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Cytoplasmic dynein-1 (dynein) is the primary retrograde-directed microtubule motor in most eukaryotes. To be active, dynein must bind to the dynactin complex and a cargo-specific adaptor to form the . There are nearly 20 adaptors that, despite having low sequence identity, all contain two discrete domains that mediate binding to the same regions of dynein and dynactin. Additionally, all adaptors seem to generate active transport complexes with grossly similar structures. Despite these similarities, active transport complexes formed with different adaptors show differences in their velocity, run length, and microtubule binding affinity. The molecular features in adaptors that underlie the differences in activity is unknown. To address this question, we first generated a library of synthetic adaptors by deleting or systematically swapping characterized dynein and dynactin binding domains for four endogenous, model adaptors, NINL, BicD2, KASH5, and Hook3. We then used binding assays and TIRF-based motility assays to assess each synthetic adaptors' ability to bind and activate dynein and dynactin. First, we found that the adaptors' coiled-coil domains, which bind dynactin and the tail domain of dynein, are necessary and sufficient for dynein activation. Second, we found that all endogenous adaptors could be modified to yield a synthetic adaptor that formed more motile active transport complexes, which suggests that there is no selective pressure for adaptors to maximize dynein motility. Indeed, our data suggest that some endogenous adaptor sequences may have evolved to generate active transport complexes that are only moderately motile. Finally, we found that one synthetic adaptor was hyperactive and generated active transport complexes that moved faster, farther, and more frequently than all other endogenous and synthetic adaptors. By performing structure-function analyses with the hyperactive adaptor, we discovered that increased random coil at key positions in an adaptor sequence increases the likelihood that dynein-dynactin-adaptor complexes that assemble will be motile. Our work supports a model where increased adaptor flexibility facilitates a type of kinetic proofreading that specifically destabilizes improperly assembled and inactive dynein-dynactin-adaptor complexes. These results provide insight into how differences in adaptor sequences could contribute to differential dynein regulation.

The Hawaiian Archipelago experienced a moderate bleaching event in 2019—the third major bleaching event over a 6-year period to impact the islands. In response, the Hawai‘i Coral Bleaching Collaborative (HCBC) conducted 2,177 coral bleaching surveys across the Hawaiian Archipelago. The HCBC was established to coordinate bleaching monitoring efforts across the state between academic institutions, non-governmental organizations, and governmental agencies to facilitate data sharing and provide management recommendations. In 2019, the goals of this unique partnership were to: 1) assess the spatial and temporal patterns of thermal stress; 2) examine taxa-level patterns in bleaching susceptibility; 3) quantify spatial variation in bleaching extent; 4) compare 2019 patterns to those of prior bleaching events; 5) identify predictors of bleaching in 2019; and 6) explore site-specific management strategies to mitigate future bleaching events. Both acute thermal stress and bleaching in 2019 were less severe overall compared to the last major marine heatwave events in 2014 and 2015. Bleaching observed was highly site- and taxon-specific, driven by the susceptibility of remaining coral assemblages whose structure was likely shaped by previous bleaching and subsequent mortality. A suite of environmental and anthropogenic predictors was significantly correlated with observed bleaching in 2019. Acute environmental stressors, such as temperature and surface light, were equally important as previous conditions (e.g. historical thermal stress and historical bleaching) in accounting for variation in bleaching during the 2019 event. We found little evidence for acclimation by reefs to thermal stress in the main Hawaiian Islands. Moreover, our findings illustrate how detrimental effects of local anthropogenic stressors, such as tourism and urban run-off, may be exacerbated under high thermal stress. In light of the forecasted increase in severity and frequency of bleaching events, future mitigation of both local and global stressors is a high priority for the future of corals in Hawai‘i.

With the increasing demand for net-zero sustainable aviation fuels (SAF), new conversion technologies are needed to process waste feedstocks and meet carbon reduction and cost targets. Wet waste is a low-cost, prevalent feedstock with the energy potential to displace over 20% of US jet fuel consumption; however, its complexity and high moisture typically relegates its use to methane production from anaerobic digestion. To overcome this, methanogenesis can be arrested during fermentation to instead produce C₂ to C₈ volatile fatty acids (VFA) for catalytic upgrading to SAF. Here, we evaluate the catalytic conversion of food waste–derived VFAs to produce n-paraffin SAF for near-term use as a 10 vol% blend for ASTM “Fast Track” qualification and produce a highly branched, isoparaffin VFA-SAF to increase the renewable blend limit. VFA ketonization models assessed the carbon chain length distributions suitable for each VFA-SAF conversion pathway, and food waste–derived VFA ketonization was demonstrated for >100 h of time on stream at approximately theoretical yield. Fuel property blending models and experimental testing determined normal paraffin VFA-SAF meets 10 vol% fuel specifications for “Fast Track.” Synergistic blending with isoparaffin VFA-SAF increased the blend limit to 70 vol% by addressing flashpoint and viscosity constraints, with sooting 34% lower than fossil jet. Techno-economic analysis evaluated the major catalytic process cost-drivers, determining the minimum fuel selling price as a function of VFA production costs. Life cycle analysis determined that if food waste is diverted from landfills to avoid methane emissions, VFA-SAF could enable up to 165% reduction in greenhouse gas emissions relative to fossil jet.

Ecosystem services play a crucial role in sustaining human well-being and economic viability. People benefit substantially from the delivery of ecosystem services, for which substitutes usually are costly or unavailable. Climate change will substantially alter or eliminate certain ecosystem services in the future. To better understand the consequences of climate change and to develop effective means of adapting to them, it is critical that we improve our understanding of the links between climate, ecosystem service production, and the economy. This study examines the impact of climate change on the terrestrial distribution and the subsequent production and value of two key ecosystem services in California: (1) carbon sequestration and (2) natural (i.e. non-irrigated) forage production for livestock. Under various scenarios of future climate change, we predict that the provision and value of ecosystem services decline under most, but not all, future greenhouse gas trajectories. The predicted changes would result in decreases in the economic output for the state and global economy and illustrate some of the hidden costs of climate change. Since existing information is insufficient to conduct impact analysis across most ecosystem services, a comprehensive research program focused on estimating the impacts of climate change on ecosystem services will be important for understanding, mitigating and adapting to future losses in ecosystem service production and the economic value they provide.

The dry mass and the orientation of biomolecules can be imaged without a label by measuring their permittivity tensor (PT), which describes how biomolecules affect the phase and polarization of light. Three-dimensional (3D) imaging of PT has been challenging. We present a label-free computational microscopy technique, PT imaging (PTI), for the 3D measurement of PT. PTI encodes the invisible PT into images using oblique illumination, polarization-sensitive detection and volumetric sampling. PT is decoded from the data with a vectorial imaging model and a multi-channel inverse algorithm, assuming uniaxial symmetry in each voxel. We demonstrate high-resolution imaging of PT of isotropic beads, anisotropic glass targets, mouse brain tissue, infected cells and histology slides. PTI outperforms previous label-free imaging techniques such as vector tomography, ptychography and light-field imaging in resolving the 3D orientation and symmetry of organelles, cells and tissue. We provide open-source software and modular hardware to enable the adoption of the method. Permittivity tensor imaging is a label-free computational microscopy approach that enables the three-dimensional measurement of molecular permittivity tensors, revealing information about a biomolecule’s dry mass and orientation in cells and tissues.

The purpose of this study was to understand Polynesian American (PA) values, preferences, and beliefs about psychotherapy in light of their culture. An Interpretative Phenomenological Analysis (IPA) was conducted to collect and analyze culturally relevant preferences and expectations of psychotherapy with Polynesian Americans. The study consisted of 13 in-depth interviews with individuals of Pacific Islander descent who are currently living in the United States. The results of the analysis showed three culturally informed themes shared by study participants that informed this sample’s expectations and preferences of psychotherapy: ʻOhana (family), Lōkahi (harmony) and Aloha (warmth, compassion, love). These values provide unique insights to therapy adaptations that should be emphasized when working with Polynesian American clients, such as using a family centered approach to therapy that takes into account the collective needs of a client’s entire family, participating in therapist self-disclosure and the sharing of personal backgrounds, looking at clients challenges through a holistic lens, and demonstrating genuine warmth in the client-counsellor relationship. We discuss clinical implications and recommendations for Polynesian Americans in future research.

Biological architecture is intrinsically tensorial. The permittivity tensor (PT) of biological material reports the density, angular anisotropy, symmetry, and 3D orientation of biomolecules. High-resolution measurement of PT can enable quantitative and label-free analysis of organelle, cell, and tissue architecture, but remains challenging. We report uniaxial permittivity tensor imaging (uPTI), a label-free computational imaging method for volumetric measurement of PT with diffraction-limited resolution. uPTI encodes the components of PT into intensity modulations using oblique illumination and polarization-resolved imaging. The high-dimensional data is decoded with a vectorial image formation model and a multi-channel convex optimization, assuming that the molecular distribution in each voxel has uniaxial symmetry. We describe a modular implementation of uPTI that can be multiplexed with complementary imaging modalities. We report volumes of uPT in mouse brain tissue, SARS-CoV-2 infected cardiomyocytes, RSV infected A549 cells, H&E stained tissue sections, isotropic beads, and anisotropic glass targets. uPTI enabled volumetric imaging of the 3D orientation and symmetry of organelles, cells, and tissue components with higher spatio-angular resolution than current vectorial tomography, ptychography, and light-field microscopy methods. We provide an open source implementation of the image formation model and reconstruction algorithms. Competing Interest Statement A patent filed by the Chan Zuckerberg Biohub with S.B.M, L.H, and I.E.I as inventors is pending and describes the uPTI method reported in this paper. B.R.C. is a founder of Tenaya Therapeutics (https://www.tenayatherapeutics.com/), a company focused on finding treatments for heart failure, including genetic cardiomyopathies. Other authors declare no competing interests. Footnotes * Main figures and text are revised to clarify the image formation, reconstruction, benchmarking, and applications. New applications of the technology are reported in Figs. 4, 5 and 6. Multiple supplemental videos and figures are updated or added. * https://github.com/mehta-lab/waveorder