AlignMiner: a Web-based tool for detection of divergent regions in multiple sequence alignments of conserved sequences

<p>Abstract</p> <p>Background</p> <p>Multiple sequence alignments are used to study gene or protein function, phylogenetic relations, genome evolution hypotheses and even gene polymorphisms. Virtually without exception, all available tools focus on conserved segments or residues. Small divergent regions, however, are biologically important for specific quantitative polymerase chain reaction, genotyping, molecular markers and preparation of specific antibodies, and yet have received little attention. As a consequence, they must be selected empirically by the researcher. AlignMiner has been developed to fill this gap in bioinformatic analyses.</p> <p>Results</p> <p>AlignMiner is a Web-based application for detection of conserved and divergent regions in alignments of conserved sequences, focusing particularly on divergence. It accepts alignments (protein or nucleic acid) obtained using any of a variety of algorithms, which does not appear to have a significant impact on the final results. AlignMiner uses different scoring methods for assessing conserved/divergent regions, <monospace>Entropy</monospace> being the method that provides the highest number of regions with the greatest length, and <monospace>Weighted</monospace> being the most restrictive. Conserved/divergent regions can be generated either with respect to the consensus sequence or to one master sequence. The resulting data are presented in a graphical interface developed in AJAX, which provides remarkable user interaction capabilities. Users do not need to wait until execution is complete and can.even inspect their results on a different computer. Data can be downloaded onto a user disk, in standard formats. <it>In silico </it>and experimental proof-of-concept cases have shown that AlignMiner can be successfully used to designing specific polymerase chain reaction primers as well as potential epitopes for antibodies. Primer design is assisted by a module that deploys several oligonucleotide parameters for designing primers "on the fly".</p> <p>Conclusions</p> <p>AlignMiner can be used to reliably detect divergent regions via several scoring methods that provide different levels of selectivity. Its predictions have been verified by experimental means. Hence, it is expected that its usage will save researchers' time and ensure an objective selection of the best-possible divergent region when closely related sequences are analysed. AlignMiner is freely available at <url>http://www.scbi.uma.es/alignminer</url>.</p

Diffuse interstitial fibrosis assessed by cardiac magnetic resonance is associated with dispersion of ventricular repolarization in patients with hypertrophic cardiomyopathy

Background Hypertrophic cardiomyopathy (HCM) is characterized by myocyte hypertrophy, disarray, fibrosis, and increased risk for ventricular arrhythmias. Increased QT dispersion has been reported in patients with HCM, but the underlying mechanisms have not been completely elucidated. In this study, we examined the relationship between diffuse interstitial fibrosis, replacement fibrosis, QTc dispersion and ventricular arrhythmias in patients with HCM. We hypothesized that fibrosis would slow impulse propagation and increase dispersion of ventricular repolarization, resulting in increased QTc dispersion on surface electrocardiogram (ECG) and ventricular arrhythmias. Methods ECG and cardiac magnetic resonance (CMR) image analyses were performed retrospectively in 112 patients with a clinical diagnosis of HCM. Replacement fibrosis was assessed by measuring late gadolinium (Gd) enhancement (LGE), using a semi-automated threshold technique. Diffuse interstitial fibrosis was assessed by measuring T1 relaxation times after Gd administration, using the Look?Locker sequence. QTc dispersion was measured digitally in the septal/anterior (V1?V4), inferior (II, III, and aVF), and lateral (I, aVL, V5, and V6) lead groups on surface ECG. Results All patients had evidence of asymmetric septal hypertrophy. LGE was evident in 70 (63%) patients; the median T1 relaxation time was 411±38æms. An inverse correlation was observed between T1 relaxation time and QTc dispersion in leads V1?V4 (p\u3c 0.001). Patients with HCM who developed sustained ventricular tachycardia had slightly higher probability of increased QTc dispersion in leads V1?V4 (odds ratio, 1.011 [1.004?1.0178, p=0.003). We found no correlation between presence and percentage of LGE and QTc dispersion. Conclusion Diffuse interstitial fibrosis is associated with increased dispersion of ventricular repolarization in leads, reflecting electrical activity in the hypertrophied septum. Interstitial fibrosis combined with ion channel/gap junction remodeling in the septum could lead to inhomogeneity of ventricular refractoriness, resulting in increased QTc dispersion in leads V1?V4

Linguistic and maternal genetic diversity are not correlated in Native Mexicans

Mesoamerica, defined as the broad linguistic and cultural area from middle southern Mexico to Costa Rica, might have played a pivotal role during the colonization of the American continent. The Mesoamerican isthmus has constituted an important geographic barrier that has severely restricted gene flow between North and South America in pre-historical times. Although the Native American component has been already described in admixed Mexican populations, few studies have been carried out in native Mexican populations. In this study, we present mitochondrial DNA (mtDNA) sequence data for the first hypervariable region (HVR-I) in 477 unrelated individuals belonging to 11 different native populations from Mexico. Almost all of the Native Mexican mtDNAs could be classified into the four pan-Amerindian haplogroups (A2, B2, C1, and D1); only two of them could be allocated to the rare Native American lineage D4h3. Their haplogroup phylogenies are clearly star-like, as expected from relatively young populations that have experienced diverse episodes of genetic drift (e.g., extensive isolation, genetic drift, and founder effects) and posterior population expansions. In agreement with this observation, Native Mexican populations show a high degree of heterogeneity in their patterns of haplogroup frequencies. Haplogroup X2a was absent in our samples, supporting previous observations where this clade was only detected in the American northernmost areas. The search for identical sequences in the American continent shows that, although Native Mexican populations seem to show a closer relationship to North American populations, they cannot be related to a single geographical region within the continent. Finally, we did not find significant population structure in the maternal lineages when considering the four main and distinct linguistic groups represented in our Mexican samples (Oto-Manguean, Uto-Aztecan, Tarascan, and Mayan), suggesting that genetic divergence predates linguistic diversification in Mexico

The first three dimensional fossils of Cretaceous sclerorhynchid sawfish Asflapristis cristadentis gen et sp nov and implications for the phylogenetic position of the Sclerorhynchoidei (Chondrichthyes)

A new fossil batoid (ray) Asflapristis cristadentis gen. et sp. nov. is described from six exceptionally well-preserved, three-dimensional skeletal remains from the Turonian (Late Cretaceous) of Morocco. Mechanical and acid preparation and CT scanning of these specimens reveal details of much of the proximal skeleton, especially the skull, synarcual and pectoral skeleton, with only the more distal parts of the skeleton missing. These fossils represent a relatively large animal (62 cm preserved length, estimated total length to approximately 2 meters) possessing a robust rostrum that lacks enlarged rostral denticles. It has a narrow and small chondrocranium with jaws that are relatively large compared to the rest of the skull and robust with highly ornamented teeth that lack cusps. The branchial skeleton shows a large second hypobranchial without anterior process which was probably fused to the basibranchial as in other sclerorhynchoids. The synarcual is large and lacks centra through its entire length, and with no direct connection to the pectoral girdle was observed. Pectoral fins probably possessed enlarged proximal elements (propterygium, mesopterygium and metapterygium), the reduced articulation facet between the coracoid with the pectoral elements was reduced. A phylogenetic analysis using both parsimony and bayesian methods was performed incorporating this new taxon. Both analyses recovered a phylogenetic topology that places the sclerorhynchoids in a close relation to rajoids and clearly separated from the morphologically similar Pristidae within the Rhinopristiformes. In respect to the extant taxa, the phylogenies generated are similar to that obtained in molecular analysis of modern batoids. The palaeoecological implication of this discovery suggests that the Asfla assemblage was not from a ‘normal’ open carbonate shelf but rather a restricted environment favouring a low diversity chondrichthyan fauna

Training dual-task walking in community-dwelling adults within 1 year of stroke: A protocol for a single-blind randomized controlled trial

Background: Community ambulation is a highly complex skill requiring the ability to adapt to increased environmental complexity and perform multiple tasks simultaneously. After stroke, individuals demonstrate a diminished ability to perform dual-tasks. Current evidence suggests that conventional rehabilitation does not adequately address gait-related dual-task impairments after stroke, which may be contributing to low levels of participation and physical inactivity in community-dwelling stroke survivors. The objective of this study is to investigate the efficacy of dual-task gait training in community-dwelling adults within 1 year of stroke. Specifically, we will compare the effects of dual-task gait training and single-task gait training on cognitive-motor interference during walking at preferred speed and at fastest comfortable speed (Aim 1), locomotor control during obstacle negotiation (Aim 2), and spontaneous physical activity (Aim 3). Methods/design: This single-blind randomized controlled trial will involve 44 individuals within 12 months of stroke. Following baseline evaluation, participants will be randomly allocated to single- or dual-task gait training. Both groups will receive 12, 30-minute sessions provided one-on-one over 4–6 weeks in an outpatient therapy setting. Single-task gait training involves practice of gait activities incorporating motor relearning principles. Dual-task gait training involves an identical gait training protocol; the critical difference being that the dual-task gait training group will practice the gait activities while simultaneously performing a cognitive task for 75% of the repetitions. Blinded assessors will measure outcomes at baseline, post-intervention, and 6 months after completion of the intervention. The primary outcome measure will be dual-task effects on gait speed and cognition during unobstructed walking. Secondary outcomes include spatiotemporal and kinetic gait parameters during unobstructed single- and dual-task walking at preferred and fastest comfortable walking speeds, gait parameters during high and low obstacle crossing, spontaneous physical activity, executive function, lower extremity motor function, Timed Up and Go, balance self-efficacy, number of falls, and stroke-related disability. Hypotheses for each aim will be tested using an intention-to-treat analysis with repeated measures ANOVA design. Discussion: This trial will provide evidence to help clinicians make decisions about the types of activities to include in rehabilitation to improve dual-task walking after stroke

Measurement of charm production at central rapidity in proton-proton collisions at s=2.76\sqrt{s} = 2.76 TeV

The $p_{\rm T}$-differential production cross sections of the prompt (B feed-down subtracted) charmed mesons D$^0$, D$^+$, and D$^{*+}$ in the rapidity range $|y|<0.5$, and for transverse momentum $1< p_{\rm T} <12$ GeV/$c$, were measured in proton-proton collisions at $\sqrt{s} = 2.76$ TeV with the ALICE detector at the Large Hadron Collider. The analysis exploited the hadronic decays D$^0 \rightarrow$K$\pi$, D$^+ \rightarrow$K$\pi\pi$, D$^{*+} \rightarrow$D$^0\pi$, and their charge conjugates, and was performed on a $L_{\rm int} = 1.1$ nb$^{-1}$ event sample collected in 2011 with a minimum-bias trigger. The total charm production cross section at $\sqrt{s} = 2.76$ TeV and at 7 TeV was evaluated by extrapolating to the full phase space the $p_{\rm T}$-differential production cross sections at $\sqrt{s} = 2.76$ TeV and our previous measurements at $\sqrt{s} = 7$ TeV. The results were compared to existing measurements and to perturbative-QCD calculations. The fraction of cdbar D mesons produced in a vector state was also determined.Comment: 20 pages, 5 captioned figures, 4 tables, authors from page 15, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/307

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

EuroPineDB: a high-coverage web database for maritime pine transcriptome

Pinus pinaster is an economically and ecologically important species that is becoming a woody gymnosperm model. Its enormous genome size makes whole-genome sequencing approaches are hard to apply. Therefore, the expressed portion of the genome has to be characterised and the results and annotations have to be stored in dedicated databases

Expansion of Signal Transduction Pathways in Fungi by Extensive Genome Duplication

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