Neurotrophic effects of conditioned media of astrocytes isolated from different brain regions on hippocampal and cortical neurons

The present study was designed to reveal whether astroglial cells from different brain regions produce diffusible factors that differentially support the survival of neurons and the establishment of neuronal morphology. For this purpose, astrocyte conditioned media (ACM) were prepared by conditioning chemically-defined medium with type I astrocyte culture dissociated from cerebral cortex, hippocampus and hypothalamus. Hippocampal and cortical neurons were cultured in ACM or in non-conditioned medium. ACM derived from three brain regions all supported the survival of hippocampal and cortical neurons better than non-conditioned control medium. Of these, hypothalamic ACM was the most effective in supporting the survival of cortical neurons. The ACM also potentiated the elongation of the longest neurite of hippocampal and cortical neurons. However, there were no significant differences in the promoting effects on neurite elongation among ACM from three brain regions.     

Specific antigen-Ia activation of transfected human T cells expressing murine Ti alpha beta-human T3 receptor complexes

The genes encoding the alpha and beta chains of the T-cell receptor (Ti) of an antigen-specific, Ia-restricted murine T-cell hybridoma were introduced into T3-positive or T3-negative human T cells. The resultant transfectants express either mouse-human or mouse-mouse Ti alpha beta molecules functionally associated with the human T3 complex. Only the complete murine Ti alpha beta dimer mediates specific functional corecognition of the appropriate antigen-Ia pair.     

Toxic metabolites ofAspergillus candidus

Zusammenfassung Zwei neue Toxine wurden aus den Mycelien und dem Zuchtmedium eines Schimmelpilzes,Aspergillus candidus, sowie aus dem experimentell mit demselben Pilz verschimmelten polierten Reis isoliert. Die beiden Substanzen sind sowohl chemisch als auch toxikologisch voneinander völlig verschieden.     

Helicobacter pylori CagA targets PAR1/MARK kinase to disrupt epithelial cell polarity

Helicobacter pylori cagA-positive strains are associated with gastritis, ulcerations and gastric adenocarcinoma. CagA is delivered into gastric epithelial cells and, on tyrosine phosphorylation, specifically binds and activates the SHP2 oncoprotein, thereby inducing the formation of an elongated cell shape known as the 'hummingbird' phenotype. In polarized epithelial cells, CagA also disrupts the tight junction and causes loss of apical-basolateral polarity. We show here that H. pylori CagA specifically interacts with PAR1/MARK kinase, which has an essential role in epithelial cell polarity. Association of CagA inhibits PAR1 kinase activity and prevents atypical protein kinase C (aPKC)-mediated PAR1 phosphorylation, which dissociates PAR1 from the membrane, collectively causing junctional and polarity defects. Because of the multimeric nature of PAR1 (ref. 14), PAR1 also promotes CagA multimerization, which stabilizes the CagA-SHP2 interaction. Furthermore, induction of the hummingbird phenotype by CagA-activated SHP2 requires simultaneous inhibition of PAR1 kinase activity by CagA. Thus, the CagA-PAR1 interaction not only elicits the junctional and polarity defects but also promotes the morphogenetic activity of CagA. Our findings revealed that PAR1 is a key target of H. pylori CagA in the disorganization of gastric epithelial architecture underlying mucosal damage, inflammation and carcinogenesis.     

Magnetic properties of perpendicularly orientated L1<Subscript>0</Subscript> FePt nanoparticles

L10 FePt films were deposited on MgO (001) substrates heated to 700°C by magnetron sputtering.Assisted by the misfit of lattice between film and substrate,strong (001) texture was formed.The film at nominal thickness t N=5 nm was composed of nanoparticles with a size of～70 nm,and showed a high coercivity of～105 kOe at 4.2 K.At t N=～50 nm,as the film changed from discontinuous to continuous,the coercivity dropped about one order of magnitude.Micromagnetic simulation implies that the magnetization reversal is...     

Mutations affecting components of the SWI/SNF complex cause Coffin-Siris syndrome

By exome sequencing, we found de novo SMARCB1 mutations in two of five individuals with typical Coffin-Siris syndrome (CSS), a rare autosomal dominant anomaly syndrome. As SMARCB1 encodes a subunit of the SWItch/Sucrose NonFermenting (SWI/SNF) complex, we screened 15 other genes encoding subunits of this complex in 23 individuals with CSS. Twenty affected individuals (87%) each had a germline mutation in one of six SWI/SNF subunit genes, including SMARCB1, SMARCA4, SMARCA2, SMARCE1, ARID1A and ARID1B.     

Dissociation of phosphoinositide hydrolysis and Ca2+ fluxes from the biological responses of a T-cell hybridoma

T lymphocytes can be activated in a variety of ways, including occupancy of the T cell antigen receptor (TCR) complex or cross-linking of certain cell-surface molecules with antibody. Two of the earliest events seen after stimulation are the hydrolysis of phosphatidylinositol bisphosphate to inositol trisphosphate (Ins P3) and 1,2-diacylglycerol (DAG), and an increase in the concentration of intracellular Ca2+ ([Ca2+]i). Later, the cell secretes lymphokines and expresses lymphokine receptors. It has been postulated that the products of the hydrolysis of phosphatidylinositols (Ptd Ins) and fluctuations in [Ca2+]i are critical 'second messengers', transmitting the signals for the initiation of the later events. We have examined the relationship between these second messengers and the secretion of IL-2 in a murine T cell variant whose missing TCR complex had been reconstituted by gene transfer. Surprisingly, although the IL-2 responses of the transfectant could not be distinguished from the original line expressing the same TCR, Ptd Ins hydrolysis and the increase in [Ca2+]i were substantially reduced or absent in the reconstituted cell. It is therefore possible to dissociate these early biochemical changes from a late biological response, raising questions about the putative causal relationship of these events.