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Atmospheric methane (CH4) is the second-most-important anthropogenic greenhouse gas and has a 20-year global warming potential 82 times greater than carbon dioxide (CO2). Anthropogenic sources account for ∼ 60 % of global CH4 emissions, of which 20 % come from oil and gas exploration, production and distribution. High-resolution satellite-based imaging spectrometers are becoming important tools for detecting and monitoring CH4 point source emissions, aiding mitigation. However, validation of these satellite measurements, such as those from the commercial GHGSat satellite constellation, has so far not been documented for active leaks. Here we present the monitoring and quantification, by GHGSat's satellites, of the CH4 emissions from an active gas leak from a downstream natural gas distribution pipeline near Cheltenham, UK, in the spring and summer of 2023 and provide the first validation of the satellite-derived emission estimates using surface-based mobile greenhouse gas surveys. We also use a Lagrangian transport model, the UK Met Office's Numerical Atmospheric-dispersion Modelling Environment (NAME), to estimate the flux from both satellite- and ground-based observation methods and assess the leak's contribution to observed concentrations at a local tall tower site (30 km away). We find GHGSat's emission estimates to be in broad agreement with those made from the in situ measurements. During the study period (March–June 2023) GHGSat's emission estimates are 236–1357 kg CH4 h−1, whereas the mobile surface measurements are 634–846 kg CH4 h−1. The large variability is likely down to variations in flow through the pipe and engineering works across the 11-week period. Modelled flux estimates in NAME are 181–1243 kg CH4 h−1, which are lower than the satellite- and mobile-survey-derived fluxes but are within the uncertainty. After detecting the leak in March 2023, the local utility company was contacted, and the leak was fixed by mid-June 2023. Our results demonstrate that GHGSat's observations can produce flux estimates that broadly agree with surface-based mobile measurements. Validating the accuracy of the information provided by targeted, high-resolution satellite monitoring shows how it can play an important role in identifying emission sources, including unplanned fugitive releases that are inherently challenging to identify, track, and estimate their impact and duration. Rapid, widespread access to such data to inform local action to address fugitive emission sources across the oil and gas supply chain could play a significant role in reducing anthropogenic contributions to climate change.

​​​​​​​The ability to detect and quantify methane emissions from offshore platforms is of considerable interest in providing actionable feedback to industrial operators. While satellites offer a distinctive advantage for remote sensing of offshore platforms which may otherwise be difficult to reach, offshore measurements of methane from satellite instruments in the shortwave infrared are challenging due to the low levels of diffuse sunlight reflected from water surfaces. Here, we use the GHGSat satellite constellation in a sun glint configuration to detect and quantify methane emissions from offshore targets around the world. We present a variety of examples of offshore methane plumes, including the largest single emission at (84 000 ± 24 000) kg h−1 observed by GHGSat from the Nord Stream 2 pipeline leak in 2022 and the smallest offshore emission measured from space at (180 ± 130) kg h−1 in the Gulf of Mexico. In addition, we provide an overview of the constellation's offshore measurement capabilities. We measure a median column precision of 2.1 % of the background methane column density and estimate a detection limit, from analytical modelling and orbital simulations, that varies between 160 and 600 kg h−1 depending on the latitude and season.

A reduction in anthropogenic methane emissions is vital to limit near-term global warming. A small number of so-called super-emitters is responsible for a disproportionally large fraction of total methane emissions. Since late 2017, the TROPOspheric Monitoring Instrument (TROPOMI) has been in orbit, providing daily global coverage of methane mixing ratios at a resolution of up to 7×5.5 km2, enabling the detection of these super-emitters. However, TROPOMI produces millions of observations each day, which together with the complexity of the methane data, makes manual inspection infeasible. We have therefore designed a two-step machine learning approach using a convolutional neural network to detect plume-like structures in the methane data and subsequently apply a support vector classifier to distinguish the emission plumes from retrieval artifacts. The models are trained on pre-2021 data and subsequently applied to all 2021 observations. We detect 2974 plumes in 2021, with a mean estimated source rate of 44 t h−1 and 5–95th percentile range of 8–122 t h−1. These emissions originate from 94 persistent emission clusters and hundreds of transient sources. Based on bottom-up emission inventories, we find that most detected plumes are related to urban areas and/or landfills (35 %), followed by plumes from gas infrastructure (24 %), oil infrastructure (21 %), and coal mines (20 %). For 12 (clusters of) TROPOMI detections, we tip and cue the targeted observations and analysis of high-resolution satellite instruments to identify the exact sources responsible for these plumes. Using high-resolution observations from GHGSat, PRISMA, and Sentinel-2, we detect and analyze both persistent and transient facility-level emissions underlying the TROPOMI detections. We find emissions from landfills and fossil fuel exploitation facilities, and for the latter, we find up to 10 facilities contributing to one TROPOMI detection. Our automated TROPOMI-based monitoring system in combination with high-resolution satellite data allows for the detection, precise identification, and monitoring of these methane super-emitters, which is essential for mitigating their emissions.

Quantitative MRI (qMRI) has been shown to be clinically useful for numerous applications in the brain and body. The development of rapid, accurate, and reproducible qMRI techniques offers access to new multiparametric data, which can provide a comprehensive view of tissue pathology. This work introduces a multiparametric qMRI protocol along with full postprocessing pipelines, optimized for brain imaging at 3 Tesla and using state-of-the-art qMRI tools. The total scan time is under 50 minutes and includes eight pulse-sequences, which produce range of quantitative maps including T1, T2, and T2* relaxation times, magnetic susceptibility, water and macromolecular tissue fractions, mean diffusivity and fractional anisotropy, magnetization transfer ratio (MTR), and inhomogeneous MTR. Practical tips and limitations of using the protocol are also provided and discussed. Application of the protocol is presented on a cohort of 28 healthy volunteers and 12 brain regions-of-interest (ROIs). Quantitative values agreed with previously reported values. Statistical analysis revealed low variability of qMRI parameters across subjects, which, compared to intra-ROI variability, was x4.1 ± 0.9 times higher on average. Significant and positive linear relationship was found between right and left hemispheres' values for all parameters and ROIs with Pearson correlation coefficients of r>0.89 (P

ABSTRACT The management of ventilator-associated and hospital-acquired pneumonia requires rapid and accurate quantitative detection of the infecting pathogen(s). To achieve this, we propose a metagenomics next-generation sequencing (mNGS) assay that includes the use of an internal sample processing control (SPC) for the quantitative detection of 20 relevant bacterial species of interest (SOI) from bronchoalveolar lavage (BAL) samples. To avoid very major errors in the identification of respiratory pathogens due to “false-negative” cases, each sample was spiked with Bacillus subtilis, at a precisely defined concentration, using rehydrated BioBall. This SPC ensured the detection and quantification of the pathogen(s) at defined minimum concentrations. In the presented mNGS workflow, absolute quantification of Staphylococcus aureus was as accurate as quantitative PCR. We defined a metagenomics threshold at 5.3 × 103 genome equivalent unit per milliliter of the sample for each SOI, to distinguish colonization from higher amounts of pathogens that may be associated with infection. Complete mNGS process and metrics were assessed on 40 clinical samples, showing >99.9% sensitivity compared to microbial culture. However, 19 out of the 29 (66%) SOI detections above the metagenomics threshold were not associated with bacterial growth above classical culture-based clinical thresholds. Taxonomic classification of 7 (37%) of the “false-positive” detections was confirmed by finding specific 16S/MetaPhlAn2 markers, the 12 other “false-positive” detections did not yield enough reads to check their taxonomic classification. Our SPC design and analytical workflow allowed efficient detection and absolute quantification of pathogens from BAL samples, even when the bacterial DNA quantity was largely below the manufacturer’s recommendations for NGS. The frequent “false-positive” detections suggested the presence of nonculturable cells within the tested BAL samples. Furthermore, mNGS detected mixed infections, including bacterial species not reported by routine cultures. IMPORTANCE The management of ventilator-associated pneumonia and hospital-acquired pneumonia requires rapid and accurate quantitative detection of the infecting pathogen. To this end, we propose a metagenomic sequencing assay that includes the use of an internal sample processing control for the quantitative detection of 20 relevant bacterial species from bronchoalveolar lavage samples.

A growing body of research suggests that movement aids facial expression recognition. However, less is known about the conditions under which the dynamic advantage occurs. The aim of this research was to test emotion recognition in static and dynamic facial expressions, thereby exploring the role of three featural parameters (prototypicality, ambiguity, and complexity) in human and machine analysis. In two studies, facial expression videos and corresponding images depicting the peak of the target and non-target emotion were presented to human observers and the machine classifier (FACET). Results revealed higher recognition rates for dynamic stimuli compared to non-target images. Such benefit disappeared in the context of target-emotion images which were similarly well (or even better) recognised than videos, and more prototypical, less ambiguous, and more complex in appearance than non-target images. While prototypicality and ambiguity exerted more predictive power in machine performance, complexity was more indicative of human emotion recognition. Interestingly, recognition performance by the machine was found to be superior to humans for both target and non-target images. Together, the findings point towards a compensatory role of dynamic information, particularly when static-based stimuli lack relevant features of the target emotion. Implications for research using automatic facial expression analysis (AFEA) are discussed.

ATP hydrolysis is required for the synthesis, transport and polymerization of monomers for macromolecules as well as for the assembly of the latter into cellular structures. Other cellular processes not directly related to synthesis of biomass, such as maintenance of membrane potential and cellular shape, also require ATP. The unicellular flagellated parasite Trypanosoma brucei has a complex digenetic life cycle. The primary energy source for this parasite in its bloodstream form (BSF) is glucose, which is abundant in the host's bloodstream. Here, we made a detailed estimation of the energy budget during the BSF cell cycle. As glycolysis is the source of most produced ATP, we calculated that a single parasite produces 6.0 x 1011 molecules of ATP/cell cycle. Total biomass production (which involves biomass maintenance and duplication) accounts for ~63% of the total energy budget, while the total biomass duplication accounts for the remaining ~37% of the ATP consumption, with in both cases translation being the most expensive process. These values allowed us to estimate a theoretical YATP of 10.1 (g biomass)/mole ATP and a theoretical [Formula: see text] of 28.6 (g biomass)/mole ATP. Flagellar motility, variant surface glycoprotein recycling, transport and maintenance of transmembrane potential account for less than 30% of the consumed ATP. Finally, there is still ~5.5% available in the budget that is being used for other cellular processes of as yet unknown cost. These data put a new perspective on the assumptions about the relative energetic weight of the processes a BSF trypanosome undergoes during its cell cycle.

Abstract Background Although psychomotor symptoms are associated with the clinical symptomatology of depression, they are rarely assessed and standardized clinical evaluation tools are lacking. Psychomotor retardation is sometimes assessed through direct patient observations by clinicians or through a clinical observation grid, in the absence of a standardized psychomotor assessment. In this pilot study, we evaluated the feasibility of standardized psychomotor examination of patients with major depressive disorder (MDD) and detailed a psychomotor semiology in these patients. Methods We used a standardized psychomotor assessment to examine 25 patients with MDD and 25 age- and sex-matched healthy controls (HC) and compared their psychomotor profiles. Using standardized tests, we assessed muscle tone and posture, gross motor skills, perceptual-motor skills, and body image/organization. Clinical assessments of depressive symptoms (levels of psychomotor retardation, anxiety, and self-esteem) comprised this detailed psychomotor examination. Results All participants were examined using the standardized psychomotor assessment. The main results of the psychomotor examination highlighted low body image of MDD participants (p

Abstract Background Natalizumab and fingolimod are used as high-efficacy treatments in relapsing–remitting multiple sclerosis. Several observational studies comparing these two drugs have shown variable results, using different methods to control treatment indication bias and manage censoring. The objective of this empirical study was to elucidate the impact of methods of causal inference on the results of comparative effectiveness studies. Methods Data from three observational multiple sclerosis registries (MSBase, the Danish MS Registry and French OFSEP registry) were combined. Four clinical outcomes were studied. Propensity scores were used to match or weigh the compared groups, allowing for estimating average treatment effect for treated or average treatment effect for the entire population. Analyses were conducted both in intention-to-treat and per-protocol frameworks. The impact of the positivity assumption was also assessed. Results Overall, 5,148 relapsing–remitting multiple sclerosis patients were included. In this well-powered sample, the 95% confidence intervals of the estimates overlapped widely. Propensity scores weighting and propensity scores matching procedures led to consistent results. Some differences were observed between average treatment effect for the entire population and average treatment effect for treated estimates. Intention-to-treat analyses were more conservative than per-protocol analyses. The most pronounced irregularities in outcomes and propensity scores were introduced by violation of the positivity assumption. Conclusions This applied study elucidates the influence of methodological decisions on the results of comparative effectiveness studies of treatments for multiple sclerosis. According to our results, there are no material differences between conclusions obtained with propensity scores matching or propensity scores weighting given that a study is sufficiently powered, models are correctly specified and positivity assumption is fulfilled.

ABSTRACT: Background: To investigate the association of ihMT (inhom signals with the demyelination and remyelination phases of the acute cuprizone mouse model in comparison with histology, and to assess the extent of tissue damage and repair from MRI data. Methods: Acute demyelination by feeding 0.2% cuprizone for five weeks, followed by a four-week remyelination period was applied on genetically modified plp-GFP mice. Animals were scanned at different time points of the demyelination and remyelination phases of the cuprizone model using a multimodal MRI protocol, including ihMT T1D-filters, MPF (Macromolecular Proton Fraction) and R1 (longitudinal relaxation rate). For histology, plp-GFP (proteolipid protein – Green Fluorescent Protein) microscopy and LFB (Luxol Fast Blue) staining were employed as references for the myelin content. Comparison of MRI with histology was performed in the medial corpus callosum (mCC) and cerebral cortex (CTX) at two brain levels whereas ROI-wise and voxel-based analyses of the MRI metrics allowed investigating in vivo the spatial extent of myelin alterations. Results: IhMT high-pass T1D-filters, targeted toward long T1D components, showed significant temporal variations in the mCC consistent with the effects induced by the cuprizone toxin. In addition, the corresponding signals correlated strongly and significantly with the myelin content assessed by GFP fluorescence and LFB staining over the demyelination and the remyelination phases. The signal of the band-pass T1D-filter, which isolates short T1D components, showed changes over time that were poorly correlated with histology, hence suggesting a sensitivity to pathological processes possibly not related to myelin. Although MPF was also highly correlated to histology, ihMT high-pass T1D-filters showed better capability to characterize the spatial-temporal patterns during the demyelination and remyelination phases of the acute cuprizone model (e.g., rostro-caudal gradient of demyelination in the mCC previously described in the literature). Conclusions: IhMT sequences selective for long T1D components are specific and sensitive in vivo markers of demyelination and remyelination and have successfully captured the spatially heterogeneous pattern of the demyelination and remyelination mechanisms in the cuprizone model. Interestingly, differences in signal variations between the ihMT high-pass and band-pass T1D-filter, suggest a sensitivity of the ihMT sequences targeted to short T1Ds to alterations other than those of myelin. Future studies will need to further address these differences by examining more closely the origin of the short T1D components and the variation of each T1D component in pathology.

Lamina propria interstitial cells that express the tyrosine kinase receptor, platelet-derived growth factor receptor alpha (PDGFRα) may play a role in urinary sensory signaling. Imatinib mesylate, also referred to as imatinib, is a tyrosine kinase inhibitor that can inhibit PDGFRα and has been widely used in urological research. We evaluated the functional effects of imatinib administration (via oral gavage or intravesical infusion) with two different experimental designs (prevention and treatment), in a cyclophosphamide (CYP)-induced cystitis (acute, intermediate, and chronic), male and female rodent model using conscious cystometry and somatic sensitivity testing. Imatinib significantly (0.0001 ≤ p ≤ 0.05) decreased voiding frequency and increased bladder capacity in acute CYP-induced cystitis, by the prevention (females) and treatment (females and males) designs. Imatinib was not effective in preventing or treating intermediate or chronic CYP-induced cystitis in either sex. Interestingly, in the prevention experiments, imatinib administration increased (0.0001 ≤ p ≤ 0.01) voiding frequency and decreased bladder capacity in control mice. However, in the treatment experiments, imatinib administration decreased (0.01 ≤ p ≤ 0.05) voiding frequency and increased bladder capacity in control mice. Bladder function improvements observed with imatinib treatment in acute CYP-induced cystitis mice remained and additionally improved with a second dose of imatinib 24 hours after CYP treatment. Imatinib administration did not affect pelvic somatic sensitivity in female mice with acute CYP-induced cystitis. Our studies suggest that (1) imatinib improves bladder function in mice with acute CYP-induced cystitis with a prevention and treatment design and (2) interstitial cells may be a useful target to improve bladder function in cystitis.

Imatinib mesylate is a tyrosine kinase inhibitor that inhibits platelet-derived growth factor receptor (PDGFR)-α, -β, stem cell factor receptor (c-KIT), and BCR-ABL. PDGFRα is expressed in a subset of interstitial cells in the lamina propria (LP) and detrusor muscle of the urinary bladder. PDGFRα + interstitial cells may contribute to bladder dysfunction conditions such as interstitial cystitis/bladder pain syndrome (IC/BPS) or overactive bladder (OAB). We have previously demonstrated that imatinib prevention via oral gavage or treatment via intravesical infusion improves urinary bladder function in mice with acute (4 hour, h) cyclophosphamide (CYP)-induced cystitis. Here, we investigate potential underlying mechanisms mediating the bladder functional improvement by imatinib using a prevention or treatment experimental design. Using qRT-PCR and ELISAs, we examined inflammatory mediators (NGF, VEGF, BDNF, CCL2, IL-6) previously shown to affect bladder function in CYP-induced cystitis. We also examined the distribution of phosphorylated (p) ERK and pAKT expression in the LP with immunohistochemistry. Imatinib prevention significantly (0.0001 ≤ p ≤ 0.05) reduced expression for all mediators examined except NGF, whereas imatinib treatment was without effect. Imatinib prevention and treatment significantly (0.0001 ≤ p ≤ 0.05) reduced pERK and pAKT expression in the upper LP (U. LP) and deeper LP (D. LP) in female mice with 4 h CYP-induced cystitis. Although we have previously demonstrated that imatinib prevention or treatment improves bladder function in mice with cystitis, the current studies suggest that reductions in inflammatory mediators contribute to prevention benefits of imatinib but not the treatment benefits of imatinib. Differential effects of imatinib prevention or treatment on inflammatory mediators may be influenced by the route and frequency of imatinib administration and may also suggest other mechanisms (e.g., changes in transepithelial resistance of the urothelium) through which imatinib may affect urinary bladder function following CYP-induced cystitis.

In addition to a multifactorial etiology of nutritional, social and environmental stressors, post-weaning diarrhea (PWD) in pigs is often related to infection with specific pathogens such as enterotoxigenic Escherichia coli (ETEC). In swine farming operations, the incidence of PWD is a global concern and is associated with an unbalanced gut status, resulting in poor performance and high antimicrobial consumption via prophylaxis and metaphylaxis. Increases in antimicrobial resistance are reinforcing an already-urgent need for sustainable, alternative solutions for maintaining optimal gut health in livestock. Tannin-rich plants and extracts contain bioactive compounds that could be of great interest in this respect. This review describes how the use of tannins around weaning could be beneficial for pigs, with special emphasis on the reduction of ETEC-related PWD. An overview of the broad chemical diversity of tannins is presented together with their physicochemical and biological properties, as well as how they may be metabolized in the digestive tract. The pharmacological effects exerted by tannins are summarized; more precisely, the possible mechanisms by which tannins can disrupt the different steps of the pathogenesis of ETEC-related PWD are highlighted. The factors affecting the bioactivity of tannins are also discussed, shedding light on the importance of chemical structure among different tannins.

Rugby players are subject to multiple impacts to their head and neck that could have adverse neurological effects and put them at increased risk of neurodegeneration.Previous studies demonstrated altered default mode network and diffusion metrics on brain, as well as more foraminal stenosis, disc protrusion and neck pain among players of contact sports as compared to healthy controls. However, the long-term effects of practice and repetitive impacts on brain and cervical spinal cord (cSC) of the rugby players have never been systematically investigated.In this study, 15 retired professional and amateur rugby players (R) and 15 age-matched healthy controls (HC) (all males; mean age R: 46.8 ± 7.6; and HC: 48.6 ± 9.5) were recruited both to investigate cord impairments and further characterize brain structure damage. Medical questionnaires including modified Japanese Orthopedic Association scale (mJOA) and Neck Disability Index (NDI) were filled by all participants. A 3 T multi-parametric MR protocol including conventional qualitative techniques such as T1-, T2-, and T2*-weighted sequences, as well as state-of-the art quantitative techniques including MP2RAGE T1 mapping and 3D ihMTRAGE, was used on both brain and cSC. Normalized brain WM and GM volumes, spine Overall Stenosis Score, cord cross-sectional area and regional T1 and ihMT metrics were derived from these acquisitions.Rugby players showed significantly higher NDI scores, as well as a faster decline of normalized brain GM volume with age as compared to HC. Moreover, higher T1 values on cSC suggestive of structural degeneration, together with higher T1 and lower ihMTsat on brain WM suggestive of demyelination, were observed in retired rugby players as compared to age-matched controls, which may suggest cumulative effects of long-term impacts on the tissues. Metrics also suggest early aging and different aging processes on brain tissue in the players.These preliminary observations provide new insights in the domain, which should now be further investigated on larger cohorts and multicentric longitudinal studies, and further correlated to the likelihood of neurodegenerative diseases and risk factors.

By examining concerns about safety, compliance, and distribution through an interdisciplinary approach of public health and history, we argue that historical and contemporary mistrust of immunizations serves to challenge the successful management of a COVID-19 vaccine program in the U.S. Unique circumstances surrounding the development of a COVID-19 vaccine, including pressure for rapid production, unclear communication from public health officials, and existing resistance to behavioral protective public health policy measures (e.g., mask-wearing) complicate widespread vaccine adoption. Currently, the demand for first and second COVID-19 vaccine doses, as well as the COVID-19 booster, continues to fluctuate in the U.S. population as COVID-19 variants continue to emerge. This hesitancy has resulted in a stalled vaccination program and the absence of herd immunity. To support the successful management of a vaccine program, we recommend public health education and communication measures that can be tailored to local community needs while preparing realistic public expectations surrounding the efficacy of a COVID-19 vaccine. A tailored approach may reduce vaccine hesitancy in American society. The perspectives offered herein present a pathway that is applicable to the current COVID-19 vaccine management program in the U.S., other global locations, and future pandemics.

Trypanosoma cruzi is a hemoflagellated parasite causing Chagas disease, which affects 6-8 million people in the Americas. More than one hundred years after the description of this disease, the available drugs for treating the T. cruzi infection remain largely unsatisfactory. Chloroquinoline and arylamidine moieties are separately found in various compounds reported for their anti-trypanosoma activities. In this work we evaluate the anti-T. cruzi activity of a collection of 26 "chimeric" molecules combining choroquinoline and amidine structures. In a first screening using epimastigote forms of the parasite as a proxy for the clinically relevant stages, we selected the compound 7-chloro-4-[4-(4,5-dihydro-1H-imidazol-2-yl)phenoxy]quinoline (named here as A6) that performed better as an anti-T. cruzi compound (IC50 of 2.2 ± 0.3 μM) and showed a low toxicity for the mammalian cell CHO-K1 (CC50 of 137.9 ± 17.3 μM). We initially investigated the mechanism of death associated to the selected compound. The A6 did not trigger phosphatidylserine exposure or plasma membrane permeabilization. Further investigation led us to observe that under short-term incubations (until 6 hours), no alterations of mitochondrial function were observed. However, at longer incubation times (4 days), A6 was able to decrease the intracellular Ca2+, to diminish the intracellular ATP levels, and to collapse mitochondrial inner membrane potential. After analysing the cell cycle, we found as well that A6 produced an arrest in the S phase that impairs the parasite proliferation. Finally, A6 was effective against the infective forms of the parasite during the infection of the mammalian host cells at a nanomolar concentration (IC50(tryps) = 26.7 ± 3.7 nM), exhibiting a selectivity index (SI) of 5,170. Our data suggest that A6 is a promising hit against T. cruzi.

In the urinary bladder, mechanosensitive ion channels (MSCs) underlie the transduction of bladder stretch into sensory signals that are relayed to the PNS and CNS. PIEZO1 is a recently identified MSC that is Ca2+ permeable and is widely expressed throughout the lower urinary tract. Recent research indicates that PIEZO1 is activated by mechanical stretch or by pharmacological agonism via Yoda1. Aberrant activation of PIEZO1 has been suggested to play a role in clinical bladder pathologies like partial bladder outlet obstruction and interstitial cystitis/bladder pain syndrome (IC/BPS). In the present study, we show that intravesical instillation of Yoda1 in female Wistar rats leads to increased voiding frequency for up to 16 hours after administration compared to vehicle treatment. In a cyclophosphamide (CYP) model of cystitis, we found that the gene expression of several candidate MSCs (Trpv1, Trpv4, Piezo1, and Piezo2) were all upregulated in the urothelium and detrusor following chronic CYP-induced cystitis, but not acute CYP-induced cystitis. Functionally with this model, we show that Ca2+ activity is increased in urothelial cells following PIEZO1 activation via Yoda1 in acute and intermediate CYP treatment, but not in naïve (no CYP) nor chronic CYP treatment. Lastly, we show that activation of PIEZO1 may contribute to pathological bladder dysfunction through the downregulation of several tight junction genes in the urothelium including claudin-1, claudin-8, and zona occludens-1. Together, these data suggest that PIEZO1 activation plays a role in dysfunctional voiding behavior and may be a future, clinical target for the treatment of pathologies like IC/BPS.