A small population of hypothalamic neurons govern fertility: the critical role of VAX1 in GnRH neuron development and fertility maintenance.

Fertility depends on the correct maturation and function of approximately 800 gonadotropin-releasing hormone (GnRH) neurons in the brain. GnRH neurons are at the apex of the hypothalamic-pituitary-gonadal axis that regulates fertility. In adulthood, GnRH neurons are scattered throughout the anterior hypothalamic area and project to the median eminence, where GnRH is released into the portal vasculature to stimulate release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) from the pituitary. LH and FSH then regulate gonadal steroidogenesis and gametogenesis. Absence of GnRH neurons or inappropriate GnRH release leads to infertility. Despite the critical role of GnRH neurons in fertility, we still have a limited understanding of the genes responsible for proper GnRH neuron development and function in adulthood. GnRH neurons originate in the olfactory placode then migrate into the brain. Homeodomain transcription factors expressed within GnRH neurons or along their migratory path are candidate genes for inherited infertility. Using a combined in vitro and in vivo approach, we have identified Ventral Anterior Homeobox 1 (Vax1) as a novel homeodomain transcription factor responsible for GnRH neuron maturation and fertility. GnRH neuron counts in Vax1 knock-out embryos revealed Vax1 to be required for the presence of GnRH-expressing cells at embryonic day 17.5 (E17.5), but not at E13.5. To localize the effects of Vax1 on fertility, we generated Vax1flox mice and crossed them with Gnrhcre mice to specifically delete Vax1 within GnRH neurons. GnRH staining in Vax1flox/flox:GnRHcre mice show a total absence of GnRH expression in the adult. We performed lineage tracing in Vax1flox/flox:GnRHcre:RosaLacZ mice which proved GnRH neurons to be alive, but incapable of expressing GnRH. The absence of GnRH leads to delayed puberty, hypogonadism and complete infertility in both sexes. Finally, using the immortalized model GnRH neuron cell lines, GN11 and GT1-7, we show that VAX1 is a direct regulator of Gnrh1 transcription by binding key ATTA sites within the Gnrh1 promoter. This study identifies VAX1 as a key transcription factor regulating GnRH expression and establishes VAX1 as a novel candidate gene implicated in heritable infertility

Effects of inter-varietal diversity, biotic stresses and environmental productivity on grain yield of spring barley variety mixtures

Varietal seed mixtures tend to increase and stabilize crop yields, yet their application is sparse. Large-scale cultivation of variety mixtures may require a better understanding of how inter-varietal interactions and their interaction with the environment may influence the grain yield of variety mixtures relative to their component varieties. For this purpose, six variety mixtures of spring barley and 14 component varieties were grown in each of 17 trial environments. A total of 28 observed and a priori plant characteristics, including grain yield, disease severity and weed competitiveness, were derived for each component variety in each trial. The relationship between inter-varietal diversity of each characteristic and the mixing effect on grain yield was analysed. Additionally, various types of yield stability were estimated and compared among mixtures and component varieties. One mixture out-yielded all of its component varieties in almost half of the trial environments. Inter-varietal diversity in grain yield potential correlated significantly with mixing effect, as did straw length diversity when weighted with weed pressure. The grain yields of most mixtures were more stable across environments than their component varieties when accounting also for the general response to environmental productivity. Hence, most mixtures adapted slightly better to environmental productivity and were less sensitive to environmental stress than their component varieties. We conclude that the efficacy of variety mixtures may be enhanced by mixing relatively high-yielding varieties differing in responsiveness to environmental productivity

Empathy Maps of the FourSight Preferences

Empathy Maps of the FourSight PreferencesThe purpose of this project is to make one empathy map for each of the FourSight preferences. The goal of the project is to add a visual representation of the four main preferences to the growing body of data of FourSight. Individuals who are interested in FourSight, both for personal and professional reasons, can use the empathy maps to form a deeper understanding of each preference

Testing the utility of a data-driven approach for assessing BMI from face images

Several lines of evidence suggest that facial cues of adiposity may be important for human social interaction. However, tests for quantifiable cues of body mass index (BMI) in the face have examined only a small number of facial proportions and these proportions were found to have relatively low predictive power. Here we employed a data-driven approach in which statistical models were built using principal components (PCs) derived from objectively defined shape and color characteristics in face images. The predictive power of these models was then compared with models based on previously studied facial proportions (perimeter-to-area ratio, width-to-height ratio, and cheek-to-jaw width). Models based on 2D shape-only PCs, color-only PCs, and 2D shape and color PCs combined each performed significantly and substantially better than models based on one or more of the previously studied facial proportions. A non-linear PC model considering both 2D shape and color PCs was the best predictor of BMI. These results highlight the utility of a “bottom-up”, data-driven approach for assessing BMI from face images

Approximate solutions in space mission design

In this paper, we address multi-objective space mission design problems. From a practical point of view, it is often the case that,during the preliminary phase of the design of a space mission, the solutions that are actually considered are not 'optimal' (in the Pareto sense)but belong to the basin of attraction of optimal ones (i.e. they are nearly optimal). This choice is motivated either by additional requirements that the decision maker has to take into account or, more often, by robustness considerations. For this, we suggest a novel MOEA which is a modification of the well-known NSGA-II algorithm equipped with a recently proposed archiving strategy which aims at storing the set of approximate solutions of a given MOP. Using this algorithm we will examine some space trajectory design problems and demonstrate the benefit of the novel approach

Das Konzept des "controlled traffic farming" im ökologischen Gemüseanbau

Problems of machinery induced soil compaction are evident in organic vegetable production, resulting in stunted root growth and reduced yield. Controlled traffic farming (CTF) provides a possibility to restrict soil compaction to wheel tracks and create traffic-free vegetable beds with improved soil structure. A field experiment was established at a commercial organic vegetable farm in Denmark to investigate the effect of CTF on the growth of cabbage (Brassica oleracea), potato (Solanum tuberosum) and beetroot (Beta vulgaris). Random traffic farming (RTF) served as the control. Preliminary results show that root intensity was higher in the CTF treatment compared to the RTF treatment for cabbage at the end of the growing season, indicating a better soil structure in this system. Crop yields were 23 to 70% higher in all three investigated crops in the CTF treatments. These results point towards the potential to increase the use of the CTF system in organic vegetable production

Chromatin status and transcription factor binding to gonadotropin promoters in gonadotrope cell lines.

BackgroundProper expression of key reproductive hormones from gonadotrope cells of the pituitary is required for pubertal onset and reproduction. To further our understanding of the molecular events taking place during embryonic development, leading to expression of the glycoproteins luteinizing hormone (LH) and follicle-stimulating hormone (FSH), we characterized chromatin structure changes, imparted mainly by histone modifications, in model gonadotrope cell lines.MethodsWe evaluated chromatin status and gene expression profiles by chromatin immunoprecipitation assays, DNase sensitivity assay, and RNA sequencing in three developmentally staged gonadotrope cell lines, αT1-1 (progenitor, expressing Cga), αT3-1 (immature, expressing Cga and Gnrhr), and LβT2 (mature, expressing Cga, Gnrhr, Lhb, and Fshb), to assess changes in chromatin status and transcription factor access of gonadotrope-specific genes.ResultsWe found the common mRNA α-subunit of LH and FSH, called Cga, to have an open chromatin conformation in all three cell lines. In contrast, chromatin status of Gnrhr is open only in αT3-1 and LβT2 cells. Lhb begins to open in LβT2 cells and was further opened by activin treatment. Histone H3 modifications associated with active chromatin were high on Gnrhr in αT3-1 and LβT2, and Lhb in LβT2 cells, while H3 modifications associated with repressed chromatin were low on Gnrhr, Lhb, and Fshb in LβT2 cells. Finally, chromatin status correlates with the progressive access of LHX3 to Cga and Gnrhr, followed by PITX1 binding to the Lhb promoter.ConclusionOur data show the gonadotrope-specific genes Cga, Gnrhr, Lhb, and Fshb are not only controlled by developmental transcription factors, but also by epigenetic mechanisms that include the modulation of chromatin structure, and histone modifications

Pharmacist-led management of chronic pain in primary care:results from a randomised controlled exploratory trial

To compare the effectiveness of pharmacist medication review, with or without pharmacist prescribing, with standard care, for patients with chronic pain

Requirements for Quality of Life Instruments in Clinical Research

AbstractThe ability to produce high quality instruments for the assessment of quality of life has advanced considerably in recent years. As the science progresses it has become clear that certain standards must be met if outcome measures are to be capable of providing useful, reliable, and valid information within the context of clinical studies and trials. This paper specifies what these standards are with particular reference to theoretical basis, practicality, acceptability to respondents, unidimensionality, scaling and psychometric properties, and cultural validity and equivalence. The paper also indicates how failure to achieve such standards results in measures that are inaccurate and insensitive to true changes in outcome