Although deficits in working memory ability have been implicated in suboptimal decision making and risk taking among adolescents, its influence on early sexual initiation has so far not been ...examined. Analyzing 2 waves of panel data from a community sample of adolescents (N = 347; Mean agebaseline = 13.4 years), assessed 1 year apart, the present study tested the hypothesis that weak working memory ability predicts early sexual initiation and explored whether this relationship is mediated by sensation seeking and 2 forms of impulsivity, namely acting-without-thinking and temporal discounting. The 2 forms of impulsivity were expected to be positively associated with early sexual initiation, whereas sensation seeking was hypothesized to be unrelated or to have a protective influence, due to its positive association with working memory. Results obtained from structural equation modeling procedures supported these predictions and in addition showed that the effects of 3 prominent risk factors (Black racial identity, low socioeconomic background, and early pubertal maturation) on early sexual initiation were entirely mediated by working memory and impulsivity. The findings are discussed in regard to their implications for preventing early sexual onset among adolescents.
What are the long-term effects of childhood experience on brain development? Research with animals shows that the quality of environmental stimulation and parental nurturance both play important ...roles in shaping lifelong brain structure and function. Human research has so far been limited to the effects of abnormal experience and pathological development. Using a unique longitudinal dataset of in-home measures of childhood experience at ages 4 and 8 and MRI acquired in late adolescence, we were able to relate normal variation in childhood experience to later life cortical thickness. Environmental stimulation at age 4 predicted cortical thickness in a set of automatically derived regions in temporal and prefrontal cortex. In contrast, age 8 experience was not predictive. Parental nurturance was not predictive at either age. This work reveals an association between childhood experience and later brain structure that is specific relative to aspects of experience, regions of brain, and timing.
NAFLD (non-alcoholic fatty liver disease) involves significant changes in liver metabolism characterized by oxidative stress, lipid accumulation and fibrogenesis. Mitochondrial dysfunction and ...bioenergetic defects also contribute to NAFLD. In the present study, we examined whether differences in mtDNA influence NAFLD. To determine the role of mitochondrial and nuclear genomes in NAFLD, MNX (mitochondrial-nuclear exchange) mice were fed an atherogenic diet. MNX mice have mtDNA from C57BL/6J mice on a C3H/HeN nuclear background and vice versa. Results from MNX mice were compared with wild-type C57BL/6J and C3H/HeN mice fed a control or atherogenic diet. Mice with the C57BL/6J nuclear genome developed more macrosteatosis, inflammation and fibrosis compared with mice containing the C3H/HeN nuclear genome when fed the atherogenic diet. These changes were associated with parallel alterations in inflammation and fibrosis gene expression in wild-type mice, with intermediate responses in MNX mice. Mice with the C57BL/6J nuclear genome had increased State 4 respiration, whereas MNX mice had decreased State 3 respiration and RCR (respiratory control ratio) when fed the atherogenic diet. Complex IV activity and most mitochondrial biogenesis genes were increased in mice with the C57BL/6J nuclear or mitochondrial genome, or both fed the atherogenic diet. These results reveal new interactions between mitochondrial and nuclear genomes and support the concept that mtDNA influences mitochondrial function and metabolic pathways implicated in NAFLD.
Lower socioeconomic status (SES) is associated with higher levels of life stress, which in turn affect stress physiology. SES is related to basal cortisol and diurnal change, but it is not clear if ...SES is associated with cortisol reactivity to stress. To address this question, we examined the relationship between two indices of SES, parental education and concentrated neighborhood disadvantage, and the cortisol reactivity of African-American adolescents to a modified version of the Trier Social Stress Test (TSST). We found that concentrated disadvantage was associated with cortisol reactivity and this relationship was moderated by gender, such that higher concentrated disadvantage predicted higher cortisol reactivity and steeper recovery in boys but not in girls. Parental education, alone or as moderated by gender, did not predict reactivity or recovery, while neither education nor concentrated disadvantage predicted estimates of baseline cortisol. This finding is consistent with animal literature showing differential vulnerability, by gender, to the effects of adverse early experience on stress regulation and the differential effects of neighborhood disadvantage in adolescent males and females. This suggests that the mechanisms underlying SES differences in brain development and particularly reactivity to environmental stressors may vary across genders.
We study neutrino-induced charged-current (CC) π0 production on carbon nuclei using events with fully imaged final-state proton-π0 systems. Novel use of final-state correlations based on transverse ...kinematic imbalance enables the first measurements of the struck nucleon's Fermi motion, of the intranuclear momentum transfer (IMT) dynamics, and of the final-state hadronic momentum configuration in neutrino pion production. Event distributions are presented for (i) the momenta of neutrino-struck neutrons below the Fermi surface, (ii) the direction of missing transverse momentum characterizing the strength of IMT, and (iii) proton-pion momentum imbalance with respect to the lepton scattering plane. The observed Fermi motion and IMT strength are compared to the previous MINERνA measurement of neutrino CC quasielastic-like production. The measured shapes and absolute rates of these distributions, as well as the cross section asymmetries, show tensions with predictions from current neutrino generator models.
Currently, patients with end-stage lung disease are limited to lung transplantation as their only treatment option. Unfortunately, the lungs available for transplantation are few. Moreover, ...transplant recipients require life-long immune suppression to tolerate the transplanted lung. A promising alternative therapeutic strategy is decellularization of whole lungs, which permits the isolation of an intact scaffold comprised of innate extracellular matrix (ECM) that can theoretically be recellularized with autologous stem or progenitor cells to yield a functional lung. Nonhuman primates (NHP) provide a highly relevant preclinical model with which to assess the feasibility of recellularized lung scaffolds for human lung transplantation. Our laboratory has successfully accomplished lung decellularization and initial stem cell inoculation of the resulting ECM scaffold in an NHP model. Decellularization of normal adult rhesus macaque lungs as well as the biology of the resulting acellular matrix have been extensively characterized. Acellular NHP matrices retained the anatomical and ultrastructural properties of native lungs with minimal effect on the content, organization, and appearance of ECM components, including collagen types I and IV, laminin, fibronectin, and sulfated glycosaminoglycans (GAG), due to decellularization. Proteomics analysis showed enrichment of ECM proteins in total tissue extracts due to the removal of cells and cellular proteins by decellularization. Cellular DNA was effectively removed after decellularization (∼92% reduction), and the remaining nuclear material was found to be highly disorganized, very-low-molecular-weight fragments. Both bone marrow- and adipose-derived mesenchymal stem cells (MSC) attach to the decellularized lung matrix and can be maintained within this environment in vitro, suggesting that these cells may be promising candidates and useful tools for lung regeneration. Analysis of decellularized lung slice cultures to which MSC were seeded showed that the cells attached to the decellularized matrix, elongated, and proliferated in culture. Future investigations will focus on optimizing the recellularization of NHP lung scaffolds toward the goal of regenerating pulmonary tissue. Bringing this technology to eventual human clinical application will provide patients with an alternative therapeutic strategy as well as significantly reduce the demand for transplantable organs and patient wait-list time.
Knowledge on how landscape heterogeneity shapes host–parasite interactions is central to understand the emergence, dynamics and evolution of infectious diseases. However, this is an underexplored ...subject, particularly for plant–virus systems. Here, we analyse how landscape heterogeneity influences the prevalence, spatial genetic structure, and temporal dynamics of Pepper golden mosaic and Pepper huasteco yellow vein begomoviruses infecting populations of the wild pepper Capsicum annuum glabriusculum (chiltepin) in Mexico. Environmental heterogeneity occurred at different nested spatial scales (host populations within biogeographical provinces), with levels of human management varying among host population within a province. Results indicate that landscape heterogeneity affects the epidemiology and genetic structure of chiltepin‐infecting begomoviruses in a scale‐specific manner, probably related to conditions favouring the viruses' whitefly vector and its dispersion. Increased levels of human management of the host populations were associated with higher virus prevalence and erased the spatial genetic structure of the virus populations. Also, environmental heterogeneity similarly shaped the spatial genetic structures of host and viruses. This resulted in the congruence between host and virus phylogenies, which does not seem to be due to host‐virus co‐evolution. Thus, results provide evidence of the key role of landscape heterogeneity in determining plant–virus interactions.
Summary Objective To determine how well measures of hip geometry can predict radiological incident hip osteoarthritis (HOA) compared to well known clinical risk factors. Design The study population ...is part of the Rotterdam Study, a prospective population-based cohort. Baseline pelvic radiographs were used to measure hip geometry by two methods: Statistical Shape Models (SSM) and predefined geometry parameters (PGPs). Incident HOA (Kellgren and Lawrence (KL) ≥ 2) was assessed in 688 participants after 6.5 years without radiographic HOA at baseline. The ability to predict HOA was quantified using the area under the Receiver Operating Characteristics (ROC) curve (AUC). Results Comparison of the two methods showed that both contain information that is not captured by the other method. At 6.5 years follow-up 132 hips had incident HOA. Five PGPs (Wiberg angle, Neck Width (NW), Pelvic Width (PW), Hip Axis Length (HAL) and Triangular Index (TI)) and two SSM (modes 5 and 9) were significant predictors of HOA ( P = 0.007). Hip geometry added 7% to the prediction obtained by clinical risk factors (AUC = 0.67 (geometry), 0.66 (gender, age, Body Mass Index (BMI)) and combining both: AUC = 0.73, respectively). Mode 12 (associated with position of the femoral head in acetabulum) and Wiberg angle were predictors of HOA in participants without radiological signs at baseline (KL = 0). Although the strength of the prediction decreased for all variables at a longer follow-up, the contribution of hip geometry was still significant ( P = 0.01). Conclusions Hip geometry has a moderate ability to predict HOA in participants with and without initial signs of osteoarthritis (OA), similar to and largely independent of the predictive value of clinical risk factors.
Obesity-related pathologies, such as nonalcoholic fatty liver disease, are linked to mitochondrial dysfunction and nitric oxide (NO) deficiency. Herein, we tested the hypothesis that a high-fat diet ...(HFD) modifies the liver mitochondrial proteome and alters proteins involved in NO metabolism, namely arginase 1 and endothelial NO synthase. Male C57BL/6 mice were fed a control or HFD and liver mitochondria were isolated for proteomics and reactive oxygen species measurements. Steatosis and hepatocyte ballooning were present in livers of HFD mice, with no pathology observed in the controls. HFD mice had increased serum glucose and decreased adiponectin. Mitochondrial reactive oxygen species was increased after 8 weeks in the HFD mice, but decreased at 16 weeks compared with the control, which was accompanied by increased uncoupling protein 2. Using proteomics, 22 proteins were altered as a consequence of the HFD. This cohort consists of oxidative phosphorylation, lipid metabolism, sulfur amino acid metabolism, and chaperone proteins. We observed a HFD-dependent increase in arginase 1 and decrease in activated endothelial NO synthase. Serum and liver nitrate + nitrite were decreased by HFD. In summary, these data demonstrate that a HFD causes steatosis, alters NO metabolism, and modifies the liver mitochondrial proteome; thus, NO may play an important role in the processes responsible for nonalcoholic fatty liver disease.
The MINERvA Collaboration reports a novel study of neutrino-nucleus charged-current deep inelastic scattering (DIS) using the same neutrino beam incident on targets of polystyrene, graphite, iron, ...and lead. Results are presented as ratios of C, Fe, and Pb to CH. The ratios of total DIS cross sections as a function of neutrino energy and flux-integrated differential cross sections as a function of the Bjorken scaling variable x are presented in the neutrino-energy range of 5-50 GeV. Based on the predictions of charged-lepton scattering ratios, good agreement is found between the data and prediction at medium x and low neutrino energy. However, the ratios appear to be below predictions in the vicinity of the nuclear shadowing region, x<0.1. This apparent deficit, reflected in the DIS cross-section ratio at high E sub(nu), is consistent with previous MINERvA observations B. Tice et al.(MINERvA Collaboration), Phys. Rev. Lett. 112, 231801 (2014). and with the predicted onset of nuclear shadowing with the axial-vector current in neutrino scattering.
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