Regulation of AMPA-type glutamate receptor homolog GLR-1 by ERAD ubiquitin ligases in C. elegans

Endoplasmic reticulum-associated degradation (ERAD) maintains cellular health by removing misfolded proteins from the endoplasmic reticulum (ER). ERAD is ubiquitin-dependent, and ubiquitination of target proteins can be catalyzed by ER-resident E3 ubiquitin ligases. In C. elegans, genes for three putative ERAD E3 ubiquitin ligases have been identified: hrd-1, hrdl-1, and marc-6 (HRD-1, GP78/AMFR, and MARCH-6 in mammalian systems). In C. elegans, these three genes cooperate to maintain the overall health of animals during ER stress. We are testing the roles of hrd-1, hrdl-1, and marc-6 in the neurons of C. elegans. GLR-1 is a glutamate receptor that is expressed in a subset of interneurons in C. elegans. It is homologous to human AMPA-type glutamate receptors, which are central for the processes of learning and memory. GLR-1 that is tagged with GFP (GLR-1::GFP) recapitulates normal biochemical GLR-1 function and allows observation of its abundance and localization in live animals. Animals harboring mutations in the ERAD E3 ligases hrd-1 and hrdl-1 have increased GLR-1::GFP abundance compared to wild-type animals. hrd-1 and hrdl-1 mutants also show defects in GLR-1::GFP localization. Double mutant analysis suggests that hrdl-1 and hrd-1 do not act redundantly, but could act in the same pathway. We are currently testing how a mutation in marc-6 affects GLR-1::GFP. Future experiments will focus on determining the mechanism(s) by which GLR-1 is selected as a substrate by the ERAD E3 ligases and their associated E2 ligases

A colorimetric competitive displacement assay for the evaluation of catalytic peptides

An assay based on competitive dye displacement was adapted to detect the formation of aldol product in crude reaction mixtures, and was used to evaluate minimal peptide aldol catalysts.</p

Regulation of the AMPA glutamate receptor homolog GLR-1 at the endoplasmic reticulum in C. elegans.

In C. elegans, the glutamate receptor GLR-1 functions in the nervous system to decode environmental stimuli and sensory experiences, and to regulate locomotion and the formation of long-term memory. C. elegans GLR-1 is homologous to mammalian glutamate receptors, and we can use this simple organism as a system to better understand the life cycle of human receptors (1). Because GLR-1 is a membrane protein, it is first assembled in the interior of a neuron, and then it is transported to the membrane at the surface of the cell so that it can receive chemical signals (glutamate) from the environment. Currently, many of the detailed cellular mechanisms that regulate the abundance of GLR-1 after it has been exported to the cell surface are known (2, 3). However, it is less clear how the abundance of GLR-1 is regulated in the interior of the cell prior to being transported to the cell surface. Before GLR-1 is exported to the cell surface it must be properly folded into its active conformation at the endoplasmic reticulum (ER). Here we investigate the role of three E3-ubiquitin ligases that function in endoplasmic reticulum associated degradation (ERAD) HRD-1, HRDL-1, and MARC-6. Using fluorescence microscopy HRDL-1 depleted C. elegans display wide patches of GLR-1::GFP suggesting accumulation of the protein at the ER. We also employ Western blotting to determine the relative concentrations of GLR-1 in the absence of E3-ubiquitin ligases. Our research suggests that the depletion of HRDL-1 causes accumulation of GLR-1

Airborne radar sounding evidence for deformable sediments and outcropping bedrock beneath Thwaites Glacier, West Antarctica

The geologic and morphologic records of prior ice sheet configurations show evidence of rapid, back-stepping, meltwater intensive retreats. However, the potential for such a retreat in a contemporary glacier depends on the lithology of the current ice sheet bed, which lies beneath kilometers of ice, making its physical properties difficult to constrain. We use radar sounding and marine bathymetry data to compare the bed configuration of Thwaites Glacier to the bed of paleo-Pine Island Glacier. Using observed and modeled radar scattering, we show that the tributaries and upper trunk of Thwaites Glacier are underlain by ice flow-aligned bedforms consistent with deformable sediment and that the lower trunk is grounded on a region of high bed roughness consistent with outcropping bedrock. This is the same configuration as paleo-Pine Island Glacier during its retreat across the inner continental shelf

Experimental and Numerical Analysis of Membrane-Patterned Meta-Materials

ABSTRACT Meta-materials show unconventional properties by virtue of their construction which normally includes physicallyperiodic formations. Various responses of these materials manifest frequencydependent occurrences of significantlyenhanced and significantly-attenuated values, thus facilitating a wealth of design possibilities. The analysis of these structures presents non-trivial challenges, hence only very simple types are presently under analytical study. In this paper, a formation which includes patterned membrane fillings is explored experimentally and numerically to see if and how well such a construction may be utilized for metamaterial applications. AKIF DUNDAR Advanced Composites an

Relative contractile motion of the rings in a switchable palindromic [3]rotaxane in aqueous solution driven by radical-pairing interactions

Artificial muscles are an essential component for the development of next-generation prosthetic devices, minimally invasive surgical tools, and robotics. This communication describes the design, synthesis, and characterisation of a mechanically interlocked molecule (MIM), capable of switchable and reversible linear molecular motion in aqueous solution that mimics muscular contraction and extension. Compatibility with aqueous solution was achieved in the doubly bistable palindromic [3]rotaxane design by using radical-based molecular recognition as the driving force to induce switching.National Institute of General Medical Sciences (U.S.) (Award F32GM105403)American Society for Engineering Education. National Defense Science and Engineering Graduate Fellowshi

Tradespace and Affordability – Phase 2

MOTIVATION AND CONTEXT: One of the key elements of the SERC’s research strategy is transforming the practice of systems engineering – “SE Transformation.” The Grand Challenge goal for SE Transformation is to transform the DoD community’s current systems engineering and management methods, processes, and tools (MPTs) and practices away from sequential, single stovepipe system, hardware-first, outside-in, document-driven, point-solution, acquisition-oriented approaches; and toward concurrent, portfolio and enterprise-oriented, hardware-software-human engineered, balanced outside-in and inside-out, model-driven, set-based, full life cycle approaches.This material is based upon work supported, in whole or in part, by the U.S. Department of Defense through the Office of the Assistant Secretary of Defense for Research and Engineering (ASD(R&E)) under Contract H98230-08- D-0171 (Task Order 0031, RT 046).This material is based upon work supported, in whole or in part, by the U.S. Department of Defense through the Office of the Assistant Secretary of Defense for Research and Engineering (ASD(R&E)) under Contract H98230-08- D-0171 (Task Order 0031, RT 046)

System Qualities Ontology, Tradespace and Affordability (SQOTA) Project Phase 5

Motivation and Context: One of the key elements of the SERC's research strategy is transforming the practice of systems engineering and associated management practices- "SE and Management Transformation (SEMT)." The Grand Challenge goal for SEMT is to transform the DoD community 's current systems engineering and management methods, processes, and tools (MPTs) and practices away from sequential, single stovepipe system, hardware-first ,document-driven, point- solution, acquisition-oriented approaches; and toward concurrent, portfolio and enterprise-oriented, hardware-software-human engineered, model-driven, set-based, full life cycle approaches.This material is based upon work supported, in whole or in part, by the U.S. Department of Defense through the Office of the Assistant Secretary of Defense for Research and Engineering (ASD(R&E)) under Contract H98230-08-D-0171 and HQ0034-13-D-0004 (TO 0060).This material is based upon work supported, in whole or in part, by the U.S. Department of Defense through the Office of the Assistant Secretary of Defense for Research and Engineering (ASD(R&E)) under Contract H98230-08-D-0171 and HQ0034-13-D-0004 (TO 0060)

Biofilter aquaponic system for nutrients removal from fresh market wastewater

Aquaponics is a significant wastewater treatment system which refers to the combination of conventional aquaculture (raising aquatic organism) with hydroponics (cultivating plants in water) in a symbiotic environment. This system has a high ability in removing nutrients compared to conventional methods because it is a natural and environmentally friendly system (aquaponics). The current chapter aimed to review the possible application of aquaponics system to treat fresh market wastewater with the intention to highlight the mechanism of phytoremediation occurs in aquaponic system. The literature revealed that aquaponic system was able to remove nutrients in terms of nitrogen and phosphorus

Tradespace and Affordability – Phase 1

One of the key elements of the SERC’s research strategy is transforming the practice of systems engineering – “SE Transformation.” The Grand Challenge goal for SE Transformation is to transform the DoD community’s current systems engineering and management methods, processes, and tools (MPTs) and practices away from sequential, single stovepipe system, hardware-first, outside-in, document-driven, point-solution, acquisition-oriented approaches; and toward concurrent, portfolio and enterprise-oriented, hardware-software-human engineered, balanced outside-in and inside-out, model-driven, set-based, full life cycle approaches.This material is based upon work supported, in whole or in part, by the U.S. Department of Defense through the Office of the Assistant Secretary of Defense for Research and Engineering (ASD(R&E)) under Contract H98230-08- D-0171 (Task Order 0031, RT 046).This material is based upon work supported, in whole or in part, by the U.S. Department of Defense through the Office of the Assistant Secretary of Defense for Research and Engineering (ASD(R&E)) under Contract H98230-08- D-0171 (Task Order 0031, RT 046)