The glycoprotein-hormones activin A and inhibin A interfere with dendritic cell maturation

<p>Abstract</p> <p>Background</p> <p>Pregnancy represents an exclusive situation in which the immune and the endocrine system cooperate to prevent rejection of the embryo by the maternal immune system. While immature dendritic cells (iDC) in the early pregnancy decidua presumably contribute to the establishment of peripheral tolerance, glycoprotein-hormones of the transforming growth factor beta (TGF-beta) family including activin A (ActA) and inhibin A (InA) are candidates that could direct the differentiation of DCs into a tolerance-inducing phenotype.</p> <p>Methods</p> <p>To test this hypothesis we generated iDCs from peripheral-blood-monocytes and exposed them to TGF-beta1, ActA, as well as InA and Dexamethasone (Dex) as controls.</p> <p>Results</p> <p>Both glycoprotein-hormones prevented up-regulation of HLA-DR during cytokine-induced DC maturation similar to Dex but did not influence the expression of CD 40, CD 83 and CD 86. Visualization of the F-actin cytoskeleton confirmed that the DCs retained a partially immature phenotype under these conditions. The T-cell stimulatory capacity of DCs was reduced after ActA and InA exposure while the secretion of cytokines and chemokines was unaffected.</p> <p>Conclusion</p> <p>These findings suggest that ActA and InA interfere with selected aspects of DC maturation and may thereby help preventing activation of allogenic T-cells by the embryo. Thus, we have identified two novel members of the TGF-beta superfamily that could promote the generation of tolerance-inducing DCs.</p

Molecular targets in the discovery and development of novel antimetastatic agents: current progress and future prospects

Tumour invasion and metastasis have been recognized as major causal factors in the morbidity and mortality among cancer patients. Many advances in the knowledge of cancer metastasis have yielded an impressive array of attractive drug targets, including enzymes, receptors and multiple signalling pathways. The present review summarizes the molecular pathogenesis of metastasis and the identification of novel molecular targets used in the discovery of antimetastatic agents. Several promising targets have been highlighted, including receptor tyrosine kinases, effector molecules involved in angiogenesis, matrix metalloproteinases (MMPs), urokinase plasminogen activator, adhesion molecules and their receptors, signalling pathways (e.g. phosphatidylinositol 3-kinase, phospholipase Cγ1, mitogen-activated protein kinases, c-Src kinase, c-Met kinases and heat shock protein. The discovery and development of potential novel therapeutics for each of the targets are also discussed in this review. Among these, the most promising agents that have shown remarkable clinical outcome are anti-angiogenic agents (e.g. bevacizumab). Newer agents, such as c-Met kinase inhibitors, are still undergoing preclinical studies and are yet to have their clinical efficacy proven. Some therapeutics, such as first-generation MMP inhibitors (MMPIs; e.g. marimastat) and more selective versions of them (e.g. prinomastat, tanomastat), have undergone clinical trials. Unfortunately, these drugs produced serious adverse effects that led to the premature termination of their development. In the future, third-generation MMPIs and inhibitors of signalling pathways and adhesion molecules could form valuable novel classes of drugs in the anticancer armamentarium to combat metastasis

Globalisation and finance

This lecture was delivered by Dr Prakash Apte during the First NIAS-DST Training Programme on ‘Impact of Globalisation’ held during October 20-24, 200

FINANCING TRANSPORTATION IN FISCALLY CONSTRAINED TIMES: TRANSPORTATION STRATEGIES FOR MUMBAI, INDIA.

The strategy detailed in this paper proposes to build on the current strengths of the existing transportation network, optimize its utilization, convert the threats into opportunities and shun the temptation to make Mumbai look like Shanghai or Singapore by taking up grandiose projects like trans- harbor sea links, elevated light rail or ‘Sky bus’ projects. In fiscally constrained times, the only alternative is to OPTIMIZE available infrastructure to; double the capacity of suburban trains with double decker coaches and bus service by dedicated bus lanes that can transform into light rail tracks in future; restrict entry of private cars in the city by area licensing, and prohibit cars 2 days a week; initiate ‘Park & Ride’ schemes at rail stations and bus depots, facilitate pedestrians and two wheelers for the east-west traffic, construct elevated pedestrian walkways as extensions of the foot over bridges at rail stations; provide a satellite air terminal in south Mumbai; reconsider construction of the Trans-Harbour link bridge using the investment instead for creation of employment opportunities on the mainland and construct a ‘calm sea channel’ along the west coast instead of the west island expressway, to facilitate plying of ferries all the year round

Global Business Finance

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Novel cantilever for biosensing applications

Chemomechanical actuation of a microcantilever beam induced by biomolecular binding such as DNA hybridization and antibody-antigren binding is an important principle useful in biosensing applications. As the magnitude of the forces involved is very small, increasing the sensitivity of the microcantilever beams involved is a priority. In this paper we are considering to achieve this by structural variation of the cantilevers. Merely decreasing the thickness of the microcantilever may improve the sensitivity, but it gives rise to the disadvantages of 'arching' and lesser reliability due to greater probability of defects during fabrication. We consider a 'ribbed' cantilever that eliminates the disadvantages while improving the sensitivity simultaneously. Simulations for validation have been performed using the finite element analysis software ANSYS 8.0. The simulations reveal that a ribbed microcantilever is almost as sensitive as a thin cantilever and has relatively very low arching effect. Simulations also reveal that higher the arching lower is the sensitivity

High yield polymer MEMS process for CMOS/MEMS integration

MEMS community is increasingly using SU-8 as a structural material because it is self-patternable, compliant and needs a low thermal budget. While the exposed layers act as the structural layers, the unexposed SU-8 layers can act as the sacrificial layers, thus making it similar to a surface micromachining process. A sequence of exposed and unexposed SU-8 layers should lead to the development of a SU-8 based MEMS chip integrated with a pre-processed CMOS wafer. A process consisting of optical lithography to obtain SU-8 structures on a CMOS wafer is described in this paper