Profound contrast adaptation early in the visual pathway

Prior exposure to a moving grating of high contrast led to a substantial and persistent reduction in the contrast sensitivity of neurons in the lateral geniculate nucleus (LGN) of macaque. This slow contrast adaptation was potent in all magnocellular (M) cells but essentially absent in parvocellular (P) cells and neurons that received input from S cones. Simultaneous recordings of M cells and the potentials of ganglion cells driving them showed that adaptation originated in ganglion cells. As expected from the spatiotemporal tuning of M cells, adaptation was broadly tuned for spatial frequency and lacked orientation selectivity. Adaptation could be induced by high temporal frequencies to which cortical neurons do not respond, but not by low temporal frequencies that can strongly adapt cortical neurons. Our observations confirm that contrast adaptation occurs at multiple levels in the visual system, and they provide a new way to reveal the function and perceptual significance of the M pathway.     

Inhibition of apoptosis blocks human motor neuron cell death in a stem cell model of spinal muscular atrophy

Spinal muscular atrophy (SMA) is a genetic disorder caused by a deletion of the survival motor neuron 1 gene leading to motor neuron loss, muscle atrophy, paralysis, and death. We show here that induced pluripotent stem cell (iPSC) lines generated from two Type I SMA subjects-one produced with lentiviral constructs and the second using a virus-free plasmid-based approach-recapitulate the disease phenotype and generate significantly fewer motor neurons at later developmental time periods in culture compared to two separate control subject iPSC lines. During motor neuron development, both SMA lines showed an increase in Fas ligand-mediated apoptosis and increased caspase-8 and-3 activation. Importantly, this could be mitigated by addition of either a Fas blocking antibody or a caspase-3 inhibitor. Together, these data further validate this human stem cell model of SMA, suggesting that specific inhibitors of apoptotic pathways may be beneficial for patients.     

A systems biology approach for the study of cumulative oncogenes with applications to the MAPK signal transduction pathway

The Extracellular signal Regulated Kinase (ERK) pathway is one of the most well-studied signaling pathways in cell cycle regulation. Disruption in the normal functioning of this pathway is linked to many forms of cancer. In a previous study [D.K. Pant, A. Ghosh, Automated oncogene detection in complex protein networks, with applications to the MAPK signal transduction pathway, Biophys. Chem. 113 (2005) 275-288.], we developed a novel approach to predict single point mutations that are likely to cause cellular transformation in signaling transduction networks. We have extended this method to study disparate pair mutation in enzyme/protein interactions and in expression levels in signal transduction pathway and have applied it to the MAPK signaling pathway to study how synergistic or cooperative mutation within signaling networks acts in unison to cause malignant transformation. The method provides a quantitative ranking of the modifier pair of ERK activation. It is seen that the highest ranking single point mutations comprise the highest ranking pair mutations. We validate some of our results with experimental literature on multiple mutations. A second order sensitivity analysis scheme is additionally used to determine the effect of correlations among mutations at different sites in the pathways.     

C-Phycocyanin-a novel protein from Spirulina platensis- In vivo toxicity,antioxidant and immunomodulatory studies

A pigment-protein highly dominant in Spirulina is known as C-Phycocyanin. Earlier, in vitro studies has shown that C-phycocyanin is having many biological activities like antioxidant and anti-inflammatory activities, antiplatelet, hepatoprotective, and cholesterol-lowering properties. Interestingly, there are scanty in vivo experimental findings on the immunomodulatory and antioxidant effects of C-phycocyanin. This work is aimed at in vivo evaluation of the effects of C-phycocyanin on immunomodulation and antioxidant potential in Balb/c mice. Our results of in vivo toxicity, immunomodulatory and antioxidant effects of C-Phycocyanin suggests that C-phycocyanin is very safe for consumption and having substantial antioxidant potential and also possess immunomodulatory activities in Balb/c mice in a dosage dependent manner. C-phycocyanin doesn’t cause acute and subacute toxicity in the animal model (male, Balb/c mice) studied. We have reported that C-phycocyanin exhibited in vivo immunomodulation performance in this animal model.     

Role of pentoxifylline in preventing radiation damage to epiphyseal growth plate chondrocytes.

Radiation therapy plays an important role as part of multimodality treatment for a number of childhood malignancies. The damaging effects of radiation on bone formation in children have been well documented. Recent work suggests that the postirradiation increase in cytosolic calcium is probably responsible for the deleterious effects of radiation on growth plate chondrocytes because it causes a specific suppression of the mitogen PTHrP. Using an in vitro model of avian growth plate chondrocytes, this study demonstrates that pentoxifylline is effective in increasing basal PTHrP mRNA levels and partially preventing the radiation-induced decrease in PTHrP mRNA. This effect of pentoxifylline is probably due to its ability to lower basal levels of cytosolic calcium and the radiation-induced increase in cytosolic calcium in chondrocytes. Pentoxifylline also prevented the radiation-induced decreases in [3H]thymidine uptake and BCL2 and PTHrP receptor mRNA levels in chondrocytes. The effects of pentoxifylline appear to be specific for the PTHrP signaling pathway because it did not alter basal TGFB mRNA levels or TGFB mRNA expression in irradiated chondrocytes. The results of the current study suggest that by decreasing basal cytosolic calcium levels and curtailing the radiation-induced increase in cytosolic calcium levels in chondrocytes, pentoxifylline is able to sustain PTHrP signaling in chondrocytes and maintains the proliferative signal that is necessary to prevent chondrocytes from undergoing apoptosis.     

CROSS-REACTIVITY OF ANTIBODIES TO HUMAN ANTIGENS WITH TISSUES OF THE BOTTLENOSE DOLPHIN, TURSIOPS TRUNCATUS, USING IMMUNOPEROXIDASE TECHNIQUES

Cross-species reactivity of 53 antibodies developed against human antigens was evaluated in the bottlenose dolphin Tursiops truncatus , using immunoperoxidase techniques, Strong cross-reactivity was demonstrated with antibodies against intermediate filaments, most hormones, but few leukocyte antigens. S100, NSE, F8RA, Factor XIIIa, and lactalbumin antibodies reacted, while HMB45, EMA, PLAP, and PSA did not. Polyclonal antibodies are much more likely to cross-react than are monoclonal antibodies. Twenty-four of 30 (80%) of polyclonals cross-reacted, while only 10 of 23 (43.5%) monoclonals cross-reacted. Some antigens are demonstrated only after using a special technique to unmask the antigen.