Plant community attributes affect dry grassland orchid establishment

Several factors have been taken into account to explain the distribution of orchid species. We explored the extent to which plant community attributes affect the abundance and reproductive fitness of three orchid species (Anacamptis morio, Himantoglossum adriaticum and Ophrys sphegodes), native to dry grasslands. Structural attributes of plant community (e.g. cover and height) were assessed in ninety 4 m(2) plots scattered on three hill massifs of the Veneto Region (NE Italy). For the three target orchid species, the height of the flowering stalk, the relative ramet height and the number of flowers and fruits were recorded in 203 tagged ramets. Generalized Linear Model revealed that plant community attributes such as cover and height of the herb layer exert a negative effect on the abundance of orchid populations. Furthermore, regression models indicated that O. sphegodes and H. adriaticum reproductive fitness, determined as fruit/flower ratio, was positively affected by relative ramet height. Our results revealed that local herbaceous vegetation structure influences the cover and fruit set of target orchid species. However, there can be substantial variation in the response of different species and variation in the structural attributes of surrounding vegetation may be associated with differences in the strength of selection. In order to achieve effective results in orchid species conservation, protocols for the in situ conservation must detail the range of vegetation covers and heights at which orchid species are favoured and can produce the most effective inflorescences

Inhibition of hypoxic response decreases stemness and reduces tumorigenic signaling due to impaired assembly of HIF1 transcription complex in pancreatic cancer

Pancreatic tumors are renowned for their extremely hypoxic centers, resulting in upregulation of a number of hypoxia mediated signaling pathways including cell proliferation, metabolism and cell survival. Previous studies from our laboratory have shown that Minnelide, a water-soluble pro-drug of triptolide (anti-cancer compound), decreases viability of cancer cells in vitro as well as in vivo. However, its mechanism of action remain elusive. In the current study we evaluated the effect of Minnelide, on hypoxia mediated oncogenic signaling as well as stemness in pancreatic cancer. Minnelide has just completed Phase 1 trial against GI cancers and is currently awaiting Phase 2 trials. Our results showed that upon treatment with triptolide, HIF-1α protein accumulated in pancreatic cancer cells even though hypoxic response was decreased in them. Our studies showed even though HIF-1α is accumulated in the treated cells, there was no decrease in HIF-1 binding to hypoxia response elements. However, the HIF-1 transcriptional activity was significantly reduced owing to depletion of co-activator p300 upon treatment with triptolide. Further, treatment with triptolide resulted in a decreased activity of Sp1 and NF-kB the two major oncogenic signaling pathway in pancreatic cancer along with a decreased tumor initiating cell (TIC) population in pancreatic tumor

Hypoxia induces pulmonary fibroblast proliferation through NFAT signaling

Abstract Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and typically fatal lung disease with a very low survival rate. Excess accumulation of fibroblasts, myofibroblasts and extracellular matrix creates hypoxic conditions within the lungs, causing asphyxiation. Hypoxia is, therefore, one of the prominent features of IPF. However, there have been few studies concerning the effects of hypoxia on pulmonary fibroblasts. In this study, we investigated the molecular mechanisms of hypoxia-induced lung fibroblast proliferation. Hypoxia increased the proliferation of normal human pulmonary fibroblasts and IPF fibroblasts after exposure for 3–6 days. Cell cycle analysis demonstrated that hypoxia promoted the G1/S phase transition. Hypoxia downregulated cyclin D1 and A2 levels, while it upregulated cyclin E1 protein levels. However, hypoxia had no effect on the protein expression levels of cyclin-dependent kinase 2, 4, and 6. Chemical inhibition of hypoxia-inducible factor (HIF)-2 reduced hypoxia-induced fibroblast proliferation. Moreover, silencing of Nuclear Factor Activated T cell (NFAT) c2 attenuated the hypoxia-mediated fibroblasts proliferation. Hypoxia also induced the nuclear translocation of NFATc2, as determined by immunofluorescence staining. NFAT reporter assays showed that hypoxia-induced NFAT signaling activation is dependent on HIF-2, but not HIF-1. Furthermore, the inhibition or silencing of HIF-2, but not HIF-1, reduced the hypoxia-mediated NFATc2 nuclear translocation. Our studies suggest that hypoxia induces the proliferation of human pulmonary fibroblasts through NFAT signaling and HIF-2