Regulation of Rap1 signaling during Dictyostelium chemotaxis and development

Over the past two decades, Rap1 has been recognized world-wide to be an important regulator in a large variety of biological events, including chemotaxis. Despite substantial efforts, the regulation of Rap1 in chemotaxis is still not completely understood. In this thesis, four Rap1 activators, GflB, RasGefL, RasGefQ, and GbpD, have been discovered and characterized in amoeba Dictyostelium discoideum. Our results indicate that chemotactic receptors recruits Rap1 activators, especially GflB, to the sides facing the highest amount of chemical waves called “leading edge”, which then communicates the signal received from receptors to locally assemble the crawling machinery that orients movement toward the source. Although some mechanisms are still not fully unraveled, our findings provide a milestone in the understanding how cells decide on the direction in which they need to migrate towards the extracellular chemical cues. We hope that our work enlightens and encourages new ideas and further investigations on understanding this process

Function and Regulation of Heterotrimeric G Proteins during Chemotaxis

Chemotaxis, or directional movement towards an extracellular gradient of chemicals, is necessary for processes as diverse as finding nutrients, the immune response, metastasis and wound healing. Activation of G-protein coupled receptors (GPCRs) is at the very base of the chemotactic signaling pathway. Chemotaxis starts with binding of the chemoattractant to GPCRs at the cell-surface, which finally leads to major changes in the cytoskeleton and directional cell movement towards the chemoattractant. Many chemotaxis pathways that are directly regulated by Gβγ have been identified and studied extensively; however, whether Gα is just a handle that regulates the release of Gβγ or whether Gα has its own set of distinct chemotactic effectors, is only beginning to be understood. In this review, we will discuss the different levels of regulation in GPCR signaling and the downstream pathways that are essential for proper chemotaxis

Bis(acetyl­acetonato)oxido(triphenyl­phosphine oxide)vanadium(IV)

In the structure of the title compound, [V(C5H7O2)2O(C18H15OP)], the V atom adopts a slightly distorted octa­hedral geometry with its coordination completed by four O atoms of two acetyl­acetonate (acac) ligands, one oxo group and one O atom of the triphenyl­phosphine oxide (OPPh3) ligand

H-ORAM: A Cacheable ORAM Interface for Efficient I/O Accesses

Oblivious RAM (ORAM) is an effective security primitive to prevent access pattern leakage. By adding redundant memory accesses, ORAM prevents attackers from revealing the patterns in the access sequences. However, ORAM tends to introduce a huge degradation on the performance. With growing address space to be protected, ORAM has to store the majority of data in the lower level storage, which further degrades the system performance. In this paper, we propose Hybrid ORAM (H-ORAM), a novel ORAM primitive to address large performance degradation when overflowing the user data to storage. H-ORAM consists of a batch scheduling scheme for enhancing the memory bandwidth usage, and a novel ORAM interface that returns data without waiting for the I/O access each time. We evaluate H-ORAM on a real machine implementation. The experimental results show that that H-ORAM outperforms the state-of-the-art Path ORAM by 19.8x for a small data set and 22.9x for a large data set

Lumbar posterior group muscle degeneration: Influencing factors of adjacent vertebral body re-fracture after percutaneous vertebroplasty

ObjectiveThe purpose of the study was to explore the influencing factors of adjacent vertebral re-fracture after percutaneous vertebroplasty (PVP) for osteoporosis vertebral compression fractures (OVCFs).MethodsWe retrospectively analyzed the clinical data of 55 patients with adjacent vertebral re-fracture after PVP operation for OVCFs in our hospital from January 2016 to June 2019, they were followed up for 1 year and included in the fracture group. According to the same inclusion and exclusion criteria, we collected the clinical data of 55 patients with OVCFs without adjacent vertebral re-fracture after PVP in the same period and included them in the non-fracture group. We performed univariate and multivariate logistic regression analysis on the influencing factors of adjacent vertebral re-fracture in patients with OVCFs after PVP.ResultsThere were significant differences in body mass index (BMI), bone mineral density (BMD) T-value, amount of bone cement injected, bone cement leakage, history of glucocorticoid use, cross-sectional area (CSA), cross-sectional area asymmetry (CSAA), fat infiltration rate (FIR), and fat infiltration rate asymmetry (FIRA) of lumbar posterior group muscles [multifidus (MF) and erector spinae (ES)] between the two groups (p < 0.05). There was no significant difference in sex, age, or time from the first fracture to operation, the CAS, CSAA, FIR, and FIRA of psoas major (PS) between the two groups (p > 0.05). Multivariate logistic regression showed that a higher dose of bone cement, greater CSAA and FIR of multifidus, and higher CSAA of erector spinae were independent risk factors for recurrent fractures of adjacent vertebrae after PVP.ConclusionThere are many risk factors for recurrent vertebral fracture after PVP in patients with OVCFs, and degeneration of paraspinal muscles (especially posterior lumbar muscles) may be one of the risks

A Gα-Stimulated RapGEF Is a Receptor-Proximal Regulator of Dictyostelium Chemotaxis

Chemotaxis, or directional movement toward extracellular chemical gradients, is an important property of cells that is mediated through G-protein-coupled receptors (GPCRs). Although many chemotaxis pathways downstream of Gβγ have been identified, few Gα effectors are known. Gα effectors are of particular importance because they allow the cell to distinguish signals downstream of distinct chemoattractant GPCRs. Here we identify GflB, a Gα2 binding partner that directly couples the Dictyostelium cyclic AMP GPCR to Rap1. GflB localizes to the leading edge and functions as a Gα-stimulated, Rap1-specific guanine nucleotide exchange factor required to balance Ras and Rap signaling. The kinetics of GflB translocation are fine-tuned by GSK-3 phosphorylation. Cells lacking GflB display impaired Rap1/Ras signaling and actin and myosin dynamics, resulting in defective chemotaxis. Our observations demonstrate that GflB is an essential upstream regulator of chemoattractant-mediated cell polarity and cytoskeletal reorganization functioning to directly link Gα activation to monomeric G-protein signaling