Highlights d Cancer cells from primary tumors are resistant to fluid shear stress (FSS) d Resistance to FSS is a physiological, mechano-adaptive response in cancer cells d Cancer cells respond to FSS by activating the RhoA-myosin II axis and formins d Myosin II activity protects CTCs from hemodynamic forces in in vivo assays Authors
Background: Traumatic brain injury (TBI) is a major cause of mortality and disability associated with increased risk of secondary infections. Identifying a readily available biomarker may help direct TBI patient care. Herein, we evaluated whether admission lymphopenia could predict outcomes of TBI patients. Methods: This is a 10-year retrospective review of TBI patients with a head Abbreviated Injury Score 2 to 6 and absolute lymphocyte counts (ALC) collected within 24 h of admission. Exclusion criteria were death within 24 h of admission and presence of bowel perforation on admission. Demographics, admission data, injury severity score, mechanism of injury, and outcomes were collected. Association between baseline variables and outcomes was analyzed. Results: We included 2,570 patients; 946 (36.8%) presented an ALC 1,000 on admission (lymphopenic group). Lymphopenic patients were significantly older, less likely to smoke, and more likely to have heart failure, hypertension, or chronic kidney disease. Lymphopenia was associated with increased risks of mortality (OR ¼ 1. 903 [1.389-2.608]; P < 0.001) and pneumonia ]; P ¼ 0.016), increased LOS ; P < 0.001), and likelihood of requiring additional healthcare resources at discharge (OR ¼ 1.669 [1.344-2.073], P < 0.001). Additionally, lymphopenia increased the risk of early in-hospital death (OR ¼ 1.459 [1.097-1.941]; P ¼ 0.009). Subgroup analysis showed that lymphopenia was associated with mortality in polytrauma patients and those who presented with two or more concurrent types of TBI. In all subgroup analyses, lymphopenia was associated with longer length of stay and discharge requiring higher level of care. Conclusion: A routine complete blood count with differential for all TBI patients may help predict patient outcomes and direct care accordingly.
RhoA and RhoC GTPases are 92% identical but demonstrate unique regulation and function. Phosphorylation of Ser188 has widely been reported to inhibit RhoA activity. RhoC possesses Arg188 in place of Ser188 but retains a canonical upstream PKA recognition sequence. We report here that RhoC-R188S was a PKA substrate in vitro and exhibited less GTP loading compared to wild-type RhoC when expressed in cells. Transiently expressed RhoC was found to be significantly more membrane associated than RhoA. Membrane association of RhoC-R188S and RhoC-R188A were similar to each other and wild-type RhoA, suggesting that Arg188 directly promotes RhoC membrane binding. The positive influence of Arg188 on RhoC membrane association was evident in a constitutively active (Q63L) background. In accordance, RhoA-S188R was significantly more membrane associated than either RhoA or RhoA-S188A. Altogether, these data suggest that swapping residue 188 identity effectively flips the membrane binding profile of wild-type RhoA and RhoC through positive arginine contribution rather than negative phosphoserine regulation.
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