Beyond Leptin: Emerging Candidates for the Integration of Metabolic and Reproductive Function during Negative Energy Balance

Reproductive status is tightly coupled to metabolic state in females, and ovarian cycling in mammals is halted when energy output exceeds energy input, a metabolic condition known as negative energy balance. This inhibition of reproductive function during negative energy balance occurs due to suppression of gonadotropin-releasing hormone (GnRH) release in the hypothalamus. The GnRH secretagogue kisspeptin is also inhibited during negative energy balance, indicating that inhibition of reproductive neuroendocrine circuits may occur upstream of GnRH itself. Understanding the metabolic signals responsible for the inhibition of reproductive pathways has been a compelling research focus for many years. A predominant theory in the field is that the status of energy balance is conveyed to reproductive neuroendocrine circuits via the adipocyte hormone leptin. Leptin is stimulatory for GnRH release and lower levels of leptin during negative energy balance are believed to result in decreased stimulatory drive for GnRH cells. However, recent evidence found that restoring leptin to physiological levels did not restore GnRH function in three different models of negative energy balance. This suggests that although leptin may be an important permissive signal for reproductive function as indicated by many years of research, factors other than leptin must critically contribute to negative energy balance-induced reproductive inhibition. This review will focus on emerging candidates for the integration of metabolic status and reproductive function during negative energy balance

Measuring individual overpotentials in an operating solid-oxide electrochemical cell

We use photo-electrons as a non-contact probe to measure local electrical potentials in a solid-oxide electrochemical cell. We characterize the cell in operando at near-ambient pressure using spatially-resolved X-ray photoemission spectroscopy. The overpotentials at the interfaces between the Ni and Pt electrodes and the yttria-stabilized zirconia (YSZ) electrolyte are directly measured. The method is validated using electrochemical impedance spectroscopy. Using the overpotentials, which characterize the cell's inefficiencies, we compare without ambiguity the electro-catalytic efficiencies of Ni and Pt, finding that on Ni H_2O splitting proceeds more rapidly than H2 oxidation, while on Pt, H2 oxidation proceeds more rapidly than H2O splitting.Comment: corrected; Phys. Chem. Chem. Phys., 201

Using Football Cultures as a Vehicle to Improve Mental Health in Men: The Case of the Redcar and Cleveland Boot Room

This paper sets out to appraise (from the perspective of members) the impact of a localized, football-based mental health intervention. Commissioned in late 2015, the ‘Redcar and Cleveland Boot Room (BR)’ was implemented in response to mass redundancy in the local area, coupled with regional suicide rates in men that exceed the national average. Interactive discussions with BR members revealed that: (a) the language of football and shared identity were important for initiating and sustaining engagement in the BR; (b) peer-support and mentoring combined with member-led activities were active ingredients of the BR and (c) that the BR was an effective vehicle for building mental health resilience. This evaluation adds to the evidence base on the value of football as a context to engage adult males in community-based interventions targeting mental health resilience

Leptin mediates the increase in blood pressure associated with obesity.

Obesity is associated with increased blood pressure (BP), which in turn increases the risk of cardiovascular diseases. We found that the increase in leptin levels seen in diet-induced obesity (DIO) drives an increase in BP in rodents, an effect that was not seen in animals deficient in leptin or leptin receptors (LepR). Furthermore, humans with loss-of-function mutations in leptin and the LepR have low BP despite severe obesity. Leptin's effects on BP are mediated by neuronal circuits in the dorsomedial hypothalamus (DMH), as blocking leptin with a specific antibody, antagonist, or inhibition of the activity of LepR-expressing neurons in the DMH caused a rapid reduction of BP in DIO mice, independent of changes in weight. Re-expression of LepRs in the DMH of DIO LepR-deficient mice caused an increase in BP. These studies demonstrate that leptin couples changes in weight to changes in BP in mammalian species

WormBase 2016: expanding to enable helminth genomic research

WormBase (www.wormbase.org) is a central repository for research data on the biology, genetics and genomics of Caenorhabditis elegans and other nematodes. The project has evolved from its original remit to collect and integrate all data for a single species, and now extends to numerous nematodes, ranging from evolutionary comparators of C. elegans to parasitic species that threaten plant, animal and human health. Research activity using C. elegans as a model system is as vibrant as ever, and we have created new tools for community curation in response to the ever-increasing volume and complexity of data. To better allow users to navigate their way through these data, we have made a number of improvements to our main website, including new tools for browsing genomic features and ontology annotations. Finally, we have developed a new portal for parasitic worm genomes. WormBase ParaSite (parasite.wormbase.org) contains all publicly available nematode and platyhelminth annotated genome sequences, and is designed specifically to support helminth genomic research

Maternal High Fat Diet Is Associated with Decreased Plasma n–3 Fatty Acids and Fetal Hepatic Apoptosis in Nonhuman Primates

To begin to understand the contributions of maternal obesity and over-nutrition to human development and the early origins of obesity, we utilized a non-human primate model to investigate the effects of maternal high-fat feeding and obesity on breast milk, maternal and fetal plasma fatty acid composition and fetal hepatic development. While the high-fat diet (HFD) contained equivalent levels of n-3 fatty acids (FA's) and higher levels of n-6 FA's than the control diet (CTR), we found significant decreases in docosahexaenoic acid (DHA) and total n-3 FA's in HFD maternal and fetal plasma. Furthermore, the HFD fetal plasma n-6∶n-3 ratio was elevated and was significantly correlated to the maternal plasma n-6∶n-3 ratio and maternal hyperinsulinemia. Hepatic apoptosis was also increased in the HFD fetal liver. Switching HFD females to a CTR diet during a subsequent pregnancy normalized fetal DHA, n-3 FA's and fetal hepatic apoptosis to CTR levels. Breast milk from HFD dams contained lower levels of eicosopentanoic acid (EPA) and DHA and lower levels of total protein than CTR breast milk. This study links chronic maternal consumption of a HFD with fetal hepatic apoptosis and suggests that a potentially pathological maternal fatty acid milieu is replicated in the developing fetal circulation in the nonhuman primate

Feeding Induced by Cannabinoids Is Mediated Independently of the Melanocortin System

Cannabinoids, the active components of marijuana, stimulate appetite, and cannabinoid receptor-1 (CB1-R) antagonists suppress appetite and promote weight loss. Little is known about how CB1-R antagonists affect the central neurocircuitry, specifically the melanocortin system that regulates energy balance

Plxdc2 Is a Mitogen for Neural Progenitors

The development of different brain regions involves the coordinated control of proliferation and cell fate specification along and across the neuraxis. Here, we identify Plxdc2 as a novel regulator of these processes, using in ovo electroporation and in vitro cultures of mammalian cells. Plxdc2 is a type I transmembrane protein with some homology to nidogen and to plexins. It is expressed in a highly discrete and dynamic pattern in the developing nervous system, with prominent expression in various patterning centres. In the chick neural tube, where Plxdc2 expression parallels that seen in the mouse, misexpression of Plxdc2 increases proliferation and alters patterns of neurogenesis, resulting in neural tube thickening at early stages. Expression of the Plxdc2 extracellular domain alone, which can be cleaved and shed in vivo, is sufficient for this activity, demonstrating a cell non-autonomous function. Induction of proliferation is also observed in cultured embryonic neuroepithelial cells (ENCs) derived from E9.5 mouse neural tube, which express a Plxdc2-binding activity. These experiments uncover a direct molecular activity of Plxdc2 in the control of proliferation, of relevance in understanding the role of this protein in various cancers, where its expression has been shown to be altered. They also implicate Plxdc2 as a novel component of the network of signalling molecules known to coordinate proliferation and differentiation in the developing nervous system

Alliance of Genome Resources Portal: unified model organism research platform

The Alliance of Genome Resources (Alliance) is a consortium of the major model organism databases and the Gene Ontology that is guided by the vision of facilitating exploration of related genes in human and well-studied model organisms by providing a highly integrated and comprehensive platform that enables researchers to leverage the extensive body of genetic and genomic studies in these organisms. Initiated in 2016, the Alliance is building a central portal (www.alliancegenome.org) for access to data for the primary model organisms along with gene ontology data and human data. All data types represented in the Alliance portal (e.g. genomic data and phenotype descriptions) have common data models and workflows for curation. All data are open and freely available via a variety of mechanisms. Long-term plans for the Alliance project include a focus on coverage of additional model organisms including those without dedicated curation communities, and the inclusion of new data types with a particular focus on providing data and tools for the non-model-organism researcher that support enhanced discovery about human health and disease. Here we review current progress and present immediate plans for this new bioinformatics resource

Alliance of Genome Resources Portal: unified model organism research platform

The Alliance of Genome Resources (Alliance) is a consortium of the major model organism databases and the Gene Ontology that is guided by the vision of facilitating exploration of related genes in human and well-studied model organisms by providing a highly integrated and comprehensive platform that enables researchers to leverage the extensive body of genetic and genomic studies in these organisms. Initiated in 2016, the Alliance is building a central portal (www.alliancegenome.org) for access to data for the primary model organisms along with gene ontology data and human data. All data types represented in the Alliance portal (e.g. genomic data and phenotype descriptions) have common data models and workflows for curation. All data are open and freely available via a variety of mechanisms. Long-term plans for the Alliance project include a focus on coverage of additional model organisms including those without dedicated curation communities, and the inclusion of new data types with a particular focus on providing data and tools for the non-model-organism researcher that support enhanced discovery about human health and disease. Here we review current progress and present immediate plans for this new bioinformatics resource