Search results for "SoMe"
showing 10 items of 5114 documents
Conformational Isomerism in Drug Action: Does the Free Energy of Binding Induce the Pharmacophoric Conformation of Semi-Rigid Muscarinic Agonists?
1974
The physiological neurotransmitter Acetylcholine has been shown to have great molecular flexibility, and because of this, the possibility of forming numerous energetically different conformations. This property makes the determination of the biologically active conformation extremely complicated. In attempts to solve this problem various research groups have tried two basically different approaches: (1) (1) The determination of the energetically most stable conformation using crystallographic methods (X-ray diffraction studies), nuclear magnetic resonance and quantum-mechanical calculations [1–16]. Same workers hypothesized that the energetically most favourable form was also the biological…
Mboat7 down-regulation by hyper-insulinemia induces fat accumulation in hepatocytes.
2020
Background: Naturally occurring variation in Membrane-bound O-acyltransferase domain-containing 7 (MBOAT7), encoding for an enzyme involved in phosphatidylinositol acyl-chain remodelling, has been associated with fatty liver and hepatic disorders. Here, we examined the relationship between hepatic Mboat7 down-regulation and fat accumulation. Methods: Hepatic MBOAT7 expression was surveyed in 119 obese individuals and in experimental models. MBOAT7 was acutely silenced by antisense oligonucleotides in C57Bl/6 mice, and by CRISPR/Cas9 in HepG2 hepatocytes. Findings: In obese individuals, hepatic MBOAT7 mRNA decreased from normal liver to steatohepatitis, independently of diabetes, inflammatio…
Enantioresolution in electrokinetic chromatography-complete filling technique using sulfated gamma-cyclodextrin. Software-free topological anticipati…
2016
Few papers have tried to predict the resolution ability of chiral selectors in capillary electrophoresis for the separation of the enantiomers of chiral compounds. In a previous work, we have used molecular information available on-line to establish enantioresolution levels of basic compounds using highly sulfated β-CD (HS-β-CD) as chiral selector in electrokinetic chromatography-complete filling technique (EKC-CFT). The present study is a continuation of this previous work, introducing some novelties. In this work, the ability of sulfated γ-cyclodextrin (S-γ-CD) as chiral selector in EKC-CFT is modelled for the first time. Thirty-three structurally unrelated cationic and neutral compounds …
Optimization of a LC method for the enantioseparation of a non-competitive glutamate receptor antagonist, by experimental design methodology
2006
Abstract The aim of this work was to obtain the direct optical resolution of a new glutamate receptor antagonist (( p -chloro)1-aryl-6,7,-dimethoxy-1,2,3,4-tetrahydroisoquinoline, PS3), by liquid chromatography on Chiralcel ® OD column. A response surface methodology (RSM) was employed to optimize the enantiomeric separation of the racemate with the lowest number of experiments; in particular, a face-centred design (FCD) was applied to evaluate the influence of critical parameters on the experimental response. Furthermore, in order to find the best compromise between several responses, a multicriteria decision-making approach, the Derringer's desirability function, was successful to simulta…
Potential of human serum albumin as chiral selector of basic drugs in affinity electrokinetic chromatography-partial filling technique
2006
The enantiomeric resolution of compounds using HSA by means of affinity EKC (AEKC)-partial filling technique is the result of a delicate balance between different experimental variables such as protein concentration, running pH (background electrophoretic buffer (BGE), protein, and compound solutions), and plug length. In this paper, the possibility of using HSA as chiral selector for enantioseparation of 28 basic drugs using this methodology is studied. The effect of the physicochemical parameters, the structural properties of compounds, and compound-HSA protein binding percentages over their chiral resolution with HSA is outlined. Based on the results obtained, a decision tree is proposed…
Comparative modelling study on enantioresolution of structurally unrelated compounds with amylose-based chiral stationary phases in reversed phase li…
2020
[EN] Polysaccharide-based chiral stationary phases (CSPs) are the most used chiral selectors in HPLC. These CSPs can be used in normal, polar organic and aqueous-organic mobile phases. However, normal and polar organic mobile phases are not adequate for chiral separation of polar compounds, for the analysis of aqueous samples and for MS detection. In these situations, reversed phase conditions, without the usual non-volatile additives incompatible with MS detection, are preferable. Moreover, in most of the reported chiral chromatographic methods, retention is too large for routine work. In this paper, the chiral separation of 53 structurally unrelated compounds is studied using three commer…
The peroxisome proliferator response element (PPRE) present at positions -681/-669 in the rat liver 3-ketoacyl-CoA thiolase B gene functionally inter…
2000
Although previous data showed that the putative thiolase B PPRE located at -681/-669 bind the PPARalpha-RXRalpha heterodimer in vitro (Kliewer et al. (1992) Nature 358, 771-774), there is no evidence about the functional role of this element. By gel mobility-shift assay, we found an interaction of this PPRE with not only PPARalpha but also with HNF-4. By transfection of cells with the putative PPRE-driven luciferase reporter vector and PPARalpha, we found no significant activation of the luciferase gene expression, in contrast to the case with reporter expression driven by the PPRE of the peroxisomal bifunctional enzyme. On the other hand, HNF-4 activated the luciferase gene expression driv…
The four murine peroxisomal ABC-transporter genes differ in constitutive, inducible and developmental expression.
1999
Four ATP-binding cassette (ABC) half-transporters have been identified in mammalian peroxisomes: adrenoleukodystrophy protein (ALDP), adrenoleukodystrophy-related protein (ALDRP), 70-kDa peroxisomal membrane protein (PMP70) and PMP70-related protein (P70R). Inherited defects in ALDP cause the neurodegenerative disorder X-linked adrenoleukodystrophy (X-ALD). By comparative Northern blot analyses we found each of the four murine peroxisomal ABC transporter mRNA species at maximum abundance only in a few tissues, which differed for each family member. The four genes were also regulated differentially during mouse brain development: ALDP mRNA was most abundant in embryonic brain and gradually d…
In situ localization of the Antennapedia gene on the chromosomes of nine Drosophila species of the obscura group.
2008
The homeotic Antennapedia gene, cloned from the genomic DNA of D. subobscura, was localized on the polytene chromosomes of nine species of the Drosophila obscura group. In all of them, the probe used hybridized on chromosomes equivalent to the E element of Muller's terminology. These results are consistent with the idea that single copy genes do not move around the genome and that chromosomal elements have conserved their genetic identity during evolution.
Human NCL Neuropathology
2015
AbstractThe neuronal ceroid lipofuscinoses (NCL) currently encompass fourteen genetically different forms, CLN1 to CLN14, but are all morphologically marked by loss of nerve cells, particularly in the cerebral and cerebellar cortices, and the cerebral and extracerebral formation of lipopigments. These lipopigments show distinct ultrastructural patterns, i.e., granular, curvilinear/rectilinear and fingerprint profiles. They contain−although to a different degree among the different CLN forms−subunit C of ATP synthase, saposins A and D, and beta-amyloid proteins. Extracerebral pathology, apart from lipopigment formation, which provides diagnostic information, is scant or non-existent. The ret…