DNA N^6-methyladenine demethylase ALKBH1 enhances osteogenic differentiation of human MSCs

ALKBH1 was recently discovered as a demethylase for DNA N6-methyladenine （N6-mA）, a new epigenetic modification, and interacts with the core transcriptional pluripotency network of embryonic stem cells. However, the role of ALKBH1 and DNA N6-mA in regulating osteogenic differentiation is largely unknown. In this study, we demonstrated that the expression of ALKBH1 in human mesenchymal stem cells （MSCs） was upregulated during osteogenic induction. Knockdown of ALKBH1 increased the genomic DNA N6-mA levels and significantly reduced the expression of osteogenic-related genes, alkaline phosphatase activity, and mineralization. ALKBHl-depleted MSCs also exhibited a restricted capacity for bone formation in vivo. By contrast, the ectopic overexpression of ALKBH1 enhanced osteoblastic differentiation. Mechanically, we found that the depletion of ALKBH1 resulted in the accumulation of N6-mA on the promoter region of ATF4, which subsequently silenced ATF4 transcription. In addition, restoring the expression of ATP by adenovirus-mediated transduction successfully rescued osteogenic differentiation. Taken together, our results demonstrate that ALKBH1 is indispensable for the osteogenic differentiation of MSCs and indicate that DNA N6-mA modifications area new mechanism for the epigenetic regulation of stem cell differentiation.

Ketamine enhances structural plasticity in human dopaminergic neurons:possible relevance for treatment-resistant depression

Depression refers to a series of mental health issues characterized by loss of interest and enjoyment in everyday life,low mood and selected emotional,cognitive,physical and behavioral symptoms.Depression is a common disorder,affecting 5–15%of the general population.When diagnosed as major depressive disorder（MDD）,patients are currentlytreated with pharmacological agents such as serotonin or noradren- aline uptake inhibitors （SSRI or SNRI） or tricyclics.

Deepening Reform, Enhancing Human Rights Development——Summary of the Symposium on Human Rights Construction and Reform

At the end of 2013, the Graduate School of the China University of . Political Science and Laworganized a symposium on t-luman Rights Construction and Reform and activities at the university in com-- memoration of the 65th anniversary of the adoption of the Universal Declaration of Human Rights.

Strengthen the Confidence of Human Rights and Enhance the Guarantee of Nomocracy of Human Rights in an All-Round Way

Since the reform and opening up of China,the Communist Party of China has been committed to the continuous development of human rights theory and the protection of human rights through legal construction,in order to promote the development of China’s human rights cause.The principle of"respecting and protecting

Developments and challenges in human performance enhancement technology

As emerging technologies have advanced,some countries have issued reports on human performance enhancement efforts in recent years.Human performance enhancement is a prominent theme in the military field.As a type of potentially disruptive technology,human performance enhancement technology(HPET)is of vital importance in promoting military combat effectiveness,developing national defense science and technology,and transforming military medicine.This paper analyzes the current development status of critical HPETs,examines challenges facing such development,and points out existing problems in the field.Finally,future development directions of HPET are suggested.We hope this review will be of interest to scientists and engineers,who should carefully develop this technology to maximize human potential and focus on our social security.