Members of the Opioid Receptor (OR) family of G protein-coupled receptors (GPCRs) are found throughout the peripheral and central nervous system where they play key roles in nociception and analgesia. Unlike the classical ORs, δ–OR, κ–OR,1 and μ-OR,2 which were delineated by pharmacological criteria in the 1970’s and 1980’s, the nociceptin/orphanin FQ (N/OFQ) peptide receptor (NOP, aka ORL-1) was discovered relatively recently via molecular cloning and characterization of an orphan GPCR3. Despite its high sequence similarity (~60%) with ORs, NOP has a strikingly distinct pharmacology4,5. Despite high sequence similarity with classical opioid G protein-coupled receptor subtypes, the nociceptin/orphanin FQ (N/OFQ) peptide receptor (NOP) has a distinct biological and pharmacological role, featuring activation by the endogenous peptide N/OFQ, and unique selectivity for exogenous ligands. This study reports the crystal structure of human NOP solved in complex with the peptide mimetic antagonist Banyu Compound-24 (C-24), revealing atomic details of ligand-receptor recognition and selectivity. C-24 mimics the first four N-terminal residues of the NOP-selective peptide antagonist UFP-101, a close derivative of N/OFQ, and provides important clues to binding of these peptides. The X-ray structure also reveals substantial conformational differences in the pocket regions between NOP and the “classical” opioid receptors κ (Ref. 1) and μ (Ref. 2), which are likely due to a small number of residues that vary between the two receptors. The NOP/C-24 structure explains the divergent selectivity profile of NOP and provides a new structural template for the design of NOP ligands.

When a powerful femtosecond laser pulse propagates in an optical medium, self-focusing occurs. Normally, it is the most powerful part (slice) of the pulse that self-focuses first during its propagation. Self-focusing is balanced by the creation of plasma in the self-focal volume, which defocuses the pulse. This balance leads to a limitation of the peak intensity (intensity clamping). The series of self-foci from different slices of the front part of the pulse give rise to the perception of a so-called filament. The back part of the pulse undergoes self-phase modulation and self-steepening resulting in a strong spectral broadening. The final pulse is a white-light laser pulse (supercontinuum). The physics of such (long distance) filamentation and the self-transformation process are reviewed both in air and in condensed matters. The self-transformation leads to a shorter pulse and is currently being studied for efficient pulse compression to the single and (or) few-cycle level. The efficient generation of a third harmonic in the filament is due to a new phenomenon called self-phase locking. The potential applications in atmospheric sensing and lightning control will be briefly discussed. The capability of melting glass leading to index change will be underlined. The paper will end with an outlook into the future of the field. PACS Nos.: 42.65, 42.65Jx, 42.25, 42.79Qx

Genetic studies aimed at understanding the molecular basis of complex human phenotypes require the genotyping of many thousands of single-nucleotide polymorphisms (SNPs) across large numbers of individuals. Public efforts have so far identified over two million common human SNPs; however, the scoring of these SNPs is labor-intensive and requires a substantial amount of automation. Here we describe a simple but effective approach, termed whole-genome sampling analysis (WGSA), for genotyping thousands of SNPs simultaneously in a complex DNA sample without locus-specific primers or automation. Our method amplifies highly reproducible fractions of the genome across multiple DNA samples and calls genotypes at >99% accuracy. We rapidly genotyped 14,548 SNPs in three different human populations and identified a subset of them with significant allele frequency differences between groups. We also determined the ancestral allele for 8,386 SNPs by genotyping chimpanzee and gorilla DNA. WGSA is highly scaleable and enables the creation of ultrahigh density SNP maps for use in genetic studies.

Background: Bone marrow-derived mesenchymal stem cells (BMSCs) are a widely researched adult stem cell population capable of differentiation into various lineages. Because many promising applications of tissue engineering require cell expansion following harvest and involve the treatment of diseases and conditions found in an aging population, the effect of donor age and ex vivo handling must be understood in order to develop clinical techniques and therapeutics based on these cells. Furthermore, there currently exists little understanding as to how these two factors may be influenced by one another.