An education revolution

No abstract available

Unraveling Novel Leptin-Dependent Signaling Pathways in the Basomedial Hypothalamus.

Leptin is secreted by the adipose tissue in proportion to fat stores and acts on the hypothalamus to inhibit appetite and promote energy expenditure. Leptin also regulates glucose homeostasis independently of feeding, and has a permissive action on reproduction. Activation of the leptin receptor (LepRb) initiates a cascade of signaling events, including the phosphorylation of residues on the intracellular domain of LepRb: Tyr985, Tyr1077 and Tyr1138. The ongoing analysis of LepRb signaling mutants in vivo has revealed a crucial role for Tyr1138 in energy homeostasis, while Tyr985 appears to be important for the attenuation of LepRb signaling. However, a number of the molecular mechanisms by which LepRb controls other physiological events, including neuronal firing, reproduction and glucose homeostasis, remain poorly defined. Also unclear are the mechanisms that control leptin regulation of a variety of signals including mTORC1. In this study, we examined the regulation of the mTORC1 pathway in the basomedial hypothalamus, and investigated the specific role of LepRb-Tyr1077 in leptin action in vivo. We found that leptin does not modulate hypothalamic mTORC1 in a uniform manner, but rather controls mTORC1 in opposite directions, in different cell types and brain regions. Indeed, neuronal activation is the main regulator of mTORC1 activity in the hypothalamus in response to metabolic perturbations. We also examined the phenotype of mice mutant for LepRb-Tyr1077 on a normal chow and a high fat diet. LepRbf1077/f1077 (f/f) mice had modestly increased body weight and food intake on both diets. Both, male and female f/f mice had increased adiposity, and mutant females presented larger pancreas and ovaries than controls. Interestingly, we found that LepRb-Tyr1077 seems to be mostly important for the regulation of reproduction and glucose homeostasis given that f/f female mice have delayed or absent estrous cycling together with improved glucose clearance. These results suggest novel pathways by which leptin regulates neuronal firing, reproduction and glycemic control. This information not only extends our understanding of leptin action, but could be crucial as we seek to understand the basis of conditions linking metabolism to reproduction and glucose homeostasis.Ph.D.Molecular and Integrative PhysiologyUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/75887/1/eneidav_1.pd

All the world is our stage: primary pupils never lost in translanguaging

No abstract available

Appropriate Inhibition of Orexigenic Hypothalamic Arcuate Nucleus Neurons Independently of Leptin Receptor/STAT3 Signaling

Leptin directly suppresses the activity of orexigenic neurons in the hypothalamic arcuate nucleus (ARC). We examined c-Fos-like immunoreactivity (CFLIR) as a marker of ARC neuronal activity in db/db mice devoid of the signaling form of the leptin receptor (LRb) and s/s mice that express LRbS1138 [which is defective for STAT3 (signal transducer and activator of transcription) signaling]. Both db/db and s/s animals are hyperphagic and obese. This analysis revealed that CFLIR in agouti related peptide-expressing orexigenic ARC neurons is basally elevated in db/db but not s/s mice. Consistent with these observations, electrophysiologic evaluation of a small number of neurons in s/s animals suggested that leptin appropriately suppresses the frequency of IPSCs on ARC proopiomelanocortin (POMC) neurons that are mediated by the release of GABA from orexigenic ARC neurons. CFLIR in POMC neurons of s/s mice was also increased compared with db/db animals. Thus, these data suggest that, although LRb→STAT3 signaling is crucial for the regulation of feeding, it is not required for the acute or chronic regulation of orexigenic ARC neurons, and the activation of STAT3-mediated transcription by leptin is not required for the appropriate development of leptin responsiveness in these neurons

Loss of Cytokine-STAT5 Signaling in the CNS and Pituitary Gland Alters Energy Balance and Leads to Obesity

Signal transducers and activators of transcription (STATs) are critical components of cytokine signaling pathways. STAT5A and STAT5B (STAT5), the most promiscuous members of this family, are highly expressed in specific populations of hypothalamic neurons in regions known to mediate the actions of cytokines in the regulation of energy balance. To test the hypothesis that STAT5 signaling is essential to energy homeostasis, we used Cre-mediated recombination to delete the Stat5 locus in the CNS. Mutant males and females developed severe obesity with hyperphagia, impaired thermal regulation in response to cold, hyperleptinemia and insulin resistance. Furthermore, central administration of GM-CSF mediated the nuclear accumulation of STAT5 in hypothalamic neurons and reduced food intake in control but not in mutant mice. These results demonstrate that STAT5 mediates energy homeostasis in response to endogenous cytokines such as GM-CSF

Translanguaging has made it to Scottish primary education and it is alive and 'coleando'!

No abstract available

Talk on Minority Languages (& AGM) [Event report]

No abstract available

All the World is Our Stage: Webinar series

This OWRI-funded project celebrates linguistic diversity and reflects on the multilingual, multicultural and superdiverse society represented in Glasgow today. This multilingual performance supports the teaching and learning journey of primary schooling in non-affluent areas of the city. Acknowledging that embedding every community language in the curriculum is not feasible, we specifically focus on creating contexts where the languages spoken at home enjoy the same status as those taught at school. Translanguaging is both design and interaction and as such, pupils work together to choose traditional songs and rhymes and script a multilingual play, which they subsequently perform in a local theatre to main language stakeholders in Scotland, families, MPs, policy makers and also other schools so it can be subsequently emulated. Signposting the pilgrimage towards a lifelong love of languages, childrens’ voices are heard and empowered with the autonomy to design and bring their own project to life

All the World is Our Stage: Primary Pupils Never Lost in Translanguaging

No abstract available

Family language policy at the intersection with the 1+2 approach to language learning in the Scottish education context (keynote)

No abstract available