Innate and adaptive type 2 immunity in lung allergic inflammation.

Allergic inflammation is a type 2 immune disorder classically characterized by high levels of immunoglobulin E (IgE) and the development of Th2 cells. Asthma is a pulmonary allergic inflammatory disease resulting in bronchial hyper-reactivity. Atopic asthma is defined by IgE antibody-mediated mast cell degranulation, while in non-atopic asthma there is no allergen-specific IgE and more involvement of innate immune cells, such as basophils, group 2 innate lymphoid cells (ILC2), and eosinophils.

Seasonally lagged effects of climatic factors on malaria incidence in South Africa.

Globally, malaria cases have drastically dropped in recent years. However, a high incidence of malaria remains in some sub-Saharan African countries. South Africa is mostly malaria-free, but northeastern provinces continue to experience seasonal outbreaks.

Notch-mediated conversion of activated T cells into stem cell memory-like T cells for adoptive immunotherapy.

Adoptive T-cell immunotherapy is a promising approach to cancer therapy. Stem cell memory T (T) cells have been proposed as a class of long-lived and highly proliferative memory T cells. CD8 T cells can be generated in vitro from naive CD8 T cells via Wnt signalling; however, methods do not yet exist for inducing T cells from activated or memory T cells.

T follicular helper and T2 cells in allergic responses.

IL-4 is a cytokine commonly secreted by T2 and follicular helper T (T) cells after antigenic sensitization. T2 cells have been thought to be the major contributor of B cell help as a source of IL-4 responsible for class switch recombination to Immunoglobulin G1 (IgG1) and Immunoglobulin E (IgE). Importantly, there are some differences in transcriptional regulation between these two T cell subsets.

Basophil-derived IL-4 promotes epicutaneous antigen sensitization concomitant with the development of food allergy.

Background: Exaggerated thymic stromal lymphopoietin (TSLP) production and infiltration of basophils are associated with the pathogenesis of atopic dermatitis (AD), a recognized risk factor for the development of food allergies. Although TSLP and basophils have been implicated in promotion of food-induced allergic disorders in response to epicutaneous sensitization, the mechanisms by which TSLP-elicited basophils guide the progression of allergic inflammation in the skin to distant mucosal sites, such as the gastrointestinal tract, are poorly understood.

Objective: We sought to test the role of basophil-intrinsic IL-4 production in T2 sensitization to food antigens in the skin and effector food-induced allergic responses in the gut.

Albugo-imposed changes to tryptophan-derived antimicrobial metabolite biosynthesis may contribute to suppression of non-host resistance to Phytophthora infestans in Arabidopsis thaliana.

Background: Plants are exposed to diverse pathogens and pests, yet most plants are resistant to most plant pathogens. Non-host resistance describes the ability of all members of a plant species to successfully prevent colonization by any given member of a pathogen species. White blister rust caused by Albugo species can overcome non-host resistance and enable secondary infection and reproduction of usually non-virulent pathogens, including the potato late blight pathogen Phytophthora infestans on Arabidopsis thaliana.

Differences in the Importance of Mast Cells, Basophils, IgE, and IgG versus That of CD4 T Cells and ILC2 Cells in Primary and Secondary Immunity to Strongyloides venezuelensis.

There is evidence that mast cells, basophils, and IgE can contribute to immune responses to parasites; however, the relative levels of importance of these effector elements in parasite immunity are not fully understood. Previous work in -deficient and c- mutant mice indicated that interleukin-3 and c-Kit contribute to expulsion of the intestinal nematode during primary infection. Our findings in mast cell-deficient mice and two types of mast cell-deficient mice that have normal c- ("Hello ty" and MasTRECK mice) confirmed prior work in mice that suggested that mast cells play an important role in egg clearance in primary infections.

Overview of BioBank Japan follow-up data in 32 diseases.

Background: We established a patient-oriented biobank, BioBank Japan, with information on approximately 200,000 patients, suffering from any of 47 common diseases. This follow-up survey focused on 32 diseases, potentially associated with poor vital prognosis, and collected patient survival information, including cause of death. We performed a survival analysis for all subjects to get an overview of BioBank Japan follow-up data.

Cross-sectional analysis of BioBank Japan clinical data: A large cohort of 200,000 patients with 47 common diseases.

Background: To implement personalized medicine, we established a large-scale patient cohort, BioBank Japan, in 2003. BioBank Japan contains DNA, serum, and clinical information derived from approximately 200,000 patients with 47 diseases. Serum and clinical information were collected annually until 2012.

Overview of the BioBank Japan Project: Study design and profile.

Background: The BioBank Japan (BBJ) Project was launched in 2003 with the aim of providing evidence for the implementation of personalized medicine by constructing a large, patient-based biobank (BBJ). This report describes the study design and profile of BBJ participants who were registered during the first 5-year period of the project.

Methods: The BBJ is a registry of patients diagnosed with any of 47 target common diseases.

Analysis of grain elements and identification of best genotypes for Fe and P in Afghan wheat landraces.

This study was carried out with the aim of developing the methodology to determine elemental composition in wheat and identify the best germplasm for further research. Orphan and genetically diverse Afghan wheat landraces were chosen and EDXRF was used to measure the content of some of the elements to establish elemental composition in grains of 266 landraces using 10 reference lines. Four elements, K, Mg, P, and Fe, were measured by standardizing sample preparation.

New techniques to collect live Sarcoptes scabiei and evaluation of methods as alternative diagnostics for infection.

Sarcoptes scabiei is a widespread, highly contagious skin disease that affects many mammals including humans. The biological characteristics of S. scabiei remain unclear.

Mitochondrial activation chemicals synergize with surface receptor PD-1 blockade for T cell-dependent antitumor activity.

Although immunotherapy by PD-1 blockade has dramatically improved the survival rate of cancer patients, further improvement in efficacy is required to reduce the fraction of less sensitive patients. In mouse models of PD-1 blockade therapy, we found that tumor-reactive cytotoxic T lymphocytes (CTLs) in draining lymph nodes (DLNs) carry increased mitochondrial mass and more reactive oxygen species (ROS). We show that ROS generation by ROS precursors or indirectly by mitochondrial uncouplers synergized the tumoricidal activity of PD-1 blockade by expansion of effector/memory CTLs in DLNs and within the tumor.

An acid-tolerant ammonia-oxidizing γ-proteobacterium from soil.

Nitrification, the microbial oxidation of ammonia to nitrate via nitrite, occurs in a wide range of acidic soils. However, the ammonia-oxidizing bacteria (AOB) that have been isolated from soil to date are acid-sensitive. Here we report the isolation and characterization of an acid-adapted AOB from an acidic agricultural soil.

DEIVA: a web application for interactive visual analysis of differential gene expression profiles.

Background: Differential gene expression (DGE) analysis is a technique to identify statistically significant differences in RNA abundance for genes or arbitrary features between different biological states. The result of a DGE test is typically further analyzed using statistical software, spreadsheets or custom ad hoc algorithms. We identified a need for a web-based system to share DGE statistical test results, and locate and identify genes in DGE statistical test results with a very low barrier of entry.

Structural analyses of the nucleosome complexes with human testis-specific histone variants, hTh2a and hTh2b.

Th2a and Th2b are the testis-specific histone variants highly expressed during spermatogenesis. Approximately 4% of the genome is retained in nucleosomes in mature human sperm, which is enriched at loci of developmental importance. Our recent studies revealed that the mouse histone variant homologs TH2a and TH2b are involved in reprogramming.

A Transcriptional Switch Point During Hematopoietic Stem and Progenitor Cell Ontogeny.

During mammalian embryogenesis, hematopoietic stem and progenitor cells (HSPCs) originate from mesoderm-derived endothelial cells in the aorta-gonad-mesonephros (AGM) region and placenta (PL). Later, HSPCs expand in fetal liver (FL) and migrate to bone marrow (BM) shortly before birth. Understanding global transcriptional regulation governing HSPC emergence from embryonic stem/induced pluripotent stem cells is necessary to devise clinical applications, such as novel transplantation approaches.

Crystal structure analysis of a hypothetical protein (MJ0366) from Methanocaldococcus jannaschii revealed a novel topological arrangement of the knot fold.

The crystal structure of a hypothetical protein MJ0366, derived from Methanocaldococcus jannaschii was solved at 1.9 Å resolution using synchrotron radiation. MJ0366 was crystallized as a monomer and has knot structural arrangement.

Protective neutralizing influenza antibody response in the absence of T follicular helper cells.

Virus infection induces the development of T follicular helper (T) and T helper 1 (T1) cells. Although T cells are important in anti-viral humoral immunity, the contribution of T1 cells to a protective antibody response remains unknown. We found that IgG2 antibodies predominated in the response to vaccination with inactivated influenza A virus (IAV) and were responsible for protective immunity to lethal challenge with pathogenic H5N1 and pandemic H1N1 IAV strains, even in mice that lacked T cells and germinal centers.

Next-generation sequencing-based small RNA profiling of cerebrospinal fluid exosomes.

MicroRNAs (miRNAs), particularly those found in human body fluids, have been suggested as potential biomarkers. Among various body fluids, the cerebrospinal fluid (CSF) shows promise as a profiling target for diagnosis and monitoring of neurological diseases. However, relevant genome-scale studies are limited and no studies have profiled exosomal miRNAs in CSF.

TSHR Gene Polymorphisms in the Enhancer Regions Are Most Strongly Associated with the Development of Graves' Disease, Especially Intractable Disease, and of Hashimoto's Disease.

Background: Graves' disease (GD) and Hashimoto's disease (HD) are autoimmune thyroid disorders distinguished by the presence or absence of antithyrotropin receptor (TSHR) antibodies (TRAb). TSHR gene polymorphisms determine the amount of TSHR expressed, which may in turn influence TRAb production. The FANTOM5 project identified six GD-associated single nucleotide polymorphisms (SNPs) within the enhancer regions of the TSHR and unknown genes.