Hinduism in a Kangra village.

In this thesis I set out to test the hypothesis that the separation of the pure from the impure is a theme which links all the various aspects of religious activity in village Hinduism, integrating them in spite of their apparent cultural diversity. In the first Chapter I describe some of the recent theoretical approaches to the analysis of Hinduism in anthropological literature, for instance the contributions of Srinivas, Marriott and Mathur. Most of these emphasize the diversity of Hindu religious activities. But Dumont, and more recently Harper, have pointed to the unifying role of the purity-pollution principle which underlies all ritual activity. In Chapter 2 I give a brief description of the village where I carried out field research, giving especial attention to the operation of rules concerning purity and pollution in social life. In Chapter 3 I describe the private religious activities of the villagers. These consist of individual acts of worship addressed to members of a pantheon which includes deities of a local nature along with scriptural deities known all over India, I describe the villagers' conception of their relationships with these gods and the techniques of the ritual they use in order to influence them. In many ways these relationships reflect the relationships between members of different castes in human society. The concern for the separation of the pure from the impure which governs contact between castes also governs contacts between men and deities. Also the relationship between a household or personal deity and his devotee is analogous to that between a powerful jajman and his low caste client. Chapter 4 consists of a description of life cycle rites and other public rituals performed with the aid of a Brahman priest. Many of the public ritual acts conducted on such occasions are directed to the preservation of the pure deities from the threat of pollution arising from contact with their less pure devotees, or from other sources of pollution. In Chapter 5 the festival cycle observed in the village is described. In calendrical rites the concern for purity is shown through activities such as purificatory fasting and bathing, which are recurrent elements in the round of festivals. The last chapter consists of a general discussion of the purity-pollution principle. Not only does this principle give unity to the diverse aspects of religious activity but it also provides continuity between Hindu religion and Hindu social life in general: the hierarchical relations between, men and deities are only an extension of the hierarchical relationships between men themselves, and between men and the other things and creatures in the universe

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Progressive regression of left ventricular hypertrophy two years after bariatric surgery.

BACKGROUND: Obesity is a systemic disorder associated with an increase in left ventricular mass and premature death and disability from cardiovascular disease. Although bariatric surgery reverses many of the hormonal and hemodynamic derangements, the long-term collective effects on body composition and left ventricular mass have not been considered before. We hypothesized that the decrease in fat mass and lean mass after weight loss surgery is associated with a decrease in left ventricular mass. METHODS: Fifteen severely obese women (mean body mass index [BMI]: 46.7+/-1.7 kg/m(2)) with medically controlled hypertension underwent bariatric surgery. Left ventricular mass and plasma markers of systemic metabolism, together with body mass index (BMI), waist and hip circumferences, body composition (fat mass and lean mass), and resting energy expenditure were measured at 0, 3, 9, 12, and 24 months. RESULTS: Left ventricular mass continued to decrease linearly over the entire period of observation, while rates of weight loss, loss of lean mass, loss of fat mass, and resting energy expenditure all plateaued at 9 [corrected] months (P \u3c.001 for all). Parameters of systemic metabolism normalized by 9 months, and showed no further change at 24 months after surgery. CONCLUSIONS: Even though parameters of obesity, including BMI and body composition, plateau, the benefits of bariatric surgery on systemic metabolism and left ventricular mass are sustained. We propose that the progressive decrease of left ventricular mass after weight loss surgery is regulated by neurohumoral factors, and may contribute to improved long-term survival

Taking reincarnation seriously: Critical discussion of some central ideas from John Hick

Reincarnation has not been entirely neglected in the philosophy of religion but it has not always been taken seriously or carefully discussed in relation to its role in believers’ lives. John Hick is exceptional insofar as he gave sustained attention to the belief, at least as it features in the philosophies of Vedānta and Buddhism. While acknowledging the value of Hick’s recognition of the variety of reincarnation beliefs, this article critically engages with certain aspects of his approach. It argues that Hick’s search for a ‘criterion’ of reincarnation is misguided, and that his distinction between ‘factual’ and ‘mythic’ forms of the doctrine is over-simplifying

Lysyl-tRNA synthetase as a drug target in malaria and cryptosporidiosis

Malaria and cryptosporidiosis, caused by apicomplexan parasites, remain major drivers of global child mortality. New drugs for the treatment of malaria and cryptosporidiosis, in particular, are of high priority; however, there are few chemically validated targets. The natural product cladosporin is active against blood- and liver-stage; Plasmodium falciparum; and; Cryptosporidium parvum; in cell-culture studies. Target deconvolution in; P. falciparum; has shown that cladosporin inhibits lysyl-tRNA synthetase (; Pf; KRS1). Here, we report the identification of a series of selective inhibitors of apicomplexan KRSs. Following a biochemical screen, a small-molecule hit was identified and then optimized by using a structure-based approach, supported by structures of both; Pf; KRS1 and; C. parvum; KRS (; Cp; KRS). In vivo proof of concept was established in an SCID mouse model of malaria, after oral administration (ED; 90; = 1.5 mg/kg, once a day for 4 d). Furthermore, we successfully identified an opportunity for pathogen hopping based on the structural homology between; Pf; KRS1 and; Cp; KRS. This series of compounds inhibit; Cp; KRS and; C. parvum; and; Cryptosporidium hominis; in culture, and our lead compound shows oral efficacy in two cryptosporidiosis mouse models. X-ray crystallography and molecular dynamics simulations have provided a model to rationalize the selectivity of our compounds for; Pf; KRS1 and; Cp; KRS vs. (human); Hs; KRS. Our work validates apicomplexan KRSs as promising targets for the development of drugs for malaria and cryptosporidiosis

Hypoxia Routes Tryptophan Homeostasis Towards Increased Tryptamine Production

The liver is the central hub for processing and maintaining homeostatic levels of dietary nutrients especially essential amino acids such as tryptophan (Trp). Trp is required not only to sustain protein synthesis but also as a precursor for the production of NAD, neurotransmitters and immunosuppressive metabolites. In light of these roles of Trp and its metabolic products, maintaining homeostatic levels of Trp is essential for health and well-being. The liver regulates global Trp supply by the immunosuppressive enzyme tryptophan-2,3-dioxygenase (TDO2), which degrades Trp down the kynurenine pathway (KP). In the current study, we show that isolated primary hepatocytes when exposed to hypoxic environments, extensively rewire their Trp metabolism by reducing constitutive Tdo2 expression and differentially regulating other Trp pathway enzymes and transporters. Mathematical modelling of Trp metabolism in liver cells under hypoxia predicted decreased flux through the KP while metabolic flux through the tryptamine branch significantly increased. In line, the model also revealed an increased accumulation of tryptamines under hypoxia, at the expense of kynurenines. Metabolic measurements in hypoxic hepatocytes confirmed the predicted reduction in KP metabolites as well as accumulation of tryptamine. Tdo2 expression in cultured primary hepatocytes was reduced upon hypoxia inducible factor (HIF) stabilisation by dimethyloxalylglycine (DMOG), demonstrating that HIFs are involved in the hypoxic downregulation of hepatic Tdo2. DMOG abrogated hepatic luciferase signals in Tdo2 reporter mice, indicating that HIF stability also recapitulates hypoxic rewiring of Trp metabolism in vivo. Also in WT mice HIF stabilization drove homeostatic Trp metabolism away from the KP towards enhanced tryptamine production, leading to enhanced levels of tryptamine in liver, serum and brain. As tryptamines are the most potent hallucinogens known, the observed upregulation of tryptamine in response to hypoxic exposure of hepatocytes may be involved in the generation of hallucinations occurring at high altitude. KP metabolites are known to activate the aryl hydrocarbon receptor (AHR). The AHR-activating properties of tryptamines may explain why immunosuppressive AHR activity is maintained under hypoxia despite downregulation of the KP. In summary our results identify hypoxia as an important factor controlling Trp metabolism in the liver with possible implications for immunosuppressive AHR activation and mental disturbances

Sampling considerations and assessment of Exetainer usage for measuring dissolved and gaseous methane and nitrous oxide in aquatic systems

Pre-evacuated Exetainers are commonly used as measurement vials for the determination of methane (CH4) and nitrous oxide (N2O) concentrations in liquid and gaseous samples from aquatic environments. The impact of residual air in these Exetainers on measurement accuracy is assessed. Residual air pressure in commercially available, pre-evacuated Exetainers varied between 0.071 +/- 0.008 atm and 0.180 +/- 0.031 atm in examined batches. This background contamination can lead to large errors when determining dissolved and gaseous CH4 and N2O concentrations particularly at low concentrations. A method for Exetainer pretreatment is suggested and verified, to reduce the residual CH4 and N2O. Vials are flushed (needle 30 G 3 0.5 '', 0.3 mm) with nitrogen gas (N-2) for 5 min, which reduces the background CH4 and N2O concentrations to 0.092 +/- 0.008 ppm and 0.016 +/- 0.001 ppm, respectively, approximately 3-4% of their respective concentrations in air. To avoid an alteration of sample concentration by variable residual gas levels left during a pre-evacuation step, liquid and gaseous samples are injected into the N-2 filled Exetainers. For gaseous samples where large volumes of gas are available, Exetainers can alternatively be flushed with 100 mL of sampling gas. For gaseous samples, measured CH4 and N2O concentrations of standard gases were statistically identical to their known concentrations. For liquid samples, measured CH4 and N2O concentrations of liquid standard dilution series showed strong linear correlations with theoretically calculated concentrations (slope CH4: 1.04, slope N2O: 1.12). Sample concentrations remained constant over a minimum storage period of 6 weeks

HP1-β is required for development of the cerebral neocortex and neuromuscular junctions

HP1 proteins are thought to be modulators of chromatin organization in all mammals, yet their exact physiological function remains unknown. In a first attempt to elucidate the function of these proteins in vivo, we disrupted the murine Cbx1 gene, which encodes the HP1-β isotype, and show that the Cbx1−/−-null mutation leads to perinatal lethality. The newborn mice succumbed to acute respiratory failure, whose likely cause is the defective development of neuromuscular junctions within the endplate of the diaphragm. We also observe aberrant cerebral cortex development in Cbx1−/− mutant brains, which have reduced proliferation of neuronal precursors, widespread cell death, and edema. In vitro cultures of neurospheres from Cbx1−/− mutant brains reveal a dramatic genomic instability. Our results demonstrate that HP1 proteins are not functionally redundant and that they are likely to regulate lineage-specific changes in heterochromatin organization