Deciphering the stem cell machinery as a basis for understanding the molecular mechanism underlying reprogramming

Stem cells provide fascinating prospects for biomedical applications by combining the ability to renew themselves and to differentiate into specialized cell types. Since the first isolation of embryonic stem (ES) cells about 30 years ago, there has been a series of groundbreaking discoveries that have the potential to revolutionize modern life science. For a long time, embryos or germ cell-derived cells were thought to be the only source of pluripotency—a dogma that has been challenged during the last decade. Several findings revealed that cell differentiation from (stem) cells to mature cells is not in fact an irreversible process. The molecular mechanism underlying cellular reprogramming is poorly understood thus far. Identifying how pluripotency maintenance takes place in ES cells can help us to understand how pluripotency induction is regulated. Here, we review recent advances in the field of stem cell regulation focusing on key transcription factors and their functional interplay with non-coding RNAs

Problematic Facebook use and problematic video gaming as mediators of relationship between impulsivity and life satisfaction among female and male gamers

Over the past few decades, many new technologies have emerged, such as portable computers, the internet and smartphones, which have contributed to improving the lives of individuals. While the benefits of these new technologies are overwhelmingly positive, negative consequences are experienced by a minority of individuals. One possible negative aspect of new technologies is their problematic use due to impulsive use which may lead to lower life satisfaction. The present study investigated the mediating role of problematic video gaming (PVG) and problematic Facebook use (PFU) in the relationship between impulsivity dimensions and life satisfaction as well as the relationship between impulsivity dimensions and problematic behaviors. Additionally, the potential impact of gender differences was also examined. The study comprised 673 gamers (391 females) aged 17–38 years (M = 21.25 years, SD = 2.67) selected from 1365 individuals who completed an offline survey. PFU was assessed using the Facebook Intrusion Scale, and PVG was assessed using the nine-item Internet Gaming Disorder Scale–Short-Form (IGDS9-SF). Impulsivity dimensions such as attention, cognitive instability, motor, perseverance, self-control, and cognitive complexity were assessed using the Barratt Impulsiveness Scale (BIS-11), and life satisfaction was assessed using the Satisfaction With Life Scale (SWLS). Depending on the specific impulsivity dimension, findings showed both positive and negative relationships between impulsivity and life satisfaction. Attention and perseverance subtypes of impulsivity were primarily associated with problematic behaviors. Additionally, cognitive complexity was associated with PFU among female gamers, whereas cognitive instability was associated with PVG among male gamers. Additionally, PVG was primarily associated with lower life satisfaction. However, there was no mediation effects between impulsivity dimensions and life satisfaction via PFU or PVG. These findings provide a better understanding of the relationship between problematic behaviors, life satisfaction, and impulsivity among gamers and the differences between male and female gamers

High prevalence of vitamin D deficiency in 2-17 year olds presenting with acute fractures in southern Australia.

AIM: To determine vitamin D deficiency risk and other lifestyle factors in children aged 2-17 years presenting with an acute fracture to Sunshine Hospital. METHODS: A prospective observational study was undertaken using a convenience sample data collected from children aged 2-17 years of age presenting with an acute fracture. Recruitment was undertaken over a 3-month period from February to May 2014. Risk factors for vitamin D deficiency (skin pigmentation, hours spent outdoors, sunscreen use and obesity) were identified. Patients providing consent, had measurements of serum 25-hydroxyvitamin D (25-OHD). Vitamin D deficiency was defined as < 50 nmol/L. RESULTS: Of the 163 patients recruited into this study, 134 (82%) had one or more risk factor(s) for vitamin D deficiency. Of these, 109 (81%) consented to 25-OHD testing, with a median of 53 nmol/l (range 14-110 nmol/l) obtained. A total of 57 (52% at risk, 35% of total participants) were found to be vitamin D deficient. 45 (80%) had mild deficiency (30-50 nmol/l) and 11 (20%) had moderate deficiency (12.5-29 nmol/l). CONCLUSIONS: One third of all participants, and the majority participants who had one or more risk factor(s) for vitamin D deficiency, were vitamin D deficient. Based on our findings we recommend that vitamin D status be assessed in all children with risk factor of vitamin D deficiency living in urban environments at higher latitudes presenting with fractures. The effect of vitamin D status on fracture risk and fracture healing in children and teenagers is yet to be determined, as do the effects of vitamin D supplementation in vitamin D deficient paediatric patients presenting with acute fracture

Shedding Light on Vitamin D Status and Its Complexities during Pregnancy, Infancy and Childhood: An Australian Perspective

Ensuring that the entire Australian population is Vitamin D sufficient is challenging, given the wide range of latitudes spanned by the country, its multicultural population and highly urbanised lifestyle of the majority of its population. Specific issues related to the unique aspects of vitamin D metabolism during pregnancy and infancy further complicate how best to develop a universally safe and effective public health policy to ensure vitamin D adequacy for all. Furthermore, as Australia is considered a "sunny country", it does not yet have a national vitamin D food supplementation policy. Rickets remains very uncommon in Australian infants and children, however it has been recognised for decades that infants of newly arrived immigrants remain particularly at risk. Yet vitamin D deficiency rickets is entirely preventable, with the caveat that when rickets occurs in the absence of preexisting risk factors and/or is poorly responsive to adequate treatment, consideration needs to be given to genetic forms of rickets

Conjunctival ultraviolet autofluorescence as a measure of past sun exposure in children

Background Conjunctival ultraviolet autofluorescence (CUVAF) area detected from UVAF photographs is a recently developed potential marker for past sun exposure but its relationship with sun-related factors have not been fully investigated. Methods The study included 339 ethnically diverse and healthy children aged 5-15 years in Melbourne, Australia. Data were collected by questionnaire and examination at school. CUVAF area was measured using a computer programme and analysed as a continuous and dichotomous outcome (any/none). Results The mean age (SD) of the study population was 9.6 (2.7) years with 45.4% males. 53 children (15.6%) had detectable CUVAF and the youngest age at which a child showed sun damage was 8 years. Compared with silicone skin cast score, there was good inter-grader agreement on grading of a random selection of UVAF photographs, with Cohen's kappa 0.85 [95% confidence interval (CI), 0.65-1.00] for total CUVAF area using both eye photographs. Perfect intra-grader agreement was achieved. Fairer pigmentation including medium/fair skin colour [adjusted odds ratio (AOR), 3.42; 95% CI, 1.02-11.48 versus dark/olive] and blue/grey eye colour (AOR, 4.07; 1.73-9.55 versus brown) were associated with increased odds of CUVAF. Increasing lifetime sunburn number (e.g., AOR, 2.89; 1.14-7.35 and 4.29; 1.04- 17.76 for sunburns 2-4 and ≥ 5 times, respectively, versus no sunburns, trend P=0.004) and freckling by the end of last summer were associated with increased odds of CUVAF. Conclusions and impact CUVAF area can be an a priori objective measure of past sun exposure in paediatric populations for future research.</p

CYP3A4 mutation causes vitamin D-dependent rickets type 3

Genetic forms of vitamin D-dependent rickets (VDDRs) are due to mutations impairing activation of vitamin D or decreasing vitamin D receptor responsiveness. Here we describe two unrelated patients with early-onset rickets, reduced serum levels of the vitamin D metabolites 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D, and deficient responsiveness to parent and activated forms of vitamin D. Neither patient had a mutation in any genes known to cause VDDR; however, using whole exome sequencing analysis, we identified a recurrent de novo missense mutation, c.902T&gt;C (p.I301T), in CYP3A4 in both subjects that alters the conformation of substrate recognition site 4 (SRS-4). In vitro, the mutant CYP3A4 oxidized 1,25-dihydroxyvitamin D with 10-fold greater activity than WT CYP3A4 and 2-fold greater activity than CYP24A1, the principal inactivator of vitamin D metabolites. As CYP3A4 mutations have not previously been linked to rickets, these findings provide insight into vitamin D metabolism and demonstrate that accelerated inactivation of vitamin D metabolites represents a mechanism for vitamin D deficiency

Expression of mRNA of parathyroid hormone-related peptide in fetal bones of the rat

Previous studies have indicated that 19-day-old fetal long bones of the rat contain an adenylyl cyclase-stimulating activity antigenically related to parathyroid hormone-related peptide. To ascertain its origin, Northern blotting and in situ hybridization histochemistry were performed. Results demonstrate that mRNA of parathyroid hormone-related peptide is present in RNA extracted from fetal long bones of the rat and that cells responsible for its production are localized in the periosteum. These cells are not mature osteoblasts because they do not synthesize mRNA of osteocalcin. Thus the present study shows that parathyroid hormone-related peptide could be produced locally, at least in part, in the skeleton of fetal rats.Journal ArticleResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe