Distributed subglacial discharge drives significant submarine melt at a Greenland tidewater glacier

Submarine melt can account for substantial mass loss at tidewater glacier termini. However, the processes controlling submarine melt are poorly understood due to limited observations of submarine termini. Here at a tidewater glacier in central West Greenland, we identify subglacial discharge outlets and infer submarine melt across the terminus using direct observations of the submarine terminus face. We find extensive melting associated with small discharge outlets. While the majority of discharge is routed to a single, large channel, outlets not fed by large tributaries drive submarine melt rates in excess of 3.0 m d−1 and account for 85% of total estimated melt across the terminus. Nearly the entire terminus is undercut, which may intersect surface crevasses and promote calving. Severe undercutting constricts buoyant outflow plumes and may amplify melt. The observed morphology and melt distribution motivate more realistic treatments of terminus shape and subglacial discharge in submarine melt models

Maternal hemoglobin depletion in a settled Northern Kenyan pastoral population

Objectives: This study examines maternal hemoglobin depletion in a cross-sectional sample of Ariaal women living in northern Kenya. Maternal hemoglobin depletion occurs when women do not have enough dietary iron to replace the high levels of iron allocated to the fetus during pregnancy. Methods: To study this phenomenon, reproductive histories, socioeconomic status, anthropometry, and hemoglobin levels were collected from a cross-section of 200 lactating Ariaal women in northern Kenya. Results: Ariaal women show increasing levels of hemoglobin with increasing time since birth and lower hemoglobin levels with increasing parity, indicating an incomplete repletion of dietary iron over women's reproductive lifetime. Women who lived in a more livestock-dependent village had higher hemoglobin levels and lower prevalence of clinical anemia than women who lived in villages more dependent on agriculture, indicating that differences in diet may alleviate the effects of iron depletion. Conclusions: These data demonstrate that Ariaal women are iron depleted due to pregnancy, incompletely replete hemoglobin during the course of lactation, and show depletion of hemoglobin with increasing parity. Women in this community may be able to improve their iron status through a greater reliance on food sources rich in dietary iron. Am. J. Hum. Biol., 2010. © 2010 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78218/1/21078_ftp.pd

Distributed subglacial discharge drives significant submarine melt at a Greenland tidewater glacier

Submarine melt can account for substantial mass loss at tidewater glacier termini. However, the processes controlling submarine melt are poorly understood due to limited observations of submarine termini. Here at a tidewater glacier in central West Greenland, we identify subglacial discharge outlets and infer submarine melt across the terminus using direct observations of the submarine terminus face. We find extensive melting associated with small discharge outlets. While the majority of discharge is routed to a single, large channel, outlets not fed by large tributaries drive submarine melt rates in excess of 3.0 m d⁻¹ and account for 85% of total estimated melt across the terminus. Nearly the entire terminus is undercut, which may intersect surface crevasses and promote calving. Severe undercutting constricts buoyant outflow plumes and may amplify melt. The observed morphology and melt distribution motivate more realistic treatments of terminus shape and subglacial discharge in submarine melt models.This is the publisher’s final pdf. The article is copyrighted by American Geophysical Union and published by John Wiley & Sons, Inc. It can be found at: http://agupubs.onlinelibrary.wiley.com/agu/journal/10.1002/%28ISSN%291944-8007

Towards intensive parenting? Changes in the composition and determinants of mothers' and fathers' time with children 1992-2006

Contemporary expectations of good parenting hold that focused, intensive parental attention is essential to children's development. Parental input is viewed as a key determinant in children's social, psychological and educational outcomes, with the early years particularly crucial. However, increased rates of maternal employment mean that more parents are juggling work and family commitments and have less non-work time available to devote to children. Yet studies find that parental childcare time has increased over recent decades. In this paper, we explore the detail of this trend using data from the Australian Bureau of Statistics (ABS) Time Use Survey (TUS), 1992 and 2006. To investigate whether discourses on intensive parenting are reflected in behaviour, we examine a greater range of parent-child activities than has been undertaken to date, looking at trends in active childcare time (disaggregated into talk-based, physical and accompanying care activities); time in childcare as a secondary activity; time spent in the company of children in leisure activities; and time spent in the company of children in total. We also investigate whether the influence of factors known to predict parental time with children (gender, education, employment status and the age of children) have changed over time. We contextualize our analyses within social and economic trends in Australia and find a compositional change in parental time, with more active childcare occurring within less overall time, which suggests more intensive, child-centred parenting. Fathers' parent-child time, particularly in physical care, increased more than mothers' (from a much lower base), and tertiary education no longer predicts significantly higher childcare time. © London School of Economics and Political Science 2014

Anti-proliferative activity of the quassinoid NBT-272 in childhood medulloblastoma cells

BACKGROUND: With current treatment strategies, nearly half of all medulloblastoma (MB) patients die from progressive tumors. Accordingly, the identification of novel therapeutic strategies remains a major goal. Deregulation of c-MYC is evident in numerous human cancers. In MB, over-expression of c-MYC has been shown to correlate with anaplasia and unfavorable prognosis. In neuroblastoma – an embryonal tumor with biological similarities to MB – the quassinoid NBT-272 has been demonstrated to inhibit cellular proliferation and to down-regulate c-MYC protein expression. METHODS: To study MB cell responses to NBT-272 and their dependence on the level of c-MYC expression, DAOY (wild-type, empty vector transfected or c-MYC transfected), D341 (c-MYC amplification) and D425 (c-MYC amplification) human MB cells were used. The cells were treated with different concentrations of NBT-272 and the impact on cell proliferation, apoptosis and c-MYC expression was analyzed. RESULTS: NBT-272 treatment resulted in a dose-dependent inhibition of cellular proliferation (IC50 in the range of 1.7 – 9.6 ng/ml) and in a dose-dependent increase in apoptotic cell death in all human MB cell lines tested. Treatment with NBT-272 resulted in up to 90% down-regulation of c-MYC protein, as demonstrated by Western blot analysis, and in a significant inhibition of c-MYC binding activity. Anti-proliferative effects were slightly more prominent in D341 and D425 human MB cells with c-MYC amplification and slightly more pronounced in c-MYC over-expressing DAOY cells compared to DAOY wild-type cells. Moreover, treatment of synchronized cells by NBT-272 induced a marked cell arrest at the G1/S boundary. CONCLUSION: In human MB cells, NBT-272 treatment inhibits cellular proliferation at nanomolar concentrations, blocks cell cycle progression, induces apoptosis, and down-regulates the expression of the oncogene c-MYC. Thus, NBT-272 may represent a novel drug candidate to inhibit proliferation of human MB cells in vivo

c-MYC expression sensitizes medulloblastoma cells to radio- and chemotherapy and has no impact on response in medulloblastoma patients

BACKGROUND: To study whether and how c-MYC expression determines response to radio- and chemotherapy in childhood medulloblastoma (MB). METHODS: We used DAOY and UW228 human MB cells engineered to stably express different levels of c-MYC, and tested whether c-MYC expression has an effect on radio- and chemosensitivity using the colorimetric 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium inner salt (MTS) assay, clonogenic survival, apoptosis assays, cell cycle analysis, and western blot assessment. In an effort to validate our results, we analyzed c-MYC mRNA expression in formalin-fixed paraffin-embedded tumor samples from well-documented patients with postoperative residual tumor and compared c-MYC mRNA expression with response to radio- and chemotherapy as examined by neuroradiological imaging. RESULTS: In DAOY - and to a lesser extent in UW228 - cells expressing high levels of c-MYC, the cytotoxicity of cisplatin, and etoposide was significantly higher when compared with DAOY/UW228 cells expressing low levels of c-MYC. Irradiation- and chemotherapy-induced apoptotic cell death was enhanced in DAOY cells expressing high levels of c-MYC. The response of 62 of 66 residual tumors was evaluable and response to postoperative radio- (14 responders (CR, PR) vs. 5 non-responders (SD, PD)) or chemotherapy (23 CR/PR vs. 20 SD/PD) was assessed. c-MYC mRNA expression was similar in primary MB samples of responders and non-responders (Mann-Whitney U test, p = 0.50, ratio 0.49, 95% CI 0.008-30.0 and p = 0.67, ratio 1.8, 95% CI 0.14-23.5, respectively). CONCLUSIONS: c-MYC sensitizes MB cells to some anti-cancer treatments in vitro. As we failed to show evidence for such an effect on postoperative residual tumors when analyzed by imaging, additional investigations in xenografts and larger MB cohorts may help to define the exact function of c-MYC in modulating response to treatment

How evolutionary principles improve the understanding of human health and disease

An appreciation of the fundamental principles of evolutionary biology provides new insights into major diseases and enables an integrated understanding of human biology and medicine. However, there is a lack of awareness of their importance amongst physicians, medical researchers, and educators, all of whom tend to focus on the mechanistic (proximate) basis for disease, excluding consideration of evolutionary (ultimate) reasons. The key principles of evolutionary medicine are that selection acts on fitness, not health or longevity; that our evolutionary history does not cause disease, but rather impacts on our risk of disease in particular environments; and that we are now living in novel environments compared to those in which we evolved. We consider these evolutionary principles in conjunction with population genetics and describe several pathways by which evolutionary processes can affect disease risk. These perspectives provide a more cohesive framework for gaining insights into the determinants of health and disease. Coupled with complementary insights offered by advances in genomic, epigenetic, and developmental biology research, evolutionary perspectives offer an important addition to understanding disease. Further, there are a number of aspects of evolutionary medicine that can add considerably to studies in other domains of contemporary evolutionary studies

RNA interference-mediated c-MYC inhibition prevents cell growth and decreases sensitivity to radio- and chemotherapy in childhood medulloblastoma cells

BACKGROUND: With current treatment strategies, nearly half of all medulloblastoma (MB) patients die from progressive tumors. Accordingly, the identification of novel therapeutic strategies remains a major goal. Deregulation of c-MYC is evident in numerous human cancers. In MB, over-expression of c-MYC has been shown to cause anaplasia and correlate with unfavorable prognosis. METHODS: To study the role of c-MYC in MB biology, we down-regulated c-MYC expression by using small interfering RNA (siRNA) and investigated changes in cellular proliferation, cell cycle analysis, apoptosis, telomere maintenance, and response to ionizing radiation (IR) and chemotherapeutics in a representative panel of human MB cell lines expressing different levels of c-MYC (DAOY wild-type, DAOY transfected with the empty vector, DAOY transfected with c-MYC, D341, and D425). RESULTS: siRNA-mediated c-MYC down-regulation resulted in an inhibition of cellular proliferation and clonogenic growth, inhibition of G1-S phase cell cycle progression, and a decrease in human telomerase reverse transcriptase (hTERT) expression and telomerase activity. On the other hand, down-regulation of c-MYC reduced apoptosis and decreased the sensitivity of human MB cells to IR, cisplatin, and etoposide. This effect was more pronounced in DAOY cells expressing high levels of c-MYC when compared with DAOY wild-type or DAOY cells transfected with the empty vector. CONCLUSION: In human MB cells, in addition to its roles in growth and proliferation, c-MYC is also a potent inducer of apoptosis. Therefore, targeting c-MYC might be of therapeutic benefit when used sequentially with chemo- and radiotherapy rather than concomitantly

Complementary intestinal mucosa and microbiota responses to caloric restriction

The intestine is key for nutrient absorption and for interactions between the microbiota and its host. Therefore, the intestinal response to caloric restriction (CR) is thought to be more complex than that of any other organ. Submitting mice to 25% CR during 14 days induced a polarization of duodenum mucosa cell gene expression characterised by upregulation, and downregulation of the metabolic and immune/inflammatory pathways, respectively. The HNF, PPAR, STAT, and IRF families of transcription factors, particularly the Pparα and Isgf3 genes, were identified as potentially critical players in these processes. The impact of CR on metabolic genes in intestinal mucosa was mimicked by inhibition of the mTOR pathway. Furthermore, multiple duodenum and faecal metabolites were altered in CR mice. These changes were dependent on microbiota and their magnitude corresponded to microbial density. Further experiments using mice with depleted gut bacteria and CR-specific microbiota transfer showed that the gene expression polarization observed in the mucosa of CR mice is independent of the microbiota and its metabolites. The holistic interdisciplinary approach that we applied allowed us to characterize various regulatory aspects of the host and microbiota response to CR