Background:The molecular mechanisms regulating brain development are unclear. Results: HDAC3 deletion disrupts the organization of certain neuronal cell types and the proportions of some glial cell types in the cortex and cerebellum. Conclusion: HDAC3 regulates brain development, and other HDACs cannot compensate for its function. Significance: Our study identifies a key player in the regulation of brain development.
Adolescence is a period when the intellectual, physical, social, emotional and all the capabilities are very high, but, unfortunately, most of the adolescents are unable to utilize their potential to maximum due to various reasons. They face many emerging issues such as global warming, famines, poverty, suicide, population explosion as well as other issues like alcoholism, drug abuse, sexual abuse, smoking, juvenile delinquency, anti-social acts, etc. that have an adverse effect on them and others too, to a large extent. The cut-throat competition, unemployment, lack of job security, etc. are some of the major concerns for the educated and as a result, they are caught in the mad race. This new challenge requires immediate and effective responses from a socially responsible system of education. ‘Education’ is important, but education to support and live life better is more important. It has been felt that life skills education bridges the gap between basic functioning and capabilities. It strengthens the ability of an individual to meet the needs and demands of the present society and helps in dealing with the above issues in a manner to get desired behavior practical. Imparting life skill training through inculcating life skill education will help youth to overcome such difficulties in life. The present paper focuses on the importance of life skills education and the benefits of imparting life skill education in our curriculum i.e. developing social, emotional & thinking skills in students, as they are the important building blocks for a dynamic citizen, who can cope up with future challenges, and survive well.
As the interest in the seismic design of structures has increased considerably over the past few years, accurate predictions of the dynamic responses of soil and structural systems has become necessary. Such predictions require a knowledge of the dynamic properties of the systems under consideration. This paper is concerned with the uniqueness of the results in the identification of such properties. More specifically, the damping and stiffness distributions, which are of importance in the linear range of response, have been investigated. An N-storied structure or an N-layered soil medium is modeled as a coupled, N-degree-of-freedom, lumped system consisting of masses, springs, and dampers. Then, assuming the mass distribution to be known, the problem of identification consists of determining the stiffness and damping distributions from the knowledge of the base excitation and the resulting response at any one mass level. It is shown that if the response of the mass immediately above the base is known, the stiffness and damping distributions can be uniquely determined. Following this, some nonuniqueness problems have been discussed in relation to the commonly used ideas of system reduction in the study of layered soil media. A numerical example is provided to verify some of these concepts and the nature of nonuniqueness of identification is indicated by showing how two very different (yet physically reasonable) systems could yield identical excitation-response pairs. Errors in the calculation of the dynamic forces, due to erroneous identification have also been illustrated thus making the results of the present study useful from the practical standpoint of the safe design of structures to ground shaking.
This paper describes a single body-mounted sensor that integrates accelerometers, gyroscopes, compasses, barometers, a GPS receiver, and a methodology to process the data for biomechanical studies. The sensor and its data processing system can accurately compute the speed, acceleration, angular velocity, and angular orientation at an output rate of 400 Hz and has the ability to collect large volumes of ecologically-valid data. The system also segments steps and computes metrics for each step. We analyzed the sensitivity of these metrics to changing the start time of the gait cycle. Along with traditional metrics, such as cadence, speed, step length, and vertical oscillation, this system estimates ground contact time and ground reaction forces using machine learning techniques. This equipment is less expensive and cumbersome than the currently used alternatives: Optical tracking systems, in-shoe pressure measurement systems, and force plates. Another advantage, compared to existing methods, is that natural movement is not impeded at the expense of measurement accuracy. The proposed technology could be applied to different sports and activities, including walking, running, motion disorder diagnosis, and geriatric studies. In this paper, we present the results of tests in which the system performed real-time estimation of some parameters of walking and running which are relevant to biomechanical research. Contact time and ground reaction forces computed by the neural network were found to be as accurate as those obtained by an in-shoe pressure measurement system.
The homologous recombination (HR) repair pathway maintains genetic integrity after DNA double-strand break (DSB) damage and is particularly crucial for maintaining fidelity of expressed genes. Histone H4 acetylation on lysine 16 (H4K16ac) is associated with transcription, but how pre-existing H4K16ac directly affects DSB repair is not known. To answer this question, we used CRISPR/Cas9 technology to introduce I-SceI sites, or repair pathway reporter cassettes, at defined locations within gene-rich (high H4K16ac/euchromatin) and gene-poor (low H4K16ac/heterochromatin) regions. The frequency of DSB repair by HR is higher in gene-rich regions. Interestingly, artificially targeting H4K16ac at specific locations using gRNA/dCas9-MOF increases HR frequency in euchromatin. Finally, inhibition/depletion of RNA polymerase II or Cockayne syndrome B protein leads to decreased recruitment of HR factors at DSBs. These results indicate that the pre-existing H4K16ac status at specific locations directly influences the repair of local DNA breaks, favoring HR in part through the transcription machinery.
The endocrine component of the stress response is regulated by glucocorticoids and sex steroids. Testosterone down-regulates hypothalamic-pituitary-adrenal (HPA) axis activity; however, the mechanisms by which it does so are poorly understood. A candidate testosterone target is the oxytocin gene (Oxt), given that it too inhibits HPA activity. Within the paraventricular nucleus of the hypothalamus, oxytocinergic neurons involved in regulating the stress response do not express androgen receptors but do express estrogen receptor-β (ERβ), which binds the dihydrotestosterone metabolite 3β,17β-diol (3β-diol). Testosterone regulation of the HPA axis thus appears to involve the conversion to the ERβ-selective ligand 5α-androstane, 3β-diol. To study mechanisms by which 3β-diol could regulate Oxt expression, we used a hypothalamic neuronal cell line derived from embryonic mice that expresses Oxt constitutively and compared 3β-diol with estradiol (E2) effects. E2 and 3β-diol elicited a phasic response in Oxt mRNA levels. In the presence of either ligand, Oxt mRNA levels were increased for at least 60 min and returned to baseline by 2 h. ERβ occupancy preceded an increase in Oxt mRNA levels in the presence of 3β-diol but not E2. In tandem with ERβ occupancy, 3β-diol increased occupancy of the Oxt promoter by cAMP response element-binding protein and steroid receptor coactivator-1 at 30 min. At the same time, 3β-diol led to the increased acetylation of histone H4 but not H3. Taken together, the data suggest that in the presence of 3β-diol, ERβ associates with cAMP response element-binding protein and steroid receptor coactivator-1 to form a functional complex that drives Oxt gene expression.
Glucocorticoids down-regulate expression of hypothalamic CRH; however, mechanisms by which they do so are not fully understood. The proximal promoter cAMP response element, negative glucocorticoid response element (nGRE), and methylated CpG islands all play a role in crh down-regulation. Dexamethasone (Dex)-repressed crh expression is associated with glucocorticoid receptor (GR) and histone deacetylase 1 (HDAC1) recruitment to the region of the crh promoter. Given that HDAC1 may be present in methylated CpG binding protein 2 (MeCP2) complexes, and that MeCP2 is known to play a role in regulating crh expression, we sought to determine whether or not HDAC1 and/or MeCP2 could interact with the GR. Dex enhanced GR interactions with both proteins. Glucocorticoid regulation of crh has also been associated with CpG methylation; thus we assessed whether GR could interact with a DNA methyltransferase (DnMT). Indeed, the GR interacted with DnMT3b, but not DnMT3a. In addition, Dex-induced occupancy of the crh promoter by HDAC1, MeCP2, and DnMT3b was associated with an increased level of promoter methylation, which appeared to be CpG site specific. Lastly, to extend previous assessment of chromatin modifications in this promoter region, the degree of histone methylation was measured. Dex increased trimethylation of histone 3-lysine 9, a marker of gene suppression; however, levels of di- and trimethylated histone 3-lysine 4, markers of gene activation, were not significantly changed. Taken together, the data suggest that Dex-mediated crh suppression involves formation of a repressor complex consisting of GR, MeCP2, and HDAC1, recruitment of DnMT3b, and associated changes in proximal promoter CpG methylation.
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