Distinct modulation of the endothelin-1 pathway in iNOS-/- and eNOS-/- mice

We hypothesized that constitutive endothelial NO synthase (eNOS) and inducible NO synthase (iNOS) have opposite effects on the regulation of endothelin and its receptors. We therefore sought to determine whether deletions of iNOS or eNOS genes in mice modulate pressor responses to endothelin and the expression of ETA and ETB receptors in a similar fashion. Despite unchanged baseline hemodynamic parameters, anesthetized iNOS-/- mice displayed reduced pressor responses to endothelin-1, but not to that of IRL-1620, a selective ETB agonist. Protein content of cardiac ETA receptors was reduced in iNOS-/- mice compared with wild-type mice, but that of ETB receptors was unchanged. Anesthetized eNOS-/- mice presented a hypertensive state, accompanied by an enhanced pressor response to intravenous endothelin-1, whereas the pressor response to IRL-1620 was reduced. Protein levels were also found to be increased for ETA receptors, but reduced for ETB receptors, in cardiac tissues of eNOS-/- mice. In conscious animals, both strains responded equally to the hypotensive effect of an ETA antagonist, ABT-627, whereas orally administered A-192621, an ETB antagonist, increased MAP to a greater extent in eNOS-/- than in wild-type mice. Furthermore, significant levels of immunoreactive endothelin were found in mesenteric arteries in eNOS-/- but not in iNOS-/- or wild-type congeners. Our study shows that repression of iNOS or eNOS has differential effects on endothelin-1 and its receptors. We have also shown that the heart is the main organ in which iNOS or eNOS repression induces important alterations in protein content of endothelin receptors in adult mice.     

Neolignans from an Aniba species

A benzene extract of the trunk of an Aniba species (Lauraceae) contained benzyl benzoate, benzyl salicylate, sitosterol and the neolignans (2S,3S,3aR)-3a-allyl-5-methoxy-3-methyl-2-piperonyl-2,3,3a,6-tetrahydro-6-oxobenzofuran (burchellin); (2S,3S,3aR)-3a-allyl-5-methoxy-3-methyl-2-veratryl-2,3,3a,6-tetrahydro-6-oxobenzofuran; (2S,3S,3aR)-3a-allyl-5,7-dimethoxy-3-methyl-2-veratryl-2,3,3a,6-tetrahydro-6-oxobenzofuran; (2S,3S,5S)-5-allyl-5-methoxy-3-methyl-2-veratryl-2,3,5,6-tetrahydro-6-oxo-benzofuran; (2R,3R)-7-methoxy-3-methyl-5-propenyl-2-veratryl-2,3-dihydrobenzofuran; rel-(1R,5R,6R,7R,8S)-1-allyl-8-hydroxy-3-methoxy-7-methyl-4-oxo-6-piperonylbicyclo[3,2,1]oct-2-ene (guianin); rel-(1S,5S,6S,7R,8R)-1-allyl-8-hydroxy-3,5-dimethoxy-7-methyl-4-oxo-6-piperonylbicyclo[3,2,1]oct-2-ene; rel-(1S,5S,6S,7R,8R)-8-acetoxy-1-allyl-3-hydroxy-5-methoxy-7-methyl-4-oxo-6-piperonyl-bicyclo[3,2,1]oct-2-ene; rel-1S,5S,6S,7R,8R)-8-acetoxy-3,5-dimethoxy-7-methyl-4-oxo-6-piperonylbicyclo[3,2,1]oct-2-ene; rel-(1R,5S,6R,7R)-1-allyl-3-methoxy-7-methyl-4,8-dioxo-6-piperonylbicyclo[3,2,1]oct-2-ene.     

Widespread Shortening of 3’ Untranslated Regions and Increased Exon Inclusion Are Evolutionarily Conserved Features of Innate Immune Responses to Infection

The contribution of pre-mRNA processing mechanisms to the regulation of immune responses remains poorly studied despite emerging examples of their role as regulators of immune defenses. We sought to investigate the role of mRNA processing in the cellular responses of human macrophages to live bacterial infections. Here, we used mRNA sequencing to quantify gene expression and isoform abundances in primary macrophages from 60 individuals, before and after infection with Listeria monocytogenes and Salmonella typhimurium. In response to both bacteria we identified thousands of genes that significantly change isoform usage in response to infection, characterized by an overall increase in isoform diversity after infection. In response to both bacteria, we found global shifts towards (i) the inclusion of cassette exons and (ii) shorter 3’ UTRs, with near-universal shifts towards usage of more upstream polyadenylation sites. Using complementary data collected in non-human primates, we show that these features are evolutionarily conserved among primates. Following infection, we identify candidate RNA processing factors whose expression is associated with individual-specific variation in isoform abundance. Finally, by profiling microRNA levels, we show that 3’ UTRs with reduced abundance after infection are significantly enriched for target sites for particular miRNAs. These results suggest that the pervasive usage of shorter 3’ UTRs is a mechanism for particular genes to evade repression by immune-activated miRNAs. Collectively, our results suggest that dynamic changes in RNA processing may play key roles in the regulation of innate immune responses.     

Biology of the first generation of a laboratory colony of Nyssomyia intermedia (Lutz & Neiva, 1912) and Nyssomyia neivai (Pinto, 1926) (Diptera: Psychodidae)

The phlebotomine sand flies Nyssomyia intermedia (Lutz & Neiva, 1912) and Nyssomyia neivai (Pinto, 1926) are very close and may be involved in the transmission of Leishmania spp. Ross, 1903 in Brazil. The biology of the first laboratory-reared generations of these species, descended from insects captured in Além Paraíba (N. intermedia) and Corinto (N. neivai) in the Brazilian state of Minas Gerais, is described here. The captured females were fed on hamsters and maintained individually in rearing pots. Laboratory temperature and relative humidity were maintained at 25-26 masculineC and 80% respectively. The productivity of the first generation of N. intermedia was greater than that of N. neivai, and its development time clearly shorter, particularly for the second and third larval instars.     

Interference of the galactose-dependent binding of lectins by novel pentapeptide ligands

A library of pentapeptides containing the sequence -Y-X-Y- based on rational design was screened with six different lectins. Sequences were identified that modulate galectin binding to its natural carbohydrate ligand. SPR showed inhibition values 2-3 times stronger than galactose and NMR studies suggested real carbohydrate mimicry.     

Folding, stability and polymerization properties of FtsZ chimeras with inserted tubulin loops involved in the interaction with the cytosolic chaperonin CCT and in microtubule formation

To attain its native conformation, the cytoskeletal protein tubulin needs the concourse of several molecular chaperones, among others the cytosolic chaperonin CCT. It has been previously described that denatured tubulin interacts with CCT in a quasi-folded conformation using several loops located throughout its sequence. These loops are also involved in microtubule formation and are absent in its prokaryote homologue FtsZ, which in vitro folds by itself and does not interact with CCT. Several FtsZ/tubulin chimeric proteins were generated by inserting consecutively one, two or three of the CCT-binding domains of tubulin into the corresponding sequence of FtsZ from Methanococccus jannaschii. The insertion of any of the CCT-binding loops generates in the FtsZ/tubulin chimeras the ability to interact with CCT. The accumulation of CCT-binding loops induces in the FtsZ/tubulin chimeras unfolding and refolding properties that are more similar to tubulin than to its prokaryote counterpart. Finally, the insertion of some of these loops generates in the FtsZ/tubulin chimeras more complex polymeric structures than those found for FtsZ. These results reinforce the notion that CCT has coevolved with tubulin to deal with the folding problems encountered by the eukaryotic protein with the appearance of the new sequences involved in microtubule formation.     

IRBAS: An online database to collate,analyze, and synthesize data on the biodiversity and ecology of intermittent rivers worldwide

Key questions dominating contemporary ecological research and management concern interactions between biodiversity, ecosystem processes, and ecosystem services provision in the face of global change. This is particularly salient for freshwater biodiversity and in the context of river drying and flow‐regime change. Rivers that stop flowing and dry, herein intermittent rivers, are globally prevalent and dynamic ecosystems on which the body of research is expanding rapidly, consistent with the era of big data. However, the data encapsulated by this work remain largely fragmented, limiting our ability to answer the key questions beyond a case‐by‐case basis. To this end, the Intermittent River Biodiversity Analysis and Synthesis (IRBAS; http://irbas.cesab.org ) project has collated, analyzed, and synthesized data from across the world on the biodiversity and environmental characteristics of intermittent rivers. The IRBAS database integrates and provides free access to these data, contributing to the growing, and global, knowledge base on these ubiquitous and important river systems, for both theoretical and applied advancement. The IRBAS database currently houses over 2000 data samples collected from six countries across three continents, primarily describing aquatic invertebrate taxa inhabiting intermittent rivers during flowing hydrological phases. As such, there is room to expand the biogeographic and taxonomic coverage, for example, through addition of data collected during nonflowing and dry hydrological phases. We encourage contributions and provide guidance on how to contribute and access data. Ultimately, the IRBAS database serves as a portal, storage, standardization, and discovery tool, enabling collation, synthesis, and analysis of data to elucidate patterns in river biodiversity and guide management. Contribution creates high visibility for datasets, facilitating collaboration. The IRBAS database will grow in content as the study of intermittent rivers continues and data retrieval will allow for networking, meta‐analyses, and testing of generalizations across multiple systems, regions, and taxa.     

Who are we sampling? Apparent survival differs between methods in a secretive species

Survival is a fundamental parameter in population dynamics with increasing importance in the management and conservation strategies of wildlife populations. Survival probability in vertebrates is usually estimated by live‐encounter data obtained by means of physical mark–capture–recapture protocols. Non‐invasive acoustic marking relying on individual‐specific features of signals has been alternatively applied as a marking technique, especially in secretive species. Nevertheless, to date no research has compared survival rate estimates obtained by acoustic and physical marking. We estimated half‐yearly and annual survival and recapture rates of a secretive and threatened passerine, the Dupont's lark Chersophilus duponti, using two separate live‐encounter data sets of males collected simultaneously by physical and acoustic marking in the same study area. The separate analysis of both methods led to different model structures, since transient individuals had to be accounted for in the acoustic marking but not in the physical marking data set. Furthermore, while reencounter probabilities did not differ between methods, survival estimates employing physical marking were lower than those obtained acoustically, especially between the postbreeding and the breeding period when the apparent survival of colour‐banded birds was twice as low as for acoustic marking. The combination of marking methods suggested the existence of different subsets of individuals differentially sampled within the population: whereas colour‐banded males seemed to represent the territorial fraction of the population, both resident and floater individuals were probably detected by acoustic marking. Using traditional mark–recapture methods exclusively could have misled our estimates of survival rates, potentially affecting prospective predictions of population dynamics. Acoustic marking has been poorly applied in mark–recapture studies, but might be a powerful complement to obtain accurate estimates of fundamental demographic parameters such as survival and dispersal.     

Polymorphism in the neotropical termite Serritermes serrifer

Serritermitidae (Isoptera) is a small and little known Neotropical termite family which includes only two genera: Glossotermes and Serritermes. Despite the lack of detailed studies, it has been assumed that these termites have a true worker caste. A recent study revealed that Glossotermes has a linear development pathway and lacks true workers. Here, we present a study of the polymorphism of Serritermes serrifer Hagen & Bates, a species endemic to the Cerrado ecoregion of central Brazil which lives as an inquiline inside nests of Cornitermes spp. A morphometric analysis was performed based on measurements taken of 11 body parts of 544 specimens of immatures, worker‐like individuals, soldiers, and alates. Sex of specimens was determined by dissection and examination of the seventh sternite. A principal component analysis (PCA) was used to evaluate morphological changes during development. Contrary with previous information from the literature and similar to Glossotermes, Serritermes shows a linear development pathway with two larval instars, two sizes of pseudergates, and a single nymphal morph. Pseudergates apparently undergo stationary molts. Sex ratio among pseudergates is male‐biased, but not as strongly as in Glossotermes. Typical colonies have a single physogastric primary queen and a single primary king. Ergatoid reproductives are relatively rare and some female ergatoids may become strongly physogastric. Nymphoid reproductives were not found. All soldiers are male and bear well‐developed testes.