178,401 research outputs found
Involvement of Na+/Ca2+ Exchanger (NCX) in Glutamate-Induced Neuroprotection in SH-SY5Y Differentiated Cells Subjected to Hypoxia/Reoxygenation (H/R) Injury
No full textL’ischemia cerebrale è una patologia caratterizzata dalla ridotta o totale assenza di ossigeno e di substrati metabolici che influiscono sulla respirazione aerobia determinando un danno mitocondriale in particolare nella sintesi di ATP e nello squilibrio ionico culminando nella morte cellulare. L’entità del danno non deriva solo dall’insulto ischemico ma anche dai successivi fenomeni deleteri stimolati dal ripristino del flusso sanguigno e dei livelli di ossigeno. Lo squilibrio metabolico cerebrale induce l’utilizzo di fonti energetiche alternative come il glutammato. Sebbene in passato il glutammato è sempre stato considerato neurotossico, recenti studi hanno evidenziato come il glutammato possa svolgere il ruolo di intermediario metabolico stimolando la sintesi di ATP e migliorando l’attività mitocondriale, grazie al ruolo essenziale svolto dallo scambiatore Na+ /Ca2+ (NCX) e dai trasportatori del glutammato Na+ dipendenti (EAATs). In particolare, il ruolo solto da NCX nella neuroprotezione indotta da glutammato è stato studiato utilizzando un modello in vitro di ischemia cerebrale, cellule di neuroblastoma umano SH-SY5Y differenziate sottoposte ad ipossia/reossigenazione (H/R). In questo modello il danno indotto da H/R determina un aumento della mortalità cellulare, una riduzione dei livelli intracellulari di ATP e un’alterazione dei livelli di Ca2+ intracellulare. L’aggiunta di glutammato all’inizio della fase di reossigenazione determina un parziale recupero del danno inducendo un significativo aumento dei livelli di ATP. Inoltre, l’aggiunta di glutammato recupera parzialmente la riduzione dell’attività reverse-mode di NCX indotto da H/R. La trasfezione con i siRNA diretti contro NCX1 ed EAAT3 bloccano gli effetti protettivi del glutammato, confermando il ruolo essenziale svolto da NCX ed EAAT3 in questo pathway. In conclusione, i risultati ottenuti mostrano un nuovo ruolo svolto dal glutammato come “fattore di sopravvivenza” nel miglioramento del danno indotto da ipossia/reossigenazione, e che l’interazione tra NCX1 ed EAAT3 è fondamentale per permettere al glutammato di esplicare la sua funzione neuroprotettiva.In brain ischemia, reduction of oxygen and substrates affects mitochondrial respiratory chain and aerobic metabolism culminating in ATP production impairment, ionic derangement and cell death. An exacerbation of the tissue damage frequently occurs during the restoration of blood flow and reoxygenation, giving rise to ischemia/reperfusion (I/R) injury. Energy dysfunction in cerebral metabolism may induce the utilization of alternative energy supplies, such as glutamate. Although glutamate has long been considered as a neurotoxin, it can also be used as a metabolic intermediate for the ATP synthesis thus improving mitochondrial activity. In this setting, both the Na+/Ca2+ exchanger (NCX) and the Na+ dependent Excitatory Amino Acid Transporters (EAATs) play a critical role. The aim of the present study is to investigate the role of NCX in the potential of glutamate to improve cell metabolism and survival of neuronal cells subjected to hypoxia/reoxygenation (H/R) injury. In SH-SY5Y neuroblastoma cells differentiated into neuron-like cells, H/R produced a significant cell damage, a drop of ATP cellular content and intracellular Ca2+ alterations. Exposure to glutamate at the onset of the reoxygenation phase induces an improvement of cell survival and a significant raise in intracellular ATP levels by stimulating mitochondrial oxidative phosphorylation. Furthermore, NCX reverse-mode is reduced in H/R cells and glutamate supplementation limits the H/R induced suppression of NCX activity. All the effects induced by glutamate exposure are lost when cells are transfected with small interfering RNA (siRNA) against NCX1 and EAAT3, suggesting that a functional interplay between these proteins is critically required for glutamate neuroprotection. Collectively, our results reveal the beneficial effect of glutamate in an in vitro model of H/R injury and focus on the essential role exerted by NCX1
sj-docx-1-cpx-10.1177_21677026221129279 – Supplemental material for Investigating Individual Variation Using Dynamic Structural Equation Modeling: A Tutorial With Tinnitus
No full textSupplemental material, sj-docx-1-cpx-10.1177_21677026221129279 for Investigating Individual Variation Using Dynamic Structural Equation Modeling: A Tutorial With Tinnitus by Thomas L. Rodebaugh, Marilyn L. Piccirillo, Madelyn R. Frumkin, Dorina Kallogjeri, Katherine M. Gerull and Jay F. Piccirillo in Clinical Psychological Science</p
BLOW-UP RESULTS FOR SOME NONLINEAR HYPERBOLIC PROBLEMS
No full textWe study the nonexistence of global solutions for equations and inequalities of the following type tt u≥ΔA(x,t,u) + B(x,t,u) on R+N+1 with nonlinearity on A and B of the form A(x,t,u) = ρ1(x,t) |u|p , B(x,t,u) = ρ2 (x,t) |u|q. We also study the nonexistence for some more general inequalities of second-order but without any assumption about the type of operator. The method relies on a suitable choice of test functions, rescaling techniques and a dimensional analysis
Drinking water and biofilm as sources of antimicrobial re-sistance in free-range organic broiler farms.
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Drinking Water and Biofilm as Sources of Antimicrobial Resistance in Free-Range Organic Broiler Farms
by Alessandra Piccirillo
1,* [ORCID] , Roberta Tolosi
1, Lapo Mughini-Gras
2,3, Jannigje G. Kers
3 [ORCID] and Andrea Laconi
1 [ORCID]
1
Department of Comparative Biomedicine and Food Science, University of Padua, Viale dell’Università 16, 35020 Legnaro, Italy
2
Center for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), Antonie van Leeuwenhoeklaan 9, 3721 BA Bilthoven, The Netherlands
3
Faculty of Veterinary Medicine, Utrecht University, Yalelaan 2, De Uithof, 3584 CL Utrecht, The Netherlands
*
Author to whom correspondence should be addressed.
Antibiotics 2024, 13(9), 808; https://doi.org/10.3390/antibiotics13090808
Submission received: 14 June 2024 / Revised: 21 August 2024 / Accepted: 24 August 2024 / Published: 26 August 2024
(This article belongs to the Special Issue Molecular Mechanism of Antibiotic Resistance in Microbial Biofilms)
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Abstract
Drinking water distribution systems (DWDSs) represent an ideal environment for biofilm formation, which can harbor pathogenic and antimicrobial-resistant bacteria. This study aimed to assess longitudinally the microbial community composition and antimicrobial resistance (AMR), as determined by 16S rRNA NGS and qPCR, respectively, in drinking water (DW) and biofilm from DWDSs, as well as faeces, of free-range organic broiler farms. The role of DWDSs in AMR gene (ARG) dissemination within the farm environment and transmission to animals, was also assessed. DW and biofilm microbial communities differed from those of faecal samples. Moreover, potentially pathogenic and opportunistic bacteria (e.g., Staphylococcaceae) were identified in water and biofilms. High prevalence and abundance of ARGs conferring resistance to carbapenems (i.e., blaNDM), 3rd and 4th generation cephalosporins (i.e., blaCMY-2), (fluoro)quinolones (i.e., qnrS), and polymyxins (i.e., mcr-3 and mcr-5) were detected in DW, biofilm, and faecal samples, which is of concern for both animal and human health. Although other factors (e.g., feed, pests, and wildlife) may contribute to the dissemination of AMR in free-range organic poultry farms, this study indicates that DWDSs can also play a role
Chiral clusters in a supersonic beam: R2PI-TOF spectroscopy of diastereomeric carboxylic esters/(R)-(+)-1-phenyl-1-propanol complexes
No full textWavelength and mass resolved resonance-enhanced two photon ionization (R2PI) excitation spectra of (R)-(+)-1-phenyl-1-propanol (P-R) and its complexes with some chiral esters, i.e. methyl lactates (L-R and L-S), methyl 3-hydroxybutyrates (H-R and H-S), and methyl 2-chloropropionates (C-R and C-S), have been recorded after a supersonic molecular beam expansion and interpreted in the light of DFT calculations. The spectral features of the selected complexes were found to depend on the nature of hydrogen-bond interactions within the diasteromeric complexes, whose intensity in turn depends upon the structure and the configuration of the estereal moiety. The study further confirms resonant two-photon ionization spectroscopy, coupled with time-of-flight mass resolution (R2PI-TOF), as an excellent tool for gathering valuable information on the interactive forces in molecular clusters and for the enantiodiscrimination of chiral molecules in the gas phase
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