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Gene expression is tightly controlled during animal development to allow the formation of specialized cell types. Our understanding of how animals evolved this exquisite regulatory control remains elusive, but evidence suggests that changes in chromatin-based mechanisms may have contributed. To investigate this possibility, here we examine chromatin-based gene regulatory features in the closest relatives of animals, choanoflagellates. Using Salpingoeca rosetta as a model system, we examined chromatin accessibility and histone modifications at the genome scale and compared these features to gene expression. We first observed that accessible regions of chromatin are primarily associated with gene promoters and found no evidence of distal gene regulatory elements resembling the enhancers that animals deploy to regulate developmental gene expression. Remarkably, a histone modification deposited by polycomb repressive complex 2, histone H3 lysine 27 trimethylation (H3K27me3), appeared to function similarly in S. rosetta to its role in animals, because this modification decorated genes with cell type-specific expression. Additionally, H3K27me3 marked transposons, retaining what appears to be an ancestral role in regulating these elements. We further uncovered a putative new bivalent chromatin state at cell type-specific genes that consists of H3K27me3 and histone H3 lysine 4 mono-methylation (H3K4me1). Together, our discoveries support the scenario that gene-associated histone modification states that underpin development emerged before the evolution of animal multicellularity.
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BACKGROUND: Sedentary behavior (SB) is one of the largest contributing factors increasing the risk of developing noncommunicable diseases, including cardiovascular disease and type 2 diabetes. Guidelines from the World Health Organization for physical activity suggest the substitution of SB with light physical activity. The Apple Watch contains a health metric known as the stand hour (SH). The SH is intended to record standing with movement for at least 1 minute per hour; however, the activity measured during the determination of the SH is unclear. OBJECTIVE: In this cross-sectional study, we analyzed the algorithm used to determine time spent standing per hour. To do this, we investigated activity measurements also recorded on Apple Watches that influence the recording of an SH. We also aimed to estimate the values of any significant SH predictors in the recording of a SH. METHODS: The cross-sectional study used anonymized data obtained in August 2022 from 20 healthy individuals gathered via convenience sampling. Apple Watch data were extracted from the Apple Health app through the use of a third-party app. Appropriate statistical models were fitted to analyze SH predictors. RESULTS: Our findings show that active energy (AE) and step count (SC) measurements influence the recording of an SH. Comparing when an SH is recorded with when an SH is not recorded, we found a significant difference in the mean and median AE and SC. Above a threshold of 97.5 steps or 100 kJ of energy, it became much more likely that an SH would be recorded when each predictor was analyzed as a separate entity. CONCLUSIONS: The findings of this study reveal the pivotal role of AE and SC measurements in the algorithm underlying the SH recording; however, our findings also suggest that a recording of an SH is influenced by more than one factor. Irrespective of the internal validity of the SH metric, it is representative of light physical activity and might, therefore, have use in encouraging individuals through various means, for example, notifications, to reduce their levels of SB.
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We uncovered an interaction between a choanoflagellate and alga, in which porphyran, a polysaccharide produced by the red alga Porphyra umbilicalis, induces multicellular development in the choanoflagellate Salpingoeca rosetta. We first noticed this possible interaction when we tested the growth of S. rosetta in media that was steeped with P. umbilicalis as a nutritional source. Under those conditions, S. rosetta formed multicellular rosette colonies even in the absence of any bacterial species that can induce rosette development. In biochemical purifications, we identified porphyran, a extracellular polysaccharide produced by red algae, as the rosette inducing factor The response of S. rosetta to porphyran provides a biochemical insight for associations between choanoflagellates and algae that have been observed since the earliest descriptions of choanoflagellates. Moreover, this work provides complementary evidence to ecological and geochemical studies that show the profound impact algae have exerted on eukaryotes and their evolution, including a rise in algal productivity that coincided with the origin of animals, the closest living relatives of choanoflagellates.
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Ecological similarity plays an important role in biotic interactions. Increased body size similarity of competing species, for example, increases the strength of their biotic interactions. Body sizes of many exothermic species are forecast to be altered under global warming, mediating shifts in existing trophic interactions among species, in particular for species with different thermal niches. Temperate rocky reefs along the southeast coast of Australia are located in a climate warming hotspot and now house a mixture of temperate native fish species and poleward range-extending tropical fishes (vagrants), creating novel species assemblages. Here, we studied the relationship between body size similarity and trophic overlap between individual temperate native and tropical vagrant fishes. Dietary niche overlap between vagrant and native fish species increased as their body sizes converged, based on both stomach content composition (short-term diet), stable isotope analyses (integrated long-term diet) and similarity in consumed prey sizes. We conclude that the warming-induced faster growth rates of tropical range-extending fish species at their cool water ranges will continue to converge their body size towards and strengthen their degree of trophic interactions and dietary overlap with co-occurring native temperate species under increasing ocean warming. The strengthening of these novel competitive interactions is likely to drive changes to temperate food web structures and reshuffle existing species community structures.
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Tamanho Corporal , Mudança Climática , Peixes , Cadeia Alimentar , Animais , Peixes/fisiologia , Dieta/veterinária , Conteúdo Gastrointestinal , AustráliaRESUMO
AIM: To assess the cost-effectiveness of dapagliflozin in addition to usual care, compared with usual care alone, in a large population of patients with heart failure (HF), spanning the full range of left ventricular ejection fraction (LVEF). METHODS AND RESULTS: Patient-level data were pooled from HF trials (DAPA-HF, DELIVER) to generate a population including HF with reduced, mildly reduced and preserved LVEF, to increase statistical power and enable exploration of interactions among LVEF, renal function and N-terminal pro-B-type natriuretic peptide levels, as they are relevant determinants of health status in this population. Survival and HF recurrent event risk equations were derived and applied to a lifetime horizon Markov model with health states defined by Kansas City Cardiomyopathy Questionnaire total symptom score quartiles; costs and utilities were in the UK setting. The base case incremental cost-effectiveness ratio (ICER) was £6470 per quality-adjusted life year (QALY) gained, well below the UK willingness-to-pay (WTP) threshold of £20 000/QALY gained. In interaction sensitivity analyses, the highest ICER was observed for elderly patients with preserved LVEF (£16 624/QALY gained), and ranged to a region of dominance (increased QALYs, decreased costs) for patients with poorer renal function and reduced/mildly reduced LVEF. Results across the patient characteristic interaction plane were mostly between £5000 and £10 000/QALY gained. CONCLUSIONS: Dapagliflozin plus usual care, versus usual care alone, yielded results well below the WTP threshold for the UK across a heterogeneous population of patients with HF including the full spectrum of LVEF, and is likely a cost-effective intervention.
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Compostos Benzidrílicos , Análise Custo-Benefício , Glucosídeos , Insuficiência Cardíaca , Anos de Vida Ajustados por Qualidade de Vida , Volume Sistólico , Humanos , Compostos Benzidrílicos/uso terapêutico , Compostos Benzidrílicos/economia , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/economia , Volume Sistólico/fisiologia , Glucosídeos/uso terapêutico , Glucosídeos/economia , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/economiaRESUMO
Climate-driven species redistributions are facilitated by niche modifications that increase a species's chances of establishment in novel communities. It is well understood how range-extending species adjust individual niche traits when entering novel environments, yet whether modification of ecological niche traits collectively alters the pace of range extensions or contractions remains unknown. We quantified habitat niche, abundance, physiological performance and cellular defence/damage of range-extending coral reef fishes and coexisting local temperate fishes along a 2000 km latitudinal gradient. We also assessed their dietary and behavioural niches, and establishment potential, to understand whether ecological generalism facilitates successful range extension of coral reef fishes. The coral reef fish that increased all ecological niches, showed stronger establishment, increased physiological performance and cellular damage, but decreased cellular defence at their cold-range edge, whereas tropical species that showed unmodified ecological niches showed lower establishment. One temperate species showed decreased abundance, habitat niche width and body condition, but increased cellular defence, cellular damage and energy reserves at their warm-trailing range, while other temperate species showed contrasting responses. Therefore, ecological generalists might be more successful than ecological specialists during the initial stages of climate change, with increasing future warming strengthening this pattern by physiologically benefitting tropical generalists but disadvantaging temperate specialists.
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Antozoários , Ecossistema , Animais , Recifes de Corais , Peixes/fisiologia , Mudança Climática , Oceanos e MaresRESUMO
This study assessed the otolith (sagittae, lapilli, and asterisci) increment deposition rate in the range-shifting damselfish, A. vaigiensis, using different concentrations of Alizain Red S and evaluated the impact of staining on increment width. Daily increment deposition was verified in all otolith types and presented clearer fluorescent markings in the lapilli and sagittae than the asterisci, with high stain concentration showing the best clarity. Higher stain concentrations were found to decrease increment width, suggesting care is needed when using stained otoliths as a proxy for growth for this species.
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Membrana dos Otólitos , Perciformes , Animais , Coloração e Rotulagem , Corantes , DemografiaRESUMO
Global warming facilitates species range-expansions, leading to novel biological interactions between local and range-expanding species. Little is still known of how such novel interactions modify the performance of interacting species or how these interactions might be altered under climate change. Here, we used an aquarium experiment to investigate the novel ecological interactions between a poleward range-extending coral reef damselfish ("tropical-vagrant") and a local temperate species ("temperate-local") collected from a climate warming hotspot in SE Australia. We measured the effect of novel interactions (isolated vs. paired fish species) on energy expenditure (activity levels, oxidative stress, and antioxidant responses), energy gain (feeding rates), and growth rates of both fish species under present-day (23 °C) and future ocean temperatures (26 °C). Short-term growth rates were faster in both species under novel interactions (paired species), regardless of elevated temperature. Compared to isolated species, activity level, feeding rate and oxidative stress level were also higher in the paired temperate fish but not in the paired tropical fish. The tropical fish showed an increased feeding rate and long-term growth under elevated temperature, irrespective of novel interactions. We conclude that novel ecological interactions under climate change can be an important driver of physiological traits in sympatric tropical and temperate fishes and can mediate critical physiological performance of fishes under ocean warming.
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Recifes de Corais , Peixes , Animais , Peixes/fisiologia , Mudança Climática , Aquecimento Global , Temperatura , Oceanos e MaresRESUMO
This work continues along a visionary path of using Semantic Web standards such as RDF and ShEx to make healthcare data easier to integrate for research and leading-edge patient care. The work extends the ability to use ShEx schemas to validate FHIR RDF data, thereby enhancing the semantic web ecosystem for working with FHIR and non-FHIR data using the same ShEx validation framework. It updates FHIR's ShEx schemas to fix outstanding issues and reflect changes in the definition of FHIR RDF. In addition, it experiments with expressing FHIRPath constraints (which are not captured in the XML or JSON schemas) in ShEx schemas. These extended ShEx schemas were incorporated into the FHIR R5 specification and used to successfully validate FHIR R5 examples that are included with the FHIR specification, revealing several errors in the examples.
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Ecossistema , Registros Eletrônicos de Saúde , Humanos , Atenção à SaúdeRESUMO
Projection models are being increasingly used to manage threatened taxa by estimating their responses to climate change. Sea turtles are particularly susceptible to climate change as they have temperature-dependent sex determination and increased sand temperatures on nesting beaches could result in the 'feminisation' of hatchling sex ratios for some populations. This study modelled likely long-term trends in sand temperatures and hatchling sex ratios at an equatorial nesting site for endangered green turtles (Chelonia mydas) and critically endangered hawksbill turtles (Eretmochelys imbricata). A total of 1078 days of sand temperature data were collected from 28 logger deployments at nest depth between 2018 and 2022 in Papua New Guinea (PNG). Long-term trends in sand temperature were generated from a model using air temperature as an environmental proxy. The influence of rainfall and seasonal variation on sand temperature was also investigated. Between 1960 and 2019, we estimated that sand temperature increased by ~0.6°C and the average hatchling sex ratio was relatively balanced (46.2% female, SD = 10.7). No trends were observed in historical rainfall anomalies and projections indicated no further changes to rainfall until 2100. Therefore, the sex ratio models were unlikely to be influenced by changing rainfall patterns. A relatively balanced sex ratio such as this is starkly different to the extremely female-skewed hatchling sex ratio (>99% female) reported for another Coral Sea nesting site, Raine Island (~850 km West). This PNG nesting site is likely rare in the global context, as it is less threatened by climate-induced feminisation. Although there is no current need for 'cooling' interventions, the mean projected sex ratios for 2020-2100 were estimated 76%-87% female, so future interventions may be required to increase male production. Our use of long-term sand temperature and rainfall trends has advanced our understanding of climate change impacts on sea turtles.
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Tartarugas , Animais , Feminino , Masculino , Temperatura , Tartarugas/fisiologia , Areia , Mudança Climática , Estações do Ano , Razão de MasculinidadeRESUMO
Sustainably managing fisheries requires regular and reliable evaluation of stock status. However, most multispecies reef fisheries around the globe tend to lack research and monitoring capacity, preventing the estimation of sustainable reference points against which stocks can be assessed. Here, combining fish biomass data for >2000 coral reefs, we estimate site-specific sustainable reference points for coral reef fisheries and use these and available catch estimates to assess the status of global coral reef fish stocks. We reveal that >50% of sites and jurisdictions with available information have stocks of conservation concern, having failed at least one fisheries sustainability benchmark. We quantify the trade-offs between biodiversity, fish length, and ecosystem functions relative to key benchmarks and highlight the ecological benefits of increasing sustainability. Our approach yields multispecies sustainable reference points for coral reef fisheries using environmental conditions, a promising means for enhancing the sustainability of the world's coral reef fisheries.
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Recifes de Corais , Pesqueiros , Animais , Benchmarking , Biodiversidade , EcossistemaRESUMO
Cilia allowed our protistan ancestors to sense and explore their environment, avoid predation, and capture bacterial prey.1,2,3 Regulated ciliogenesis was likely critical for early animal evolution,2,4,5,6 and in modern animals, deploying cilia in the right cells at the right time is crucial for development and physiology. Two transcription factors, RFX and FoxJ1, coordinate ciliogenesis in animals7,8,9 but are absent from the genomes of many other ciliated eukaryotes, raising the question of how the regulation of ciliogenesis in animals evolved.10,11 By comparing the genomes of animals with those of their closest living relatives, the choanoflagellates, we found that the genome of their last common ancestor encoded at least three RFX paralogs and a FoxJ1 homolog. Disruption of the RFX homolog cRFXa in the model choanoflagellate Salpingoeca rosetta resulted in delayed cell proliferation and aberrant ciliogenesis, marked by the collapse and resorption of nascent cilia. In cRFXa mutants, ciliogenesis genes and foxJ1 were significantly downregulated. Moreover, the promoters of S. rosetta ciliary genes are enriched for DNA motifs matching those bound by the cRFXa protein in vitro. These findings suggest that an ancestral cRFXa homolog coordinated ciliogenesis in the progenitors of animals and choanoflagellates and that the selective deployment of the RFX regulatory module may have been necessary to differentiate ciliated from non-ciliated cell types during early animal evolution.
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Proteínas de Ligação a DNA , Fatores de Transcrição , Animais , Fatores de Transcrição/metabolismo , Proteínas de Ligação a DNA/metabolismo , Fatores de Transcrição de Fator Regulador X/genética , Fatores de Transcrição de Fator Regulador X/metabolismo , Regulação da Expressão Gênica , Regiões Promotoras Genéticas , Cílios/metabolismo , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismoRESUMO
AIMS: To determine the cost-effectiveness of dapagliflozin, added to usual care, in patients with heart failure (HF) with mildly reduced or preserved ejection fraction for the UK, German and Spanish payers using detailed patient-level data from the Dapagliflozin Evaluation to Improve the LIVEs of Patients with Preserved Ejection Fraction Heart Failure (DELIVER) trial. METHODS AND RESULTS: A lifetime Markov state-transition cohort model was developed. Quartiles of the Kansas City Cardiomyopathy Questionnaire total symptom score (KCCQ-TSS) defined health states and monthly transition count data informed transition probabilities. Multivariable generalized estimating equations captured the incidence of HF hospitalizations and urgent HF visits, while cardiovascular deaths and all-cause mortality were estimated using adjusted parametric survival models. Health state costs were assigned to KCCQ-TSS quartiles (2021 British pound [GBP]/Euro) and patient-reported outcomes were sourced from DELIVER. Future values of costs and effects were discounted according to country-specific rates. In the UK, dapagliflozin treatment was predicted to increase quality-adjusted life years (QALYs) and life-years by 0.231 and 0.354, respectively, and extend the time spent in the best quartile of KCCQ-TSS by 4.2 months. Comparable outcomes were projected for Germany and Spain. The incremental cost-effectiveness ratios were £7761, 9540 and 5343/QALY in the UK, Germany and Spain, respectively. According to regional willingness-to-pay thresholds, 91%, 89% and 92% of simulations in the UK, Germany and Spain, respectively, were cost-effective following probabilistic sensitivity analyses. CONCLUSION: Dapagliflozin, added to usual care, is very likely cost-effective for HF with mildly reduced or preserved ejection fraction in several European countries.
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Insuficiência Cardíaca , Humanos , Insuficiência Cardíaca/diagnóstico , Análise Custo-Benefício , Compostos Benzidrílicos/uso terapêutico , Glucosídeos/uso terapêutico , Volume SistólicoRESUMO
A signature feature of the animal kingdom is the presence of epithelia: sheets of polarized cells that both insulate the organism from its environment and mediate interactions with it. Epithelial cells display a marked apico-basal polarity, which is highly conserved across the animal kingdom, both in terms of morphology and of molecular regulators. How did this architecture first evolve? Although the last eukaryotic common ancestor almost certainly possessed a simple form of apico-basal polarity (marked by the presence of one or several flagella at a single cellular pole), comparative genomics and evolutionary cell biology reveal that the polarity regulators of animal epithelial cells have a surprisingly complex and stepwise evolutionary history. Here, we retrace their evolutionary assembly. We suggest that the "polarity network" that polarized animal epithelial cells evolved by integration of initially independent cellular modules that evolved at distinct steps of our evolutionary ancestry. The first module dates back to the last common ancestor of animals and amoebozoans and involved Par1, extracellular matrix proteins, and the integrin-mediated adhesion complex. Other regulators, such as Cdc42, Dlg, Par6 and cadherins evolved in ancient unicellular opisthokonts, and might have first been involved in F-actin remodeling and filopodial dynamics. Finally, the bulk of "polarity proteins" as well as specialized adhesion complexes evolved in the metazoan stem-line, in concert with the newly evolved intercellular junctional belts. Thus, the polarized architecture of epithelia can be understood as a palimpsest of components of distinct histories and ancestral functions, which have become tightly integrated in animal tissues.
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Polaridade Celular , Células Epiteliais , Animais , Polaridade Celular/genética , Epitélio/metabolismo , Caderinas/metabolismo , Actinas/metabolismoRESUMO
Walking gait data acquired with force platforms may be used for person re-identification (re-ID) in various authentication, surveillance, and forensics applications. Current force platform-based re-ID systems classify a fixed set of identities (IDs), which presents a problem when IDs are added or removed from the database. We formulated force platform-based re-ID as a deep metric learning (DML) task, whereby a deep neural network learns a feature representation that can be compared between inputs using a distance metric. The force platform dataset used in this study is one of the largest and the most comprehensive of its kind, containing 193 IDs with significant variations in clothing, footwear, walking speed, and time between trials. Several DML model architectures were evaluated in a challenging setting where none of the IDs were seen during training (i.e., zero-shot re-ID) and there was only one prior sample per ID to compare with each query sample. The best architecture was 85% accurate in this setting, though an analysis of changes in walking speed and footwear between measurement instances revealed that accuracy was 28% higher on same-speed, same-footwear comparisons, compared to cross-speed, cross-footwear comparisons. These results demonstrate the potential of DML algorithms for zero-shot re-ID using force platform data, and highlight challenging cases.
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Climate change can directly (physiology) and indirectly (novel species interactions) modify species responses to novel environmental conditions during the initial stages of range shifts. Whilst the effects of climate warming on tropical species at their cold-water leading ranges are well-established, it remains unclear how future seasonal temperature changes, ocean acidification, and novel species interactions will alter the physiology of range-shifting tropical and competing temperate fish in recipient ecosystems. Here we used a laboratory experiment to examine how ocean acidification, future summer vs winter temperatures, and novel species interactions could affect the physiology of competing temperate and range-extending coral reef fish to determine potential range extension outcomes. In future winters (20 °C + elevated pCO2) coral reef fish at their cold-water leading edges showed reduced physiological performance (lower body condition and cellular defence, and higher oxidative damage) compared to present-day summer (23 °C + control pCO2) and future summer conditions (26 °C + elevated pCO2). However, they showed a compensatory effect in future winters through increased long-term energy storage. Contrastingly, co-shoaling temperate fish showed higher oxidative damage, and reduced short-term energy storage and cellular defence in future summer than in future winter conditions at their warm-trailing edges. However, temperate fish benefitted from novel shoaling interactions and showed higher body condition and short-term energy storage when shoaling with coral reef fish compared to same-species shoaling. We conclude that whilst during future summers, ocean warming will likely benefit coral reef fishes extending their ranges, future winter conditions may still reduce coral reef fish physiological functioning, and may therefore slow their establishment at higher latitudes. In contrast, temperate fish species benefit from co-shoaling with smaller-sized tropical fishes, but this benefit may dissipate due to their reduced physiological functioning under future summer temperatures and increasing body sizes of co-shoaling tropical species.
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Recifes de Corais , Ecossistema , Animais , Temperatura , Água , Concentração de Íons de Hidrogênio , Acidificação dos Oceanos , Estações do Ano , Água do Mar , Mudança Climática , Peixes/fisiologiaRESUMO
The public's trust in the science of avoiding unhealthy weight depends on a radical reform of the design and execution of weight loss programmes and their clinical trials. This Perspective reiterates the longstanding argument for measuring the effectiveness of each component of an intervention on obesity. Body energy content change results from a difference in rates between input and output. These rates are determined by the frequencies of specific patterns of dietary behaviour, physical activity and thermal comfort, plus the cost of resting metabolism. Since fat-free mass changes alongside fat mass, the amount of change in weight from a change in the frequency of a behaviour pattern comes to an asymptote. That step change in weight per unit of behaviour change is measured by regression from the change in frequency of the behaviour that has been maintained from baseline to follow-up. For hard evidence, weight loss programme participants' own words must be used to specify behaviour. In RCTs of multiple-component programmes, sequences of the behaviour patterns to be changed are randomised among groups. The resulting evidence on effective slimming practices can be delivered directly into therapeutic services and public health interventions for the culture investigated.
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Obesidade , Programas de Redução de Peso , Humanos , Obesidade/terapia , Exercício Físico , Redução de PesoRESUMO
Bacterial catabolic pathways have considerable potential as industrial biocatalysts for the valorization of lignin, a major component of plant-derived biomass. Here, we describe a pathway responsible for the catabolism of acetovanillone, a major component of several industrial lignin streams. Rhodococcus rhodochrous GD02 was previously isolated for growth on acetovanillone. A high-quality genome sequence of GD02 was generated. Transcriptomic analyses revealed a cluster of eight genes up-regulated during growth on acetovanillone and 4-hydroxyacetophenone, as well as a two-gene cluster up-regulated during growth on acetophenone. Bioinformatic analyses predicted that the hydroxyphenylethanone (Hpe) pathway proceeds via phosphorylation and carboxylation, before ß-elimination yields vanillate from acetovanillone or 4-hydroxybenzoate from 4-hydroxyacetophenone. Consistent with this prediction, the kinase, HpeHI, phosphorylated acetovanillone and 4-hydroxyacetophenone. Furthermore, HpeCBA, a biotin-dependent enzyme, catalyzed the ATP-dependent carboxylation of 4-phospho-acetovanillone but not acetovanillone. The carboxylase's specificity for 4-phospho-acetophenone (kcat/KM = 34 ± 2 mM-1 s-1) was approximately an order of magnitude higher than for 4-phospho-acetovanillone. HpeD catalyzed the efficient dephosphorylation of the carboxylated products. GD02 grew on a preparation of pine lignin produced by oxidative catalytic fractionation, depleting all of the acetovanillone, vanillin, and vanillate. Genomic and metagenomic searches indicated that the Hpe pathway occurs in a relatively small number of bacteria. This study facilitates the design of bacterial strains for biocatalytic applications by identifying a pathway for the degradation of acetovanillone.
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Biotina , Lignina , Lignina/metabolismo , Acetofenonas , Trifosfato de AdenosinaRESUMO
BACKGROUND: Knowledge graphs (KGs) play a key role to enable explainable artificial intelligence (AI) applications in healthcare. Constructing clinical knowledge graphs (CKGs) against heterogeneous electronic health records (EHRs) has been desired by the research and healthcare AI communities. From the standardization perspective, community-based standards such as the Fast Healthcare Interoperability Resources (FHIR) and the Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM) are increasingly used to represent and standardize EHR data for clinical data analytics, however, the potential of such a standard on building CKG has not been well investigated. OBJECTIVE: To develop and evaluate methods and tools that expose the OMOP CDM-based clinical data repositories into virtual clinical KGs that are compliant with FHIR Resource Description Framework (RDF) specification. METHODS: We developed a system called FHIR-Ontop-OMOP to generate virtual clinical KGs from the OMOP relational databases. We leveraged an OMOP CDM-based Medical Information Mart for Intensive Care (MIMIC-III) data repository to evaluate the FHIR-Ontop-OMOP system in terms of the faithfulness of data transformation and the conformance of the generated CKGs to the FHIR RDF specification. RESULTS: A beta version of the system has been released. A total of more than 100 data element mappings from 11 OMOP CDM clinical data, health system and vocabulary tables were implemented in the system, covering 11 FHIR resources. The generated virtual CKG from MIMIC-III contains 46,520 instances of FHIR Patient, 716,595 instances of Condition, 1,063,525 instances of Procedure, 24,934,751 instances of MedicationStatement, 365,181,104 instances of Observations, and 4,779,672 instances of CodeableConcept. Patient counts identified by five pairs of SQL (over the MIMIC database) and SPARQL (over the virtual CKG) queries were identical, ensuring the faithfulness of the data transformation. Generated CKG in RDF triples for 100 patients were fully conformant with the FHIR RDF specification. CONCLUSION: The FHIR-Ontop-OMOP system can expose OMOP database as a FHIR-compliant RDF graph. It provides a meaningful use case demonstrating the potentials that can be enabled by the interoperability between FHIR and OMOP CDM. Generated clinical KGs in FHIR RDF provide a semantic foundation to enable explainable AI applications in healthcare.
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Inteligência Artificial , Reconhecimento Automatizado de Padrão , Data Warehousing , Atenção à Saúde , Registros Eletrônicos de Saúde , HumanosRESUMO
The implications of logger accuracy and precision are rarely considered prior to their application in many ecological studies. We assessed the accuracy and precision of three temperature data loggers widely used in ecological studies (Hobo®, iButton® and TinyTag®). Accuracy was highest in TinyTags (95% of readings were within 0.23°C of the true temperature) and lowest in HOBOs and iButtons (95% of were readings within 0.43°C and 0.49°C of the true temperature, respectively). The precision (standard deviation of the repeat measurements) was greatest in TinyTags (0.04°C), followed by iButtons (0.17°C) and then HOBOs (0.22°C). As a case study, we then considered how modelled estimates of sea turtle hatchling sex ratios (derived from temperature), could vary as a function of logger accuracy. For example, at 29°C when the mean sex ratio derived was 0.47 female, the sex ratio estimate from a single logger could vary between 0.40 and 0.50 for TinyTags and 0.29 and 0.56 for both HOBOs and iButtons. Our results suggest that these temperature loggers can provide reliable descriptions of sand temperature if they are not over-interpreted. Logger accuracy must be considered in future ecological studies in which temperature thresholds are important.