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The development of crop varieties with stable performance in future environmental conditions represents a critical challenge in the context of climate change. Environmental data collected at the field level, such as soil and climatic information, can be relevant to improve predictive ability in genomic prediction models by describing more precisely genotype-by-environment interactions, which represent a key component of the phenotypic response for complex crop agronomic traits. Modern predictive modeling approaches can efficiently handle various data types and are able to capture complex nonlinear relationships in large datasets. In particular, machine learning techniques have gained substantial interest in recent years. Here we examined the predictive ability of machine learning-based models for two phenotypic traits in maize using data collected by the Maize Genomes to Fields (G2F) Initiative. The data we analyzed consisted of multi-environment trials (METs) dispersed across the United States and Canada fro also revealed that temperature at flowering stage, frequency and amount of water received during the vegetative and grain filling stage, and soil organic matter content appeared as important predictors for grain yield in our panel of environments.
We previously reported algorithms based on clinical parameters and plasma cell characteristics to identify patients with smoldering multiple myeloma (SMM) with higher risk of progressing who could benefit from early treatment. In this work, we analyzed differences in the immune bone marrow (BM) microenvironment in SMM to better understand the role of immune surveillance in disease progression and to identify immune biomarkers associated to higher risk of progression.
Gene expression analysis of BM cells from 28 patients with SMM, 22 patients with monoclonal gammopathy of undetermined significance (MGUS) and 22 patients with symptomatic MM was performed by using Nanostring Technology.
BM cells in SMM compared to both MGUS and symptomatic MM showed upregulation of genes encoding for key molecules in cytotoxicity. However, some of these cytotoxic molecules positively correlated with inhibitory immune checkpoints, which may impair the effector function of BM cytotoxic cells. Analysis of 28 patients with SMMimmune gene profile in combination with clinical parameters and PC characterization may be useful to identify SMM patients with higher risk of progression.[This corrects the article DOI 10.3389/fimmu.2020.613638.].
Pancreatic cancer has a poor prognosis, and it is traditionally treated with chemotherapy. this website Fortunately, immunotherapy has rapidly changed the landscape of solid tumor treatment, and improving the survival of cancer patients. However, pancreatic cancer is non-immunogenic, and single agent immunotherapies are unfavorable to its prognosis.
Here, we report a case of stage IV pancreatic cancer in a patient with TSC2 and SMAD4 mutations treated with immunotherapy when the disease progressed after multi-line chemotherapy. Next generation sequencing (NGS) confirmed the presence of TSC2 and SMAD4 mutations and microsatellite stability (MSS). When the disease progressed after chemotherapy, a combination strategy was devised consisting of chemotherapy (S-1) and sintilimab. The patient had a partial response to therapy with this regimen, the lesions were significantly reduced and nearly disappeared. In metastatic pancreatic cancer, responses of this magnitude are rarely seen.
This outcome reveals that this combination can be effective in treating metastatic pancreatic cancer, especially in pancreatic cancer patients with SMAD4 and TSC2 mutations. This may help increase the use of this therapy in large-scale clinical research.
This outcome reveals that this combination can be effective in treating metastatic pancreatic cancer, especially in pancreatic cancer patients with SMAD4 and TSC2 mutations. This may help increase the use of this therapy in large-scale clinical research.The members of the protein tyrosine phosphatase (PTP) family are key regulators in multiple signal transduction pathways and therefore they play important roles in many cellular processes, including immune response. As a member of PTP family, protein tyrosine phosphatase receptor type O (PTPRO) belongs to the R3 receptor-like protein tyrosine phosphatases. The expression of PTPRO isoforms is tissue-specific and the truncated PTPRO (PTPROt) is mainly observed in hematopoietic cells, including B cells, T cells, macrophages and other immune cells. link2 Therefore, PTPROt may play an important role in immune cells by affecting their growth, differentiation, activation and immune responses. In this review, we will focus on the regulatory roles and underlying molecular mechanisms of PTPRO/PTPROt in immune cells, including B cells, T cells, and macrophages.Successful eradication of tumors by the immune system depends on generation of antigen-specific T cells that migrate to tumor sites and kill cancerous cells. However, presence of suppressive Treg populations inside tumor microenvironment hinders effector T cell function and decreases antitumor immunity. In this study we independently evaluated and confirmed prognostic signature of 17-Treg-related-lncRNA. Immune cell infiltration analysis using 17-lncRNA signature as a probe, accurately described Treg populations in tumor immune microenvironment. 17-lncRNA signature model predicted prognosis with excellent accuracy in all three cohorts training cohort (AUC=0.82), testing cohort (AUC=0.61) and total cohort (AUC=0.72). The Kaplan-Meier analysis confirmed that the overall survival of patients in the low-risk group was significantly better than those in the high-risk group(P less then 0.001). CIBERSORT analysis confirmed that low risk group had higher infiltration of tumor killer CD8 T cells, memory activated CD4 T cells, follicular helper T cells and T cells regulatory (Tregs), and lower expression of M0 macrophages and Mast cells activated. These results indicate that the 17-lncRNA signature is a novel prognostic and support the use of lncRNA as a stratification tool to help guide the course of treatment and clinical decision making in patients at high risk of HNSCC.Helminth parasite infections of humans and livestock are a global health and economic problem. Resistance of helminths to current drug treatment is an increasing problem and alternative control approaches, including vaccines, are needed. Effective vaccine design requires knowledge of host immune mechanisms and how these are stimulated. Mouse models of helminth infection indicate that tuft cells, an unusual type of epithelial cell, may 'sense' infection in the small intestine and trigger a type 2 immune response. Currently nothing is known of tuft cells in immunity in other host species and in other compartments of the gastrointestinal (GI) tract. Here we address this gap and use immunohistochemistry and single cell RNA-sequencing to detail the presence and gene expression profile of tuft cells in sheep following nematode infections. We identify and characterize tuft cells in the ovine abomasum (true stomach of ruminants) and show that they increase significantly in number following infection with the globallytodes.Defensins are host defense peptides present in nearly all living species, which play a crucial role in innate immunity. These peptides provide protection to the host, either by killing microbes directly or indirectly by activating the immune system. In the era of antibiotic resistance, there is a need to develop a fast and accurate method for predicting defensins. In this study, a systematic attempt has been made to develop models for predicting defensins from available information on defensins. We created a dataset of defensins and non-defensins called the main dataset that contains 1,036 defensins and 1,035 AMPs (antimicrobial peptides, or non-defensins) to understand the difference between defensins and AMPs. Our analysis indicates that certain residues like Cys, Arg, and Tyr are more abundant in defensins in comparison to AMPs. We developed machine learning technique-based models on the main dataset using a wide range of peptide features. Our SVM (support vector machine)-based model discriminates defensins and AMPs with MCC of 0.88 and AUC of 0.98 on the validation set of the main dataset. In addition, we created an alternate dataset that consists of 1,036 defensins and 1,054 non-defensins obtained from Swiss-Prot. Models were also developed on the alternate dataset to predict defensins. Our SVM-based model achieved maximum MCC of 0.96 with AUC of 0.99 on the validation set of the alternate dataset. All models were trained, tested, and validated using standard protocols. Finally, we developed a web-based service "DefPred" to predict defensins, scan defensins in proteins, and design the best defensins from their analogs. The stand-alone software and web server of DefPred are available at https//webs.iiitd.edu.in/raghava/defpred.The ocular mucosal tissues are exposed to potentially harmful foreign antigens in the air and tear fluid. The tear duct-associated lymphoid tissue (TALT) may contribute to immune surveillance in the eye region. Follicle-associated epithelium (FAE) of TALTs is classified as stratified squamous epithelium and consists of squamous epithelial cells arranged in layers on the basement membrane. In contrast, most mucosa-associated lymphoid tissue is covered by a monolayer of epithelium containing microfold (M) cells. Therefore, antigen uptake and the presence of M cells in TALT are not fully understood. link3 The present study found that a small population of FAE cells in the TALT expressed intestinal M-cell markers, namely Sox8, Tnfaip2, GP2, and OPG. This cell population was identified as functional M cells because of their uptake capacity of luminal nanoparticles. In addition, RANKL, which is essential for M-cell differentiation, was expressed by stroma-like cells at the subepithelial region and its receptor RANK by the FAE in the TALT. The administration of RANKL markedly increased the number of Sox8+ M cells. In contrast, deficiency in OPG, an endogenous inhibitor of RANKL, increased the number of M cells in the TALT. These data demonstrate that the RANKL-RANK axis is essential for M-cell differentiation in the TALT. Furthermore, immunization via eye drops elicited the production of antigen-specific antibodies in tears, which was enhanced by RANKL administration. Thus, TALT M cells play an important role in the immunosurveillance of the eye region.Strict control of B lymphocyte development is required for the ability to mount humoral immune responses to diverse foreign antigens while remaining self-tolerant. In the bone marrow, B lineage cells transit through several developmental stages in which they assemble a functional B cell receptor in a stepwise manner. The immunoglobulin heavy chain gene is rearranged at the pro-B stage. At the large pre-B stage, cells with a functional heavy chain expand in response to signals from IL-7 and the pre-BCR. Cells then cease proliferation at the small pre-B stage and rearrange the immunoglobulin light chain gene. The fully formed BCR is subsequently expressed on the surface of immature B cells and autoreactive cells are culled by central tolerance mechanisms. Once in the periphery, transitional B cells develop into mature B cell subsets such as marginal zone and follicular B cells. These developmental processes are controlled by transcription factor networks, central to which are IRF4 and IRF8. These were thought to act redundantly during B cell development in the bone marrow, with their functions diverging in the periphery where IRF4 limits the number of marginal zone B cells and is required for germinal center responses and plasma cell differentiation.