The role of GTPase-activating protein ARHGAP26 in human cancers

Rho GTPases are molecular switches that play an important role in regulating the behavior of a variety of tumor cells. RhoA GTPase-activating protein 26 (ARHGAP26) is a GTPase-activating protein and inhibits the activity of Rho GTPases by promoting the hydrolytic ability of Rho GTPases. It also affects tumorigenesis and progression of various tumors through several methods, including formation of abnormal fusion genes and circular RNA. This review summarizes the biological functions and molecular mechanisms of ARHGAP26 in different tumors, proposes the potential clinical value of ARHGAP26 in cancer treatment, and discusses current issues that need to be addressed.

     

街区尺度屋顶绿化热效应及其与城市形态结构之间的关系

研究探讨大面积屋顶绿化如何改善城市冠层内部三维空间的热环境,改善效果与城市形态结构之间存在的关系。基于三维小气候模型ENVI-met 4.2,开展街区尺度屋顶绿化热效应研究。在南京市选择具有不同形态结构特征的8个典型样区,每个样区设置2种朝向(街道与主导风向平行或相交)、3种屋顶绿化情景(传统光屋顶、简易型绿化、复合型绿化),共对48种情景进行了微气候模拟与分析。结果表明,街区尺度屋顶绿化产生的"冷岛"可从屋面扩散到地面空间,缓解城市冠层热岛效应。白天14:00时,8个样区屋顶1.5 m高处的降温强度最高可达0.64℃,样区平均降温强度最大值为0.44℃;地面1.5 m高处的降温最大值为0.55℃,样区平均降温强度最大值为0.25℃。建筑高度、高宽比、容积率与屋面、地面降温强度之间均存在显著负相关关系;建筑密度与屋面降温强度显著正相关,但与地面降温强度之间无显著相关性。总的来说,紧凑低层建筑区和开敞低层建筑区实施屋顶绿化后产生的降温效应明显高于紧凑和开敞高层建筑区;建筑高度和密度相同时,街道走向与主导风向呈45°夹角比与主导风向平行具有更高的降温强度。研究结果能够促进对亚热带城市地区建筑-植被-大气相互关系的深入认识,并为屋顶绿化实践提供指导。     

Differentiation of Human T Cells Alters Their Repertoire of G Protein α-Subunits

Because T cell differentiation leads to an expanded repertoire of chemokine receptors, a subgroup of G protein-coupled receptors, we hypothesized that the repertoire of G proteins might be altered in parallel. We analyzed the abundance of mRNA and/or protein of six G protein α-subunits in human CD4⁺ and CD8⁺ T cell subsets from blood. Although most G protein α-subunits were similarly expressed in all subsets, the abundance of Gα_o, a protein not previously described in hematopoietic cells, was much higher in memory versus naive cells. Consistent with these data, activation of naive CD4⁺ T cells in vitro significantly increased the abundance of Gα_o in cells stimulated under nonpolarizing or T_H17 (but not T_H1 or T_H2)-polarizing conditions. In functional studies, the use of a chimeric G protein α-subunit, Gα_qo5, demonstrated that chemokine receptors could couple to Gα_o-containing G proteins. We also found that Gα_i1, another α-subunit not described previously in leukocytes, was expressed in naive T cells but virtually absent from memory subsets. Corresponding to their patterns of expression, siRNA-mediated knockdown of Gα_o in memory (but not naive) and Gα_i1 in naive (but not memory) CD4⁺ T cells inhibited chemokine-dependent migration. Moreover, although even in Gα_o- and Gα_i1-expressing cells mRNAs of these α-subunits were much less abundant than Gα_i2 or Gα_i3, knockdown of any of these subunits impaired chemokine receptor-mediated migration similarly. Together, our data reveal a change in the repertoire of Gα_i/o subunits during T cell differentiation and suggest functional equivalence among Gα_i/o subunits irrespective of their relative abundance.     

Iron accumulation in deep cortical layers accounts for MRI signal abnormalities in ALS: correlating 7 Tesla MRI and pathology

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by cortical and spinal motor neuron dysfunction. Routine magnetic resonance imaging (MRI) studies have previously shown hypointense signal in the motor cortex on T(2)-weighted images in some ALS patients, however, the cause of this finding is unknown. To investigate the utility of this MR signal change as a marker of cortical motor neuron degeneration, signal abnormalities on 3T and 7T MR images of the brain were compared, and pathology was obtained in two ALS patients to determine the origin of the motor cortex hypointensity. Nineteen patients with clinically probable or definite ALS by El Escorial criteria and 19 healthy controls underwent 3T MRI. A 7T MRI scan was carried out on five ALS patients who had motor cortex hypointensity on the 3T FLAIR sequence and on three healthy controls. Postmortem 7T MRI of the brain was performed in one ALS patient and histological studies of the brains and spinal cords were obtained post-mortem in two patients. The motor cortex hypointensity on 3T FLAIR images was present in greater frequency in ALS patients. Increased hypointensity correlated with greater severity of upper motor neuron impairment. Analysis of 7T T(2)(*)-weighted gradient echo imaging localized the signal alteration to the deeper layers of the motor cortex in both ALS patients. Pathological studies showed increased iron accumulation in microglial cells in areas corresponding to the location of the signal changes on the 3T and 7T MRI of the motor cortex. These findings indicate that the motor cortex hypointensity on 3T MRI FLAIR images in ALS is due to increased iron accumulation by microglia.