Particulate matter exposure during pregnancy is associated with birth weight, but not gestational age, 1962-1992: a cohort study

<p>Abstract</p> <p>Background</p> <p>Exposure to air pollutants is suggested to adversely affect fetal growth, but the evidence remains inconsistent in relation to specific outcomes and exposure windows.</p> <p>Methods</p> <p>Using birth records from the two major maternity hospitals in Newcastle upon Tyne in northern England between 1961 and 1992, we constructed a database of all births to mothers resident within the city. Weekly black smoke exposure levels from routine data recorded at 20 air pollution monitoring stations were obtained and individual exposures were estimated via a two-stage modeling strategy, incorporating temporally and spatially varying covariates. Regression analyses, including 88,679 births, assessed potential associations between exposure to black smoke and birth weight, gestational age and birth weight standardized for gestational age and sex.</p> <p>Results</p> <p>Significant associations were seen between black smoke and both standardized and unstandardized birth weight, but not for gestational age when adjusted for potential confounders. Not all associations were linear. For an increase in whole pregnancy black smoke exposure, from the 1^st(7.4 μg/m³) to the 25^th(17.2 μg/m³), 50^th(33.8 μg/m³), 75^th(108.3 μg/m³), and 90^th(180.8 μg/m³) percentiles, the adjusted estimated decreases in birth weight were 33 g (SE 1.05), 62 g (1.63), 98 g (2.26) and 109 g (2.44) respectively. A significant interaction was observed between socio-economic deprivation and black smoke on both standardized and unstandardized birth weight with increasing effects of black smoke in reducing birth weight seen with increasing socio-economic disadvantage.</p> <p>Conclusions</p> <p>The findings of this study progress the hypothesis that the association between black smoke and birth weight may be mediated through intrauterine growth restriction. The associations between black smoke and birth weight were of the same order of magnitude as those reported for passive smoking. These findings add to the growing evidence of the harmful effects of air pollution on birth outcomes.</p

Activation of liver X receptors with T0901317 attenuates cardiac hypertrophy in vivo

Liver X receptor (LXR) is a nuclear receptor regulating cholesterol metabolism. Liver X receptor has also been shown to exert anti-proliferative and anti-inflammatory properties. In this study, we evaluated the effect of LXR activation on cardiac hypertrophy in vitro and in vivo. Treatment with the synthetic LXR agonist T0901317 (T09) attenuated the hypertrophic response of cultured cardiomyocytes to endothelin-1 almost to control levels. siRNA interference showed that this effect was indeed LXR specific. To corroborate these findings in vivo, abdominal aortic constriction (AC) was used as a pressure overload model to induce cardiac hypertrophy in wild-type and LXR-alpha-deficient (LXR-alpha(-/-)) mice. In wild-type mice, T09 treatment resulted in a decrease of cardiac wall thickening 4 and 7 weeks after AC. Also, after 7 weeks of AC, mean arterial blood pressure and left ventricular weight/body weight (LVW/BW) ratios were decreased in T09 treated mice. These effects were not observed in LXR-alpha(-/-) mice, indicating that the beneficial effect of LXR activation on cardiac hypertrophy is attributable to the LXR-alpha isoform. T09 induced robust cardiac expression of metabolic genes which are downstream of LXR-alpha, such as SREBP-1c, ABCA1, and ABCG1. Together these results indicate that LXR exerts salutary effects in cardiac hypertrophy, possibly via metabolic remodelling

Anthropogenic initiation and acceleration of aeolian dune activity within the northern European Sand Belt and societal feedbacks over the last ~ 2500 yrs

In North-Western Europe, Pleistocene sand sheets have been reactivated during phases of Holocene deforestation and agricultural land use. Although there are temporal overlaps between anthropogenic activity and sand sheet reactivation, the root cause and subsequent feedbacks between aeolian activity and societal response remain largely unknown. Here, we seek to establish cause and effect by examining the detailed co-variation in both timing and magnitude of aeolian and anthropogenic activity through the quantification of Holocene dune sediments in combination with archaeological and pollen records. These records indicate a series of complex phases of aeolian activity followed by landscape stabilization, which we attribute primarily to changing patterns of human impact. We find that a steady increase in dune deposition rates in the Medieval Period corresponds to an increase in settlement activity and deforestation (~AD 1000–1500). At their peak, Medieval deposition rates were 3.4 times larger than during the late Pleistocene, the period experiencing the most favourable natural conditions for aeolian sediment transport. Prior to the Medieval Period, relative land-surface stability (represented by a depositional hiatus) persisted from the late Pleistocene until the Roman Iron Age Period (AD 0–400). Deforestation to fuel iron production had minor impact on aeolian activity, as indicated by the lowest recorded deposition rate (0.12 ± 0.02 t/ha/a). Following the Medieval Period peak in deposition rates, aeolian activity diminished rapidly and coincided with the abandonment of nearby human settlement. This sequence of events provides evidence of a direct positive feedback in which Medieval agricultural overexploitation favoured aeolian activity that rendered the landscape practically unworkable for cropping agriculture. Based on our findings and a comprehensive review of Northern European sand belt activity, we interpret a very high sensitivity of aeolian activity to past and present human impact and argue that unsustainable land-use practices have been the cause for widespread settlement abandonment

Mitochondria Are Linked to Calcium Stores in Striated Muscle by Developmentally Regulated Tethering Structures

Bi-directional calcium (Ca2+) signaling between mitochondria and intracellular stores (endoplasmic/sarcoplasmic reticulum) underlies important cellular functions, including oxidative ATP production. In striated muscle, this coupling is achieved by mitochondria being located adjacent to Ca2+ stores (sarcoplasmic reticulum [SR]) and in proximity of release sites (Ca2+ release units [CRUs]). However, limited information is available with regard to the mechanisms of mitochondrial-SR coupling. Using electron microscopy and electron tomography, we identified small bridges, or tethers, that link the outer mitochondrial membrane to the intracellular Ca2+ stores of muscle. This association is sufficiently strong that treatment with hypotonic solution results in stretching of the SR membrane in correspondence of tethers. We also show that the association of mitochondria to the SR is 1) developmentally regulated, 2) involves a progressive shift from a longitudinal clustering at birth to a specific CRU-coupled transversal orientation in adult, and 3) results in a change in the mitochondrial polarization state, as shown by confocal imaging after JC1 staining. Our results suggest that tethers 1) establish and maintain SR–mitochondrial association during postnatal maturation and in adult muscle and 2) likely provide a structural framework for bi-directional signaling between the two organelles in striated muscle