Hypoxia induces a transcriptional early primitive streak signature in pluripotent cells enhancing spontaneous elongation and lineage representation in gastruloids

The cellular microenvironment, together with intrinsic regulators, shapes stem cell identity and differentiation capacity. Mammalian early embryos are exposed to hypoxia in vivo and appear to benefit from hypoxic culture in vitro. Yet, how hypoxia influences stem cell transcriptional networks and lineage choices remain poorly understood. Here, we investigated the molecular effects of acute and prolonged hypoxia on embryonic and extra-embryonic stem cells as well as the functional impact on differentiation potential. We find a temporal and cell type-specific transcriptional response including an early primitive streak signature in hypoxic embryonic stem cells mediated by HIF1α. Using a 3D gastruloid differentiation model, we show that hypoxia-induced T expression enables symmetry breaking and axial elongation in the absence of exogenous WNT activation. When combined with exogenous WNT activation, hypoxia enhances lineage representation in gastruloids, as demonstrated by highly enriched signatures of gut endoderm, notochord, neuromesodermal progenitors and somites. Our findings directly link the microenvironment to stem cell function and provide a rationale supportive of applying physiological conditions in models of embryo development

The impact of transposable element activity on therapeutically relevant human stem cells

Human stem cells harbor significant potential for basic and clinical translational research as well as regenerative medicine. Currently ~ 3000 adult and ~ 30 pluripotent stem cell-based, interventional clinical trials are ongoing worldwide, and numbers are increasing continuously. Although stem cells are promising cell sources to treat a wide range of human diseases, there are also concerns regarding potential risks associated with their clinical use, including genomic instability and tumorigenesis concerns. Thus, a deeper understanding of the factors and molecular mechanisms contributing to stem cell genome stability are a prerequisite to harnessing their therapeutic potential for degenerative diseases. Chemical and physical factors are known to influence the stability of stem cell genomes, together with random mutations and Copy Number Variants (CNVs) that accumulated in cultured human stem cells. Here we review the activity of endogenous transposable elements (TEs) in human multipotent and pluripotent stem cells, and the consequences of their mobility for genomic integrity and host gene expression. We describe transcriptional and post-transcriptional mechanisms antagonizing the spread of TEs in the human genome, and highlight those that are more prevalent in multipotent and pluripotent stem cells. Notably, TEs do not only represent a source of mutations/CNVs in genomes, but are also often harnessed as tools to engineer the stem cell genome; thus, we also describe and discuss the most widely applied transposon-based tools and highlight the most relevant areas of their biomedical applications in stem cells. Taken together, this review will contribute to the assessment of the risk that endogenous TE activity and the application of genetically engineered TEs constitute for the biosafety of stem cells to be used for substitutive and regenerative cell therapiesS.R.H. and P.T.R. are funded by the Government of Spain (MINECO, RYC-2016- 21395 and SAF2015–71589-P [S.R.H.]; PEJ-2014-A-31985 and SAF2015–71589- P [P.T.R.]). GGS is supported by a grant from the Ministry of Health of the Federal Republic of Germany (FKZ2518FSB403)

Diabetic ketoacidosis

Diabetic ketoacidosis (DKA) is the most common acute hyperglycaemic emergency in people with diabetes mellitus. A diagnosis of DKA is confirmed when all of the three criteria are present — ‘D’, either elevated blood glucose levels or a family history of diabetes mellitus; ‘K’, the presence of high urinary or blood ketoacids; and ‘A’, a high anion gap metabolic acidosis. Early diagnosis and management are paramount to improve patient outcomes. The mainstays of treatment include restoration of circulating volume, insulin therapy, electrolyte replacement and treatment of any underlying precipitating event. Without optimal treatment, DKA remains a condition with appreciable, although largely preventable, morbidity and mortality. In this Primer, we discuss the epidemiology, pathogenesis, risk factors and diagnosis of DKA and provide practical recommendations for the management of DKA in adults and children

BOUN-NKU in mediaeval 2017 emotional impact of movies task

2017 Multimedia Benchmark Workshop, MediaEval 2017 -- 13 September 2017 through 15 September 2017 -- -- 131670In this paper, we present our approach for the Emotional Impact of Movies task of Mediaeval 2017 Challenge, involving multimodal fusion for predicting arousal and valence for movie clips. In our system, we have two pipelines. In the first one, we extracted audio/visual features, and used a combination of PCA, Fisher vector encoding, feature selection, and extreme learning machine classifiers. In the second one, we focused on the classifiers, rather than on feature selection. © 2017 Author/owner(s).BAP 16A01P4; Bilim AkademisiThis work is supported by Bogazici University Project BAP 16A01P4 and by the BAGEP Award of the Science Academy

Influence of prenatal risks of pregnant women on mental symptoms [Gebelerin prenatal risklerinin ruhsal belirtilere etkisi]

Objective: In this study, it was aimed to investigate the influence of prenatal risk indicator scores of pregnant women on mental symptoms. Methods: This cross-sectional study was carried out with 142 pregnant women who were admitted to obstetrics clinic of a state hospital in İzmir province and who stated that they were not diag-nosed with any psychiatric diseases. A form questioning socio-demographic and obstetric characteristics of preg-nant women, Prenatal Risk Indicator aiming at determining risk of pregnant women and Brief Symptom Inventory (BSI) aiming at screening mental symptoms were used for data collection. Results: The most common risk fac-tors according to risk indicator were detected as experiencing urinary tract infection during the current pregnancy, being nulliparous, receiving late or insufficient prenatal care and inadequate weight gain and almost half of the pregnant women were found to be high risk. In addition, it was found that BSI scores were low, paranoid thought scores were high in high risk women and there was a positive correlation and phobic anxiety scores of all preg-nant women were equal. Conclusion: High risk pregnant women were detected to have paranoid thoughts and all pregnant women found to experience phobic anxiety equally

Devonian shallow-water sequences from the North Gondwana coastal margin (Central and Eastern Taurides, Turkey): Sedimentology, facies and global events

Turkey is an integral part of the Alpine-Himalayan orogenic belt with a number of tectonostratigraphic units striking in an E-W direction These belts consist of terranes of different tectonic settings. ranging from oceanic basins to active and passive continental margins The age of incorporated units of continental margin ongin ranges from the Cambrian to the Cenozoic, and includes unmetamorphosed to low-grade Devonian rocks in the Pontides, Taurides and oil the Arabian Plate. This paper describes the detailed sedimentology, facies and biostratigraphy of three 900 to 1200 m thick Devonian successions in the Central and Eastern Taurides (Eceli, Halevikdere and Kocadere) During the Devonian, the Central and Eastern Taundes were situated at the northern margin of Gondwana The sediments described were deposited on this margin in coastal to shelf environments Despite similar large-scale trends, regional differences in the sedimentary sequences can be distinguished, especially for the lower part of the Devonian For the first time, sufficient biostratigraphical data have been recovered to allow the successions to be subdivided at a stage scale, permitting their approximate correlation and comparison with the regional lithostratigraphy. The temporal development of sedimentary processes, facies changes, and hinterland signatures recorded in the individual sections have been reconstructed, allowing their correspondence to global events to be recognized and discussed for the first time. The palaeobiogeographic distribution of various organisms within these succession Suggests a comparatively narrow sea ('Rheic Ocean') between Laurasia and Gondwana/Peri-Gondwana during the Devonian. (C) 2009 International Association for Gondwana Research Published by Elsevier B V All rights reserved