Rare Variant Analysis of Human and Rodent Obesity Genes in Individuals with Severe Childhood Obesity

Obesity is a genetically heterogeneous disorder. Using targeted and whole-exome sequencing, we studied 32 human and 87 rodent obesity genes in 2,548 severely obese children and 1,117 controls. We identified 52 variants contributing to obesity in 2% of cases including multiple novel variants in GNAS, which were sometimes found with accelerated growth rather than short stature as described previously. Nominally significant associations were found for rare functional variants in BBS1, BBS9, GNAS, MKKS, CLOCK and ANGPTL6. The p.S284X variant in ANGPTL6 drives the association signal (rs201622589, MAF∼0.1%, odds ratio = 10.13, p-value = 0.042) and results in complete loss of secretion in cells. Further analysis including additional case-control studies and population controls (N = 260,642) did not support association of this variant with obesity (odds ratio = 2.34, p-value = 2.59 × 10 -3 ), highlighting the challenges of testing rare variant associations and the need for very large sample sizes. Further validation in cohorts with severe obesity and engineering the variants in model organisms will be needed to explore whether human variants in ANGPTL6 and other genes that lead to obesity when deleted in mice, do contribute to obesity. Such studies may yield druggable targets for weight loss therapies

Rare Variant Analysis of Human and Rodent Obesity Genes in Individuals with Severe Childhood Obesity

Obesity is a genetically heterogeneous disorder. Using targeted and whole-exome sequencing, we studied 32 human and 87 rodent obesity genes in 2,548 severely obese children and 1,117 controls. We identified 52 variants contributing to obesity in 2% of cases including multiple novel variants in GNAS, which were sometimes found with accelerated growth rather than short stature as described previously. Nominally significant associations were found for rare functional variants in BBS1, BBS9, GNAS, MKKS, CLOCK and ANGPTL6. The p.S284X variant in ANGPTL6 drives the association signal (rs201622589, MAF~0.1%, odds ratio = 10.13, p-value = 0.042) and results in complete loss of secretion in cells. Further analysis including additional case-control studies and population controls (N = 260,642) did not support association of this variant with obesity (odds ratio = 2.34, p-value = 2.59 × 10(-3)), highlighting the challenges of testing rare variant associations and the need for very large sample sizes. Further validation in cohorts with severe obesity and engineering the variants in model organisms will be needed to explore whether human variants in ANGPTL6 and other genes that lead to obesity when deleted in mice, do contribute to obesity. Such studies may yield druggable targets for weight loss therapies

Investigation on the Dependencies Between HRV, Physical Training, and Focus of Attention in Virtual Environment

In this study we investigate the dependencies between human focus of attention and heart rate variability while performing concentration task in virtual environment, using attention improvement device, and taking into account daily physical activity of the participants. For this purpose, a virtual testing environment – football arena – was developed. A volunteer had to “kick” a ball to the gate. He scores a goal if he has reached high attention focus level. The experiments were performed using NeuroSky device for attention level recording, Polar V800 device for heart rate (RR intervals) recording and ElfEmmit device as a better focus stimulator. At the same time, some virtual environment parameters and human action in it were recorded as well. We have used RMSSD parameter as heart rate variability measure. The results showed some unexpected tendencies. RMSSD parameter was in normal range and outside it for both: volunteers who have regular trainings and who do not have any training at all. A tendency was noticed that ElfEmmit device might increase focus of attention during virtual reality gameBaltijos pažangių technologijų institutasLietuvos sporto universitetasSistemų analizės katedraTaikomosios informatikos katedraVytauto Didžiojo universiteta

The Influence of Methyl Jasmonate and Salicylic Acid on Secondary Metabolite Production in Rehmannia Glutinosa Libosch. Hairy Root Culture

Rehmannia glutinosa hairy roots were used to evaluate the effect of methyl jasmonate (MeJa) and salicylic acid (SA) on increase of root biomass and production of iridoids (catalpol, harpagide) and phenylethanoids (verbascoside and isoverbascoside). The elicitors were added to 23-day-old culture separately at concentrations between 50 and 200 μM or in combinations at concentrations of 50 and 100 μM. Roots were harvested 72 h and 120 h after elicitation. The type of elicitor, its concentration and exposure time were found to strongly affect the content of each analyzed compound. A 72-hour treatment with 200 μM MeJa was the most effective in increase of verbascoside content (60.07 mg·DWˉ¹ equivalent to 845.45 mg·Lˉ¹) and isoverbascoside (1.77 mg·DWˉ¹ equivalent to 24.94 mg·Lˉ¹): these respective amounts were roughly 10- and 6.4-fold higher than the control values (unelicited roots). Exposure to 150 μM MeJa provided optimal harpagide content after 72 hours (0.136 mg·DWˉ¹; 7.5-fold increase compared to the control), and catalpol content after 120 hours (up to 2.145 mg·DWˉ¹). The combination of MeJa and SA also resulted in higher levels of secondary metabolites compared to the control culture, although these levels were lower than those observed for MeJa alone at the optimal concentration and exposure time. SA alone was less efficient in enhancing metabolite production than MeJa