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Biomedical subjects

S Kumar

Publications and source records attributed to S Kumar.

At least 613 records · Page 34Linked to original sources

Efficiency of the neighbor-joining method in reconstructing deep and shallow evolutionary relationships in large phylogenies.

The neighbor-joining (NJ) method is widely used in reconstructing large phylogenies because of its computational speed and the high accuracy in phylogenetic inference as revealed in computer simulation studies. However, most computer simulation studies have quantified the overall performance of the NJ method in terms of the percentage of branches inferred correctly or the percentage of replications in which the correct tree is recovered. We have examined other aspects of its performance, such as the relative efficiency in correctly reconstructing shallow (close to the external branches of the tree) and deep branches in large phylogenies; the contribution of zero-length branches to topological errors in the inferred trees; and the influence of increasing the tree size (number of sequences), evolutionary rate, and sequence length on the efficiency of the NJ method. Results show that the correct reconstruction of deep branches is no more difficult than that of shallower branches. The presence of zero-length branches in realized trees contributes significantly to the overall error observed in the NJ tree, especially in large phylogenies or slowly evolving genes. Furthermore, the tree size does not influence the efficiency of NJ in reconstructing shallow and deep branches in our simulation study, in which the evolutionary process is assumed to be homogeneous in all lineages.

Computer Simulation↗

Transgene repeats in aspen: molecular characterisation suggests simultaneous integration of independent T-DNAs into receptive hotspots in the host genome.

Rearrangements of T-DNAs during genetic transformation of plants can result in the insertion of transgenes in the form of repeats into the host genome and frequently lead to loss of transgene expression. To obtain insight into the mechanism of repeat formation we screened 45 transgenic lines of aspen and hybrid aspen transformed with six different gene constructs. The frequency of T-DNA repeat formation among randomly screened transgenic lines was found to be about 21%. In ten transgenic lines direct repeats were detected. An inverted repeat was found in one other transgenic line. Sequencing of the junctions between the T-DNA inserts revealed identical residual right-border repeat sequences at the repeat junctions in all ten transgenic lines that had direct repeats. Formation of "precise" junctions based on short regions of sequence similarity between recombining strands was observed in three transgenic lines transformed with the same plasmid. Additional DNA sequences termed filler DNAs were found to be inserted between the T-DNA repeats at eight junctions where there was no similarity between recombining ends. The length of the filler DNAs varied from 4 to almost 300 bp. Small filler DNAs--a few base pairs long--were in most cases copied from T-DNA near the break points. The large filler sequences of about 300 bp in two transgenic lines were found to be of host plant origin, suggesting that transgene repeat formation occurred as a result of the simultaneous invasion of a receptive site in the host genome by two independent T-DNA strands. On the basis of the results obtained, and in the light of previous reports on T-DNA/plant DNA junctions in aspen and other crop plants, a mechanistic model for transgene rearrangement and filler formation is suggested.

Agrobacterium tumefaciens↗

Role of awareness in head-neck acceleration in low velocity rear-end impacts.

Fourteen normal healthy seated and restrained young adults were delivered rear-end impacts of four intensities of acceleration. The chair was delivered a regulated and controlled pneumatic blow using a 30 cm cylinder to cause an acceleration of 0.5, 0.9, 1.1 and 1.4g. The accelerated chair was stopped suddenly by impacting the stopper at the other end of the 2 m long friction reduced track. In one set of trials, subjects were informed about the impending impact and in the other they were blindfolded and provided with loud auditory input to eliminate cues of the impact. The accelerations of the chair, shoulder and head of the participating subjects were measured triaxially and compared between levels of acceleration and expectation. The multiple analyses of variance revealed that the peak acceleration was significantly affected by the gender (P < 0.01), intensity of impact (P < 0.001), and expectation (P < 0.0001). The accelerations were significantly different in different axes (P < 0.001). A significant two-way interaction between acceleration and expectation (P < 0.03), and expectation and axes of acceleration (P < 0.02) would imply that awareness of the impending impact serves to significantly reduce the level of accelerations of head and neck.

Acceleration↗

Evaluating contraceptive choice through the method-mix approach. An Indian Council of Medical Research (ICMR) task force study.

The method-mix approach was used to evaluate informed contraceptive choices in the present study. A total of 8,077 potential clients were given a balanced presentation of all available contraceptive methods in the national program, ie, the CuT 200 intrauterine device (IUD), low-dose combined oral pills (OC), condom, and sterilization (female/male) along with a new method, Norplant(R).(1) The majority of women opted for spacing methods; among them, the IUD was preferred by about 60% of clients, followed by condoms (9%), OC (6%), and Norplant (5%). Sterilization, mainly female, was accepted by about 17% of the women making an informed choice. The economic status of couples did not influence the contraceptive choices, as all the methods were offered free of cost in the present study, which is the current practice in the national program. Illiterate women more often accepted sterilization (about 25%) than did literate women (15%). This is because illiterate women had more children; about 30% of illiterate women had three or more children, as opposed to 16.2% of literate women. However, literacy status did not influence the choice of any specific spacing method. The study also revealed that, by encouraging potential clients to make an informed choice, they could override the provider's bias while accepting a particular type of spacing method. This is evident from the observation that Norplant was the first choice of the provider for 35% of the women, whereas only 5% of women preferred and accepted Norplant. The present study stresses an urgent need to promote the practice of informed choices in the national program with a variety of contraceptive options-especially, spacing methods for improving contraceptive prevalence and reproductive health in the country.

Adolescent↗

The significance of CD105, TGFbeta and CD105/TGFbeta complexes in coronary artery disease.

We have quantified levels of CD105, its ligand TGFbeta and receptor-ligand complexes in sera from healthy individuals (n=31), patients with triple vessel disease documented by coronary angiography (TVD; n=36) and patients with chest pain and a positive exercise electrocardiogram but with normal coronary angiogram (NCA; n=30). Both active TGFbeta1 and active plus acid-activatable TGFbeta1 [(a+l)TGFbeta1] were significantly depressed in patients with TVD compared with the other two groups (P</=0.04). CD105 levels in TVD patients were also diminished but elevated in NCA patients. In contrast, patients with TVD had more CD105/TGFbeta1 complex in their sera than the other two groups, suggesting that this may be the reason why TVD patients had low levels of receptor and ligand. TGFbeta3 levels were similar in the three groups, but elevated CD105/TGFbeta3 levels were noted in patients with NCA compared with those with TVD and healthy individuals (P< or =0.02). CD105 was correlated with both active TGFbeta1 and (a+l)TGFbeta1 (P=0.02). CD105 also strongly correlated with TGFbeta3 and CD105/TGFbeta3 complexes (P=0.001 in both cases). The changes in levels of CD105, TGFbeta1 and the receptor-ligand complexes in sera of patients with atherosclerosis suggest that these molecules may be important in the pathobiology of the atherosclerotic disease. Further studies on sequential samples from a larger cohort of patients are needed to define a causal relationship between these molecules and the disease progression.

Aged↗

Euphane triterpenoid and lipid constituents from Butea monosperma.

Besides stigmasterol, stigmasterol-betaD-glucopyranoside and nonacosanoic acid, two new compounds isolated from the stems of Butea monosperma have been characterised as 3alpha-hydroxyeuph-25-ene and 2,14-dihydroxy-11,12-dimethyl-8-oxo-octadec-11-enylcyclohexane+ ++ by spectral data and chemical studies.

Molecular Structure↗

Iridoid glycosides from Lonicera quinquelocularis.

A new iridoid glycoside 6'-O-beta-apiofuranosylsweroside was isolated from the ethanolic extract of the roots of Lonicera quinquelocularis along with the known compounds loganin and sweroside.

Disaccharides↗

Inhibition of p38 MAP kinase as a therapeutic strategy.

Since the discovery of p38 MAP kinase in 1994, our understanding of its biology has progressed dramatically. The key advances include (1) identification of p38 MAP kinase homologs and protein kinases that act upstream and downstream from p38 MAP kinase, (2) identification of interesting and potentially important substrates, (3) elucidation of the role of p38 MAP kinase in cellular processes and (4) the establishment of the mechanism by which the pyridinylimidazole p38 MAP kinase inhibitors inhibit enzyme activity. It is now known that there are four members of the p38 MAP kinase family. They differ in their tissue distribution, regulation of kinase activation and subsequent phosphorylation of downstream substrates. They also differ in terms of their sensitivities toward the p38 MAP kinase inhibitors. The best-studied isoform is p38 alpha, whose activation has been observed in many hematopoietic and non-hematopoietic cell types upon treatment with appropriate stimuli. The pyridinylimidazole compounds, exemplified by SB 203580, were originally prepared as inflammatory cytokine synthesis inhibitors that subsequently were found to be selective inhibitors of p38 MAP kinase. SB 203580 inhibits the catalytic activity of p38 MAP kinase by competitive binding in the ATP pocket. X-ray crystallographic studies of the target enzyme complexed with inhibitor reinforce the observations made from site-directed mutagenesis studies, thereby providing a molecular basis for understanding the kinase selectivity of these inhibitors. The p38 MAP kinase inhibitors are efficacious in several disease models, including inflammation, arthritis and other joint diseases, septic shock, and myocardial injury. In all cases, p38 activation in key cell types correlated with disease initiation and progression. Treatment with p38 MAP kinase inhibitors attenuated both p38 activation and disease severity. Structurally diverse p38 MAP kinase inhibitors have been tested extensively in preclinical studies.

Animals↗

Effects of interruption of apicoplast function on malaria infection, development, and transmission.

A chloroplast-like organelle is present in many species of the Apicomplexa phylum. We have previously demonstrated that the plastid organelle of Plasmodium faciparum is essential to the survival of the blood-stage malaria parasite in culture. One known function of the plastid organelle in another Apicomplexan, Toxoplasma gondii, involves the formation of the parasitophorous vacuole. The effects of interruption of plastid function on sporozoites and sexual-stage parasites have not been investigated. In our previous studies of the effects of thiostrepton, a polypeptide antibiotic from streptococcus spp., on erythrocytic schizongony of the human malaria P. falciparium, we found that this antibiotic appears to interact with the guanosine triphosphatase (GTPase) binding domain of the organellar large subunit ribosomal RNA, as it does in bacteria. We investigate here the effects of this drug on life-cycle stages of the malaria parasite in vivo. Preincubation of mature infective sporozoites with thiostrepton has no observable effect on their infectivity. Sporozoite infection both by mosquito bite and sporozoite injection was prevented by pretreatment of mice with thiostrepton. Thiostrepton eliminates infection with erythrocytic forms of Plasmodium berghei in mice. Clearance of infected red blood cells follows the delayed kinetics associated with drugs that interact with the apicoplast. Thiostrepton treatment of infected mice reduces transmission of parasites by more than ten-fold, indicating that the plastid has a role in sexual development of the parasite. These results indicate that the plastid function is accessible to drug action in vivo and important to the development of both sexual and asexual forms of the parasite.

Animals↗

Caesarean section delivery in Kerala, India: evidence from a National Family Health Survey.

Ensuring safe pregnancy and motherhood occupies a pivotal role and has been considered as one of the key issues in the framework of reproductive and child health programmes. Evidence from research studies indicate that there is a growing tendency for caesarean section deliveries especially during complications confronted at the time of pregnancy and delivery. The present study focuses on the demographic, antenatal care, spatial and socio-economic variables associated with caesarean section delivery in Kerala, India. The data from the National Family Health Survey has been utilised for this purpose. The results from logistic regression models indicate that maternal age, birth order, current age, births in health institutions and spatial differences were significantly associated with caesarean section deliveries in Kerala. The older cohorts of mothers were found at higher risk to have caesarean section when compared to their younger counterparts. When controlled for demographic variables, the odds for caesarean section was about 1.7 times more likely to occur in private health institutions. The inclusion of spatial and socio-economic variables has neither influenced the demographic and antenatal care variables nor showed any significant association with caesarean section delivery in the state. The present study calls for that a detailed investigation on behavioural aspects of both the physician and the patient with regard to type of delivery in the state. Information related to pregnancy and health related aspects needs to be monitored more accurately, both in the public and private hospitals, to understand the determinants associated with caesarean section.

Cesarean Section↗

Hyperglycemia, hyperlipemia, and periodic paralysis: a case report of new side effects of clozapine.

1. This case report of a Chinese male schizophrenic patient describes new side effects that have not been documented previously for patients treated with clozapine. At certain doses of clozapine, the patient showed direct adverse reactions, which include a combination of hyperglycemia, hyperlipemia, and periodic paralysis. 2. In a four-year study of this patient who had no previous episodes of diabetes in his or his family history, the authors found that these symptoms disappeared upon withdrawal of clozapine and relapsed with re-treatment of the drug. This study indicates that hyperglycemia, hyperlipemia, and periodic paralysis may need to be monitored on patients treated with clozapine.

Adult↗

Modulatory effects of a tannin fraction isolated from Terminalia arjuna on the genotoxicity of mutagens in Salmonella typhimurium.

A fraction isolated from Terminalia arjuna was studied for its antimutagenic effect against 4-nitro-o-phenylenediamine (NPD) in TA98, sodium azide in TA100 and 2-aminofluorene (2AF, S9-dependent), a promutagen, in both TA98 and TA 100 tester strains of Salmonella typhimurium using the Ames assay. The fraction inhibited the mutagenicity of 2AF very significantly in both strains while the revertant colonies induced by NPD and sodium azide were reduced moderately. 1H-NMR, 13C-NMR, IR and UV-spectroscopic data of the fraction revealed it to be tannin in nature.

Antimutagenic Agents↗

Two approaches to isolate cytoplasmic dynein ATPase from Neurospora crassa.

Cytoplasmic dynein is a force-producing enzyme that, in association with dynactin, conducts minus-end directed transport of various organelles along microtubules. Biochemical analyses of cytoplasmic dynein and dynactin have been conducted primarily in vertebrate systems, whereas genetic analyses have been explored mainly in yeast and the filamentous fungi. To provide a complementary biochemical approach for the study of fungal dynein, we isolated/partially purified cytoplasmic dynein ATPase from the filamentous fungus Neurospora crassa. N. crassa dynein was partially purified by slightly modifying the existing procedures, described for mammalian cytoplasmic dynein that uses dynein-microtubule binding, followed by release with ATP and sucrose gradient fractionation. A novel approach was also used to isolate dynein-specific ATPase by gel filtration (Sepharose CL-4B). The K(m), ATP obtained by isolating dynein ATPase using gel filtration was similar to that obtained by using conventional method, suggests that contaminant proteins do not interfere with the dynein ATPase activity. Like vertebrate dynein, N. crassa dynein is a general NTPase with highest activity toward ATP, and only the ATPase activity is stimulated by microtubules. The K(m), ATP for N. crassa cytoplasmic dynein is 10- to 15-fold higher than that of the vertebrate enzyme.

Adenosine Triphosphate↗