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During the maternal-to-zygotic transition (MZT), maternal RNAs are actively degraded and replaced by newly synthesized zygotic transcripts in a highly coordinated manner. However, it remains largely unknown how maternal mRNA decay is triggered in early vertebrate embryos. Here, through genome-wide profiling of RNA abundance and 3' modification, we show that uridylation is induced at the onset of maternal mRNA clearance. The temporal control of uridylation is conserved in vertebrates. When the homologs of terminal uridylyltransferases TUT4 and TUT7 (TUT4/7) are depleted in zebrafish and Xenopus, maternal mRNA clearance is significantly delayed, leading to developmental defects during gastrulation. Short-tailed mRNAs are selectively uridylated by TUT4/7, with the highly uridylated transcripts degraded faster during the MZT than those with unmodified poly(A) tails. Our study demonstrates that uridylation plays a crucial role in timely mRNA degradation, thereby allowing the progression of early development.
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Embrião de Mamíferos/enzimologia , Embrião não Mamífero/enzimologia , Nucleotidiltransferases/metabolismo , Estabilidade de RNA , RNA Mensageiro/metabolismo , Transcriptoma , Xenopus laevis/genética , Peixe-Zebra/genética , Animais , Animais Geneticamente Modificados , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Drosophila melanogaster/embriologia , Drosophila melanogaster/enzimologia , Drosophila melanogaster/genética , Gastrulação , Regulação da Expressão Gênica no Desenvolvimento , Idade Gestacional , Camundongos Endogâmicos ICR , Nucleotidiltransferases/genética , Processamento Pós-Transcricional do RNA , RNA Mensageiro/genética , Proteínas de Xenopus/genética , Proteínas de Xenopus/metabolismo , Xenopus laevis/embriologia , Xenopus laevis/metabolismo , Peixe-Zebra/embriologia , Peixe-Zebra/metabolismoRESUMO
Disruption of colonic homeostasis caused by aberrant M1/M2 macrophage polarization and dysbiosis contributes to inflammatory bowel disease (IBD) pathogenesis. However, the molecular factors mediating colonic homeostasis are not well characterized. Here, we found that Ninjurin1 (Ninj1) limits colon inflammation by regulating macrophage polarization and microbiota composition under homeostatic conditions and during colitis development. Ninj1 deletion in mice induced hypersusceptibility to colitis, with increased prevalence of colitogenic Prevotellaceae strains and decreased immunoregulatory Lachnospiraceae strains. Upon co-housing (CoH) with WT mice, Ninj1-/- mice showed increased Lachnospiraceae and decreased Prevotellaceae abundance, with subsequent improvement of colitis. Under homeostatic conditions, M1 macrophage frequency was higher in the Ninj1-/- mouse colons than wild-type (WT) mouse colons, which may contribute to increased basal colonic inflammation and microbial imbalance. Following colitis induction, Ninj1 expression was increased in macrophages; meanwhile Ninj1-/- mice showed severe colitis development and impaired recovery, associated with decreased M2 macrophages and escalated microbial imbalance. In vitro, Ninj1 knockdown in mouse and human macrophages activated M1 polarization and restricted M2 polarization. Finally, the transfer of WT macrophages ameliorated severe colitis in Ninj1-/- mice. These findings suggest that Ninj1 mediates colonic homeostasis by modulating M1/M2 macrophage balance and preventing extensive dysbiosis, with implications for IBD prevention and therapy.
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Moléculas de Adesão Celular Neuronais/deficiência , Colite/metabolismo , Colite/patologia , Microbioma Gastrointestinal/fisiologia , Macrófagos/metabolismo , Macrófagos/patologia , Fatores de Crescimento Neural/deficiência , Animais , Moléculas de Adesão Celular Neuronais/metabolismo , Diferenciação Celular/fisiologia , Linhagem Celular Tumoral , Colite/microbiologia , Colo/metabolismo , Colo/microbiologia , Colo/patologia , Modelos Animais de Doenças , Homeostase/fisiologia , Humanos , Inflamação/metabolismo , Inflamação/microbiologia , Inflamação/patologia , Doenças Inflamatórias Intestinais/metabolismo , Doenças Inflamatórias Intestinais/microbiologia , Doenças Inflamatórias Intestinais/patologia , Ativação de Macrófagos/fisiologia , Masculino , Camundongos , Fatores de Crescimento Neural/metabolismo , Células THP-1/metabolismoRESUMO
The combination of quantum Hall conductance and charge-trap memory operation was qualitatively examined using a graphene field-effect transistor. The characteristics of two terminal quantum Hall conductance appeared clearly on the background of a huge conductance hysteresis during a gate-voltage sweep for a device using monolayer graphene as a channel,hexagonal boron-nitride flakes as a tunneling dielectric and defective silicon oxide as the charge storage node. Even though there was a giant shift of the charge neutrality point, the deviation of quantized resistance value at the state of filling factor 2 was less than 1.6% from half of the von Klitzing constant. At high Landau level indices, the behaviors of quantum conductance oscillation between the increasing and the decreasing electron densities were identical in spite ofa huge memory window exceeding 100 V. Our results indicate that the two physical phenomena, two-terminal quantum Hall conductance and charge-trap memory operation, can be integrated into one device without affecting each other.
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TM4SF5 (transmembrane 4 L six family member 5) is involved in EMT (epithelial-mesenchymal transition) for liver fibrosis and cancer metastasis; however, the function(s) of TM4SF5 during embryogenesis remains unknown. In the present study the effects of TM4SF5 on embryogenesis of zebrafish were investigated. tm4sf5 mRNA was expressed in the posterior somites during somitogenesis and in whole myotome 1 dpf (day post-fertilization). tm4sf5 suppression impaired development of the trunk with aberrant morphology of muscle fibres and altered expression of integrin α5. The arrangement and adhesion of muscle cells were abnormally disorganized in tm4sf5 morphants with reduced muscle fibre masses, where integrin α5-related signalling molecules, including fibronectin, FAK (focal adhesion kinase), vinculin and actin were aberrantly localized, compared with those in control fish. Aberrant muscle developments in tm4sf5 morphants were recovered by additional tm4sf5 or integrin α5 mRNA injection. Such a role for TM4SF5 was observed in the differentiation of C2C12 mouse myoblast cells to multinuclear muscle cells. Taken together, the results show that TM4SF5 controls muscle differentiation via co-operation with integrin α5-related signalling.
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Integrina alfa5/fisiologia , Proteínas de Membrana/genética , Desenvolvimento Muscular/fisiologia , Animais , Diferenciação Celular , Movimento Celular , Células Cultivadas , Transição Epitelial-Mesenquimal , Integrina alfa5/biossíntese , Proteínas de Membrana/biossíntese , Camundongos , Transdução de Sinais/fisiologia , Somitos/metabolismo , Peixe-Zebra/embriologiaRESUMO
Swimming behavior in fish is driven by coordinated contractions of muscle fibers. In zebrafish, slow muscle cell migration is crucial for the formation of the muscle network; slow myoblasts, which arise from medial adaxial cells, migrate radially to the lateral surface of the trunk and tail during embryogenesis. This study found that the zebrafish A-kinase anchoring protein (akap)12 isoforms akap12α and akap12ß are required for muscle morphogenesis and locomotor activity. Embryos deficient in akap12 exhibited reduced spontaneous coiling, touch response, and free swimming. Akap12-depleted slow but not fast muscle cells were misaligned, suggesting that the behavioral abnormalities resulted from specific defects in slow muscle patterning; indeed, slow muscle cells and muscle pioneers in these embryos showed abnormal migration in a cell-autonomous manner. Taken together, these results suggest that akap12 plays a critical role in the development of zebrafish locomotion by regulating the normal morphogenesis of muscles.
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Proteínas de Ancoragem à Quinase A/metabolismo , Morfogênese , Músculo Esquelético/metabolismo , Natação , Proteínas de Peixe-Zebra/metabolismo , Proteínas de Ancoragem à Quinase A/genética , Animais , Músculo Esquelético/embriologia , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Peixe-Zebra , Proteínas de Peixe-Zebra/genéticaRESUMO
PURPOSE: To evaluate characteristics of delayed ischemic stroke after stent-assisted coil placement in cerebral aneurysms and to determine the optimal duration of dual antiplatelet therapy for its prevention. MATERIALS AND METHODS: This retrospective study was approved by the institutional review board, and the requirement to obtain written informed consent was waived. Of 1579 patients with 1661 aneurysms, 395 patients (25.0%) with 403 aneurysms (24.3%) treated with stent-assisted coil placement were included and assigned to groups stratified as early (126 patients [31.9%]; 3 months of coil placement), midterm (160 patients [40.5%]; 6 months), or late (109 patients [27.6%]; ≥ 9 months), according to the time points of switching dual antiplatelet therapy to monotherapy from coil placement. Cumulative rates of delayed ischemic stroke in each group were calculated by using Kaplan-Meier estimates that were compared with log-rank tests. Risk factors of delayed ischemic stroke were identified by using Cox proportional hazard analysis. RESULTS: Delayed ischemic stroke occurred in 3.5% of all cases (embolism, 3.0%; thrombotic occlusion, 0.5%) within 2 months following the switch. Late switch yielded no delayed ischemic stroke, unlike early (seven of 126 patients [5.6%]; P = .013) or midterm (seven of 160 patients [4.4%]; P = .028) switch. Incomplete occlusion (hazard ratio, 6.68 [95% confidence interval: 1.490, 29.900]) was identified as a risk factor. CONCLUSION: Delayed ischemic stroke after stent-assisted coil placement is caused by embolism from or thrombotic occlusion of stent-containing vessels after switching from dual antiplatelet therapy to monotherapy. The stent-containing vessel with incomplete aneurysm occlusion presents as a long-term thromboembolic source. Therefore, dual antiplatelet therapy for more than 9 months and late switch to monotherapy are recommended for its prevention.
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Aspirina/administração & dosagem , Embolização Terapêutica/efeitos adversos , Aneurisma Intracraniano/terapia , Inibidores da Agregação Plaquetária/administração & dosagem , Stents/efeitos adversos , Acidente Vascular Cerebral/etiologia , Ticlopidina/análogos & derivados , Clopidogrel , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Estudos Retrospectivos , Acidente Vascular Cerebral/prevenção & controle , Ticlopidina/administração & dosagem , Resultado do TratamentoRESUMO
Objectives: The aim of this nationwide longitudinal cohort study is to determine the risk of congestive heart failure (CHF) associated with a seropositive rheumatoid arthritis (RA) population in Korea. Methods: In this study, National Health Insurance Service-Health Screening Cohort (NHIS-HEALS) data from 2002 to 2003 were used. The cohort was followed up with for 12 years until December of 2015. Seropositive RA was defined as a patient prescribed with a disease-modifying anti-rheumatic drug (DMARD) among patients with the International Classification of Diseases code M05 (seropositive RA). Patients who were diagnosed before 2004 were excluded. The seropositive RA group consisted of 2765 patients, and a total of 13,825 patients were in the control group. The Kaplan-Meier method was used to calculate the 12-year CHF incidence rate for each group. A Cox proportional hazards regression analysis was used to estimate the hazard ratio of CHF. Results: The hazard ratio of CHF in the seropositive RA group was 2.41 (95% confidence interval (CI): 1.40-4.14) after adjusting for age and sex. The adjusted hazard ratio of CHF in the seropositive RA group was 2.50 (95% CI: 1.45-4.30) after adjusting for age, sex, income, and comorbidities. In females aged ≥65 and aged <65, the incidence rates in the non-hypertension, non-diabetes mellitus, and non-dyslipidemia subgroups were significantly higher in the seropositive RA group than in the control group. Conclusions: This nationwide longitudinal cohort study shows an increased risk of CHF in patients with seropositive RA.
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Sulfated polysaccharides isolated from seaweeds are thought of as ideal ingredients in the pharmaceutical, nutraceutical, and cosmetics industries. Our previous study isolated and characterized sulfated polysaccharides from Padina boryana. The sulfated polysaccharides of Padina boryana (PBP) were extracted, and the antioxidant activity of PBP was evaluated. The results indicate that PBP possesses antioxidant effects and potential in the cosmetic industry. To further investigate the potential of PBP in cosmetics, the photoprotective and anti-melanogenesis effects of PBP were evaluated. The anti-melanogenesis test results display that PBP reduced the melanin content in the murine melanoma cells stimulated by alpha melanocyte-stimulating hormone from 203.7% to 183.64%, 144.63%, and 127.57% at concentrations of 25 µg/mL, 50 µg/mL, and 100 µg/mL, respectively. The anti-photodamage test results showed that PBP significantly protected skin cells against UVB-stimulated photodamage. PBP suppressed human epidermal keratinocyte (HaCaT cell) death by inhibiting apoptosis and reducing the level of intracellular reactive oxygen species. The intracellular reactive oxygen species level of HaCaT cells irradiated by UVB was reduced from 192.67% to 181.22%, 170.25%, and 160.48% by 25 µg/mL, 50 µg/mL, and 100 µg/mL PBP, respectively. In addition, PBP remarkably reduced UVB-induced human dermal fibroblast damage by suppressing oxidative damage, inhibiting collagen degradation, and attenuating inflammatory responses. These results indicate that PBP possesses photoprotective and anti-melanogenesis activities and suggest that PBP is a potential ingredient in the cosmetic industry.
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An 8-week feeding trial was conducted to evaluate the effects of various dietary levels of garlic juice processing waste (GJPW) on the growth, feed utilization, digestive and antioxidant enzyme activity, growth- and antioxidant-related gene expression, and resistance to Streptococcus iniae infection of juvenile black rockfish (Sebastes schlegelii). A total of 450 juvenile rockfish were randomly distributed into 30 L rectangular tanks (30 fish per tank). Five experimental diets were prepared in triplicate. The fish were fed experimental diets supplemented with GJPW at concentrations of 0 (GJPW0, control), 2.5 (GJPW2.5), 5 (GJPW5), 7.5 (GJPW7.5), and 10 g kg-1 (GJPW10) diet. All of the GJPW-supplemented treatments (2.5, 5, 7.5, and 10 g kg-1) significantly enhanced weight gain (WG), specific growth rate (SGR), feed efficiency (FE), protein efficiency ratio (PER), and digestive enzyme activity (amylase, trypsin, and lipase). A decreasing trend was seen in plasma aspartate aminotransferase (ALT), alanine aminotransferase (AST), and glucose (GLU) content with increasing dietary levels of GJPW. In contrast, plasma lysozyme and antioxidant enzyme activities were significantly increased with increasing dietary GJPW levels. Furthermore, GJPW administration significantly upregulated the expression of insulin-like growth factor-1 (IGF-1), superoxide dismutase (SOD), catalase (CAT), and glutathione S-transferase (GST) in the liver of rockfish. A challenge test with S. iniae showed significantly higher resistance in the GJPW-supplemented treatments than in the control. In short, dietary supplementation GJPW enhanced growth performance and antioxidant response in juvenile black rockfish, with suitable effects in fish fed with 2.5 g kg-1 GJPW for 8 weeks.
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Background With the occurrence of a number of major disasters around the world, there is growing interest in chemical disaster medicine. In South Korea, there is a training program for mass casualty incidents (MCI) and backup by legal regulations by the Framework Act on the Management of Disasters and Safety. However, there is no program focusing on chemical disasters. Thus, the authors newly created a program, the Chemical-Mass Casualty Incident Response Education Module (C-MCIREM) in September 2019. This was a pilot study to verify the educational effect of the program. Method A pre/post study was conducted of a chemical MCI training program based on simulation. A total of 25 representative and qualified participants were recruited from fire departments, administrative staff of public health centers, and healthcare workers of hospitals in the Gyeonggi-do province of South Korea. They participated in a one-day training program. A knowledge test and confidence survey were provided to participants just before training, and again immediately following the training online. The authors compared improvements of pre/post-test results. In the tabletop drill exercise, quantified qualitative analyses were used to measure the educational effect on the participants. Results In the knowledge test, the mean (standard deviation) scores for all 25 participants at baseline and after training were 41.72 (15.186) and 77.96 (11.227), respectively (pâ <â 0.001). In the confidence survey for chemical MCI response for all 25 participants, all the sub-items concerning personal protective equipment selection, antidote selection, antidote stockpiling and passing on knowledge to colleagues, zone setup and decontamination, and chemical triage were improved compared to the baseline score (pâ <â 0.001). The tabletop exercise represented a prehospital setting and had 11 participants. The self-efficacy qualitative survey showed pre- and post-exercise scores of 64/100 and 84/100 respectively. For a hospital setting exercise, it had 14 participants. The survey showed pre/post-exercise scores of 26/100 and 73/100 respectively. Twenty-two (88%) participants responded to the final satisfaction survey, and their overall mean scores regarding willingness to recommend this training program to others, overall satisfaction with theoretical education, overall satisfaction with tabletop drill simulation, and opinion about whether policymakers need this training were all over 8 out of 10 respectively. Conclusion C-MCIREM, the newly created chemical MCI program, provided effective education to the selected 25 participants among Korean chemical MCI responders in terms of both knowledge and practice at a single pilot trial. Participants were highly satisfied with the educational material and their confidence in disaster preparedness was clearly improved. In order to prove the universal educational effect of this C-MCIREM in the future, more education is needed.
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We report unusual absolute negative resistance phenomena in twisted superconducting yarns consisting of niobium-nitride (NbN) nanowires formed on a template of aligned carbon nanotube (CNT) sheets. In the vicinity of the superconducting critical temperature and critical current, the electrical resistance with a standard four-probe configuration exhibits negative values for many wire-shaped twisted yarns. This anomalous behavior at the superconducting transition stage is analyzed using a simplified circuit model, where the charge conduction is determined by the combination between the intra- and internanofiber transports inside the yarn. The superconducting transition of intrafibrillar transport along CNT-templated NbN nanowires was distinguished from that of an interfibrillar one, where the latter exhibits the ensemble property of superconducting weak links among adjacent NbN nanowires. Furthermore, the topological similarity between the sheet of an aligned array of nanowires and the yarn of twisted nanofibrils enables the occurrence of this anomaly. This study indicates that the quantitative network-based approach is effective for the analysis of anomalous charge conduction through nanowire-based anisotropic materials.
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BACKGROUND: This nationwide study aimed to compare the medical burdens of pyogenic spondylitis (PS) and tuberculous spondylitis (TS) between 2007 and 2016 in Korea. METHODS: We used a national database managed by the National Health Insurance Service (NHIS) with data from the years 2007 and 2016. A total of 9655 newly diagnosed patients with PS or TS were correspondingly enrolled in the PS or TS group. Chi square test analyses were used to compare the PS and TS groups. RESULTS: The overall incidence of infectious spondylitis during the study period was 9655 persons. The PS and TS groups consisted of 7305 and 2350 cases, respectively. Individual medical costs in the PS group (USD 10,049 ± 94 vs. USD 16,672 ± 17,729, P < 0.001) and the TS group (USD 4882 ± 6869 vs. USD 8531 ± 10,709, P < 0.001) both increased. The total medical cost for the PS group increased significantly between 2007 and 2016 in Korea (USD 24,428,560 vs. USD 81,044,196, P < 0.001). In contrast, the total medical cost for the TS group decreased between 2007 and 2016 in Korea (USD 8,573,038 vs. USD 4,879,520, P < 0.001). CONCLUSION: This nationwide study shows that the total medical cost of PS has increased and that the total medical cost of TS has decreased between 2007 and 2016 in Korea.
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BACKGROUND: This nationwide study aimed to compare the medical burdens of pyogenic spondylitis (PS) and tuberculous spondylitis (TS) between 2007 and 2016 in Korea. METHODS: We used a national database managed by the National Health Insurance Service (NHIS) with data from the years 2007 and 2016. A total of 9655 newly diagnosed patients with PS or TS were correspondingly enrolled in the PS or TS group. Chi square test analyses were used to compare the PS and TS groups. RESULTS: The overall incidence of infectious spondylitis during the study period was 9655 persons. The PS and TS groups consisted of 7305 and 2350 cases, respectively. Individual medical costs in the PS group (USD 10,049 ± 94 vs. USD 16,672 ± 17,729, P < 0.001) and the TS group (USD 4882 ± 6869 vs. USD 8531 ± 10,709, P < 0.001) both increased. The total medical cost for the PS group increased significantly between 2007 and 2016 in Korea (USD 24,428,560 vs. USD 81,044,196, P < 0.001). In contrast, the total medical cost for the TS group decreased between 2007 and 2016 in Korea (USD 8,573,038 vs. USD 4,879,520, P < 0.001). CONCLUSION: This nationwide study shows that the total medical cost of PS has increased and that the total medical cost of TS has decreased between 2007 and 2016 in Korea.
Assuntos
Espondilite/epidemiologia , Tuberculose da Coluna Vertebral/epidemiologia , Adulto , Idoso , Estudos de Coortes , Doenças Transmissíveis , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , República da Coreia/epidemiologia , Estudos Retrospectivos , Adulto JovemRESUMO
The vertebrate body plan is accomplished by left-right asymmetric organ development and the heart is a representative asymmetric internal organ which jogs to the left-side. Kupffer's vesicle (KV) is a spherical left-right organizer during zebrafish embryogenesis and is derived from a cluster of dorsal forerunner cells (DFCs). Cadherin1 is required for collective migration of a DFC cluster and failure of DFC collective migration by Cadherin1 decrement causes KV malformation which results in defective heart laterality. Recently, loss of function mutation of A-kinase anchoring protein 12 (AKAP12) is reported as a high-risk gene in congenital heart disease patients. In this study, we demonstrated the role of akap12ß in asymmetric heart development. The akap12ß, one of the akap12 isoforms, was expressed in DFCs which give rise to KV and akap12ß-deficient zebrafish embryos showed defective heart laterality due to the fragmentation of DFC clusters which resulted in KV malformation. DFC-specific loss of akap12ß also led to defective heart laterality as a consequence of the failure of collective migration by cadherin1 reduction. Exogenous akap12ß mRNA not only restored the defective heart laterality but also increased cadherin1 expression in akap12ß morphant zebrafish embryos. Taken together, these findings provide the first experimental evidence that akap12ß regulates heart laterality via cadherin1. [BMB Reports 2019; 52(8): 525-530].
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Proteínas de Ancoragem à Quinase A/metabolismo , Coração/embriologia , Células de Kupffer/metabolismo , Proteínas de Peixe-Zebra/metabolismo , Peixe-Zebra/metabolismo , Animais , Caderinas/metabolismo , Células de Kupffer/citologiaRESUMO
Pertaining to an association between Acute Myocardial Infarction (AMI) and Ankylosing Spondylitis (AS) is sparse. The purpose of this nationwide longitudinal study was to investigate the prevalence of AMI in newly diagnosed AS patients. A total of 12,988 patients were enrolled in the AS group from January 1, 2010 to December 31, 2014 from the Korean National Health Insurance Service (NHIS). The control group consisted of 64,940 subjects according to 1:5 age-sex stratified matching. The AMI incidence rates in AS and control group were compared using the Kaplan-Meier method. The hazard ratio of AMI and the control group was estimated by Cox proportional hazards regression analyses. During a 6â¯year follow up, 62 patients (0.48%) in the AS group and 157 persons (0.24%) in the control group developed AMI. The hazard ratio of AMI in the AS group was 1.99 (95% confidence interval [95% CI], 1.48-2.67) after adjusting for sex and age. The hazard ratio of AMI in the AS group was 1.81 (95% CI, 1.34-2.43) after adjusting for demographics and comorbid medical disorders. The incidence rate of AMI increases in newly diagnosed AS patients.
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Infarto do Miocárdio/epidemiologia , Espondilite Anquilosante/complicações , Adulto , Idoso , Estudos de Coortes , Feminino , Seguimentos , Humanos , Incidência , Estudos Longitudinais , Pessoa de Meia-Idade , Infarto do Miocárdio/etiologia , Modelos de Riscos Proporcionais , Fatores de RiscoRESUMO
AKAP12 belongs to A-kinase anchoring protein (AKAP) family of scaffold proteins and is known as a tumor suppressor in several human cancer types. Its role as a tumor suppressor in hepatocellular carcinoma (HCC) was proposed due to its downregulation and epigenetic modification in human HCC; however, the effect of its deficiency on liver injuries, such as liver fibrosis and cancer has been poorly studied. By analyzing tumor and non-tumor tissues of 15 patients with HCC, it was confirmed that AKAP12 expression was downregulated in human HCC as compared with adjacent non-tumor tissues. Immunohistochemical staining of mouse liver tissue for AKAP12 revealed that its sinusoidal expression was diminished in capillarized endothelium after 8 weeks of thioacetamide (TAA) administration. AKAP12 deficiency resulted in the promotion of ductular response of biliary epithelial cells, whereas overall fibrosis and myofibroblast activation were comparable between genotypes after short-term TAA treatment. The mRNA expressions of some fibrosis-related genes such as those encoding epithelial cell adhesion molecule, collagen type 1 α1 and elastin were upregulated in liver tissues of AKAP12-knockout mice. Long-term administration of TAA for 26 weeks led to the development of liver tumors; the incidence of tumor development was higher in AKAP12-deficient mice than in wild-type littermates. Together, these results suggest that AKAP12 functions as a tumor suppressor in liver cancer and is associated with the regulation of hepatic non-parenchymal cells.
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Left-right asymmetric organ development is critical to establish a proper body plan of vertebrates. In zebrafish, the Kupffer's vesicle (KV) is a fluid-filled sac which controls asymmetric organ development, and a properly inflated KV lumen by means of fluid influx is a prerequisite for the asymmetric signal transmission. However, little is known about the components that support the paracellular tightness between the KV luminal epithelial cells to sustain hydrostatic pressure during KV lumen expansion. Here, we identified that the claudin5a (cldn5a) is highly expressed at the apical surface of KV epithelial cells and tightly seals the KV lumen. Downregulation of cldn5a in zebrafish showed a failure in organ laterality that resulted from malformed KV. In addition, accelerated fluid influx into KV by combined treatment of forskolin and 3-isobutyl-1-methylxanthine failed to expand the partially-formed KV lumen in cldn5a morphants. However, malformed KV lumen and defective heart laterality in cldn5a morphants were significantly rescued by exogenous cldn5a mRNA, suggesting that the tightness between the luminal epithelial cells is important for KV lumen formation. Taken together, these findings suggest that cldn5a is required for KV lumen inflation and left-right asymmetric organ development.
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Padronização Corporal/fisiologia , Cílios/fisiologia , Claudina-5/metabolismo , Embrião não Mamífero/citologia , Lateralidade Funcional/fisiologia , Morfogênese/fisiologia , Proteínas de Peixe-Zebra/metabolismo , Peixe-Zebra/crescimento & desenvolvimento , Animais , Embrião não Mamífero/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Peixe-Zebra/metabolismoRESUMO
Ethanol extracts from developed kimchi condiments (KME, KMEE) and mixtures of sub-ingredients (ME, MEE) showed high nitrite scavenging activity. ME was able to scavenge 89% of total nitrite at 50 mg/mL ME and pH 1.2. The nitrite scavenging abilities of KME and KMEE were significantly higher than in ethanol extract from the control condiment. The inhibitory effects on N-nitrosodimethylamine (NDMA) formation by decrease of salted-fermented fish products (Jeot-gal) and increase of condiments in the composition of kimchi were investigated. The modified kimchi (KM) was prepared with new condiments, which included new sub-ingredients and reduced Jeot-gal. The NDMA and its precursor levels were significantly decreased in KM compared with those in the control kimchi (KC). The KM also obtained higher sensory scores than KC. Therefore, the increase of sub-ingredients and reduction of Jeot-gal in kimchi would be recommended for production of reduced-NDMA kimchi while maintaining or even enhancing flavor profiles.
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Herein, we report the advanced-concept triple-functionality of a metal-organic nanotube (MONT), which acts as a reservoir for unstable reactants, a photoreaction platform, and a scavenger for byproduct iodine. Self-assembly of CdI2 with a new Y-type ligand (L) produces the substantial 1D MOF, [CdI2(L)], thus forming a thick nanotube with a 1.4 nm diameter.
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We report the synthesis of centimeter-scale, uniform 1T'- and 2H-MoTe2 thin films via the tellurization of Mo thin films. 1T'-MoTe2 was initially grown and converted gradually to 2H-MoTe2 over a prolonged growth time under a Te atmosphere. Maintaining excessive Te was essential for obtaining the stable stoichiometric 2H-MoTe2 phase. Further annealing under a lower partial pressure of Te at the same temperature, followed by a rapid quenching, led to the reverse phase transition from 2H-MoTe2 to 1T'-MoTe2. The orientation of the 2H-MoTe2 film was determined by the tellurization rate. Slow tellurization was the key for obtaining a highly oriented 2H-MoTe2 film over the entire area, while fast tellurization led to a 2H-MoTe2 film with a randomly oriented c-axis.