RUNX1T1, a potential prognostic marker in breast cancer,is co-ordinately expressed with ERα, and regulated by estrogen receptor signalling in breast cancer cells

Molecular Biology Reports - RUNX1T1 is extensively studied in the context of AML1-RUNX1T1 fusion protein in acute myeloid leukemia. Little is known about the function of RUNX1T1 itself, although...     

Circulating plasma microRNAs in colorectal neoplasia: A pilot study in assessing response to therapy

IntroductionCurrent serological surveillance markers to monitor colorectal cancer (CRC) or colorectal advanced adenomas (CAA) are hampered by poor sensitivity and specificity. The aim of this study is to identify and validate a panel of plasma microRNAs which change in expression after resection of such lesions.MethodsA prospectively maintained colorectal surgery database was queried for patients in whom both pre- and post-procedural serum samples had been obtained. An initial screening analysis of CRC and CAA patients (5 each) was conducted using screening cards for 380 miRNAs. Four identified miRNAs were combined with a previously described panel of 7 miRNAs that were diagnostically predictive of CRC and CAA. Differential miRNA expression was assessed using quantitative real-time polymerase chain reaction(qRT-PCR).ResultsFifty patients were included (n = 27 CRC, n = 23 CAA). There was no difference in age, gender, or race profile of CRC patients compared to CAA patients. Six miRNA were significantly increased after CRC resection (miR-324, let7b, miR-454, miR-374a, miR-122, miR-19b, all p<0.05), while three miRNAs were significantly increased following CAA resection (miR-454, miR-374a, miR-122, all p<0.05). Three miRNA were increased in common for both (miR-454, miR-374a, miR-122).DiscussionThe expression of miRNAs associated with neoplasia (either CRC or CAA) was significantly increased following surgical resection or endoscopic removal of CRC or CAA. Future studies should focus on the evaluation of these miRNAs in CRC and CAA prognosis.     

Inactivation of ntcA gene revealed differential proteome expression and induction of some hypothetical proteins in the cyanobacterium Anabaena sp. PCC 7120 and its derivative ntcA mutant under different levels of calcium

Abstract

Calcium is an important macronutrient for both prokaryotes and eukaryotes. It acts as an important second messenger mediating rapid response to environmental conditions. The present investigation deals with proteome profiling of Anabaena 7120 and its derivative ntcA mutant in response to varied calcium doses (0, 1 and 10?mM CaCl₂). Concentration of 1?mM CaCl₂ salt was the optimum concentration whereas 10?mM CaCl₂ was the inhibitory concentration for both the wild type and mutant strains. The results showed highly significant alteration in terms of protein abundance and differential response related to key processes of photosynthesis, energy and metabolism, nitrogen metabolism, oxidative and antioxidative defence, transport and signalling and fatty acid metabolism. In the wild type proteins related to photosynthesis and nitrogen metabolism showed upregulation at 1?mM CaCl₂ concentration while antioxidative defence related proteins were down-regulated. In the mutant however, proteins related to photosynthesis and nitrogen metabolism exhibited severe down-regulation. Some hypothetical proteins were also realized during proteome analysis. Overall, our results suggested that NtcA have a potential role in regulation of calcium ion dependent key processes underlying in various metabolic activities of the cyanobacterium Anabaena 7120.     

Consequences of MnSOD interactions with nitric oxide: Nitric oxide dismutation and the generation of peroxynitrite and hydrogen peroxide

The present study demonstrates that manganese superoxide dismutase (MnSOD) (Escherichia coli), binds nitric oxide (^√NO) and stimulates its decay under both anaerobic and aerobic conditions. The results indicate that previously observed MnSOD-catalyzed ^√NO disproportionation (dismutation) into nitrosonium (NO⁺) and nitroxyl (NO^? ) species under anaerobic conditions is also operative in the presence of molecular oxygen. Upon sustained aerobic exposure to ^√NO, MnSOD-derived NO^? species initiate the formation of peroxynitrite (ONOO^? ) leading to enzyme tyrosine nitration, oxidation and (partial) inactivation. The results suggest that both ONOO^? decomposition and ONOO^? -dependent tyrosine residue nitration and oxidation are enhanced by metal centre-mediated catalysis. We show that the generation of ONOO^? is accompanied by the formation of substantial amounts of H₂O₂. MnSOD is a critical mitochondrial antioxidant enzyme, which has been found to undergo tyrosine nitration and inactivation in various pathologies associated with the overproduction of ^√NO. The results of the present study can account for the molecular specificity of MnSOD nitration in vivo. The interaction of ^√NO with MnSOD may represent a novel mechanism by which MnSOD protects the cell from deleterious effects associated with overproduction of ^√NO.     

The Novel 6–(N-Pyrrolyl)purine Acyclic Nucleosides: 1H and 13C NMR and X-ray Structural Study†

Abstract

Synthesis of the novel nucleoside analogues containing exocyclic pyrrolo moiety and acyclic side chains attached to the purine ring at N-9 and N-7 is described. The site of alkylation was determined by ¹H and ¹³C NMR on the basis of chemical shifts, C-H coupling constants and connectivity in NOESY and HETCOR spectra. The N-9 substitution of 7 was proved by its X-ray crystallographic analysis.

     

Distribution and development of P2Y1-purinoceptors in the mouse retina

There is increasing evidence that ATP acts on purinergic receptors and mediates synaptic transmission in the retina. In a previous study, we raised the possibility that P2X-purinoceptors, presumably P2X₂-purinoceptors in OFF-cholinergic amacrine cells, play a key role in the formation of OFF pathway-specific modulation. In this study, we examined whether the P2Y₁-purinoceptors can function in cholinergic amacrine cells in the mouse retina since cholinergic amacrine cells in the rat retina express P2Y₁-purinoceptors. P2Y₁-purinoceptors were shown to be expressed in dendrites of both ON- and OFF-cholinergic amacrine cells in adults. At postnatal day 7, there was immunoreactivity for P2Y₁-purinoceptors in the soma of cholinergic amacrine cells. At postnatal day 14, weak immunoreactivity for P2Y₁-purinoceptors was detected in the dendrites but not in the soma of cholinergic amacrine cells. At postnatal day 21, strong immunoreactivity for P2Y₁-purinoceptors was detected in dendrites of cholinergic amacrine cells. The expression pattern of P2Y₁-purinoceptors was not affected by visual experience. We concluded that P2Y₁-purinoceptors are not involved in the OFF-pathway-specific signal transmission in cholinergic amacrine cells of the mouse retina.     

The Light Skin Allele of SLC24A5 in South Asians and Europeans Shares Identity by Descent

Skin pigmentation is one of the most variable phenotypic traits in humans. A non-synonymous substitution (rs1426654) in the third exon of SLC24A5 accounts for lighter skin in Europeans but not in East Asians. A previous genome-wide association study carried out in a heterogeneous sample of UK immigrants of South Asian descent suggested that this gene also contributes significantly to skin pigmentation variation among South Asians. In the present study, we have quantitatively assessed skin pigmentation for a largely homogeneous cohort of 1228 individuals from the Southern region of the Indian subcontinent. Our data confirm significant association of rs1426654 SNP with skin pigmentation, explaining about 27% of total phenotypic variation in the cohort studied. Our extensive survey of the polymorphism in 1573 individuals from 54 ethnic populations across the Indian subcontinent reveals wide presence of the derived-A allele, although the frequencies vary substantially among populations. We also show that the geospatial pattern of this allele is complex, but most importantly, reflects strong influence of language, geography and demographic history of the populations. Sequencing 11.74 kb of SLC24A5 in 95 individuals worldwide reveals that the rs1426654-A alleles in South Asian and West Eurasian populations are monophyletic and occur on the background of a common haplotype that is characterized by low genetic diversity. We date the coalescence of the light skin associated allele at 22–28 KYA. Both our sequence and genome-wide genotype data confirm that this gene has been a target for positive selection among Europeans. However, the latter also shows additional evidence of selection in populations of the Middle East, Central Asia, Pakistan and North India but not in South India.     

Adherence to Antiretroviral Therapy and Its Effect on Survival of HIV-Infected Individuals in Jharkhand,India

Introduction

Research in India has extensively examined the factors associated with non-adherence to antiretroviral therapy (ART) with limited focus on examining the relationship between adherence to ART regimen and survival status of HIV infected patients. This study examines the effect of optimal adherence to ART on survival status of HIV infected patients attending ART centers in Jharkhand, India.

Materials and Methods

Data from a cohort of 239 HIV infected individuals who were initiated ART in 2007 were compiled from medical records retrospectively for 36 months. Socio-demographic characteristics, CD4 T cell count, presence of opportunistic infections at the time of ART initiation and ART regimen intake and survival status was collected periodically. Optimal adherence was assessed using pill count methods; patients who took <95% of the specified regimens were identified as non-adherent. Cox-proportional hazard model was used to determine the relative hazards of mortality.

Results

More than three-fourths of the patients were male, on an average 34 year old and median CD4 T cell count was 118 cells/cmm at the time of ART registration. About 57% of the patients registered for ART were found to be adherent to ART. A total of 104 patients died in 358.5 patient-years of observation resulting in a mortality rate of 29 per 100 patient-years (95% confidence interval (CI): 23.9–35.2) and median survival time of 6.5 months (CI: 2.7–10.9). The mortality rate was higher among patients who were non-adherent to ART (64.5, CI: 50.5–82.4) than who were adherent (15.4, CI: 11.3–21.0). The risk of mortality was fourfold higher among individuals who were non-adherent to ART than who were adherent (Adjusted hazard ratio: 3.9, CI: 2.6–6.0).

Conclusion

Adherence to ART is associated with a higher chance of survival of HIV infected patients, ascertaining the need for interventions to improve the ART adherence and early initiation of ART.     

NO and ROS implications in the organization of root system architecture

Over the past decades the role of nitric oxide (NO) and reactive oxygen species (ROS) in signaling and cellular responses to stress has witnessed an exponential trend line. Despite advances in the subject, our knowledge of the role of NO and ROS as regulators of stress and plant growth and their implication in signaling pathways is still partial. The crosstalk between NO and ROS during root formation offers new domains to be explored, as it regulates several plant functions. Previous findings indicate that plants utilize these signaling molecules for regulating physiological responses and development. Depending upon cellular concentration, NO either can stimulate or impede root system architecture (RSA) by modulating enzymes through post-translational modifications. Similarly, the ROS signaling molecule network, in association with other hormonal signaling pathways, control the RSA. The spatial regulation of ROS controls cell growth and ROS determine primary root and act in concert with NO to promote lateral root primordia. NO and ROS are two central messenger molecules which act differentially to upregulate or downregulate the expression of genes pertaining to auxin synthesis and to the configuration of root architecture. The investigation concerning the contribution of donors and inhibitors of NO and ROS can further aid in deciphering their role in root development. With this background, this review provides comprehensive details about the effect and function of NO and ROS in the development of RSA.     

Herbal remedies for the management of seed-borne fungal pathogens by an edible plant Decalepis hamiltonii (Wight & Arn)

Abstract

Antifungal activity-guided assay of solvent extracts of Decalepis hamiltonii (Wight & Arn) (Asclepiadaceae) against important phytopathogenic fungi, known to cause diseases in sorghum, maize and paddy proved to be highly significant. Among the five solvent extracts tested, Petroleum ether extract showed highly significant antifungal activity. Phytochemical analysis revealed that the antifungal active principle is a phenolic compound. TLC separation of the phenolic fraction using chloroform as an eluting solvent revealed the presence of seven bands but the antifungal activity was observed only in band five with R_f value 0.77. The antifungal active compound is identified as 2-hydroxy-4-methoxybenzaldehyde based on Nuclear Magnetic Resonance (NMR) and mass spectral analysis. The Minimal inhibitory concentration (MIC) varied between 200 μg ml^?1 and 700 μg ml^?1 depending on the fungal species. Seed treatment of the active principle significantly increased seed germination and seed vigour with a corresponding decrease in seed mycoflora. The antifungal active compound was effective against all the 24 fungal species tested suggesting broad-spectrum antifungal activity. Comparative evaluation of the active principle with the synthetic fungicides revealed that the antifungal activity of the active principle obtained from the plant is better than that of synthetic fungicide. This plant being an edible one can be exploited in the management of seed-borne pathogenic fungi and the prevention of biodeterioration of grains and mycotoxin elaboration during storage.