Maternal Mental Health Symptom Profiles and Infant Sleep: A Cross-Sectional Survey.

The distinct influence of different, but comorbid, maternal mental health (MMH) difficulties (postpartum depression, anxiety, childbirth-related posttraumatic stress disorder) on infant sleep is unknown, although associations between MMH and infant sleep were reported. This cross-sectional survey aimed: (1) to examine associations between MMH symptoms and infant sleep; (2) to extract data-driven maternal MMH symptom profiles from MMH symptoms; and (3) to investigate the distinct influence of these MMH symptom profiles on infant sleep when including mediators and moderators. Mothers of 3-12-month-old infants (n = 410) completed standardized questionnaires on infant sleep, maternal perception of infant negative emotionality, and MMH symptoms. Data was analyzed using: (1) simple linear regressions; (2) factor analysis; and (3) structural equation modelling. MMH symptoms were all negatively associated with nocturnal sleep duration and only postpartum depression and anxiety symptoms were associated with night waking. Three MMH symptom profiles were extracted: depressive, anxious, and birth trauma profiles. Maternal perception of infant negative emotionality mediated the associations between the depressive or anxious profiles and infant sleep but only for particular infant ages or maternal education levels. The birth trauma profile was not associated with infant sleep. The relationships between MMH and infant sleep may involve distinct mechanisms contingent on maternal symptomatology

Chemical regulators of epithelial plasticity reveal a nuclear receptor pathway controlling myofibroblast differentiation

Plasticity in epithelial tissues relates to processes of embryonic development, tissue fibrosis and cancer progression. Pharmacological modulation of epithelial transitions during disease progression may thus be clinically useful. Using human keratinocytes and a robotic high-content imaging platform, we screened for chemical compounds that reverse transforming growth factor β (TGF-β)-induced epithelial-mesenchymal transition. In addition to TGF-β receptor kinase inhibitors, we identified small molecule epithelial plasticity modulators including a naturally occurring hydroxysterol agonist of the liver X receptors (LXRs), members of the nuclear receptor transcription factor family. Endogenous and synthetic LXR agonists tested in diverse cell models blocked α-smooth muscle actin expression, myofibroblast differentiation and function. Agonist-dependent LXR activity or LXR overexpression in the absence of ligand counteracted TGF-β-mediated myofibroblast terminal differentiation and collagen contraction. The protective effect of LXR agonists against TGF-β-induced pro-fibrotic activity raises the possibility that anti-lipidogenic therapy may be relevant in fibrotic disorders and advanced cancer

Kinetics of CO<inf>2</inf>-fluid-rock reactions in a basalt aquifer, Soda Springs, Idaho

The dissolution of silicate minerals by CO2–rich fluids and the subsequent precipitation of CO2 as carbonate minerals represent a means of permanently storing anthropogenic CO2 waste products in a solid and secure form. Modelling the progression of these reactions is hindered by our poor understanding of the rates of mineral dissolution-precipitation reactions and mineral surface properties in natural systems. This study evaluates the chemical evolution of groundwater flowing through a basalt aquifer, which forms part of the leaking CO2-charged system of the Blackfoot Volcanic Field in south-eastern Idaho, USA. Reaction progress is modelled using changes in groundwater chemistry by inverse mass balance techniques. The CO2-promoted fluid-mineral reactions include the dissolution of primary plagioclase, orthoclase, pyroxene and gypsum which is balanced by the precipitation of secondary albite, calcite, zeolite, kaolinite and silica. Mineral mole transfers and groundwater flow rates estimated from hydraulic head data are used to determine the kinetics of plagioclase and orthoclase feldspar dissolution. Plagioclase surface area measurements were determined using the evolution of the U-series isotope ratios in the groundwater and are compared to published surface area measurements. Calculated rates of dissolution for plagioclase range from 2.4 x 10-12 to 4.6 x 10-16 mol/m2/s and orthoclase from 2.0 x 10-13 to 6.8 x 10-16 mol/m2/s respectively. These feldspar reaction rates, correlate with the degree of mineral-fluid disequilibrium and are similar to the dissolution rates for these mineral measured in other natural CO2-charged groundwater systems.Carbon research at Cambridge is supported by Natural Environment Research Council grant NE/F004699/1, part of the UK CRIUS (Carbon Research Into Underground Storage) consortium and DECC through the ‘£20 million’ competition. Niko Kampman acknowledges financial support from Shell Global Solutions International.This is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/j.apgeochem.2015.06.01

On the DNA cleavage mechanism of Type I restriction enzymes

Although the DNA cleavage mechanism of Type I restriction-modification enzymes has been extensively studied, the mode of cleavage remains elusive. In this work, DNA ends produced by EcoKI, EcoAI and EcoR124I, members of the Type IA, IB and IC families, respectively, have been characterized by cloning and sequencing restriction products from the reactions with a plasmid DNA substrate containing a single recognition site for each enzyme. Here, we show that all three enzymes cut this substrate randomly with no preference for a particular base composition surrounding the cleavage site, producing both 5′- and 3′-overhangs of varying lengths. EcoAI preferentially generated 3′-overhangs of 2-3 nt, whereas EcoKI and EcoR124I displayed some preference for the formation of 5′-overhangs of a length of ∼6-7 and 3-5 nt, respectively. A mutant EcoAI endonuclease assembled from wild-type and nuclease-deficient restriction subunits generated a high proportion of nicked circular DNA, whereas the wild-type enzyme catalyzed efficient cleavage of both DNA strands. We conclude that Type I restriction enzymes require two restriction subunits to introduce DNA double-strand breaks, each providing one catalytic center for phosphodiester bond hydrolysis. Possible models for DNA cleavage are discusse

On the DNA cleavage mechanism of Type I restriction enzymes

Although the DNA cleavage mechanism of Type I restriction–modification enzymes has been extensively studied, the mode of cleavage remains elusive. In this work, DNA ends produced by EcoKI, EcoAI and EcoR124I, members of the Type IA, IB and IC families, respectively, have been characterized by cloning and sequencing restriction products from the reactions with a plasmid DNA substrate containing a single recognition site for each enzyme. Here, we show that all three enzymes cut this substrate randomly with no preference for a particular base composition surrounding the cleavage site, producing both 5′- and 3′-overhangs of varying lengths. EcoAI preferentially generated 3′-overhangs of 2–3 nt, whereas EcoKI and EcoR124I displayed some preference for the formation of 5′-overhangs of a length of ∼6–7 and 3–5 nt, respectively. A mutant EcoAI endonuclease assembled from wild-type and nuclease-deficient restriction subunits generated a high proportion of nicked circular DNA, whereas the wild-type enzyme catalyzed efficient cleavage of both DNA strands. We conclude that Type I restriction enzymes require two restriction subunits to introduce DNA double-strand breaks, each providing one catalytic center for phosphodiester bond hydrolysis. Possible models for DNA cleavage are discussed

The Joint Observation in Neonatology and Neurodevelopmental Outcome of Preterm Infants at Six Months Corrected Age: Secondary Outcome Data from a Randomised Controlled Trial.

This study aimed to evaluate the impact of a standardised joint observation (JOIN) performed in the neonatal intensive care unit (NICU) on the neurodevelopment of preterm infants at six months corrected age (CA) compared with a preterm control group. In this monocentric interventional randomised controlled trial, we allocated 76 mothers and their preterm neonates to either JOIN, an early one-session intervention, or standard care during the NICU hospitalisation. The neurodevelopment of the preterm infants was assessed by standardised developmental tests at six months CA and compared between the intervention and the control groups. This randomised controlled trial was registered on clinicaltrials.gov (NCT02736136) in April 2016. Sixty-five infants underwent neurodevelopmental assessment at six months CA. There were no significant differences between the two groups in neurodevelopmental outcome measures. The JOIN intervention was not associated with significant improvement in neurodevelopment at six months CA in preterm infants

4′-Acylated thymidine 5′-triphosphates: a tool to increase selectivity towards HIV-1 reverse transcriptase

4′-Acylated thymidines represent a new class of DNA chain terminators, since they have been shown to act as post-incorporation chain-terminating nucleotides despite the presence of a free 3′-hydroxyl group. Here, we describe the action of the 4′-acetyl- (MeTTP) and 4′-propanoylthymidine 5′-triphosphate (EtTTP) on HIV-1 reverse transcriptase in RNA- and DNA-dependent DNA synthesis and on DNA synthesis catalyzed by the cellular DNA polymerases α, β, δ and ε. MeTTP exhibits a high selectivity towards HIV-1 reverse transcriptase. By the use of the bulkier propanoyl group as the 4′-substituent of the nucleoside 5′-triphosphate, selectivity towards HIV-1 reverse transcriptase could be increased without affecting substrate efficiency. Thus, 4′-modifications may serve as a tool to increase selectivity towards HIV-1 reverse transcriptas

Chemical weathering outputs from the flood plain of the Ganga

Transport of sediment across riverine flood plains contributes a significant but poorly constrained fraction of the total chemical weathering fluxes from rapidly eroding mountain belts which has impor- tant implications for chemical fluxes to the oceans and the impact of orogens on long term climate. We report water and bedload chemical analyses from the Ganges flood-plain, a major transit reservoir of sediment from the Himalayan orogen. Our data comprise six major southern tributaries to the Ganga, 31 additional analyses of major rivers from the Himalayan front in Nepal, 79 samples of the Ganga collected close to the mouth below the Farakka barrage every two weeks over three years and 67 water and 8 bedload samples from tributaries confined to the Ganga flood plain,. The flood plain tributaries are characterised by a shallow d 18 O - dD array, compared to the meteoric water line, with a low dD excess from evaporative loss from the flood plain which is mirrored in the higher dD excess of the mountain rivers in Nepal. The stable-isotope data confirms that the waters in the flood plain tributaries are domi- nantly derived from flood plain rainfall and not by redistribution of waters from the mountains. The flood plain tributaries are chemically distinct from the major Himalayan rivers. They can be divided into two groups. Tributaries from a small area around the Kosi river have 87 Sr/ 86 Sr ratios > 0.75 and molar Na/Ca ratios as high as 6. Tributaries from the rest of the flood plain have 87 Sr/ 86 Sr ratios <0.74 and most have Na/Ca ratios <1. One sample of the Gomti river and seven small adjacent tributaries have elevated Na concentrations likely caused by dissolution of Na carbonate salts. The compositions of the carbonate and silicate components of the sediments were determined from sequential leaches of floodplain bedloads and these were used to partition the dissolved cation load between silicate and car- bonate sources. The 87 Sr/ 86 Sr and Sr/Ca ratios of the carbonate inputs were derived from the ace- tic-acid leach compositions and silicate Na/Ca and 87 Sr/ 86 Sr ratios derived from silicate residues from leaching. Modelling based on the 87 Sr/ 86 Sr and Sr/Ca ratios of the carbonate inputs and 87 Sr/ 86 Sr ratios of the silicates indicates that the flood plain waters have lost up to 70% of their Ca (average ~ 50%) to precipitation of secondary calcite which is abundant as a diagenetic cement in the flood plain sedi- ments. 31% of the Sr, 8% of the Ca and 45% of the Mg are calculated to be derived from silicate miner- als. Because of significant evaporative loss of water across the flood plain, and in the absence of hy- drological data for flood plain tributaries, chemical weathering fluxes from the flood plain are best calculated by mass balance of the Na, K, Ca, Mg, Sr, SO 4 and 87 Sr/ 86 Sr compositions of the inputs, comprising the flood plain tributaries, Himalayan rivers and southern rivers, with the chemical dis- charge in the Ganga at Farakka. The calculated fluxes from the flood plain for Na, K, Ca and Mg are within error of those estimated from changes in sediment chemistry across the flood plain (Lupker et al., 2012, Geochemica Cosmochimica Acta). Flood plain weathering supplies between 33 and 48% of the major cation and Sr fluxes and 58% of the alkalinity flux carried by the Ganga at Farakka which compares with 24% supplied by Himalayan rivers and 18% by the southern tributaries