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Dynamics of Neuronal and Astrocytic Energy Molecules in Epilepsy
No full textABSTRACT The dynamics of energy molecules in the mouse brain during metabolic challenges induced by epileptic seizures were examined. A transgenic mouse line expressing a fluorescence resonance energy transfer (FRET)‐based adenosine triphosphate (ATP) sensor, selectively expressed in the cytosol of neurons, was used. An optical fiber was inserted into the hippocampus, and changes in cytosolic ATP concentration were estimated using the fiber photometry method. To induce epileptic neuronal hyperactivity, a train of electrical stimuli was delivered to a bipolar electrode placed alongside the optical fiber. Although maintaining a steady cytosolic ATP concentration is crucial for cell survival, a single episode of epileptic neuronal hyperactivity drastically reduced neuronal ATP levels. Interestingly, the magnitude of ATP reduction did not increase with the exacerbation of epilepsy, but rather decreased. This suggests that the primary consumption of ATP during epileptic neuronal hyperactivity may not be solely directed toward restoring the Na + and K + ionic imbalance caused by action potential bursts. Cytosolic ATP concentration reflects the balance between supply and consumption. To investigate the metabolic flux leading to neuronal ATP production, a new FRET‐based pyruvate sensor was developed and selectively expressed in the cytosol of astrocytes in transgenic mice. Upon epileptic neuronal hyperactivity, an increase in astrocytic pyruvate concentration was observed. Changes in the supply of energy molecules, such as glucose and oxygen, due to blood vessel constriction or dilation, as well as metabolic alterations in astrocyte function, may contribute to cytosolic ATP dynamics in neurons. imageJapan Society for the Promotion of Science https://doi.org/10.13039/501100001691Japan Agency for Medical Research and Development https://doi.org/10.13039/100009619Uehara Memorial Foundation https://doi.org/10.13039/100008732Takeda Science Foundation https://doi.org/10.13039/100007449Research Foundation for Opto-Science and Technology https://doi.org/10.13039/50110001201
Label-free metabolic fingerprinting of motile mammalian spermatozoa with subcellular resolution
No full textGrantová Agentura České Republiky http://dx.doi.org/10.13039/501100001824Akademie Věd České Republiky http://dx.doi.org/10.13039/501100004240Ministerstvo Školství, Mládeže a Tělovýchovy http://dx.doi.org/10.13039/501100001823European Regional Development Fund http://dx.doi.org/10.13039/50110000853
Environmental and microhabitat influences on microbiota of snow-active Collembola in sub-zero temperatures
No full textDiagnostic value of serum survivin, Ki-67 and thymidine kinase in dogs with nasal cavity disease
No full textOpen-Access-Publikationsfonds 202
Chronic Vanadium Exposure Promotes Aggregation of Alpha‐Synuclein, Tau and Amyloid Beta in Mouse Brain
No full textABSTRACT The interaction of toxic environmental metals and metalloids with brain proteins and polypeptides can result in pathological aggregations and formation of toxic oligomers, which are key features of many neurodegenerative diseases. Occupational and environmental exposure to vanadium is connected to a neurological syndrome that includes psychiatric symptoms, cognitive decline, and neurodegeneration. In this study, we hypothesized that prolonged vanadium exposure may be a potential risk factor for Alzheimer's and Parkinson's diseases. A total of 72 male BALB/c mice, each 4 weeks' old, were used. Vanadium‐treated groups received intraperitoneal injections of 3 mg/kg body weight of vanadium three times a week for 6, 12, or 18 months. The control group received sterile water while the withdrawal group were given vanadium injection for 3 months, followed by withdrawal of the metal, but treatment with sterile water only, and were sacrificed at 3‐, 9‐, or 15‐months post vanadium exposure. Sagittal sections of brain paraffin‐embedded tissue were prepared and analyzed using immunofluorescence to study the immunoreactivity and cellular localization of α‐synuclein (α‐syn), amyloid‐β (Aβ), and tau proteins. Our findings revealed pathological aggregation of these proteins in the frontoparietal cortices and the dorsal CA1 and CA3 regions. Double immunolabeling with glial cells and neurons showed neuronal degeneration, functional gliosis, and activation of astrocytes and microglia at sites of α‐synuclein immunoreactivity. We observed increased immunoreactivity of phosphorylated nuclei tau both in the parietal cortices and corpus callosum white matter while we observed intraneuronal accumulation of Aβ deposits in the cortex and dorsal hippocampal regions in vanadium treated brains. These cellular changes and proteinopathies, although persisting, were significantly attenuated after vanadium withdrawal. Our findings show that prolonged vanadium exposure promotes abnormal accumulation of neurodegeneration‐associated proteins (α‐syn, Tau, and Aβ) in the brain, which is further exacerbated by aging in the context of extended exposure to the metal. imageDeutsche Forschungsgemeinschaft https://doi.org/10.13039/501100001659International Society for Neurochemistry https://doi.org/10.13039/501100008992Bassir-Thomas Biomedical Foundation https://doi.org/10.13039/50110000821
Label-free single cell phenotyping to determine tumor cell heterogeneity in pancreatic cancer in real-time
No full textPrenominal a and determiners in three Mabia/Gur languages: Dagara, Mooré and Koromfe
No full textAbstract This paper discusses the different syntactic status of the prenominal marker a in three languages spoken in Burkina Faso and neighbouring countries (Dagara, Mooré and Koromfe) and its respective relation to the determiner system. We argue that the marker is a head-initial determiner in Dagara, a proprial article in Mooré and a nominal expletive in Koromfe and tentatively suggest a possible common pronominal origin. The paper also addresses further points of variation in the higher nominal structure of the three languages concerning DP directionality and the co-occurrence of determiners, demonstratives and possessors, providing a basis for future wider investigations across the Mabia/Gur family
Hot water treatment combined with <i>Trichoderma</i> inoculation in the nursery protects planting material against grapevine trunk disease
No full textGrapevine trunk diseases (GTDs) cause significant losses in viticulture. To enhance the phytosanitary quality of planting material, a method was developed to control the common GTD pathogens Phaeomoniella chlamydospora, Phaeoacremonium minimum, and Diplodia seriata using hot water treatment (HWT) and inoculation with the biocontrol agent Trichoderma atroviride SC1 (Vintec®, Certis Belchim B. V.) (Ta SC1). Sensitivity of P. minimum and P. chlamydospora isolates to HWT was tested in vitro and in autoclaved wood at conidial and mycelium stages and at various time/temperature combinations (30 and 40 min at 40 °C, 45 °C, 50 °C and 55 °C). The results showed that P. minimum had greater tolerance to HWT compared to P. chlamydospora. Spore germination of all P. chlamydospora isolates was completely inhibited at 45 °C, while P. minimum isolate 117607 tolerated 50 °C. Mycelium growth of both pathogens was completely inhibited at 55 °C. In autoclaved wood, P. chlamydospora growth was inhibited after 30 min at 50 °C, while treatments for 45 min were necessary to inhibit the growth of P. minimum. In nursery experiments, cuttings were artificially inoculated and incubated with the pathogens and treated with HWT at 50 °C for 45 min under conditions of common viticultural practice. In these conditions, no recovery was recorded for P. chlamydospora and D. seriata seven days post-inoculation (dpi), but the survival rate of P. minimum was 5 %. In 2021, P. minimum recovered in 40 % of the samples six months post-inoculation, P. chlamydospora in 7 % twelve months post-inoculation, and D. seriata was eliminated. In 2022, D. seriata was detected in 10 % of samples six months post-inoculation and P. chlamydospora in 25 % of the samples twelve months post-inoculation. P. minimum recovered at all sampling time points during the assessment period. Combined applications of HWT and Ta SC1 provided protection of the planting material over the twelve months assessment period, with molecular analysis confirming 90 % recovery of Ta SC1. Field experiments carried out with naturally infected scions showed that HWT at 50 °C for 45 min significantly reduced the incidence of Diplodia spp. Overall, HWT effectively reduced GTD pathogens in grapevine planting material, and the combined treatment with Ta SC1 enhanced long-lasting protection in the nursery
Empirical antibiotic therapy in life-threatening infections—current concepts and controversies
No full textMultimodal Web-Based Telerehabilitation for Patients With Post–COVID-19 Condition: Protocol for a Randomized Controlled Trial
No full textBackground Patients with post–COVID-19 condition (PCC) experience persistent, long-term health consequences following SARS-CoV-2 infection, including fatigue, hyperventilation, cognitive impairment, and limitations in daily activities. There is emerging evidence suggesting that exercise and respiratory therapy–based telerehabilitation is safe and could potentially improve physical capacity while reducing health care costs. Objective This study aims to evaluate the superiority of a multimodal, symptom-titrated telerehabilitation program over standard care in patients with PCC who are severely affected, using the highest oxygen uptake rate (VO2peak [mL/min/kg]) achieved during the cardiopulmonary exercise test (CPET) and minute ventilation/carbon dioxide production slope (VE/VCO2 [full slope]) as primary outcomes. In addition, this study seeks to provide novel insights into the clinical and physiological adaptations associated with PCC, informing future rehabilitation strategies. Methods This prospective, randomized, waitlist-controlled trial was approved by the Rhineland-Palatinate Medical Association ethics committee. All procedures comply with the Declaration of Helsinki. This study comprises 3 examination time points, which include patient-reported outcomes, clinical assessments, and a CPET. It is structured into an 8-week intervention phase followed by an 8-week follow-up phase. Following baseline assessment, patients will be randomly assigned to either the intervention group (IG) or the control group (CG). During the intervention phase, IG participants will receive a web-based, multimodal, symptom-titrated telerehabilitation program consisting of sports medicine consultations, weekly teleconsultations, a structured pacing approach, and exercise and respiratory therapy. In contrast, CG participants will receive treatment as usual, which includes a single sports medicine consultation on healthy habits and a self-directed pacing approach for managing symptoms and daily activities. During the follow-up phase, IG participants will continue training independently without teleconsultations, whereas CG participants will undergo the same telerehabilitation intervention as the IG. A follow-up assessment will be conducted for both groups to evaluate long-term effects. This study adheres to the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) guidelines and follows the Consensus on Exercise Reporting Template. Results Recruitment began in August 2023 and was extended until March 2025. As of March 2025, 80 participants have been recruited, and data analysis is ongoing. Final results are expected by December 2025, with a cross-sectional analysis of baseline data anticipated by July 2025. Conclusions This study is the first randomized controlled trial investigating the effectiveness of multimodal and symptom-titrated telerehabilitation in patients with PCC who are severely affected. The integration of various objective diagnostic systems will provide valuable insights into emerging postviral fatigue syndromes, supporting the development of CPET-based diagnostics, personalized rehabilitation strategies, and future research on long-term telerehabilitation effectiveness. The findings will be disseminated through peer-reviewed publications, professional networks, and patient advocacy groups to ensure scientific, clinical, and public impact. Trial Registration German Clinical Trials Register (DRKS) DRKS00032394; https://drks.de/search/de/trial/DRKS00032394 International Registered Report Identifier (IRRID) DERR1-10.2196/6504