TAC3/TACR3 Mutations Reveal Preferential Activation of Gonadotropin-Releasing Hormone Release by Neurokinin B in Neonatal Life Followed by Reversal in Adulthood

Context: Mutations in TAC3 and TACR3 (encoding neurokinin B and its receptor) have been identified in Turkish patients with idiopathic hypogonadotropic hypogonadism (IHH), but broader populations have not yet been tested and genotype-phenotype correlations have not been established. Objective: A broad cohort of normosmic IHH probands was screened for mutations in TAC3/TACR3 to evaluate the prevalence of such mutations and define the genotype/phenotype relationships. Design and Setting: The study consisted of sequencing of TAC3/TACR3, in vitro functional assays, and neuroendocrine phenotyping conducted in tertiary care centers worldwide. Patients or Other Participants: 345 probands, 18 family members, and 292 controls were studied. Intervention: Reproductive phenotypes throughout reproductive life and before and after therapy were examined. Main Outcome Measure: Rare sequence variants in TAC3/TACR3 were detected. Results: In TACR3, 19 probands harbored 13 distinct coding sequence rare nucleotide variants [three nonsense mutations, six nonsynonymous, four synonymous (one predicted to affect splicing)]. In TAC3, one homozygous single base pair deletion was identified, resulting in complete loss of the neurokinin B decapeptide. Phenotypic information was available on 16 males and seven females with coding sequence variants in TACR3/TAC3. Of the 16 males, 15 had microphallus; none of the females had spontaneous thelarche. Seven of the 16 males and five of the seven females were assessed after discontinuation of therapy; six of the seven males and four of the five females demonstrated evidence for reversibility of their hypogonadotropism. Conclusions: Mutations in the neurokinin B pathway are relatively common as causes of hypogonadism. Although the neurokinin B pathway appears essential during early sexual development, its importance in sustaining the integrity of the hypothalamic-pituitary-gonadal axis appears attenuated over time. (J Clin Endocrinol Metab 95: 2857-2867, 2010)

Future contributions of crop modelling - from heuristics and supporting decision making to understanding genetic regulation and aiding crop improvement

Crop modelling has evolved over the last 30 or so years in concert with advances in crop physiology, crop ecology and computing technology. Having reached a respectable degree of acceptance, it is appropriate to review briefly the course of developments in crop modelling and to project what might be major contributions of crop modelling in the future. Two major opportunities are envisioned for increased modelling activity in the future. One opportunity is in a continuing central, heuristic role to support scientific investigation, to facilitate decision making by crop managers, and to aid in education. Heuristic activities will also extend to the broader system-level issues of environmental and ecological aspects of crop production. The second opportunity is projected as a prime contributor in understanding and advancing the genetic regulation of plant performance and plant improvement. Physiological dissection and modelling of traits provides an avenue by which crop modelling could contribute to enhancing integration of molecular genetic technologies in crop improvement. Crown Copyright (C) 2002 Published by Elsevier Science B.V. All rights reserved.

Making developmental biology relevant to undergraduates in an era of economic rationalism in Australia

This report describes the road map we followed at our university to accommodate three main factors: financial pressure within the university system; desire to enhance the learning experience of undergraduates; and motivation to increase the prominence of the discipline of developmental biology in our university. We engineered a novel, multi-year undergraduate developmental biology program which was student-oriented, ensuring that students were continually exposed to the underlying principles and philosophy of this discipline throughout their undergraduate career. Among its key features are introductory lectures in core courses in the first year, which emphasize the relevance of developmental biology to tissue engineering, reproductive medicine, therapeutic approaches in medicine, agriculture and aquaculture. State-of-the-art animated computer graphics and images of high visual impact are also used. In addition, students are streamed into the developmental biology track in the second year, using courses like human embryology and courses shared with cell biology, which include practicals based on modern experimental approaches. Finally, fully dedicated third-year courses in developmental biology are undertaken in conjunction with stand-alone practical courses where students experience first-hand work in a research laboratory. Our philosophy is a cradle-to-grave approach to the education of undergraduates so as to prepare highly motivated, enthusiastic and well-educated developmental biologists for entry into graduate programs and ultimately post-doctoral research.

Sport-specific practice and the development of expert decision-making in team ball sports

The role of sport-specific practice in the development of decision-making expertise in the sports of field hockey, netball, and basketball was examined. Fifteen expert decision-makers and 13 experienced non-expert athletes provided detailed information about the quantity and type of sport-specific and other related practice activities they had undertaken throughout their careers. Experts accumulated more hours of sport-specific practice from age 12 years onwards than did non-experts, spending on average some 13 years and 4,000 hours on concentrated sport-specific practice before reaching international standard. A significant negative correlation existed between the number of additional activities undertaken and the hours of sportspecific training required before attaining expertise, suggesting a functional role for activities other than sport-specific training in the development of expert decision-making.