Genetic analysis of attractin homologs

Attractin (ATRN) and Attractin-like 1 (ATRNL1) are highly similar type I transmembrane proteins. Atrn null mutant mice have a pleiotropic phenotype including dark fur, juvenile-onset spongiform neurodegeneration, hypomyelination, tremor, and reduced body weight and adiposity, implicating ATRN in numerous biological processes. Bioinformatic analysis indicated that Atrn and Atrnl1 arose from a common ancestral gene early in vertebrate evolution. To investigate the genetics of the ATRN system and explore potential redundancy between Atrn and Atrnl1, we generated and characterized Atrnl1 loss- and gain-of-function mutations in mice. Atrnl1 mutant mice were grossly normal with no alterations of pigmentation, central nervous system pathology or body weight. Atrn null mutant mice carrying a beta-actin promoter-driven Atrnl1 transgene had normal, agouti-banded hairs and significantly delayed onset of spongiform neurodegeneration, indicating that over-expression of ATRNL1 compensates for loss of ATRN. Thus, the two genes are redundant from the perspective of gain-of-function but not loss-of-function mutations.     

Effect of Akkermansia muciniphila,Faecalibacterium prausnitzii,and Their Extracellular Vesicles on the Serotonin System in Intestinal Epithelial Cells

Probiotics and Antimicrobial Proteins - The gastrointestinal (GI) tract is an essential reservoir of serotonin or 5-hydroxytryptamine (5-HT), which possesses a set of bacterial species communities....     

Synthesis of new ultrasonic-assisted palladium oxide nanoparticles: an in vitro evaluation on cytotoxicity and DNA/BSA binding properties

Abstract

Better solubility and improved toxicity of palladium complexes compared with cisplatin were major reasons for synthesis of novel Pd(II) complex, [Pd(8Q)(bpy)]NO₃ (8Q=8-hydroxyquinolinate, bpy=2,2′-bipyridine). Interaction between the [Pd(8Q)(bpy)]NO₃ complex and calf thymus DNA in aqueous solution has been investigated by circular dichroism (CD), UV-Visible absorption and fluorescence spectroscopic techniques. These experiments showed that prepared Pd(II) complex can effectively intercalate into CT-DNA and weakly bind to BSA in which the bovine serum albumin molecule was unfolded slightly. The cytotoxicity of the prepared complex has been evaluated on the MCF-7 and DU145 cell lines by MTT and TUNEL assay. The MTT results were showed that in DU145, the CC₅₀ values of [Pd(8Q)(bpy)]NO₃ and cisplatin are very close together (10.4 and 8.3?μM, respectively), unlike MCF-7. Accordingly, TUNEL assay was performed on DU145 and apoptosis was clearly obvious by 43% DNA fragmentation in the treated cell lines. So, we can suggest the [Pd(8Q)(bpy)]NO₃ as alternative drug for cisplatin in the future which has great potential in DNA denaturation and apoptosis specially on prostate cancer. PdO nanoparticles were successfully prepared without supported any surfactants via sonochemical approach. The synthesized PdONPs were characterized using UV-Vis and FTIR spectroscopy, X-ray diffraction (XRD), dynamic light scattering (DLS), energy-dispersive X-ray spectroscopy (EDX), scanning electron microscopy (SEM) and transmission electron microscopy (TEM).

Communicated by Ramaswamy H. Sarma     

The effect of dextran on subunit exchange of the molecular chaperone alphaA-crystallin

Alpha-crystallin, a member of small heat shock protein (sHsp) family, is comprised of alphaA and alphaB subunits and acts as a molecular chaperone by interacting with unfolding proteins to prevent their aggregation. The alphaA-crystallin homopolymer consists of 30-40 subunits that are undergoing dynamic exchange. In vivo, alpha-crystallin elicits its chaperone action in a crowded cellular environment (e.g. in the lens). In vitro, inert molecular crowding agents (e.g. dextran) are often used to mimic crowded conditions. In this study, it was found that alpha-crystallin and alphaA-crystallin are poorer chaperones in the presence of dextran. Using fluorescence resonance energy transfer, it is shown that the alphaA-crystallin subunit exchange rate strongly increases with temperature. Binding of reduced ovotransferrin to alphaA-crystallin markedly decreases the rate of subunit exchange, as does the presence of dextran. In addition, in the presence of dextran the effect of reduced ovotransferrin on decreasing the rate of subunit exchange of alphaA-crystallin is greater than in the absence of dextran. Under the conditions of molecular crowding, the alphaA-crystallin subunit exchange rate is not temperature-dependent. In the absence of dextran, the exchange rate of alphaA-crystallin subunits correlates with its chaperone efficiency, i.e. the chaperone ability of alphaA-crystallin increases with temperature. However in the presence of dextran, the temperature dependence of the chaperone ability of alphaA-crystallin is eliminated.     

Molecular simulation study of assembly of DNA-grafted nanoparticles: effect of bidispersity in DNA strand length

In this paper, we use molecular dynamics simulations to study the assembly of DNA-grafted nanoparticles to demonstrate specifically the effect of bidispersity in grafted DNA strand length on the thermodynamics and structure of nanoparticle assembly at varying number of grafted single-stranded DNA (ssDNA) strands and number of guanine/cytosine (G/C) bases per strand. At constant number of grafted ssDNA strands and G/C nucleotides per strand, as bidispersity in strand lengths increases, the number of nanoparticles that assemble as well as the number of neighbours per particle in the assembled cluster increases. When the number of G/C nucleotides per strand in short and long strands is equal, the long strands hybridise with the other long strands with higher frequency than the short strands hybridise with short/long strands. This dominance of the long strands leads to bidisperse systems having similar thermodynamics to that in corresponding systems with monodisperse long strands. Structurally, however, as a result of long–long, long–short and short–short strand hybridisation, bidispersity in DNA strand length leads to a broader inter-particle distance distribution within the assembled cluster than seen in systems with monodisperse short or monodisperse long strands. The effect of increasing the number of G/C bases per strand or increasing the number of grafted DNA strands on the thermodynamics of assembly is similar for bidisperse and monodisperse systems. The effect of increasing the number of grafted ssDNA strands on the structure of the assembled cluster is dependent on the extent of strand bidispersity because the presence of significantly shorter ssDNA strands among long ssDNA strands reduces the crowding among the strands at high grafting density. This relief in crowding leads to larger number of strands hybridised and as a result larger coordination number in the assembled cluster in systems with high bidispersity in strands than in corresponding monodisperse or low bidispersity systems.