84 research outputs found
On the importance of the cross-body approach in planetary aeronomy
Cross-disciplinary and cross-body approaches can be applied to study universal processes occurring in the heliosphere. Magnetospheric, interplanetary, and heliospheric plasmas, all of which are low density plasmas, host similar processes. A cross-disciplinary approach is thus of great relevance for a universal understanding of processes occurring within these various plasmas. On the other hand, the upper atmosphere of planets and moons are a highly collisional medium acting differently compared to a collisionless plasma. Therefore, the comparative study between solar system bodies hosting atmospheres under different settings is a more suitable approach for assessing universal processes in aeronomy. For the past several years the aeronomy community has undertaken many initiatives in comparative studies of solar system atmospheres. We highlight the maturity of this field and illustrate its relevance by applying the comparative approach to key scientific topics. We would like to encourage aeronomers interested in comparative studies to consider participating to International Heliophysical Year (IHY) focused activities. More information on the comparative initiative can be found at the IHY website (http://ihy.gsfc.nasa.gov/) as well as at: http://www.bu.edu/csp/uv/ cp-aeronomy/aeronomy-sol-sys.html
Heat shock factor gene family in rice: genomic organization and transcript expression profiling in response to high temperature, low temperature and oxidative stresses
Binding of heat shock factors (HSFs) with heat shock element sequence is critical for the transcriptional induction of heat shock genes. Rice genome sequence shows 26 OsHsf genes out of which 25 possess various important domains noted in HSFs i.e. DNA binding domain (DBD), oligomerization domain (OD), nuclear localization signal (NLS), nuclear export signal (NES) and AHA type activation domain. OsHsf entry LOC_Os06g226100 has the oligomerization domain but lacks the above other domains. Also, there are no ESTs or full-length cDNA noted for this entry in database. Expression profiling showed that 22 OsHsf genes are induced by high temperature. Induction of 10 and 14 OsHsf genes was also noted against low temperature stress and oxidative stress, respectively. All OsHsf genes induced by oxidative stress were also induced by high temperature. On the other hand, induction of 6 and 1 OsHsf genes was noted to be exclusive to high and low temperature stresses, respectively. Seven OsHsf genes showed induced expression in response to all the three stresses examined. While in silico promoter analysis showed that OsHsf genes contain upstream regulatory elements corresponding to different abiotic stresses, there was lack of correlation noted between the in silico profiling of the elements and their corresponding transcript expression patterns. Apart from stress inducibility, EST database suggests that various OsHsf genes are developmentally regulated in diverse tissue types
Globally, CYP1B1 mutations in primary congenital glaucoma are strongly structured by geographic and haplotype backgrounds
Purpose: To obtain a global perspective on the distribution and evolution of CYP1B1 mutations in primary congenital glaucoma (PCG) worldwide. Methods. Five intragenic single-nucleotide polymorphisms in CYP1B1-R48G, A119S, V432L, D449D, and N453S-were used to generate haplotype data from 138 Indian patients with PCG and 132 ethnically matched normal controls, which were then analyzed in conjunction with data from other populations. Maximum-likelihood estimates of haplotype frequencies were estimated from the genotype data. Subsets of patients and normal control subjects were also genotyped with respect to eight short tandem repeat (STR) markers around the CYP1B1 locus (D2S305, D2S165, D2S367, D2S2259, D2S391, D2S3337, D2S23678, and D2S286), to gain evolutionary insights. Results: Common mutations in CYP1B1 that are causal of PCG occurred on a uniform haplotype background among Indian patients, which is completely distinct from the modal haplotype background found among unaffected control subjects. Comparison of these data with data from other global regions reveals strong clustering of CYP1B1 mutations by geographic and haplotype backgrounds. The two distinct modal haplotypes found among Indian patients with PCG and control subjects are both ancient with ages of similar magnitudes, as indicated by large variances in the number of repeats at eight STR loci. Together with data from chimpanzee and normal control subjects from India and other global regions, it was possible to make a parsimonious reconstruction of the evolution of these haplotypes. Conclusions: The strong association of specific haplotypes with some predominant CYP1B1 mutations underlying PCG and the observed geographical clustering, probably due to founder effects, may be useful for predictive testing
Mutation spectrum of the CYP1B1 gene in Indian primary congenital glaucoma patients
Purpose: The human Cytochrome P450 gene CYP1B1 has been implicated in primary congenital glaucoma worldwide. The aim of this study was to understand the role of CYP1B1 mutations in causing primary congenital glaucoma in Indian populations. Methods: The study included 64 new and unrelated cases of primary congenital glaucoma from different ethnic groups of India. Direct sequencing screened the coding and the promoter regions of CYP1B1. Results: Sixteen pathogenic mutations were observed in 24 cases, of which 7 were novel. These included two frameshift mutations leading to deletions of 23 bp (g.3905del23bp) and 2 bp (g.7900-7901delCG) in exons II and III, respectively. Four novel missense mutations viz. A115P, M132R, Q144P, S239R were noted in exon II, and one in exon III (G466D), whose residue is a part of the "signature sequence" (NH2-FXXGXXXCXG-COOH) and is present in all heme binding cytochromes. Overall, CYP1B1 was involved in 37.50% (24/64) cases and homozygosity of the mutant allele was seen in 29.68% (19/64) and compound heterozygosity in 3.12% (2/64) of the cases, respectively. The frequency of CYP1B1 mutations was comparatively lower than Saudi Arabian, Slovakian Gypsys, and Turkish populations, largely due to genetic heterogeneity and ethnic diversities in Indian populations. Genotype-phenotype correlation indicated variable prognosis that could be due to the type of mutation, leading to alteration of CYP1B1 protein. Conclusions: This study provides a mutation spectrum of CYP1B1 causing primary congenital glaucoma in Indian populations that has implications in devising molecular diagnostics for rapid screening
"The fruits of independence": Satyajit Ray, Indian nationhood and the spectre of empire
Challenging the longstanding consensus that Satyajit Ray's work is largely free of ideological concerns and notable only for its humanistic richness, this article shows with reference to representations of British colonialism and Indian nationhood that Ray's films and stories are marked deeply and consistently by a distinctively Bengali variety of liberalism. Drawn from an ongoing biographical project, it commences with an overview of the nationalist milieu in which Ray grew up and emphasizes the preoccupation with colonialism and nationalism that marked his earliest unfilmed scripts. It then shows with case studies of Kanchanjangha (1962), Charulata (1964), First Class Kamra (First-Class Compartment, 1981), Pratidwandi (The Adversary, 1970), Shatranj ke Khilari (The Chess Players, 1977), Agantuk (The Stranger, 1991) and Robertsoner Ruby (Robertson's Ruby, 1992) how Ray's mature work continued to combine a strongly anti-colonial viewpoint with a shifting perspective on Indian nationhood and an unequivocal commitment to cultural cosmopolitanism. Analysing how Ray articulated his ideological positions through the quintessentially liberal device of complexly staged debates that were apparently free, but in fact closed by the scenarist/director on ideologically specific notes, this article concludes that Ray's reputation as an all-forgiving, ‘everybody-has-his-reasons’ humanist is based on simplistic or even tendentious readings of his work
An Oligopeptide Transporter of Mycobacterium tuberculosis Regulates Cytokine Release and Apoptosis of Infected Macrophages
Background: The Mycobacterium tuberculosis genome encodes two peptide transporters encoded by Rv3665c-Rv3662c and Rv1280c-Rv1283c. Both belong to the family of ABC transporters containing two nucleotide-binding subunits, two integral membrane proteins and one substrate-binding polypeptide. However, little is known about their functions in M. tuberculosis. Here we report functional characterization of the Rv1280c-Rv1283c-encoded transporter and its substrate-binding polypeptide OppA(MTB). Methodology/Principal Findings: OppA(MTB) was capable of binding the tripeptide glutathione and the nonapeptide bradykinin, indicative of a somewhat broad substrate specificity. Amino acid residues G109, N110, N230, D494 and F496, situated at the interface between domains I and III of OppA, were required for optimal peptide binding. Complementaton of an oppA knockout mutant of M. smegmatis with OppA(MTB) confirmed the role of this transporter in importing glutathione and the importance of the aforesaid amino acid residues in peptide transport. Interestingly, this transporter regulated the ability of M. tuberculosis to lower glutathione levels in infected compared to uninfected macrophages. This ability was partly offset by inactivation of oppD. Concomitantly, inactivation of oppD was associated with lowered levels of methyl glyoxal in infected macrophages and reduced apoptosis-inducing ability of the mutant. The ability to induce the production of the cytokines IL-1 beta, IL-6 and TNF-alpha was also compromised after inactivation of oppD. Conclusions: Taken together, these studies uncover the novel observations that this peptide transporter modulates the innate immune response of macrophages infected with M. tuberculosis
Baseline natural killer and T cell populations correlation with virologic outcome after regimen simplification to atazanavir/ritonavir alone (ACTG 5201)
Objectives: Simplified maintenance therapy with ritonavir-boosted atazanavir (ATV/r) provides an alternative treatment option for HIV-1 infection that spares nucleoside analogs (NRTI) for future use and decreased toxicity. We hypothesized that the level of immune activation (IA) and recovery of lymphocyte populations could influence virologic outcomes after regimen simplification. Methods: Thirty-four participants with virologic suppression ≥48 weeks on antiretroviral therapy (2 NRTI plus protease inhibitor) were switched to ATV/r alone in the context of the ACTG 5201 clinical trial. Flow cytometric analyses were performed on PBMC isolated from 25 patients with available samples, of which 24 had lymphocyte recovery sufficient for this study. Assessments included enumeration of T-cells (CD4/CD8), natural killer (NK) (CD3+CD56 +CD16+) cells and cell-associated markers (HLA-DR, CD's 38/69/94/95/158/279). Results: Eight of the 24 patients had at least one plasma HIV-1 RNA level (VL) <50 copies/mL during the study. NK cell levels below the group median of 7.1% at study entry were associated with development of VL <50 copies/mL following simplification by regression and survival analyses (p = 0.043 and 0.023), with an odds ratio of 10.3 (95% CI: 1.92-55.3). Simplification was associated with transient increases in naïve and CD25+ CD4+ T-cells, and had no impact on IA levels. Conclusions: Lower NK cell levels prior to regimen simplification were predictive of virologic rebound after discontinuation of nucleoside analogs. Regimen simplification did not have a sustained impact on markers of IA or T lymphocyte populations in 48 weeks of clinical monitoring. Trial Registration: ClinicalTrials.gov NCT00084019
Association of acute toxic encephalopathy with litchi consumption in an outbreak in Muzaffarpur, India, 2014: a case-control study
Background Outbreaks of unexplained illness frequently remain under-investigated. In India, outbreaks of an acute
neurological illness with high mortality among children occur annually in Muzaffarpur, the country’s largest litchi
cultivation region. In 2014, we aimed to investigate the cause and risk factors for this illness.
Methods In this hospital-based surveillance and nested age-matched case-control study, we did laboratory
investigations to assess potential infectious and non-infectious causes of this acute neurological illness. Cases were
children aged 15 years or younger who were admitted to two hospitals in Muzaffarpur with new-onset seizures or
altered sensorium. Age-matched controls were residents of Muzaffarpur who were admitted to the same two hospitals
for a non-neurologic illness within seven days of the date of admission of the case. Clinical specimens (blood,
cerebrospinal fluid, and urine) and environmental specimens (litchis) were tested for evidence of infectious
pathogens, pesticides, toxic metals, and other non-infectious causes, including presence of hypoglycin A or
methylenecyclopropylglycine (MCPG), naturally-occurring fruit-based toxins that cause hypoglycaemia and metabolic
derangement. Matched and unmatched (controlling for age) bivariate analyses were done and risk factors for illness
were expressed as matched odds ratios and odds ratios (unmatched analyses).
Findings Between May 26, and July 17, 2014, 390 patients meeting the case definition were admitted to the two referral
hospitals in Muzaffarpur, of whom 122 (31%) died. On admission, 204 (62%) of 327 had blood glucose concentration
of 70 mg/dL or less. 104 cases were compared with 104 age-matched hospital controls. Litchi consumption (matched
odds ratio [mOR] 9·6 [95% CI 3·6 – 24]) and absence of an evening meal (2·2 [1·2–4·3]) in the 24 h preceding illness
onset were associated with illness. The absence of an evening meal significantly modified the effect of eating litchis
on illness (odds ratio [OR] 7·8 [95% CI 3·3–18·8], without evening meal; OR 3·6 [1·1–11·1] with an evening meal).
Tests for infectious agents and pesticides were negative. Metabolites of hypoglycin A, MCPG, or both were detected in
48 [66%] of 73 urine specimens from case-patients and none from 15 controls; 72 (90%) of 80 case-patient specimens
had abnormal plasma acylcarnitine profiles, consistent with severe disruption of fatty acid metabolism. In 36 litchi
arils tested from Muzaffarpur, hypoglycin A concentrations ranged from 12·4 μg/g to 152·0 μg/g and MCPG ranged
from 44·9 μg/g to 220·0 μg/g.
Interpretation Our investigation suggests an outbreak of acute encephalopathy in Muzaffarpur associated with both
hypoglycin A and MCPG toxicity. To prevent illness and reduce mortality in the region, we recommended minimising
litchi consumption, ensuring receipt of an evening meal and implementing rapid glucose correction for suspected
illness. A comprehensive investigative approach in Muzaffarpur led to timely public health recommendations,
underscoring the importance of using systematic methods in other unexplained illness outbreaks
- …