Proline-rich tyrosine kinase 2 mediates gonadotropin-releasing hormone signaling to a specific extracellularly regulated kinase-sensitive transcriptional locus in the luteinizing hormone beta-subunit gene

G protein-coupled receptor regulation of gene transcription primarily occurs through the phosphorylation of transcription factors by MAPKs. This requires transduction of an activating signal via scaffold proteins that can ultimately determine the outcome by binding signaling kinases and adapter proteins with effects on the target transcription factor and locus of activation. By investigating these mechanisms, we have elucidated how pituitary gonadotrope cells decode an input GnRH signal into coherent transcriptional output from the LH β-subunit gene promoter. We show that GnRH activates c-Src and multiple members of the MAPK family, c-Jun NH(2)-terminal kinase 1/2, p38MAPK, and ERK1/2. Using dominant-negative point mutations and chemical inhibitors, we identified that calcium-dependent proline-rich tyrosine kinase 2 specifically acts as a scaffold for a focal adhesion/cytoskeleton-dependent complex comprised of c-Src, Grb2, and mSos that translocates an ERK-activating signal to the nucleus. The locus of action of ERK was specifically mapped to early growth response-1 (Egr-1) DNA binding sites within the LH β-subunit gene proximal promoter, which was also activated by p38MAPK, but not c-Jun NH(2)-terminal kinase 1/2. Egr-1 was confirmed as the transcription factor target of ERK and p38MAPK by blockade of protein expression, transcriptional activity, and DNA binding. We have identified a novel GnRH-activated proline-rich tyrosine kinase 2-dependent ERK-mediated signal transduction pathway that specifically regulates Egr-1 activation of the LH β-subunit proximal gene promoter, and thus provide insight into the molecular mechanisms required for differential regulation of gonadotropin gene expression

The Satellite Cell in Male and Female, Developing and Adult Mouse Muscle: Distinct Stem Cells for Growth and Regeneration

Satellite cells are myogenic cells found between the basal lamina and the sarcolemma of the muscle fibre. Satellite cells are the source of new myofibres; as such, satellite cell transplantation holds promise as a treatment for muscular dystrophies. We have investigated age and sex differences between mouse satellite cells in vitro and assessed the importance of these factors as mediators of donor cell engraftment in an in vivo model of satellite cell transplantation. We found that satellite cell numbers are increased in growing compared to adult and in male compared to female adult mice. We saw no difference in the expression of the myogenic regulatory factors between male and female mice, but distinct profiles were observed according to developmental stage. We show that, in contrast to adult mice, the majority of satellite cells from two week old mice are proliferating to facilitate myofibre growth; however a small proportion of these cells are quiescent and not contributing to this growth programme. Despite observed changes in satellite cell populations, there is no difference in engraftment efficiency either between satellite cells derived from adult or pre-weaned donor mice, male or female donor cells, or between male and female host muscle environments. We suggest there exist two distinct satellite cell populations: one for muscle growth and maintenance and one for muscle regeneration

Sociotechnical agendas: reviewing future directions for energy and climate research

The field of science and technology studies (STS) has introduced and developed a “sociotechnical” perspective that has been taken up by many disciplines and areas of inquiry. The aims and objectives of this study are threefold: to interrogate which sociotechnical concepts or tools from STS are useful at better understanding energy-related social science, to reflect on prominent themes and topics within those approaches, and to identify current research gaps and directions for the future. To do so, the study builds on a companion project, a systematic analysis of 262 articles published from 2009 to mid-2019 that categorized and reviewed sociotechnical perspectives in energy social science. It identifies future research directions by employing the method of “co-creation” based on the reflections of sixteen prominent researchers in the field in late 2019 and early 2020. Drawing from this co-created synthesis, this study first identifies three main areas of sociotechnical perspectives in energy research (sociotechnical systems, policy, and expertise and publics) with 15 topics and 39 subareas. The study then identifies five main themes for the future development of sociotechnical perspectives in energy research: conditions of systematic change; embedded agency; justice, power, identity and politics; imaginaries and discourses; and public engagement and governance. It also points to the recognized need for pluralism and parallax: for research to show greater attention to demographic and geographical diversity; to stronger research designs; to greater theoretical triangulation; and to more transdisciplinary approaches

Obesity, Identity and Community: Leveraging Social Networks for Behavior Change in Public Health

Obesity is a public health problem influenced by behavioral patterns that span an ecological spectrum of individual-level factors, social network factors and environmental factors. Both individual and environmental approaches necessarily include significant influences from social networks, but how and under what conditions social networks influence behavior change is often not clearly mapped out either in the obesity literature or in many intervention designs. In this paper, we provide an analysis of recent empirical work in obesity research that explicates social network influences on eating behaviors. We argue that a relational rather than individualistic view of personhood should help us better understand the content and context of social network relations that inform health behavior choices. We introduce the concept of ‘identity-constitutive affiliations’ as the glue that binds these social relationships together. Finally, we outline the implications for public health ethics in the development of effective interventions to address overweight and obesity, leveraging the content and context of social network ties to reinforce healthy (or alter unhealthy) eating. More complex treatment of positive and negative behaviors stemming from social network connections should lead to more comprehensive theoretical models of health behavior change and more effective public health interventions

Feminist Bioethics Meets Experimental Philosophy: Benefits of Embracing the Qualitative and Experiential

Abstract Experimental philosophers advocate expansion of philosophical methods to include empirical investigation into the concepts used by ordinary people in reasoning and action. We propose also including methods of qualitative social science, which we argue serve both moral and epistemic goals. Philosophical analytical tools applied to interdisciplinary research designs can provide ways to extract rich contextual information from subjects. We argue that this approach has important implications for bioethics; it provides both epistemic and moral reasons to use the experiences and perspectives of diverse populations to better identify underlying concepts as well as to develop effective interventions within particular communities