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1.
Commun Biol ; 4(1): 1070, 2021 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-34522000

RESUMO

G protein-coupled receptors (GPCRs) are notoriously difficult to detect in native tissues. In an effort to resolve this problem, we have developed a novel mouse model by fusing the hemagglutinin (HA)-epitope tag sequence to the amino-terminus of the µ-opioid receptor (MOP). Although HA-MOP knock-in mice exhibit reduced receptor expression, we found that this approach allowed for highly efficient immunodetection of low abundant GPCR targets. We also show that the HA-tag facilitates both high-resolution imaging and immunoisolation of MOP. Mass spectrometry (MS) confirmed post-translational modifications, most notably agonist-selective phosphorylation of carboxyl-terminal serine and threonine residues. MS also unequivocally identified the carboxyl-terminal 387LENLEAETAPLP398 motif, which is part of the canonical MOP sequence. Unexpectedly, MS analysis of brain lysates failed to detect any of the 15 MOP isoforms that have been proposed to arise from alternative splicing of the MOP carboxyl-terminus. For quantitative analysis, we performed multiple successive rounds of immunodepletion using the well-characterized rabbit monoclonal antibody UMB-3 that selectively detects the 387LENLEAETAPLP398 motif. We found that >98% of HA-tagged MOP contain the UMB-3 epitope indicating that virtually all MOP expressed in the mouse brain exhibit the canonical amino acid sequence.

2.
Chembiochem ; 2021 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-34547164

RESUMO

The butterfly Heliconius erato occurs in various mimetic morphs. The male clasper scent gland releases an anti-aphrodisiac pheromone and additionally contains a complex mixture of up to 350 components, varying between individuals. In 114 samples of five different mimicry groups and their hybrids 750 different compounds were detected by gas chromatography/mass spectrometry (GC/MS). Many unknown components occurred, which were identified using their mass spectra, gas chromatography/infrared spectroscopy (GC/IR)-analyses, derivatization, and synthesis. Key compounds proved to be various esters of 3-oxohexan-1-ol and (Z)-3-hexen-1-ol with (S)-2,3-dihydrofarnesoic acid, accompanied by a large variety of other esters with longer terpene acids, fatty acids, and various alcohols. In addition, linear terpenes with up to seven uniformly connected isoprene units occur, e. g. farnesylfarnesol. A large number of the compounds have not been reported before from nature. Discriminant analyses of principal components of the gland contents showed that the iridescent mimicry group differs strongly from the other, mostly also separated, mimicry groups. Comparison with data from other species indicated that Heliconius recruits different biosynthetic pathways in a species-specific manner for semiochemical formation.

3.
Ger Med Sci ; 19: Doc11, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34539301

RESUMO

Background: The study aimed to assess the mental well-being of healthcare professionals at a German department of anesthesiology and critical care with a specialized ICU for treatment of COVID-19 patients during the first two peaks of the 2020 pandemic, and identifying risk and protective factors. Methods: A single-center longitudinal, online-based survey was conducted in healthcare workers from a department of anesthesiology and critical care in Bavaria, the most affected federal state in Germany at the time of assessment. Validated scores for depression, anxiety, somatic disorders, burnout, resilience, and self-management were used and complemented by questions about perceived COVID-19-related stressors. In parallel, patient characteristics in the ICU were collected. Results: 24 and 23 critically ill COVID-19 patients were treated during both observation periods in April/May and November/December 2020, respectively. 87.5% and 78.2% of patients had moderate to severe acute respiratory distress syndrome. From March 6, 2020 onwards, the hospital had switched to a command and control-based hospital incident command system (HICS) and increased work forces. Point prevalence of depression-like symptoms (13.6% and 12.8%) and burnout (21.6% and 17.4%) in the department's healthcare professionals was high. Exposure to SARS-CoV-2 did not increase psychological burden. Consequences of the lockdown were rated as highly distressing by a majority of all ICU personnel. High self-reported trait resilience was protective against signs of depression, generalized anxiety, and burnout. Conclusions: During the pandemic, healthcare professionals have been suffering from increased psychological distress compared to reference data for both the general population and ICU personnel. General effects of the lockdown appear more relevant than actual COVID-19 patient contact. High trait resilience has a protective effect, yet vulnerable individuals may require specific support. Prevention against potential after effects of the lockdown, and in particular measures allowing to avoid another lockdown, appear warranted.


Assuntos
Serviço Hospitalar de Anestesia , COVID-19/terapia , Cuidados Críticos , Pessoal de Saúde/psicologia , Saúde Mental , Adulto , COVID-19/epidemiologia , Feminino , Alemanha/epidemiologia , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Pandemias , SARS-CoV-2 , Inquéritos e Questionários
4.
Naturwissenschaften ; 108(5): 38, 2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34448943

RESUMO

Chemical communication plays a fundamental role in many aspects of an animal's life from assessing habitat quality to finding mating partners. Behavioural observations show that chemical communication likewise plays an important role in spiders, but the contexts and the substances involved are little explored. Here, we investigate the chemical communication in the garden cross spider Araneus diadematus (Clerck, 1757) between and within the sexes. Using choice trials, we demonstrate that males are attracted to odours of adult females, but not to those of subadult females. Our data further suggest that adult females avoid odours of conspecific adult females, possibly in order to reduce reproductive competition with other females. Cuticle and silk extracts as well as headspace samples of subadult and adult virgin females were analysed via GC-MS. Available candidate compounds for the female sex pheromone were tested via electroantennography on palps (electropalpography) of adult virgin females and on females in behavioural trials. We propose sulcatone (6-methyl-5-hepten-2-one) as a candidate substance for the female volatile pheromone and several long-chained alkanes and alcohols as candidates for contact pheromones. Apart from demonstrating that attraction of males to females depends on the latter's developmental stage, our study suggests that pheromones can also play an important role between females, an aspect that requires further attention.

5.
Biochim Biophys Acta Gene Regul Mech ; 1864(10): 194745, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34389511

RESUMO

The Sequence Ontology (SO) is a structured, controlled vocabulary that provides terms and definitions for genomic annotation. The Gene Regulation Ensemble Effort for the Knowledge Commons (GREEKC) initiative has gathered input from many groups of researchers, including the SO, the Gene Ontology (GO), and gene regulation experts, with the goal of curating information about how gene expression is regulated at the molecular level. Here we discuss recent updates to the SO reflecting current knowledge. We have developed more accurate human-readable terms (also known as classes), including new definitions, and relationships related to the expression of genes. New findings continue to give us insight into the biology of gene regulation, including the order of events, and participants in those events. These updates to the SO support logical reasoning with the current understanding of gene expression regulation at the molecular level.


Assuntos
Ontologias Biológicas , Regulação da Expressão Gênica , Elementos Reguladores de Transcrição , Região de Controle de Locus Gênico
6.
Molecules ; 26(15)2021 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-34361663

RESUMO

Opioid-associated overdoses and deaths due to respiratory depression are a major public health problem in the US and other Western countries. In the past decade, much research effort has been directed towards the development of G-protein-biased µ-opioid receptor (MOP) agonists as a possible means to circumvent this problem. The bias hypothesis proposes that G-protein signaling mediates analgesia, whereas ß-arrestin signaling mediates respiratory depression. SR-17018 was initially reported as a highly biased µ-opioid with an extremely wide therapeutic window. It was later shown that SR-17018 can also reverse morphine tolerance and prevent withdrawal via a hitherto unknown mechanism of action. Here, we examined the temporal dynamics of SR-17018-induced MOP phosphorylation and dephosphorylation. Exposure of MOP to saturating concentrations of SR-17018 for extended periods of time stimulated a MOP phosphorylation pattern that was indistinguishable from that induced by the full agonist DAMGO. Unlike DAMGO-induced MOP phosphorylation, which is reversible within minutes after agonist washout, SR-17018-induced MOP phosphorylation persisted for hours under otherwise identical conditions. Such delayed MOP dephosphorylation kinetics were also found for the partial agonist buprenorphine. However, buprenorphine, SR-17018-induced MOP phosphorylation was fully reversible when naloxone was included in the washout solution. SR-17018 exhibits a qualitative and temporal MOP phosphorylation profile that is strikingly different from any other known biased, partial, or full MOP agonist. We conclude that detailed analysis of receptor phosphorylation may provide novel insights into previously unappreciated pharmacological properties of newly synthesized MOP ligands.


Assuntos
Analgésicos Opioides/farmacologia , Buprenorfina/farmacologia , Ala(2)-MePhe(4)-Gly(5)-Encefalina/farmacologia , Receptores Opioides mu/agonistas , Receptores Opioides mu/metabolismo , Analgésicos Opioides/química , Buprenorfina/química , Tolerância a Medicamentos , Ala(2)-MePhe(4)-Gly(5)-Encefalina/química , Proteínas de Ligação ao GTP/metabolismo , Células HEK293 , Humanos , Ligantes , Estrutura Molecular , Naloxona/farmacologia , Antagonistas de Entorpecentes/farmacologia , Overdose de Opiáceos/tratamento farmacológico , Fosforilação/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Transfecção , beta-Arrestina 2/metabolismo
7.
Appl Environ Microbiol ; 87(19): e0076921, 2021 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-34288701

RESUMO

Phaeobacter inhibens 2.10 is an effective biofilm former on marine surfaces and has the ability to outcompete other microorganisms, possibly due to the production of the plasmid-encoded secondary metabolite tropodithietic acid (TDA). P. inhibens 2.10 biofilms produce phenotypic variants with reduced competitiveness compared to the wild type. In the present study, we used longitudinal, genome-wide deep sequencing to uncover the genetic foundation that contributes to the emergent phenotypic diversity in P. inhibens 2.10 biofilm dispersants. Our results show that phenotypic variation is not due to the loss of the plasmid that carries the genes for TDA synthesis but instead show that P. inhibens 2.10 biofilm populations become rapidly enriched in single nucleotide variations in genes involved in the synthesis of TDA. While variants in genes previously linked to other phenotypes, such as lipopolysaccharide production (i.e., rfbA) and cellular persistence (i.e., metG), also appear to be selected for during biofilm dispersal, the number and consistency of variations found for genes involved in TDA production suggest that this metabolite imposes a burden on P. inhibens 2.10 cells. Our results indicate a strong selection pressure for the loss of TDA in monospecies biofilm populations and provide insight into how competition (or a lack thereof) in biofilms might shape genome evolution in bacteria. IMPORTANCE Biofilm formation and dispersal are important survival strategies for environmental bacteria. During biofilm dispersal, cells often display stable and heritable variants from the parental biofilm. Phaeobacter inhibens is an effective colonizer of marine surfaces, in which a subpopulation of its biofilm dispersal cells displays a noncompetitive phenotype. This study aimed to elucidate the genetic basis of these phenotypic changes. Despite the progress made to date in characterizing the dispersal variants in P. inhibens, little is understood about the underlying genetic changes that result in the development of the specific variants. Here, P. inhibens phenotypic variation was linked to single nucleotide polymorphisms (SNPs), in particular in genes affecting the competitive ability of P. inhibens, including genes related to the production of the antibiotic tropodithietic acid (TDA) and bacterial cell-cell communication (e.g., quorum sensing). This work is significant as it reveals how the biofilm lifestyle might shape genome evolution in a cosmopolitan bacterium.


Assuntos
Biofilmes/crescimento & desenvolvimento , Rhodobacteraceae , Evolução Molecular , Variação Genética , Mutação , Fenótipo , Rhodobacteraceae/genética , Rhodobacteraceae/crescimento & desenvolvimento , Rhodobacteraceae/metabolismo , Rhodobacteraceae/fisiologia , Tropolona/análogos & derivados , Tropolona/metabolismo
8.
Artigo em Inglês | MEDLINE | ID: mdl-34210565

RESUMO

The aim of this study was to translate the Liverpool Oral Rehabilitation Questionnaire version 3 (LORQv3) into German and validate this version in order to assess oral-health-related quality of life (OHRQoL) among head and neck cancer patients. This study was conducted at a German university clinic among patients who had completed therapy for squamous cell carcinoma of the head and neck (HNSCC). The original English-language LORQv3 was translated into German according to the forward-backward approach. Validity and reliability were evaluated using further questionnaires related to OHRQoL and psychological impairments. Subgroups were built with reference to oral rehabilitation status and type of cancer therapy. Furthermore, OHRQoL was evaluated. Test-retest reliability was assessed by weighted kappa with a 10-14 day interval. Data were analysed by using Spearman's correlation and the following tests: Shapiro-Wilk, Kruskal-Wallis, Mann-Whitney U and Cronbach's alpha. The level of significance was set at α = 0.05. Analysis of the LORQv3 evaluations revealed excellent Cronbach's alpha and high test-retest reliability. Construct validity were supported by the data. LORQv3 summary score and domains were significantly affected by status of oral rehabilitation (p = 0.003, p = 0.008, p = 0.024) and treatment approach (p < 0.001, p = 0.025, p = 0.035). The German version of the LORQv3 showed high reliability and validity and an impaired OHRQoL of HNSCC patients. It can therefore be recommended for the assessment of OHRQoL.

9.
Cancers (Basel) ; 13(12)2021 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-34205778

RESUMO

Invasive nonfunctioning pituitary tumors (NFPTs) are non-resectable neoplasms associated with frequent relapse and significant comorbidities. Current treatments, including somatostatin receptor 2 (SSTR2)-directed somatostatin analogs (SSAs), often fail against NFPTs. Thus, identifying effective therapies is clinically relevant. As NFPTs express SSTR3 at high levels, pasireotide, a multireceptor-targeted SSA, might be beneficial. Here we evaluated pasireotide in the only representative model of spontaneous NFPTs (MENX rats) in vivo. Octreotide long-acting release (LAR), pasireotide LAR, or placebo, were administered to age-matched, tumor-bearing MENX rats of both sexes for 28 d or 56 d. Longitudinal high-resolution magnetic resonance imaging monitored tumor growth. While tumors in placebo-treated rats increased in volume over time, PTs in drug-treated rats displayed significant growth suppression, and occasional tumor shrinkage. Pasireotide elicited stronger growth inhibition. Radiological responses correlated with tumors' proliferation rates. Both SSAs, but especially pasireotide, were more effective in female vs. male rats. Basal Sstr3 expression was significantly higher in the former group. It is noteworthy that female human NFPTs patients also have a trend towards higher SSTR3 expression. Altogether, our studies provide the rationale for testing pasireotide in patients with residual/recurrent NFPTs. If confirmed, the sex-related SSTR3 expression might be used as criteria to stratify NFPTs patients for treatment with pasireotide.

11.
Front Microbiol ; 12: 688754, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34262548

RESUMO

Secondary metabolites are key components in microbial ecology by mediating interactions between bacteria and their environment, neighboring species or host organisms. Bioactivities can be beneficial for both interaction partners or provide a competitive advantage only for the producer. Colonizers of confined habitats such as biofilms are known as prolific producers of a great number of bioactive secondary metabolites and are a potential source for novel compounds. We investigated the strain Paracoccus marcusii CP157, which originates from the biofilm on the carapace of a shell disease-affected Cancer pagurus specimen, for its potential to produce bioactive secondary metabolites. Its closed genome contains 22 extrachromosomal elements and several gene clusters potentially involved in biosynthesis of bioactive polyketides, bacteriocins, and non-ribosomal peptides. Culture extracts of CP157 showed antagonistic activities against bacteria from different phyla, but also against microalgae and crustacean larvae. Different HPLC-fractions of CP157 culture extracts had antibacterial properties, indicating that several bioactive compounds are produced by CP157. The bioactive extract contains several small, antibacterial compounds that partially withstand elevated temperatures, extreme pH values and exposure to proteolytic enzymes, providing high stability toward environmental conditions in the natural habitat of CP157. Further, screening of 17 Paracoccus spp. revealed that antimicrobial activity, hemolysis and production of N-acyl homoserine lactones are common features within the genus. Taking into account the large habitat diversity and phylogenetic distance of the tested strains, we hypothesize that bioactive secondary metabolites play a central role in the ecology of Paracoccus spp. in their natural environments.

12.
Sci Rep ; 11(1): 14104, 2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34238949

RESUMO

Local crystallization of ferromagnetic layers is crucial in the successful realization of miniaturized tunneling magnetoresistance (TMR) devices. In the case of Co-Fe-B TMR devices, used most successfully so far in applications and devices, Co-Fe-B layers are initially deposited in an amorphous state and annealed post-deposition to induce crystallization in Co-Fe, thereby increasing the device performance. In this work, first direct proof of locally triggered crystallization of 10 nm thick Co-Fe-B films by laser irradiation is provided by means of X-ray diffraction (XRD) using synchrotron radiation. A comparison with furnace annealing is performed for benchmarking purposes, covering different annealing parameters, including temperature and duration in the case of furnace annealing, as well as laser intensity and scanning speed for the laser annealing. Films of Co-Fe-B with different stoichiometry sandwiched between a Ru and a Ta or MgO layer were systematically assessed by XRD and SQUID magnetometry in order to elucidate the crystallization mechanisms. The transformation of Co-Fe-B films from amorphous to crystalline is revealed by the presence of pronounced CoFe(110) and/or CoFe(200) reflexes in the XRD θ-2θ scans, depending on the capping layer. For a certain window of parameters, comparable crystallization yields are obtained with furnace and laser annealing. Samples with an MgO capping layer required a slightly lower laser intensity to achieve equivalent Co-Fe crystallization yields, highlighting the potential of laser annealing to locally enhance the TMR ratio.

13.
Mol Pharmacol ; 100(1): 7-18, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33958480

RESUMO

Agonists at the nociceptin opioid peptide receptor (NOP) are under investigation as therapeutics for nonaddicting analgesia, opioid use disorder, Parkinson's disease, and other indications. NOP full and partial agonists have both been of interest, particularly since NOP partial agonists show a reduced propensity for behavioral disruption than NOP full agonists. Here, we investigated the in vitro pharmacological properties of chemically diverse NOP receptor agonists in assays measuring functional activation of the NOP receptor such as guanosine 5'-O-[gamma-thio]triphosphate (GTPγS) binding, cAMP inhibition, G protein-coupled inwardly rectifying potassium (GIRK) channel activation, phosphorylation, ß-arrestin recruitment and receptor internalization. When normalized to the efficacy of the natural agonist nociceptin/orphanin FQ (N/OFQ), we found that different functional assays that measure intrinsic activity produce inconsistent levels of agonist efficacy, particularly for ligands that were partial agonists. Agonist efficacy obtained in the GTPγS assay tended to be lower than that in the cAMP and GIRK assays. These structurally diverse NOP agonists also showed differential receptor phosphorylation profiles at the phosphosites we examined and induced varying levels of receptor internalization. Interestingly, although the rank order for ß-arrestin recruitment by these NOP agonists was consistent with their ability to induce receptor internalization, their phosphorylation signatures at the time point we investigated were not indicative of the levels of ß-arrestin recruitment or internalization induced by these agonists. It is possible that other phosphorylation sites, yet to be identified, drive the recruitment of NOP receptor ensembles and subsequent receptor trafficking by some nonpeptide NOP agonists. These findings potentially help understand NOP agonist pharmacology in the context of ligand-activated receptor trafficking. SIGNIFICANCE STATEMENT: Chemically diverse agonist ligands at the nociceptin opioid receptor G protein-coupled receptor showed differential efficacy for activating downstream events after receptor binding, in a suite of functional assays measuring guanosine 5'-O-[gamma-thio]triphosphate binding, cAMP inhibition, G protein-coupled inwardly rectifying protein channel activation, ß-arrestin recruitment, receptor internalization and receptor phosphorylation. These analyses provide a context for understanding nociceptin opioid peptide receptor (NOP) agonist pharmacology driven by ligand-induced differential NOP receptor signaling.


Assuntos
Proteínas de Ligação ao GTP/metabolismo , Receptores Opioides/agonistas , Bibliotecas de Moléculas Pequenas/farmacologia , beta-Arrestinas/metabolismo , Animais , Linhagem Celular , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Ligantes , Estrutura Molecular , Fosforilação , Transdução de Sinais/efeitos dos fármacos , Bibliotecas de Moléculas Pequenas/química
14.
Stud Health Technol Inform ; 281: 178-182, 2021 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-34042729

RESUMO

We present an approach called MTP (multiple translation paths) aiming at assisting human translation in SNOMED CT localisation projects based on free, web-based machine translation tools. For a chosen target language, MTP generates a scored output of translation candidates (TCs) for each input concept. This paper describes the basic idea of MTP, the distribution of its output TCs and discusses typical examples with German as target language. The MTP approach capitalises on combinatorial growth by the combination of input languages, support languages, and translation engines. We applied MTP on the SNOMED CT Starter Set, using Google Translator, DeepL and Systran, together with the four source languages English, Spanish, Swedish and French, and Danish, Dutch, Norwegian, Italian, Portuguese, Polish and Russian as support languages. The descriptive assessment of TC variety, together with an analysis of typical results is the focus of this paper. MTP defines, for each input concept, TPs by the combination of input languages, support languages and translation engines, resulting in 91 translation results with various degrees of co-incidence (cardinality). The most configurations produce an average number of TCs indicating that the same TC is often derived via different translation paths. Combinations of translation engines result in distributions with a higher number of distinct TCs per concept. We present work in progress on using machine translation (MT) for terminology translation, by leveraging several free MT tools fed by different languages and language combinations. A first qualitative analysis was promising and supports our hypothesis that a majority voting applied to many translation candidates yields higher quality results than from one single engine and input language.


Assuntos
Idioma , Systematized Nomenclature of Medicine , Humanos , Federação Russa , Tradução , Unified Medical Language System
15.
Stud Health Technol Inform ; 281: 377-381, 2021 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-34042769

RESUMO

Transfer learning has demonstrated its potential in natural language processing tasks, where models have been pre-trained on large corpora and then tuned to specific tasks. We applied pre-trained transfer models to a Spanish biomedical document classification task. The main goal is to analyze the performance of text classification by clinical specialties using state-of-the-art language models for Spanish, and compared them with the results using corresponding models in English and with the most important pre-trained model for the biomedical domain. The outcomes present interesting perspectives on the performance of language models that are pre-trained for a particular domain. In particular, we found that BioBERT achieved better results on Spanish texts translated into English than the general domain model in Spanish and the state-of-the-art multilingual model.


Assuntos
Multilinguismo , Processamento de Linguagem Natural , Feminino , Idioma , Aprendizagem , Aprendizado de Máquina
16.
Stud Health Technol Inform ; 278: 224-230, 2021 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-34042898

RESUMO

INTRODUCTION: The aim of this study is to evaluate the use of a natural language processing (NLP) software to extract medication statements from unstructured medical discharge letters. METHODS: Ten randomly selected discharge letters were extracted from the data warehouse of the University Hospital Erlangen (UHE) and manually annotated to create a gold standard. The AHD NLP tool, provided by MIRACUM's industry partner was used to annotate these discharge letters. Annotations by the NLP tool where then compared to the gold standard on two levels: phrase precision (whether or not the whole medication statement has been identified correctly) and token precision (whether or not the medication name has been identified correctly within correctly discovered medication phrases). RESULTS: The NLP tool detected medication related phrases with an overall F-measure of 0.852. The medication name has been identified correctly with an overall F-measure of 0.936. DISCUSSION: This proof-of-concept study is a first step towards an automated scalable evaluation system for MIRACUM's industry partner's NLP tool by using a gold standard. Medication phrases and names have been correctly identified in most cases by the NLP system. Future effort needs to be put into extending and validating the gold standard.


Assuntos
Processamento de Linguagem Natural , Alta do Paciente , Humanos , Software
17.
BMC Med Inform Decis Mak ; 21(1): 145, 2021 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-33947365

RESUMO

BACKGROUND: Controlled vocabularies are fundamental resources for information extraction from clinical texts using natural language processing (NLP). Standard language resources available in the healthcare domain such as the UMLS metathesaurus or SNOMED CT are widely used for this purpose, but with limitations such as lexical ambiguity of clinical terms. However, most of them are unambiguous within text limited to a given clinical specialty. This is one rationale besides others to classify clinical text by the clinical specialty to which they belong. RESULTS: This paper addresses this limitation by proposing and applying a method that automatically extracts Spanish medical terms classified and weighted per sub-domain, using Spanish MEDLINE titles and abstracts as input. The hypothesis is biomedical NLP tasks benefit from collections of domain terms that are specific to clinical subdomains. We use PubMed queries that generate sub-domain specific corpora from Spanish titles and abstracts, from which token n-grams are collected and metrics of relevance, discriminatory power, and broadness per sub-domain are computed. The generated term set, called Spanish core vocabulary about clinical specialties (SCOVACLIS), was made available to the scientific community and used in a text classification problem obtaining improvements of 6 percentage points in the F-measure compared to the baseline using Multilayer Perceptron, thus demonstrating the hypothesis that a specialized term set improves NLP tasks. CONCLUSION: The creation and validation of SCOVACLIS support the hypothesis that specific term sets reduce the level of ambiguity when compared to a specialty-independent and broad-scope vocabulary.


Assuntos
Processamento de Linguagem Natural , Unified Medical Language System , Humanos , Idioma , Systematized Nomenclature of Medicine , Vocabulário Controlado
18.
Proc Natl Acad Sci U S A ; 118(14)2021 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-33795512

RESUMO

Bacteria have evolved a diverse array of signaling pathways that enable them to quickly respond to environmental changes. Understanding how these pathways reflect environmental conditions and produce an orchestrated response is an ongoing challenge. Herein, we present a role for collective modifications of environmental pH carried out by microbial colonies living on a surface. We show that by collectively adjusting the local pH value, Paenibacillus spp., specifically, regulate their swarming motility. Moreover, we show that such pH-dependent regulation can converge with the carbon repression pathway to down-regulate flagellin expression and inhibit swarming in the presence of glucose. Interestingly, our results demonstrate that the observed glucose-dependent swarming repression is not mediated by the glucose molecule per se, as commonly thought to occur in carbon repression pathways, but rather is governed by a decrease in pH due to glucose metabolism. In fact, modification of the environmental pH by neighboring bacterial species could override this glucose-dependent repression and induce swarming of Paenibacillus spp. away from a glucose-rich area. Our results suggest that bacteria can use local pH modulations to reflect nutrient availability and link individual bacterial physiology to macroscale collective behavior.

19.
Sci Rep ; 11(1): 8288, 2021 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-33859231

RESUMO

The dopamine D2 receptor (D2R) is the target of drugs used to treat the symptoms of Parkinson's disease and schizophrenia. The D2R is regulated through its interaction with and phosphorylation by G protein receptor kinases (GRKs) and interaction with arrestins. More recently, D2R arrestin-mediated signaling has been shown to have distinct physiological functions to those of G protein signalling. Relatively little is known regarding the patterns of D2R phosphorylation that might control these processes. We aimed to generate antibodies specific for intracellular D2R phosphorylation sites to facilitate the investigation of these mechanisms. We synthesised double phosphorylated peptides corresponding to regions within intracellular loop 3 of the hD2R and used them to raise phosphosite-specific antibodies to capture a broad screen of GRK-mediated phosphorylation. We identify an antibody specific to a GRK2/3 phosphorylation site in intracellular loop 3 of the D2R. We compared measurements of D2R phosphorylation with other measurements of D2R signalling to profile selected D2R agonists including previously described biased agonists. These studies demonstrate the utility of novel phosphosite-specific antibodies to investigate D2R regulation and signalling.

20.
Children (Basel) ; 8(4)2021 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-33916723

RESUMO

Vaginal colonization with Ureaplasma (U.) spp. has been shown to be associated with adverse pregnancy outcome; however, data on neonatal outcome are scarce. The aim of the study was to investigate whether maternal vaginal colonization with U. spp. in early pregnancy represents a risk factor for adverse short- or long-term outcome of preterm infants. Previously, 4330 pregnant women were enrolled in an observational multicenter study, analyzing the association between vaginal U. spp. colonization and spontaneous preterm birth. U. spp. colonization was diagnosed via PCR analysis from vaginal swabs. For this study, data on short-term outcome were collected from medical records and long-term outcome was examined via Bayley Scales of Infant Development at 24 months adjusted age. Two-hundred-and-thirty-eight children were born <33 weeks gestational age. After exclusion due to asphyxia, malformations, and lost-to-follow-up, data on short-term and long-term outcome were available from 222 and 92 infants, respectively. Results show a significant association between vaginal U. spp. colonization and severe intraventricular hemorrhage (10.4% vs. 2.6%, p = 0.03), retinopathy of prematurity (21.7% vs. 10.3%, p = 0.03), and adverse psychomotor outcome (24.3% vs. 1.8%, OR 13.154, 95%CI 1.6,110.2, p = 0.005). The data suggest an association between vaginal U. spp. colonization in early pregnancy and adverse short- and long-term outcome of very preterm infants.

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