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null (Ed.)Abstract. Recent research on fold-switching metamorphic proteins has revealed some notable exceptions to Anfinsen's hypothesis of protein folding. We have previously described how a single point mutation can enable a well-folded protein domain, one of the two PAS (Per-ARNT-Sim) domains of the human ARNT (aryl hydrocarbon receptor nuclear translocator) protein, to interconvert between two conformers related by a slip of an internal β strand. Using this protein as a test case, we advance the concept of a “fragile fold”, a protein fold that can reversibly rearrange into another fold that differs by a substantial number of hydrogen bonds, entailing reorganization of single secondary structure elements to more drastic changes seen in metamorphic proteins. Here we use a battery of biophysical tests to examine several factors affecting the equilibrium between the two conformations of the switching ARNT PAS-B Y456T protein. Of note is that we find that factors which impact the HI loop preceding the shifted Iβ strand affect both the equilibrium levels of the two conformers and the denatured state which links them in the interconversion process. Finally, we describe small molecules that selectively bind to and stabilize the wild-type conformation of ARNT PAS-B. These studies form a toolkit for studying fragile protein folds and could enable ways to modulate the biological functions of such fragile folds, both in natural and engineered proteins.more » « less
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Abstract The processes and deposits of tide‐dominated river deltas and estuaries are well‐understood, but the sedimentary dynamics of tide‐dominated straits and seaways are relatively little studied. Although recent depositional models have started to fill this gap, many aspects of tidal strait sedimentation such as interaction with strait‐margin alluvial fans and marginal marine systems remain poorly understood. This paper presents a study of the late Miocene basal carbonate member of the Bouse Formation exposed along the lower Colorado River, where prior studies have suggested a tidal influence on deposition. This study explores the applicability of tidal strait models in a continental oblique‐rift setting, and tests hypotheses for depositional processes and environments through detailed analysis of sedimentary facies, cross‐bedding architecture and palaeocurrent data. Mixed carbonate–siliciclastic facies on the west margin of the southern Blythe Basin record sedimentation in alluvial fans and fan‐fringing tidal flats at the retreating margin of a transgressive tidal strait. Pre‐Bouse normal faults established a narrow, tectonically confined basin architecture that led to amplification of tidal currents. Basin‐margin deposits pass laterally and up‐section into high‐energy cross‐bedded grainstone facies that record southward migration of compound dunes in the dune‐bedded strait zone of a shallow (
ca 25 m) tidal strait. These findings provide the basis for recognition of strait‐margin facies in other settings where complex facies associations result from along‐strike variations in palaeobathymetry and current velocity. The results support a tidal origin for the southern Bouse Formation and provide new evidence for post‐Miocene uplift of the lower Colorado River Valley and adjacent areas. -
The need to train sustainability scientists and engineers to address the complex problems of our world has never been more apparent. We organized an interdisciplinary team of instructors from universities in the states of Maine, New Hampshire, and Rhode Island who designed, taught, and assessed a multi-university course to develop the core competencies necessary for advancing sustainability solutions. Lessons from the course translate across sustainability contexts, but our specific focus was on the issues and trade-offs associated with dams. Dams provide numerous water, energy, and cultural services to society while exacting an ecological toll that disrupts the flow of water, fish, and sediment in rivers. Like many natural resource management challenges, effective dam decisions require collaboration among diverse stakeholders and disciplines. We linked key sustainability principles and practices related to interdisciplinarity, stakeholder engagement, and problem-solving to student learning outcomes that are generalizable beyond our dam-specific context. Students and instructors co-created class activities to build capacity for interdisciplinary collaboration and encourage student leadership and creativity. Assessment results show that students responded positively to activities related to stakeholder engagement and interdisciplinary collaboration, particularly when practicing nested discussion and intrapersonal reflection. These activities helped broaden students’ perspectives on sustainability problems and built greater capacity for constructive communication and student leadership.more » « less