2. The Role of Rock

Rho kinases (ROCKs) are involved in regulating a variety of physiologic functions including cytoskeletal reorganization, migration, adhesion, survival and proliferation. They do so via activating several different downstream substrates such as myosin light chain phosphatase, LIM kinase and ezrin/radixin/moesin proteins. To date, most of the conclusions with regard to the function of ROCKs have involved the use of cell line models, pharmacologic inhibitors and dominant negative approaches. Importantly, the role of ROCK in hematopoiesis or leukemogenesis in the context of whole organism remains poorly understood. Recent studies utilizing mice deficient in the expression of ROCK1 have begun to shed some light into the physiologic role(s) of ROCK in both normal and abnormal hematopoiesis. Findings, thus far, suggest that ROCK plays an essential role in regulating growth and survival in different hematopoietic lineages via distinct mechanisms, in part, by utilizing distinct downstream substrates including maintaining the activation of tumor-suppressor genes. In blood cells, emerging data suggest that ROCK plays an essential role in negatively regulating inflammatory and erythropoietic stress and positively regulates the growth and survival of leukemic cells.

Insulin signaling in pancreatic β-cell is critical for normal insulin secretion. ROCK1 plays an important role in the regulation of insulin and leptin signaling in the context of glucose and energy metabolism. However, the role of ROCK1 in pancreatic β-cell remains unknown. The current study was to determine whether deleting ROCK1 from β-cell affects insulin secretion and glucose metabolism in mice and cultured cell lines. Here we show that β-cell-specific deletion of ROCK1 results in a significant decrease insulin secretion in mice fed a normal chow diet, leading to hyperglycemia. These effects were independent of changes in adiposity. Consistent with this, in vitro studies with INS-1 and MIN6 cells indicated that inhibition of ROCK1 decreased insulin secretion in response to glucose without changes in β-cell proliferation and apoptosis. In addition, β-cell-ROCK1 deficient mice displayed glucose intolerance, as evidenced by the fact that the area under the glucose curve was increased 53% in β-cell-ROCK1 deficient mice compared with control mice. However, neither body weight, food intake nor insulin sensitivity was changed in theses mice. Upon insulin stimulation, proximal insulin signaling components, including p-IRS2, p-PI3K and p-Akt were impaired when ROCK1 expression was inhibited in INS-1 cells, suggesting a role for ROCK1 in insulin signaling. These data indicate that activation of ROCK1 in pancreatic β-cell is required for the maintenance of normal insulin secretion. Thus, pancreatic ROCK1 might be a key regulator of glucose homeostasis. Disclosure B. Sung: None. K. Hur: None. J. Kim: None. Y. Kim: None.M. Lee: None.

BackgroundRho kinases (ROCKs) are the typical downstream effectors of RhoA, which can regulate corneal epithelial wound healing. In this study, the role of ROCK1 in lipopolysaccharide (LPS)-induced cornea inflammation was investigated.Material/MethodsThe expression of ROCK1 in human corneal epithelial cells (HCECs) was bilaterally modulated with ROCK1 expression vector and ROCK1 inhibitor Y-27632. The effects of ROCK1 modulation on the inflammatory response, cell viability, cell apoptosis, and cell cycle distribution were detected by ELISA assay, MTT assay, and flow cytometry, respectively. The pathways involved in the effect of ROCK1 in HCECs was preliminarily explained by detecting changes of TLR4-mediated NF-κB and ERK signaling using western blotting and electrophoretic mobility shift assays.ResultsOverexpression of ROCK1 promoted LPS-induced production of IL-6, IL-8, IL-1β, and TNF-α, and the apoptotic process in HCECs. Augmented inflammation and apoptosis were associated with stronger activation of TLR4-mediated signal transduction; the phosphorylation of IκBα, JNK, ERK1/2, and p38, and nuclear translocation of NF-κB p65 induced by LPS were further increased by overexpression of ROCK1. Inhibition of ROCK1 function by Y-27632 blocked the effect of LPS on HCECs; both LPS-induced inflammation and apoptosis was alleviated by Y-27632, which was associated with suppression of TLR4-mediated NF-κB and ERK signaling.ConclusionsLPS-induced inflammation and apoptosis in HCECs depended on the function of ROCK1, inhibition of which would attenuate impairments on cornea cells due to LPS.

The current study looks at the metaphors for rocks in Isabella Hammad's novel The Parisian (2019). It seeks to demonstrate how Isabella Hammad employs rock analogies to describe and provide an understanding into her characters, Midhat, Jamil, and Fatima. Midhat, who studied abroad, has a hyphenated identity and is portrayed as a compromise—less resistant, delicate, and adaptable. The inverse of the properties of the rocks/stones. The other characters who have not fled Palestine, such as Fatima and Jamil, are portrayed as more strong, resilient, and unstoppable. Their characteristics are described as rocks or stones. Hammad compares Midhat's personality and qualities to those of other characters, such as Fatima and Jamil, using rock and stone metaphors. The work is examined through the prism of postcolonialism, specifically Edward Said's views on Orientalism. Hammad describes the characters using metaphors such as rocks and stones. According to the investigation, Jamil and Fatima's traits reflect those of stones and rocks. Midhat, on the other hand, has certain features that are diametrically opposed to those of stones and rocks. Hammad deliberately portrays Midhat in this manner to highlight the contrast between Palestinians who abandon their territory and indigenous who remain on their land, participate in revolts, and protect their homeland. To the researcher's knowledge, there have been few studies that evaluate and discuss Isabella Hammad's literary works, particularly her novel The Parisian (2019).

Knowledge of dispersion and attenuation is essential for better reservoir characterization and hydrocarbon identification. However, limited by reliable laboratory data at seismic frequency bands, the roles of rock and fluid properties in inducing dispersion and attenuation are still poorly understood. Here we perform a series of laboratory measurements on Bentheimer and Bandera sandstone under both vacuum-dry and partially water-saturated conditions at frequencies ranging from 2 to 600 Hz. At vacuum-dry conditions, the bulk dispersion and attenuation in Bandera sandstone with more clay contents are distinctly larger than those in Bentheimer sandstone, suggesting clay contents might contribute to the inelasticity of the rock frame. The partially water-saturated results show the combined effects of rock permeability and fluid saturation on bulk dispersion and attenuation. Even a few percent of gas can substantially dominate the pore-fluid relaxation by providing a quick and short communication path for pore pressure gradients. The consequent bulk dispersion and attenuation are negligible. Only as the samples are approaching fully water-saturated conditions, rock permeability begins to play an essential role in the pore-fluid relaxation. For Bandera sandstone with lower permeability, a partially relaxed status of pore fluids is achieved when the gas saturation is lower than 5%, accompanied by significant attenuation and dispersion. Cited as : Wei, Q., Wang, Y., Han, D., Sun, M., Huang, Q. Combined effects of permeability and fluid saturation on seismic wave dispersion and attenuation in partially-saturated sandstone. Advances in Geo-Energy Research, 2021, 5(2): 181-190, doi: 10.46690/ager.2021.02.07

the highly similar rho kinases ROCK I and II have drawn a lot of attention over the past decade as potential targets for novel treatment options for a variety of cardiovascular disorders such as (pulmonary) hypertension, ischemic stroke, and vascular leakage ([27][1]). Several previous in vivo

Rocks are quasi-brittle materials that inherently contain different types of flaws, microcracks and inhomogeneity, which are weak under tensile loading. The tensile strength of rock is significant parameter for rock mechanics designers, which plays the dominant role in rock cutting, fracturing and fragmentation on blasting. In general, fractures in rock initiate from tiny cavities and micro-fractures, then coalescence to form macro-fractures, and finally fail. Most of the well-known failure criteria address only the ultimate stage of failure and ignore progressive damage on loading of the rock. To take account of the effect of micro-fractures in quasibrittle materials such as rocks, Continuum Damage Mechanics (CDM) has been used in this study. Recently, micro-fracture effects in rock and concrete have been investigated by using damage evolution in conjunction with thermodynamics theory. As micro-cracking and damage directly influence the rock elastic properties and elastic wave velocities, the ultrasonic properties of rock under loading provide a clear view of the development of micro-fracturing. The Brazilian test has been used to apply indirect tensile loading and has been coupled with the measurement of ultrasonic P and S-wave velocities.

The homologous Rho kinases, ROCK1 and ROCK2, are involved in stress fiber assembly and cell adhesion and are assumed to be functionally redundant. Using mouse embryonic fibroblasts (MEFs) derived from ROCK1−/− and ROCK2−/− mice, we have recently reported that they play different roles in regulating doxorubicin-induced stress fiber disassembly and cell detachment: ROCK1 is involved in destabilizing the actin cytoskeleton and cell detachment, whereas ROCK2 is required for stabilizing the actin cytoskeleton and cell adhesion. Here, we present additional insights into the roles of ROCK1 and ROCK2 in regulating stress-induced impairment of cell-matrix and cell-cell adhesion. In response to doxorubicin, ROCK1−/− MEFs showed significant preservation of both focal adhesions and adherens junctions, while ROCK2−/− MEFs exhibited impaired focal adhesions but preserved adherens junctions compared with the wild-type MEFs. Additionally, inhibition of focal adhesion or adherens junction formations by chemical inhibitors abolished the anti-detachment effects of ROCK1 deletion. Finally, ROCK1−/− MEFs, but not ROCK2−/− MEFs, also exhibited preserved central stress fibers and reduced cell detachment in response to serum starvation. These results add new insights into a novel mechanism underlying the anti-detachment effects of ROCK1 deletion mediated by reduced peripheral actomyosin contraction and increased actin stabilization to promote cell-cell and cell-matrix adhesion. Our studies further support the differential roles of ROCK isoforms in regulating stress-induced loss of central stress fibers and focal adhesions as well as cell detachment.

Background: Rho kinase (ROCK) is the major effector protein of RhoA and is known to mediate F-actin stress fibers. ROCK activates myosin motors. Actomyosin-generated contractile forces can be transmitted to cell-cell junctions, resulting in increased junctional tension, junctional disassembly and endothelial hyperpermeability. In apparent contrast, basal ROCK activity is required for maintenance of barrier integrity . We hypothesize that these dual roles of ROCK could be contributed to the two highly homologous expressed isoforms. Methods: Traction force microscopy was utilized to study the endothelium-generated contractile forces after depletion of ROCK1 and/or ROCK2 by SiRNA approach in the absence and presence of the vaso-active agent thrombin. Results: The traction force landscape showed that ROCK is a major contributor to endothelial contraction and permeability. Depletion of ROCK1 and ROCK2 resulted in a blockade of contractile response to thrombin and a marked reduction in endothelial hyperpermeability. Detailed force distribution maps revealed that the absence of ROCK1, but not of ROCK2, resulted in an increase in baseline contractile forces (siROCK1: 88.1 ± 4.1 Pa, siROCK2: 53.6 ± 3.4 Pa, Control: 56.2 ± 6.1 Pa), which was associated with the formation of numerous inter-endothelial gaps upon stimulation with thrombin. Knockdown of ROCK2 stabilized the endothelial barrier and largely prevented traction force enhancements. Exposure to thrombin resulted in all conditions in an increase of traction forces and hyperpermeability. Conclusion: Both ROCK isoforms have a distinct function in endothelial contractility and permeability. ROCK1 is predominantly contributing to barrier maintenance under baseline conditions, whereas ROCK2 mediates the thrombin-induced contractile force enhancements and subsequent barrier dysfunction. Funding: Dutch Heart Foundation 2011T072