RESUMEN
OBJECTIVES: To prospectively compare systemic anti-tumour immune responses induced by irreversible electroporation (IRE) and robot-assisted radical prostatectomy (RARP) in patients with localised intermediate-risk prostate cancer (PCa). PATIENTS AND METHODS: Between February 2021 and June 2022, before and after treatment (at 5, 14 and 30 days) peripheral blood samples of 30 patients with localised PCa were prospectively collected. Patient inclusion criteria were: International Society of Urological Pathologists Grade 2-3, clinical cancer stage ≤T2c, prostate-specific antigen level <20 ng/mL). Patients were treated with IRE (n = 20) or RARP (n = 10). Frequency and activation status of lymphocytic and myeloid immune cell subsets were determined using flow cytometry. PCa-specific T-cell responses to prostatic acid phosphatase (PSAP) and cancer testis antigen (New York oesophageal squamous cell carcinoma 1 [NY-ESO-1]) were determined by interferon-γ enzyme-linked immunospot assay (ELISpot). Repeated-measures analysis of variance and two-sided Student's t-tests were used to compare immune responses over time and between treatment cohorts. RESULTS: Patient and tumour characteristics were similar between the cohorts except for age (median 68 years [IRE] and 62 years [RARP], P = 0.01). IRE induced depletion of systemic regulatory T cells (P = 0.0001) and a simultaneous increase in activated cytotoxic T-lymphocyte antigen 4 (CTLA-4)+ cluster of differentiation (CD)4+ (P < 0.001) and CD8+ (P = 0.032) T cells, consistent with reduction of systemic immune suppression allowing for effector T-cell activation, peaking 14 days after IRE. Effects were positively correlated with tumour volume/ablation size. Accordingly, IRE induced expansion of PSAP and/or NY-ESO-1 specific T-cell responses in four of the eight immune competent patients. Temporarily increased activated myeloid derived suppressor cell frequencies (P = 0.047) were consistent with transient immunosuppression after RARP. CONCLUSIONS: Irreversible electroporation induces a PCa-specific systemic immune response in patients with localised PCa, aiding conversion of the tumour microenvironment into a more immune permissive state. Therapeutic efficacy might be further enhanced by combination with CTLA-4 checkpoint inhibition, potentially opening up a new synergistic treatment paradigm for high-risk localised or (oligo)metastatic disease.
RESUMEN
BACKGROUND: Understanding biodiversity patterns is a central topic in biogeography and ecology, and it is essential for conservation planning and policy development. Diversity estimates that consider the evolutionary relationships among species, such as phylogenetic diversity and phylogenetic endemicity indices, provide valuable insights into the functional diversity and evolutionary uniqueness of biological communities. These estimates are crucial for informed decision-making and effective global biodiversity management. However, the current methodologies used to generate these metrics encounter challenges in terms of efficiency, accuracy, and data integration. RESULTS: We introduce PhyloNext, a flexible and data-intensive computational pipeline designed for phylogenetic diversity and endemicity analysis. The pipeline integrates GBIF occurrence data and OpenTree phylogenies with the Biodiverse software. PhyloNext is free, open-source, and provided as Docker and Singularity containers for effortless setup. To enhance user accessibility, a user-friendly, web-based graphical user interface has been developed, facilitating easy and efficient navigation for exploring and executing the pipeline. PhyloNext streamlines the process of conducting phylogenetic diversity analyses, improving efficiency, accuracy, and reproducibility. The automated workflow allows for periodic reanalysis using updated input data, ensuring that conservation strategies remain relevant and informed by the latest available data. CONCLUSIONS: PhyloNext provides researchers, conservationists, and policymakers with a powerful tool to facilitate a broader understanding of biodiversity patterns, supporting more effective conservation planning and policy development. This new pipeline simplifies the creation of reproducible and easily updatable phylogenetic diversity analyses. Additionally, it promotes increased interoperability and integration with other biodiversity databases and analytical tools.
Asunto(s)
Biodiversidad , Filogenia , Programas InformáticosRESUMEN
AIM: To understand and evaluate the uptake and local adaptations of proven targeted implementation interventions that have effectively reduced unnecessary investigations and therapies in infants with bronchiolitis within emergency departments. METHODS: A multi-centred, mixed-methods quality improvement study in four Australian hospitals that provide paediatric emergency and inpatient care from May to December 2021. All hospitals were provided with the same implementation intervention package and training. Real-time tracking logs of adaptions were completed followed by semi-structured interviews. Interviews were recorded, transcribed and subsequently coded using FRAME-IS to further describe the adaptions made. RESULTS: Tracking logs were summarised and data from 12 interviews were compared from participating sites. The intervention resulted in 116 education sessions and a total of 23 adaptations made to educational materials, both content and contextual. Shortening education presentations, addition of bronchiolitis definitions, formatting of materials and novel interventions were the most common modifications. Audit and feedback were completed across all sites with varying utilisation. Targeted teaching was noted to dictate adaptions prior to and during implementation. CONCLUSION: Quantitative and qualitative analysis of clinical 'real-world' adaptations to proven targeted implementation interventions allows invaluable insight for future de-implementation initiatives and national roll-out of implementation packages in the ED setting.
Asunto(s)
Bronquiolitis , Lactante , Humanos , Niño , Australia , Bronquiolitis/terapia , Hospitalización , Servicio de Urgencia en Hospital , Mejoramiento de la CalidadRESUMEN
Produced water (PW) generated by Australian offshore oil and gas activities is typically discharged to the ocean after treatment. These complex mixtures of organic and inorganic compounds can pose significant environmental risk to receiving waters, if not managed appropriately. Oil and gas operators in Australia are required to demonstrate that environmental impacts of their activity are managed to levels that are as low as reasonably practicable, for example, through risk assessments comparing predicted no-effect concentrations (PNECs) with predicted environmental concentrations of PW. Probabilistic species sensitivity distribution (SSD) approaches are increasingly being used to derive PW PNECs and subsequently calculating dilutions of PW (termed "safe" dilutions) required to protect a nominated percentage of species in the receiving environment (e.g., 95% and 99% or PC95 and PC99, respectively). Limitations associated with SSDs include fitting a single model to small (six to eight species) data sets, resulting in large uncertainty (very wide 95% confidence limits) in the region associated with PC99 and PC95 results. Recent advances in SSD methodology, in the form of model averaging, claim to overcome some of these limitations by applying the average model fit of multiple models to a data set. We assessed the advantages and limitations of four different SSD software packages for determining PNECs for five PWs from a gas and condensate platform off the North West Shelf of Australia. Model averaging reduced occurrences of extreme uncertainty around PC95 and PC99 values compared with single model fitting and was less prone to the derivation of overly conservative PC99 and PC95 values that resulted from lack of fit to single models. Our results support the use of model averaging for improved robustness in derived PNEC and subsequent "safe" dilution values for PW discharge management and risk assessment. In addition, we present and discuss the toxicity of PW considering the paucity of such information in peer-reviewed literature. Integr Environ Assess Manag 2024;20:498-517. © 2023 Commonwealth Scientific and Industrial Research Organisation. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).
Asunto(s)
Contaminantes Químicos del Agua , Agua , Australia , Medición de Riesgo , Ecotoxicología , Contaminantes Químicos del Agua/toxicidad , Contaminantes Químicos del Agua/análisisRESUMEN
Tens of millions of images from biological collections have become available online over the last two decades. In parallel, there has been a dramatic increase in the capabilities of image analysis technologies, especially those involving machine learning and computer vision. While image analysis has become mainstream in consumer applications, it is still used only on an artisanal basis in the biological collections community, largely because the image corpora are dispersed. Yet, there is massive untapped potential for novel applications and research if images of collection objects could be made accessible in a single corpus. In this paper, we make the case for infrastructure that could support image analysis of collection objects. We show that such infrastructure is entirely feasible and well worth investing in.
RESUMEN
The standardization of data, encompassing both primary and contextual information (metadata), plays a pivotal role in facilitating data (re-)use, integration, and knowledge generation. However, the biodiversity and omics communities, converging on omics biodiversity data, have historically developed and adopted their own distinct standards, hindering effective (meta)data integration and collaboration. In response to this challenge, the Task Group (TG) for Sustainable DwC-MIxS Interoperability was established. Convening experts from the Biodiversity Information Standards (TDWG) and the Genomic Standards Consortium (GSC) alongside external stakeholders, the TG aimed to promote sustainable interoperability between the Minimum Information about any (x) Sequence (MIxS) and Darwin Core (DwC) specifications. To achieve this goal, the TG utilized the Simple Standard for Sharing Ontology Mappings (SSSOM) to create a comprehensive mapping of DwC keys to MIxS keys. This mapping, combined with the development of the MIxS-DwC extension, enables the incorporation of MIxS core terms into DwC-compliant metadata records, facilitating seamless data exchange between MIxS and DwC user communities. Through the implementation of this translation layer, data produced in either MIxS- or DwC-compliant formats can now be efficiently brokered, breaking down silos and fostering closer collaboration between the biodiversity and omics communities. To ensure its sustainability and lasting impact, TDWG and GSC have both signed a Memorandum of Understanding (MoU) on creating a continuous model to synchronize their standards. These achievements mark a significant step forward in enhancing data sharing and utilization across domains, thereby unlocking new opportunities for scientific discovery and advancement.
RESUMEN
AIM: To evaluate the impact of locally adapted targeted implementation interventions on bronchiolitis management through reduction in ineffective investigation and therapies within emergency departments. METHODS: A multi-centred, quality improvement study in four different grades of hospitals in Western Australia that provide paediatric emergency and inpatient care. All hospitals incorporated an adapted implementation intervention package for infants under 1 year with bronchiolitis. The proportion whose care complied with guideline recommendations to not receive investigations and therapies of minimal benefit were compared to pre-intervention care in a previous bronchiolitis season. RESULTS: A total of 457 infants in 2019 (pre-intervention) and 443 in 2021 (post-intervention) were included, with mean age of 5.6 months (SD 3.2, 2019; SD 3.0, 2021). In 2019, compliance was 78.1% versus 85.6% in 2021, RD 7.4 (95% CI -0.6; 15.5). The strongest evidence was reduced salbutamol use (compliance improvement: 88.6% to 95.7%, RD 7.1 95% CI (1.7; 12.4)). Hospitals initially at <80% compliance demonstrated greatest improvements (Hospital 2: 95 (78.5%) to 108 (90.8%) RD 12.2 95% CI (3.3; 21.2); Hospital 3: 67 (62.6%) to 63 (76.8%) RD 14.2 95% CI (1.3; 27.2)). CONCLUSION: Targeted site-adapted implementation interventions resulted in improvement in compliance with guideline recommendations, particularly for those hospitals with initial low compliance. Maximising benefits through guidance on how to adapt and effectively use interventions will enhance sustainable practice change.
Asunto(s)
Bronquiolitis , Adhesión a Directriz , Niño , Humanos , Lactante , Bronquiolitis/terapia , Servicio de Urgencia en Hospital , Hospitalización , Hospitales , Mejoramiento de la CalidadRESUMEN
Organic semiconductors have many desirable properties including improved manufacturing and flexible mechanical properties. Due to the vastness of chemical space, it is essential to efficiently explore chemical space when designing new materials, including through the use of generative techniques. New generative machine learning methods for molecular design continue to be published in the literature at a significant rate but successfully adapting methods to new chemistry and problem domains remains difficult. These challenges necessitate continual method evaluation to probe method viability for use in alternative applications not covered in the original works. In continuation of our previous work, we evaluate four additional machine-learning-based de novo methods for generating molecules with high predicted hole mobility for use in semiconductor applications. The four generative methods evaluated here are (1) Molecule Deep Q-Networks (MolDQN), which utilizes Deep-Q learning to directly optimize molecular structure graphs for desired properties instead of generating SMILES, (2) Graph-based Genetic Algorithm (GraphGA), which uses a genetic algorithm for optimization where crossovers and mutations are defined in terms of RDKit's reaction SMILES, (3) Generative Tensorial Reinforcement Learning (GENTRL), which is a variational autoencoder (VAE) with a learned prior distribution and optimized using reinforcement learning, and (4) Monte Carlo tree search exploration of chemical space in conjunction with a recurrent neural network (RNN) decoder (ChemTS). The generated molecules were evaluated using density functional theory (DFT) and we discovered better performing molecules with the GraphGA method compared to the other approaches.
RESUMEN
BACKGROUND: Diagnosing urinary tract infections (UTIs) in children in the emergency department (ED) is challenging due to the variable clinical presentations and difficulties in obtaining a urine sample free from contamination. Clinicians need to weigh a range of observations to make timely diagnostic and management decisions, a difficult task to achieve without support due to the complex interactions among relevant factors. Directed acyclic graphs (DAG) and causal Bayesian networks (BN) offer a way to explicitly outline the underlying disease, contamination and diagnostic processes, and to further make quantitative inference on the event of interest thus serving as a tool for decision support. METHODS: We prospectively collected data on children present to ED with suspected UTIs. Through knowledge elicitation workshops and one-on-one meetings, a DAG was co-developed with clinical domain experts (the Expert DAG) to describe the causal relationships among variables relevant to paediatric UTIs. The Expert DAG was combined with prospective data and further domain knowledge to inform the development of an application-oriented BN (the Applied BN), designed to support the diagnosis of UTI. We assessed the performance of the Applied BN using quantitative and qualitative methods. RESULTS: We summarised patient background, clinical and laboratory characteristics of 431 episodes of suspected UTIs enrolled from May 2019 to November 2020. The Expert DAG was presented with a narrative description, elucidating how infection, specimen contamination and management pathways causally interact to form the complex picture of paediatric UTIs. Parameterised using prospective data and expert-elicited parameters, the Applied BN achieved an excellent and stable performance in predicting Escherichia coli culture results, with a mean area under the receiver operating characteristic curve of 0.86 and a mean log loss of 0.48 based on 10-fold cross-validation. The BN predictions were reviewed via a validation workshop, and we illustrate how they can be presented for decision support using three hypothetical clinical scenarios. CONCLUSION: Causal BNs created from both expert knowledge and data can integrate case-specific information to provide individual decision support during the diagnosis of paediatric UTIs in ED. The model aids the interpretation of culture results and the diagnosis of UTIs, promising the prospect of improved patient care and judicious use of antibiotics.
Asunto(s)
Infecciones Urinarias , Antibacterianos/uso terapéutico , Teorema de Bayes , Niño , Humanos , Estudios Prospectivos , Curva ROC , Infecciones Urinarias/diagnóstico , Infecciones Urinarias/tratamiento farmacológicoRESUMEN
INTRODUCTION: The objective of this study was to explore the demographic characteristics, disease specifics and outcomes of adult patients with suspected sepsis presenting to a remote Australian emergency department (ED). A retrospective, uninterrupted time series audit of ED patients presenting with suspected sepsis was conducted. A total of 189 remote presentations were reviewed based on the time of clinician identification of sepsis. METHODS: Retrospective cohort analysis was performed for all adult patients with suspected or confirmed sepsis. RESULTS: A majority of patients presenting with sepsis to a remote hospital were Indigenous (61.9%) with a large proportion (34.9%) presenting by ambulance. Median age was 50 years. Indigenous patients (44.7%, 95%CI 34.1-55.9) were more likely to meet the quick Sequential (sepsis-related) Organ Failure Assessment criteria compared to non-Indigenous patients (27.1% 95%CI 16.6-41.0) (p=0.05 95%CI -1.1-34.3) with higher rates of critical care admission (34.2% v 10.4%) (difference 23.8, p=0.003, 95%CI 7.7-37.5). Congruent with previous research, Indigenous status did not confer a difference in sepsis mortality (12.1% v 11.8%, p=0.91). CONCLUSION: Remote Indigenous patients have worse clinical sepsis scores, are more likely to present by ambulance and require skin and soft tissue source control. This cohort has higher lactate values and critical care requirements but similar mortality rates. Improving access to culturally safe medical care could address this disparity.
Asunto(s)
Sepsis , Adulto , Australia/epidemiología , Servicio de Urgencia en Hospital , Mortalidad Hospitalaria , Humanos , Persona de Mediana Edad , Estudios Retrospectivos , Sepsis/diagnóstico , Sepsis/epidemiología , Sepsis/terapiaRESUMEN
Materials exhibiting higher mobilities than conventional organic semiconducting materials such as fullerenes and fused thiophenes are in high demand for applications in printed electronics. To discover new molecules in the heteroacene family that might show improved hole mobility, three de novo design methods were applied. Machine learning (ML) models were generated based on previously calculated hole reorganization energies of a quarter million examples of heteroacenes, where the energies were calculated by applying density functional theory (DFT) and a massive cloud computing environment. The three generative methods applied were (1) the continuous space method, where molecular structures are converted into continuous variables by applying the variational autoencoder/decoder technique; (2) the method based on reinforcement learning of SMILES strings (the REINVENT method); and (3) the junction tree variational autoencoder method that directly generates molecular graphs. Among the three methods, the second and third methods succeeded in obtaining chemical structures whose DFT-calculated hole reorganization energy was lower than the lowest energy in the training dataset. This suggests that an extrapolative materials design protocol can be developed by applying generative modeling to a quantitative structure-property relationship (QSPR) utility function.
RESUMEN
Petroleum hydrocarbons can be discharged into the marine environment during offshore oil and gas production or as a result of oil spills, with potential impacts on marine organisms. Ecotoxicological assay durations (typically 24-96 h) used to characterize risks to exposed organisms may not always reflect realistic environmental exposure durations in a high-energy offshore environment where hydrocarbons are mixed and diluted rapidly in the water column. To investigate this, we adapted 3 sensitive toxicity tests to incorporate a short-term pulse exposure to 3 petroleum-based products: a produced water, the water-accommodated fraction (WAF) of a condensate, and a crude oil WAF. We measured 48-h mobility of the copepod Acartia sinjiensis, 72-h larval development of the sea urchin Heliocidaris tuberculata, and 48-h embryo survival and deformities of yellowtail kingfish Seriola lalandi, after exposure to a dilution series of each of the 3 products for 2, 4 to 12, and 24 h and for the standard duration of each toxicity test (continuous exposure). Effects on copepod survival and sea urchin larval development were significantly reduced in short-term exposures to produced water and WAFs compared to continuous exposures. Fish embryos, however, showed an increased frequency of deformities at elevated concentrations regardless of exposure duration, although there was a trend toward increased severity of deformities with continuous exposure. The results demonstrate how exposure duration alters toxic response and how incorporating relevant exposure duration to contaminants into toxicity testing may aid interpretation of more realistic effects (and hence an additional line of evidence in risk assessment) in the receiving environment. Environ Toxicol Chem 2021;40:2587-2600. © 2021 CSIRO. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.
Asunto(s)
Copépodos , Contaminación por Petróleo , Petróleo , Hidrocarburos Policíclicos Aromáticos , Contaminantes Químicos del Agua , Animales , Organismos Acuáticos , Peces , Hidrocarburos , Petróleo/análisis , Petróleo/toxicidad , Hidrocarburos Policíclicos Aromáticos/toxicidad , Erizos de Mar , Pruebas de Toxicidad , Agua/química , Contaminantes Químicos del Agua/análisisRESUMEN
The increasing availability of digitized biodiversity data worldwide, provided by an increasing number of institutions and researchers, and the growing use of those data for a variety of purposes have raised concerns related to the "fitness for use" of such data and the impact of data quality (DQ) on the outcomes of analyses, reports, and decisions. A consistent approach to assess and manage data quality is currently critical for biodiversity data users. However, achieving this goal has been particularly challenging because of idiosyncrasies inherent in the concept of quality. DQ assessment and management cannot be performed if we have not clearly established the quality needs from a data user's standpoint. This paper defines a formal conceptual framework to support the biodiversity informatics community allowing for the description of the meaning of "fitness for use" from a data user's perspective in a common and standardized manner. This proposed framework defines nine concepts organized into three classes: DQ Needs, DQ Solutions and DQ Report. The framework is intended to formalize human thinking into well-defined components to make it possible to share and reuse concepts of DQ needs, solutions and reports in a common way among user communities. With this framework, we establish a common ground for the collaborative development of solutions for DQ assessment and management based on data fitness for use principles. To validate the framework, we present a proof of concept based on a case study at the Museum of Comparative Zoology of Harvard University. In future work, we will use the framework to engage the biodiversity informatics community to formalize and share DQ profiles related to DQ needs across the community.
Asunto(s)
Biodiversidad , Biología ComputacionalRESUMEN
With the rapidly growing number of data publishers, the process of harvesting and indexing information to offer advanced search and discovery becomes a critical bottleneck in globally distributed primary biodiversity data infrastructures. The Global Biodiversity Information Facility (GBIF) implemented a Harvesting and Indexing Toolkit (HIT), which largely automates data harvesting activities for hundreds of collection and observational data providers. The team of the Botanic Garden and Botanical Museum Berlin-Dahlem has extended this well-established system with a range of additional functions, including improved processing of multiple taxon identifications, the ability to represent associations between specimen and observation units, new data quality control and new reporting capabilities. The open source software B-HIT can be freely installed and used for setting up thematic networks serving the demands of particular user groups.
Asunto(s)
Biodiversidad , Programas Informáticos , Indización y Redacción de Resúmenes , Clasificación , Minería de Datos , Bases de Datos Factuales , InternetRESUMEN
In 2010, the international community, under the auspices of the Convention on Biological Diversity, agreed on 20 biodiversity-related "Aichi Targets" to be achieved within a decade. We provide a comprehensive mid-term assessment of progress toward these global targets using 55 indicator data sets. We projected indicator trends to 2020 using an adaptive statistical framework that incorporated the specific properties of individual time series. On current trajectories, results suggest that despite accelerating policy and management responses to the biodiversity crisis, the impacts of these efforts are unlikely to be reflected in improved trends in the state of biodiversity by 2020. We highlight areas of societal endeavor requiring additional efforts to achieve the Aichi Targets, and provide a baseline against which to assess future progress.
Asunto(s)
Biodiversidad , Conservación de los Recursos Naturales , Extinción BiológicaRESUMEN
The planet is experiencing an ongoing global biodiversity crisis. Measuring the magnitude and rate of change more effectively requires access to organized, easily discoverable, and digitally-formatted biodiversity data, both legacy and new, from across the globe. Assembling this coherent digital representation of biodiversity requires the integration of data that have historically been analog, dispersed, and heterogeneous. The Integrated Publishing Toolkit (IPT) is a software package developed to support biodiversity dataset publication in a common format. The IPT's two primary functions are to 1) encode existing species occurrence datasets and checklists, such as records from natural history collections or observations, in the Darwin Core standard to enhance interoperability of data, and 2) publish and archive data and metadata for broad use in a Darwin Core Archive, a set of files following a standard format. Here we discuss the key need for the IPT, how it has developed in response to community input, and how it continues to evolve to streamline and enhance the interoperability, discoverability, and mobilization of new data types beyond basic Darwin Core records. We close with a discussion how IPT has impacted the biodiversity research community, how it enhances data publishing in more traditional journal venues, along with new features implemented in the latest version of the IPT, and future plans for more enhancements.
Asunto(s)
Biodiversidad , Internet , Edición , Programas InformáticosRESUMEN
Biodiversity data derive from myriad sources stored in various formats on many distinct hardware and software platforms. An essential step towards understanding global patterns of biodiversity is to provide a standardized view of these heterogeneous data sources to improve interoperability. Fundamental to this advance are definitions of common terms. This paper describes the evolution and development of Darwin Core, a data standard for publishing and integrating biodiversity information. We focus on the categories of terms that define the standard, differences between simple and relational Darwin Core, how the standard has been implemented, and the community processes that are essential for maintenance and growth of the standard. We present case-study extensions of the Darwin Core into new research communities, including metagenomics and genetic resources. We close by showing how Darwin Core records are integrated to create new knowledge products documenting species distributions and changes due to environmental perturbations.
Asunto(s)
Biodiversidad , Biota , Bases de Datos Factuales/normas , Aptitud Genética/fisiología , Selección Genética , Animales , Recolección de Datos/normas , Ambiente , Evolución Molecular , Aptitud Genética/genética , Guías como Asunto , Humanos , Almacenamiento y Recuperación de la Información/normas , Modelos Biológicos , Estudios de Validación como AsuntoRESUMEN
The concept of semantic tagging and its potential for semantic enhancements to taxonomic papers is outlined and illustrated by four exemplar papers published in the present issue of ZooKeys. The four papers were created in different ways: (i) written in Microsoft Word and submitted as non-tagged manuscript (doi: 10.3897/zookeys.50.504); (ii) generated from Scratchpads and submitted as XML-tagged manuscripts (doi: 10.3897/zookeys.50.505 and doi: 10.3897/zookeys.50.506); (iii) generated from an author's database (doi: 10.3897/zookeys.50.485) and submitted as XML-tagged manuscript. XML tagging and semantic enhancements were implemented during the editorial process of ZooKeys using the Pensoft Mark Up Tool (PMT), specially designed for this purpose. The XML schema used was TaxPub, an extension to the Document Type Definitions (DTD) of the US National Library of Medicine Journal Archiving and Interchange Tag Suite (NLM). The following innovative methods of tagging, layout, publishing and disseminating the content were tested and implemented within the ZooKeys editorial workflow: (1) highly automated, fine-grained XML tagging based on TaxPub; (2) final XML output of the paper validated against the NLM DTD for archiving in PubMedCentral; (3) bibliographic metadata embedded in the PDF through XMP (Extensible Metadata Platform); (4) PDF uploaded after publication to the Biodiversity Heritage Library (BHL); (5) taxon treatments supplied through XML to Plazi; (6) semantically enhanced HTML version of the paper encompassing numerous internal and external links and linkouts, such as: (i) vizualisation of main tag elements within the text (e.g., taxon names, taxon treatments, localities, etc.); (ii) internal cross-linking between paper sections, citations, references, tables, and figures; (iii) mapping of localities listed in the whole paper or within separate taxon treatments; (v) taxon names autotagged, dynamically mapped and linked through the Pensoft Taxon Profile (PTP) to large international database services and indexers such as Global Biodiversity Information Facility (GBIF), National Center for Biotechnology Information (NCBI), Barcode of Life (BOLD), Encyclopedia of Life (EOL), ZooBank, Wikipedia, Wikispecies, Wikimedia, and others; (vi) GenBank accession numbers autotagged and linked to NCBI; (vii) external links of taxon names to references in PubMed, Google Scholar, Biodiversity Heritage Library and other sources. With the launching of the working example, ZooKeys becomes the first taxonomic journal to provide a complete XML-based editorial, publication and dissemination workflow implemented as a routine and cost-efficient practice. It is anticipated that XML-based workflow will also soon be implemented in botany through PhytoKeys, a forthcoming partner journal of ZooKeys. The semantic markup and enhancements are expected to greatly extend and accelerate the way taxonomic information is published, disseminated and used.
RESUMEN
RNA-binding proteins play many essential roles in the regulation of gene expression in the cell. Despite the significant increase in the number of structures for RNA-protein complexes in the last few years, the molecular basis of specificity remains unclear even for the best-studied protein families. We have developed a distance and orientation-dependent hydrogen-bonding potential based on the statistical analysis of hydrogen-bonding geometries that are observed in high-resolution crystal structures of protein-DNA and protein-RNA complexes. We observe very strong geometrical preferences that reflect significant energetic constraints on the relative placement of hydrogen-bonding atom pairs at protein-nucleic acid interfaces. A scoring function based on the hydrogen-bonding potential discriminates native protein-RNA structures from incorrectly docked decoys with remarkable predictive power. By incorporating the new hydrogen-bonding potential into a physical model of protein-RNA interfaces with full atom representation, we were able to recover native amino acids at protein-RNA interfaces.
Asunto(s)
Biología Computacional/métodos , Modelos Moleculares , Proteínas de Unión al ARN/química , Secuencia de Aminoácidos , Sitios de Unión , Proteínas de Unión al ADN/química , Proteínas de Unión al ADN/metabolismo , Interpretación Estadística de Datos , Bases de Datos de Proteínas , Enlace de Hidrógeno , Estructura Molecular , Unión Proteica , ARN/química , ARN/metabolismo , Proteínas de Unión al ARN/metabolismoRESUMEN
We use the Rosetta de novo structure prediction method to produce three-dimensional structure models for all Pfam-A sequence families with average length under 150 residues and no link to any protein of known structure. To estimate the reliability of the predictions, the method was calibrated on 131 proteins of known structure. For approximately 60% of the proteins one of the top five models was correctly predicted for 50 or more residues, and for approximately 35%, the correct SCOP superfamily was identified in a structure-based search of the Protein Data Bank using one of the models. This performance is consistent with results from the fourth critical assessment of structure prediction (CASP4). Correct and incorrect predictions could be partially distinguished using a confidence function based on a combination of simulation convergence, protein length and the similarity of a given structure prediction to known protein structures. While the limited accuracy and reliability of the method precludes definitive conclusions, the Pfam models provide the only tertiary structure information available for the 12% of publicly available sequences represented by these large protein families.