The genomics of neonatal abstinence syndrome

Significant variability has been observed in the development and severity of neonatal abstinence syndrome (NAS) among neonates exposed to prenatal opioids. Since maternal opioid dose does not appear to correlate directly with neonatal outcome, maternal, placental, and fetal genomic variants may play important roles in NAS. Previous studies in small cohorts have demonstrated associations of variants in maternal and infant genes that encode the μ-opioid receptor (OPRM1), catechol-O-methyltransferase (COMT), and prepronociceptin (PNOC) with a shorter length of hospital stay and less need for treatment in neonates exposed to opioids in utero. Consistently falling genomic sequencing costs and computational approaches to predict variant function will permit unbiased discovery of genomic variants and gene pathways associated with differences in maternal and fetal opioid pharmacokinetics and pharmacodynamics and with placental opioid transport and metabolism. Discovery of pathogenic variants should permit better delineation of the risk of developing more severe forms of NAS. This review provides a summary of the current role of genomic factors in the development of NAS and suggests strategies for further genomic discovery

Preferred Molecular Orientation of Coumarin 343 on TiO2 Surfaces: Application to Dye-Sensitized Solar Cells.

The dye···TiO2 interfacial structure in working electrodes of dye-sensitized solar cells (DSCs) is known to influence its photovoltaic device performance. Despite this, direct and quantitative reports of such structure remain sparse. This case study presents the application of X-ray reflectometry to determine the preferred structural orientation and molecular packing of the organic dye, Coumarin 343, adsorbed onto amorphous TiO2. Results show that the dye molecules are, on average, tilted by 61.1° relative to the TiO2 surface, and are separated from each other by 8.2 Å. These findings emulate the molecular packing arrangement of a monolayer of Coumarin 343 within its crystal structure. This suggests that the dye adsorbs onto TiO2 in one of its lowest energy configurations; that is, dye···TiO2 self-assembly is driven more by thermodynamic rather than kinetic means. Complementary DSC device tests illustrate that this interfacial structure compromises photovoltaic performance, unless a suitably sized coadsorbant is interdispersed between the Coumarin 343 chromophores on the TiO2 surface.J. M.-G. acknowledges ANSTO for a part-funded PhD studentship. J. M. C. is grateful to the 1851 Royal Commission for the 2014 Design Fellowship, and Argonne National Laboratory where work done was supported by DOE Office of Science, Office of Basic Energy Sciences, under Contract No. DE-AC02-06CH11357.This is the author accepted manuscript. The final version is available from ACS via http://dx.doi.org/10.1021/acsami.5b0357

Composition and degradation of salp fecal pellets: Implications for vertical flux in oceanic environments

Changes in the sinking rates, ash-free dry weights, particulate carbon and nitrogen content, and carbon:nitrogen ratios from the fecal pellets of several species of oceanic salps were examined in ten-day decomposition studies. Although bacteria and protozoa became abundant in the incubation vessels, most of the fecal pellets remained physically intact throughout the study. Bacterial activity in the pellets (measured by the rate of uptake of 3H-thymidine) increased, but microbial degradation had little effect on the sinking speeds of most of the fecal pellets. The average losses of ash-free dry weight and carbon and nitrogen content, along with changes in carbon:nitrogen ratio, were small compared to their initial values. We conclude that microbial degradation of large salp fecal pellets would not prevent the vertical flux to the deep ocean of a significant fraction of the particulate organic material contained in the pellets. The fecal pellets of oceanic salps provide a rapid, and potentially important, mechanism for the consolidation and vertical transport of organic and lithogenic material associated with minute particles in the open ocean

Primary and bacterial production in lakes: are they coupled over depth

Abstract. The coupling of prlmary and bacterial production over depth was examined in three lakes which differed greatly in vertical patterns of primary productivity. We measured bacterial production, chlorophyll and light, and estimated primary production in Paul Lake (Gogebic County, Michigan) and Crystal and Trout lakes (Vilas County, Wisconsin) during the summer strat~fication period (May-September 1991). Bacterial productivity was measured using the ['Hlleucine incorporation method and primary productivity estimated from measured photosynthesis-irradiance relationships. Three distinct vertical patterns were observed. In Paul Lake, bacterial production was highest at the interface between the aerobic and anaerobic layers, well below the depth of maximum primary production. In Crystal Lake, bacterial production was uniform with depth, although primary b 4-' gaductivity was highest in the hypolimnion. In the largest lake, Trout Lake, primary and bacterial production tended to co-vary with maximum rates of both processes occurring in the metalimnion. Overall, bacterial productivity was poorly related to contemporaneous primary production in the three lakes, suggesting that other factors, such as nutrient recycling, phytoplankton loss rates and allocthonous loading, determine patterns in the depth distribution of bacterial productivity

Distinct patterns of neurodegeneration after TBI and in Alzheimer's disease

INTRODUCTION: Traumatic brain injury (TBI) is a dementia risk factor, with Alzheimer's disease (AD) more common following injury. Patterns of neurodegeneration produced by TBI can be compared to AD and aging using volumetric MRI. METHODS: A total of 55 patients after moderate to severe TBI (median age 40), 45 with AD (median age 69), and 61 healthy volunteers underwent magnetic resonance imaging over 2 years. Atrophy patterns were compared. RESULTS: AD patients had markedly lower baseline volumes. TBI was associated with increased white matter (WM) atrophy, particularly involving corticospinal tracts and callosum, whereas AD rates were increased across white and gray matter (GM). Subcortical WM loss was shared in AD/TBI, but deep WM atrophy was TBI-specific and cortical atrophy AD-specific. Post-TBI atrophy patterns were distinct from aging, which resembled AD. DISCUSSION: Post-traumatic neurodegeneration 1.9-4.0 years (median) following moderate-severe TBI is distinct from aging/AD, predominantly involving central WM. This likely reflects distributions of axonal injury, a neurodegeneration trigger. HIGHLIGHTS: We compared patterns of brain atrophy longitudinally after moderate to severe TBI in late-onset AD and healthy aging. Patients after TBI had abnormal brain atrophy involving the corpus callosum and other WM tracts, including corticospinal tracts, in a pattern that was specific and distinct from AD and aging. This pattern is reminiscent of axonal injury following TBI, and atrophy rates were predicted by the extent of axonal injury on diffusion tensor imaging, supporting a relationship between early axonal damage and chronic neurodegeneration

Reverse engineering of force integration during mitosis in the Drosophila embryo

The mitotic spindle is a complex macromolecular machine that coordinates accurate chromosome segregation. The spindle accomplishes its function using forces generated by microtubules (MTs) and multiple molecular motors, but how these forces are integrated remains unclear, since the temporal activation profiles and the mechanical characteristics of the relevant motors are largely unknown. Here, we developed a computational search algorithm that uses experimental measurements to ‘reverse engineer' molecular mechanical machines. Our algorithm uses measurements of length time series for wild-type and experimentally perturbed spindles to identify mechanistic models for coordination of the mitotic force generators in Drosophila embryo spindles. The search eliminated thousands of possible models and identified six distinct strategies for MT–motor integration that agree with available data. Many features of these six predicted strategies are conserved, including a persistent kinesin-5-driven sliding filament mechanism combined with the anaphase B-specific inhibition of a kinesin-13 MT depolymerase on spindle poles. Such conserved features allow predictions of force–velocity characteristics and activation–deactivation profiles of key mitotic motors. Identified differences among the six predicted strategies regarding the mechanisms of prometaphase and anaphase spindle elongation suggest future experiments

Lake-size dependency of wind shear and convection as controls on gas exchange

High-frequency physical observations from 40 temperate lakes were used to examine the relative contributions of wind shear (u*) and convection (w*) to turbulence in the surface mixed layer. Seasonal patterns of u* and w* were dissimilar; u* was often highest in the spring, while w * increased throughout the summer to a maximum in early fall. Convection was a larger mixed-layer turbulence source than wind shear (u */w*-1 for lakes* and w* differ in temporal pattern and magnitude across lakes, both convection and wind shear should be considered in future formulations of lake-air gas exchange, especially for small lakes. © 2012 by the American Geophysical Union.Jordan S. Read, David P. Hamilton, Ankur R. Desai, Kevin C. Rose, Sally MacIntyre, John D. Lenters, Robyn L. Smyth, Paul C. Hanson, Jonathan J. Cole, Peter A. Staehr, James A. Rusak, Donald C. Pierson, Justin D. Brookes, Alo Laas, and Chin H. W

Ancient origins of low lean mass among South Asians and implications for modern type 2 diabetes susceptibility

Abstract: Living South Asians have low lean tissue mass relative to height, which contributes to their elevated type 2 diabetes susceptibility, particularly when accompanied by obesity. While ongoing lifestyle transitions account for rising obesity, the origins of low lean mass remain unclear. We analysed proxies for lean mass and stature among South Asian skeletons spanning the last 11,000 years (n = 197) to investigate the origins of South Asian low lean mass. Compared with a worldwide sample (n = 2,003), South Asian skeletons indicate low lean mass. Stature-adjusted lean mass increased significantly over time in South Asia, but to a very minor extent (0.04 z-score units per 1,000 years, adjusted R2 = 0.01). In contrast stature decreased sharply when agriculture was adopted. Our results indicate that low lean mass has characterised South Asians since at least the early Holocene and may represent long-term climatic adaptation or neutral variation. This phenotype is therefore unlikely to change extensively in the short term, so other strategies to address increasing non-communicable disease rates must be pursued

Research frontiers in the analysis of coupled biogeochemical cycles

Author Posting. © Ecological Society of America, 2011. This article is posted here by permission of Ecological Society of America for personal use, not for redistribution. The definitive version was published in Frontiers in Ecology and the Environment 9 (2011): 74–80, doi:10.1890/100137.The analysis of coupled biogeochemical cycles (CBCs) addresses the scientific basis for some of today's major environmental problems. Drawing from information presented at a series of sessions on CBCs held at the 2009 Annual Meeting of the Ecological Society of America and from the research community's expertise, we identify several principal research themes that justify action and investment. Critical areas for research include: coupling of major element cycles to less studied yet equally important trace element cycles; analyzing CBCs across ecosystem boundaries; integrating experimental results into regional- and global-scale models; and expanding the analysis of human interactions with CBCs arising from human population growth, urbanization, and geoengineering. To advance the current understanding of CBCs and to address the environmental challenges of the 21st century, scientists must maintain and synthesize data from existing observational and experimental networks, develop new instrumentation networks, and adopt emerging technologies.We thank the National Science Foundation (NSF) and the Ecological Society of America (ESA) for their financial and logistical support of the Coupled Biogeochemical Cycles sessions held at the 2009 ESA Annual Meeting, and the publication of this special feature issue of Frontiers. ACF was supported by the NSF (DEB- 0743564) and the US Department of Energy’s (DOE’s) Office of Biological and Environmental Research (10- DOE-1053). SCD was supported by the Center for Microbial Oceanography, Research and Education (NSF EF-0424599). RBJ was supported by the NSF (DEB #0717191) and by the DOE’s National Institute for Climate Change Research