Constitutive expression of TNF-related activation-induced cytokine (TRANCE)/receptor activating NF-κB ligand (RANK)-L by rat plasmacytoid dendritic cells

Plasmacytoid dendritic cells (pDCs) are a subset of DCs whose major function relies on their capacity to produce large amount of type I IFN upon stimulation via TLR 7 and 9. This function is evolutionary conserved and place pDC in critical position in the innate immune response to virus. Here we show that rat pDC constitutively express TNF-related activation-induced cytokine (TRANCE) also known as Receptor-activating NF-κB ligand (RANKL). TRANCE/RANKL is a member of the TNF superfamily which plays a central role in osteoclastogenesis through its interaction with its receptor RANK. TRANCE/RANK interaction are also involved in lymphoid organogenesis as well as T cell/DC cross talk. Unlike conventional DC, rat CD4(high) pDC were shown to constitutively express TRANCE/RANKL both at the mRNA and the surface protein level. TRANCE/RANKL was also induced on the CD4(low) subsets of pDC following activation by CpG. The secreted form of TRANCE/RANKL was also produced by rat pDC. Of note, levels of mRNA, surface and secreted TRANCE/RANKL expression were similar to that observed for activated T cells. TRANCE/RANKL expression was found on pDC in all lymphoid organs as well blood and BM with a maximum expression in mesenteric lymph nodes. Despite this TRANCE/RANKL expression, we were unable to demonstrate in vitro osteoclastogenesis activity for rat pDC. Taken together, these data identifies pDC as novel source of TRANCE/RANKL in the immune system.     

Geographic range determinants of two commercially important marine molluscs

Aim We modelled the spatial abundance patterns of two abalone species (Haliotis rubra Donovan 1808 and H. laevigata Leach 1814) inhabiting inshore rocky reefs to better understand the importance of current sea surface temperature (SST) (among other predictors) and, ultimately, the effect of future climate change, on marine molluscs. Location Southern Australia. Methods We used an ensemble species distribution modelling approach that combined likelihood‐based generalized linear models and boosted regression trees. For each modelling technique, a two‐step procedure was used to predict: (1) the current probability of presence, followed by (2) current abundance conditional on presence. The resulting models were validated using an independent, spatially explicit dataset of abalone abundance patterns in Victoria. Results For both species, the presence of reef was the main driver of abalone occurrence, while SST was the main driver of spatial abundance patterns. Predictive maps at c. 1‐km resolution showed maximal abundance on shallow coastal reefs characterized by mild winter SSTs for both species. Main conclusions Sea surface temperature was a major driver of abundance patterns for both abalone species, and the resulting ensemble models were used to build fine‐resolution predictive range maps (c. 1 km) that incorporate measures of habitat suitability and quality in support of resource management. By integrating this output with structured spatial population models, a more robust understanding of the potential impacts of threatening human processes such as climate change can be established.     

Enhanced nitrite reductase activity associated with the haptoglobin complexed hemoglobin dimer: functional and antioxidative implications

The presence of acellular hemoglobin (Hb) within the circulation is generally viewed as a pathological state that can result in toxic consequences. Haptoglobin (Hp), a globular protein found in the plasma, binds with high avidity the αβ dimers derived from the dissociation of Hb tetramer and thus helps clear free Hb. More recently there have been compelling indications that the redox properties of the Hp bound dimer (Hb-Hp) may play a more active role in controlling toxicity by limiting the potential tissue damage caused by propagation of the free-radicals generated within the heme containing globin chains. The present study further examines the potential protective effect of Hp through its impact on the production of nitric oxide (NO) from nitrite through nitrite reductase activity of the Hp bound αβ Hb dimer. The presented results show that the Hb dimer in the Hb-Hp complex has oxygen binding, CO recombination and spectroscopic properties consistent with an Hb species having properties similar to but not exactly the same as the R quaternary state of the Hb tetramer. Consistent with these observations is the finding that the initial nitrite reductase rate for Hb-Hp is approximately ten times that of HbA under the same conditions. These results in conjunction with the earlier redox properties of the Hb-Hp are discussed in terms of limiting the pathophysiological consequences of acellular Hb in the circulation.     

Systematic analysis of cell cycle effects of common drugs leads to the discovery of a suppressive interaction between gemfibrozil and fluoxetine

Screening chemical libraries to identify compounds that affect overall cell proliferation is common. However, in most cases, it is not known whether the compounds tested alter the timing of particular cell cycle transitions. Here, we evaluated an FDA-approved drug library to identify pharmaceuticals that alter cell cycle progression in yeast, using DNA content measurements by flow cytometry. This approach revealed strong cell cycle effects of several commonly used pharmaceuticals. We show that the antilipemic gemfibrozil delays initiation of DNA replication, while cells treated with the antidepressant fluoxetine severely delay progression through mitosis. Based on their effects on cell cycle progression, we also examined cell proliferation in the presence of both compounds. We discovered a strong suppressive interaction between gemfibrozil and fluoxetine. Combinations of interest among diverse pharmaceuticals are difficult to identify, due to the daunting number of possible combinations that must be evaluated. The novel interaction between gemfibrozil and fluoxetine suggests that identifying and combining drugs that show cell cycle effects might streamline identification of drug combinations with a pronounced impact on cell proliferation.     

The Mediterranean Sea under siege: spatial overlap between marine biodiversity,cumulative threats and marine reserves

Aim A large body of knowledge exists on individual anthropogenic threats that have an impact on marine biodiversity in the Mediterranean Sea, although we know little about how these threats accumulate and interact to affect marine species and ecosystems. In this context, we aimed to identify the main areas where the interaction between marine biodiversity and threats is more pronounced and to assess their spatial overlap with current marine protected areas in the Mediterranean. Location Mediterranean Sea. Methods We first identified areas of high biodiversity of marine mammals, marine turtles, seabirds, fishes and commercial or well‐documented invertebrates. We mapped potential areas of high threat where multiple threats are occurring simultaneously. Finally we quantified the areas of conservation concern for biodiversity by looking at the spatial overlap between high biodiversity and high cumulative threats, and we assessed the overlap with protected areas. Results Our results show that areas with high marine biodiversity in the Mediterranean Sea are mainly located along the central and north shores, with lower values in the south‐eastern regions. Areas of potential high cumulative threats are widespread in both the western and eastern basins, with fewer areas located in the south‐eastern region. The interaction between areas of high biodiversity and threats for invertebrates, fishes and large animals in general (including large fishes, marine mammals, marine turtles and seabirds) is concentrated in the coastal areas of Spain, Gulf of Lions, north‐eastern Ligurian Sea, Adriatic Sea, Aegean Sea, south‐eastern Turkey and regions surrounding the Nile Delta and north‐west African coasts. Areas of concern are larger for marine mammal and seabird species. Main conclusions These areas may represent good candidates for further research, management and protection activities, since there is only a maximum 2% overlap between existing marine protected areas (which cover 5% of the Mediterranean Sea) and our predicted areas of conservation concern for biodiversity.     

Dipeptides as Leaving Group in the Enzyme‐Catalyzed DNA Synthesis

Conjugates of 2′‐deoxyadenosine monophosphate with dipeptides have been synthesized and tested as substrates for several polymerases. Although the incorporation efficiency is not very high, it demonstrates that some of these dipeptides can be accommodated in the active site of polymerases and function as leaving groups in the enzymatic synthesis of DNA.