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  • 1
    Online Resource
    Online Resource
    Frontiers Media SA ; 2021
    In:  Frontiers in Plant Science Vol. 12 ( 2021-7-30)
    In: Frontiers in Plant Science, Frontiers Media SA, Vol. 12 ( 2021-7-30)
    Abstract: Plant phytochromes are known as autophosphorylating serine/threonine protein kinases. However, the functional importance of their kinase activity is not fully elucidated. Previously, the kinase activity is shown to be necessary for the function of Avena sativa phytochrome A (AsphyA) using transgenic plants with mutants displaying reduced kinase activity, such as K411L and T418D. In this study, we isolated and analyzed two AsphyA mutants, K411R and T418V, that showed increased kinase activity. Transgenic phyA-201 plants with these mutants showed hypersensitive responses to far-red (FR) light, such as shorter hypocotyls and more expanded cotyledons than those of control plant (i.e., transgenic phyA-201 plant with wild-type AsphyA). Contrary to the mutants with reduced kinase activity, these mutants accelerated FR-induced phosphorylation and subsequent degradation of phytochrome-interacting factor 3 (PIF3) in Arabidopsis. Moreover, elongated hypocotyl 5 (HY5), a critical positive regulator of photoresponses in plants, accumulated in higher amounts in the transgenic plants under FR light than in the control plant. In addition, PIF1 degradation was accelerated in the transgenic plants. Consequently, the transgenic plants exhibit higher germination frequencies than the control plant. Collectively, our results demonstrate that the AsphyA mutants with increased kinase activity are hyperactive in plants, supporting a positive relationship between the kinase activity of phytochromes and photoresponses in plants.
    Type of Medium: Online Resource
    ISSN: 1664-462X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2687947-5
    detail.hit.zdb_id: 2613694-6
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  • 2
    Online Resource
    Online Resource
    Frontiers Media SA ; 2021
    In:  Frontiers in Plant Science Vol. 12 ( 2021-9-28)
    In: Frontiers in Plant Science, Frontiers Media SA, Vol. 12 ( 2021-9-28)
    Abstract: Phytochromes are red and far-red photoreceptors that regulate plant growth and development under ambient light conditions. During phytochrome-mediated photomorphogenesis, phytochrome-interacting factors (PIFs) are the most important signaling partners that regulate the expression of light-responsive genes. However, the function of PIFs in monocots has not been studied well. In this study, using RNA interference (RNAi), we investigated the functions of BdPIL1 and BdPIL3 , two PIF-like genes identified in Brachypodium distachyon , which are closely related to Arabidopsis PIF1 and PIF3 . The expression of their genes is light-inducible, and both BdPIL1 and BdPIL3 proteins interact with phytochromes in an active form-specific manner. Transgenic Brachypodium seedlings with the RNAi constructs of BdPIL1 and BdPIL3 showed decreased coleoptile lengths and increased leaf growth when exposed to both red and far-red light. In addition, the transgenic plants were taller with elongated internodes than wild-type Bd21-3 plant, exhibiting late flowering. Moreover, RNA-seq analysis revealed downregulation of many genes in the transgenic plants, especially those related to the regulation of cell number, floral induction, and chlorophyll biosynthesis, which were consistent with the phenotypes of increased plant height, delayed flowering, and pale green leaves. Furthermore, we demonstrated the DNA-binding ability of BdPIL1 and BdPIL3 to the putative target promoters and that the DNA-binding was inhibited in the presence of phytochromes. Therefore, this study determines a molecular mechanism underlying phytochrome-mediated PIF regulation in Brachypodium, i.e., sequestration, and also elucidates the functions of BdPIL1 and BdPIL3 in the growth and development of the monocot plant.
    Type of Medium: Online Resource
    ISSN: 1664-462X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2687947-5
    detail.hit.zdb_id: 2613694-6
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  • 3
    Online Resource
    Online Resource
    Frontiers Media SA ; 2023
    In:  Frontiers in Endocrinology Vol. 14 ( 2023-2-13)
    In: Frontiers in Endocrinology, Frontiers Media SA, Vol. 14 ( 2023-2-13)
    Abstract: Adequate iodine intake is essential for growing children, as both deficient and excessive iodine status can result in thyroid dysfunction. We investigated the iodine status and its association with thyroid function in 6-year-old children from South Korea. Methods A total of 439 children aged 6 (231 boys and 208 girls) were investigated from the Environment and Development of Children cohort study. The thyroid function test included free thyroxine (FT4), total triiodothyronine (T3), and thyroid-stimulating hormone (TSH). Urine iodine status was evaluated using urine iodine concentration (UIC) in morning spot urine and categorized into iodine deficient ( & lt; 100 μg/L), adequate (100–199 μg/L), more than adequate (200–299 μg/L), mild excessive (300–999 μg/L), and severe excessive (≥ 1000 μg/L) groups. The estimated 24-hour urinary iodine excretion (24h-UIE) was also calculated. Results The median TSH level was 2.3 μIU/mL, with subclinical hypothyroidism detected in 4.3% of patients without sex differences. The median UIC was 606.2 μg/L, with higher levels in boys (684 μg/L vs. 545 μg/L, p = 0.021) than girls. Iodine status was categorized as deficient (n = 19, 4.3%), adequate (n = 42, 9.6%), more than adequate (n = 54, 12.3%), mild excessive (n = 170, 38.7%), or severe excessive (n = 154, 35.1%). After adjusting for age, sex, birth weight, gestational age, body mass index z-score, and family history, both the mild and severe excess groups showed lower FT4 (β = − 0.04, p = 0.032 for mild excess; β = − 0.04, p = 0.042 for severe excess) and T3 levels (β = − 8.12, p = 0.009 for mild excess; β = − 9.08, p = 0.004 for severe excess) compared to the adequate group. Log-transformed estimated 24h-UIE showed a positive association with log-transformed TSH levels (β = 0.04, p = 0.046). Conclusion Excess iodine was prevalent (73.8%) in 6-year-old Korean children. Excess iodine was associated with a decrease in FT4 or T3 levels and an increase in TSH levels. The longitudinal effects of iodine excess on later thyroid function and health outcomes require further investigation.
    Type of Medium: Online Resource
    ISSN: 1664-2392
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2592084-4
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  • 4
    Online Resource
    Online Resource
    Frontiers Media SA ; 2022
    In:  Frontiers in Endocrinology Vol. 13 ( 2022-10-20)
    In: Frontiers in Endocrinology, Frontiers Media SA, Vol. 13 ( 2022-10-20)
    Abstract: Considering the roles of 25-hydroxyvitamin D (25OHD) in glucose homeostasis and immune modulation, vitamin D deficiency may be related to the development of type 1 diabetes (T1DM) and diabetic ketoacidosis (DKA). We evaluated the total, free, bioavailable 25OHD levels and vitamin D binding protein (VDBP) levels and genotypes between T1DM patients and controls. Methods This retrospective, cross-sectional study included 84 children with T1DM (38 boys and 46 girls, 8.0 ± 3.6 years) and 1:1 age- and sex-matched healthy controls. A multiplex liquid chromatography-tandem mass spectrometry-based assay was used to simultaneously measure vitamin D metabolites. Results Patients with T1DM had lower levels of total 25OHD (16.3 ± 5.1 vs. 19.9 ± 6.5 ng/mL, P & lt; 0.001) and VDBP (146.0 ± 27.8 vs. 224.9 ± 36.1 µg/mL, P = 0.001), but higher free 25OHD (8.0 ± 2.5 vs. 6.5 ± 2.3 pg/mL, P & lt; 0.001) than controls. Patients who presented with DKA had lower levels of 25OHD in the total (15.0 ± 4.6 vs. 17.6 ± 5.2 ng/mL, P = 0.020), free (7.5 ± 2.6 vs. 8.4 ± 2.4 pg/mL, P = 0.059), and bioavailable (2.3 ± 0.9 vs. 2.8 ± 0.8 ng/mL, P = 0.014) forms than those without DKA at the T1DM diagnosis. The lower the total, free, and bioavailable 25OHD levels at diagnosis, the lower the pH and HCO3-. The proportions of the VDBP genotypes did not differ between the patients and controls. Conclusion Patients with T1DM had higher levels of free 25OHD than healthy children, despite lower levels of total 25OHD. However, patients with DKA exhibited lower levels of bioavailable 25OHD than those without DKA at the T1DM diagnosis. The lower the concentrations of free and bioavailable 25OHD, the more severe the acidosis at the initial T1DM presentation.
    Type of Medium: Online Resource
    ISSN: 1664-2392
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2592084-4
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  • 5
    Online Resource
    Online Resource
    Frontiers Media SA ; 2022
    In:  Frontiers in Endocrinology Vol. 13 ( 2022-7-29)
    In: Frontiers in Endocrinology, Frontiers Media SA, Vol. 13 ( 2022-7-29)
    Abstract: Autosomal recessive hypophosphatemic rickets type 2 (ARHR2) is a rare form of hereditary rickets, which is characterized by defective bone mineralization and renal phosphate wasting due to a loss-of-function variant in the ectonucleotide pyrophosphatase/phosphodiesterase 1 ( ENPP1 ) gene. Although pathogenic variant of ENPP1 has been known to manifest other phenotypes including arterial calcification, hearing loss, ossification of posterior longitudinal ligament, or pseudoxanthoma elasticum, there have been few reports including systematic examination in individuals diagnosed with ARHR2 to date. Herein, we report a case of ARHR2 with a bi-allelic pathogenic variant of ENPP1 , in which the patient presented with gait abnormalities with severe genu varum at 26 months of age. Targeted gene panel sequencing was performed to investigate the genetic cause of rickets, and a homozygous nonsense variant in ENPP1 , c.783C & gt;G (p.Tyr261*), was identified. The patient was treated with oral phosphate and active vitamin D supplements and underwent corrective osteotomy for varus deformity. His phenotype was limited to rickets. A periodic systematic evaluation is needed to identify any comorbidities in ARHR2 patients since ENPP1 variants may present phenotypes other than rickets and symptoms may evolve or change over time.
    Type of Medium: Online Resource
    ISSN: 1664-2392
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2592084-4
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  • 6
    Online Resource
    Online Resource
    Frontiers Media SA ; 2022
    In:  Frontiers in Immunology Vol. 13 ( 2022-11-15)
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 13 ( 2022-11-15)
    Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing coronavirus disease 2019 (COVID-19) has been a global health concern since 2019. The viral spike protein infects the host by binding to angiotensin-converting enzyme 2 (ACE2) expressed on the cell surface, which is then processed by type II transmembrane serine protease. However, ACE2 does not react to SARS-CoV-2 in inbred wild-type mice, which poses a challenge for preclinical research with animal models, necessitating a human ACE2 (hACE2)-expressing transgenic mouse model. Cytokeratin 18 ( K18 ) promoter-derived hACE2 transgenic mice [B6.Cg-Tg(K18-ACE2)2Prlmn/J] are widely used for research on SARS-CoV-1, MERS-CoV, and SARS-CoV-2. However, SARS-CoV-2 infection is lethal at ≥10 5 PFU and SARS-CoV-2 target cells are limited to type-1 alveolar pneumocytes in K18-hACE2 mice, making this model incompatible with infections in the human lung. Hence, we developed lung-specific SARS-CoV-2 infection mouse models with surfactant protein B ( SFTPB ) and secretoglobin family 1a member 1 ( Scgb1a1 ) promoters. After inoculation of 10 5 PFU of SARS-CoV-2 to the K18-hACE2, SFTPB-hACE2, and SCGB1A1-hACE2 models, the peak viral titer was detected at 2 days post-infection and then gradually decreased. In K18-hACE2 mice, the body temperature decreased by approximately 10°C, body weight decreased by over 20%, and the survival rate was reduced. However, SFTPB-hACE2 and SCGB1A1-hACE2 mice showed minimal clinical signs after infection. The virus targeted type I pneumocytes in K18-hACE2 mice; type II pneumocytes in SFTPB-hACE2 mice; and club, goblet, and ciliated cells in SCGB1A1-hACE2 mice. A time-dependent increase in severe lung lesions was detected in K18-hACE2 mice, whereas mild lesions developed in SFTPB-hACE2 and SCGB1A1-hACE2 mice. Spleen, small intestine, and brain lesions developed in K18-hACE2 mice but not in SFTPB-hACE2 and SCGB1A1-hACE2 mice. These newly developed SFTPB-hACE2 and SCGB1A1-hACE2 mice should prove useful to expand research on hACE2-mediated respiratory viruses.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2606827-8
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  • 7
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 13 ( 2022-12-2)
    Type of Medium: Online Resource
    ISSN: 1664-3224
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2606827-8
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  • 8
    In: Frontiers in Public Health, Frontiers Media SA, Vol. 12 ( 2024-4-11)
    Abstract: Recent evidence has revealed associations between endocrine-disrupting chemicals (EDCs) and placental insufficiency due to altered placental growth, syncytialization, and trophoblast invasion. However, no epidemiologic study has reported associations between exposure to EDCs and asymmetric fetal growth restriction (FGR) caused by placenta insufficiency. The aim of this study was to evaluate the association between EDC exposure and asymmetric FGR. This was a prospective cohort study including women admitted for delivery to the Maternal Fetal Center at Seoul St. Mary’s Hospital between October 2021 and October 2022. Maternal urine and cord blood samples were collected, and the levels of bisphenol-A (BPA), monoethyl phthalates, and perfluorooctanoic acid in each specimen were analyzed. We investigated linear and non-linear associations between the levels of EDCs and fetal growth parameters, including the head circumference (HC)/abdominal circumference (AC) ratio as an asymmetric parameter. The levels of EDCs were compared between fetuses with and without asymmetric FGR. Of the EDCs, only the fetal levels of BPA showed a linear association with the HC/AC ratio after adjusting for confounding variables ( β = 0.003, p & lt; 0.05). When comparing the normal growth and asymmetric FGR groups, the asymmetric FGR group showed significantly higher maternal and fetal BPA levels compared to the normal growth group (maternal urine BPA, 3.99 μg/g creatinine vs. 1.71 μg/g creatinine [ p & lt; 0.05]; cord blood BPA, 1.96 μg/L vs. −0.86 μg/L [ p & lt; 0.05]). In conclusion, fetal exposure levels of BPA show linear associations with asymmetric fetal growth patterns. High maternal and fetal exposure to BPA might be associated with asymmetric FGR.
    Type of Medium: Online Resource
    ISSN: 2296-2565
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2024
    detail.hit.zdb_id: 2711781-9
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  • 9
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 13 ( 2023-8-22)
    Abstract: Upfront autologous stem cell transplantation (ASCT) has been recommended for patients who are newly diagnosed with peripheral T-cell lymphoma (PTCL), and CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone), an anthracycline-based chemotherapy has been the frontline chemotherapy for PTCL. However, it is not clear whether anthracycline-based chemotherapies such as CHOP could be standard induction therapy for PTCL. Methods We conducted a randomized phase II study to compare CHOP with fractionated ifosfamide, carboplatin, etoposide, and dexamethasone (ICED) for patients eligible for ASCT. The primary endpoint was progression-free survival (PFS) and secondary endpoints included objective response rate, overall survival (OS), and safety profiles. Results Patients were randomized into either CHOP (n = 69) or ICED (n = 66), and the characteristics of both arms were not different. PTCL-not otherwise specified (NOS, n = 60) and angioimmunoblastic T-cell lymphoma (AITL, n = 53) were dominant. The objective response rate was not different between CHOP (59.4%) and ICED (56.1%), and the 3-year PFS was not different between CHOP (36.7%) and ICED (33.1%). In AITL patients, CHOP was favored over ICED whereas ICED was associated with more cytopenia and reduced dose intensity. Patients who received upfront ASCT after achieving complete response to CHOP or ICED showed 80% of 3-year OS. Discussion In summary, our study showed no therapeutic difference between CHOP and ICED in terms of response and PFS. Thus, CHOP might remain the reference regimen especially for AITL based on its better outcome in AITL, and upfront ASCT could be recommended as a consolidation of complete response in patients with PTCL.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2649216-7
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  • 10
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 13 ( 2023-2-28)
    Abstract: Although transarterial radioembolization (TARE) using yttrium-90 ( 90 Y) is a treatment option for large hepatocellular carcinoma (HCC), a fraction of patients are ineligible for TARE due to high lung shunt fraction (LSF). Methods We evaluated if treatment with transarterial chemoembolization (TACE), owing to TARE ineligibility was associated with early HCC progression. Consecutive patients with HCC who were initially TARE candidates were included. Patients with vascular invasion or metastasis were excluded. Primary endpoints were time-to-progression (TTP) and overall survival (OS). The secondary endpoint was objective response rate. Results In total, 175 patients were included: 144 underwent TARE (TARE-eligible group) and 31 underwent TACE due to high LSF (TARE-ineligible group). This latter group had larger tumors (13.8 cm vs . 7.8 cm, P & lt;0.001) and higher MoRAL scores (1,385.8 vs . 413.3, P =0.002) than the TARE-eligible group. After balancing baseline characteristics with an inverse probability of treatment weighting (IPTW), the TARE-ineligible group showed shorter TTP [adjusted hazard ratio (aHR)=2.16, 95% confidence interval (CI)=1.14–4.07, P =0.02] and OS (aHR=1.80, 95% CI=0.85–3.80, P =0.12), although the latter was not statistically significant. The TARE-ineligible group had a significantly lower objective response rate than the TARE-eligible group (9.7% vs . 56.9%, P & lt;0.001). Conclusion TARE-ineligible patients had larger tumors and higher MoRAL scores than TARE-eligible patients. Treatment with TACE, owing to high LSF, was associated with a shorter TTP even after balancing tumor size and MoRAL scores.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2649216-7
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