RESUMEN
Actin-binding protein Profilin1 is an important regulator of actin cytoskeletal dynamics in cells and critical for embryonic development in higher eukaryotes. The objective of the present study was to examine the consequence of loss-of-function of Pfn1 in vascular endothelial cells (ECs) in vivo. We utilized a mouse model engineered for tamoxifen-inducible biallelic inactivation of the Pfn1 gene selectively in EC (Pfn1EC-KO). Widespread deletion of EC Pfn1 in adult mice leads to severe health complications presenting overt pathologies (endothelial cell death, infarct, and fibrosis) in major organ systems and evidence for inflammatory infiltrates, ultimately compromising the survival of animals within 3 weeks of gene ablation. Mice deficient in endothelial Pfn1 exhibit selective bias toward the proinflammatory myeloid-derived population of immune cells, a finding further supported by systemic elevation of proinflammatory cytokines. We further show that triggering Pfn1 depletion not only directly upregulates proinflammatory cytokine/chemokine gene expression in EC but also potentiates the paracrine effect of EC on proinflammatory gene expression in macrophages. Consistent with these findings, we provide further evidence for increased activation of Interferon Regulatory Factor 7 (IRF7) and STAT1 in EC when depleted of Pfn1. Collectively, these findings for the first time demonstrate a prominent immunological consequence of loss of endothelial Pfn1 and an indispensable role of endothelial Pfn1 in mammalian survival unlike tolerable phenotypes of Pfn1 loss in other differentiated cell types.
RESUMEN
After stroke, capacity to complete tasks in the treatment setting with the more-affected arm is an unreliable index of actual use of that extremity in daily life. Available objective methods for monitoring real-world arm use rely on placing movement sensors on patients. These methods provide information on amount but not type of arm activity, e.g., functional versus nonfunctional movement. This paper presents an approach that places sensors on patients and household objects, overcoming this limitation. An accelerometer and the transmitter component of a radio-frequency proximity sensor are attached to objects; the receiver component is attached to the arm of interest. The receiver triggers an on-board radio-frequency identification tag to signal proximity when that arm is within 23 cm of an instrumented object. In benchmark testing, this system detected perfectly which arm was used to move the target object on 200 trials. In a laboratory study with 35 undergraduates, increasing the amount of time target objects were moved with the arm of interest resulted in a corresponding increase in system output . Moreover, measurement error was low ( ≤ 2.5%). The results support this system's reliability and validity in individuals with unimpaired movement; testing is now warranted in stroke patients.
