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Contribution of Apaf-1 for the pathogenesis associated with cancers as well as neurodegenerative conditions.
In the century since the notion of the 'engram' was first introduced to describe the physical manifestation of memory, new technologies for identifying cellular activity have enabled us to deepen our understanding of the possible physical substrate of memory. A number of studies have shown that memories are stored in a sparse population of neurons known as a neural ensemble or engram cells. While earlier investigations highlighted that the stability of neural ensembles underlies a memory representation, recent studies have found that neural ensembles are more dynamic and fluid than previously understood. Additionally, a number of studies have begun to dissect the cellular and molecular diversity of functionally distinct subpopulations of cells contained within an engram. We propose that ensemble fluidity and compositional heterogeneity support memory flexibility and functional diversity.
Primary ciliary dyskinesia (PCD) is a rare genetic disease arising from motile ciliary dysfunction and associated with recurrent and chronic upper and lower respiratory tract infections. Pediatric otolaryngologists may see these patients prior to the development of lung disease. Features of PCD may overlap with other suppurative respiratory diseases, creating diagnostic challenges. A simple screening tool would be beneficial to identify potential patients who have chronic upper respiratory tract disease requiring further specialist evaluation.

To test a simple screening tool consisting of four questions to detect PCD in children with chronic otitis media and chronic rhinosinusitis seen in a tertiary otolaryngology clinic.

A prospective, single site, observational study in a tertiary care pediatric otolaryngology clinic. Children aged 3-17 years diagnosed with chronic otitis media or rhinosinusitis with onset at less than 2 years of age were recruited. All study subjects had at least one of four key clin. Four referrals were made for further evaluation on the basis of clinical symptoms and nasal nitric oxide results. While no new cases of PCD were detected, a subject and his sibling with recurrent sinopulmonary infections were referred for immunologic evaluation.

The use of standardized screening questions can be used in an otolaryngology clinic to identify patients who require further evaluation for PCD or primary immunodeficiency.
The use of standardized screening questions can be used in an otolaryngology clinic to identify patients who require further evaluation for PCD or primary immunodeficiency.Differences in the rhamnolipid structures must result in its different activities, thus affecting its application effect. The rhlC gene in Pseudomonas aeruginosa SG was knocked out to construct strain P. aeruginosa SGΔrhlC. Rhamnolipid production was enhanced by 23.3% through knocking out rhlC gene. P. aeruginosa SGΔrhlC produced 14.22 g/L of rhamnolipid using glycerol and nitrate. Five kinds of mono-rhamnolipid but no di-rhamnolipid were produced by strain SGΔrhlC. The main rhamnolipid homologues were Rha-C10-C10, Rha-C10-C121 and Rha-C10-C12. Mono-rhamnolipid exhibited better antimicrobial activity to Escherichia coli, Staphylococcus aureus, Aspergillus niger and Penicillium chrysogenum. Rhamnolipid produced from strain SGΔrhlC showed greater emulsifying activity to crude oil with EI24 of 84.73%. Rhamnolipid produced from strain SGΔrhlC efficiently washed oily sludge at 35 °C. High-producing strain P. aeruginosa SGΔrhlC and its produced mono-rhamnolipid are more promising in agriculture and petroleum industry. This study is a step forward to the tailor-made biosynthesis and application of rhamnolipid.The effects of binary and ternary trace elements (TEs) (Fe/Co, Fe/Ni, and Fe/Co/Ni) on the anaerobic digestion (AD) of cattle manure were investigated using kinetic models (first-order, logistic, modified Gompertz, and Coats-Redfern) and experimental measurements. Binary and ternary TEs can significantly improve the biogas production rate and yield potential. The deviation between the predicted and measured data for biogas yield with logistic model (2.1%-5.3%) and modified Gompertz model (0.32%-2.9%) was smaller than that with first-order kinetic model (6.9%-9.9%). The Coats-Redfern model fitting indicated that the activation energy of digestates with trace elements during pyrolysis was reduced by 3.9%-26.2% compared with the control group. Meanwhile, digestates with TEs showed remarkable fertility (5.72%-5.95%). The combination of kinetic models and experimental measurements can effectively quantify the effect of TEs on AD performance and provide an informed choice for industrial production.UV irradiation exposure may induce photoaging of the skin tissue. Various plant extracts have been recognized as effective protectants against UV-induced damage. Here, a mixture of marigold and rosemary extracts was evaluated for its anti-photoaging effects as a potential nutraceutical product for skin health. Hexane extract of marigold and ethanolic extract of rosemary were prepared, and the formulated mixture was investigated. A UV-induced photoaged mouse model was prepared, and the protective effects of the extract mixture were compared with those of hyaluronic acid (positive control). Expression of various photoaging-related biomarkers such as matrix metalloproteinases (MMPs), interleukins, tumor necrosis factor-alpha, procollagen type I, 8-hydroxy-deoxyguanosine, superoxide dismutase, glutathione peroxidase, and catalase were determined. UV irradiation significantly enhanced the expression of these biomarkers through an inflammatory response, however, the mixture of marigold and rosemary extracts exerted inhibitory effects and protected from UV-induced damage. Suppression of inflammatory response were the mechanisms underlying this protective function of the mixture of marigold and rosemary extracts. Histological evaluation also supported these protective effects against photoaging.Outer membrane protein A (OmpA) of Acinetobacter baumannii (A. baumannii) is associated with autophagy, which plays an important role in its pathogenicity. However, its exact pathophysiological role in the process of lung tissue cell autophagy remains unclear. In this study, animal and cell infection models were established by wild A. baumannii strain and An OmpA knockout mutant (OmpA-/- A. baumannii) strain. The expression levels of markers autophagy, histological change, cell viability and protein expression levels of inflammatory cytokines were examined. find more OmpA-/-A. baumannii was successfully constructed. The capacities of bacterial adhesion and invasion to host cells increased more obviously in the AB group and the AB + Rapa group than in the OmpA-/- AB group and AB + CQ group. The AB group and AB + Rapa group could produce double membrane vacuoles, endoplasmic reticulum dilation, mitochondrial ridge rupture, and mitochondrial vacuoles. OmpA could lead to increased LC3, AMPK, and PAMPK protein release, and decreased levels of P62, mTOR and pmTOR proteins in vivo and in vitro. OmpA caused lung pathology and the release of inflammatory cytokines. A. baumannii OmpA promotes autophagy in lung cells through the mTOR signalling pathway, which increases the bacterial colonization ability in the double-layer membrane autophagosome formed by the autophagy reaction to escape the clearance of bacteria by the host, promote the release of inflammatory mediators and aggravate the damage to the host.Microbiota has a role in the host blood pressure (BP) regulation. The immunosuppressive drug mofetil mycophenolate (MMF) ameliorates hypertension. The present study analyzes whether MMF improves dysbiosis in a genetic model of hypertension. Twenty weeks old male spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY) were randomly divided into three groups untreated WKY, untreated SHR, and SHR treated with MMF for 5 weeks. MMF treatment restored gut bacteria from the phyla Firmicutes and Bacteroidetes, and acetate- and lactate-producing bacteria to levels similar to those found in WKY, increasing butyrate-producing bacteria. MMF increased the percentage of anaerobic bacteria in the gut. The improvement of gut dysbiosis was associated with an enhanced colonic integrity and a decreased sympathetic drive in the gut. MMF inhibited neuroinflammation in the paraventricular nuclei in the hypothalamus. MMF increased the lower regulatory T cells proportion in mesenteric lymph nodes and Th17 and Th1 infiltration in aorta, improved aortic endothelial function and reduced systolic BP. This study demonstrates for the first time that MMF reduces gut dysbiosis in SHR. This effect could be related to its capability to improve gut integrity due to reduced sympathetic drive in the gut associated to the reduced brain neuroinflammation.Leishmania infantum is the main cause of human visceral leishmaniasis (HVL; also known as kala-azar) in the Middle East and may be fatal if left untreated. This disease was first reported in 1949 in Iran. Despite marked improvements in hygiene and sanitation conditions, the disease is still endemic in some parts of Iran. It is difficult to determine the current prevalence of HVL in Iran due to the scarcity of comprehensive studies in this regard. In response to this gap, a systematic review and meta-analysis was conducted to gain better understanding of HVL epidemiology in the general population of Iran. English and Persian databases were searched for studies reporting the prevalence and risk factors associated with HVL in the Iranian people from January 1995 to December 2019. The reported data were selected according to inclusion and exclusion criteria. The pooled prevalence of HVL infection and its 95 % confidence intervals were calculated. Quality assessment, heterogeneity testing and publication bias assesesults showed a low seroprevalence of HVL infection. However, the lack of published reports of HVL in an area does not exclusively mean the absence of the disease or carrier. We therefore recommend further studies in this regard.The spread of antibiotic resistance within the ESKAPE group of human pathogenic bacteria poses severe challenges in the treatment of infections and maintenance of safe hospital environments. This motivates efforts to validate novel target proteins within these species that could be pursued as potential targets for antibiotic development. Genetic data suggest that the enzyme FabG, which is part of the bacterial fatty acid biosynthetic system FAS-II, is essential in several ESKAPE pathogens. FabG catalyzes the NADPH dependent reduction of 3-keto-acyl-ACP during fatty acid elongation, thus enabling lipid supply for production and maintenance of the cell envelope. Here we report on small-molecule screening on the FabG enzymes from A. baumannii and S. typhimurium to identify a set of µM inhibitors, with the most potent representative (1) demonstrating activity against six FabG-orthologues. A co-crystal structure with FabG from A. baumannii (PDB6T65) confirms inhibitor binding at an allosteric site located in the subunit interface, as previously demonstrated for other sub-µM inhibitors of FabG from P. aeruginosa. We show that inhibitor binding distorts the oligomerization interface in the FabG tetramer and displaces crucial residues involved in the interaction with the co-substrate NADPH. These observations suggest a conserved allosteric site across the FabG family, which can be potentially targeted for interference with fatty acid biosynthesis in clinically relevant ESKAPE pathogens.
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