AKT as locus of cancer angiogenic robustness and fragility

Angiogenesis get full robustness in metastatic cancer, relapsed leukemia or lymphoma when complex positive feedback loop signaling systems become integrative. A cancer hypoxic microenvironment generates positive loops inducing formation of the vascular functional shunts. AKT is an upstream angiogenic locus of integrative robustness and fragility activated by the positive loops. AKT controls two downstream nodes the mTOR and NOS in nodal organization of the signaling genes. AKT phosphorylation is regulated by a balance of an oxidant/antioxidant. Targeting AKT locus represents new principle to control integrative angiogenic robustness by the locus chemotherapy. J. Cell. Physiol. 228: 21–24, 2013. © 2012 Wiley Periodicals, Inc.     

Ataxia-telangiectasia: Linkage analysis in highly inbred Arab and Druze families and differentiation from an ataxia-microcephaly-cataract syndrome

Summary Ataxia-telangiectasia (A-T) is a progressive autosomal recessive disease featuring neurodegeneration, immunodeficiency, chromosomal instability, radiation sensitivity and a highly increased proneness to cancer. A-T is ethnically widespread and genetically heterogeneous, as indicated by the existence of four complementation groups in this disease. Several A-T-like genetic diseases share various clinical and cellular characteristics with A-T. By using linkage analysis to study North American and Turkish A-O families, the ATA (A-T, complementation group A) gene has been mapped to chromosome 11q23. A number of Israeli Arab A-T patients coming from large, highly inbred families were assigned to group A In one of these families, an additional autosomal recessive disease was identified, characterized by ataxia, hypotonia, microcephaly and bilateral congenital cataracts. In two patients with this syndrome, normal levels of serum immunoglobulins and alpha-fetoprotein, chromosomal stability in peripheral blood lymphocytes and skin fibroblasts, and normal cellular response to treatments with X-rays and the radiomimetic drug neocarzinostatin indicated that this disease does not share, with A-T, any additional features other than ataxia. These tests also showed that another patient in this family, who is also mentally retarded, is affected with both disorders. This conclusion was further supported by linkage analysis with 11q23 markers. Lod scores between A-O and these markers, cumulated over three large Arab families, were significant and confirmed the localization of the ATA gene to aq23. However, another Druze family unassigned to a specific complementation group, showed several recombinants between A-T and the same markers, leaving the localization of the A-T gene in this family open.     

The decolorization of the polymeric dye Poly-Blue (polyvinalamine sulfonate-anthroquinone) by lignin degrading fungi

Summary In this work we have investigated the decolorization of the polymeric dye Poly-B411 by several fungi. Only fungi with known lignin degrading ability were able to decolorize the dye. Pleurotus ostreatus sp. florida decolorized the dye both in solid and liquid media. Decolorizing ability developed in the absence of the dye but only when the fungus had been previously cultivated on lignin containing substrates.The work was supported by a grant from the Charles Wolfson Trust     

Cytoplasmic granule formation in mouse pancreatic acinar cells. Evidence for formation of immature granules (condensing vacuoles) by aggregation and fusion of progranules of unit size,and for reductions in membrane surface area and immature granule volume during granule maturation

We used a computer-assisted morphometry approach to analyze quantitatively the process of cytoplasmic granule formation in mouse pancreatic acinar cells stimulated with pilocarpine to induce secretion. Our findings suggest that each condensing vacuole/immature granule of pancreatic acinar cells is formed by the progressive aggregation of 106 to 128 unit progranules of narrowly fixed volume, define a range of 7.7 to 9.2 for the factor of volume condensation between the largest immature granules and the mature unit granule, and predict that the formation of a single mature unit granule by the aggregation and fusion of unit progranules involves a net reduction of at least 95% in the amount of membrane surface area associated with these structures.     

Growth inhibition of breast cancer cells induced by exogenous ATP

Addition of ATP (>0.1 mM) to cultures of human breast cancer T47D cells resulted in an inhibition of cell proliferation. The inhibition was found to be specific for ATP, and dependent on its concentration. Growth inhibition continued for at least three days, although ATP and its hydrolysis products were metabolized within one day. Conditioned medium from ATP-treated cultures (CM+) was found to inhibit the growth of cells that were not exposed to ATP. This is an indication that extracellular factors, besides ATP, are involved in the inhibition process. The inhibition was maintained after dialysis of the CM+, using an 8 kDa cut-off membrane. Conditioned medium from untreated cultures (CM-), however, only slightly affected cell growth. The data suggest that the CM+ -induced cell growth inhibition is mediated by an ATP-activated growth inhibiting factor. Flow microfluorometry and thymidine incorporation experiments have shown that the growth arrest is mainly due to the elongation of the S-phase of the cell cycle. © 1993 Wiley-Liss, Inc.     

Ultrastructure of human dermal mast cells in 29 different lysosomal storage diseases

The effect of lysosomal storage diseases on the ultrastructure of human mast cells has not previously been reported. Indeed, there has been little published evidence indicating that mast cells contain typical lysosomes. However, mast cell cytoplasmic granules contain hydrolases similar to those found in lysosomes, but which differ from lysosomal hydrolases in exhibiting optimal activity at higher pH. We therefore examined by transmission electron microscopy the dermal mast cells in 58 biopsies of patients exhibiting 1 of 29 different lysosomal storage diseases. We found mast cells containing abnormal lysosomes in 16 of these disorders. In 6 of these 16 diseases, the mast cells' cytoplasmic granules appeared normal. These observations indicate that human mast cells can contain lysosomes, and provide evidence that the enzymes affected by lysosomal storage diseases are active in mast cells.     

Maximal ecological diversity exceeds evolutionary diversity in model ecosystems

Understanding community saturation is fundamental to ecological theory. While investigations of the diversity of evolutionary stable states (ESSs) are widespread, the diversity of communities that have yet to reach an evolutionary endpoint is poorly understood. We use Lotka–Volterra dynamics and trait-based competition to compare the diversity of randomly assembled communities to the diversity of the ESS. We show that, with a large enough founding diversity (whether assembled at once or through sequential invasions), the number of long-time surviving species exceeds that of the ESS. However, the excessive founding diversity required to assemble a saturated community increases rapidly with the dimension of phenotype space. Additionally, traits present in communities resulting from random assembly are more clustered in phenotype space compared to random, although still markedly less ordered than the ESS. By combining theories of random assembly and ESSs we bring a new viewpoint to both the saturation and random assembly literature.     

Cloning and molecular characterization of a gene involved in Salmonella adherence and invasion of cultured epithelial cells

Our laboratories have independently identified a gene in Salmonella choleraesuis and Salmonella typhimurium that is necessary for efficient adherence and entry of these organisms into cultured epithelial cells. Introduction of a mutated gene into several Salmonella strains belonging to different serotypes rendered these organisms deficient for adherence and invasion of cultured cells. This effect was most pronounced in the host-adapted serotypes Salmonella gallinarum, S. choleraesuis, and Salmonella typhi. The nucleotide sequence of this gene, which we have termed invH, encodes a predicted 147-amino-acid polypeptide containing a signal sequence. The InvH predicted polypeptide is highly conserved in S. typhimurium and S. choleraesuis, differing at only three residues. The invH gene was expressed in Escherichia coli using a T7 RNA polymerase expression system and a polypeptide of ～16000 molecular weight was observed, in agreement with the predicted size of its gene product. Upon fractionation, the expressed polypeptide was localized in the bacterial membrane fraction. Southern and colony hybridization analyses indicated that the invH gene is present in all Salmonella strains tested (91 strains belonging to 37 serotypes) with the exception of strains of Salmonella arizonae. No homologous sequences were detected in Yersinia, Shigella, Proteus, and several strains of enteroinvasive and enteropathogenic E. coli. Downstream from the S. choleraesuis (but not S. typhimurium) invH gene, a region with extensive homology to the insertion sequence IS3 was detected.