Management of hyperandrogenism in adolescent girls.

Hyperandrogenism in adolescent girls can be a troubling problem because of the difficulty in establishing a diagnosis and in prescribing appropriate therapy. Androgen excess in adolescent patients encompasses a spectrum of clinical presentations, including acne, hirsutism, oligomenorrhea, amenorrhea, virilism, and ovarian cysts. Androgen excess is a clinical and chemical feature of idiopathic hirsutism, late-onset forms of congenital adrenal hyperplasia, and polycystic ovarian disease; in some cases, functional hyperandrogenism is discussed. We recommend screening for hyperandrogenism by measuring blood levels of testosterone, dehydroepiandrosterone sulfate, and delta 4-androstenedione, while others propose a first dexamethasone suppression test for evaluation of free testosterone, dehydroepiandrosterone sulfate, and cortisol. Treatment will be chosen according to particular symptoms such as acne, hirsutism, obesity, or oligomenorrhea.     

ECM Protein Nanofibers and Nanostructures Engineered Using Surface-initiated Assembly

The extracellular matrix (ECM) in tissues is synthesized and assembled by cells to form a 3D fibrillar, protein network with tightly regulated fiber diameter, composition and organization. In addition to providing structural support, the physical and chemical properties of the ECM play an important role in multiple cellular processes including adhesion, differentiation, and apoptosis. In vivo, the ECM is assembled by exposing cryptic self-assembly (fibrillogenesis) sites within proteins. This process varies for different proteins, but fibronectin (FN) fibrillogenesis is well-characterized and serves as a model system for cell-mediated ECM assembly. Specifically, cells use integrin receptors on the cell membrane to bind FN dimers and actomyosin-generated contractile forces to unfold and expose binding sites for assembly into insoluble fibers. This receptor-mediated process enables cells to assemble and organize the ECM from the cellular to tissue scales. Here, we present a method termed surface-initiated assembly (SIA), which recapitulates cell-mediated matrix assembly using protein-surface interactions to unfold ECM proteins and assemble them into insoluble fibers. First, ECM proteins are adsorbed onto a hydrophobic polydimethylsiloxane (PDMS) surface where they partially denature (unfold) and expose cryptic binding domains. The unfolded proteins are then transferred in well-defined micro- and nanopatterns through microcontact printing onto a thermally responsive poly(N-isopropylacrylamide) (PIPAAm) surface. Thermally-triggered dissolution of the PIPAAm leads to final assembly and release of insoluble ECM protein nanofibers and nanostructures with well-defined geometries. Complex architectures are possible by engineering defined patterns on the PDMS stamps used for microcontact printing. In addition to FN, the SIA process can be used with laminin, fibrinogen and collagens type I and IV to create multi-component ECM nanostructures. Thus, SIA can be used to engineer ECM protein-based materials with precise control over the protein composition, fiber geometry and scaffold architecture in order to recapitulate the structure and composition of the ECM in vivo.     

Shared Cultural History as a Predictor of Political and Economic Changes among Nation States

Political and economic risks arise from social phenomena that spread within and across countries. Regime changes, protest movements, and stock market and default shocks can have ramifications across the globe. Quantitative models have made great strides at predicting these events in recent decades but incorporate few explicitly measured cultural variables. However, in recent years cultural evolutionary theory has emerged as a major paradigm to understand the inheritance and diffusion of human cultural variation. Here, we combine these two strands of research by proposing that measures of socio-linguistic affiliation derived from language phylogenies track variation in cultural norms that influence how political and economic changes diffuse across the globe. First, we show that changes over time in a country’s democratic or autocratic character correlate with simultaneous changes among their socio-linguistic affiliations more than with changes of spatially proximate countries. Second, we find that models of changes in sovereign default status favor including socio-linguistic affiliations in addition to spatial data. These findings suggest that better measurement of cultural networks could be profoundly useful to policy makers who wish to diversify commercial, social, and other forms of investment across political and economic risks on an international scale.     

Comparison of molecular and morphological data on St Helena: Elaphoglossum

The endemic elaphoglossoid ferns, Elaphoglossum dimorphum, E. nervosum and Microstaphyla furcata of St Helena, form a closely related group within section Lepidoglossa when analysed phylogenetically using sequences from the chloroplast trnL intron (partial) and trnL-F intergenic spacer. Microstaphyla furcata, traditionally placed in its own genus, is clearly shown to belong to Elaphoglossum confirming the previous transfer of this species to Elaphoglossum as E. bifurcatum. There is hardly any trnL-F sequence divergence between the species, in fact sequences of E. nervosum and E. dimorphum are identical. These results are consistent with the possible origin of E. dimorphum as a hybrid between E. bifurcatum and E. nervosum or with the view that the three species are the result of a recent radiation. The potential conflict between phylogenetic and morphological distinctness in determining species conservation priorities is discussed.     

Total Internal Reflection Accounts for the Bright Color of the Saharan Silver Ant

The Saharan silver ant Cataglyphis bombycina is one of the terrestrial living organisms best adapted to tolerate high temperatures. It has recently been shown that the hairs covering the ant’s dorsal body part are responsible for its silvery appearance. The hairs have a triangular cross-section with two corrugated surfaces allowing a high optical reflection in the visible and near-infrared (NIR) range of the spectrum while maximizing heat emissivity in the mid-infrared (MIR). Those two effects account for remarkable thermoregulatory properties, enabling the ant to maintain a lower thermal steady state and to cope with the high temperature of its natural habitat. In this paper, we further investigate how geometrical optical and high reflection properties account for the bright silver color of C. bombycina. Using optical ray-tracing models and attenuated total reflection (ATR) experiments, we show that, for a large range of incidence angles, total internal reflection (TIR) conditions are satisfied on the basal face of each hair for light entering and exiting through its upper faces. The reflection properties of the hairs are further enhanced by the presence of the corrugated surface, giving them an almost total specular reflectance for most incidence angles. We also show that hairs provide an almost 10-fold increase in light reflection, and we confirm experimentally that they are responsible for a lower internal body temperature under incident sunlight. Overall, this study improves our understanding of the optical mechanisms responsible for the silver color of C. bombycina and the remarkable thermoregulatory properties of the hair coat covering the ant’s body.     

Electromyogram as an indicator of neuromuscular fatigue during incremental exercise

This study analysed the changes in the electromyographic activity (EMG) of the vastus lateralis muscle (VL) during an incremental maximal oxygen uptake test on a treadmill. A breakpoint in the integrated electromyogram (iEMG)-velocity relationship has already been interpreted in two ways: either as a sign of neuromuscular fatigue or as an expression of the iEMG-velocity relationship characteristics. The aim of this study was to test a method of distinguishing fatigue effects from those due to increases in exercise power. Eight well-trained male runners took part in the study. They completed a running protocol consisting of 4-min stages of increments in power output. Between each stage (about 15 s after the start of a minute at rest), the subjects had to maintain a standard effort: a 10-s isometric leg extension contraction [50% isometric maximal voluntary contraction (IMVC)]. The EMG was recorded during the running and isometric protocols, a change in the EMG signal during the isometric exercise being considered as the sign of fatigue. The iEMG-velocity relationships were strongly fitted by a second-order polynomial function for data taken at both the start (r = 0.98) and the end (r = 0.98) of the stage. Based on the stability of the 50%IMVC-iEMG relationship noted between stages, the start-iEMG has been identified as expressing the iEMG-velocity relationship without fatigue. The stage after which end-iEMG increased significantly more steeply than start-iEMG was considered as the iEMG threshold and was simultaneous with the ventilatory equivalent for carbon dioxide threshold. The parallel changes of minute ventilation and iEMG would suggest the existence of common regulation stimuli linked either to effort intensity and/or to metabolic conditions. The fall in intracellular [K⁺] has been discussed as being one of the main factors in regulating ventilation. Accepted: 16 December 1997     

Metabolite Proofreading in Carnosine and Homocarnosine Synthesis: MOLECULAR IDENTIFICATION OF PM20D2 AS β-ALANYL-LYSINE DIPEPTIDASE*

Carnosine synthase is the ATP-dependent ligase responsible for carnosine (β-alanyl-histidine) and homocarnosine (γ-aminobutyryl-histidine) synthesis in skeletal muscle and brain, respectively. This enzyme uses, also at substantial rates, lysine, ornithine, and arginine instead of histidine, yet the resulting dipeptides are virtually absent from muscle or brain, suggesting that they are removed by a “metabolite repair” enzyme. Using a radiolabeled substrate, we found that rat skeletal muscle, heart, and brain contained a cytosolic β-alanyl-lysine dipeptidase activity. This enzyme, which has the characteristics of a metalloenzyme, was purified ≈200-fold from rat skeletal muscle. Mass spectrometry analysis of the fractions obtained at different purification stages indicated parallel enrichment of PM20D2, a peptidase of unknown function belonging to the metallopeptidase 20 family. Western blotting showed coelution of PM20D2 with β-alanyl-lysine dipeptidase activity. Recombinant mouse PM20D2 hydrolyzed β-alanyl-lysine, β-alanyl-ornithine, γ-aminobutyryl-lysine, and γ-aminobutyryl-ornithine as its best substrates. It also acted at lower rates on β-alanyl-arginine and γ-aminobutyryl-arginine but virtually not on carnosine or homocarnosine. Although acting preferentially on basic dipeptides derived from β-alanine or γ-aminobutyrate, PM20D2 also acted at lower rates on some “classic dipeptides” like α-alanyl-lysine and α-lysyl-lysine. The same activity profile was observed with human PM20D2, yet this enzyme was ∼100–200-fold less active on all substrates tested than the mouse enzyme. Cotransfection in HEK293T cells of mouse or human PM20D2 together with carnosine synthase prevented the accumulation of abnormal dipeptides (β-alanyl-lysine, β-alanyl-ornithine, γ-aminobutyryl-lysine), thus favoring the synthesis of carnosine and homocarnosine and confirming the metabolite repair role of PM20D2.