Cyclodextrin

The invention provides a method for preparing sulphoalkyl ether-β-cyclodextrin. The method comprises first contacting cyclodextrin with a base to form activated cyclodextrin. The method then comprises separately contacting the activated cyclodextrin with an alkyl sultone to form sulphoalkyl ether-β-cyclodextrin. The activation reaction is carried in batch and the sulphoalkylation reaction is carried out under continuous flow conditions

Retinoic acid enhances skeletal muscle progenitor formation and bypasses inhibition by bone morphogenetic protein 4 but not dominant negative β-catenin

<p>Abstract</p> <p>Background</p> <p>Understanding stem cell differentiation is essential for the future design of cell therapies. While retinoic acid (RA) is the most potent small molecule enhancer of skeletal myogenesis in stem cells, the stage and mechanism of its function has not yet been elucidated. Further, the intersection of RA with other signalling pathways that stimulate or inhibit myogenesis (such as Wnt and BMP4, respectively) is unknown. Thus, the purpose of this study is to examine the molecular mechanisms by which RA enhances skeletal myogenesis and interacts with Wnt and BMP4 signalling during P19 or mouse embryonic stem (ES) cell differentiation.</p> <p>Results</p> <p>Treatment of P19 or mouse ES cells with low levels of RA led to an enhancement of skeletal myogenesis by upregulating the expression of the mesodermal marker, Wnt3a, the skeletal muscle progenitor factors Pax3 and Meox1, and the myogenic regulatory factors (MRFs) MyoD and myogenin. By chromatin immunoprecipitation, RA receptors (RARs) bound directly to regulatory regions in the Wnt3a, Pax3, and Meox1 genes and RA activated a β-catenin-responsive promoter in aggregated P19 cells. In the presence of a dominant negative β-catenin/engrailed repressor fusion protein, RA could not bypass the inhibition of skeletal myogenesis nor upregulate Meox1 or MyoD. Thus, RA functions both upstream and downstream of Wnt signalling. In contrast, it functions downstream of BMP4, as it abrogates BMP4 inhibition of myogenesis and Meox1, Pax3, and MyoD expression. Furthermore, RA downregulated BMP4 expression and upregulated the BMP4 inhibitor, Tob1. Finally, RA inhibited cardiomyogenesis but not in the presence of BMP4.</p> <p>Conclusion</p> <p>RA can enhance skeletal myogenesis in stem cells at the muscle specification/progenitor stage by activating RARs bound directly to mesoderm and skeletal muscle progenitor genes, activating β-catenin function and inhibiting bone morphogenetic protein (BMP) signalling. Thus, a signalling pathway can function at multiple levels to positively regulate a developmental program and can function by abrogating inhibitory pathways. Finally, since RA enhances skeletal muscle progenitor formation, it will be a valuable tool for designing future stem cell therapies.</p

Continuous tank reactor synthesis of highly substituted sulphobutylether β-cyclodextrins

Batch synthesis of sulphobutyl ether β-cyclodextrin (also known as SBE-β-CD or SBECD) is a process effectively divided into three main stages, i.e. initial reagent dissolution, a sulphoalkylation reaction and final reaction quenching. This reaction is followed by downstream processing and purification, and ultimate isolation of the solid SBECD material. However, a feature associated with using this synthetic method is that a high proportion of lower substituted SBECD is observed. There is therefore a need to provide an improved synthetic method for producing higher substituted cyclodextrins. The authors here present a Continuous Tank Reactor (CTR) method for preparing sulphobutyl ether-cyclodextrins. The method comprises first contacting cyclodextrin with a base to form activated cyclodextrin. The method then involves separately contacting the activated cyclodextrin with an 1,4-butane sultone to form sulphoalkyl ether-cyclodextrin. The activation reaction is carried out in batch synthesis mode and the sulphoalkylation reaction is carried out under continuous flow conditions resulting in a novel method for the synthesis of highly derivatised cyclodextrins. The work is particularly concerned with producing controlled substitution in sulphobutyl ether β-cyclodextrins and novel compositions of highly substituted sulphoalkyl ether β-cyclodextrins are described

Be prepared: communism and the politics of scouting in 1950s Britain

This article examines the exposure, and in some cases dismissal, of Boy Scouts who belonged or sympathised with the Young Communist League in Britain during the early 1950s. A focus on the rationale and repercussions of the organisation's approach and attitudes towards ‘Red Scouts’ found within their ‘ranks’ extends our understanding of youth movements and their often complex and conflicting ideological foundations. In particular, the post-World War Two period presented significant challenges to these spaces of youth work in terms of broader social and political change in Britain. An analysis of the politics of scouting in relation to Red Scouts questions not only the assertion that British McCarthyism was ‘silent’, but also brings young people firmly into focus as part of a more everyday politics of communism in British society

US20160024229A1 Cyclodextrin

The invention provides a method for preparing sulphoalkyl ether-β-cyclodextrin. The method comprises first contacting cyclodextrin with a base to form activated cyclodextrin. The method then comprises separately contacting the activated cyclodextrin with an alkyl sultone to form sulphoalkyl ether-β-cyclodextrin. The activation reaction is carried in batch and the sulphoalkylation reaction is carried out under continuous flow conditions

The AMA Proposal to Mandate Nicotine Reduction in Cigarettes: A Simulation of the Population Health Impacts

Background. The American Medical Association (AMA) has advocated gradually reducing the nicotine content of cigarettes to decrease smoking prevalence. Some experts have voiced concerns that smokers may “compensate” by smoking more cigarettes or inhaling more deeply. Further, a black market may emerge, perpetuating cigarette availability. Thus, it is unclear whether a federal mandate would result in a net increase or decrease in population health. The purpose of this research is to estimate the long-term health gains or losses that are likely to accrue to the US population if the nicotine content of cigarettes is gradually reduced to trace levels over a 6-year period. Methods. To estimate health impacts, we created the Tobacco Policy Model, a computer simulation model. The model simulates the US population as they age and change their smoking behavior over time. Secondary data for model parameters were obtained from publicly available sources. Population health impacts were measured as the change in cumulative quality-adjusted life-years (QALYs) in the US population over 50 years. Results. Following a mandate to reduce nicotine, smoking prevalence is likely to decline from 23% to 5% of the population. Accordingly, a cumulative gain of 157 million QALYs is expected over 50 years. Conclusions. Despite any mortality increases due to compensatory smoking or the emergence of a black market, implementation of the AMA proposal would likely prevent the addiction of scores of new smokers and result in important gains to the nation\u27s health. This research should prove useful to Congress as they contemplate giving the FDA the authority to regulate tobacco

Additionality in Grassland Easements to Provide Migratory Bird Habitat in the Northern Plains

Native grassland in the Prairie Pothole Region (PPR) is important habitat for migratory birds, particularly ducks. Much of this grassland is at risk for conversion to cropland. Permanent easements, managed by the U.S. Fish and Wildlife Service, protect high-quality habitat but do not currently consider vulnerability to cropland conversion. We find that (i) grassland easements are protecting native grassland from conversion, although the level of protection is modest; (ii) it may be possible to increase habitat protection by targeting grassland that is vulnerable to cropland conversion; and (iii) conversion estimates that fail to account for easements are biased downward

Nutritional Status Differs by Prescription Opioid Use among Women of Reproductive Age: NHANES 1999–2018

Prescription opioid use among pregnant women has increased in recent years. Prenatal exposure to opioids and poor nutrition can both negatively impact maternal–fetal outcomes. The objective of this study was to characterize the nutrition and health status of reproductive-age women taking prescription opioids, compared to women not taking opioids. Using NHANES 1999–2018 data, non-pregnant women aged 20–44 years were classified as taking a prescription opioid in the last 30 days (n = 404) or unexposed controls (n = 7234). Differences in anthropometric, cardiovascular, hematologic, and micronutrient status indicators between opioid-exposed and unexposed women were examined. Opioid-exposed women were older, had lower income and education, and were more likely to be non-Hispanic White, to smoke, and to have chronic health conditions compared to unexposed women. In unadjusted analyses, several nutrition and health markers were significantly different between opioid exposure groups. After controlling for covariates, women taking opioids had higher odds of Class II (OR = 1.6, 95% CI = 1.1–2.3) or III obesity (OR = 1.6, 95% CI = 1.1–2.5), and lower levels of serum folate, iron, and transferrin saturation. Reproductive-age women taking prescription opioids may be at risk for poorer nutritional and cardiometabolic health. Future research is needed to explore whether nutritional status impacts maternal–fetal outcomes for women exposed to opioids during pregnancy