The role of ECL2 in CGRP receptor activation: a combined modelling and experimental approach

The calcitonin gene-related peptide (CGRP) receptor is a complex of a calcitonin receptor-like receptor (CLR), which is a family B G-protein-coupled receptor (GPCR) and receptor activity modifying protein 1. The role of the second extracellular loop (ECL2) of CLR in binding CGRP and coupling to Gs was investigated using a combination of mutagenesis and modelling. An alanine scan of residues 271–294 of CLR showed that the ability of CGRP to produce cAMP was impaired by point mutations at 13 residues; most of these also impaired the response to adrenomedullin (AM). These data were used to select probable ECL2-modelled conformations that are involved in agonist binding, allowing the identification of the likely contacts between the peptide and receptor. The implications of the most likely structures for receptor activation are discussed.</jats:p

Tradeoffs in Brush Management for Water Yield and Habitat Management in Texas: Twin Buttes Drainage Area and Edwards Aquifer Recharge Zone

With the current population boom, the number of Texas residents will almost double by 2030. With the expected increase in demand for water, the scarcity of water is an urgent issue and research is being conducted to find ways to improve water yield. Rangelands provide the major catchments for both surface reservoirs and aquifers. Brush control as a means of increasing water yields was first studied in the 1970s (Bach and Conner 2000) and a number of studies have reviewed the feasibility of removing brush as a means to increase water yields (Wilcox 2002). For example, a study on the North Concho River watershed (Upper Colorado River Authority, 1998) indicated that removing brush could result in a significant increase in water yield and, in response to this report, the Legislature for the State of Texas appropriated funds to study the feasibility of this practice on eight additional watersheds (Bednarz et al., 2000). The Texas Agricultural Experiment Station sponsored additional studies for two of these eight watersheds (Twin Buttes and Edwards Aquifer) to determine the tradeoff between brush management for increased water yield and wildlife habitat improvement. These two watershed areas are the subjects of this report. Since a significant portion of Texas lands are privately owned, it is important to account for landowners’ willingness to participate in any brush management program, especially when such programs are intended to produce off-site benefits. Landowner participation is generally dependent upon expected economic benefits received (Bach and Conner 2000). In our study, 300 questionnaires were each sent to randomly selected landowners from both the Edwards Aquifer Recharge Zone and the Twin Buttes (Middle and South Concho River) Drainage Area. Names and addresses of rural landowners with tracts of 50 or more acres were compiled with the help of local county appraisal districts. In the questionnaire, survey participants were asked several questions to measure their willingness to participate in different scenarios, as well as the amount of compensation required. This report examines the results of the survey. Of the 300 questionnaires sent to the Edwards Aquifer area, 131 were returned and usable, 50 were returned but unusable, and 119 were never returned. In the Twin Buttes area, 141 questionnaires were returned and usable, 38 were returned but were unusable, and 121 were not returned. This report examines each watershed separately. All survey questions are considered. Results include mean, median, and quartile data, and frequency distributions

Processes Contributing to Resilience of Coastal Wetlands to Sea-Level Rise

The objectives of this study were to identify processes that contribute to resilience of coastal wetlands subject to rising sea levels and to determine whether the relative contribution of these processes varies across different wetland community types. We assessed the resilience of wetlands to sea-level rise along a transitional gradient from tidal freshwater forested wetland (TFFW) to marsh by measuring processes controlling wetland elevation. We found that, over 5 years of measurement, TFFWs were resilient, although some marginally, and oligohaline marshes exhibited robust resilience to sea-level rise. We identified fundamental differences in how resilience is maintained across wetland community types, which have important implications for management activities that aim to restore or conserve resilient systems. We showed that the relative importance of surface and subsurface processes in controlling wetland surface elevation change differed between TFFWs and oligohaline marshes. The marshes had significantly higher rates of surface accretion than the TFFWs, and in the marshes, surface accretion was the primary contributor to elevation change. In contrast, elevation change in TFFWs was more heavily influenced by subsurface processes, such as root zone expansion or compaction, which played an important role in determining resilience of TFFWs to rising sea level. When root zone contributions were removed statistically from comparisons between relative sea-level rise and surface elevation change, sites that previously had elevation rate deficits showed a surplus. Therefore, assessments of wetland resilience that do not include subsurface processes will likely misjudge vulnerability to sea-level rise

Processes Contributing to Resilience of Coastal Wetlands to Sea-Level Rise

The objectives of this study were to identify processes that contribute to resilience of coastal wetlands subject to rising sea levels and to determine whether the relative contribution of these processes varies across different wetland community types. We assessed the resilience of wetlands to sea-level rise along a transitional gradient from tidal freshwater forested wetland (TFFW) to marsh by measuring processes controlling wetland elevation. We found that, over 5 years of measurement, TFFWs were resilient, although some marginally, and oligohaline marshes exhibited robust resilience to sea-level rise. We identified fundamental differences in how resilience is maintained across wetland community types, which have important implications for management activities that aim to restore or conserve resilient systems. We showed that the relative importance of surface and subsurface processes in controlling wetland surface elevation change differed between TFFWs and oligohaline marshes. The marshes had significantly higher rates of surface accretion than the TFFWs, and in the marshes, surface accretion was the primary contributor to elevation change. In contrast, elevation change in TFFWs was more heavily influenced by subsurface processes, such as root zone expansion or compaction, which played an important role in determining resilience of TFFWs to rising sea level. When root zone contributions were removed statistically from comparisons between relative sea-level rise and surface elevation change, sites that previously had elevation rate deficits showed a surplus. Therefore, assessments of wetland resilience that do not include subsurface processes will likely misjudge vulnerability to sea-level rise

Understanding the molecular functions of the second extracellular loop (ECL2) of the calcitonin gene-related peptide (CGRP) receptor using a comprehensive mutagenesis approach

The extracellular loop 2 (ECL2) region is the most conserved of the three ECL domains in family B G protein-coupled receptors (GPCRs) and has a fundamental role in ligand binding and activation across the receptor super-family. ECL2 is fundamental for ligand-induced activation of the calcitonin gene related peptide (CGRP) receptor, a family B GPCR implicated in migraine and heart disease. In this study we apply a comprehensive targeted non-alanine substitution analysis method and molecular modelling to the functionally important residues of ECL2 to reveal key molecular interactions. We identified an interaction network between R274/Y278/D280/W283. These amino acids had the biggest reduction in signalling following alanine substitution analysis and comprise a group of basic, acidic and aromatic residues conserved in the wider calcitonin family of class B GPCRs. This study identifies key and varied constraints at each locus, including diverse biochemical requirements for neighbouring tyrosine residues and a W283H substitution that recovered wild-type (WT) signalling, despite the strictly conserved nature of the central ECL2 tryptophan and the catastrophic effects on signalling of W283A substitution. In contrast, while the distal end of ECL2 requires strict conservation of hydrophobicity or polarity in each position, mutation of these residues never has a large effect. This approach has revealed linked networks of amino acids, consistent with structural models of ECL2 and likely to represent a shared structural framework at an important ligand-receptor interface that is present across the family B GPCRs

Two-dimensional optomechanical crystal resonator in gallium arsenide

In the field of quantum computation and communication there is a compelling need for quantum-coherent frequency conversion between microwave electronics and infra-red optics. A promising platform for this is an optomechanical crystal resonator that uses simultaneous photonic and phononic crystals to create a co-localized cavity coupling an electromagnetic mode to an acoustic mode, which then via electromechanical interactions can undergo direct transduction to electronics. The majority of work in this area has been on one-dimensional nanobeam resonators which provide strong optomechanical couplings but, due to their geometry, suffer from an inability to dissipate heat produced by the laser pumping required for operation. Recently, a quasi-two-dimensional optomechanical crystal cavity was developed in silicon exhibiting similarly strong coupling with better thermalization, but at a mechanical frequency above optimal qubit operating frequencies. Here we adapt this design to gallium arsenide, a natural thin-film single-crystal piezoelectric that can incorporate electromechanical interactions, obtaining a mechanical resonant mode at f_m ~ 4.5 GHz ideal for superconducting qubits, and demonstrating optomechanical coupling g_om/(2pi) ~ 650 kHz

Prey handling and diet of Louisiana pine snakes (Pituophis ruthveni) and black pine snakes (P. melanoleucus lodingi), with comparisons to other selected colubrid snakes

Diet and prey handling behavior were determined for Louisiana pine snakes (Pituophis ruthveni) and black pine snakes (P. melanoleucus lodingi). Louisiana pine snakes prey heavily on Baird\u27s pocket gophers (Geomys breviceps), with which they are sympatric, and exhibit specialized behaviors that facilitate handling this prey species within the confines of burrow systems. Black pine snakes, which are not sympatric with pocket gophers, did not exhibit these specialized behaviors. For comparative purposes, prey handling of P. sayi sayi and Elaphe obsoleta lindheimeri was also examined

Quantum erasure using entangled surface acoustic phonons

Using the deterministic, on-demand generation of two entangled phonons, we demonstrate a quantum eraser protocol in a phononic interferometer where the which-path information can be heralded during the interference process. Omitting the heralding step yields a clear interference pattern in the interfering half-quanta pathways; including the heralding step suppresses this pattern. If we erase the heralded information after the interference has been measured, the interference pattern is recovered, thereby implementing a delayed-choice quantum erasure. The test is implemented using a closed surface-acoustic-wave communication channel into which one superconducting qubit can emit itinerant phonons that the same or a second qubit can later re-capture. If the first qubit releases only half of a phonon, the system follows a superposition of paths during the phonon propagation: either an itinerant phonon is in the channel, or the first qubit remains in its excited state. These two paths are made to constructively or destructively interfere by changing the relative phase of the two intermediate states, resulting in a phase-dependent modulation of the first qubit's final state, following interaction with the half-phonon. A heralding mechanism is added to this construct, entangling a heralding phonon with the signalling phonon. The first qubit emits a phonon herald conditioned on the qubit being in its excited state, with no signaling phonon, and the second qubit catches this heralding phonon, storing which-path information which can either be read out, destroying the signaling phonon's self-interference, or erased.Comment: 16 pages, 8 figure