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Phylogenetics has been foundational to SARS-CoV-2 research and public health policy, assisting in genomic surveillance, contact tracing, and assessing emergence and spread of new variants. However, phylogenetic analyses of SARS-CoV-2 have often relied on tools designed for de novo phylogenetic inference, in which all data are collected before any analysis is performed and the phylogeny is inferred once from scratch. SARS-CoV-2 data sets do not fit this mold. There are currently over 14 million sequenced SARS-CoV-2 genomes in online databases, with tens of thousands of new genomes added every day. Continuous data collection, combined with the public health relevance of SARS-CoV-2, invites an "online" approach to phylogenetics, in which new samples are added to existing phylogenetic trees every day. The extremely dense sampling of SARS-CoV-2 genomes also invites a comparison between likelihood and parsimony approaches to phylogenetic inference. Maximum likelihood (ML) and pseudo-ML methods may be more accurate when there are multiple changes at a single site on a single branch, but this accuracy comes at a large computational cost, and the dense sampling of SARS-CoV-2 genomes means that these instances will be extremely rare because each internal branch is expected to be extremely short. Therefore, it may be that approaches based on maximum parsimony (MP) are sufficiently accurate for reconstructing phylogenies of SARS-CoV-2, and their simplicity means that they can be applied to much larger data sets. Here, we evaluate the performance of de novo and online phylogenetic approaches, as well as ML, pseudo-ML, and MP frameworks for inferring large and dense SARS-CoV-2 phylogenies. Overall, we find that online phylogenetics produces similar phylogenetic trees to de novo analyses for SARS-CoV-2, and that MP optimization with UShER and matOptimize produces equivalent SARS-CoV-2 phylogenies to some of the most popular ML and pseudo-ML inference tools. MP optimization with UShER and matOptimize is thousands of times faster than presently available implementations of ML and online phylogenetics is faster than de novo inference. Our results therefore suggest that parsimony-based methods like UShER and matOptimize represent an accurate and more practical alternative to established ML implementations for large SARS-CoV-2 phylogenies and could be successfully applied to other similar data sets with particularly dense sampling and short branch lengths.

SUMMARY: Treenome Browser is a web browser tool to interactively visualize millions of genomes alongside huge phylogenetic trees. AVAILABILITY AND IMPLEMENTATION: Treenome Browser for SARS-CoV-2 can be accessed at cov2tree.org, or at taxonium.org for user-provided trees. Source code and documentation are available at github.com/theosanderson/taxonium and docs.taxonium.org/en/latest/treenome.html. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

There is massive variation in intron numbers across eukaryotic genomes, yet the major drivers of intron content during evolution remain elusive. Rapid intron loss and gain in some lineages contrast with long-term evolutionary stasis in others. Episodic intron gain could be explained by recently discovered specialized transposons called Introners, but so far Introners are only known from a handful of species. Here, we performed a systematic search across 3,325 eukaryotic genomes and identified 27,563 Introner-derived introns in 175 genomes (5.2%). Species with Introners span remarkable phylogenetic diversity, from animals to basal protists, representing lineages whose last common ancestor dates to over 1.7 billion years ago. Aquatic organisms were 6.5 times more likely to contain Introners than terrestrial organisms. Introners exhibit mechanistic diversity but most are consistent with DNA transposition, indicating that Introners have evolved convergently hundreds of times from nonautonomous transposable elements. Transposable elements and aquatic taxa are associated with high rates of horizontal gene transfer, suggesting that this combination of factors may explain the punctuated and biased diversity of species containing Introners. More generally, our data suggest that Introners may explain the episodic nature of intron gain across the eukaryotic tree of life. These results illuminate the major source of ongoing intron creation in eukaryotic genomes.

MotivationPhylogenetic tree optimization is necessary for precise analysis of evolutionary and transmission dynamics, but existing tools are inadequate for handling the scale and pace of data produced during the coronavirus disease 2019 (COVID-19) pandemic. One transformative approach, online phylogenetics, aims to incrementally add samples to an ever-growing phylogeny, but there are no previously existing approaches that can efficiently optimize this vast phylogeny under the time constraints of the pandemic.ResultsHere, we present matOptimize, a fast and memory-efficient phylogenetic tree optimization tool based on parsimony that can be parallelized across multiple CPU threads and nodes, and provides orders of magnitude improvement in runtime and peak memory usage compared to existing state-of-the-art methods. We have developed this method particularly to address the pressing need during the COVID-19 pandemic for daily maintenance and optimization of a comprehensive SARS-CoV-2 phylogeny. matOptimize is currently helping refine on a daily basis possibly the largest-ever phylogenetic tree, containing millions of SARS-CoV-2 sequences.Availability and implementationThe matOptimize code is freely available as part of the UShER package (https://github.com/yatisht/usher) and can also be installed via bioconda (https://bioconda.github.io/recipes/usher/README.html). All scripts we used to perform the experiments in this manuscript are available at https://github.com/yceh/matOptimize-experiments.Supplementary informationSupplementary data are available at Bioinformatics online.

The vast scale of SARS-CoV-2 sequencing data has made it increasingly challenging to comprehensively analyze all available data using existing tools and file formats. To address this, we present a database of SARS-CoV-2 phylogenetic trees inferred with unrestricted public sequences, which we update daily to incorporate new sequences. Our database uses the recently proposed mutation-annotated tree (MAT) format to efficiently encode the tree with branches labeled with parsimony-inferred mutations, as well as Nextstrain clade and Pango lineage labels at clade roots. As of June 9, 2021, our SARS-CoV-2 MAT consists of 834,521 sequences and provides a comprehensive view of the virus' evolutionary history using public data. We also present matUtils-a command-line utility for rapidly querying, interpreting, and manipulating the MATs. Our daily-updated SARS-CoV-2 MAT database and matUtils software are available at http://hgdownload.soe.ucsc.edu/goldenPath/wuhCor1/UShER_SARS-CoV-2/ and https://github.com/yatisht/usher, respectively.

This article documents the coping strategies adopted by women victims of spousal violence in Pakistan. By drawing on 21 in-depth interviews conducted in Lahore and Sialkot (Pakistan), we found that the women tried to cope with violence by using various strategies, both emotion focused (e.g., use of religion, placating the husband, etc.) and problem focused (e.g., seeking support from formal institutions, etc.). The data showed that a majority of the women used emotion-focused strategies, especially spiritual therapies, which somehow reduced the violence and provided them with psychosocial solace. Nonetheless, these strategies incurred some costs, such as the consumption of scarce resources, time, and emotional energy. Our data also showed that few women opted for problem-focused strategies, such as seeking help from formal institutions, as these strategies could lead to overt confrontation with their husbands and may result in divorce, the outcome least desired by most of the Pakistani women. We noted that the coping behavior of Pakistani women was complex, subjective, and nonlinear and that the boundaries between emotion-focused and problem-focused strategies were diffuse and blurred. Although the women never surrendered to violence, they were fully aware of their structural limitations and vulnerabilities. Being mindful of the consequences of their actions, women carefully tailored a combination of strategies which could be helpful in resisting or reducing violence but, at the same time, should not be counterproductive. This article argues that Pakistani women alone cannot effectively resist violence while living under a harshly patriarchal regime, where violence against women is embedded in the social, political, and legal structures of society. There are no quick fixes to change the status quo. The Pakistani government, civil society, and formal institutions must proactively support women in reducing their vulnerabilities and facilitate them in expanding their capabilities to address the real causes of violence against them. (Contains 1 table, 1 figure, and 1 note.)

Objective: To assess alcohol use and problem drinking among university students in the German Federal State of North Rhine-Westphalia (NRW) and to examine the associated factors. Method: A multicenter cross-sectional study was conducted in 16 universities in 2006-2007 in NRW by a standardized questionnaire and 3,306 students provided information (response rate of 88%). Problem drinking was measured by the CAGE questionnaire. Results: Alcohol consumption in the last 3 months was reported by greater than 90% of students. About 80% reported heavy drinking, and 20% displayed problem drinking. Male students, students living in residence halls, and students from sport faculties had a higher risk of heavy drinking and problem drinking. When students were compared across study years, frequency of heavy drinking decreased with higher semesters. Conclusions: Overall, heavy drinking and problem drinking are common among university students in this sample. Intervention programs should be designed for students at a particularly high risk. (Contains 1 note and 2 tables.)

A total of 450 women were interviewed in Mother and Child Health Care Centers in three cities in West Bank, Palestine, to assess attitudes toward wife beating. Overall, women perceived wife beating to be justified if a wife insults her husband (59%), if she disobeys her husband (49%), if she neglects her children (37%), if she goes out without telling her husband (25%), if she argues with her husband (11%), and if she burns the food (5%). Sixty-five percent of women agreed with at least one reason for wife beating, but there were statistically significant regional differences: Wife beating was most accepted in Jenin (73% acceptance of at least one reason) and least accepted in Hebron (55%). Lower level of education, not being employed, having more than one child, being married for fewer than 10 years, and making few household decisions were all associated with women's acceptance of wife beating. The implications of these results are discussed. (Contains 3 tables.)

The authors used a standardized questionnaire to survey 201 international and 193 German students at the University of Bielefeld, Germany, to determine differences in health practices between the 2 groups and to identify targets for health-promoting interventions. Multivariate logistic regression models revealed that long-term female international students (those whose duration of residency in Germany was more than 2 years) had lower levels of physical activity and alcohol consumption than their German counterparts and higher rates of smoking independently associated with international citizenship. Short-term international female students were less likely than German students to receive social support. Among men, long-term international student status was associated with daily smoking and inconsistent seat belt use, whereas short-term student status was associated with a lower rate of seat belt use, a higher level of perceived stress, and a healthier diet, compared with domestic students. Findings from the study could give rise to health-promotion activities for international students at German universities: additional studies at other European universities are necessary before making further recommendations.

The objective of this study was to identify factors associated with misperceptions of body shape for 1,681 first-year University students from Germany and Lithuania. The perception of body shape was rated on a five-point scale. Multifactorial logistic regression showed that German students were more likely to perceive themselves as being fatter than their BMI suggested compared with their Lithuanian peers. The results indicated that misperception of body shape was a substantial problem for these university students, particularly those from Germany. (Contains 3 tables.)

Objective To assess levels, trends and gaps between the poorest and the richest in selected health and human development indicators in Bangladesh. Methods Data for selected indicators associated with sociodemographic [...]

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ydbio.2009.02.029 Byline: Yi-Hsien Su (a), Enhu Li (a), Gary K. Geiss (b), William J.R. Longabaugh (c), Alexander Kramer (a), Eric H. Davidson (a) Keywords: Sea urchin embryo ectoderm; Regulatory genes; Embryonic specification Abstract: The current gene regulatory network (GRN) for the sea urchin embryo pertains to pregastrular specification functions in the endomesodermal territories. Here we extend gene regulatory network analysis to the adjacent oral and aboral ectoderm territories over the same period. A large fraction of the regulatory genes predicted by the sea urchin genome project and shown in ancillary studies to be expressed in either oral or aboral ectoderm by 24 h are included, though universally expressed and pan-ectodermal regulatory genes are in general not. The loci of expression of these genes have been determined by whole mount in situ hybridization. We have carried out a global perturbation analysis in which expression of each gene was interrupted by introduction of morpholino antisense oligonucleotide, and the effects on all other genes were measured quantitatively, both by QPCR and by a new instrumental technology (NanoString Technologies nCounter Analysis System). At its current stage the network model, built in BioTapestry, includes 22 genes encoding transcription factors, 4 genes encoding known signaling ligands, and 3 genes that are yet unknown but are predicted to perform specific roles. Evidence emerged from the analysis pointing to distinctive subcircuit features observed earlier in other parts of the GRN, including a double negative transcriptional regulatory gate, and dynamic state lockdowns by feedback interactions. While much of the regulatory apparatus is downstream of Nodal signaling, as expected from previous observations, there are also cohorts of independently activated oral and aboral ectoderm regulatory genes, and we predict yet unidentified signaling interactions between oral and aboral territories. Author Affiliation: (a) Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA (b) NanoString Technologies, Seattle, WA 98119, USA (c) Institute for Systems Biology, Seattle, WA 98103, USA Article History: Received 11 September 2008; Revised 27 January 2009; Accepted 25 February 2009

Summary Nurses are becoming increasingly involved in collaborative international research teams. This article describes a European-wide research consortium that is implementing research across Europe. The experiences of members of a [...]

The DNA of functional cis-regulatory modules displays extensive sequence conservation in comparisons of genomes from modestly distant species. Patches of sequence that are several hundred base pairs in length within these modules are often seen to be 80-95% identical, although the flanking sequence cannot even be aligned. However, it is unlikely that base pairs located between the transcription factor target sites of cis-regulatory modules have sequence-dependent function, and the mechanism that constrains evolutionary change within cis-regulatory modules is incompletely understood. We chose five functionally characterized cis-regulatory modules from the Strongylocentrotus purpuratus (sea urchin) genome and obtained orthologous regulatory and flanking sequences from a bacterial artificial chromosome genome library of a congener, Strongylocentrotus franciscanus. As expected, single-nucleotide substitutions and small indels occur freely at many positions within the regulatory modules of these two species, as they do outside the regulatory modules. However, large indels (>20 bp) are statistically almost absent within the regulatory modules, although they are common in flanking intergenic or intronic sequence. The result helps to explain the patterns of evolutionary sequence divergence characteristic of cis-regulatory DNA. genomic sequence conservation | indels | regulatory evolution

The vast scale of SARS-CoV-2 sequencing data has made it increasingly challenging to comprehensively analyze all available data using existing tools and file formats. To address this, we present a database of SARS-CoV-2 phylogenetic trees inferred with unrestricted public sequences, which we update daily to incorporate new sequences. Our database uses the recently proposed mutation-annotated tree (MAT) format to efficiently encode the tree with branches labeled with parsimony-inferred mutations, as well as Nextstrain clade and Pango lineage labels at clade roots. As of June 9, 2021, our SARS-CoV-2 MAT consists of 834,521 sequences and provides a comprehensive view of the virus' evolutionary history using public data. We also present matUtils—a command-line utility for rapidly querying, interpreting, and manipulating the MATs. Our daily-updated SARS-CoV-2 MAT database and matUtils software are available at http://hgdownload.soe.ucsc.edu/goldenPath/wuhCor1/UShER%5fSARS-CoV-2/ and https://github.com/yatisht/usher , respectively. [ABSTRACT FROM AUTHOR]