bluuebunny/crossref_metadata_2025_split huggingface dataset:
Investigation of neurobiological responses to Theta Burst Stimulation during recovery from mild traumatic brain injury (mTBI)
Authors: Coyle Hannah L. , Bailey Neil W. , Ponsford Jennie , Hoy Kate E. 
Published: June 2022

AbstractThe ability of the brain to recover following neurological insult is of considerable interest in mild traumatic brain injury (mTBI) populations. To date, a limited amount of research has examined changes in brain function over time following mTBI. Investigating whether non-invasive brain stimulation (NIBS) can modulate neurophysiology and cognitive performance is particularly relevant for therapeutic targeting post injury. The purpose of the current study was to investigate the neurobiological effects of a single session of intermittent theta burst stimulation (iTBS) applied to the dorsolateral prefrontal cortex (DLPFC) in participants with mTBI during recovery. Changes to neurophysiology were assessed with electroencephalography (EEG) and transcranial magnetic stimulation combined with EEG (TMS-EEG). Digit span working memory accuracy was assessed as a marker of cognitive performance. 30 patients in the subacute phase following mTBI (within one month post-injury) and 26 demographically matched controls were assessed. Participants also completed 3-month (mTBI: N = 21, control: N = 26) and 6-month (mTBI: N = 15, control: N = 24) follow up sessions. Cluster-based analyses demonstrated iTBS did not reliably modulate neurophysiological activity, and no differences were found in cognitive performance in either mTBI or control group participants across any of the assessment time points. The factors that may have contributed to our results are unclear, and possible limitations to our experimental design are discussed. Our findings highlight additional research is required to establish the effects of iTBS on plasticity and cognition in a mTBI population prior to therapeutic application.
Peripheral signature of altered synaptic integrity in young onset Cannabis Use Disorder: A proteomic study of circulating extracellular vesicles
Authors: Ganesh Suhas , Lam TuKiet T. , Garcia-Milian Rolando , D’Souza Deepak , Nairn Angus C. , Elgert Katya , Eitan Erez , Ranganathan Mohini 
Published: June 2022

AbstractBackgroundThe prevalence of cannabis use and Cannabis Use Disorder (CUD) are highest amongst adolescents and young adults. A lack of brain tissues from patients with CUD limits the ability to examine the molecular basis of cannabis related neuropathology. Proteomic studies of neuron-derived extracellular vesicles (NDEs) isolated from the biofluids may reveal markers of neuropathology in CUD.MethodsNDEs were extracted using ExoSORT, an immunoaffinity method, from plasma samples of 10 patients with young onset CUD and 10 matched controls. Differential proteomic profiles of NDEs between groups was explored with Label Free Quantification (LFQ) mass spectrometry. Selected differentially abundant proteins were validated using orthogonal methods.ResultsA total of 231 (+/- 10) unique proteins were identified in NDE preparations of which 28 were differentially abundant between groups. The difference in abundance properdin, encoded by the CFP gene surpassed the significance threshold after false discovery rate correction.Notably, SHANK1 (SH3 and multiple ankyrin repeat domains protein 1), an adapter protein at the post-synaptic density, was found to be depleted in the CUD compared to control NDE preparations.DiscussionThe study shows that LFQ mass spectrometry proteomic analysis of NDEs derived from plasma may yield important insights into the synaptic pathology associated with CUD. Optimization of this approach may lead to a novel assay to study altered proteomic signalling in the brain using liquid biopsy in diverse neuropsychiatric syndromes.
Is COVID-19 seasonal? A time series modeling approach
Authors: Wiemken Timothy L , Khan Farid , Nguyen Jennifer L , Jodar Luis , McLaughlin John M 
Published: June 2022

ABSTRACTBackgroundDetermining whether SARS-CoV-2 is or will be seasonal like other respiratory viruses is critical for public health planning, including informing vaccine policy regarding the optimal timing for deploying booster doses. To help answer this urgent public health question, we evaluated whether COVID-19 case rates in the United States and Europe followed a seasonal pattern using time series models.MethodsWe analyzed COVID-19 data from Our World in Data from Mar 2020 through Apr 2022 for the United States (and Census Region) and five European countries (Italy, France, Germany, Spain, and the United Kingdom). For each, anomalies were identified using Twitter’s decomposition method and Generalized Extreme Studentized Deviate tests. We performed sensitivity analyses to determine the impact of data source (i.e., using US Centers for Disease Control and Prevention [CDC] data instead of OWID) and whether findings were similar after adjusting for multiple covariates. Finally, we determined whether our time series models accurately predicted seasonal influenza trends using US CDC FluView data.ResultsAnomaly plots detected COVID-19 rates that were higher than expected between November and March each year in the United States and Europe. In the US Southern Census Region, in addition to seasonal peaks in the fall/winter, a second peak in Aug/Sep 2021 was identified as anomalous. Results were robust to sensitivity analyses.ConclusionsOur results support employing annual protective measures against SARS-CoV-2 such as administration of seasonal booster vaccines or other non-pharmaceutical interventions in a similar timeframe as those already in place for influenza prevention.Summary of the Main PointAlthough SARS-CoV-2 continues to cause morbidity and mortality year-round due to its high transmissibility and rapid viral evolution, our results suggest that COVID-19 activity in the United States and Europe peaks during the traditional winter viral respiratory season.
Rethinking the Human Resource Crisis in Africa’s Health Systems: Evidence across Ten Countries
Authors: Sheffel Ashley , Andrews Kathryn G. , Conner Ruben , Giorgio Laura Di , Evans David K. , Gatti Roberta , Lindelow Magnus , Sharma Jigyasa , Svensson Jakob , Wane Waly , Welander Anna 
Published: June 2022

AbstractSub-Saharan Africa has fewer medical workers per capita than any region of the world, and that shortage has been highlighted consistently as a critical constraint to improving health outcomes in the region. This paper draws on newly available, systematic, comparable data from ten countries in the region to explore the dimensions of this shortage. We find wide variation in human resources performance metrics, both within and across countries. Many facilities are barely staffed, and effective staffing levels fall further when adjusted for absenteeism. However, caseloads—while also varying widely within and across countries—are also low in many settings, suggesting that even within countries, deployment rather than shortages, together with barriers to demand, may be the principal challenges. Beyond raw numbers, we observe significant proportions of health workers with very low levels of clinical knowledge on standard maternal and child health conditions. This work demonstrates that countries may need to invest broadly in health workforce deployment, improvements in capacity and performance of the health workforce, and on addressing demand constraints, rather than focusing narrowly on increases in staffing numbers.Key messagesThis study analyzed health worker surveys from ten countries in Sub-Saharan Africa for a deeper understanding of human resource challenges.Average staffing across facilities is far below the stated staffing norms for each country.Half of health centers and health posts have one or fewer clinical staff assigned to them.Staffing is even lower when adjusted for absence, which is highest in small facilities and public facilities.Massive within-country variation in caseload suggests that staffing problems may be solved in part by reallocation of clinical staff.Health workers lack basic clinical competencies, caseloads are imbalanced, and there is substantial absence of workers from health facilities.
Determinants of sugar-induced influx in the mammalian fructose transporter GLUT5
Authors: McComas Sarah E. , Reichenbach Tom , Mitrovic Darko , Alleva Claudia , Bonaccorsi Marta , Delemotte Lucie , Drew David 
Published: June 2022

AbstractIn mammals, glucose transporters (GLUT) control organism-wide blood glucose homeostasis. In human, this is accomplished by fourteen different GLUT isoforms, that transport glucose and other monosaccharides with varying substrate preferences and kinetics. Nevertheless, there is little difference between the sugar-coordinating residues in the GLUT proteins and even the malarialplasmodium falciparumtransporterPfHT1, which is uniquely able to transport a wide range of different sugars.PfHT1 was captured in an intermediate “occluded” state, revealing how the extracellular gating helix TM7b has moved to break and occlude the sugar-binding site. Sequence difference and kinetics indicated that the TM7b gating helix dynamics and interactions likely evolved to enable substrate promiscuity inPfHT1, rather than the sugar-binding site itself. It was unclear, however, if the TM7b structural transitions observed inPfHT1 would be similar in the other GLUT proteins. Here, using enhanced sampling molecular dynamics simulations, we show that the fructose transporter GLUT5 spontaneously transitions through an occluded state that closely resemblesPfHT1. The coordination of fructose lowers the energetic barriers between the outward and inward-facing states, and the observed binding mode for fructose is consistent with biochemical analysis. Rather than a substrate binding site that achieves strict specificity by having a high-affinity for the substrate, we conclude GLUT proteins have allosterically coupled sugar binding with an extracellular gate that forms the high-affinity transition-state instead. This substrate-coupling pathway presumably enables the catalysis of fast sugar flux at physiological relevant blood-glucose concentrations.
Genetic regulation of the human plasma proteome in 54,306 UK Biobank participants
Authors: Sun Benjamin B. , Chiou Joshua , Traylor Matthew , Benner Christian , Hsu Yi-Hsiang , Richardson Tom G. , Surendran Praveen , Mahajan Anubha , Robins Chloe , Vasquez-Grinnell Steven G. , Hou Liping , Kvikstad Erika M. , Burren Oliver S. , Cule Madeleine , Davitte Jonathan , Ferber Kyle L. , Gillies Christopher E. , Hedman Åsa K. , Hu Sile , Lin Tinchi , Mikkilineni Rajesh , Pendergrass Rion K. , Pickering Corran , Prins Bram , Raj Anil , Robinson Jamie , Sethi Anurag , Ward Lucas D. , Welsh Samantha , Willis Carissa M. ,   Alnylam Human Genetics,   AstraZeneca Genomics Initiative,   Biogen Biobank Team,   Bristol Myers Squibb,   Genentech Human Genetics,   GlaxoSmithKline Genomic Sciences,   Pfizer Integrative Biology,   Population Analytics of Janssen Data Sciences,   Regeneron Genetics Center, Burkitt-Gray Lucy , Black Mary Helen , Fauman Eric B. , Howson Joanna M. M. , Kang Hyun Min , McCarthy Mark I. , Melamud Eugene , Nioi Paul , Petrovski Slavé , Scott Robert A. , Smith Erin N. , Szalma Sándor , Waterworth Dawn M. , Mitnaul Lyndon J. , Szustakowski Joseph D. , Gibson Bradford W. , Miller Melissa R. , Whelan Christopher D. 
Published: June 2022

AbstractThe UK Biobank Pharma Proteomics Project (UKB-PPP) is a collaboration between the UK Biobank (UKB) and thirteen biopharmaceutical companies characterising the plasma proteomic profiles of 54,306 UKB participants. Here, we describe results from the first phase of UKB-PPP, including protein quantitative trait loci (pQTL) mapping of 1,463 proteins that identifies 10,248 primary genetic associations, of which 85% are newly discovered. We also identify independent secondary associations in 92% of cis and 29% of trans loci, expanding the catalogue of genetic instruments for downstream analyses. The study provides an updated characterisation of the genetic architecture of the plasma proteome, leveraging population-scale proteomics to provide novel, extensive insights into trans pQTLs across multiple biological domains. We highlight genetic influences on ligand-receptor interactions and pathway perturbations across a diverse collection of cytokines and complement proteins, and illustrate long-range epistatic effects of ABO blood group and FUT2 secretor status on proteins with gastrointestinal tissue-enriched expression. We demonstrate the utility of these data for drug target discovery by extending the genetic proxied effect of PCSK9 levels on lipid concentrations, cardio- and cerebro-vascular diseases, and additionally disentangle specific genes and proteins perturbed at COVID-19 susceptibility loci. This public-private partnership provides the scientific community with an open-access proteomics resource of unprecedented breadth and depth to help elucidate biological mechanisms underlying genetic discoveries and accelerate the development of novel biomarkers and therapeutics.
TheLegionella-driven PtdIns(4)Pgradient at LCV-ER membrane contact sites promotes Vap-, OSBP- and Sac1-dependent pathogen vacuole remodeling
Authors: Vormittag Simone , Hüsler Dario , Haneburger Ina , Kroniger Tobias , Anand Aby , Prantl Manuel , Barisch Caroline , Maaß Sandra , Becher Dörte , Letourneur François , Hilbi Hubert 
Published: June 2022

AbstractThe causative agent of Legionnaires’ disease,Legionella pneumophila, governs interactions with host cells by secreting ca. 330 different “effector” proteins. The facultative intracellular bacteria replicate in macrophages and amoeba within a unique compartment, theLegionella-containing vacuole (LCV). Hallmarks of LCV formation are the phosphoinositide (PI) lipid conversion from PtdIns(3)Pto PtdIns(4)P, fusion with endoplasmic reticulum (ER)-derived vesicles and a tight association with the ER. Proteomics of purified LCVs revealed the presence of membrane contact sites (MCS) proteins implicated in lipid exchange. Using dually fluorescence-labeledDictyostelium discoideumamoeba, we reveal that the VAMP-associated protein (Vap), the PtdIns(4)P4-phosphatase Sac1, and the large fusion GTPase Sey1/atlastin-3 localize to the ER, but not to the LCV membrane, and that these ER-resident proteins promote intracellular replication ofL. pneumophilaand LCV remodeling. Moreover, oxysterol binding proteins (OSBPs) preferentially localize to the ER (OSBP8) or the LCV membrane (OSBP11), respectively, and promote (OSBP8) or restrict (OSBP11) intracellular replication ofL. pneumophilaand LCV expansion. Furthermore, the PtdIns(4)P-subvertingL. pneumophilaeffectors LepB and SidC also promote LCV remodeling. Taken together, theLegionella- and host cell-driven PtdIns(4)Pgradient at LCV-ER MCSs promotes Vap-, OSBP- and Sac1-dependent pathogen vacuole remodeling.
Single-cell characterization of human GBM reveals regional differences in tumor-infiltrating leukocyte activation
Authors: Schmassmann Philip , Roux Julien , Dettling Steffen , Hogan Sabrina , Shekarian Tala , Martins Tomás A. , Ritz Marie-Françoise , Herter Sylvia , Bacac Marina , Hutter Gregor 
Published: June 2022

AbstractGlioblastoma (GBM) harbors a highly immunosuppressive tumor microenvironment (TME) which influences glioma growth. Major efforts have been undertaken to describe the TME on a single-cell level. However, human data on regional differences within the TME remain scarce. Here, we performed high-depth single-cell RNA sequencing (scRNAseq) on paired biopsies from the tumor center, peripheral infiltration zone and blood of five primary GBM patients. Through analysis of > 45’000 cells, we revealed a regionally distinct transcription profile of microglia (MG) and monocyte-derived macrophages (MdMs) and an impaired activation signature in the tumor-peripheral cytotoxic-cell compartment. Comparing tumor-infiltrating CD8+T cells with circulating cells identified CX3CR1highand CX3CR1intCD8+T cells with effector and memory phenotype, respectively, enriched in blood but absent in the TME. Tumor CD8+T cells displayed a tissue-resident memory phenotype with dysfunctional features. Our analysis provides a regionally resolved mapping of transcriptional states in GBM-associated leukocytes, serving as an additional asset in the effort towards novel therapeutic strategies to combat this fatal disease.
The mechanosensitive ion channel Piezo1 modulates the migration and immune response of microglia
Authors: Zhu Ting , Kala Shashwati , Guo Jinghui , Wu Yong , Chen Hui , Zhu Jiejun , Wong Kin Fung , Cheung Chi Pong , Huang Xiaohui , Zhao Xinyi , Lei Ting , Yang Minyi , Sun Lei 
Published: June 2022

AbstractMicroglia are the brain’s resident immune cells, performing surveillance to promote homeostasis and healthy functioning. While chemical signaling in microglia is well-studied, the mechanical cues regulating their function are less well-understood. Here, we investigate the role of the mechanosensitive ion channel Piezo1 in microglia migration, pro-inflammatory cytokine production and stiffness sensing. We demonstrated the functional expression of Piezo1 in microglia and identified genes whose expression was affected by conditional Piezo1 knockout in transgenic mice. Functional assays revealed that Piezo1-deficiency in microglia enhanced migration towards amyloid β-protein, and decreased levels of pro-inflammatory cytokines produced upon stimulation by lipopolysaccharide, both in vitro and in vivo. The phenomenon could be mimicked or reversed using a Piezo1-specific agonist or antagonist. Finally, we also showed that Piezo1 mediated the effect of substrate stiffness-induced migration and cytokine expression. Altogether, we show that Piezo1 is an important molecular mediator for microglia, its activation modulating their migration and immune responses.
Sex-Specific Role of Myostatin Signaling in Neonatal Muscle Growth, Denervation Atrophy, and Neuromuscular Contractures
Authors: Emmert Marianne E , Aggarwal Parul , Shay-Winkler Kritton , Lee Se-Jin , Goh Qingnian , Cornwall Roger 
Published: June 2022

AbstractNeonatal brachial plexus injury (NBPI) causes disabling and incurable muscle contractures that result from impaired longitudinal growth of denervated muscles. This deficit in muscle growth is driven by increased proteasome-mediated protein degradation, suggesting a dysregulation of muscle proteostasis. The myostatin (MSTN) pathway, a prominent muscle-specific regulator of proteostasis, is a putative signaling mechanism by which neonatal denervation could impair longitudinal muscle growth, and thus a potential target to prevent NBPI-induced contractures. Through a mouse model of NBPI, our present study revealed that pharmacologic inhibition of MSTN signaling induces hypertrophy, restores longitudinal growth, and prevents contractures in denervated muscles of female but not male mice, despite inducing hypertrophy of normally innervated muscles in both sexes. Additionally, the MSTN-dependent impairment of longitudinal muscle growth after NBPI in female mice is associated with perturbation of 20S proteasome activity, but not through alterations in canonical MSTN signaling pathways. These findings reveal a sex dimorphism in the regulation of neonatal longitudinal muscle growth and contractures, thereby providing insights into contracture pathophysiology, identifying a potential muscle-specific therapeutic target for contracture prevention, and underscoring the importance of sex as a biological variable in the pathophysiology of neuromuscular disorders.
‘’Reproductive response of laying chickens to ameliorative method of aflatoxin
Authors: Ojo Olayinka Abosede , Bitto Immanuel , Ewuola Emmanuel Olubisi 
Published: June 2022

AbstractAflatoxin is toxic, carcinogenic and ubiquitous in nature, affecting both crops and livestock. Mitigating aflatoxin effect using toxin binders has not been very effective. Information on the use of biological methods in aflatoxin mitigation has not been adequately documented. Consequently, influence of bio-control method of aflatoxin on some reproductive hormones, ovarian weight and histopathological parameters of laying chickens (LC) were investigated. Point-of-lay Bovan Nera (n=700) were harphazardly distributed to four dietary treatments; Aflasafe maize-based diet (AMBD), farm feed (FF), aflatoxin-contaminated diet with toxin binder (ACDTB) and aflatoxin-contaminated diet without toxin binder (ACDWTB). The contaminated diets contained 306.3ppb aflatoxin and the experimental design was completely randomized into four treatments (n= 175) of five replicates (n=35) per treatment for a period of 14 weeks. Blood (5mL) was collected at 14th week for LC to determine the estrogen, luteinising hormone (LH), follicle stimulating hormone (FSH), histopathology of the ovary using standard procedures. Data were analysed using descriptive statistics and ANOVA at a0.05. The ROW (%) ranged from 0.34±0.2 (ACDTB) to 0.93±0.3 (AMBD). Estrogen (mg/dL) value was highest in LC fed ACDWTB (2.75±1.08) and least in FF (2.07±0.52). The LH (iu/L) value was highest in LC fed AMBD (1.29±1.68) and least in ACDTB (0.36±0.32). Histopathology of the ovary showed cysts, observed along the oviduct wall in LC fed ACDTB. AMBD enhanced active laying period in LC with no sign of aflatoxocosis. The use of aflasafe maize grain in poultry diet is recommended.
GRINtrode: A neural implant for simultaneous two-photon imaging and extracellular electrophysiology in freely moving animals
Authors: McCullough Connor M. , Ramirez-Gordillo Daniel , Hall Michael , Futia Gregory L. , Moran Andrew K. , Gibson Emily A. , Restrepo Diego 
Published: June 2022

AbstractSignificanceIn vivo imaging and electrophysiology are powerful tools to explore neuronal function that each offer unique complementary information with advantages and limitations. Capturing both data types from the same neural population in the freely moving animal would allow researchers to take advantage of the capabilities of both modalities and further understand how they relate to each other.AimHere we present a head-mounted neural implant suitable for in vivo two-photon imaging of neuronal activity with simultaneous extracellular electrical recording in head-fixed or freely moving animals.ApproachA GRIN lens-based head-mounted neural implant with extracellular electrical recording provided by tetrodes on the periphery of the GRIN lens was chronically implanted. The design of the neural implant allows for recording from head-fixed animals, as well as freely moving animals by coupling the imaging system to a coherent imaging fiber bundle.ResultsWe demonstrate simultaneous two-photon imaging of GCaMP and extracellular electrophysiology of neural activity in awake head-fixed, and freely moving mice. Using the collected information, we perform correlation analysis to reveal positive correlation between optical and local field potential recordings.ConclusionSimultaneously recording neural activity using both optical and electrical methods provides complementary information from each modality. Designs that can provide such bimodal recording in freely moving animals allow for the investigation of neural activity underlying a broader range of behavioral paradigms.