Search results for "chemical compounds"
showing 10 items of 90 documents
Manipulating mtDNA in vivo reprograms metabolism via novel response mechanisms.
2019
Mitochondria have been increasingly recognized as a central regulatory nexus for multiple metabolic pathways, in addition to ATP production via oxidative phosphorylation (OXPHOS). Here we show that inducing mitochondrial DNA (mtDNA) stress in Drosophila using a mitochondrially-targeted Type I restriction endonuclease (mtEcoBI) results in unexpected metabolic reprogramming in adult flies, distinct from effects on OXPHOS. Carbohydrate utilization was repressed, with catabolism shifted towards lipid oxidation, accompanied by elevated serine synthesis. Cleavage and translocation, the two modes of mtEcoBI action, repressed carbohydrate rmetabolism via two different mechanisms. DNA cleavage activ…
Robust Conditional Independence maps of single-voxel Magnetic Resonance Spectra to elucidate associations between brain tumours and metabolites.
2020
The aim of the paper is two-fold. First, we show that structure finding with the PC algorithm can be inherently unstable and requires further operational constraints in order to consistently obtain models that are faithful to the data. We propose a methodology to stabilise the structure finding process, minimising both false positive and false negative error rates. This is demonstrated with synthetic data. Second, to apply the proposed structure finding methodology to a data set comprising single-voxel Magnetic Resonance Spectra of normal brain and three classes of brain tumours, to elucidate the associations between brain tumour types and a range of observed metabolites that are known to b…
In Candida parapsilosis the ATC1 Gene Encodes for an Acid Trehalase Involved in Trehalose Hydrolysis, Stress Resistance and Virulence
2014
An ORF named CPAR2-208980 on contig 005809 was identified by screening a Candida parapsilosis genome data base. Its 67% identity with the acid trehalase sequence from C. albicans (ATC1) led us to designate it CpATC1. Homozygous mutants that lack acid trehalase activity were constructed by gene disruption at the two CpATC1 chromosomal alleles. Phenotypic characterization showed that atc1Δ null cells were unable to grow on exogenous trehalose as carbon source, and also displayed higher resistance to environmental challenges, such as saline exposure (1.2 M NaCl), heat shock (42°C) and both mild and severe oxidative stress (5 and 50 mM H2O2). Significant amounts of intracellular trehalose were …
Rational Design of a Carrier Protein for the Production of Recombinant Toxic Peptides in Escherichia coli
2016
Commercial uses of bioactive peptides require low cost, effective methods for their production. We developed a new carrier protein for high yield production of recombinant peptides in Escherichia coli very well suited for the production of toxic peptides like antimicrobial peptides. GKY20, a short antimicrobial peptide derived from the C-terminus of human thrombin, was fused to the C-terminus of Onconase, a small ribonuclease (104 amino acids), which efficiently drove the peptide into inclusion bodies with very high expression levels (about 200-250 mg/L). After purification of the fusion protein by immobilized metal ion affinity chromatography, peptide was obtained by chemical cleavage in d…
Geosphere-biosphere interactions in bio-activity volcanic lakes: Evidences from Hule and Rìo Cuarto (Costa Rica)
2014
Hule and R ́ıo Cuarto are maar lakes located 11 and 18 km N of Poa ́s volcano along a 27 km long fracture zone, in the Central Volcanic Range of Costa Rica. Both lakes are characterized by a stable thermic and chemical stratification and recently they were affected by fish killing events likely related to the uprising of deep anoxic waters to the surface caused by rollover phenomena. The vertical profiles of temperature, pH, redox potential, chemical and isotopic compositions of water and dissolved gases, as well as prokaryotic diversity estimated by DNA fingerprinting and massive 16S rRNA pyrosequencing along the water column of the two lakes, have highlighted that different bio-geochemica…
In silico identification and experimental validation of hits active against KPC-2 β-lactamase
2018
Bacterial resistance has become a worldwide concern, particularly after the emergence of resistant strains overproducing carbapenemases. Among these, the KPC-2 carbapenemase represents a significant clinical challenge, being characterized by a broad substrate spectrum that includes aminothiazoleoxime and cephalosporins such as cefotaxime. Moreover, strains harboring KPC-type β-lactamases are often reported as resistant to available β-lactamase inhibitors (clavulanic acid, tazobactam and sulbactam). Therefore, the identification of novel non β-lactam KPC-2 inhibitors is strongly necessary to maintain treatment options. This study explored novel, non-covalent inhibitors active against KPC-2, …
Improvement of ALT decay kinetics by all-oral HCV treatment: Role of NS5A inhibitors and differences with IFN-based regimens
2017
Background Intracellular HCV-RNA reduction is a proposed mechanism of action of direct-acting antivirals (DAAs), alternative to hepatocytes elimination by pegylated-interferon plus ribavirin (PR). We modeled ALT and HCV-RNA kinetics in cirrhotic patients treated with currently-used all-DAA combinations to evaluate their mode of action and cytotoxicity compared with telaprevir (TVR)+PR. Study design Mathematical modeling of ALT and HCV-RNA kinetics was performed in 111 HCV-1 cirrhotic patients, 81 treated with all-DAA regimens and 30 with TVR+PR. Kinetic-models and Cox-analysis were used to assess determinants of ALT-decay and normalization. Results HCV-RNA kinetics was biphasic, reflecting …
Characterization of a fractured basement reservoir using high-resolution 3D seismic and logging datasets: A case study of the Sab'atayn Basin, Yemen.
2018
The Sab'atayn Basin is one of the most prolific Mesozoic hydrocarbon basins located in central Yemen. It has many oil producing fields including the Habban Field with oil occurrences in fractured basement rocks. A comprehensive seismic analysis of fractured basement reservoirs was performed to identify the structural pattern and mechanism of hydrocarbon entrapment and reservoir characteristics. A 3D post-stack time migration seismic cube and logging data of 20 wells were used and several 2D seismic sections were constructed and interpreted. Depth structure maps were generated for the basement reservoir and overlying formations. The top of the basement reservoir is dissected by a set of NW-S…
Hsp60 chaperonopathies and chaperonotherapy: targets and agents
2014
Hsp60 (Cpn60) assembles into a tetradecamer that interacts with the co-chaperonin Hsp10 (Cpn10) to assist client polypeptides to fold, but it also has other roles, including participation in pathogenic mechanisms.Hsp60 chaperonopathies are pathological conditions, inherited or acquired, in which the chaperone plays a determinant etiologic-pathogenic role. These diseases justify selection of Hsp60 as a target for developing agents that interfere with its pathogenic effects. We provide information on how to proceed.The information available encourages the development of ways to improve Hsp60 activity (positive chaperonotherapy) when deficient or to block it (negative chaperonotherapy) when pa…
Essential oil of Cyphostemma juttae (Vitaceae): Chemical composition and antitumor mechanism in triple negative breast cancer cells
2019
The genus Cyphostemma (Planch.) Alston (Vitaceae) includes about 150 species distrib- uted in eastern and southern Africa and Madagascar. Some species are used in traditional medicine and their biological activities, including antiproliferative effects against cancer cell lines, have been demonstrated. To date no investigations on Cyphostemma essential oils have been carried out. Essential oils, which play important roles in plant defenses have been demonstrated to be active in the treatment of several human diseases and to enhance bioavability of other drugs. The aim of this paper was to identify the chemical composition of the essential oil of the leaves of Cyphostemma juttae (Dinter &…