bluuebunny/crossref_metadata_2025_split huggingface dataset:
Physiological activity within peripheral nerves influences neural output in response to electrical stimulation: anin vivostudy
Authors: Madden Lauren R. , Liu Richard , Ivanescu Sergiu , Bruns Tim M. 
Published: December 2024

AbstractNeuromodulation therapies are often applied to peripheral nerves. These nerves can have physiological activity that interacts with the activity evoked by electrical stimulation, potentially influencing targeted neural output and clinical outcomes. Our goal was to quantify changes in sensory neural unit activity in response to variations in electrical stimulation frequency and amplitude. In a feline model, we applied cutaneous brushing to evoke pudendal nerve afferent activity with and without electrical stimulation via a pudendal nerve cuff electrode. We recorded neural output with microelectrode arrays implanted in ipsilateral sacral dorsal root ganglia (DRG). Combined inter-spike interval distributions for all DRG units showed ranges of flattening, increases, and shifts in response to electrical stimulation. These distributions and changes within them due to electrical stimulation were largely driven by a select few units. Mixed-effects models revealed that quicker firing units generally decreased in firing rate in response to electrical stimulation and, conversely, slower firing units increased in firing rate. A unit’s underlying firing rate also drove the magnitude of change in mean output firing rate in response to stimulation. Further, the models reported a small, negative correlation between the output mean unit firing rate and the applied electrical stimulation frequency. These results demonstrate the potential impact of electrical stimulation on underlying neural firing activity and output. Peripheral neuromodulation may normalize abnormal firing patterns in nerves contributing to pathological disorders or alter unrelated physiological activity in off-target neurons. These factors should be considered when selecting neuromodulation settings in animal subjects and human patients.
The Universal Receptive System acts as a novel regulator in the production of antimicrobial and anticancer bioactive compounds by white blood cells
Authors: Tetz Victor , Kardava Kristina , Vecherkovskaya Maria , Khodadadi-Jamayran Alireza , Tsirigos Aristotelis , Tetz George 
Published: December 2024

AbstractDespite recent advances, the regulation of anticancer and antimicrobial bioactive compound (AABC) production by leukocytes remains poorly understood. Here, we demonstrate that inactivation of the DNA- and RNA-based Teazeled receptors of the Universal Receptive System in human leukocytes generated so called “Leukocyte-Tells,” which showed enhanced AABC production. Comprehensive analysis of the AABCs produced by Leukocyte-Tells based on LC/MS identified 707 unique or differentially produced peptide or non-peptide metabolites. Functional testing demonstrated that many of these metabolites exhibited increased antibacterial, antifungal, and anticancer activities.The AABCs produced by the Leukocyte-Tells were effective against different multidrug-resistant clinical isolates of fungi and gram-positive and gram-negative bacteria (including their biofilms), as well as various cancer cell lines, with >100,000-fold activity than AABCs derived from control leukocytes. Notably, the AABCs produced by the Leukocyte-Tells exhibited greater stability under adverse environmental conditions. Our findings highlight the important role of the Universal Receptive System in regulating AABC production through a process named here as cell genome memory management, offering new insights into immune functions and suggesting potential therapeutic applications.SummaryThe Universal Receptive System acts as a novel regulator of biosynthetic activity in leukocytes. Modulating the leukocyte Universal Receptive System by inactivating Teazeled receptors triggers the production of new compounds not observed in naïve cells. We refer to these TezR-modified cells as “Leukocyte-Tells.” Leukocytes produce unique metabolites with strong anticancer and antimicrobial activities. Reproducibility in generating leukocytes from the blood of different donors suggests that the observed alterations in cell activity were preprogrammed.
Age-Related Changes in Functional Balance Ability Predict Alpha Activity During Multisensory Integration
Authors: Pepper Jessica L. , Yao Bo , Braithwaite Jason J. , Bampouras Theodoros M. , Nuttall Helen E. 
Published: December 2024

AbstractThe increased multisensory integration and weaker attentional control experienced by older adults during audiovisual processing can result in inaccurate perceptions of their dynamic, everyday environment. These inaccurate representations of our environment can contribute to increased fall risk in older adults. A neural correlate of the attentional difference between younger and older adults could be oscillatory alpha activity (8-12Hz), indexing inhibitory processes during multisensory integration. The current study investigated whether age-related changes in alpha activity underlie weaker attentional control in older adults during a multisensory task, and if alpha associates with fall risk.Thirty-six younger (18-35 years old) and thirty-six older (60-80 years old) adults completed a cued-spatial-attention stream-bounce task, assessing audiovisual integration when attending to validly-cued or invalidly-cued locations, at 0ms or 300ms stimulus-onset asynchronies. Oscillatory alpha activity was recorded throughout using EEG to index participants’ inhibitory abilities. Functional ability and balance were measured to index fall risk.Multiple linear regression models revealed that even when attending to the validly-cued location, less accurate multisensory integration was exhibited by older adults compared to younger adults, suggesting that older adults demonstrate weaker top-down modulation of multisensory integration through failing to inhibit task-irrelevant information. However, alpha power across the trials did not predict the extent of multisensory integration within the task. A significant interaction between age and functional ability scores predicted alpha power, suggesting that older adults may rely on attentional mechanisms for functional ability more than younger adults do. Potential implications in the design of clinical treatments to reduce falls are discussed.
C1q and immunoglobulins mediate activity-dependent synapse loss in the adult brain
Authors: Crowley Gerard , Turkes Emir , Kim Minjung , De Schepper Sebastiaan , Tan Benjy J. Y. , Rueda-Carrasco Javier , Toneva Margarita , Fajardo John Christian , Ge Judy Z. , Yang Zhengyue Grace , Paoletti Camille , Sow Tammie , Posner David , Sierksma Annerieke , Ferreira Laís S. S. , Sokolova Dimitra , Konstantellos Viktoras , MacAskill Andrew F. , Clatworthy Menna R. , Hong Soyon 
Published: December 2024

AbstractC1q, the initiating protein of the classical complement cascade, mediates synapse loss in development and disease. In various mouse models of neurologic diseases, including Alzheimer’s disease, C1q, which is secreted by microglia, the brain’s resident macrophages, is found deposited on synapses in vulnerable brain regions. However, what underlies C1q deposition on synapses in the adult brain is unclear. Usingin vivochemogenetics, we demonstrate that neuronal hyperactivity acts as a trigger for region-specific deposition of C1q, which is required for activity-dependent synapse loss. Further, using spatial transcriptomics, live cell tracking, super-resolution microscopy and other molecular and cellular tools, we report a role for B lymphocyte lineage cells and immunoglobulins in the activity-dependent C1q deposition and synapse loss. Overall, our work suggests a link between neuronal hyperactivity and C1q-mediated synapse loss in the adult brain and introduces immunoglobulins as players in this process.
The Aging Synapse: An Integrated Proteomic And Transcriptomic Analysis
Authors: Caterino Cinzia , Ugolini Martino , Durso William , Jevdokimenko Kristina , Groth Marco , Riege Konstantin , Görlach Matthias , Fornasiero Eugenio , Ori Alessandro , Hoffmann Steve , Cellerino Alessandro 
Published: December 2024

ABSTRACTAn important hallmark of aging is the loss of proteostasis, which can lead to the formation of protein aggregates and mitochondrial dysfunction in neurons. Although it is well known that protein synthesis is finely regulated in the brain, especially at synapses, where mRNAs are locally translated in activity-dependent manner, little is known as to the changes in the synaptic proteome and transcriptome during aging. Therefore, this work aims to elucidate the relationship between transcriptome and proteome at soma and synaptic level during aging.Proteomic and transcriptomic data analysis reveal that, in young animals, proteins and transcripts are correlated and synaptic regulation is driven by changes in the soma. During aging, there is a decoupling between transcripts and proteins and between somatic and synaptic compartments. Furthermore, soma-synapse gradient of ribosomal genes changes upon aging, i.e. ribosomal transcripts are less abundant and ribosomal proteins are more abundant in synaptic compartment of old mice with respect to younglings. Additionally, transcriptomics data highlight a difference in the splicing of certain synaptic mRNA with aging. Taken together, our data provide a valuable resource for the study of the aging synapse.
Metabolic rerouting by gain-of-function mutations overcomesplsXessentiality inStaphylococcus aureus
Authors: Wongdontree Paprapach , Palmier Milya , Leguillier Vincent , Gloux Karine , Halpern David , Anba-Mondoloni Jamila , Gruss Alexandra 
Published: December 2024

AbstractPhospholipids are essential components of most bacterial membranes. The PlsX acyltransferase initiates phospholipid synthesis by reversibly converting acyl-ACP (ACP, acyl carrier protein) to acyl-PO4, the first phospholipid precursor. PlsX is dispensable in some bacteria, as alternative functions assure acyl-PO4production. In contrast, PlsX is considered indispensable inStaphylococcus aureus, unless exogenous fatty acids (FA) are provided. Here we report that gain-of-function suppressors of ΔplsX enableS. aureusgrowth without FA addition. The suppressors map to either the FA synthesis (FASII) enzyme FabF, or to a putative acyl-CoA thioesterase/ACP binding protein, designated FadM. The ΔplsXsuppressors alleviate accumulation of long chain acyl-ACP, and produce shorter chain membrane FAs than the parental strain. Unlike wild typeS. aureus, which can adapt to FASII inhibitors, ΔplsXsuppressors remain fully sensitive, indicating that PlsX reverse activity is not compensated. Importantly, an interdependency between FabF and FadM functions shown here suggests a more general role for FadM in facilitating FA release from FabF-FA-ACP intermediates. In summary,S. aureus fabFandfadMmutations promote enzymatic flexibility that overcomes ΔplsX growth arrest by restoring phospholipid synthesis.ImportancePhospholipids are common and vital cell membrane components. Many bacteria initiate phospholipid synthesis using an enzyme called PlsX; some of them also have a backup system to ensure phospholipid synthesis and survival even if PlsX is disabled. HoweverStaphylococcus aureus, a major pathogen, reportedly lacked a PlsX backup system. Here we used a genetic selection approach to show thatS. aureusgenerates “gain-of-function” mutations, allowing bacteria to initiate phospholipid synthesis when PlsX is inactive. Bacteria survive thanks to a mutation in FabF, a fatty acid biosynthesis enzyme, or in FadM, a little-studied protein; our data indicate that FabF and FadM cooperate to compensate a PlsX defect. The outcome with either mutation is that bacteria produce and release fatty acids to patch into phospholipid synthesis. This study illustrates how new enzymatic circuitry is created by mutation to rescue bacteria from a potentially lethal membrane phospholipid synthesis defect.
Real-Time Nanoscale Investigation of Spore Coat Assembly inBacillus subtilis
Authors: Lablaine Armand , Juillot Dimitri , Condon Ciarán , Carballido-López Rut 
Published: December 2024

AbstractSpores ofBacillaceae, ubiquitous in soil, can withstand extreme conditions virtually indefinitely. The spore coat, one of the most sophisticated multiprotein complexes built by bacteria, protects the spore from environmental stresses and predators. InBacillus subtilis, assembly of the multilayered coat initiates at the forespore pole and is perceived as a stable process that progresses continuously until covering the entire forespore surface. In contrast, inBacillus cereus, coat formation initiates in the midspore region and extends outward to the spore poles. Using Structured Illumination Microscopy, we monitoredB. subtiliscoat development in real-time at the single-sporangium level with lateral resolution of 70-nm. We found that late-synthesized proteins from the innermost coat layers first assemble in the midspore region and are subsequently displaced towards the poles. This process is coupled with a unique redistribution of pre-assembled coat material across the forespore surface and influenced by outer coat development, highlighting a dynamic interplay in coat layers co-construction.
Longitudinal prevalence and co-carriage of pathogens associated with nursing home acquired pneumonia in three long-term care facilities
Authors: Whealy Ryann N. , Roberts Alexander , Furstenau Tara N. , Timm Skylar , Maltinsky Sara , Wells Sydney , Drake Kylie , Ramirez Kayla , Bolduc Candice , Ross Ann , Pearson Talima , Fofanov Viacheslav Y. 
Published: December 2024

AbstractNursing home acquired pneumonia (NHAP), and its subset – aspiration-associated pneumonia, is a leading cause of morbidity and mortality among residents in long-term care facilities (LTCFs). Understanding colonization dynamics of respiratory pathogens in LTCF residents is essential for effective infection control. This study examines the longitudinal trends in prevalence, persistence, bacterial load, and co-colonization patterns of five respiratory pathogens in three LTCFs in Phoenix, Arizona. Anterior nares and oral swabs were collected every other week and tested using qPCR forHaemophilus influenzae, Pseudomonas aeruginosa, Streptococcus pneumoniae, Staphylococcus aureus, andChlamydia pneumoniae. Weekly average positivity rates were 17.75% forH. influenzae(0% - 39.39%), 9.95% forP. aeruginosa(0% - 37.74%), 31.89% forS. pneumoniae(1.79% - 41.67%), and for 28.00% forS. aureus(0% - 55.36%).C. pneumoniaewas not detected.H. influenzaeandS. pneumoniaepredominantly colonized the oral cavity, whileP. aeruginosaandS. aureuspredominantly colonized the nasal cavity.S. pneumoniaeandS. aureuscolonizations were significantly more persistent thanH. influenzaeandP. aeruginosa, with persistence correlating with significantly higher bacterial loads. Co-colonization did occur in ∼20% of positive samples, but appeared to be due to random chance. This study reveals distinct colonization patterns among respiratory pathogens in LTCF residents, highlighting differences in site-specific prevalence, persistence, and bacterial load. These findings underscore the importance of longitudinal monitoring to inform targeted infection control strategies in LTCFs.
Infectious potential and circulation of SARS-CoV-2 in wild rats
Authors: Beissat Kevyn , Lattard Virginie , Picard-Meyer Evelyne , Fafournoux Ambre , Soro Sionfoungo Daouda , Servat Alexandre , Vincent-Hubert Françoise , Boué Franck , Chatron Nolan , Monchâtre-Leroy Elodie , Wasniewski Marine 
Published: December 2024

AbstractSince the beginning of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, a wide range of animal species (pets, mink…) have been naturally infected with this betacoronavirus. The emergence of new variants has increased the ability of SARS-CoV-2 to infect species that were not susceptible to the “original” SARS-CoV-2, such as mice and rats.This work attempted to evaluate the role of urban rats in the SARS-CoV-2 transmission by combining surveillance studies of rat populations in urban environments,in vivoexperimental inoculation of SARS-CoV-2 and comparative viral-receptor interaction insilicoanalyses.We studied the circulation of SARS-CoV-2 in wildRattus norvegicus(n=401) captured in urban areas and sewage systems of several French cities. Except for 3 inconclusive samples (2/75 from Bordeaux and 1/261 from Lyon) none of the 353 sera tested showed anti-SARS-CoV-2 antibodies by microsphere immunoassay. However, the 3 inconclusive sera samples were negative by virus neutralisation assay. No SARS-CoV-2 viral RNA was detected in all lungs collected from the 401 captured urban brown rats. In complement, four rat groups (two wild-type colonies,Rattus norvegicusandRattus rattus, and two laboratory strains, Sprague-Dawley and Wistar) were inoculated with the SARS-CoV-2 Omicron BA.5. At 4 days post-inoculation, no infectious viral particles were detected in the lungs and upper respiratory tract (URT) while viral RNA was detected at a low level only in the URT of all groups. In addition, seroconversion was observed 14 days after inoculation in the four groups. By molecular modelling, the Omicron BA.5 receptor binding domain (RBD) had lower affinities forRattus norvegicusandRattus rattusACE2 thanHomo sapiensACE2.Based on these results the SARS-CoV-2 Omicron BA.5 was unable to infect laboratory and wild type rats. In addition,Rattus norvegicuscollected for this study in different areas of France were not infected with SARS-CoV-2.
Genetically Encoded Red Fluorescent Indicators for Imaging Intracellular and Extracellular Potassium Ions
Authors: Yang Lina , Pathiranage Vishaka , Zhou Shihao , Sun Xiaoting , Zhang Hanbin , Lai Cuixin , Gu Chenglei , Subach Fedor V. , Walker Alice R. , Piatkevich Kiryl D. 
Published: December 2024

AbstractPotassium ion (K+) dynamics are vital for various biological processes. However, the limited availability of detection tools for tracking intracellular and extracellular K+has impeded a comprehensive understanding of the physiological roles of K+in intact biological systems. In this study, we developed two novel red genetically encoded potassium indicators (RGEPOs), RGEPO1 and RGEPO2, through a combination of directed evolution inE. coliand subsequent optimization in mammalian cells. RGEPO1, targeted to the extracellular membrane, and RGEPO2, localized in the cytoplasm, exhibited positive K+-specific fluorescence response with affinities of 3.55 mM and 14.81 mM in HEK293FT cells, respectively. We employed RGEPOs for real-time monitoring of subsecond K+dynamics in cultured neurons, astrocytes, acute brain slices, and the awake mouse in both intracellular and extracellular environments. Using RGEPOs, we were able, for the first time, to visualize intracellular and extracellular potassium transients during seizures in the brains of awake mice. Furthermore, molecular dynamics simulations provided new insights into the potassium-binding mechanisms of RGEPO1 and RGEPO2, revealing distinct K+-binding pockets and structural features. Thus, RGEPOs represent a significant advancement in potassium imaging, providing enhanced tools for real-time visualization of K+dynamics in various cell types and cellular environments.
Nebulized 2-deoxylated glucose analogues inhibit respiratory viral infection in advancedin vitroairway models
Authors: Wideman Sarah K. , Wali Laxmikant , Kovtunyk Vitalii , Chou Scharon , Gusel Vanessa , Telimaa Heta , Najmi Chama , Stoeva Delyana , Stöckl Johannes , Gualdoni Guido A. , Gorki Anna-Dorothea , Radivojev Snezana 
Published: December 2024

AbstractRespiratory viral infections caused by rhinoviruses (RVs), influenza A virus (IAV) and endemic corona viruses (HCoV) result in a serious strain on healthcare systems and public health, underscoring an urgent need for inhaled broad-spectrum antiviral therapies. However, their development is challenging, as no standardizedin vitromethodologies that can fully replicate thein vivoenvironment have been established. In this work, we aimed to investigate the antiviral and anti-inflammatory effect of three 2-deoxylated glucose analogues (2-DGA): 2-deoxy-D-glucose, 2-fluoro-2-dexoy-D-glucose and 2-fluoro-2-dexoy-D-mannose (2-FDM), by utilizing advancedin vitroair-liquid interface (ALI) airway models. We demonstrated that commonly used ALI models have variable susceptibility to RV, IAV and HCoV infection. Further, we showed that 2-DGA have an anti-inflammatory effect and suppress respiratory viral replication in models mimicking the upper and lower respiratory airways. Moreover, we confirmed that 2-DGA can be delivered via nebulizationin vitro, highlighting their potential to be used as broad-spectrum inhaled antivirals. Finally, our results demonstrate the importance of incorporating complexin vitromethodologies, such as primary cell ALI cultures and aerosol exposure, at an early stage of drug development.
The crucial role of intercellular calcium wave propagation triggered by influenza A virus in promoting infection
Authors: Kozawa Fumiya , Tamura Tomokazu , Takahashi Naoki , Kakizuka Taishi , Ichimura Taro , Shimada Rumi , Hashimoto Yasuyuki , Onituska Hironoshin , Kashiwagi Sayaka , Kamasaki Tomoko , Amano Maho , Nagai Takeharu , Fukuhara Takasuke , Fujioka Yoichiro , Ohba Yusuke 
Published: December 2024

AbstractInfluenza A viruses (IAVs) initially infect a few host cells, and the infection subsequently spreads to neighboring cells. However, the molecular mechanisms underlying this expansion remain unclear. Here, we show that IAV infection upregulates the frequency of intercellular calcium wave propagations (iCWPs) that mediate the spread of IAVs. ADP released from initially infected cells mediated iCWPs via the P2Y1receptor. The generation of iCWPs and spread of viral infection were inhibited by a P2Y1antagonist. Enhanced endocytosis in the surrounding cells that received ADP signaling upregulated viral entry. Expression of IAV matrix protein 2 (M2) in initially infected cells triggered iCWPs through ADP diffusion, thereby increasing infection, whereas an ion permeability-deficient mutation of M2 or inhibition of its ion channel activity suppressed iCWPs. Therefore, intercellular calcium signaling is essential for early expansion and potential establishment of IAV infection, which offers a promising target for IAV prophylaxis.
Study on phase change energy storage process in hot-water oil displacement system with composite fin structure
Authors: Cui Qiang , Liu Xiao , Zhang Zhen , Li Xiaoqin , Yang Shasha 
Published: December 2024

Purpose
This study aims to propose a new composite metal fin structure to enhance heat transfer efficiency during the phase change energy storage (PCES) process in a hot water oil displacement system.

Design/methodology/approach
PCES numerical unit is developed by varying the radii of annular fins and the number of corrugated fins. The impact of the finned structure on melting characteristics, energy storage performance and rate of heat storage is analyzed.

Findings
This study indicate the presence of non-uniform melting behavior in PCES unit during the heat charging process, which can be mitigated by increasing the number of corrugated fins and the radius of annular fins.

Originality/value
The impact of the finned structure on melting characteristics, energy storage performance and rate of heat storage is analyzed. This study indicates the presence of non-uniform melting behavior in PCES unit during the heat charging process, which can be mitigated by increasing the number of corrugated fins and the radius of annular fins.