RESUMEN
Asymptotic giant branch stars are responsible for the production of most of the heavy isotopes beyond Sr observed in the solar system. Among them, isotopes shielded from the r-process contribution by their stable isobars are defined as s-only nuclei. For a long time the abundance of ^{204}Pb, the heaviest s-only isotope, has been a topic of debate because state-of-the-art stellar models appeared to systematically underestimate its solar abundance. Besides the impact of uncertainties from stellar models and galactic chemical evolution simulations, this discrepancy was further obscured by rather divergent theoretical estimates for the neutron capture cross section of its radioactive precursor in the neutron-capture flow, ^{204}Tl (t_{1/2}=3.78 yr), and by the lack of experimental data on this reaction. We present the first ever neutron capture measurement on ^{204}Tl, conducted at the CERN neutron time-of-flight facility n_TOF, employing a sample of only 9 mg of ^{204}Tl produced at the Institute Laue Langevin high flux reactor. By complementing our new results with semiempirical calculations we obtained, at the s-process temperatures of kT≈8 keV and kT≈30 keV, Maxwellian-averaged cross sections (MACS) of 580(168) mb and 260(90) mb, respectively. These figures are about 3% lower and 20% higher than the corresponding values widely used in astrophysical calculations, which were based only on theoretical calculations. By using the new ^{204}Tl MACS, the uncertainty arising from the ^{204}Tl(n,γ) cross section on the s-process abundance of ^{204}Pb has been reduced from â¼30% down to +8%/-6%, and the s-process calculations are in agreement with the latest solar system abundance of ^{204}Pb reported by K. Lodders in 2021.
RESUMEN
Planets with radii between that of the Earth and Neptune (hereafter referred to as 'sub-Neptunes') are found in close-in orbits around more than half of all Sun-like stars1,2. However, their composition, formation and evolution remain poorly understood3. The study of multiplanetary systems offers an opportunity to investigate the outcomes of planet formation and evolution while controlling for initial conditions and environment. Those in resonance (with their orbital periods related by a ratio of small integers) are particularly valuable because they imply a system architecture practically unchanged since its birth. Here we present the observations of six transiting planets around the bright nearby star HD 110067. We find that the planets follow a chain of resonant orbits. A dynamical study of the innermost planet triplet allowed the prediction and later confirmation of the orbits of the rest of the planets in the system. The six planets are found to be sub-Neptunes with radii ranging from 1.94Râ to 2.85Râ. Three of the planets have measured masses, yielding low bulk densities that suggest the presence of large hydrogen-dominated atmospheres.
RESUMEN
Neutron capture reaction cross sections on 74 Ge are of importance to determine 74 Ge production during the astrophysical slow neutron capture process. We present new resonance data on 74 Ge( n , γ ) reactions below 70 keV neutron energy. We calculate Maxwellian averaged cross sections, combining our data below 70 keV with evaluated cross sections at higher neutron energies. Our stellar cross sections are in agreement with a previous activation measurement performed at Forschungszentrum Karlsruhe by Marganiec et al., once their data has been re-normalised to account for an update in the reference cross section used in that experiment.
RESUMEN
The primary focus of environmental toxicological studies is to address the direct effects of chemicals on exposed organisms (parental generation - F0), mostly overlooking effects on subsequent non-exposed generations (F1 and F2 - intergenerational and F3 transgenerational, respectively). Here, we addressed the effects of simvastatin (SIM), one of the most widely prescribed human pharmaceuticals for the primary treatment of hypercholesterolemia, using the keystone crustacean Gammarus locusta. We demonstrate that SIM, at environmentally relevant concentrations, has significant inter and transgenerational (F1 and F3) effects in key signaling pathways involved in crustaceans' neuroendocrine regulation (Ecdysteroids, Catecholamines, NO/cGMP/PKG, GABAergic and Cholinergic signaling pathways), concomitantly with changes in apical endpoints, such as depressed reproduction and growth. These findings are an essential step to improve hazard and risk assessment of biological active compounds, such as SIM, and highlight the importance of studying the transgenerational effects of environmental chemicals in animals' neuroendocrine regulation.
Asunto(s)
Anfípodos , Contaminantes Químicos del Agua , Animales , Reproducción , Simvastatina/toxicidad , Contaminantes Químicos del Agua/toxicidadRESUMEN
PURPOSE: The aim of this study was to compare the results of intrastromal arcuate incisions (AIs) and transepithelial AIs to treat corneal astigmatism during femtosecond laser-assisted cataract surgery (FLACS). METHODS: This retrospective study included 20 patients with corneal astigmatism between 0.70 and 2.00 diopters (D) who underwent FLACS with concurrent intrastromal AIs in one eye and transepithelial AIs in the fellow eye. The main outcomes measures at 2-3 months of follow-up were the difference between pre-operative and postoperative keratometric corneal cylinder (Kcyl), the correction index (CI) and the percentage of overcorrection. RESULTS: The mean difference between preoperative and postoperative Kcyl revealed a mean value of 0.36⯱â¯0.37 D in the transepithelial group and 0.53⯱â¯0.42 D in the intrastromal group (pâ¯<â¯0.001). The mean CI was 0.83⯱â¯0.71 in the transepithelial group and 0.68⯱â¯0.29 in intrastromal group (pâ¯=â¯0.17). Five eyes (25 %) had an astigmatism overcorrection in the transepithelial group and 1 eye (5%) in the intrastromal group. CONCLUSIONS: Both intrastromal and transepithelial AIs showed potential for mild to moderate astigmatism correction and appeared to be a safe procedure. Despite transepithelial AIs presented a higher CI, the intrastromal AIs results were more predictable.
Asunto(s)
Astigmatismo , Catarata , Astigmatismo/cirugía , Topografía de la Córnea , Humanos , Terapia por Láser , Rayos Láser , Refracción Ocular , Estudios Retrospectivos , Agudeza VisualRESUMEN
Embryonic muscle forces are necessary for normal vertebral development and spinal curvature, but their involvement in intervertebral disc (IVD) development remains unclear. The aim of the current study was to determine how muscle contractions affect (1) notochord involution and vertebral segmentation, and (2) IVD development including the mechanical properties and morphology, as well as collagen fibre alignment in the annulus fibrosus. Muscular dysgenesis (mdg) mice were harvested at three prenatal stages: at Theiler Stage (TS)22 when notochord involution starts, at TS24 when involution is complete, and at TS27 when the IVD is formed. Vertebral and IVD development were characterised using histology, immunofluorescence, and indentation testing. The results revealed that notochord involution and vertebral segmentation occurred independently of muscle contractions between TS22 and TS24. However, in the absence of muscle contractions, we found vertebral fusion in the cervical region at TS27, along with (i) a displacement of the nucleus pulposus towards the dorsal side, (ii) a disruption of the structural arrangement of collagen in the annulus fibrosus, and (iii) an increase in viscous behaviour of the annulus fibrosus. These findings emphasise the important role of mechanical forces during IVD development, and demonstrate a critical role of muscle loading during development to enable proper annulus fibrosus formation. They further suggest a need for mechanical loading in the creation of fibre-reinforced tissue engineering replacement IVDs as a therapy for IVD degeneration.
Asunto(s)
Disco Intervertebral/fisiología , Músculos/fisiología , Notocorda/fisiología , Animales , Anillo Fibroso/metabolismo , Anillo Fibroso/fisiología , Colágeno/metabolismo , Matriz Extracelular/metabolismo , Matriz Extracelular/fisiología , Femenino , Disco Intervertebral/metabolismo , Degeneración del Disco Intervertebral/metabolismo , Degeneración del Disco Intervertebral/fisiopatología , Masculino , Ratones , Ratones Endogámicos C57BL , Músculos/metabolismo , Notocorda/metabolismo , Núcleo Pulposo/metabolismo , Núcleo Pulposo/fisiologíaRESUMEN
Copper molybdate nanoplates were synthesized by a sonochemical process at room temperature, which we report as a simple and cost-effective route. Structural analysis of the material by the Rietveld method of X-ray diffraction (XRD) data revealed lindgrenite Cu3(MoO4)2(OH)2 in a single-phase structure. All the vibrational modes characteristic of the space group were identified by Raman vibrational and near-infrared (NIR) spectroscopies. The profile obtained for N2 adsorption/desorption was type III hysteresis, characteristic of mesoporous materials, with a surface area of 70.77(1) m2 g-1. The micrographs of the material obtained by scanning electron microscopy showed nanoplates with nanometric sizes and an anisotropic growth aspect. The catalytic activity of lindgrenite was evaluated by esterifying oleic acid with methanol, showing high conversion rate to methyl oleate and good catalyst stability after seven recycling cycles. Above all, the best catalytic performance was reached when we optimized parameters such as oleic acid:methanol molar ratio of 1:5, 5% of catalyst dosage, and reaction time of 5 h, resulting in 98.38% of conversion at 413 K. Therefore, sonochemically synthesized lindgrenite proved to be a high potential material for biofuel production by oleic acid esterification.
RESUMEN
Rotating Modulation Collimators (RMC) are devices that can be used to determine the location of a radiation source. In this work, a design with extended field-of-view (FOV) is proposed to allow faster measurements by providing a wider scanned area. Monte Carlo simulations were used to calculate the response of the RMC system, system matrix and modulation profiles. The Maximum Likelihood Expectation Maximization algorithm was used for image reconstruction. The proposed design provides a FOV up to 60° with a maximum error of 5° or up to 70° with a maximum error of 15°.
RESUMEN
The neutron capture cross sections of several unstable nuclides acting as branching points in the s process are crucial for stellar nucleosynthesis studies. The unstable ^{171}Tm (t_{1/2}=1.92 yr) is part of the branching around mass Aâ¼170 but its neutron capture cross section as a function of the neutron energy is not known to date. In this work, following the production for the first time of more than 5 mg of ^{171}Tm at the high-flux reactor Institut Laue-Langevin in France, a sample was produced at the Paul Scherrer Institute in Switzerland. Two complementary experiments were carried out at the neutron time-of-flight facility (n_TOF) at CERN in Switzerland and at the SARAF liquid lithium target facility at Soreq Nuclear Research Center in Israel by time of flight and activation, respectively. The result of the time-of-flight experiment consists of the first ever set of resonance parameters and the corresponding average resonance parameters, allowing us to make an estimation of the Maxwellian-averaged cross sections (MACS) by extrapolation. The activation measurement provides a direct and more precise measurement of the MACS at 30 keV: 384(40) mb, with which the estimation from the n_TOF data agree at the limit of 1 standard deviation. This value is 2.6 times lower than the JEFF-3.3 and ENDF/B-VIII evaluations, 25% lower than that of the Bao et al. compilation, and 1.6 times larger than the value recommended in the KADoNiS (v1) database, based on the only previous experiment. Our result affects the nucleosynthesis at the Aâ¼170 branching, namely, the ^{171}Yb abundance increases in the material lost by asymptotic giant branch stars, providing a better match to the available pre-solar SiC grain measurements compared to the calculations based on the current JEFF-3.3 model-based evaluation.
RESUMEN
The hypothesis that exposure to certain environmental chemicals during early life stages may disrupt reproduction across multiple non-exposed generations has significant implications for understanding disease etiology and adverse outcomes. We demonstrate here reproductive multi and transgenerational effects, at environmentally relevant levels, of one of the most prescribed human pharmaceuticals, simvastatin, in a keystone species, the amphipod Gammarus locusta. The transgenerational findings has major implications for hazard and risk assessment of pharmaceuticals and other contaminants of emerging concern given that transgenerational effects of environmental chemicals are not addressed in current hazard and risk assessment schemes. Considering that the mevalonate synthesis, one of the key metabolic pathways targeted by simvastatin, is highly conserved among metazoans, these results may also shed light on the potential transgenerational effects of simvastatin on other animals, including humans.
Asunto(s)
Anfípodos , Simvastatina , Animales , Epigénesis Genética , Humanos , Reproducción , Simvastatina/toxicidadRESUMEN
The newly developed mesh-type reference computational phantoms (MRCPs) represent the evolution of the previous reference phantoms and a more detailed description of the human body, addressing the voxel reference phantom limitations. These allow for a more accurate dose calculation in the human body, which in some cases results in a significant difference of the calculated quantities. In this work, the absorbed dose calculation due to neutrons and gammas was calculated using a voxel and a mesh-type computational phantom. The goal was to understand how a more accurate description of the human body affects the estimated neutron dose. The phantoms were tested in a real-case scenario: they were placed in front of a neutron Howitzer container model using PHITS. This model corresponds to the neutron Howitzer container at the Neutron Measurements Laboratory of the Energy Engineering Department of the Polytechnic University of Madrid (UPM), and at the time of measurement it was equipped with a 241Am-Be neutron source of 74 GBq in its center. The container allows the source to be in either the irradiation or the storage position. Results show that when dealing with neutrons, the dose deviation when using GOLEM or the MRCP leads to a general 20%-30% deviation that goes up to above 400% in small thin structures such as the eye.
Asunto(s)
Modelos Anatómicos , Dosis de Radiación , Radiometría/instrumentación , Diseño de Equipo , Rayos gamma , Humanos , Método de Montecarlo , NeutronesRESUMEN
OBJECTIVES: The long-term success of dental implants is established by literature. Although clinically well defined, the complex genetic pathways underlying osseointegration have not yet been fully elucidated. Furthermore, patients with osteopenia/osteoporosis are considered to present as higher risk for implant failure. Porous tantalum trabecular metal (PTTM), an open-cell porous biomaterial, is suggested to present enhanced biocompatibility and osteoconductivity. The goal of this study was to evaluate the expression patterns of a panel of genes closely associated with osteogenesis and wound healing in osteopenic patients receiving either traditional titanium (Ti) or PTTM cylinders to assess the pathway of genes activation in the early phases of osseointegration. MATERIAL AND METHODS: Implant cylinders made of Ti and PTTM were placed in osteopenic volunteers. At 2- and 4 weeks of healing, one Ti and one PTTM cylinder were removed from each subject for RT-PCR analysis using osteogenesis PCR array. RESULTS: Compared to Ti, PTTM-associated bone displayed upregulation of bone matrix proteins, BMP/TGF tisuperfamily, soluble ligand and integrin receptors, growth factors, and collagen genes at one or both time points. Histologically, PTTM implants displayed more robust osteogenesis deposition and maturity when compared to Ti implants from the same patient. CONCLUSIONS: Our results indicate that PTTM properties could induce an earlier activation of genes associated with osteogenesis in osteopenic patients suggesting that PTTM implants may attenuate the relative risk of placing dental implants in this population.
RESUMEN
This study aims to evaluate the use of assistive devices as a strategy in non-pharmacological treatment for hand osteoarthritis (HOA). This is a randomized, prospective, parallel, assessor-blinded clinical trial, in which patients with a diagnosis of HOA were randomly allocated to an intervention group (IG), where they received assistive devices for daily life activities, or to a control group (CG), where they received a guideline leaflet with information on joint protection and disease features. The primary outcomes considered were occupational performance, measured by the Canadian Occupational Performance Measure (COPM), and hand function was evaluated through the Score for the Assessment and Quantification of Chronic Rheumatoid Affections of the Hands (SACRAH). The secondary outcomes were pain, measured by the visual analog scale (VAS), and quality of life, measured by the World Health Organization Quality of Life Instrument, Short Form (WHOQOL-BREF). We compared both outcomes before and after interventions and outcomes between groups. Participants from the two groups were assessed at the time of inclusion in the study, 30, and 90 days after initial evaluation. Out of the 39 patients included, 19 were allocated to the IG and 20 to the CG. Only two patients from the CG did not complete the follow-up period. The patients' hand function and occupational performance improved after intervention (30 days-SACRAH-p < 0.05; COPM-p < 0.05; VAS-p < 0.05). When comparing results between the groups, there was a statistical difference in COPM (performance-p < 0.001; and satisfaction-p < 0.001), in the first reevaluation carried out. The use of assistive devices has proved to be an effective alternative in non-pharmacological treatment for HOA. CLINICAL TRIAL REGISTRATION: NCT02667145.
Asunto(s)
Actividades Cotidianas , Ergonomía , Articulaciones de la Mano/fisiopatología , Artículos Domésticos , Osteoartritis/terapia , Dispositivos de Autoayuda , Anciano , Fenómenos Biomecánicos , Brasil , Evaluación de la Discapacidad , Diseño de Equipo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Osteoartritis/diagnóstico , Osteoartritis/fisiopatología , Dimensión del Dolor , Estudios Prospectivos , Calidad de Vida , Recuperación de la Función , Encuestas y Cuestionarios , Factores de Tiempo , Resultado del TratamientoRESUMEN
Rheumatic fever (RF) and rheumatic heart disease (RHD) follow untreated S. pyogenes throat infections in children who present susceptible genes that favor the development of autoimmune reactions. In this review, we focus on the genes that confer susceptibility and on the autoimmune reactions that occur due to molecular mimicry between human-tissue proteins and streptococcal M protein. Polyarthritis is the initial manifestation, which can evolve to carditis and severe valve damage; these culminate in rheumatic heart disease (RHD) or Sydenham's chorea, which affects the central nervous system. A perspective on vaccine development to prevent the disease is also discussed.
Asunto(s)
Cardiopatía Reumática/metabolismo , Cardiopatía Reumática/prevención & control , Vacunas/uso terapéutico , Autoinmunidad , Corea/etiología , Corea/inmunología , Corea/metabolismo , Corea/prevención & control , Citocinas/metabolismo , Antígenos de Histocompatibilidad Clase II/genética , Humanos , Imitación Molecular , Fiebre Reumática/etiología , Fiebre Reumática/inmunología , Fiebre Reumática/metabolismo , Fiebre Reumática/prevención & control , Cardiopatía Reumática/etiología , Cardiopatía Reumática/inmunología , Streptococcus pyogenesRESUMEN
Although the use of the posterior mediastinum and the stomach as a reconstruction option after esophagectomy has large acceptance all over the world, there are concerns about the potential respiratory impairment it could cause. We prospectively studied 35 patients regarding the forced expiratory volume and vital capacity. The patients were studied preoperatively and between the 45th and 60th postoperative days. The value of both parameters decreased, although they were still within normal clinical ranges. We concluded that this type of reconstruction does not harm the patients regarding the respiratory flow rates.
Asunto(s)
Neoplasias Esofágicas/cirugía , Esofagoplastia/efectos adversos , Esófago/cirugía , Sistema Respiratorio/fisiopatología , Estómago/cirugía , Anciano , Anastomosis Quirúrgica , Esofagectomía , Femenino , Volumen Espiratorio Forzado , Humanos , Masculino , Mediastino , Persona de Mediana Edad , Periodo Posoperatorio , Periodo Preoperatorio , Estudios Prospectivos , Capacidad VitalRESUMEN
Molecular methods are fundamental tools for the diagnosis of viral infections. While interpretation of results is straightforward for unvaccinated animals, where positivity represents ongoing or past infections, the presence of vaccine virus in the tissues of recently vaccinated animals may mislead diagnosis. In this study, we investigated the interference of RHDV2 vaccination in the results of a RT-qPCR for RHDV2 detection, and possible associations between mean Cq values of five animal groups differing in age, vaccination status and origin (domestic/wild). Viral sequences from vaccinated rabbits that died of RHDV2 infection (n=14) were compared with the sequences from the commercial vaccines used in those animals. Group Cq means were compared through Independent t-test and One-way ANOVA. We proved that RHDV2 vaccine-RNA is not detected by the RT-qPCR as early as 15days post-vaccination, an important fact in assisting results interpretation for diagnosis. Cq values of vaccinated and non-vaccinated infected domestic adults showed a statistically significant difference (p<0.05), demonstrating that vaccination-induced immunity reduces viral loads and delays disease progression. Contrarily, in vaccinated young rabbits higher viral loads were registered compared to non-vaccinated kittens. No significant variation (p=0.3824) was observed between viral loads of non-vaccinated domestic and wild RHDV2-victimised rabbits. Although the reduced number of vaccinated young animals analysed hampered a robust statistical analysis, this occurrence suggests that passively acquired maternal antibodies may inhibit the active immune response to vaccination, delaying protection and favouring disease progression. Our finding emphasises the importance of adapting kitten RHDV2 vaccination schedules to circumvent this interference phenomenon.
Asunto(s)
Infecciones por Caliciviridae/veterinaria , Virus de la Enfermedad Hemorrágica del Conejo/genética , Virus de la Enfermedad Hemorrágica del Conejo/inmunología , Patología Molecular/normas , Vacunación/veterinaria , Vacunas Virales/inmunología , Análisis de Varianza , Animales , Infecciones por Caliciviridae/diagnóstico , Infecciones por Caliciviridae/inmunología , Infecciones por Caliciviridae/virología , Hígado/inmunología , Hígado/virología , Pulmón/inmunología , Pulmón/virología , Reacción en Cadena de la Polimerasa/veterinaria , ARN Viral/análisis , Conejos , Vacunación/normas , Vacunas Virales/genéticaRESUMEN
The energy-dependent cross section of the ^{7}Be(n,α)^{4}He reaction, of interest for the so-called cosmological lithium problem in big bang nucleosynthesis, has been measured for the first time from 10 meV to 10 keV neutron energy. The challenges posed by the short half-life of ^{7}Be and by the low reaction cross section have been overcome at n_TOF thanks to an unprecedented combination of the extremely high luminosity and good resolution of the neutron beam in the new experimental area (EAR2) of the n_TOF facility at CERN, the availability of a sufficient amount of chemically pure ^{7}Be, and a specifically designed experimental setup. Coincidences between the two alpha particles have been recorded in two Si-^{7}Be-Si arrays placed directly in the neutron beam. The present results are consistent, at thermal neutron energy, with the only previous measurement performed in the 1960s at a nuclear reactor. The energy dependence reported here clearly indicates the inadequacy of the cross section estimates currently used in BBN calculations. Although new measurements at higher neutron energy may still be needed, the n_TOF results hint at a minor role of this reaction in BBN, leaving the long-standing cosmological lithium problem unsolved.
RESUMEN
OBJECTIVE: This study evaluated the influence of parathyroid hormone (PTH) (1-34) intermittent administration on rat eruption rates of lower incisors under normo, hyper and hypofunctional conditions, Sharpey fibers insertion, and alveolar bone formation. MATERIALS AND METHODS: Wistar male rats received PTH (1-34) three times a week during the entire experimental period, 31days. Control animals received the same concentration of the vehicle solution during the same period. Three injections of alizarin were also performed. The experiment evaluated the eruptive rate, the alveolar bone formation and also the morphology, and the area density of Sharpey fibers. After the sacrifice, the mandibles were dissected and samples were prepared for fluorescence and scanning electron microscopy observations. RESULTS: PTH-treated animals showed significantly reduced eruption rates in all different functional conditions. Analysis evidenced that PTH-treated rats present an increase in bone formation and area density of the Sharpey fibers. CONCLUSION: We concluded that the PTH (1-34) intermittent administration reduced the eruptive process rates, through bone formation enhancement and increase in the area density of Sharpey fibers.
Asunto(s)
Incisivo/efectos de los fármacos , Hormona Paratiroidea/administración & dosificación , Hormona Paratiroidea/farmacología , Erupción Dental/efectos de los fármacos , Ácido Acético , Proceso Alveolar/efectos de los fármacos , Animales , Antraquinonas/farmacología , Incisivo/crecimiento & desarrollo , Incisivo/ultraestructura , Masculino , Mandíbula/patología , Microscopía Electrónica de Rastreo , Microscopía Fluorescente , Modelos Animales , Odontogénesis/efectos de los fármacos , Osteogénesis/efectos de los fármacos , Osteogénesis/fisiología , Ligamento Periodontal/efectos de los fármacos , Ratas , Ratas Wistar , Erupción Dental/fisiologíaRESUMEN
The purpose of this study was to evaluate the microbial community (MC) composition as it relates to salivary metabolites and periodontal clinical parameters in a 21-d biofilm-overgrowth model. Subjects (N = 168) were enrolled equally into 5 categories of periodontal status per the biofilm-gingival interface classification. Microbial species within subgingival plaque samples were identified by human microbiome identification microarray. Whole saliva was analyzed by liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry for metabolite identification. Phylum was grouped into MCs according to principal component analysis. Generalized linear and regression models were used to examine the association among MC, species, periodontal clinical parameters, and salivary metabolome. Multiple comparisons were adjusted with the false discovery rate. The study population was distributed into 8 distinct MC profiles, designated MC-1 to MC-8. MC-2 explained 14% of the variance and was dominated by Synergistetes and Spirochaetes. It was the only community structure significantly associated with high probing depth (P = 0.02) and high bleeding on probing (P = 0.008). MC-2 was correlated with traditional periodontal pathogens and several newly identified putative periodontal pathogens: Fretibacterium fastidiosum, Fretibacterium sp. OT360/OT362, Filifactor alocis, Treponema lecithinolyticum, Eubacterium saphenum, Desulfobulbus sp./OT041, and Mogibacterium timidum. Synergistetes phylum was strongly associated with 2 novel metabolites-cyclo (-leu-pro) and cyclo (-phe-pro)-at 21 d of biofilm overgrowth (P = 0.02). In subjects with severe periodontitis (P2 and P3), cyclo (-leu-pro) and cyclo (-phe-pro) were significantly associated with increased changes in probing depth at 21 d of biofilm overgrowth (P ≤ 0.05). The analysis identified a MC dominated by Synergistetes, with classic and putative newly identified pathogens/pathobionts associated with clinical disease. The metabolomic discovery of 2 novel cyclodipeptides that have been reported to serve as quorum-sensing and/or bacteriocidal/bacteriostatic molecules, in association with Synergistetes, suggests a potential role in periodontal biofilm dysbiosis and periodontal disease that warrants further investigation.
Asunto(s)
Dipéptidos/análisis , Bacterias Anaerobias Gramnegativas , Infecciones por Bacterias Gramnegativas/complicaciones , Péptidos Cíclicos/análisis , Periodontitis/microbiología , Biopelículas , Placa Dental/microbiología , Cromatografía de Gases y Espectrometría de Masas , Infecciones por Bacterias Gramnegativas/microbiología , Humanos , Metaboloma , Periodontitis/etiología , Saliva/química , Saliva/microbiología , SpirochaetalesRESUMEN
Bacterial infections are known to alter glucose metabolism within tissues via mechanisms of inflammation. We conducted this study to examine whether insulin response genes are differentially expressed in gingival tissues, comparing samples from experimental gingivitis and periodontitis subjects to those from healthy individuals. Total RNA was extracted from gingival biopsies from 26 participants: 8 periodontally healthy, 9 experimental gingivitis, and 9 periodontitis subjects. Gene expression patterns were evaluated with a polymerase chain reaction array panel to examine 84 candidate genes involved with glucose metabolism, insulin resistance, and obesity. Array data were evaluated with a t test adjusted by the false discover rate (P < 0.05), and ingenuity pathway analysis was performed for statistical testing of pathways. Although tissue samples were not sufficient to enable protein quantification, we confirmed the upregulation of the key gene using lipopolysaccharide-stimulated primary gingival epithelial cells by Western blot. The mRNA expression patterns of genes that are associated with insulin response and glucose metabolism are markedly different in experimental gingivitis subjects compared with healthy controls. Thirty-two genes are upregulated significantly by at least 2-fold, adjusted for false discover rate (P < 0.05). Periodontitis subjects show similar but attenuated changes in gene expression patterns, and no genes meet the significance criteria. Ingenuity pathway analysis demonstrates significant activation of the carbohydrate metabolism network in experimental gingivitis but not in periodontitis. G6PD protein increases in response to lipopolysaccharide stimulation in primary gingival epithelial cells, which is in the same direction as upregulated mRNA in tissues. Acute gingival inflammation may be associated with tissue metabolism changes, but these changes are not evident in chronic periodontitis. This study suggests that acute gingival inflammation may induce localized changes that modify tissue insulin/glucose metabolism.