Licensing virus-specific T cells to secrete the neutrophil attracting chemokine CXCL-8 during hepatitis B virus infection

T cell functional plasticity helps tailor antiviral immunity during different phases of infections. We tested whether, during different phases of HBV infection, virus-specific T cells can acquire specific proinflammatory functions that could drive granulocyte/mononuclear cell liver infiltration. Multifunctional analysis of HBV-specific T cells during acute and chronic HBV infection revealed that HBV-specific T cells had the capacity to produce the neutrophil chemokine CXCL-8 but not IL-17. CXCL-8 producing T cells were detectable in the liver of chronic HBV patients with active hepatitis; while in acute HBV patients CXCL-8 production by T cells was temporally limited to the acute phase of disease, concomitant with the peak of liver inflammation. Characterization of the conditions necessary for the development of CXCL-8 producing T cells showed a requirement for IL-7 and IL-15 during T cell expansion. These data show that functional plasticity of virus-specific T cells spontaneously occurs during HBV infection and that an environment rich IL-7 and IL-15 can license T cells with the ability to produce CXCL-8 and potentially influence liver pathology.     

Down-regulation of Tripartite-motif containing 22 expression in breast cancer is associated with a lack of p53-mediated induction

Tripartite-motif containing 22 (TRIM22) is a direct p53 target gene and inhibits the clonogenic growth of leukemic cells. Its expression in Wilms tumors is negatively associated with disease relapse. This study addresses if TRIM22 expression is de-regulated in breast carcinoma. Western blotting analysis of a panel of 10 breast cancer cell lines and 3 non-malignant mammary epithelial cell lines with a well-characterized TRIM22 monoclonal antibody showed that TRIM22 protein is greatly under-expressed in breast cancer cells as compared to non-malignant cell lines. Similarly, TRIM22 protein is significantly down-regulated in breast tumors as compared to matched normal breast tissues. Study of cell lines with methylation inhibitor and bisulfite sequencing indicates that TRIM22 promoter hypermethylation may not be the cause for TRIM22 under-expression in breast cancer. Instead, we found that TRIM22 protein level correlates strongly (R = 0.79) with p53 protein level in normal breast tissue, but this correlation is markedly impaired (R = 0.48) in breast cancer tissue, suggesting that there is some defects in p53 regulation of TRIM22 gene in breast cancer. This notion is supported by cell line studies, which showed that TRIM22 was no longer inducible by p53-activating genotoxic drugs in breast cancer cell lines and in a p53 null cell line H1299 transfected with wild type p53. In conclusion, this study shows that TRIM22 is greatly under-expressed in breast cancer. p53 dysfunction may be one of the mechanisms for TRIM22 down-regulation.     

The formins Cdc12 and For3 cooperate during contractile ring assembly in cytokinesis

Both de novo–assembled actin filaments at the division site and existing filaments recruited by directional cortical transport contribute to contractile ring formation during cytokinesis. However, it is unknown which source is more important. Here, we show that fission yeast formin For3 is responsible for node condensation into clumps in the absence of formin Cdc12. For3 localization at the division site depended on the F-BAR protein Cdc15, and for3 deletion was synthetic lethal with mutations that cause defects in contractile ring formation. For3 became essential in cells expressing N-terminal truncations of Cdc12, which were more active in actin assembly but depended on actin filaments for localization to the division site. In tetrad fluorescence microscopy, double mutants of for3 deletion and cdc12 truncations were severely defective in contractile ring assembly and constriction, although cortical transport of actin filaments was normal. Together, these data indicate that different formins cooperate in cytokinesis and that de novo actin assembly at the division site is predominant for contractile ring formation.     

Epidermal Growth Factor Receptor (EGFR) Signaling Regulates Epiphyseal Cartilage Development through β-Catenin-dependent and -independent Pathways

The epidermal growth factor receptor (EGFR) is an essential player in the development of multiple organs during embryonic and postnatal stages. To understand its role in epiphyseal cartilage development, we generated transgenic mice with conditionally inactivated EGFR in chondrocytes. Postnatally, these mice exhibited a normal initiation of cartilage canals at the perichondrium, but the excavation of these canals into the cartilage was strongly suppressed, resulting in a delay in the formation of the secondary ossification center (SOC). This delay was accompanied by normal chondrocyte hypertrophy but decreased mineralization and apoptosis of hypertrophic chondrocytes and reduced osteoclast number at the border of marrow space. Immunohistochemical analyses demonstrated that inactivation of chondrocyte-specific EGFR signaling reduced the amounts of matrix metalloproteinases (MMP9, -13, and -14) and RANKL (receptor activator of NF-κB ligand) in the hypertrophic chondrocytes close to the marrow space and decreased the cartilage matrix degradation in the SOC. Analyses of EGFR downstream signaling pathways in primary epiphyseal chondrocytes revealed that up-regulation of MMP9 and RANKL by EGFR signaling was partially mediated by the canonical Wnt/β-catenin pathway, whereas EGFR-enhanced MMP13 expression was not. Further biochemical studies suggested that EGFR signaling stimulates the phosphorylation of LRP6, increases active β-catenin level, and induces its nuclear translocation. In line with these in vitro studies, deficiency in chondrocyte-specific EGFR activity reduced β-catenin amount in hypertrophic chondrocytes in vivo. In conclusion, our work demonstrates that chondrocyte-specific EGFR signaling is an important regulator of cartilage matrix degradation during SOC formation and epiphyseal cartilage development and that its actions are partially mediated by activating the β-catenin pathway.     

Five chemically rich species of tropical marine cyanobacteria of the genus Okeania gen. nov. (Oscillatoriales,Cyanoprokaryota)

An adverse consequence of applying morphology‐based taxonomic systems to catalog cyanobacteria, which generally are limited in the number of available morphological characters, is a fundamental underestimation of natural biodiversity. In this study, we further dissect the polyphyletic cyanobacterial genus Lyngbya and delineate the new genus Okeania gen. nov. Okeania is a tropical and subtropical, globally distributed marine group abundant in the shallow‐water benthos. Members of Okeania are of considerable ecological and biomedical importance because specimens within this group biosynthesize biologically active secondary metabolites and are known to form blooms in coastal benthic environments. Herein, we describe five species of the genus Okeania: O. hirsuta (type species of the genus), O. plumata, O. lorea, O. erythroflocculosa, and O. comitata, under the provisions of the International Code of Nomenclature for Algae, Fungi, and Plants. All five Okeania species were morphologically, phylogenetically, and chemically distinct. This investigation provides a classification system that is able to identify Okeania spp. and predict their production of bioactive secondary metabolites.     

The temporal development and additivity of plant-soil feedback in perennial grasses

Background

Current knowledge of plant-soil feedback is based largely on single end point studies with soils conditioned by monocultures, but accounting for variability in the ecological impacts of feedback effects may require understanding how feedback develops over time and in multi-species plant communities.

Methods

To examine temporal development and additivity of feedback, two pairs of native and non-native congeneric grasses were grown alone or in mixtures to create six soil conditioning treatments. We measured plant growth and feedback on the soils over 19 months and addressed whether plant biomass was additive or non-additive between soils treated by mixtures and their constituent monocultures.

Results

For native grasses, plant-soil feedback either became progressively more negative through time or switched from neutral to negative. Feedback to non-native grasses was variably neutral to positive. Final biomass of the grasses growing on soils conditioned by mixtures was generally an additive function of growth on soils conditioned by the component monocultures, except native grasses growing in soils conditioned by their own congener mixtures, which were non-additive.

Conclusions

Temporal variation and non-additivity in feedback suggest that extrapolation to communities may be complex. More work is needed to assess the generality of temporal and scaling effects.     

Genetic structure and diversity of coffee (Coffea) across Africa and the Indian Ocean islands revealed using microsatellites

Background and Aims

The coffee genus (Coffea) comprises 124 species, and is indigenous to the Old World Tropics. Due to its immense economic importance, Coffea has been the focus of numerous genetic diversity studies, but despite this effort it remains insufficiently studied. In this study the genetic diversity and genetic structure of Coffea across Africa and the Indian Ocean islands is investigated.

Methods

Genetic data were produced using 13 polymorphic nuclear microsatellite markers (simple sequence repeats, SSRs), including seven expressed sequence tag-SSRs, and the data were analysed using model- and non-model-based methods. The study includes a total of 728 individuals from 60 species.

Key Results

Across Africa and the Indian Ocean islands Coffea comprises a closely related group of species with an overall pattern of genotypes running from west to east. Genetic structure was identified in accordance with pre-determined geographical regions and phylogenetic groups. There is a good relationship between morpho-taxonomic species delimitations and genetic units. Genetic diversity in African and Indian Ocean Coffea is high in terms of number of alleles detected, and Madagascar appears to represent a place of significant diversification in terms of allelic richness and species diversity.

Conclusions

Cross-species SSR transferability in African and Indian Ocean islands Coffea was very efficient. On the basis of the number of private alleles, diversification in East Africa and the Indian Ocean islands appears to be more recent than in West and West-Central Africa, although this general trend is complicated in Africa by the position of species belonging to lineages connecting the main geographical regions. The general pattern of phylogeography is not in agreement with an overall east to west (Mascarene, Madagascar, East Africa, West Africa) increase in genome size, the high proportion of shared alleles between the four regions or the high numbers of exclusive shared alleles between pairs or triplets of regions.     

Impact of nitrogen and climate change interactions on ambient air pollution and human health

Nitrogen oxides (NO_x) are important components of ambient and indoor air pollution and are emitted from a range of combustion sources, including on-road mobile sources, electric power generators, and non-road mobile sources. While anthropogenic sources dominate, NO_x is also formed by lightning strikes and wildland fires and is also emitted by soil. Reduced nitrogen (e.g., ammonia, NH₃) is also emitted by various sources, including fertilizer application and animal waste decomposition. Nitrogen oxides, ozone (O₃) and fine particulate matter (PM_2.5) pollution related to atmospheric emissions of nitrogen (N) and other pollutants can cause premature death and a variety of serious health effects. Climate change is expected to impact how N-related pollutants affect human health. For example, changes in temperature and precipitation patterns are projected to both lengthen the O₃ season and intensify high O₃ episodes in some areas. Other climate-related changes may increase the atmospheric release of N compounds through impacts on wildfire regimes, soil emissions, and biogenic emissions from terrestrial ecosystems. This paper examines the potential human health implications of climate change and N cycle interactions related to ambient air pollution.     

Changes to soil organic N dynamics with leguminous woody plant encroachment into grasslands

Encroachment of nitrogen-fixing trees and shrubs into grasslands and savannas is a well-documented land cover change that occurs worldwide. In the Rio Grande Plains region of southern Texas, previous studies have shown woody encroachment by leguminous Prosopis glandulosa (mesquite) trees increases soil C and N, decreases microbial biomass N relative to soil N, and accelerates N mineralization and nitrification. We examined responses of the dominant organic N components in soil (amino acids and amino sugars) and two soil-bound protein-N acquiring enzymes (arylamidase and β-N-acetylglucosaminidase) along a grassland-to-woodland successional chronosequence to determine changes to soil N chemistry and extractability. The proportion of total N held within amino compounds was significantly lower in the woodlands (47 %) relative to the grassland soils (62 %). This increase in non-hydrolysable N was accompanied by increases in plant cell wall derived amino acids (e.g. hydroxyproline, serine) and losses of microbial amino sugars, indicating the woodland organic N pool was altered in composition and potentially in quality, either because it was more structurally protected or difficult to degrade due to polymerization/condensation reactions. Soil carbon-normalized activities of both soil-bound N-acquiring enzymes were significantly higher in woodland soils, consistent with changes in the biochemical composition of organic N. Although soil total N increases following woody encroachment, this additional organic N appears to be less extractable by chemical hydrolysis and thus potentially in more refractory forms, which may limit microbial N accessibility, slow the cycling of soil organic carbon, and contribute to observed soil C and N accrual in these systems.