Mutations in the colony stimulating factor 1 receptor (CSF1R) gene cause hereditary diffuse leukoencephalopathy with spheroids

Hereditary diffuse leukoencephalopathy with spheroids (HDLS) is an autosomal-dominant central nervous system white-matter disease with variable clinical presentations, including personality and behavioral changes, dementia, depression, parkinsonism, seizures and other phenotypes. We combined genome-wide linkage analysis with exome sequencing and identified 14 different mutations affecting the tyrosine kinase domain of the colony stimulating factor 1 receptor (encoded by CSF1R) in 14 families with HDLS. In one kindred, we confirmed the de novo occurrence of the mutation. Follow-up sequencing identified an additional CSF1R mutation in an individual diagnosed with corticobasal syndrome. In vitro, CSF-1 stimulation resulted in rapid autophosphorylation of selected tyrosine residues in the kinase domain of wild-type but not mutant CSF1R, suggesting that HDLS may result from partial loss of CSF1R function. As CSF1R is a crucial mediator of microglial proliferation and differentiation in the brain, our findings suggest an important role for microglial dysfunction in HDLS pathogenesis.     

Ciliary proteins link basal body polarization to planar cell polarity regulation

Planar cell polarity (PCP) refers to coordinated polarization of cells within the plane of a cell sheet. A conserved signaling pathway is required for the establishment of PCP in epithelial tissues and for polarized cellular rearrangements known as convergent extension. During PCP signaling, core PCP proteins are sorted asymmetrically along the polarization axis; this sorting is thought to direct coordinated downstream morphogenetic changes across the entire tissue. Here, we show that a gene encoding a ciliary protein (a 'ciliary gene'), Ift88, also known as Polaris, is required for establishing epithelial PCP and for convergent extension of the cochlear duct of Mus musculus. We also show that the proper positioning of ciliary basal bodies and the formation of polarized cellular structures are disrupted in mice with mutant ciliary proteins ('ciliary mutants'), whereas core PCP proteins are partitioned normally along the polarization axis. Thus, our data uncover a distinct requirement for ciliary genes in basal body positioning and morphological polarization during PCP regulation.     

Viscous fingering of HCl through gastric mucin.

The HCl in the mammalian stomach is concentrated enough to digest the stomach itself, yet the gastric epithelium remains undamaged. One protective factor is gastric mucus, which forms a protective layer over the surface epithelium and acts as a diffusion barrier Bicarbonate ions secreted by the gastric epithelium are trapped in the mucus gel, establishing a gradient from pH 1-2 at the lumen to pH 6-7 at the cell surface. How does HCl, secreted at the base of gastric glands by parietal cells, traverse the mucus layer without acidifying it? Here we demonstrate that injection of HCl through solutions of pig gastric mucin produces viscous fingering patterns dependent on pH, mucin concentration and acid flow rate. Above pH 4, discrete fingers are observed, whereas below pH 4, HCl neither penetrates the mucin solution nor forms fingers. Our in vitro results suggest that HCl secreted by the gastric gland can penetrate the mucus gel layer (pH 5-7) through narrow fingers, whereas HCl in the lumen (pH 2) is prevented from diffusing back to the epithelium by the high viscosity of gastric mucus gel on the luminal side.     

Enzymatic profile ofKluyvera species

Summary Kluyvera, a proposed genus formerly known as Enteric group 8, was found to have similar enzyme profiles among the present 3 groups.Kluyvera species group 3 showed the most heterogeneous enzyme reactions.To whom reprint requests should be addressed.     

Binding of aluminium ions byStaphylococcus aureus 893

Résumé Deux types de liaisons ont lieu quand des ions d'aluminium réagissent avec les parois cellulaires isolées deStraphylococcus aureus espèce 893. La première interaction a comme résultat la formation d'un complexe stable qui affecte des groupes occupant le mur de la cellule avec un pK _a 5. On suppose l'existence d'un composant de surface constitué par de la protéine combinée à de l'acide teichoique. La deuxième liaison consiste en ions interchangeables dans la couche mobile de cations recouvrant la paroi.     

The facilities for practical instruction in science during the early years of the Ecole Polytechnique

The facilities provided for practical teaching at the Ecole Polytechnique, at the time of its foundation and during the Napoleonic period, have been the subject for much research and conjecture. Documents are discussed and presented which throw light on the actual situation, the number of laboratories, their equipment and apparatus, and the amount of practical instruction provided for the students.     

Biodiversity loss and its impact on humanity

The most unique feature of Earth is the existence of life, and the most extraordinary feature of life is its diversity. Approximately 9 million types of plants, animals, protists and fungi inhabit the Earth. So, too, do 7 billion people. Two decades ago, at the first Earth Summit, the vast majority of the world's nations declared that human actions were dismantling the Earth's ecosystems, eliminating genes, species and biological traits at an alarming rate. This observation led to the question of how such loss of biological diversity will alter the functioning of ecosystems and their ability to provide society with the goods and services needed to prosper.