Sirtuins: multifaceted drug targets

Sirtuin (Sir2) proteins being key regulators of numerous cellular processes have been, over the recent past, the subject of intense study. Sirs have been implicated in diverse physiological processes ranging from aging and cancer to neurological dysfunctions. Studies on Sir2s using tools of genetics, molecular biology, biochemistry and structural biology have provided significant insight into the diverse functions of this class of deacetylases. This apart, medicinal chemistry approaches have enabled the discovery of modulators (both activators and inhibitors) of Sir2 activity of diverse chemical structures and properties. The availability of these small molecule modulators of Sir2 activity not only has pharmacological significance but also opens up the possibility of exploiting chemical genetic approaches in understanding the role of this multi-functional enzyme in cellular processes.     

Law-medicine interfacing: patenting of human genes and mutations

Mutations, Single Nucleotide Polymorphisms (SNPs), deletions and genetic rearrangements in specific genes in the human genome account for not only our physical characteristics and behavior, but can lead to many in-born and acquired diseases. Such changes in the genome can also predispose people to cancers, as well as significantly affect the metabolism and efficacy of many drugs, resulting in some cases in acute toxicity to the drug. The testing of the presence of such genetic mutations and rearrangements is of great practical and commercial value, leading many of these genes and their mutations/deletions and genetic rearrangements to be patented. A recent decision by a judge in the Federal District Court in the Southern District of New York, has created major uncertainties, based on the revocation of BRCA1 and BRCA2 gene patents, in the eligibility of all human and presumably other gene patents. This article argues that while patents on BRCA1 and BRCA2 genes could be challenged based on a lack of utility, the patenting of the mutations and genetic rearrangements is of great importance to further development and commercialization of genetic tests that can save human lives and prevent suffering, and should be allowed.     

Brain Imaging Investigation of the Neural Correlates of Emotional Autobiographical Recollection

Recollection of emotional autobiographical memories (AMs) is important to healthy cognitive and affective functioning ¹ - remembering positive AMs is associated with increased personal well-being and self-esteem ², whereas remembering and ruminating on negative AMs may lead to affective disorders ³. Although significant progress has been made in understanding the brain mechanisms underlying AM retrieval in general (reviewed in ^{4, 5}), less is known about the effect of emotion on the subjective re-experience of AMs and the associated neural correlates. This is in part due to the fact that, unlike the investigations of the emotion effect on memory for laboratory-based microevents (reviewed in ^{6, 7-9}), often times AM studies do not have a clear focus on the emotional aspects of remembering personal events (but see ¹⁰). Here, we present a protocol that allows investigation of the neural correlates of recollecting emotional AMs using functional magnetic resonance imaging (fMRI). Cues for these memories are collected prior to scanning by means of an autobiographical memory questionnaire (AMQ), therefore allowing for proper selection of emotional AMs based on their phenomenological properties (i.e., intensity, vividness, personal significance). This protocol can be used in healthy and clinical populations alike.Download video file.^{(70M, mov)}     

Oxidative stress and antioxidant activity as the basis of senescence in chrysanthemum florets

Stems of chrysanthemum (Chrysanthemum morifolium Ramat.) cv. Maghi were harvested when half of the buds showed colour and were put in distilled water at 21°C. Flowers showed visible senescence symptoms after 12–15 d. Reactive oxygen species (ROS) concentration and lipid peroxidation increased from young floret stage to the senescent stage. Activities of superoxide dismutase (SOD), ascorbate peroxidase (APX), peroxidase (POD) and catalase (CAT) showed uniform increases from young floret through to the mature stage and thereafter, declined. Among the SOD isoforms, Fe-SOD and Cu/Zn-SOD were induced during the onset of senescence. Similarly different isoforms of APX and glutathione reductase (GR) also appeared during the senescence process. The capacity of the antioxidative defence system increased during the onset of senescence but the imbalance between ROS production and antioxidant defences ultimately led to oxidative damage. It is proposed that a decrease in the activity of a number of antioxidant enzymes that normally prevent the build up of free radicals can at least partially account for the observed senescence of chrysanthemum florets.     

The use of fish community structure as a measure of ecological degradation: a case study in two tropical rivers of India

Fish community structure and water chemistry of two tropical rivers of West Bengal, an eastern province of India, were studied for two annual cycles (January 2003-December 2004) and a higher degree of pollution was found in one river (the Churni) than in the other river (the Jalangi). This was reflected in the water quality as well as in fish community structure of the rivers. We observed that 63.6% of fish species appeared to have been eliminated from the polluted Churni river since 1983 in 20 years. For the protection of fish biodiversity and enhancement of fish production, a rational management program should be implemented for the Churni river.