Mccluremayer3672

Quinacrine also inhibited autophagic flux in cell culture. Other compounds tested were not effective. When injected into mice, chloroquine caused accumulation of LC3B-II in heart tissue, and quinacrine was effective at blocking LC3B-II degradation in male, but not female skeletal muscle. None of the compounds tested were useful for measuring autophagic flux in the brain. During this study we also noted that the vehicle DMSO powerfully up-regulated LC3B-II abundance in tissues. This study shows that chloroquine and quinacrine can both be used to measure autophagic flux in cells, and in some peripheral tissues. FHT-1015 However, measurement of flux in the brain using lysosomal inhibitors remains an unresolved research challenge.Dendritic cells (DCs), as potent phagocytes engulf dead cells and present peptide fragments of tumor antigens or pathogens derived from infected cells to naïve CD8+ T-lymphocytes. Dendritic cells can also induce apoptosis in target cells, thus getting an opportunity to sample their microenvironment. Here, we present that the supernatants of LPS- or CL075-activated DCs induced cell death in different cell lines, but during the differentiation to mature DCs, they lost their cytotoxic potential. Dexamethasone-pre-treated tolerogenic DCs induced less intensive death indicating that the tissue microenvironment can downregulate DC-mediated killing. Exploring the signaling of DC-induced cell death, we observed that the supernatant of activated DCs induced TNF-dependent cell death, since TNF antagonist blocked the cytotoxic activity of DCs, contrary to inhibitors of Fas and TRAIL receptors. We identified that the DC-induced killing is at least partially a RIPK1-dependent process, as RIPK1 positive target cells were more susceptible to DC-induced cell death than their RIPK1 deficient counterparts. Moreover, both the elevated phosphorylation of RIPK1 and the increase in RIPK1-caspase-8 interaction in target cells suggest that RIPK1-mediated signals contribute to DC supernatant-induced cell death. We also proved that the cytotoxic activity of DC-derived supernatant induced apoptosis in the target cells and not necroptosis, as it was completely abrogated with the pan caspase inhibitor (Z-VAD), while the necroptosis inhibitor (Nec-1) had no effect. Our work revealed that the supernatant of activated DCs induces the apoptosis of target cells in a RIPK1-dependent manner. This phenomenon could be relevant for the initiation of cross-presentation and may broaden the plethora of cytotoxic mechanisms acting against tumor cells.Assessment of scapulothoracic and glenohumeral contributions to shoulder function during baseball pitching are limited by challenges in accurately measuring dynamic scapular orientation. A recently validated individualized linear model approach that estimates scapular orientation based on measurable humerothoracic orientation has yet to be adapted for pitching and may improve upon currently recommended methods such as the acromion marker cluster (AMC). This study evaluates the ability of a pitching-specific individualized linear model to estimate scapular orientation in static positions throughout a throwing motion by comparing against palpation and an AMC. Individualized linear models were created for 14 collegiate pitchers by determining scapulothoracic and humerothoracic orientations at static arm postures throughout their individual dynamic throwing motions. Linear model and AMC estimates were compared against palpation at intermediate test positions within the throwing motion that were excluded from model creation. Linear model estimates were similar to palpation at all test positions and on all scapulothoracic axes while AMC estimates differed on internal/external rotation and anterior/posterior tilt during cocking (p = 0.001, p = 0.018) and follow-through (p = 0.003, p = 0.006). Linear model root mean square error (RMSE) values were smaller than AMC values for all positions/axes. Linear model RMSE values (2.8-6.3°) were within a range of published values previously deemed acceptable, while AMC values (5.1-15.8°) went beyond this range. The linear model approach accurately estimates static scapular orientation throughout a pitching motion and improves upon current methods. Future applications to dynamic pitching may facilitate understanding of how scapulothoracic and glenohumeral joint function relate to injury risks, rehabilitation, and performance.When recovering balance from a lateral perturbation, younger adults tend to stabilize balance with a single lateral sidestep while older adults often take multistep responses. Using multiple steps to recover balance is consistently associated with increased fall risk, altered body center of mass (CoM) control and instability. The aim of this study was to compare the spatio-temporal stepping characteristics and the margin of stability (MoS) of single lateral sidesteps (LSS1) with the first and second steps of a two-step protective step sequence. Two-step sequences begin with either a cross-over step to the front or back, or a medial step followed by a lateral sidestep. Seventy-one older adults received random lateral waist-pull perturbations to either side. We hypothesized that LSS1 would be more stable (larger MoS) than either step in a two-step sequence. With some exceptions, utilizing a two-step sequence was associated with a reduced CoM velocity and distance between the base of support and CoM and decreased stability in the frontal plane following limb loading of the first and second step. There were no differences in the time available to arrest the extrapolated CoM at the end of a single lateral sidestep or the final step of a two-step sequence. Two-step sequences involving a cross-over step include more complex stepping trajectories and also challeng stability in the sagittal plane requiring a multidimensional balance correction. These results indicate important step type differences in center of mass control in recovering balance with a single lateral sidestep as opposed to a two-step sequence among older adults.Morular metaplasia (MM) is a peculiar type of metaplastic change commonly observed in endometrial lesions, which is defined by the absence of overt squamous features and a characteristic immunophenotype. The nature of MM and its relationship with conventional squamous differentiation (SD) is still undefined. Here, we present a morphological and immunophenotypical study of cases with mixed MM/SD and conventional SD, providing new insights on this field. Twenty cases of endometrioid carcinoma (10 with mixed MM and SD and 10 with conventional SD) were assessed by immunohistochemistry for β-catenin, CD10, CDX2, ki67, p63, p40, estrogen receptor (ER), progesterone receptor (PR) and cytokeratins (CK) 5/6, 7, 8/18 and 19. In mixed MM/SD cases, SD was mostly located within the MM areas; several degrees of SD development were observed within MM, from cells with larger cytoplasm and prominent membrane, to overt SD with morular shape and ghost cell keratinization. In the MM→SD transition, there was progressive loss of nuclear β-catenin, CD10, CDX2 and CK8/18 expression, increase of CK5/6 and CK7 expression, and stable CK19 positivity.