An archaeal peptidase assembles into two different quaternary structures: A tetrahedron and a giant octahedron

Cellular proteolysis involves large oligomeric peptidases that play key roles in the regulation of many cellular processes. The cobalt-activated peptidase TET1 from the hyperthermophilic Archaea Pyrococcus horikoshii (PhTET1) was found to assemble as a 12-subunit tetrahedron and as a 24-subunit octahedral particle. Both quaternary structures were solved by combining x-ray crystallography and cryoelectron microscopy data. The internal organization of the PhTET1 particles reveals highly self-compartmentalized systems made of networks of access channels extended by vast catalytic chambers. The two edifices display aminopeptidase activity, and their organizations indicate substrate navigation mechanisms different from those described in other large peptidase complexes. Compared with the tetrahedron, the octahedron forms a more expanded hollow structure, representing a new type of giant peptidase complex. PhTET1 assembles into two different quaternary structures because of quasi-equivalent contacts that previously have only been identified in viral capsids.     

The early light-inducible protein (ELIP) gene is expressed during the chloroplast-to-chromoplast transition in ripening tomato fruit

Chloroplast-to-chromoplast transitions during fruit ripening require massive transformation of the plastid internal membrane structure as the photosynthetic apparatus is disassembled. Early Light-Inducible Proteins (ELIPs) are known to accumulate in chloroplasts during thylakoid biogenesis and under stressful conditions. To determine if ELIP may also play a role in thylakoid disassembly during the chloroplast-to-chromoplast transition, ELIP mRNA expression was measured in tomato, Lycopersicon esculentum Mill. cv. Rutgers. An EST clone was identified in the Tomato Genome Project/Solanaceae Genomics Network database that has high sequence similarity with the amino acid sequence of Arabidopsis ELIP1 and ELIP2. It has complete identity in the two conserved regions of the protein. Genomic Southern blots indicate that the gene is a single copy in tomato. The genomic sequence shows the three-exon structure typical of ELIP sequences from other species. mRNA for this gene is barely detectable on northern blots from etiolated seedlings, but transiently accumulates to high levels 2 h after transfer to the light. Greenhouse-grown tomatoes were used to measure ELIP mRNA accumulation during fruit development and ripening. Tomato ELIP mRNA is detectable in all stages of fruit ripening, but is most abundant in the breaker/turning stage of development. A survey of tomato EST databases revealed that ELIP cDNA is also relatively abundant in developing flowers, which contain yellow chromoplasts. Combined, these results suggest that ELIP may play a newly-recognized role in the chloroplast-to-chromoplast transition process.     

Mitochondrial respiratory chain dysfunction, a non-receptor-mediated effect of synthetic PPAR-ligands: biochemical and pharmacological implications

Peroxisome proliferator activated receptors (PPARs) are a class of nuclear receptors involved in lipid and glucidic metabolism, immune regulation, and cell differentiation. Many of their biological activities have been studied by using selective synthetic activators (mainly fibrates and thiazolidinediones) which have been already employed in therapeutic protocols. Both kinds of drugs, however, showed pharmacotoxicological profiles, which cannot be ascribed by any means to receptor activation. To better understand these non-receptorial or extrareceptorial aspects, the effect of different PPAR-ligands on the metabolic status of human HL-60 cell line has been investigated. At this regard, NMR analysis of cell culture supernatants was accomplished in order to monitor modifications at the level of cell metabolism. Cell growth and chemiluminescence assays were employed to verify cell differentiation. Results showed that all the considered PPAR-ligands, although with different potencies and independently from their PPAR binding specificity, induced a significant derangement of the mitochondrial respiratory chain consisting in a strong inhibition of NADH-cytochrome c reductase activity. This derangement has been shown to be strictly correlated to the adaptive metabolic modifications, as evidenced by the increased formation of lactate and acetate, due to the stimulation of anaerobic glycolysis and fatty acid beta-oxidation. It is worthy noting that the mitochondrial dysfunction appeared also linked to the capacity of any given PPAR-ligand to induce cell differentiation. These data could afford an explanation of biochemical and toxicological aspects related to the therapeutic use of synthetic PPAR-ligands and suggest a revision of PPAR pathophysiologic mechanisms.     

A Global Analysis of the Effectiveness of Marine Protected Areas in Preventing Coral Loss

Background

A variety of human activities have led to the recent global decline of reef-building corals [1], [2]. The ecological, social, and economic value of coral reefs has made them an international conservation priority [2], [3]. The success of Marine Protected Areas (MPAs) in restoring fish populations [4] has led to optimism that they could also benefit corals by indirectly reducing threats like overfishing, which cause coral degradation and mortality [2], [5]. However, the general efficacy of MPAs in increasing coral reef resilience has never been tested.

Methodology/Principal Findings

We compiled a global database of 8534 live coral cover surveys from 1969–2006 to compare annual changes in coral cover inside 310 MPAs to unprotected areas. We found that on average, coral cover within MPAs remained constant, while coral cover on unprotected reefs declined. Although the short-term differences between unprotected and protected reefs are modest, they could be significant over the long-term if the effects are temporally consistent. Our results also suggest that older MPAs were generally more effective in preventing coral loss. Initially, coral cover continued to decrease after MPA establishment. Several years later, however, rates of coral cover decline slowed and then stabilized so that further losses stopped.

Conclusions/Significance

These findings suggest that MPAs can be a useful tool not only for fisheries management, but also for maintaining coral cover. Furthermore, the benefits of MPAs appear to increase with the number of years since MPA establishment. Given the time needed to maximize MPA benefits, there should be increased emphasis on implementing new MPAs and strengthening the enforcement of existing MPAs.     

Floristic studies on freshwater algae of Lake Gondwana,Northern Victoria Land (Antarctica)

Benthic algal mats and phytoplankton of Lake Gondwana (Northern Victoria Land, Antarctica) were investigated. Biomass, chlorophyll content and floristic analyses were carried out on algal mats. The mats are composed of two layers different in colour, floristic composition and chlorophyll content. The algal flora of the mats amount to 34 taxa (19 Cyanophyta, 7 Bacillariophyta, 8 Chlorophyta). The phytoplankton community is species-poor (only 5 taxa). Crytophyta account for about 98% of total algal density.     

Metallothionein concentration in the mussel Mytilus galloprovincialis as a biomarker of response to metal contamination: validation in the field

Mussels were translocated from a shell-fish breeding area (Sète, on the French Mediterranean coast) to sites exposed to trace element inputs in April 2000. They were recovered 3 months later. Whole soft tissues from all of the sites (n = 97) were analysed for arsenic, cadmium, chromium, copper, mercury, nickel, lead and zinc. Metallothioneins (MTs) were also measured in the digestive gland and in the remaining tissues (allowing calculation of whole soft tissue concentrations) at 22 of the 97 sites. MT concentrations in the digestive gland and the whole soft tissues were strongly correlated. The condition index varied with food availability at different sites. This did not influenced MT concentrations in the whole soft tissues, whereas the condition index was negatively correlated to trace element concentrations. A model is proposed to minimize this influence of condition. Metal concentrations adjusted using this model showed significant correlations with MT levels for those metals (cadmium, copper, nickel and zinc) that are known to bind to this protein, with the exception of mercury. Even in moderately contaminated sites, measurement of the MT level in the soft tissues of mussels was generally able to discriminate between different levels of contamination, allowing the use of a simplified procedure compared with dissection of the digestive gland. It is recommended to avoid translocation and sampling during the reproductive period, which is well documented for commercial species such as Mytilus sp.     

Biomarkers of Good EULAR Response to the B Cell Depletion Therapy in All Seropositive Rheumatoid Arthritis Patients: Clues for the Pathogenesis

Objective

To find out whether a high number of auto-antibodies can increase the probability of a “good-EULAR response” and to identify the possible biomarkers of response in seropositive rheumatoid arthritis (RA) patients undergoing the B cell depletion therapy (BCDT).

Patients and Methods

One hundred and thirty-eight patients with long standing RA (LSRA), 75% non or poorly responsive to one or more TNFα blockers, all seropositive for at least one autoantibody (AAB) (RF-IgM, RF-IgA, RF-IgG, anti-MCV, ACPA-IgG, ACPA-IgA, ACPA-IgM) received one full course of BCDT. The major outcomes (moderate or good-EULAR response) were assessed after 6 months of therapy. The IL6 and BAFF levels were also determined.

Results

At a 6-month follow-up, 33 (23.9%) of the RA patients achieved a good EULAR response. Having up to 5-AABs positivity increased the chances for treatment response. After a logistic regression analysis, however, only 4 baseline factors arose as associated with a good-EULAR response: no steroid therapy (OR = 6.25), a lymphocyte count <1875/uL (OR = 10.74), a RF-IgG level >52.1 IU/ml (OR = 8.37) and BAFF levels <1011 pg/ml (OR = 7.38). When all the AABs, except for RF-IgM and ACPA-IgG, were left in the analysis, the two final predictors were no-steroid therapy and low lymphocyte count.

Discussion

The number of AABs increased the chances of being a “good-EULAR” responder. The only predictors, however, at the baseline of a good response in this seropositive cohort of RA patients were 2 simple variables – no steroids and lymphocyte count – and two laboratory assays – IgG-RF and BAFF.     

Beyond the river: underlying determinants of population acoustic signal variability in Amazonian direct-developing Allobates (Anura: Dendrobatoidea)

The multidimensional nature of animal signals makes acoustic traits potentially subject to different determinants. The Amazonian frogs Allobates nidicola and Allobates masniger have an allopatric distribution, occurring along the left and right sides of the Madeira River, respectively. These are two sister, phenotypically similar species whose eggs are deposited and develop entirely in a terrestrial nest. In this study, we analyzed 2,000 advertisement calls recorded from ten localities across Central Amazonia, in order to understand the role of determinants of acoustic signal variability at the population and species levels. We assessed, through nested analyses of variance, the differentiation of six characters of this sexual signal among populations and between interfluves. Moreover, we measured the degree of variability and the extent of temperature- and body size-induced plasticity in call traits. We also tested for isolation-by-distance effects in phenotypic differentiation through Mantel tests. Coefficients of variation were higher among than within populations for all call measurements. Spectral call properties were more distinctive than temporal traits among populations and species. Advertisement call traits showed strong temperature-induced plasticity (e.g., 45?% of the variation in note duration). In contrast, the effects of body size were restricted to frequency-related characters. The river barrier effect was significant among all the acoustic variables analyzed even after controlling for male body size. Geography (sampling locality) and body size also jointly affected call variability. No correlation between geographical and acoustic distances among populations was observed, suggesting that local stabilizing selective pressures have an important role in the evolution of call differentiation.