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The metabolism plays a fundamental role in cellular signaling pathways, but commonly used cell culture media do not reflect physiological metabolite concentrations. The metabolic control hub mammalian target of rapamycin complex 1 (mTORC1) kinase is an illuminating example that it is about time to advance our cell culture to become more physiological and relevant.
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Transducción de Señal , Serina-Treonina Quinasas TOR , Serina-Treonina Quinasas TOR/metabolismo , Transducción de Señal/fisiología , Complejos Multiproteicos/metabolismo , Diana Mecanicista del Complejo 1 de la Rapamicina/metabolismo , Técnicas de Cultivo de CélulaRESUMEN
Cell cycle-dependent gene transcription is tightly controlled by the retinoblastoma (RB):E2F and DREAM complexes, which repress all cell cycle genes during quiescence. Cyclin-dependent kinase (CDK) phosphorylation of RB and DREAM allows for the expression of two gene sets. The first set of genes, with peak expression in G1/S, is activated by E2F transcription factors (TFs) and is required for DNA synthesis. The second set, with maximum expression during G2/M, is required for mitosis and is coordinated by the MuvB complex, together with B-MYB and Forkhead box M1 (FOXM1). In this review, we summarize the key findings that established the distinct control mechanisms regulating G1/S and G2/M gene expression in mammals and discuss recent advances in the understanding of the temporal control of these genes.
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Proteínas de Ciclo Celular , Proteínas Represoras , Animales , Proteínas Represoras/genética , Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Mitosis , Quinasas Ciclina-Dependientes/genética , Expresión Génica , MamíferosRESUMEN
The increasing availability of high-throughput datasets allows amalgamating research information across a large body of genome regulation studies. Given the recent success of meta-analyses on transcriptional regulators, epigenetic marks, and enhancer:gene associations, we expect that such surveys will continue to provide novel and reproducible insights. However, meta-analyses are severely hampered by the diversity of available data, concurring protocols, an eclectic amount of bioinformatics tools, and myriads of conceivable parameter combinations. Such factors can easily bar life scientists from synthesizing omics data and substantially curb their interpretability. Despite statistical challenges of the method, we would like to emphasize the advantages of joining data from different sources through vote-counting and showcase examples that achieve a simple but highly intuitive data integration.
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Biología Computacional , Genoma , Biología Computacional/métodosRESUMEN
The Gram-positive bacterium Listeria monocytogenes occurs widespread in the environment and infects humans when ingested along with contaminated food. Such infections are particularly dangerous for risk group patients, for whom they represent a life-threatening disease. To invent novel strategies to control contamination and disease, it is important to identify those cellular processes that maintain pathogen growth inside and outside the host. Here, we have applied transposon insertion sequencing (Tn-Seq) to L. monocytogenes for the identification of such processes on a genome-wide scale. Our approach identified 394 open reading frames that are required for growth under standard laboratory conditions and 42 further genes, which become necessary during intracellular growth in macrophages. Most of these genes encode components of the translation machinery and act in chromosome-related processes, cell division, and biosynthesis of the cellular envelope. Several cofactor biosynthesis pathways and 29 genes with unknown functions are also required for growth, suggesting novel options for the development of antilisterial drugs. Among the genes specifically required during intracellular growth are known virulence factors, genes compensating intracellular auxotrophies, and several cell division genes. Our experiments also highlight the importance of PASTA kinase signaling for general viability and of glycine metabolism and chromosome segregation for efficient intracellular growth of L. monocytogenes.
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Reconstructing the locomotion of extinct vertebrates offers insights into their palaeobiology and helps to conceptualize major transitions in vertebrate evolution1-4. However, estimating the locomotor behaviour of a fossil species remains a challenge because of the limited information preserved and the lack of a direct correspondence between form and function5,6. The evolution of advanced locomotion on land-that is, locomotion that is more erect, balanced and mechanically power-saving than is assumed of anamniote early tetrapods-has previously been linked to the terrestrialization and diversification of amniote lineages7. To our knowledge, no reconstructions of the locomotor characteristics of stem amniotes based on multiple quantitative methods have previously been attempted: previous methods have relied on anatomical features alone, ambiguous locomotor information preserved in ichnofossils or unspecific modelling of locomotor dynamics. Here we quantitatively examine plausible gaits of the stem amniote Orobates pabsti, a species that is known from a complete body fossil preserved in association with trackways8. We reconstruct likely gaits that match the footprints, and investigate whether Orobates exhibited locomotor characteristics that have previously been linked to the diversification of crown amniotes. Our integrative methodology uses constraints derived from biomechanically relevant metrics, which also apply to extant tetrapods. The framework uses in vivo assessment of locomotor mechanics in four extant species to guide an anatomically informed kinematic simulation of Orobates, as well as dynamic simulations and robotics to filter the parameter space for plausible gaits. The approach was validated using two extant species that have different morphologies, gaits and footprints. Our metrics indicate that Orobates exhibited more advanced locomotion than has previously been assumed for earlier tetrapods7,9, which suggests that advanced terrestrial locomotion preceded the diversification of crown amniotes. We provide an accompanying website for the exploration of the filters that constrain our simulations, which will allow revision of our approach using new data, assumptions or methods.
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Fósiles , Locomoción , Filogenia , Vertebrados/fisiología , Caimanes y Cocodrilos/anatomía & histología , Caimanes y Cocodrilos/fisiología , Animales , Tamaño Corporal , Femenino , Iguanas/anatomía & histología , Iguanas/fisiología , Urodelos/anatomía & histología , Urodelos/fisiología , Vertebrados/anatomía & histologíaRESUMEN
Nanopore sequencing has shown the potential to democratize genomic pathogen surveillance due to its ease of use and low entry cost. However, recent genotyping studies showed discrepant results compared to gold-standard short-read sequencing. Furthermore, although essential for widespread application, the reproducibility of nanopore-only genotyping remains largely unresolved. In our multicenter performance study involving five laboratories, four public health-relevant bacterial species were sequenced with the latest R10.4.1 flow cells and V14 chemistry. Core genome MLST analysis of over 500 data sets revealed highly strain-specific typing errors in all species in each laboratory. Investigation of the methylation-related errors revealed consistent DNA motifs at error-prone sites across participants at read level. Depending on the frequency of incorrect target reads, this either leads to correct or incorrect typing, whereby only minimal frequency deviations can randomly determine the final result. PCR preamplification, recent basecalling model updates and an optimized polishing strategy notably diminished the non-reproducible typing. Our study highlights the potential for new errors to appear with each newly sequenced strain and lays the foundation for computational approaches to reduce such typing errors. In conclusion, our multicenter study shows the necessity for a new validation concept for nanopore sequencing-based, standardized bacterial typing, where single nucleotide accuracy is critical.
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BACKGROUND: Klebsiella (K.) pneumoniae is a ubiquitous Gram-negative bacterium and a common coloniser of animals and humans. Today, K. pneumoniae is one of the most persistent nosocomial pathogens worldwide and poses a severe threat/burden to public health by causing urinary tract infections, pneumonia and bloodstream infections. Infections mainly affect immunocompromised individuals and hospitalised patients. In recent years, a new type of K. pneumoniae has emerged associated with community-acquired infections such as pyogenic liver abscess in otherwise healthy individuals and is therefore termed hypervirulent K. pneumoniae (hvKp). The aim of this study was the characterisation of K. pneumoniae isolates with properties of hypervirulence from Germany. METHODS: A set of 62 potentially hypervirulent K. pneumoniae isolates from human patients was compiled. Inclusion criteria were the presence of at least one determinant that has been previously associated with hypervirulence: (I) clinical manifestation, (II) a positive string test as a marker for hypermucoviscosity, and (III) presence of virulence associated genes rmpA and/or rmpA2 and/or magA. Phenotypic characterisation of the isolates included antimicrobial resistance testing by broth microdilution. Whole genome sequencing (WGS) was performed using Illumina® MiSeq/NextSeq to investigate the genetic repertoire such as multi-locus sequence types (ST), capsule types (K), further virulence associated genes and resistance genes of the collected isolates. For selected isolates long-read sequencing was applied and plasmid sequences with resistance and virulence determinants were compared. RESULTS: WGS analyses confirmed presence of several signature genes for hvKp. Among them, the most prevalent were the siderophore loci iuc and ybt and the capsule regulator genes rmpA and rmpA2. The most dominant ST among the hvKp isolates were ST395 capsule type K2 and ST395 capsule type K5; both have been described previously and were confirmed by our data as multidrug-resistant (MDR) isolates. ST23 capsule type K1 was the second most abundant ST in this study; this ST has been described as commonly associated with hypervirulence. In general, resistance to beta-lactams caused by the production of extended-spectrum beta-lactamases (ESBL) and carbapenemases was observed frequently in our isolates, confirming the threatening rise of MDR-hvKp strains. CONCLUSIONS: Our study results show that K. pneumoniae strains that carry several determinants of hypervirulence are present for many years in Germany. The detection of carbapenemase genes and hypervirulence associated genes on the same plasmid is highly problematic and requires intensified screening and molecular surveillance. However, the non-uniform definition of hvKp complicates their detection. Testing for hypermucoviscosity alone is not specific enough to identify hvKp. Thus, we suggest that the classification of hvKp should be applied to isolates that not only fulfil phenotypical criteria (severe clinical manifestations, hypermucoviscosity) but also (I) the presence of at least two virulence loci e.g. iuc and ybt, and (II) the presence of rmpA and/or rmpA2.
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Infecciones Comunitarias Adquiridas , Infecciones por Klebsiella , Humanos , Klebsiella pneumoniae , Virulencia/genética , Factores de Virulencia/genética , Plásmidos , Infecciones Comunitarias Adquiridas/microbiología , Infecciones por Klebsiella/microbiología , Antibacterianos/farmacologíaRESUMEN
Metals are essential for all living organisms, but the type of metal and its concentration determines its action. Even low concentrations of metals may have toxic effects on organisms and therefore exhibit antimicrobial activities. In this study, we investigate the evolutionary adaptation processes of Staphylococcus aureus to metals and common genes for metal tolerance. Laboratory and clinical isolates were treated with manganese, cobalt, zinc, or nickel metal salts to generate growth-adapted mutants. After growth in medium supplemented with zinc, whole-genome sequencing identified, among others, two genes, mgtE (SAUSA300_0910), a putative magnesium transporter and spoVG (SAUSA300_0475), a global transcriptional regulator, as hot spots for stress-induced single-nucleotide polymorphisms (SNPs). SNPs in mgtE were also detected in mutants treated with high levels of cobalt or nickel salts. To investigate the effect of these genes on metal tolerance, deletion mutants and complementation strains in an S. aureus USA300 LAC* laboratory strain were generated. Both, the mgtE and spoVG deletion strains were more tolerant to cobalt, manganese, and zinc. The mgtE mutant was also more tolerant to nickel exposure. Inductively coupled plasma mass spectrometry analysis demonstrated that the mgtE deletion mutant accumulated less intracellular zinc than the wild type, explaining increased tolerance. From these results, we conclude that mgtE gene inactivation increases zinc tolerance presumably due to reduced uptake of zinc. For the SpoVG mutant, no direct effect on the intracellular zinc concentration was detected, indicating toward different pathways to increase tolerance. Importantly, inactivation of these genes offers a growth advantage in environments containing certain metals, pointing toward a common tolerance mechanism. IMPORTANCE: Staphylococcus aureus is an opportunistic pathogen causing tremendous public health burden and high mortality in invasive infections. Treatment is becoming increasingly difficult due to antimicrobial resistances. The use of metals in animal husbandry and aquaculture to reduce bacterial growth and subsequent acquisition of metal resistances has been shown to co-select for antimicrobial resistance. Therefore, understanding adaptive mechanisms that help S. aureus to survive metal exposure is essential. Using a screening approach, we were able to identify two genes encoding the transporter MgtE and the transcriptional regulator SpoVG, which conferred increased tolerance to specific metals such as zinc when inactivated. Further testing showed that the deletion of mgtE leads to reduced intracellular zinc levels, suggesting a role in zinc uptake. The accumulation of mutations in these genes when exposed to other metals suggests that inactivation of these genes could be a common mechanism for intrinsic tolerance to certain metals.
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Proteínas Bacterianas , Staphylococcus aureus , Zinc , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/genética , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Zinc/metabolismo , Regulación Bacteriana de la Expresión Génica/efectos de los fármacos , Polimorfismo de Nucleótido Simple , Infecciones Estafilocócicas/microbiologíaRESUMEN
The current study examined predictions from embodied cognition for effects of finger counting on number processing. Although finger counting is spontaneous and nearly universal, counting habits reflect learning and culture. European cultures use a sub-base-five system, requiring a full hand plus additional fingers to express numbers exceeding 5. Chinese culture requires only one hand to express such numbers. We investigated the differential impact of early-acquired finger-based number representations on adult symbolic number processing. In total, 53 European and 56 Chinese adults performed two versions of the magnitude classification task, where numbers were presented either as Arabic symbols or as finger configurations consistent with respective cultural finger-counting habits. Participants classified numbers as smaller/larger than 5 with horizontally aligned buttons. Finger-based size and distance effects were larger in Chinese compared with Europeans. These differences did not, however, induce reliably different symbol processing signatures. This dissociation challenges the idea that sensory and motor habits shape our conceptual representations and implies notation-specific processing patterns.
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Comparación Transcultural , Dedos , Humanos , Femenino , Masculino , Adulto , Adulto Joven , Población Blanca/psicología , Pueblo Asiatico , Adolescente , CogniciónRESUMEN
In many Western cultures, the processing of temporal words related to the past and to the future is associated with left and right space, respectively - a phenomenon known as the horizontal Mental Time Line (MTL). While this mapping is apparently quite ubiquitous, its regularity and consistency across different types of temporal concepts remain to be determined. Moreover, it is unclear whether such spatial mappings are an essential and early constituent of concept activation. In the present study, we used words denoting time units at different scales (hours of the day, days of the week, months of the year) associated with either left space (e.g., 9 a.m., Monday, February) or right space (e.g., 8 p.m., Saturday, November) as cues in a line bisection task. Fifty-seven healthy adults listened to temporal words and then moved a mouse cursor to the perceived midpoint of a horizontally presented line. We measured movement trajectories, initial line intersection coordinates, and final bisection response coordinates. We found movement trajectory displacements for left- vs. right-biasing hour and day cues. Initial line intersections were biased specifically by month cues, while final bisection responses were biased specifically by hour cues. Our findings offer general support to the notion of horizontal space-time associations and suggest further investigation of the exact chronometry and strength of this association across individual time units.
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Percepción Espacial , Percepción del Tiempo , Humanos , Percepción Espacial/fisiología , Adulto , Adulto Joven , Percepción del Tiempo/fisiología , Femenino , Masculino , Señales (Psicología) , Factores de Tiempo , Desempeño Psicomotor/fisiologíaRESUMEN
BackgroundThe war in Ukraine led to migration of Ukrainian people. Early 2022, several European national surveillance systems detected multidrug-resistant (MDR) bacteria related to Ukrainian patients.AimTo investigate the genomic epidemiology of New Delhi metallo-ß-lactamase (NDM)-producing Providencia stuartii from Ukrainian patients among European countries.MethodsWhole-genome sequencing of 66 isolates sampled in 2022-2023 in 10 European countries enabled whole-genome multilocus sequence typing (wgMLST), identification of resistance genes, replicons, and plasmid reconstructions. Five bla NDM-1-carrying-P. stuartii isolates underwent antimicrobial susceptibility testing (AST). Transferability to Escherichia coli of a bla NDM-1-carrying plasmid from a patient strain was assessed. Epidemiological characteristics of patients with NDM-producing P. stuartii were gathered by questionnaire.ResultswgMLST of the 66 isolates revealed two genetic clusters unrelated to Ukraine and three linked to Ukrainian patients. Of these three, two comprised bla NDM-1-carrying-P. stuartii and the third bla NDM-5-carrying-P. stuartii. The bla NDM-1 clusters (PstCluster-001, n = 22 isolates; PstCluster-002, n = 8 isolates) comprised strains from seven and four countries, respectively. The bla NDM-5 cluster (PstCluster-003) included 13 isolates from six countries. PstCluster-001 and PstCluster-002 isolates carried an MDR plasmid harbouring bla NDM-1, bla OXA-10, bla CMY-16, rmtC and armA, which was transferrable in vitro and, for some Ukrainian patients, shared by other Enterobacterales. AST revealed PstCluster-001 isolates to be extensively drug-resistant (XDR), but susceptible to cefiderocol and aztreonam-avibactam. Patients with data on age (n = 41) were 19-74 years old; of 49 with information on sex, 38 were male.ConclusionXDR P. stuartii were introduced into European countries, requiring increased awareness and precautions when treating patients from conflict-affected areas.
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Antibacterianos , Farmacorresistencia Bacteriana Múltiple , Infecciones por Enterobacteriaceae , Pruebas de Sensibilidad Microbiana , Tipificación de Secuencias Multilocus , Plásmidos , Providencia , Secuenciación Completa del Genoma , beta-Lactamasas , Humanos , Ucrania/epidemiología , beta-Lactamasas/genética , Infecciones por Enterobacteriaceae/microbiología , Infecciones por Enterobacteriaceae/epidemiología , Infecciones por Enterobacteriaceae/tratamiento farmacológico , Farmacorresistencia Bacteriana Múltiple/genética , Providencia/genética , Providencia/aislamiento & purificación , Providencia/efectos de los fármacos , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Europa (Continente)/epidemiología , Plásmidos/genética , Masculino , Adulto , Femenino , Persona de Mediana Edad , Anciano , Adulto JovenRESUMEN
BACKGROUND: Entrustable professional activities (EPAs) are observable process descriptions of clinical work units. EPAs support learners and tutors in assessment within healthcare settings. For use amongst our pharmacy students as well as pre-registration pharmacists we wanted to develop and validate an EPA for use in a clinical pharmacy setting at LMU University Hospital. METHODS: The development of the clinical pharmacy EPA followed a set pathway. A rapid literature review informed the first draft, an interprofessional consensus group consisting of pharmacists, nurses, and medical doctors refined this draft. The refined version was then validated via online survey utilising clinical pharmacists from Germany. RESULTS: We designed, refined and validated an EPA regarding medication reconciliation for assessment of pharmacy students and trainees within the pharmacy department at LMU University Hospital in Munich. Along with the EPA description an associated checklist to support the entrustment decision was created. For validation an online survey with 27 clinical pharmacists from all over Germany was conducted. Quality testing with the EQual rubric showed a good EPA quality. CONCLUSIONS: We developed the first clinical pharmacy EPA for use in a German context. Medication reconciliation is a suitable EPA candidate as it describes a clinical activity performed by pharmacists in many clinical settings. The newly developed and validated EPA 'Medication Reconciliation' will be used to assess pharmacy students and trainees.
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Conciliación de Medicamentos , Humanos , Alemania , Competencia Clínica/normas , Educación en Farmacia , Servicio de Farmacia en Hospital , Estudiantes de Farmacia , Educación Basada en Competencias , Encuestas y Cuestionarios , Evaluación EducacionalRESUMEN
BACKGROUND: Undergraduate training in hand hygiene is a keystone of infection control. Several studies have shown overconfidence effects in hand hygiene practices, which can impair metacognition. We hypothesized that overconfidence might be prevalent in the early education stages of nursing students and that these effects could be reduced through frequent interactive learning formats, such as learning groups. METHODS: We conducted a multicenter cross-sectional questionnaire with 196 German nursing students, including general, surgical, and anesthetic nursing specializations. RESULTS: Overconfidence was observed in nursing students across all specialties and years of education. The cluster analyses showed three different types of learners: two characterized by overconfidence and one demonstrating justifiable confidence. Furthermore, the moderation analysis indicated that providing feedback and promoting metacognition regarding students' learning achievements could mitigate overplacement, particularly through the frequent implementation of interactive teaching formats. DISCUSSION: Despite some limitations, these findings highlight the prevalence of overconfidence effects in nursing students, the presence of different learning profiles, and the importance of incorporating feedback within interactive learning formats concerning hand hygiene. Accordingly, educators need to be trained and supervised to deliver these learning formats and provide feedback to students effectively.
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INTRODUCTION: Radiographic diagnostic competences are a primary focus of dental education. This study assessed two feedback methods to enhance learning outcomes and explored the feasibility of artificial intelligence (AI) to support education. MATERIALS AND METHODS: Fourth-year dental students had access to 16 virtual radiological example cases for 8 weeks. They were randomly assigned to either elaborated feedback (eF) or knowledge of results feedback (KOR) based on expert consensus. Students´ diagnostic competences were tested on bitewing/periapical radiographs for detection of caries, apical periodontitis, accuracy for all radiological findings and image quality. We additionally assessed the accuracy of an AI system (dentalXrai Pro 3.0), where applicable. Data were analysed descriptively and using ROC analysis (accuracy, sensitivity, specificity, AUC). Groups were compared with Welch's t-test. RESULTS: Among 55 students, the eF group by large performed significantly better than the KOR group in detecting enamel caries (accuracy 0.840 ± 0.041, p = .196; sensitivity 0.638 ± 0.204, p = .037; specificity 0.859 ± 0.050, p = .410; ROC AUC 0.748 ± 0.094, p = .020), apical periodontitis (accuracy 0.813 ± 0.095, p = .011; sensitivity 0.476 ± 0.230, p = .003; specificity 0.914 ± 0.108, p = .292; ROC AUC 0.695 ± 0.123, p = .001) and in assessing the image quality of periapical images (p = .031). No significant differences were observed for the other outcomes. The AI showed almost perfect diagnostic performance (enamel caries: accuracy 0.964, sensitivity 0.857, specificity 0.074; dentin caries: accuracy 0.988, sensitivity 0.941, specificity 1.0; overall: accuracy 0.976, sensitivity 0.958, specificity 0.983). CONCLUSION: Elaborated feedback can improve student's radiographic diagnostic competences, particularly in detecting enamel caries and apical periodontitis. Using an AI may constitute an alternative to expert labelling of radiographs.
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A Gram-positive, motile, aerobic, rod-shaped, endospore-forming strain designated IRB4-01T was isolated from fermented African locust beans (Iru) obtained from Bodija market in the city of Ibadan, southwestern Nigeria, during a screening process from food-related sources. IRB4-01T grew at 10-50â°C (optimum, 35-37â°C), pH 6-10 (optimum, pH 7) and in 0-6â% NaCl (optimum, 1-3â%). Phylogenetic analyses based on 16S rRNA and combined short- and long-read genome sequencing revealed that IRB4-01T is closely related to Lysinibacillus cavernae SYSU K30005T and Lysinibacillus boronitolerans 10aT. The cell-wall peptidoglycan type was A4α (Lys-Asp), containing the diagnostic diamino acid lysine. The major polar lipids in strain IRB4-01T were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol and an unidentified phospholipid, while the predominant menaquinone was MK-7. The major cellular fatty acids were iso-C15â:â0, anteiso-C15â:â0 and iso-C16â:â0. Genomic DNA G+C content was 37.4ââmol%, while the digital DNA-DNA hybridization revealed 33.6 and 32.3â% relatedness to L. cavernae SYSU K30005T and L. boronitolerans 10aT, respectively. Based on phenotypic, physiological and chemotaxonomic characteristics, as well as genome comparisons, strain IRB4-01T represents a novel species of the genus Lysinibacillus, for which the name Lysinibacillus irui sp. nov. is proposed. The type strain is IRB4-01T (NCIMB 15452T=LMG 32887T). Hybrid genome data are provided on the NCBI database using the Bioproject number PRJNA906010 and accession numbers CP113527 and CP113528. Additionally, a representative 16S rRNA sequence is available with the GenBank accession number OQ566940.
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Ácidos Grasos , Saltamontes , Animales , Composición de Base , Ácidos Grasos/química , Nigeria , Filogenia , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN , ADN Bacteriano/genética , Técnicas de Tipificación BacterianaRESUMEN
Clinical reasoning theories agree that knowledge and the diagnostic process are associated with diagnostic success. However, the exact contributions of these components of clinical reasoning to diagnostic success remain unclear. This is particularly the case when operationalizing the diagnostic process with diagnostic activities (i.e., teachable practices that generate knowledge). Therefore, we conducted a study investigating to what extent knowledge and diagnostic activities uniquely explain variance in diagnostic success with virtual patients among medical students. The sample consisted of N = 106 medical students in their third to fifth year of university studies in Germany (6-years curriculum). Participants completed professional knowledge tests before diagnosing virtual patients. Diagnostic success with the virtual patients was assessed with diagnostic accuracy as well as a comprehensive diagnostic score to answer the call for more extensive measurement of clinical reasoning outcomes. The three diagnostic activities hypothesis generation, evidence generation, and evidence evaluation were tracked. Professional knowledge predicted performance in terms of the comprehensive diagnostic score and displayed a small association with diagnostic accuracy. Diagnostic activities predicted comprehensive diagnostic score and diagnostic accuracy. Hierarchical regressions showed that the diagnostic activities made a unique contribution to diagnostic success, even when knowledge was taken into account. Our results support the argument that the diagnostic process is more than an embodiment of knowledge and explains variance in diagnostic success over and above knowledge. We discuss possible mechanisms explaining this finding.
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Curriculum , Estudiantes de Medicina , Humanos , Razonamiento Clínico , Alemania , Competencia ClínicaRESUMEN
Despite its prominence, the mechanisms through which the tumor suppressor p53 regulates most genes remain unclear. Recently, the regulatory factor X 7 (RFX7) emerged as a suppressor of lymphoid neoplasms, but its regulation and target genes mediating tumor suppression remain unknown. Here, we identify a novel p53-RFX7 signaling axis. Integrative analysis of the RFX7 DNA binding landscape and the RFX7-regulated transcriptome in three distinct cell systems reveals that RFX7 directly controls multiple established tumor suppressors, including PDCD4, PIK3IP1, MXD4, and PNRC1, across cell types and is the missing link for their activation in response to p53 and stress. RFX7 target gene expression correlates with cell differentiation and better prognosis in numerous cancer types. Interestingly, we find that RFX7 sensitizes cells to Doxorubicin by promoting apoptosis. Together, our work establishes RFX7's role as a ubiquitous regulator of cell growth and fate determination and a key node in the p53 transcriptional program.
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Regulación de la Expresión Génica , Redes Reguladoras de Genes , Genes Supresores de Tumor , Factores de Transcripción del Factor Regulador X/metabolismo , Estrés Fisiológico/genética , Proteína p53 Supresora de Tumor/metabolismo , Animales , Antibióticos Antineoplásicos/farmacología , Apoptosis , Diferenciación Celular/genética , Línea Celular Tumoral , ADN/metabolismo , Doxorrubicina/farmacología , Humanos , Ratones , Neoplasias/genética , Neoplasias/mortalidad , Pronóstico , Regiones Promotoras Genéticas , Factores de Transcripción del Factor Regulador X/fisiología , Transducción de Señal , Transactivadores/metabolismo , TranscriptomaRESUMEN
BACKGROUND: For seafarers on the high seas health hazards are various and due to the setting also specific. The spectrum of job-related health impairments and accidents is mainly influenced by the maritime characteristics. The aim of this study is to assess the kind of accidents and the frequency of diseases and health complaints among seafarers on German container ships by evaluating medical log books. METHODS: A systematic analysis of 14,628 medical entries from 95 medical log books of 58 container ships under German flag from 1995 to 2015 was performed. This monocentric retrospective and descriptive study used information on accidents, diseases and health complaints among different occupational groups and medical treatment procedures for the analysis and evaluation. RESULTS: The analysis showed that more than one third of all consultations with the Health Officer on board are related to internal (33.7%) and surgical (31.3%) symptoms. Almost twenty percent of consultations were due to respiratory infections (19.6%) and accidents (17.9%). Accidents represented the most frequent reason for unfitness for sea service (31.2%). Based on occupational categories, most injuries occurred among deck crew (22.5%), followed by ratings working in the engine room (18.9%). In 106 cases, telemedical contact with a physician ashore was necessary. In total, 15 seafarers had to be evacuated from the ship for further medical treatment onshore. Medicine/drug application was the most common therapeutic measure on board, accounting for 77% of all consultations. CONCLUSIONS: The high proportion of health complaints and accidents among seafarers shows that there is a need to optimize medical care at sea and accident prevention, e.g. by standardized treatment algorithms or improving the medical training of Health Officers. The development and introduction of a digital patient file to record medical treatments on the vessels could also improve medical documentation on board.
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Enfermedades Profesionales , Telemedicina , Humanos , Navíos , Enfermedades Profesionales/diagnóstico , Estudios Retrospectivos , Prevención de Accidentes , Accidentes de TrabajoRESUMEN
It is still unclear how spatially associated concepts (e.g., directional expressions, object names, metaphors) shape our cognitive experience. Here, two experiments (N = 156) investigated the mechanisms by which words with either explicit or implicit spatial meaning induce spatial attention shifts. Participants performed a visual target-discrimination task according to response rules that required different degrees of prime and target processing depth. For explicit prime words, we found spatial congruency effects independent of processing depth, while implicit prime words generated congruency effects only when participants had to compute the congruency relationship. These results were robust across different prime-target intervals and imply that spatial connotations alone do not automatically activate spatial attention shifts. Instead, explicit semantic analysis is a prerequisite for conceptual cueing.
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Sesgo Atencional , Lenguaje , Percepción Espacial , Percepción Espacial/fisiología , Humanos , Masculino , Femenino , Adulto Joven , Adulto , Israel , Señales (Psicología) , Sesgo Atencional/fisiología , Cognición/fisiología , Semántica , AdolescenteRESUMEN
BackgroundCarbapenemase-producing Enterobacterales (CPE) are rapidly increasing worldwide, also in Europe. Although prevalence of CPE in Germany is comparatively low, the National Reference Centre for Multidrug-resistant Gram-negative Bacteria noted annually increasing numbers of NDM-5-producing Escherichia coli isolates.AimAs part of our ongoing surveillance programme, we characterised NDM-5-producing E. coli isolates received between 2013 and 2019 using whole genome sequencing (WGS).MethodsFrom 329 identified NDM-5-producing E. coli, 224 isolates from known geographical locations were subjected to Illumina WGS. Analyses of 222 sequenced isolates included multilocus sequence typing (MLST), core genome (cg)MLST and single-nucleotide polymorphism (SNP)-based analyses.ResultsResults of cgMLST revealed genetically distinct clusters for many of the 43 detected sequence types (ST), of which ST167, ST410, ST405 and ST361 predominated. The SNP-based phylogenetic analyses combined with geographical information identified sporadic cases of nosocomial transmission on a small spatial scale. However, we identified large clusters corresponding to clonal dissemination of ST167, ST410, ST405 and ST361 strains in consecutive years in different regions in Germany.ConclusionOccurrence of NDM-5-producing E. coli rose in Germany, which was to a large extent due to the increased prevalence of isolates belonging to the international high-risk clones ST167, ST410, ST405 and ST361. Of particular concern is the supra-regional dissemination of these epidemic clones. Available information suggest community spread of NDM-5-producing E. coli in Germany, highlighting the importance of epidemiological investigation and an integrated surveillance system in the One Health framework.