The early transcriptomic response to interleukin 1β and interleukin 33 in rat neonatal cardiomyocytes

In the heart, inflammatory cytokines including interleukin (IL) 1β are implicated in regulating adaptive and maladaptive changes, whereas IL33 negatively regulates cardiomyocyte hypertrophy and promotes cardioprotection. These agonists signal through a common co-receptor but, in cardiomyocytes, IL1β more potently activates mitogen-activated protein kinases and NFκB, pathways that regulate gene expression. We compared the effects of external application of IL1β and IL33 on the cardiomyocyte transcriptome. Neonatal rat cardiomyocytes were exposed to IL1β or IL33 (0.5, 1 or 2h). Transcriptomic profiles were determined using Affymetrix rat genome 230 2.0 microarrays and data were validated by quantitative PCR. IL1β induced significant changes in more RNAs than IL33 and, generally, to a greater degree. It also had a significantly greater effect in downregulating mRNAs and in regulating mRNAs associated with selected pathways. IL33 had a greater effect on a small, select group of specific transcripts. Thus, differences in intensity of intracellular signals can deliver qualitatively different responses. Quantitatively different responses in production of receptor agonists and transcription factors may contribute to qualitative differences at later times resulting in different phenotypic cellular responses.

Phosphorylation of the voltage-gated potassium channel Kv2.1 by AMP-activated protein kinase regulates membrane excitability

Firing of action potentials in excitable cells accelerates ATP turnover. The voltage-gated potassium channel Kv2.1 regulates action potential frequency in central neurons, whereas the ubiquitous cellular energy sensor AMP-activated protein kinase (AMPK) is activated by ATP depletion and protects cells by switching off energy-consuming processes. We show that treatment of HEK293 cells expressing Kv2.1 with the AMPK activator A-769662 caused hyperpolarizing shifts in the current-voltage relationship for channel activation and inactivation. We identified two sites (S440 and S537) directly phosphorylated on Kv2.1 by AMPK and, using phosphospecific antibodies and quantitative mass spectrometry, show that phosphorylation of both sites increased in A-769662-treated cells. Effects of A-769662 were abolished in cells expressing Kv2.1 with S440A but not with S537A substitutions, suggesting that phosphorylation of S440 was responsible for these effects. Identical shifts in voltage gating were observed after introducing into cells, via the patch pipette, recombinant AMPK rendered active but phosphatase-resistant by thiophosphorylation. Ionomycin caused changes in Kv2.1 gating very similar to those caused by A-769662 but acted via a different mechanism involving Kv2.1 dephosphorylation. In cultured rat hippocampal neurons, A-769662 caused hyperpolarizing shifts in voltage gating similar to those in HEK293 cells, effects that were abolished by intracellular dialysis with Kv2.1 antibodies. When active thiophosphorylated AMPK was introduced into cultured neurons via the patch pipette, a progressive, time-dependent decrease in the frequency of evoked action potentials was observed. Our results suggest that activation of AMPK in neurons during conditions of metabolic stress exerts a protective role by reducing neuronal excitability and thus conserving energy.

A dramatic isotope effect in the reaction of ClSiH with trimethylsilane-1-d: experimental evidence for intermediate complexes in silylene Si-H(D) insertion reactions

A kinetic isotope effect (kD/kH) of 7.4 has been found for the reaction of chlorosilylene with trimethysilane (Me3SiD vs Me3SiH). Such a value can be accounted for by theoretical modelling, but only if an internal rearrangement of the initially form complex is included in the mechanism. This provides the first concrete evidence for such complexes.

The GODAE high resolution sea surface temperature pilot project

Sea surface temperature (SST) measurements are required by operational ocean and atmospheric forecasting systems to constrain modeled upper ocean circulation and thermal structure. The Global Ocean Data Assimilation Experiment (GODAE) High Resolution SST Pilot Project (GHRSST-PP) was initiated to address these needs by coordinating the provision of accurate, high-resolution, SST products for the global domain. The pilot project is now complete, but activities continue within the Group for High Resolution SST (GHRSST). The pilot project focused on harmonizing diverse satellite and in situ data streams that were indexed, processed, quality controlled, analyzed, and documented within a Regional/Global Task Sharing (R/GTS) framework implemented in an internationally distributed manner. Data with meaningful error estimates developed within GHRSST are provided by services within R/GTS. Currently, several terabytes of data are processed at international centers daily, creating more than 25 gigabytes of product. Ensemble SST analyses together with anomaly SST outputs are generated each day, providing confidence in SST analyses via diagnostic outputs. Diagnostic data sets are generated and Web interfaces are provided to monitor the quality of observation and analysis products. GHRSST research and development projects continue to tackle problems of instrument calibration, algorithm development, diurnal variability, skin temperature deviation, and validation/verification of GHRSST products. GHRSST also works closely with applications and users, providing a forum for discussion and feedback between SST users and producers on a regular basis. All data within the GHRSST R/GTS framework are freely available. This paper reviews the progress of GHRSST-PP, highlighting achievements that have been fundamental to the success of the pilot project.

Catch-up strategies in the Indian auto components industry: domestic firms’ responses to market liberalization

Market liberalization in emerging-market economies and the entry of multinational firms spur significant changes to the industry/institutional environment faced by domestic firms. Prior studies have described how such changes tend to be disruptive to the relatively backward domestic firms, and negatively affect their performance and survival prospects. In this paper, we study how domestic supplier firms may adapt and continue to perform, as market liberalization progresses, through catch-up strategies aimed at integrating with the industry's global value chain. Drawing on internalization theory and the literatures on upgrading and catch-up processes, learning and relational networks, we hypothesize that, for continued performance, domestic supplier firms need to adapt their strategies from catching up initially through technology licensing/collaborations and joint ventures with multinational enterprises (MNEs) to also developing strong customer relationships with downstream firms (especially MNEs). Further, we propose that successful catch-up through these two strategies lays the foundation for a strategy of knowledge creation during the integration of domestic industry with the global value chain. Our analysis of data from the auto components industry in India during the period 1992–2002, that is, the decade since liberalization began in 1991, offers support for our hypotheses.

Participatory crop improvement: the challenges of and opportunities for institutionalisation in the Indian public research sector

This thesis considers Participatory Crop Improvement (PCI) methodologies and examines the reasons behind their continued contestation and limited mainstreaming in conventional modes of crop improvement research within National Agricultural Research Systems (NARS). In particular, it traces the experiences of a long-established research network with over 20 years of experience in developing and implementing PCI methods across South Asia, and specifically considers its engagement with the Indian NARS and associated state-level agricultural research systems. In order to address the issues surrounding PCI institutionalisation processes, a novel conceptual framework was derived from a synthesis of the literatures on Strategic Niche Management (SNM) and Learning-based Development Approaches (LBDA) to analyse the socio-technical processes and structures which constitute the PCI ‘niche’ and NARS ‘regime’. In examining the niche and regime according to their socio-technical characteristics, the framework provides explanatory power for understanding the nature of their interactions and the opportunities and barriers that exist with respect to the translation of lessons and ideas between niche and regime organisations. The research shows that in trying to institutionalise PCI methods and principles within NARS in the Indian context, PCI proponents have encountered a number of constraints related to the rigid and hierarchical structure of the regime organisations; the contractual mode of most conventional research, which inhibits collaboration with a wider group of stakeholders; and the time-limited nature of PCI projects themselves, which limits investment and hinders scaling up of the innovations. It also reveals that while the niche projects may be able to induce a ‘weak’ form of PCI institutionalisation within the Indian NARS by helping to alter their institutional culture to be more supportive of participatory plant breeding approaches and future collaboration with PCI researchers, a ‘strong’ form of PCI institutionalisation, in which NARS organisations adopt participatory methodologies to address all their crop improvement agenda, is likely to remain outside of the capacity of PCI development projects to deliver.