Loss of cell adhesion in Xenopus laevis embryos mediated by the cytoplasmic domain of XLerk, an erythropoietin-producing hepatocellular ligand

The erythropoietin-producing hepatocellular (Eph) family of ligands and receptors has been implicated in the control of axon guidance and the segmental restriction of cells during embryonic development. In this report, we show that ectopic expression of XLerk, a Xenopus homologue of the murine Lerk-2 (ephrin-B1) transmembrane ligand, causes dissociation of Xenopus embryonic blastomeres by the mid-blastula transition. Moreover, a mutant that lacks the extracellular receptor binding domain can induce this phenotype. The carboxyl-terminal 19 amino acids of the cytoplasmic domain of XLerk are necessary but not sufficient to induce cellular dissociation. Basic fibroblast growth factor, but not activin, can rescue both the loss of cell adhesion and mesoderm induction in ectodermal explants expressing XLerk. Collectively, these results show that the cytoplasmic domain of XLerk has a signaling function that is important for cell adhesion, and fibroblast growth factor signaling modulates this function.     

Autoimmune manifestations of the Wiskott-Aldrich syndrome

OBJECTIVE: To describe and review the autoimmune features and typical manifestations of Wiskott-Aldrich syndrome (WAS). DESIGN: Case series and review of the literature. SETTING: Tertiary care medical center and pediatric referral center. PATIENTS: The presentation, diagnosis, and management of two cases are reported. In addition to the typical features of WAS, the first patient had hemolytic anemia, arthritis, leukocytoclastic vasculitis, and colitis. The second patient had colitis and arthralgias. Detailed review of features and therapeutic options in WAS as exemplified by these two patients are presented. Both patients had bone marrow transplantation, the only definitive treatment for WAS. CONCLUSIONS: WAS has variable clinical and autoimmune manifestations. Diagnosis must be suspected in a boy with small, decreased number of platelets and autoimmune problems or infections. Bone marrow transplantation is the only successful mode of treatment for all aspects of WAS.     

The treatment of chronic ischemic heart disease: the potentials for hypolipidemic correction using current drugs

The data obtained by the authors suggest that lipanor may correct those lipid metabolic disturbances that are most pronounced in each individual case. Moreover, the above drug is capable of lowering substantially the level of total blood cholesterol and atherogenic fractions of lipoproteins as early as at day 14 after its intake. Being associated with minimum adverse effects, and intended to be taken on a once-daily schedule, the drug will, we believe, come in wide use.     

Generation of specific deoxynojirimycin-type inhibitors of the non-lysosomal glucosylceramidase

The existence of a non-lysosomal glucosylceramidase in human cells has been documented (van Weely, S., Brandsma, M., Strijland, A., Tager, J. M., and Aerts, J. M. F. G. (1993) Biochim. Biophys. Acta 1181, 55-62). Hypothetically, the activity of this enzyme, which is localized near the cell surface, may influence ceramide-mediated signaling processes. To obtain insight in the physiological importance of the non-lysosomal glucosylceramidase, the availability of specific inhibitors would be helpful. Here we report on the generation of hydrophobic deoxynojirimycin (DNM) derivatives that potently inhibit the enzyme. The inhibitors were designed on the basis of the known features of the non-lysosomal glucosylceramidase and consist of a DNM moiety, an N-alkyl spacer, and a large hydrophobic group that promotes insertion in membranes. In particular, N-(5-adamantane-1-yl-methoxy)pentyl)-DNM is a very powerful inhibitor of the non-lysosomal glucosylceramidase at nanomolar concentrations. At such concentrations, the lysosomal glucocerebrosidase and alpha-glucosidase, the glucosylceramide synthase, and the N-linked glycan-trimming alpha-glucosidases of the endoplasmic reticulum are not affected.     

Clinical applications of detecting dysfunctional p53 tumor suppressor protein

The p53 gene encodes for a protein, p53, which plays a critical role in controlling the cell cycle, in DNA repair and in programmed cell death (apoptosis). p53 is one of the most frequently mutated genes in human neoplasms and a variety of techniques have been developed to detect these mutations. These range from advanced molecular-genetic analyses to immunohistochemical staining for the p53 protein. This review will summarize our current understanding of the function of p53 as well as current methods to detect dysfunctional p53 and the clinical value of such analyses.     

Correlation of chemiluminescent parameters of blood in non-irradiated animals with their survival after irradiation

Blood chemiluminescence is a reflection of the free radical oxidation process in every organism. The changes of its intensity, as a consequence of changes in the rate of this process, are connected, in its turn, with the changes, in the functional state of the organism. It is supposed that the differences in the radiosensitivity depend on the conditions in which free radical oxidation processes take place. Therefore, the indices of blood chemiluminescence of intact rats have been studied. The aim of the investigation is to find the correlations between these indices and the survival of animals irradiated with gamma-quantas in doses of 3.5, 7.0 and 9.0 Gr. It is established that the coefficients of the reaction rate (k1, k2 and k3) most reliably correlate with survival, whereas no correlation is observed between the other indices of chemiluminescence and survival.     

Cognitive resource demands of reading normal and transformed typography.

Tested the hypothesis that reading sentences presented in transformed typography involves cognitive processes that may not be involved in, or may be automatized during, the reading of normal typography, thus causing superior memory for the transformed sentences. In 2 experiments, 48 undergraduates read normal and inverted sentences while performing a secondary auditory task. Secondary task performance suffered reliably more when the task was carried out while reading transformed as opposed to normal typography. The size of this effect was consistent across the 2 experiments. It is concluded that greater attention demands may be associated with the additional processes invoked when reading transformed typography. Differences in procedures involved in encoding normal and transformed sentences are considered. (French abstract) (26 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Fast Li+ conduction in fluoroborate glasses

Following recent measurements of very high d.c. conductivities in complex Li fluoride-borate-sulfate glasses, we have performed systematic measurements in the Li₂OLiFB₂O₃ system. All glasses studied have essentially the same Arrhenius pre-exponential constant. Converting the data to conductivity relaxation times the pre-exponential constant corresponds to a frequency considerably higher than the Li⁺ - cage “rattling” frequency. Connections between the a.c. conductivity and the IR absorptivity are discussed.     

Phosphoprotein isotope-coded affinity tags: application to the enrichment and identification of low-abundance phosphoproteins

The use of a phosphoprotein isotope-coded affinity tag (PhIAT), which employs differential isotopic labeling and biotinylation, has been shown capable of enriching and identifying mixtures of low-abundance phosphopeptides. A denatured solution of beta-casein was labeled using the PhIAT method, and after proteolytic digestion, the labeled peptides were isolated using immobilized avidin. The recovered peptides were separated by capillary reversed-phase liquid chromatography and identified by tandem mass spectrometry. PhIAT-labeled peptides corresponding to known O-phosphorylated peptides from beta-casein were identified along with the phosphorylated peptides from alphas1-casein and alphas2-casein, known low-level (<5%) contaminants of commercially available beta-casein. All of the casein-phosphorylated residues identified by the present PhIAT approach correspond to previously documented sites of phosphorylation. The results illustrate the efficacy of the PhIAT-labeling strategy to not only enrich mixtures for phosphopeptides but also, more importantly, permit the detection and identification of low-level phosphopeptides. In addition, the differences in the phosphorylation state could be determined between phosphopeptides in comparative samples by stoichiometric conversion using the light and heavy isotopic versions of the PhIAT reagents. Overall, our results exemplify the application of the PhIAT approach and demonstrate its utility for proteome-wide phosphoprotein identification and quantitation.