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Mao, E.

Publications and source records attributed to Mao, E..

3 recordsLinked to original sources

A molecular clutch governs stator engagement and flagellar torque

Motile bacteria must continuously adjust their motility to navigate and colonize diverse environments, including mammalian hosts, yet the underlying mechanisms remain poorly understood. Here, using in situ single-particle cryo-electron microscopy, we determine near-atomic structures of the flagellar motor in the Lyme disease spirochete Borrelia burgdorferi and uncover a novel mechanism for controlling torque generation. We identify a distinct neutral state in which individual torque-generating MotA5B2 stator complexes remain incorporated in the motor but adopt an extended, tilted conformation disengaged from the rotor. Two conserved flagellar proteins, FliL and FlcA, form a transmembrane scaffold that retains 16 stator complexes, while FapA, a newly identified multidomain flagellar protein, binds the cytoplasmic base of the stator complex and stabilizes its rotor-disengaged conformation. Strikingly, rotor-engaged and rotor-disengaged stators coexist within individual motors, demonstrating that stator retention and torque engagement are separable states. Our findings establish a motor-retained neutral stator state and reveal a molecular-clutch mechanism that independently controls the engagement of individual stator units with the rotor, enabling rapid and precise regulation of flagellar torque and motility.

microbiology↗

Low hemoglobin causes hematoma expansion and poor intracerebral hemorrhage outcomes

ObjectivesAlthough lower hemoglobin levels associate with worse intracerebral hemorrhage (ICH) outcomes, causal drivers for this relationship remain unclear. We investigated the hypothesis that lower hemoglobin relates to increased hematoma expansion (HE) risk and poor outcomes using human observational data and assessed causal relationships using a translational murine model of anemia and ICH. MethodsICH patients with baseline hemoglobin measurements and serial CT neuroimaging enrolled between 2010-2016 to a multicenter, prospective observational cohort study were studied. Patients with systemic evidence of coagulopathy were excluded. Separate regression models assessed relationships of baseline hemoglobin with HE ([≥]33% and/or [≥]6mL growth) and poor long-term neurological outcomes (modified Rankin Scale 4-6) after adjusting for relevant covariates. Using a murine collagenase ICH model with serial neuroimaging in anemic vs. non-anemic C57/BL6 mice, intergroup differences in ICH lesion volume, ICH volume changes, and early mortality were assessed. ResultsAmong 1190 ICH patients analyzed, lower baseline hemoglobin levels associated with increased odds of HE (adjusted OR per -1g/dL hemoglobin decrement: 1.10 [1.02-1.19]) and poor 3-month clinical outcomes (adjusted OR per -1g/dL hemoglobin decrement: 1.11 [1.03-1.21]). Similar relationships were seen with poor 6 and 12-month outcomes. In our animal model, anemic mice had significantly greater ICH lesion expansion, final lesion volumes, and greater mortality, as compared to non-anemic mice. ConclusionsThese results, in a human cohort and a mouse model, provide novel evidence suggesting that anemia has causal roles in HE and poor ICH outcomes. Additional studies are required to clarify whether correcting anemia can improve these outcomes.

pathology↗

Ligament injury in adult zebrafish triggers ECM remodeling and cell dedifferentiation for scar-free regeneration

After traumatic injury, healing of mammalian ligaments is typically associated with fibrotic scarring as opposed to scar-free regeneration. In contrast, here we show that the ligament supporting the jaw joint of adult zebrafish is capable of rapid and complete scar-free healing. Following surgical transection of the jaw joint ligament, we observe breakdown of ligament tissue adjacent to the cut sites, expansion of mesenchymal tissue within the wound site, and then remodeling of extracellular matrix (ECM) to a normal ligament morphology. Lineage tracing of mature ligamentocytes following transection shows that they dedifferentiate, undergo cell cycle re-entry, and contribute to the regenerated ligament. Single-cell RNA sequencing of the regenerating ligament reveals dynamic expression of ECM genes in neural-crest-derived mesenchymal cells, as well as diverse immune cells expressing the endopeptidase-encoding gene legumain. Analysis of legumain mutant zebrafish shows a requirement for early ECM remodeling and efficient ligament regeneration. Our study establishes a new model of adult scar-free ligament regeneration and highlights roles of immune-mesenchyme cross-talk in ECM remodeling that initiates regeneration. HighlightsO_LIRapid regeneration of the jaw joint ligament in adult zebrafish C_LIO_LIDedifferentiation of mature ligamentocytes contributes to regeneration C_LIO_LIscRNAseq reveals dynamic ECM remodeling and immune activation during regeneration C_LIO_LIRequirement of Legumain for ECM remodeling and ligament healing C_LI

molecular biology↗