Itk Derived Signals Regulate the Expression of Th-POK and Controls the Development of CD4+ T Cells

T cell development is critically dependent on both the environment and signals delivered by the T cell Receptor (TCR). The Tec family kinase Itk has been suggested to be an amplifier of signals emanating from the TCR and the loss of Itk partially affects most stages of thymopoiesis. Loss of Itk also differentially affects the development of conventional vs. non-conventional or innate memory phenotype T cells. Here, we examine whether these lineage choices are affected by a combination of TCR affinity and Itk by analyzing mice lacking Itk and carrying two TCR transgenes with differing affinities, OT-II and DO11.10. Our results show that developing thymocytes receive a gradient of signals, DO11.10>OT-II>DO11.10/Itk−/−>OT-II/Itk−/−. We also show that the development of CD4+ T cells is controlled by TCR signaling via Itk, which regulates the expression of the transcription factor, Th-POK, an enforcement factor for CD4 commitment. This results in a reduction in CD4+ T cell development, and an increase in the development of MHC class II restricted TCR transgenic CD8+ T cells that resemble non-conventional or innate memory phenotype CD8 T cells. This alteration accompanies increased expression of Runx3 and its target genes Eomesodermin, Granzyme B and Perforin in Itk null OT-II CD4+ thymocytes. All together, these data suggest that Itk plays an important role in CD4/CD8 commitment by regulating signal thresholds for the lineage commitment. Our data also suggest that the lower level of TCR signaling that occurs with a low affinity TCR in the absence of Itk can redirect some MHC class II restricted CD4+ T cell to class II-restricted CD8+ innate memory phenotype T cells

Organic geochemistry evidence for wildfire and elevated pO2 at the Frasnian–Famennian boundary

The Devonian experienced radiations of plants and animals, as well as a major mass extinction event during the Frasnian–Famennian (Fsingle bondF) interval. Proposed triggers have been linked to volcanism, extraterrestrial impact, sea-level fluctuations, and climate cooling, etc. However, the nature of the wildfires and its role in the biotic evolution have been rarely investigated for the Fsingle bondF interval. Here, we report organic geochemistry proxies (e.g., polycyclic aromatic hydrocarbons, PAHs) in three sections from New York (USA) to further investigate the wildfire activity and its potential link with the environmental and biotic perturbations around the Fsingle bondF interval. The studied intervals are dominated by three-ring PAHs which display an increasing abundance stratigraphically towards the Fsingle bondF boundary (FFB). An increase of 6-ring over 3-ring PAHs across the FFB is also observed for the studied sections, indicating elevated burning temperature. Additionally, slightly increased plant wax abundance and average chain length values and relatively constant Pr/Ph ratios are observed. Collectively, these results propose an increased burning frequency over the Fsingle bondF interval caused by elevated pO2 level, rather than a change in aridity. Terrestrial input only slightly increased across the FFB, and there is limited evidence for ocean anoxia. This correlates with the hypothesis that pCO2 drawdown and climate cooling could have been a driving mechanism of the Fsingle bondF biocrisis

Research on the Employment Promotion Countermeasures of post-00s college students

The post-00s (the Generation after 00s) college students in the new era show the characteristics of slow employment. In order to promote the employment of contemporary college students, this paper analyzes the psychological and ideological problems of slow employment of post-00s college students through questionnaire survey on the dynamic employment thought, value orientation, employment location, professional satisfaction and other issues of contemporary college students. A series of employment promotion strategies adapted to the characteristics of college students under the new situation are put forward from the aspects of perfecting the curriculum system of employment guidance, improving the guidance ability of employment guidance teachers, perfecting the employment guidance and service system of graduates

A New Approach for Large-Scale Scene Image Retrieval Based on Improved Parallel k

The rapid growth of digital images has caused the traditional image retrieval technology to be faced with new challenge. In this paper we introduce a new approach for large-scale scene image retrieval to solve the problems of massive image processing using traditional image retrieval methods. First, we improved traditional k-Means clustering algorithm, which optimized the selection of the initial cluster centers and iteration procedure. Second, we presented a parallel design and realization method for improved k-Means algorithm applied it to feature clustering of scene images. Finally, a storage and retrieval scheme for large-scale scene images was put forward using the large storage capacity and powerful parallel computing ability of the Hadoop distributed platform. The experimental results demonstrated that the proposed method achieved good performance. Compared with the traditional algorithms with single node architecture and parallel k-Means algorithm, the proposed method has obvious advantages for use in large-scale scene image data retrieval in terms of retrieval accuracy, retrieval time overhead, and computational performance (speedup and efficiency, sizeup, and scaleup), which is a significant improvement from applying parallel processing to intelligent algorithms with large-scale datasets

4-CPA (4-chlorophenoxyacetic acid) induces the formation and development of defective “fenghou” (vitis vinifera × v. labrusca) grape seeds

For some horticultural plants, auxins can not only induce normal fruit setting but also form fake seeds in the induced fruits. This phenomenon is relatively rare, and, so far, the underlying mechanism remains unclear. In this study, “Fenghou” (Vitis vinifera × V. labrusca) grapes were artificially emasculated before flowering and then sprayed with 4-CPA (4-chlorophenoxyacetic acid) to analyze its effect on seed formation. The results show that 4-CPA can induce normal fruit setting in “Fenghou” grapes. Although more seeds were detected in the fruits of the 4-CPA-treated grapevine, most seeds were immature. There was no significant difference in the seed shape; namely, both fruit seeds of the grapevines with and without 4-CPA treatment contained a hard seed coat. However, the immature seeds lacked embryo and endosperm tissue and could not germinate successfully; these were considered defective seeds. Tissue structure observation of defective seeds revealed that a lot of tissue redifferentiation occurred at the top of the ovule, which increased the number of cell layers of the outer integument; some even differentiated into new ovule primordia. The qRT-PCR results demonstrated that 4-CPA application regulated the expression of the genes VvARF2 and VvAP2, which are associated with integument development in “Fenghou” grape ovules. Together, this study evokes the regulatory role of 4-CPA in the division and continuous redifferentiation of integument cells, which eventually develop into defective seeds with thick seed coats in grapes

Molecular Basis of the Differentiation and Function of Virus Specific Follicular Helper CD4+ T Cells

During viral infection, virus-specific follicular helper T cells provide important help to cognate B cells for their survival, consecutive proliferation and mutation and eventual differentiation into memory B cells and antibody-secreting plasma cells. Similar to Tfh cells generated in other conditions, the differentiation of virus-specific Tfh cells can also be characterized as a process involved multiple factors and stages, however, which also exhibits distinct features. Here, we mainly focus on the current understanding of Tfh fate commitment, functional maturation, lineage maintenance and memory transition and formation in the context of viral infection

Coronary artery disease as an independent predictor of short-term and long-term outcomes in patients with type-B aortic dissection undergoing thoracic endovascular repair

Background and aimsPrevious studies reported a high prevalence of concomitant coronary artery disease (CAD) in patients with Type B aortic dissection (TBAD). However, there is too limited data on the impact of CAD on prognosis in patients with TBAD. The present study aimed to assess the short-term and long-term impact of CAD on patients with acute or subacute TBAD undergoing thoracic endovascular aortic repair (TEVAR).MethodsWe retrospectively evaluated 463 patients with acute or subacute TBAD undergoing TEVAR from a prospectively maintained database from 2010 to 2017. CAD was defined before TEVAR by coronary angiography. Multivariable logistic and cox regression analyses were performed to evaluate the relationship between CAD and the short-term as well as long-term outcomes.ResultsAccording to the results of coronary angiography, the 463 patients were divided into the following two groups: CAD group (N = 148), non-CAD group (N = 315). In total, 12 (2.6%) in-hospital deaths and 54 (12%) all-cause deaths following a median follow-up of 48.1 months were recorded. Multivariable analysis revealed that CAD was an independent predictor of in-hospital major adverse clinical events (MACE) (odd ratio [OR], 2.33; 95% confidence interval [CI], 1.07–5.08; p = 0.033), long-term mortality [hazard ratio (HR), 2.11, 95% CI, 1.19–3.74, P = 0.011] and long-term MACE (HR, 1.95, 95% CI, 1.26–3.02, P = 0.003). To further clarify the relationship between the severity of CAD and long-term outcomes, we categorized patients into three groups: zero-vessel disease, single-vessel disease and multi-vessel disease. The long-term mortality (9.7 vs. 14.4 vs. 21.2%, P = 0.045), and long-term MACE (16.8 vs. 22.2 vs. 40.4%, P = 0.001) increased with the number of identified stenosed coronary vessels. Multivariable analysis indicated that, multi-vessel disease was independently associated with long-term mortality (HR, 2.38, 95% CI, 1.16–4.89, P = 0.018) and long-term MACE (HR, 2.79, 95% CI, 1.65–4.73, P = 0.001), compared with zero-vessel disease.ConclusionsCAD was associated with short-term and long-term worse outcomes in patients with acute or subacute TBAD undergoing TEVAR. Furthermore, the severity of CAD was also associated with worse long-term prognosis. Therefore, CAD could be considered as a useful independent predictor for pre-TEVAR risk stratification in patients with TBAD

Multi-Locus Genome-Wide Association Studies for 14 Main Agronomic Traits in Barley

The agronomic traits, including morphological and yield component traits, are important in barley breeding programs. In order to reveal the genetic foundation of agronomic traits of interest, in this study 122 doubled haploid lines from a cross between cultivars “Huaai 11” (six-rowed and dwarf) and “Huadamai 6” (two-rowed) were genotyped by 9680 SNPs and phenotyped 14 agronomic traits in 3 years, and the two datasets were used to conduct multi-locus genome-wide association studies. As a result, 913 quantitative trait nucleotides (QTNs) were identified by five multi-locus GWAS methods to be associated with the above 14 traits and their best linear unbiased predictions. Among these QTNs and their adjacent genes, 39 QTNs (or QTN clusters) were repeatedly detected in various environments and methods, and 10 candidate genes were identified from gene annotation. Nineteen QTNs and two genes (sdw1/denso and Vrs1) were previously reported, and eight candidate genes need to be further validated. The Vrs1 gene, controlling the number of rows in the spike, was found to be associated with spikelet number of main spike, spikelet number per plant, grain number per plant, grain number per spike, and 1,000 grain weight in multiple environments and by multi-locus GWAS methods. Therefore, the above results evidenced the feasibility and reliability of genome-wide association studies in doubled haploid population, and the QTNs and their candidate genes detected in this study are useful for marker-assisted selection breeding, gene cloning, and functional identification in barley