Single Amino Acid Variation Underlies Species-Specific Sensitivity to Amphibian Skin-Derived Opioid-like Peptides

It has been suggested that the evolution of vertebrate opioid receptors (ORs) follow a vector of increased functionality. Here we test this idea comparing human and frog ORs. Interestingly, some of the most potent opioid peptides known have been isolated from amphibian skin secretions. Here we show that such peptides (dermorphin and deltorphin) are highly potent in the human receptors and inactive in frog ORs. The molecular basis for the insensitivity of the frog ORs to these peptides was studied using chimeras and molecular modeling. Interestingly, the insensitivity of the delta opioid receptor (DOR) to deltorphin was due to variation of a single amino acid– Trp7.35—which is a leucine in mammalian DORs. Notably, Trp7.35 is completely conserved in all known DOR sequences from lamprey, fish and amphibians. The deltorphin-insensitive phenotype was verified in fish. Our results provide a molecular explanation for the species selectivity of skin-derived opioid peptides

Coupled transcriptome and proteome analysis of human lymphotropic tumor viruses: insights on the detection and discovery of viral genes

<p>Abstract</p> <p>Background</p> <p>Kaposi's sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV) are related human tumor viruses that cause primary effusion lymphomas (PEL) and Burkitt's lymphomas (BL), respectively. Viral genes expressed in naturally-infected cancer cells contribute to disease pathogenesis; knowing which viral genes are expressed is critical in understanding how these viruses cause cancer. To evaluate the expression of viral genes, we used high-resolution separation and mass spectrometry coupled with custom tiling arrays to align the viral proteomes and transcriptomes of three PEL and two BL cell lines under latent and lytic culture conditions.</p> <p>Results</p> <p>The majority of viral genes were efficiently detected at the transcript and/or protein level on manipulating the viral life cycle. Overall the correlation of expressed viral proteins and transcripts was highly complementary in both validating and providing orthogonal data with latent/lytic viral gene expression. Our approach also identified novel viral genes in both KSHV and EBV, and extends viral genome annotation. Several previously uncharacterized genes were validated at both transcript and protein levels.</p> <p>Conclusions</p> <p>This systems biology approach coupling proteome and transcriptome measurements provides a comprehensive view of viral gene expression that could not have been attained using each methodology independently. Detection of viral proteins in combination with viral transcripts is a potentially powerful method for establishing virus-disease relationships.</p

Extension\u27s Evolving Alignment of Programs Serving Families and Youth: Organizational Change and Its Implications

Extension is experiencing a trend toward closer alignment of its programs serving families and youth, notably Family and Consumer Sciences and 4-H Youth Development. Projects are more multidisciplinary and comprehensive than in the past, and, in many states, FCS and 4-HYD are also becoming more administratively integrated. Several reasons for this shift are recent developments in social science intervention theory, Extension budget reductions, and land-grant universities\u27 long-term organizational strategies. We discuss implications for Extension faculty and the need to track and understand the restructuring process. Overall, the emphasis on collaboration and comprehensiveness provide opportunities for more effective Extension programming

Low temperature X-ray investigation of structural distributions in myoglobin

The results of X-ray structure analysis of metmyoglobin at 300 K, 185 K, 165 K, 115 K and 80 K are reported. The lattice vectorsa andb decrease linearly with temperature whilec shows non-linearity above 180 K, indicating some type of phase transition. Cooling does change the myoglobin structure but only within the structural distribution as determined by individual 〈x$^2$〉 at room temperature. Two residues showed significant alternative positions for sidechains at higher temperatures while only one position is occupied at low temperatures. In the case of LEU 61 a jump between different positions of the side-chain reduces the potential barrier for the entrance of the O$^2$ molecule to the heme pocket.The mean square displacements, 〈x$^2$〉, of the individual residues decrease linearly with temperature in most cases, indicating a parabolic envelope for the potential responsible for motions. A separation of rotational and translational disorder of the entire molecule is discussed. Comparison with Mössbauer spectroscopy indicates that protein dynamics on a time scale faster than 10$^{-7} s is not simply a harmonic process. Extrapolation of the structural distributions to T=0 K shows that a large zero point distribution of the myoglobin structure exists, thus proving that there is no absolute energy minimum for one well defined conformation

Baugestaltung und Recht Ueberlegungen zur Anwendung baurechtlicher Gestaltungsvorschriften auf landwirtschaftliche Gebaeude

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