RESUMEN
High sensitivity of scotopic vision (vision in dim light conditions) is achieved by the rods' low background noise, which is attributed to a much lower thermal activation rate (kth) of rhodopsin compared with cone pigments. Frogs and nocturnal geckos uniquely possess atypical rods containing noncanonical cone pigments that exhibit low kth, mimicking rhodopsin. Here, we investigated the convergent mechanism underlying the low kth of rhodopsins and noncanonical cone pigments. Our biochemical analysis revealed that the kth of canonical cone pigments depends on their absorption maximum (λmax). However, rhodopsin and noncanonical cone pigments showed a substantially lower kth than predicted from the λmax dependency. Given that the λmax is inversely proportional to the activation energy of the pigments in the Hinshelwood distribution-based model, our findings suggest that rhodopsin and noncanonical cone pigments have convergently acquired low frequency of spontaneous-activation attempts, including thermal fluctuations of the protein moiety, in the molecular evolutionary processes from canonical cone pigments, which contributes to highly sensitive scotopic vision.
Asunto(s)
Evolución Molecular , Visión Nocturna , Rodopsina , Animales , Luz , Visión Nocturna/fisiología , Rodopsina/química , Rodopsina/metabolismo , Vertebrados , Opsinas de los Conos/química , Opsinas de los Conos/metabolismoRESUMEN
Most vertebrates have a rhodopsin gene with a five-exon structure for visual photoreception. By contrast, teleost fishes have an intron-less rhodopsin gene for visual photoreception and an intron-containing rhodopsin (exo-rhodopsin) gene for pineal photoreception. Here, our analysis of non-teleost and teleost fishes in various lineages of the Actinopterygii reveals that retroduplication after branching of the Polypteriformes produced the intron-less rhodopsin gene for visual photoreception, which converted the parental intron-containing rhodopsin gene into a pineal opsin in the common ancestor of the Teleostei. Additional analysis of a pineal opsin, pinopsin, shows that the pinopsin gene functions as a green-sensitive opsin together with the intron-containing rhodopsin gene for pineal photoreception in tarpon as an evolutionary intermediate state but is missing in other teleost fishes, probably because of the redundancy with the intron-containing rhodopsin gene. We propose an evolutionary scenario where unique retroduplication caused a "domino effect" on the functional diversification of teleost visual and pineal opsin genes.
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Evolución Molecular , Peces , Opsinas , Filogenia , Glándula Pineal , Rodopsina , Animales , Peces/genética , Glándula Pineal/metabolismo , Opsinas/genética , Opsinas/metabolismo , Rodopsina/genética , Rodopsina/metabolismo , Intrones/genética , Secuencia de Aminoácidos , Duplicación de GenRESUMEN
Mammalian type opsin 5 (Opn5m), a UV-sensitive G protein-coupled receptor opsin highly conserved in vertebrates, would provide a common basis for UV sensing from lamprey to humans. However, G protein coupled with Opn5m remains controversial due to variations in assay conditions and the origin of Opn5m across different reports. Here, we examined Opn5m from diverse species using an aequorin luminescence assay and Gα-KO cell line. Beyond the commonly studied major Gα classes, Gαq, Gα11, Gα14, and Gα15 in the Gq class were individually investigated in this study, as they can drive distinct signaling pathways in addition to a canonical calcium response. UV light triggered a calcium response via all the tested Opn5m proteins in 293T cells, which was abolished by Gq-type Gα deletion and rescued by cotransfection with mouse and medaka Gq-type Gα proteins. Opn5m preferentially activated Gα14 and close relatives. Mutational analysis implicated specific regions, including α3-ß5 and αG-α4 loops, αG and α4 helices, and the extreme C terminus, in the preferential activation of Gα14 by Opn5m. FISH revealed co-expression of genes encoding Opn5m and Gα14 in the scleral cartilage of medaka and chicken eyes, supporting their physiological coupling. This suggests that the preferential activation of Gα14 by Opn5m is relevant for UV sensing in specific cell types.
Asunto(s)
Subunidades alfa de la Proteína de Unión al GTP Gq-G11 , Opsinas , Humanos , Ratones , Animales , Opsinas/genética , Opsinas/metabolismo , Subunidades alfa de la Proteína de Unión al GTP Gq-G11/genética , Subunidades alfa de la Proteína de Unión al GTP Gq-G11/metabolismo , Calcio/metabolismo , Transducción de Señal , Receptores Acoplados a Proteínas G/metabolismo , Opsinas de Bastones/metabolismo , Mamíferos/metabolismoRESUMEN
Opsins are universal photosensitive proteins in animals. Vertebrates have a variety of opsin genes for visual and non-visual photoreceptions. Analysis of the gene structures shows that most opsin genes have introns in their coding regions. However, teleosts exceptionally have several intron-less opsin genes that are presumed to have been duplicated by an RNA-based gene duplication mechanism, retroduplication. Among these retrogenes, we focused on the Opn4 (melanopsin) gene responsible for non-image-forming photoreception. Many teleosts have five Opn4 genes including one intron-less gene, which is speculated to have been formed from a parental intron-containing gene in the Actinopterygii. In this study, to reveal the evolutionary history of Opn4 genes, we analyzed them in teleost (zebrafish and medaka) and non-teleost (bichir, sturgeon, and gar) fishes. Our synteny analysis suggests that the intron-less Opn4 gene emerged by retroduplication after the branching of the bichir lineage. In addition, our biochemical and histochemical analyses showed that, in the teleost lineage, the newly acquired intron-less Opn4 gene became abundantly used without substantial changes in the molecular properties of the Opn4 protein. This stepwise evolutionary model of Opn4 genes is quite similar to that of rhodopsin genes in the Actinopterygii. The unique acquisition of rhodopsin and Opn4 retrogenes would have contributed to the diversification of the opsin gene repertoires in the Actinopterygii and the adaptation of teleosts to various aquatic environments.
Asunto(s)
Evolución Molecular , Peces , Intrones , Opsinas , Animales , Peces/genética , Peces/fisiología , Opsinas/genética , Opsinas/metabolismo , Filogenia , Rodopsina/genética , Rodopsina/metabolismo , Pez Cebra/genética , Oryzias/genética , Sintenía/genéticaRESUMEN
OBJECTIVES: We aim to assess the early use of contrast-enhanced computed tomography (CECT) of patients with severe acute pancreatitis (SAP) using the computed tomography severity index (CTSI) in prognosis prediction. The CTSI combines quantification of pancreatic and extrapancreatic inflammation with the extent of pancreatic necrosis. METHODS: Post-hoc retrospective analysis of a large, multicentric database (44 institutions) of SAP patients in Japan. The area under the curve (AUC) of the CTSI for predicting mortality and the odds ratio (OR) of the extent of pancreatic inflammation and necrosis were calculated using multivariable analysis. RESULTS: In total, 1097 patients were included. The AUC of the CTSI for mortality was 0.65 (95 % confidence interval [CI:] [0.59-0.70]; p < 0.001). In multivariable analysis, necrosis 30-50 % and >50 % in low-enhanced pancreatic parenchyma (LEPP) was independently associated with a significant increase in mortality, with OR 2.04 and 95 % CI 1.01-4.12 (P < 0.05) and OR 3.88 and 95 % CI 2.04-7.40 (P < 0.001), respectively. However, the extent of pancreatic inflammation was not associated with mortality, regardless of severity. CONCLUSIONS: The degree of necrosis in LEPP assessed using early CECT of SAP was a better predictor of mortality than the extent of pancreatic inflammation.
Asunto(s)
Medios de Contraste , Necrosis , Páncreas , Pancreatitis , Tomografía Computarizada por Rayos X , Humanos , Femenino , Masculino , Persona de Mediana Edad , Anciano , Pancreatitis/diagnóstico por imagen , Pancreatitis/patología , Pancreatitis/mortalidad , Estudios Retrospectivos , Páncreas/diagnóstico por imagen , Páncreas/patología , Estudios de Cohortes , Pronóstico , Adulto , Índice de Severidad de la Enfermedad , Inflamación/diagnóstico por imagen , Japón/epidemiología , Pancreatitis Aguda Necrotizante/diagnóstico por imagen , Pancreatitis Aguda Necrotizante/mortalidad , Pancreatitis Aguda Necrotizante/patologíaRESUMEN
BACKGROUND: The Tohoku Medical Megabank Project (TMM) was established to realize personalized healthcare and medicine using genomic and omics data. This study evaluated the validity and reproducibility of food group intakes derived from a self-administered food frequency questionnaire (TMM-FFQ) that included the response option "constitutionally unable to eat/drink it" among community-dwelling Japanese adults. METHODS: Participants comprised 89 men and 124 women aged ≥20 years from Miyagi Prefecture. Participants completed weighed food records (WFRs) for 3 consecutive days per season as reference intake and FFQs in 2019 (FFQ1) and 2021 (FFQ3). Spearman's rank correlation coefficients (CCs) were calculated for correlations between food group intakes estimated from the 12-day WFR and FFQ3 (validity), and for correlations between those estimated from the FFQ1 and FFQ3 (reproducibility). Cross-classification according to quintiles using FFQ and WFR data was also performed. RESULTS: The percentage of participants who chose the "constitutionally unable to eat/drink it" option was non-negligible for some food groups. In the validity analysis, CCs were >0.40 for many food groups; the median across 21 food groups was 0.49 in men and 0.45 in women. The median percentages of cross-classification into exact plus adjacent quintiles were 73.0% in men and 66.9% in women. In the reproducibility analysis, CCs were >0.50 for many food groups; the median across 21 food groups was 0.60 in men and 0.51 in women. CONCLUSIONS: The validity of the TMM-FFQ compared with 12-day WFR and the reproducibility of the TMM-FFQ were reasonable for food groups in the TMM cohort studies.
RESUMEN
Although serum troponin level is the gold standard under the universal definition of acute myocardial infarction (AMI), serum creatinine kinase (CK) and creatine kinase-myocardial band (CK-MB) is still measured in clinical practice as the compliment of troponin level. The purpose of this retrospective study is to illustrate the dramatic change of CK-MB/CK ratio by comparing CK-MB/CK ratio in patients with ST-segment elevation myocardial infarction (STEMI) among ≤ 24 h before reaching peak CK, peak CK, ≤ 24 h after reaching peak CK, and 24-48 h after reaching peak CK. We included 502 patients with STEMI. We calculated each average CK-MB/CK ratio at ≤ 24 h before reaching peak CK, peak CK, ≤ 24 h after reaching peak CK, and 24-48 h after reaching peak CK. The average values were compared using Friedman test. The average CK-MB/CK ratio at ≤ 24 h before reaching peak CK, peak CK, ≤ 24 h after reaching peak CK, and 24-48 h after reaching peak CK was 0.096 (9.6% of CK), 0.098 (9.8% of peak CK), 0.076 (7.6% of CK), and 0.028 (2.8% of CK), respectively. The Friedman test suggested that the CK-MB/CK ratio significantly declined after reaching peak CK (p < 0.001). In conclusion, the CK-MB/CK ratio was around 0.1 (10% of CK) until CK-MB and CK reached the peak, but dropped sharply after reaching peak CK. The CK-MB/CK ratio less than 0.1 (10% of CK) cannot be used to rule out the possibility of AMI, when the onset of symptom is unclear or late presentation.
Asunto(s)
Biomarcadores , Forma MB de la Creatina-Quinasa , Creatina Quinasa , Infarto del Miocardio con Elevación del ST , Humanos , Infarto del Miocardio con Elevación del ST/sangre , Infarto del Miocardio con Elevación del ST/diagnóstico , Estudios Retrospectivos , Masculino , Femenino , Forma MB de la Creatina-Quinasa/sangre , Biomarcadores/sangre , Persona de Mediana Edad , Creatina Quinasa/sangre , Anciano , Factores de Tiempo , Electrocardiografía , Valor Predictivo de las PruebasRESUMEN
Eyes shut homolog (EYS) encodes a proteoglycan and the human mutation causes retinitis pigmentosa type 25 (RP25) with progressive retinal degeneration. RP25 most frequently affects autosomal recessive RP patients with many ethnic backgrounds. Although studies using RP models have facilitated the development of therapeutic medications, Eys has been lost in rodent model animals. Here we examined the roles for Eys in the maintenance of photoreceptor structure and function by generating eys-null medaka fish using the CRISPR-Cas9 system. Medaka EYS protein was present near the connecting cilium of wild-type photoreceptors, while it was absent from the eys-/- retina. The mutant larvae exhibited a reduced visual motor response compared with wild-type. In contrast to reported eys-deficient zebrafish at the similar stage, no retinal cell death was detected in the 8-month post-hatching (8-mph) medaka eys mutant. Immunohistochemistry showed a significant reduction in the length of cone outer segments (OSs), retention of OS proteins in the inner segments of photoreceptors, and abnormal filamentous actin network at the base of cone OSs in the mutant retina by 8 mph. Electron microscopy revealed aberrant structure of calyceal processes, numerous vesiculation and lamellar interruptions, and autophagosomes in the eys-mutant cone photoreceptors. In situ hybridization showed an autophagy component gene, gabarap, was ectopically expressed in the eys-null retina. These results suggest eys is required for regeneration of OS, especially of cone photoreceptors, and transport of OS proteins by regulating actin filaments. Enhanced autophagy may delay the progression of retinal degeneration when lacking EYS in the medaka retina.
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Oryzias , Degeneración Retiniana , Animales , Humanos , Oryzias/genética , Oryzias/metabolismo , Degeneración Retiniana/genética , Pez Cebra/metabolismo , Proteínas del Ojo/genética , Proteínas del Ojo/metabolismo , Células Fotorreceptoras de Vertebrados/metabolismo , Mutación/genética , Opsinas/metabolismo , Autofagia/genéticaRESUMEN
Opsins are universal photoreceptive proteins in animals. Vertebrate rhodopsin in ciliary photoreceptor cells photo-converts to a metastable active state to regulate cyclic nucleotide signaling. This active state cannot photo-convert back to the dark state, and thus vertebrate rhodopsin is categorized as a mono-stable opsin. By contrast, mollusk and arthropod rhodopsins in rhabdomeric photoreceptor cells photo-convert to a stable active state to stimulate IP3/calcium signaling. This active state can photo-convert back to the dark state, and thus these rhodopsins are categorized as bistable opsins. Moreover, the negatively charged counterion position crucial for the visible light sensitivity is different between vertebrate rhodopsin (Glu113) and mollusk and arthropod rhodopsins (Glu181). This can be explained by an evolutionary scenario where vertebrate rhodopsin newly acquired Glu113 as a counterion, which is thought to have led to higher signaling efficiency of vertebrate rhodopsin. However, the detailed evolutionary steps which led to the higher efficiency in vertebrate rhodopsin still remain unknown. Here, we analyzed the xenopsin group, which is phylogenetically distinct from vertebrate rhodopsin and functions in protostome ciliary cells. Xenopsins are blue-sensitive bistable opsins that regulate cAMP signaling. We found that a bistable xenopsin of Leptochiton asellus had Glu113 as a counterion but did not exhibit elevated signaling efficiency. Therefore, our results show that vertebrate rhodopsin and L. asellus xenopsin regulate cyclic nucleotide signaling in ciliary cells and displaced the counterion position from Glu181 to Glu113 via convergent evolution, whereas subsequently only vertebrate rhodopsin elevated its signaling efficiency by acquiring the mono-stable property.
Asunto(s)
Opsinas , Rodopsina , Animales , Nucleótidos Cíclicos/metabolismo , Opsinas/genética , Opsinas/metabolismo , Células Fotorreceptoras/metabolismo , Rodopsina/genética , Rodopsina/metabolismo , VertebradosRESUMEN
Light-induced extrasynaptic dopamine release in the retina reduces adenosine 3',5'-cyclic monophosphate (cAMP) in rod photoreceptor cells, which is thought to mediate light-dependent desensitization. However, the fine time course of the cAMP dynamics in rods remains elusive due to technical difficulty. Here, we visualized the spatiotemporal regulation of cAMP-dependent protein kinase (PKA) in mouse rods by two-photon live imaging of retinal explants of PKAchu mice, which express a fluorescent biosensor for PKA. Unexpectedly, in addition to the light-on-induced suppression, we observed prominent light-off-induced PKA activation. This activation required photopic light intensity and was confined to the illuminated rods. The estimated maximum spectral sensitivity of 489 nm and loss of the light-off-induced PKA activation in rod-transducin-knockout retinas strongly suggest the involvement of rhodopsin. In support of this notion, rhodopsin-deficient retinal explants showed only the light-on-induced PKA suppression. Taken together, these results suggest that, upon photopic light stimulation, rhodopsin and dopamine signals are integrated to shape the light-off-induced cAMP production and following PKA activation. This may support the dark adaptation of rods.
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Proteínas Quinasas Dependientes de AMP Cíclico/metabolismo , Dopamina/metabolismo , Células Fotorreceptoras Retinianas Bastones/enzimología , Rodopsina/metabolismo , Animales , Activación Enzimática , Ratones Transgénicos , Microscopía de Fluorescencia por Excitación Multifotónica , Transducina/metabolismoRESUMEN
Numerous rhodopsin mutations have been implicated in night blindness and retinal degeneration, often with unclear etiology. D190N-rhodopsin (D190N-Rho) is a well-known inherited human mutation causing retinitis pigmentosa. Both higher-than-normal spontaneous-isomerization activity and misfolding/mistargeting of the mutant protein have been proposed as causes of the disease, but neither explanation has been thoroughly examined. We replaced wild-type rhodopsin (WT-Rho) in RhoD190N/WT mouse rods with a largely "functionally silenced" rhodopsin mutant to isolate electrical responses triggered by D190N-Rho activity, and found that D190N-Rho at the single-molecule level indeed isomerizes more frequently than WT-Rho by over an order of magnitude. Importantly, however, this higher molecular dark activity does not translate into an overall higher cellular dark noise, owing to diminished D190N-Rho content in the rod outer segment. Separately, we found that much of the degeneration and shortened outer-segment length of RhoD190N/WT mouse rods was not averted by ablating rod transducin in phototransduction-also consistent with D190N-Rho's higher isomerization activity not being the primary cause of disease. Instead, the low pigment content, shortened outer-segment length, and a moderate unfolded protein response implicate protein misfolding as the major pathogenic problem. Finally, D190N-Rho also provided some insight into the mechanism of spontaneous pigment excitation.
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Degeneración Retiniana/metabolismo , Rodopsina/metabolismo , Animales , Línea Celular , Modelos Animales de Enfermedad , Células HEK293 , Humanos , Fototransducción/fisiología , Ratones , Mutación/fisiología , Células Fotorreceptoras Retinianas Bastones/metabolismo , Retinitis Pigmentosa/metabolismo , Segmento Externo de la Célula en Bastón/metabolismoRESUMEN
BACKGROUND: Anterior cruciate ligament reconstruction (ACLR) is reportedly associated with a higher incidence of deep vein thrombosis (DVT) incidence than other arthroscopic surgical procedures. The aim of this study is to retrospectively investigate the incidence and type of DVT and evaluate the relationship between DVT and risk factors among all patients who underwent ACLR under uniform conditions consisting of mechanical prophylaxis, no medical prophylaxis, and preoperative and postoperative lower extremity venous ultrasonography. METHODS: Of the 114 patients who underwent arthroscopic primary ACLR at our hospital who did not have a compound ligament injury or revision surgery, 112 patients were included. Two patients were not examined. DVT evaluation consisted of whole-leg ultrasonography at 1 week after surgery. We evaluated age, sex, body mass index, comorbidities, operative time, tourniquet time, presence of concurrent surgery (meniscus repair/resection or osteochondral column grafting), and non-weight-bearing status at 1 week after surgery as risk factors for DVT. RESULTS: DVT was found in 33 (29.5%) of 112 patients. Of these, 22 (19.6%) had distal DVT and 11 (9.8%) had proximal DVT. Non-weight-bearing status at 1 week after surgery was a statistically significant risk factor for proximal DVT (P = .034). CONCLUSIONS: Non-weight-bearing status is an independent risk factor for DVT, suggesting that early weight bearing may reduce the occurrence of DVT.
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Lesiones del Ligamento Cruzado Anterior , Reconstrucción del Ligamento Cruzado Anterior , Trombosis de la Vena , Humanos , Trombosis de la Vena/diagnóstico por imagen , Trombosis de la Vena/epidemiología , Trombosis de la Vena/etiología , Estudios Retrospectivos , Factores de Riesgo , Incidencia , Reconstrucción del Ligamento Cruzado Anterior/efectos adversos , Reconstrucción del Ligamento Cruzado Anterior/métodos , Lesiones del Ligamento Cruzado Anterior/cirugía , Lesiones del Ligamento Cruzado Anterior/complicacionesRESUMEN
PURPOSE: This study aimed to investigate the relationship between periprosthetic osteolysis around the talar component and the amount of talar component subsidence after total ankle arthroplasty (TAA). METHODS: This study included forty patients who underwent TAA with a mean follow-up of 67.5 ± 17.0 months. The patients were divided into two groups based on the amount of osteolysis around the talar component, as measured by computed tomography at the latest clinic visit: none to 2 mm (N group, n = 20) and greater than or equal to 2 mm (O group, n = 20). The average amount of talar component subsidence, clinical outcomes, and complications were compared between the two groups. In the O group, the correlation between osteolysis and talar component subsidence was evaluated. RESULTS: The average talar component subsidence was significantly different between the N (0.22 ± 0.94 mm) and O groups (2.12 ± 2.28 mm). Five out of 20 ankles in the O group required revision surgery owing to talar component subsidence. The Japanese Society for Surgery of the Foot scores in the N and O groups were significantly different: 93.5 ± 7.7 and 85.3 ± 15.4, respectively. In the O group, we found that osteolysis tended to develop on the lateral side, and the amount of osteolysis was positively correlated with the talar component subsidence (r = 0.59, P = .007). CONCLUSION: In the O group, a positive correlation between osteolysis and talar component subsidence was found, and five patients required revision surgery.
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Artroplastia de Reemplazo de Tobillo , Prótesis Articulares , Osteólisis , Humanos , Tobillo/cirugía , Osteólisis/diagnóstico por imagen , Osteólisis/etiología , Osteólisis/cirugía , Estudios Retrospectivos , Radiografía , Artroplastia de Reemplazo de Tobillo/efectos adversos , Prótesis Articulares/efectos adversos , Articulación del Tobillo/diagnóstico por imagen , Articulación del Tobillo/cirugía , ReoperaciónRESUMEN
The association between fruit and vegetable consumption before and during pregnancy and offspring's physical growth has been well reported, but no study has focused on offspring's neurological development. We aimed to explore the association between maternal fruit and vegetable consumption before and during pregnancy and developmental delays in their offspring aged 2 years. Between July 2013 and March 2017, 23 406 women were recruited for the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study. Fruit and vegetable consumption was calculated using FFQ, and offspring's developmental delays were evaluated by the Ages & Stages Questionnaires, Third Edition (ASQ-3) for infants aged 2 years. Finally, 10 420 women and 10 543 infants were included in the analysis. Totally, 14·9 % of children had developmental delay when screened using the ASQ-3. Women in the highest quartile of vegetable consumption from pre-pregnancy to early pregnancy and from early to mid-pregnancy had lower odds of offspring's developmental delays (OR 0·74; 95 % CI 0·63, 0·89 and OR 0·70; 95 % CI 0·59, 0·84, respectively) than women in the lowest quartile. Women in the highest quartile of fruit consumption from early to mid-pregnancy had lower odds of offspring's developmental delays (OR 0·78; 95 % CI 0·66, 0·92) than women in the lowest quartile. In conclusion, high fruit and vegetable consumption before and during pregnancy was associated with a lower risk of developmental delays in offspring aged 2 years.
Asunto(s)
Frutas , Verduras , Niño , Preescolar , Estudios de Cohortes , Femenino , Humanos , Lactante , Japón , Embarazo , Encuestas y CuestionariosRESUMEN
BACKGROUND: Although small for gestational age (SGA) is a serious problem worldwide, the association of dietary patterns before and during pregnancy with SGA risk is unclear. We evaluated this association among Japanese pregnant women using three methods: reduced rank regression (RRR) and partial least squares (PLS), methods for extracting dietary patterns that can explain the variation of response variables, and principal component analysis (PCA), a method for extracting dietary patterns of the population. METHODS: Between July 2013 and March 2017, 22,493 pregnant women were recruited to the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study, a population-based prospective birth cohort study in Japan. Information on dietary intake was obtained using food frequency questionnaires, and dietary patterns were extracted using RRR, PLS, and PCA. Information on birth weight was obtained from obstetric records, and the birth weight SD score and SGA were defined by the method of the Japan Pediatric Society. The associations of dietary patterns with birth weight SD score and SGA risk were investigated using multiple linear regression and multiple logistic regression, respectively. RESULTS: A total of 17,728 mother-child pairs were included. The birth weight SD score was 0.15 ± 0.96, and the prevalence of SGA was 6.3%. The dietary patterns extracted by RRR and PLS were similar and characterized by a high intake of cereals and fruits and a low intake of alcoholic and non-alcoholic beverages in both pre- to early pregnancy and from early to mid-pregnancy. Higher adoption of the RRR and PLS patterns in both periods was associated with an increased birth weight SD score and lower risk of SGA. In contrast, the PCA1 pattern was not associated with birth weight SD score or SGA risk in either period. Although the PCA2 pattern was associated with increased birth weight SD score from early to mid-pregnancy, no other associations with birth weight SD score or SGA risk were observed. CONCLUSIONS: The dietary pattern with a high intake of cereals and fruits and a low intake of alcoholic and non-alcoholic beverages before and during pregnancy was associated with a decreased SGA risk in Japan.
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Cohorte de Nacimiento , Peso al Nacer , Niño , Estudios de Cohortes , Femenino , Edad Gestacional , Humanos , Japón/epidemiología , Embarazo , Estudios ProspectivosRESUMEN
G protein-coupled receptor (GPCR) signaling is crucial for many physiological processes. A signature of such pathways is high amplification, a concept originating from retinal rod phototransduction, whereby one photoactivated rhodopsin molecule (Rho*) was long reported to activate several hundred transducins (GT*s), each then activating a cGMP-phosphodiesterase catalytic subunit (GT*·PDE*). This high gain at the Rho*-to-GT* step has been challenged more recently, but estimates remain dispersed and rely on some nonintact rod measurements. With two independent approaches, one with an extremely inefficient mutant rhodopsin and the other with WT bleached rhodopsin, which has exceedingly weak constitutive activity in darkness, we obtained an estimate for the electrical effect from a single GT*·PDE* molecular complex in intact mouse rods. Comparing the single-GT*·PDE* effect to the WT single-photon response, both in Gcaps-/- background, gives an effective gain of only â¼12-14 GT*·PDE*s produced per Rho*. Our findings have finally dispelled the entrenched concept of very high gain at the receptor-to-G protein/effector step in GPCR systems.
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Células Fotorreceptoras Retinianas Bastones/metabolismo , Transducina/metabolismo , Secuencias de Aminoácidos , Animales , GMP Cíclico/metabolismo , Subunidades alfa de la Proteína de Unión al GTP/metabolismo , Fototransducción , Ratones Transgénicos , Mutación/genética , Hidrolasas Diéster Fosfóricas/metabolismo , Fotones , Rodopsina/química , Rodopsina/metabolismoRESUMEN
Low energy consumption treatment of high-strength wastewater is crucial in controlling groundwater pollution and eutrophication in closed waterbodies. In this study, the sulfate reduction, denitrification/anammox, and partial nitrification (SRDAPN) process, which is an effective organic carbon and nitrogen removal process with low energy consumption for low strength wastewater, was applied to treat livestock wastewater with high COD and sulfate concentration, and microbial reaction and community were examined using an anaerobic-anoxic biological filter reactor that simulates circulation from an aerobic reactor. At a total organic carbon loading rate of 2.7-5.8 kgC/m3·day, sulfate reduction and methane production occurred simultaneously in the anaerobic column of the reactor. Specifically, sulfate reduction resulted in organic matter removal rates of 38 and 26% at ambient temperature and 25 °C, respectively. Furthermore, both heterotrophic and autotrophic denitrification occurred in the anoxic column, and when the organic loading rate in the anoxic reactor was below 0.2 kgC/m3·day, 33%-37% of ammonium and 33%-34% of nitrite were removed by the anammox reaction. Heterotrophic denitrification bacteria (Thauera, Comamonas, and Denitratisoma) and sulfur denitrification bacteria (Sulfurimonas denitriï¬cans) grew in the lower and middle parts of the anoxic column, whereas anammox bacteria (2.5% of Candidatus Brocadia at ambient temperature and 9.4% of Candidatus Kuenenia at 25 °C) grew in the upper part of the anoxic column. These results indicate that the SRDAPN process based on sulfur cycle and anammox is useful for treatment of high strength wastewater with low energy consumption.
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Nitrificación , Aguas Residuales , Oxidación Anaeróbica del Amoníaco , Reactores Biológicos , Carbono , Desnitrificación , Nitrógeno/análisis , Oxidación-Reducción , Aguas del Alcantarillado , Sulfuros , Aguas Residuales/análisisRESUMEN
Apigenin is a flavonoid with antioxidant and anticancer effects. It has been reported that apigenin inhibits proliferation, migration, and invasion and induces apoptosis in cultured lung cancer cells. However, there is little information on the involvement of microRNAs (miRNAs) in its effects. miRNA microarray analysis and polymerase-chain-reaction analysis of miRNAs revealed that treatment of human lung cancer A549 cells with apigenin up-regulated the level of miR-34a-5p. Furthermore, mRNA microarray analysis and the results of three microRNA target prediction tools showed that Snail Family Transcriptional Repressor 1 (SNAI1), which inhibits the induction of apoptosis, had its mRNA expression down-regulated in A549 cells treated with apigenin. Our findings suggest that apigenin might induce apoptosis by down-regulation of SNAI1 through up-regulation of miR-34a-5p in A549 cells.
Asunto(s)
Apigenina/farmacología , Apoptosis/genética , Regulación hacia Abajo/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , MicroARNs/metabolismo , Factores de Transcripción de la Familia Snail/genética , Células A549 , Apoptosis/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/genética , Regulación hacia Abajo/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , MicroARNs/genética , Modelos Biológicos , ARN Mensajero/genética , ARN Mensajero/metabolismo , Factores de Transcripción de la Familia Snail/metabolismo , Regulación hacia Arriba/efectos de los fármacos , Regulación hacia Arriba/genéticaRESUMEN
Recent progress in printable electronics has enabled the fabrication of printed strain sensors for diverse applications. These include the monitoring of civil infrastructure, the gradual aging of which raises concerns about its effective maintenance and safety. Therefore, there is a need for automated sensing systems that provide information on the performance and behavior of engineering structures that are subjected to dynamic and static loads. The application of printed strain sensors in structural health monitoring is of growing interest owing to its large-area and cost-effective fabrication process. Previous studies have proven the suitability of printable strain sensors for dynamic strain measurements on bridges; however, the analysis of the long-term stability of printed sensors during static strain measurements is still lacking. Thus, this study aims to assess the long-term stability of printed strain sensor arrays and their suitability for the static strain analysis of large civil structures. The developed sensors and a dedicated wireless data acquisition system were deployed inside a gravity dam, which was selected as the field test environment. This test environment was chosen owing to the relatively stable temperature inside the dam and the very slow static strain changes associated with periodic water level changes. The results exhibited an average signal drift of 20 µÏµ over 127 days. One of the sensor arrays was installed on a small crack in the dam structure; it showed that the sensors can track static strain changes owing to variations in the crack opening, which are related to the water level changes in the dam. Overall, the results of the developed sensors exhibit good strain sensitivity and low signal drift. This indicates the potential suitability of printed sensors for applications in the static strain analysis of engineering structures.
Asunto(s)
Dispositivos Electrónicos Vestibles , Electrónica , TemperaturaRESUMEN
BACKGROUND AND OBJECTIVES: Although large-scale natural disasters and the resultant changes in living environments worsen dietary habits among adults immediately after the disasters, whether this association remains for a long period is unclear. This is particularly important for recent mothers because lactating women require additional nutrition for milk production. Thus, we investigated the association of living environments with dietary habits and nutritional intake of recent mothers between four and seven years after the Great East Japan Earthquake (11th March, 2011). METHODS AND STUDY DESIGN: We analyzed 8,551 mothers who participated to the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study. Living environments were characterized into four categories: "same home before the earthquake", "rental housing", "reconstructed home", and "acquaintance's home". Dietary habits and nutritional intake were evaluated using a food frequency questionnaire answered 12 months after their deliveries (the questionnaire was answered between March 2015 and July 2018). RESULTS: Multiple linear regression analyses demonstrated that mothers in 'rental housing' or 'reconstructed home' had a significantly lower intake of almost all nutrients or certain nutrients, respectively, compared with those residing in 'same home before the earthquake'. However, fewer significant differences were detected between the nutritional intake of the mothers lodging in an 'acquaintance's home' and that of those living in 'same home before the earthquake'. CONCLUSIONS: Our findings indicate that living environments long-term after largescale disasters are associated with dietary habits and nutritional intake among recent mothers.