Gain of 20q11.21 in human pluripotent stem cells impairs TGF-β-dependent neuroectodermal commitment

Gain of 20q11.21 is one of the most common recurrent genomic aberrations in human pluripotent stem cells. Although it is known that overexpression of the antiapoptotic gene Bcl-xL confers a survival advantage to the abnormal cells, their differentiation capacity has not been fully investigated. RNA sequencing of mutant and control hESC lines, and a line transgenically overexpressing Bcl-xL, shows that overexpression of Bcl-xL is sufficient to cause most transcriptional changes induced by the gain of 20q11.21. Moreover, the differentially expressed genes in mutant and Bcl-xL overexpressing lines are enriched for genes involved in TGF-beta- and SMAD-mediated signaling, and neuron differentiation. Finally, we show that this altered signaling has a dramatic negative effect on neuroectodermal differentiation, while the cells maintain their ability to differentiate to mesendoderm derivatives. These findings stress the importance of thorough genetic testing of the lines before their use in research or the clinic

Деформационное упрочнение начально-изотропных металлов при деформировании по траекториям малой кривизны

На примере стали мартенситного класса исследованы закономерности деформационного упрочнения при нагружении по траекториям, имеющим вид двухзвенных ломаных, которым соответствуют траектории деформирования малой кривизны. Показано, что поверхность нагружения, разделяющая области упругого и упругопластического деформирования, смещается в направлении вектора, который соединяет центр поверхности нагружения и изображающую точку на траектории нагружения, при этом не изменяется форма ее фронтальной части. Зависимость величины смещения центра поверхности нагружения от интенсивности накопленных пластических деформаций описывается кривой, инвариантной к виду траектории нагружения.На прикладі сталі мартенситного класу досліджено закономірності деформаційного зміцнення при навантаженні по траєкторіях, що мають вигляд дволанкових ламаних, яким відповідають траєкторії деформування малої кривини. Показано, що поверхня навантаження, яка розділяє області пружного та пружнопластичного деформування, зміщується у напрямку вектора, який з ’єднує центр поверхні навантаження та відображуючу точку на траєкторії навантаження, при цьому форма фронтальної частини не змінюється. Залежність величини зміщення центра поверхні навантаження від інтенсивності накопичених пластичних деформацій описується кривою, яка є інваріантною відносно траєкторії навантаження.By the example of martensitic steel we study regularities of strain hardening under loading along two-section broken lines corresponding to slightly curved strain paths. It is shown that the loading surface separating domains of elastic and elastoplastic strains (yield surface) is displaced in the direction of a vector connecting the surface center with the loading trajectory image point, while the shape of its frontal part remains unchanged. The yield surface center displacement versus the intensity of accumulated plastic strains is described by a curve invariant to the loading trajectory

Triplet Exciton Generation in Bulk-Heterojunction Solar Cells based on Endohedral Fullerenes

Organic bulk-heterojunctions (BHJ) and solar cells containing the trimetallic nitride endohedral fullerene 1-[3-(2-ethyl)hexoxy carbonyl]propyl-1-phenyl-Lu3N@C80 (Lu3N@C80-PCBEH) show an open circuit voltage (VOC) 0.3 V higher than similar devices with [6,6]-phenyl-C[61]-butyric acid methyl ester (PC61BM). To fully exploit the potential of this acceptor molecule with respect to the power conversion efficiency (PCE) of solar cells, the short circuit current (JSC) should be improved to become competitive with the state of the art solar cells. Here, we address factors influencing the JSC in blends containing the high voltage absorber Lu3N@C80-PCBEH in view of both photogeneration but also transport and extraction of charge carriers. We apply optical, charge carrier extraction, morphology, and spin-sensitive techniques. In blends containing Lu3N@C80-PCBEH, we found 2 times weaker photoluminescence quenching, remainders of interchain excitons, and, most remarkably, triplet excitons formed on the polymer chain, which were absent in the reference P3HT:PC61BM blends. We show that electron back transfer to the triplet state along with the lower exciton dissociation yield due to intramolecular charge transfer in Lu3N@C80-PCBEH are responsible for the reduced photocurrent

Parthenogenic Blastocysts Derived from Cumulus-Free In Vitro Matured Human Oocytes

Approximately 20% of oocytes are classified as immature and discarded following intracytoplasmic sperm injection (ICSI) procedures. These oocytes are obtained from gonadotropin-stimulated patients, and are routinely removed from the cumulus cells which normally would mature the oocytes. Given the ready access to these human oocytes, they represent a potential resource for both clinical and basic science application. However culture conditions for the maturation of cumulus-free oocytes have not been optimized. We aimed to improve maturation conditions for cumulus-free oocytes via culture with ovarian paracrine/autocrine factors identified by single cell analysis..Human cumulus-free oocytes from hormone-stimulated cycles are capable of developing to blastocysts when cultured with ovarian factor supplementation. Our improved IVM culture conditions may be used for obtaining mature oocytes for clinical purposes and/or for derivation of embryonic stem cells following parthenogenesis or nuclear transfer

F4+ ETEC infection and oral immunization with F4 fimbriae elicits an IL-17-dominated immune response

Enterotoxigenic Escherichia coli (ETEC) are an important cause of post-weaning diarrhea (PWD) in piglets. Porcine-specific ETEC strains possess different fimbrial subtypes of which F4 fimbriae are the most frequently associated with ETEC-induced diarrhea in piglets. These F4 fimbriae are potent oral immunogens that induce protective F4-specific IgA antibody secreting cells at intestinal tissues. Recently, T-helper 17 (Th17) cells have been implicated in the protection of the host against extracellular pathogens. However, it remains unknown if Th17 effector responses are needed to clear ETEC infections. In the present study, we aimed to elucidate if ETEC elicits a Th17 response in piglets and if F4 fimbriae trigger a similar response. F4+ ETEC infection upregulated IL-17A, IL-17F, IL-21 and IL-23p19, but not IL-12 and IFN-γ mRNA expression in the systemic and mucosal immune system. Similarly, oral immunization with F4 fimbriae triggered a Th17 signature evidenced by an upregulated mRNA expression of IL-17F, RORγt, IL-23p19 and IL-21 in the peripheral blood mononuclear cells (PBMCs). Intriguingly, IL-17A mRNA levels were unaltered. To further evaluate this difference between systemic and mucosal immune responses, we assayed the cytokine mRNA profile of F4 fimbriae stimulated PBMCs. F4 fimbriae induced IL-17A, IL-17F, IL-22 and IL-23p19, but downregulated IL-17B mRNA expression. Altogether, these data indicate a Th17 dominated response upon oral immunization with F4 fimbriae and F4+ ETEC infection. Our work also highlights that IL-17B and IL-17F participate in the immune response to protect the host against F4+ ETEC infection and could aid in the design of future ETEC vaccines

Critical evaluation of key evidence on the human health hazards of exposure to bisphenol A

Despite the fact that more than 5000 safety-related studies have been published on bisphenol A (BPA), there seems to be no resolution of the apparently deadlocked controversy as to whether exposure of the general population to BPA causes adverse effects due to its estrogenicity. Therefore, the Advisory Committee of the German Society of Toxicology reviewed the background and cutting-edge topics of this BPA controversy. The current tolerable daily intake value (TDI) of 0.05 mg/kg body weight [bw]/day, derived by the European Food Safety Authority (EFSA), is mainly based on body weight changes in two- and three-generation studies in mice and rats. Recently, these studies and the derivation of the TDI have been criticized. After having carefully considered all arguments, the Committee had to conclude that the criticism was scientifically not justified; moreover, recently published additional data further support the reliability of the two-and three-generation studies demonstrating a lack of estrogen-dependent effects at and below doses on which the current TDI is based. A frequently discussed topic is whether doses below 5 mg/ kg bw/day may cause adverse health effects in laboratory animals. Meanwhile, it has become clear that positive results from some explorative studies have not been confirmed in subsequent studies with higher numbers of animals or a priori defined hypotheses. Particularly relevant are some recent studies with negative outcomes that addressed effects of BPA on the brain, behavior, and the prostate in rodents for extrapolation to the human situation. The Committee came to the conclusion that rodent data can well be used as a basis for human risk evaluation. Currently published conjectures that rats are insensitive to estrogens compared to humans can be refuted. Data from toxicokinetics studies show that the half-life of BPA in adult human subjects is less than 2 hours and BPA is completely recovered in urine as BPA-conjugates. Tissue deconjugation of BPA-glucuronide and -sulfate may occur. Because of the extremely low quantities, it is only of minor relevance for BPA toxicity. Biomonitoring studies have been used to estimate human BPA exposure and show that the daily intake of BPA is far below the TDI for the general population. Further topics addressed in this article include reasons why some studies on BPA are not reproducible; the relevance of oral versus non-oral exposure routes; the degree to which newborns are at higher systemic BPA exposure; increased BPA exposure by infusions in intensive care units; mechanisms of action other than estrogen receptor activation; and the current regulatory status in Europe, as well as in the USA, Canada, Japan, New Zealand, and Australia. Overall, the Committee concluded that the current TDI for BPA is adequately justified and that the available evidence indicates that BPA exposure represents no noteworthy risk to the health of the human population, including newborns and babies

Religion in the making: the Lived Ancient Religion approach

For the past five years (2012–2017), the Max Weber Center of Erfurt University has hosted a project on ‘Lived Ancient Religion: Questioning “cults” and “polis religion”’, financed by the European Research Council and embedded in the research group on ‘Religious individualisation in historical perspective’ (see Fuchs and Rüpke. [2015. “Religious Individualisation in Historical Perspective.” Religion 45 (3): 323–329. doi:10.1080/0048721X.2015.1041795]). It was designed to supplement existing accounts of the religious history of the Mediterranean area at the time of the long Roman Empire, accounts traditionally centred upon public or civic institutions. The new model focuses on the interaction of individuals with a variety of religious specialists and traditions, taking the form of material culture, spaces and text. It emphasises religious experience, embodiment and ‘culture in interaction’. On the basis of research into the history of religion of the Roman Empire, this co-authored article sets out to offer new tools for research into religion by formulating three major perspectives, namely religious agency, instantiated religion and narrated religion. We have tried to illustrate their potential value by means of 13 short case studies deriving from different geographical areas of the central and eastern Mediterranean area, and almost all relating to the period 150 BCE to 300 CE. These short descriptions are summarising research pursued by the members of the team of authors, published or to be published in extended form elsewhere, as indicated by the references

BMC Public Health

BACKGROUND: In 2009, the World Health Organization's Commission on Social Determinants of Health set out its recommendations for action, which included establishing equity from early childhood onwards by enabling all children and their mothers to benefit from a comprehensive package of quality programmes. In order to address social inequalities in health, it is recommended that action be taken from early childhood, and actions providing support for parenting are an effective lever in this respect. The aim of this review of systematic reviews is to analyse, on the one hand, the components and characteristics of effective interventions in parenting support and, on the other, the extent to which the reviews took into account social inequalities in health. METHODS: A total of 796 reviews were selected from peer-reviewed journals published between 2009 and 2016 in French or English. Of these, 21 reviews responding to the AMSTAR and selected ROBIS criteria were retained. These were analysed in relation to the consideration they gave to social inequalities in health according to PRISMA-equity. RESULTS: The reviews confirmed that parenting support programmes improved infants' sleep, increased mothers' self-esteem and reduced mothers' anger, anxiety and stress levels. The mainly authors noted that the contexts in which the interventions had taken place were described either scantly or not at all, making it difficult to evaluate them. Only half of the reviews had addressed the question of social inequalities in health. In particular, there had been little research conducted on the relational aspect and the social link. CONCLUSION: In terms of addressing social inequalities in perinatal health, the approach remains both modest and reductive. Understanding how, for whom and in what conditions interventions operate is one way of optimising their results. Further research is needed to study the interactions between the interventions and their contexts