A Comparison of Phylogenetic Network Methods Using Computer Simulation

Background: We present a series of simulation studies that explore the relative performance of several phylogenetic network approaches (statistical parsimony, split decomposition, union of maximum parsimony trees, neighbor-net, simulated history recombination upper bound, median-joining, reduced median joining and minimum spanning network) compared to standard tree approaches, (neighbor-joining and maximum parsimony) in the presence and absence of recombination. Principal Findings: In the absence of recombination, all methods recovered the correct topology and branch lengths nearly all of the time when the substitution rate was low, except for minimum spanning networks, which did considerably worse. At a higher substitution rate, maximum parsimony and union of maximum parsimony trees were the most accurate. With recombination, the ability to infer the correct topology was halved for all methods and no method could accurately estimate branch lengths. Conclusions: Our results highlight the need for more accurate phylogenetic network methods and the importance of detecting and accounting for recombination in phylogenetic studies. Furthermore, we provide useful information for choosing a network algorithm and a framework in which to evaluate improvements to existing methods and nove

Origin and Epidemiological History of HIV-1 CRF14_BG

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Users must also make clear the license terms under which the work was published. CC BY Licence: http://creativecommons.org/licenses/by/4.0/Background: CRF14_BG isolates, originally found in Spain, are characterized by CXCR4 tropism and rapid disease progression. This study aimed to identify the origin of CRF14_BG and reconstruct its epidemiological history based on new isolates from Portugal.Methodology/Principal Findings: C2V3C3 env gene sequences were obtained from 62 samples collected in 1993–1998 from Portuguese HIV-1 patients. Full-length genomic sequences were obtained from three patients. Viral subtypes, diversity, divergence rate and positive selection were investigated by phylogenetic analysis. The molecular structure of the genomes was determined by bootscanning. A relaxed molecular clock model was used to date the origin of CRF14_BG. Geno2pheno was used to predict viral tropism. Subtype B was the most prevalent subtype (45 sequences; 73%) followed by CRF14_BG (8; 13%), G (4; 6%), F1 (2; 3%), C (2; 3%) and CRF02_AG (1; 2%). Three CRF14_BG sequences were derived from 1993 samples. Near full-length genomic sequences were strongly related to the CRF14_BG isolates from Spain. Genetic diversity of the Portuguese isolates was significantly higher than the Spanish isolates (0.044 vs 0.014, P,0.0001). The mean date of origin of the CRF14_BG cluster was estimated to be 1992 (range, 1989 and 1996) based on the subtype G genomic region and 1989 (range, 1984–1993) based on the subtype B genomic region. Most CRF14_BG strains (78.9%) were predicted to be CXCR4. Finally, up to five amino acids were under selective pressure in subtype B V3 loop whereas only one was found in the CRF14_BG cluster.Conclusions: CRF14_BG emerged in Portugal in the early 1990 s soon after the beginning of the HIV-1 epidemics, spread to Spain in late 1990 s as a consequence of IVDUs migration and then to the rest of Europe. CXCR4 tropism is a general characteristic of this CRF that may have been selected for by escape from neutralizing antibody response

Brain metastasis development and poor survival associated with carcinoembryonic antigen (CEA) level in advanced non-small cell lung cancer: a prospective analysis

<p>Abstract</p> <p>Background</p> <p>Central nervous system is a common site of metastasis in NSCLC and confers worse prognosis and quality of life. The aim of this prospective study was to evaluate the prognostic significance of clinical-pathological factors (CPF), serum CEA levels, and EGFR and HER2 tissue-expression in brain metastasis (BM) and overall survival (OS) in patients with advanced NSCLC.</p> <p>Methods</p> <p>In a prospective manner, we studied 293 patients with NSCLC in IIIB-IV clinical stage. They received standard chemotherapy. CEA was measured prior to treatment; EGFR and HER2 were evaluated by immunohistochemistry. BM development was confirmed by MRI in symptomatic patients.</p> <p>Results</p> <p>BM developed in 27, and 32% of patients at 1 and 2 years of diagnosis with adenocarcinoma (RR 5.2; 95% CI, 1.002–29; p = 0.05) and CEA ≥ 40 ng/mL (RR 11.4; 95% CI, 1.7–74; <it>p </it>< 0.01) as independent associated factors. EGFR and HER2 were not statistically significant. Masculine gender (RR 1.4; 95% CI, 1.002–1.9; <it>p </it>= 0.048), poor performance status (RR 1.8; 95% CI, 1.5–2.3; <it>p </it>= 0.002), advanced clinical stage (RR 1.44; 95% CI, 1.02–2; <it>p </it>= 0.04), CEA ≥ 40 ng/mL (RR 1.5; 95% CI, 1.09–2.2; <it>p </it>= 0.014) and EGFR expression (RR 1.6; 95% CI, 1.4–1.9; <it>p </it>= 0.012) were independent associated factors to worse OS.</p> <p>Conclusion</p> <p>High CEA serum level is a risk factor for BM development and is associated with poor prognosis in patients with advanced NSCLC. Surface expression of CEA in tumor cells could be the physiopathological mechanism for invasion to CNS.</p

Extensive HIV-1 Intra-Host Recombination Is Common in Tissues with Abnormal Histopathology

There is evidence that immune-activated macrophages infected with the Human Immunodeficiency Virus (HIV) are associated with tissue damage and serve as a long-lived viral reservoir during therapy. In this study, we analyzed 780 HIV genetic sequences generated from 53 tissues displaying normal and abnormal histopathology. We found up to 50% of the sequences from abnormal lymphoid and macrophage rich non-lymphoid tissues were intra-host viral recombinants. The presence of extensive recombination, especially in non-lymphoid tissues, implies that HIV-1 infected macrophages may significantly contribute to the generation of elusive viral genotypes in vivo. Because recombination has been implicated in immune evasion, the acquisition of drug-resistance mutations, and alterations of viral co-receptor usage, any attempt towards the successful eradication of HIV-1 requires therapeutic approaches targeting tissue macrophages

RARE-Bestpractices: a platform for sharing best practices for the management of rare diseases

From 7th European Conference on Rare Diseases and Orphan Products (ECRD 2014).Rare diseases; clinical practice guidelines; recommendations. RARE-Bestpractices (http://www.rarebestpractices.eu) is a 4-year project (2013-2016) funded by the EC FP7. The project aims at improving clinical management of patients with rare diseases (RD) and at narrowing the existing gap in quality of healthcare among countries. Methods: RARE-Bestpractices (http://www.rarebestpractices.eu) involves 9 EU countries, including 15 partners from academic institutions, governmental bodies, patient organizations and networks, which will exploit the added value of integrating different contributions and viewpoints. The platform is developed involving both experts in RD research as well as experts in clinical practice guidelines (CPG) and systematic reviews. Results: Project expected outputs include: 1) identification of challenges to be considered in deriving high quality standards for CPG on RD; 2) transparent procedures and criteria for the evaluation of CPG and their collection in a publicly searchable database; 3) identification of notation criteria to improve user understandability and implementation of CPG; 4) production of mechanisms to assess RD clinical research needs; 5) development of training activities targeted to key stakeholders to disseminate process and tools for developing and evaluating CPG; 6) the publication of a new scientific journal (http://rarejournal.org). Discussion: RARE-Bestpractices addresses the demands from both patients and health care providers for updated and high quality CPG on RD. The project will meet the requirements laid down by to the Directive 2011/24/EU, which endorses EU MS to develop European Reference Networks (ERNs) for RD; in fact, one main criterion for ERNs should be the competence to produce CPG and actively disseminate them among Centers of Expertise.N

Where are you from, stranger? The enigmatic biogeography of North African pond turtles (Emys orbicularis) .

Abstract The European pond turtle (Emys orbicularis) is a Nearctic element in the African fauna and thought to have invaded North Africa from the Iberian Peninsula. All North African populations are currently identified with the subspecies E. o. occidentalis. However, a nearly range-wide sampling in North Africa used for analyses of mitochondrial and microsatellite DNA provides evidence that only Moroccan populations belong to this taxon, while eastern Algerian and Tunisian pond turtles represent an undescribed distinct subspecies. These two taxa are most closely related to E. o. galloitalica with a native distribution along the Mediterranean coast of northern Spain through southern France to western and southern Italy. This group is sister to a clade comprising several mitochondrial lineages and subspecies of E. orbicularis from Central and Eastern Europe plus Asia, and the successive sisters are E. o. hellenica and E. trinacris. Our results suggest that E. orbicularis has been present in North Africa longer than on the Iberian Peninsula and that after an initial invasion of North Africa by pond turtles from an unknown European source region, there was a phase of diversification in North Africa, followed by a later re-invasion of Europe by one of the African lineages. The differentiation of pond turtles in North Africa parallels a general phylogeographic paradigm in amphibians and reptiles, with deeply divergent lineages in the western and eastern Maghreb. Acknowledging their genetic similarity, we propose to synonymize the previously recognized Iberian subspecies E. o. fritzjuergenobsti with E. o. occidentalis sensu stricto. The seriously imperiled Moroccan populations of E. o. occidentalis represent two Management Units different in mitochondrial haplotypes and microsatellite markers. The conservation status of eastern Algerian pond turtles is unclear, while Tunisian populations are endangered. Considering that Algerian and Tunisian pond turtles represent an endemic taxon, their situation throughout the historical range should be surveyed to establish a basis for conservation measures

Genome size evolution at the speciation level: The cryptic species complex Brachionus plicatilis (Rotifera)

<p>Abstract</p> <p>Background</p> <p>Studies on genome size variation in animals are rarely done at lower taxonomic levels, e.g., slightly above/below the species level. Yet, such variation might provide important clues on the tempo and mode of genome size evolution. In this study we used the flow-cytometry method to study the evolution of genome size in the rotifer <it>Brachionus plicatilis</it>, a cryptic species complex consisting of at least 14 closely related species.</p> <p>Results</p> <p>We found an unexpectedly high variation in this species complex, with genome sizes ranging approximately seven-fold (haploid '1C' genome sizes: 0.056-0.416 pg). Most of this variation (67%) could be ascribed to the major clades of the species complex, i.e. clades that are well separated according to most species definitions. However, we also found substantial variation (32%) at lower taxonomic levels - within and among genealogical species - and, interestingly, among species pairs that are not completely reproductively isolated. In one genealogical species, called <it>B</it>. 'Austria', we found greatly enlarged genome sizes that could roughly be approximated as multiples of the genomes of its closest relatives, which suggests that whole-genome duplications have occurred early during separation of this lineage. Overall, genome size was significantly correlated to egg size and body size, even though the latter became non-significant after controlling for phylogenetic non-independence.</p> <p>Conclusions</p> <p>Our study suggests that substantial genome size variation can build up early during speciation, potentially even among isolated populations. An alternative, but not mutually exclusive interpretation might be that reproductive isolation tends to build up unusually slow in this species complex.</p