Production of Embryonic and Fetal-Like Red Blood Cells from Human Induced Pluripotent Stem Cells

We have previously shown that human embryonic stem cells can be differentiated into embryonic and fetal type of red blood cells that sequentially express three types of hemoglobins recapitulating early human erythropoiesis. We report here that we have produced iPS from three somatic cell types: adult skin fibroblasts as well as embryonic and fetal mesenchymal stem cells. We show that regardless of the age of the donor cells, the iPS produced are fully reprogrammed into a pluripotent state that is undistinguishable from that of hESCs by low and high-throughput expression and detailed analysis of globin expression patterns by HPLC. This suggests that reprogramming with the four original Yamanaka pluripotency factors leads to complete erasure of all functionally important epigenetic marks associated with erythroid differentiation regardless of the age or the tissue type of the donor cells, at least as detected in these assays. The ability to produce large number of erythroid cells with embryonic and fetal-like characteristics is likely to have many translational applications

Income Attainment among Victims of Violence: Results From a Preliminary Study

Violent victimisation may have many short-term psychological and physical outcomes. Occasionally, the negative aftermath of violence persists over time or induces other and more far-reaching consequences. Income attainment after victimisation is one of these outcomes. To date, previous studies have focussed on the income effects of violent victimisation during childhood and adolescence. Violence exposure during the early stages of the life course may frustrate processes of educational and occupational attainment and consequentially result in lower income levels. However, in addition or alternatively, many other and age-independent pathways between violent victimisation and income may be suggested. Prior studies appear to have paid little attention to this issue. Therefore, the purpose of the current study was to explore whether violent victimisation is associated with income levels several years after victimisation, irrespective of the age at which victimisation occurs. Victims of violence were recruited through the Dutch Victim Compensation Fund. To preliminary estimate the effect of violent victimisation on income, a comparable control group of non-victims was composed. The study sample contained 206 victims and 173 non-victims. Both bivariate correlational and multivariate statistical techniques suggested that violent victimisation is a significant predictor of income. Implications of the presented results were discussed with regard to future research and policy practice

2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation: executive summary.

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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)

Cross Adaptation - Heat and Cold Adaptation to Improve Physiological and Cellular Responses to Hypoxia

To prepare for extremes of heat, cold or low partial pressures of O2, humans can undertake a period of acclimation or acclimatization to induce environment specific adaptations e.g. heat acclimation (HA), cold acclimation (CA), or altitude training. Whilst these strategies are effective, they are not always feasible, due to logistical impracticalities. Cross adaptation is a term used to describe the phenomenon whereby alternative environmental interventions e.g. HA, or CA, may be a beneficial alternative to altitude interventions, providing physiological stress and inducing adaptations observable at altitude. HA can attenuate physiological strain at rest and during moderate intensity exercise at altitude via adaptations allied to improved oxygen delivery to metabolically active tissue, likely following increases in plasma volume and reductions in body temperature. CA appears to improve physiological responses to altitude by attenuating the autonomic response to altitude. While no cross acclimation-derived exercise performance/capacity data have been measured following CA, post-HA improvements in performance underpinned by aerobic metabolism, and therefore dependent on oxygen delivery at altitude, are likely. At a cellular level, heat shock protein responses to altitude are attenuated by prior HA suggesting that an attenuation of the cellular stress response and therefore a reduced disruption to homeostasis at altitude has occurred. This process is known as cross tolerance. The effects of CA on markers of cross tolerance is an area requiring further investigation. Because much of the evidence relating to cross adaptation to altitude has examined the benefits at moderate to high altitudes, future research examining responses at lower altitudes should be conducted given that these environments are more frequently visited by athletes and workers. Mechanistic work to identify the specific physiological and cellular pathways responsible for cross adaptation between heat and altitude, and between cold and altitude, is warranted, as is exploration of benefits across different populations and physical activity profiles

Discrete Systolic Potentials During Ventricular Tachycardia in Patients with Prior Myocardial Infarction

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/71829/1/j.1540-8167.1999.tb00684.x.pd