bluuebunny/crossref_metadata_2025_split huggingface dataset:
Glucose uptake in pigment glia suppresses tau-induced inflammation and photoreceptor degeneration inDrosophila
Authors: Oka Mikiko , Nakajima Sho , Suzuki Emiko , Yamamoto Shinya , Ando Kanae 
Published: August 2024

AbstractBrain inflammation contributes to the pathogenesis of neurodegenerative diseases such as Alzheimer’s disease (AD). Glucose hypometabolism and glial activation are pathological features seen in AD brains; however, the connection between the two is not fully understood. Using aDrosophilamodel of AD, we identified that glucose metabolism in glia plays a critical role in neuroinflammation under disease conditions. Expression of human Tau in the retinal cells, including photoreceptor neurons and pigment glia, causes photoreceptor degeneration accompanied by inclusion formation and swelling of the lamina cortex. We found that inclusions are formed by glial phagocytosis, and swelling of the laminal cortex correlates with the expression of antimicrobial peptides. Co-expression of human glucose transporter 3 (GLUT3) with Tau in the retina does not affect tau levels but suppresses these inflammatory responses and photoreceptor degeneration. We also found that expression ofGLUT3, specifically in the pigment glia, is sufficient to suppress inflammatory phenotypes and mitigate photoreceptor degeneration in the tau-expressing retina. Our results suggest that glial glucose metabolism contributes to inflammatory responses and neurodegeneration in tauopathy.Summary StatementGlucose uptake into pigment glia suppresses inflammatory responses and photoreceptor degeneration in the fly model of tauopathy.
Center of mass states render multi-joint torques throughout standing balance recovery
Authors: Jakubowski Kristen L. , Martino Giovanni , Beck Owen N. , Sawicki Gregory S. , Ting Lena H. 
Published: August 2024

ABSTRACTSuccessful reactive balance control requires coordinated modulation of hip, knee, and ankle torques. Stabilizing joint torques arise from feedforward neural signals that modulate the musculoskeletal system’s intrinsic mechanical properties, namely muscle short-range stiffness, and neural feedback pathways that activate muscles in response to sensory input. Although feedforward and feedback pathways are known to modulate the torque at each joint, the role of each pathway to the balance-correcting response across joints is poorly understood. Since the feedforward and feedback torque responses act at different delays following perturbations to balance, we modified the sensorimotor response model (SRM), previously used to analyze the muscle activation response to perturbations, to consist of parallel feedback loops with different delays. Each loop within the model is driven by the same information, center of mass (CoM) kinematics, but each loop has an independent delay. We evaluated if a parallel loop SRM could decompose the reactive torques into the feedforward and feedback contributions during balance-correcting responses to backward support surface translations at four magnitudes. The SRM accurately reconstructed reactive joint torques at the hip, knee, and ankle, across all perturbation magnitudes (R2>0.84 & VAF>0.83). Moreover, the hip and knee exhibited feedforward and feedback components, while the ankle only exhibited feedback components. The lack of a feedforward component at the ankle may occur because the compliance of the Achilles tendon attenuates muscle short-range stiffness. Our model may provide a framework for evaluating changes in the feedforward and feedback contributions to balance that occur due to aging, injury, or disease.NEWS AND NOTEWORTHYReactive balance control requires coordination of neurally-mediated feedforward and feedback pathways to generate stabilizing joint torques at the hip, knee, and ankle. Using a sensorimotor response model, we decomposed reactive joint torques into feedforward and feedback contributions based on delays relative to center of mass kinematics. Responses across joints were driven by the same signals, but contributions from feedforward versus feedback pathways differed, likely due to differences in musculotendon properties between proximal and distal muscles.
Epidemiological Study and Analysis of Factors Related to Skin Lesions Caused by Medical Disinfectants, and Personal Protective Equipment among Epidemic-Prevention Workers During the SARS-CoV-2 Pandemic Lockdown Period
Authors: Jingyi Hu , Xiao Xiu-Li , Lu Yi , Su Jian-Yong , Zhang Yan , Shang Ting , Zhang Chun-Hua , Guo Lian , Wang Jian-Chao 
Published: August 2024

Objective: The aim of this study was to investigate the prevalence of and potential risk factors associated with skin lesions resulting from the use of medical disinfectants and personal protective equipment (PPE) among epidemic prevention workers (including healthcare professionals, temporary sampling site workers, community members and volunteers) during the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic lockdown period in China. Methods: We conducted a survey to investigate the prevalence and factors associated with skin lesions during SARS-CoV-2 pandemic lockdown period among epidemic prevention workers in Gaojing town of Baoshan distract, Shanghai, China. Results: A total of 1033 questionnaires were reviewed, with 995 deemed valid. Among the 995 respondents, 209 (21.01%) reported comorbidities, while 786 (78.99%) were considered as controls. Autoimmune diseases, family history of dermatitis, cardiovascular diseases (CVDs), palmar and plantar hyperhidrosis, allergic diseases and the total time spent on skin cleansing and antisepsis procedures were identified as independent risk factors for these skin lesions. Conclusion: During the SARS-CoV-2 pandemic lockdown period, skin lesions among epidemic prevention workers was prevalent, which was primarily attributed to the use of medical disinfectants and PPE. These skin lesions frequently manifested as a combination of various subtypes across different areas of the body. Several individual factors, along with the total time spent on skin cleansing and skin antisepsis procedures, were identified as significant risk factors for the development of these skin lesions.
Perinatal liver inflammation is associated with persistent elevation of CXCL10 and its canonical receptor CXCR3 on common myeloid progenitors
Authors: Alkhani Anas , Baskaran Suruthi , Murti Abhishek , Rapp Blaine , Levy Claire S , Wang Bruce , Nijagal Amar 
Published: August 2024

AbstractBiliary atresia (BA) is a leading cause of liver failure in infants. Despite effective surgical drainage, patients with BA exhibit attenuated immune responses to childhood vaccines, suggesting there are long-lasting alterations to immune function. The perinatal liver is home to hematopoietic stem and progenitor cells (HSPCs) and serves as the epicenter for rapidly progressive and significantly morbid inflammatory diseases like BA. We have previously established the role of neonatal myeloid progenitors in the pathogenesis of perinatal liver inflammation (PLI) and hypothesize that PLI leads to long-term changes to HSPCs in mice that recovered from PLI. To test this hypothesis, we compared the changes that occur to HSPCs and mature myeloid populations in the bone marrow of adult mice during homeostasis and during PLI. Our results demonstrate that HSPCs from animals that recover from PLI (“PLI-recovered”) undergo long-term expansion with a reduced proliferative capacity. Notably, PLI leads to persistent activation of common myeloid progenitors through the involvement of CXCL10 and its canonical receptor, CXCR3. Our data suggests that the CXCR3-CXCL10 axis may mediate the changes in HSPCs that lead to altered immune function observed in BA, providing support for a targetable pathway to mitigate the detrimental long-term immune effects observed in patients with BA.
Bidirectional Optogenetic Modulations of Peripheral Sensory Nerve Activity: Induction vs. Suppression through Channelrhodopsin and Halorhodopsin
Authors: Kosugi Akito , Inoue Ken-ichi , Takada Masahiko , Seki Kazuhiko 
Published: August 2024

AbstractIn this study, we investigated the potential of optogenetics for modulating activity of peripheral sensory nerves, particularly tactile and proprioceptive afferents, which are vital for movement control. Using adeno-associated virus serotype 9 vector, we selectively transduced channelrhodopsin (ChR2) and halorhodopsin (eNpHR3.0) into large-diameter sciatic nerve afferents of rats. Diverging from conventional dorsal root ganglion (DRG) approaches, we applied optical stimulation at the distal portion of the afferent nerve. The intensity of optical stimulation varied to modulate the extent of induction and suppression of afferent activity. Then, the effect of optical stimulation was determined by the activity recorded in the dorsal root of the same afferents. Our findings show successful induction and suppression of activity in large-diameter afferents via optical stimulation. By increasing the intensity of blue (for ChR2) and yellow (for eNpHR3.0) light stimulation, the activity of fast-conducting afferent fibers was preferentially evoked or inhibited in an intensity-dependent manner. These data indicate that the activity of large-diameter afferents can systematically be regulated by optogenetics. The present innovative methodology for manipulating specific sensory modalities at the nerve level offers a targeted and accessible alternative to DRG stimulation, expanding the therapeutic scope of optogenetics for treating sensory disorders.
On the relationship between spatial environmental variability, dispersion and biodiversity
Authors: Bernardini Giulia , Roberts Gareth G. , Sutton Mark 
Published: August 2024

AbstractAimWe establish quantitative relationships between species richness and the rate of spatial change in controlled, digital, environments. We use a simplified, first-principles, stochastic, evolutionary model in which artificial organisms can evolve and disperse. We develop an understanding of how environmental variability in space influences species richness and how it is affected by organisms’ ability to disperse.Time periodAt each time step of the experiment, each organism can reproduce sexually, disperse and die. Each experiment is run for 100,000 time steps. The life span of each organism is 15 time steps.LocationThe model uses an artificial, digital, landscape consisting of a uniform (x, y) grid of cells, with a single environmental variable that changes sinusoidally in thexdirection.Major taxa studiedOrganisms are defined by a 64-bit genome and reproduce sexually. These digital organisms are designed to mimic the basic principles of biological evolution.MethodsEach experiment starts with a single organism, which can mutate and reproduce sexually, producing offspring that can do all of the above and disperse in the environment. Monte Carlo experimentation is used to generate statistical insight into species richness by producing thousands of replicate simulations.ResultsA strong correlation is observed between mean species richness and the rate of spatial change in the environmental variable. This relationship holds true for a wide range of dispersal abilities, but diminishes when dispersal ability is very low.Main ConclusionsWe predict that the rate of change of environmental variables (e.g. the derivative of elevation) is a driver of real-world biodiversity where dispersal is sufficient. Our results suggest that the ability of organisms to disperse plays an important role in determining how biodiversity responds to environmental gradients.
Comparison of test-retest reproducibility of DESPOT and 3D-QALAS for waterT1andT2mapping
Authors: Simegn Gizeaddis Lamesgin , Gagoski Borjan , Song Yulu , Dean Douglas C. , Hupfeld Kathleen E. , Murali-Manohar Saipavitra , Davies-Jenkins Christopher W. , Simičić Dunja , Wisnowski Jessica , Yedavalli Vivek , Gudmundson Aaron T. , Zöllner Helge J. , Oeltzschner Georg , Edden Richard A. E. 
Published: August 2024

AbstractPurposeRelaxometry, specificallyT1andT2mapping, has become an essential technique for assessing the properties of biological tissues related to various physiological and pathological conditions. Many techniques are being used to estimateT1andT2relaxation times, ranging from the traditional inversion or saturation recovery and spin-echo sequences to more advanced methods. Choosing the appropriate method for a specific application is critical since the precision and accuracy ofT1andT2measurements are influenced by a variety of factors including the pulse sequence and its parameters, the inherent properties of the tissue being examined, the MRI hardware, and the image reconstruction. The aim of this study is to evaluate and compare the test-retest reproducibility of two advanced MRI relaxometry techniques (Driven Equilibrium Single Pulse Observation ofT1andT2, DESPOT, and 3D Quantification using an interleaved Look-Locker acquisition Sequence with aT2preparation pulse, QALAS), forT1andT2mapping in a healthy volunteer cohort.Methods10 healthy volunteers underwent brain MRI at 1.3 mm3isotropic resolution, acquiring DESPOT and QALAS data (∼11.8 and ∼5 minutes duration, including field maps, respectively), test-retest with subject repositioning, on a 3.0 Tesla Philips Ingenia Elition scanner. To reconstruct theT1andT2maps, we used an equation-based algorithm for DESPOT and a dictionary-based algorithm that incorporates inversion efficiency andB1-field inhomogeneity for QALAS. The test-retest reproducibility was assessed using the coefficient of variation (CoV), intraclass correlation coefficient (ICC) and Bland-Altman plots.ResultsOur results indicate that both the DESPOT and QALAS techniques demonstrate good levels of test-retest reproducibility forT1andT2mapping across the brain. Higher whole-brain voxel-to-voxel ICCs are observed in QALAS forT1(0.84 ± 0.039) and in DESPOT forT2(0.897 ± 0.029). The Bland-Altman plots show smaller bias and variability ofT1estimates for QALAS (mean of -0.02 s, and upper and lower limits of -0.14 and 0.11 s, 95% CI) than for DESPOT (mean of -0.02 s, and limits of -0.31 and 0.27 s). QALAS also showed less variability (mean 1.08 ms, limits –1.88 to 4.04 ms) forT2compared to DESPOT (mean of 2.56 ms, and limits -17.29 to 22.41 ms). The within-subject CoVs for QALAS range from 0.6% (T2in CSF) to 5.8% (T2in GM), while for DESPOT they range from 2.1% (T2in CSF) to 6.7% (T2in GM). The between-subject CoVs for QALAS range from 2.5% (T2in GM) to 12% (T2in CSF), and for DESPOT they range from 3.7% (T2in WM) to 9.3% (T2in CSF).ConclusionOverall, QALAS demonstrated better reproducibility forT1andT2measurements than DESPOT, in addition to reduced acquisition time.
The Identification of Key Genes and Biological Pathways in Cardiac Arrest by Integrated Bioinformatics and Next Generation Sequencing Data Analysis
Authors: Vastrad Basavaraj , Vastrad Chanabasayya 
Published: August 2024

AbstractCardiac arrest (CA) is a common cause of death world wide. The disease has lacks effective treatment. Efforts have been made to elucidate the molecular pathogenesis of CA, but the molecular mechanisms remain elusive. To identify key genes and pathways in CA, the next generation sequencing (NGS) GSE200117 dataset was downloaded from the Gene Expression Omnibus (GEO) database. DESeq2 tool was used to recognize differentially expressed genes (DEGs). Gene ontology (GO) and REACTOME pathway enrichment analyses were performed to analyze the DEGs and associated signal pathways in the g:Profiler database. The IID database was used to construct the protein-protein interaction (PPI) network, and modules analysis was performed using Cytoscape. A miRNA-hub gene regulatory network and TF-hub gene regulatory network were then constructed to screen miRNAs, TFs and hub genes by miRNet and NetworkAnalyst database and Cityscape software. Receiver operating characteristic curve (ROC) analysis used to verified the hub genes. In total, 844 DEGs were identified, comprising 414 up regulated genes and 430 down regulated genes. GO and REACTOME pathway enrichment analyses indicated that the DEGs for CA were mainly enriched in organonitrogen compound metabolic process, response to stimulus, translation and immune system. Ten hub genes (up-regulated: HSPA8, HOXA1, INCA1 and TP53; down-regulated: HSPB1, LMNA, SNCA, ADAMTSL4 and PDLIM7) were screened. We also predicted miRNAs (hsa-mir-1914-5p and hsa-mir-598-3p) and TFs (JUN and PRRX2) targeting hub genes. This study uses a series of bioinformatics technologies to obtain hug genes, miRNAs and TFs, and key pathways related to CA. These analysis results provide us with new ideas for finding biomarkers and treatment methods for CA.
Neural mechanisms of awareness of action
Authors: Jin David S. , Agdali Oumayma , Yadav Taruna , Kronemer Sharif I. , Kunkler Sydney , Majumder Shweta , Khurana Maya , McCusker Marie C. , Fu Ivory , Siff Emily J. , Khalaf Aya , Christison-Lagay Kate L. , Aerts Shanae L. , Xin Qilong , Li Jing-Jing , McGill Sarah H. , Crowley Michael J. , Blumenfeld Hal 
Published: August 2024

AbstractThe origins of awareness of action (AoA), the ability to report an action just performed, remain elusive. Differing theories ascribe AoA to pre-action, efferent motor/volitional mechanisms versus post-action, afferent sensory/perceptual neural mechanisms. To study these two types of mechanisms and others, we developed a paradigm where very similar aware and unaware actions occur repeatedly. Aware actions demonstrated larger neurophysiological signals both preceding and following movement. The differences included well-known volitional and perceptual event related potentials (PMP, N140, P300), as well as frontal midline theta, event-related alpha/beta desynchronization, and post-move blink rates. On longer time scales, we identified a novel event related potential preceding unaware moves, and found behavioral and pupillometric evidence for decreased attention and arousal over minutes concurrent with AoA loss. Our findings suggest that both dynamic, individual action-associated volitional and perceptual neural activity, as well as long-term attention and arousal states play a role in maintaining AoA.
Low hemoglobin causes hematoma expansion and poor intracerebral hemorrhage outcomes
Authors: Cottarelli Azzurra , Mamoon Rayan , Ji Robin , Mao Eric , Boehme Amelia , Kumar Aditya , Song Sandy , Allegra Valentina , Sharma Sabrina V. , Konofagou Elisa , Spektor Vadim , Guo Jia , Connolly E. Sander , Sekar Padmini , Woo Daniel , Roh David J. 
Published: August 2024

ABSTRACTObjectivesAlthough lower hemoglobin levels associate with worse intracerebral hemorrhage (ICH) outcomes, causal drivers for this relationship remain unclear. We investigated the hypothesis that lower hemoglobin relates to increased hematoma expansion (HE) risk and poor outcomes using human observational data and assessed causal relationships using a translational murine model of anemia and ICH.MethodsICH patients with baseline hemoglobin measurements and serial CT neuroimaging enrolled between 2010-2016 to a multicenter, prospective observational cohort study were studied. Patients with systemic evidence of coagulopathy were excluded. Separate regression models assessed relationships of baseline hemoglobin with HE (≥33% and/or ≥6mL growth) and poor long-term neurological outcomes (modified Rankin Scale 4-6) after adjusting for relevant covariates. Using a murine collagenase ICH model with serial neuroimaging in anemic vs. non-anemic C57/BL6 mice, intergroup differences in ICH lesion volume, ICH volume changes, and early mortality were assessed.ResultsAmong 1190 ICH patients analyzed, lower baseline hemoglobin levels associated with increased odds of HE (adjusted OR per -1g/dL hemoglobin decrement: 1.10 [1.02-1.19]) and poor 3-month clinical outcomes (adjusted OR per -1g/dL hemoglobin decrement: 1.11 [1.03-1.21]). Similar relationships were seen with poor 6 and 12-month outcomes. In our animal model, anemic mice had significantly greater ICH lesion expansion, final lesion volumes, and greater mortality, as compared to non-anemic mice.ConclusionsThese results, in a human cohort and a mouse model, provide novel evidence suggesting that anemia has causal roles in HE and poor ICH outcomes. Additional studies are required to clarify whether correcting anemia can improve these outcomes.
Could a female athlete run a 4-minute mile with improved aerodynamic drafting?
Authors: da Silva Edson Soares , Hoogkamer Wouter , Kipp Shalaya , Kram Rodger 
Published: August 2024

AbstractIn 2023, Faith Kipyegon set the female world record for running one mile (4:07.64). Here, we quantitively explore if improved aerodynamic drafting could allow her to run just 3.19% faster and thus break the 4-minute mile barrier. Drafting involves other athletes (pacers) running in formation around a designated athlete to reduce the aerodynamic drag force acting on the designated runner. Drafting allows the designated athlete to run faster at the same rate of metabolic energy consumption. Our overall approach was to estimate Kipyegon’s metabolic energy consumption during her mile world record performance. Then, we used empirically established relationships between horizontal resistive force, running velocity and metabolic power to estimate how much faster she could run at the same metabolic power if the aerodynamic force was reduced via drafting. Our calculations suggest that Kipyegon could run ∼3:59.37 with drafting provided by one pacer in front and one in back who change out with two other pacers at 800 m.
The Clonal Hematopoiesis-associated GeneSrcapPlays an Essential Role in Hematopoiesis
Authors: Wong Terrence N. , Mychalowych Anna , Feldpausch Ellie R. , Carson Alexander , Karpova Darja , Link Daniel C. 
Published: August 2024

AbstractSomatic mutations arising in hematopoietic stem cells (HSCs) may provide the latter with a fitness advantage, allowing the mutant HSC to clonally expand. Such mutations have been recurrently identified in the chromatin modifier,SRCAP, in both non-malignant and leukemic clones, suggesting that this gene plays a significant role in hematopoiesis. We generated a conditionalSrcaploss of function murine model and determined the consequences of hematopoietic-specific loss of this gene. We show thatSrcapis essential for normal fetal liver erythropoiesis and monocytopoiesis. InSrcapdeficient fetal livers, the number of phenotypic HSCs is similar to that of controls, but these HSCs exhibit a profound repopulating defect. Likewise, conditional deletion ofSrcapduring adult hematopoiesis results in a rapid loss of HSCs. Loss ofSrcapis associated with evidence of increased DNA damage in HSCs and lineage-restricted progenitors as assessed by y-H2AX expression. Consistent with this finding, we observed strong transcriptional upregulation of the p53 pathway inSrcapdeficient erythroid precursors. Collectively our data highlight the importance ofSrcapin maintaining HSC function and supporting hematopoietic differentiation and suggests that it plays an essential role in maintaining genomic integrity.Key Points(1)Srcapplays an essential role in supporting normal hematopoietic differentiation. and in maintaining HSC function.(2)Loss ofSrcapis associated with evidence of increased DNA damage and transcriptional upregulation of the p53 pathway.