Implication of BBM lipid composition and fluidity in mitigated alkaline phosphatase activity in renal cell carcinoma

Previous study has documented reduced alkaline phosphatase (ALP) activity in brush border membrane (BBM) isolated from renal cell carcinoma (RCC). Diminished activity of ALP is associated with alteration in both increased K (m) as well as decreased V (max) of enzyme suggests that there may be a change in the conformation of enzyme as well as decreased number of ALP active molecules. The present study was conducted to find out any role of BBM lipid composition and its fluidity in diminished activity of alkaline phosphatase in renal cell carcinoma. Total phospholipids and glycolipids were significantly augmented in BBM from RCC as compared to control. Fractional analysis of total phospholipids revealed significantly increased phosphatidylethanolamine. Decreased fractions of sphingomyelin and phosphatidylinositol were observed. Cholesterol-to-total phospholipid molar ratios in tumor BBM was a significantly lower in tumor BBM. A significant reduction in polarization and microviscosity was found in BBM from RCC. Therefore, we conclude that alteration in membrane lipid composition and fluidity may play a substantial role in reduced activity of ALP in RCC.     

Interferon stimulated gene 15 (ISG15): Molecular characterization and expression profile in endometrium of buffalo (Bubalus bubalis)

A sequential medium was evaluated on the survival, activation and growth rates of caprine preantral follicles submitted to a long-term culture period, aiming to establish an ideal in vitro culture system. Ovarian fragments were cultured for 16 days in α-MEM(+) alone or supplemented with hormones (GH and/or FSH) added sequentially on different days of culture. Ovarian fragments were cultured in the first (days 0-8) and second (days 8-16) halves of the culture period, generating 10 treatments: α-MEM(+)/α-MEM(+), FSH/FSH, FSH/GH, FSH/FSH+GH, GH/GH, GH/FSH, GH/FSH+GH, FSH+GH/FSH+GH, FSH+GH/FSH and FSH+GH/GH. Follicle morphology, viability and ultrastructure were analyzed. After day 1 of culture, FSH treatments maintained the percentage of normal follicles similar to the fresh control. At day 16 of culture, the treatment FSH/GH showed the highest (P<0.05) percentage of normal follicles. The ultrastructure of follicles was preserved in the fresh control and FSH/GH treatment. Follicles cultured with FSH/GH had a higher (P<0.05) viability than α-MEM(+); however the viability was lower (P<0.05) when compared to the fresh control. The FSH/GH treatment showed the highest (P<0.05) percentage of follicular activation and secondary follicle formation and produced the largest (P<0.05) mean follicular diameter after 16 days of culture. In conclusion, a sequential medium supplemented with FSH followed by GH during a long-term culture maintains the survival, viability and ultrastructure of goat preantral follicles, and promotes activation and secondary follicles.     

A protective role for human IL-10-expressing CD4+ T cells in colitis

IL-10 is an immunoregulatory cytokine expressed by numerous cell types. Studies in mice confirm that different IL-10-expressing cell subsets contribute differentially to disease phenotypes. However, little is known about the relationship between cell- or tissue-specific IL-10 expression and disease susceptibility in humans. In this study, we used the previously described human (h)IL10BAC transgenic model to examine the role of hIL-10 in maintaining intestinal homeostasis. Genomically controlled hIL-10 expression rescued Il10(-/-) mice from Helicobacter-induced colitis and was associated with control of proinflammatory cytokine expression and Th17 cell accumulation in gut tissues. Resistance to colitis was associated with an accumulation of hIL-10-expressing CD4(+)Foxp3(+) regulatory T cells specifically within the lamina propria but not other secondary lymphoid tissues. Cotransfer of CD4(+)CD45RB(lo) cells from Il10(-/-)/hIL10BAC mice rescued Rag1(-/-) mice from colitis, further suggesting that CD4(+) T cells represent a protective source of hIL-10 in the colon. In concordance with an enhanced capacity to express IL-10, CD4(+)CD44(+) T cells isolated from the lamina propria exhibited lower levels of the repressive histone mark H3K27Me3 and higher levels of the permissive histone mark acetylated histone H3 in both the human and mouse IL10 locus compared with the spleen. These results provide experimental evidence verifying the importance of T cell-derived hIL-10 expression in controlling inflammation within the colonic mucosa. We also provide molecular evidence suggesting the tissue microenvironment influences IL-10 expression patterns and chromatin structure in the human (and mouse) IL10 locus.     

Synthesis, characterization and in vitro biological evaluation of some novel diarylsulfonylureas as potential cytotoxic and antimicrobial agents

A series of novel diarylsulfonylureas (1-28) have been synthesized and characterized by FTIR, (1)H NMR, (13)C NMR and LC mass spectral analysis. All the synthesized compounds were evaluated for their in vitro cytotoxicity and antimicrobial activities. Among the tested compounds for cytotoxicity using Brine Shrimp Lethality assay, compounds 18 and 22 exhibited significant cytotoxicity at ED(50) values 3.96±0.21 and 4.02±0.19μg/mL, respectively. This level of activity was found comparable to that of the reference drug podophyllotoxin with ED(50) value 3.61±0.17μg/mL and it could be a remarkable starting point to develop new lead molecules with major cytotoxicity. Antimicrobial activity was screened using agar well diffusion assay method against selected Gram-positive, Gram-negative and fungal strains. Most of the compounds showed promising antibacterial and antifungal activity and the activity expressed as the minimum inhibitory concentration (MIC) in μg/mL.     

A DNA-Damage Selective Role for BRCA1 E3 Ligase in Claspin Ubiquitylation,CHK1 Activation,and DNA Repair

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Highlights? BRCA1 E3 ligase activity is essential for a subset of DNA damage responses ? BRCA1 V26A mutant cells are sensitive to topoisomerase inhibitors but not mitomycin C ? BRCA1 selectively ubiquitylates claspin after topoisomerase inhibition ? BRCA1 E3 ligase inactivation selectively impairs CHK1 activation     

Forward dynamic optimization of handle path and muscle activity for handle based isokinetic wheelchair propulsion: A simulation study

Push-rim wheelchair propulsion is biomechanically inefficient and physiologically stressful to the musculoskeletal structure of human body. This study focuses to obtain a new, optimized propulsion shape for wheelchair users, which is within the ergonomic ranges of joint motion, thus reducing the probability of injuries. To identify the propulsion movement, forward dynamic optimization was performed on a 3D human musculoskeletal model linked to a handle based propulsion mechanism, having shape and muscle excitations as optimization variables. The optimization resulted in a handle path shape with a circularity ratio of 0.95, and produced a net propulsion power of 34.7 watts for an isokinetic propulsion cycle at 50?rpm. Compared to push-rim propulsion, the compact design of the new propulsion mechanism along with the ergonomically optimized propulsion shape may help to reduce the risk of injuries and thus improve the quality of life for wheelchair users.     

Plant endemism in the Nepal Himalayas and phytogeographical implications

Nepal is located in the central part of the greater Himalayan range with a unique series of mountain chains formed by recent mountain building geological events. As one of the youngest mountains in the world it contributes to diversity of plants and also provided barriers to and corridors through which plants migrated during the ice ages. The higher altitudinal variation with the high mountains, deep river valleys and lowland plains combine with the effects of the summer monsoon and dry winter result with an extraordinary diversity of ecosystems including flora and fauna in a relatively small land area. The existing checklists for Nepal record some 6000 species of flowering plants and about 530 ferns. However, the botanical experts estimate that numbers may go up to 7000 when the poorly known remote regions are fully explored. The information on plant endemism in Nepal Himalaya is not adequately known as Nepal is still struggling to complete long awaited Flora of Nepal project. Endemic species are confined to specific areas and are the first to be affected by land use and other global changes. We sought to explore the spatial distribution of endemic plant species in Nepal in relation to the consequences associated with climatic and geologic changes over time in the region with the help of published literature. It was found that the endemism showed marked spatial variation between open moist habitat and dry inner valleys, the former with higher endemism. The updated records showed 312 flowering plant species to be endemic to Nepal with higher endemism around the elevation of 3800e4200 m at sea level. The recent human population explosion, intensified deforestation, habitat fragmentation and modern day environmental changes are posing greater threats to endemic plant in Nepal. The conservation status and threats to these peculiar species are unknown. Nevertheless, environmental degradation and high poverty rates create a potent mix of threats to biodiversity in this landscape.     

Probing the iron-substrate orientation for taurine/alpha-ketoglutarate dioxygenase using deuterium electron spin echo envelope modulation spectroscopy

The structural relationship between substrate taurine and the non-heme Fe(II) center of taurine/alpha-ketoglutarate (alphaKG) dioxygenase (TauD) was measured using electron spin echo envelope modulation (ESEEM) spectroscopy. Studies were conducted on TauD samples treated with NO, cosubstrate alphaKG, and either protonated or specifically deuterated taurine. Stimulated echo ESEEM data were divided to eliminate interference from 1H and 14N modulations and accentuate modulations from 2H. For taurine that was deuterated at the C1 position (adjacent to the sulfonate group), 2H ESEEM spectra show features that arise from dipole-dipole and deuterium nuclear quadrupole interactions from a single deuteron. Parallel measurements taken for taurine deuterated at both C1 and C2 show an additional ESEEM feature at the deuterium Larmor frequency. Analysis of these data at field positions ranging from g = 4 to g = 2 have allowed us to define the orientation of substrate taurine with respect to the magnetic axes of the Fe(II)-NO, S = 3/2, paramagnetic center. These results are discussed in terms of previous X-ray crystallographic studies and the proposed catalytic mechanism for this family of enzymes.