The Metabolic Transitions Regulated by the Estrogen-related Receptor (ERR) in Drosophila melanogaster

In multicellular organism, bioenergetic metabolism is strictly regulated toward efficient generation of ATP. However, in certain situations, such as in limiting oxygen or in the rapidly proliferating system like growing juvenile or cancer cells, organisms apply the metabolic strategy that favors the production of biomass (e.g., nucleotides, amino acids, and lipids) over efficiency of ATP generation. The conserved estrogen-related receptors (ERRs) are master regulators in controlling metabolic homeostasis, and good candidates for mediating the metabolic transition induced by hypoxia and development. First, we investigate how dERR influences hypoxic adaptation in Drosophila melanogaster. We find that dERR is required for a competent hypoxic response alone, or together with hypoxia inducible factor (HIF), which is the main transcription factor modulating the hypoxic adaptation. We show that dERR binds to dHIFα and participates in the HIF-dependent transcriptional program in hypoxia. In addition, dERR acts in the absence of dHIFα in hypoxia and a significant portion of HIF-independent transcriptional responses can be attributed to dERR actions, including up-regulation of glycolytic transcripts. These results indicate that competent hypoxic responses arise from complex interactions between HIF-dependent and -independent mechanisms, and that dERR plays a central role in both of these programs. Secondly, we examine how dERR modulates metabolic transition toward the fatty acid oxidation at late L3 larva stage. We show that dERR is essential for the expression of an uncharacterized long-chain-fatty-acid acyl-CoA synthetase, CG4500, which is subject to induction by starvation. Furthermore, late L3 larvae of dERR mutants exhibit altered lipid profiles with elevated medium-chain and long-chain fatty acids. Together, with the previous finding that ERR directs an early switch toward glycolysis in the embryo, our studies indicate that ERR is a master regulator of programmed metabolic shifts through Drosophila development

HIF- and Non-HIF-Regulated Hypoxic Responses Require the Estrogen-Related Receptor in Drosophila melanogaster

Low-oxygen tolerance is supported by an adaptive response that includes a coordinate shift in metabolism and the activation of a transcriptional program that is driven by the hypoxia-inducible factor (HIF) pathway. The precise contribution of HIF-1a in the adaptive response, however, has not been determined. Here, we investigate how HIF influences hypoxic adaptation throughout Drosophila melanogaster development. We find that hypoxic-induced transcriptional changes are comprised of HIF-dependent and HIF-independent pathways that are distinct and separable. We show that normoxic set-points of carbohydrate metabolites are significantly altered in sima mutants and that these animals are unable to mobilize glycogen in hypoxia. Furthermore, we find that the estrogen-related receptor (dERR), which is a global regulator of aerobic glycolysis in larvae, is required for a competent hypoxic response. dERR binds to dHIFa and participates in the HIF-dependent transcriptional program in hypoxia. In addition, dERR acts in the absence of dHIFa in hypoxia and a significant portion of HIF-independent transcriptional responses can be attributed to dERR actions, including upregulation of glycolytic transcripts. These results indicate that competent hypoxic responses arise from complex interactions between HIF-dependent and -independent mechanisms, and that dERR plays a central role in both of these programs

Not All Explanations Predict Satisfactorily, and Not All Good Predictions Explain

This short comment on Epstein's (2008) paper and on the response by Thompson and Derr argues that the symmetry between explanation and prediction cannot satisfactorily be discussed without making clear what prediction means - depending on which connotations the authors have with 'prediction' their arguments can or cannot be accepted.[No keywords]

Electrostatically controlled heat shutter

A heat transfer assembly for conducting thermal energy is described. The assembly includes a hermetically sealed container enclosing a quantity of inert gas such as nitrogen. Two opposed walls of the container have high thermal conducting characteristics while the connecting walls have low thermal conducting characteristics. Electrodes are positioned adjacent to the high thermal conducing walls and biased relative to the conducting walls to a corona potential for creating an ionic gas wind which must contact the conducting walls to be neutralized. The contact of the gas molecules permits the maximum thermal energy transfer between the walls. Baffles can be positioned adjacent to the electrodes to regulate gas flow between the high thermal conducting surfaces

Heated bimetal strip prevents damage of bearings by vibration

Strip of bimetal is shaped as split ring; when properly fabricated from thin sheet, width of strip increases when it is heated. When width of strip increases, outer races are forced apart, thus pressing balls tightly against inner races. Strip applies axial load to bearing, amount of load being function of temperature to which strip is heated

On uniform continuous dependence of solution of Cauchy problem on a parameter

Suppose that an $n$-dimensional Cauchy problem \frac{dx}{dt}=f(t,x,\mu) (t \in I, \mu \in M), x(t_0)=x^0 satisfies the conditions that guarantee existence, uniqueness and continuous dependence of solution x(t,t_0,\mu) on parameter \mu in an open set M. We show that if one additionally requires that family \{f(t,x,\cdot)\}_{(t,x)} is equicontinuous, then the dependence of solution x(t,t_0,\mu) on parameter \mu \in M is uniformly continuous. An analogous result for a linear n \times n-dimensional Cauchy problem \frac{dX}{dt}=A(t,\mu)X+\Phi(t,\mu) (t \in I, \mu \in M), X(t_0,\mu)=X^0(\mu) is valid under the assumption that the integrals \int_I\|A(t,\mu_1)-A(t,\mu_2)\|dt and \int_I \|\Phi(t,\mu_1)-\Phi(t,\mu_2)\|dt can be made smaller than any given constant (uniformly with respect to \mu_1, \mu_2 \in M) provided that \|\mu_1-\mu_2\| is sufficiently small

Disconjugacy of a second order linear differential equation and periodic solutions

The present paper is devoted to a new criterion for disconjugacy of a second order linear differential equation. Unlike most of the classical sufficient conditions for disconjugacy, our criterion does not involve assumptions on the smallness of the coefficients of the equation. We compare our criterion with several known criteria for disconjugacy, for which we provide detailed proofs, and discuss the applications of the property of disconjugacy to the problem of factorization of linear ordinary differential operators, and to the proof of the generalized Rolle's theorem. The paper is self-contained, and may serve as a brief introduction to theory of disconjugacy of a second order linear differential equation

Meeting Minutes, October 15th, 2019

Agenda: In Attendance; Call to order, introduction to site, introductions, approval of agenda - McKean; Approval of meeting minutes from March - McKean, Boatner; March minutes approved.; Update on various items-Sheley; Chetco Bar Fire - Derr; National Wildfire Institute\u27s Call to Action document - Derr; NAFSR: Workforce Capacity Study and Letter to Secretary Perdue - Derr, Cooper, & Berry; Various items, Cooper; Report on Trails Program; Higgins Ridge Project; Miss Montana; 1939 Experiment Book; Smokejumper collections status at National Museum of Forest Service History; Annual Giving - Bina; Motion made to pursue the Keep-the Flame Legacy Jump List program; Facebook update - Berry; Treasurer\u27s Report - Berry (Russ by phone); Investment Committee Report - Packard & Berry; Budget FY 2019-2020 - Lufkin; Motion made and approved to approve the budget; Scholarship Program - Cherry; Website Report - Lufkin; Smokejumper Reunion - Sheley, Boatner; Membership Report - McDaniel; Conflict of Interest Policy Recommendation - Berry; Life Member Policy Recommendation - McKean; Board Member Make Up - Berry; Presenters for upcoming meeting, a concept - McKean; Presidents Items - McKean; Request for special recognition of Lisa Tate; Date for March 2020 meeting in Boise; Agenda Items for Next Meeting