Mesothelioma Tumor Cells Modulate Dendritic Cell Lipid Content,Phenotype and Function

Dendritic cells (DCs) play an important role in the generation of anti-cancer immune responses, however there is evidence that DCs in cancer patients are dysfunctional. Lipid accumulation driven by tumor-derived factors has recently been shown to contribute to DC dysfunction in several human cancers, but has not yet been examined in mesothelioma. This study investigated if mesothelioma tumor cells and/or their secreted factors promote increases in DC lipid content and modulate DC function. Human monocyte-derived DCs (MoDCs) were exposed to human mesothelioma tumor cells and tumor-derived factors in the presence or absence of lipoproteins. The data showed that immature MoDCs exposed to mesothelioma cells or factors contained increased lipid levels relative to control DCs. Lipid accumulation was associated with reduced antigen processing ability (measured using a DQ OVA assay), upregulation of the co-stimulatory molecule, CD86, and production of the tolerogenic cytokine, IL-10. Increases in DC lipid content were further enhanced by co-exposure to mesothelioma-derived factors and triglyceride-rich lipoproteins, but not low-density lipoproteins. In vivo studies using a murine mesothelioma model showed that the lipid content of tumor-infiltrating CD4⁺CD8α^- DCs, CD4^-CD8α^- DCs DCs and plasmacytoid DCs increased with tumor progression. Moreover, increasing tumor burden was associated with reduced proliferation of tumor-antigen-specific CD8⁺ T cells in tumor-draining lymph nodes. This study shows that mesothelioma promotes DC lipid acquisition, which is associated with altered activation status and reduced capacity to process and present antigens, which may impair the ability of DCs to generate effective anti mesothelioma T cell responses.     

Antimicrobial activity and cytotoxicity trait of a bioactive peptide purified from Lactococcus garvieae subsp. bovis BSN307T

A bioactive peptide of 8595 Da was purified from the cell free supernatant of Lactococcus garvieae subsp. bovis BSN307^T. MALDI MS/MS peptide mapping and the data base search displayed no significant similarity to any reported antimicrobial peptide of LAB. This peptide at a dose concentration of 200 µg ml⁻¹ inhibited the growth of both Gram-positive and Gram-negative bacteria by 58–89% and a dose of 500 µg ml⁻¹ scavenged 50% of DPPH-free radicals generated. Interestingly, cytotoxicity assay demonstrated that 17 µg ml⁻¹ of peptide selectively inhibited 50% proliferation of mammalian cancer cell lines HeLa and MCF-7 whereas normal H9c2 cells remained unaffected. Fluorescent microscopic analysis after DAPI nuclear staining of HeLa cells showed characteristics of apoptosis and activation of caspase-3 was ascertained by caspase-3 fluorescence assay.     

Alkaloids of the leaves of Voacanga grandifolia

Besides vobtusine and vobtusine-lactone, deoxyvobtusine was isolated from the leaves of Voacanga grandifolia (Miq. Rolfe. Spectral and chemical evi     

Development of an Automated and Sensitive Microfluidic Device for Capturing and Characterizing Circulating Tumor Cells (CTCs) from Clinical Blood Samples

Current analysis of circulating tumor cells (CTCs) is hindered by sub-optimal sensitivity and specificity of devices or assays as well as lack of capability of characterization of CTCs with clinical biomarkers. Here, we validate a novel technology to enrich and characterize CTCs from blood samples of patients with metastatic breast, prostate and colorectal cancers using a microfluidic chip which is processed by using an automated staining and scanning system from sample preparation to image processing. The Celsee system allowed for the detection of CTCs with apparent high sensitivity and specificity (94% sensitivity and 100% specificity). Moreover, the system facilitated rapid capture of CTCs from blood samples and also allowed for downstream characterization of the captured cells by immunohistochemistry, DNA and mRNA fluorescence in-situ hybridization (FISH). In a subset of patients with prostate cancer we compared the technology with a FDA-approved CTC device, CellSearch and found a higher degree of sensitivity with the Celsee instrument. In conclusion, the integrated Celsee system represents a promising CTC technology for enumeration and molecular characterization.     

Orthostatic hypotension,catecholamines, and alpha-adrenergic receptors in mitral valve prolapse.

The reported association of mitral valve prolapse with autonomic dysfunction and neuroendocrine abnormalities is derived from studies of patients selected because of symptoms or specifically referred for investigation. To determine whether such associations occur in nonreferred and unselected women with mitral valve prolapse, we measured blood pressure, heart rate, and norepinephrine response to standing in 13 volunteers with mitral valve prolapse and in 11 control subjects. Platelet alpha-adrenergic receptor quantity and affinity on standing also were determined in all persons. No significant differences were found between the groups in any of these measurements. Although small subsets of women with mitral valve prolapse may indeed have associated neuroendocrine epiphenomena and autonomic dysfunction, it is probably incorrect to generalize these findings to the vast spectrum of those with mitral valve prolapse.     

Evolution of tryptophan biosynthetic pathway in microbial genomes: a comparative genetic study

Biosynthetic pathway evolution needs to consider the evolution of a group of genes that code for enzymes catalysing the multiple chemical reaction steps leading to the final end product. Tryptophan biosynthetic pathway has five chemical reaction steps that are highly conserved in diverse microbial genomes, though the genes of the pathway enzymes show considerable variations in arrangements, operon structure (gene fusion and splitting) and regulation. We use a combined bioinformatic and statistical analyses approach to address the question if the pathway genes from different microbial genomes, belonging to a wide range of groups, show similar evolutionary relationships within and between them. Our analyses involved detailed study of gene organization (fusion/splitting events), base composition, relative synonymous codon usage pattern of the genes, gene expressivity, amino acid usage, etc. to assess inter- and intra-genic variations, between and within the pathway genes, in diverse group of microorganisms. We describe these genetic and genomic variations in the tryptophan pathway genes in different microorganisms to show the similarities across organisms, and compare the same genes across different organisms to find the possible variability arising possibly due to horizontal gene transfers. Such studies form the basis for moving from single gene evolution to pathway evolutionary studies that are important steps towards understanding the systems biology of intracellular pathways.     

Natural Conditions Override Differences in Emergence Rhythm among Closely Related Drosophilids

Previous studies on adult emergence rhythm of Drosophila melanogaster (DM) done under semi-natural conditions have shown that emergence is correlated to daily changes in temperature, humidity and light at dawn. Recently we showed that under laboratory conditions D. ananassae (DA), a closely related species of DM exhibits patterns in its activity/rest rhythm distinct from the latter. Here, we report the results of a study aimed at examining whether this difference in activity/rest rhythm among species extends to other circadian behaviours such as the adult emergence rhythm under a more natural environment with multiple cyclic time cues. We monitored the adult emergence rhythm of recently wild-caught DM and DA populations in parallel with those of a related species D. malerkotliana (DK), both in the laboratory and under semi-natural conditions. We find that although DM, DK and DA showed marked difference from one another under laboratory conditions, such differences were not detectable in the emergence behaviour of these three species under semi-natural conditions, and that they respond very similarly to seasonal changes in the environment. The results suggest that seasonal changes in temperature and humidity contribute largely to the variation in adult emergence waveform in terms of gate width, phase and amplitude of the peak and day-to-day variance in the timing of the emergence peak. In all three species, seasons with cooler and wetter conditions make the rhythm less tightly gated, with low amplitude peak and high day-to-day variation in timing of the peak of emergence. We show that in nature the emergence rhythm of DM, DK and DA is strongly influenced by environmental factors such that in a given season all of them exhibit similar time course and waveform and that with the changing season, they all modify their emergence patterns in a similar manner.     

Selection of Powdery Mildew and Yellow Mosaic-Resistant Greengram Plants Regenerated Through Organogenesis

Several regenerants through organogenesis were obtained in greengram ( Vigna radiata L. wilczek). Cytokinins appear to be important in inducing organogenesis and IAA induces root induction. Heritable variations could be seen among organogenesis regenerants. Some of the regenerants showed resistance to powdery mildew while some others showed resistance to yellow mosaic virus disease. The disease resistant characters were stable also in R 3 and R 4 generations.