The discovery of novel isoflavone pan peroxisome proliferator-activated receptor agonists

Twenty three dual PPARα and γ molecules of natural product origin, previously reported by our group, were further investigated for pan PPAR transactivation against PPARδ. The in vitro cell toxicity profile, as well as, in silico study of the most active molecules within this new class of pan PPAR agonists are also described. 3′,5′ Dimethoxy-7 hydroxyisoflavone 6, Ψ-baptigenin 7, 4′ fluoro-7 hydroxyisoflavone 8, and 3′ methoxy-7 hydroxyisoflavone 9 were identified as the most potent molecules studied within the set compared to the commercially available pan PPAR agonist, bezafibrate 1. These novel active molecules may thus be useful as future leads in PPAR-related disorders, including type II diabetes mellitus and metabolic syndrome.     

Effect of polyamines on the structure, thermal stability and 2,2,2-trifluoroethanol-induced aggregation of alpha-chymotrypsin

Naturally occurring polyamines are known to interact with a variety of biomolecules and critically involve in some important physiological processes. They have also been shown to influence protein aggregation in vitro in some cases. The aim of the present study was to investigate how polyamines may influence the structure and thermal stability of alpha-chymotrypsin and modulate alcohol-induced aggregation of this protein. Various techniques, including turbidity measurements, tensiometry, DSC, intrinsic fluorescence and far- and near-UV circular dichroism spectroscopy were used to examine the effect of putrescine and spermidine on alpha-chymotrypsin. While slight changes in the secondary and tertiary structure of the protein was observed, a clear stabilizing effect against its thermal unfolding was achieved. Moreover, the polyamines were found to inhibit TFE-induced aggregation at 32% TFE and promote formation of non-native alpha-helices in the protein structure. Based on the observed increase in surface tension induced by polyamines, it is suggested that their effects on enhancing thermal stability and alcohol-induced alpha-helices formation may be due to their kosmotropic properties.     

An investigation of the anti-inflammatory effects of gabapentin on acetic acid-induced colitis in rats

Molecular Biology Reports - Inflammatory bowel disease (IBD) is considered a chronic inflammatory gastrointestinal disease with treatment options which exhibit low efficacies and lead to...     

Mutation analysis of androgen receptor gene: Multiple uses for a single test

Androgen receptor gene mutations are one of the leading causes of disorders of sex development (DSD) exhibited by sexual ambiguity or sex reversal. In this study, 2 families with patients whom diagnosed clinically as androgen insensitivity syndrome (AIS) were physically and genetically examined. This evaluation carried out by cytogenetic and molecular analysis including karyotype and sequencing of SRY and AR genes. In family 1, two brothers and their mother were hemizygous and heterozygous respectively for c.2522G > A variant, while one of their healthy brother was a completely normal hemizygote. Family 2 assessment demonstrated the c.639G > A (rs6152) mutation in two siblings who were reared as girls. The SRY gene was intact in all of the study's participants.     

Method for assembling and expressing multiple genes in the nucleus of microalgae

The green alga, Chlamydomonas reinhardtii, is a model organism used in the study of photosynthesis and biotechnological research. Despite its importance, a complete set of genetic tools has yet to be developed. Here, we report the development of a new method for constructing a multi-gene pathway in Saccharomyces cerevisiae and integrating the assembled pathway into the nuclear genome of C. reinhardtii. To demonstrate the use of this method, we assembled and functionally expressed up to three reporter proteins (Ble, AphVIII, and GFP) simultaneously in the nucleus of C. reinhardtii. This new molecular tool should aid efforts to engineer microalgae for biofuel and biopharmaceutical production.     

In silico and experimental improvement of bacteriorhodopsin production in Halobacterium salinarum R1 by increasing DNA-binding affinity of Bat through Q661R/Q665R substitutions in HTH motif

Extremophiles - DNA-binding motif of bacterioopsin activator (Bat) protein is a Helix–Turn–Helix motif, which binds to bop promoter and induces bacterioopsin (Bop) expression under...     

Lactic acid production by loofah-immobilized Rhizopus oryzae through one-step fermentation process using starch substrate

Rhizopus oryzae PTCC 5263 capacity in synthesis of lactic acid (LA) from 10 g/l of soluble potato starch was determined using one-step fermentation process. Pellets were the favorable growing form of the free cells. The extent of the natural ability of the test fungus on biofilm formation on loofah sponge was examined by immobilizing R. oryzae (LIRO). The maximum LA concentration for the free cells and LIRO within 96 h was 3 and 4 g/l, respectively. In terms of specific starch utilization rate (\(q_{\text{s}}\)) and specific LA formation (\(q_{\text{p}}\)), LIRO performed more favorably compared to the free cells (\(q_{{{\text{s}}_{\text{F}} }} > q_{{{\text{s}}_{\text{LIRO}} }}\) and \(q_{{{\text{p}}_{\text{F}} }} < q_{{{\text{p}}_{\text{LIRO}} }}\)). Cell immobilization strategy was undertaken for the column reactor studies based on the statistically optimized levels of the inoculum size and temperature. Maximum production of the LA by the LIRO using an airlift reactor with net draft tube was 5 g/l obtainable within 48 h.

     

iPSC modeling of stage-specific leukemogenesis reveals BAALC as a key oncogene in severe congenital neutropenia

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