Characterization of Luteinizing hormone-releasing hormone (LH-RH-I) receptor type I as a potential molecular target in OCM-1 and OCM-3 human uveal melanoma cell lines

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Factors shaping the composition of the cutaneous microbiota

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The structure of the complex of calmodulin with KAR-2: a novel mode of binding explains the unique pharmacology of the drug

3'-(beta- Chloroethyl)-2',4'-dioxo-3,5'-spiro-oxazolidino-4-deacetoxyvinblastine (KAR-2) is a potent anti-microtubular agent that arrests mitosis in cancer cells without significant toxic side effects. In this study we demonstrate that in addition to targeting microtubules, KAR-2 also binds calmodulin, thereby countering the antagonistic effects of trifluoperazine. To determine the basis of both properties of KAR-2, the three-dimensional structure of its complex with Ca2+-calmodulin has been characterized both in solution using NMR and when crystallized using x-ray diffraction. Heterocorrelation (H-1-N-15 heteronuclear single quantum coherence) spectra of N-15-labeled calmodulin indicate a global conformation change (closure) of the protein upon its binding to KAR-2. The crystal structure at 2.12-Angstrom resolution reveals a more complete picture; KAR-2 binds to a novel structure created by amino acid residues of both the N- and C- terminal domains of calmodulin. Although first detected by x-ray diffraction of the crystallized ternary complex, this conformational change is consistent with its solution structure as characterized by NMR spectroscopy. It is noteworthy that a similar tertiary complex forms when calmodulin binds KAR-2 as when it binds trifluoperazine, even though the two ligands contact (for the most part) different amino acid residues. These observations explain the specificity of KAR-2 as an anti-microtubular agent; the drug interacts with a novel drug binding domain on calmodulin. Consequently, KAR-2 does not prevent calmodulin from binding most of its physiological targets

Folytonos anyagtovábbítású mikrohullámú kezelőegység fejlesztése

Most branches in the food industry have a considerable wastewater output. The problem is not only the total amount of wastewater production, but also the high content of organic matter. Anaerobic digestion is an effective way of treating wastewater for yielding profitable biogas and alleviating environmental concerns. Pre-treatment of sludge to break down its complex structure can be used for enhancing anaerobic digestibility. Research group of the Department of Process Engineering at the University of Szeged has investigated the applicability and the efficiency of microwave pre-treatment for food industry sludge. The results showed that the microwave treatment of sludge solution resulted in higher biodegradability and enhanced biogas production as well. According to these results a continuous-flow microwave toroidal cavity resonator treating-system was developed

A Previously Uncharacterized Factor associated with Metabolism and Energy (FAME/C14orf105/CCDC198/1700011H14Rik) is related to Evolutionary Adaptation, Energy Balance, and Kidney Physiology

In this study we use comparative genomics to uncover a gene with uncharacterized function ( 1700011H14Rik/C14orf105/CCDC198 ), which we hereby name FAME (Factor Associated with Metabolism and Energy). We observe that FAME shows an unusually high evolutionary divergence in birds and mammals. Through the comparison of single nucleotide polymorphisms, we identify gene flow of FAME from Neandertals into modern humans. We conduct knockout experiments on animals and observe altered body weight and decreased energy expenditure in Fame knockout animals, corresponding to genome-wide association studies linking FAME with higher body mass index in humans. Gene expression and subcellular localization analyses reveal that FAME is a membrane-bound protein enriched in the kidneys. Although the gene knockout results in structurally normal kidneys, we detect higher albumin in urine and lowered ferritin in the blood. Through experimental validation, we confirm interactions between FAME and ferritin and show co-localization in vesicular and plasma membranes

Antimycobacterial activity of peptide conjugate of pyridopyrimidine derivative against Mycobacterium tuberculosis in a series of in vitro and in vivo models

New pyridopyrimidine derivatives were defined using a novel HTS in silico docking method (FRIGATE). The target protein was a dUTPase enzyme (EC 3.6.1.23; Rv2697) which plays a key role in nucleotide biosynthesis of Mycobacterium tuberculosis (Mtb). Top hit molecules were assayed in vitro for their antimycobacterial effect on Mtb H37Rv culture. In order to enhance the cellular uptake rate, the TB820 compound was conjugated to a peptid-based carrier and a nanoparticle type delivery system (polylactide-co-glycolide, PLGA) was applied. The conjugate had relevant in vitro antitubercular activity with low in vitro and in vivo toxicity. In a Mtb H37Rv infected guinea pig model the in vivo efficacy of orally administrated PLGA encapsulated compound was proved: animals maintained a constant weight gain and no external clinical signs of tuberculosis were observed. All tissue homogenates from lung, liver and kidney were found negative for Mtb, and diagnostic autopsy showed that no significant malformations on the tissues occurred