Mobility Measurements Probe Conformational Changes in Membrane Proteins due to Tension

The function of membrane-embedded proteins such as ion channels depends crucially on their conformation. We demonstrate how conformational changes in asymmetric membrane proteins may be inferred from measurements of their diffusion. Such proteins cause local deformations in the membrane, which induce an extra hydrodynamic drag on the protein. Using membrane tension to control the magnitude of the deformations and hence the drag, measurements of diffusivity can be used to infer--- via an elastic model of the protein--- how conformation is changed by tension. Motivated by recent experimental results [Quemeneur et al., Proc. Natl. Acad. Sci. USA, 111 5083 (2014)] we focus on KvAP, a voltage-gated potassium channel. The conformation of KvAP is found to change considerably due to tension, with its `walls', where the protein meets the membrane, undergoing significant angular strains. The torsional stiffness is determined to be 26.8 kT at room temperature. This has implications for both the structure and function of such proteins in the environment of a tension-bearing membrane.Comment: Manuscript: 4 pages, 4 figures. Supplementary Material: 8 pages, 1 figur

Costs of hauling bulk milk from farm to plant

Also available online.Digitized 2007 AES

Moessbauer Spectroscopy of Martian and Sverrefjell Carbonates

Mars, in its putative "warmer, wetter: early history, could have had a CO2 atmosphere much denser than its current value of <10 mbar. The question of where all this early CO2 has gone has long been debated. Now, several instruments on Mars Exploration Rover (MER) Spirit, including its Moessbauer spectrometer MIMOS II, have identified Mg-Fe carbonate in rock outcrops at Comanche Spur in the Columbia Hills of Gusev Crater. With this finding, carbonate cements in volcanic breccia collected on Sverrefjell Volcano on Spitzbergen Island in the Svalbard Archipelago (Norway) during the AMASE project are mineralogical and possible process analogues of the newly discovered martian carbonate. We report further analyses of Mossbauer spectra from Comanche Spur and discuss their relationship to Mossbauer data acquired on Sverrefjell carbonates. The spectra were velocity calibrated with MERView and fit using MERFit. Instead of the "average temperature" Comanche spectrum (data from all temperature windows summed), we refit the Comanche data for QS within each temperature window, modeling as doublets for Fe2+(carbonate), Fe2+(olivine), and Fe3+(npOx). The temperature dependences of QS for the Comanche carbonate and for a low-Ca carbonate from Chocolate Pots in Yellowstone National Park (YNP) are shown; they are the same within error. For Comanche carbonate summed over 210-270 K, (CS, QS) = (1.23, 1.95) mm/s. The value of QS for Sverrefjell carbonate at 295 K, (CS, QS) = (1.25, 1.87) mm/s, is also plotted, and the plot shows that the QS for the Sverrefjell carbonate agrees within error with the Comanche data extrapolated to 295 K. This agreement is additional evidence that the Sverrefjell carbonates are Mossbauer analogues for the Comanche carbonates, and that both carbonates might have precipitated from solutions that became carbonate rich by passing through buried carbonate deposits

Memory: looking back and looking forward

This review brings together past and present achievements in memory research, ranging from molecular to psychological discoveries. Despite some false starts, major advances include our growing understanding of learning-related neural plasticity and the characterisation of different classes of memory. One striking example is the ability to reactivate targeted neuronal ensembles so that an animal will seemingly re-experience a particular memory, with the further potential to modify such memories. Meanwhile, human functional imaging studies can distinguish individual episodic memories based on voxel activation patterns. While the hippocampus continues to provide a rich source of information, future progress requires broadening our research to involve other sites. Related challenges include the need to understand better the role of glial-neuron interactions and to look beyond the synapse as the sole site of experience-dependent plasticity. Unmet goals include translating our neuroscientific knowledge in order to optimise learning and memory, especially amongst disadvantaged populations

Synaptic tagging and capture : differential role of distinct calcium/calmodulin kinases in protein synthesis-dependent long-term potentiation

Weakly tetanized synapses in area CA1 of the hippocampus that ordinarily display long-term potentiation lasting ~3 h (called early-LTP) will maintain a longer-lasting change in efficacy (late-LTP) if the weak tetanization occurs shortly before or after strong tetanization of an independent, but convergent, set of synapses in CA1. The synaptic tagging and capture hypothesis explains this heterosynaptic influence on persistence in terms of a distinction between local mechanisms of synaptic tagging and cell-wide mechanisms responsible for the synthesis, distribution, and capture of plasticity-related proteins (PRPs). We now present evidence that distinct CaM kinase (CaMK) pathways serve a dissociable role in these mechanisms. Using a hippocampal brain-slice preparation that permits stable long-term recordings in vitro for >10 h and using hippocampal cultures to validate the differential drug effects on distinct CaMK pathways, we show that tag setting is blocked by the CaMK inhibitor KN-93 (2-[N-(2-hydroxyethyl)]-N-(4-methoxybenzenesulfonyl)amino-N-(4-chlorocinnamyl)-N-methylbenzylamine) that, at low concentration, is more selective for CaMKII. In contrast, the CaMK kinase inhibitor STO-609 [7H-benzimidazo(2,1-a)benz(de)isoquinoline-7-one-3-carboxylic acid] specifically limits the synthesis and/or availability of PRPs. Analytically powerful three-pathway protocols using sequential strong and weak tetanization in varying orders and test stimulation over long periods of time after LTP induction enable a pharmacological dissociation of these distinct roles of the CaMK pathways in late-LTP and so provide a novel framework for the molecular mechanisms by which synaptic potentiation, and possibly memories, become stabilized