The differential regulation of Lck kinase phosphorylation sites by CD45 is critical for T cell receptor signaling responses

SummaryThe molecular mechanisms whereby the CD45 tyrosine phosphatase (PTPase) regulates T cell receptor (TCR) signaling responses remain to be elucidated. To investigate this question, we have reconstituted CD45 (encoded by Ptprc)-deficient mice, which display severe defects in thymic development, with five different expression levels of transgenic CD45RO, or with mutant PTPase null or PTPase-low CD45R0. Whereas CD45 PTPase activity was absolutely required for the reconstitution of thymic development, only 3% of wild-type CD45 activity restored T cell numbers and normal cytotoxic T cell responses. Lowering the CD45 expression increased CD4 lineage commitment. Peripheral T cells with very low activity of CD45 phosphatase displayed reduced TCR signaling, whereas intermediate activity caused hyperactivation of CD4+ and CD8+ T cells. These results are explained by a rheostat mechanism whereby CD45 differentially regulates the negatively acting pTyr-505 and positively acting pTyr-394 p56lck tyrosine kinase phosphorylation sites. We propose that high wild-type CD45 expression is necessary to dephosphorylate p56lck pTyr-394, suppressing CD4 T+ cell lineage commitment and hyperactivity

Towards a state-space geometry of neural responses to natural scenes: A steady-state approach

Our understanding of information processing by the mammalian visual system has come through a variety of techniques ranging from psychophysics and fMRI to single unit recording and EEG. Each technique provides unique insights into the processing framework of the early visual system. Here, we focus on the nature of the information that is carried by steady state visual evoked potentials (SSVEPs). To study the information provided by SSVEPs, we presented human participants with a population of natural scenes and measured the relative SSVEP response. Rather than focus on particular features of this signal, we focused on the full state-space of possible responses and investigated how the evoked responses are mapped onto this space. Our results show that it is possible to map the relatively high-dimensional signal carried by SSVEPs onto a 2-dimensional space with little loss. We also show that a simple biologically plausible model can account for a high proportion of the explainable variance (~73%) in that space. Finally, we describe a technique for measuring the mutual information that is available about images from SSVEPs. The techniques introduced here represent a new approach to understanding the nature of the information carried by SSVEPs. Crucially, this approach is general and can provide a means of comparing results across different neural recording methods. Altogether, our study sheds light on the encoding principles of early vision and provides a much needed reference point for understanding subsequent transformations of the early visual response space to deeper knowledge structures that link different visual environments

Predicting Student Depression With Measures of General and Academic Anxieties

Universities are increasingly cognizant of the importance of attending to the psychological and emotional needs of undergraduate learners, recognizing that anxiety and depression have significant negative impacts on student retention and success. The focus of the current study was to evaluate the connections among various forms of anxiety and examine the relationships these indicators of anxiety have with depression. The results demonstrated that a broad measure of neuroticism was a meaningful predictor for depression. However, precision in detecting depressive symptoms was improved when examining an additional measure specifically focused on academic anxiety. The results provide support for a nested model of anxiety, which suggests that broad neuroticism, then academic anxiety, and finally test anxiety are progressively more specific manifestations of anxiety in university students. The collection of these findings provide early indication of avenues that may support learners who are beginning to exhibit signs of emotional distress, potentially reducing the tendency to progress from a contextual anxiety response to more serious mental health concerns

Boundary Layer Transition Results From STS-114

The tool for predicting the onset of boundary layer transition from damage to and/or repair of the thermal protection system developed in support of Shuttle Return to Flight is compared to the STS-114 flight results. The Boundary Layer Transition (BLT) Tool is part of a suite of tools that analyze the aerothermodynamic environment of the local thermal protection system to allow informed disposition of damage for making recommendations to fly as is or to repair. Using mission specific trajectory information and details of each damage site or repair, the expected time of transition onset is predicted to help determine the proper aerothermodynamic environment to use in the subsequent thermal and stress analysis of the local structure. The boundary layer transition criteria utilized for the tool was developed from ground-based measurements to account for the effect of both protuberances and cavities and has been calibrated against flight data. Computed local boundary layer edge conditions provided the means to correlate the experimental results and then to extrapolate to flight. During STS-114, the BLT Tool was utilized and was part of the decision making process to perform an extravehicular activity to remove the large gap fillers. The role of the BLT Tool during this mission, along with the supporting information that was acquired for the on-orbit analysis, is reviewed. Once the large gap fillers were removed, all remaining damage sites were cleared for reentry as is. Post-flight analysis of the transition onset time revealed excellent agreement with BLT Tool predictions

Biosynthesis of Mitochondrial Porin and Insertion into the Outer Mitochondrial Membrane of Neuruspora crassa

Mitochondrial porin, the major protein of the outer mitochondrial membrane is synthesized by free cytoplasmic polysomes. The apparent molecular weight of the porin synthesized in homologous or heterologous cell-free systems is the same as that of the mature porin. Transfer in vitro of mitochondrial porin from the cytosolic fraction into the outer membrane of mitochondria could be demonstrated. Before membrane insertion, mitochondrial porin is highly sensitive to added proteinase; afterwards it is strongly protected. Binding of the precursor form to mitochondria occurs at 4°C and appears to precede insertion into the membrane. Unlike transfer of many precursor proteins into or across the inner mitochondrial membrane, assembly of the porin is not dependent on an electrical potential across the inner membrane

Erasure detection of a dual-rail qubit encoded in a double-post superconducting cavity

Qubits with predominantly erasure errors present distinctive advantages for quantum error correction(QEC) and fault tolerant quantum computing. Logical qubits based on dual-rail encoding that exploit erasure detection have been recently proposed in superconducting circuit architectures, either with coupled transmons or cavities. Here, we implement a dual-rail qubit encoded in a compact, double-post superconducting cavity. Using an auxiliary transmon, we perform erasure detection on the dual-rail subspace. We characterize the behaviour of the codespace by a novel method to perform joint-Wigner tomography. This is based on modifying the cross-Kerr interaction between the cavity modes and the transmon. We measure an erasure rate of 3.981 +/- 0.003 (ms)-1 and a residual dephasing error rate up to 0.17 (ms)-1 within the codespace. This strong hierarchy of error rates, together with the compact and hardware-efficient nature of this novel architecture, hold promise in realising QEC schemes with enhanced thresholds and improved scaling

Thermal Imaging Efficacy in Predicting Trim Loss from Cull Sow Carcasses

Abattoir-level digital image measurement and assessments recorded during the harvest process could contribute to better estimates of the economic value of each animal and could be used as animal health and well-being assessment tools to provide information/feedback for commercial pork producers. This study evaluated the association between live animal infrared images and nonedible trim loss from cull sows. Eighty sow carcasses selected from cull sows normally presented at a Midwest cull sow abattoir were evaluated. A thermal image and corresponding trim losses were collected from each sow.Regions of interest, referred to as hotspots, were isolated from the thermal images of individual sows. The relationships between the thermal hotspots, trim loss weight, and trim loss percentage from each carcass were evaluated using Pearson correlation coefficients, stepwise regression, and prediction equations. The most predictive model included covariates for the number of hotspots, live identification category, hotspot location, and explanatory continuous covariates for pixels with elevated temperature. Live animal defect classification and hotspot location categories significantly contributed to variation in percent trim. This suggests that visually identifying defects like abscesses, poor condition, mammary infection, or a combination on live cull sows is associated with trim losses from their carcass

Detection of transcriptional difference of porcine imprinted genes using different microarray platforms

BACKGROUND: Presently, multiple options exist for conducting gene expression profiling studies in swine. In order to determine the performance of some of the existing microarrays, Affymetrix Porcine, Affymetrix Human U133+2.0, and the U.S. Pig Genome Coordination Program spotted glass oligonucleotide microarrays were compared for their reproducibility, coverage, platform independent and dependent sensitivity using fibroblast cell lines derived from control and parthenogenic porcine embryos. RESULTS: Array group correlations between technical replicates demonstrated comparable reproducibility in both Affymetrix arrays. Glass oligonucleotide arrays showed greater variability and, in addition, approximately 10% of probes had to be discarded due to slide printing defects. Probe level analysis of Affymetrix Human arrays revealed significant variability within probe sets due to the effects of cross-species hybridization. Affymetrix Porcine arrays identified the greatest number of differentially expressed genes amongst probes common to all arrays, a measure of platform sensitivity. Affymetrix Porcine arrays also identified the greatest number of differentially expressed known imprinted genes using all probes on each array, an ad hoc measure of realistic performance for this particular experiment. CONCLUSION: We conclude that of the platforms currently available and tested, the Affymetrix Porcine array is the most sensitive and reproducible microarray for swine genomic studies