Molecular mechanisms of phagocytic uptake in mammalian cells

Phagocytosis is a highly conserved, complex process that has evolved to counter the constant threat posed by pathogens, effete cells and debris. Classically defined as a mechanism for internalising and destroying particles greater than 0.5 mum in size, it is a receptor-mediated, actin-driven process. The best-studied phagocytic receptors are the opsono-receptors, FcgammaR and CR3. Phagocytic uptake involves actin dynamics including polymerisation, bundling, contraction, severing and depolymerisation of actin filaments. Recent evidence points to the importance of membrane remodelling during phagocytosis, both in terms of changes in lipid composition and delivery of new membrane to the sites of particle binding. Here we review the molecular mechanisms of phagocytic uptake and some of the strategies developed by microbial pathogens to manipulate this process.     

Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes

Genome-wide association (GWA) studies have identified multiple loci at which common variants modestly but reproducibly influence risk of type 2 diabetes (T2D). Established associations to common and rare variants explain only a small proportion of the heritability of T2D. As previously published analyses had limited power to identify variants with modest effects, we carried out meta-analysis of three T2D GWA scans comprising 10,128 individuals of European descent and approximately 2.2 million SNPs (directly genotyped and imputed), followed by replication testing in an independent sample with an effective sample size of up to 53,975. We detected at least six previously unknown loci with robust evidence for association, including the JAZF1 (P = 5.0 x 10(-14)), CDC123-CAMK1D (P = 1.2 x 10(-10)), TSPAN8-LGR5 (P = 1.1 x 10(-9)), THADA (P = 1.1 x 10(-9)), ADAMTS9 (P = 1.2 x 10(-8)) and NOTCH2 (P = 4.1 x 10(-8)) gene regions. Our results illustrate the value of large discovery and follow-up samples for gaining further insights into the inherited basis of T2D.     

Lack of major cytoplasmic protein contamination of rat liver nuclear chromatin

Résumé Des mesures quantitatives et des modèles sur gels d'acrilamide ont permi de conclure que les protéines cytoplasmiques préparées de cette manière ne produisent pas de contamination appréciable.

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Supported by grant No. CA-07746 from the United States Public Health Service and grant No. G-138 from the Robert A. Welch Foundation.     

PCR amplification of the Irish potato famine pathogen from historic specimens

Late blight, caused by the oomycete plant pathogen Phytophthora infestans, is a devastating disease of potato and was responsible for epidemics that led to the Irish potato famine in 1845 (refs 1,2,3,4,5). Before the 1980s, worldwide populations of P. infestans were dominated by a single clonal lineage, the US-1 genotype or Ib mitochondrial DNA (mtDNA) haplotype, and sexual reproduction was not documented outside Mexico, the centre of diversity of the pathogen. Here we describe the amplification and sequencing of 100-base-pair fragments of DNA from the internal transcribed spacer region 2 from 28 historic herbarium samples including Irish and British samples collected between 1845 and 1847, confirming the identity of the pathogen. We amplified a variable region of mtDNA that is present in modern Ib haplotypes of P. infestans, but absent in the other known modern haplotypes (Ia, IIa and IIb). Lesions in samples tested were not caused by the Ib haplotype of P. infestans, and so theories that assume that the Ib haplotype is the ancestral strain need to be re-evaluated. Our data emphasize the importance of using historic specimens when making inferences about historic populations.     

Actions of interferon in tissue cultures harboring mouse leukemia virus

Zusammenfassung Das Virus der vesikulären Stomatitis verursacht Zellverschmelzung und Syncytienbildung in mit Mäuse-Leukämie-Virus infizierten Gewebskulturen. Interferon konnte diese Zellzerstörung in der Kultur nicht verhindern.

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This work was supported by U.S.P.H.S. research grant No. CA-7923 and award No. K3-CA-16747.     

Subspecies in Przewalski’s gazelle Procapra przewalskii and its conservation implication

Przewalski’s gazelle Procapra przewalskii is an endangered species endemic to China. A question remains about subspecific variation in this species. Skulls of Przewalski’s gazelle collected from its current remnant ranges around the Qinghai Lake in combination with those collected prior to the 20th century were measured and analyzed using Hierarchical Cluster Analysis in order to clarify the question. Unexpectedly, P. p. diversicornis, extirpated from its historic range, has spread to the Qinghai Lake region where it has replaced nominotypical P. p. przewalskii and is now restricted to a few small isolated populations around the lake. We discuss the causes of this unexpected replacement. In this study, we discuss the possibility of a new form, possibly a new subspecies, in the Guide Basin, adjacent to Qinghai Lake; it is unclear whether the new form has long existed and was only discovered in recent years, or whether it evolved in recent times due to the geographical isolation and anthropogenic landscape features. The study sheds light on the processes of microevolution and subspeciation in Procapra przewalskii, and based on the findings, we propose measures for conservation strategies for Przewalski’s gazelle.     

The activity of neurons in the lateral geniculate body during wakefulness and natural sleep

Résumé On a montré que l'activité neuronique du corps genouillé externe du chat diminue lorsque l'animal passe de l'éveil au sommeil à ondes lentes, et augmente lorsque l'animal passe au sommeil à ondes rapides de bas voltage.     

Mammalian cochlear supporting cells can divide and trans-differentiate into hair cells

Sensory hair cells of the mammalian organ of Corti in the inner ear do not regenerate when lost as a consequence of injury, disease, or age-related deafness. This contrasts with other vertebrates such as birds, where the death of hair cells causes surrounding supporting cells to re-enter the cell cycle and give rise to both new hair cells and supporting cells. It is not clear whether the lack of mammalian hair cell regeneration is due to an intrinsic inability of supporting cells to divide and differentiate or to an absence or blockade of regenerative signals. Here we show that post-mitotic supporting cells purified from the postnatal mouse cochlea retain the ability to divide and trans-differentiate into new hair cells in culture. Furthermore, we show that age-dependent changes in supporting cell proliferative capacity are due in part to changes in the ability to downregulate the cyclin-dependent kinase inhibitor p27(Kip1) (also known as Cdkn1b). These results indicate that postnatal mammalian supporting cells are potential targets for therapeutic manipulation.