The Glucagon Receptor Is Required for the Adaptive Metabolic Response to Fasting

SummaryGlucagon receptor (Gcgr) signaling maintains hepatic glucose production during the fasting state; however, the importance of the Gcgr for lipid metabolism is unclear. We show here that fasted Gcgr−/− mice exhibit a significant increase in hepatic triglyceride secretion and fasting increases fatty acid oxidation (FAO) in wild-type (WT) but not in Gcgr−/− mice. Moreover fasting upregulated the expression of FAO-related hepatic mRNA transcripts in Gcgr+/+ but not in Gcgr−/− mice. Exogenous glucagon administration reduced plasma triglycerides in WT mice, inhibited TG synthesis and secretion, and stimulated FA beta oxidation in Gcgr+/+ hepatocytes. The actions of glucagon on TG synthesis and FAO were abolished in PPARα−/− hepatocytes. These findings demonstrate that the Gcgr receptor is required for control of lipid metabolism during the adaptive metabolic response to fasting

Cost effectiveness of a cultural physical activity intervention to reduce blood pressure among Native Hawaiians with hypertension

Objective: The aim of this study was to calculate the costs and assess whether a culturally grounded physical activity intervention offered through community-based organizations is cost effective in reducing blood pressure among Native Hawaiian adults with hypertension. Methods: Six community-based organizations in Hawai'i completed a randomized controlled trial between 2015 and 2019. Overall, 263 Native Hawaiian adults with uncontrolled hypertension (≥ 140 mmHg systolic, ≥ 90 mmHg diastolic) were randomized to either a 12-month intervention group of hula (traditional Hawaiian dance) lessons and self-regulation classes, or to an education-only waitlist control group. The primary outcome was change in systolic blood pressure collected at baseline and 3, 6, and 12 months for the intervention compared with the control group. Incremental cost-effectiveness ratios (ICERs) were calculated for primary and secondary outcomes. Non-parametric bootstrapping and sensitivity analyses evaluated uncertainty in parameters and outcomes. Results: The mean intervention cost was US$361/person, and the 6-month ICER was US$103/mmHg reduction in systolic blood pressure and US$95/mmHg in diastolic blood pressure. At 12 months, the intervention group maintained reductions in blood pressure, which exceeded reductions for usual care based on blood pressure outcomes. The change in blood pressure at 12 months resulted in ICERs of US$100/mmHg reduction in systolic blood pressure and US$93/mmHg in diastolic blood pressure. Sensitivity analyses suggested that at the estimated intervention cost, the probability that the program would lower systolic blood pressure by 5 mmHg was 67 and 2.5% at 6 and 12 months, respectively. Conclusion: The 6-month Ola Hou program may be cost effective for low-resource community-based organizations. Maintenance of blood pressure reductions at 6 and 12 months in the intervention group contributed to potential cost effectiveness. Future studies should further evaluate the cost effectiveness of indigenous physical activity programs in similar settings and by modeling lifetime costs and quality-adjusted life-years. Trial registration number: NCT02620709.Sociolog

Environmental and biological controls on Mg and Li in deep-sea scleractinian corals

Author Posting. © The Author(s), 2010. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Earth and Planetary Science Letters 300 (2010): 215-225, doi:10.1016/j.epsl.2010.09.029.Deep-sea scleractinian corals precipitate aragonite skeletons that provide valuable archives of past ocean conditions. During calcification biological mediation causes variability in trace metal incorporation and isotopic ratios of the aragonite such that signals caused by environmental controls can be overwhelmed. This complicates the interpretation of geochemical proxies used for paleo-reconstructions. In this study we examine the environmental controls on the Mg/Li ratio of 34 individuals from seven genera of deep-sea scleractinian corals: Desmophyllum, Balanophyllia, Caryophyllia, Enallopsammia, Flabellum, Trochocyanthus, and Lophelia. In addition we examine the distributions of Mg and Li in Desmophyllum and Balanophyllia using laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS). Both Mg/Ca and Li/Ca ratios increased by more than a factor of 2 in the center of calcification regions compared to the outer, fibrous regions of the coral skeleton. As a result, replicate ~10 mg subsamples of coral show less variability in the Mg/Li ratio than Mg/Ca. Microscale Mg and Li results are consistent with Rayleigh-type incorporation of trace metals with additional processes dominating composition within centers of calcification. Comparison of Mg/Li to seawater properties near the site of collection shows that the ratio is not controlled by either carbonate ion or salinity. It appears that temperature is the major control on the Mg/Li ratio. For all 34 samples the temperature correlation (R2=0.62) is significantly better than for Mg/Ca (R2=0.06). For corals of the family Caryophyllidae the R2 value increases to 0.82 with the exclusion of one sample that was observed to have an altered, chalky texture. Despite this excellent correlation the scatter in the data suggests that the Mg/Li ratio of deep-sea corals cannot be used to reconstruct temperature to better than approximately ±1.6°C without better temperature control and additional calibration points on modern coral samples.Financial Support was provided by the USGS WHOI Co-operative agreement, NSF-ANT grant numbers 0636787 and 80295700 and the WHOI Ocean Life Institute. David Case was supported by the WHOI Summer Student Fellowship

Coalescing: A comparative case study of antecedents to cohesion in child welfare teaming

Human service organizations increasingly rely upon teams to address complex human problems. Research suggests that workplace teams benefit workers, improve work processes, and yield improved work products and outcomes. However, most child welfare workers perform their jobs based on a traditional practice model - with one caseworker assigned to a family and each worker carrying a caseload of several families. The literature implicates this traditional casework model in workplace conditions (e.g. isolation, burnout and vicarious trauma) linked to diminished worker well-being and increased staff turnover. This comparative case study draws from systems theory and extends Hackman's model of team effectiveness to the case of child welfare units implementing a team-based approach to practice. It explores how workers accustomed to functioning independently coalesce as a team in which members share responsibility for casework tasks and outcomes. Adapting Hackman's model, the study posits five cohesion-enabling conditions: Real team; compelling direction; enabling structure; organizational support; and expert coaching. Capturing multiple perspectives across four teaming units, the study conceptualizes the five enabling conditions as antecedents to cohesion. Thirty-three respondents - including frontline child welfare supervisors and workers, administrative supervisors, and expert coaches - participated in group and individual interviews. Interview questions explored the relationship between respondents' perceptions regarding the presence or absence of the five enabling conditions, and two indicators of team cohesion - worker well-being and team efficacy. Study results offer preliminary support for the five enabling conditions as antecedents to team cohesion. When enabled, these conditions empower individual workers to create teams that encourage mutual support, shared expertise, and peer-learning. Given the history of child welfare case practice, dating back to the mid-20th century, a team-based approach presents an innovative idea with potential benefits for teaming units; e.g., improved worker well-being and increased team efficacy. Preliminary study findings suggest implications for practice and directions for future research

Public engagement in forest governance in Canada: whose values are being represented anyway?

Researchers and advocates have long argued that on-going engagement by broad segments of the public can help make forests and forest-based communities more sustainable and decisions more enduring. In Canada, public engagement in sustainable forest management has primarily taken one of two approaches – advisory forums through forest-sector advisory committees (FACs) and direct decision-making authority through community forest boards (CFBs). The purpose of this paper is to compare these two approaches by focusing on who participates and the values participants bring to their deliberations. We conducted a national survey of FACs and CFBs, involving 402 participants. Results showed that both models favoured well-educated, Caucasian men and fell short on the representation of women and Indigenous peoples. Additionally, despite different levels of authority in relation to forest management decisions, participants in CFBs and FACs shared similar forest values. Hence, we conclude neither model of forest governance encourages participation from a diverse public. Our findings suggest the need to find new ways of recruiting diverse participants and to investigate more deeply whether local and extra-local pressures and power dynamics shape these processes. Such information can inform the establishment of more robust institutions for decision making in support of sustainable forest management.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Release from meiotic arrest in ascidian eggs requires the activity of two phosphatases but not CaMKII

International audienceThe fertilising sperm triggers a transient Ca2+ increase that releases eggs from cell cycle arrest in the vast majority of animal eggs. In vertebrate eggs, Erp1, an APC/C-cdc20 inhibitor, links release from metaphase II arrest with the Ca2+ transient and its degradation is triggered by the Ca2+-induced activation of CaMKII. By contrast, many invertebrate groups have mature eggs that arrest at metaphase I, and these species do not possess the CaMKII target Erp1 in their genomes. As a consequence, it is unknown exactly how cell cycle arrest at metaphase I is achieved and how the fertilisation Ca2+ transient overcomes the arrest in the vast majority of animal species. Using live-cell imaging with a novel cyclin reporter to study cell cycle arrest and its release in urochordate ascidians, the closest living invertebrate group to the vertebrates, we have identified a new signalling pathway for cell cycle resumption in which CaMKII plays no part. Instead, we find that the Ca2+-activated phosphatase calcineurin (CN) is required for egg activation. Moreover, we demonstrate that parthenogenetic activation of metaphase I-arrested eggs by MEK inhibition, independent of a Ca2+ increase, requires the activity of a second egg phosphatase: PP2A. Furthermore, PP2A activity, together with CN, is required for normal egg activation during fertilisation. As ascidians are a sister group of the vertebrates, we discuss these findings in relation to cell cycle arrest and egg activation in chordates