27 research outputs found
Individual participant data (IPD)-level meta-analysis of randomised controlled trials to estimate the vitamin D dietary requirements in dark-skinned individuals resident at high latitude
Context and purpose There is an urgent need to develop vitamin D dietary recommendations for dark-skinned populations resident at high latitude. Using data from randomised controlled trials (RCTs) with vitamin D3-supplements/fortified foods, we undertook an individual participant data-level meta-regression (IPD) analysis of the response of wintertime serum 25-hydroxyvitamin (25(OH)D) to total vitamin D intake among dark-skinned children and adults residing at ≥ 40° N and derived dietary requirement values for vitamin D. Methods IPD analysis using data from 677 dark-skinned participants (of Black or South Asian descent; ages 5–86 years) in 10 RCTs with vitamin D supplements/fortified foods identified via a systematic review and predefined eligibility criteria. Outcome measures were vitamin D intake estimates across a range of 25(OH)D thresholds. Results To maintain serum 25(OH)D concentrations ≥ 25 and 30 nmol/L in 97.5% of individuals, 23.9 and 27.3 µg/day of vitamin D, respectively, were required among South Asian and 24.1 and 33.2 µg/day, respectively, among Black participants. Overall, our age-stratified intake estimates did not exceed age-specific Tolerable Upper Intake Levels for vitamin D. The vitamin D intake required by dark-skinned individuals to maintain 97.5% of winter 25(OH)D concentrations ≥ 50 nmol/L was 66.8 µg/day. This intake predicted that the upper 2.5% of individuals could potentially achieve serum 25(OH)D concentrations ≥ 158 nmol/L, which has been linked to potential adverse effects in older adults in supplementation studies. Conclusions Our IPD-derived vitamin D intakes required to maintain 97.5% of winter 25(OH)D concentrations ≥ 25, 30 and 50 nmol/L are substantially higher than the equivalent estimates for White individuals. These requirement estimates are also higher than those currently recommended internationally by several agencies, which are based predominantly on data from Whites and derived from standard meta-regression based on aggregate data. Much more work is needed in dark-skinned populations both in the dose–response relationship and risk characterisation for health outcomes.Peer reviewe
Climate drives the geography of marine consumption by changing predator communities
Este artículo contiene 7 páginas, 3 figuras, 1 tabla.The global distribution of primary production and consumption by
humans (fisheries) is well-documented, but we have no map linking
the central ecological process of consumption within food
webs to temperature and other ecological drivers. Using standardized
assays that span 105° of latitude on four continents, we show
that rates of bait consumption by generalist predators in shallow
marine ecosystems are tightly linked to both temperature and the
composition of consumer assemblages. Unexpectedly, rates of
consumption peaked at midlatitudes (25 to 35°) in both Northern
and Southern Hemispheres across both seagrass and unvegetated
sediment habitats. This pattern contrasts with terrestrial systems,
where biotic interactions reportedly weaken away from the equator,
but it parallels an emerging pattern of a subtropical peak in
marine biodiversity. The higher consumption at midlatitudes was
closely related to the type of consumers present, which explained
rates of consumption better than consumer density, biomass, species
diversity, or habitat. Indeed, the apparent effect of temperature
on consumption was mostly driven by temperature-associated turnover
in consumer community composition. Our findings reinforce
the key influence of climate warming on altered species composition
and highlight its implications for the functioning of Earth’s
ecosystems.We acknowledge funding from the Smithsonian
Institution and the Tula Foundation.Peer reviewe
Women and ARVâ based prevention: opportunities and challenges
Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138349/1/jia29419.pd
A dominant negative zebrafish Ahr2 partially protects developing zebrafish from dioxin toxicity.
The toxicity by 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD) is thought to be caused by activation of the aryl hydrocarbon receptor (AHR). However, our understanding of how AHR activation by TCDD leads to toxic effects is poor. Ideally we would like to manipulate AHR activity in specific tissues and at specific times. One route to this is expressing dominant negative AHRs (dnAHRs). This work describes the construction and characterization of dominant negative forms of the zebrafish Ahr2 in which the C-terminal transactivation domain was either removed, or replaced with the inhibitory domain from the Drosophila engrailed repressor protein. One of these dnAhr2s was selected for expression from the ubiquitously active e2fα promoter in transgenic zebrafish. We found that these transgenic zebrafish expressing dnAhr2 had reduced TCDD induction of the Ahr2 target gene cyp1a, as measured by 7-ethoxyresorufin-O-deethylase activity. Furthermore, the cardiotoxicity produced by TCDD, pericardial edema, heart malformation, and reduced blood flow, were all mitigated in the zebrafish expressing the dnAhr2. These results provide in vivo proof-of-principle results demonstrating the effectiveness of dnAHRs in manipulating AHR activity in vivo, and demonstrating that this approach can be a means for blocking TCDD toxicity
Statistically Enhanced Spectral Counting Approach to TCDD Cardiac Toxicity in the Adult Zebrafish Heart
2,3,7,8-Tetrachlorodibenzo-<i>p</i>-dioxin (TCDD) is
a persistent environmental pollutant and teratogen that produces cardiac
toxicity in the developing zebrafish. Here we adopted a label free
quantitative proteomic approach based on normalized spectral abundance
factor (NSAF) to investigate the disturbance of the cardiac proteome
induced by TCDD in the adult zebrafish heart. The protein expression
level changes between heart samples from TCDD-treated and control
zebrafish were systematically evaluated by a large scale MudPIT analysis,
which incorporated triplicate analyses for both control and TCDD-exposed
heart proteomic samples to overcome the data-dependent variation in
shotgun proteomic experiments and obtain a statistically significant
protein data set with improved quantification confidence. A total
of 519 and 443 proteins were identified in hearts collected from control
and TCDD-treated zebrafish, respectively, among which 106 proteins
showed statistically significant expression changes. After correcting
for the experimental variation between replicate analyses by statistical
evaluation, 55 proteins exhibited NSAF ratios above 2 and 43 proteins
displayed NSAF ratios smaller than 0.5, with statistical significance
by <i>t</i> test (<i>p</i> < 0.05). The proteins
identified as altered by TCDD encompass a wide range of biological
functions including calcium handling, myocardium cell architecture,
energy production and metabolism, mitochondrial homeostasis, and stress
response. Collectively, our results indicate that TCDD exposure alters
the adult zebrafish heart in a way that could result in cardiac hypertrophy
and heart failure and suggests a potential mechanism for the diastolic
dysfunction observed in TCDD-exposed embryos
Statistically Enhanced Spectral Counting Approach to TCDD Cardiac Toxicity in the Adult Zebrafish Heart
2,3,7,8-Tetrachlorodibenzo-<i>p</i>-dioxin (TCDD) is
a persistent environmental pollutant and teratogen that produces cardiac
toxicity in the developing zebrafish. Here we adopted a label free
quantitative proteomic approach based on normalized spectral abundance
factor (NSAF) to investigate the disturbance of the cardiac proteome
induced by TCDD in the adult zebrafish heart. The protein expression
level changes between heart samples from TCDD-treated and control
zebrafish were systematically evaluated by a large scale MudPIT analysis,
which incorporated triplicate analyses for both control and TCDD-exposed
heart proteomic samples to overcome the data-dependent variation in
shotgun proteomic experiments and obtain a statistically significant
protein data set with improved quantification confidence. A total
of 519 and 443 proteins were identified in hearts collected from control
and TCDD-treated zebrafish, respectively, among which 106 proteins
showed statistically significant expression changes. After correcting
for the experimental variation between replicate analyses by statistical
evaluation, 55 proteins exhibited NSAF ratios above 2 and 43 proteins
displayed NSAF ratios smaller than 0.5, with statistical significance
by <i>t</i> test (<i>p</i> < 0.05). The proteins
identified as altered by TCDD encompass a wide range of biological
functions including calcium handling, myocardium cell architecture,
energy production and metabolism, mitochondrial homeostasis, and stress
response. Collectively, our results indicate that TCDD exposure alters
the adult zebrafish heart in a way that could result in cardiac hypertrophy
and heart failure and suggests a potential mechanism for the diastolic
dysfunction observed in TCDD-exposed embryos
Statistically Enhanced Spectral Counting Approach to TCDD Cardiac Toxicity in the Adult Zebrafish Heart
2,3,7,8-Tetrachlorodibenzo-<i>p</i>-dioxin (TCDD) is
a persistent environmental pollutant and teratogen that produces cardiac
toxicity in the developing zebrafish. Here we adopted a label free
quantitative proteomic approach based on normalized spectral abundance
factor (NSAF) to investigate the disturbance of the cardiac proteome
induced by TCDD in the adult zebrafish heart. The protein expression
level changes between heart samples from TCDD-treated and control
zebrafish were systematically evaluated by a large scale MudPIT analysis,
which incorporated triplicate analyses for both control and TCDD-exposed
heart proteomic samples to overcome the data-dependent variation in
shotgun proteomic experiments and obtain a statistically significant
protein data set with improved quantification confidence. A total
of 519 and 443 proteins were identified in hearts collected from control
and TCDD-treated zebrafish, respectively, among which 106 proteins
showed statistically significant expression changes. After correcting
for the experimental variation between replicate analyses by statistical
evaluation, 55 proteins exhibited NSAF ratios above 2 and 43 proteins
displayed NSAF ratios smaller than 0.5, with statistical significance
by <i>t</i> test (<i>p</i> < 0.05). The proteins
identified as altered by TCDD encompass a wide range of biological
functions including calcium handling, myocardium cell architecture,
energy production and metabolism, mitochondrial homeostasis, and stress
response. Collectively, our results indicate that TCDD exposure alters
the adult zebrafish heart in a way that could result in cardiac hypertrophy
and heart failure and suggests a potential mechanism for the diastolic
dysfunction observed in TCDD-exposed embryos