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showing 10 items of 8115 documents
The swinholide biosynthesis gene cluster from a terrestrial cyanobacterium, Nostoc sp. strain UHCC 0450
2017
ABSTRACT Swinholides are 42-carbon ring polyketides with a 2-fold axis of symmetry. They are potent cytotoxins that disrupt the actin cytoskeleton. Swinholides were discovered from the marine sponge Theonella sp. and were long suspected to be produced by symbiotic bacteria. Misakinolide, a structural variant of swinholide, was recently demonstrated to be the product of a symbiotic heterotrophic proteobacterium. Here, we report the production of swinholide A by an axenic strain of the terrestrial cyanobacterium Nostoc sp. strain UHCC 0450. We located the 85-kb trans -AT polyketide synthase (PKS) swinholide biosynthesis gene cluster from a draft genome of Nostoc sp. UHCC 0450. The swinholide …
Strategies against nonsense: oxadiazoles as translational readthrough-inducing drugs (TRIDs)
2019
This review focuses on the use of oxadiazoles as translational readthrough-inducing drugs (TRIDs) to rescue the functional full-length protein expression in mendelian genetic diseases caused by nonsense mutations. These mutations in specific genes generate premature termination codons (PTCs) responsible for the translation of truncated proteins. After a brief introduction on nonsense mutations and their pathological effects, the features of various classes of TRIDs will be described discussing differences or similarities in their mechanisms of action. Strategies to correct the PTCs will be presented, particularly focusing on a new class of Ataluren-like oxadiazole derivatives in comparison …
A Two-Component regulatory system with opposite effects on glycopeptide antibiotic biosynthesis and resistance
2020
AbstractThe glycopeptide A40926, produced by the actinomycete Nonomuraea gerenzanensis, is the precursor of dalbavancin, a second-generation glycopeptide antibiotic approved for clinical use in the USA and Europe in 2014 and 2015, respectively. The final product of the biosynthetic pathway is an O-acetylated form of A40926 (acA40926). Glycopeptide biosynthesis in N. gerenzanensis is dependent upon the dbv gene cluster that encodes, in addition to the two essential positive regulators Dbv3 and Dbv4, the putative members of a two-component signal transduction system, specifically the response regulator Dbv6 and the sensor kinase Dbv22. The aim of this work was to assign a role to these two ge…
Unexpected Bacterial Origin of the Antibiotic Icosalide: Two-Tailed Depsipeptide Assembly in Multifarious Burkholderia Symbionts.
2018
Icosalide is an unusual two-tailed lipocyclopeptide antibiotic that was originally isolated from a fungal culture. Yet, its biosynthesis and ecological function have remained enigmatic. By genome mining and metabolic profiling of a bacterial endosymbiont ( Burkholderia gladioli) of the pest beetle Lagria villosa, we unveiled a bacterial origin of icosalide. Functional analysis of the biosynthetic gene locus revealed an unprecedented nonribosomal peptide synthetase (NRPS) that incorporates two β-hydroxy acids by means of two starter condensation domains in different modules. This unusual assembly line, which may inspire new synthetic biology approaches, is widespread among many symbiotic Bur…
Heat Shock Protein 60 Antibodies Are Associated With a Risk Factor for Cardiovascular Disease in Bedridden Elderly Patients
2020
Made available in DSpace on 2020-12-12T02:12:50Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-06-12 Frailty, in elderly people, represents multiple deficiencies in different organs and is characterized by decreased physiological reserves and greater vulnerability to stressors. Bedridden elderly, with cardiovascular disease (CVD), have a worse prognosis than non-bedridden patients. Heat-shock proteins (HSPs) are molecular chaperones that under physiological conditions facilitate the transport, folding and assembly of proteins. Serum HSP 60-kDa concentrations and their antibodies are increased, in response to non-physiological conditions, suggesting the involvement of HSPs and their …
Serum metabolites in non-alcoholic fatty-liver disease development or reversion; a targeted metabolomic approach within the PREDIMED trial
2017
Background Limited prospective studies have examined changes in non-alcoholic fatty-liver disease (NAFLD) related serum-metabolites and none the effects of NAFLD-reversion. We aimed to evaluate whether perturbations in metabolites indicate predisposition to NAFLD development and to assess the effects of NAFLD reversion on metabolite profiles. Methods A targeted liquid-chromatography tandem mass-spectrometry metabolic profiling (n = 453 metabolites) approach was applied, using serum from 45 subjects of the PREDIMED study, at baseline and after a median 3.8-year follow-up. NAFLD was determined using the hepatic steatosis index; with three groups classified and studied: Group 1, not characteri…
Blastocystis subtypes and their association with Irritable Bowel Syndrome.
2018
Blastocystis spp. is a common intestinal protozoan that affects humans and animals. The role of this parasite as a pathogen is still controversial and it is suspected to be linked to Irritable Bowel Syndrome (IBS), a functional bowel disorder characterized by chronic or recurrent abdominal pain associated with altered intestinal habits. A broad search in electronic databases, libraries, portals of journals, etc. for reports on the association between the parasite and IBS without language restriction was performed. The selection was not restricted by date, but articles published in the last seven years were given preference. We investigated the evidence regarding Blastocystis and IBS coexist…
Protective effect of quercetin on high-fat diet-induced non-alcoholic fatty liver disease in mice is mediated by modulating intestinal microbiota imb…
2016
Gut microbiota is involved in obesity, metabolic syndrome and the progression of nonalcoholic fatty liver disease (NAFLD). It has been recently suggested that the flavonoid quercetin may have the ability to modulate the intestinal microbiota composition, suggesting a prebiotic capacity which highlights a great therapeutic potential in NAFLD. The present study aims to investigate benefits of experimental treatment with quercetin on gut microbial balance and related gut-liver axis activation in a nutritional animal model of NAFLD associated to obesity. C57BL/6J mice were challenged with high fat diet (HFD) supplemented or not with quercetin for 16 weeks. HFD induced obesity, metabolic syndrom…
Pathways of care for HIV infected children in Beira, Mozambique: pre-post intervention study to assess impact of task shifting
2018
Abstract Background In 2013, Mozambique implemented task-shifting (TS) from clinical officers to maternal and child nurses to improve care for HIV positive children < 5 years old. A retrospective, pre-post intervention study was designed to evaluate effectiveness of a new pathway of care in a sample of Beira District Local Health Facilities (LHFs), the primary, local, community healthcare services. Methods The study was conducted by accessing registries of At Risk Children Clinics (ARCCs) and HIV Health Services. Two time periods, pre- and post-intervention, were compared using a set of endpoints. Variables distribution was explored using descriptive statistics. T-student, Mann Whitney and …
Metabolismo lipídico y clasificación de las hiperlipemias
2021
This chapter summarises, and updates, lipid metabolism. Both pathways, exogenous metabolisms route via the chylomicrons, and the endogenous pathway of very low-density lipoproteins (VLDL) and low-density lipoproteins (LDL). The reverse cholesterol metabolism will also be mentioned. It also includes the current classification of hyperlipidaemias or hyperlipoproteinaemias, with a reminder of the phenotype classification, and further developments of the aetiological classification. Both parts have updated references, with which knowledge of this vast subject can be expanded.