Interplay between hydrophobic cluster and loop propensity in beta-hairpin formation

Autonomously folding beta-hairpins have recently emerged as powerful tools for elucidating the origins of antiparallel beta-sheet folding preferences. Analysis of such model systems has suggested four potential sources of beta-sheet stability: (1) the conformational propensity of the loop segment that connects adjacent strands; (2) favorable contacts between side-chains on adjacent strands; (3) interstrand hydrogen bonds; and (4) the intrinsic beta-sheet propensities of the strand residues. We describe the design and analysis of a series of isomeric 20 residue peptides in which factors (1)-(4) are identical. Differences in beta-hairpin formation within this series demonstrate that these four factors, individually, are not sufficient to explain beta-sheet stability. In agreement with the prediction of a simple statistical mechanical model for beta-hairpin formation, our results show that the separation between the loop segment and an interstrand cluster of hydrophobic side-chains strongly influences beta-hairpin size and stability, with a smaller separation leading to greater stability.     

Arsenic,Cadmium and Lead Erythrocyte Concentrations in Men with a High,Moderate and Low Level of Physical Training

Biological Trace Element Research - The aim of the present study was to determine changes occurring in the erythrocyte concentrations of arsenic (As), cadmium (Cd) and lead (Pb) in highly trained...     

Hfq Is a Global Regulator That Controls the Pathogenicity of Staphylococcus aureus

The Hfq protein is reported to be an RNA chaperone, which is involved in the stress response and the virulence of several pathogens. In E. coli, Hfq can mediate the interaction between some sRNAs and their target mRNAs. But it is controversial whether Hfq plays an important role in S. aureus. In this study, we found that the deletion of hfq gene in S. aureus 8325-4 can increase the surface carotenoid pigments. The hfq mutant was more resistant to oxidative stress but the pathogenicity of the mutant was reduced. We reveal that the Hfq protein can be detected only in some S. aureus strains. Using microarray and qRT-PCR, we identified 116 genes in the hfq mutant which had differential expression from the wild type, most of which are related to the phenotype and virulence of S. aureus. Among the 116 genes, 49 mRNAs can specifically bind Hfq protein, which indicates that Hfq also acts as an RNA binding protein in S. aureus. Our data suggest that Hfq protein of S. aureus is a multifunctional regulator involved in stress and virulence.     

The USDA Barley Core Collection: Genetic Diversity,Population Structure,and Potential for Genome-Wide Association Studies

New sources of genetic diversity must be incorporated into plant breeding programs if they are to continue increasing grain yield and quality, and tolerance to abiotic and biotic stresses. Germplasm collections provide a source of genetic and phenotypic diversity, but characterization of these resources is required to increase their utility for breeding programs. We used a barley SNP iSelect platform with 7,842 SNPs to genotype 2,417 barley accessions sampled from the USDA National Small Grains Collection of 33,176 accessions. Most of the accessions in this core collection are categorized as landraces or cultivars/breeding lines and were obtained from more than 100 countries. Both STRUCTURE and principal component analysis identified five major subpopulations within the core collection, mainly differentiated by geographical origin and spike row number (an inflorescence architecture trait). Different patterns of linkage disequilibrium (LD) were found across the barley genome and many regions of high LD contained traits involved in domestication and breeding selection. The genotype data were used to define ‘mini-core’ sets of accessions capturing the majority of the allelic diversity present in the core collection. These ‘mini-core’ sets can be used for evaluating traits that are difficult or expensive to score. Genome-wide association studies (GWAS) of ‘hull cover’, ‘spike row number’, and ‘heading date’ demonstrate the utility of the core collection for locating genetic factors determining important phenotypes. The GWAS results were referenced to a new barley consensus map containing 5,665 SNPs. Our results demonstrate that GWAS and high-density SNP genotyping are effective tools for plant breeders interested in accessing genetic diversity in large germplasm collections.     

Autophagy regulates apoptosis by targeting NOXA for degradation

Apoptosis and autophagy mutually regulate various cellular physiological and pathological processes. The crosstalk between autophagy and apoptosis is multifaceted and complicated. Elucidating the molecular mechanism of their crosstalk will advance the therapeutic applications of autophagy for treating cancer and other diseases. NOXA, a BH3-only member of the BCL-2 family, was reported to induce apoptosis and promote autophagy. Here, we report that autophagy regulates apoptosis by targeting NOXA for degradation. Inhibiting autophagy increases NOXA protein levels by extending the protein half-life. NOXA accumulation effectively suppresses tumor cell growth by inducing apoptosis, which is further enhanced when p53 is present. Mechanistically, NOXA is hijacked by p62 as autophagic cargo, and its three lysine residues at the C-terminus are necessary for NOXA degradation in lysosomes. Taken together, our study demonstrates that NOXA serves as a bridge in the crosstalk between autophagy and apoptosis and implies that autophagy inhibitors could be an effective therapy for cancer, especially wild-type p53-containing cancer.