Metabolism of the mesoionic compound (MI‐D) by mouse liver microsome,detection of its metabolite In Vivo,and acute toxicity in mice

The mesoionic derivative 4‐phenyl‐5‐[4‐nitrocinnamoyl]‐1,3,4‐thiadiazolyl‐2‐phenylamine chloride (MI‐D) has antitumoral and anti‐inflammatory effects. In this study, we present aspects of its metabolism and toxicity in mice. MI‐D was metabolized in vitro by liver microsome, generating a main product with a much shorter retention time than MI‐D in high‐performance liquid chromatography (HPLC) analysis but with a spectrum similar to that of the original molecule. Mass spectrometry with electrospray ionization in positive mode analysis of the purified compound by HPLC indicated that the product of metabolism has four additional hydroxyl groups (m/z = 465) compared with MI‐D (m/z = 401). The HPLC analyses of plasma and urine samples from mice treated with MI‐D showed the presence of the metabolite product. The kinetic parameters K_m (19.5 ± 4.5 μM) and V_max [1.5 ± 0.4 units of fluorescence/(100 μg of microsomal protein/mL/s)] were estimated, confirming the metabolism of MI‐D and indicating that the reaction follows Michaelis‐Menten kinetics. Acute toxicity was established on the basis of an estimation of mean lethal dose (LD‐50; 181.2 mg/kg) and histopathological analysis of animals that survived the LD‐50 test. Abdominal adhesions, inflammatory foci, and formation of granulomas were observed. Altogether, the results contribute to the advancement of research in support of MI‐D as a future chemotherapeutic drug. © 2009 Wiley Periodicals, Inc. J Biochem Mol Toxicol 23:394–405, 2009; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/jbt.20303     

Phylogeographic analysis of paternal lineages in NE Portuguese Jewish communities

The establishment of Jewish communities in the territory of contemporary Portugal is archaeologically documented since the 3rd century CE, but their settlement in Trás‐os‐Montes (NE Portugal) has not been proved before the 12th century. The Decree of Expulsion followed by the establishment of the Inquisition, both around the beginning of the 16th century, accounted for a significant exodus, as well as the establishment of crypto‐Jewish communities. Previous Y chromosome studies have shown that different Jewish communities share a common origin in the Near East, although they can be quite heterogeneous as a consequence of genetic drift and different levels of admixture with their respective host populations. To characterize the genetic composition of the Portuguese Jewish communities from Trás‐os‐Montes, we have examined 57 unrelated Jewish males, with a high‐resolution Y‐chromosome typing strategy, comprising 16 STRs and 23 SNPs. A high lineage diversity was found, at both haplotype and haplogroup levels (98.74 and 82.83%, respectively), demonstrating the absence of either strong drift or founder effects. A deeper and more detailed investigation is required to clarify how these communities avoided the expected inbreeding caused by over four centuries of religious repression. Concerning haplogroup lineages, we detected some admixture with the Western European non‐Jewish populations (R1b1b2‐M269, ～28%), along with a strong ancestral component reflecting their origin in the Middle East [J1(xJ1a‐M267), ～12%; J2‐M172, ～25%; T‐M70, ～16%] and in consequence Trás‐os‐Montes Jews were found to be more closely related with other Jewish groups, rather than with the Portuguese non‐Jewish population. Am J Phys Anthropol 2010. © 2009 Wiley‐Liss, Inc.     

Immune response dynamics and Lutzomyia longipalpis exposure characterize a biosignature of visceral leishmaniasis susceptibility in a canine cohort

BackgroundReports have shown correlations between the immune response to vector saliva and Leishmaniasis outcome. We followed dogs in an endemic area for two years characterizing resistance or susceptibility to canine visceral leishmaniasis (CVL) according to Leishmania infantum diagnosis and clinical development criteria. Then, we aimed to identify a biosignature based on parasite load, serum biological mediators’ interactions, and vector exposure intensity associated with CVL resistance and susceptibility.Methodology/Principal findingsA prospective two-year study was conducted in an area endemic for CVL. Dogs were evaluated at 6-month intervals to determine infection, clinical manifestations, immune profile, and sandfly exposure. CVL resistance or susceptibility was determined upon the conclusion of the study. After two years, 78% of the dogs were infected with L. infantum (53% susceptible and 47% resistant to CVL). Susceptible dogs presented higher splenic parasite load as well as persistence of the parasite during the follow-up, compared to resistant ones. Susceptible dogs also displayed a higher number of correlations among the investigated biological mediators, before and after infection diagnosis. At baseline, anti-saliva antibodies, indicative of exposure to the vector, were detected in 62% of the dogs, reaching 100% in one year. Higher sandfly exposure increased the risk of susceptibility to CVL by 1.6 times (CI: 1.11–2.41). We identified a discriminatory biosignature between the resistant and susceptible dogs assessing splenic parasite load, interaction of biological mediators, PGE₂ serum levels and intensity of exposure to sandfly. All these parameters were elevated in susceptible dogs compared to resistant animals.Conclusions/SignificanceThe biosignature identified in our study reinforces the idea that CVL is a complex multifactorial disease that is affected by a set of factors which are correlated and, for a better understanding of CVL, should not be evaluated in an isolated way.     

Rediscovery of Leptopanchax splendens (Cyprinodontiformes: Aplocheilidae): a seasonal killifish from the Atlantic Forest of south-eastern Brazil that was recently considered extinct

A recent collection of the seasonal killifish found Leptopanchax splendens c. 5 km from the type locality, 74 years after its last record. The species was historically common in its type locality, the Estrela River basin in south-eastern Brazil, until 1950, after which it was not encountered and thought to have become extinct due to widespread deforestation and urbanization in the region. Despite the rediscovery, this study finds that other recently published reports of L. splendens are misidentifications.     

Long-term stability of the hawkmoth fauna (Lepidoptera,Sphingidae) in a protected area of Brazilian Atlantic Rain Forest

Hawkmoths are an important component of tropical ecosystems, with significant roles as herbivores and pollinators. These moths can be used as indicators in biodiversity assessments because they can be easily sampled and identified. However, hawkmoths have seldom been surveyed over the long term for this purpose, especially in the Neotropical region. Considering that long-term datasets are of indisputable importance for understanding and monitoring temporal changes in biodiversity, this study assessed long-term changes in the hawkmoth fauna in a protected Atlantic Rain Forest area over a period of 64 years. We used historical and recent empirical datasets to ask whether faunal-diversity patterns and species composition have changed over time. We used individual- and sample-based rarefaction and extrapolation curves based on Hill number (diversity order of q = 0) to compare species richness, and the probability version of the abundance-based Chao-Jaccard index to assess beta diversity over time. To assess changes in faunal composition, we conducted a nonmetric multidimensional scaling analysis and performed an analysis of similarities to test whether the community composition has changed. Our results clearly showed long-term stability of the hawkmoth community over the 64 years, despite the growing human-induced landscape changes that occurred in the region surrounding the study area during the last 6 decades. This study emphasizes the importance of large remnants of Atlantic Forest for long-term maintenance of both functional diversity and ecosystem functioning.     

Reconstructing biogeographic temporal events in the evolution of the livebearer fish genus Jenynsia based on total evidence analysis (Cyprinodontiformes: Anablepidae)

The current distribution of the Neotropical ichthyofauna has been widely affected by the main geological events that occurred in South and Central America. However, robust biogeographic information is still scarce or absent for most fish families. The biogeographic relationships of the most diverse anablepid genus, Jenynsia, are herein analysed, using temporal and spatial approaches based on a total evidence dataset, including 167 morphological characters and seven nuclear genes, totalling 6075?bp. A time calibrated analysis recovered the origin of Jenynsia at the Miocene and the diversification of its two subgenera between the Late Miocene and Early Pliocene. This result combined with the analysis of reconstruction of ancestral states indicates that the ancestor of Jenynsia colonized the Paranean Sea, and the current distribution of the species of the genus is probably a result of geological events, including: (1) ancient connections between Iguaçu and upper Uruguay River basins; (2) sea level variation along the Pliocene in the South American Atlantic coast; and (3) the decrease of the Paranean Sea along the Pliocene and Pleistocene.     

Molecular Detection of Circovirus and Adenovirus in Feces of Fur Seals (<Emphasis Type="Italic">Arctocephalus</Emphasis> spp.)

In some regions, little is known about exposure to viruses in coastal marine mammals. The present study aimed to detect viral RNA or DNA in 23 free-ranging fur seals on the northern coastline of Rio Grande do Sul State, Brazil. Polymerase chain reaction was used to detect nucleic acids of circoviruses, adenoviruses, morbilliviruses, vesiviruses, and coronaviruses in the feces from twenty-one South American fur seals (Arctocephalus australis) and two Subantarctic fur seals (A. tropicalis). Adenovirus DNA fragments were detected in two South American fur seals; nucleotide sequences of these fragments revealed a high degree of similarity to human adenovirus type C. Circovirus DNA fragments were detected in six animals of the same species. Two were phylogenetically similar to the Circovirus genus, whereas the other four nucleotide fragments showed no similarity to any of the known genera within the family Circoviridae. RNA fragments indicating the presence of coronavirus, vesivirus, and morbillivirus were not detected. These findings suggest that adenoviruses and circoviruses are circulating in fur seal populations found along the coast of Rio Grande do Sul State, Brazil.