Acoustic characterization of crack damage evolution in sandstone deformed under conventional and true triaxial loading

We thank the Associate Editor, Michelle Cooke, and the reviewers, Ze'ev Reches and Yves Guéguen, for useful comments which helped to improve the manuscript. We thank J.G. Van Munster for providing access to the true triaxial apparatus at KSEPL and for technical support during the experimental program. We thank R. Pricci for assistance with technical drawings of the apparatus. This work was partly funded by NERC award NE/N002938/1 and by a NERC Doctoral Studentship, which we gratefully acknowledge. Supporting data are included in a supporting information file; any additional data may be obtained from J.B. (e-mail: [email protected]).Peer reviewedPublisher PD

Roles of forest bioproductivity, transpiration and fire in a nine-year record of cave dripwater chemistry from southwest Australia

Forest biomass has the potential to significantly impact the chemistry and volume of diffuse recharge to cave dripwater via the processes of nutrient uptake, transpiration and forest fire. Yet to-date, this role has been under-appreciated in the interpretation of speleothem trace element records from forested catchments. In this study, the impact of vegetation is examined and quantified in a long-term monitoring program from Golgotha Cave, SW Australia. The contribution of salts from rain and dry-deposition of aerosols and dissolved elements from soil mineral and bedrock dissolution to dripwater chemistry are also examined. This study is an essential pre-requisite for the future interpretation of trace element data from SW Australian stalagmite records, whose record of past environmental change will include alterations in these biogeochemical fluxes. Solute concentrations in dripwater vary spatially, supporting the existence of distinct flow paths governed by varying amounts of transpiration as well as nutrient uptake by deeply-rooted biomass. Applying principal components analysis, we identify a common pattern of variation in dripwater Cl, Mg, K, Ca, Sr and Si, interpreted as reflecting increasing transpiration, due to forest growth. Mass-balance calculations show that increasing elemental sequestration into biomass has the largest impact on SO4, providing an explanation for the overall falling dripwater SO4 concentrations through time, in contrast to the transpiration-driven rising trend dominating other ions. The long-term rise in transpiration and nutrient uptake driven by increased forest bioproductivity and its impact on our dripwater chemistry is attributed to i. the post-fire recovery of the forest understorey after fire impacted the site in 2006 CE; ii. and/or increased water and nutrient demand as trees in the overlying forest mature. The impact of climate-driven changes on the water balance is also examined. Finally, the implications for interpreting SW Australian speleothem trace element records are discussed

Mapping the world's coral reefs using a global multiscale earth observation framework

Coral reefs are among the most diverse and iconic ecosystems on Earth, but a range of anthropogenic pressures are threatening their persistence. Owing to their remoteness, broad spatial coverage and cross‐jurisdictional locations, there are no high‐resolution remotely sensed maps available at the global scale. Here we present a framework that is capable of mapping coral reef habitats from individual reefs (~200 km2) to entire barrier reef systems (200 000 km2) and across vast ocean extents (>6 000 000 km2). This is the first time this has been demonstrated using a consistent and transparent remote sensing mapping framework. The ten maps that we present achieved good accuracy (78% mean overall accuracy) from multiple input image datasets and training data sources, and our framework was shown to be adaptable to either benthic or geomorphic reef features and across diverse coral reef environments. These new generation high‐resolution map data will be useful for supporting ecosystem risk assessments, detecting change in ecosystem dynamics and targeting efforts to monitor local‐scale changes in coral cover and reef health

Copy Number Variation of CCL3-like Genes Affects Rate of Progression to Simian-AIDS in Rhesus Macaques (Macaca mulatta)

Variation in genes underlying host immunity can lead to marked differences in susceptibility to HIV infection among humans. Despite heavy reliance on non-human primates as models for HIV/AIDS, little is known about which host factors are shared and which are unique to a given primate lineage. Here, we investigate whether copy number variation (CNV) at CCL3-like genes (CCL3L), a key genetic host factor for HIV/AIDS susceptibility and cell-mediated immune response in humans, is also a determinant of time until onset of simian-AIDS in rhesus macaques. Using a retrospective study of 57 rhesus macaques experimentally infected with SIVmac, we find that CCL3L CNV explains approximately 18% of the variance in time to simian-AIDS (p<0.001) with lower CCL3L copy number associating with more rapid disease course. We also find that CCL3L copy number varies significantly (p<10−6) among rhesus subpopulations, with Indian-origin macaques having, on average, half as many CCL3L gene copies as Chinese-origin macaques. Lastly, we confirm that CCL3L shows variable copy number in humans and chimpanzees and report on CCL3L CNV within and among three additional primate species. On the basis of our findings we suggest that (1) the difference in population level copy number may explain previously reported observations of longer post-infection survivorship of Chinese-origin rhesus macaques, (2) stratification by CCL3L copy number in rhesus SIV vaccine trials will increase power and reduce noise due to non-vaccine-related differences in survival, and (3) CCL3L CNV is an ancestral component of the primate immune response and, therefore, copy number variation has not been driven by HIV or SIV per se

Spine Calcium Transients Induced by Synaptically-Evoked Action Potentials Can Predict Synapse Location and Establish Synaptic Democracy

CA1 pyramidal neurons receive hundreds of synaptic inputs at different distances from the soma. Distance-dependent synaptic scaling enables distal and proximal synapses to influence the somatic membrane equally, a phenomenon called “synaptic democracy”. How this is established is unclear. The backpropagating action potential (BAP) is hypothesised to provide distance-dependent information to synapses, allowing synaptic strengths to scale accordingly. Experimental measurements show that a BAP evoked by current injection at the soma causes calcium currents in the apical shaft whose amplitudes decay with distance from the soma. However, in vivo action potentials are not induced by somatic current injection but by synaptic inputs along the dendrites, which creates a different excitable state of the dendrites. Due to technical limitations, it is not possible to study experimentally whether distance information can also be provided by synaptically-evoked BAPs. Therefore we adapted a realistic morphological and electrophysiological model to measure BAP-induced voltage and calcium signals in spines after Schaffer collateral synapse stimulation. We show that peak calcium concentration is highly correlated with soma-synapse distance under a number of physiologically-realistic suprathreshold stimulation regimes and for a range of dendritic morphologies. Peak calcium levels also predicted the attenuation of the EPSP across the dendritic tree. Furthermore, we show that peak calcium can be used to set up a synaptic democracy in a homeostatic manner, whereby synapses regulate their synaptic strength on the basis of the difference between peak calcium and a uniform target value. We conclude that information derived from synaptically-generated BAPs can indicate synapse location and can subsequently be utilised to implement a synaptic democracy

The Brain-Specific Beta4 Subunit Downregulates BK Channel Cell Surface Expression

The large-conductance K+ channel (BK channel) can control neural excitability, and enhanced channel currents facilitate high firing rates in cortical neurons. The brain-specific auxiliary subunit β4 alters channel Ca++- and voltage-sensitivity, and β4 knock-out animals exhibit spontaneous seizures. Here we investigate β4's effect on BK channel trafficking to the plasma membrane. Using a novel genetic tag to track the cellular location of the pore-forming BKα subunit in living cells, we find that β4 expression profoundly reduces surface localization of BK channels via a C-terminal ER retention sequence. In hippocampal CA3 neurons from C57BL/6 mice with endogenously high β4 expression, whole-cell BK channel currents display none of the characteristic properties of BKα+β4 channels observed in heterologous cells. Finally, β4 knock-out animals exhibit a 2.5-fold increase in whole-cell BK channel current, indicating that β4 also regulates current magnitude in vivo. Thus, we propose that a major function of the brain-specific β4 subunit in CA3 neurons is control of surface trafficking

SLO-2 Is Cytoprotective and Contributes to Mitochondrial Potassium Transport

Mitochondrial potassium channels are important mediators of cell protection against stress. The mitochondrial large-conductance “big” K+ channel (mBK) mediates the evolutionarily-conserved process of anesthetic preconditioning (APC), wherein exposure to volatile anesthetics initiates protection against ischemic injury. Despite the role of the mBK in cardioprotection, the molecular identity of the channel remains unknown. We investigated the attributes of the mBK using C. elegans and mouse genetic models coupled with measurements of mitochondrial K+ transport and APC. The canonical Ca2+-activated BK (or “maxi-K”) channel SLO1 was dispensable for both mitochondrial K+ transport and APC in both organisms. Instead, we found that the related but physiologically-distinct K+ channel SLO2 was required, and that SLO2-dependent mitochondrial K+ transport was triggered directly by volatile anesthetics. In addition, a SLO2 channel activator mimicked the protective effects of volatile anesthetics. These findings suggest that SLO2 contributes to protection from hypoxic injury by increasing the permeability of the mitochondrial inner membrane to K+

High Speed Two-Photon Imaging of Calcium Dynamics in Dendritic Spines: Consequences for Spine Calcium Kinetics and Buffer Capacity

Rapid calcium concentration changes in postsynaptic structures are crucial for synaptic plasticity. Thus far, the determinants of postsynaptic calcium dynamics have been studied predominantly based on the decay kinetics of calcium transients. Calcium rise times in spines in response to single action potentials (AP) are almost never measured due to technical limitations, but they could be crucial for synaptic plasticity. With high-speed, precisely-targeted, two-photon point imaging we measured both calcium rise and decay kinetics in spines and secondary dendrites in neocortical pyramidal neurons. We found that both rise and decay kinetics of changes in calcium-indicator fluorescence are about twice as fast in spines. During AP trains, spine calcium changes follow each AP, but not in dendrites. Apart from the higher surface-to-volume ratio (SVR), we observed that neocortical dendritic spines have a markedly smaller endogenous buffer capacity with respect to their parental dendrites. Calcium influx time course and calcium extrusion rate were both in the same range for spines and dendrites when fitted with a dynamic multi-compartment model that included calcium binding kinetics and diffusion. In a subsequent analysis we used this model to investigate which parameters are critical determinants in spine calcium dynamics. The model confirmed the experimental findings: a higher SVR is not sufficient by itself to explain the faster rise time kinetics in spines, but only when paired with a lower buffer capacity in spines. Simulations at zero calcium-dye conditions show that calmodulin is more efficiently activated in spines, which indicates that spine morphology and buffering conditions in neocortical spines favor synaptic plasticity