Jun 
Published: February 2020

Abstract
Density and mechanical properties (e.g., compressibility or bulk modulus) are important cellular biophysical markers. As such, developing a method to separate cells directly based on these properties can benefit various applications including biological research, diagnosis, prognosis, and therapeutics. As a potential solution, surface acoustic wave (SAW)-based cell separation has demonstrated advantages in terms of biocompatibility and compact device size. However, most SAW-reliant cell separations are achieved using an entangled effect of density, various mechanical properties, and size. In this work, we demonstrate SAW-based separation of cells/particles based on their density and compressibility, irrespective of their sizes, by manipulating the acoustic properties of the fluidic medium. Using our platform, SAW-based separation is achieved by varying the dimensions of the microfluidic channels, the wavelengths of acoustic signals, and the properties of the fluid media. Our method was applied to separate paraformaldehyde-treated and fresh Hela cells based on differences in mechanical properties; a recovery rate of 85% for fixed cells was achieved. It was also applied to separate red blood cells (RBCs) and white blood cells (WBCs) which have different densities. A recovery rate of 80.5% for WBCs was achieved.
Historical Review of Combined Experimental and Computational Approaches for Investigating Annulus Fibrosus Mechanics
Authors: Zhou Minhao , Werbner Benjamin , O'Connell Grace 
Published: February 2020

AbstractIntervertebral disc research has sought to develop a deeper understanding of spine biomechanics, the complex relationship between disc health and back pain, and the mechanisms of spinal injury and repair. To do so, many researchers have focused on characterizing tissue-level properties of the disc, where the roles of tissue subcomponents can be more systematically investigated. Unfortunately, experimental challenges often limit the ability to measure important disc tissue- and subtissue-level behaviors, including fiber–matrix interactions, transient nutrient and electrolyte transport, and damage propagation. Numerous theoretical and numerical modeling frameworks have been introduced to explain, complement, guide, and optimize experimental research efforts. The synergy of experimental and computational work has significantly advanced the field, and these two aspects have continued to develop independently and jointly. Meanwhile, the relationship between experimental and computational work has become increasingly complex and interdependent. This has made it difficult to interpret and compare results between experimental and computational studies, as well as between solely computational studies. This paper seeks to explore issues of model translatability, robustness, and efficient study design, and to propose and motivate potential future directions for experimental, computational, and combined tissue-level investigations of the intervertebral disc.
Sloshing in Regular Polygonal Basins—Frequencies, Modes, and Tileability
Authors: Wang C. Y. 
Published: February 2020

Abstract
The classical theory of small amplitude shallow water waves is applied to regular polygonal basins. The natural frequencies of the basins are related to the eigenvalues of the Helmholtz equation. Exact solutions are presented for triangular, square, and circular basins while pentagonal, hexagonal, and octagonal basins are solved, for the first time, by an efficient Ritz method. The first five eigenvalues of each basin are tabulated and the corresponding mode shapes are discussed. Tileability conditions are presented. Some modes (eigenmodes) can be tiled into larger domains.
Machining Response and Damage Evolution of Amorphous Carbon Coated Tools in High-Speed Micromilling of Ti–6Al–4V
Authors: Mittal Rinku K. , Kulkarni Salil S. , Barshilia Harish , Singh Ramesh 
Published: February 2020

Abstract
Micromilling process is widely used to create complex 3D miniature products due to its flexibility and its ability to process difficult-to-cut material like Titanium alloys. High rotational speeds are used to overcome the limited flexural stiffness of the tool but the cutting zone temperatures rise due to the high rotational speeds. In addition to this, friction between the tool workpiece and tool chip also plays a major role in the temperature rise. The friction and temperature affect the cutting forces, tool life and stability of the process. To reduce the friction and heat generation, nanostructured solid lubricant coatings can be used. This study is focused on characterizing the effect of amorphous carbon (WC/a-C) coating on the micromachining response during high-speed micromilling of Ti–6Al–4V. A decrease in cutting forces for coated tools is observed for lower feed. A comprehensive tool coating damage assessment has been done in terms of debonding area on flank and rake faces. An increase in debonding area has been observed with lengths of cut but at a feed/flute of 4 μm, tool breakage occurs after a machining length of 60 mm.