Abrogation of junctional adhesion molecule-A expression induces cell apoptosis and reduces breast cancer progression

Intercellular junctions promote homotypic cell to cell adhesion and transfer intracellular signals which control cell growth and apoptosis. Junctional adhesion molecule-A (JAM-A) is a transmembrane immunoglobulin located at tight junctions of normal epithelial cells of mammary ducts and glands. In the present paper we show that JAM-A acts as a survival factor for mammary carcinoma cells. JAM-A null mice expressing Polyoma Middle T under MMTV promoter develop significantly smaller mammary tumors than JAM-A positive mice. Angiogenesis and inflammatory or immune infiltrate were not statistically modified in absence of JAM-A but tumor cell apoptosis was significantly increased. Tumor cells isolated from JAM-A null mice or 4T1 cells incubated with JAM-A blocking antibodies showed reduced growth and increased apoptosis which paralleled altered junctional architecture and adhesive function. In a breast cancer clinical data set, tissue microarray data show that JAM-A expression correlates with poor prognosis. Gene expression analysis of mouse tumor samples showed a correlation between genes enriched in human G3 tumors and genes over expressed in JAM-A +/+ mammary tumors. Conversely, genes enriched in G1 human tumors correlate with genes overexpressed in JAM-A-/- tumors. We conclude that down regulation of JAM-A reduces tumor aggressive behavior by increasing cell susceptibility to apoptosis. JAM-A may be considered a negative prognostic factor and a potential therapeutic target.     

Exposure to warming and CO2 enrichment promotes greater above-ground biomass, nitrogen, phosphorus and arbuscular mycorrhizal colonization in newly established grasslands

Aims

In view of the projected increase in global air temperature and CO₂ concentration, the effects of climatic changes on biomass production, CO₂ fluxes and arbuscular mycorrhizal fungi (AMF) colonization in newly established grassland communities were investigated. We hypothesized that above- and below-ground biomass, gross primary productivity (GPP), AMF root colonization and nutrient acquisition would increase in response to the future climate conditions. Furthermore, we expected that increased below-ground C allocation would enhance soil respiration (R_soil).

Methods

Grassland communities were grown either at ambient temperatures with 375?ppm CO₂ (Amb) or at ambient temperatures +3°C with 620?ppm CO₂ (T+CO₂).

Results

Total biomass production and GPP were stimulated under T+CO₂. Above-ground biomass was increased under T+CO₂ while belowground biomass was similar under both climates. The significant increase in root colonization intensity under T+CO₂, and therefore the better contact between roots and AMF, probably determined the higher above-ground P and N content. R_soil was not significantly affected by the future climate conditions, only showing a tendency to increase under future climate at the end of the season.

Conclusions

Newly established grasslands benefited from the exposure to elevated CO₂ and temperature in terms of total biomass production; higher root AMF colonization may partly provide the nutrients required to sustain this growth response.     

Using changes in basal area increments to map relative risk of HWA impacts on hemlock growth across the Northeastern U.S.A

Eastern hemlock (Tsuga canadensis) is a critical species in eastern North American forests, providing a multitude of ecological and societal benefits while also acting as a foundation species in many habitats. In recent decades, however, hemlock has become threatened by hemlock woolly adelgid (HWA; Adelges tsugae), an invasive sap-feeding insect from Asia. In addition to causing the more commonly assessed metrics of foliar damage, crown decline, and hemlock mortality, HWA also decreases hemlock growth and productivity. Dendrochronological methods provide a more nuanced assessment of HWA impacts on hemlock by quantifying variable rates of radial-growth decline that follow incipient infestation. This information is necessary to better understand the variable response of hemlock to HWA, and identify the characteristics of stands with the highest potential for tolerance and recovery. To quantify decline, we calculated changes in hemlock yearly radial growth using basal area increment (BAI) measurements to identify periods of growth decline from 41 hemlock stands across New England covering a range of infestation density, duration and hemlock vigor. The onset of growth decline periods were predominantly associated with either HWA infestation or drought. However, the magnitude of change in BAI values pre- and post-decline was significantly related to HWA infestation density and crown impacts, indicating that radial growth metrics can be used to identify locations where HWA infestations have incited significant reductions in hemlock health and productivity. Additional site characteristics (slope, hillshade, and January minimum temperatures), were also significantly associated with hemlock health and productivity decline rates. In order to develop a model to identify stands likely to tolerate HWA infestation, these metrics were used to build a logit model to differentiate high- and low-BAI-reduction stands with 78% accuracy. Independent validation of the model applied to 15 hemlock sites in Massachusetts classified high and low BAI reduction classes with 80% accuracy. The model was then applied to GIS layers for New England and eastern New York to produce a spatially-explicit model that predicts the likelihood of severe hemlock growth declines if/when HWA arrives. Currently 26% of the region’s hemlock stands fall into this high risk category. Under projected climate change, this could increase to 43%. This model, along with knowledge of current HWA infestation borders, can be used to direct management efforts of potentially tolerant hemlock stands in eastern North America, with the intention of minimizing HWA-induced hemlock mortality.     

Activation of p38(MAPK) mediates the angiostatic effect of the chemokine receptor CXCR3-B

Chemokines binding the CXCR3 receptor have been shown to inhibit angiogenesis via the CXCR3-B isoform, but the underlying molecular mechanisms are unknown. Aim of this study was to elucidate the effects of CXCR3-B on activation of members of the mitogen-activated protein kinase family, and to explore the relevance of defined signaling pathways to the angiostatic effects of CXCR3-B ligands. Human embryonic kidney (HEK) 293 cells were transfected with expression vectors encoding for CXCR3-A or CXCR3-B. In cells expressing CXCR3-A, CXCL10 (IP-10) at nanomolar concentrations induced activation of ERK, Akt, and Src, as previously described in human vascular pericytes. In HEK-293 cells expressing CXCR3-B, exposure to CXCL10 in the micromolar concentration range led to activation of the p38(MAPK) pathway, as indicated by phosphorylation of p38(MAPK) itself, and of MKK3/6 and MAPKAPK-2, that lie upstream and downstream of p38(MAPK), respectively. Similar results were obtained in cells stimulated with CXCL4 (PF4), a specific ligand of CXCR3-B. In contrast, CXCL4 was unable to activate p38(MAPK) in mock-transfected HEK-293 cells. Only a modest induction of ERK or JNK was observed upon CXCR3-B activation. In human microvascular endothelial cells, which selectively express CXCR3-B, in a cell cycle-dependent fashion, CXCL10 and CXCL4 increased the enzymatic activity of p38(MAPK). Pharmacologic inhibition of p38(MAPK) by SB302580 resulted in a significant increase in DNA synthesis and in reversal of the inhibitory action of CXCL10. In conclusion, the p38(MAPK) pathway is a downstream effector of CXCR3-B implicated in the angiostatic action of this chemokine receptor.     

Deciphering the functional role of endothelial junctions by using in vivo models

Endothelial cell-to-cell junctions are vital for the formation and integrity of blood vessels. The main adhesive junctional complexes in endothelial cells, adherens junctions and tight junctions, are formed by transmembrane adhesive proteins that are linked to intracellular signalling partners and cytoskeletal-binding proteins. Gene inactivation and blocking antibodies in mouse models have revealed some of the functions of the individual junctional components in vivo, and are increasing our understanding of the functional role of endothelial cell junctions in angiogenesis and vascular homeostasis. Adherens-junction organization is required for correct vascular morphogenesis during embryo development. By contrast, the data available suggest that tight-junction proteins are not essential for vascular development but are necessary for endothelial barrier function.     

Late Miocene brackish Loxoconchidae (Crustacea, Ostracoda) from Italy

The Late Miocene Italian brackish Loxoconchidae are herein discussed and illustrated. Three genera and two subgenera have been recognized in the brackish Italian basins: Loxoconcha, Loxocorniculina, Loxoconchissa (Loxoconchissa) and Loxoconchissa (Loxocaspia). Taking into account the diagnostic characters of several Loxoconchidae genera, in this paper Loxocorniculina is raised at a generic rank, Loxocaspia is confirmed as a subgenus within genus Loxoconchissa and several new species are established: Loxoconchissa (Loxoconchissa) kinoi nov. sp., Loxoconchissa (Loxocaspia) cosentinoi nov. sp., Loxoconchissa (Loxocaspia) nuda nov. sp., Loxoconchissa (Loxocaspia) punctata nov. sp., Loxoconchissa (Loxocaspia) reticulata nov. sp., Loxoconchissa (Loxocaspia) tuberosa nov. sp. and Loxoconchissa (Loxocaspia) velonae nov. sp. Loxocorniculina is a typical Paratethyan genus which widespread into the Palaeo-Mediterranean during the late Messinian Lago-Mare event. Loxoconchissa was known to be widespread only in the Paratethyan realm and in this paper it is signalled for the first time in the Late Tortonian-early Messinian of Italy. The palaeobiogeography of these genera is discussed and the observed continuous distribution of Loxocorniculina against the disjunct distribution of Loxoconchissa leads to suggest that this latter genus underwent a passive dispersal via aquatic birds.     

High salinity alters chloroplast morpho-physiology in a freshwater Kirchneriella species (Selenastraceae) from Ethiopian Lake Awasa

Plants differ in their ability to tolerate salt stress. In aquatic ecosystems, it is important to know the responses of microalgae to increased salinity levels, especially considering that global warming will increase salinity levels in some regions of the Earth, e.g., Ethiopia. A green microalga, Kirchneriella sp. (Selenastraceae, Chlorophyta), isolated from freshwater Lake Awasa in the Rift Valley, Ethiopia, was cultured in media amended with 0, 0.4, 1.9, 5.9, and 19.4 g NaCl·L(-1) adjusted with NaCl to five salinity levels adjusted with NaCl. Growth was monitored for 3 mo, then samples were collected for photosynthetic pigment determinations, microspectrofluorimetric analyses, and micro- and submicroscopic examinations. The best growth was found at 1.9 g NaCl·L(-1). In the chloroplast, excess NaCl affected the coupling of light harvesting complex II and photosystem II (LHCII-PSII), but changes in thylakoid architecture and in the PSII assembly state allowed sufficient integrity of the photosynthetic membrane. The mucilaginous capsule around the cell probably provided partial protection against NaCl excess. On the whole, the microalga is able to acclimate to a range of NaCl concentrations, and this plasticity indicates that Kirchneriella sp. may survive future changes in water quality.