Upon antigen binding, the B cell receptor (BCR) undergoes clustering to form a signalosome that propagates downstream signaling required for normal B cell development and physiology. BCR clustering is dependent on remodeling of the cortical actin network, but the mechanisms that regulate actin remodeling in this context remain poorly defined. In this study, we identify the inositol 5-phosphatase INPP5B as a key regulator of actin remodeling, BCR clustering, and downstream signaling in antigen-stimulated B cells. INPP5B acts via dephosphorylation of the inositol lipid PI(4,5)P2 that in turn is necessary for actin disassembly, BCR mobilization, and cell spreading on immobilized surface antigen. These effects can be explained by increased actin severing by cofilin and loss of actin linking to the plasma membrane by ezrin, both of which are sensitive to INPP5B-dependent PI(4,5)P2 hydrolysis. INPP5B is therefore a new player in BCR signaling and may represent an attractive target for treatment of B cell malignancies caused by aberrant BCR signaling. 相似文献
Seventy children were studied during 1959 in a special school program because of major language problems. A team of medical and educational personnel studied each child during a ten-day school enrollment. The results of the medical and educational studies were of great value in establishing the correct diagnosis and devising a suitable educational program for the children. 相似文献
Therapeutic administration of mesenchymal stem cells (MSCs) by systemic delivery utilizes the innate ability of the cells to home to damaged tissues, but it can be an inefficient process due to a limited knowledge of cellular cues that regulate migration and homing. Our lab recently discovered that a potent pro-inflammatory cytokine, macrophage migration inhibitory factor (MIF), inhibits MSC migration. Because MIF may act on multiple cellular targets, an activating antibody (CD74Ab) was employed in this study to examine the effect of one MIF receptor, CD74 (major histocompatibility complex class II-associated invariant chain), on MSC motility. CD74 activation inhibits in a dose-dependent manner up to 90% of in vitro migration of MSCs at 40 μg/ml CD74Ab (p?<?0.001), with consistent effects observed among three MSC donor preparations. A blocking peptide from the C-terminus of CD74 eliminates the effect of CD74Ab on MSCs. This suggests that MIF may act on MSCs, at least in part, through CD74. Late-passage MSCs exhibit less chemokinesis than those at passage 2. However, MSCs remain responsive to CD74 activation during ex vivo expansion: MSC migration is inhibited ~2-fold in the presence of 5 µg/ml CD74Ab at passage 9 vs. ~3-fold at passage 2 (p?<?0.001). Consistent with this result, there were no significant differences in CD74 expression at all tested passages or after CD74Ab exposure. Targeting CD74 to regulate migration and homing potentially may be a useful strategy to improve the efficacy of a variety of MSC therapies, including those that require ex vivo expansion. 相似文献
Within 48 h of administration of radiolabelled 10-formylfolate, folic acid and the polyglutamate derivative 10-formylfolate tetraglutamate to the rat, fragmentation products are found in the urine. The major catabolite was identified as p-acetamidobenzoate by chromatography and reverse isotope-dilution analysis. 相似文献
Parkinson’s disease (PD) is a neurodegenerative disorder primarily characterized by progressive loss of dopamine neurons, leading to loss of motor coordination. However, PD is associated with a high rate of non-motor neuropsychiatric comorbities that often develop before the onset of movement symptoms. The MitoPark transgenic mouse model is the first to recapitulate the cardinal clinical features, namely progressive neurodegeneration and death of neurons, loss of motor function and therapeutic response to L-DOPA. To investigate whether MitoPark mice exhibit early onset of cognitive impairment, a non-motor neuropsychiatric comorbidity, we measured performance on a spatial learning and memory task before (∼8 weeks) or after (∼20 weeks) the onset of locomotor decline in MitoPark mice or in littermate controls. Consistent with previous studies, we established that a progressive loss of spontaneous locomotor activity began at 12 weeks of age, which was followed by progressive loss of body weight beginning at 16–20 weeks. Spatial learning and memory was measured using the Barnes Maze. By 20 weeks of age, MitoPark mice displayed a substantial reduction in overall locomotor activity that impaired their ability to perform the task. However, in the 8-week-old mice, locomotor activity was no different between genotypes, yet MitoPark mice took longer, traveled further and committed more errors than same age control mice, while learning to successfully navigate the maze. The modest between-day learning deficit of MitoPark mice was characterized by impaired within-day learning during the first two days of testing. No difference was observed between genotypes during probe trials conducted one or twelve days after the final acquisition test. Additionally, 8-week-old MitoPark mice exhibited impaired novel object recognition when compared to control mice. Together, these data establish that mild cognitive impairment precedes the loss of motor function in a novel rodent model of PD, which may provide unique opportunities for therapeutic development. 相似文献
Wetlands Ecology and Management - We compared a rapid bioassessment protocol (Traveling Sweep Approach [TSA]) with a more conventional time intensive protocol (Composite Transect Approach [CTA]) to... 相似文献
Plant and Soil - Tussock microhabitat is a universal phenomenon in wetlands, where soil and plant properties differ from their surrounding lawns. This study aims to investigate the differences of... 相似文献
Winter is a challenging period for aquatic research—weather is uncomfortable, ice is hazardous, equipment fails, and daylength is short. Consequently, until recently relatively little research on freshwater fishes has included winter. Telemetry methods for tracking fish and observing movement behavior are an obvious solution to working in harsh conditions because much of the data can be collected remotely, and passive methods collect data year-round without winter maintenance. Yet, many telemetry studies do not collect data during winter or, if they do, only report data from the ice-free seasons while the remaining data are unused. Here, we briefly summarize the advantages and limitations of using telemetry methods in winter, including acoustic and radio telemetry and passive integrated transponder technology, then review the range of questions related to fish ecology, behavior, bioenergetics, and habitat use that can be addressed in winter using telemetry. Our goals are to highlight the untapped potential of winter fish biology and to motivate scientists to revisit their four-season telemetry data and incorporate objectives specific to winter biology in future study plans.