Engaging with sustainability issues in metropolitan Chennai : city report

Chennai is the largest metropolitan city in South India (8.7 million in 2011) and the provincial capital of the large state of Tamil Nadu (population 72 million in 2011). Before that, under British rule, the city was the capital of the Madras Presidency, and was known as Madras until 1996, when the name was officially changed to Chennai. Located on the east coast of India, on the Bay of Bengal, sea trade has been an important aspect of the regional economy since at least the colonial period. Still today, the city combines political functions with economic command functions for both manufacturing and services, reflecting the region's diversified economy. The Chennai metropolitan area has witnessed strong growth over the last 20 years in automobile manufacturing, software services, hardware manufacturing, healthcare and financial services (CDP 2009). However, it should be noted that only 30% of total employment in the city takes place in the formal sector i.e., is covered by contracts and labour laws, the remaining 70% falls in the informal sector. This underscores the importance of small and micro enterprises and self-employment for providing goods, services and livelihoods in the local economy

Similar NF-κB Gene Signatures in TNF-α Treated Human Endothelial Cells and Breast Tumor Biopsies

BACKGROUND: Endothelial dysfunction has been implicated in the pathogenesis of diverse pathologies ranging from vascular and immune diseases to cancer. TNF-α is one of the mediators of endothelial dysfunction through the activation of transcription factors, including NF-κB. While HUVEC (macrovascular cells) have been largely used in the past, here, we documented an NF-κB gene signature in TNFα-stimulated microvascular endothelial cells HMEC often used in tumor angiogenesis studies. METHODOLOGY/PRINCIPAL FINDINGS: We measured mRNA expression of 55 NF-κB related genes using quantitative RT-PCR in HUVEC and HMEC. Our study identified twenty genes markedly up-regulated in response to TNFα, including adhesion molecules, cytokines, chemokines, and apoptosis regulators, some of them being identified as TNF-α-inducible genes for the first time in endothelial cells (two apoptosis regulators, TNFAIP3 and TNFRSF10B/Trail R2 (DR5), the chemokines GM-CSF/CSF2 and MCF/CSF1, and CD40 and TNF-α itself, as well as NF-κB components (RELB, NFKB1 or 50/p105 and NFKB2 or p52/p100). For eight genes, the fold induction was much higher in HMEC, as compared to HUVEC. Most importantly, our study described for the first time a connection between NF-κB activation and the induction of most, if not all, of these genes in HMEC as evaluated by pharmacological inhibition and RelA expression knock-down by RNA interference. Moreover, since TNF-α is highly expressed in tumors, we further applied the NF-κB gene signature documented in TNFα-stimulated endothelial cells to human breast tumors. We found a significant positive correlation between TNF and the majority (85 %) of the identified endothelial TNF-induced genes in a well-defined series of 96 (48 ERα positive and 48 ERα negative) breast tumors. CONCLUSION/SIGNIFICANCE: Taken together these data suggest the potential use of this NF-κB gene signature in analyzing the role of TNF-α in the endothelial dysfunction, as well as in breast tumors independently of the presence of ERα

The analysis of 2-amino-2-thiazoline-4-carboxylic acid in the plasma of smokers and non-smokers

ATCA (2-amino-2-thiazoline-4-carboxylic acid) is a promising marker to assess cyanide exposure because of several advantages of ATCA analysis over direct determination of cyanide and alternative cyanide biomarkers (i.e. stability in biological matrices, consistent recovery, and relatively small endogenous concentrations). Concentrations of ATCA in the plasma of smoking and non-smoking human volunteers were analyzed using gas-chromatography mass-spectrometry to establish the feasibility of using ATCA as a marker for cyanide exposure. The levels of ATCA in plasma of smoking volunteers, 17.2 ng/ml, were found to be significantly (p < 0.001) higher than that of non-smoking volunteers, 11.8 ng/ml. Comparison of ATCA concentrations of smokers relative to non-smokers in both urine and plasma yielded relatively similar results. The concentration ratio of ATCA for smokers versus non-smokers in plasma and urine was compared to similar literature studies of cyanide and thiocyanate, and correlations are discussed. This study supports previous evidence that ATCA can be used to determine past cyanide exposure and indicates that further studies should be pursued to validate the use of ATCA as a marker of cyanide exposure

Performance of the CMS Cathode Strip Chambers with Cosmic Rays

The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device in the CMS endcaps. Their performance has been evaluated using data taken during a cosmic ray run in fall 2008. Measured noise levels are low, with the number of noisy channels well below 1%. Coordinate resolution was measured for all types of chambers, and fall in the range 47 microns to 243 microns. The efficiencies for local charged track triggers, for hit and for segments reconstruction were measured, and are above 99%. The timing resolution per layer is approximately 5 ns

Synergy between medical informatics and bioinformatics: facilitating genomic medicine for future health care

Medical Informatics (MI) and Bioinformatics (BI) are two interdisciplinary areas located at the intersection between computer science and medicine and biology, respectively. Historically, they have been separated and only occasionally have researchers of both disciplines collaborated. The completion of the Human Genome Project has brought about in this post genomic era the need for a synergy of these two disciplines to further advance in the study of diseases by correlating essential genotypic information with expressed phenotypic information. Biomedical Informatics (BMI) is the emerging technology that aims to put these two worlds together in the new rising genomic medicine. In this regard, institutions such as the European Commission have recently launched several initiatives to support a new combined research agenda, based on the potential for synergism of both disciplines. In this paper we review the results the BIOINFOMED study one of these projects funded by the E

Performance and Operation of the CMS Electromagnetic Calorimeter

The operation and general performance of the CMS electromagnetic calorimeter using cosmic-ray muons are described. These muons were recorded after the closure of the CMS detector in late 2008. The calorimeter is made of lead tungstate crystals and the overall status of the 75848 channels corresponding to the barrel and endcap detectors is reported. The stability of crucial operational parameters, such as high voltage, temperature and electronic noise, is summarised and the performance of the light monitoring system is presented

Arabidopsis seed secrets unravelled after a decade of genetic and omics-driven research

Seeds play a fundamental role in colonization of the environment by spermatophytes, and seeds harvested from crops are the main food source for human beings. Knowledge of seed biology is therefore important for both fundamental and applied issues. This review on seed biology illustrates the important progress made in the field of Arabidopsis seed research over the last decade. Access to ‘omics’ tools, including the inventory of genes deduced from sequencing of the Arabidopsis genome, has speeded up the analysis of biological functions operating in seeds. This review covers the following processes: seed and seed coat development, seed reserve accumulation, seed dormancy and seed germination. We present new insights in these various fields and describe ongoing biotechnology approaches to improve seed characteristics in crops

Design of proteasome inhibitors with oral efficacy in vivo against Plasmodium falciparum and selectivity over the human proteasome

The Plasmodium falciparum proteasome is a potential antimalarial drug target. We have identified a series of amino-amide boronates that are potent and specific inhibitors of the P. falciparum 20S proteasome (Pf20S) beta5 active site and that exhibit fast-acting antimalarial activity. They selectively inhibit the growth of P. falciparum compared with a human cell line and exhibit high potency against field isolates of P. falciparum and Plasmodium vivax They have a low propensity for development of resistance and possess liver stage and transmission-blocking activity. Exemplar compounds, MPI-5 and MPI-13, show potent activity against P. falciparum infections in a SCID mouse model with an oral dosing regimen that is well tolerated. We show that MPI-5 binds more strongly to Pf20S than to human constitutive 20S (Hs20Sc). Comparison of the cryo-electron microscopy (EM) structures of Pf20S and Hs20Sc in complex with MPI-5 and Pf20S in complex with the clinically used anti-cancer agent, bortezomib, reveal differences in binding modes that help to explain the selectivity. Together, this work provides insights into the 20S proteasome in P. falciparum, underpinning the design of potent and selective antimalarial proteasome inhibitors

Dimeric SecA Couples the Preprotein Translocation in an Asymmetric Manner

The Sec translocase mediates the post-translational translocation of a number of preproteins through the inner membrane in bacteria. In the initiatory translocation step, SecB targets the preprotein to the translocase by specific interaction with its receptor SecA. The latter is the ATPase of Sec translocase which mediates the post-translational translocation of preprotein through the protein-conducting channel SecYEG in the bacterial inner membrane. We examined the structures of Escherichia coli Sec intermediates in solution as visualized by negatively stained electron microscopy in order to probe the oligomeric states of SecA during this process. The symmetric interaction pattern between the SecA dimer and SecB becomes asymmetric in the presence of proOmpA, and one of the SecA protomers predominantly binds to SecB/proOmpA. Our results suggest that during preprotein translocation, the two SecA protomers are different in structure and may play different roles