A novel role for reciprocal CD30-CD30L signaling in the cross-talk between natural killer and dendritic cells

The interplay between dendritic cells (DCs) and natural killer (NK) cells directs adaptive immune responses. The molecular basis of the cross-talk is largely undefined. Here, we provide evidence for a contribution of CD30 (TNFRSF8) and its ligand CD30L (TNFSF8) expressed on NK cells and DCs, respectively. We demonstrate that CD30-mediated engagement of CD30L induced cytokine secretion from immature DCs via the mitogen-activated protein kinase pathway. Moreover, CD30L engagement promoted differentiation to mature DCs. On the contrary, the engagement of CD30 on NK cells resulted in an NF-κB-dependent release of TNF-α/IFN-γ. These data uncover a novel and unexpected role for CD30/CD30L that contributes to proinflammatory immune responses.     

Factors affecting birth weight of a newborn--a community based study in rural Karnataka, India

Background

Low birth weight (LBW) is a major public health problem in many developing countries, especially so in India. Although we do not know all the causes of LBW, maternal and environmental factors appear to be significant risk factors in its occurrence.

Objectives

To know the factors affecting the birth weight of a newborn and to estimate the prevalence of LBW.

Methods

The present study was carried out amongst 1138 pregnant women and their newborns residing in area covered by Kinaye Primary Health Centre in rural Karnataka, India. The study was conducted from 1^st June 2008 to 31^st December 2009.

Results

The mean birth weight of newborns was 2.6 kg with a range of 1.2 to 3.8 kg. The prevalence of LBW was 22.9%. Among the studied risk factors, 25 of them were significantly associated with the birth weight of a newborn on univariate logistic regression analysis. Maternal education [Odds Ratio (OR) 3.2], exposure to passive smoking [OR 2.3], age at first pregnancy ≥25 years [OR 3.6], birth interval <2 years [OR 2.4], previous history of LBW baby [OR 3.3], weight gain ≤4 kg during pregnancy [OR 7.0], maternal weight at last week of gestation ≤45 kg [OR 2.3], pregnancy induced hypertension [OR 3.3], high risk pregnancy [OR 3.6] and late antenatal registration [OR 3.6] emerged as significant risk factors on multivariate analysis.

Conclusion

The problem of LBW is multidimensional, and hence, we need an integrated approach incorporating medical, social, economical and educational measures to address this issue.     

DNA, protein binding, cytotoxicity, cellular uptake and antibacterial activities of new palladium(II) complexes of thiosemicarbazone ligands: effects of substitution on biological activity

The coordination propensities of 4(N,N')-diethylaminosalicylaldehyde-4(N)-substituted thiosemicarbazones (H(2)L(1-4)) were investigated by reacting with an equimolar amount of [PdCl(2)(PPh(3))(2)]. The new complexes were characterized by various spectroscopic techniques. The structure determination of the complexes [Pd(DeaSal-tsc)(PPh(3))] (1), [Pd(DeaSal-mtsc)(PPh(3))] (2) and [Pd(DeaSal-etsc)(PPh(3))] (3) by X-ray crystallography showed that ligands are coordinated in a dibasic tridentate ONS donor fashion forming stable five and six membered chelate rings. The binding ability of complexes (1-4) to calf-thymus DNA (CT DNA) has been explored by absorption and emission titration methods. Based on the observations, an electrostatic and an intercalative binding mode have been proposed. The protein binding studies have been monitored by quenching of tryptophan and tyrosine residues in the presence of complexes using lysozyme as a model protein. As determined by MTT assays, complex 3 exhibited a higher cytotoxic effect towards human lung cancer cell line (A549) and liver cancer cells (HepG2). LDH, NO assay and cellular uptake of the complexes have been studied. Further, antibacterial activity studies of the complexes have been screened against the pathogenic bacteria such as Enterococcus faecalis, Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa, MIC50 values of the complexes showed that the complexes exhibited significant activity against the pathogens and among the complexes, 3 exhibited higher activity.     

Cardiac Troponin T (TNNT2) mutations are less prevalent in Indian hypertrophic cardiomyopathy patients

We sought to determine the frequency of the genetic variations in the Troponin T (TNNT2) gene and its association in Indian cardiomyopathy patients. Sequencing of the entire TNNT2 gene in 162 hypertrophic cardiomyopathy (HCM) patients, along with 179 healthy controls, revealed a total of 15 variants. These included an A28V missense mutation, a novel single-nucleotide polymorphism (SNP) (g.7239;G→A) predicted to disturb the splicing significantly, three SNPs, rs3729547 (C→T), rs3729843 (G→A), rs3729842 (C→T), which were in high linkage disequilibrium, and a 5 bp polymorphism that skipped exon 4 during splicing, which was found to be significantly higher in HCM patients (del/del genotype, p=0.00011; deletion allele, p=0.00008). Further studies on the 5 bp polymorphism in 2092 randomly selected individuals belonging to 39 ethnic and endogamous populations from 19 states of India, and representing the major linguistic Indian families, revealed that the South and the Northwest Indians have a high frequency of 5 bp deletions. The missense mutations in TNNT2 are responsible for 15%-20% of familial HCM by impairing the function of the heart muscle. However, other than the 5 bp polymorphism, our comprehensive study on the Indian HCM patients have lowered the occurrence and overall prevalence of supposedly more aggressive and worst disease causing percentage of missense mutations in TNNT2 dramatically.     

The Chlamydia trachomatis CT149 protein exhibits esterase activity in vitro and catalyzes cholesteryl ester hydrolysis when expressed in HeLa cells

Chlamydia, like other intracellular bacteria, are auxotrophic for a variety of essential metabolites and obtain cholesterol and fatty acids from their eukaryotic host cell, however not many Chlamydia-specific enzymes have been identified that are involved in lipid metabolism. In silico analysis of one candidate Chlamydia trachomatis enzyme, annotated as a conserved putative hydrolase (CT149), identified two lipase/esterase GXSXG motifs, and a potential cholesterol recognition/interaction amino acid consensus (CRAC) sequence. His-tag purified recombinant CT149 exhibited ester hydrolysis activity in a nitrophenyl acetate-based cell-free assay system. When cholesteryl linoleate was used as substrate, ester hydrolysis occurred and production of cholesterol was detected by high performance liquid chromatography. Exogenous expression of transfected CT149 in HeLa cells resulted in a significant decrease of cytoplasmic cholesteryl esters within 48 h. These results demonstrate that CT149 has cholesterol esterase activity and is likely to contribute to the hydrolysis of eukaryotic cholesteryl esters during intracellular chlamydial growth.     

Early secretory antigenic target-6 of Mycobacterium tuberculosis: enigmatic factor in pathogen–host interactions

T helper (Th) 1 and 17 cells play important roles in host protective responses against tuberculosis. Early Secretory Antigenic Target 6; a Region of Difference 1 (RD1) encoded protein, mounts Th17-responses in the lung. Therefore, lack of RD-1 region makes Bacillus Calmette–Guérin (BCG) less vaccine efficacious than parent strains.     

Cardioprotective effect of zinc requires ErbB2 and Akt during hypoxia/reoxygenation

Recent literature suggests that exogenous zinc can prevent ischemia reperfusion injury by activating phosphoinositide-3 kinase (PI3K)/Akt and by targeting the mitochondrial permeability transition pore (mPTP). It is known that ErbB2 expression promotes association and activation of PI3-kinase/Akt, resulting in growth and survival of cardiac myocytes. In this study, we found that zinc-induced ErbB2 protein expression and Akt activation are required for preventing reperfusion injury. Neonatal rat cardiac myocytes subjected to 8 h of hypoxia, followed by 16 h of reoxygenation induced cardiomyocyte apoptosis, as assessed by increased caspase-3 activity, annexin V staining and lowered MTT reduction and ATP levels. However, addition of zinc-pyrithione (ZPT) before onset of reoxygenation effectively lowered the apoptotic indices and restored the ATP levels. ZPT induced a significant increase in ErbB2 protein expression and Akt activation. Pretreatment with Hsp 90 inhibitor, geldanamycin or PI3-kinase inhibitor, wortmannin prevented the increase in ATP levels and abrogated the protective effect of zinc-pyrithione. Taken together, these data suggest that zinc prevents reperfusion injury by modulating the ErbB2 protein expression and Akt activation.     

Phytochrome Regulation of Nitrite Reductase--a Chloroplast Enzyme--in Etiolated Maize Leaves

Nitrite reductase in the excised etiolated leaves of maize showedthe photoreversibility by red and far-red light. Five minutesof red light illumination lead to a 130% increase in the enzymeactivity which was reversed by far-red light. The kinetics ofnitrite reductase activity under continuous far-red light showeda lag phase of 1 hr. (Received January 17, 1981; Accepted February 20, 1981)