Chipping away at gamma-H2AX foci

The mammalian histone H2AX protein functions as a dosage-dependent genomic caretaker and tumor suppressor. Phosphorylation of H2AX to form gamma-H2AX in chromatin around DNA double strand breaks (DSBs) is an early event following induction of these hazardous lesions. For a decade, mechanisms that regulate H2AX phosphorylation have been investigated mainly through two-dimensional immunofluorescence (IF). We recently used chromatin immunoprecipitation (ChIP) to measure gamma-H2AX densities along chromosomal DNA strands broken in G(1) phase mouse lymphocytes. Our experiments revealed that (1) gamma-H2AX densities in nucleosomes form at high levels near DSBs and at diminishing levels farther and farther away from DNA ends, and (2) ATM regulates H2AX phosphorylation through both MDC1-dependent and MDC1-independent means. Neither of these mechanisms were discovered by previous if studies due to the inherent limitations of light microscopy. Here, we compare data obtained from parallel gamma-H2AX ChIP and three-dimensional IF analyses and discuss the impact of our findings upon molecular mechanisms that regulate H2AX phosphorylation in chromatin around DNA breakage sites

Benthic invertebrates that form habitat on deep banks off southern California, with special reference to deep sea coral

There is increasing interest in the potential impacts that fishing activities have on megafaunal benthic invertebrates occurring in continental shelf and slope ecosystems. We examined how the structure, size, and high-density aggregations of invertebrates provided structural relief for fishes in continental shelf and slope ecosystems off southern California. We made 112 dives in a submersible at 32−320 m water depth, surveying a variety of habitats from high-relief rock to flat sand and mud. Using quantitative video transect methods, we made 12,360 observations of 15 structure-form-ing invertebrate taxa and 521,898 individuals. We estimated size and incidence of epizoic animals on 9105 sponges, black corals, and gorgonians. Size variation among structure-form-ing invertebrates was significant and 90% of the individuals were <0.5 m high. Less than 1% of the observations of organisms actually sheltering in or located on invertebrates involved fishes. From the analysis of spatial associations between fishes and large invertebrates, six of 108 fish species were found more often adjacent to invertebrate colonies than the number of fish predicted by the fish-density data from transects. This finding indicates that there may be spatial associations that do not necessarily include physical contact with the sponges and corals. However, the median distances between these six fish species and the invertebrates were not particularly small (1.0−5.5 m). Thus, it is likely that these fishes and invertebrates are present together in the same habitats but that there is not necessarily a functional relationship between these groups of organisms. Regardless of their associations with fishes, these invertebrates provide structure and diversity for continental shelf ecosystems off southern California and certainly deserve the attention of scientists undertaking future conservation efforts

Tumor Vessel Development and Expansion in Ewing's Sarcoma: A Review of the Vasculogenesis Process and Clinical Trials with Vascular-Targeting Agents

Ewing's sarcoma accounts for a disproportionately high portion of the overall pediatric mortality rate compared to its rare incidence in the pediatric population. Little progress has been made since the introduction of traditional chemotherapies, and understanding the biology of the tumor is critical for developing new therapies. Ewing's sarcomas rely on a functional vascular supply, which is formed by a combination of angiogenesis and vasculogenesis. Recent insights into the molecular regulation of bone marrow (BM) cell participation in vascular development have identified VEGF, SDF-1α, and DLL4 as critical players in the vasculogenesis process. Clinical trials using vascular targeting agents, specifically targeting VEGF or DLL4, are underway

Dangerous dietary supplements: Garcinia cambogia-associated hepatic failure requiring transplantation.

Commercial dietary supplements are marketed as a panacea for the morbidly obese seeking sustainable weight-loss. Unfortunately, many claims cited by supplements are unsupported and inadequately regulated. Most concerning, however, are the associated harmful side effects, often unrecognized by consumers. Garcinia cambogia extract and Garcinia cambogia containing products are some of the most popular dietary supplements currently marketed for weight loss. Here, we report the first known case of fulminant hepatic failure associated with this dietary supplement. One active ingredient in this supplement is hydroxycitric acid, an active ingredient also found in weight-loss supplements banned by the Food and Drug Administration in 2009 for hepatotoxicity. Heightened awareness of the dangers of dietary supplements such as Garcinia cambogia is imperative to prevent hepatoxicity and potential fulminant hepatic failure in additional patients

Household Food Insecurity Predictive of Health Status in Early Adolescence? A Structural Analysis Using the 2002 NSAF Data Set

We used data from the 2002 National Survey of American Families to examine a structural model of the relations among food insecurity, poor nutritional status, parental mental health problems, quality of parenting, adolescents’ emotional distress, and poor health status for a national sample of 5366 12-to-14 year-olds. The results revealed that: first, food insecurity was associated with elevated levels of parental mental health problems, diminished quality of parenting, elevated levels of adolescents’ emotional problems, and higher incidence of poor nutritional and health statuses. Second, parental mental health problems were associated with diminished quality of parenting and higher incidence of poor health status; and quality of parenting had a negative effect on emotional distress, but not on health status. Finally, poor nutritional status was associated with elevated levels of emotional distress and higher incidence of poor health status; and emotional distress was predictive of poor health status. The findings of this study highlight the mediating role of nutritional status, parenting factors and adolescents’ emotional well-being in the link between food insecurity and health; and point to the complex interaction between food insecurity and health status

Children's Health Status: Examining the Associations among Income Poverty, Material Hardship, and Parental Factors

BACKGROUND: We examined a model of multiple mediating pathways of income poverty, material hardship, parenting factors, and child health status to understand how material hardship and parental factors mediate the effects of poverty on child health. We hypothesized that: (a) poverty will be directly associated with material hardship, parental depression, and health status, and indirectly with parenting behaviors through its effects on parental depression and material hardship; (b) material hardship will be associated with parental depression, parenting behaviors, and health status; and (c) parental depression will be correlated with parenting behaviors, and that both parental depression and parenting behaviors will predict child health. METHODS AND RESULTS: We used data from the 2002 National Survey of American Families for a sample of 9,645 6-to-11 year-olds to examine a 4-step structural equation model. The baseline model included covariates and income poverty. In the hardship model, food insufficiency and medical need were added to the baseline model. The parental model included parental depression and parenting behavior and baseline model. In the full model, all the constructs were included. First, income poverty had a direct effect on health status, and an indirect effect through its association with material hardship, parental depressive affect, and parenting behaviors. Medical need and food insufficiency had negative effects on child health, and indirect effects on health through their association with parental depression and parenting behaviors. Finally, parental depression and parenting behaviors were associated with child health, and part of the effect of parental depression on health was explained by its association with parenting behaviors. CONCLUSIONS: Poverty has an independent effect on health, however, its effects are partially explained by material hardship, parental depression and parental behaviors. To improve children's health would require a multi-pronged approach involving income transfers, health insurance coverage, food and nutrition assistance, and parenting interventions

People and Nature: Toward an Ecological Model of Health Promotion

Striving for a healthier relationship among individuals, families, communities, nations, and the environment is imperative at a time in history when humankind can change the face of the earth in monumental ways. This dynamic health relationship, with an emphasis on the contributions of parks, recreation, and tourism to health promotion, is the subject of this article. A broader conception of health that moves beyond human physical and mental health to include familial, communal, national, international, and global ecological health is called for, and a more comprehensive ecological model of health promotion, including consideration of health from a holistic ecological perspective, is presented. New directions for leisure research based on an ecological orientation to health promotion conclude the article

Inclusive Semileptonic b→cℓνˉb \to c \ell \bar{\nu} Decays to Order 1/mb51/m_b^5

Inclusive semileptonic $B\to X_c \ell\bar{\nu}$ decays can be described in the Heavy Quark Expansion (HQE) and allow for a precision determination of the CKM element $|V_{cb}|$. We calculate the terms of $1/m_b^5$ and derive a ``trace formula'' which allows for the computation of the decay rate and kinematic moments of the spectrum up to this order in the HQE. We focus specifically on the reparametrization invariant (RPI) dilepton invariant mass $q^2$ moments of the spectrum, which depend on a reduced set of HQE parameters. At this order, ``intrinsic charm'' (IC) contributions proportional to $1/(m_b^3m_c^2)$ enter, which are numerically expected to be sizeable. Using the ``lowest-lying state saturation ansatz'' (LLSA), we estimate the size of these contributions. Within this approximation, we observe a partial cancellation between the IC and the ``genuine'' $1/m_b^5$ contributions, resulting in a small overall contribution.Comment: 36 pages, 4 figure

Technology Lightning Round

Four different websites are discussed on how they can help with research and classroom activities: Dimensions: Dimensions brings together grants, publications, citations, alternative metrics, clinical trials, patents and policy documents to deliver a platform that enables users to find and access the most relevant information faster, analyze the academic and broader outcomes of research, and gather insights to inform future strategy. Open Science Framework (OSF): Cloud-based data management for research projects. Kudos: Community of researchers to communicate work more effectively and accelerate its positive impact in the world. It networks your journal articles! Abine’s Do Not Track Me: anti-tracking and password protection softwar

Older Adults with Hoarding Behaviour Aging in Place: Looking to a Collaborative Community-Based Planning Approach for Solutions

This paper reports on and synthesizes new research that examines how a collaborative community response can promote successful aging in place for older adults with hoarding behaviour. Through interviews with older adults with hoarding behaviour, who used a particular community support and a focus group interview with members of the community collaborative that directed supports for this population, our findings suggest that there were valuable outcomes for both groups. These older adults with hoarding behaviour were able to remain in their own homes, their safety was enhanced, their sense of isolation was minimized, empowerment was fostered, and they gained valuable insight into their behaviour. The members of the community collaborative were able to access the expertise of other professionals, maximize their own expertise, and they generated an enhanced understanding of the experience of older adults living with hoarding behaviour in Edmonton. This study is a significant addition to the much too sparse literature about the community planning needs of older adults with hoarding behaviour. It offers knowledge that is integral to theories and principles of better aging in place but attempts to translate this into practice