RESUMEN
KaiC is the central oscillator protein in the cyanobacterial circadian clock. KaiC oscillates autonomously between phosphorylated and dephosphorylated states on a 24-h cycle in vitro by mixing with KaiA and KaiB in the presence of ATP. KaiC forms a C6 -symmetrical hexamer, which is a double ring structure of homologous N-terminal and C-terminal domains termed CI and CII, respectively. Here, through the characterization of an isolated CII domain protein, CIIKaiC , we show that phosphorylation of KaiC Thr432 destabilizes the hexameric state of the CII ring to a monomeric state. The results suggest that the stable hexameric CI ring acts as a molecular bundle to hold the CII ring, which undergoes dynamic structural changes upon phosphorylation.
Asunto(s)
Proteínas Bacterianas/química , Proteínas Bacterianas/metabolismo , Péptidos y Proteínas de Señalización del Ritmo Circadiano/química , Péptidos y Proteínas de Señalización del Ritmo Circadiano/metabolismo , Proteínas Bacterianas/genética , Relojes Circadianos , Péptidos y Proteínas de Señalización del Ritmo Circadiano/genética , Cinética , Simulación de Dinámica Molecular , Fosforilación , Dominios y Motivos de Interacción de Proteínas , Estabilidad Proteica , Estructura Cuaternaria de Proteína , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Synechococcus/citología , Synechococcus/genética , Synechococcus/metabolismo , Treonina/químicaRESUMEN
In this study, the relationship between ground-glass opacity (GGO) visibility and physical detectability index in low-dose computed tomography (LDCT) for lung cancer screening was investigated. An anthropomorphic chest phantom that included synthetic GGOs with CT numbers of -630 Hounsfield units (HU; high attenuation GGO: HGGO) and -800 HU (low attenuation GGO: LGGO), and three phantoms for physical measurements were employed. The phantoms were scanned using 12 CT systems located in 11 screening centers in Japan. The slice thicknesses and CT dose indices (CTDI(vol)) varied over 1.0-5.0 mm and 0.85-3.30 mGy, respectively, and several reconstruction kernels were used. Physical detectability index values were calculated from measurements of resolution, noise, and slice thickness properties for all image sets. Five radiologists and one thoracic surgeon, blind to one another's observations, evaluated GGO visibility using a five-point scoring system. The physical detectability index correlated reasonably well with the GGO visibility (R² = 0.709, p < 0.01 for 6 mm HGGO and R² = 0.646, p < 0.01 for 10 mm LGGO), and was nearly proportional to the CTDI(vol). Consequently, the CTDI(vol) also correlated reasonably well with the GGO visibility (R² = 0.701, p < 0.01 for 6 mm HGGO and R² = 0.680, p < 0.01 for 10 mm LGGO). As a result, the CTDI(vol) was nearly dominant in the GGO visibility for image sets with different reconstruction kernels and slice thicknesses, used in this study.
Asunto(s)
Algoritmos , Neoplasias Pulmonares/diagnóstico por imagen , Fantasmas de Imagen , Radiografía Torácica , Nódulo Pulmonar Solitario/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Antropometría , Humanos , Dosis de Radiación , Interpretación de Imagen Radiográfica Asistida por ComputadorRESUMEN
Severe hypomagnesemia is a serious clinical condition. Proton pump inhibitor (PPI) induced hypomagnesemia has been recognized since 2006. In March 2011 the U.S. Food and Drug Administration advised that long-term use of PPI can induce hypomagnesemia. We report the first Japanese case of hypomagnesemia associated with chronic use of PPIs in a 64-year-old man hospitalized for nausea, bilateral ankle arthritis, and tremor of the extremities who had convulsions 3 days after admission. Blood analysis showed severe hypomagnesemia. He had been taking rabeprazole (10 mg/day) for 5 years. After stopping rabeprazole and correcting the electrolytes imbalances, his symptoms improved without recurrence.
Asunto(s)
2-Piridinilmetilsulfinilbencimidazoles/efectos adversos , Magnesio/sangre , Inhibidores de la Bomba de Protones/efectos adversos , 2-Piridinilmetilsulfinilbencimidazoles/uso terapéutico , Reflujo Gastroesofágico/inducido químicamente , Humanos , Deficiencia de Magnesio/inducido químicamente , Masculino , Persona de Mediana Edad , Inhibidores de la Bomba de Protones/uso terapéutico , RabeprazolRESUMEN
AIM: There is little evidence that dehydroepiandrosterone (DHEA) has beneficial effects on physical and psychological functions in older women. We investigated the effect of DHEA supplementation on cognitive function and ADL in older women with cognitive impairment. METHODS: A total of 27 women aged 65-90 years (mean ± standard deviation, 83 ± 6) with mild to moderate cognitive impairment (Mini-Mental State Examination, MMSE; 10-28/30 points), receiving long-term care at a facility in Japan were enrolled. Twelve women were assigned to receive DHEA 25 mg/day p.o. for 6 months. The control group (n = 15) matched for age and cognitive function was followed without hormone replacement. Cognitive function was assessed by MMSE and Hasegawa Dementia Scale-Revised (HDS-R), and basic activities of daily living (ADL) by Barthel Index at baseline, 3 and 6 months. Plasma hormone levels including testosterone, DHEA, DHEA-sulfate and estradiol were also followed up. RESULTS: After 6 months, DHEA treatment significantly increased plasma testosterone, DHEA and DHEA-sulfate levels by 2-3-fold but not estradiol level compared to baseline. DHEA administration increased cognitive scores and maintained basic ADL score, while cognition and basic ADL deteriorated in the control group (6-month change in DHEA group vs control group; MMSE, +0.6 ± 3.2 vs -2.1 ± 2.2, P < 0.05; HDS-R, +2.8 ± 2.8 vs -0.3 ± 4.1, P < 0.05; Barthel Index, +3.7 ± 7.1 vs -2.7 ± 4.6, P = 0.05). Among the cognitive domains, DHEA treatment improved verbal fluency (P < 0.05). CONCLUSION: DHEA supplementation in older women with cognitive impairment may have beneficial effects on cognitive function and ADL.
