Testosterone Trajectories and Reference Ranges in a Large Longitudinal Sample of Male Adolescents

Pubertal dynamics plays an important role in physical and psychological development of children and adolescents. We aim to provide reference ranges of plasma testosterone in a large longitudinal sample. Furthermore, we describe a measure of testosterone trajectories during adolescence that can be used in future investigations of development.We carried out longitudinal measurements of plasma testosterone in 2,216 samples obtained from 513 males (9 to 17 years of age) from the Avon Longitudinal Study of Parents and Children. We used integration of a model fitted to each participant's testosterone trajectory to calculate a measure of average exposure to testosterone over adolescence. We pooled these data with corresponding values reported in the literature to provide a reference range of testosterone levels in males between the ages of 6 and 19 years.The average values of total testosterone in the ALSPAC sample range from 0.82 nmol/L (Standard Deviation [SD]: 0.09) at 9 years of age to 16.5 (SD: 2.65) nmol/L at 17 years of age; these values are congruent with other reports in the literature. The average exposure to testosterone is associated with different features of testosterone trajectories such as Peak Testosterone Change, Age at Peak Testosterone Change, and Testosterone at 17 years of age as well as the timing of the growth spurt during puberty.The average exposure to testosterone is a useful measure for future investigations using testosterone trajectories to examine pubertal dynamics

Hydrogen bond topology and the ice VII/VIII and Ih/XI proton ordering phase transitions

Ice Ih, ordinary ice at atmospheric pressure, is a proton-disordered crystal that when cooled under special conditions is believed to transform to ferroelectric proton-ordered ice XI, but this transformation is still subject to controversy. Ice VII, also proton disordered throughout its region of stability, transforms to proton-ordered ice VIII upon cooling. In contrast to the ice Ih/XI transition, the VII/VIII transition and the crystal structure of ice VIII are well characterized. In order to shed some light on the ice Ih proton ordering transition, we present the results of periodic electronic density functional theory calculations and statistical simulations. We are able to describe the small energy differences among the innumerable H-bond configurations possible in a large simulation cell by using an analytic theory to extrapolate from electronic DFT calculations on small unit cells to cells large enough to approximate the thermodynamic limit. We first validate our methods by comparing our predictions to the well-characterized ice VII/VIII proton ordering transition, finding agreement with respect to both the transition temperature and structure of the low-temperature phase. For ice Ih, our results indicate that a proton-ordered phase is attainable at low temperatures, the structure of which is in agreement with the experimentally proposed ferroelectric Cmc2_1 structure. The predicted transition temperature of 98 K is in qualitative agreement with the observed transition at 72 K on KOH-doped ice samples

Do different multi-segment foot models detect the same changes in kinematics when wearing foot orthoses?

Background: Different multi-segment foot models have been used to explore the effect of foot orthoses. Previous studies have compared the kinematic output of different multi-segment foot models, however, no study has explored if different multi-segment foot models detect similar kinematic changes when wearing a foot orthoses. The aim of this study was to compare the ability of two different multi-segment foot models to detect kinematic changes at the hindfoot and forefoot during the single and double support phases of gait when wearing a foot orthosis. Methods: Foot kinematics were collected during walking from a sample of 32 individuals with and without a foot orthosis with a medial heel bar using an eight-camera motion capture system. The Oxford Foot Model (OFM) and a multi-segment foot model using the Calibrated Anatomical System Technique (CAST) were applied simultaneously. Vector field statistical analysis was used to explore the kinematic effects of a medial heel bar using the two models, and the ability of the models to detect any changes in kinematics was compared. Results: For the hindfoot, both models showed very good agreement of the effect of the foot orthosis across all three anatomical planes during the single and double support phases. However, for the forefoot, the level of agreement between the models varied with both models showing good agreement of the effect in the coronal plane but poorer agreement in the transverse and sagittal planes. Conclusions: This study showed that while consistency exists across both models for the hindfoot and forefoot in the coronal plane, the forefoot in the transverse and sagittal planes showed inconsistent responses to the foot orthoses. This should be considered when interpreting the efficacy of different interventions which aim to change foot biomechanics

Atoh1 \u3csup\u3e+\u3c/sup\u3e secretory progenitors possess renewal capacity independent of Lgr5 \u3csup\u3e+\u3c/sup\u3e cells during colonic regeneration

During homeostasis, the colonic epithelium is replenished every 3–5 days by rapidly cycling Lgr5 + stem cells. However, various insults can lead to depletion of Lgr5 + stem cells, and colonic epithelium can be regenerated from Lgr5-negative cells. While studies in the small intestine have addressed the lineage identity of the Lgr5-negative regenerative cell population, in the colon this question has remained unanswered. Here, we set out to identify which cell(s) contribute to colonic regeneration by performing genetic fate-mapping studies of progenitor populations in mice. First, using keratin-19 (Krt19) to mark a heterogeneous population of cells, we found that Lgr5-negative cells can regenerate colonic crypts and give rise to Lgr5 + stem cells. Notch1 + absorptive progenitor cells did not contribute to epithelial repair after injury, whereas Atoh1 + secretory progenitors did contribute to this process. Additionally, while colonic Atoh1 + cells contributed minimally to other lineages during homeostasis, they displayed plasticity and contributed to epithelial repair during injury, independent of Lgr5 + cells. Our findings suggest that promotion of secretory progenitor plasticity could enable gut healing in colitis

Buying to share: How prosumption promotes purchases in peer-to-peer asset sharing

Advocates of the sharing economy cite sharing as a viable alternative to asset purchases and ownership. However, Peer-to-peer (P2P) asset sharing, as a service innovation in the sharing economy, enables consumers to capitalize on their asset ownership by providing others with access to those assets for a fee. These prosumers acquire and consume the asset but also provide it as a service sold to others. In exploring the connection between prosumers and asset manufacturers, this study particularly notes the implications of prosumption for initial asset acquisition. A review of existing P2P asset sharing initiatives, three focus groups, and two experimental studies illustrate a positive effect of prosumption on willingness to acquire an asset from manufacturers, especially expensive assets. These results challenge the conventional notion that sharing is exclusively an alternative to ownership. A mediation analysis further indicates that reduced burdens of ownership can explain the positive link between prosumption and willingness to purchase assets from manufacturers. As another novel contribution, this study reveals an interdependency between prosumers and P2P service users, such that prosumers consider their own and also other P2P users’ brand preferences when acquiring assets. In summary, and contrary to conventional wisdom, promoting prosumption via P2P asset sharing might increase sales by manufacturers

Published online in Wiley InterScience (www.interscience.wiley. com)

ABSTRACT The mouse incisor has two unusual features: it grows continuously and it is covered by enamel exclusively on the labial side. The continuous growth is driven in part by epithelial stem cells in the cervical loop region that can both self-renew and give rise to ameloblasts. We have previously reported that ectopic enamel is found on the lingual side of the incisor in mice with loss-of-function of sprouty (spry) genes. Spry2 1/À ; Spry4 À/À mice, in which three sprouty alleles have been inactivated, have ectopic enamel as a result of upregulation of epithelial-mesenchymal FGF signaling in the lingual part of the cervical loop. Interestingly, lingual enamel is also present in the early postnatal period in Spry4 À/À mice, in which only two sprouty alleles have been inactivated, but ectopic enamel is not found in adults of this genotype. To explore the mechanisms underlying the disappearance of lingual enamel in Spry4 À/À adults, we studied the fate of the lingual enamel in Spry4 À/À mice by comparing the morphology and growth of their lower incisors with wild type and Spry2 1/À ; Spry4 À/À mice at several timepoints between the perinatal period and adulthood. Ameloblasts and enamel were detected on the lingual side in postnatal Spry2 1/À ; Spry4 1/À incisors. By contrast, new ectopic ameloblasts ceased to differentiate after postnatal day 3 in Spry4 À/À incisors, which was followed by a progressive loss of lingual enamel. Both the posterior extent of lingual enamel and the time of its last deposition were variable early postnatally in Spry4 À/À incisors, but in all Spry4 À/À adult incisors the lingual enamel was ultimately lost through continuous growth and abrasion of the incisor

Toll-like receptor signaling in thymic epithelium controls monocyte-derived dendritic cell recruitment and Treg generation

The development of thymic regulatory T cells (Treg) is mediated by Aire-regulated self-antigen presentation on medullary thymic epithelial cells (mTECs) and dendritic cells (DCs), but the cooperation between these cells is still poorly understood. Here we show that signaling through Toll-like receptors (TLR) expressed on mTECs regulates the production of specific chemokines and other genes associated with post-Aire mTEC development. Using single-cell RNA-sequencing, we identify a new thymic CD14(+)Sirp alpha (+) population of monocyte-derived dendritic cells (CD14(+)moDC) that are enriched in the thymic medulla and effectively acquire mTEC-derived antigens in response to the above chemokines. Consistently, the cellularity of CD14(+)moDC is diminished in mice with MyD88-deficient TECs, in which the frequency and functionality of thymic CD25(+)Foxp3(+) Tregs are decreased, leading to aggravated mouse experimental colitis. Thus, our findings describe a TLR-dependent function of mTECs for the recruitment of CD14(+)moDC, the generation of Tregs, and thereby the establishment of central tolerance. Immune tolerance is mediated by the deletion of autoreactive T cells via medullary thymic epithelial cells (mTEC) and dendritic cells (DC), and by the induction of regulatory T cells (Treg). Here the authors show that mTEC receiving toll-like receptor signaling control the recruitment of CD14(+)Sirp alpha (+) DC population that is capable of inducing Treg for establishing tolerance

Genetic Variation in DNA Repair Pathways and Risk of Non-Hodgkin's Lymphoma

Molecular and genetic evidence suggests that DNA repair pathways may contribute to lymphoma susceptibility. Several studies have examined the association of DNA repair genes with lymphoma risk, but the findings from these reports have been inconsistent. Here we provide the results of a focused analysis of genetic variation in DNA repair genes and their association with the risk of non-Hodgkin's lymphoma (NHL). With a population of 1,297 NHL cases and 1,946 controls, we have performed a two-stage case/control association analysis of 446 single nucleotide polymorphisms (SNPs) tagging the genetic variation in 81 DNA repair genes. We found the most significant association with NHL risk in the ATM locus for rs227060 (OR = 1.27, 95% CI: 1.13–1.43, p = 6.77×10−5), which remained significant after adjustment for multiple testing. In a subtype-specific analysis, associations were also observed for the ATM locus among both diffuse large B-cell lymphomas (DLBCL) and small lymphocytic lymphomas (SLL), however there was no association observed among follicular lymphomas (FL). In addition, our study provides suggestive evidence of an interaction between SNPs in MRE11A and NBS1 associated with NHL risk (OR = 0.51, 95% CI: 0.34–0.77, p = 0.0002). Finally, an imputation analysis using the 1,000 Genomes Project data combined with a functional prediction analysis revealed the presence of biologically relevant variants that correlate with the observed association signals. While the findings generated here warrant independent validation, the results of our large study suggest that ATM may be a novel locus associated with the risk of multiple subtypes of NHL

Understanding how excess lead iodide precursor improves halide perovskite solar cell performance

The presence of excess lead iodide in halide perovskites has been key for surpassing 20% photon-to-power conversion efficiency. To achieve even higher power conversion efficiencies, it is important to understand the role of remnant lead iodide in these perovskites. To that end, we explored the mechanism facilitating this effect by identifying the impact of excess lead iodide within the perovskite film on charge diffusion length, using electron-beam-induced current measurements, and on film formation properties, from grazing-incidence wide-angle X-ray scattering and high-resolution transmission electron microscopy. Based on our results, we propose that excess lead iodide in the perovskite precursors can reduce the halide vacancy concentration and lead to formation of azimuthal angle-oriented cubic alpha-perovskite crystals in-between 0 degrees and 90 degrees. We further identify a higher perovskite carrier concentration inside the nanostructured titanium dioxide layer than in the capping layer. These effects are consistent with enhanced lead iodide-rich perovskite solar cell performance and illustrate the role of lead iodide