Contribution of brain size to IQ and educational underperformance in extremely preterm adolescents

OBJECTIVES:Extremely preterm (EP) survivors have smaller brains, lower IQ, and worse educational achievement than their term-born peers. The contribution of smaller brain size to the IQ and educational disadvantages of EP is unknown. This study aimed (i) to compare brain volumes from multiple brain tissues and structures between EP-born (< 28 weeks) and term-born (≥ 37 weeks) control adolescents, (ii) to explore the relationships of brain tissue volumes with IQ and basic educational skills and whether this differed by group, and (iii) to explore how much total brain tissue volume explains the underperformance of EP adolescents compared with controls. METHODS:Longitudinal cohort study of 148 EP and 132 term controls born in Victoria, Australia in 1991-92. At age 18, magnetic resonance imaging-determined brain volumes of multiple tissues and structures were calculated. IQ and educational skills were measured using the Wechsler Abbreviated Scale of Intelligence (WASI) and the Wide Range Achievement Test(WRAT-4), respectively. RESULTS:Brain volumes were smaller in EP adolescents compared with controls (mean difference [95% confidence interval] of -5.9% [-8.0, -3.7%] for total brain tissue volume). The largest relative differences were noted in the thalamus and hippocampus. The EP group had lower IQs(-11.9 [-15.4, -8.5]), spelling(-8.0 [-11.5, -4.6]), math computation(-10.3 [-13.7, -6.9]) and word reading(-5.6 [-8.8, -2.4]) scores than controls; all p-values<0.001. Volumes of total brain tissue and other brain tissues and structures correlated positively with IQ and educational skills, a relationship that was similar for both the EP and controls. Total brain tissue volume explained between 20-40% of the IQ and educational outcome differences between EP and controls. CONCLUSIONS:EP adolescents had smaller brain volumes, lower IQs and poorer educational performance than controls. Brain volumes of multiple tissues and structures are related to IQ and educational outcomes. Smaller total brain tissue volume is an important contributor to the cognitive and educational underperformance of adolescents born EP

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

Current and emerging developments in subseasonal to decadal prediction

Weather and climate variations of subseasonal to decadal timescales can have enormous social, economic and environmental impacts, making skillful predictions on these timescales a valuable tool for decision makers. As such, there is a growing interest in the scientific, operational and applications communities in developing forecasts to improve our foreknowledge of extreme events. On subseasonal to seasonal (S2S) timescales, these include high-impact meteorological events such as tropical cyclones, extratropical storms, floods, droughts, and heat and cold waves. On seasonal to decadal (S2D) timescales, while the focus remains broadly similar (e.g., on precipitation, surface and upper ocean temperatures and their effects on the probabilities of high-impact meteorological events), understanding the roles of internal and externally-forced variability such as anthropogenic warming in forecasts also becomes important. The S2S and S2D communities share common scientific and technical challenges. These include forecast initialization and ensemble generation; initialization shock and drift; understanding the onset of model systematic errors; bias correct, calibration and forecast quality assessment; model resolution; atmosphere-ocean coupling; sources and expectations for predictability; and linking research, operational forecasting, and end user needs. In September 2018 a coordinated pair of international conferences, framed by the above challenges, was organized jointly by the World Climate Research Programme (WCRP) and the World Weather Research Prograame (WWRP). These conferences surveyed the state of S2S and S2D prediction, ongoing research, and future needs, providing an ideal basis for synthesizing current and emerging developments in these areas that promise to enhance future operational services. This article provides such a synthesis

Effects of anthropogenic structures and a wetland on macroinvertebrate diversity and water chemistry along the Maple River.

General EcologyAquatic systems play an integral role in wide ranging ecological contexts by providing an outlet of nutrient and chemical buildup. Rivers are particularly vulnerable to deleterious anthropogenic effects given their popularity as transit and recreation waterways. The health of a stream can accurately be assessed using an index of macroinvertebrate diversity as well as a battery of chemical concentration tests. Our study found that the Maple River shows few negative effects of anthropogenic structures on macroinvertebrate health and on overall stream health. The presence of a wetland may also have served to mitigate the possible human effects.http://deepblue.lib.umich.edu/bitstream/2027.42/96208/1/Alanouf_Cote_Henke_Hsieh_2012.pd

Effects of antibiotic interaction on antimicrobial resistance development in wastewater

Abstract While wastewater is understood to be a critically important reservoir of antimicrobial resistance due to the presence of multiple antibiotic residues from industrial and agricultural runoff, there is little known about the effects of antibiotic interactions in the wastewater on the development of resistance. We worked to fill this gap in quantitative understanding of antibiotic interaction in constant flow environments by experimentally monitoring E. coli populations under subinhibitory concentrations of combinations of antibiotics with synergistic, antagonistic, and additive interactions. We then used these results to expand our previously developed computational model to account for the effects of antibiotic interaction. We found that populations grown under synergistic and antagonistic antibiotic conditions exhibited significant differences from predicted behavior. E. coli populations grown with synergistically interacting antibiotics developed less resistance than predicted, indicating that synergistic antibiotics may have a suppressive effect on resistance development. Furthermore E. coli populations grown with antagonistically interacting antibiotics showed an antibiotic ratio-dependent development of resistance, suggesting that not only antibiotic interaction, but relative concentration is important in predicting resistance development. These results provide critical insight for quantitatively understanding the effects of antibiotic interactions in wastewater and provide a basis for future studies in modelling resistance in these environments

Analyzing Health of Forcibly Displaced Communities through an Integrated Ecological Lens

Health care among forcibly displaced persons is frequently driven by siloed approaches. Aspects of the built environment, social factors, and the bidirectional relationship between the changing ecosystem and residents are often ignored in health policy design and implementation. While recognizing factors that create a preference for siloed approaches and appreciating the work of humanitarian agencies, we argue for a new data-driven and holistic approach to understand the health of the forcibly displaced. It should be rooted in the realities of the emergence of new diseases, dynamic demographics, and degrading environments around the displaced communities. Such an approach envisions refugee and internally displaced camps as dynamic, complex ecosystems that alter, and are altered by, spatial and temporal factors. At the root of this approach is the necessity to work across disciplines, to think holistically, to go beyond treating single ailments, and to develop ethical approaches that provide dignity to those who are forcibly displaced

GanR represses the <i>gan</i> operon and the <i>ganR</i> gene.

<p><b>(A)</b> Assays of β-galactosidase activities by the reporter strains bearing either P_<i>ganS</i>-<i>lacZ</i>, or P_<i>ganR</i>-<i>lacZ</i>, or P_<i>ganB</i>-<i>lacZ</i> in the wild type strain (blue bars; YC1073, YC1085, and YC1088) and the <i>ganR</i> mutant (red bars; YC1074, YC1086, and YC1089). A deletion mutation in <i>ganA</i> was also introduced into the above strains. Cells were grown in LB shaking broth to OD₆₀₀ = 1 before harvest and analyses. Assays were done in triplicates and error bars represent standard deviations. <b>(B-C)</b> Assays of ß-galactosidase activities by the wild type reporter strains bearing either P_<i>ganS</i>-<i>lacZ</i>(YC1073, panel B) or P_<i>ganR</i>-<i>lacZ</i>(YC1085, panel C). Cells were grown in LB shaking culture over a period of 5.5 hours after inoculation. Both culture densities (red squares, right-hand y-axis) and ß-galactosidase activities of cells (blue diamonds, left-hand y-axis) were measured. Assays were repeated multiple times and representative data was shown here. <b>(D)</b> Assays of ß-galactosidase activities by the P_<i>ganS</i>-<i>lacZ</i> reporter strains in the wild type background (YC1071), the Δ<i>sinR</i> (YC1091), Δ<i>spo0A</i> (YC1092), Δ<i>degU</i> (YC1248), and Δ<i>ccpA</i> (YC1249) mutants. The <i>ganA</i> deletion mutation was not introduced into the above strains. In some mutants, an <i>epsH</i> deletion mutation was also introduced to prevent cell aggregation during shaking growth [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0179761#pone.0179761.ref045" target="_blank">45</a>]. Cells were grown in LB shaking culture to OD₆₀₀ = 1 before harvest and analyses. Error bars represent standard deviations. <b>(E)</b> Display of the promoter regions of <i>ganS</i> and <i>ganR</i> from <i>B</i>. <i>subtilis</i> NCIB3610 and <i>B</i>. <i>licheniformis</i> ATCC8480. The inverted repeats are highlighted in red, the -35 and -10 motifs of the sigma A-dependent promoter are underlined and shown in italic. ATG or GTG start codons of <i>ganS</i> or <i>ganR</i> are highlighted in blue. The <i>cre</i> box for putative CcpA binding sequences in the <i>ganS</i> promoter regions is highlighted in green. The transcriptional start of the <i>ganS</i> gene in <i>B</i>. <i>subtilis</i> was determined in a very recent study [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0179761#pone.0179761.ref029" target="_blank">29</a>] and labeled as +1. <b>(F)</b> The consensus DNA motif logo was generated from a multiple sequence alignment of the putative motifs from the selected promoters using WebLogo [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0179761#pone.0179761.ref031" target="_blank">31</a>]. The height of each stack, displayed in bits, is representative of the frequency of the nucleotide in the motif.</p