Generic relationships and dating of lineages in Winteraceae based on nuclear (ITS) and plastid (rpS16 and psbA-trnH) sequence data

Phylogenetic analyses of representative species from the five genera of Winteraceae (Drimys, Pseudowintera, Takhtajania, Tasmannia, and Zygogynum s.l.) were performed using ITS nuclear sequences and a combined data-set of ITS + psbA-trnH + rpS16 sequences (sampling of 30 and 15 species, respectively). Indel informativity using simple gap coding or gaps as a fifth character was examined in both data-sets. Parsimony and Bayesian analyses support the monophyly of Drimys, Tasmannia, and Zygogynum s.l., but do not support the monophyly of Belliolum, Zygogynum s.s., and Bubbia. Within Drimys, the combined data-set recovers two subclades. Divergence time estimates suggest that the splitting between Drimys and its sister clade (Pseudowintera + Zygogynum s.l.) occurred around the end of the Cretaceous; in contrast, the divergence between the two subclades within Drimys is more recent (15.5-18.5 MY) and coincides in time with the Andean uplift. Estimates suggest that the earliest divergences within Winteraceae could have predated the first events of Gondwana fragmentation. (C) 2009 Elsevier Inc. All rights reserved.

Phylogenetic relationships, diversification and biogeography in Neotropical Brotogeris parakeets

Aim We present a molecular phylogenetic analysis of Brotogeris (Psittacidae) using several distinct and complementary approaches: we test the monophyly of the genus, delineate the basal taxa within it, uncover their phylogenetic relationships, and finally, based on these results, we perform temporal and spatial comparative analyses to help elucidate the historical biogeography of the Neotropical region. Location Neotropical lowlands, including dry and humid forests. Methods Phylogenetic relationships within Brotogeris were investigated using the complete sequences of the mitochondrial genes cyt b and ND2, and partial sequences of the nuclear intron 7 of the gene for Beta Fibrinogen for all eight species and 12 of the 17 taxa recognized within the genus (total of 63 individuals). In order to delinetae the basal taxa within the genus we used both molecular and plumage variation, the latter being based on the examination of 597 skin specimens. Dates of divergence and confidence intervals were estimated using penalized likelihood. Spatial and temporal comparative analyses were performed including several closely related parrot genera. Results Brotogeris was found to be a monophyletic genus, sister to Myiopsitta. The phylogenetic analyses recovered eight well-supported clades representing the recognized biological species. Although some described subspecies are diagnosably distinct based on morphology, there was generally little intraspecific mtDNA variation. The Amazonian species had different phylogenetic affinities and did not group in a monophyletic clade. Brotogeris diversification took place during the last 6 Myr, the same time-frame as previously found for Pionus and Pyrilia. Main conclusions The biogeographical history of Brotogeris implies a dynamic history for South American biomes since the Pliocene. It corroborates the idea that the geological evolution of Amazonia has been important in shaping its biodiversity, argues against the idea that the region has been environmentally stable during the Quaternary, and suggests dynamic interactions between wet and dry forest habitats in South America, with representatives of the Amazonian biota having several independent close relationships with taxa endemic to other biomes.

Morphology and phylogenetic relationships of a remarkable new genus and two new species of Neotropical freshwater stingrays from the Amazon basin (Chondrichthyes: Potamotrygonidae)

The morphology and phylogenetic relationships of a new genus and two new species of Neotropical freshwater stingrays, family Potamotrygonidae, are investigated and described in detail. The new genus, Heliotrygon, n. gen., and its two new species, Heliotrygon gomesi, n. sp. (type-species) and Heliotrygon rosai, n. sp., are compared to all genera and species of potamotrygonids, based on revisions in progress. Some of the derived features of Heliotrygon include its unique disc proportions (disc highly circular, convex anteriorly at snout region, its width and length very similar), extreme subdivision of suborbital canal (forming a complex honeycomb-like pattern anterolaterally on disc), stout and triangular pelvic girdle, extremely reduced caudal sting, basibranchial copula with very slender and acute anterior extension, and precerebral and frontoparietal fontanellae of about equal width, tapering very little posteriorly. Both new species can be distinguished by their unique color patterns: Heliotrygon gomesi is uniform gray to light tan or brownish dorsally, without distinct patterns, whereas Heliotrygon rosai is characterized by numerous white to creamy-white vermiculate markings over a light brown, tan or gray background color. Additional proportional characters that may further distinguish both species are also discussed. Morphological descriptions are provided for dermal denticles, ventral lateral-line canals, skeleton, and cranial, hyoid and mandibular muscles of Heliotrygon, which clearly corroborate it as the sister group of Paratrygon. Both genera share numerous derived features of the ventral lateral-line canals, neurocranium, scapulocoracoid, pectoral basals, clasper morphology, and specific patterns of the adductor mandibulae and spiracularis medialis muscles. Potamotrygon and Plesiotrygon are demonstrated to share derived characters of their ventral lateral-line canals, in addition to the presence of angular cartilages. Our morphological phylogeny is further corroborated by a molecular phylogenetic analysis of cytochrome b based on four sequences (637 base pairs in length), representing two distinct haplotypes for Heliotrygon gomesi. Parsimony analysis produced a single most parsimonious tree revealing Heliotrygon and Paratrygon as sister taxa (boot-strap proportion of 70%), which together are the sister group to a clade including Plesiotrygon and species of Potamotrygon. These unusual stingrays highlight that potamotrygonid diversity, both in terms of species composition and undetected morphological and molecular patterns, is still poorly known.

Phylogenetic position of Dendropsophus gaucheri (Lescure and Marty 2000) highlights the need for an in-depth investigation of the phylogenetic relationships of Dendropsophus (Anura: Hylidae)

Dendropsophus gaucheri is a recently described species which inhabits open areas of the eastern part of the Guiana Shield and is currently assigned to the D. parviceps species group based on the presence of a subocular cream spot. Herein we investigate its phylogenetic position including material from the type locality and newly documented populations from Suriname and Brazil based on mtDNA sequences. The species, as well as D. riveroi which is assigned to the D. minimus species group, were recovered nested within the D. microcephalus species group which implies the paraphyly of the three Dendropsophus species groups. Such result, along with other evidences, highlights the need for a thorough revision of the genus. The genetic distances among D. gaucheri samples studied are low confirming their conspecificity and suggesting recent connections among populations from open areas currently isolated by rainforest in the lowlands of the Guiana Shield.

Phylogenetic relationships of the Neotropical spider genus Itatiaya (Araneae)

A cladistic analysis using parsimony under equal weights is applied to test the phylogenetic relationships of Itatiaya Mello-Leitao, previously described in Ctenidae. The data matrix comprised 25 taxa scored for a total of 47 characters. The cladistic analysis yielded two equally parsimonious trees of 124 steps. The consensus of the two most parsimonious trees is used to discuss the phylogenetic relationships and justify taxonomic modifications. The results indicate that this genus is a representative of Zoropsidae, which is newly recorded from the Neotropical region. The monophyly of Itatiaya is supported by three non-ambiguous synapomorphies and three homoplastic synapomorphies. A new diagnosis is provided for Itatiaya. Itatiaya pucupucu is placed as sister species to the remaining species of the genus. A polytomic clade composed of Itatiaya modesta, Itatiaya iuba, Itatiaya apipema and the clade formed by Itatiaya tacamby + Itatiaya pykyyra is supported by the presence of modified cylindrical gland spigots. Additionally, the male of I. pykyyra Polotow & Brescovit is described for the first time.

Molecular phylogenetics and character evolution of the ""sacaca"" clade: Novel relationships of Croton section Cleodora (Euphorbiaceae)

Phylogenetic relationships of Croton section Cleodora (Klotzsch) Baill. were evaluated using the nuclear ribosomal ITS and the chloroplast trnl-F and trnH-psbA regions. Our results show a strongly supported clade containing most previously recognized section Cleodora species, plus some other species morphologically similar to them. Two morphological synapomorphies that support section Cleodora as a clade include pistillate flowers in which the sepals overlap to some degree, and styles that are connate at the base to varying degrees. The evolution of vegetative and floral characters that have previously been relied on for taxonomic decisions within this group are evaluated in light of the phylogenetic hypotheses. Within section Cleodora there are two well-supported clades, which are proposed here as subsections (subsection Sphaerogyni and subsection Spruceani). The resulting phylogenetic hypothesis identifies the closest relatives of the medicinally important and essential oil-rich Croton cajucara Benth. as candidates for future screening in phytochemical and pharmacological studies. (C) 2011 Elsevier Inc. All rights reserved.

Genes of cathepsin L-like proteases in Trypanosoma rangeli isolates: Markers for diagnosis, genotyping and phylogenetic relationships

We have sequenced genes encoding cathepsin L-like (CatL-like) cysteine proteases from isolates of Trypanosoma rangeli from humans, wild mammals and Rhodnius species of Central and South America. Phylogenetic trees of sequences encoding mature CatL-like enzymes of T rangeli and homologous genes from other trypanosomes, Leishmania spp. and bodonids positioned sequences of T rangeli (rangelipain) closest to T cruzi (cruzipain). Phylogenetic tree of kinetoplastids based on sequences of CatL-like was totally congruent with those derived from SSU rRNA and gGAPDH genes. Analysis of sequences from the CatL-like catalytic domains of 17 isolates representative of the overall phylogenetic diversity and geographical range of T rangeli supported all the lineages (A-D) previously defined using ribosomal and spliced leader genes. Comparison of the proteolytic activities of T rangeli isolates revealed heterogeneous banding profiles of cysteine proteases in gelatin gels, with differences even among isolates of the same lineage. CatL-like sequences proved to be excellent targets for diagnosis and genotyping of T rangeli by PCR. Data from CatL-like encoding genes agreed with results from previous studies of kDNA markers, and ribosomal and spliced leader genes, thereby corroborating clonal evolution, independent transmission cycles and the divergence of T rangeli lineages associated with sympatric species of Rhodnius. (c) 2009 Elsevier B.V. All rights reserved.

Cathepsin L-like genes of Trypanosoma vivax from Africa and South America - characterization, relationships and diagnostic implications

We characterized sequences from genes encoding cathepsin L-like (CatL-like) cysteine proteases from African and South American isolates of Trypanosoma vivax and T. vivax-like organisms, and evaluated their suitability as genetic markers for population structure analysis and diagnosis. Phylogenetic analysis of sequences corresponding to CatL-like catalytic domains revealed substantial polymorphism, and clades of sequences (TviCatL1-9) were separated by large genetic distances. TviCatL1-4 sequences were from cattle isolates from West Africa (Nigeria and Burkina Faso) and South America (Brazil and Venezuela), which belonged to the same T. vivax genotype. T. vivax-like genotypes from East Africa showed divergent sequences, including TviCatL5-7 for isolates from Mozambique and TviCatL8-9 for an isolate from Kenya. Phylogenetic analysis of CatL-like gene data supported the relationships among trypanosome species reflected in the phylogenies based on the analysis of small subunit (SSU) of ribosomal RNA gene sequence data. The discovery of different CatL-like sequences for each genotype, defined previously by ribosomal DNA data, indicate that these sequences provide useful targets for epidemiological and population genetic studies. Regions in CatL-like sequences shared by all T. vivax genotypes but not by other trypanosomes allowed the establishment of a specific and sensitive diagnostic PCR for epidemiological studies in South America and Africa. (C) 2008 Elsevier Ltd. All rights reserved.

Investigating relationships within and between category networks in Wikipedia

This work maps and analyses cross-citations in the areas of Biology, Mathematics, Physics and Medicine in the English version of Wikipedia, which are represented as an undirected complex network where the entries correspond to nodes and the citations among the entries are mapped as edges. We found a high value of clustering coefficient for the areas of Biology and Medicine, and a small value for Mathematics and Physics. The topological organization is also different for each network, including a modular structure for Biology and Medicine, a sparse structure for Mathematics and a dense core for Physics. The networks have degree distributions that can be approximated by a power-law with a cut-off. The assortativity of the isolated networks has also been investigated and the results indicate distinct patterns for each subject. We estimated the betweenness centrality of each node considering the full Wikipedia network, which contains the nodes of the four subjects and the edges between them. In addition, the average shortest path length between the subjects revealed a close relationship between the subjects of Biology and Physics, and also between Medicine and Physics. Our results indicate that the analysis of the full Wikipedia network cannot predict the behavior of the isolated categories since their properties can be very different from those observed in the full network. (C) 2011 Elsevier Ltd. All rights reserved.

Quantitative structure-activity relationships for a series of inhibitors of cruzain from Trypanosoma cruzi: Molecular modeling, CoMFA and CoMSIA studies

Human parasitic diseases are the foremost threat to human health and welfare around the world. Trypanosomiasis is a very serious infectious disease against which the currently available drugs are limited and not effective. Therefore, there is an urgent need for new chemotherapeutic agents. One attractive drug target is the major cysteine protease from Trypanosoma cruzi, cruzain. In the present work, comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) studies were conducted on a series of thiosemicarbazone and semicarbazone derivatives as inhibitors of cruzain. Molecular modeling studies were performed in order to identify the preferred binding mode of the inhibitors into the enzyme active site, and to generate structural alignments for the three-dimensional quantitative structure-activity relationship (3D QSAR) investigations. Statistically significant models were obtained (CoMFA. r(2) = 0.96 and q(2) = 0.78; CoMSIA, r(2) = 0.91 and q(2) = 0.73), indicating their predictive ability for untested compounds. The models were externally validated employing a test set, and the predicted values were in good agreement with the experimental results. The final QSAR models and the information gathered from the 3D CoMFA and CoMSIA contour maps provided important insights into the chemical and structural basis involved in the molecular recognition process of this family of cruzain inhibitors, and should be useful for the design of new structurally related analogs with improved potency. (C) 2009 Elsevier Inc. All rights reserved.

Three-dimensional quantitative structure-activity relationships for a large series of potent antitubercular agents

Comparative molecular field analysis (CoMFA) studies were conducted on a series of 100 isoniazid derivatives as anti-tuberculosis agents using two receptor-independent structural data set alignment strategies: (1) rigid-body fit, and (2) pharmacophore-based. Significant cross-validated correlation coefficients were obtained (CoMFA(1), q(2) = 0,75 and CoMFA(2), q(2) = 0.74), indicating the potential of the models for untested compounds. The models were then used to predict the inhibitory potency of 20 test set compounds that were not included in the training set, and the predicted values were in good agreement with the experimental results.

Fragment-based and classical quantitative structure-activity relationships for a series of hydrazides as antituberculosis agents

Worldwide, tuberculosis (TB) is the leading cause of death among curable infectious diseases. Multidrug-resistant Mycobacterium tuberculosis is an emerging problem of great importance to public health, and there is an urgent need for new anti-TB drugs. In the present work, classical 2D quantitative structure-activity relationships (QSAR) and hologram QSAR (HQSAR) studies were performed on a training set of 91 isoniazid derivatives. Significant statistical models (classical QSAR, q(2) = 0.68 and r(2) = 0.72; HQSAR, q(2) = 0.63 and r(2) = 0.86) were obtained, indicating their consistency for untested compounds. The models were then used to evaluate an external test set containing 24 compounds which were not included in the training set, and the predicted values were in good agreement with the experimental results (HQSAR, r(pred)(2) = 0.87; classical QSAR, r(pred)(2) = 0.75).

Classical and fragment-based hologram structure-activity relationships for a series of analgesic cyclic imides

Cyclic imides have been widely employed in drug design research due to their multiple pharmacological and biological properties. In the present study, two-dimensional quantitative structure-activity relationship (2D QSAR) studies were conducted on a series of potent analgesic cyclic imides using both classical and hologram QSAR (HQSAR) methods, yielding significant statistical models (classical QSAR, q(2) = 0.80; HQSAR, q(2) = 0.84). The models were then used to evaluate an external data test, and the predicted values were in good agreement with the experimental results, indicating their consistency for untested compounds.

Structure-activity relationships for a class of selective inhibitors of the major cysteine protease from Trypanosoma cruzi

Chagas` disease is a parasitic infection widely distributed throughout Latin America, with devastating consequences in terms of human morbidity and mortality. Cruzain, the major cysteine protease from Trypanosoma cruzi, is an attractive target for antitrypanosomal chemotherapy. In the present work, classical two-dimensional quantitative structure-activity relationships (2D QSAR) and hologram QSAR (HQSAR) studies were performed on a training set of 45 thiosemicarbazone and semicarbazone derivatives as inhibitors of T. cruzi cruzain. Significant statistical models (HQSAR, q2=0.75 and r2=0.96; classical QSAR, q2=0.72 and r2=0.83) were obtained, indicating their consistency for untested compounds. The models were then used to evaluate an external test set containing 10 compounds which were not included in the training set, and the predicted values were in good agreement with the experimental results (HQSAR, [image omitted]=0.95; classical QSAR, [image omitted]=0.91), indicating the existence of complementary between the two ligand-based drug design techniques.

Structural relationships in the solid state of the anti-chagas agent (E)-phenylethenylbenzofuroxan

The crystal structure and the vibrational spectrum of a potential drug for Chagas`s disease treatment, the (E)-isomer of phenylethenylbenzofuroxan 1 (5(6)(E)-[(2-phenylethenyl)]benzo[1,2-c]1,2,5-oxadiazole N-oxide), are reported. In order to provide insights into structural relationships, quantum mechanical calculations were employed starting from crystal structure. These results have given theoretical support to state interesting structural features, such as the effect of some intermolecular contacts on the molecule conformation and the electronic delocalization decreasing through atoms of the benzofuroxan moiety. Furthermore, the MOGUL comparative analysis in the Cambridge Structural Database provided additional evidences on these structural behaviors of compound 1. Intermolecular contacts interfere on the intramolecular geometry, as, for instance, on the phenyl group orientation, which is twisted by 12.32(6)A degrees from the ethenylbenzofuroxan plane. The experimental Raman spectrum of compound 1 presents unexpected frequency shift and also anomalous Raman activities. At last, the molecule skeleton deformation and the characteristic vibrational modes were correlated by matching the experimental Raman spectrum to the calculated one.