CENP-C unwraps the human CENP-A nucleosome through the H2A C-terminal tail

Centromeres are defined epigenetically by nucleosomes containing the histone H3 variant CENP-A, upon which the constitutive centromere-associated network of proteins (CCAN) is built. CENP-C is considered to be a central organizer of the CCAN. We provide new molecular insights into the structure of human CENP-A nucleosomes, in isolation and in complex with the CENP-C central region (CENP-C-CR), the main CENP-A binding module of human CENP-C. We establish that the short alpha N helix of CENP-A promotes DNA flexibility at the nucleosome ends, independently of the sequence it wraps. Furthermore, we show that, in vitro, two regions of human CENP-C (CENP-C-CR and CENP-C-motif) both bind exclusively to the CENP-A nucleosome. We find CENP-C-CR to bind with high affinity due to an extended hydrophobic area made up of CENP-A(V)(532) and CENP-A(V)(533). Importantly, we identify two key conformational changes within the CENP-A nucleosome upon CENP-C binding. First, the loose DNA wrapping of CENP-A nucleosomes is further exacerbated, through destabilization of the H2A C-terminal tail. Second, CENP-C-CR rigidifies the N-terminal tail of H4 in the conformation favoring H4(K20) monomethylation, essential for a functional centromere

Structural characterization of the closed conformation of mouse guanylate kinase

Guanylate kinase (GMPK) is a nucleoside monophosphate kinase that catalyzes the reversible phosphoryl transfer from ATP to GMP to yield ADP and GDP. In addition to phosphorylating GMP, antiviral prodrugs such as acyclovir, ganciclovir, and carbovir and anticancer prodrugs such as the thiopurines are dependent on GMPK for their activation. Hence, structural information on mammalian GMPK could play a role in the design of improved antiviral and antineoplastic agents. Here we present the structure of the mouse enzyme in an abortive complex with the nucleotides ADP and GMP, refined at 2.1 Angstrom resolution with a final crystallographic R factor of 0.19 (R-free = 0.23). Guanylate kinase is a member of the nucleoside monophosphate (NMP) kinase family, a family of enzymes that despite having a low primary structure identity share a similar fold, which consists of three structurally distinct regions termed the CORE, LID, and NMP-binding regions. Previous studies on the yeast enzyme have shown that these parts move as rigid bodies upon substrate binding. It has been proposed that consecutive binding of substrates leads to "closing" of the active site bringing the NMP-binding and LID regions closer to each other and to the CORE region. Our structure, which is the first of any guanylate kinase with both substrates bound, supports this hypothesis. It also reveals the binding site of ATP and implicates arginines 44, 137, and 148 (in addition to the invariant P-loop lysine) as candidates for catalyzing the chemical step of the phosphoryl transfer

Analysis of the relationship between tobacco smoking and physical activity in adolescence: a gender specific study

Background and Objective: Although smoking and the physical activity level (PAL) are important determinants of health status in adolescence, there is a lack of information on the relationship between smoking and PAL in early adolescence. The objective of this study was to evaluate the gender-specific relationship between smoking and PAL in 14-to-16-year-old adolescents. Materials and Methods: The sample included 650 adolescents (337 girls, 14.7 ± 0.5 years at first testing wave) from Bosnia and Herzegovina. During the first testing wave, participants were tested using struc-tured questionnaires. Second testing was commenced after approximately 20 months (16.4 ± 0.6 years). The variables were age, gender, socioeconomic status, living environment, cigarette smoking (predictors), and PAL (criterion). Predictors were measured at the first wave, and criterion at the first-wave and second-wave. Results: For girls, smoking was negatively correlated to PAL at the first-wave (OR: 0.75, 95% CI: 0.55–0.95) and at the second-wave (OR: 0.73, 95% CI: 0.71–0.96). No significant association between smoking and PAL was found for boys. Results suggest that adolescent boys and girls do not follow the equal trajectories when it comes to relationships between smoking and PAL. Conclusions: In developing promotional public health actions related to a decrease of smoking and increase of PAL, a gender-specific approach is highly recommended. Further studies analyzing the cause–effect relationship between consumption of other types of psychoactive substances and PAL in this age group are warranted

Levels and changes of physical activity in adolescents during the COVID-19 Pandemic: Contextualizing urban vs. Rural living environment

The COVID-19 pandemic and the social distancing implemented shortly after influence physical activity levels (PALs). The purpose of this investigation was to evaluate the changes in PAL and factors associated with PALs among Croatian adolescents while considering the impact of community (urban vs. rural living environment). The sample included 823 adolescents (mean age: 16.5 ± 2.1 years) who were tested on baseline (from October 2019 to March 2020; before COVID-19 pandemic in Croatia) and follow-up (in April 2020; during the COVID-19 pandemic and imposed rules of social distancing). Baseline testing included anthropometrics, physical fitness status, and evaluation of PALs, while follow-up included only PALs (evaluated by a standardized questionnaire through an internet application). The results showed a significant influence of the living environment on the decrease of PAL, with a larger decrease in urban adolescents. Logistic regression showed a higher likelihood for normal PALs at baseline in adolescents who had better fitness status, with no strong confounding effect of the urban/rural environment. The fitness status of urban adolescents predicted their PALs at follow-up. The differences between urban and rural adolescents with regard to the established changes in PALs and relationships between the predictors and PALs are explained by the characteristics of the living communities (lack of organized sports in rural areas), and the level of social distancing in the studied period and region/country

Structural and electrical properties of Ti doped α-Fe2O3

In this work we have analyzed the effects of Ti doping on structural and electrical properties of α-Fe2O3. When the amount of added Ti (5 wt.%TiO2) was within the solubility degree and XRD, SEM and EDS analysis revealed a homogenous hematite structure, with lattice parameters a= 5.03719(3) Å, c=13.7484(1) Å slightly increased due to incorporation of Ti into the rhombohedral hematite lattice. Higher amounts of Ti (10 wt.%TiO2) resulted in the formation of pseudobrookite, besides hematite, confirmed by SEM and EDS analysis. Studies of electric properties in the temperature range 25-225oC at different frequencies (100 - 1Mz) showed that Ti doping improved electrical conductivity. Impedance analysis was performed using an equivalent circuit, showing one relaxation process and suggesting dominant grain boundary contribution. [Projekat Ministarstva nauke Republike Srbije, br. III45014 i br. III43008

Parental and familial factors influencing physical activity levels in early adolescence: a prospective study

Parental/familial factors are important determinants of the physical activity level (PAL) in children and adolescents, but studies rarely prospectively evaluate their relationships. This study aimed to evaluate the changes in physical activity levels among adolescents from Bosnia and Herzegovina over a two-year period and to determine parental/familial predictors of PAL in early adolescence. A total of 651 participants (50.3% females) were tested at baseline (beginning of high school education; 14 years old on average) and at follow-up (approximately 20 months later). The predictors included sociodemographic characteristics (age, gender) and parental/familial factors (socioeconomic status of the family, maternal and paternal education, conflict with parents, parental absence from home, parental questioning, and parental monitoring). Physical activity levels were evidenced by the Physical Activity Questionnaire for Adolescents (PAQ-A; criterion). Boys were more active than girls, both at baseline (t-test = 3.09, p < 0.001) and at follow-up (t-test = 3.4, p < 0.001). Physical activity level decreased over the observed two-year period (t-test = 16.89, p < 0.001), especially in boys, which is probably a consequence of drop-out from the sport in this period. Logistic regression evidenced parental education as a positive predictor of physical activity level at baseline (OR [95% CI]; 1.38 [1.15–170], 1.35 [1.10–1.65]), and at follow-up (1.35 [1.11–1.69], 1.29 [1.09–1.59], for maternal and paternal education, respectively). Parents with a higher level of education are probably more informed about the importance of physical activity on health status, and thus transfer this information to their children as well. The age from 14 to 16 years is likely a critical period for maintaining physical activity levels in boys, while further studies of a younger age are necessary to evaluate the dynamics of changes in physical activity levels for girls. For maintaining physical activity levels in adolescence, special attention should be paid to children whose parents are less educated, and to inform them of the benefits of an appropriate physical activity level and its necessity for maintaining proper health and growth

Prospective analysis of the influence of sport and educational factors on the prevalence and initiation of smoking in older adolescents from Croatia

The prevalence of smoking among Croatian adolescents is alarmingly high, but no previous study has prospectively examined the sport- and academic-factors associated with smoking and smoking initiation. This study aimed to prospectively examine the associations between scholastic (educational) achievement and sport factors and smoking in 16- to 18-year-old adolescents. This twoyear prospective cohort study included 644 adolescents who were 16 years of age at baseline (46% females). Baseline testing was implemented at the beginning of the 3rd year of high school (September 2014) when participants were 16 years old. Follow-up testing was completed at the end of the fourth year of high school, which occurred 20 months later. The evaluated predictor variables were educational-achievement- and sport-related-factors. The outcome variables were (i) smoking at baseline; (ii) smoking at follow-up; and (iii) smoking initiation over the course of the study. We assessed the associations between predictors and outcomes using logistic regression models adjusted for age, gender, socioeconomic status, and conflict with parents. The educational variables were consistently associated with smoking, with lower grade-point-average (Baseline: odd ratio (OR): 2.01, 95% confidence interval (CI): 1.61\u20132.55; Follow-up: 1.59, 1.31\u20131.94), more frequent absence from school (Baseline: OR: 1.40, 95% CI: 1.19\u20131.69; Follow-up: 1.30, 1.08\u20131.58), and lower behavioral grades (Baseline: OR: 1.80, 95% CI: 1.10\u20132.89; Follow-up: 1.57, 1.03\u20132.41) in children who smoke. Adolescents who reported quitting sports were at greater odds of being smokers (Baseline: 2.07, 1.31\u20133.32; Followup: 1.66, 1.09\u20132.56). Sport competitive achievement at baseline was protective against smoking initiation during following two-year period (0.45, 0.21\u20130.91). While the influence of the educational variables on smoking initiation has been found to be established earlier; sport achievement was identified as a significant protective factor against initiating smoking in older adolescents. Results should be used in development of an anti-smoking preventive campaign in older adolescents