IL-12 and Related Cytokines: Function and Regulatory Implications in Candida albicans Infection

IL-12 is a cytokine with links to both innate and adaptive immunity systems. In mice, its deletion leads to acute susceptibility to oral infection with the yeast Candida albicans, whereas such mice are resistant to systemic disease. However, it is an essential component of the adaptive response that leads to the generation of Th1-type cytokine responses and protection against disseminated disease. This paper presents an overview of the role of IL-12 in models of systemic and mucosal infection and the possible relationships between them

Bone Marrow Colony-Formation In Vitro After Infection of Genetically Defined Inbred Mice with Candida Albicans

The effect of C. albicans infection on the production of haematopoietic precursor cells in the bone marrow of CBA/CaH and BALB/c mice was evaluated by assay of colony formation in vitro. In immunocompetent mice, neither systemic nor oral infection induced significant alterations in colony formation by bone marrow from the two mouse strains, and Candida infection did not alter the proportion of morphological cell types in the colonies. However, the number of neutrophil-like was relatively greater in colonies derived from acutely infected CBA/CaH nude mice than in those from BALB/c nude mice, whereas small mononuclear cells were present in higher proportions in the latter strain. In both strains of nude mice, there was an increase in colony formation at 6 days after oral infection, but at 8 weeks, when the infection had become chronic, the production of bone marrow cells by CBA/CaH nude mice was significantly less than that by BALB/c nude mice. Reconstitution of nude mice with syngeneic lymphocytes enhanced the production of bone marrow precursor cells by BALB/c, but not by CBA/CaH mice, suggesting that T cells can enhance host resistance by promoting the colony-forming response of the bone marrow in BALB/c mice that are genetically resistant to tissue damage, but not in CBA/CaH that are prone to severe lesions. Finally, culture with Candida antigen in vitro decreased the number of colony-forming cells in cultures from CBA/CaH, but not from BALB/c mice

Mincle polarizes human monocyte and neutrophil responses to Candida albicans

The distribution and function of the C-type lectin Mincle has not previously been investigated in human cells, although mouse models have demonstrated a non-redundant role for Mincle in the host response to fungal infections. This study identified an unusual pattern of reciprocal expression of Mincle on peripheral blood monocytes or neutrophils isolated from the same donor. Expression on monocytes was inversely correlated with phagocytosis and yeast killing, but was necessary for the induction of inflammatory cytokines in response to ex vivo Candida challenge. In contrast, Mincle expression on neutrophils was associated with phagocytic and candidacidal potential of those cells. Candida challenge upregulated Mincle expression but only in Mincle+ cells. These data highlight species-specific differences between the regulation of Mincle expression in mouse and man. Reciprocal expression of Mincle modified the candidacidal potential of monocytes or neutrophils, suggesting it may also polarize the type of host response to fungal infection. Immunology and Cell Biology (2012) 90, 889-895; doi:10.1038/icb.2012.24; published online 29 May 201

Genetic models of Candida infection and host resistance factors

Infections caused by the yeast Candida albicans can occur on the skin, on mucous surfaces, or in disseminated form throughout the body and corresponding models have been developed in vivo. Patterns of infection differ in inbred mice, and the variability has been shown to be genetically regulated. The availability of gene-knockout mice has also contributed significantly to an understanding of the cellular and molecular basis of the host response

TRY plant trait database - enhanced coverage and open access

Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives

The case for the continued use of the genus name Mimulus for all monkeyflowers

The genus Mimulus is a well-studied group of plant species, which has for decades allowed researchers to address a wide array of fundamental questions in biology (Wu & al. 2008; Twyford & al. 2015). Linnaeus named the type species of Mimulus (ringens L.), while Darwin (1876) used Mimulus (luteus L.) to answer key research questions. The incredible phenotypic diversity of this group has made it the focus of ecological and evolutionary study since the mid-20th century, initiated by the influential work of Clausen, Keck, and Hiesey as well as their students and collaborators (Clausen & Hiesey 1958; Hiesey & al. 1971, Vickery 1952, 1978). Research has continued on this group of diverse taxa throughout the 20th and into the 21st century (Bradshaw & al. 1995; Schemske & Bradshaw 1999; Wu & al. 2008; Twyford & al. 2015; Yuan 2019), and Mimulus guttatus was one of the first non-model plants to be selected for full genome sequencing (Hellsten & al. 2013). Mimulus has played a key role in advancing our general understanding of the evolution of pollinator shifts (Bradshaw & Schemske 2003; Cooley & al. 2011; Byers & al. 2014), adaptation (Lowry & Willis 2010; Kooyers & al. 2015; Peterson & al. 2016; Ferris & Willis 2018; Troth & al. 2018), speciation (Ramsey & al. 2003; Wright & al. 2013; Sobel & Streisfeld 2015; Zuellig & Sweigart 2018), meiotic drive (Fishman & Saunders 2008), polyploidy (Vallejo-Marín 2012; Vallejo-Marín & al. 2015), range limits (Angert 2009; Sexton et al. 2011; Grossenbacher & al. 2014; Sheth & Angert 2014), circadian rhythms (Greenham & al. 2017), genetic recombination (Hellsten & al. 2013), mating systems (Fenster & Ritland 1994; Dudash & Carr 1998; Brandvain & al. 2014) and developmental biology (Moody & al. 1999; Baker & al. 2011, 2012; Yuan 2019). This combination of a rich history of study coupled with sustained modern research activity is unparalleled among angiosperms. Across many interested parties, the name Mimulus therefore takes on tremendous biological significance and is recognizable not only by botanists, but also by zoologists, horticulturalists, naturalists, and members of the biomedical community. Names associated with a taxonomic group of this prominence should have substantial inertia, and disruptive name changes should be avoided. As members of the Mimulus community, we advocate retaining the genus name Mimulus to describe all monkeyflowers. This is despite recent nomenclature changes that have led to a renaming of most monkeyflower species to other genera.Additional co-authors: Jannice Friedman, Dena L Grossenbacher, Liza M Holeski, Christopher T Ivey, Kathleen M Kay, Vanessa A Koelling, Nicholas J Kooyers, Courtney J Murren, Christopher D Muir, Thomas C Nelson, Megan L Peterson, Joshua R Puzey, Michael C Rotter, Jeffrey R Seemann, Jason P Sexton, Seema N Sheth, Matthew A Streisfeld, Andrea L Sweigart, Alex D Twyford, John H Willis, Kevin M Wright, Carrie A Wu, Yao-Wu Yua

Transcriptomic analysis supports similar functional roles for the two thymuses of the tammar wallaby

Background: The thymus plays a critical role in the development and maturation of T-cells. Humans have a single thoracic thymus and presence of a second thymus is considered an anomaly. However, many vertebrates have multiple thymuses. The tammar wallaby has two thymuses: a thoracic thymus (typically found in all mammals) and a dominant cervical thymus. Researchers have known about the presence of the two wallaby thymuses since the 1800s, but no genome-wide research has been carried out into possible functional differences between the two thymic tissues. Here, we used pyrosequencing to compare the transcriptomes of a cervical and thoracic thymus from a single 178 day old tammar wallaby.Results: We show that both the tammar thoracic and the cervical thymuses displayed gene expression profiles consistent with roles in T-cell development. Both thymuses expressed genes that mediate distinct phases of T-cells differentiation, including the initial commitment of blood stem cells to the T-lineage, the generation of T-cell receptor diversity and development of thymic epithelial cells. Crucial immune genes, such as chemokines were also present. Comparable patterns of expression of non-coding RNAs were seen. 67 genes differentially expressed between the two thymuses were detected, and the possible significance of these results are discussed.Conclusion: This is the first study comparing the transcriptomes of two thymuses from a single individual. Our finding supports that both thymuses are functionally equivalent and drive T-cell development. These results are an important first step in the understanding of the genetic processes that govern marsupial immunity, and also allow us to begin to trace the evolution of the mammalian immune system

TRY plant trait database - enhanced coverage and open access

This article has 730 authors, of which I have only listed the lead author and myself as a representative of University of HelsinkiPlant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives.Peer reviewe

The genetic architecture of membranous nephropathy and its potential to improve non-invasive diagnosis

Membranous Nephropathy (MN) is a rare autoimmune cause of kidney failure. Here we report a genome-wide association study (GWAS) for primary MN in 3,782 cases and 9,038 controls of East Asian and European ancestries. We discover two previously unreported loci, NFKB1 (rs230540, OR = 1.25, P = 3.4 × 10-12) and IRF4 (rs9405192, OR = 1.29, P = 1.4 × 10-14), fine-map the PLA2R1 locus (rs17831251, OR = 2.25, P = 4.7 × 10-103) and report ancestry-specific effects of three classical HLA alleles: DRB1*1501 in East Asians (OR = 3.81, P = 2.0 × 10-49), DQA1*0501 in Europeans (OR = 2.88, P = 5.7 × 10-93), and DRB1*0301 in both ethnicities (OR = 3.50, P = 9.2 × 10-23 and OR = 3.39, P = 5.2 × 10-82, respectively). GWAS loci explain 32% of disease risk in East Asians and 25% in Europeans, and correctly re-classify 20-37% of the cases in validation cohorts that are antibody-negative by the serum anti-PLA2R ELISA diagnostic test. Our findings highlight an unusual genetic architecture of MN, with four loci and their interactions accounting for nearly one-third of the disease risk