Regulated portals of entry into the cell

The plasma membrane is the interface between cells and their harsh environment. Uptake of nutrients and all communication among cells and between cells and their environment occurs through this interface. 'Endocytosis' encompasses several diverse mechanisms by which cells internalize macromolecules and particles into transport vesicles derived from the plasma membrane. It controls entry into the cell and has a crucial role in development, the immune response, neurotransmission, intercellular communication, signal transduction, and cellular and organismal homeostasis. As the complexity of molecular interactions governing endocytosis are revealed, it has become increasingly clear that it is tightly coordinated and coupled with overall cell physiology and thus, must be viewed in a broader context than simple vesicular trafficking.     

Recurrent de novo point mutations in lamin A cause Hutchinson-Gilford progeria syndrome

Hutchinson-Gilford progeria syndrome (HGPS) is a rare genetic disorder characterized by features reminiscent of marked premature ageing. Here, we present evidence of mutations in lamin A (LMNA) as the cause of this disorder. The HGPS gene was initially localized to chromosome 1q by observing two cases of uniparental isodisomy of 1q-the inheritance of both copies of this material from one parent-and one case with a 6-megabase paternal interstitial deletion. Sequencing of LMNA, located in this interval and previously implicated in several other heritable disorders, revealed that 18 out of 20 classical cases of HGPS harboured an identical de novo (that is, newly arisen and not inherited) single-base substitution, G608G(GGC > GGT), within exon 11. One additional case was identified with a different substitution within the same codon. Both of these mutations result in activation of a cryptic splice site within exon 11, resulting in production of a protein product that deletes 50 amino acids near the carboxy terminus. Immunofluorescence of HGPS fibroblasts with antibodies directed against lamin A revealed that many cells show visible abnormalities of the nuclear membrane. The discovery of the molecular basis of this disease may shed light on the general phenomenon of human ageing.     

CEACAM1 regulates insulin clearance in liver

We hypothesized that insulin stimulates phosphorylation of CEACAM1 which in turn leads to upregulation of receptor-mediated insulin endocytosis and degradation in the hepatocyte. We have generated transgenic mice over-expressing in liver a dominant-negative, phosphorylation-defective S503A-CEACAM1 mutant. Supporting our hypothesis, we found that S503A-CEACAM1 transgenic mice developed hyperinsulinemia resulting from impaired insulin clearance. The hyperinsulinemia caused secondary insulin resistance with impaired glucose tolerance and random, but not fasting, hyperglycemia. Transgenic mice developed visceral adiposity with increased amounts of plasma free fatty acids and plasma and hepatic triglycerides. These findings suggest a mechanism through which insulin signaling regulates insulin sensitivity by modulating hepatic insulin clearance.     

An evaluation of five algorithms for generating an initial configuration for SINDSCAL

Five different methods for obtaining a rational initial estimate of the stimulus space in the INDSCAL model were compared using the SINDSCAL program for fitting INDSCAL. The effect of the number of stimuli, the number of subjects, the dimensionality, and the amount of error on the quality and efficiency of the final SINDSCAL solution were investigated in a Monte Carlo study. We found that the quality of the final solution was not affected by the choice of the initialization method, suggesting that SINDSCAL finds a global optimum regardless of the initialization method used. The most efficient procedures were the methods proposed by by de Leeuw and Pruzansky (1978) and by Flury and Gautschi (1986) for the simultaneous diagonalization of several positive definite symmetric matrices, and a method based on linearly constraining the stimulus space using the CANDELINC approach developed by Carroll, Pruzansky, and Kruskal (1980).Geert De Soete is supported as Bevoegdverklaard Navorser of the Belgian Nationaal Fonds voor Wetenschappelijk Onderzoek. The authors gratefully acknowledge the helpful comments and suggestions of the reviewers.     

The draft genome of the parasitic nematode Trichinella spiralis

Genome evolution studies for the phylum Nematoda have been limited by focusing on comparisons involving Caenorhabditis elegans. We report a draft genome sequence of Trichinella spiralis, a food-borne zoonotic parasite, which is the most common cause of human trichinellosis. This parasitic nematode is an extant member of a clade that diverged early in the evolution of the phylum, enabling identification of archetypical genes and molecular signatures exclusive to nematodes. We sequenced the 64-Mb nuclear genome, which is estimated to contain 15,808 protein-coding genes, at ～35-fold coverage using whole-genome shotgun and hierarchal map-assisted sequencing. Comparative genome analyses support intrachromosomal rearrangements across the phylum, disproportionate numbers of protein family deaths over births in parasitic compared to a non-parasitic nematode and a preponderance of gene-loss and -gain events in nematodes relative to Drosophila melanogaster. This genome sequence and the identified pan-phylum characteristics will contribute to genome evolution studies of Nematoda as well as strategies to combat global parasites of humans, food animals and crops.     

List of Montana Scolytidae (Coleoptera) and notes on new records

Listed are 96 species of Scolytidae (Coleoptera) from Montana. Eighteen species reported from Montana for the first time are: Scierus pubescens Swaine, Hylastinus obscurus (Marsham), Hylesinus aculeatus Say, Hylesinus californicus (Swaine), Hylesinus criddlei (Swaine), Pseudohylesinus granulatus (LeConte), Dendroctunus punctatus LeConte, Phloeosinus hoferi Blackman, Phloeosinus pini Swaine, Carphoborus pinicolens Wood, Scolytus subscaber LeConte, Ips grandicollis (Eichhoff), Trypodendron betulae Swaine, Trypodendron retusum (LeConte), Trypophloeus populi Hopkins, Procryphalus mucronatus, (LeConte), Pityophthorus alpinensis G. Hopping, and Gnathotrichus denticulatus Blackman.