Search results for "RCU"
showing 10 items of 6516 documents
NOX2ko Mice Show Largely Increased Expression of a Mutated NOX2 mRNA Encoding an Inactive NOX2 Protein
2020
Background: The superoxide-generating enzyme nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX2 or gp91phox, the phagocytic isoform) was reported as a major source of oxidative stress in various human diseases. Genetic deletion is widely used to study the impact of NOX2-derived reactive oxygen species (ROS) on disease development and progression in various animal models. Here, we investigate why NOX2 knockout mice show no NOX2 activity but express NOX2 mRNA and protein. Methods and Results: Oxidative burst (NOX2-dependent formation of ROS) was measured by L-012-based chemiluminescence and was largely absent in whole blood of NOX2 knockout mice. Protein expression was still de…
DNA Damage Signaling Instructs Polyploid Macrophage Fate in Granulomas.
2018
Granulomas are immune cell aggregates formed in response to persistent inflammatory stimuli. Granuloma macrophage subsets are diverse and carry varying copy numbers of their genomic information. The molecular programs that control the differentiation of such macrophage populations in response to a chronic stimulus, though critical for disease outcome, have not been defined. Here, we delineate a macrophage differentiation pathway by which a persistent Toll-like receptor (TLR) 2 signal instructs polyploid macrophage fate by inducing replication stress and activating the DNA damage response. Polyploid granuloma-resident macrophages formed via modified cell divisions and mitotic defects and not…
First molecular detection of mycobacterium bovis in environmental samples from a French region with endemic bovine tuberculosis
2016
Aims The aim of the study was to determine the prevalence of Mycobacterium bovis (the causative agent of bovine tuberculosis, bTB) in environmental matrices within a French region (Cote d'Or) affected by this zoonotic disease. Methods and Results We report here the development and the use of molecular detection assays based on qPCR (double fluorescent dye labelled probe) to monitor the occurrence of Mycobacterium tuberculosis complex (MTBC) or M. bovis in environmental samples collected in pastures where infected cattle and wildlife had been reported. Three qPCR assays targeting members of the MTBC (IS1561’ and Rv3866 loci) or M. bovis (RD4 locus) were developed or refined from existing ass…
Diabetic microangiopathy: Pathogenetic insights and novel therapeutic approaches.
2017
Diabetic microangiopathy, including retinopathy, is characterized by abnormal growth and leakage of small blood vessels, resulting in local edema and functional impairment of the depending tissues. Mechanisms leading to the impairment of microcirculation in diabetes are multiple and still largely unclear. However, a dysregulated vascular regeneration appears to play a key role. In addition, oxidative and hyperosmolar stress, as well as the activation of inflammatory pathways triggered by advanced glycation end-products and toll-like receptors, have been recognized as key underlying events. Here, we review recent knowledge on cellular and molecular pathways of microvascular disease in diabet…
Genetic Diversity of O-Antigens in Hafnia alvei and the Development of a Suspension Array for Serotype Detection.
2016
Hafnia alvei is a facultative and rod-shaped gram-negative bacterium that belongs to the Enterobacteriaceae family. Although it has been more than 50 years since the genus was identified, very little is known about variations among Hafnia species. Diversity in O-antigens (O-polysaccharide, OPS) is thought to be a major factor in bacterial adaptation to different hosts and situations and variability in the environment. Antigenic variation is also an important factor in pathogenicity that has been used to define clones within a number of species. The genes that are required to synthesize OPS are always clustered within the bacterial chromosome. A serotyping scheme including 39 O-serotypes has…
Hg and Se exposure in brain tissues of striped dolphin (Stenella coeruleoalba) and bottlenose dolphin (Tursiops truncatus) from the Tyrrhenian and Ad…
2017
In this study we analyzed Hg and Se concentrations in dolphin brain tissues of fifteen specimens of striped dolphin (Stenella coeruleoalba) and eight specimens of bottlenose dolphin (Tursiops truncatus) stranded in the Tyrrhenian and Adriatic Seas, in order to assess the toxicological risks associated with Hg exposure. High Hg concentrations were found in brain tissues of both analyzed specie (1.86–243 mg/kg dw for striped dolphin and 2.1–98.7 mg/kg dw for bottlenose dolphin), exceeding levels associated with marine mammals neurotoxicity. Althougth the results clearly suggest that the protective effects of Se against Hg toxicity occur in cetaceans’ brain tissues, a molar excess of mercury w…
Deciphering Alzheimer’s Disease Pathogenic Pathway: Role of Chronic Brain Hypoperfusion on p-Tau and mTOR
2021
This review examines new biomolecular findings that lend support to the hemodynamic role played by chronic brain hypoperfusion (CBH) in driving a pathway to Alzheimer’s disease (AD). CBH is a common clinical feature of AD and the current topic of intense investigation in AD models. CBH is also the basis for the vascular hypothesis of AD which we originally proposed in 1993. New biomolecular findings reveal the interplay of CBH in increasing tau phosphorylation (p-Tau) in the hippocampus and cortex of AD mice, damaging fast axonal transport, increasing signaling of mammalian target of rapamycin (mTOR), impairing learning-memory function, and promoting the formation of neurofibrillary tangles…
High-Performance Biocomputing in Synthetic Biology-Integrated Transcriptional and Metabolic Circuits
2019
Biocomputing uses molecular biology parts as the hardware to implement computational devices. By following pre-defined rules, often hard-coded into biological systems, these devices are able to process inputs and return outputs-thus computing information. Key to the success of any biocomputing endeavor is the availability of a wealth of molecular tools and biological motifs from which functional devices can be assembled. Synthetic biology is a fabulous playground for such purpose, offering numerous genetic parts that allow for the rational engineering of genetic circuits that mimic the behavior of electronic functions, such as logic gates. A grand challenge, as far as biocomputing is concer…
Epigenetic IVD Tests for Personalized Precision Medicine in Cancer
2019
Epigenetic alterations play a key role in the initiation and progression of cancer. Therefore, it is possible to use epigenetic marks as biomarkers for predictive and precision medicine in cancer. Precision medicine is poised to impact clinical practice, patients, and healthcare systems. The objective of this review is to provide an overview of the epigenetic testing landscape in cancer by examining commercially available epigenetic-based in vitro diagnostic tests for colon, breast, cervical, glioblastoma, lung cancers, and for cancers of unknown origin. We compile current commercial epigenetic tests based on epigenetic biomarkers (i.e., DNA methylation, miRNAs, and histones) that can actua…
Linear-time sequence comparison using minimal absent words & applications
2016
Sequence comparison is a prerequisite to virtually all comparative genomic analyses. It is often realized by sequence alignment techniques, which are computationally expensive. This has led to increased research into alignment-free techniques, which are based on measures referring to the composition of sequences in terms of their constituent patterns. These measures, such as q-gram distance, are usually computed in time linear with respect to the length of the sequences. In this article, we focus on the complementary idea: how two sequences can be efficiently compared based on information that does not occur in the sequences. A word is an absent word of some sequence if it does not occur in…