Determination of genetic variability of Asian rice (Oryza sativa L.) varieties using microsatellite markers

The microsatellite or simple sequence repeat (SSR) marker analysis was done to determine the allelic diversity and relationship among thirty-five Asian cultivars of rice including 19 aromatic, 13 nonaromaticand 3 japonica type cultivars. A total of 144 alleles were detected at the 32 SSR loci, of which 141 (98%) were polymorphic. The number of alleles generated by each marker ranged from 2 to 13 with an average of 4.5 alleles per marker. The size of smallest and largest allele ranged from 8(RM122) to as high as 71 (RM302). Polymorphism information content (PIC) values ranged between 0.157 (RM19, RM55) and 0.897 (RM70), with an average of 0.603 per marker. Basmati rice varieties amplified different alleles at 15 of the SSR loci than those in the japonica and/ or indica rice varieties. A number of SSRs were identified that could be utilized to differentiate between basmati and other non-basmati rice varieties. The RM252 and RM310 showed a clear differentiation of japonica cultivarsfrom other ones. Pair-wise Nei and Li’s similarity coefficients ranged from 0.19 to 0.90. The dendrogram based on the cluster analysis by microsatellite polymorphism, grouped 35 rice cultivars into two major groups effectively differentiating the tall, late maturing and slender aromatic cultivars from the short statured, early, short bold and long bold non-aromatic cultivars. These results could be useful for monitoring purity, genotype identification and for plant variety protection

Caregivers knowledge, practices about childhood diarrhea and pneumonia and their perceptions of lady health worker program; findings from NIGRAAN implementation research project

Background: Despite 60% coverage by Lady Health Worker (LHW) Program, 30% of child deaths in Pakistan are still due to diarrhea and pneumonia. Caregivers are an important stakeholder yet there is little information on their case management practices and utilization of LHW Program. This study explored caregivers’ knowledge and practices about childhood diarrhea and pneumonia and utility of LHW services before and after a supportive supervision intervention.Methods: Cross sectional surveys were conducted with caregivers’ (mothers) pre and post intervention in project NIGRAAN. The intervention aimed to improve LHSs clinical and supervisory skills of lady health supervisors in order to improve LHW performance and ultimately impact caregiver practices. 4250 households were surveyed. Questionnaire was adapted from PDHS 2012-13. Differences between intervention and control groups were assessed using chi square test. P-value of Results: Comparing baseline to end line, there were significant overall improvements in caregivers’knowledge of loose motion (62 to 84%) and dehydration (12 to 18%) as signs and symptoms of childhood diarrhea. There was also a significant overall increase in caregivers’ knowledge of presenting features of pneumonia- i.e. fever (58 to 86%), cough (51 to 61%) and breathing problems (25 to 57%). The proportion of caregivers seeking advice for diarrhea from public sector significantly improved in intervention arm from 20% to 29%. Private sector however remained overall preferred choice for care seeking. There was significant overall improvement in awareness about LHWs functioning (93 to 99%) and household visits (91 to 98%). Actual care seeking from LHWs however stayed low (≤ 0.3%) Conclusion: In order to improve utility and expand coverage of LHW Program interventions aimed at providing supportive supervision have the potential to improve caregiver practices and utilization of available services and decrease childhood deaths due to preventable illnesses

Laminin isoform expression in breast tumors

Certain laminins of vascular basement membranes have been identified in human breast tumors and brain gliomas that share the same β1 chain. These laminins are new carcinoma angiogenic markers and might represent potential targets for antiangiogenic therapy

The Relationship Between Bleeding on Probing and Subgingival Deposits. An Endoscopical Evaluation

none4Background: Bleeding on probing (BOP) is an indicator of tissue inflammatory response to bacterial pathogens. Because anatomical limitations the entity and physical state of microbial aggregations located under the gingival margin and their relations to BOP have been hardly investigated till now. The recent introduction of the endoscopy has allowed clinicians to view the subgingival environment in a non-traumatic way. Aim of this study is to evaluate the correlation between BOP and subgingival deposits by using this new technology. Methods: At one-month revaluation of 16 periodontal patients treated with scaling and root planning, 107 teeth (642 individual sites) were evaluated for plaque index (PI), gingival index (GI), probing pocket depth (PPD), bleeding on probing (BOP), endoscopic biofilm index (EBI) and endoscopic calculus index (ECI). Results: A linear association between BOP and PD, EBI, and ECI was detected. The BOP provided a high level of specificity but quite low sensitivity values both for ECI (sensitivity 40%, specificity 86%) and EBI (sensitivity 37%, specificity 89%). The BOP sensitivity was directly linked to the amount of subgingival deposits. Conclusions: This study demonstrates a direct relationship between BOP and presence/amount of subgingival deposits. More investigations on larger samples are however needed.noneChecchi l.; Montevecchi M.; Checchi V.; Zappulla F.Checchi l.; Montevecchi M.; Checchi V.; Zappulla F

Synergistic activity of troxacitabine (Troxatyl™) and gemcitabine in pancreatic cancer

<p>Abstract</p> <p>Background</p> <p>Gemcitabine, a deoxycytidine nucleoside analog, is the current standard chemotherapy used as first-line treatment for patients with locally advanced or metastatic cancer of the pancreas, and extends life survival by 5.7 months. Advanced pancreatic cancer thus remains a highly unmet medical need and new therapeutic agents are required for this patient population. Troxacitabine (Troxatyl™) is the first unnatural L-nucleoside analog to show potent preclinical antitumor activity and is currently under clinical investigation. Troxacitabine was recently evaluated as a first-line therapy in 54 patients with advanced adenocarcinoma of the pancreas and gave comparable overall results to those reported with gemcitabine in recently published randomized trials.</p> <p>Methods</p> <p>The human pancreatic adenocarcinoma cell lines, AsPC-1, Capan-2, MIA PaCa-2 and Panc-1, were exposed to troxacitabine or gemcitabine alone or in combination, for 72 h, and the effects on cell growth were determined by electronic particle counting. Synergistic efficacy was determined by the isobologram and combination-index methods of Chou and Talalay. Mechanistic studies addressed incorporation of troxacitabine into DNA and intracellular levels of troxacitabine and gemcitabine metabolites. For <it>in vivo </it>studies, we evaluated the effect of both drugs, alone and in combination, on the growth of established human pancreatic (AsPC-1) tumors implanted subcutaneously in nude mice. Statistical analysis was calculated by a one-way ANOVA with Dunnett as a post-test and the two-tailed unpaired <it>t </it>test using GraphPad prism software.</p> <p>Results</p> <p>Synergy, evaluated using the CalcuSyn Software, was observed in all four cell-lines at multiple drug concentrations resulting in combination indices under 0.7 at Fa of 0.5 (50% reduction of cell growth). The effects of drug exposures on troxacitabine and gemcitabine nucleotide pools were analyzed, and although gemcitabine reduced phosphorylation of troxacitabine when cells were exposed at equal drug concentrations, there was no effect on phosphorylated pools at drug combinations that were synergistic. The amount of troxacitabine incorporated into DNA was also not affected by the presence of gemcitabine. <it>In vivo </it>testing against a human pancreatic (AsPC-1) xenograft mouse tumor model indicated that both drugs were more than additive at well-tolerated doses and schedule. The biological basis for this synergy is unclear as we did not observe changes in apoptosis, DNA repair, troxacitabine incorporation into DNA or troxacitabine metabolism in the presence of gemcitabine.</p> <p>Conclusion</p> <p>These data, together with phase I clinical data showing tolerability of both agents when combined, suggest combination therapy with troxacitabine and gemcitabine warrants further evaluation in advanced pancreatic cancer patients.</p

Genome-wide association study with 1000 genomes imputation identifies signals for nine sex hormone-related phenotypes.

Genetic factors contribute strongly to sex hormone levels, yet knowledge of the regulatory mechanisms remains incomplete. Genome-wide association studies (GWAS) have identified only a small number of loci associated with sex hormone levels, with several reproductive hormones yet to be assessed. The aim of the study was to identify novel genetic variants contributing to the regulation of sex hormones. We performed GWAS using genotypes imputed from the 1000 Genomes reference panel. The study used genotype and phenotype data from a UK twin register. We included 2913 individuals (up to 294 males) from the Twins UK study, excluding individuals receiving hormone treatment. Phenotypes were standardised for age, sex, BMI, stage of menstrual cycle and menopausal status. We tested 7,879,351 autosomal SNPs for association with levels of dehydroepiandrosterone sulphate (DHEAS), oestradiol, free androgen index (FAI), follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin, progesterone, sex hormone-binding globulin and testosterone. Eight independent genetic variants reached genome-wide significance (P<5 × 10(-8)), with minor allele frequencies of 1.3-23.9%. Novel signals included variants for progesterone (P=7.68 × 10(-12)), oestradiol (P=1.63 × 10(-8)) and FAI (P=1.50 × 10(-8)). A genetic variant near the FSHB gene was identified which influenced both FSH (P=1.74 × 10(-8)) and LH (P=3.94 × 10(-9)) levels. A separate locus on chromosome 7 was associated with both DHEAS (P=1.82 × 10(-14)) and progesterone (P=6.09 × 10(-14)). This study highlights loci that are relevant to reproductive function and suggests overlap in the genetic basis of hormone regulation.We thank Roche Diagnostics Australia Pty Limited, Castle Hill, Australia, who provided support for the analysis of the hormones. We thank the volunteer twins for their participation in the study. Twins UK received funding support from NIHR Biomedical Research Centre (grant to Guys’ and St. Thomas’ Hospitals and King’s College London); the Chronic Disease Research Foundation; Canadian Institutes of Health Research, the Canadian Foundation for Innovation, the Fonds de la Recherche en Santé Québec, The Lady Davis Institute, the Jewish General Hospital and Ministère du Développement économique, de l'Innovation et de l'Exportation du Quebec. The Australian National Health and Medical Research Council (NHMRC project grants 1010494, 1048216), and Sir Charles Gairdner Hospital Research (grant PP2009/028). This work was supported by funding from the Wellcome Trust (092447/Z/10/Z) and Medical Research Council (MC_U106179472).This is the final version of the article. It first appeared from NPG via http://dx.doi.org/10.1038/ejhg.2015.10

Maspin is a tumour suppressor that inhibits breast cancer tumour metastasis in vivo

Maspin is a member of the serpin family of serine proteases and functions as a tumour suppressor. A study using a new syngeneic mouse model for breast cancer suggests that maspin can inhibit metastasis in vivo