100 research outputs found
The StrongWomen Change Clubs: Engaging Residents to Catalyze Positive Change in Food and Physical Activity Environments
Introduction. The epidemic of obesity is a multifaceted public health issue. Positive policy and environmental changes are needed to support healthier eating and increased physical activity. Methods. StrongWomen Change Clubs (SWCCs) were developed through an academic-community research partnership between researchers at Cornell University and Tufts University and community partners (cooperative extension educators) in rural towns in seven U.S. states. Extension educators served as the local leader and each recruited 10ā15 residents to undertake a project to improve some aspect of the nutrition or physical activity environment. Most residents had limited (or no) experience in civic engagement. At 6 and 12 months after implementation, the research team conducted key informant interviews with SWCC leaders to capture their perceptions of program process, benchmark achievement, and self-efficacy. Results. At 12 months, each SWCC had accomplished one benchmark; the majority had completed three or more benchmarks. They described common processes for achieving benchmarks such as building relationships and leveraging stakeholder partnerships. Barriers to benchmark achievement included busy schedules and resistance to and slow pace of change. Conclusion. Findings suggest that community change initiatives that involve stakeholders, build upon existing activities and organizational resources, and establish feasible timelines and goals can successfully catalyze environmental change
PKCĪµ-CREB-Nrf2 signalling induces HO-1 in the vascular endothelium and enhances resistance to inflammation and apoptosis
Aims
Vascular injury leading to endothelial dysfunction is a characteristic feature of chronic renal disease, diabetes mellitus, and systemic inflammatory conditions, and predisposes to apoptosis and atherogenesis. Thus, endothelial dysfunction represents a potential therapeutic target for atherosclerosis prevention. The observation that activity of either protein kinase C epsilon (PKCĪµ) or haem oxygenase-1 (HO-1) enhances endothelial cell (EC) resistance to inflammation and apoptosis led us to test the hypothesis that HO-1 is a downstream target of PKCĪµ.
Methods and results
Expression of constitutively active PKCĪµ in human EC significantly increased HO-1 mRNA and protein, whereas conversely aortas or cardiac EC from PKCĪµ-deficient mice exhibited reduced HO-1 when compared with wild-type littermates. Angiotensin II activated PKCĪµ and induced HO-1 via a PKCĪµ-dependent pathway. PKCĪµ activation significantly attenuated TNFĪ±-induced intercellular adhesion molecule-1, and increased resistance to serum starvation-induced apoptosis. These responses were reversed by the HO antagonist zinc protoporphyrin IX. Phosphokinase antibody array analysis identified CREB1(Ser133) phosphorylation as a PKCĪµ signalling intermediary, and cAMP response element-binding protein 1 (CREB1) siRNA abrogated PKCĪµ-induced HO-1 up-regulation. Likewise, nuclear factor (erythroid-derived 2)-like 2 (Nrf2) was identified as a PKCĪµ target using nuclear translocation and DNA-binding assays, and Nrf2 siRNA prevented PKCĪµ-mediated HO-1 induction. Moreover, depletion of CREB1 inhibited PKCĪµ-induced Nrf2 DNA binding, suggestive of transcriptional co-operation between CREB1 and Nrf2.
Conclusions
PKCĪµ activity in the vascular endothelium regulates HO-1 via a pathway requiring CREB1 and Nrf2. Given the potent protective actions of HO-1, we propose that this mechanism is an important contributor to the emerging role of PKCĪµ in the maintenance of endothelial homeostasis and resistance to injury
The climate of a retrograde rotating Earth
To enhance understanding of Earth's climate, numerical experiments are
performed contrasting a retrograde and prograde rotating Earth using the Max
Planck Institute Earth system model. The experiments show that the sense of
rotation has relatively little impact on the globally and zonally averaged
energy budgets but leads to large shifts in continental climates, patterns
of precipitation, and regions of deep water formation.Changes in the zonal asymmetries of the continental climates are expected
given ideas developed more than a hundred years ago. Unexpected was, however,
the switch in the character of the EuropeanāAfrican climate with that of the
Americas, with a drying of the former and a greening of the latter. Also
unexpected was a shift in the storm track activity from the oceans to the
land in the Northern Hemisphere. The different patterns of storms and changes
in the direction of the trades influence fresh water transport, which may
underpin the change of the role of the North Atlantic and the Pacific in
terms of deep water formation, overturning and northward oceanic heat
transport. These changes greatly influence northern hemispheric climate and
atmospheric heat transport by eddies in ways that appear energetically
consistent with a southward shift of the zonally and annually averaged
tropical rain bands. Differences between the zonally averaged energy budget
and the rain band shifts leave the door open, however, for an important role
for stationary eddies in determining the position of tropical rains. Changes
in ocean biogeochemistry largely follow shifts in ocean circulation, but the
emergence of a super oxygen minimum zone in the Indian Ocean is not
expected. The upwelling of phosphate-enriched and nitrate-depleted water
provokes a dominance of cyanobacteria over bulk phytoplankton over vast areas ā a phenomenon not observed in the prograde model.What would the climate of Earth look like if it would rotate in the reversed
(retrograde) direction? Which of the characteristic climate patterns in the
ocean, atmosphere, or land that are observed in a present-day climate are the
result of the direction of Earth's rotation? Is, for example, the structure
of the oceanic meridional overturning circulationĀ (MOC) a consequence of the
interplay of basin location and rotation direction? In experiments with the
Max Planck Institute Earth system modelĀ (MPI-ESM), we investigate the effects
of a retrograde rotation in all aspects of the climate system.The expected consequences of a retrograde rotation are reversals of the zonal
wind and ocean circulation patterns. These changes are associated with major
shifts in the temperature and precipitation patterns. For example, the
temperature gradient between Europe and eastern Siberia is reversed, and the
Sahara greens, while large parts of the Americas become deserts.
Interestingly, the Intertropical Convergence ZoneĀ (ITCZ) shifts southward and
the modeled double ITCZ in the Pacific changes to a single ITCZ, a result of
zonal asymmetries in the structure of the tropical circulation.One of the most prominent non-trivial effects of a retrograde rotation is a
collapse of the Atlantic MOC, while a strong overturning cell emerges in the
Pacific. This clearly shows that the position of the MOC is not controlled by
the sizes of the basins or by mountain chains splitting the continents in
unequal runoff basins but by the location of the basins relative to the
dominant wind directions. As a consequence of the changes in the ocean
circulation, a super oxygen minimum zone develops in the Indian Ocean
leading to upwelling of phosphate-enriched and nitrate-depleted water. These
conditions provoke a dominance of cyanobacteria over bulk phytoplankton over
vast areas, a phenomenon not observed in the prograde model.</p
Protein kinase CĪø is required for cardiomyocyte survival and cardiac remodeling
Protein kinase Cs (PKCs) constitute a family of serine/threonine kinases, which has distinguished and specific roles in regulating cardiac responses, including those associated with heart failure. We found that the PKCĪø isoform is expressed at considerable levels in the cardiac muscle in mouse, and that it is rapidly activated after pressure overload. To investigate the role of PKCĪø in cardiac remodeling, we used PKCĪøā/ā mice. In vivo analyses of PKCĪøā/ā hearts showed that the lack of PKCĪø expression leads to left ventricular dilation and reduced function. Histological analyses showed a reduction in the number of cardiomyocytes, combined with hypertrophy of the remaining cardiomyocytes, cardiac fibrosis, myofibroblast hyper-proliferation and matrix deposition. We also observed p38 and JunK activation, known to promote cell death in response to stress, combined with upregulation of the fetal pattern of gene expression, considered to be a feature of the hemodynamically or metabolically stressed heart. In keeping with these observations, cultured PKCĪøā/ā cardiomyocytes were less viable than wild-type cardiomyocytes, and, unlike wild-type cardiomyocytes, underwent programmed cell death upon stimulation with Ī±1-adrenergic agonists and hypoxia. Taken together, these results show that PKCĪø maintains the correct structure and function of the heart by preventing cardiomyocyte cell death in response to work demand and to neuro-hormonal signals, to which heart cells are continuously exposed
Protein kinase C and cardiac dysfunction: a review
Heart failure (HF) is a physiological state in which cardiac output is insufficient to meet the needs of the body. It is a clinical syndrome characterized by impaired ability of the left ventricle to either fill or eject blood efficiently. HF is a disease of multiple aetiologies leading to progressive cardiac dysfunction and it is the leading cause of deaths in both developed and developing countries. HF is responsible for about 73,000 deaths in the UK each year. In the USA, HF affects 5.8 million people and 550,000 new cases are diagnosed annually. Cardiac remodelling (CD), which plays an important role in pathogenesis of HF, is viewed as stress response to an index event such as myocardial ischaemia or imposition of mechanical load leading to a series of structural and functional changes in the viable myocardium. Protein kinase C (PKC) isozymes are a family of serine/threonine kinases. PKC is a central enzyme in the regulation of growth, hypertrophy, and mediators of signal transduction pathways. In response to circulating hormones, activation of PKC triggers a multitude of intracellular events influencing multiple physiological processes in the heart, including heart rate, contraction, and relaxation. Recent research implicates PKC activation in the pathophysiology of a number of cardiovascular disease states. Few reports are available that examine PKC in normal and diseased human hearts. This review describes the structure, functions, and distribution of PKCs in the healthy and diseased heart with emphasis on the human heart and, also importantly, their regulation in heart failure
Contribution of Maternal Antiretroviral Therapy and Breastfeeding to 24-Month Survival in Human Immunodeficiency Virus-Exposed Uninfected Children: An Individual Pooled Analysis of African and Asian Studies
Background:
Increasing numbers of HIV-infected pregnant women receive antiretroviral therapy (ART) to prevent mother-to-child transmission (PMTCT). Studies suggested that HIV-exposed uninfected (HEU) children face higher mortality than HIV-unexposed children, but evidence mostly relates to the pre-ART era, breastfeeding of limited duration and considerable maternal mortality. Maternal ART and prolonged breastfeeding under cover of ART may improve survival, although this has not been reliably quantified.
Methods:
Individual data on 19,219 HEU children from 21 PMTCT trials/cohorts undertaken 1995-2015 in Africa and Asia were pooled and the association between 24-month mortality and maternal/infant factors quantified using random-effects Cox proportional hazards models accounting for between-study heterogeneity. Adjusted attributable fractions of risks computed using the predict function in the R package "frailtypack" estimate the relative contribution of risk factors to overall mortality in HEU children.
Results:
Cumulative incidence of death was 5.5% (95%CI: 5.1-5.9) by age 24 months. Low birth weight (LBW<2500g, adjusted Hazard Ratio (aHR: 2.9), no breastfeeding (aHR: 2.5) and maternal death (aHR: 11.1) were significantly associated with increased mortality. Maternal ART (aHR: 0.5) was significantly associated with lower mortality. At population level, LBW accounted for 16.2% of child deaths by 24 months, never breastfeeding for 10.8%, mother not receiving ART for 45.6%, and maternal death for 4.3%; these factors combined explained 63.6% of deaths by age 24 months.
Conclusion:
Survival of HEU children could be substantially improved if public health strategies provided all mothers living with HIV with ART and supported optimal infant feeding and care for LBW neonates
A Case Study Evaluating Water Quality and Reach-, Buffer-, and Watershed-Scale Explanatory Variables of an Urban Coastal Watershed
Land use land cover within a watershed influences stream water quality, habitat quality, and biological community structure. As development and associated impervious surface increases in a watershed, changes in storm water and nutrient inputs generally cause declines in habitat conditions and biodiversity. The first goal of our study was to evaluate the water quality in the Charles River watershed, in which our objective (G1O1) was to establish ten 100-meter reach-scale sampling stations and conduct physical, chemical, and biological assessments. The second goal of this study was to better understand the direct and indirect effects of hierarchical variables on water quality in the Charles River watershed. Our first objective of our second goal (G2O1) was to calculate land use land cover percentages at the pour-point subwatershed and local 100-meter buffer scale for each of our ten 100-meter reach sampling stations. Our second objective of our second goal (G2O2) was to use path analysis to determine the direct and indirect effects of land use land cover and impervious surface on water quality in the Charles River watershed. The results of G1O1 were that habitat quality assessments ranged from “marginal” to “optimal” and biological quality assessments ranged from “fair” to “good“, indicating overall “fair” or better water quality conditions in the watershed. The results of G2O2 were that our path analysis resulted in differences in effects of development between the buffer and sub-watershed scale. At the buffer scale, water quality was influenced more negatively by the percentage of developed land area versus the percentage of impervious cover. While both buffer development and habitat quality had a direct effect on Streamside Biosurvey Macroinvertebrates, buffer development also directly hindered habitat quality, thus having an indirect effect on Streamside Biosurvey Macroinvertebrates through habitat. Streamside Biosurvey Macroinvertebrate scores were shown to be more sensitive to development within the buffer versus at the sub-watershed scale, where impervious cover was a more important indicator of stream water quality. Through this small case study of 10 stations within the Charles River watershed, we illustrated how citizen-science level water quality assessments can be combined with water chemistry and hierarchical LULC data to provide insights into potential direct and indirect effects on water quality. As the fields of landscape ecology and conservation continue to grow, so does our ability to determine changes in land development and devise management strategies aimed at improving water quality
A Case Study Evaluating Water Quality and Reach-, Buffer-, and Watershed-Scale Explanatory Variables of an Urban Coastal Watershed
Land use land cover within a watershed influences stream water quality, habitat quality, and biological community structure. As development and associated impervious surface increases in a watershed, changes in storm water and nutrient inputs generally cause declines in habitat conditions and biodiversity. The first goal of our study was to evaluate the water quality in the Charles River watershed, in which our objective (G1O1) was to establish ten 100-meter reach-scale sampling stations and conduct physical, chemical, and biological assessments. The second goal of this study was to better understand the direct and indirect effects of hierarchical variables on water quality in the Charles River watershed. Our first objective of our second goal (G2O1) was to calculate land use land cover percentages at the pour-point subwatershed and local 100-meter buffer scale for each of our ten 100-meter reach sampling stations. Our second objective of our second goal (G2O2) was to use path analysis to determine the direct and indirect effects of land use land cover and impervious surface on water quality in the Charles River watershed. The results of G1O1 were that habitat quality assessments ranged from āmarginalā to āoptimalā and biological quality assessments ranged from āfairā to āgoodā, indicating overall āfairā or better water quality conditions in the watershed. The results of G2O2 were that our path analysis resulted in differences in effects of development between the buffer and sub-watershed scale. At the buffer scale, water quality was influenced more negatively by the percentage of developed land area versus the percentage of impervious cover. While both buffer development and habitat quality had a direct effect on Streamside Biosurvey Macroinvertebrates, buffer development also directly hindered habitat quality, thus having an indirect effect on Streamside Biosurvey Macroinvertebrates through habitat. Streamside Biosurvey Macroinvertebrate scores were shown to be more sensitive to development within the buffer versus at the sub-watershed scale, where impervious cover was a more important indicator of stream water quality. Through this small case study of 10 stations within the Charles River watershed, we illustrated how citizen-science level water quality assessments can be combined with water chemistry and hierarchical LULC data to provide insights into potential direct and indirect effects on water quality. As the fields of landscape ecology and conservation continue to grow, so does our ability to determine changes in land development and devise management strategies aimed at improving water quality
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