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The near-Earth asteroid (162173) Ryugu is thought to be a primitive carbonaceous object that contains hydrated minerals and organic molecules. We report sample collection from Ryugu's surface by the Hayabusa2 spacecraft on 21 February 2019. Touchdown images and global observations of surface colors are used to investigate the stratigraphy of the surface around the sample location and across Ryugu. Latitudinal color variations suggest the reddening of exposed surface material by solar heating and/or space weathering. Immediately after touchdown, Hayabusa2's thrusters disturbed dark, fine grains that originate from the redder materials. The stratigraphic relationship between identified craters and the redder material indicates that surface reddening occurred over a short period of time. We suggest that Ryugu previously experienced an orbital excursion near the Sun.
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The incidence of stress-induced psychological and somatic diseases has been increasing rapidly, and it is important to clarify the neurophysiological mechanisms of stress response in order to establish effective stress management methods. We previously reported that the prefrontal cortex (PFC) plays an important role in stress response. In the present study, we employed near-infrared spectroscopy (NIRS) and electroencephalography (EEG) to investigate the characteristics of PFC activity during mental arithmetic tasks. A two-channel NIRS device was used to measure hemoglobin (Hb) concentration changes in the bilateral PFC during a mental arithmetic task (2 min) in normal adults. Simultaneously, EEG was used to also measure bilateral PFC activity during the same task. We evaluated concentration changes of oxy-Hb induced by the task while analyzing α wave changes using power spectrum analysis. It was observed that oxy-Hb in the bilateral PFC increased significantly during the task (p < 0.05), while α wave power in the PFC decreased significantly (p < 0.01). The present results indicate that mental stress tasks caused the activation of the bilateral PFC. Simultaneous measurements of NIRS and EEG are useful for evaluating the neurophysiological mechanism of stress responses in the brain.
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Electroencefalografía , Fenómenos Electromagnéticos , Oxígeno , Espectroscopía Infrarroja Corta , Estrés Psicológico , Adulto , Hemoglobinas/análisis , Humanos , Oxígeno/sangre , Oxihemoglobinas/análisis , Corteza Prefrontal/fisiopatología , Estrés Psicológico/fisiopatologíaRESUMEN
We present an IoT-based monitoring system for healthcare that allows for long-term measurements of blood pressure (BP), heart rate (HR), and body weight (BW), as well as near-infrared spectroscopy (NIRS) for measurement of prefrontal cortex (PFC) activity. To verify the applicability of the system, it was set up in a local fitness gym for a preliminary study. A total of 39 subjects, selected from members of the gym, participated in the study. We analyzed the BP, HR, and BW data, collected from the subjects over one half-year. In addition, to assess the degree of mental stress of the subjects, we analysed left-right asymmetry of the PFC activity using the laterality index at rest (LIR) of the NIRS parameter. Results show that the subjects were able to measure their physiological data by themselves when they visited the gym, after being instructed how to perform the measurements. Furthermore, the results also indicate that ordinary people can continuously monitor physiological functions such as brain function in a non-medical facility, such as a fitness gym.
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Monitoreo Fisiológico , Corteza Prefrontal , Espectroscopía Infrarroja Corta , Anciano , Femenino , Lateralidad Funcional , Frecuencia Cardíaca , Humanos , Masculino , Persona de Mediana Edad , Monitoreo Fisiológico/instrumentación , Monitoreo Fisiológico/métodos , Monitoreo Fisiológico/normas , Autoexamen/normas , Estrés PsicológicoRESUMEN
Industrialization often causes polycyclic aromatic hydrocarbon (PAH) and heavy metal contamination of soil and water. In this study, we isolated a bacterium from bottom mud water around a park of Kawasaki Port, Japan, that degrades the 5-ring PAH dibenz[a,h]anthracene (DBA). The strain, Comamonas sp. 3ah48, degraded 29% of DBA (30 µg ml-1 ) in 7 days, and the degradation level increased drastically, to 59%, by the addition of glutamate to the medium. The strain also degraded 40, 14, 15 and 19% of pyrene (Pyr), benzo[b]fluoranthene (BbF), benzo[k]fluoranthene (BkF) and benzo[g,h,i]perylene (BghiP) respectively. Benzo[a]pyrene (BaP) was degraded only when glutamate was added to the medium. Strain 3ah48 retained its degradation levels in the presence of 2 mmol l-1 Co2+ , Zn2+ or Cr2+ , at almost the same level as that without metal, and increased the DBA degradation level to 57% in the presence of 2 mmol l-1 Cu2+ , suggesting the possibility of the presence of laccase. SIGNIFICANCE AND IMPACT OF THE STUDY: Sixteen polycyclic aromatic hydrocarbons (PAHs) are listed as priority pollutants by the United States Environmental Protection Agency (USEPA). Information about the biodegradation of one of those PAHs, dibenz[a,h]anthracene (DBA), is limited. The present study focuses on DBA degradation by Comamonas sp. 3ah48 strain isolated around Kawasaki Port, Japan. Comamonas sp. 3ah48, cultured with the addition of glutamate to the medium, was found to increase the degradation level of DBA and to degrade DBA even in the presence of high concentrations of heavy metals.
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Benzo(a)Antracenos/metabolismo , Benzo(a)pireno/metabolismo , Biodegradación Ambiental , Comamonas/metabolismo , Metales Pesados/toxicidad , Comamonas/efectos de los fármacos , Sedimentos Geológicos/microbiología , Ácido Glutámico/metabolismo , Japón , Hidrocarburos Policíclicos Aromáticos/metabolismo , Suelo/química , Microbiología del SueloRESUMEN
This study investigated the genetic basis of an unusual autosomal dominant phenotype characterized by familial absent uvula, with a short posterior border of the soft palate, abnormal tonsillar pillars, and velopharyngeal insufficiency. Cytogenetic analysis and single-nucleotide polymorphism-based linkage analysis were investigated in a 4-generation family with 8 affected individuals. Whole exome sequencing data were overlaid, and segregation analysis identified a single missense variant, p.Q433P in the FOXF2 transcription factor, that fully segregated with the phenotype. This was found to be in linkage disequilibrium with a small 6p25.3 tandem duplication affecting FOXC1 and GMDS. Notably, the copy number imbalances of this region are commonly associated with pathologies that are not present in this family. Bioinformatic predictions with luciferase reporter studies of the FOXF2 missense variant indicated a negative impact, affecting both protein stability and transcriptional activation. Foxf 2 is expressed in the posterior mouse palate, and knockout animals develop an overt cleft palate. Since mice naturally lack the structural equivalent of the uvula, we demonstrated FOXF2 expression in the developing human uvula. Decipher also records 2 individuals with hypoplastic or bifid uvulae with copy number variants affecting FOXF2. Nevertheless, given cosegregation with the 6p25.3 duplications, we cannot rule out a combined effect of these gains and the missense variant on FOXF2 function, which may account for the rare palate phenotype observed.
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Factores de Transcripción Forkhead/genética , Paladar Blando/patología , Úvula/patología , Preescolar , Análisis Mutacional de ADN , Egipto , Femenino , Humanos , Desequilibrio de Ligamiento , Masculino , Tonsila Palatina/patología , Linaje , Polimorfismo de Nucleótido SimpleRESUMEN
BACKGROUND: Urinary incontinence (UI) is a frequent, but neglected geriatric syndrome, particularly in vulnerable older patients. Optimizing screening procedures is necessary. OBJECTIVE: To compare the clinometric performances of the "continence" item of the Katz's ADL scale and the ICIQ-UI-sf for the screening of UI in vulnerable aged patients. METHODS: A prospective study was conducted in the acute care for elders (ACE) unit of an academic centre. Two independent nurses screened all patients with spontaneous urination for UI with Katz's ADL item and ICIQ-UI-sf upon the hospital admission. The diagnosis of UI resulted from an interdisciplinary conciliating meeting for urinary functional disorders (TOFU), gathering geriatricians and neuro-urologists and was considered as reference. RESULTS: 294 consecutive patients (mean age 86.2 ± 6.5 years; 76.5% female) admitted to the ACE unit were screened; 169 were incontinent (57.5%) according to TOFU. The Katz's ADL item identified 106 incontinent patients with 20 false positives; 83 incontinent patients were not identified. If the sensitivity and specificity of the ICIQ-UI-sf were 100.0%, they were, respectively, 50.9 and 84.0% for the Katz's ADL item. Positive and negative predictive values were 100.0% for ICIQ-UI-sf; 81.1 and 55.9% for ADL, respectively. CONCLUSION: This study validates the ICIQ-UI-sf as a simple and effective screening tool for UI in vulnerable and complex hospitalized aged patients. It also demonstrates that the "continence" item of the Katz's ADL scale is not sensitive enough for UI screening in this population.
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BACKGROUND: Anatomical knowledge of the duodenojejunal flexure is necessary for abdominal surgeries, and also important for physiologic studies about the duodenum. But little is known about the anatomy of this region in mammals. Here, we examined comparative anatomy to understand the anatomical formation of the duodenojejunal flexure in mammals. MATERIALS AND METHODS: The areas around the duonenojejunal flexure were ob-served in mouse, rat, dog, pig, and human, and the anatomical structures around the duodenojejunal junction in the animals were compared with those in human. RESULTS: The superior and inferior duodenal folds, and the superior and inferior duodenal fossae were identified in all examined humans. In pig, the structures were not clearly identified because the duodenum strongly adhered to the retroperitoneum and to the mesocolon. In mouse, rat, and dog, only the plica duodenocolica, which is regarded as the animal counterpart of the superior duo-denal fold in human, was identified, and other folds or fossae were not observed, probably because the duodenum was not fixed to the parietal peritoneum in those animals. Transection of the plica duodenocolica could return the normally rotated intestine back to the state of non-rotation in rat. CONCLUSIONS: This study showed the anatomical similarities and dissimilarities of the duodenojejunal flexure among the mammals. Anatomical knowledge of the area is useful for duodenal and pancreatic surgeries, and for animal studies about the duodenum. (Folia Morphol 2018; 77, 2: 286-292).
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Duodeno/anatomía & histología , Yeyuno/anatomía & histología , Anatomía Comparada , Animales , Perros , Humanos , Ratas , Especificidad de la Especie , PorcinosRESUMEN
Neural tube defects (NTDs) affecting the brain (anencephaly) are lethal before or at birth, whereas lower spinal defects (spina bifida) may lead to lifelong neurological handicap. Collectively, NTDs rank among the most common birth defects worldwide. This study focuses on anencephaly, which despite having a similar frequency to spina bifida and being the most common type of NTD observed in mouse models, has had more limited inclusion in genetic studies. A genetic influence is strongly implicated in determining risk of NTDs and a molecular diagnosis is of fundamental importance to families both in terms of understanding the origin of the condition and for managing future pregnancies. Here we used a custom panel of 191 NTD candidate genes to screen 90 patients with cranial NTDs (n = 85 anencephaly and n = 5 craniorachischisis) with a targeted exome sequencing platform. After filtering and comparing to our in-house control exome database (N = 509), we identified 397 rare variants (minor allele frequency, MAF < 1%), 21 of which were previously unreported and predicted damaging. This included 1 frameshift (PDGFRA), 2 stop-gained (MAT1A; NOS2) and 18 missense variations. Together with evidence for oligogenic inheritance, this study provides new information on the possible genetic causation of anencephaly.
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Anencefalia/genética , Epistasis Genética , Defectos del Tubo Neural/genética , Disrafia Espinal/genética , Anencefalia/fisiopatología , Animales , Modelos Animales de Enfermedad , Femenino , Estudios de Asociación Genética , Humanos , Masculino , Ratones , Mutación , Defectos del Tubo Neural/fisiopatología , Fenotipo , Embarazo , Cráneo/anomalías , Cráneo/fisiopatología , Disrafia Espinal/fisiopatología , Secuenciación del ExomaRESUMEN
PurposeTo determine the correlation of the degree of aniseikonia with the retinal displacements and metamorphopsia in patients that have undergone successful epiretinal membrane (ERM) surgery.MethodsSubjects were 28 eyes with an ERM in 28 patients. The New Aniseikonia Test (NAT) and M-CHARTS were used to quantify the degree of preoperative and postoperative aniseikonia and metamorphopsia. We also evaluated the distance between the intersections of 2 sets of retinal vessels situated vertically or horizontally by using spectral-domain optical coherence tomography (SD-OCT) images in 28 patients.ResultsThe vertical score of M-CHARTS (MV) was not significantly improved, but the horizontal score of M-CHARTS (MH) was significantly improved at 1 week, 1 month, and 3 months postoperatively. The preoperative NAT score was significantly correlated with the preoperative MH. The NAT score at 3 months was significantly correlated with the MH at 3 months and the MV at 3 months. The preoperative NAT score was significantly correlated with the ratio of the vertical retinal displacement at 1 month and at 3 months after surgery. However, the NAT scores did not improve significantly at any postoperative times.ConclusionsThe degree of aniseikonia was significantly correlated with the degree of metamorphopsia and the tangential displacement of the retina after ERM surgery. Aniseikonia is difficult to improve and metamorphopsia may be a more sensitive parameter to detect the functional recovery after successful ERM surgery.
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Aniseiconia/patología , Membrana Epirretinal/cirugía , Retina/patología , Trastornos de la Visión/patología , Vitrectomía , Anciano , Anciano de 80 o más Años , Aniseiconia/etiología , Membrana Epirretinal/complicaciones , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tomografía de Coherencia Óptica/métodos , Trastornos de la Visión/etiología , Agudeza Visual , Vitrectomía/métodosRESUMEN
Studies of chemotactic cell migration rely heavily on various assay systems designed to evaluate the ability of cells to move in response to attractant molecules. In particular, the development of microfluidics-based devices in recent years has made it possible to spatially distribute attractant molecules in graded profiles that are sufficiently stable and precise to test theoretical predictions regarding the accuracy and efficiency of chemotaxis and the underlying mechanism of stimulus perception. However, because the gradient is fixed in a direction orthogonal to the laminar flow and thus the chamber geometry, conventional devices are limited for the study of cell re-orientation to gradients that move or change directions. Here, we describe the development of a simple radially symmetric microfluidics device that can deliver laminar flow in 360°. A stimulant introduced either from the central inlet or by photo uncaging is focused into the laminar flow in a direction determined by the relative rate of regulated flow from multiple side channels. Schemes for flow regulation and an extended duplexed device were designed to generate and move gradients in desired orientations and speed, and then tested to steer cell migration of Dictyostelium and neutrophil-like HL60 cells. The device provided a high degree of freedom in the positioning and orientation of attractant gradients, and thus may serve as a versatile platform for studying cell migration, re-orientation, and steering.
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Dispositivos Laboratorio en un Chip , Movimiento Celular , Dictyostelium/citología , Difusión , Diseño de Equipo , Células HL-60 , Humanos , CinéticaRESUMEN
Investigations into mechanisms in various cortical areas can be greatly improved and supported by stable recording of single neuronal activity. In this study, fine silicon wire electrodes (diameter 3 µm, length 160 µm) are fabricated by vapor-liquid-solid (VLS) growth with the aim of stabilizing recording and reducing the invasiveness on the measurement procedure. The electrode is fabricated on a modular 1 × 1 mm2 conductive silicon block that can be assembled into a number of different device packages, for example on rigid or flexible printed circuit boards (PCB). After plating with a 5 µm diameter platinum black, the needle exhibits an electrical impedance of ~100 kΩ at 1 kHz in saline. The in vivo recording capability of the device is demonstrated using mice, and spike signals with peak-to-peak amplitudes of 200-300 µV in the range 0.5-3 kHz are stably detected, including single-unit activities in cortical layer 2/3. In addition, the device packaged with a flexible PCB shows stable unit recordings for 98.5 min (n = 4). Consequently, our modular, low-invasive needle electrode block devices present an effective route for single-unit recordings in vivo, as well as demonstrating adaptability in device design for a diverse range of experiments.
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Electrodos Implantados , Microelectrodos , Análisis de la Célula Individual/instrumentación , Corteza Somatosensorial/fisiología , Corteza Visual/fisiología , Animales , Impedancia Eléctrica , Diseño de Equipo , Masculino , Ratones , Neuronas/fisiología , Estimulación Luminosa , Análisis de la Célula Individual/métodos , Corteza Visual/citologíaRESUMEN
BACKGROUND: Vonoprazan, a potassium-competitive acid blocker, is expected to improve the healing of endoscopic submucosal dissection (ESD)-induced gastric ulcers compared with proton pump inhibitors (PPIs). AIM: To compare the healing status of ESD-induced gastric ulcers and the incidence of post-ESD bleeding between subjects treated with vonoprazan for 5 weeks and those treated with PPIs for 8 weeks. METHODS: Patients in the vonoprazan group (n = 75) were prospectively enrolled, whereas patients in the PPI group (n = 150) were selected for a 2:1 matched historical control cohort according to baseline characteristics including gastric ulcer size immediately following ESD, age, sex and status of Helicobacter pylori infection. Two controls per case of vonoprazan-treated group were matched with a margin of 20% in terms of ulcer size and a margin of 5 years in terms of their age. RESULTS: Although a higher number of completely healed ulcers was observed in the PPI group (95/150, 63.3%) than that in the vonoprazan group (14/75, 18.7%; P < 0.001), the ulcer size reduction rates, which were 96.0 ± 6.7% in the vonoprazan group and 94.7 ± 11.6% in the PPI group, were not significantly different (P = 0.373). The post-ESD bleeding incidence in the vonoprazan group (1/75, 1.3%) was less than that in the PPI group (15/150, 10.0%; P = 0.01). The factors affecting post-ESD bleeding incidence were the type of acid secretion inhibitor (P = 0.016) and use of an anti-thrombotic agent (P = 0.014). CONCLUSION: Vonoprazan significantly reduced post-endoscopic submucosal dissection bleeding compared with PPIs.
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Resección Endoscópica de la Mucosa/efectos adversos , Hemorragia Gastrointestinal/prevención & control , Complicaciones Posoperatorias/tratamiento farmacológico , Inhibidores de la Bomba de Protones/uso terapéutico , Pirroles/uso terapéutico , Úlcera Gástrica/tratamiento farmacológico , Úlcera Gástrica/etiología , Sulfonamidas/uso terapéutico , Adenoma/cirugía , Anciano , Anciano de 80 o más Años , Femenino , Hemorragia Gastrointestinal/etiología , Humanos , Masculino , Persona de Mediana Edad , Rabeprazol/uso terapéutico , Neoplasias Gástricas/cirugía , Cicatrización de Heridas/efectos de los fármacosRESUMEN
Recent basic and clinical studies have assessed the use of highly sensitive imaging modalities for visualizing transplanted islets. We investigated the utility of enhanced ultrasonography, combined with fluorescent acoustic liposome nano/microbubbles (FALs), for evaluating angiogenesis and the endocrine function of transplanted islets. BALB/c mice were classified into three groups: Diabetic mice that underwent syngeneic islet transplantation into the subrenal capsule and achieved normoglycemia (Tx group); those that failed to achieve normoglycemia (Tx-DM group); and those not receiving any treatment (DM group). Mice were examined by FAL-enhanced high frequency ultrasonography. The echogenicity of the islets increased rapidly within the first minute after injection of FALs and remained at a higher level in the Tx group, while small increases were observed in the other two groups. In histological assessments, fluorescently stained erythrocytes could be seen in and around the transplanted islets, indicating that the transplanted islets were enhanced by infusion of FALs via vessel networks between the engrafted islets and tissue. Furthermore, the echogenicity correlated significantly with endocrine parameters, including blood glucose (BG), serum insulin, and the BG change in the glucose tolerance test. In conclusion, the echogenicity of the islets under FAS-enhanced ultrasonosonography correlated with the endocrine status of transplanted islets.
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Medios de Contraste , Diabetes Mellitus Experimental/cirugía , Trasplante de Islotes Pancreáticos/diagnóstico por imagen , Islotes Pancreáticos/diagnóstico por imagen , Microburbujas , Ultrasonografía/métodos , Animales , Glucemia/metabolismo , Diabetes Mellitus Experimental/inducido químicamente , Modelos Animales de Enfermedad , Insulina/sangre , Islotes Pancreáticos/irrigación sanguínea , Islotes Pancreáticos/fisiología , Ratones , Ratones Endogámicos BALB C , Neovascularización Fisiológica/fisiología , Estreptozocina/efectos adversos , Resultado del TratamientoRESUMEN
Islet autotransplantation following total pancreatectomy differs from allograft transplantation with respect to the requirement of biliary reconstruction. Although it is known that careful consideration should be given to postoperative cholestatic liver injury after biliary reconstruction, its direct effects on transplanted islets have not been completely elucidated. In this study, we developed a murine model of postoperative cholestatic liver injury after biliary reconstruction with islet autotransplantation that involved syngeneic intraportal islet transplantation into chemically induced diabetic mice and common bile duct ligation. We assessed the viability and function of the transplanted islets. The impaired viability of transplanted islets and increased blood glucose levels indicated restoration of the diabetic state after common bile duct ligation in this murine model. Furthermore, impaired islet viability and function occurred earlier in the transplanted islets than in the surrounding liver tissues, which was consistent with the faster and higher expression of oxidative stress markers in the transplanted islets. Transplanted islets may be more vulnerable to oxidative stress caused by cholestatic liver injury than the surrounding liver tissue. Therefore, patients should be intensively managed after total pancreatectomy with islet autotransplantation to preserve viability and function of the transplanted islets.
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Sistema Biliar/fisiopatología , Colestasis/prevención & control , Islotes Pancreáticos/fisiología , Animales , Masculino , Ratones , Ratones Endogámicos BALB C , Estrés OxidativoRESUMEN
Silver-Russell syndrome (SRS) is a clinically heterogeneous disorder characterised by severe in utero growth restriction and poor postnatal growth, body asymmetry, irregular craniofacial features and several additional minor malformations. The aetiology of SRS is complex and current evidence strongly implicates imprinted genes. Approximately, half of all patients exhibit DNA hypomethylation at the H19/IGF2 imprinted domain, and around 10% have maternal uniparental disomy of chromosome 7. We measured DNA methylation in 18 SRS patients at >485,000 CpG sites using DNA methylation microarrays. Using a novel bioinformatics methodology specifically designed to identify subsets of patients with a shared epimutation, we analysed methylation changes genome-wide as well as at known imprinted regions to identify SRS-associated epimutations. Our analysis identifies epimutations at the previously characterised domains of H19/IGF2 and at imprinted regions on chromosome 7, providing proof of principle that our methodology can detect DNA methylation changes at imprinted loci. In addition, we discovered two novel epimutations associated with SRS and located at imprinted loci previously linked to relevant mouse and human phenotypes. We identify RB1 as an additional imprinted locus associated with SRS, with a region near the RB1 differentially methylated region hypermethylated in 13/18 (~70%) patients. We also report 6/18 (~33%) patients were hypermethylated at a CpG island near the ANKRD11 gene. We do not observe consistent co-occurrence of epimutations at multiple imprinted loci in single SRS individuals. SRS is clinically heterogeneous and the absence of multiple imprinted loci epimutations reflects the heterogeneity at the molecular level. Further stratification of SRS patients by molecular phenotypes might aid the identification of disease causes.
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Metilación de ADN , Síndrome de Silver-Russell/genética , Adolescente , Estudios de Casos y Controles , Niño , Preescolar , Islas de CpG , Femenino , Genoma Humano , Estudio de Asociación del Genoma Completo , Impresión Genómica , Humanos , Lactante , Masculino , Análisis de Secuencia por Matrices de Oligonucleótidos , Regiones Promotoras Genéticas , ARN Largo no Codificante/genética , Proteínas Represoras/genética , Proteína de Retinoblastoma/genética , Análisis de Secuencia de ADN , Adulto JovenRESUMEN
The spin Seebeck effect refers to the generation of spin voltage as a result of a temperature gradient in ferromagnetic or ferrimagnetic materials. When a conductor is attached to a magnet under a temperature gradient, the thermally generated spin voltage in the magnet injects a spin current into the conductor, which in turn produces electric voltage owing to the spin-orbit interaction. The spin Seebeck effect is of increasing importance in spintronics, since it enables direct generation of a spin current from heat and appears in a variety of magnets ranging from metals and semiconductors to insulators. Recent studies on the spin Seebeck effect have been conducted mainly in paramagnetic metal/ferrimagnetic insulator junction systems in the longitudinal configuration in which a spin current flowing parallel to the temperature gradient is measured. This 'longitudinal spin Seebeck effect' (LSSE) has been observed in various sample systems and exclusively established by separating the spin-current contribution from extrinsic artefacts, such as conventional thermoelectric and magnetic proximity effects. The LSSE in insulators also provides a novel and versatile pathway to thermoelectric generation in combination of the inverse spin-Hall effects. In this paper, we review basic experiments on the LSSE and discuss its potential thermoelectric applications with several demonstrations.
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OBJECTIVE: Bacterial lipopolysaccharide (LPS) can induce inflammatory bone loss such as periodontal disease. The formation of osteoclasts depends on macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor kb ligand (RANKL). It has recently been reported that administration of an antibody of the M-CSF receptor c-Fms completely blocked osteoclastogenesis and bone erosion induced by LPS in mouse calvaria. In this study, the effect of antibody against c-Fms in the mouse periodontitis model by injection of LPS was investigated. MATERIALS AND METHODS: C57BL6/J mice were injected with LPS and anti-c-Fms antibody into the mesial gingiva of the first molar in the left mandible. Histological sections of periodontal tissue were stained for tartrate-resistant acid phosphatase, and osteoclast numbers and ratio of alveolar bone resorption determined. RESULTS: The number of osteoclasts and ratio of alveolar bone resorption in mice administered both LPS and anti-c-Fms antibody was lower than those in mice administered LPS alone. The expression of RANKL receptor, RANK, was inhibited by the anti-c-Fms antibody in periodontal tissue. CONCLUSION: M-CSF and/or its receptor are potential therapeutic targets for the treatment of bone resorption, caused by LPS, in periodontitis. Injection of an anti-c-Fms antibody might be useful for inhibition of pathological bone resorption in periodontitis.
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Anticuerpos/inmunología , Osteoclastos/fisiología , Periodontitis/inmunología , Receptor de Factor Estimulante de Colonias de Macrófagos/inmunología , Animales , Diferenciación Celular , Modelos Animales de Enfermedad , Masculino , Ratones , Ratones Endogámicos C57BLRESUMEN
To improve the function of the polyvinyl alcohol (PVA) bioartificial pancreas, we focused on bone marrow-derived mesenchymal stem cells (MSCs). We examined whether the function of PVA-encapsulated rat islets could be improved by coencapsulation with syngeneic MSCs. We macroencapsulated 1,500 rat islet equivalents (IEQ) with or without 1 × 10(6) MSCs with the use of 3% PVA solution before implantation intraperitoneally into diabetic BALB/c mice. We evaluated the function of the device in vitro (the residual rate, viability, and insulin-releasing function of the islets) and in vivo assessments (blood glucose and serum C-peptide changes after transplantation and glucose tolerance test). Although cultured islets also were destroyed, the shapes of the islets cocultured with MSCs were preserved but not different from encapsulated islets without MSCs. At 96 hours after culture the residual rates of islet recovery among those cocultured with versus without MSCs were 66% versus 39.5%, respectively, (P = .03). On the other hand, there was no significant difference between encapsulated islets with versus without MSCs. Furthermore, the stimulation index of the islets was improved by coculture with MSCs (2.6 ± 0.6 vs 1.4 ± 0.1; P = .03), but no beneficial effects were observed between islets encapsulated with versus without MSCs. The viability of islets cocultured with MSCs was significantly better than that without MSCs (84.2 ± 2.5 vs 73.3 ± 0.9; P = .037), but MSCs did not improve the viability of encapsulated islets. There were no significant differences in blood glucose or serum C-peptide between islets encapsulated with versus without MSCs. The histologic findings showed many degenerative islets and MSCs soon after transplantation. In conclusion, further studies are necessary to develop a novel PVA bioartificial pancreas that can be used with MSCs.