bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrative Multiomic Analyses of Diabetic Neuropathic Pain in Dorsal Root Ganglia: Proteomics, Phospho-proteomics, and Metabolomics
Authors: Doty Megan , Yun Sijung , Wang Yan , Hu Minghan , Cassidy Margaret , Hall Bradford , Kulkarni Ashok B. 
Published: August 2022

AbstractDiabetic peripheral neuropathy (DPN) is characterized by spontaneous pain in the extremities. Incidence of DPN continues to rise with the global diabetes epidemic. However, there remains a lack of safe, effective analgesics to control this chronic painful condition. Dorsal root ganglia (DRG) contain soma of sensory neurons and modulate sensory signal transduction into the central nervous system. In this study, we aimed to gain a deeper understanding of changes in molecular pathways in the DRG of DPN patients with chronic pain. We recently reported transcriptomic changes in the DRG with DPN. Here, we expand upon those results with integrated metabolomic, proteomic, and phospho-proteomic analyses to compare the molecular profiles of DRG from DPN donors and DRG from control donors without diabetes or chronic pain. Our analyses identified decreases of select amino acids and phospholipid metabolites in the DRG from DPN donors, which are important for cellular maintenance. Additionally, our analyses revealed changes suggestive of extracellular matrix (ECM) remodeling and altered mRNA processing. These results reveal new insights into changes in the molecular profiles associated with DPN.
Appetitive and aversive cue reactivities differentiate biotypes of alcohol drinkers
Authors: Chen Yu , Li Chiang-Shan R. 
Published: August 2022

AbstractCraving reflects the subjective urge to use drugs and can be triggered by both positive and negative emotional states. However, no studies have systematically investigated the relative roles of these mechanisms in the pathophysiology of substance misuse or distinguished the mechanisms in individual vulnerability to substance use disorders. In the current study, we performed meta-analyses of drug cue-elicited reactivity and win and loss processing in the monetary incentive delay task to identify distinct neural correlates of appetitive and aversive responses during cue exposure. We then characterized the appetitive and aversive cue responses in seventy-six alcohol drinkers performing a cue craving task during fMRI. Imaging data were processed according to published routines. The appetitive circuit involved medial cortical regions and the ventral striatum, and the aversive circuit involved the insula, caudate and mid-cingulate cortex. We observed a significant correlation ofβestimates of cue-elicited activity of the appetitive and aversive circuit. However, individuals varied in appetitive and aversive cue responses. From the regression of appetitive (y) vs. aversive (x)β, we identified participants in the top 1/3 each of those with positive (n = 15) and negative (n = 11) residuals as “approach” and “avoidance” biotype, with the others as the “mixed” biotype (n = 50). For clinical characteristics, the avoidance biotype showed higher sensitivity to punishment. In contrast, the approach biotype showed higher levels of sensation seeking and alcohol expectancy for social and physical pressure. The findings highlighted distinct neural underpinnings of appetitive and aversive components of cue-elicited reactivity and substantiated the importance of biotyping substance misuse.
IGF-1 therapy improves muscle size and function in experimental peripheral arterial disease
Authors: Dong Gengfu , Moparthy Chatick , Thome Trace , Kim Kyoungrae , Ryan Terence E. 
Published: August 2022

CONDENSED ABSTRACTLower extremity peripheral arterial disease (PAD) has continued to increase in prevalence over the past several decades, yet therapeutic development has remained stagnant. Skeletal muscle health and function has been strongly linked to quality of life and medical outcomes in PAD patients. Using a rodent model of PAD, this study demonstrates that treatment of the ischemic limb with adeno-associated virus-mediated expression of insulin-like growth factor 1 (IGF1) significantly increases muscle size and strength, without improving limb hemodynamics. Interestingly, the effect size of IGF1 therapy was larger in female mice compared to their male counterparts, where substantial improvements in muscle specific force and a reduction in the progression of limb necrosis were observed. These findings indicate that clinical trials should carefully examine sex-dependent effects in experimental PAD therapies.
Precise targeting for 3D cryo-correlative light and electron microscopy volume imaging of tissues using a FinderTOP
Authors: de Beer Marit , Daviran Deniz , Roverts Rona , Rutten Luco , Sánchez Elena Macías , Metz Jurriaan R. , Sommerdijk Nico , Akiva Anat 
Published: August 2022

AbstractCryo-correlative light and electron microscopy (cryoCLEM) is a powerful strategy to high resolution imaging in the unperturbed hydrated state. In this approach fluorescence microscopy aids localizing the area of interest, and cryogenic focused ion beam/scanning electron microscopy (cryoFIB/SEM) allows preparation of thin cryo-lamellae for cryoET. However, the current method cannot be accurately applied on bulky (3D) samples such as tissues and organoids. 3D cryo-correlative imaging of large volumes is needed to close the resolution gap between cryo-light microscopy and cryoET, placing sub-nanometer observations in a larger biological context. Currently technological hurdles render 3D cryoCLEM an unexplored approach.Here we demonstrate a cryoCLEM workflow for tissues, correlating cryo-Airyscan confocal microscopy with 3D cryoFIB/SEM volume imaging. Accurate correlation is achieved by imprinting a FinderTOP pattern in the sample surface during high pressure freezing, and allows precise targeting for cryoFIB/SEM volume imaging.
An Integrative Approach to Dissect the Drug Resistance Mechanism of the H172Y Mutation of SARS-CoV-2 Main Protease
Authors: Clayton Joseph , de Oliveira Vinicius Martins , Ibraham Mohamed Fouad , Sun Xinyuanyuan , Mahinthichaichan Paween , Shen Mingzhe , Hilgenfeld Rolf , Shen Jana 
Published: August 2022

AbstractNirmatrelvir is an orally available inhibitor of SARS-CoV-2 main protease (Mpro) and the main ingredient of PAXLOVID, a drug approved by FDA for high-risk COVID-19 patients. Recently, a rare natural mutation, H172Y, was found to significantly reduce nirmatrelvir’s inhibitory activity. As the COVID-19 cases skyrocket in China and the selective pressure of antiviral therapy builds up in the US, there is an urgent need to characterize and understand how the H172Y mutation confers drug resistance. Here we investigated the H172Y Mpro’s conformational dynamics, folding stability, catalytic efficiency, and inhibitory activity using all-atom constant pH and fixed-charge molecular dynamics simulations, alchemical and empirical free energy calculations, artificial neural networks, and biochemical experiments. Our data suggests that the mutation significantly weakens the S1 pocket interactions with the N-terminus and perturbs the conformation of the oxyanion loop, leading to a decrease in the thermal stability and catalytic efficiency. Importantly, the perturbed S1 pocket dynamics weakens the nirma-trelvir binding in the P1 position, which explains the decreased inhibitory activity of nirmatrelvir. Our work demonstrates the predictive power of the combined simulation and artificial intel-ligence approaches, and together with biochemical experiments they can be used to actively surveil continually emerging mutations of SARS-CoV-2 Mpro and assist the discovery of new antiviral drugs. The presented workflow can be applicable to characterize mutation effects on any protein drug targets.
Relative changes in the cochlear summating potentials to paired-clicks predict speech-in-noise perception and subjective hearing acuity
Authors: Lai Jesyin , Bidelman Gavin M. 
Published: August 2022

AbstractObjective assays of human cochlear synaptopathy (CS) have been challenging to develop. It’s suspected if relative summating potential (SP) changes are different in CS listeners. In this proof-of-concept study, young, normal-hearing adults were recruited and assigned to a low/high-risk group for having CS based on their audiograms at 9-16 kHz. SPs to paired-clicks with varying inter-click intervals isolated non-refractory receptor components of cochlear activity. Abrupt increases in SPs to paired- vs. single-clicks were observed in high-risk listeners. Critically, overexaggerated SPs predicted speech-in-noise and subjective hearing abilities, suggesting relative SP changes to rapid clicks might help identify putative synaptopathic listeners.
ZmWRKY82-ZmSLG regulate seed development by modulating brassionsteroid homeostasis in maize
Authors: Li Hui , Wang Yayun , Luo Li , Hu Yufeng , Li Yangping , Zhang Junjie , Huang Yubi 
Published: August 2022

AbstractSeed development is a crucial biological process affecting crop yield. Brassionsteroids (BRs) plays essential role in seed development. Although part of genes participated in BR regulate seed development have been cloned in maize, their genetic and mechanisms are still unclear. In the previous experiment, we found that exogenous spray BL promote seed development. Here, RNA-sequence analysis of BL treated seeds revealed that 12 candidate function genes and 62 candidate transcription factors among the differentially expressed genes (DEGs) were regulated by BL. Combining with previous QTL and GWAS research results in maize and homologous gene analysis, ZmSLG1 was screened out from 12 candidate function genes for further study. Overexpression of ZmSLG1 displayed round seed and delayed embryo development in maize. Moreover, overexpression of ZmSLG1 decreased BR content and increased expression of BR synthesis related genes in seed. To understand the mechanism of BL regulating ZmSLG1 expression, ZmWRKY82 was identified from 62 candidate transcription factors and examined its function. Transient expression, EMSA and ChIP analysis showed ZmWRKY82 can directly bind to the ZmSLG1 promoter to regulate ZmSLG1 expression. Collectively, exogenous BL regulate the ZmSLG1 gene expression through ZmWRKY82 transcription factor, and ZmSLG1 negatively regulates the endogenous BR contents in seed.HighlightWe conclude that ZmWRKY82-ZmSLG1 is required for BR homeostasis and that modification of ZmSLG1 expression to an appropriate level may provide a way to increase yield.
Phylophenomic and Phylogenomic analysis for Ovis aries reveals distinct identity of newly reported breed
Authors: Pal Aruna , Banerjee Samiddha , karmakar Prabir 
Published: August 2022

AbstractDomestication and phylogenetics for Ovis aries is an important species to study, since there exists enormous biodiversity in terms of habitat and utility of sheep. The present study aimed at identification of the biodiversity existing within sheep breeds reared in different agroclimatic zones of the state West Bengal (Garole, Birbhum, Bonpala and Chotanagpuri) through phylogenetic analysis of phenotypic traits as growth and biomorphometric traits through principal component analysis, factor analysis, genetic correlation, multivariate cluster analysis through Hierarchial classification and k-means cluster analysis. Confirmation of the phylophenomic studies were later on carried out with phylogenomic analysis with microsatellite markers for sheep. Birbhum sheep from dry arid region of West Bengal is reported as the newly reported breed of sheep with distinct genetic identity.
EVALUATION OF THE PERFORMANCE OF THE ROUTINE EPIDEMIOLOGICAL SURVEILLANCE SYSTEM IN THE HEALTH DISTRICT OF TAMBACOUNDA (SENEGAL) IN 2020
Authors: Gadiaga Tidiane , Ba Mouhamadou Faly , Sagna Siré , Cissé Bayal , Diallo Amadou , Ndiaye Samba , Diop Boly , Ndiaye Mbouna , Ndoye Babacar , Ba Mamadou Sarifou , Sall Yoro , Sougou Ndeye Mareme , Tine Jean Augustin Diégane , Leye Mamadou Makhtar Mbacké 
Published: August 2022

AbstractIntroductionEpidemiological surveillance (ES) which is a continuous systematic process of data collection, analysis and interpretation for decision-making is of paramount importance for a good health system. Thus, to contribute to the improvement of the health system in Senegal, a study of the functioning of the routine epidemiological surveillance system was conducted in Tambacounda from S1 to S53 of the year 2020.MethodologyA descriptive and analytical cross-sectional study was conducted from 1 to 17 July 2021. Comprehensive recruitment of the district’s 44 health care points was carried out. Data collection was carried out through a questionnaire prepared, pre-tested and administered to the 44 heads of public and non-public health facilities. The analyses were carried out with R software version 4.0.5.ResultsOf the 44 health facilities surveyed, 64% were public and 36% were non-public. The completeness and timeliness of the data were 100% and 97.5%, respectively. Suspected cases of tuberculosis were the most reported. For the providers surveyed (n=44), only 65.9% had knowledge of disease under epidemiological surveillance (DUES) and 93.2% managed suspected cases. On-site data analysis is only performed by 20.5% of providers. Only 38.6% of the service delivery point (SDP) had a health area card and the ES was under the responsibility of 77.3% of the paramedics. The training of ES officials was effective for only 45.5% of them. Despite the availability of dry tubes (69.8%), only 29.5% of PSD had COVID sampling equipment. The contribution of local authorities and technical and financial partners (TFP) to the SE was 22.7% and 29.5% respectively.There was a statistically significant link between public SDP with knowledge of DUES (p <0.001), display of case definitions (p <0.001), feedback of reported cases, knowledge of indicators (p<0.001), existence of a health area map (p <0.001), advocacy with authorities (p=0.003), staff training (p=0.002), availability of DUES vaccines (p <0.001), availability of notification form (p<0.001) and partner contribution to ES activities.ConclusionStaff training, regular monitoring of ES activities with greater involvement of non-public structures, and the availability of inputs applied to the six pillars of the health system, are essential elements on which action must be taken. for an efficient ES system in the Tambacounda health district for the benefit of the country’s health system.
Does Influenza vaccination reduce the risk of contracting COVID-19?
Authors: Alòs Francesc , Zaldúa Yoseba Cánovas , Feijóo M Victoria , Del-Val José Luís , Sanchez-Callejas Andrea , Colomer MA 
Published: August 2022

AbstractThe concurrent timing of the COVID-19 pandemic and the seasonal occurrence of influenza, makes it especially important to analyze the possible effect of the influenza vaccine on the risk of contracting COVID-19, or in reducing the complications caused by both diseases, especially in vulnerable populations. There is very little scientific information on the possible protective role of the influenza vaccine against the risk of contracting COVID-19, particularly in groups at high-risk of influenza complications. Reducing the risk of contracting COVID-19 in high-risk patients (those with a higher risk of infection, complications, and death) is essential to improve public well-being and to reduce hospital pressure and the collapse of primary health centers. Apart from overlapping in time, COVID-19 and flu share common aspects of transmission, so that measures to protect against flu might be effective in reducing the risk of contracting COVID-19.In this study, we conclude that the risk of contracting COVID-19 is reduced if patients are vaccinated against flu, but the reduction is small (0.22%) and therefore not clinically important. When this reduction is analysed based on the risk factor suffered by the patient, statistically significant differences have been obtained for patients with cardiovascular problems, diabetics, chronic lung and chronic kidney, in all four cases the reduction in the risk of contagion does not reach 1%.It is worth highlighting the behaviour that is completely different from the rest of the data for institutionalized patients. The data for these patients does not suggest a reduction in the risk of contagion for patients vaccinated against the flu, but rather the opposite, a significant increase of 6%.Socioeconomic conditions, as measured by the MEDEA deprivation index, explain increases in the risk of contracting COVID-19, and awareness campaigns should be increased to boost vaccination programs.
Intermediate levels of asymptomatic transmission can lead to the highest levels of epidemic fatalities
Authors: Park Sang Woo , Dushoff Jonathan , Grenfell Bryan T. , Weitz Joshua S. 
Published: August 2022

AbstractAsymptomatic infections have hampered the ability to characterize and prevent the transmission of SARS-CoV-2 throughout the ongoing pandemic. Even though asymptomatic infections reduce severity at the individual level, they can make population-level outcomes worse if asymptomatic individuals—unaware they are infected—transmit more than symptomatic individuals. Using an epidemic model, we show that intermediate levels of asymptomatic infection lead to the highest levels of epidemic fatalities when the increase in asymptomatic transmission, due either to individual behavior or mitigation efforts, is strong. We generalize this result to include presymptomatic transmission, showing how intermediate levels of non-symptomatic transmission can lead to the highest levels of fatalities. Finally, we extend our framework to illustrate how the intersection of asymptomatic spread and immunity profiles determine epidemic trajectories, including population-level severity, of future variants.
The role of motion in the neural representation of social interactions in the posterior temporal cortex
Authors: Landsiedel Julia , Daughters Katie , Downing Paul E. , Koldewyn Kami 
Published: August 2022

AbstractHumans are an inherently social species, with multiple focal brain regions sensitive to various visual social cues such as faces, bodies, and biological motion. More recently, research has begun to investigate how the brain responds to more complex, naturalistic social scenes, identifying a region in the posterior superior temporal sulcus (SI-pSTS; i.e., social interaction pSTS), among others, as an important region for processing social interaction. This research, however, has presented images or videos, and thus the contribution of motion to social interaction perception in these brain regions is not yet understood. In the current study, 22 participants viewed videos, image sequences, scrambled image sequences and static images of either social interactions or non-social independent actions. Combining univariate and multivariate analyses, we confirm that bilateral SI-pSTS plays a central role in dynamic social interaction perception but is much less involved when ‘interactiveness’ is conveyed solely with static cues. Regions in the social brain, including SI-pSTS and extrastriate body area (EBA), showed sensitivity to both motion and interactive content. While SI-pSTS is somewhat more tuned to video interactions than is EBA, both bilateral SI-pSTS and EBA showed a greater response to social interactions compared to non-interactions and both regions responded more strongly to videos than static images. Indeed, both regions showed higher responses to interactions than independent actions in videos and intact sequences, but not in other conditions. Exploratory multivariate regression analyses suggest that selectivity for simple visual motion does not in itself drive interactive sensitivity in either SI-pSTS or EBA. Rather, selectivity for interactions expressed in point-light animations, and selectivity for static images of bodies, make positive and independent contributions to this effect across the LOTC region. Our results strongly suggest that EBA and SI-pSTS work together during dynamic interaction perception, at least when interactive information is conveyed primarily via body information. As such, our results are also in line with proposals of a third visual stream supporting dynamic social scene perception.
Cold-induced expression of a truncated Adenylyl Cyclase 3 acts as rheostat to brown fat function
Authors: Khani Sajjad , Topel Hande , Josephrajan Ajeetha , Larsen Bjørk Ditlev Marcher , de Almeida Tavanez Ana Rita Albuquerque , Gaudry Michael James , Leyendecker Philipp , Stanic Natasa , Gaziano Isabella , Hansmeier Nils Rouven , Schmidt Elena , Klemm Paul , Vagliano Lara-Marie , Engelhard Christoph Andreas , Nielsen Søren , Jespersen Naja Zenius , Rehimi Rizwan , Gohlke Sabrina , Frommolt Peter , Gnad Thorsten , Rada-Iglesias Alvaro , Pradas-Juni Marta , Schulz Tim Julius , Wunderlich Frank Thomas , Pfeifer Alexander , Jastroch Martin , Wachten Dagmar , Kornfeld Jan-Wilhelm 
Published: August 2022

AbstractPromoting brown adipose tissue (BAT) activity has been recognized as innovative therapeutic approach to improve obesity and metabolic disease. Whilst the molecular circuitry underlying thermogenic activation of BAT is well understood, the processes underlying rheostatic regulation of BAT to maintain homeostasis and avoid excessive energy dissipation remain ill-defined. Increasing cyclic AMP (cAMP) biosynthesis is key for BAT activation. Here, we demonstrate that ADCY3, an adenylyl cyclase whose expression is induced during cold exposure and regulates cAMP homeostasis in thermogenic fat, is dispensable for BAT function in lean mice, but becomes critical during obesity. Furthermore, by combining RNA-seq with epigenomic H3K4me3 profiling, we detected a novel, cold-inducible promoter that generates a 5’ truncated Adcy3-at mRNA isoform, Adcy3-at. Mice lacking only Adcy3-at, but not full-length Adcy3, displayed increased energy expenditure already under lean conditions and were protected against obesity and ensuing metabolic imbalances. Subcellularly, translated ADCY3-AT proteins are retained in the endoplasmic reticulum (ER), did not translocate to the cell membrane, and lacked enzymatic activity. By interacting with ADCY3, ADCY3-AT retained ADCY3 in the ER and, thereby, reduced the plasma membrane pool of ADCYs available for G-protein mediated cAMP synthesis. Thereby, ADCY3-AT acts as a signaling rheostat in BAT, limiting adverse consequences of uncurbed cAMP activity after long-term BAT activation. Adcy3-at induction was driven by a cold-induced, truncated isoform of the transcriptional cofactor PPARGC1A (PPARG Coactivator 1 Alpha, PPARGC1A-AT). Expression of Ppargc1a-at and Adcy3-at are evolutionary conserved, indicating that transcriptional rewiring by commissioning of alternative promoters is key for thermogenic fat function.