Terrestrial isopods and myriapods in a forested scree slope: subterranean biodiversity,depth gradient and annual dynamics

Diversity, depth distribution and seasonal activity of isopods and myriapods were studied using subterranean traps buried in a forested limestone scree slope in the ?ierna Hora Mts, Western Carpathians, Slovakia, throughout the depth gradient from 5 to 95 cm. A total of five isopod, 13 diplopod and 11 chilopod species were identified. Most edaphic species strongly preferred the uppermost organic soil layers. Among the species captured, some represented rare stenoecous Carpathian endemics, namely the isopod Trichoniscus carpaticus, and diplopods Julus curvicornis and Leptoiulus mariae. Others were subterranean forms, partly adapted to hypogean conditions: the isopod Mesoniscus graniger, and diplopods Mecogonopodium carpathicum and Trachysphaera costata. The annual activity in the vast majority of the species ceased completely in winter, and was gradually relaunched in spring. In evaluating the age structure of two predominant diplopods Polydesmus denticulatus and Mecogonopodium carpathicum, both widespread across the depth gradient, a vertical segregation of early post-embryonic stages was found. While P. denticulatus tended to undergo the early stages of development in the soil-filled topmost levels, the early juvenile stage of M. carpathicum was distributed deep in the scree slope profile.     

Immobile survival of motoneuron (SMN) protein stored in Cajal bodies can be mobilized by protein interactions

Reduced levels of survival of motoneuron (SMN) protein lead to spinal muscular atrophy, but it is still unknown how SMN protects motoneurons in the spinal cord against degeneration. In the nucleus, SMN is associated with two types of nuclear bodies denoted as gems and Cajal bodies (CBs). The 23 kDa isoform of fibroblast growth factor-2 (FGF-2²³) is a nuclear protein that binds to SMN and destabilizes the SMN-Gemin2 complex. In the present study, we show that FGF-2²³ depletes SMN from CBs without affecting their general structure. FRAP analysis of SMN-EGFP in CBs demonstrated that the majority of SMN in CBs remained mobile and allowed quantification of fast, slow and immobile nuclear SMN populations. The potential for SMN release was confirmed by in vivo photoconversion of SMN-Dendra2, indicating that CBs concentrate immobile SMN that could have a specialized function in CBs. FGF-2²³ accelerated SMN release from CBs, accompanied by a conversion of immobile SMN into a mobile population. Furthermore, FGF-2²³ caused snRNP accumulation in CBs. We propose a model in which Cajal bodies store immobile SMN that can be mobilized by its nuclear interaction partner FGF-2²³, leading to U4 snRNP accumulation in CBs, indicating a role for immobile SMN in tri-snRNP assembly.     

Identification of renal Cd36 as a determinant of blood pressure and risk for hypertension

To identify renally expressed genes that influence risk for hypertension, we integrated expression quantitative trait locus (QTL) analysis of the kidney with genome-wide correlation analysis of renal expression profiles and blood pressure in recombinant inbred strains derived from the spontaneously hypertensive rat (SHR). This strategy, together with renal transplantation studies in SHR progenitor, transgenic and congenic strains, identified deficient renal expression of Cd36 encoding fatty acid translocase as a genetically determined risk factor for spontaneous hypertension.     

Tumour micro-environment elicits innate resistance to RAF inhibitors through HGF secretion

Drug resistance presents a challenge to the treatment of cancer patients. Many studies have focused on cell-autonomous mechanisms of drug resistance. By contrast, we proposed that the tumour micro-environment confers innate resistance to therapy. Here we developed a co-culture system to systematically assay the ability of 23 stromal cell types to influence the innate resistance of 45 cancer cell lines to 35 anticancer drugs. We found that stroma-mediated resistance is common, particularly to targeted agents. We characterized further the stroma-mediated resistance of BRAF-mutant melanoma to RAF inhibitors because most patients with this type of cancer show some degree of innate resistance. Proteomic analysis showed that stromal cell secretion of hepatocyte growth factor (HGF) resulted in activation of the HGF receptor MET, reactivation of the mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3-OH kinase (PI(3)K)-AKT signalling pathways, and immediate resistance to RAF inhibition. Immunohistochemistry experiments confirmed stromal cell expression of HGF in patients with BRAF-mutant melanoma and showed a significant correlation between HGF expression by stromal cells and innate resistance to RAF inhibitor treatment. Dual inhibition of RAF and either HGF or MET resulted in reversal of drug resistance, suggesting RAF plus HGF or MET inhibitory combination therapy as a potential therapeutic strategy for BRAF-mutant melanoma. A similar resistance mechanism was uncovered in a subset of BRAF-mutant colorectal and glioblastoma cell lines. More generally, this study indicates that the systematic dissection of interactions between tumours and their micro-environment can uncover important mechanisms underlying drug resistance.     

Co-occurrence of three Aristolochia-feeding Papilionids (Archon apollinus,Zerynthia polyxena and Zerynthia cerisy) in Greek Thrace

Comparative studies of co-occurring species using overlapping resources may help in understanding the mechanisms supporting biotic diversity in species-rich regions, such as the Mediterranean region of Europe. Three Papilionidae butterflies, Archon apollinus, Zerynthia cerisy and Zerynthia polyxena, develop on Aristolochia plants and co-occur in Greek Thrace. We used mark–recapture to describe adult demography and dispersal, and searched for eggs and larvae to assess host plants and microhabitat preferences. Adult flight timing followed a sequence from earliest A. apollinus, through Z. polyxena to late Z. cerisy; this was more prominent in 2010 (warm early spring) than in 2011 (cold delayed spring). Population densities were highest for A. apollinus and lowest for Z. cerisy, whereas dispersal ability followed a reverse pattern. Adults of all three species crossed distances > 3 km and used all habitat types present. Four Aristolochia host plants were used at the study locality: small Aristolochia pallida, intermediate Aristolochia rotunda and Aristolochia hirta, and bulky, late-sprouting Aristolochia clematitis. Both A. apollinus and Z. polyxena used all four Aristolochia species, the former preferring Aristolochia rotunda and Aristolochia hirta, the latter Aristolochia rotunda and Aristolochia pallida. Zerynthia cerisy did not use the early-growing Aristolochia pallida while frequently using the late-growing Aristolochia clematitis. Further parameters affecting oviposition were biotope and canopy closure: early A. apollinus tolerated shady sites but late Z. cerisy avoided them. The simultaneous use of several host plants differing in phenology and habitat requirements, combined with rather high dispersal ability, arguably buffers the butterflies’ population dynamics against yearly variation in weather, while allowing efficient occupation of the diverse Mediterranean landscapes. The regional habitat diversity, created during millennia of human activity, is currently threatened by land abandonment, which may diminish the resource base for the studied butterflies.