Catalytic Peptide Dendrimers as Artificial Proteins： Functional Selection and Optimization from Combinatorial Libraries

1 Introduction In de novo protein design one attempts to create artificial proteins with defined structure and function from first principles, usually with the help of trial-and-error procedures that scan a large number of possible amino acid sequences. Our approach to de novo protein design is based on peptide dendrimers. Dendrimers are tree-like structures that adopt a globular or disk-shaped structure as a consequence of topology rather than folding. Our peptide dendrimers are obtained by a…     

Sub-poissonian loading of single atoms in a microscopic dipole trap.

The ability to manipulate individual atoms, ions or photons allows controlled engineering of the quantum state of small sets of trapped particles; this is necessary to encode and process information at the quantum level. Recent achievements in this direction have used either trapped ions or trapped photons in cavity quantum-electrodynamical systems. A third possibility that has been studied theoretically is to use trapped neutral atoms. Such schemes would benefit greatly from the ability to trap and address individual atoms with high spatial resolution. Here we demonstrate a method for loading and detecting individual atoms in an optical dipole trap of submicrometre size. Because of the extremely small trapping volume, only one atom can be loaded at a time, so that the statistics of the number of atoms in the trap, N, are strongly sub-poissonian (DeltaN2 approximately 0.5N). We present a simple model for describing the observed behaviour, and we discuss the possibilities for trapping and addressing several atoms in separate traps, for applications in quantum information processing.     

核物理学基础——从核结构到宇宙学

本书是法国埃库勒理工学院一套著名的教科书中的一本．是作者为高年级大学生讲授原子核物理相关的一些专题课发展而成的教材。作者们认为大多数核现象都可以从基于泡利原理与库仑势垒的一些简单的论证理解。因此本书并不打算对于核理论现代发展深人讨论，而是把重点放在核物理学各方面的实际应用。本书充分利用了从网上可以得到的大量核物理的实验数据资源。     

Endocytosis and inositol hexakisphosphate levels inras transformants ofDictyostelium discoideum amoebae

Summary Fluid-phase pinocytosis kinetics and lysosomal enzyme secretion parameters were measured inDictyostelium discoideum amoebae constructed from strain AX3 by transformation with a multicopy plasmid carrying either a normalras gene (ras-Gly12), a mutatedras gene (ras-Thr12) or by the vector carrying the geneticin resistance gene only (pDNEO2). It was found that the pinocytosis rate and extent as well as the lysosomal enzyme secretion were slightly different in the three strains. These changes, however, were related to minor modifications of the cellular volumes. The overall concentration of inositol hexakisphosphate was similar in the three strains.This work was supported in part by a grant from the Ligue Nationale Française contre le Cancer (n^o 880258) to MS, and by a grant from the Fonds National Suisse de la Recherche Scientifique (No. 3.623-087) to CR.     

A deletion in the gene encoding sphingomyelin phosphodiesterase 3 (Smpd3) results in osteogenesis and dentinogenesis imperfecta in the mouse

The mouse mutation fragilitas ossium (fro) leads to a syndrome of severe osteogenesis and dentinogenesis imperfecta with no detectable collagen defect. Positional cloning of the locus identified a deletion in the gene encoding neutral sphingomyelin phosphodiesterase 3 (Smpd3) that led to complete loss of enzymatic activity. Our knowledge of SMPD3 function is consistent with the pathology observed in mutant mice and provides new insight into human pathologies.     

Catalytic Peptide Dendrimers as Artificial Proteins: Functional Selection and Optimization from Combinatorial Libraries

1Introduction In de novo protein design one attempts to create artificial proteins with defined structure and function from first principles, usually with the help of trial-and-error procedures that scan a large number of possible amino acid sequences. Our approach to de novo protein design is based on peptide dendrimers. Dendrimers are tree-like structures that adopt a globular or disk-shaped structure as a consequence of topology rather than folding. Our peptide dendrimers are obtained by alternating alpha-aminoacids with branching diaminoacids[1].Dendrimers containing combinations of histidine, serine and aspartate display enzyme-like catalytic properties for the hydrolysis of esters, including enantiomeric discrimination[1d]. The catalytic effect involves cooperative substrate binding and catalysis by a positive dendritic effect[1d].     

BBS10 encodes a vertebrate-specific chaperonin-like protein and is a major BBS locus

Bardet-Biedl syndrome (BBS) is a genetically heterogeneous ciliopathy. Although nine BBS genes have been cloned, they explain only 40-50% of the total mutational load. Here we report a major new BBS locus, BBS10, that encodes a previously unknown, rapidly evolving vertebrate-specific chaperonin-like protein. We found BBS10 to be mutated in about 20% of an unselected cohort of families of various ethnic origins, including some families with mutations in other BBS genes, consistent with oligogenic inheritance. In zebrafish, mild suppression of bbs10 exacerbated the phenotypes of other bbs morphants.     

Conserved noncoding sequences are selectively constrained and not mutation cold spots

Noncoding genetic variants are likely to influence human biology and disease, but recognizing functional noncoding variants is difficult. Approximately 3% of noncoding sequence is conserved among distantly related mammals, suggesting that these evolutionarily conserved noncoding regions (CNCs) are selectively constrained and contain functional variation. However, CNCs could also merely represent regions with lower local mutation rates. Here we address this issue and show that CNCs are selectively constrained in humans by analyzing HapMap genotype data. Specifically, new (derived) alleles of SNPs within CNCs are rarer than new alleles in nonconserved regions (P = 3 x 10(-18)), indicating that evolutionary pressure has suppressed CNC-derived allele frequencies. Intronic CNCs and CNCs near genes show greater allele frequency shifts, with magnitudes comparable to those for missense variants. Thus, conserved noncoding variants are more likely to be functional. Allele frequency distributions highlight selectively constrained genomic regions that should be intensively surveyed for functionally important variation.