Growth and Mass Spectrometry Profile of Alternaria Alternata Pigment Grown in Maize Grain extract

Alternaria species are common saprophytes found in a variety of habitats as ubiquitous agents of decay. Alternaria spp. produces about sixty different secondary metabolites. In the present investigation, growth and production of pigment from Alternaria alternata was studied in maize grain extract at pH 4-9. The reddish brown pigment was extracted, estimated and partially purified by fractionation. Through mass spectrometry, major constituents of pigment from Alternaria alternata such as Tenuazoic acid (m/z 198), Stemphyperylenol (m/z 253), Alterperylenol (m/z 351), Alternariol (m/z 259.200), Altenuene (m/z 292), Alternarienoic acid (m/z 279.35) and Alternariol 5 methyl ether (m/z 273.20) were identified. The bio-prospecting of these secondary metabolites in industrial applications is also discussed

Knockdown of MBP-1 in Human Foreskin Fibroblasts Induces p53-p21 Dependent Senescence

MBP-1 acts as a general transcriptional repressor. Overexpression of MBP-1 induces cell death in a number of cancer cells and regresses tumor growth. However, the function of endogenous MBP-1 in normal cell growth regulation remains unknown. To unravel the role of endogenous MBP-1, we knocked down MBP-1 expression in primary human foreskin fibroblasts (HFF) by RNA interference. Knockdown of MBP-1 in HFF (HFF-MBPsi-4) resulted in an induction of premature senescence, displayed flattened cell morphology, and increased senescence-associated beta-galactosidase activity. FACS analysis of HFF-MBPsi-4 revealed accumulation of a high number of cells in the G1-phase. A significant upregulation of cyclin D1 and reduction of cyclin A was detected in HFF-MBPsi-4 as compared to control HFF. Senescent fibroblasts exhibited enhanced expression of phosphorylated and acetylated p53, and cyclin-dependent kinase inhibitor, p21. Further analysis suggested that promyolocytic leukemia protein (PML) bodies are dramatically increased in HFF-MBPsi-4. Together, these results demonstrated that knockdown of endogenous MBP-1 is involved in cellular senescence of HFF through p53-p21 pathway

Widespread sex differences in gene expression and splicing in the adult human brain

There is strong evidence to show that men and women differ in terms of neurodevelopment, neurochemistry and susceptibility to neurodegenerative and neuropsychiatric disease. The molecular basis of these differences remains unclear. Progress in this field has been hampered by the lack of genome-wide information on sex differences in gene expression and in particular splicing in the human brain. Here we address this issue by using post-mortem adult human brain and spinal cord samples originating from 137 neuropathologically confirmed control individuals to study whole-genome gene expression and splicing in 12 CNS regions. We show that sex differences in gene expression and splicing are widespread in adult human brain, being detectable in all major brain regions and involving 2.5% of all expressed genes. We give examples of genes where sex-biased expression is both disease-relevant and likely to have functional consequences, and provide evidence suggesting that sex biases in expression may reflect sex-biased gene regulatory structures

Integrating Factor Analysis and a Transgenic Mouse Model to Reveal a Peripheral Blood Predictor of Breast Tumors

Abstract Background Transgenic mouse tumor models have the advantage of facilitating controlled in vivo oncogenic perturbations in a common genetic background. This provides an idealized context for generating transcriptome-based diagnostic models while minimizing the inherent noisiness of high-throughput technologies. However, the question remains whether models developed in such a setting are suitable prototypes for useful human diagnostics. We show that latent factor modeling of the peripheral blood transcriptome in a mouse model of breast cancer provides the basis for using computational methods to link a mouse model to a prototype human diagnostic based on a common underlying biological response to the presence of a tumor. Methods We used gene expression data from mouse peripheral blood cell (PBC) samples to identify significantly differentially expressed genes using supervised classification and sparse ANOVA. We employed these transcriptome data as the starting point for developing a breast tumor predictor from human peripheral blood mononuclear cells (PBMCs) by using a factor modeling approach. Results The predictor distinguished breast cancer patients from healthy individuals in a cohort of patients independent from that used to build the factors and train the model with 89% sensitivity, 100% specificity and an area under the curve (AUC) of 0.97 using Youden's J-statistic to objectively select the model's classification threshold. Both permutation testing of the model and evaluating the model strategy by swapping the training and validation sets highlight its stability. Conclusions We describe a human breast tumor predictor based on the gene expression of mouse PBCs. This strategy overcomes many of the limitations of earlier studies by using the model system to reduce noise and identify transcripts associated with the presence of a breast tumor over other potentially confounding factors. Our results serve as a proof-of-concept for using an animal model to develop a blood-based diagnostic, and it establishes an experimental framework for identifying predictors of solid tumors, not only in the context of breast cancer, but also in other types of cancer.</p

Nutritional Indices of the Cotton Bollworm, Helicoverpa armigera, on 13 Soybean Varieties

The effects of 13 soybean varieties (356, M4, M7, M9, Clark, Sahar, JK, BP, Williams, L17, Zane, Gorgan3, and DPX) on nutritional indices of the cotton bollworm, Helicoverpa armigera (Hübner) (Lepidoptera: Noctuidae), were determined at 25 ± 1° C, 65 ± 5% RH and a photoperiod of 16:8 L:D. Fourth instar larvae reared on Zane showed the highest efficiency of conversion of digested food (ECD) and approximate digestibility (AD) values (0.299 and 0.867, respectively) compared with other varieties. The lowest value of ECD and food consumed (FC) was on 356 (0.133 and 53.82 mg, respectively). The highest and lowest efficiency of conversion of ingested food (ECI) of fifth instar larvae (0.235 and 0.156, respectively) were on Zane and M4, respectively. The ECI and ECD values of whole larval instars were the highest on M7 (0.524 and 0.820, respectively) and lowest on Sahar (0.279 and 0.353, respectively). However, the highest and lowest value of consumption index (CI) was on M7 (7.351) and BP (3.462). Among the different varieties of soybean, the highest AD value was on M9 (0.858), and the lowest was on Zane (0.597). The results indicated that M4, Sahar, and JK were partially resistant to H. armigera

Hypoxia induces differential translation of enolase/MBP-1

<p>Abstract</p> <p>Background</p> <p>Hypoxic microenvironments in tumors contribute to transformation, which may alter metabolism, growth, and therapeutic responsiveness. The α-enolase gene encodes both a glycolytic enzyme (α-enolase) and a DNA-binding tumor suppressor protein, c-myc binding protein (MBP-1). These divergent α-enolase gene products play central roles in glucose metabolism and growth regulation and their differential regulation may be critical for tumor adaptation to hypoxia. We have previously shown that MBP-1 and its binding to the c-myc P₂promoter regulates the metabolic and cellular growth changes that occur in response to altered exogenous glucose concentrations.</p> <p>Results</p> <p>To examine the regulation of α-enolase and MBP-1 by a hypoxic microenvironment in breast cancer, MCF-7 cells were grown in low, physiologic, or high glucose under 1% oxygen. Our results demonstrate that adaptation to hypoxia involves attenuation of MBP-1 translation and loss of MBP-1-mediated regulation of c-myc transcription, evidenced by decreased MBP-1 binding to the c-myc P₂promoter. This allows for a robust increase in c-myc expression, "early c-myc response", which stimulates aerobic glycolysis resulting in tumor acclimation to oxidative stress. Increased α-enolase mRNA and preferential translation/post-translational modification may also allow for acclimatization to low oxygen, particularly under low glucose concentrations.</p> <p>Conclusions</p> <p>These results demonstrate that malignant cells adapt to hypoxia by modulating α-enolase/MBP-1 levels and suggest a mechanism for tumor cell induction of the hyperglycolytic state. This important "feedback" mechanism may help transformed cells to escape the apoptotic cascade, allowing for survival during limited glucose and oxygen availability.</p

Paniya Voices: A Participatory Poverty and Health Assessment among a marginalized South Indian tribal population

<p>Abstract</p> <p>Background</p> <p>In India, indigenous populations, known as <it>Adivasi </it>or Scheduled Tribes (STs), are among the poorest and most marginalized groups. 'Deprived' ST groups tend to display high levels of resignation and to lack the capacity to aspire; consequently their health perceptions often do not adequately correspond to their real health needs. Moreover, similar to indigenous populations elsewhere, STs often have little opportunity to voice perspectives framed within their own cultural worldviews. We undertook a study to gather policy-relevant data on the views, experiences, and priorities of a marginalized and previously enslaved tribal group in South India, the Paniyas, who have little 'voice' or power over their own situation.</p> <p>Methods/design</p> <p>We implemented a Participatory Poverty and Health Assessment (PPHA). We adopted guiding principles and an ethical code that promote respect for Paniya culture and values. The PPHA, informed by a vulnerability framework, addressed five key themes (health and illness, well-being, institutions, education, gender) using participatory approaches and qualitative methods. We implemented the PPHA in five Paniya colonies (clusters of houses in a small geographical area) in a <it>gram panchayat </it>(lowest level decentralized territorial unit) to generate data that can be quickly disseminated to decision-makers through interactive workshops and public forums.</p> <p>Preliminary findings</p> <p>Findings indicated that the Paniyas are caught in multiple 'vulnerability traps', that is, they view their situation as vicious cycles from which it is difficult to break free.</p> <p>Conclusion</p> <p>The PPHA is a potentially useful approach for global health researchers working with marginalized communities to implement research initiatives that will address those communities' health needs in an ethical and culturally appropriate manner.</p

Patterning in Birthweight in India: Analysis of Maternal Recall and Health Card Data

National data on birthweight from birth certificates or medical records are not available in India. The third Indian National Family Health Survey included data on birthweight of children obtained from health cards and maternal recall. This study aims to describe the population that these data represent and compares the birthweight obtained from health cards with maternal recall data in terms of its socioeconomic patterning and as a risk factor for childhood growth failure.The analytic sample consisted of children aged 0 to 59 months with birthweight data obtained from health cards (n = 3227) and maternal recall (n = 16,787). The difference between the card sample and the maternal recall sample in the distribution across household wealth, parental education, caste, religion, gender, and urban residence was compared using multilevel models. We also assessed the ability of birthweight to predict growth failure in infancy and childhood in the two groups. The survey contains birthweight data from a majority of household wealth categories (>5% in every category for recall), both genders, all age groups, all caste groups, all religion groups, and urban and rural dwellers. However, children from the lowest quintile of household wealth were under-represented (4.73% in card and 8.62% in recall samples). Comparison of data across health cards and maternal recall revealed similar social patterning of low birthweight and ability of birthweight to predict growth failure later in life. Children were less likely to be born with low birthweight if they had mothers with over 12 years of education compared to 1-5 years of education with relative risk (RR) of 0.79 (95% confidence interval [CI]: 0.52, 1.2) in the card sample and 0.70 (95% CI: 0.59, 0.84) in the recall sample. A 100 gram difference in a child's birthweight was associated with a decreased likelihood of underweight in both the card (RR: 0.95; 95% CI: 0.94, 0.96) and recall (RR: 0.96; 95% CI: 0.96, 0.97) samples.Our results suggest that in the absence of other sources, the data on birthweight in the third Indian National Family Health Survey is valuable for epidemiologic research

E2F1 Mediated Apoptosis Induced by the DNA Damage Response Is Blocked by EBV Nuclear Antigen 3C in Lymphoblastoid Cells

EBV latent antigen EBNA3C is indispensible for in vitro B-cell immortalization resulting in continuously proliferating lymphoblastoid cell lines (LCLs). EBNA3C was previously shown to target pRb for ubiquitin-proteasome mediated degradation, which facilitates G1 to S transition controlled by the major transcriptional activator E2F1. E2F1 also plays a pivotal role in regulating DNA damage induced apoptosis through both p53-dependent and -independent pathways. In this study, we demonstrate that in response to DNA damage LCLs knocked down for EBNA3C undergo a drastic induction of apoptosis, as a possible consequence of both p53- and E2F1-mediated activities. Importantly, EBNA3C was previously shown to suppress p53-induced apoptosis. Now, we also show that EBNA3C efficiently blocks E2F1-mediated apoptosis, as well as its anti-proliferative effects in a p53-independent manner, in response to DNA damage. The N- and C-terminal domains of EBNA3C form a stable pRb independent complex with the N-terminal DNA-binding region of E2F1 responsible for inducing apoptosis. Mechanistically, we show that EBNA3C represses E2F1 transcriptional activity via blocking its DNA-binding activity at the responsive promoters of p73 and Apaf-1 apoptosis induced genes, and also facilitates E2F1 degradation in an ubiquitin-proteasome dependent fashion. Moreover, in response to DNA damage, E2F1 knockdown LCLs exhibited a significant reduction in apoptosis with higher cell-viability. In the presence of normal mitogenic stimuli the growth rate of LCLs knockdown for E2F1 was markedly impaired; indicating that E2F1 plays a dual role in EBV positive cells and that active engagement of the EBNA3C-E2F1 complex is crucial for inhibition of DNA damage induced E2F1-mediated apoptosis. This study offers novel insights into our current understanding of EBV biology and enhances the potential for development of effective therapies against EBV associated B-cell lymphomas