Impacts of urban emissions and air quality in São Paulo State, Brazil.

Daily violations of air quality have an impact on urban populations and cause damage to the environment. Thus, the study evaluated the violations of the daily concentrations of SO2, NO2, and PM10, in regions of the State of São Paulo (SSP), based on the National Environment Council (CONAMA) resolution no 491/2018 and the World Health Organization (WHO - World Health Organization. (2016). Ambient air pollution: a global assessment of exposure and burden of disease.) criteria. Daily SO2, NO2, and PM10data from 6 air quality stations operated by Environmental Company of the State of São Paulo CETESB (1996-2011) were organized and submitted to quality control, with data faults (gaps) being identified. The imputation of data via spline proved satisfactory in filling in the gaps (r > 0.7 and low values of Standard Error of the Estimate (SEE) and Root Mean Square Error (RMSE). The cluster analysis (CA) applied to SO2 formed only one homogeneous group (G1). Contrariwise, NO2 and PM10 formed two homogeneous groups (G1 and G2) each. The stations that showed the greatest similarity according to the CA were Cerqueira Cesar and Osasco. The cophenetic matrix generated for SO2 (0.83), NO2 (0.79), and PM10 (0.77) indicate a satisfactory adjustment of the dendrograms. The exploratory statistics applied to groups G1 and G2 point to the high variability of outliers. The WHO criteria are more restrictive than CONAMA regarding daily violations, with a reduction in SO2 and an increase in specific years for NO2 and PM10. Such variability is due to the adoption of public policies by the SSP and the influence of meteorological systems, being confirmed by the Run test that indicated oscillations in the time series, mainly in PM10, and also recognized well-defined biannual cycles.

Fire foci dynamics and their relationship with socioenvironmental factors and meteorological systems in the state of Alagoas, Northeast Brazil.

The objective is to evaluate the fire foci dynamics via environmental satellites and their relationship with socioenvironmental factors and meteorological systems in the state of Alagoas, Brazil. Data considered the period between 2000 and 2017 and was obtained from CPTEC/INPE. Annual and monthly analyzes were performed based on descriptive, exploratory (boxplot) and multivariate statistics analyzes (cluster analysis (CA), principal component analysis (PCA)) and Poisson regression models (based on 2000 and 2010 census data). CA based on the Ward method identified five fire foci homogeneous groups (G1 to G5), while Coruripe did not classify within any group (NA); therefore, the CA technique was consistent (CCC = 0.772). Group G1 is found in all regions of Alagoas, while G2, G5, and NA groups are found in Baixo São Francisco, Litoral, and Zona da Mata regions. Most fire foci were observed in the Litoral region. Seasonally, the largest records were from October to December months for all groups, influenced by the sugarcane harvesting period. The G4 group and Coruripe accounted for 60,767 foci (32.1%). The highest number of fire foci occurred in 2012 and 2015 (between 8000 and 9000 foci), caused by the action of the El Niño-Southern Oscillation. The Poisson regression showed that the dynamics of fire foci are directly associated with the Gini index and Human Development Index (models 1 and 3). Based on the PCA, the three components captured 78.8% of the total variance explained, and they were strongly influenced by the variables: population, GDP, and demographic density. The municipality of Maceió has the largest contribution from the fire foci, with values higher than 40%, and in PC1 and PC2 are related to urban densification and population growth.

Amazonian deforestation and soil biodiversity.

Clearance and perturbation of Amazonian forests are one of the greatest threats to tropical biodiversity conservation of our times. A better understanding of how soil communities respond to Amazonian deforestation is crucially needed to inform policy interventions that effectively protect biodiversity and the essential ecosystem services it provides. We assessed the impact of deforestation and ecosystem conversion to arable land on Amazonian soil biodiversity through a meta-analysis. We analyzed 274 pairwise comparisons of soil biodiversity in Amazonian primary forests and sites under different stages of deforestation and land-use conversion: disturbed (wildfire and selective logging) and slash-and-burnt forests, pastures, and cropping systems. Overall, 60% and 51% of responses of soil macrofauna and microbial community attributes (i.e., abundance, biomass, richness, and diversity indexes) to deforestation were negative, respectively. We found few studies on mesofauna (e.g., microarthropods) and microfauna (e.g., protozoa and nematodes), so those groups could not be analyzed. Macrofauna abundance and biomass were more vulnerable to the displacement of forests by pastures than by agricultural fields, whereas microbes showed the opposite pattern. Effects of Amazonian deforestation on macrofauna were more detrimental at sites with mean annual precipitation >1900 mm, and higher losses of microbes occurred in highly acidic soils (pH < 4.5). Limited geographic coverage, omission of meso- and microfauna, and low taxonomic resolution were main factors impairing generalizations from the data set. Few studies assessed the impacts of within-forest disturbance (wildfires and selective logging) on soil species in Amazonia, where logging operations rapidly expand across public lands and more frequent severe dry seasons are increasing the prevalence of wildfires.

Deforestación en el Amazonas y Biodiversidad del Suelo Resumen Actualmente, el despeje y la perturbación de los bosques del Amazonas son las principales amenazas para la conservación de la biodiversidad tropical. Se requiere urgentemente de un mejor entendimiento sobre cómo las comunidades del suelo responden a la deforestación amazónica para informar a las intervenciones políticas que protegen efectivamente a la biodiversidad y a los servicios ambientales esenciales que proporciona. Evaluamos el impacto de la deforestación y la conversión del ecosistema a suelo arable sobre la biodiversidad del suelo amazónico por medio de un meta-análisis. Analizamos 274 comparaciones por pares de la biodiversidad del suelo amazónico en bosques primarios y sitios bajo diferentes etapas de deforestación y conversión de uso de suelo: bosques perturbados (incendios forestales y tala selectiva) y de corte-y-quema, pasturas, y sistemas agrícolas. En general, el 60% y el 51% de las respuestas de los atributos (es decir, abundancia, biomasa, riqueza, e índices de biodiversidad) de la macrofauna del suelo y de las comunidades microbianas ante la deforestación fueron negativas, respectivamente. Encontramos pocos estudios sobre la mesofauna (p. ej.: microartrópodos) y la microfauna (p. ej.: protozoarios y nematodos), así que estos grupos no pudieron ser analizados. La abundancia de la macrofauna y la biomasa fueron más vulnerables al desplazamiento de bosques por las pasturas que por los campos agrícolas, mientras que los microbios mostraron el patrón opuesto. Los efectos de la deforestación amazónica sobre la macrofauna fueron más dañinos en sitios con una precipitación anual media mayor a los 1,900 mm, y ocurrieron pérdidas más elevadas de microbios en suelos con una acidez alta (pH < 4.5). La cobertura geográfica limitada, la omisión de la mesofauna y la microfauna, y la baja resolución taxonómica fueron los factores principales que obstaculizaron las generalizaciones del conjunto de datos. Pocos estudios evaluaron los impactos de las perturbaciones internas del bosque (incendios forestales y tala selectiva) sobre las especies del suelo amazónico, a la vez que las operaciones de tala se expanden rápidamente en los terrenos públicos y la ocurrencia con mayor frecuencia de temporadas con sequía grave aumentan la prevalencia de los incendios forestales.

Curation, integration and visualization of bacterial virulence factors in PATRIC.

MOTIVATION: We've developed a highly curated bacterial virulence factor (VF) library in PATRIC (Pathosystems Resource Integration Center, www.patricbrc.org) to support infectious disease research. Although several VF databases are available, there is still a need to incorporate new knowledge found in published experimental evidence and integrate these data with other information known for these specific VF genes, including genomic and other omics data. This integration supports the identification of VFs, comparative studies and hypothesis generation, which facilitates the understanding of virulence and pathogenicity. RESULTS: We have manually curated VFs from six prioritized NIAID (National Institute of Allergy and Infectious Diseases) category A-C bacterial pathogen genera, Mycobacterium, Salmonella, Escherichia, Shigella, Listeria and Bartonella, using published literature. This curated information on virulence has been integrated with data from genomic functional annotations, trancriptomic experiments, protein-protein interactions and disease information already present in PATRIC. Such integration gives researchers access to a broad array of information about these individual genes, and also to a suite of tools to perform comparative genomic and transcriptomics analysis that are available at PATRIC. AVAILABILITY AND IMPLEMENTATION: All tools and data are freely available at PATRIC (http://patricbrc.org). SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

RNA-Rocket: an RNA-Seq analysis resource for infectious disease research.

MOTIVATION: RNA-Seq is a method for profiling transcription using high-throughput sequencing and is an important component of many research projects that wish to study transcript isoforms, condition specific expression and transcriptional structure. The methods, tools and technologies used to perform RNA-Seq analysis continue to change, creating a bioinformatics challenge for researchers who wish to exploit these data. Resources that bring together genomic data, analysis tools, educational material and computational infrastructure can minimize the overhead required of life science researchers. RESULTS: RNA-Rocket is a free service that provides access to RNA-Seq and ChIP-Seq analysis tools for studying infectious diseases. The site makes available thousands of pre-indexed genomes, their annotations and the ability to stream results to the bioinformatics resources VectorBase, EuPathDB and PATRIC. The site also provides a combination of experimental data and metadata, examples of pre-computed analysis, step-by-step guides and a user interface designed to enable both novice and experienced users of RNA-Seq data. AVAILABILITY AND IMPLEMENTATION: RNA-Rocket is available at rnaseq.pathogenportal.org. Source code for this project can be found at github.com/cidvbi/PathogenPortal. CONTACT: anwarren@vt.edu SUPPLEMENTARY INFORMATION: Supplementary materials are available at Bioinformatics online.

PATRIC, the bacterial bioinformatics database and analysis resource.

The Pathosystems Resource Integration Center (PATRIC) is the all-bacterial Bioinformatics Resource Center (BRC) (http://www.patricbrc.org). A joint effort by two of the original National Institute of Allergy and Infectious Diseases-funded BRCs, PATRIC provides researchers with an online resource that stores and integrates a variety of data types [e.g. genomics, transcriptomics, protein-protein interactions (PPIs), three-dimensional protein structures and sequence typing data] and associated metadata. Datatypes are summarized for individual genomes and across taxonomic levels. All genomes in PATRIC, currently more than 10,000, are consistently annotated using RAST, the Rapid Annotations using Subsystems Technology. Summaries of different data types are also provided for individual genes, where comparisons of different annotations are available, and also include available transcriptomic data. PATRIC provides a variety of ways for researchers to find data of interest and a private workspace where they can store both genomic and gene associations, and their own private data. Both private and public data can be analyzed together using a suite of tools to perform comparative genomic or transcriptomic analysis. PATRIC also includes integrated information related to disease and PPIs. All the data and integrated analysis and visualization tools are freely available. This manuscript describes updates to the PATRIC since its initial report in the 2007 NAR Database Issue.

The condition-dependent transcriptional landscape of Burkholderia pseudomallei.

Burkholderia pseudomallei (Bp), the causative agent of the often-deadly infectious disease melioidosis, contains one of the largest prokaryotic genomes sequenced to date, at 7.2 Mb with two large circular chromosomes (1 and 2). To comprehensively delineate the Bp transcriptome, we integrated whole-genome tiling array expression data of Bp exposed to >80 diverse physical, chemical, and biological conditions. Our results provide direct experimental support for the strand-specific expression of 5,467 Sanger protein-coding genes, 1,041 operons, and 766 non-coding RNAs. A large proportion of these transcripts displayed condition-dependent expression, consistent with them playing functional roles. The two Bp chromosomes exhibited dramatically different transcriptional landscapes--Chr 1 genes were highly and constitutively expressed, while Chr 2 genes exhibited mosaic expression where distinct subsets were expressed in a strongly condition-dependent manner. We identified dozens of cis-regulatory motifs associated with specific condition-dependent expression programs, and used the condition compendium to elucidate key biological processes associated with two complex pathogen phenotypes--quorum sensing and in vivo infection. Our results demonstrate the utility of a Bp condition-compendium as a community resource for biological discovery. Moreover, the observation that significant portions of the Bp virulence machinery can be activated by specific in vitro cues provides insights into Bp's capacity as an "accidental pathogen", where genetic pathways used by the bacterium to survive in environmental niches may have also facilitated its ability to colonize human hosts.

Comparative phylogenomics and evolution of the Brucellae reveal a path to virulence.

Brucella species include important zoonotic pathogens that have a substantial impact on both agriculture and human health throughout the world. Brucellae are thought of as "stealth pathogens" that escape recognition by the host innate immune response, modulate the acquired immune response, and evade intracellular destruction. We analyzed the genome sequences of members of the family Brucellaceae to assess its evolutionary history from likely free-living soil-based progenitors into highly successful intracellular pathogens. Phylogenetic analysis split the genus into two groups: recently identified and early-dividing "atypical" strains and a highly conserved "classical" core clade containing the major pathogenic species. Lateral gene transfer events brought unique genomic regions into Brucella that differentiated them from Ochrobactrum and allowed the stepwise acquisition of virulence factors that include a type IV secretion system, a perosamine-based O antigen, and systems for sequestering metal ions that are absent in progenitors. Subsequent radiation within the core Brucella resulted in lineages that appear to have evolved within their preferred mammalian hosts, restricting their virulence to become stealth pathogens capable of causing long-term chronic infections.

Proteomic comparison of historic and recently emerged hypervirulent Clostridium difficile strains.

Clostridium difficile in recent years has undergone rapid evolution and has emerged as a serious human pathogen. Proteomic approaches can improve the understanding of the diversity of this important pathogen, especially in comparing the adaptive ability of different C. difficile strains. In this study, TMT labeling and nanoLC-MS/MS driven proteomics were used to investigate the responses of four C. difficile strains to nutrient shift and osmotic shock. We detected 126 and 67 differentially expressed proteins in at least one strain under nutrition shift and osmotic shock, respectively. During nutrient shift, several components of the phosphotransferase system (PTS) were found to be differentially expressed, which indicated that the carbon catabolite repression (CCR) was relieved to allow the expression of enzymes and transporters responsible for the utilization of alternate carbon sources. Some classical osmotic shock associated proteins, such as GroEL, RecA, CspG, and CspF, and other stress proteins such as PurG and SerA were detected during osmotic shock. Furthermore, the recently emerged strains were found to contain a more robust gene network in response to both stress conditions. This work represents the first comparative proteomic analysis of historic and recently emerged hypervirulent C. difficile strains, complementing the previously published proteomics studies utilizing only one reference strain.

The Hows of Resident-Driven Community Empowerment toward Health Equity.

BACKGROUND: This article details community engagement, design, and implementation strategies for the Raices-Xidid-Roots (RXR) Academy. RXR provided a linguistically accessible and culturally relevant curriculum to residents of Spanish and Somali-speaking immigrant, asylee, and refugee backgrounds. OBJECTIVES: This study examined the implementation of the RXR program, including participation and adjustments needed to foster participant engagement and active voice, and explored participant actions to address self-identified aspirations as part of participation. RXR's goal was to empower Morgan County, Colorado, Spanish- and Somalispeaking cohorts of residents from immigrant, asylee, and refugee backgrounds such that they could autonomously plan, create, and sustain programs and organizations to meet their community needs. METHODS: The observational study design included process and implementation evaluative approaches, including interview, project team meeting debriefings, and course organizer reflections, to identify and address implementation challenges, learn how the program met participants' needs, and understand keys to maintaining participant engagement. RESULTS: Cultural adaptation of the content was key to maintaining consistent participant engagement, including delivering programming in participant preferred languages and tailoring curriculum to participant cultural practices. Participants indicated that language barriers had previously prevented them from accessing the content provided by the program's curriculum. Adaptations included adjusting meeting logistics, participant compensation, and unit timing. The Two RXR Academy cohorts developed initiatives that addressed community-identified needs. LESSONS LEARNED: Three RXR design elements supported participant engagement and development of community power: 1) language access beyond the language justice model by providing programming in the participants' preferred language, 2) cultural adaptation of programming, and 3) community ownership and active voiceConclusions: The RXR program provided opportunities for skill development among Morgan County's non-native English-speaking residents and led to the design and implementation of resident-driven projects.

A Rickettsia genome overrun by mobile genetic elements provides insight into the acquisition of genes characteristic of an obligate intracellular lifestyle.

We present the draft genome for the Rickettsia endosymbiont of Ixodes scapularis (REIS), a symbiont of the deer tick vector of Lyme disease in North America. Among Rickettsia species (Alphaproteobacteria: Rickettsiales), REIS has the largest genome sequenced to date (>2 Mb) and contains 2,309 genes across the chromosome and four plasmids (pREIS1 to pREIS4). The most remarkable finding within the REIS genome is the extraordinary proliferation of mobile genetic elements (MGEs), which contributes to a limited synteny with other Rickettsia genomes. In particular, an integrative conjugative element named RAGE (for Rickettsiales amplified genetic element), previously identified in scrub typhus rickettsiae (Orientia tsutsugamushi) genomes, is present on both the REIS chromosome and plasmids. Unlike the pseudogene-laden RAGEs of O. tsutsugamushi, REIS encodes nine conserved RAGEs that include F-like type IV secretion systems similar to that of the tra genes encoded in the Rickettsia bellii and R. massiliae genomes. An unparalleled abundance of encoded transposases (>650) relative to genome size, together with the RAGEs and other MGEs, comprise ~35% of the total genome, making REIS one of the most plastic and repetitive bacterial genomes sequenced to date. We present evidence that conserved rickettsial genes associated with an intracellular lifestyle were acquired via MGEs, especially the RAGE, through a continuum of genomic invasions. Robust phylogeny estimation suggests REIS is ancestral to the virulent spotted fever group of rickettsiae. As REIS is not known to invade vertebrate cells and has no known pathogenic effects on I. scapularis, its genome sequence provides insight on the origin of mechanisms of rickettsial pathogenicity.

Overview of the ID, EPI and REL tasks of BioNLP Shared Task 2011.

We present the preparation, resources, results and analysis of three tasks of the BioNLP Shared Task 2011: the main tasks on Infectious Diseases (ID) and Epigenetics and Post-translational Modifications (EPI), and the supporting task on Entity Relations (REL). The two main tasks represent extensions of the event extraction model introduced in the BioNLP Shared Task 2009 (ST'09) to two new areas of biomedical scientific literature, each motivated by the needs of specific biocuration tasks. The ID task concerns the molecular mechanisms of infection, virulence and resistance, focusing in particular on the functions of a class of signaling systems that are ubiquitous in bacteria. The EPI task is dedicated to the extraction of statements regarding chemical modifications of DNA and proteins, with particular emphasis on changes relating to the epigenetic control of gene expression. By contrast to these two application-oriented main tasks, the REL task seeks to support extraction in general by separating challenges relating to part-of relations into a subproblem that can be addressed by independent systems. Seven groups participated in each of the two main tasks and four groups in the supporting task. The participating systems indicated advances in the capability of event extraction methods and demonstrated generalization in many aspects: from abstracts to full texts, from previously considered subdomains to new ones, and from the ST'09 extraction targets to other entities and events. The highest performance achieved in the supporting task REL, 58% F-score, is broadly comparable with levels reported for other relation extraction tasks. For the ID task, the highest-performing system achieved 56% F-score, comparable to the state-of-the-art performance at the established ST'09 task. In the EPI task, the best result was 53% F-score for the full set of extraction targets and 69% F-score for a reduced set of core extraction targets, approaching a level of performance sufficient for user-facing applications. In this study, we extend on previously reported results and perform further analyses of the outputs of the participating systems. We place specific emphasis on aspects of system performance relating to real-world applicability, considering alternate evaluation metrics and performing additional manual analysis of system outputs. We further demonstrate that the strengths of extraction systems can be combined to improve on the performance achieved by any system in isolation. The manually annotated corpora, supporting resources, and evaluation tools for all tasks are available from http://www.bionlp-st.org and the tasks continue as open challenges for all interested parties.

Abscisic acid regulates inflammation via ligand-binding domain-independent activation of peroxisome proliferator-activated receptor gamma.

Abscisic acid (ABA) has shown efficacy in the treatment of diabetes and inflammation; however, its molecular targets and the mechanisms of action underlying its immunomodulatory effects remain unclear. This study investigates the role of peroxisome proliferator-activated receptor γ (PPAR γ) and lanthionine synthetase C-like 2 (LANCL2) as molecular targets for ABA. We demonstrate that ABA increases PPAR γ reporter activity in RAW 264.7 macrophages and increases ppar γ expression in vivo, although it does not bind to the ligand-binding domain of PPAR γ. LANCL2 knockdown studies provide evidence that ABA-mediated activation of macrophage PPAR γ is dependent on lancl2 expression. Consistent with the association of LANCL2 with G proteins, we provide evidence that ABA increases cAMP accumulation in immune cells. ABA suppresses LPS-induced prostaglandin E(2) and MCP-1 production via a PPAR γ-dependent mechanism possibly involving activation of PPAR γ and suppression of NF-κB and nuclear factor of activated T cells. LPS challenge studies in PPAR γ-expressing and immune cell-specific PPAR γ null mice demonstrate that ABA down-regulates toll-like receptor 4 expression in macrophages and T cells in vivo through a PPAR γ-dependent mechanism. Global transcriptomic profiling and confirmatory quantitative RT-PCR suggest novel candidate targets and demonstrate that ABA treatment mitigates the effect of LPS on the expression of genes involved in inflammation, metabolism, and cell signaling, in part, through PPAR γ. In conclusion, ABA decreases LPS-mediated inflammation and regulates innate immune responses through a bifurcating pathway involving LANCL2 and an alternative, ligand-binding domain-independent mechanism of PPAR γ activation.

Integration and visualization of host-pathogen data related to infectious diseases.

MOTIVATION: Infectious disease research is generating an increasing amount of disparate data on pathogenic systems. There is a growing need for resources that effectively integrate, analyze, deliver and visualize these data, both to improve our understanding of infectious diseases and to facilitate the development of strategies for disease control and prevention. RESULTS: We have developed Disease View, an online host-pathogen resource that enables infectious disease-centric access, analysis and visualization of host-pathogen interactions. In this resource, we associate infectious diseases with corresponding pathogens, provide information on pathogens, pathogen virulence genes and the genetic and chemical evidences for the human genes that are associated with the diseases. We also deliver the relationships between pathogens, genes and diseases in an interactive graph and provide the geolocation reports of associated diseases around the globe in real time. Unlike many other resources, we have applied an iterative, user-centered design process to the entire resource development, including data acquisition, analysis and visualization. AVAILABILITY AND IMPLEMENTATION: Freely available at http://www.patricbrc.org; all major web browsers supported. CONTACT: cmao@vbi.vt.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Selection of a phylogenetically informative region of the norovirus genome for outbreak linkage.

The recognition of a common source norovirus outbreak is supported by finding identical norovirus sequences in patients. Norovirus sequencing has been established in many (national) public health laboratories and academic centers, but often partial and different genome sequences are used. Therefore, agreement on a target sequence of sufficient diversity to resolve links between outbreaks is crucial. Although harmonization of laboratory methods is one of the keystone activities of networks that have the aim to identify common source norovirus outbreaks, this has proven difficult to accomplish, particularly in the international context. Here, we aimed at providing a method enabling identification of the genomic region informative of a common source norovirus outbreak by bio-informatic tools. The data set of 502 unique full length capsid gene sequences available from the public domain, combined with epidemiological data including linkage information was used to build over 3,000 maximum likelihood (ML) trees for different sequence lengths and regions. All ML trees were evaluated for robustness and specificity of clustering of known linked norovirus outbreaks against the background diversity of strains. Great differences were seen in the robustness of commonly used PCR targets for cluster detection. The capsid gene region spanning nucleotides 900-1,400 was identified as the region optimally substituting for the full length capsid region. Reliability of this approach depends on the quality of the background data set, and we recommend periodic reassessment of this growing data set. The approach may be applicable to multiple sequence-based data sets of other pathogens.

PATRIC: the comprehensive bacterial bioinformatics resource with a focus on human pathogenic species.

Funded by the National Institute of Allergy and Infectious Diseases, the Pathosystems Resource Integration Center (PATRIC) is a genomics-centric relational database and bioinformatics resource designed to assist scientists in infectious-disease research. Specifically, PATRIC provides scientists with (i) a comprehensive bacterial genomics database, (ii) a plethora of associated data relevant to genomic analysis, and (iii) an extensive suite of computational tools and platforms for bioinformatics analysis. While the primary aim of PATRIC is to advance the knowledge underlying the biology of human pathogens, all publicly available genome-scale data for bacteria are compiled and continually updated, thereby enabling comparative analyses to reveal the basis for differences between infectious free-living and commensal species. Herein we summarize the major features available at PATRIC, dividing the resources into two major categories: (i) organisms, genomes, and comparative genomics and (ii) recurrent integration of community-derived associated data. Additionally, we present two experimental designs typical of bacterial genomics research and report on the execution of both projects using only PATRIC data and tools. These applications encompass a broad range of the data and analysis tools available, illustrating practical uses of PATRIC for the biologist. Finally, a summary of PATRIC's outreach activities, collaborative endeavors, and future research directions is provided.

PIG--the pathogen interaction gateway.

Protein-protein interactions (PPIs) play a vital role in initiating infection in a number of pathogens. Identifying which interactions allow a pathogen to infect its host can help us to understand methods of pathogenesis and provide potential targets for therapeutics. Public resources for studying host-pathogen systems, in particular PPIs, are scarce. To facilitate the study of host-pathogen PPIs, we have collected and integrated host-pathogen PPI (HP-PPI) data from a number of public resources to create the Pathogen Interaction Gateway (PIG). PIG provides a text based search and a BLAST interface for searching the HP-PPI data. Each entry in PIG includes information such as the functional annotations and the domains present in the interacting proteins. PIG provides links to external databases to allow for easy navigation among the various websites. Additionally, PIG includes a tool for visualizing a single HP-PPI network or two HP-PPI networks. PIG can be accessed at http://pig.vbi.vt.edu.

"It depends:" a qualitative study on digital health academic-industry collaboration.

BACKGROUND: Academic-industry collaborations (AICs) are endorsed to alleviate challenges in digital health, but partnership experiences remain understudied. The qualitative study's objective investigated collaboration experiences between academic institutions and digital health companies. METHODS: A phenomenology methodology captured experiences of AICs, eliciting perspectives from academic researchers and industry affiliates (e.g., leadership, company investigators). Semi-structured interviews probed eligible collaborators about their experiences in digital health. Analysts coded and organized data into significant statements reaching thematic saturation. RESULTS: Participants (N=20) were interviewed from 6 academic institutions and 14 unique industry partners. Seven themes emerged: (I) Collaboration evolves with time, relationships, funding, and evidence; (II) Collaboration demands strong relationships and interpersonal dynamics; (III) Operational processes vary across collaborations; (IV) Collaboration climate and context matters; (V) Shared expectations lead to a better understanding of success; (VI) Overcoming challenges with recommendations; (VII) Collaboration may help navigate the global pandemic. CONCLUSIONS: Digital health academic industry collaboration demands strong relationships, requiring flexible mechanisms of collaboration and cultural fit. Diverse models of collaboration exist and remain dependent on contextual factors. While no collaboration conquers all challenges in digital health, AICs may serve as a facilitator for improved digital health products, thus advancing science, promoting public health, and benefiting the economy.

Phylogeny of gammaproteobacteria.

The phylogeny of the large bacterial class Gammaproteobacteria has been difficult to resolve. Here we apply a telescoping multiprotein approach to the problem for 104 diverse gammaproteobacterial genomes, based on a set of 356 protein families for the whole class and even larger sets for each of four cohesive subregions of the tree. Although the deepest divergences were resistant to full resolution, some surprising patterns were strongly supported. A representative of the Acidithiobacillales routinely appeared among the outgroup members, suggesting that in conflict with rRNA-based phylogenies this order does not belong to Gammaproteobacteria; instead, it (and, independently, "Mariprofundus") diverged after the establishment of the Alphaproteobacteria yet before the betaproteobacteria/gammaproteobacteria split. None of the orders Alteromonadales, Pseudomonadales, or Oceanospirillales were monophyletic; we obtained strong support for clades that contain some but exclude other members of all three orders. Extreme amino acid bias in the highly A+T-rich genome of Candidatus Carsonella prevented its reliable placement within Gammaproteobacteria, and high bias caused artifacts that limited the resolution of the relationships of other insect endosymbionts, which appear to have had multiple origins, although the unbiased genome of the endosymbiont Sodalis acted as an attractor for them. Instability was observed for the root of the Enterobacteriales, with nearly equal subsets of the protein families favoring one or the other of two alternative root positions; the nematode symbiont Photorhabdus was identified as a disruptor whose omission helped stabilize the Enterobacteriales root.

Phylogenomics reveals a diverse Rickettsiales type IV secretion system.

With an obligate intracellular lifestyle, Alphaproteobacteria of the order Rickettsiales have inextricably coevolved with their various eukaryotic hosts, resulting in small, reductive genomes and strict dependency on host resources. Unsurprisingly, large portions of Rickettsiales genomes encode proteins involved in transport and secretion. One particular transporter that has garnered recent attention from researchers is the type IV secretion system (T4SS). Homologous to the well-studied archetypal vir T4SS of Agrobacterium tumefaciens, the Rickettsiales vir homolog (rvh) T4SS is characterized primarily by duplication of several of its genes and scattered genomic distribution of all components in several conserved islets. Phylogeny estimation suggests a single event of ancestral acquirement of the rvh T4SS, likely from a nonalphaproteobacterial origin. Bioinformatics analysis of over 30 Rickettsiales genome sequences illustrates a conserved core rvh scaffold (lacking only a virB5 homolog), with lineage-specific diversification of several components (rvhB1, rvhB2, and rvhB9b), likely a result of modifications to cell envelope structure. This coevolution of the rvh T4SS and cell envelope morphology is probably driven by adaptations to various host cells, identifying the transporter as an important target for vaccine development. Despite the genetic intractability of Rickettsiales, recent advancements have been made in the characterization of several components of the rvh T4SS, as well as its putative regulators and substrates. While current data favor a role in effector translocation, functions in DNA uptake and release and/or conjugation cannot at present be ruled out, especially considering that a mechanism for plasmid transfer in Rickettsia spp. has yet to be proposed.