Mediators of PGE2 synthesis and signalling downstream of COX-2 represent potential targets for the prevention/treatment of colorectal cancer

Colorectal cancer is a major cause of mortality and whilst up to 80% of sporadic colorectal tumours are considered preventable, trends toward increasing obesity suggest the potential for a further increase in its worldwide incidence. Novel methods of colorectal cancer prevention and therapy are therefore of considerable importance. Non-steroidal anti-inflammatory drugs (NSAIDs) are chemopreventive against colorectal cancer, mainly through their inhibitory effects on the cyclooxygenase isoform COX-2. COX enzymes represent the committed step in prostaglandin biosynthesis and it is predominantly increased COX-2-mediated prostaglandin-E2 (PGE2) production that has a strong association with colorectal neoplasia, by promoting cell survival, cell growth, migration, invasion and angiogenesis. COX-1 and COX-2 inhibition by traditional NSAIDs (for example, aspirin) although chemopreventive have some side effects due to the role of COX-1 in maintaining the integrity of the gastric mucosa. Interestingly, the use of COX-2 selective NSAIDs has also shown promise in the prevention/treatment of colorectal cancer while having a reduced impact on the gastric mucosa. However, the prolonged use of high dose COX-2 selective inhibitors is associated with a risk of cardiovascular side effects. Whilst COX-2 inhibitors may still represent viable adjuvants to current colorectal cancer therapy, there is an urgent need to further our understanding of the downstream mechanisms by which PGE2 promotes tumorigenesis and hence identify safer, more effective strategies for the prevention of colorectal cancer. In particular, PGE2 synthases and E-prostanoid receptors (EP1-4) have recently attracted considerable interest in this area. It is hoped that at the appropriate stage, selective (and possibly combinatorial) inhibition of the synthesis and signalling of those prostaglandins most highly associated with colorectal tumorigenesis, such as PGE2, may have advantages over COX-2 selective inhibition and therefore represent more suitable targets for long-term chemoprevention. Furthermore, as COX-2 is found to be overexpressed in cancers such as breast, gastric, lung and pancreatic, these investigations may also have broad implications for the prevention/treatment of a number of other malignancies.     

Changes in soil carbon stock after deforestation and subsequent establishment of “Imperata” grassland in the Asian humid tropics

Globally, tropical deforestation is often followed by the establishment of fire-prone grassland. In Southeast Asia, Imperata cylindrica grassland is the dominant land cover after deforestation. No quantitative data are available on the changes in soil carbon (C) stock upon such land conversion. We aimed to elucidate changes in soil C stock after deforestation followed by the occurrence and persistence of I. cylindrica grassland in the Asian humid tropics. We compared soil C stock between primary forests (n?=?20) and grasslands (n?=?14) with a wide range of soil textures in East Kalimantan (Indonesian Borneo). We also assessed the temporal change in soil C stock in the grassland sites between 1992 and 2004 by comparing identical soil pits (n?=?7). Soil C stock (0–100 cm deep) increased by 23% following transition from primary forest to grassland during about 10 years. Over 12 years at the grassland sites, however, soil C stock did not change in the 0–100 cm depth, but we observed increased blackness of soil, especially coarse-textured soils. The increase in C stock following the transition was largely attributed to the organic matter supply by grass roots, rhizomes, and charred materials from wildfires to the subsurface soils and subsoils (5–100 cm). The unchanged soil C stock (0–100 cm) over 12 years at the grassland sites suggests that the soil C stock level there has nearly reached a new equilibrium state. However, the increased blackness of the soil suggests changes in the quality of soil organic matter by higher subsoil root input and deeper bioturbation by earthworms.     

Variability of Pinus halepensis Mill. Essential Oils and Their Antioxidant Activities Depending on the Stage of Growth During Vegetative Cycle

The impact of growth stages during vegetative cycle (B₀ – B₅) on chemical composition and antioxidant activities of Pinus halepensis Mill . needles essential oils was investigated for the first time. GC and GC/MS analyses pointed to a quantitative variability of components; terpene hydrocarbons derivatives, represented by α‐pinene (8.5 – 12.9%), myrcene (17.5 – 21.6%), p‐cymene (7.9 – 11.9%) and (Z)‐β‐caryophyllene (17.3 – 21.2%) as major components, decreased from 88.9% at B₀ growth stage to 66.9% at B₅ growth stage, whereas oxygenated derivatives, represented by caryophyllene oxide (5.4 – 12.6%) and terpinen‐4‐ol (0.4 – 3.3%) as major components, increased from 7% at B₀ growth stage to 28.4% at B₅ growth stage. Furthermore, our findings showed that essential oil of P. halepensis needles collected at B₅ growth stage possess higher antioxidant activities by four different testing systems than those collected at B₀ – B₄ growth stages. This highlighted variability led to conclude that we should select essential oils to be investigated carefully depending on growth stage, in order to have the highest effectiveness of essential oil in terms of biological activities for human health purposes.     

Prion protein protects against DNA damage induced by paraquat in cultured cells

Exposure of cells to paraquat leads to production of superoxide anion (O2*-). This reacts with hydrogen peroxide to give the hydroxyl radical (*OH), leading to lipid peroxidation and cell death. In this study, we investigated the effects of cellular prion protein (PrPC) overexpression on paraquat-induced toxicity by using an established model system, rabbit kidney epithelial A74 cells, which express a doxycycline-inducible murine PrPC gene. PrPC overexpression was found to significantly reduce paraquat-induced cell toxicity, DNA damage, and malondialdehyde acid levels. Superoxide dismutase (total SOD and CuZn-SOD) and glutathione peroxidase activities were higher in doxycycline-stimulated cells. Our findings clearly show that PrPC overexpression plays a protective role against paraquat toxicity, probably by virtue of its superoxide dismutase-like activity.     

Role of PKCalpha in feedback regulation of Na(+) transport in an electrically tight epithelium

It has long been known thatNa⁺ channels in electrically tight epithelia are regulatedby homeostatic mechanisms that maintain a steady state and allow newlevels of transport to be sustained in hormonally challenged cells.Little is known about the potential pathways involved in theseprocesses. In addition to short-term effect, recent evidence alsoindicates the involvement of PKC in the long-term regulation of theepithelial Na⁺ channel (ENaC) at the protein level(40). To determine whether stimulation of ENaC involvesfeedback regulation of PKC levels, we utilized Western blot analysis todetermine the distribution of PKC isoforms in polarized A6 epithelia.We found the presence of PKC isoforms in the conventional ( and), novel (, , and ), and atypical (, , and) groups. Steady-state stimulation of Na⁺ transport withaldosterone was accompanied by a specific decrease of PKC proteinlevels in both the cytoplasmic and membrane fractions. Similarly,overnight treatment with an uncharged amiloride analog (CDPC), aprocedure that through feedback regulation causes a stimulation ofNa⁺ transport, also decreased PKC levels. These effectswere additive, indicating separate mechanisms that converge at thelevel of PKC. These effects were not accompanied by changes ofPKC mRNA levels as determined by Northern blot analysis. We proposethat this may represent a novel regulatory feedback mechanism necessary for sustaining an increase of Na⁺ transport.

     

Phylogeography and ecological niche modeling unravel the evolutionary history of the African green toad,Bufotes boulengeri boulengeri (Amphibia: Bufonidae), through the Quaternary

Recent integration of ecological niche models in phylogeographic studies is improving our understanding of the processes structuring genetic variation across landscapes. Previous studies on the amphibian Bufotes boulengeri boulengeri uncovered a surprisingly weak intraspecific differentiation across the Maghreb region. We widely sampled this species from Morocco to Egypt and sequenced one nuclear and three mitochondrial (mtDNA) genes to determine the level of genetic variability across its geographic range. We evaluated these data with ecological niche modeling to reveal its evolutionary history in response to climate change during the Quaternary. Our results highlight some mtDNA phylogeographic structure within this species, with one haplogroup endemic to coastal Morocco, and one haplogroup widely distributed throughout North Africa. No or little genetic differentiation is observed between isolated populations from the Hoggar Mountains, the Sabha district and the islands of Kerkennah and Lampedusa, compared to others populations. This can be explained by the expansion of the distribution range of B. b. boulengeri during glacial periods. This might have facilitated the species’ dispersal and subsequent gene flow between most North African localities.     

Phylogeographic patterns in North African water frog Pelophylax saharicus (Anura: Ranidae)

We studied the phylogeography of the Sahara frog in North Africa. We widely sampled frogs from Morocco to Tunisia (195 individuals) and sequenced two mitochondrial (16S and CO1) and one nuclear (Rag1) genes. Our results confirm that Moroccan populations of Pelophylax saharicus are genetically distinct from Algerian ones. Specimens from Alger and Djelfa (central Algeria) are genetically closer to Moroccan specimens than to east Algerian ones, and the split between these two lineages may have occurred approximately 2.6 Mya. A similar pattern of differentiation was observed in several other species and was hypothesized to be linked to the formation of the fossil island called the ‘Edough Peninsula’ in eastern Algeria around 4.2 Ma and then to have been reinforced by Pleistocene climatic changes. At the Moroccan scale, we found a low level of genetic diversity and no clear phylogeographic pattern within P. saharicus. However, our SAShA analyses revealed a mixture of random and underdistributed haplotypes, which may indicate a complex population genetic or biogeographic history.     

Canopy chlorophyll fluorescence applied to stress detection using an easy-to-build micro-lidar

Photosynthesis Research - The dark-to-light transitions enable energization of the thylakoid membrane (TM), which is reflected in fast and slow (OJIPSMT or OABCDE) stages of fluorescence induction...