Nonalcoholic fatty liver disease (NAFLD) is a global epidemic in obese children and adults, and the onset might have fetal origins. A growing body of evidence supports the role of developmental ...programming, whereby the maternal environment affects fetal and infant development, altering the risk profile for disease later in life. Human and nonhuman primate studies of maternal obesity demonstrate that risk factors for pediatric obesity and NAFLD begin in utero. The pathologic mechanisms for NAFLD are multifactorial but have centered on altered mitochondrial function/dysfunction that might precede insulin resistance. Compared with the adult liver, the fetal liver has fewer mitochondria, low activity of the fatty acid metabolic enzyme carnitine palmitoyl-CoA transferase-1, and little or no gluconeogenesis. Exposure to excess maternal fuels during fetal life uniquely alters hepatic fatty acid oxidation, tricarboxylic acid cycle activity, de novo lipogenesis, and mitochondrial health. These events promote increased oxidative stress and excess triglyceride storage, and, together with altered immune function and epigenetic changes, they prime the fetal liver for NAFLD and might drive the risk for nonalcoholic steatohepatitis in the next generation.
Data analysis projects invariably involve a series of steps such as reading, cleaning, summarizing and plotting data, statistical analysis and reporting. To facilitate reproducible research, rather ...than employing a relatively ad-hoc point-and-click cut-and-paste approach, we typically break down these tasks into manageable chunks by employing separate files of statistical, programming or text processing syntax for each step including the final report. Real world data analysis often requires an iterative process because many of these steps may need to be repeated any number of times. Manually repeating these steps is problematic in that some necessary steps may be left out or some reported results may not be for the most recent data set or syntax. GNU Make may be used to automate the mundane task of regenerating output given dependencies between syntax and data files. In addition to facilitating the management of and documenting the workflow of a complex data analysis project, such automation can help minimize errors and make the project more reproducible. It is relatively simple to construct Makefiles for small data analysis projects. As projects increase in size, difficulties arise because GNU Make does not have inbuilt rules for statistical and related software. Without such rules, Makefiles can become unwieldy and error-prone. This article addresses these issues by providing GNU Make pattern rules for R, Sweave, rmarkdown, SAS, Stata, Perl and Python to streamline management of data analysis and reporting projects. Rules are used by adding a single line to project Makefiles. Additional flexibility is incorporated for modifying standard program options. An overall strategy is outlined for Makefile construction and illustrated via simple and complex examples.
This article approaches the latest work of Alberto Moreiras on infrapolitics
as self-conscious acts of writing which thinks its own conditions, or its
own contingent textual inscription. In this ...sense, I propose that we can
read this work as being informed by a question, even a preoccupation, over
what form or style of writing is appropriate to announce or re-veal the
existential dimensions proposed by the notion of infrapolitics. In exploring
three such untimely textual inscriptions, the article approaches the stakes
of what Moreiras thematises under the name of infrapolitics through how it
informs the performativity of Moreiras?s own writing practice, exploring in
the process the relationship that infrapolitics supposes to politics and to
a certain critique of late capitalism, as well as other important concepts
such as marranismo, the second turn of deconstruction, auto-graphic writing
and demetaphorisation, among others.
Halide perovskite solar cells containing a mixture of A-site cations are attracting considerable interest due to their improved stability and high power conversion efficiencies. Ionic transport is ...known to be an important predictor of perovskite behaviour, but the impact of partial A-site substitution on iodide ion diffusion is poorly understood. Here, we combine
ab initio
modelling, impedance spectroscopy and muon spin relaxation to investigate the effect on iodide ion transport of incorporating a low concentration of each of seven different sized cations (from small rubidium to large guanidinium) into methylammonium lead iodide. Experimental and simulation results are in good agreement, indicating that these cation substitutions increase the activation energy for iodide ion diffusion. We show for the first time that partial guanidinium substitution into methylammonium lead iodide strongly suppresses iodide ion transport. The insights gained from this multi-technique study are important for the future design of mixed-cation perovskite solar cells with enhanced performance.
Perovskite solar cells containing a mixture of A-site cations show increased activation energies for iodide diffusion.
Maternal obesity increases the risk for pediatric obesity; however, the molecular mechanisms in human infants remain poorly understood. We hypothesized that mesenchymal stem cells (MSCs) from infants ...born to obese mothers would demonstrate greater potential for adipogenesis and less potential for myogenesis, driven by differences in β-catenin, a regulator of MSC commitment. MSCs were cultured from the umbilical cords of infants born to normal-weight (prepregnancy pp BMI 21.1 ± 0.3 kg/m(2); n = 15; NW-MSCs) and obese mothers (ppBMI 34.6 ± 1.0 kg/m(2); n = 14; Ob-MSCs). Upon differentiation, Ob-MSCs exhibit evidence of greater adipogenesis (+30% Oil Red O stain ORO, +50% peroxisome proliferator-activated receptor (PPAR)-γ protein; P < 0.05) compared with NW-MSCs. In undifferentiated cells, total β-catenin protein content was 10% lower and phosphorylated Thr41Ser45/total β-catenin was 25% higher (P < 0.05) in Ob-MSCs versus NW-MSCs (P < 0.05). Coupled with 25% lower inhibitory phosphorylation of GSK-3β in Ob-MSCs (P < 0.05), these data suggest greater β-catenin degradation in Ob-MSCs. Lithium chloride inhibition of GSK-3β increased nuclear β-catenin content and normalized nuclear PPAR-γ in Ob-MSCs. Last, ORO in adipogenic differentiating cells was positively correlated with the percent fat mass in infants (r = 0.475; P < 0.05). These results suggest that altered GSK-3β/β-catenin signaling in MSCs of infants exposed to maternal obesity may have important consequences for MSC lineage commitment, fetal fat accrual, and offspring obesity risk.
The sharing and viewing of peptide identification results from search engines analyzing mass-spectrometry-based proteomic data is made difficult by the range of analysis tools employed, in that each ...produces a different output format. Annotated results associated with a journal article often have to be made available, but providing these in a format that can be queried by other researchers is often difficult. This is because although standard formats for results have been developed, these are not necessarily easy to produce. In this manuscript we describe the MS-Viewer program, part of the Protein Prospector Web package, which uses easy-to-create tabular files as input for providing highly interactive viewing of search engine results. Thanks to the simplicity and flexibility of the input format, results from a wide variety of search engines have been successfully viewed through the Web interface of this tool.
The discovery of high-temperature superconductivity in a layered iron arsenide has led to an intensive search to optimize the superconducting properties of iron-based superconductors by changing the ...chemical composition of the spacer layer between adjacent anionic iron arsenide layers. Superconductivity has been found in iron arsenides with cationic spacer layers consisting of metal ions (for example, Li(+), Na(+), K(+), Ba(2+)) or PbO- or perovskite-type oxide layers, and also in Fe(1.01)Se (ref. 8) with neutral layers similar in structure to those found in the iron arsenides and no spacer layer. Here we demonstrate the synthesis of Li(x)(NH(2))(y)(NH(3))(1-y)Fe(2)Se(2) (x~0.6; y~0.2), with lithium ions, lithium amide and ammonia acting as the spacer layer between FeSe layers, which exhibits superconductivity at 43(1) K, higher than in any FeSe-derived compound reported so far. We have determined the crystal structure using neutron powder diffraction and used magnetometry and muon-spin rotation data to determine the superconducting properties. This new synthetic route opens up the possibility of further exploitation of related molecular intercalations in this and other systems to greatly optimize the superconducting properties in this family.
Cyanobacteria are one of the principal sources of volatile organic compounds (VOCs) which cause offensive taste and odor (T&O) in drinking and recreational water, fish, shellfish and other seafood. ...Although non-toxic to humans, these T&O compounds severely undermine public trust in these commodities, resulting in substantial costs in treatment, and lost revenue to drinking water, aquaculture, food and beverage and tourist/hospitality industries. Mitigation and control have been hindered by the complexity of the communities and processes which produce and modify T&O events, making it difficult to source-track the major producer(s) and the factors governing VOC production and fate. Over the past decade, however, advances in bioinformatics, enzymology, and applied detection technologies have greatly enhanced our understanding of the pathways, the enzymes and the genetic coding for some of the most problematic VOCs produced by cyanobacteria. This has led to the development of tools for rapid and sensitive detection and monitoring for the VOC production at source, and provided the basis for further diagnostics of endogenous and exogenous controls. This review provides an overview of current knowledge of the major cyanobacterial VOCs, the producers, the biochemistry and the genetics and highlight the current applications and further research needs in this area.
The effect of a systematic increase in the bromide content on mixed anion methyl ammonium lead halide, MAPb(I 1−x Br x ) 3 , perovskite solar cells is investigated. We show that at a critical bromide ...concentration (7.5%) we supress the slow impedance response from the cells. We link the changing impedance spectrum to a large increase in the activation energy for iodide motion. These results are corroborated by muon spin relaxation measurements, where we show that at the concentration of bromide typically used in high performance perovskite solar cells (17%) there is no sign of iodide motion in powders. Finally, we show JV curve hysteresis as a function of bromide content. The scan rate at which the maximum hysteresis index is observed does not change as the % Br is increased, leading us to conclude that the low frequency impedance response and the JV curve hysteresis are not caused by the same mobile ions.
Increased maternal body mass index (BMI) is a robust risk factor for later pediatric obesity. Accumulating evidence suggests that human milk (HM) may attenuate the transfer of obesity from mother to ...offspring, potentially through its effects on early development of the infant microbiome.
Our objective was to identify early differences in intestinal microbiota in a cohort of breastfeeding infants born to obese compared with normal-weight (NW) mothers. We also investigated relations between HM hormones (leptin and insulin) and both the taxonomic and functional potentials of the infant microbiome.
Clinical data and infant stool and fasting HM samples were collected from 18 NW prepregnancy BMI (in kg/m(2)) <24.0 and 12 obese (prepregnancy BMI >30.0) mothers and their exclusively breastfed infants at 2 wk postpartum. Infant body composition at 2 wk was determined by air-displacement plethysmography. Infant gastrointestinal microbes were estimated by using 16S amplicon and whole-genome sequencing. HM insulin and leptin were determined by ELISA; short-chain fatty acids (SCFAs) were measured in stool samples by using gas chromatography. Power was set at 80%.
Infants born to obese mothers were exposed to 2-fold higher HM insulin and leptin concentrations (P < 0.01) and showed a significant reduction in the early pioneering bacteria Gammaproteobacteria (P = 0.03) and exhibited a trend for elevated total SCFA content (P < 0.06). Independent of maternal prepregnancy BMI, HM insulin was positively associated with both microbial taxonomic diversity (P = 0.03) and Gammaproteobacteria (e.g., Enterobacteriaceae; P = 0.04) and was negatively associated with Lactobacillales (e.g., Streptococcaceae; P = 0.05). Metagenomic analysis showed that HM leptin and insulin were associated with decreased bacterial proteases, which are implicated in intestinal permeability, and reduced concentrations of pyruvate kinase, a biomarker of pediatric gastrointestinal inflammation.
Our results indicate that, although maternal obesity may adversely affect the early infant intestinal microbiome, HM insulin and leptin are independently associated with beneficial microbial metabolic pathways predicted to increase intestinal barrier function and reduce intestinal inflammation. This trial was registered at clinicaltrials.gov as NCT01693406.
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