A randomised control trial of low glycaemic index carbohydrate diet versus no dietary intervention in the prevention of recurrence of macrosomia

<p>Abstract</p> <p>Background</p> <p>Maternal weight and maternal weight gain during pregnancy exert a significant influence on infant birth weight and the incidence of macrosomia. Fetal macrosomia is associated with an increase in both adverse obstetric and neonatal outcome, and also confers a future risk of childhood obesity. Studies have shown that a low glycaemic diet is associated with lower birth weights, however these studies have been small and not randomised <abbrgrp><abbr bid="B1">1</abbr><abbr bid="B2">2</abbr></abbrgrp>. Fetal macrosomia recurs in a second pregnancy in one third of women, and maternal weight influences this recurrence risk <abbrgrp><abbr bid="B3">3</abbr></abbrgrp>.</p> <p>Methods/Design</p> <p>We propose a randomised control trial of low glycaemic index carbohydrate diet vs. no dietary intervention in the prevention of recurrence of fetal macrosomia.</p> <p>Secundigravid women whose first baby was macrosomic, defined as a birth weight greater than 4000 g will be recruited at their first antenatal visit.</p> <p>Patients will be randomised into two arms, a control arm which will receive no dietary intervention and a diet arm which will be commenced on a low glycaemic index diet.</p> <p>The primary outcome measure will be the mean birth weight centiles and ponderal indices in each group.</p> <p>Discussion</p> <p>Altering the source of maternal dietary carbohydrate may prove to be valuable in the management of pregnancies where there has been a history of fetal macrosomia. Fetal macrosomia recurs in a second pregnancy in one third of women. This randomised control trial will investigate whether or not a low glycaemic index diet can affect this recurrence risk.</p> <p>Current Controlled Trials Registration Number</p> <p>ISRCTN54392969</p

Synergistic binding of transcription factors to cell-specific enhancers programs motor neuron identity

Efficient transcriptional programming promises to open new frontiers in regenerative medicine. However, mechanisms by which programming factors transform cell fate are unknown, preventing more rational selection of factors to generate desirable cell types. Three transcription factors, Ngn2, Isl1 and Lhx3, were sufficient to program rapidly and efficiently spinal motor neuron identity when expressed in differentiating mouse embryonic stem cells. Replacement of Lhx3 by Phox2a led to specification of cranial, rather than spinal, motor neurons. Chromatin immunoprecipitation–sequencing analysis of Isl1, Lhx3 and Phox2a binding sites revealed that the two cell fates were programmed by the recruitment of Isl1-Lhx3 and Isl1-Phox2a complexes to distinct genomic locations characterized by a unique grammar of homeodomain binding motifs. Our findings suggest that synergistic interactions among transcription factors determine the specificity of their recruitment to cell type–specific binding sites and illustrate how a single transcription factor can be repurposed to program different cell types.Project ALS FoundationNational Institutes of Health (U.S.) (Grant P01 NS055923

Predicting DNA-Binding Specificities of Eukaryotic Transcription Factors

Today, annotated amino acid sequences of more and more transcription factors (TFs) are readily available. Quantitative information about their DNA-binding specificities, however, are hard to obtain. Position frequency matrices (PFMs), the most widely used models to represent binding specificities, are experimentally characterized only for a small fraction of all TFs. Even for some of the most intensively studied eukaryotic organisms (i.e., human, rat and mouse), roughly one-sixth of all proteins with annotated DNA-binding domain have been characterized experimentally. Here, we present a new method based on support vector regression for predicting quantitative DNA-binding specificities of TFs in different eukaryotic species. This approach estimates a quantitative measure for the PFM similarity of two proteins, based on various features derived from their protein sequences. The method is trained and tested on a dataset containing 1 239 TFs with known DNA-binding specificity, and used to predict specific DNA target motifs for 645 TFs with high accuracy

A census of baryons in the Universe from localized fast radio bursts

More than three quarters of the baryonic content of the Universe resides in a highly diffuse state that is difficult to observe, with only a small fraction directly observed in galaxies and galaxy clusters. Censuses of the nearby Universe have used absorption line spectroscopy to observe these invisible baryons, but these measurements rely on large and uncertain corrections and are insensitive to the majority of the volume, and likely mass. Specifically, quasar spectroscopy is sensitive either to only the very trace amounts of Hydrogen that exists in the atomic state, or highly ionized and enriched gas in denser regions near galaxies. Sunyaev-Zel'dovich analyses provide evidence of some of the gas in filamentary structures and studies of X-ray emission are most sensitive to gas near galaxy clusters. Here we report the direct measurement of the baryon content of the Universe using the dispersion of a sample of localized fast radio bursts (FRBs), thus utilizing an effect that measures the electron column density along each sight line and accounts for every ionised baryon. We augment the sample of published arcsecond-localized FRBs with a further four new localizations to host galaxies which have measured redshifts of 0.291, 0.118, 0.378 and 0.522, completing a sample sufficiently large to account for dispersion variations along the line of sight and in the host galaxy environment to derive a cosmic baryon density of $\Omega_{b} = 0.051_{-0.025}^{+0.021} \, h_{70}^{-1}$ (95% confidence). This independent measurement is consistent with Cosmic Microwave Background and Big Bang Nucleosynthesis values.Comment: Published online in Nature 27 May, 202

Large Scale Comparison of Innate Responses to Viral and Bacterial Pathogens in Mouse and Macaque

Viral and bacterial infections of the lower respiratory tract are major causes of morbidity and mortality worldwide. Alveolar macrophages line the alveolar spaces and are the first cells of the immune system to respond to invading pathogens. To determine the similarities and differences between the responses of mice and macaques to invading pathogens we profiled alveolar macrophages from these species following infection with two viral (PR8 and Fuj/02 influenza A) and two bacterial (Mycobacterium tuberculosis and Francisella tularensis Schu S4) pathogens. Cells were collected at 6 time points following each infection and expression profiles were compared across and between species. Our analyses identified a core set of genes, activated in both species and across all pathogens that were predominantly part of the interferon response pathway. In addition, we identified similarities across species in the way innate immune cells respond to lethal versus non-lethal pathogens. On the other hand we also found several species and pathogen specific response patterns. These results provide new insights into mechanisms by which the innate immune system responds to, and interacts with, invading pathogens

In Silico Simulation of Corticosteroids Effect on an NFkB- Dependent Physicochemical Model of Systemic Inflammation

During the onset of an inflammatory response signaling pathways are activated for "translating" extracellular signals into intracellular responses converging to the activation of nuclear factor (NF)-kB, a central transcription factor in driving the inflammatory response. An inadequate control of its transcriptional activity is associated with the culmination of a hyper-inflammatory response making it a desired therapeutic target. Predicated upon the nature of the response, a systems level analysis might provide rational leads for the development of strategies that promote the resolution of the response.A physicochemical host response model is proposed to integrate biological information in the form of kinetic rules and signaling cascades with pharmacokinetic models of drug action for the modulation of the response. The unifying hypothesis is that the response is triggered by the activation of the NFkB signaling module and corticosteroids serve as a template for assessing anti-inflammatory strategies. The proposed in silico model is evaluated through its ability to predict and modulate uncontrolled responses. The pre-exposure of the system to hypercortisolemia, i.e. 6 hr before or simultaneously with the infectious challenge "reprograms" the dynamics of the host towards a balanced inflammatory response. However, if such an intervention occurs long before the inflammatory insult a symptomatic effect is observed instead of a protective relief while a steroid infusion after inducing inflammation requires much higher drug doses.We propose a reversed engineered inflammation model that seeks to describe how the system responds to a multitude of external signals. Timing of intervention and dosage regimes appears to be key determinants for the protective or symptomatic effect of exogenous corticosteroids. Such results lie in qualitative agreement with in vivo human studies exposed both to LPS and corticosteroids under various time intervals thus improving our understanding of how interacting modules generate a behavior

Defining the Plasticity of Transcription Factor Binding Sites by Deconstructing DNA Consensus Sequences: The PhoP-Binding Sites among Gamma/Enterobacteria

Transcriptional regulators recognize specific DNA sequences. Because these sequences are embedded in the background of genomic DNA, it is hard to identify the key cis-regulatory elements that determine disparate patterns of gene expression. The detection of the intra- and inter-species differences among these sequences is crucial for understanding the molecular basis of both differential gene expression and evolution. Here, we address this problem by investigating the target promoters controlled by the DNA-binding PhoP protein, which governs virulence and Mg2+ homeostasis in several bacterial species. PhoP is particularly interesting; it is highly conserved in different gamma/enterobacteria, regulating not only ancestral genes but also governing the expression of dozens of horizontally acquired genes that differ from species to species. Our approach consists of decomposing the DNA binding site sequences for a given regulator into families of motifs (i.e., termed submotifs) using a machine learning method inspired by the “Divide & Conquer” strategy. By partitioning a motif into sub-patterns, computational advantages for classification were produced, resulting in the discovery of new members of a regulon, and alleviating the problem of distinguishing functional sites in chromatin immunoprecipitation and DNA microarray genome-wide analysis. Moreover, we found that certain partitions were useful in revealing biological properties of binding site sequences, including modular gains and losses of PhoP binding sites through evolutionary turnover events, as well as conservation in distant species. The high conservation of PhoP submotifs within gamma/enterobacteria, as well as the regulatory protein that recognizes them, suggests that the major cause of divergence between related species is not due to the binding sites, as was previously suggested for other regulators. Instead, the divergence may be attributed to the fast evolution of orthologous target genes and/or the promoter architectures resulting from the interaction of those binding sites with the RNA polymerase

Process to practice: The evolving role of the academic middle manager in English further education colleges

The English further education sector has undergone significant change since the Further and Higher Education Act (1992) encouraged a culture of entrepreneurship, competition and the use of what was seen as best practice from the commercial sector. This led to a cultural shift and the introduction of many new initiatives – a situation that still exists now. The implementation of these initiatives was often delegated to middle managers – a group of people who occupied the gap between the senior leaders and the lecturers in the classroom. Current austerity measures, restructuring and the shift towards the creation of larger organizations have resulted in reorganizations that could present opportunities for middle managers to participate in the strategic processes and leadership of the organization, further developing their role (Greatbatch and Tate, 2018). The purpose of this article is to investigate the leadership and management aspects of the middle-manager’s role within the context of further education in England. Although many managers in the sector are reluctant to identify as leaders (Briggs, 2006), our research shows that their role has evolved so that they are undertaking a range of activities that could be classified as leadership. We suggest that using ‘practice’ rather than ‘process’ as a descriptor of the role would reframe, identify and bring forward the leadership aspects of what they do. Encouraging a focus on a holistic, practice-based approach, rather than a succession of process-driven tasks, could help managers to perform their role more effectively. Findings taken from interviews with 32 participants and a questionnaire with 302 responses are used to illustrate our argument. © 2019 British Educational Leadership, Management & Administration Society (BELMAS)

Standardized Assessment of Biodiversity Trends in Tropical Forest Protected Areas: The End Is Not in Sight

Extinction rates in the Anthropocene are three orders of magnitude higher than background and disproportionately occur in the tropics, home of half the world’s species. Despite global efforts to combat tropical species extinctions, lack of high-quality, objective information on tropical biodiversity has hampered quantitative evaluation of conservation strategies. In particular, the scarcity of population-level monitoring in tropical forests has stymied assessment of biodiversity outcomes, such as the status and trends of animal populations in protected areas. Here, we evaluate occupancy trends for 511 populations of terrestrial mammals and birds, representing 244 species from 15 tropical forest protected areas on three continents. For the first time to our knowledge, we use annual surveys from tropical forests worldwide that employ a standardized camera trapping protocol, and we compute data analytics that correct for imperfect detection. We found that occupancy declined in 22%, increased in 17%, and exhibited no change in 22% of populations during the last 3–8 years, while 39% of populations were detected too infrequently to assess occupancy changes. Despite extensive variability in occupancy trends, these 15 tropical protected areas have not exhibited systematic declines in biodiversity (i.e., occupancy, richness, or evenness) at the community level. Our results differ from reports of widespread biodiversity declines based on aggregated secondary data and expert opinion and suggest less extreme deterioration in tropical forest protected areas. We simultaneously fill an important conservation data gap and demonstrate the value of large-scale monitoring infrastructure and powerful analytics, which can be scaled to incorporate additional sites, ecosystems, and monitoring methods. In an era of catastrophic biodiversity loss, robust indicators produced from standardized monitoring infrastructure are critical to accurately assess population outcomes and identify conservation strategies that can avert biodiversity collapse. © 2016 Beaudrot et al