I. Structure-Function Analysis of the Mechanosensitive Channel of Large Conductance. II. Design of Novel Magnetic Materials using Crystal Engineering

The work presented here encompasses two distinct areas, with the first section addressing structure-function relationships in the mechanosensitive channel of large conductance (MscL) from bacteria. A high-throughput fluorescent screening technique has been developed for the E. coli homologue of MscL. This technique has been applied to a large library of random E. coli MscL mutations to provide insights into channel function. Additionally, attempts have been made to characterize the functionally important regions of MscL and comparisons have been made between the E. coli and M. tuberculosis homologues of MscL. The second section addresses the design of novel magnetic materials. The guanidinium sulfonate "Ward lattice" from crystal engineering has been used to develop a new family of frustrated magnetic materials.</p

Generation and evaluation of a large mutational library from the Escherichia coli mechanosensitive channel of large conductance, MscL - Implications for channel gating and evolutionary design

Random mutagenesis of the mechanosensitive channel of large conductance (MscL) from Escherichia coli coupled with a high-throughput functional screen has provided new insights into channel structure and function. Complementary interactions of conserved residues proposed in a computational model for gating have been evaluated, and important functional regions of the channel have been identified. Mutational analysis shows that the proposed S1 helix, despite having several highly conserved residues, can be heavily mutated without significantly altering channel function. The pattern of mutations that make MscL more difficult to gate suggests that MscL senses tension with residues located near the lipid headgroups of the bilayer. The range of phenotypical changes seen has implications for a proposed model for the evolutionary origin of mechanosensitive channels

Evaluation of Hexagon Imagery for Regional Mass Balance Study in the Bhutan Himalayas

There is much uncertainty regarding the present and future state of Himalayan glaciers, which supply meltwater for river systems vital to more than 1.4 billion people living throughout Asia. Previous assessments of regional glacier mass balance in the Himalayas using various remote sensing and field-based methods give inconsistent results. In this study, declassified Hexagon stereo imagery is processed to generate a digital elevation model (DEM) in the Bhutan Himalayas. Results indicate that the Hexagon imagery database represents a largely untapped resource for understanding decadal scale patterns of mass balance in the region. Future research will utilize the imagery and DEMs to quantify changes in volume and extent of glaciers in the Bhutan Himalayas by comparing the historical imagery to more recent data and calculating changes in ice volume over an approximately 40 year period

Comparing and contrasting Escherichia coli and Mycobacterium tuberculosis mechanosensitive channels (MscL) - New gain of function mutations in the loop region

Sequence analysis of 35 putative MscL homologues was used to develop an optimal alignment for Escherichia coli and Mycobacterium tuberculosis MscL and to place these homologues into sequence subfamilies. By using this alignment, previously identified E. coli MscL mutants that displayed severe and very severe gain of function phenotypes were mapped onto the M. tuberculosis MscL sequence. Not all of the resulting M. tuberculosis mutants displayed a gain of function phenotype; for instance, normal phenotypes were noted for mutations at Ala20, the analogue of the highly sensitive Gly22 site in E. coli. A previously unnoticed intersubunit hydrogen bond in the extracellular loop region of the M. tuberculosis MscL crystal structure has been analyzed. Cross-linkable residues were substituted for the residues involved in the hydrogen bond, and cross-linking studies indicated that these sites are spatially close under physiological conditions. In general, mutation at these positions results in a gain of function phenotype, which provides strong evidence for the importance of the loop region in MscL channel function. No analogue to this interesting interaction could be found in E. coli MscL by sequence alignment. Taken together, these results indicate that caution should be exercised in using the M. tuberculosis MscL crystal structure to analyze previous functional studies of E. coli MscL

Mountain Glacier Change Across Regions and Timescales

Mountain glaciers have influenced the surface of our planet throughout geologic time. These large reservoirs of water ice sculpt alpine landscapes, regulate downstream river flows, perturb climate-tectonic feedbacks, contribute to sea level change, and guide human migration and settlement patterns. Glaciers are especially relevant in modern times, acting as buffers which supply seasonal meltwater to densely populated downstream communities and support economies via hydropower generation. Anthropogenic warming is accelerating ice loss in most glacierized regions of the world. This has sparked concerns regarding water resources and natural hazards, and placed glaciers at the forefront of climate research. Here we provide new observations of glacier change in key mountain regions to quantify rates of ice loss, better understand climate drivers, and help establish a more unified framework for studying glacier change across timescales. In Chapter 1 we use seismic observations, numerical modeling, and geomorphic analysis to investigate a destructive glacial lake outburst flood (GLOF) which occurred in Bhutan. GLOFs are a substantial hazard for downstream communities in many vulnerable regions. Yet key aspects of GLOF dynamics remain difficult to quantify, as in situ measurements are scarce due to the unpredictability and remote source locations of these events. Here we apply cross-correlation based seismic analyses to track the evolution of the GLOF remotely (~100 km from the source region), use the seismic observations along with eyewitness reports and a downstream gauge station to constrain a numerical flood model, then assess geomorphic change and current state of the unstable lakes via satellite imagery. Coherent seismic energy is evident from 1 to 5 Hz beginning approximately 5 hours before the flood impacted Punakha village, which originated at the source lake and advanced down the valley during the GLOF duration. Our analysis highlights potential benefits of using real-time seismic monitoring to improve early warning systems. The next two chapters in this work focus on quantifying multi-decadal glacier ice loss in the Himalayas. Himalayan glaciers supply meltwater to densely populated catchments in South Asia, and regional observations of glacier change are needed to understand climate drivers and assess impacts on glacier-fed rivers. Here we utilize a set of digital elevation models derived from cold war–era spy satellite film and modern stereo satellite imagery to evaluate glacier responses to changing climate over the last four decades. In Chapter 2 we focus on the eastern Himalayas, centered on the Bhutan–China border. The wide range of glacier types allows for the first mass balance comparison between clean, debris, and lake-terminating (calving) glaciers in the area. Measured glaciers show significant ice loss, with statistically similar mass balance values for both clean-ice and debris-covered glacier groups. Chapter 3 extends the same methodology to quantify glacier change across the entire Himalayan range during 1975–2000 and 2000–2016. We observe consistent ice loss along the entire 2000-km transect for both intervals and find a doubling of the average loss rate during 2000–2016 compared to 1975–2000. The similar magnitude and acceleration of ice loss across the Himalayas suggests a regionally coherent climate forcing, consistent with atmospheric warming and associated energy fluxes as the dominant drivers of glacier change. Chapter 4 investigates millennial-scale glacier changes during the Late Glacial period (15-11 ka). Here we present a high-precision beryllium-10 chronology and geomorphic map from a sequence of well-preserved moraines in the Nendaz valley of the western European Alps, with the goal to shed light on the timing and magnitude of glacier responses during an interval of dramatic natural climate variability. Our chronology brackets a coherent glacier recession through the Younger Dryas stadial into the early Holocene, similar to glacier records from the southern hemisphere and a new chronology from Arctic Norway. These results highlight a general agreement between mountain glacier changes and atmospheric greenhouse gas records during the Late Glacial. In Chapter 5 we use a numerical glacier model to simulate glacier change across a typical alpine region in the European Alps. Model results suggest that shorter observational timespans focused on modern periods (when glaciers are far from equilibrium and undergoing rapid change) exhibit greater spatial variability of mean annual ice thickness changes, compared to intervals which extend further back in time (to include decades when climate was more stable). The model agrees with multi-decadal satellite observations of glacier change, and clarifies the positive correlation between glacier disequilibrium and spatial variability of glacier mass balance. This relationship should be taken into account in regional glacier studies, particularly when analyzing recent spatial patterns of ice loss. Advances made in this work are of practical value for societies vulnerable to glacier change. This includes potential improvements to GLOF early warning systems via seismic monitoring, better constraints on glacier-sourced water scenarios in South Asia, strengthened understanding of long-term glacier responses to baseline natural climate variability, and a clarified relationship between glacier disequilibrium and spatial variability of ice loss. When placed within a global context, our observations highlight the correlation between regional mountain glacier change and greenhouse gas forcing through time

Projected climate-induced faunal change in the western hemisphere

Climate change is predicted to be one of the greatest drivers of ecological change in the coming century. Increases in temperature over the last century have clearly been linked to shifts in species distributions. Given the magnitude of projected future climatic changes, we can expect even larger range shifts in the coming century. These changes will, in turn, alter ecological communities and the functioning of ecosystems. Despite the seriousness of predicted climate change, the uncertainty in climate-change projections makes it difficult for conservation managers and planners to proactively respond to climate stresses. To address one aspect of this uncertainty, we identified predictions of faunal change for which a high level of consensus was exhibited by different climate models. Specifically, we assessed the potential effects of 30 coupled atmosphere–ocean general circulation model (AOGCM) future-climate simulations on the geographic ranges of 2954 species of birds, mammals, and amphibians in the Western Hemisphere. Eighty percent of the climate projections based on a relatively low greenhouse-gas emissions scenario result in the local loss of at least 10% of the vertebrate fauna over much of North and South America. The largest changes in fauna are predicted for the tundra, Central America, and the Andes Mountains where, assuming no dispersal constraints, specific areas are likely to experience over 90% turnover, so that faunal distributions in the future will bear little resemblance to those of today

A New DEM Extraction Method for Hexagon Spy Imagery and Application to Bhutan Glaciers

Declassified Hexagon stereo spy images have near-global coverage extending back to the 1970’s, yet remain a largely untapped resource for land change studies. Unavailable satellite exterior orientation data for these images make digital elevation model (DEM) extraction difficult in terms of time and accuracy. A new automated workflow for DEM extraction is presented that eliminates the need for manual ground control point selection. The method is applied to reconstruct a DEM from 1974 imagery over a large glacierized region in the Bhutan Himalayas. Glacier changes over several decades are visualized using a DEM differencing method. These results demonstrate the value of Hexagon imagery when applied to land change studies

Tools for Assessing Climate Impacts on Fish and Wildlife

Climate change is already affecting many fish and wildlife populations. Managing these populations requires an understanding of the nature, magnitude, and distribution of current and future climate impacts. Scientists and managers have at their disposal a wide array of models for projecting climate impacts that can be used to build such an understanding. Here, we provide a broad overview of the types of models available for forecasting the effects of climate change on key processes that affect fish and wildlife habitat (hydrology, fire, and vegetation), as well as on individual species distributions and populations. We present a framework for how climate-impacts modeling can be used to address management concerns, providing examples of model-based assessments of climate impacts on salmon populations in the Pacific Northwest, fire regimes in the boreal region of Canada, prairies and savannas in the Willamette Valley-Puget Sound Trough-Georgia Basin ecoregion, and marten Martes americana populations in the northeastern United States and southeastern Canada. We also highlight some key limitations of these models and discuss how such limitations should be managed. We conclude with a general discussion of how these models can be integrated into fish and wildlife management