Search results for "Synthesis"

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 …

Assessing the Contribution of Relative Macrophage Frequencies to Subcutaneous Adipose Tissue

2021

Background: Macrophages play an important role in regulating adipose tissue function, while their frequencies in adipose tissue vary between individuals. Adipose tissue infiltration by high frequencies of macrophages has been linked to changes in adipokine levels and low-grade inflammation, frequently associated with the progression of obesity. The objective of this project was to assess the contribution of relative macrophage frequencies to the overall subcutaneous adipose tissue gene expression using publicly available datasets.Methods: Seven publicly available microarray gene expression datasets from human subcutaneous adipose tissue biopsies (n = 519) were used together with TissueDecod…

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…

Exercise and Conjugated Linoleic Acid Supplementation Induce Changes in the Composition of Liver Fatty Acids

2019

Exercise and supplementation with conjugated linoleic acid (CLA) are used to reduce body weight and to improve health. Applied together, they may exert a synergistic effect. However, the effects of exercise and CLA supplementation on liver metabolism are poorly understood. The aim of this study was to examine the influence of exercise and CLA supplementation on fatty acids (FA) composition in mouse liver. We analyzed 44 of known FAs of this organ by gas chromatography-mass spectrometry. Our results demonstrated that exercise contributed to a decrease in odd-chain FA and an increase in n-6 polyunsaturated FA contents. In turn, CLA stimulated an increase in branched-chain FAs and n-3 polyunsa…

X-linked protoporphyria: Iron supplementation improves protoporphyrin overload, liver damage and anaemia

2015

Role of Redox Signaling and Inflammation in Skeletal Muscle Adaptations to Training

2016

The inflammatory response to exercise-induced muscle damage has been extensively described. Exercise has important modulatory effects on immune function. These effects are mediated by diverse factors including pro-inflammatory cytokines, classical stress hormones, and hemodynamic effects leading to cell redistribution. As has been reported regarding oxidative stress, inflammation can have both detrimental and beneficial effects in skeletal muscle. In this review we will address the role of inflammation on protein metabolism in skeletal muscle. Specifically, we will review studies showing that treatment with cyclooxygenase-inhibiting drugs modulate the protein synthesis response to one bout …

Insulin Dissociates the Effects of Liver X Receptor on Lipogenesis, Endoplasmic Reticulum Stress, and Inflammation

2016

IF 4.258; International audience; Diabetes is characterized by increased lipogenesis as well as increased endoplasmic reticulum (ER) stress and inflammation. The nuclear hormone receptor liver X receptor (LXR) is induced by insulin and is a key regulator of lipid metabolism. It promotes lipogenesis and cholesterol efflux, but suppresses endoplasmic reticulum stress and inflammation. The goal of these studies was to dissect the effects of insulin on LXR action. We used antisense oligonucleotides to knock down Lxr alpha in mice with hepatocytespecific deletion of the insulin receptor and their controls. We found, surprisingly, that knock-out of the insulin receptor and knockdown of Lxr alpha …

The genomic sequence of Exiguobacterium chiriqhucha str. N139 reveals a species that thrives in cold waters and extreme environmental conditions

2017

We report the genome sequence of Exiguobacterium chiriqhucha str. N139, isolated from a high-altitude Andean lake. Comparative genomic analyses of the Exiguobacterium genomes available suggest that our strain belongs to the same species as the previously reported E. pavilionensis str. RW-2 and Exiguobacterium str. GIC 31. We describe this species and propose the chiriqhucha name to group them. ‘Chiri qhucha’ in Quechua means ‘cold lake’, which is a common origin of these three cosmopolitan Exiguobacteria. The 2,952,588-bp E. chiriqhucha str. N139 genome contains one chromosome and three megaplasmids. The genome analysis of the Andean strain suggests the presence of enzymes that confer E. ch…

Ataluren for the Treatment of Usher Syndrome 2A Caused by Nonsense Mutations

2019

The identification of genetic defects that underlie inherited retinal diseases (IRDs) paves the way for the development of therapeutic strategies. Nonsense mutations caused approximately 12% of all IRD cases, resulting in a premature termination codon (PTC). Therefore, an approach that targets nonsense mutations could be a promising pharmacogenetic strategy for the treatment of IRDs. Small molecules (translational read-through inducing drugs