When chronically activated, the PI3K pathway can drive malignant transformation. Here, we discuss the insulin-PI3K signalling cascade and emphasize its roles in normal cells (including coordinating cell metabolism and growth), highlighting the features of this network that make it ideal for co-option by cancer cells. Furthermore, we discuss how this signalling network can affect therapeutic responses and how novel metabolic-based strategies might enhance treatment efficacy for cancer.An amendment to this paper has been published and can be accessed via a link at the top of the paper.In the field of human history, ancient DNA has provided answers to long-standing debates about major movements of people and has begun to inform on other important facets of the human experience. The field is now moving from mostly large-scale supraregional studies to a more local perspective, shedding light on socioeconomic processes, inheritance rules, marriage practices and technological diffusion. In this Review, we summarize recent studies showcasing these types of insights, focusing on methods used to infer sociocultural aspects of human behaviour. This approach often involves working across disciplines - such as anthropology, archaeology, linguistics and genetics - that have until recently evolved in separation. Multidisciplinary dialogue is important for an integrated reconstruction of human history, which can yield extraordinary insights about past societies, reproductive behaviours and even lifestyle habits that would not be possible to obtain otherwise.OBJECTIVES Vitamin D deficiency was associated with obesity. However, the causal relationship remains controversial. https://www.selleckchem.com/products/r-hts-3.html We hypothesized that there would be family-based associations in both vitamin D deficient families and obese families for the SNPs associated with vitamin D deficiency, if vitamin D deficiency was a causal factor of obesity. We aimed to investigate the family-based association of SNPs in CYP27B1 with both vitamin D deficiency and obesity. METHODS Four hundred and nineteen pedigrees containing 1505 rural individuals aged from 18 to 79 years in Henan Province of China were included in this study. Family-based associations of rs10877012 and rs4646536 in CYP27B1 with vitamin D deficiency and obesity were investigated. Serum 25(OH)D3 concentration  0.05). In addition, there is linkage disequilibrium between rs10877012 and rs4646536 (D' = 1.0, r2 = 0.992). CONCLUSION Vitamin D deficiency may be a causal factor of obesity. Maintaining sufficient vitamin D is beneficial to obesity prevention.BACKGROUND The prevalence of iron deficiency in the Lebanese pediatric population is unknown. The aim of this study is to estimate this prevalence in Lebanese schoolchildren and to assess the relation between iron status and related factors. SUBJECTS/METHODS A total of 903 children aged 8-18 years (466 boys and 437 girls) were included in the study. Recruitment was done from ten schools with different SES levels and located in the Great Beirut and Mount Lebanon areas. Serum ferritin was measured in all participants and testosterone was measured only in boys using Immulite chemiluminescent assays. RESULTS For the entire sample, the median serum ferritin concentration was 30.0 [19.8-44.8] ng/mL and the prevalence of iron deficiency (ferritin  less then  15 ng/mL) was 14.2%. Iron deficiency was higher in girls compared with boys (respectively, 20.8% and 7.9%). This prevalence varied with the SES (respectively, 11.6%, 11.9%, and 16.8% in high, middle, and low SES, p = 0.09). Iron deficiency increased with age (9.5%, 15.7%, and 17.5%, respectively, for the age groups 8-11, 12-14, and 15-18, p = 0.014) and did not differ between normal, overweight, and obese groups (p = 0.07). In boys, a significant positive correlation was observed between ferritin and total testosterone (rho = 0.150, p = 0.001). CONCLUSION The prevalence of iron deficiency is relatively low in Lebanon. Younger boys, menstruating girls, and children from low SES are more prone to iron deficiency, while BMI has no impact.Dairy pastoralism is integral to contemporary and past lifeways on the eastern Eurasian steppe, facilitating survival in agriculturally challenging environments. While previous research has indicated that ruminant dairy pastoralism was practiced in the region by circa 1300 BC, the origin, extent and diversity of this custom remain poorly understood. Here, we analyse ancient proteins from human dental calculus recovered from geographically diverse locations across Mongolia and spanning 5,000 years. We present the earliest evidence for dairy consumption on the eastern Eurasian steppe by circa 3000 BC and the later emergence of horse milking at circa 1200 BC, concurrent with the first evidence for horse riding. We argue that ruminant dairying contributed to the demographic success of Bronze Age Mongolian populations and that the origins of traditional horse dairy products in eastern Eurasia are closely tied to the regional emergence of mounted herding societies during the late second millennium BC.Metazoans must develop from zygotes to feeding organisms. In doing so, developing offspring consume up to 60% of the energy provided by their parent. The cost of development depends on two rates metabolic rate, which determines the rate that energy is used; and developmental rate, which determines the length of the developmental period. Both development and metabolism are highly temperature-dependent such that developmental costs should be sensitive to the local thermal environment. Here, we develop, parameterize and test developmental cost theory, a physiologically explicit theory that reveals that ectotherms have narrow thermal windows in which developmental costs are minimized (Topt). Our developmental cost theory-derived estimates of Topt predict the natural thermal environment of 71 species across seven phyla remarkably well (R2 ~0.83). Developmental cost theory predicts that costs of development are much more sensitive to small changes in temperature than classic measures such as survival. Warming-driven changes to developmental costs are predicted to strongly affect population replenishment and developmental cost theory provides a mechanistic foundation for determining which species are most at risk.