314 research outputs found

    Feeling the heat: The campylobacter jejuni HrcA transcriptional repressor is an intrinsic protein thermosensor

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    The heat-shock response, a universal protective mechanism consisting of a transcriptional reprogramming of the cellular transcriptome, results in the accumulation of proteins which coun-teract the deleterious effects of heat-stress on cellular polypeptides. To quickly respond to thermal stress and trigger the heat-shock response, bacteria rely on different mechanisms to detect temperature variations, which can involve nearly all classes of biological molecules. In Campylobacter jejuni the response to heat-shock is transcriptionally controlled by a regulatory circuit involving two re-pressors, HspR and HrcA. In the present work we show that the heat-shock repressor HrcA acts as an intrinsic protein thermometer. We report that a temperature upshift up to 42°C negatively affects HrcA DNA-binding activity to a target promoter, a condition required for de-repression of regu-lated genes. Furthermore, we show that this impairment of HrcA binding at 42°C is irreversible in vitro, as DNA-binding was still not restored by reversing the incubation temperature to 37°C. On the other hand, we demonstrate that the DNA-binding activity of HspR, which controls, in combi-nation with HrcA, the transcription of chaperones’ genes, is unaffected by heat-stress up to 45°C, portraying this master repressor as a rather stable protein. Additionally, we show that HrcA binding activity is enhanced by the chaperonin GroE, upon direct protein–protein interaction. In conclu-sion, the results presented in this work establish HrcA as a novel example of intrinsic heat-sensing transcriptional regulator, whose DNA-binding activity is positively modulated by the GroE chap-eronin

    Hematological parameters in subadult female dolphins (Grampus griseus)

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    The purpose of this study is to identify CBC Reference Intervals on Risso’s dolphins. There is no database of blood parameters in cetacean species and the correct evaluation is fundamental to interpret any pathological variations. In three years, 818 blood samples were collected from 9 pre-pubertal females hosted under human care during clinical routine checks. Blood was obtained from periarterial venous rete in ventral side of the flukes and then placed in EDTA tubes. The Complete Blood Count (CBC) parameters were considered and are going to be reported as mean ± sd (MIN; MAX). Studies on CBC parameters for dolphins are rare and obsolete. This is the first study carried out on a large number of samples of Risso's dolphins, which differ in feeding habits and in some ethological aspects from the other genera of the family. This is a preliminary research for future studies related to the difference for sex and age

    Paradigm Shift in Gastric Cancer Prevention: Harnessing the Potential of Aristolochia olivieri Extract

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    Gastric cancer, particularly adenocarcinoma, is a significant global health concern. Environmental risk factors, such as Helicobacter pylori infection and diet, play a role in its development. This study aimed to characterize the chemical composition and evaluate the in vitro antibacterial and antitumor activities of an Aristolochia olivieri Colleg. ex Boiss. Leaves’ methanolic extract (AOME). Additionally, morphological changes in gastric cancer cell lines were analyzed. AOME was analyzed using HPLC-MS/MS, and its antibacterial activity against H. pylori was assessed using the broth microdilution method. MIC and MBC values were determined, and positive and negative controls were included in the evaluation. Anticancer effects were assessed through in vitro experiments using AGS, KATO-III, and SNU-1 cancer cell lines. The morphological changes were examined through SEM and TEM analyses. AOME contained several compounds, including caffeic acid, rutin, and hyperoside. The extract displayed significant antimicrobial effects against H. pylori, with consistent MIC and MBC values of 3.70 ± 0.09 mg/mL. AOME reduced cell viability in all gastric cancer cells in a dose- and time-dependent manner. Morphological analyses revealed significant ultrastructural changes in all tumor cell lines, suggesting the occurrence of cellular apoptosis. This study demonstrated that AOME possesses antimicrobial activity against H. pylori and potent antineoplastic properties in gastric cancer cell lines. AOME holds promise as a natural resource for innovative nutraceutical approaches in gastric cancer management. Further research and in vivo studies are warranted to validate its potential clinical applications

    Circulating miR-184 is a potential predictive biomarker of cardiac damage in Anderson–Fabry disease

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    open21noFunding: This work was supported by the Italian Ministry of Health (PE-2013-02356818) to GCEnzyme replacement therapy (ERT) is a mainstay of treatment for Anderson–Fabry disease (AFD), a pathology with negative effects on the heart and kidneys. However, no reliable biomarkers are available to monitor its efficacy. Therefore, we tested a panel of four microRNAs linked with cardiac and renal damage in order to identify a novel biomarker associated with AFD and modulated by ERT. To this end, 60 patients with a definite diagnosis of AFD and on chronic ERT, and 29 age- and sex-matched healthy individuals, were enrolled by two Italian university hospitals. Only miR-184 met both conditions: its level discriminated untreated AFD patients from healthy individuals (c-statistic = 0.7522), and it was upregulated upon ERT (P < 0.001). On multivariable analysis, miR-184 was independently and inversely associated with a higher risk of cardiac damage (odds ratio = 0.86; 95% confidence interval [CI] = 0.76–0.98; P = 0.026). Adding miR-184 to a comprehensive clinical model improved the prediction of cardiac damage in terms of global model fit, calibration, discrimination, and classification accuracy (continuous net reclassification improvement = 0.917, P < 0.001; integrated discrimination improvement [IDI] = 0.105, P = 0.017; relative IDI = 0.221, 95% CI = 0.002–0.356). Thus, miR-184 is a circulating biomarker of AFD that changes after ERT. Assessment of its level in plasma could be clinically valuable in improving the prediction of cardiac damage in AFD patients.openSalamon I.; Biagini E.; Kunderfranco P.; Roncarati R.; Ferracin M.; Taglieri N.; Nardi E.; Laprovitera N.; Tomasi L.; Santostefano M.; Ditaranto R.; Vitale G.; Cavarretta E.; Pisani A.; Riccio E.; Aiello V.; Capelli I.; La Manna G.; Galie N.; Spinelli L.; Condorelli G.Salamon I.; Biagini E.; Kunderfranco P.; Roncarati R.; Ferracin M.; Taglieri N.; Nardi E.; Laprovitera N.; Tomasi L.; Santostefano M.; Ditaranto R.; Vitale G.; Cavarretta E.; Pisani A.; Riccio E.; Aiello V.; Capelli I.; La Manna G.; Galie N.; Spinelli L.; Condorelli G
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