A Gene for Autosomal Dominant Congenital Nystagmus Localizes to 6p12

Congenital nystagmus is an idiopathic disorder characterized by bilateral ocular oscillations usually manifest during infancy. Vision is typically decreased due to slippage of images across the fovea. As such, visual acuity correlates with nystagmus intensity, which is the amplitude and frequency of eye movements at a given position of gaze. X-linked, autosomal dominant, and autosomal recessive pedigrees have been described, but no mapping studies have been published. We recently described a large pedigree with autosomal dominant congenital nystagmus. A genome-wide search resulted in six markers on 6p linked by two-point analysis at θ = 0 (D6S459, D6S452, D6S465, FTHP1, D6S257, D6S430). Haplotype analysis localizes the gene for autosomal dominant congenital motor nystagmus to an 18-cM region between D6S271 and D6S455.     

Hyperpolarization-activated inward chloride current in protoplasts from suspension-cultured carrot cells

Summary Plasmalemmal ionic currents from enzymatically-isolated protoplasts of suspension-cultured carrot cells were investigated by patch-clamp techniques. Among other currents, a novel hyperpolarization-activated, inwardly-rectifying, whole-cell current was observed. The activation of this current was fast in onset, and for large hyperpolarizations a characteristic, rapid voltage-dependent inactivation was seen. Ion substitution experiments indicate that this inward current was due mainly to efflux of chloride ions. No dependence on either internal or external calcium was found, and internal MgATP was not necessary. Surprisingly, zinc did not block this current. In hyperpolarized outside-out patches, inward single-channel chloride currents having an elementary conductance of ca. 100 pS were observed. The open probability increased with hyperpolarization. Similar single-channel currents were activated by slight negative pressure applied to the pipette. These chloride currents could contribute both to the control of membrane potential and in the regulation of osmotic balance in carrot cells.Abbreviations BAPTA 1,2-bis (2-aminophenoxy)ethane-N,N,N,N-tetraacetic acid - 2,4-D 2,4-dichlorophenoxyacetic acid - E_x Nernst equilibrium potential for ion x - NMDG N-methyl-D-glucamine - PMSF phenylmethylsulfonyl fluoride     

Relationship between osmoprotection and the structure and intracellular accumulation of betaines by Escherichia coli

Abstract Naturally occuring betaines, especially glycine betaine and proline betaine, were accumulated by Escherichia coli from urine. In synthetic hyperosmotic medium, with an homologous series of added betaines, (CH₃)₃N⁺-(CH₂) _n -COO⁻, osmoprotective activity and intracellular accumulation decreased monotonically as n increased from 1 to 5. In contrast, α -substituted glycine betaines were accumulated in a similar manner to glycine betaine, but with different osmoprotective activities. Arsenobetaine, with a quaternary arsonium group, was also accumulated but amino acids which can become negatively charged in a chemically basic environment were not.     

The oxidative stress response in Bacillus subtilis

Abstract Bacillus subtilis undergoes a typical bacterial stress response when exposed to low concentrations (0.1 mM) of hydrogen peroxide. Protection is thereby induced against otherwise lethal, challenge concentrations (10 mM) of this oxidant and a number of proteins are induced including the scavenging enzymes, catalase and alkyl hydroperoxide reductase, and a putative DNA binding and protecting protein. Induced protection against higher concentrations (10–30 mM) of hydrogen peroxide is eliminated in a catalase-deficient mutant. Both RecA and Spo0A influence the basal but not the induced resistance to hydrogen peroxide. A regulatory mutation has been characterized that affects the inducible phenotype and is constitutively resistant to high concentrations of hydrogen peroxide. This mutant constitutively overexpresses the proteins induced by hydrogen peroxide in the wild-type. The resistance of spores to hydrogen peroxide is partly attributable to binding of small acid soluble proteins by the spore DNA and partly to a second step which coincides with the depletion of the NADH pool, which may inhibit the generation of hydroxyl radicals from hydrogen peroxide.     

Inhibition of G1 phase cyclin dependent kinases by transforming growth factor β1

Transforming growth factor β1 (TGFβ1) inhibits epithelial cell proliferation late in the G1 phase of the cell cycle. We examined the effect of TGFβ1 on known late G1 cell cycle regulators in an attempt to determine the molecular mechanism of growth inhibition by this physiological inhibitor. The results demonstrate the TGFβ1 inhibits the late G1 and S phase specific histone H1 kinase activity of p33^cdk2. This inhibitiion is not dur to TGFβ1's effect on p33^cdk2 synthesis, but rather due to its negative effect on the late G1 phosphorylation of p33^cdk2. It is also shown that TGFβ1 inhibits both late G1 cyclin A and cyclin E associated histon H1 kinase activities. The inhibitor has no effects on the synthesis of cyclin E but to inhibit the synthesis of cyclin A protein in a cell cycle dependent manner. If TGFβ1 is added to cells which have progressed futher than 8 hours into G1, then it is without inhibitory effect on cyclin A synthesis. These effect on TGFβ1 on late G1 cell cycle regulators correlate well with its inhibitory effects on cellular growth and suggest that these G1 cyclin dependent kinases might serve as targets for TGFβ1-mediated growth arrest.     

The disulfide bridges of the immunoglobulin-like domains of FcγRIIIB are essential for efficient expression and biological activity

The immunoglobulin G receptor FcRIIIB belongs to the immunoglobulin superfamily as two extracellular domains show homology to the immunoglobulin domains. Since some residues in these domains, such as the two cysteines, are supposed to form an intrachain disulfide bridge are so commonly conserved, they may be of importance for correct folding. Site-directed mutagenesis and expression in BHK21 confirmed this supposition for the FcRIIIB. Replacing both cysteines in the first and/or second domain by serines reduced the surface expression level by 50%, whereas the ligand binding capability was 20–30% of that seen in cells expressing the wild-type receptor. Replacing one of the four cysteines resulted in the loss of surface expression. Exchanging the conserved tryptophan in the first domain by phenylalanine only slightly affected the ligand binding (25%), whereas the surface expression remained unchanged.