Galactose intoxication pathologic study in the chick

Résumé Des poussins nourris avec une ration contenant plus de 10% de galactose développent des tremblements, des convulsions et meurent. Une dégénération des neurons et de l'oedéma péri-cellulaire se présente dans la zone des ganglions basals, dans la zone médullaire et dans les lobes optiques.

---

---

Supported by grant B 2951 (C1) from the National Institute of Neurological Diseases and Blindness, National Institutes of Health, United States Public Health Service.     

A giant stream of metal-rich stars in the halo of the galaxy M31.

Recent observations have revealed streams of gas and stars in the halo of the Milky Way that are the debris from interactions between our Galaxy and some of its dwarf companion galaxies; the Sagittarius dwarf galaxy and the Magellanic clouds. Analysis of the material has shown that much of the halo is made up of cannibalized satellite galaxies, and that dark matter is distributed nearly spherically in the Milky Way. It remains unclear, however, whether cannibalized substructures are as common in the haloes of galaxies as predicted by galaxy-formation theory. Here we report the discovery of a giant stream of metal-rich stars within the halo of the nearest large galaxy, M31 (the Andromeda galaxy). The source of this stream could be the dwarf galaxies M32 and NGC205, which are close companions of M31 and which may have lost a substantial number of stars owing to tidal interactions. The results demonstrate that the epoch of galaxy building still continues, albeit at a modest rate, and that tidal streams may be a generic feature of galaxy haloes.     

A genetic pathway for the specification of the vulval cell lineages of Caenorhabditis elegans

Twenty-three genes have been assigned to particular steps in a genetic pathway for the specification of the vulval cell lineages of the nematode Caenorhabditis elegans. Mutations in most of these genes cause homoeotic transformations in the fates of individual cells, suggesting that these lineages may be specified by a series of decisions that distinguish between alternative cell fates. Fifteen of the genes function in a system involved in the intracellular response to the extracellular signal that induces vulval formation.     

Age-related disappearance of Mayer-like heart rate waves

Healthy elderly subjects (greater than or equal to 65 years) did not show the prominent low frequency (0.07-0.09 Hz) heart rate oscillations (Mayer waves) recorded in young adults immediately following passive upright tilt. This difference may be related to altered autonomic function with physiologic aging.     

Effects of chronic lithium administration on concanavalin A binding to plasma membranes from the corpus striatum of rat brain

Summary The effects of chronic in vivo lithium administration on mannose-containing components of plasma membranes from rat corpus striatum were examined by a³H-concanavalin A binding displacement method. No difference in Con A binding was observed between sodium or lithium-treated rats during a 1-month period.We thank Dr S. Gershon of this research unit for his encouragement and support during these studies.     

Estimating the impact of school closure on influenza transmission from Sentinel data

The threat posed by the highly pathogenic H5N1 influenza virus requires public health authorities to prepare for a human pandemic. Although pre-pandemic vaccines and antiviral drugs might significantly reduce illness rates, their stockpiling is too expensive to be practical for many countries. Consequently, alternative control strategies, based on non-pharmaceutical interventions, are a potentially attractive policy option. School closure is the measure most often considered. The high social and economic costs of closing schools for months make it an expensive and therefore controversial policy, and the current absence of quantitative data on the role of schools during influenza epidemics means there is little consensus on the probable effectiveness of school closure in reducing the impact of a pandemic. Here, from the joint analysis of surveillance data and holiday timing in France, we quantify the role of schools in influenza epidemics and predict the effect of school closure during a pandemic. We show that holidays lead to a 20-29% reduction in the rate at which influenza is transmitted to children, but that they have no detectable effect on the contact patterns of adults. Holidays prevent 16-18% of seasonal influenza cases (18-21% in children). By extrapolation, we find that prolonged school closure during a pandemic might reduce the cumulative number of cases by 13-17% (18-23% in children) and peak attack rates by up to 39-45% (47-52% in children). The impact of school closure would be reduced if it proved difficult to maintain low contact rates among children for a prolonged period.     

Synthetic lethal screen identification of chemosensitizer loci in cancer cells

Abundant evidence suggests that a unifying principle governing the molecular pathology of cancer is the co-dependent aberrant regulation of core machinery driving proliferation and suppressing apoptosis. Anomalous proteins engaged in support of this tumorigenic regulatory environment most probably represent optimal intervention targets in a heterogeneous population of cancer cells. The advent of RNA-mediated interference (RNAi)-based functional genomics provides the opportunity to derive unbiased comprehensive collections of validated gene targets supporting critical biological systems outside the framework of preconceived notions of mechanistic relationships. We have combined a high-throughput cell-based one-well/one-gene screening platform with a genome-wide synthetic library of chemically synthesized small interfering RNAs for systematic interrogation of the molecular underpinnings of cancer cell chemoresponsiveness. NCI-H1155, a human non-small-cell lung cancer line, was employed in a paclitaxel-dependent synthetic lethal screen designed to identify gene targets that specifically reduce cell viability in the presence of otherwise sublethal concentrations of paclitaxel. Using a stringent objective statistical algorithm to reduce false discovery rates below 5%, we isolated a panel of 87 genes that represent major focal points of the autonomous response of cancer cells to the abrogation of microtubule dynamics. Here we show that several of these targets sensitize lung cancer cells to paclitaxel concentrations 1,000-fold lower than otherwise required for a significant response, and we identify mechanistic relationships between cancer-associated aberrant gene expression programmes and the basic cellular machinery required for robust mitotic progression.     

Complete structure of the glycosyl phosphatidylinositol membrane anchor of rat brain Thy-1 glycoprotein

Glycosyl-phosphatidylinositol (GPI) anchors have recently been identified as alternatives to hydrophobic amino acid sequences for the attachment of a variety of eukaryotic cell surface molecules to the lipid bilayer. In single cell eukaryotes the GPI group appears to be the predominant form of membrane attachment, and in vertebrates a substantial minority of molecules have this anchor including cell surface hydrolytic enzymes, antigens and cell adhesion molecules. Analysis of different GPI anchors suggests they share common structural features including linkage to the COOH group of the terminal amino acid via ethanolamine phosphate, the presence of phosphatidylinositol lipid and a glycan between the bridging ethanolamine phosphate and the lipid. In the case of the Trypanosoma brucie variant surface glycoprotein (VSG) the full structure of the GPI anchor has been determined and this provides a prototype for comparison with other molecules. We now report the structure of the GPI anchor of rat brain Thy-1 glycoprotein. It has an identical backbone to the VSG anchor but shows significant differences in side chain moieties.     

Plasmodium falciparum-infected erythrocytes modulate the maturation of dendritic cells.

The malaria parasite Plasmodium falciparum is one of the most successful human pathogens. Specific virulence factors remain poorly defined, although the adhesion of infected erythrocytes to the venular endothelium has been associated with some of the syndromes of severe disease. Immune responses cannot prevent the development of symptomatic infections throughout life, and clinical immunity to the disease develops only slowly during childhood. An understanding of the obstacles to the development of protective immunity is crucial for developing rational approaches to prevent the disease. Here we show that intact malaria-infected erythrocytes adhere to dendritic cells, inhibit the maturation of dendritic cells and subsequently reduce their capacity to stimulate T cells. These data demonstrate both a novel mechanism by which malaria parasites induce immune dysregulation and a functional role beyond endothelial adhesion for the adhesive phenotypes expressed at the surface of infected erythrocytes.