Parkinson's disease proteins: Novel mitochondrial targets for cardioprotection

Ischemic heart disease (IHD) is the leading cause of death and disability worldwide. Therefore, novel therapeutic targets for protecting the heart against acute ischemia/reperfusion injury (IRI) are required to attenuate cardiomyocyte death, preserve myocardial function, and prevent the onset of heart failure. In this regard, a specific group of mitochondrial proteins, which have been linked to familial forms of Parkinson's disease (PD), may provide novel therapeutic targets for cardioprotection. In dopaminergic neurons of the substantia nigra, these PD proteins, which include Parkin, PINK1, DJ-1, LRRK2, and α-synuclein, play essential roles in preventing cell death-through maintaining normal mitochondrial function, protecting against oxidative stress, mediating mitophagy, and preventing apoptosis. These rare familial forms of PD may therefore provide important insights into the pathophysiology underlying mitochondrial dysfunction and the development of PD. Interestingly, these PD proteins are also present in the heart, but their role in myocardial health and disease is not clear. In this article, we review the role of these PD proteins in the heart and explore their potential as novel mitochondrial targets for cardioprotection

High Energy Gamma-Ray Emission From Blazars: EGRET Observations

We will present a summary of the observations of blazars by the Energetic Gamma Ray Experiment Telescope (EGRET) on the Compton Gamma Ray Observatory (CGRO). EGRET has detected high energy gamma-ray emission at energies greater than 100 MeV from more that 50 blazars. These sources show inferred isotropic luminosities as large as $3\times 10^{49}$ ergs s$^{-1}$. One of the most remarkable characteristics of the EGRET observations is that the gamma-ray luminosity often dominates the bolometric power of the blazar. A few of the blazars are seen to exhibit variability on very short time-scales of one day or less. The combination of high luminosities and time variations seen in the gamma-ray data indicate that gamma-rays are an important component of the relativistic jet thought to characterize blazars. Currently most models for blazars involve a beaming scenario. In leptonic models, where electrons are the primary accelerated particles, gamma-ray emission is believed to be due to inverse Compton scattering of low energy photons, although opinions differ as to the source of the soft photons. Hardronic models involve secondary production or photomeson production followed by pair cascades, and predict associated neutrino production.Comment: 16 pages, 7 figures, style files included. Invited review paper in "Observational Evidence for Black Holes in the Universe," 1999, ed. S. K. Chakrabarti (Dordrecht: Kluwer), 215-23

Multifrequency Strategies for the Identification of Gamma-Ray Sources

More than half the sources in the Third EGRET (3EG) catalog have no firmly established counterparts at other wavelengths and are unidentified. Some of these unidentified sources have remained a mystery since the first surveys of the gamma-ray sky with the COS-B satellite. The unidentified sources generally have large error circles, and finding counterparts has often been a challenging job. A multiwavelength approach, using X-ray, optical, and radio data, is often needed to understand the nature of these sources. This chapter reviews the technique of identification of EGRET sources using multiwavelength studies of the gamma-ray fields.Comment: 35 pages, 22 figures. Chapter prepared for the book "Cosmic Gamma-ray Sources", edited by K.S. Cheng and G.E. Romero, to be published by Kluwer Academic Press, 2004. For complete article and higher resolution figures, go to: http://www.astro.columbia.edu/~muk/mukherjee_multiwave.pd

Exploring the experiences of social workers in working with children suspected of having fetal alcohol spectrum disorders

Fetal alcohol spectrum disorder (FASD) is one outcome from prenatal alcohol exposure. Social workers are likely to encounter children with the condition, due to the greater likelihood of prenatal alcohol exposure among children in social services settings. This study explores the experiences of social workers in working with children suspected of having FASD and the support offered to social workers, the children and their families. Semi-structured interviews followed by qualitative framework analysis were conducted with seven child and family social workers along with one child protection solicitor who had experience of handling FASD cases. The two main themes that emerged from the data were a lack of knowledge about FASD and the paucity of diagnosis. Lack of knowledge among the social workers was linked to difficulty in managing children suspected to have the condition, feelings of frustration and normalisation of challenging behaviours. The paucity of diagnosis led to an under-emphasis of FASD in assessments, a dearth of specialist services and confusion about its specific effects in contexts of multiple substance misuse and harmful socio-environmental factors. The need for increased FASD awareness within social services and the development of FASD-targeted support for children and families is highlighted. Social workers would benefit from the inclusion of FASD-focused training in their curricula and professional development plans. Improving the diagnostic capacities of health institutions would address the paucity of diagnosis and raise the profile of FASD, especially in the social services setting

Risk Assessment of a Synthetic Pyrethroid, Bifenthrin on Pulses

This work was undertaken to determine the pre-harvest interval of bifenthrin and to minimize its residues in pulses and thereby ensure consumer safety and avoid non-compliance in terms of residues violations in export market. Furthermore the residue dynamics in the soil under pulses was explored to assess the environmental safety. The residues of bifenthrin dissipated following first order kinetics. The residues in harvest time grains were below the maximum residue limit (MRL) of 0.02 mg/kg applicable for European Union. In soil the degradation rate was fast with a half life of 2–3 days. This work is of high practical significance to the domestic and export pulse industry of India to ensure safety compliance in respect of bifenthrin residues, keeping in view the requirements of international trade

Loss of PINK1 Increases the Heart's Vulnerability to Ischemia-Reperfusion Injury.

Mutations in PTEN inducible kinase-1 (PINK1) induce mitochondrial dysfunction in dopaminergic neurons resulting in an inherited form of Parkinson's disease. Although PINK1 is present in the heart its exact role there is unclear. We hypothesized that PINK1 protects the heart against acute ischemia reperfusion injury (IRI) by preventing mitochondrial dysfunction

Gamma-Ray Background from Structure Formation in the Intergalactic Medium

The universe is filled with a diffuse and isotropic extragalactic background of gamma-ray radiation, containing roughly equal energy flux per decade in photon energy between 3 MeV-100 GeV. The origin of this background is one of the unsolved puzzles in cosmology. Less than a quarter of the gamma-ray flux can be attributed to unresolved discrete sources, but the remainder appears to constitute a truly diffuse background whose origin has hitherto been mysterious. Here we show that the shock waves induced by gravity during the formation of large-scale structure in the intergalactic medium, produce a population of highly-relativistic electrons with a maximum Lorentz factor above 10^7. These electrons scatter a small fraction of the microwave background photons in the present-day universe up to gamma-ray energies, thereby providing the gamma-ray background. The predicted diffuse flux agrees with the observed background over more than four decades in photon energy, and implies a mean cosmological density of baryons which is consistent with Big-Bang nucleosynthesis.Comment: 7 pages, 1 figure. Accepted for publication in Nature. (Press embargo until published.

Case studies on heat stress related perceptions in different industrial sectors in southern India

Linkages between thermal loads and its physiological consequences have been widely studied in non-tropical developed country settings. In many developing countries like India, despite the widespread recognition of the problem, limited attempts have been made to estimate health impacts related to occupational heat stress and fewer yet to link heat stress with potential productivity losses. This is reflected in the ubiquity of workplaces with limited or no controls to reduce exposures. As a prelude to understanding the feasibility of alternative interventions in different industrial sectors, we present case studies from 10 different industrial units in Tamil Nadu, Chennai, which describe perceptions of occupational heat stress among the workers and supervisors/management

Unambiguous observation of blocked states reveals altered, blocker-induced, cardiac ryanodine receptor gating

The flow of ions through membrane channels is precisely regulated by gates. The architecture and function of these elements have been studied extensively, shedding light on the mechanisms underlying gating. Recent investigations have focused on ion occupancy of the channel’s selectivity filter and its ability to alter gating, with most studies involving prokaryotic K+ channels. Some studies used large quaternary ammonium blocker molecules to examine the effects of altered ionic flux on gating. However, the absence of blocking events that are visibly distinct from closing events in K+ channels makes unambiguous interpretation of data from single channel recordings difficult. In this study, the large K+ conductance of the RyR2 channel permits direct observation of blocking events as distinct subconductance states and for the first time demonstrates the differential effects of blocker molecules on channel gating. This experimental platform provides valuable insights into mechanisms of blocker-induced modulation of ion channel gating