CD24 interacts with and promotes the activity of c-src within lipid rafts in breast cancer cells, thereby increasing integrin-dependent adhesion

Expression of the glycosylphosphatidylinositol-anchored membrane protein CD24 correlates with a poor prognosis for many human cancers, and in experimental tumors can promote metastasis. However, the mechanism by which CD24 contributes to tumor progression remains unclear. Here we report that in MTLy breast cancer cells CD24 interacts with and augments the kinase activity of c-src, a protein strongly implicated in promoting invasion and metastasis. This occurs within and is dependent upon intact lipid rafts. CD24-augmented c-src kinase activity increased formation of focal adhesion complexes, accelerated phosphorylation of FAK and paxillin and consequently enhanced integrin-mediated adhesion. Loss and gain of function approaches showed that c-src activity is necessary and sufficient to mediate the effects of CD24 on integrin-dependent adhesion and cell spreading, as well as on invasion. Together these results indicate that c-src is a CD24-activated mediator that promotes integrin-mediated adhesion and invasion, and suggest a mechanism by which CD24 might contribute to tumor progression through stimulating the activity of c-src or another member of the Src family.     

Neuronal synchrony does not correlate with motion coherence in cortical area MT

Natural visual scenes are cluttered with multiple objects whose individual features must somehow be selectively linked (or 'bound') if perception is to coincide with reality. Recent neurophysiological evidence supports a 'binding-by-synchrony' hypothesis: neurons excited by features of the same object fire synchronously, while neurons excited by features of different objects do not. Moving plaid patterns offer a straightforward means to test this idea. By appropriate manipulations of apparent transparency, the component gratings of a plaid pattern can be seen as parts of a single coherently moving surface or as two non-coherently moving surfaces. We examined directional tuning and synchrony of area-MT neurons in awake, fixating primates in response to perceptually coherent and non-coherent plaid patterns. Here we show that directional tuning correlated highly with perceptual coherence, which is consistent with an earlier study. Although we found stimulus-dependent synchrony, coherent plaids elicited significantly less synchrony than did non-coherent plaids. Our data therefore do not support the binding-by-synchrony hypothesis as applied to this class of motion stimuli in area MT.     

Über die Speicherung von Lipiden durch Knallgasbakterien

Summary The ability to accumulate lipids was investigated in two strains of hydrogen oxidizing bacteria (Hydrogenomonas H 16 and strain 11/x). Along with the deposition of poly--hydroxybutyrate the amount of other lipids is shown to increase 1.8 times in strain H 16. It is suggested that the increase of the latter lipids is due to the formation of membrane lipids that are needed for the formation of membranes around the intracellular globules of poly--hydroxybutyrate. In strain 11/x the amount of lipids increases 7 times along with the storage of carbohydrates. In this case, the majority of lipids consists of triglycerides. It is suggested that there is a true storage of neutral fat in strain 11/x.     

Heterozygous mutations in ANKH, the human ortholog of the mouse progressive ankylosis gene, result in craniometaphyseal dysplasia

Craniometaphyseal dysplasia (CMD) is a bone dysplasia characterized by overgrowth and sclerosis of the craniofacial bones and abnormal modeling of the metaphyses of the tubular bones. Hyperostosis and sclerosis of the skull may lead to cranial nerve compressions resulting in hearing loss and facial palsy. An autosomal dominant form of the disorder (MIM 123000) was linked to chromosome 5p15.2-p14.1 (ref. 3) within a region harboring the human homolog (ANKH) of the mouse progressive ankylosis (ank) gene. The ANK protein spans the outer cell membrane and shuttles inorganic pyrophosphate (PPi), a major inhibitor of physiologic and pathologic calcification, bone mineralization and bone resorption. Here we carry out mutation analysis of ANKH, revealing six different mutations in eight of nine families. The mutations predict single amino acid substitutions, deletions or insertions. Using a helix prediction program, we propose for the ANK molecule 12 membrane-spanning helices with an alternate inside/out orientation and a central channel permitting the passage of PPi. The mutations occur at highly conserved amino acid residues presumed to be located in the cytosolic portion of the protein. Our results link the PPi channel ANK with bone formation and remodeling.     

Decreased expression of N-myc precedes retinoic acid-induced morphological differentiation of human neuroblastoma

Proto-oncogenes may be important in the cellular processes central for the growth and differentiation of normal cells. N-myc is a DNA sequence which shares limited homology to the proto-oncogene c-myc and has been found to be amplified in both primary tissue and cell lines from neuroblastoma, a childhood tumour of neuroectodermal origin. Differentiation of this embryonal tumour is of clinical importance, since occasional tumours have been noted to differentiate in vivo to benign ganglioneuroma. In vitro, many human neuroblastoma cell lines can be induced to differentiate morphologically and biochemically by a variety of agents. Retinoic acid (RA), an analogue of vitamin A, has been shown to inhibit neuroblastoma cell growth and clonability in soft agar, and to induce extensive neurite outgrowth. Therefore we examined the relationship of N-myc expression to the in vitro differentiation of these cells. We report here that in the case of RA-induced differentiation, a decreased level of expression is detected within 6 h of treatment and precedes both cell-cycle changes and morphological differentiation.