Miscarriage rates after dehydroepiandrosterone (DHEA) supplementation in women with diminished ovarian reserve: a case control study

<p>Abstract</p> <p>Background</p> <p>Dehydroepinadrosterone (DHEA) supplementation improves pregnancy chances in women with diminished ovarian reserve (DOR), by possibly reducing aneuploidy. Since a large majority of spontaneous miscarriages are associated with aneuploidy, one can speculate that DHEA supplementation may also reduce miscarriage rates.</p> <p>Methods</p> <p>We retroactively compared, utilizing two independent statistical models, miscarriage rates in 73 DHEA supplemented pregnancies at two independent North American infertility centers, age-stratified, to miscarriages reported in a national U.S. in vitro fertilization (IVF) data base.</p> <p>Results</p> <p>After DHEA supplementation the miscarriage rate at both centers was 15.1% (15.0% and 15.2%, respectively). For DHEA supplementation Mantel-Hänszel common odds ratio (and 95% confidence interval), stratified by age, was significantly lower, relative to odds of miscarriage in the general IVF control population [0.49 (0.25-0.94; p = 0.04)]. Miscarriage rates after DHEA were significantly lower at all ages but most pronounced above age 35 years.</p> <p>Discussion</p> <p>Since DOR patients in the literature are reported to experience significantly higher miscarriage rates than average IVF patients, the here observed reduction in miscarriages after DHEA supplementation exceeds, however, all expectations. Miscarriage rates after DHEA not only were lower than in an average national IVF population but were comparable to rates reported in normally fertile populations. Low miscarriage rates, comparable to those of normal fertile women, are statistically impossible to achieve in DOR patients without assumption of a DHEA effect on embryo ploidy. Beyond further investigations in infertile populations, these data, therefore, also suggest the investigations of pre-conception DHEA supplementation in normal fertile populations above age 35 years.</p

The Velvet Cage of Educational Con(pro)sumption

In the year that George Ritzer publishes the ninth edition of The McDonaldization of Society, moving his famous theory firmly Into the Digital Age, critical educator Petar Jandrić and sociologist Sarah Hayes invited George to a dialogue on the digital transformation of McDonaldization and its relationship to consumer culture. In this article, George first traces for us the origins of his theory that has endured for four decades. A key dimension of McDonaldization is the ‘iron cage’ of control, via rationalization, that was once contained within physical sites of bricks and mortar. Increasingly now, we encounter a ‘velvet cage’ in sites of digital consumption, at the hands of non-human technologies, that threaten human labour and autonomy. Exploited as unpaid con(pro)sumers, we labour to provide information for corporate digital billionaires, keeping McDonaldization alive, well, and even more predominant in augmented settings, including Higher Education, in the form of the McUniversity. With the rise of prosuming machines such as blockchain and bitcoin, that can both produce and consume without intervention from human prosumers, George concludes that prosumer capitalism will explode into unprecedented and unpredictable directions in the years to come

Singularities of nn-fold integrals of the Ising class and the theory of elliptic curves

We introduce some multiple integrals that are expected to have the same singularities as the singularities of the $n$-particle contributions $\chi^{(n)}$ to the susceptibility of the square lattice Ising model. We find the Fuchsian linear differential equation satisfied by these multiple integrals for $n=1, 2, 3, 4$ and only modulo some primes for $n=5$ and $6$, thus providing a large set of (possible) new singularities of the $\chi^{(n)}$. We discuss the singularity structure for these multiple integrals by solving the Landau conditions. We find that the singularities of the associated ODEs identify (up to $n= 6$) with the leading pinch Landau singularities. The second remarkable obtained feature is that the singularities of the ODEs associated with the multiple integrals reduce to the singularities of the ODEs associated with a {\em finite number of one dimensional integrals}. Among the singularities found, we underline the fact that the quadratic polynomial condition $1+3 w +4 w^2 = 0$, that occurs in the linear differential equation of $\chi^{(3)}$, actually corresponds to a remarkable property of selected elliptic curves, namely the occurrence of complex multiplication. The interpretation of complex multiplication for elliptic curves as complex fixed points of the selected generators of the renormalization group, namely isogenies of elliptic curves, is sketched. Most of the other singularities occurring in our multiple integrals are not related to complex multiplication situations, suggesting an interpretation in terms of (motivic) mathematical structures beyond the theory of elliptic curves.Comment: 39 pages, 7 figure

A Re-Examination of Global Suppression of RNA Interference by HIV-1

The nature of the interaction between replicating HIV-1 and the cellular RNAi pathway has been controversial, but it is clear that it can be complex and multifaceted. It has been proposed that the interaction is bi-directional, whereby cellular silencing pathways can restrict HIV-1 replication, and in turn, HIV-1 can suppress silencing pathways. Overall suppression of RNAi has been suggested to occur via direct binding and inhibition of Dicer by the HIV-1 Tat protein or through sequestration of TRBP, a Dicer co-factor, by the structured TAR element of HIV-1 transcripts. The role of Tat as an inhibitor of Dicer has been questioned and our results support and extend the conclusion that Tat does not inhibit RNAi that is mediated by either exogenous or endogenous miRNAs. Similarly, we find no suppression of silencing pathways in cells with replicating virus, suggesting that viral products such as the TAR RNA elements also do not reduce the efficacy of cellular RNA silencing. However, knockdown of Dicer does allow increased viral replication and this occurs at a post-transcriptional level. These results support the idea that although individual miRNAs can act to restrict HIV-1 replication, the virus does not counter these effects through a global suppression of RNAi synthesis or processing

Cryo-EM model validation recommendations based on outcomes of the 2019 EMDataResource challenge

This paper describes outcomes of the 2019 Cryo-EM Model Challenge. The goals were to (1) assess the quality of models that can be produced from cryogenic electron microscopy (cryo-EM) maps using current modeling software, (2) evaluate reproducibility of modeling results from different software developers and users and (3) compare performance of current metrics used for model evaluation, particularly Fit-to-Map metrics, with focus on near-atomic resolution. Our findings demonstrate the relatively high accuracy and reproducibility of cryo-EM models derived by 13 participating teams from four benchmark maps, including three forming a resolution series (1.8 to 3.1 Å). The results permit specific recommendations to be made about validating near-atomic cryo-EM structures both in the context of individual experiments and structure data archives such as the Protein Data Bank. We recommend the adoption of multiple scoring parameters to provide full and objective annotation and assessment of the model, reflective of the observed cryo-EM map density

Modulation of MicroRNA-194 and cell migration by HER2-targeting trastuzumab in breast cancer

Conceived and designed the experiments: XFL GAC RCB. Performed the experiments: XFL MIA WM RS MSN SZ. Analyzed the data: XFL SR. Contributed reagents/materials/analysis tools: YW GAC. Wrote the paper: XFL RCB.Trastuzumab, a humanized monoclonal antibody directed against the extracellular domain of the HER2 oncoprotein, can effectively target HER2-positive breast cancer through several mechanisms. Although the effects of trastuzumab on cancer cell proliferation, angiogenesis and apoptosis have been investigated in depth, the effect of trastuzumab on microRNA (miRNA) has not been extensively studied. We have performed miRNA microarray profiling before and after trastuzumab treatment in SKBr3 and BT474 human breast cancer cells that overexpress HER2. We found that trastuzumab treatment of SKBr3 cells significantly decreased five miRNAs and increased three others, whereas treatment of BT474 cells significantly decreased two miRNAs and increased nine. The only change in miRNA expression observed in both cell lines following trastuzumab treatment was upregulation of miRNA-194 (miR-194) that was further validated in vitro and in vivo. Forced expression of miR-194 in breast cancer cells that overexpress HER2 produced no effect on apoptosis, modest inhibition of proliferation, significant inhibition of cell migration/invasion in vitro and significant inhibition of xenograft growth in vivo. Conversely, knockdown of miR-194 promoted cell migration. Increased miR-194 expression markedly reduced levels of the cytoskeletal protein talin2 and specifically inhibited luciferase reporter activity of a talin2 wild-type 39-untranslated region, but not that of a mutant reporter, indicating that talin2 is a direct downstream target of miR-194. Trastuzumab treatment inhibited breast cancer cell migration and reduced talin2 expression in vitro and in vivo. Knockdown of talin2 inhibited cell migration/invasion. Knockdown of trastuzumab-induced miR-194 expression with a miR-194 inhibitor compromised trastuzumab-inhibited cell migration in HER2-overexpressing breast cancer cells. Consequently, trastuzumab treatment upregulates miR-194 expression and may exert its cell migration-inhibitory effect through miR-194-mediated downregulation of cytoskeleton protein talin2 in HER2-overexpressing human breast cancer cells.This work was supported by the Anne and Henry Zarrow Foundation, kind gifts from Stuart and Gaye Lynn Zarrow and from Mrs. Delores Wilkenfeld, the Laura and John Arnold Foundation, the RGK Foundation, and the MD Anderson NCI CCSG P30 CA16672. G.A.C. is supported as a Fellow at the University of Texas MD Anderson Research Trust, as a University of Texas System Regents Research Scholar and by the CLL Global Research Foundation

RE: pedagogy – after neutrality

Within the UK and in many parts of the world, official accounts of what it is to make sense of religion are framed within a rhetorics of neutrality in which such study is premised upon the possibility of dispassionate engagement and analysis. This paper, which is largely theoretical in scope, explores both the affordances and the costs of such an approach which has become ‘black boxed’ on account of the work that it achieves. A series of new orientations within the academy that are broadly associated with post-structuralist philosophies, feminist and post-colonial studies, together with insights from Science and Technology Studies, question the plausibility of these claims for neutrality whilst in turn raising a series of new questions and priorities. It therefore becomes necessary to re-think and re-frame what it is to make sense of religious and cultural difference after neutrality. The gathering and co-ordination of new planes of sense-making that are responsive to an emergent series of epistemological, ontological, and ethical orientations are considered. Some of the distinctive pedagogical implications of such an approach that engages material practice, difference and uncertainty are then entertained

Regulation of microRNA biogenesis and turnover by animals and their viruses

Item does not contain fulltextMicroRNAs (miRNAs) are a ubiquitous component of gene regulatory networks that modulate the precise amounts of proteins expressed in a cell. Despite their small size, miRNA genes contain various recognition elements that enable specificity in when, where and to what extent they are expressed. The importance of precise control of miRNA expression is underscored by functional studies in model organisms and by the association between miRNA mis-expression and disease. In the last decade, identification of the pathways by which miRNAs are produced, matured and turned-over has revealed many aspects of their biogenesis that are subject to regulation. Studies in viral systems have revealed a range of mechanisms by which viruses target these pathways through viral proteins or non-coding RNAs in order to regulate cellular gene expression. In parallel, a field of study has evolved around the activation and suppression of antiviral RNA interference (RNAi) by viruses. Virus encoded suppressors of RNAi can impact miRNA biogenesis in cases where miRNA and small interfering RNA pathways converge. Here we review the literature on the mechanisms by which miRNA biogenesis and turnover are regulated in animals and the diverse strategies that viruses use to subvert or inhibit these processes