85 research outputs found

    The Palaeolithic Sites of Mitoc, on the Prut river (Romania)

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    editorial reviewedThe first Palaeolithic discoveries in Romania were made in the 19 th century in Mitoc (Botoșani department). Five main stations were excavated, yielding Middle and Upper Palaeolithic industries (including Aurignacian, Gravettian and Epipalaeolithic). Some have yielded mixed industries; others were better preserved and understood, like Malu Galben

    A mechanical G2 checkpoint controls epithelial cell division through E-cadherin-mediated regulation of Wee1-Cdk1

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    Epithelial cell divisions are coordinated with cell loss to preserve epithelial integrity. However, how epithelia adapt their rate of cell division to changes in cell number, for instance during homeostatic turnover or wounding, is not well understood. Here, we show that epithelial cells sense local cell density through mechanosensitive E-cadherin adhesions to control G2/M cell-cycle progression. As local cell density increases, tensile forces on E-cadherin adhesions are reduced, which prompts the accumulation of the G2 checkpoint kinase Wee1 and downstream inhibitory phosphorylation of Cdk1. Consequently, dense epithelia contain a pool of cells that are temporarily halted in G2 phase. These cells are readily triggered to divide following epithelial wounding due to the consequent increase in intercellular forces and resulting degradation of Wee1. Our data collectively show that epithelial cell division is controlled by a mechanical G2 checkpoint, which is regulated by cell-density-dependent intercellular forces sensed and transduced by E-cadherin adhesions.Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved

    Stress as a determinant of saliva-mediated adherence and coadherence of oral and nonoral microorganisms

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    Objective:: The mucosal secretory proteins, such as the salivary proteins, play a key role in the acquisition and regulation of the mucosal microflora. Most notably, some microorganisms utilize the host's secretory proteins to adhere to the mucosa; a first step in colonization and infection. The secretory proteins also influence colonization by affecting the binding among microorganisms, a process denoted as coadherence. Previously we reported that acute stressors cause specific changes in saliva composition. The present study investigated to what extent these changes influence saliva-mediated microbial adherence and coadherence (ex vivo). Methods:: Thirty-two male undergraduates provided unstimulated saliva before and during a control condition and two stressors: A memory test and a surgery video presentation. We used saliva-coated microplates to test the adherence of bacteria for which the oral cavity is either a natural reservoir (eg, viridans streptococci) or a portal of entry (eg, Helicobacter pylori). We also tested the saliva-mediated co-adherence between Streptococcus gordonii and the yeast Candida albicans. Correlation analyses were performed to determine the relationships between changes in microbial adherence and the concentrations of potential salivary ligands, viz. cystatin S, the mucins MUC5B and MUC7, S-IgA, lactoferrin, [alpha]-amylase, and total salivary protein. Results:: During the memory test, saliva-mediated adhesion of Streptococcus sanguis, Streptococcus gordonii, and H. pylori increased, whereas the coadherence of C. albicans with S. gordonii decreased. During the surgical video presentation the saliva-mediated adherence of H. pylori, S. sanguis, and Streptococcus mitis increased. These changes were independent of salivary flow rate, but correlated with specific changes in salivary protein composition. Conclusion:: The results show that even moderate stressors, by altering the activity of the mucosal secretory glands, may affect microbial colonization processes such as adherence and coadherence. This study hereby presents a mechanism by which stress may affect the mucosal microflora and susceptibility to infectious disease

    Virus-specific T<sub>RM</sub> cells of both donor and recipient origin reside in human kidney transplants

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    Tissue-resident lymphocytes (TRLs) are critical for local protection against viral pathogens in peripheral tissue. However, it is unclear if TRLs perform a similar role in transplanted organs under chronic immunosuppressed conditions. In this study, we aimed to characterize the TRL compartment in human kidney transplant nephrectomies and examine its potential role in antiviral immunity. The TRL compartment of kidney transplants contained diverse innate, innate-like, and adaptive TRL populations expressing the canonical residency markers CD69, CD103, and CD49a. Chimerism of donor and recipient cells was present in 43% of kidney transplants and occurred in all TRL subpopulations. Paired single-cell transcriptome and T cell receptor (TCR) sequencing showed that donor and recipient tissue–resident memory T (TRM) cells exhibit striking similarities in their transcriptomic profiles and share numerous TCR clonotypes predicted to target viral pathogens. Virus dextramer staining further confirmed that CD8 TRM cells of both donor and recipient origin express TCRs with specificities against common viruses, including CMV, EBV, BK polyomavirus, and influenza A. Overall, the study results demonstrate that a diverse population of TRLs resides in kidney transplants and offer compelling evidence that TRM cells of both donor and recipient origin reside within this TRL population and may contribute to local protection against viral pathogens.</p

    Гибридная интегральная схема для обработки звукового сигнала

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    Разработана гибридная интегральная схема с номинальным напряжением питания 1,4 В, током потребления 0,7 мА и габаритными размерами 8x4x3 мм для обработки звукового сигнала в автономной аппаратуре.Розроблена гібридна інтегральна схема з номінальною напругою живлення 1,4 В, струмом споживання 0,7 мА і габаритними розмірами 8x4x3 мм забезпечує багатофункціональну обробку звуковою сигналу в аналоговій мікроелектронній апаратурі. Наведено її конструкторсько-технологічні та електричні параметри.Developed hybrid integrated circuit with rated supply voltage of 1,4 V, current consumption 0,7 mA and overall dimensions 8x4x3 mm provides soft processing of the audio signal in analog microelectronic equipment. Given its design, technological and electrical parameters

    Guidelines on uncomplicated urinary tract infections are difficult to follow: perceived barriers and suggested interventions

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    Contains fulltext : 88451.pdf (publisher's version ) (Open Access)BACKGROUND: Urinary tract infections (UTI) are among the most common health problems seen in general practice. Evidence-based guidelines on UTI are available, but adherence to these guidelines varies widely among practitioners for reasons not well understood. The aim of this study was to identify the barriers to the implementation of a guideline on UTI perceived by Dutch general practitioners (GPs) and to explore interventions to overcome these barriers. METHODS: A focus group study, including 13 GPs working in general practices in the Netherlands, was conducted. Key recommendations on diagnosis and treatment of uncomplicated UTI were selected from the guideline. Barriers to guideline adherence and possible interventions to address these barriers were discussed. The focus group session was audio-taped and transcribed verbatim. Barriers were classified according to an existing framework. RESULTS: Lack of agreement with the recommendations, unavailable and inconvenient materials (i.e. dipslides), and organisational constraints were perceived as barriers for the diagnostic recommendations. Barriers to implementing the treatment recommendations were lack of applicability and organisational constraints related to the availability of drugs in pharmacies. Suggested interventions were to provide small group education to GPs and practice staff members, to improve organisation and coordination of care in out of hour services, to improve the availability of preferred dosages of drugs, and to pilot-test guidelines regionally. CONCLUSIONS: Despite sufficient knowledge of the recommendations on UTI, attitudinal and external barriers made it difficult to follow them in practice. The care concerning UTI could be optimized if these barriers are adequately addressed in implementation strategies. The feasibility and success of these strategies could be improved by involving the target group of the guideline in selecting useful interventions to address the barriers to implementation

    Serological response and breakthrough infection after COVID-19 vaccination in patients with cirrhosis and post-liver transplant

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    BACKGROUND: Vaccine hesitancy and lack of access remain major issues in disseminating COVID-19 vaccination to liver patients globally. Factors predicting poor response to vaccination and risk of breakthrough infection are important data to target booster vaccine programs. The primary aim of the current study was to measure humoral responses to 2 doses of COVID-19 vaccine. Secondary aims included the determination of factors predicting breakthrough infection. METHODS: COVID-19 vaccination and Biomarkers in cirrhosis And post-Liver Transplantation is a prospective, multicenter, observational case-control study. Participants were recruited at 4-10 weeks following first and second vaccine doses in cirrhosis [n = 325; 94% messenger RNA (mRNA) and 6% viral vaccine], autoimmune liver disease (AILD) (n = 120; 77% mRNA and 23% viral vaccine), post-liver transplant (LT) (n = 146; 96% mRNA and 3% viral vaccine), and healthy controls (n = 51; 72% mRNA, 24% viral and 4% heterologous combination). Serological end points were measured, and data regarding breakthrough SARS-CoV-2 infection were collected. RESULTS: After adjusting by age, sex, and time of sample collection, anti-Spike IgG levels were the lowest in post-LT patients compared to cirrhosis (p < 0.0001), AILD (p < 0.0001), and control (p = 0.002). Factors predicting reduced responses included older age, Child-Turcotte-Pugh B/C, and elevated IL-6 in cirrhosis; non-mRNA vaccine in AILD; and coronary artery disease, use of mycophenolate and dysregulated B-call activating factor, and lymphotoxin-α levels in LT. Incident infection occurred in 6.6%, 10.6%, 7.4%, and 15.6% of cirrhosis, AILD, post-LT, and control, respectively. The only independent factor predicting infection in cirrhosis was low albumin level. CONCLUSIONS: LT patients present the lowest response to the SARS-CoV-2 vaccine. In cirrhosis, the reduced response is associated with older age, stage of liver disease and systemic inflammation, and breakthrough infection with low albumin level
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