The arginine stimulation test: Timing of peak is not a helpful parameter in the diagnosis of growth hormone deficiency

Background: A typical peak timing in the glucagon stimulation test has been reported as an indication of growth hormone (GH) deficiency. Other stimulation tests have not been evaluated.Objective: To evaluate the clinical usefulness of peak timing in the arginine stimulation test (AST) for growth hormone deficiency.Methods: Retrospective review of 199 ASTs from one center. Outcomes included correlation of peak times with (a) frequency of deficient peak; (b) growth velocity standard deviation scores (GVSDSs); (c) other evidence of pituitary pathology; (d) results of confirmatory clonidine test; and (e) response to GH treatment.Results: The peak in 83/109 (76.14%) sufficient tests occurred at typical times vs. 45/72 (62.5%) deficient tests (p < 0.05). GVSDS on GH treatment was greater among patients with typical timing in the AST compared with atypical timing (2.67 +/- 0.59 vs. 0.46 +/- 1.17, p = 0.021). No other variable correlated significantly with AST timing.Conclusions: Timing of peak in the AST is not a clinically useful parameter

Cyclin C Regulated Oxidative Stress Responsive Transcriptome in Mus Musculus Embryonic Fibroblasts

The transcriptional changes that occur in response to oxidative stress help direct the decision to maintain cell viability or enter a cell death pathway. Cyclin C-Cdk8 is a conserved kinase that associates with the RNA polymerase II Mediator complex that stimulates or represses transcription depending on the locus. In response to oxidative stress, cyclin C, but not Cdk8, displays partial translocation into the cytoplasm. These findings open the possibility that cyclin C relocalization is a regulatory mechanism governing oxidative stress-induced transcriptional changes. In the present study, the cyclin C-dependent transcriptome was determined and compared to transcriptional changes occurring in oxidatively stresse

Snf1 Dependent Destruction of Med13 is Required for Programmed Cell Death Following Oxidative Stress in Yeast

All eukaryotic cells, when faced with unfavorable environmental conditions, have to decide whether to mount a survival or cell death response. The conserved cyclin C and its kinase partner Cdk8 play a key role in this decision. Both are members of the Cdk8 kinase module that, along with Med12 and Med13, associate with the core mediator complex of RNA polymerase II. In S. cerevisiae, oxidative stress triggers Med13 destruction1, which thereafter releases cyclin Ci nto the cytoplasm. Cytoplasmic cyclin C associates with mitochondria where it induces hyper-fragmentation and programmed cell death2. This suggests a model in which oxidative stress mediated destruction o fMed13 represents a key molecular switch which commits the cell to programmed cell death. Thus it is important to decipher the precise molecular mechanisms that control Med13 destruction following exposure to oxidative stress

The Role of MAPK and SCF in the Destruction of Med13 in Cyclin C Mediated Cell Death

In response to stress, the yeast1 and mammalian2 cyclin C translocate from the nucleus to the cytoplasm, where it associates with the GTPase Drp1/Dnm1 to drive mitochondrial fragmentation and apoptosis. Therefore, the decision to release cyclin C represents a key life or death decision. In unstressed cells, the cyclin C‐Cdk8 kinase regulates transcription by associating with the Mediator of RNA polymerase II. We previously reported that the Mediator component Med13 anchors cyclin C in the nucleus3. Loss of Med13 function leads to constitutive cytoplasmic localization of cyclin C, resulting in fragmented mitochondria, hypersensitivity to stress and mitochondrial dysfunction due to loss of mtDNA. Recently we showed that this molecular switch operates in a two-step process

Snf1 cooperates with the CWI MAPK pathway to mediate the degradation of Med13 following oxidative stress

Eukaryotic cells, when faced with unfavorable environmental conditions, mount either pro-survival or pro-death programs. The conserved cyclin C-Cdk8 kinase plays a key role in this decision. Both are members of the Cdk8 kinase module that, along with Med12 and Med13, associate with the core Mediator complex of RNA polymerase II. In Saccharomyces cerevisiae, oxidative stress triggers Med13 destruction, which releases cyclin C into the cytoplasm to promote mitochondrial fission and programmed cell death. The SCFGrr1 ubiquitin ligase mediates Med13 degradation dependent on the cell wall integrity pathway, MAPK Slt2. Here we show that the AMP kinase Snf1 activates a second SCFGrr1 responsive degron in Med13. Deletion of Snf1 resulted in nuclear retention of cyclin C and failure to induce mitochondrial fragmentation. This degron was able to confer oxidative-stress-induced destruction when fused to a heterologous protein in a Snf1 dependent manner. Although snf1∆ mutants failed to destroy Med13, deleting the degron did not prevent destruction. These results indicate that the control of Med13 degradation following H2O2 stress is complex, being controlled simultaneously by CWI and MAPK pathways

Exploring students' understandings and perspectives of place : the case of place in a Skagit Valley school

Drawing upon notions of Aldo Leopold’s Land Ethic and Robin Wall Kimmerer’s Becoming Naturalized to Place, this dissertation explored how students revealed their perspectives and understandings of place at their school in the Skagit Valley, Washington State. This study employed an ethnographic case study approach guided by phenomenographic principles and informed by Indigenous perspectives to document students’ stories of place. Data were collected through an introductory questionnaire and stationary and walking interviews. Findings revealed that the students’ understandings and perspectives of place were situated within the following themes: Place as Action; Place as People; Place as Social Arena; Place as Nature; Place as Journey and Time; and Place as Displacement. This study contributes to the current research on Place and related phenomena due to the unique context of the school and the individual students’ stories which give voice to diverse and distinctive narratives of place.Education, Faculty ofCurriculum and Pedagogy (EDCP), Department ofGraduat

Time to menarche and final height after histrelin implant treatment for central precocious puberty

Objective To compare final height, change in body mass index (BMI), and time from end of treatment until menarche in girls with central precocious puberty treated with the histrelin implant versus depot gonadotropin releasing hormone agonist injections.Study design Chart review, interview, and final height measurements of 2 groups of girls with central precocious puberty; triptorelin depot (TD) group: 23 girls were treated from age 8.4 +/- 0.3 with monthly injections of TD, for 26.7 +/- 2.5 months; histrelin implant group: 11 girls were treated from age 8.7 +/- 0.3 years for 28.4 +/- 3.7 months, of whom 9 initially received monthly TD injections for 1.5-39 months. Final height, BMI (pretreatment vs recent), and time between either implant removal or last injection to menarche were compared.Results Time between removal of implant or last injection and menarche was 9.3 +/- 1.5 (histrelin implant group) versus 16.1 +/- 1.7 (TD group) months (P = .02). Predicted height at implant insertion was 156.8 +/- 2.6 cm, and final height was 161.1 +/- 2.0 cm (not significant [NS]). Predicted height for TD was 155.2 +/- 1.9 cm and final height was 157.9 +/- 1.7 cm (NS). Change from onset of treatment to final BMI-SDS for histrelin implant was -0.41 +/- 0.3, and for TD was -0.03 +/- 0.2 (NS).Conclusions Menarche occurred sooner after implant removal. There was no difference in final height or BMI outcomes between the 2 treatment modalities

Acts of Reading and Gathering in Place: Our Stories so Far…

This article maps the ongoing journey of our reading group’s investigation of outdoor and environmental learning and early childhood education as a form of conceptual and practical activism. The journey is presented as three ‘streams’ exemplifying the fluid, non-linear ways in which the reading group and our ideas appeared. Place, Environmental Education, and Activism are currents guiding our emerging understandings of the relations between activism, stories, local and global communities, and the importance of education happening outdoors. Our monthly gatherings act as confluences of these topics via readings of local and international papers, and contributions from our members, a diverse set of local and international academics, students, teachers and community organizations. We offer a glimpse into our learning, our dynamic journey, and our discoveries. We invite readers to enter these conversational streams, and to consider how a local outdoor reading group might become a form of activism in their own international contexts