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Two juvenile specimens of a new species of Oreaster were collected at Parque Nacional Arrecife Alacranes and Triángulos Oeste in the southern Gulf of Mexico. DNA of mitochondrial loci identifies them as members of the same clade as cloning larvae of Oreaster found abundantly in waters of the Florida Current-Gulf Stream system, and distinct from Oreaster clavatus and Oreaster reticulatus , the two known Oreasteridae species in the North Atlantic. Larvae from the new species of Oreaster persist as clones but also metamorphose and settle to the benthos with typical asteroid morphology. [ABSTRACT FROM AUTHOR]

Abstract: We applied a novel strategy to infer sequence circularity and complete assembly of four mitochondrial genomes (mitogenomes) of the frog families Bufonidae (Melanophryniscus moreirae), Dendrobatidae (Hyloxalus subpunctatus and Phyllobates terribilis), and Scaphiopodidae (Scaphiopus holbrookii). These are the first complete mitogenomes of these four genera and Scaphiopodidae. We assembled mitogenomes from short genomic sequence reads using a baiting and iterative mapping strategy followed by a new ad hoc mapping strategy developed to test for assembly circularization. To assess the quality of the inferred circularization, we used Bowtie2 alignment scores and a new per‐position sequence coverage value (which we named “connectivity”). Permutation tests with 400 iterations per specimen and 1% or 5% chance of mutation at the ends of the putative circular sequences showed that the proposed method is highly sensitive, with a single nucleotide insertion or deletion being sufficient for circularity to be rejected. False positives comprised only 2% of all observations and possessed significantly lower alignment scores. The size, gene content, and gene arrangement of each mitogenome differed among the species but matched the expectations for their clades. We argue that basic studies on circular sequences can benefit from the results and bioinformatics procedures introduced here, especially when closely related references are lacking. [ABSTRACT FROM AUTHOR]

Background: One of our goals for the echinoderm tree of life project (http://echinotol.org) is to identify orthologs suitable for phylogenetic analysis from next-generation transcriptome data. The current dataset is the largest assembled for echinoderm phylogeny and transcriptomics. We used RNA-Seq to profile adult tissues from 42 echinoderm specimens from 24 orders and 37 families. In order to achieve sampling members of clades that span key evolutionary divergence, many of our exemplars were collected from deep and polar seas. Description: A small fraction of the transcriptome data we produced is being used for phylogenetic reconstruction. Thus to make a larger dataset available to researchers with a wide variety of interests, we made a web-based application, EchinoDB (http://echinodb.uncc.edu). EchinoDB is a repository of orthologous transcripts from echinoderms that is searchable via keywords and sequence similarity. Conclusions: From transcripts we identified 749,397 clusters of orthologous loci. We have developed the information technology to manage and search the loci their annotations with respect to the Sea Urchin (Strongylocentrotus purpuratus) genome. Several users have already taken advantage of these data for spin-off projects in developmental biology, gene family studies, and neuroscience. We hope others will search EchinoDB to discover datasets relevant to a variety of additional questions in comparative biology. [ABSTRACT FROM AUTHOR]

Viruses of influenza A subtype H7 can be highly pathogenic and periodically infect humans. For example, there have been numerous outbreaks of H7 in the Americas and Europe since 1996. More recently, a reassortant H7N9 has emerged among humans and birds during 2013-2014 in China, Taiwan and Hong Kong. This H7N9 genome consists of genetic segments that assort with H7 and H9 viruses previously circulating in chickens and wild birds in China and ducks in Korea. Epidemic risk modellers have used agricultural, climatic and demographic data to predict that the virus will spread to northern Vietnam via poultry. To shed light on the traffic of H7 viruses in general, we examine genetic segments of influenza that have assorted with many strains of H7 viruses dating back to 1902. We focus on use cases from the United States, Italy and China. We apply a novel metric, betweenness, an associated phylogenetic visualization technique, transmission networks, and compare these with another technique, route mapping. In contrast to traditional views, our results illustrate that segments that assort with H7 viruses are spread frequently between the Americas and Eurasia. In summary, genetic segments that historically assort with H7 influenza viruses have been spread from China to: Australia, Czech Republic, Denmark, Egypt, Germany, Hong Kong, Italy, Japan, Mongolia, the Netherlands, New Zealand, Pakistan, South Africa, South Korea, Spain, Sweden, the UK, the US, and Vietnam. [ABSTRACT FROM AUTHOR]

It has been proposed that supertree approaches should be applied to large multilocus datasets to achieve computational tractability. Large datasets such as those derived from phylogenomics studies can be broken into many locus-specific tree searches and the resulting trees can be stitched together via a supertree method. Using simulated data, workers have reported that they can rapidly construct a supertree that is comparable to the results of heuristic tree search on the entire dataset. To test this assertion with organismal data, we compare tree length under the parsimony criterion and computational time for 20 multilocus datasets using supertree (SuperFine and SuperTriplets) and supermatrix (heuristic search in TNT) approaches. Tree length and computational times were compared among methods using the Wilcoxon matched-pairs signed rank test. Supermatrix searches produced significantly shorter trees than either supertree approach (SuperFine or SuperTriplets; P < 0.0002 in both cases). Moreover, the processing time of supermatrix search was significantly lower than SuperFine+locus-specific search ( P < 0.01) but roughly equivalent to that of SuperTriplets+locus-specific search ( P > 0.4, not significant). In conclusion, we show by using real rather than simulated data that there is no basis, either in time tractability or in tree length, for use of supertrees over heuristic tree search using a supermatrix for phylogenomics. [ABSTRACT FROM AUTHOR]

We have reported previously on use of a web-based application, Supramap (http://supramap.org) for the study of biogeographic, genotypic, and phenotypic evolution. Using Supramap we have developed maps of the spread of drug-resistant influenza and host shifts in H1N1 and H5N1 influenza and coronaviruses such as SARS. Here we report on another zoonotic pathogen, H7 influenza, and provide an update on the implementation of Supramap as a web service. We find that the emergence of pathogenic strains of H7 is labile with many transitions from high to low pathogenicity, and from low to high pathogenicity. We use Supramap to put these events in a temporal and geospatial context. We identify several lineages of H7 influenza with biomarkers of high pathogenicity in regions that have not been reported in the scientific literature. The original implementation of Supramap was built with tightly coupled client and server software. Now we have decoupled the components to provide a modular web service for POY (http://poyws.org) that can be consumed by a data provider to create a novel application. To demonstrate the web service, we have produced an application, Geogenes (http://geogenes.org). Unlike in Supramap, in which the user is required to create and upload data files, in Geogenes the user works from a graphical interface to query an underlying dataset. Geogenes demonstrates how the web service can provide underlying processing for any sequence and metadata database. © The Willi Hennig Society 2012. [ABSTRACT FROM AUTHOR]

Reconstruction of the phylogeny of the five extant classes of the phylum Echinodermata has proven difficult. Results concerning higher-level taxonomic relationships among echinoderms are sensitive to the choice of analytical parameters and methods. Moreover, the proposal of a putative sixth class based on a small enigmatic disc-shaped echinoderm, Xyloplax, from the deep seas of the Bahamas and New Zealand in the 1980s further complicated the problem. Although clearly an echinoderm, Xyloplax did not have clear affinity among known groups. Using molecular sequence and developmental data from recently collected Xyloplax adults and embryos, we show that rather than representing an ancient distinct lineage as implied by its status as a class, Xyloplax is simply a starfish that is closely related to the asteroid family Pterasteridae. Many members of the Pterasteridae and all Xyloplax inhabit deep or polar seas and brood young. Brooding pterasterids and Xyloplax hold their young in specialized adult chambers until the young reach an advanced juvenile stage after which they are released as free-living individuals. We hypothesize that the unique morphology of Xyloplax evolved via progenesis—the truncation of somatic growth at a juvenile body plan but with gonadal growth to maturity. Although the overall phylogeny of extant echinoderms remains sensitive to the choice of analytical methods, the placement of Xyloplax as sister to pterasterid asteroids is unequivocal. Based on this, we argue that the proposed class and infraclass status of Xyloplax should be suppressed. [ABSTRACT FROM PUBLISHER]

Novel pathogens have the potential to become critical issues of national security, public health and economic welfare. As demonstrated by the response to Severe Acute Respiratory Syndrome (SARS) and influenza, genomic sequencing has become an important method for diagnosing agents of infectious disease. Despite the value of genomic sequences in characterizing novel pathogens, raw data on their own do not provide the information needed by public health officials and researchers. One must integrate knowledge of the genomes of pathogens with host biology and geography to understand the etiology of epidemics. To these ends, we have created an application called Supramap () to put information on the spread of pathogens and key mutations across time, space and various hosts into a geographic information system (GIS). To build this application, we created a web service for integrated sequence alignment and phylogenetic analysis as well as methods to describe the tree, mutations, and host shifts in Keyhole Markup Language (KML). We apply the application to 239 sequences of the polymerase basic 2 (PB2) gene of recent isolates of avian influenza (H5N1). We map a mutation, glutamic acid to lysine at position 627 in the PB2 protein (E627K), in H5N1 influenza that allows for increased replication of the virus in mammals. We use a statistical test to support the hypothesis of a correlation of E627K mutations with avian-mammalian host shifts but reject the hypothesis that lineages with E627K are moving westward. Data, instructions for use, and visualizations are included as supplemental materials at: . © The Willi Hennig Society 2010. [ABSTRACT FROM AUTHOR]

Emerging infectious diseases are critical issues of public health and the economic and social stability of nations. As demonstrated by the international response to the severe acute respiratory syndrome (SARS) and influenza A, rapid genomic sequencing is a crucial tool to understand diseases that occur at the interface of human and animal populations. However, our ability to make sense of sequence data lags behind our ability to acquire the data. The potential of sequence data on pathogens is not fully realized until raw data are translated into public health intelligence. Sequencing technologies have become highly mechanized. If the political will for data sharing remains strong, the frontier for progress in emerging infectious diseases will be in analysis of sequence data and translation of results into better public health science and policy. For example, applying analytical tools such as Supramap (http:// supramap.osu.edu) to genomic data for pathogens, public health scientists can track specific mutations in pathogens that confer the ability to infect humans or resist drugs. The results produced by the Supramap application are compelling visualizations of pathogen lineages and features mapped into geographic information systems that can be used to test hypotheses and to follow the spread of diseases across geography and hosts and communicate the results to a wide audience. [ABSTRACT FROM AUTHOR]

Background: In Spring 2009, a novel reassortant strain of H1N1 influenza A emerged as a lineage distinct from seasonal H1N1. On June 11, the World Heath Organization declared a pandemic - the first since 1968. There are currently two main branches of H1N1 circulating in humans, a seasonal branch and a pandemic branch. The primary treatment method for pandemic and seasonal H1N1 is the antiviral drug Tamiflu® (oseltamivir). Although many seasonal H1N1 strains around the world are resistant to oseltamivir, initially, pandemic H1N1 strains have been susceptible to oseltamivir. As of February 3, 2010, there have been reports of resistance to oseltamivir in 225 cases of H1N1 pandemic influenza. The evolution of resistance to oseltamivir in pandemic H1N1 could be due to point mutations in the neuraminidase or a reassortment event between seasonal H1N1 and pandemic H1N1 viruses that provide a neuraminidase carrying an oseltamivir-resistant genotype to pandemic H1N1. Results: Using phylogenetic analysis of neuraminidase sequences, we show that both seasonal and pandemic lineages of H1N1 are evolving to direct selective pressure for resistance to oseltamivir. Moreover, seasonal lineages of H1N1 that are resistant to oseltamivir co-circulate with pandemic H1N1 throughout the globe. By combining phylogenetic and geographic data we have thus far identified 53 areas of co-circulation where reassortment can occur. At our website POINTMAP, http://pointmap.osu.edu we make available a visualization and an application for updating these results as more data are released. Conclusions: As oseltamivir is a keystone of preparedness and treatment for pandemic H1N1, the potential for resistance to oseltamivir is an ongoing concern. Reassortment and, more likely, point mutation have the potential to create a strain of pandemic H1N1 against which we have a reduced number of treatment options. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome (SARS) is a novel human illness caused by a previously unrecognized coronavirus (CoV) termed SARS-CoV. There are conflicting reports on the animal reservoir of SARS-CoV. Many of the groups that argue carnivores are the original reservoir of SARS-CoV use a phylogeny to support their argument. However, the phylogenies in these studies often lack outgroup and rooting criteria necessary to determine the origins of SARS-CoV. Recently, SARS-CoV has been isolated from various species of Chiroptera from China (e.g., Rhinolophus sinicus) thus leading to reconsideration of the original reservoir of SARS-CoV. We evaluated the hypothesis that SARS-CoV isolated from Chiroptera are the original zoonotic source for SARS-CoV by sampling SARS-CoV and non-SARS-CoV from diverse hosts including Chiroptera, as well as carnivores, artiodactyls, rodents, birds and humans. Regardless of alignment parameters, optimality criteria, or isolate sampling, the resulting phylogenies clearly show that the SARS-CoV was transmitted to small carnivores well after the epidemic of SARS in humans that began in late 2002. The SARS-CoV isolates from small carnivores in Shenzhen markets form a terminal clade that emerged recently from within the radiation of human SARS-CoV. There is evidence of subsequent exchange of SARS-CoV between humans and carnivores. In addition SARS-CoV was transmitted independently from humans to farmed pigs ( Sus scrofa). The position of SARS-CoV isolates from Chiroptera are basal to the SARS-CoV clade isolated from humans and carnivores. Although sequence data indicate that Chiroptera are a good candidate for the original reservoir of SARS-CoV, the structural biology of the spike protein of SARS-CoV isolated from Chiroptera suggests that these viruses are not able to interact with the human variant of the receptor of SARS-CoV, angiotensin-converting enzyme 2 (ACE2). In SARS-CoV we study, both visually and statistically, labile genomic fragments and, putative key mutations of the spike protein that may be associated with host shifts. We display host shifts and candidate mutations on trees projected in virtual globes depicting the spread of SARS-CoV. These results suggest that more sampling of coronaviruses from diverse hosts, especially Chiroptera, carnivores and primates, will be required to understand the genomic and biochemical evolution of coronaviruses, including SARS-CoV. © The Willi Hennig Society 2008. [ABSTRACT FROM AUTHOR]

Abstract: Behavior, color, body size, spicules, and mitochondrial DNA were examined in two morphs from the Bohadschia marmorata (Jaeger, 1833) species complex in Micronesia to test whether they are conspecific. This complex consists of eight morphs that have been described as separate species and combined in various ways for over a century. We examined the classic B. marmorata type and the type originally described as the species B. bivittata (Mitsukuri, 1912); B. bivittata was combined with B. marmorata by Panning (1944). Several observations and a phylogenetic analysis led us to conclude that B. marmorata and B. bivittata should return to their status as separate species. First, B. marmorata lives in shallow areas with strong currents, and B. bivittata lives on open sand between corals in deeper water. Second, the coloration of B. bivittata is distinct from B. marmorata, and although specimens collected on Yap Island differed from Mitsukuri''s original description of B. bivittata, no specimens were collected with coloration intermediate between B. bivittata and B. marmorata. Third, spicules are more highly branched, perforated, and spiked in B. bivittata than in B. marmorata (and, in our study, spicule complexity did not correlate with body size). Finally, our phylogenetic analysis, based on partial nucleotide sequences of 16s, 12s, and COI mitochondrial genes, resulted in a tree—(Pearsonothuria graeffei (Bohadschia marmorata) (B. argus (B. bivittata)))—which shows that B. marmorata and B. bivittata are not even sister species, with B. bivittata more closely related to B. argus. Support for the clades for each Bohadschia species was strong, but the clade containing B. argus and B. bivittata had weaker support. Color and spicule examinations made of preserved B. marmorata-complex specimens from the Indo-Pacific as well as behavioral observations in the field also support the resurrection of B. bivittata. [Copyright &y& Elsevier]

A well-supported phylogeny of echinoderm classes has eluded morphological, embryological, molecular, and combined analyses. From this body of work it is apparent that (i) echinoids (sea urchins) and holothuroids (sea cucumbers) are related, and (ii) crinoids (sea lilies) are the sister taxon to extant eleutherozoan classes (asteroids, ophiuroids, echinoids, and holothuroids). However, the relationships of asteroids and ophiuroids to other echinoderm classes have been difficult to recover. To address relationships between the asteroids and ophiuroids and other echinoderms, I have sequenced additional nuclear loci and taxa and used novel computational approaches for co-optimizing morphological with molecular evidence at the level of sequence alignment. Support for the monophyly of each class is strong. Support for a monophyletic Asteroidea + Xyloplax is as strong as for Asteroidea. Support for Asterozoa (Asteroidea + Ophiuroidea) is apparent, albeit not as strong as for other clades (e.g., Echinozoa, Eleutherozoa, and Echinodermata). I also present detailed sensitivity analyses to provide (i) a test of the monophyly of groups under a variety of evolutionary models and (ii) a statement of the evidential value of various character systems.Les analyses morphologiques, embryologiques, moléculaires et combinée n'ont pas encore permis d'établir une phylogénie solide des classes d'échinodermes. D'après le bilan de ces travaux, il est évident que (i) les échinoïdes (oursins de mer) et les holothuroïdes (concombres de mer) sont des groupes apparentés et (ii) que les crinoïdes (lys de mer) forment le taxon soeur des classes d'éleuthérozoaires actuels (astéroïdes, ophuroïdes, échinoïdes et holothuroïdes). Cependant, la relation entre les astéroïdes et les ophiuroïdes et les autres classes d'échinodermes est difficile à établir. Pour examiner cette relation, j'ai procédé au séquençage de nouveaux locus nucléaires et examiné d'autres taxons et j'ai utilisé de nouvelles approches informatiques pour cooptimiser les données morphologiques et moléculaires à l'alignement des séquences. Tous les indices appuient l'hypothèse du monophylétisme de chacune des classes. Le monophylétisme des Asteroidea + Xyloplax est aussi corroboré que celui des Asteroidea. L'appuie en faveur des Astero zoa (Asteroidea + Ophiuroidea) est également corroboré, mais pas aussi fortement que pour les autres clades (p. ex., Echinozoa, Eleutherozoa et Echinodermata). Je présente également ici des analyses détaillées de sensibilité : (i) un test du monophylétisme des groupes à la lumière de plusieurs modèles évolutifs et (ii) un jugement sur la valeur indicatrice de différents systèmes de caractères.[Traduit par la Rédaction] [ABSTRACT FROM AUTHOR]

Introduces a series of articles about the relationships among starfishes.

Examines the coelemic development of the starfish Pteraster tesselatus. Arisal from seven separate enterocoels; Water-vascular coelemic system; Mode of coelem formation; Rotation in the site of origin of the anterior enterocoels relative to the archenteron.

Motivation Epistasis reflects the distortion on a particular trait or phenotype resulting from the combinatorial effect of two or more genes or genetic variants. Epistasis is an important genetic foundation underlying quantitative traits in many organisms as well as in complex human diseases. However, there are two major barriers in identifying epistasis using large genomic datasets. One is that epistasis analysis will induce over-fitting of an over-saturated model with the high-dimensionality of a genomic dataset. Therefore, the problem of identifying epistasis demands efficient statistical methods. The second barrier comes from the intensive computing time for epistasis analysis, even when the appropriate model and data are specified. Results In this study, we combine statistical techniques and computational techniques to scale up epistasis analysis using Empirical Bayesian Elastic Net (EBEN) models. Specifically, we first apply a matrix manipulation strategy for pre-computing the correlation matrix and pre-filter to narrow down the search space for epistasis analysis. We then develop a parallelized approach to further accelerate the modeling process. Our experiments on synthetic and empirical genomic data demonstrate that our parallelized methods offer tens of fold speed up in comparison with the classical EBEN method which runs in a sequential manner. We applied our parallelized approach to a yeast dataset, and we were able to identify both main and epistatic effects of genetic variants associated with traits such as fitness. Availability and implementation The software is available at github.com/shilab/parEBEN. [ABSTRACT FROM AUTHOR]

Classification of the Class Echinoidea is under significant revision in light of emerging molecular phylogenetic evidence. In particular, the sister-group relationships within the superorder Luminacea (Echinoidea: Irregularia) have been considerably updated. However, the placement of many families remains largely unresolved due to a series of incongruent evidence obtained from morphological, paleontological, and genetic data for the majority of extant representatives. In this study, we investigated the phylogenetic relationships of 25 taxa, belonging to eleven luminacean families. We proposed three new superfamilies: Astriclypeoidea, Mellitoidea, and Taiwanasteroidea (including Dendrasteridae, Taiwanasteridae, Scutellidae, and Echinarachniidae), instead of the currently recognized superfamily Scutelloidea Gray, 1825. In light of the new data obtained from ten additional species, the historical biogeography reconstructed shows that the tropical western Pacific and eastern Indian Oceans are the cradle for early sand dollar diversification. Hothouse conditions during the late Cretaceous and early Paleogene were coupled with diversification events of major clades of sand dollars. We also demonstrate that Taiwan fauna can play a key role in terms of understanding the major Cenozoic migration and dispersal events in the evolutionary history of Luminacea. [ABSTRACT FROM AUTHOR]

This study employs landscape genetics to investigate the environmental drivers of a deadly vector‐borne disease, malaria caused by Plasmodium falciparum, in a more spatially comprehensive manner than any previous work. With 1804 samples from 44 sites collected in western Kenya in 2012 and 2013, we performed resistance surface analysis to show that Lake Victoria acts as a barrier to transmission between areas north and south of the Winam Gulf. In addition, Mantel correlograms clearly showed significant correlations between genetic and geographic distance over short distances (less than 70 km). In both cases, we used an identity‐by‐state measure of relatedness tailored to find highly related individual parasites in order to focus on recent gene flow that is more relevant to disease transmission. To supplement these results, we performed conventional population genetics analyses, including Bayesian clustering methods and spatial ordination techniques. These analyses revealed some differentiation on the basis of geography and elevation and a cluster of genetic similarity in the lowlands north of the Winam Gulf of Lake Victoria. Taken as a whole, these results indicate low overall genetic differentiation in the Lake Victoria region, but with some separation of parasite populations north and south of the Winam Gulf that is explained by the presence of the lake as a geographic barrier to gene flow. We recommend similar landscape genetics analyses in future molecular epidemiology studies of vector‐borne diseases to extend and contextualize the results of traditional population genetics. [ABSTRACT FROM AUTHOR]

Background: Here we release a new version of EchinoDB, EchinoDB v2.0 (). EchinoDB is a database of genomic and transcriptomic data on echinoderms. The initial database consisted of groups of 749,397 orthologous and paralogous transcripts arranged in orthoclusters by sequence similarity. Results: The updated version of EchinoDB includes two new major datasets: the RNA-Seq data of the brittle star Ophioderma brevispinum and the high-quality genomic assembly data of the green sea urchin Lytechinus variegatus. In addition, we enabled keyword searches for annotated data and installed an updated version of Sequenceserver to allow Basic Local Alignment Search Tool (BLAST) searches. The data are downloadable in FASTA format. The first version of EchinoDB appeared in 2016 and was implemented in GO on a local server. The new version has been updated using R Shiny to include new features and improvements in the application. Furthermore, EchinoDB now runs entirely in the cloud for increased reliability and scaling. Conclusion: EchinoDB serves a user base drawn from the fields of phylogenetics, developmental biology, genomics, physiology, neurobiology, and regeneration. As use cases, we illustrate the function of EchinoDB in retrieving components of signaling pathways involved in the tissue regeneration process of different echinoderms, including the emerging model species Ophioderma brevispinum. Moreover, we use EchinoDB to shed light on the conservation of the molecular components involved in two echinoderm-specific phenomena: spicule matrix proteins involved in the formation of stereom endoskeleton and the tensilin protein that contributes to the capacity of the connective tissues to quickly change its mechanical properties. The genes involved in the former had been previously studied in echinoids, while gene sequences involved in the latter had been previously described in holothuroids. Specifically, we ask (a) if the biomineralization-related proteins previously reported only in sea urchins are also present in other, non-echinoid, echinoderms and (b) if tensilin, the protein responsible for the control of stiffness of the mutable collagenous tissue, previously described in sea cucumbers, is conserved across the phylum. [ABSTRACT FROM AUTHOR]

Background: Here we release a new version of EchinoDB, EchinoDB v2.0 (https://echinodb.uncc.edu). EchinoDB is a database of genomic and transcriptomic data on echinoderms. The initial database consisted of groups of 749,397 orthologous and paralogous transcripts arranged in orthoclusters by sequence similarity. Results: The updated version of EchinoDB includes two new major datasets: the RNA-Seq data of the brittle star Ophioderma brevispinum and the high-quality genomic assembly data of the green sea urchin Lytechinus variegatus. In addition, we enabled keyword searches for annotated data and installed an updated version of Sequenceserver to allow Basic Local Alignment Search Tool (BLAST) searches. The data are downloadable in FASTA format. The first version of EchinoDB appeared in 2016 and was implemented in GO on a local server. The new version has been updated using R Shiny to include new features and improvements in the application. Furthermore, EchinoDB now runs entirely in the cloud for increased reliability and scaling. Conclusion: EchinoDB serves a user base drawn from the fields of phylogenetics, developmental biology, genomics, physiology, neurobiology, and regeneration. As use cases, we illustrate the function of EchinoDB in retrieving components of signaling pathways involved in the tissue regeneration process of different echinoderms, including the emerging model species Ophioderma brevispinum. Moreover, we use EchinoDB to shed light on the conservation of the molecular components involved in two echinoderm-specific phenomena: spicule matrix proteins involved in the formation of stereom endoskeleton and the tensilin protein that contributes to the capacity of the connective tissues to quickly change its mechanical properties. The genes involved in the former had been previously studied in echinoids, while gene sequences involved in the latter had been previously described in holothuroids. Specifically, we ask (a) if the biomineralization-related proteins previously reported only in sea urchins are also present in other, non-echinoid, echinoderms and (b) if tensilin, the protein responsible for the control of stiffness of the mutable collagenous tissue, previously described in sea cucumbers, is conserved across the phylum. [ABSTRACT FROM AUTHOR]

Background: Echinoderms are established models in experimental and developmental biology, however genomic resources are still lacking for many species. Here, we present the draft genome of Ophioderma brevispinum, an emerging model organism in the field of regenerative biology. This new genomic resource provides a reference for experimental studies of regenerative mechanisms. Results: We report a de novo nuclear genome assembly for the brittle star O. brevispinum and annotation facilitated by the transcriptome assembly. The final assembly is 2.68 Gb in length and contains 146,703 predicted protein-coding gene models. We also report a mitochondrial genome for this species, which is 15,831 bp in length, and contains 13 protein-coding, 22 tRNAs, and 2 rRNAs genes, respectively. In addition, 29 genes of the Notch signaling pathway are identified to illustrate the practical utility of the assembly for studies of regeneration. Conclusions: The sequenced and annotated genome of O. brevispinum presented here provides the first such resource for an ophiuroid model species. Considering the remarkable regenerative capacity of this species, this genome will be an essential resource in future research efforts on molecular mechanisms regulating regeneration. [ABSTRACT FROM AUTHOR]

Background: Echinoderms are a phylum of marine invertebrates with close phylogenetic relationships to chordates. Many members of the phylum Echinodermata are capable of extensive post-traumatic regeneration and life-long indeterminate growth. Different from regeneration, the life-long elongation of the main body axis in adult echinoderms has received little attention. The anatomical location and the nature of the dividing progenitor cells contributing to adults' growth is unknown. Results: We show that the proliferating cells that drive the life-long growth of adult brittle star arms are mostly localized to the subterminal (second from the tip) arm segment. Each of the major anatomical structures contains dividing progenitors. These structures include: the radial nerve, water-vascular canal, and arm coelomic wall. Some of those proliferating progenitor cells are capable of multiple rounds of cell division. Within the nervous system, the progenitor cells were identified as a subset of radial glial cells that do not express Brn1/2/4, a transcription factor with a conserved role in the neuronal fate specification. In addition to characterizing the growth zone and the nature of the precursor cells, we provide a description of the microanatomy of the four distal-most arm segments contrasting the distal with the proximal segments, which are more mature. Conclusions: The growth of the adult brittle star arms occurs via proliferation of progenitor cells in the distal segments, which are most abundant in the second segment from the tip. At least some of the progenitors are capable of multiple rounds of cell division. Within the nervous system the dividing cells were identified as Brn1/2/4-negative radial glial cells. [ABSTRACT FROM AUTHOR]

Mathematical models are critical tools to characterize COVID-19 dynamics and take action accordingly. We identified 4 major challenges associated with the current modeling paradigm (SEIR) that hinder the efforts to accurately characterize the emerging COVID-19 and future epidemics. These challenges included (1) lack of consistent definition of "case"; (2) discrepancy between patient-level clinical insights and population-level modeling efforts; (3) lack of adequate inclusion of individual behavioral and social influence; and (4) allowing little flexibility of including new evidence and insights when our knowledge evolved rapidly during the pandemic. Therefore, these challenges made the current SEIR modeling paradigm less practical to handle the complex COVID-19 and future pandemics. Novel and more reliable data sources and alternative modeling paradigms are needed to address these issues. [ABSTRACT FROM AUTHOR]

Background: The recent detection of the South Asian malaria vector Anopheles stephensi in the Horn of Africa (HOA) raises concerns about the impact of this mosquito on malaria transmission in the region. Analysis of An. stephensi genetic diversity and population structure can provide insight into the history of the mosquito in the HOA to improve predictions of future spread. We investigated the genetic diversity of An. stephensi in eastern Ethiopia, where detection suggests a range expansion into this region, in order to understand the history of this invasive population. Methods: We sequenced the cytochrome oxidase subunit I (COI) and cytochrome B gene (CytB) in 187 An. stephensi collected from 10 sites in Ethiopia in 2018. Population genetic, phylogenetic, and minimum spanning network analyses were conducted for Ethiopian sequences. Molecular identification of blood meal sources was also performed using universal vertebrate CytB sequencing. Results: Six An. stephensi COI-CytB haplotypes were observed, with the highest number of haplotypes in the northeastern sites (Semera, Bati, and Gewana towns) relative to the southeastern sites (Kebridehar, Godey, and Degehabur) in eastern Ethiopia. We observed population differentiation, with the highest differentiation between the northeastern sites compared to central sites (Erer Gota, Dire Dawa, and Awash Sebat Kilo) and the southeastern sites. Phylogenetic and network analysis revealed that the HOA An. stephensi are more genetically similar to An. stephensi from southern Asia than from the Arabian Peninsula. Finally, molecular blood meal analysis revealed evidence of feeding on cows, goats, dogs, and humans, as well as evidence of multiple (mixed) blood meals. Conclusion: We show that An. stephensi is genetically diverse in Ethiopia and with evidence of geographical structure. Variation in the level of diversity supports the hypothesis for a more recent introduction of An. stephensi into southeastern Ethiopia relative to the northeastern region. We also find evidence that supports the hypothesis that HOA An. stephensi populations originate from South Asia rather than the Arabian Peninsula. The evidence of both zoophagic and anthropophagic feeding support the need for additional investigation into the potential for livestock movement to play a role in vector spread in this region. [ABSTRACT FROM AUTHOR]

Plasmodium vivax malaria was thought to be rare in Africa, but an increasing number of P. vivax cases reported across Africa and in Duffy-negative individuals challenges this dogma. The genetic characteristics of P. vivax in Duffy-negative infections, the transmission of P. vivax in East Africa, and the impact of environments on transmission remain largely unknown. This study examined genetic and transmission features of P. vivax from 107 Duffy-negative and 305 Duffy-positive individuals in Ethiopia and Sudan. No clear genetic differentiation was found in P. vivax between the 2 Duffy groups, indicating between-host transmission. P. vivax from Ethiopia and Sudan showed similar genetic clusters, except samples from Khartoum, possibly due to distance and road density that inhibited parasite gene flow. This study is the first to show that P. vivax can transmit to and from Duffy-negative individuals and provides critical insights into the spread of P. vivax in sub-Saharan Africa. [ABSTRACT FROM AUTHOR]

Background: Rapid diagnostic tests (RDT) are commonly used for the diagnosis of malaria caused by Plasmodium falciparum. However, false negative results of RDT caused by genetic variation of P. falciparum histidine-rich protein 2 and 3 genes (pfhrp2/3) threaten existing malaria case management and control efforts. The main objective of this study was to investigate the genetic variations of the pfhrp2/3 genes. Methods: A cross-sectional study was conducted from malaria symptomatic individuals in 2018 in Assosa zone, Ethiopia. Finger-prick blood samples were collected for RDT and microscopic examination of thick and thin blood films. Dried blood spots (DBS) were used for genomic parasite DNA extraction and molecular detection. Amplification of parasite DNA was made by quantitative PCR. DNA amplicons of pfhrp2/3 were purified and sequenced. Results: The PfHRP2 amino acid repeat type isolates were less conserved compared to the PfHRP3 repeat type. Eleven and eight previously characterized PfHRP2 and PfHRP3 amino acid repeat types were identified, respectively. Type 1, 4 and 7 repeats were shared by PfHRP2 and PfHRP3 proteins. Type 2 repeats were found only in PfHRP2, while types 16 and 17 were found only in PfHRP3 with a high frequency in all isolates. 18 novel repeat types were found in PfHRP2 and 13 novel repeat types were found in PfHRP3 in single or multiple copies per isolate. The positivity rate for PfHRP2 RDT was high, 82.9% in PfHRP2 and 84.3% in PfHRP3 sequence isolates at parasitaemia levels > 250 parasites/µl. Using the Baker model, 100% of the isolates in group A (If product of types 2 × type 7 repeats ≥ 100) and 73.7% of the isolates in group B (If product of types 2 × type 7 repeats 50–99) were predicted to be detected by PfHRP2 RDT at parasitaemia level > 250 parasite/μl. Conclusion: The findings of this study indicate the presence of different PfHRP2 and PfHRP3 amino acid repeat including novel repeats in P. falciparum from Ethiopia. These results indicate that there is a need to closely monitor the performance of PfHRP2 RDT associated with the genetic variation of the pfhrp2 and pfhrp3 gene in P. falciparum isolates at the country-wide level. [ABSTRACT FROM AUTHOR]

The severe acute respiratory syndrome coronavirus (SARS‐CoV) emerged in humans in 2002. Despite reports showing Chiroptera as the original animal reservoir of SARS‐CoV, many argue that Carnivora‐hosted viruses are the most likely origin. The emergence of the Middle East respiratory syndrome coronavirus (MERS‐CoV) in 2012 also involves Chiroptera‐hosted lineages. However, factors such as the lack of comprehensive phylogenies hamper our understanding of host shifts once MERS‐CoV emerged in humans and Artiodactyla. Since 2019, the origin of SARS‐CoV‐2, causative agent of coronavirus disease 2019 (COVID‐19), added to this episodic history of zoonotic transmission events. Here we introduce a phylogenetic analysis of 2006 unique and complete genomes of different lineages of Orthocoronavirinae. We used gene annotations to align orthologous sequences for total evidence analysis under the parsimony optimality criterion. Deltacoronavirus and Gammacoronavirus were set as outgroups to understand spillovers of Alphacoronavirus and Betacoronavirus among ten orders of animals. We corroborated that Chiroptera‐hosted viruses are the sister group of SARS‐CoV, SARS‐CoV‐2 and MERS‐related viruses. Other zoonotic events were qualified and quantified to provide a comprehensive picture of the risk of coronavirus emergence among humans. Finally, we used a 250 SARS‐CoV‐2 genomes dataset to elucidate the phylogenetic relationship between SARS‐CoV‐2 and Chiroptera‐hosted coronaviruses. [ABSTRACT FROM AUTHOR]

Background: Rapid diagnostic tests (RDTs) targeting histidine rich protein 2(HRP2) are widely used for diagnosis of Plasmodium falciparum infections. Besides PfHRP2, the PfHRP3 antigen contributes to the detection of P. falciparum infections in PfHRP2 RDTs. However, the performance HRP2-based RDT is affected by pfhrp2/3 gene deletions resulting in false-negative test results. The objective of this study was to determine the presence and prevalence of pfhrp2/3 gene deletions including the respective flanking regions among symptomatic patients in Assosa zone, Northwest Ethiopia. Methods: A health-facility based cross-sectional study was conducted in febrile patients seeking a malaria diagnosis in 2018. Blood samples were collected by finger-prick for microscopic examination of blood smears, malaria RDT, and molecular analysis using dried blood spots (DBS) prepared on Whatman filter paper. A total of 218 P. falciparum positive samples confirmed by quantitative PCR were included for molecular assay of pfhrp2/3 target gene. Results: Of 218 P. falciparum positive samples, exon 2 deletions were observed in 17.9% of pfhrp2 gene and in 9.2% of pfhrp3 gene. A high proportion of deletions in short segments of pfhrp2 exon1-2 (50%) was also detected while the deletions of the pfhrp3 exon1-2 gene were 4.1%. The deletions were extended to the downstream and upstream of the flanking regions in pfhrp2/3 gene (above 30%). Of eighty-six PfHRP2 RDT negative samples, thirty-six lacked pfhrp2 exon 2. Five PfHRP2 RDT negative samples had double deletions in pfhrp2 exon 2 and pfhrp3 exon2. Of these double deletions, only two of the samples with a parasite density above 2000 parasite/µl were positive by the microscopy. Three samples with intact pfhrp3 exon2 in the pfhrp2 exon2 deleted parasite isolates were found to be positive by PfHRP2 RDT and microscopy with a parasite density above 10,000/µl. Conclusion: This study confirms the presence of deletions of pfhrp2/3 gene including the flanking regions. Pfhrp2/3 gene deletions results in false-negative results undoubtedly affect the current malaria control and elimination effort in the country. However, further countrywide investigations are required to determine the magnitude of pfhrp2/3 gene deletions and its consequences on routine malaria diagnosis. [ABSTRACT FROM AUTHOR]

Background: Rapid diagnostic tests (RDTs) targeting histidine rich protein 2(HRP2) are widely used for diagnosis of Plasmodium falciparum infections. Besides PfHRP2, the PfHRP3 antigen contributes to the detection of P. falciparum infections in PfHRP2 RDTs. However, the performance HRP2-based RDT is affected by pfhrp2/3 gene deletions resulting in false-negative test results. The objective of this study was to determine the presence and prevalence of pfhrp2/3 gene deletions including the respective flanking regions among symptomatic patients in Assosa zone, Northwest Ethiopia. Methods: A health-facility based cross-sectional study was conducted in febrile patients seeking a malaria diagnosis in 2018. Blood samples were collected by finger-prick for microscopic examination of blood smears, malaria RDT, and molecular analysis using dried blood spots (DBS) prepared on Whatman filter paper. A total of 218 P. falciparum positive samples confirmed by quantitative PCR were included for molecular assay of pfhrp2/3 target gene. Results: Of 218 P. falciparum positive samples, exon 2 deletions were observed in 17.9% of pfhrp2 gene and in 9.2% of pfhrp3 gene. A high proportion of deletions in short segments of pfhrp2 exon1-2 (50%) was also detected while the deletions of the pfhrp3 exon1-2 gene were 4.1%. The deletions were extended to the downstream and upstream of the flanking regions in pfhrp2/3 gene (above 30%). Of eighty-six PfHRP2 RDT negative samples, thirty-six lacked pfhrp2 exon 2. Five PfHRP2 RDT negative samples had double deletions in pfhrp2 exon 2 and pfhrp3 exon2. Of these double deletions, only two of the samples with a parasite density above 2000 parasite/µl were positive by the microscopy. Three samples with intact pfhrp3 exon2 in the pfhrp2 exon2 deleted parasite isolates were found to be positive by PfHRP2 RDT and microscopy with a parasite density above 10,000/µl. Conclusion: This study confirms the presence of deletions of pfhrp2/3 gene including the flanking regions. Pfhrp2/3 gene deletions results in false-negative results undoubtedly affect the current malaria control and elimination effort in the country. However, further countrywide investigations are required to determine the magnitude of pfhrp2/3 gene deletions and its consequences on routine malaria diagnosis. [ABSTRACT FROM AUTHOR]

Mathematical models are powerful tools to investigate, simulate, and evaluate potential interventions for infectious diseases dynamics. Much effort has focused on the Susceptible-Infected-Recovered (SIR)-type compartment models. These models consider host populations and measure change of each compartment. In this study, we propose an alternative patch dynamic modeling framework from pathogens' perspective. Each patch, the basic module of this modeling framework, has four standard mechanisms of pathogen population size change: birth (replication), death, inflow, and outflow. This framework naturally distinguishes between-host transmission process (inflow and outflow) and within-host infection process (replication) during the entire transmission-infection cycle. We demonstrate that the SIR-type model is actually a special cross-sectional and discretized case of our patch dynamics model in pathogens' viewpoint. In addition, this patch dynamics modeling framework is also an agent-based model from hosts' perspective by incorporating individual host's specific traits. We provide an operational standard to formulate this modular-designed patch dynamics model. Model parameterization is feasible with a wide range of sources, including genomics data, surveillance data, electronic health record, and from other emerging technologies such as multiomics. We then provide two proof-of-concept case studies to tackle some of the existing challenges of SIR-type models: sexually transmitted disease and healthcare acquired infections. This patch dynamics modeling framework not only provides theoretical explanations to known phenomena, but also generates novel insights of disease dynamics from a more holistic viewpoint. It is also able to simulate and handle more complicated scenarios across biological scales such as the current COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

Plasmodium vivax malaria is much less common in Africa than the rest of the world because the parasite relies primarily on the Duffy antigen/chemokine receptor (DARC) to invade human erythrocytes, and the majority of Africans are Duffy negative. Recently, there has been a dramatic increase in the reporting of P. vivax cases in Africa, with a high number of them being in Duffy negative individuals, potentially indicating P. vivax has evolved an alternative invasion mechanism that can overcome Duffy negativity. Here, we analyzed single nucleotide polymorphism (SNP) and copy number variation (CNV) in Whole Genome Sequence (WGS) data from 44 P. vivax samples isolated from symptomatic malaria patients in southwestern Ethiopia, where both Duffy positive and Duffy negative individuals are found. A total of 123,711 SNPs were detected, of which 22.7% were nonsynonymous and 77.3% were synonymous mutations. The largest number of SNPs were detected on chromosomes 9 (24,007 SNPs; 19.4% of total) and 10 (16,852 SNPs, 13.6% of total). There were particularly high levels of polymorphism in erythrocyte binding gene candidates including merozoite surface protein 1 (MSP1) and merozoite surface protein 3 (MSP3.5, MSP3.85 and MSP3.9). Two genes, MAEBL and MSP3.8 related to immunogenicity and erythrocyte binding function were detected with significant signals of positive selection. Variation in gene copy number was also concentrated in genes involved in host-parasite interactions, including the expansion of the Duffy binding protein gene (PvDBP) on chromosome 6 and MSP3.11 on chromosome 10. Based on the phylogeny constructed from the whole genome sequences, the expansion of these genes was an independent process among the P. vivax lineages in Ethiopia. We further inferred transmission patterns of P. vivax infections among study sites and showed various levels of gene flow at a small geographical scale. The genomic features of P. vivax provided baseline data for future comparison with those in Duffy-negative individuals and allowed us to develop a panel of informative Single Nucleotide Polymorphic markers diagnostic at a micro-geographical scale. Author summary: Plasmodium vivax is the most geographically widespread parasite species that causes malaria in humans. Although it occurs in Africa as a member of a mix of Plasmodium species, P. vivax is dominant in other parts of the world outside of Africa (e.g., Brazil). It was previously thought that most African populations were immune to P. vivax infections due to the absence of Duffy antigen chemokine receptor (DARC) gene expression required for erythrocyte invasion. However, several recent reports have indicated the emergence and potential spread of P. vivax across human populations in Africa. Compared to Southeast Asia and South America where P. vivax is highly endemic, data on polymorphisms in erythrocyte binding gene candidates of P. vivax from Africa is limited. Filling this knowlege gap is critical for identifying functional genes in erythrocyte invasion, biomarkers for tracking the P. vivax isolates from Africa, as well as potential gene targets for vaccine development. This paper examined the level of genetic polymorphisms in a panel of 43 potential erythrocyte binding protein genes based on whole genome sequences and described transmission patterns of P. vivax infections from different study sites in Ethiopia based on the genetic variants. Our analyses showed that chromosomes 9 and 10 of the P. vivax genomes isolated in Ethiopia had the most high-quality genetic polymorphisms. Among all erythrocyte binding protein gene candidates, the merozoite surface proteins 1 and merozoite surface protein 3 showed high levels of polymorphism. MAEBL and MSP3.8 related to immunogenicity and erythrocyte binding function were detected with significant signals of positive selection. The expansion of the Duffy binding protein and merozoite surface protein 3 gene copies was an independent process among the P. vivax lineages in Ethiopia. Various levels of gene flow were observed even at a smaller geographical scale. Our study provided baseline data for future comparison with P. vivax in Duffy negative individuals and help develop a panel of genetic markers that are informative at a micro-geographical scale. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance (AMR) in pathogenic strains of bacteria, such as Escherichia coli (E. coli), adversely impacts personal and public health. In this study, we examine competing hypotheses for the evolution of AMR including (i) 'genetic capitalism' in which genotypes that confer antibiotic resistance are gained and not often lost in lineages, and (ii) 'stabilizing selection' in which genotypes that confer antibiotic resistance are gained and lost often. To test these hypotheses, we assembled a dataset that includes annotations for 409 AMR genotypes and a phylogenetic tree based on genome‐wide single nucleotide polymorphisms from 29 255 isolates of E. coli collected over the past 134 years. We used phylogenetic methods to count the times each AMR genotype was gained and lost across the tree and used model‐based clustering of the genotypes with respect to their gain and loss rates. We demonstrate that many genotypes cluster to support the hypothesis for genetic capitalism while a few genotypes cluster to support the hypothesis for stabilizing selection. Comparing the sets of genotypes that fall under each of the hypotheses, we found a statistically significant difference in the breakdown of resistance mechanisms through which the AMR genotypes function. The result that many AMR genotypes cluster under genetic capitalism reflects that strong positive selective forces, primarily induced by human industrialization of antibiotics, outweigh the potential fitness costs to the bacterial lineages for carrying the AMR genotypes. We expect genetic capitalism to further drive bacterial lineages to resist antibiotics. We find that antibiotics that function via replacement and efflux tend to behave under stabilizing selection and thus may be valuable in an antibiotic cycling strategy. [ABSTRACT FROM AUTHOR]

Cell signaling pathways play key roles in coordinating cellular events in development. The Notch signaling pathway is highly conserved across all multicellular animals and is known to coordinate a multitude of diverse cellular events, including proliferation, differentiation, fate specification, and cell death. Specific functions of the pathway are, however, highly context-dependent and are not well characterized in post-traumatic regeneration. Here, we use a small-molecule inhibitor of the pathway (DAPT) to demonstrate that Notch signaling is required for proper arm regeneration in the brittle star Ophioderma brevispina, a highly regenerative member of the phylum Echinodermata. We also employ a transcriptome-wide gene expression analysis (RNA-seq) to characterize the downstream genes controlled by the Notch pathway in the brittle star regeneration. We demonstrate that arm regeneration involves an extensive cross-talk between the Notch pathway and other cell signaling pathways. In the regrowing arm, Notch regulates the composition of the extracellular matrix, cell migration, proliferation, and apoptosis, as well as components of the innate immune response. We also show for the first time that Notch signaling regulates the activity of several transposable elements. Our data also suggests that one of the possible mechanisms through which Notch sustains its activity in the regenerating tissues is via suppression of Neuralized1. [ABSTRACT FROM AUTHOR]

Background: The movement of malaria vectors into new areas is a growing concern in the efforts to control malaria. The recent report of Anopheles stephensi in eastern Ethiopia has raised the necessity to understand the insecticide resistance status of the vector in the region to better inform vector-based interventions. The aim of this study was to evaluate insecticide resistance in An. stephensi in eastern Ethiopia using two approaches: (1) World Health Organization (WHO) bioassay tests in An. stephensi; and (2) genetic analysis of insecticide resistance genes in An. stephensi in eastern Ethiopia. Methods: Mosquito larvae and pupae were collected from Kebri Dehar. Insecticide susceptibility of An. stephensi was tested with malathion 5%, bendiocarb 0.1%, propoxur 0.1%, deltamethrin 0.05%, permethrin 0.75%, pirimiphos-methyl 0.25% and DDT 4%, according to WHO standard protocols. In this study, the knockdown resistance locus (kdr) in the voltage gated sodium channel (vgsc) and ace1R locus in the acetylcholinesterase gene (ace-1) were analysed in An. stephensi. Results: All An. stephensi samples were resistant to carbamates, with mortality rates of 23% and 21% for bendiocarb and propoxur, respectively. Adult An. stephensi was also resistant to pyrethroid insecticides with mortality rates 67% for deltamethrin and 53% for permethrin. Resistance to DDT and malathion was detected in An. stephensi with mortality rates of 32% as well as An. stephensi was resistance to pirimiphos-methyl with mortality rates 14%. Analysis of the insecticide resistance loci revealed the absence of kdr L1014F and L1014S mutations and the ace1R G119S mutation. Conclusion: Overall, these findings support that An. stephensi is resistant to several classes of insecticides, most notably pyrethroids. However, the absence of the kdr L1014 gene may suggest non-target site resistance mechanisms. Continuous insecticide resistance monitoring should be carried out in the region to confirm the documented resistance and exploring mechanisms conferring resistance in An. stephensi in Ethiopia. [ABSTRACT FROM AUTHOR]

Recent disease outbreaks have raised awareness of tropical pathogens, especially mosquito‐borne viruses. Dengue virus (DENV) is a widely studied mammalian pathogen transmitted by various species of mosquito in the genus Aedes, especially Aedes aegypti and Aedes albopictus. The prevailing view of the research community is that endemic viral lineages that cause epidemics of DENV in humans have emerged over time from sylvatic viral lineages, which persist in wild, non‐human primates. These notions have been examined by researchers through phylogenetic analyses of the envelope gene (E) from the four serotypes of DENV (serotypes DENV‐1 to DENV‐4). In these previous reports, researchers used visual inspection of a phylogeny in order to assert that sylvatic lineages lead to endemic clades. In making this assertion, these researchers also reasserted the model of periodic sylvatic to endemic disease outbreaks. Since that study, there has been a significant increase in data both in terms of metadata (e.g., place and host of isolation) and genetic sequences of DENV. Here, we re‐examine the model of sylvatic to endemic shifts in viral lineages through a phylogenetic tree search and character evolution study of metadata on the tree. We built a dataset of nucleotide sequences for 188 isolates of DENV that have metadata on sylvatic or endemic sampling along with three orthologous sequences from West Nile virus as the outgroup for the phylogenetic analysis. In contrast to previous research, we find that there are several shifts from endemic to sylvatic lineages as well as sylvatic to endemic lineages, indicating a much more dynamic model of evolution. We propose that a model that allows oscillation between sylvatic and endemic hosts better captures the dynamics of DENV transmission. [ABSTRACT FROM AUTHOR]

Morphologic and molecular data often lead to different hypotheses of phylogenetic relationships. Such incongruence has been found in the echinoderm class Echinoidea. In particular, the phylogenetic status of the order Clypeasteroida is not well resolved. Complete mitochondrial genomes are currently available for 29 echinoid species, but no clypeasteroid had been sequenced to date. DNA extracted from a single live individual of Sinaechinocyamus mai was sequenced with 10× Genomics technology. This first complete mitochondrial genome (mitogenome) for the order Clypeasteroida is 15,756 base pairs in length. Phylogenomic analysis based on 34 ingroup taxa belonging to nine orders of the class Echinoidea show congruence between our new genetic inference and published trees based on morphologic characters, but also includes some intriguing differences that imply the need for additional investigation. • The first mitochondrial genome (15,756 bp) of the enigmatic sand dollar Sinaechinocyamus mai. • Phylogenomic analyses of the class Echinoidea based on complete mitogenomes. • Filtering protocol for extracting valid echinoid data from contaminated 10× Genomics raw data prior to genome assembly. [ABSTRACT FROM AUTHOR]

Background: The recent detection of the South Asian malaria vector Anopheles stephensi in Ethiopia and other regions in the Horn of Africa has raised concerns about its potential impact on malaria transmission. We report here the findings of a survey for this species in eastern Ethiopia using both morphological and molecular methods for species identification. Methods: Adult and larval/pupal collections were conducted at ten sites in eastern Ethiopia and Anopheles specimens were identified using standard morphological keys and genetic analysis. Results: In total, 2231 morphologically identified An. stephensi were collected. A molecular approach incorporating both PCR endpoint assay and sequencing of portions of the internal transcribed spacer 2 (ITS2) and cytochrome c oxidase subunit 1 (cox1) loci confirmed the identity of the An. stephensi in most cases (119/124 of the morphologically identified An. stephensi confirmed molecularly). Additionally, we observed Aedes aegypti larvae and pupae at many of the An. stephensi larval habitats. Conclusions: Our findings show that An. stephensi is widely distributed in eastern Ethiopia and highlight the need for further surveillance in the southern, western and northern parts of the country and throughout the Horn of Africa. [ABSTRACT FROM AUTHOR]

Plasmodium vivax invasion of human erythrocytes depends on the Duffy Binding Protein (PvDBP) which interacts with the Duffy antigen. PvDBP copy number has been recently shown to vary between P. vivax isolates in Sub-Saharan Africa. However, the extent of PvDBP copy number variation, the type of PvDBP multiplications, as well as its significance across broad samples are still unclear. We determined the prevalence and type of PvDBP duplications, as well as PvDBP copy number variation among 178 Ethiopian P. vivax isolates using a PCR-based diagnostic method, a novel quantitative real-time PCR assay and whole genome sequencing. For the 145 symptomatic samples, PvDBP duplications were detected in 95 isolates, of which 81 had the Cambodian and 14 Malagasy-type PvDBP duplications. PvDBP varied from 1 to >4 copies. Isolates with multiple PvDBP copies were found to be higher in symptomatic than asymptomatic infections. For the 33 asymptomatic samples, PvDBP was detected with two copies in two of the isolates, and both were the Cambodian-type PvDBP duplication. PvDBP copy number in Duffy-negative heterozygotes was not significantly different from that in Duffy-positives, providing no support for the hypothesis that increased copy number is a specific association with Duffy-negativity, although the number of Duffy-negatives was small and further sampling is required to test this association thoroughly. [ABSTRACT FROM AUTHOR]

Abstract Malaria is a major public health concern in Ethiopia. With the increase in malaria cases in the Somali Region of Ethiopia, understanding the distribution and identifying the species of malaria vectors is vital to public health. Here we report the first detection of Anopheles stephensi in Ethiopia, a malaria vector typically found in the Middle East, the Indian subcontinent, and China, but recently found in Djibouti. An entomological investigation was conducted during November to December 2016 in Kebri Dehar town of the Ethiopian Somali Regional State as ancillary work for Anopheles spp. surveillance. Mosquito larvae were collected from water reservoirs. Larvae were reared in the laboratory to the adult stage and identified morphologically. PCR and sequencing of cytochrome oxidase 1 (COI) and internal transcribed spacer 2 (ITS2) loci were performed. Basic Local Alignment Search Tool (BLAST) was used to compare sample sequences to sequences in the NCBI nucleotide database for species identification. To further analyze the relationship between the specimen we collected in Kebri Dehar and other Anopheles samples available in Genbank, phylogenetic analysis was performed using a maximum likelihood approach. Molecular and morphological results confirm specimens were An. stephensi. The closest high scoring hit was for all specimens was for the An. stephensi sequence. Independent phylogenetic analyses of COI and ITS2 sequences revealed in both cases strong bootstrap (100) support for our sequence forming a clade with other An. stephensi sequences to the exclusion of any other species of Anopheles. In conclusion, Anopheles stephensi is present in Kebri Dehar town in Ethiopia. These findings highlight the need for additional research to examine the role of An. stephensi in malaria transmission in Ethiopia. [ABSTRACT FROM AUTHOR]

Background: While overall rates of meningococcal disease have been declining in the United States for the past several decades, New York City (NYC) has experienced two serogroup C meningococcal disease outbreaks in 2005–2006 and in 2010–2013. The outbreaks were centered within drug use and sexual networks, were difficult to control, and required vaccine campaigns. Methods: Whole Genome Sequencing (WGS) was used to analyze preserved meningococcal isolates collected before and during the two outbreaks. We integrated and analyzed epidemiologic, geographic, and genomic data to better understand transmission networks among patients. Betweenness centrality was used as a metric to understand the most important geographic nodes in the transmission networks. Comparative genomics was used to identify genes associated with the outbreaks. Results: Neisseria meningitidis serogroup C (ST11/ET-37) was responsible for both outbreaks with each outbreak having distinct phylogenetic clusters. WGS did identify some misclassifications of isolates that were more distant from the outbreak strains, as well as those that should have been included based on high genomic similarity. Genomes for the second outbreak were more similar than the first and no polymorphism was found to either be unique or specific to either outbreak lineage. Betweenness centrality as applied to transmission networks based on phylogenetic analysis demonstrated that the outbreaks were transmitted within focal communities in NYC with few transmission events to other locations. Conclusions: Neisseria meningitidis is an ever changing pathogen and comparative genomic analyses can help elucidate how it spreads geographically to facilitate targeted interventions to interrupt transmission. [ABSTRACT FROM AUTHOR]

In October 2021, the world's first malaria vaccine RTS,S was endorsed by WHO for broad use in children, despite its low efficacy. This study examined polyclonal infections and the associations of parasite genetic variations with binding affinity to human leukocyte antigen (HLA). Multiplicity of infection was determined by amplicon deep sequencing of PfMSP1. Genetic variations in PfCSP were examined across 88 samples from Ghana and analyzed together with 1655 PfCSP sequences from other African and non-African isolates. Binding interactions of PfCSP peptide variants and HLA were predicted using NetChop and HADDOCK. High polyclonality was detected among infections, with each infection harboring multiple non-3D7 PfCSP variants. Twenty-seven PfCSP haplotypes were detected in the Ghanaian samples, and they broadly represented PfCSP diversity across Africa. The number of genetic differences between 3D7 and non-3D7 PfCSP variants does not influence binding to HLA. However, CSP peptide length after proteolytic degradation significantly affects its molecular weight and binding affinity to HLA. Despite the high diversity of HLA, the majority of the HLAI and II alleles interacted/bound with all Ghana CSP peptides. Multiple non-3D7 strains among P. falciparum infections could impact the effectiveness of RTS,S. Longer peptides of the Th2R/Th3R CSP regions should be considered in future versions of RTS,S. • The world's first malaria vaccine RTS,S has low efficacy against P. falciparum. • Infections were highly polyclonal each with multiple non-3D7 PfCSP variants. • Genetic differences between 3D7 and non-3D7 PfCSP do not affect binding to HLA. • CSP peptide length significantly affects its binding affinity to the HLA. [ABSTRACT FROM AUTHOR]

Summary In exploring the epidemiology of infectious diseases, networks have been used to reconstruct contacts among individuals and/or populations. Summarizing networks using pathogen metadata (e.g. host species and place of isolation) and a phylogenetic tree is a nascent, alternative approach. In this paper, we introduce a tool for reconstructing transmission networks in arbitrary space from phylogenetic information and metadata. Our goals are to provide a means of deriving new insights and infection control strategies based on the dynamics of the pathogen lineages derived from networks and centrality metrics. We created a web-based application, called StrainHub, in which a user can input a phylogenetic tree based on genetic or other data along with characters derived from metadata using their preferred tree search method. StrainHub generates a transmission network based on character state changes in metadata, such as place or source of isolation, mapped on the phylogenetic tree. The user has the option to calculate centrality metrics on the nodes including betweenness, closeness, degree and a new metric, the source/hub ratio. The outputs include the network with values for metrics on its nodes and the tree with characters reconstructed. All of these results can be exported for further analysis. Availability and implementation strainhub.io and https://github.com/abschneider/StrainHub. [ABSTRACT FROM AUTHOR]

Aim We sought to illuminate the history of the arachnid orders Schizomida and Uropygi, neither of which have previously been subjected to global molecular phylogenetic and biogeographical analyses. Location Specimens used in this study were collected in all major tropical and subtropical areas where they are presently found, including the Americas, Africa, Australia and the Indo-Pacific region. Methods From field-collected specimens, we sequenced two nuclear and two mitochondrial markers, combined these with publicly available data, and conducted multi-gene phylogenetic analyses on 240 Schizomida, 24 Uropygi and 12 other arachnid outgroups. Schizomid specimens included one specimen from the small family Protoschizomidae; other schizomid specimens were in Hubbardiidae, subfamily Hubbardiinae, which holds 289 of the order's 305 named species. We inferred ancestral areas using the Dispersal-Extinction-Cladogenesis model of range evolution, and we used fossil calibrations to estimate divergence times. Results We recovered monophyletic Schizomida and Uropygi as each other's sister group, forming the clade Thelyphonida, and terminals from the New World were usually positioned as the earliest diverging lineages. The ancestral area for schizomids reconstructed unambiguously to the region comprised of Mexico, Southern California and Florida (the xeric New World subtropics). Optimal trees suggested a single colonization of the Indo-Pacific in both orders, although this did not receive bootstrap support. Molecular dating gave an Upper Carboniferous origin for each order, and a mid-Cretaceous expansion of Schizomida, including the origin and initial diversification of those in the Indo-Pacific. Main conclusions Ancestral area reconstructions, molecular dating and fossil evidence all support an Upper Carboniferous, tropical Pangean origin for Thelyphonida, Schizomida and perhaps Uropygi. Much of this region became unsuitable habitat for these arachnids during the breakup of Pangea, but they persisted in the area that is now Meso- and South America. From there they then expanded to the Indo-Pacific, where schizomids today display an idiosyncratic combination of microendemism and long-range dispersal. [ABSTRACT FROM AUTHOR]

Multi-locus phylogenetic studies of echinoderms based on Sanger and RNA-seq technologies and the fossil record have provided evidence for the Asterozoa-Echinozoa hypothesis. This hypothesis posits a sister relationship between asterozoan classes (Asteroidea and Ophiuroidea) and a similar relationship between echinozoan classes (Echinoidea and Holothuroidea). Despite this consensus around Asterozoa-Echinozoa, phylogenetic relationships within the class Asteroidea (sea stars or starfish) have been controversial for over a century. Open questions include relationships within asteroids and the status of the enigmatic taxon Xyloplax . Xyloplax is thought by some to represent a newly discovered sixth class of echinoderms – and by others to be an asteroid. To address these questions, we applied a novel workflow to a large RNA-seq dataset that encompassed a broad taxonomic and genomic sample. This study included 15 species sampled from all extant orders and 13 families, plus four ophiuroid species as an outgroup. To expand the taxonomic coverage, the study also incorporated five previously published transcriptomes and one previously published expressed sequence tags (EST) dataset. We developed and applied methods that used a range of alignment parameters with increasing permissiveness in terms of gap characters present within an alignment. This procedure facilitated the selection of phylogenomic data subsets from large amounts of transcriptome data. The results included 19 nested data subsets that ranged from 37 to 4,281 loci. Tree searches on all data subsets reconstructed Xyloplax as a velatid asteroid rather than a new class. This result implies that asteroid morphology remains labile well beyond the establishment of the body plan of the group. In the phylogenetic tree with the highest average asteroid nodal support several monophyletic groups were recovered. In this tree, Forcipulatida and Velatida are monophyletic and form a clade that includes Brisingida as sister to Forcipulatida. Xyloplax is consistently recovered as sister to Pteraster . Paxillosida and Spinulosida are each monophyletic, with Notomyotida as sister to the Paxillosida. Valvatida is recovered as paraphyletic. The results from other data subsets are largely consistent with these results. Our results support the hypothesis that the earliest divergence event among extant asteroids separated Velatida and Forcipulatacea from Valvatacea and Spinulosida. [ABSTRACT FROM AUTHOR]

Zika virus was previously considered to cause only a benign infection in humans. Studies of recent outbreaks of Zika virus in the Pacific, South America, Mexico and the Caribbean have associated the virus with severe neuropathology. Viral evolution may be one factor contributing to an apparent change in Zika disease as it spread from Southeast Asia across the Pacific to the Americas. To address this possibility, we have employed computational tools to compare the phylogeny, geography, immunology and RNA structure of Zika virus isolates from Africa, Asia, the Pacific and the Americas. In doing so, we compare and contrast methods and results for tree search and rooting of Zika virus phylogenies. In some phylogenetic analyses we find support for the hypothesis that there is a deep common ancestor between African and Asian clades (the 'Asia/Africa' hypothesis). In other phylogenetic analyses, we find that Asian lineages are descendent from African lineages (the 'out of Africa' hypothesis). In addition, we identify and evaluate key mutations in viral envelope protein coding and untranslated terminal RNA regions. We find stepwise mutations that have altered both immunological motif sets and regulatory sequence elements. Both of these sets of changes distinguish viruses found in Africa from those in the emergent Asia-Pacific-Americas lineage. These findings support the working hypothesis that mutations acquired by Zika virus in the Pacific and Americas contribute to changes in pathology. These results can inform experiments required to elucidate the role of viral genetic evolution in changes in neuropathology, including microcephaly and other neurological and skeletomuscular issues in infants, and Guillain-Barré syndrome in adults. [ABSTRACT FROM AUTHOR]

Background Some metazoa have the capacity to regenerate lost body parts. This phenomenon in adults has been classically described in echinoderms, especially in sea stars (Asteroidea). Sea star bipinnaria larvae can also rapidly and effectively regenerate a complete larva after surgical bisection. Understanding the capacity to reverse cell fates in the larva is important from both a developmental and biomedical perspective; yet, the mechanisms underlying regeneration in echinoderms are poorly understood. Results Here, we describe the process of bipinnaria regeneration after bisection in the bat star Patiria miniata . We tested transcriptional, translational, and cell proliferation activity after bisection in anterior and posterior bipinnaria halves as well as expression of SRAP, reported as a sea star regeneration associated protease (Vickery et al., 2001b). Moreover, we found several genes whose transcripts increased in abundance following bisection, including: Vasa, dysferlin, vitellogenin 1 and vitellogenin 2. Conclusion These results show a transformation following bisection, especially in the anterior halves, of cell fate reassignment in all three germ layers, with clear and predictable changes. These results define molecular events that accompany the cell fate changes coincident to the regenerative response in echinoderm larvae. [ABSTRACT FROM AUTHOR]

Introduction: Reports of high rates of primary microcephaly and Guillain–Barré syndrome associated with Zika virus infection in French Polynesia and Brazil have raised concerns that the virus circulating in these regions is a rapidly developing neuropathic, teratogenic, emerging infectious public health threat. There are no licensed medical countermeasures (vaccines, therapies or preventive drugs) available for Zika virus infection and disease. The Pan American Health Organization (PAHO) predicts that Zika virus will continue to spread and eventually reach all countries and territories in the Americas with endemic Aedes mosquitoes. This paper reviews the status of the Zika virus outbreak, including medical countermeasure options, with a focus on how the epidemiology, insect vectors, neuropathology, virology and immunology inform options and strategies available for medical countermeasure development and deployment. Methods: Multiple information sources were employed to support the review. These included publically available literature, patents, official communications, English and Lusophone lay press. Online surveys were distributed to physicians in the US, Mexico and Argentina and responses analyzed. Computational epitope analysis as well as infectious disease outbreak modeling and forecasting were implemented. Field observations in Brazil were compiled and interviews conducted with public health officials. [ABSTRACT FROM AUTHOR]

Background: Using a novel combination of whole-genome sequencing (WGS) analysis and geographic metadata, we traced the origins of Salmonella Bareilly isolates collected in 2012 during a widespread food-borne outbreak in the United States associated with scraped tuna imported from India.Methods: Using next-generation sequencing, we sequenced the complete genome of 100 Salmonella Bareilly isolates obtained from patients who consumed contaminated product, from natural sources, and from unrelated historically and geographically disparate foods. Pathogen genomes were linked to geography by projecting the phylogeny on a virtual globe and produced a transmission network.Results: Phylogenetic analysis of WGS data revealed a common origin for outbreak strains, indicating that patients in Maryland and New York were infected from sources originating at a facility in India.Conclusions: These data represent the first report fully integrating WGS analysis with geographic mapping and a novel use of transmission networks. Results showed that WGS vastly improves our ability to delimit the scope and source of bacterial food-borne contamination events. Furthermore, these findings reinforce the extraordinary utility that WGS brings to global outbreak investigation as a greatly enhanced approach to protecting the human food supply chain as well as public health in general. [ABSTRACT FROM AUTHOR]