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1. A Spatially Detailed and Economically Complete Blue Water Footprint of the United States

   https://doi.org/10.5194/hess-2017-650  

   Rushforth, Richard R.; Ruddell, Benjamin L. (January 2017, Hydrology and Earth System Sciences Discussions)

   This paper quantifies and maps a spatially detailed and economically complete blue water footprint for the United States, utilizing the National Water Economy Database version 1.1 (NWED). NWED utilizes multiple mesoscale federal data resources from the United States Geological Survey (USGS), the United States Department of Agriculture (USDA), the U.S. Energy Information Administration (EIA), the U.S. Department of Transportation (USDOT), the U.S. Department of Energy (USDOE), and the U.S. Bureau of Labor Statistics (BLS) to quantify water use, economic trade, and commodity flows to construct this water footprint. Results corroborate previous studies in both the magnitude of the U.S. water footprint (F) and in the observed pattern of virtual water flows. The median water footprint (F_CUMed) of the U.S. is 181 966 Mm³ (F_Withdrawal: 400 844 Mm³; F_CUMax: 222 144 Mm³; F_CUMin: 61 117 Mm³) and the median per capita water footprint (F'_CUMed) of the U.S. is 589 m³ capita^−1 (F'_Withdrawal: 1298 m³ capita^−1; F'_CUMax: 720 m³ capita^−1; F'_CUMin: 198 m³ capita^−1). The U.S. hydro-economic network is centered on cities and is dominated by the local and regional scales. Approximately (58 %) of U.S. water consumption is for the direct and indirect use by cities. Further, the water footprint of agriculture and livestock is 93 % of the total U.S. water footprint, and is dominated by irrigated agriculture in the Western U.S. The water footprint of the industrial, domestic, and power economic sectors is centered on population centers, while the water footprint of the mining sector is highly dependent on the location of mineral resources. Owing to uncertainty in consumptive use coefficients alone, the mesoscale blue water footprint uncertainty ranges from 63 % to over 99 % depending on location. Harmonized region-specific, economic sector-specific consumption coefficients are necessary to reduce water footprint uncertainties and to better understand the human economy's water use impact on the hydrosphere. 

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2. Atypical peripheral actin band formation via overactivation of RhoA and nonmuscle myosin II in mitofusin 2-deficient cells

   https://doi.org/10.7554/eLife.88828  

   Wang, Yueyang; Troughton, Lee D; Xu, Fan; Chatterjee, Aritra; Ding, Chang; Zhao, Han; Cifuentes, Laura P; Wagner, Ryan B; Wang, Tianqi; Tan, Shelly; et al (September 2023, eLife)

   Cell spreading and migration play central roles in many physiological and pathophysiological processes. We have previously shown that MFN2 regulates the migration of human neutrophil-like cells via suppressing Rac activation. Here, we show that in mouse embryonic fibroblasts, MFN2 suppresses RhoA activation and supports cell polarization. After initial spreading, the wild-type cells polarize and migrate, whereas theMfn2^-/-cells maintain a circular shape. Increased cytosolic Ca²⁺resulting from the loss of Mfn2 is directly responsible for this phenotype, which can be rescued by expressing an artificial tether to bring mitochondria and endoplasmic reticulum to close vicinity. Elevated cytosolic Ca²⁺activates Ca²⁺/calmodulin-dependent protein kinase II, RhoA, and myosin light-chain kinase, causing an overactivation of nonmuscle myosin II, leading to a formation of a prominent F-actin ring at the cell periphery and increased cell contractility. The peripheral actin band alters cell physics and is dependent on substrate rigidity. Our results provide a novel molecular basis to understand how MFN2 regulates distinct signaling pathways in different cells and tissue environments, which is instrumental in understanding and treating MFN2-related diseases. 

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3. Gd ^III ‐ ¹⁹ F Distance Measurements for Proteins in Cells by Electron‐Nuclear Double Resonance

   https://doi.org/10.1002/anie.202218780  

   Seal, Manas; Zhu, Wenkai; Dalaloyan, Arina; Feintuch, Akiva; Bogdanov, Alexey; Frydman, Veronica; Su, Xun‐Cheng; Gronenborn, Angela M.; Goldfarb, Daniella (April 2023, Angewandte Chemie International Edition)

   Abstract Studies of protein structure and dynamics are usually carried out in dilute buffer solutions, conditions that differ significantly from the crowded environment in the cell. The double electron‐electron resonance (DEER) technique can track proteins’ conformations in the cell by providing distance distributions between two attached spin labels. This technique, however, cannot access distances below 1.8 nm. Here, we show that Gd^III‐¹⁹F Mims electron‐nuclear double resonance (ENDOR) measurements can cover part of this short range. Low temperature solution and in‐cell ENDOR measurements, complemented with room temperature solution and in‐cell Gd^III‐¹⁹F PRE (paramagnetic relaxation enhancement) NMR measurements, were performed on fluorinated GB1 and ubiquitin (Ub), spin‐labeled with rigid Gd^IIItags. The proteins were delivered into human cells via electroporation. The solution and in‐cell derived Gd^III‐¹⁹F distances were essentially identical and lie in the 1–1.5 nm range revealing that both, GB1 and Ub, retained their overall structure in the Gd^IIIand¹⁹F regions in the cell. 

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4. TGF-β blockade drives a transitional effector phenotype in T cells reversing SIV latency and decreasing SIV reservoirs in vivo

   https://doi.org/10.1038/s41467-024-45555-x  

   Kim, Jinhee; Bose, Deepanwita; Araínga, Mariluz; Haque, Muhammad R; Fennessey, Christine M; Caddell, Rachel A; Thomas, Yanique; Ferrell, Douglas E; Ali, Syed; Grody, Emanuelle; et al (December 2024, Nature Communications)

   Abstract HIV-1 persistence during ART is due to the establishment of long-lived viral reservoirs in resting immune cells. Using an NHP model of barcoded SIVmac239 intravenous infection and therapeutic dosing of anti-TGFBR1 inhibitor galunisertib (LY2157299), we confirm the latency reversal properties of in vivo TGF-β blockade, decrease viral reservoirs and stimulate immune responses. Treatment of eight female, SIV-infected macaques on ART with four 2-weeks cycles of galunisertib leads to viral reactivation as indicated by plasma viral load and immunoPET/CT with a⁶⁴Cu-DOTA-F(ab’)₂-p7D3-probe. Post-galunisertib, lymph nodes, gut and PBMC exhibit lower cell-associated (CA-)SIV DNA and lower intact pro-virus (PBMC). Galunisertib does not lead to systemic increase in inflammatory cytokines. High-dimensional cytometry, bulk, and single-cell (sc)RNAseq reveal a galunisertib-driven shift toward an effector phenotype in T and NK cells characterized by a progressive downregulation in TCF1. In summary, we demonstrate that galunisertib, a clinical stage TGF-β inhibitor, reverses SIV latency and decreases SIV reservoirs by driving T cells toward an effector phenotype, enhancing immune responses in vivo in absence of toxicity. 

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5. Morphodynamics facilitate cancer cells to navigate 3D extracellular matrix

   https://doi.org/10.1038/s41598-021-99902-9  

   Eddy, Christopher Z.; Raposo, Helena; Manchanda, Aayushi; Wong, Ryan; Li, Fuxin; Sun, Bo (October 2021, Scientific Reports)

   Abstract Cell shape is linked to cell function. The significance of cell morphodynamics, namely the temporal fluctuation of cell shape, is much less understood. Here we study the morphodynamics of MDA-MB-231 cells in type I collagen extracellular matrix (ECM). We systematically vary ECM physical properties by tuning collagen concentrations, alignment, and gelation temperatures. We find that morphodynamics of 3D migrating cells are externally controlled by ECM mechanics and internally modulated by Rho/ROCK-signaling. We employ machine learning to classify cell shape into four different morphological phenotypes, each corresponding to a distinct migration mode. As a result, we map cell morphodynamics at mesoscale into the temporal evolution of morphological phenotypes. We characterize the mesoscale dynamics including occurrence probability, dwell time and transition matrix at varying ECM conditions, which demonstrate the complex phenotype landscape and optimal pathways for phenotype transitions. In light of the mesoscale dynamics, we show that 3D cancer cell motility is a hidden Markov process whereby the step size distributions of cell migration are coupled with simultaneous cell morphodynamics. Morphological phenotype transitions also facilitate cancer cells to navigate non-uniform ECM such as traversing the interface between matrices of two distinct microstructures. In conclusion, we demonstrate that 3D migrating cancer cells exhibit rich morphodynamics that is controlled by ECM mechanics, Rho/ROCK-signaling, and regulate cell motility. Our results pave the way to the functional understanding and mechanical programming of cell morphodynamics as a route to predict and control 3D cell motility. 

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