bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cross-attractor repertoire provides new perspective on structure-function relationship in the brain
Authors: Zhang Mengsen , Sun Yinming , Saggar Manish 
Published: May 2020

AbstractThe brain is a complex system exhibiting ever-evolving activity patterns without any external inputs or tasks. Such intrinsic dynamics (or lack thereof) are thought to play crucial roles in typical as well as atypical cognitive functioning. Linking the ever-changing intrinsic dynamics to the rather static anatomy is a challenging endeavor. Dynamical systems models are important tools for understanding how structure and function are linked in the brain. Here, we provide a novel modeling framework to examine such structure-function relations. Our deterministic approach complements previous modeling frameworks, which typically focus on noise-driven (or stochastic) dynamics near a single attractor. We examine the overall organizations of and coordination between all putative attractors. Using our approach, we first provide evidence that examining cross-attractor coordination between brain regions could better predict human functional connectivity than examining noise-driven near-attractor dynamics. Further, we observed that structural connections across scales modulate the energy costs of such cross-attractor coordination. Overall, our work provides a systematic framework for characterizing intrinsic brain dynamics as a web of cross-attractor transitions and associated energy costs. The framework may be used to predict transitions and energy costs associated with experimental or clinical interventions.
Three distinct neural mechanisms support movement-induced analgesia
Authors: Lu Xuejing , Yao Xinru , Thompson William Forde , Hu Li 
Published: May 2020

AbstractPain is essential for our survival by protecting us from severe injuries. Pain signals may be exacerbated by continued physical activities but can also be interrupted or over-ridden by physical movements, a process called movement-induced analgesia. A number of neural mechanisms have been proposed to account for this effect, including the reafference principle, the gate control theory of pain, and the top-down psychological modulation. Given that the analgesic effects of these mechanisms are temporally overlapping, it is unclear whether movement-induced analgesia results from a single neural mechanism or the joint action of multiple neural mechanisms. To address this question, we conducted five experiments on 130 healthy human subjects. First, the frequency of hand shaking was manipulated in order to quantify the relationship between the strength of the voluntary movement and the analgesic effect. Second, the temporal delay (between hand shaking and nociceptive laser stimuli) and the stimulated side (nociceptive laser stimuli were delivered on the hand ipsilateral or contralateral to the shaken one) were manipulated to quantify the temporal and spatial characteristics of the analgesic effect induced by voluntary movement. Combining psychophysics and electroencephalographic recordings, we demonstrated that movement-induced analgesia is a result of the joint action of multiple neural mechanisms. This investigation is the first to disentangle the distinct contributions of different neural mechanisms to the analgesic effect of voluntary movement. These findings extend our understanding of sensory attenuation arising from voluntary movement and may prove instrumental in the development of new strategies in pain management.
Elevated dietary ω-6 polyunsaturated fatty acids induce reversible peripheral nerve dysfunction that exacerbates comorbid pain conditions
Authors: Boyd Jacob T. , LoCoco Peter M. , Furr Ashley R. , Bendele Michelle R. , Tram Meilinn , Li Qun , Chang Fang-Mei , Colley Madeline E. , Arris Dominic A. , Locke Erin E. , Bach Stephan B.H. , Tobon Alejandro , Ruparel Shivani B. , Hargreaves Kenneth M. 
Published: May 2020

ABSTRACTChronic pain is the leading cause of disability worldwide1 and commonly associated with comorbid disorders2. However, the role of diet in chronic pain is poorly understood. Of particular interest is the Western-style diet, enriched with ω-6 polyunsaturated fatty acids (PUFAs) that accumulate in membrane phospholipids and oxidize into pronociceptive oxylipins3,4. Here we report that mice administered a diet enriched with ω-6 PUFAs develop persistent nociceptive hypersensitivities, spontaneously-active and hyper-responsive glabrous afferent fibers, and histologic markers of peripheral nerve damage reminiscent of a peripheral neuropathy. Linoleic and arachidonic acids accumulate in lumbar dorsal root ganglia, with increased liberation via elevated PLA2 activity. Pharmacological and molecular inhibition of PLA2g7 or diet reversal with high ω-3 PUFAs attenuate nociceptive behaviors, neurophysiologic abnormalities, and afferent histopathology induced by high ω-6 intake. In addition, ω-6 accumulation exacerbates the intensity or duration of allodynia observed in preclinical inflammatory and neuropathic pain models, as well as in clinical diabetic neuropathy. Collectively, these data reveal diet as a novel etiology of peripheral neuropathy and risk factor for chronic pain, and implicate multiple therapeutic considerations for clinical pain management.
Evaluation of cerebellar function scores in relation to cerebellar axonal loss in multiple sclerosis
Authors: Boonstra F. , Gajamange S. , Noffs G. , Perera T. , Strik M. , Vogel A. , Butzkueven H. , Evans A. , van der Walt A. , Kolbe S. 
Published: May 2020

AbstractBackgroundCerebellar damage is common in people with multiple sclerosis (pwMS) and is associated with worse progression and relapse recovery. Studies into the importance of the cerebellum in pwMS are hampered by limited understanding of cerebellar damage and its relation to cerebellar function in pwMS.ObjectiveExamine axonal loss, as a primary driver of progressive neurological decline, in the cerebellum using advanced diffusion MRI and compare axonal loss with cerebellar dysfunction in pwMSMethodsWe recruited 55 pwMS and 14 healthy controls. Clinical assessments included scale for the assessment and rating of ataxia (SARA), and Bain tremor ratings. Subjects underwent FLAIR, T1-weighted and diffusion MRI. Cerebellar grey and white matter and lesion volume were calculated. Cerebellar axonal loss was examined with fibre-specific markers. Fibre density and cross-section (FDC) accounts for microscopic and macroscopic changes in a fibre bundle.ResultsLoss of cerebellar FDC was associated with increased SARA (r=-0.42, p<0.01) and tremor severity (rho=-0.35, p=0.01). Cerebellar lesion volume correlated with SARA (r=0.49, p<0.01) and tremor severity (rho=0.41, p=0.01).ConclusionFibre-specific measures of cerebellar pathology could provide a functionally relevant marker of cerebellar damage in MS. Future trials using fibre-specific markers are needed to further characterize cerebellar pathology in pwMS and understand its significance in disease progression.
Comparative genomics of ocularPseudomonas aeruginosastrains from keratitis patients with different clinical outcomes
Authors: Kandasamy Kathirvel , Thirumalmuthu Kannan , Prajna Namperumalsamy Venkatesh , Lalitha Prajna , Mohankumar Vidyarani , Devarajan Bharanidharan 
Published: May 2020

AbstractBacterial keratitis caused byPseudomonas aeruginosais a destructive disease of cornea. Pseudomonas keratitis progresses rapidly and leads to vision loss if untreated. Even with adequate treatment, many patients show poor visual outcomes. The virulence factors or multiple drug-resistant (MDR) mechanisms of the ocular strains responsible for poor clinical outcomes remain largely unknown. Here, we performed whole-genome sequencing of fiveP. aeruginosastrains cultured from corneal scrapings of the healed and corneal buttons of the poor outcome keratitis patients. We investigated the distribution of virulence factors, resistance genes and resistance-associated mutations, the efflux-pump system in all five genomes, and as groups between poor and good clinical outcome as well as MDR vs. non-MDR. We detected several resistance genes and mutations associated with drug resistance in MDR groups; however, a large number of virulence genes were detected in all our genomes. Among the virulence genes, exoU and exoS exotoxin of the Type III secretion system detected in MDR and non-MDR strains, respectively, considered as main virulence contributors of keratitis pathogenesis. Despite this fact, this study did not show an association between MDR with exoU and poor clinical outcomes. However, strain-specific resistance and virulence genes were observed in this study, suggesting their role in the clinical outcome. Mainly, the flagellar genes fliC and fliD, reported to altering the host immune response, might impact the clinical outcome. This comparative study may provide new insights into the genome of ocular strains and requires further functional studies.
Acute Exercise Following Skill Practice Promotes Motor Memory Consolidation in Parkinson’s Disease
Authors: Wanner Philipp , Winterholler Martin , Gaßner Heiko , Winkler Jürgen , Klucken Jochen , Pfeifer Klaus , Steib Simon 
Published: May 2020

AbstractAcute cardiovascular exercise has shown to promote neuroplastic processes, and thus to improve the consolidation of newly acquired motor skills in healthy adults. First results suggest that this concept may be transferred to populations with motor and cognitive dysfunctions. In this context, Parkinson’s disease (PD) is highly relevant since patients demonstrate deficits in motor learning. Hence, in the present study we sought to explore the effect of a single post-practice exercise bout on motor memory consolidation in PD patients.For this purpose, 17 PD patients (Hoehn and Yahr: 1 – 2.5, age: 60.1 ± 7.9 y) practiced a whole-body task followed by either (i) a moderate-intense bout of cycling, or (ii) seated rest for a total of 30 minutes. The motor task required the participants to balance on a tiltable platform (stabilometer) for 30 seconds. During skill practice, patients performed 15 trials followed by a retention test 1 day and 7 days later. We calculated time in balance (platform within ± 5° from horizontal) for each trial and within- and between-group differences in memory consolidation (i.e. offline learning = skill change from last acquisition block to retention tests) were analyzed.Groups revealed similar improvements during skill practice (F4,60= .316, p = .866), but showed differences in offline learning, which was only evident after 7 days (F1,14= 5.602, p = .033).Our results suggest that a single post-practice exercise bout is effective in enhancing long-term motor memory consolidation in a population with motor learning impairments. This may point at unique promoting effects of exercise on dopamine neurotransmission involved in memory formation. Future studies should investigate the potential role of exercise-induced effects on the dopaminergic system.HighlightsAcute exercise enhanced motor memory consolidation in PDEffects were evident only at 7-day retentionResults may indicate unique exercise-effects on the dopaminergic systemFindings show promising potential of exercise for motor rehabilitation
GALA: gap-free chromosome-scale assembly with long reads
Authors: Awad Mohamed , Gan Xiangchao 
Published: May 2020

AbstractHigh-quality genome assembly has wide applications in genetics and medical studies. However, it is still very challenging to achieve gap-free chromosome-scale assemblies using current workflows for long-read platforms. Here we propose GALA (Gap-freelong-readassembler), a chromosome-by-chromosome assembly method implemented through a multi-layer computer graph that identifies mis-assemblies within preliminary assemblies or chimeric raw reads and partitions the data into chromosome-scale linkage groups. The subsequent independent assembly of each linkage group generates a gap-free assembly free from the mis-assembly errors which usually hamper existing workflows. This flexible framework also allows us to integrate data from various technologies, such as Hi-C, genetic maps, a reference genome and even motif analyses, to generate gap-free chromosome-scale assemblies. Wede novoassembled theC. elegansandA. thalianagenomes using combined Pacbio and Nanopore sequencing data from publicly available datasets. We also demonstrated the new method’s applicability with a gap-free assembly of a human genome with the help a reference genome. In addition, GALA showed promising performance for Pacbio high-fidelity long reads. Thus, our method enables straightforward assembly of genomes with multiple data sources and overcomes barriers that at present restrict the application ofde novogenome assembly technology.
HerpesDRG: a comprehensive resource for human herpesvirus antiviral drug resistance genotyping
Authors: Charles OJ , Venturini C , Goldstein RA , Breuer J 
Published: May 2020

AbstractThe prevention and treatment of many herpesvirus associated diseases is based on the utilization of antiviral therapies, however therapeutic success is limited by the development of drug resistance. A comprehensive point of truth of resistance conferring mutations has been missing but would be important to aid the development of antiviral drugs and in management of infections. We therefore developed HerpesDRG, a drug resistance mutation database for all the known important genes and current treatment options, built from a systematic review of available genotype to phenotype literature. The database is released along with an R package to provide a low barrier of entry to variant resistance annotation and clinical implication analysis from common sanger and NGS sequence data. This represents the first openly available and community maintainable knowledgebase of drug resistance mutations for the human herpes viruses (HHV), developed for the community of researchers and clinicians tackling HHV drug resistance.AvailabilityThe HerpesDRG database is available at github.com/ojcharles/herpesdrg-db. The R package for resistance genotyping data is available at github.com/ojcharles/herpesdrg. A user-friendly webserver is available at cmv-resistance.ucl.ac.uk/herpesdrg
Community-scale Synchronization and Temporal Partitioning of Gene Expression, Metabolism, and Lipid Biosynthesis in Oligotrophic Ocean Surface Waters
Authors: Muratore Daniel , Boysen Angie K. , Harke Matthew J. , Becker Kevin W. , Casey John R. , Coesel Sacha N. , Mende Daniel R. , Wilson Samuel T. , Aylward Frank O. , Eppley John M. , Vislova Alice , Peng Shengyun , Rodriguez-Gonzalez Rogelio A. , Beckett Stephen J. , Armbrust E. Virginia , DeLong Edward F. , Karl David M. , White Angelicque E. , Zehr Jonathan P. , Van Mooy Benjamin A.S. , Dyhrman Sonya T. , Ingalls Anitra E. , Weitz Joshua S. 
Published: May 2020

AbstractSunlight drives daily rhythms of photosynthesis, growth, and division of photoautotrophs throughout the surface oceans. However, the cascading impacts of oscillatory light input on diverse microbial communities and community-scale metabolism remains unclear. Here we use an unsupervised machine learning approach to show that a small number of diel archetypes can explain pervasive periodic dynamics amongst more than 65,000 distinct time series, including transcriptional activity, macromolecules, lipids, and metabolites from the North Pacific Subtropical Gyre. Overall, we find evidence for synchronous timing of carbon-cycle gene expression that underlie daily oscillations in the concentrations of particulate organic carbon. In contrast, we find evidence of asynchronous timing in gene transcription related to nitrogen metabolism and related metabolic processes consistent with temporal niche partitioning amongst microorganisms in the bacterial and eukaryotic domains.
Molecular and clinical characterization of 5mC regulators in glioma: results of a multicenter study
Authors: Zhao Liang , Zhang Jiayue , Liu Zhiyuan , Wang Yu , Xuan Shurui , Zhao Peng 
Published: May 2020

AbstractDNA methylation has been widely reported to associate with the progression of glioma. DNA methylation at the 5 position of cytosine (5-methylcytosine, 5mC), which is regulated by 5mC regulators (“writers”, “erasers” and “readers”), is the most critical modification pattern. However, a systematic study on the role of these regulators in glioma is still lacking. In this study, we collected gene expression profiles and corresponding clinical information of gliomas from three independent public datasets. Gene expression of 21 5mC regulators was analyzed and linked to clinicopathological features. A novel molecular classification of glioma was developed using consensus non-negative matrix factorization (CNMF) algorithm, and the tight association with molecular characteristics as well as tumor immune microenvironment was clarified. Sixteen prognostic factors were identified using univariate Cox regression analysis, and a 5mC regulator-based gene signature was further constructed via the least absolute shrinkage and selection operator (LASSO) cox analysis. This risk model was proved as an efficient predictor of overall survival for diffuse glioma, glioblastoma (GBM), and low-grade glioma (LGG) patients in three glioma cohorts. The significant correlation between risk score and intratumoral infiltrated immune cells, as well as immunosuppressive pathways, was found, which explained the difference in clinical outcomes between high and low-risk groups. Finally, a nomogram incorporating the gene signature and other clinicopathological risk factors was established, which might direct clinical decision making. In summary, our work highlights the potential clinical application value of 5mC regulators in prognostic stratification of glioma and their potentialities for developing novel treatment strategies.
Diet-Induced Vitamin D Deficiency Results in Reduced Skeletal Muscle Mitochondrial Respiration in C57BL/6J Mice
Authors: Ashcroft Stephen P. , Fletcher Gareth , Philp Ashleigh M. , Atherton Philip J. , Philp Andrew 
Published: May 2020

AbstractVitamin D deficiency is known to be associated with symptoms of skeletal muscle myopathy including muscle weakness and fatigue. Recently, vitamin D related metabolites have been linked to the maintenance of mitochondrial function within skeletal muscle. However, current evidence is limited toin vitromodels and the effects of diet-induced vitamin D deficiency upon skeletal muscle mitochondrial functionin vivohave received little attention. In order to examine the role of vitamin D in the maintenance of mitochondrial functionin vivo, we utilised an established model of diet-induced vitamin D deficiency in C57BL/6J mice. Mice were fed either a control (2,200 IU/kg) or a vitamin D deplete (0 IU/kg) diet for periods of 1-, 2- and 3-months. Skeletal muscle mitochondrial function and ADP sensitivity were assessed via high-resolution respirometry and mitochondrial protein content via immunoblotting. As a result of 3-month of diet-induced vitamin D deficiency, respiration supported via CI+IIPand ETC were 35% and 37% lower when compared to vitamin D replete mice (P< 0.05). Despite functional alterations, the protein expression of electron transfer chain subunits remained unchanged in response to dietary intervention (P> 0.05). In conclusion, we report that 3-months of diet-induced vitamin D deficiency reduced skeletal muscle mitochondrial function in C57BL/6J mice. Our data, when combined with previousin vitroobservations, suggests that vitamin D mediated regulation of mitochondrial function may underlie the exacerbated muscle fatigue and performance deficits observed during vitamin D deficiency.
ER Proteostasis Regulators Reduce Amyloidogenic Light Chain Secretion Through an On-Target, ATF6-Independent Mechanism
Authors: Rius Bibiana , Mesgarzadeh Jaleh S. , Romine Isabelle C. , Paxman Ryan J. , Kelly Jeffery W. , Wiseman R. Luke 
Published: May 2020

SUMMARYThe plasma cell secretion and toxic aggregation of amyloidogenic immunoglobulin light chains (LCs) causes proteotoxicity in Light Chain Amyloidosis (AL). We recently identified endoplasmic reticulum (ER) proteostasis regulators such as compound147that reduce secretion and aggregation of LCs implicated in AL (Plate, Cooley et al., 2016). Compound147promotes adaptive ER proteostasis remodeling through a mechanism involving covalent modification of multiple protein disulfide isomerases (PDIs) and subsequent activation of the ATF6 unfolded protein response (UPR) -associated transcriptional signaling pathway (Paxman, Plate et al., 2018). Here, we show that the147-dependent reduction in amyloidogenic LC secretion from AL patient plasma cells is independent of ATF6 activation, but instead requires on-target PDI modification. Our results reveal pharmacologic targeting of PDIs as a potential strategy to ameliorate AL-associated proteotoxicity and demonstrate that147can influence ER proteostasis through multiple on-target mechanisms including ATF6 activation and PDI modification.IMPACT STATEMENTThis study demonstrates the broad potential for endoplasmic reticulum proteostasis regulator compounds such as147to influence secretory proteostasis of disease-associated proteins through multiple on target mechanisms.
Algorithms for the selection of fluorescent reporters
Authors: Vaidyanathan Prashant , Appleton Evan , Tran David , Vahid Alexander , Church George , Densmore Douglas 
Published: May 2020

ABSTRACTMolecular biologists rely on the use of fluorescent probes to take measurements of their model systems. These fluorophores fall into various classes (e.g. fluorescent dyes, fluorescent proteins, etc.), but they all share some general properties (such as excitation and emission spectra, brightness) and require similar equipment for data acquisition. Selecting an ideal set of fluorophores for a particular measurement technology or vice versa is a multidimensional problem that is difficult to solve withad hocmethods due to the enormous solution space of possible fluorophore panels. Choosing sub-optimal fluorophore panels can result in unreliable or erroneous measurements of biochemical properties in model systems. Here, we describe a set of algorithms, implemented in an open-source software tool, for solving these problems efficiently to arrive at fluorophore panels optimized for maximal signal and minimal bleed-through.