RESUMEN
OBJECTIVES: Examine differences in multidimensional well-being from before (January 2020) to three timepoints during the COVID-19 pandemic (June 2020, January 2021, January 2022). STUDY DESIGN: Repeated cross-sectional design. METHODS: Nationally representative cross-sectional cohorts of US adults completed the Secure Flourish Index before (January 2020 cohort: N = 1010) and during the COVID-19 pandemic (June 2020 cohort: N = 3020; January 2021 cohort: N = 3366; January 2022 cohort: N = 2598). We estimated differences in indicators, domains, and composite well-being between the January 2020 cohort and each of the subsequent cohorts. We also explored whether changes in well-being between January 2020 and January 2022 varied based on age, gender, and race/ethnicity. RESULTS: Initial declines in well-being observed by June 2020 were largely followed by a return to prepandemic levels in January 2022, with some exceptions. Notably, general declines in mental health have persisted through to January 2022. On the other hand, there was evidence of general improvements in character & virtue that exceeded prepandemic levels in January 2022. Young adults and racial/ethnic minorities reported lower financial & material stability in January 2022 compared to before the COVID-19 pandemic. CONCLUSIONS: Although there are promising signs that the well-being of US adults has mostly recovered to prepandemic levels, a coordinated response is urgently needed to support population mental health and the financial security of vulnerable groups. As society continues the journey toward postpandemic recovery, continued tracking of multidimensional well-being will be important for making informed decisions about public health priorities.
Asunto(s)
COVID-19 , Adulto Joven , Humanos , Estados Unidos/epidemiología , COVID-19/epidemiología , Estudios Transversales , Pandemias , Toma de Decisiones , EtnicidadRESUMEN
The ν=2/3 fractional quantum Hall state is the hole-conjugate state to the primary Laughlin ν=1/3 state. We investigate transmission of edge states through quantum point contacts fabricated on a GaAs/AlGaAs heterostructure designed to have a sharp confining potential. When a small but finite bias is applied, we observe an intermediate conductance plateau with G=0.5(e^{2}/h). This plateau is observed in multiple QPCs, and persists over a significant range of magnetic field, gate voltage, and source-drain bias, making it a robust feature. Using a simple model that considers scattering and equilibration between counterflowing charged edge modes, we find this half-integer quantized plateau to be consistent with full reflection of an inner counterpropagating -1/3 edge mode while the outer integer mode is fully transmitted. In a QPC fabricated on a different heterostructure which has a softer confining potential, we instead observe an intermediate conductance plateau at G=(1/3)(e^{2}/h). These results provide support for a model at ν=2/3 in which the edge transitions from a structure having an inner upstream -1/3 charge mode and outer downstream integer mode to a structure with two downstream 1/3 charge modes when the confining potential is tuned from sharp to soft and disorder prevails.
RESUMEN
Quantum Hall interferometers have been used to probe fractional charge and statistics of quasiparticles. We present measurements of a small Fabry-Perot interferometer in which the electrostatic coupling constants which affect interferometer behavior can be determined experimentally. Near the center of the ν = 1/3 state this device exhibits Aharonov-Bohm interference interrupted by a few discrete phase jumps, and Φ0 oscillations at higher and lower magnetic fields, consistent with theoretical predictions for detection of anyonic statistics. We estimate the electrostatic parameters KI and KIL by two methods: using the ratio of oscillation periods in compressible versus incompressible regions, and from finite-bias conductance measurements. We find that the extracted KI and KIL can account for the deviation of the phase jumps from the theoretical anyonic phase θa = 2π/3. At integer states, we find that KI and KIL can account for the Aharonov-Bohm and Coulomb-dominated behavior of different edge states.
RESUMEN
Maternal immune activation (MIA) during pregnancy is an established environmental risk factor for schizophrenia. Timing of immune activation exposure as well as sex of the exposed offspring are critical factors in defining the effects of MIA. However, the specificity of MIA on the component structure of schizophrenia, especially cognition, has been difficult to assess due to a lack of translational validity of maze-like testing paradigms. We aimed to assess cognitive domains relevant to schizophrenia using highly translational touchscreen-based tasks in male and female mice exposed to the viral mimetic, poly(I:C) (5 mg/k, i.p.), during early (gestational day (GD) 9-11) and late (GD13-15) gestational time points. Gene expression of schizophrenia candidate pathways were assessed in fetal brain immediately following poly(I:C) exposure and in adulthood to identify its influence on neurodevelopmental processes. Sex and window specific alterations in cognitive performance were found with the early window of MIA exposure causing female-specific disruptions to working memory and reduced perseverative behaviour, while late MIA exposure caused male-specific changes to working memory and deficits in reversal learning. GABAergic specification marker, Nkx2.1 gene expression was reduced in fetal brains and reelin expression was reduced in adult hippocampus of both early and late poly(I:C) exposed mice. Neuregulin and EGF signalling were initially upregulated in the fetal brain, but were reduced in the adult hippocampus, with male mice exposed in the late window showing reduced Nrg3 expression. Serine racemase was reduced in both fetal and adult brain, but again, adult reductions were specific to male mice exposed at the late time point. Overall, we show that cognitive constructs relevant to schizophrenia are altered by in utero exposure to maternal immune activation, but are highly dependent on the timing of infection and the sex of the offspring. Glutamatergic and epidermal growth factor pathways were similarly altered by MIA in a timing and sex dependent manner, while MIA-induced GABAergic deficits were independent of timing or sex.
Asunto(s)
Efectos Tardíos de la Exposición Prenatal , Esquizofrenia , Animales , Conducta Animal/fisiología , Cognición , Modelos Animales de Enfermedad , Femenino , Masculino , Ratones , Neurregulinas , Poli I-C/farmacología , EmbarazoRESUMEN
Liquid crystalline phases of matter permeate nature and technology, with examples ranging from cell membranes to liquid-crystal displays. Remarkably, electronic liquid-crystal phases can exist in two-dimensional electron systems (2DES) at half Landau-level filling in the quantum Hall regime. Theory has predicted the existence of a liquid-crystal smectic phase that breaks both rotational and translational symmetries. However, previous experiments in 2DES are most consistent with an anisotropic nematic phase breaking only rotational symmetry. Here we report three transport phenomena at half-filling in ultra-low disorder 2DES: a non-monotonic temperature dependence of the sample resistance, dramatic onset of large time-dependent resistance fluctuations, and a sharp feature in the differential resistance suggestive of depinning. These data suggest that a sequence of symmetry-breaking phase transitions occurs as temperature is lowered: first a transition from an isotropic liquid to a nematic phase and finally to a liquid-crystal smectic phase.
RESUMEN
BACKGROUND AND OBJECTIVES: Human leukocyte antigen (HLA) antibodies, which are involved in the development of transfusion-related side effects such as transfusion-related lung injury, are sometimes found in males without a history of alloimmunization (eg, transplantation and transfusion). Whether HLA antibodies in male donors can interact with their target HLA specificities expressed on cells have not been completely investigated. MATERIALS AND METHODS: The HLA antibodies detected in 7 male donors were characterized. Flow cytometry and immunocomplex capture fluorescence analysis were performed to evaluate the ability of these antibodies to bind with target HLA specificities expressed on cells. The association of these antibodies with complement was examined using anti-C1q antibody. Sustainability of HLA antibodies over time was compared in 26 male vs 57 female donors. RESULTS: The antibodies from all 7 donors recognized intact HLA molecules coated onto microbeads. The antibodies in 2 of 7 donors also recognized their target HLA specificities expressed on cells. Furthermore, the antibodies in one of these 2 donors showed HLA specificities that involved complement binding. Twenty-one of 26 initially positive male donors had turned negative for HLA antibody at least 1 year after their initial positive screening, whereas HLA antibody positivity was maintained for a long time in most female donors. CONCLUSION: Males without apparent alloimmunization could have HLA antibodies that recognize their target HLA specificities on cells and that could potentially modify molecular events in affected cells.
Asunto(s)
Complejo Antígeno-Anticuerpo/sangre , Donantes de Sangre , Proteínas del Sistema Complemento/metabolismo , Antígenos HLA/sangre , Isoanticuerpos/sangre , Adulto , Especificidad de Anticuerpos , Femenino , Citometría de Flujo , Humanos , Masculino , Unión Proteica , Factores Sexuales , Lesión Pulmonar Aguda Postransfusional/prevención & controlRESUMEN
Long non-coding RNAs (lncRNAs) are frequently dysregulated in a variety of human cancers. However, their biological roles in these cancers remain incompletely understood. In this study, we analyze the gene expression profiles of colon cancer tissues and identify a previously unannotated lncRNA, FLJ39051, that we term GSEC (G-quadruplex-forming sequence containing lncRNA), as a lncRNA that is upregulated in colorectal cancer. We further demonstrate that knockdown of GSEC results in the reduction of colon cancer cell motility. We also show that GSEC binds to the DEAH box polypeptide 36 (DHX36) RNA helicase via its G-quadruplex-forming sequence and inhibits DHX36 G-quadruplex unwinding activity. Moreover, knockdown of DHX36 restores the reduced migratory activity of colon cancer cells caused by GSEC knockdown. These results suggest that GSEC plays an important role in colon cancer cell migration by inhibiting the function of DHX36 via its G-quadruplex structure.
Asunto(s)
Movimiento Celular , Neoplasias del Colon/patología , ARN Helicasas DEAD-box/antagonistas & inhibidores , G-Cuádruplex , ARN Largo no Codificante/genética , ARN Neoplásico/metabolismo , Apoptosis , Sitios de Unión , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Proliferación Celular , Neoplasias del Colon/genética , Neoplasias del Colon/metabolismo , ARN Helicasas DEAD-box/genética , ARN Helicasas DEAD-box/metabolismo , Humanos , Estadificación de Neoplasias , Pronóstico , Unión Proteica , ARN Largo no Codificante/metabolismo , ARN Neoplásico/genética , Células Tumorales CultivadasRESUMEN
AIMS: To investigate the effects of mannosylerythritol lipids (MELs) on the hydrophobicity of solid surfaces, their suppressive activity against the early infection behaviours of several phytopathogenic fungal conidia, and their suppressive activity against disease occurrences on fungal host plant leaves. METHODS AND RESULTS: The changes in the hydrophobicity of plastic film surfaces resulting from treatments with MEL solutions (MEL-A, MEL-B, MEL-C and isoMEL-B) and synthetic surfactant solutions were evaluated based on the changes in contact angles of water droplets placed on the surfaces. The droplet angles on surfaces treated with MELs were verified to decrease within 100 s after placement, with contact angles similar to those observed on Tween 20-treated surfaces, indicating decreases in surface hydrophobicity after MEL treatments. Next, conidial germination, germ tube elongation and the formation of appressorium of Blumeria graminis f. sp. tritici, Colletotrichum dematium, Glomerella cingulata and Magnaporthe grisea were evaluated on plastic surfaces that were pretreated with surfactant solutions. On the surfaces of MEL-treated plastic film, inhibition of conidial germination, germ tube elongation, and suppression of appressoria formation tended to be observed, although the level of effect was dependent on the combination of fungal species and type of MEL. Inoculation tests revealed that the powdery mildew symptom caused by B. graminis f. sp. tritici was significantly suppressed on wheat leaf segments treated with MELs. CONCLUSIONS: MELs exhibited superior abilities in reducing the hydrophobicity of solid surfaces, and have the potential to suppress powdery mildew in wheat plants, presumably due to the inhibition of conidial germination. SIGNIFICANCE AND IMPACT OF THE STUDY: This study provides significant evidence of the potential for MELs to be used as novel agricultural chemical pesticides.
Asunto(s)
Ascomicetos/química , Glucolípidos/farmacología , Enfermedades de las Plantas/microbiología , Tensoactivos/farmacología , Triticum/microbiología , Ascomicetos/efectos de los fármacos , Ascomicetos/crecimiento & desarrollo , Ascomicetos/patogenicidad , Interacciones Hidrofóbicas e Hidrofílicas , Hojas de la Planta/microbiología , Esporas Fúngicas/química , Esporas Fúngicas/efectos de los fármacos , Esporas Fúngicas/crecimiento & desarrollo , Virulencia/efectos de los fármacosRESUMEN
Inorganic sol-gel solutions were electrospun to produce the first bioactive three-dimensional (3-D) scaffolds for bone tissue regeneration with a structure like cotton-wool (or cotton candy). This flexible 3-D fibrous structure is ideal for packing into complex defects. It also has large inter-fiber spaces to promote vascularization, penetration of cells and transport of nutrients throughout the scaffold. The 3-D fibrous structure was obtained by electrospinning, where the applied electric field and the instabilities exert tremendous force on the spinning jet, which is required to be viscoelastic to prevent jet break up. Previously, polymer binding agents were used with inorganic solutions to produce electrospun composite two-dimensional fibermats, requiring calcination to remove the polymer. This study presents novel reaction and processing conditions for producing a viscoelastic inorganic sol-gel solution that results in fibers by the entanglement of the intermolecularly overlapped nanosilica species in the solution, eliminating the need for a binder. Three-dimensional cotton-wool-like structures were only produced when solutions containing calcium nitrate were used, suggesting that the charge of the Ca(2+) ions had a significant effect. The resulting bioactive silica fibers had a narrow diameter range of 0.5-2µm and were nanoporous. A hydroxycarbonate apatite layer was formed on the fibers within the first 12h of soaking in simulated body fluid. MC3T3-E1 preosteoblast cells cultured on the fibers showed no adverse cytotoxic effect and they were observed to attach to and spread in the material.
Asunto(s)
Adhesión Celular/fisiología , Movimiento Celular/fisiología , Nanoestructuras/química , Dióxido de Silicio/química , Andamios del Tejido , Lana/química , Células 3T3 , Animales , Materiales Biomiméticos/síntesis química , Líquidos Corporales/química , Regeneración Ósea/fisiología , Fibra de Algodón , Vidrio/química , Gossypium/química , Humanos , Ensayo de Materiales , Ratones , Nanoestructuras/ultraestructura , PorosidadRESUMEN
Siloxane-containing vaterite (SiV) particles with spherical- to discoidal-morphologies were selectively prepared by a CO2 gas carbonation process in a methanol-acetone mixed solvent; they are intended for application as osteogenic devices in bone tissue engineering. Moreover, the c/ab-face ratio of vaterite was successfully tuned through the selection of methanol-acetone volume fractions. The solvent increased the supersaturation of CO3 2- ions and accelerated the crystal growth along the ab-axis in the presence of silsesquioxane. The particles released soluble silica species and calcium ions upon soaking in physiological pH buffer solution, which are expected to genetically stimulate osteoblasts to enhance bone reconstruction. An initial calcium ion release from the particles significantly decreased from 3.1 to 1.6 mmol L-1 as the c/ab-face ratio increased, while the composition of the particle and release profiles of soluble silica remained consistent. This demonstrated the possibility of tuning the calcium ion release from SiV particles by controlling the degree of crystalline plane orientation.
RESUMEN
GABA is thought to function as a paracrine factor in adrenal medullary (AM) cells. Thus, we electrophysiologically and immunologically examined the properties of GABAA receptors (GABAARs) in guinea-pig AM cells. Bath application of GABA produced an inward current at -60 mV in a dose-dependent manner with an EC50 of 32.3 µM. This GABA-induced current was enhanced by allopregnanolone at concentrations of 0.01 µM and more. A prior exposure to allopregnanolone resulted in a decrease in an EC50 for GABA in activating GABAARs. The GABA-induced current was suppressed by Zn(2+) in a dose-dependent manner with an IC50 of 18 µM, whereas it was enhanced by 100 µM La(3+). The benzodiazepine analog diazepam was three times more potent than zolpidem in enhancing the GABA current, and it was also augmented by L-838,417, which has no action on α1-containing GABAARs. The GABAAR α3, but not α1, and γ2 subunits were immunologically detected at the cell periphery. The expression of α3 subunits in PC12 cells was enhanced by glucocorticoid activity. The results indicated that GABAARs in guinea-pig AM cells mainly comprise α3, ß, and γ2 subunits and are enhanced by allopreganalone and glucocorticoids may play a major role in the expression of α3 subunits.
Asunto(s)
Médula Suprarrenal/efectos de los fármacos , Médula Suprarrenal/metabolismo , Receptores de GABA-A/metabolismo , Esteroides/farmacología , Abortivos Esteroideos/farmacología , Potenciales de Acción/efectos de los fármacos , Anestésicos/farmacología , Animales , Proteínas Portadoras/metabolismo , Relación Dosis-Respuesta a Droga , Agonistas de Receptores de GABA-A/farmacología , Antagonistas de Receptores de GABA-A/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , Cobayas , Masculino , Proteínas de la Membrana/metabolismo , Mifepristona/farmacología , Células PC12 , Técnicas de Placa-Clamp , Pregnanolona/farmacología , Ratas , Zinc/farmacología , Ácido gamma-Aminobutírico/farmacologíaRESUMEN
Association between response to antidepressant treatment and genetic polymorphisms was examined in two independent Japanese samples of patients with major depressive disorder (MDD). Genome-wide approach using the Illumina Human CNV370-quad Bead Chip was utilized in the analysis of the 92 MDD patients in the first sample. In all, 11 non-intergenic single-nucleotide polymorphisms with uncorrected allelic P-value <0.0001 were selected for the subsequent association analyses in the second sample of 136 MDD patients. Difference in allele distribution between responders and nonresponders were found in the second-stage sample for rs365836 and rs201522 of the CUX1 gene (P=0.005 and 0.004, respectively). The allelic P-values for rs365836 and rs201522 in both samples combined were 0.0000023 and 0.0000040, respectively. Our results provide the first evidence that polymorphisms of the CUX1 gene may be associated with response to antidepressant treatment in Japanese patients with MDD.
Asunto(s)
Trastorno Depresivo Mayor/tratamiento farmacológico , Trastorno Depresivo Mayor/genética , Estudio de Asociación del Genoma Completo , Proteínas de Homeodominio/genética , Proteínas Nucleares/genética , Proteínas Represoras/genética , Adulto , Anciano , Antidepresivos/administración & dosificación , Trastorno Depresivo Mayor/patología , Femenino , Humanos , Japón , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Factores de TranscripciónRESUMEN
INTRODUCTION: Smoking is a leading global cause of avoidable mortality. It has been reported that the nicotinic acetylcholine receptor (CHRNA4 and CHRNB2) genes might be associated with smoking behavior in several ethnic populations. However, no study between the 2 genes and nicotine dependence (ND) using a Japanese population has been reported. METHODS: We examined the association between ND and 5 single nucleotide polymorphisms (SNPs) within the CHRNA4 and 3 SNPs within the CHRNB2 using a well characterized sample of 558 Japanese healthy male workers with a relatively homogeneous background. The Fagerström test for nicotine dependence (FTND) was used to quantify the degree of ND. Additionally, we explored the effect of gene-gene interactions of the 2 genes on ND. RESULTS: We found CHRNB2 rs4845652 genotypes to be associated with FTND scores under an additive genetic model: rs4845652 T-allele carriers had lower ND levels (p=0.038; when adjusted for smoking duration: p=0.052). Furthermore, we demonstrated a possible gene-gene interaction of CHRNA4 and CHRNB2 on ND in a dose-dependent manner: those smokers with CHRNA4 rs1044397 GG or GA genotypes along with CHRNB2 rs4845652 CC genotype are likely to demonstrate higher ND scores. DISCUSSION: These findings suggest that CHRNB2 rs4845652 T-allele carriers may be associated with lower levels of ND, and that certain allelic combinations of CHRNA4 and CHRNB2 might be correlated with higher ND levels. This preliminary study has certain limitations (issues such as sample size/power and multiple testing) that need to be taken into account, and the present work thus has an experimental nature.
Asunto(s)
Pueblo Asiatico/genética , Predisposición Genética a la Enfermedad/genética , Receptores Nicotínicos/genética , Tabaquismo/genética , Adulto , Alelos , Pueblo Asiatico/psicología , Epistasis Genética/genética , Humanos , Masculino , Polimorfismo de Nucleótido Simple/genéticaRESUMEN
OBJECTIVE: To investigate the longitudinal angiogenic activity of subchondral bone and cartilage during the progression of osteoarthritis (OA) using a rabbit model of OA. MATERIALS AND METHODS: OA was surgically induced by anterior cruciate ligament transaction (ACLT) in left knee of 12 months old female New Zealand white rabbits (n = 33). Histological examination, immunohistochemistry, and angiogenic activity assay was done at 0, 2, 4, 6, 8, 12 weeks after ACLT. Histologic evaluation was performed with haematoxylin and eosin, safranin-O staining to assess the OA change of medial femoral condyle (MFC) and lateral femoral condyle (LFC). CD31 immunohistochemistry was performed to confirm the vascular invasion at osteochondral junction. A co-cultured tubule formation assay was conducted to evaluate angiogenic activity of the subchondral bone and cartilage of MFC and LFC as well as synovium. Association between histological changes, angiogenic activity, and vascular invasion were evaluated. RESULTS: OA changes increased in a time-dependent manner both in MFC and LFC. Angiogenic activity of subchondral bone showed a monomodal change during the OA progression, achieved a peak in the early to progressive stage and decreased to normal level in the late stage of OA. Surge of vascular invasion was observed following the increase of angiogenic activity in the progressive stage of OA. Angiogenic activity of cartilage did not change during the course of OA progression. CONCLUSION: Angiogenic activity of subchondral bone was elevated in the early to progressive stage of OA and vascular invasion into the osteochondral junction followed.
Asunto(s)
Ligamento Cruzado Anterior/cirugía , Artritis Experimental/patología , Cartílago Articular/irrigación sanguínea , Fémur/irrigación sanguínea , Articulación de la Rodilla/patología , Neovascularización Patológica/patología , Osteoartritis de la Rodilla/patología , Animales , Progresión de la Enfermedad , Femenino , Fémur/patología , Inmunohistoquímica , ConejosRESUMEN
OBJECTIVES: The purpose of this study was to assess N-acetyl aspartate changes in the thalamus in patients with osteoarthritis of the hip using proton magnetic resonance spectroscopy. METHODS: Nine patients with osteoarthritis of the hip (symptomatic group, nine women; mean age 61.4 years (48 to 78)) and nine healthy volunteers (control group, six men, three women; mean age 30.0 years (26 to 38)) underwent proton magnetic resonance spectroscopy to assess the changes of N-acetyl aspartate in the thalamus. RESULTS: The ratio of N-acetyl aspartate to creatine plus phosphocreatine in the thalamus contralateral to the symptomatic hip in patients with osteoarthritis of the hip was significantly lower than the ratio of N-acetyl aspartate to creatine plus phosphocreatine in the thalamus in the control group (1.611 (range; 1.194-1.882) vs 1.355 (range; 1.043-1.502), p < 0.001). And, a strong negative correlation was detected between the ratio of N-acetyl aspartate to creatine plus phosphocreatine in the thalamus contralateral to the symptomatic hip in patients with osteoarthritis of the hip and pain duration (r = -0.83, p = 0.018). CONCLUSIONS: We evaluated the ratio of N-acetyl aspartate to creatine plus phosphocreatine in the thalamus of patients with osteoarthritis of the hip by using proton magnetic resonance spectroscopy. We concluded that the ratio of N-acetyl aspartate to creatine plus phosphocreatine in the thalamus contralateral to the symptomatic hip in patients with osteoarthritis of the hip were significantly lower than those in the thalamus of the control group, and that pain duration was strongly related to the decrease of the ratio of N-acetyl aspartate to creatine plus phosphocreatine.
RESUMEN
Disturbance of blood supply to the femoral head is a risk factor for corticosteroid-associated osteonecrosis. The aim was to measure blood supply of the proximal femur during corticosteroid therapy in systemic lupus erythematosus (SLE) patients. We repeatedly performed 78 dynamic MRIs of 19 hip joints in 19 SLE patients after initiation of corticosteroid administration for one year. Blood supply of the femoral head (epiphysis, growth plate, and metaphysis), the femoral neck, and the medial circumflex femoral artery were measured in terms of peak percent enhancement. At the first month, blood supply of the growth plate was significantly higher in the pediatric group (<15 years old) than in the adolescent and adult group (>15 years old). At the fourth month, blood supply in every part of the femoral head (epiphysis, growth plate, and metaphysis) was significantly higher in the pediatric group than in the adolescent and adult group. Multiple regression analysis revealed that blood supply to the femoral head depended on the number of days after initiation of corticosteroid administration and the age at the time of dynamic MRI. Blood supply to the femoral head is abundant in pediatric patients and is a function of the number of days after initiation of corticosteroid administration.
Asunto(s)
Cabeza Femoral/irrigación sanguínea , Glucocorticoides/efectos adversos , Lupus Eritematoso Sistémico/tratamiento farmacológico , Adolescente , Adulto , Factores de Edad , Niño , Femenino , Cabeza Femoral/efectos de los fármacos , Cuello Femoral/irrigación sanguínea , Cuello Femoral/efectos de los fármacos , Glucocorticoides/administración & dosificación , Glucocorticoides/uso terapéutico , Placa de Crecimiento/irrigación sanguínea , Placa de Crecimiento/efectos de los fármacos , Articulación de la Cadera/irrigación sanguínea , Articulación de la Cadera/efectos de los fármacos , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Osteonecrosis/inducido químicamente , Estudios Prospectivos , Análisis de Regresión , Factores de Riesgo , Factores de Tiempo , Adulto JovenRESUMEN
AIMS/HYPOTHESIS: In populations of East Asian descent, we performed a replication study of loci previously identified in populations of European descent as being associated with obesity measures such as BMI and type 2 diabetes. METHODS: We genotyped 14 single nucleotide polymorphisms (SNPs) from 13 candidate loci that had previously been identified by genome-wide association meta-analyses for obesity measures in Europeans. Genotyping was done in 18,264 participants from two general Japanese populations. For SNPs showing an obesity association in Japanese individuals, we further examined diabetes associations in up to 6,781 cases and 7,307 controls from a subset of the original, as well as from additional populations. RESULTS: Significant obesity associations (p < 0.1 two-tailed, concordant direction with previous reports) were replicated for 11 SNPs from the following ten loci in Japanese participants: SEC16B, TMEM18, GNPDA2, BDNF, MTCH2, BCDIN3D-FAIM2, SH2B1-ATP2A1, FTO, MC4R and KCTD15. The strongest effect was observed at TMEM18 rs4854344 (p = 7.1 × 10(-7) for BMI). Among the 11 SNPs showing significant obesity association, six were also associated with diabetes (OR 1.05-1.17; p = 0.04-2.4 × 10(-7)) after adjustment for BMI in the Japanese. When meta-analysed with data from the previous reports, the BMI-adjusted diabetes association was found to be highly significant for the FTO locus in East Asians (OR 1.13; 95% CI 1.09-1.18; p = 7.8 × 10(-10)) with substantial inter-ethnic heterogeneity (p = 0.003). CONCLUSIONS/INTERPRETATION: We confirmed that ten candidate loci are associated with obesity measures in the general Japanese populations. Six (of ten) loci exert diabetogenic effects in the Japanese, although relatively modest in size, and independently of increased adiposity.
Asunto(s)
Pueblo Asiatico/genética , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/genética , Predisposición Genética a la Enfermedad/genética , Obesidad/epidemiología , Obesidad/genética , Polimorfismo de Nucleótido Simple/genética , Adulto , Anciano , Pueblo Asiatico/etnología , Índice de Masa Corporal , Factor Neurotrófico Derivado del Encéfalo/genética , Estudios de Casos y Controles , Comorbilidad , Diabetes Mellitus Tipo 2/etnología , Femenino , Predisposición Genética a la Enfermedad/etnología , Genotipo , Humanos , Japón , Masculino , Proteínas de la Membrana/genética , Proteínas de Transporte de Membrana/genética , Persona de Mediana Edad , Proteínas de Transporte de Membrana Mitocondrial , Proteínas Mitocondriales/genética , Obesidad/etnologíaRESUMEN
BACKGROUND: N-acetylaspartate (NAA) levels and serum brain-derived neurotrophic factor (BDNF) levels in patients with first-episode schizophrenia psychosis and age- and sex-matched healthy control subjects were investigated. In addition, plasma levels of homovanillic acid (HVA) and 3-methoxy-4-hydroxyphenylglycol (MHPG) were compared between the two groups. METHOD: Eighteen patients (nine males, nine females; age range: 13-52 years) were enrolled in the study, and 18 volunteers (nine males, nine females; age range: 15-49 years) with no current or past psychiatric history were also studied by magnetic resonance spectroscopy (MRS) as sex- and age-matched controls. RESULTS: Levels of NAA/Cr in the left basal ganglia (p=0.0065) and parieto-occipital lobe (p=0.00498), but not in the frontal lobe, were significantly lower in patients with first-episode schizophrenia psychosis than in control subjects. No difference was observed between the serum BDNF levels of patients with first-episode schizophrenia psychosis and control subjects. In regard to the plasma levels of catecholamine metabolites, plasma MHPG, but not HVA, was significantly lower in the patients with first-episode psychosis than in control subjects. In addition, a significantly positive correlation was observed between the levels of NAA/Cr of the left basal ganglia and plasma MHPG in all subjects. CONCLUSION: These results suggest that brain NAA levels in the left basal ganglia and plasma MHPG levels were significantly reduced at the first episode of schizophrenia psychosis, indicating that neurodegeneration via noradrenergic neurons might be associated with the initial progression of the disease.
Asunto(s)
Ácido Aspártico/análogos & derivados , Química Encefálica , Factor Neurotrófico Derivado del Encéfalo/análisis , Esquizofrenia/metabolismo , Adolescente , Adulto , Ácido Aspártico/análisis , Ganglios Basales/química , Estudios de Casos y Controles , Femenino , Ácido Homovanílico/sangre , Humanos , Espectroscopía de Resonancia Magnética , Masculino , Metoxihidroxifenilglicol/sangre , Persona de Mediana Edad , Lóbulo Occipital/química , Lóbulo Parietal/química , Esquizofrenia/sangre , Esquizofrenia/etiología , Adulto JovenRESUMEN
Peripheral neuropathy has been reported to prevail in obese or pre-diabetic individuals, yet its etiology remains unknown. Palmitate, a saturated fatty acid increased in obesity and diabetes, is known to induce apoptosis in multiple types of cells and this effect may be mediated by ceramide, a member of the sphingolipid family. To clarify whether de novo ceramide synthesis from palmitate contributes to apoptosis of Schwann cells, we cultured immortalized mouse Schwann cells (IMS) and rat primary Schwann cells with palmitate, a ceramide analogue C2-ceramide as well as inhibitors of the de novo ceramide synthesis (myriocin and fumonisin B1). Apoptosis of IMS detected by nuclear staining and cell membrane inversion was significantly increased by incubation with palmitate for 48 h in a dose-dependent fashion. This enhanced apoptosis was partially but significantly suppressed by myriocin and fumonisin B1. Western blot analysis and immunostaining revealed that palmitate clearly activated caspase-3 in IMS. Unexpectedly, the ceramide synthesis inhibitors failed to suppress the palmitate-induced caspase-3 activation in spite of complete restoration in ceramide accumulation. The results seemed relevant to the observations that C2-ceramide did not activate caspase-3 while provoking apoptosis with a clear dose-dependency. In agreement, the pro-apoptotic action of C2-ceramide was not attenuated by caspase inhibitors that partially suppressed palmitate-induced apoptosis. These results in IMS were well reproducible in rat primary Schwann cells, indicating that the observed phenomena are not specific to the cell line. Collectively, we have reached a conclusion that palmitate induces apoptosis in Schwann cells via both a ceramide-mediated, caspase-3-independent pathway and ceramide-independent, caspase-3-dependent pathways. Given the fact that palmitate and ceramide are increased in obese or pre-diabetic subjects, these lipids may be implicated in the pathogenesis of peripheral neuropathy observed in these disorders.
Asunto(s)
Apoptosis/fisiología , Ceramidas/metabolismo , Palmitatos/toxicidad , Células de Schwann/patología , Transducción de Señal/fisiología , Animales , Apoptosis/efectos de los fármacos , Western Blotting , Células Cultivadas , Neuropatías Diabéticas/metabolismo , Técnica del Anticuerpo Fluorescente , Ratones , Obesidad/complicaciones , Obesidad/metabolismo , Palmitatos/metabolismo , Enfermedades del Sistema Nervioso Periférico/etiología , Enfermedades del Sistema Nervioso Periférico/metabolismo , Ratas , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Células de Schwann/efectos de los fármacos , Células de Schwann/metabolismo , Transducción de Señal/efectos de los fármacosRESUMEN
UNLABELLED: We undertook this to determine the formaldehyde concentration in Japanese houses and the relationship between formaldehyde levels and the age and temperature of a house using a sensor element that we developed for time-integrated measurements of formaldehyde concentration in actual environments. We evaluated the correlation between the formaldehyde concentration estimated by the dinitrophenylhydrazine (DNPH)-derivatization method and that obtained with our sensor element. We found a linear relationship between the two results indicating that reliable measurements can be performed using the developed sensor element in actual environments. The indoor concentration of formaldehyde was determined in a study of 34 homes in the Kanto area of Japan, between September 28 and October 27, 2007. We obtained the highest formaldehyde concentrations of 92 ± 15 µg/m(3) for apartments 0-2 years after their renovation, and a simple linear relationship was found between formaldehyde concentration and the age of the apartment. We also found that the formaldehyde concentration in a room containing furniture increased by 10% when the temperature increased by 1°C. PRACTICAL IMPLICATIONS: This study contributed to the measurements of indoor formaldehyde levels. We have used a newly developed sensor for time-integrated measurements of formaldehyde concentrations. This sensor does not need a power supply during exposure to air, and does not need special skills to use. This research showed that homeowners successfully deployed the sensor at the desired place and desired period in their house by themselves. Formaldehyde is emitted by various off-gassing sources, such as furniture. Therefore, for example, homeowners may want to measure the change of formaldehyde levels in their house before and after installing new furniture. This sensor may also be deployed by occupants to reduce the cost of a large-scale exposure assessment study.