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1.
Plant Cell ; 35(6): 1868-1887, 2023 05 29.
Article in English | MEDLINE | ID: mdl-36945744

ABSTRACT

Small RNAs (sRNAs) associate with ARGONAUTE (AGO) proteins forming effector complexes with key roles in gene regulation and defense responses against molecular parasites. In multicellular eukaryotes, extensive duplication and diversification of RNA interference (RNAi) components have resulted in intricate pathways for epigenetic control of gene expression. The unicellular alga Chlamydomonas reinhardtii also has a complex RNAi machinery, including 3 AGOs and 3 DICER-like proteins. However, little is known about the biogenesis and function of most endogenous sRNAs. We demonstrate here that Chlamydomonas contains uncommonly long (>26 nt) sRNAs that associate preferentially with AGO1. Somewhat reminiscent of animal PIWI-interacting RNAs, these >26 nt sRNAs are derived from moderately repetitive genomic clusters and their biogenesis is DICER-independent. Interestingly, the sequences generating these >26-nt sRNAs have been conserved and amplified in several Chlamydomonas species. Moreover, expression of these longer sRNAs increases substantially under nitrogen or sulfur deprivation, concurrently with the downregulation of predicted target transcripts. We hypothesize that the transposon-like sequences from which >26-nt sRNAs are produced might have been ancestrally targeted for silencing by the RNAi machinery but, during evolution, certain sRNAs might have fortuitously acquired endogenous target genes and become integrated into gene regulatory networks.


Subject(s)
Chlamydomonas reinhardtii , Chlamydomonas , Animals , Chlamydomonas/genetics , Chlamydomonas/metabolism , RNA Interference , Gene Expression Regulation , Argonaute Proteins/genetics , Argonaute Proteins/metabolism , Chlamydomonas reinhardtii/genetics , Chlamydomonas reinhardtii/metabolism
2.
Physiol Plant ; 176(3): e14339, 2024.
Article in English | MEDLINE | ID: mdl-38736185

ABSTRACT

Caulerpa is a marine green macroalga distinguished by a large single cell with multiple nuclei. It also exhibits remarkable morphological intraspecies variations, in response to diverse environmental types. However, the molecular mechanisms underlying this phenotypic plasticity remain poorly understood. In this work, we compare the transcriptomes of Caulerpa okamurae Weber Bosse, 1897 displaying altered phenotypes of cultivation and natural phenotypes and investigate significantly regulated genes and their biological functions using differential expression analyses. We observe light-harvesting complex upregulation and cellular framework stability downregulation in altered phenotypes compared to the natural phenotypes. Intertidal macrophytes reduce light capture to avoid photodamage and regulate their morphology to protect against wave damage. In contrast, the lower light conditions and the cultivation environment augment light capture and increase a morphology prioritizing light trapping. Moreover, the addition of simulated wave-sweeping stimuli induces a return to the natural morphology under high-light conditions, showing how mechanical stress affects morphological organization in C. okamurae. We provide detailed gene expression patterns in C. okamurae under varying light intensities and water conditions, suggesting a distinct influence on its morphological traits.


Subject(s)
Caulerpa , Phenotype , Transcriptome , Transcriptome/genetics , Caulerpa/genetics , Caulerpa/physiology , Light , Gene Expression Regulation, Plant , Gene Expression Profiling
3.
Ecotoxicol Environ Saf ; 269: 115820, 2024 Jan 01.
Article in English | MEDLINE | ID: mdl-38103469

ABSTRACT

Perfluorooctanesulfonate (PFOS) is a ubiquitous environmental pollutant associated with increasing health concerns and environmental hazards. Toxicological analyses of PFOS exposure are hampered by large interspecies variations and limited studies on the mechanistic details of PFOS-induced toxicity. We investigated the effects of PFOS exposure on Xenopus laevis embryos based on the reported developmental effects in zebrafish. X. laevis was selected to further our understanding of interspecies variation in response to PFOS, and we built upon previous studies by including transcriptomics and an assessment of ciliogenic effects. Midblastula-stage X. laevis embryos were exposed to PFOS using the frog embryo teratogenesis assay Xenopus (FETAX). Results showed teratogenic effects of PFOS in a time- and dose-dependent manner. The morphological abnormalities of skeleton deformities, a small head, and a miscoiled gut were associated with changes in gene expression evidenced by whole-mount in situ hybridization and transcriptomics. The transcriptomic profile of PFOS-exposed embryos indicated the perturbation in the expression of genes associated with cell death, and downregulation in adenosine triphosphate (ATP) biosynthesis. Moreover, we observed the effects of PFOS exposure on cilia development as a reduction in the number of multiciliated cells and changes in the directionality and velocity of the cilia-driven flow. Collectively, these data broaden the molecular understanding of PFOS-induced developmental effects, whereby ciliary dysfunction and disrupted ATP synthesis are implicated as the probable modes of action of embryotoxicity. Furthermore, our findings present a new challenge to understand the links between PFOS-induced developmental toxicity and vital biological processes.


Subject(s)
Alkanesulfonic Acids , Fluorocarbons , Gene Expression Profiling , Zebrafish , Animals , Xenopus laevis/genetics , Adenosine Triphosphate , Embryo, Nonmammalian , Teratogens/toxicity
4.
BMC Med Inform Decis Mak ; 24(1): 81, 2024 Mar 20.
Article in English | MEDLINE | ID: mdl-38509511

ABSTRACT

BACKGROUND: Effective communication and information delivery enhance doctor-patient relationships, improves adherence to treatment, reduces work burden, and supports decision-making. The study developed a head and neck cancer (HNC) communication platform to support effective delivery of information about HNC treatment and improve the doctor-patient relationship. METHODS: This study was structured in three main phases: 1) The requirement elicitation phase sought an understanding of the HNC treatment journey and service failure points (FPs) obtained through patient/medical staff interviews and observations, along with a review of the electronic health record system; 2) The development phase involved core needs analysis, solutions development through a co-creation workshop, and validation of the solutions through focus groups; and 3) the proposed HNC communication platform was integrated with the current treatment system, and the flow and mechanism of the interacting services were structured using a service blueprint (SB). RESULTS: Twenty-two service FPs identified through interviews and observations were consolidated into four core needs, and solutions were proposed to address each need: an HNC treatment journey map, cancer survivor stories, operation consent redesign with surgical illustrations, and a non-verbal communication toolkit. The communication platform was designed through the SB in terms of the stage at which the solution was applied and the actions and interactions of the service providers. CONCLUSIONS: The developed platform has practical significance, reflecting a tangible service improvement for both patients and medical staff, making it applicable in hospital settings.


Subject(s)
Head and Neck Neoplasms , Physician-Patient Relations , Humans , Head and Neck Neoplasms/therapy , Communication , Focus Groups , Patients
5.
Proc Natl Acad Sci U S A ; 117(1): 761-770, 2020 01 07.
Article in English | MEDLINE | ID: mdl-31871206

ABSTRACT

Small RNAs (sRNAs) associate with Argonaute (AGO) proteins in effector complexes, termed RNA-induced silencing complexes (RISCs), which regulate complementary transcripts by translation inhibition and/or RNA degradation. In the unicellular alga Chlamydomonas, several metazoans, and land plants, emerging evidence indicates that polyribosome-associated transcripts can be translationally repressed by RISCs without substantial messenger RNA (mRNA) destabilization. However, the mechanism of translation inhibition in a polyribosomal context is not understood. Here we show that Chlamydomonas VIG1, an ortholog of the Drosophila melanogaster Vasa intronic gene (VIG), is required for this process. VIG1 localizes predominantly in the cytosol and comigrates with monoribosomes and polyribosomes by sucrose density gradient sedimentation. A VIG1-deleted mutant shows hypersensitivity to the translation elongation inhibitor cycloheximide, suggesting that VIG1 may have a nonessential role in ribosome function/structure. Additionally, FLAG-tagged VIG1 copurifies with AGO3 and Dicer-like 3 (DCL3), consistent with it also being a component of the RISC. Indeed, VIG1 is necessary for the repression of sRNA-targeted transcripts at the translational level but is dispensable for cleavage-mediated RNA interference and for the association of the AGO3 effector with polyribosomes or target transcripts. Our results suggest that VIG1 is an ancillary ribosomal component and plays a role in sRNA-mediated translation repression of polyribosomal transcripts.


Subject(s)
Chlamydomonas reinhardtii/physiology , Plant Proteins/metabolism , Protein Biosynthesis/physiology , RNA, Small Interfering/metabolism , RNA-Induced Silencing Complex/metabolism , Argonaute Proteins/metabolism , Cycloheximide/pharmacology , Cytosol/metabolism , Gene Expression Regulation, Plant , Introns/genetics , Mutation , Plant Proteins/genetics , Plants, Genetically Modified , Polyribosomes/genetics , Polyribosomes/metabolism , Protein Biosynthesis/drug effects , Ribosomes/drug effects , Ribosomes/metabolism
6.
Gerodontology ; 2023 Nov 05.
Article in English | MEDLINE | ID: mdl-37927103

ABSTRACT

OBJECTIVE: To assess the association between the usage of interdental cleaning and periodontal status among older people in Korea. BACKGROUND: In order to maintain oral health in older people, it is very important to use interdental cleaning devices. However, there is a lack of research on periodontal status and interdental cleaning device use in older people. METHODS: This study used data collected from the 7th National Health Nutrition Survey (KNHANES VII: 2016-2018). A total of 3426 older people adults aged 65 years or older were selected from 16 489 participants. Data on sociodemographic status (sex, age, level of education, income, residential area), personal health practice (subjective health status, smoking, physical activity, hypertension, and diabetes mellitus), oral health practice (subjective oral health status, tooth brushing frequency, dental visits, and chewing problem), the number of teeth and periodontitis were collected. Periodontitis was defined as having a World Health Organisation community periodontal index (CPI) code greater than or equal to three, and severe periodontitis was defined as a CPI code 4. Participants having a CPI code of 3 or 4 were considered to have periodontal disease in this study. Logistic regression analysis investigated the association between interdental cleaning devices usage and periodontitis controlling the confounding factors. RESULTS: Those who do not use dental floss had a higher rate of periodontal disease (AOR = 1.47, 95% confidence interval [CI]: 1.05 to 2.1). However, there were no significant differences by interdental brush use. In those with 20 or more teeth, non-users of dental floss had a higher risk of periodontitis in all models. Conversely, in those with fewer than 20 teeth, no significant differences were observed. CONCLUSIONS: Older people with mostly intact dentitions have better periodontal health if they clean between their teeth.

7.
Gerodontology ; 2023 Nov 15.
Article in English | MEDLINE | ID: mdl-37965782

ABSTRACT

OBJECTIVE: To describe the oral health of older people by region and family status using data from the National Health and Nutrition Survey. BACKGROUND: As the ageing of Korean society intensifies, health inequalities based on region and family status are also deepening. METHODS: Data from the 8th National Health and Nutrition Survey (2020-2021) conducted by the Korea Centers for Disease Control and Prevention were used, and a total of 3437 older people aged 65 or older were selected as study participants. Chewing discomfort and oral health behaviours were assessed by region and family status using multivariable logistic regression analysis with the complex sample survey design. RESULTS: We found an association between living alone and greater chewing discomfort. Residing in rural areas was also associated with a higher prevalence of this. In urban areas, chewing discomfort was 1.27 times higher among older people living alone than in those not living alone, while in rural areas, the discomfort was 1.52 times higher among the older people who lived alone. CONCLUSIONS: Region and family status were associated with greater chewing discomfort in older people. In Korean society, where the number of single-person older people households is increasing, along with the ageing population, attention to resolving the disparities in oral health in older people is needed.

8.
J Hepatol ; 76(4): 850-861, 2022 04.
Article in English | MEDLINE | ID: mdl-34958836

ABSTRACT

BACKGROUND & AIMS: Owing to the lack of genetic animal models that adequately recreate key clinical characteristics of cirrhosis, the molecular pathogenesis of cirrhosis has been poorly characterized, and treatments remain limited. Hence, we aimed to better elucidate the pathological mechanisms of cirrhosis using a novel murine model. METHODS: We report on the first murine genetic model mimicking human cirrhosis induced by hepatocyte-specific elimination of microspherule protein 1 (MCRS1), a member of non-specific lethal (NSL) and INO80 chromatin-modifier complexes. Using this genetic tool with other mouse models, cell culture and human samples, combined with quantitative proteomics, single nuclei/cell RNA sequencing and chromatin immunoprecipitation assays, we investigated mechanisms of cirrhosis. RESULTS: MCRS1 loss in mouse hepatocytes modulates the expression of bile acid (BA) transporters - with a pronounced downregulation of Na+-taurocholate cotransporting polypeptide (NTCP) - concentrating BAs in sinusoids and thereby activating hepatic stellate cells (HSCs) via the farnesoid X receptor (FXR), which is predominantly expressed in human and mouse HSCs. Consistently, re-expression of NTCP in mice reduces cirrhosis, and genetic ablation of FXR in HSCs suppresses fibrotic marks in mice and in vitro cell culture. Mechanistically, deletion of a putative SANT domain from MCRS1 evicts histone deacetylase 1 from its histone H3 anchoring sites, increasing histone acetylation of BA transporter genes, modulating their expression and perturbing BA flow. Accordingly, human cirrhosis displays decreased nuclear MCRS1 and NTCP expression. CONCLUSIONS: Our data reveal a previously unrecognized function of MCRS1 as a critical histone acetylation regulator, maintaining gene expression and liver homeostasis. MCRS1 loss induces acetylation of BA transporter genes, perturbation of BA flow, and consequently, FXR activation in HSCs. This axis represents a central and universal signaling event in cirrhosis, which has significant implications for cirrhosis treatment. LAY SUMMARY: By genetic ablation of MCRS1 in mouse hepatocytes, we generate the first genetic mouse model of cirrhosis that recapitulates human features. Herein, we demonstrate that the activation of the bile acid/FXR axis in liver fibroblasts is key in cirrhosis development.


Subject(s)
Histones , RNA-Binding Proteins , Receptors, Cytoplasmic and Nuclear , Acetylation , Animals , Bile Acids and Salts/metabolism , Carrier Proteins , Histones/metabolism , Liver/pathology , Liver Cirrhosis/pathology , Membrane Glycoproteins , Mice , RNA-Binding Proteins/genetics , RNA-Binding Proteins/metabolism , Receptors, Cytoplasmic and Nuclear/genetics , Receptors, Cytoplasmic and Nuclear/metabolism
9.
Small ; 18(40): e2202912, 2022 Oct.
Article in English | MEDLINE | ID: mdl-36058645

ABSTRACT

Development of efficient surface passivation methods for semiconductor devices is crucial to counter the degradation in their electrical performance owing to scattering or trapping of carriers in the channels induced by molecular adsorption from the ambient environment. However, conventional dielectric deposition involves the formation of additional interfacial defects associated with broken covalent bonds, resulting in accidental electrostatic doping or enhanced hysteretic behavior. In this study, centimeter-scaled van der Waals passivation of transition metal dichalcogenides (TMDCs) is demonstrated by stacking hydrocarbon (HC) dielectrics onto MoSe2 field-effect transistors (FETs), thereby enhancing the electric performance and stability of the device, accompanied with the suppression of chemical disorder at the HC/TMDCs interface. The stacking of HC onto MoSe2 FETs enhances the carrier mobility of MoSe2 FET by over 50% at the n-branch, and a significant decrease in hysteresis, owing to the screening of molecular adsorption. The electron mobility and hysteresis of the HC/MoSe2 FETs are verified to be nearly intact compared to those of the fabricated HC/MoSe2 FETs after exposure to ambient environment for 3 months. Consequently, the proposed design can act as a model for developing advanced nanoelectronics applications based on layered materials for mass production.

10.
Eur J Dent Educ ; 26(2): 223-231, 2022 May.
Article in English | MEDLINE | ID: mdl-33977601

ABSTRACT

INTRODUCTION: This study introduces the curriculum of a discussion-based learning class for dental hygiene ethics education and evaluates the educational effect of discussion-based learning as applied to a dental hygiene ethics class. MATERIALS AND METHODS: This study was conducted with 48 sophomores from the Department of Dental Hygiene who took dental hygiene ethics in the second semester of 2019. For the DBL class, the following steps were conducted: (1) a pre-class group activity (discussion); (2) a group presentation and team discussion; and (3) a discussion among all groups. To improve the ability to aggregate, organise, and prepare the learner's resources, data, information search skills, and opinions by the team and to improve communication skills by actively listening to other people's opinions, the presentation team's opinions were modified after the discussion, and the performance of rational opinions on topics was added. The professor provided feedback and summarised and ended the discussion. The survey was conducted before and after the DBL class. RESULTS: Concerning critical thinking ability, critical objectivity increased significantly from 8.88 before to 9.38 after the DBL class, and critical confidence also increased significantly. The change in professional attitude significantly increased from 3.21 out of 5 points before the DBL class to 3.53 after the DBL class in the logical and critical thinking skills category and significantly increased from 3.27 to 3.66 in decision-making skills. CONCLUSION: Teaching methods applied in DBL classes, not traditional lecture-style classes, consistent with changing educational paradigms, are very effective and should change gradually. These results will be particularly helpful to faculty members who are inexperienced in DBL courses and performance but interested in them.


Subject(s)
Dental Hygienists , Oral Hygiene , Curriculum , Dental Hygienists/education , Education, Dental , Humans , Learning , Teaching
11.
Ann Neurol ; 88(3): 526-543, 2020 09.
Article in English | MEDLINE | ID: mdl-32562430

ABSTRACT

OBJECTIVE: Genetic variants of the cytoplasmic FMR1-interacting protein 2 (CYFIP2) encoding an actin-regulatory protein are associated with brain disorders, including intellectual disability and epilepsy. However, specific in vivo neuronal defects and potential treatments for CYFIP2-associated brain disorders remain largely unknown. Here, we characterized Cyfip2 heterozygous (Cyfip2+/- ) mice to understand their neurobehavioral phenotypes and the underlying pathological mechanisms. Furthermore, we examined a potential treatment for such phenotypes of the Cyfip2+/- mice and specified a neuronal function mediating its efficacy. METHODS: We performed behavioral analyses of Cyfip2+/- mice. We combined molecular, ultrastructural, and in vitro and in vivo electrophysiological analyses of Cyfip2+/- prefrontal neurons. We also selectively reduced CYFIP2 in the prefrontal cortex (PFC) of mice with virus injections. RESULTS: Adult Cyfip2+/- mice exhibited lithium-responsive abnormal behaviors. We found increased filamentous actin, enlarged dendritic spines, and enhanced excitatory synaptic transmission and excitability in the adult Cyfip2+/- PFC that was restricted to layer 5 (L5) neurons. Consistently, adult Cyfip2+/- mice showed increased seizure susceptibility and auditory steady-state responses from the cortical electroencephalographic recordings. Among the identified prefrontal defects, lithium selectively normalized the hyperexcitability of Cyfip2+/- L5 neurons. RNA sequencing revealed reduced expression of potassium channel genes in the adult Cyfip2+/- PFC. Virus-mediated reduction of CYFIP2 in the PFC was sufficient to induce L5 hyperexcitability and lithium-responsive abnormal behavior. INTERPRETATION: These results suggest that L5-specific prefrontal dysfunction, especially hyperexcitability, underlies both the pathophysiology and the lithium-mediated amelioration of neurobehavioral phenotypes in adult Cyfip2+/- mice, which can be implicated in CYFIP2-associated brain disorders. ANN NEUROL 2020;88:526-543.


Subject(s)
Adaptor Proteins, Signal Transducing/genetics , Lithium Compounds/pharmacology , Prefrontal Cortex/drug effects , Prefrontal Cortex/physiopathology , Seizures/genetics , Animals , Behavior, Animal/drug effects , Haploinsufficiency , Mice , Mice, Mutant Strains , Neurons/drug effects , Neurons/pathology , Prefrontal Cortex/pathology , Seizures/physiopathology
12.
Hepatology ; 70(1): 358-371, 2019 07.
Article in English | MEDLINE | ID: mdl-30810242

ABSTRACT

Liver-resident memory T (liver TRM ) cells exert protective immune responses following liver infection by malaria parasites. However, how these TRM cells are developed and what the consequence is if they are not properly maintained remain poorly understood. Here, we show that the transcriptional repressor, Capicua (CIC), controls liver CD8+ TRM cell development to maintain normal liver function. Cic-deficient mice have a greater number of liver CD8+ TRM cells and liver injury phenotypes accompanied by increased levels of proinflammatory cytokine genes in liver tissues. Excessive formation of CD69+ CD8+ TRM -like cells was also observed in mice with acetaminophen-induced liver injury (AILI). Moreover, expansion of liver CD8+ TRM cell population and liver injury phenotypes in T-cell-specific Cic null mice were rescued by codeletion of ETS translocation variant [Etv]5 alleles, indicating that Etv5 is a CIC target gene responsible for regulation of CD8+ TRM cell development and liver function. We also discovered that ETV5 directly regulates expression of Hobit, a master transcription factor for TRM cell development, in CD8+ T cells. Conclusion: Our findings suggest the CIC-ETV5 axis as a key molecular module that controls CD8+ TRM cell development, indicating a pathogenic role for CD8+ TRM cells in liver injury.


Subject(s)
CD8-Positive T-Lymphocytes/physiology , Chemical and Drug Induced Liver Injury/immunology , DNA-Binding Proteins/metabolism , Liver/immunology , Repressor Proteins/metabolism , Transcription Factors/metabolism , Acetaminophen , Animals , Female , Immunologic Memory , Male , Mice, Inbred C57BL , Random Allocation
13.
Cancer Cell Int ; 20: 42, 2020.
Article in English | MEDLINE | ID: mdl-32042269

ABSTRACT

BACKGROUND: Although major driver gene mutations have been identified, the complex molecular heterogeneity of colorectal cancer (CRC) remains unclear. Capicua (CIC) functions as a tumor suppressor in various types of cancers; however, its role in CRC progression has not been examined. METHODS: Databases for gene expression profile in CRC patient samples were used to evaluate the association of the levels of CIC and Polyoma enhancer activator 3 (PEA3) group genes (ETS translocation variant 1 (ETV1), ETV4, and ETV5), the best-characterized CIC targets in terms of CIC functions, with clinicopathological features of CRC. CIC and ETV4 protein levels were also examined in CRC patient tissue samples. Gain- and loss-of function experiments in cell lines and mouse xenograft models were performed to investigate regulatory functions of CIC and ETV4 in CRC cell growth and invasion. qRT-PCR and western blot analyses were performed to verify the CIC regulation of ETV4 expression in CRC cells. Rescue experiments were conducted using siRNA against ETV4 and CIC-deficient CRC cell lines. RESULTS: CIC expression was decreased in the tissue samples of CRC patients. Cell invasion, migration, and proliferation were enhanced in CIC-deficient CRC cells and suppressed in CIC-overexpressing cells. Among PEA3 group genes, ETV4 levels were most dramatically upregulated and inversely correlated with the CIC levels in CRC patient samples. Furthermore, derepression of ETV4 was more prominent in CIC-deficient CRC cells, when compared with that observed for ETV1 and ETV5. The enhanced cell proliferative and invasive capabilities in CIC-deficient CRC cells were completely recovered by knockdown of ETV4. CONCLUSION: Collectively, the CIC-ETV4 axis is not only a key module that controls CRC progression but also a novel therapeutic and/or diagnostic target for CRC.

14.
Europace ; 22(8): 1216-1223, 2020 08 01.
Article in English | MEDLINE | ID: mdl-32514579

ABSTRACT

AIMS: Cardiac amyloidosis (CA) is associated with increased mortality due to arrhythmias, heart failure, and electromechanical dissociation. However, the role of an implantable cardioverter-defibrillator (ICD) remains unclear. We conducted case-control study to assess survival in CA patients with and without a primary prevention ICD and compared outcomes to an age, sex, and device implant year-matched non-CA group with primary prevention ICD. METHODS AND RESULTS: There were 91 subjects with CA [mean age= 71.2 ± 10.2, female 22.0%, 49 AL with Mayo Stage 2.9 ± 1.0, 41 transthyretin amyloidosis (ATTR), 1 other] followed by Vanderbilt Amyloidosis centre. Patients with ICD (n = 23) were compared with those without (n = 68) and a non-amyloid group with ICD (n = 46). All subjects with ICD had implantation for primary prevention. Mean left ventricular ejection fraction was 36.2% ± 14.4% in CA with ICD, 41.0% ± 10.6% in CA without ICD, and 33.5% ± 14.4% in non-CA patients. Over 3.5 ± 3.1 years, 6 (26.1%) CA, and 12 (26.1%) non-CA subjects received ICD therapies (P = 0.71). Patients with CA had a significantly higher mortality (43.9% vs. 17.4%, P = 0.002) compared with the non-CA group. Mean time from device implantation to death was 21.8 months in AL and 22.8 months in ATTR patients. There was no significant difference in mortality between CA patients who did and did not receive an ICD (39.0% vs. 46.0%, P = 0.59). CONCLUSIONS: Despite comparable event rates patients with CA had a significantly higher mortality and ICDs were not associated with longer survival. With the emergence of effective therapy for AL amyloidosis, further study of ICD is needed in this group.


Subject(s)
Amyloidosis , Defibrillators, Implantable , Aged , Aged, 80 and over , Amyloidosis/diagnosis , Amyloidosis/therapy , Case-Control Studies , Death, Sudden, Cardiac , Female , Humans , Middle Aged , Risk Factors , Stroke Volume , Treatment Outcome , Ventricular Function, Left
15.
Hepatology ; 67(6): 2287-2301, 2018 06.
Article in English | MEDLINE | ID: mdl-29251790

ABSTRACT

Hepatocellular carcinoma (HCC) is developed by multiple steps accompanying progressive alterations of gene expression, which leads to increased cell proliferation and malignancy. Although environmental factors and intracellular signaling pathways that are critical for HCC progression have been identified, gene expression changes and the related genetic factors contributing to HCC pathogenesis are still insufficiently understood. In this study, we identify a transcriptional repressor, Capicua (CIC), as a suppressor of HCC progression and a potential therapeutic target. Expression of CIC is posttranscriptionally reduced in HCC cells. CIC levels are correlated with survival rates in patients with HCC. CIC overexpression suppresses HCC cell proliferation and invasion, whereas loss of CIC exerts opposite effects in vivo as well as in vitro. Levels of polyoma enhancer activator 3 (PEA3) group genes, the best-known CIC target genes, are correlated with lethality in patients with HCC. Among the PEA3 group genes, ETS translocation variant 4 (ETV4) is the most significantly up-regulated in CIC-deficient HCC cells, consequently promoting HCC progression. Furthermore, it induces expression of matrix metalloproteinase 1 (MMP1), the MMP gene highly relevant to HCC progression, in HCC cells; and knockdown of MMP1 completely blocks the CIC deficiency-induced HCC cell proliferation and invasion. CONCLUSION: Our study demonstrates that the CIC-ETV4-MMP1 axis is a regulatory module controlling HCC progression. (Hepatology 2018;67:2287-2301).


Subject(s)
Adenovirus E1A Proteins/physiology , Carcinoma, Hepatocellular/etiology , Liver Neoplasms/etiology , Matrix Metalloproteinase 1/physiology , Proto-Oncogene Proteins/physiology , Repressor Proteins/physiology , Animals , Disease Progression , Humans , Mice , Proto-Oncogene Proteins c-ets
16.
Proc Natl Acad Sci U S A ; 113(38): 10720-5, 2016 09 20.
Article in English | MEDLINE | ID: mdl-27582463

ABSTRACT

Canonical microRNAs (miRNAs) are embedded in duplexed stem-loops in long precursor transcripts and are excised by sequential cleavage by DICER nuclease(s). In this miRNA biogenesis pathway, dsRNA-binding proteins play important roles in animals and plants by assisting DICER. However, these RNA-binding proteins are poorly characterized in unicellular organisms. Here we report that a unique RNA-binding protein, Dull slicer-16 (DUS16), plays an essential role in processing of primary-miRNA (pri-miRNA) transcripts in the unicellular green alga Chlamydomonas reinhardtii In animals and plants, dsRNA-binding proteins involved in miRNA biogenesis harbor two or three dsRNA-binding domains (dsRBDs), whereas DUS16 contains one dsRBD and also an ssRNA-binding domain (RRM). The null mutant of DUS16 showed a drastic reduction in most miRNA species. Production of these miRNAs was complemented by expression of full-length DUS16, but the expression of RRM- or dsRBD-truncated DUS16 did not restore miRNA production. Furthermore, DUS16 is predominantly localized to the nucleus and associated with nascent (unspliced form) pri-miRNAs and the DICER-LIKE 3 protein. These results suggest that DUS16 recognizes pri-miRNA transcripts cotranscriptionally and promotes their processing into mature miRNAs as a component of a microprocessor complex. We propose that DUS16 is an essential factor for miRNA production in Chlamydomonas and, because DUS16 is functionally similar to the dsRNA-binding proteins involved in miRNA biogenesis in animals and land plants, our report provides insight into this mechanism in unicellular eukaryotes.


Subject(s)
Algal Proteins/genetics , Chlamydomonas reinhardtii/genetics , MicroRNAs/genetics , RNA-Binding Proteins/genetics , Arabidopsis Proteins/genetics , DNA, Single-Stranded/genetics , MicroRNAs/biosynthesis , RNA Processing, Post-Transcriptional/genetics , Ribonuclease III/genetics
17.
Article in English | MEDLINE | ID: mdl-30116157

ABSTRACT

BACKGROUND: The purpose of this study was to examine whether allergic rhinitis is associated with periodontal disease in a representative sample of elderly Korean people that was adjusted for socio-demographic factors, oral and general health behaviors, and systemic health status. METHODS: A total of 10,643 subjects who were between 20 and 59 years of age participated in the Korean National Health and Nutrition Examination Survey and underwent cross-sectional examination. Medical history of allergic rhinitis was collected from participants by questionnaire; additionally, periodontal status was assessed using a Community Periodontal Index score of 3 or 4. Multivariate logistic regression analysis was conducted to adjust for socio-demographic variables, oral health status and behaviors, and general health status and behaviors. All analyses were performed using a complex sampling design. RESULTS: Allergic rhinitis and periodontitis showed a significant inverse association. After adjusting for all confounders, a trend of decreasing periodontitis risk was observed as allergic rhinitis increased. The adjusted odds ratio of periodontitis was 0.79 (0.66-0.95) for patients with allergic rhinitis. CONCLUSION: A significant inverse association between allergic rhinitis and periodontal status was demonstrated in this patient population.

18.
Gerodontology ; 35(2): 129-138, 2018 Jun.
Article in English | MEDLINE | ID: mdl-29569737

ABSTRACT

OBJECTIVE: To compare the nutritional factors and oral status of elders living alone and elders living with their families in Korea. BACKGROUND: Numerous studies have found that the presence of fewer remaining teeth is associated with decreased nutrient intake; however, there is no study comparing the nutritional status and oral status of elders living alone with that of elders living with family based on a nationally representative sample. METHODS: A sample of 2904 individuals who participated in the sixth Korean National Health and Nutrition Examination Survey was reviewed (65-84 years of age). Living status was defined according to the participants' self-reported questionnaire, and a nutrient intake questionnaire was designed as an open questionnaire and used during the face-to-face interviews. The number of existing teeth was used to determine oral status. A complex-sample general linear analysis and multivariate logistic regression analysis were used to evaluate the association between the number of teeth and nutrient intake among elders living with family and elders living alone after adjusting for confounders. RESULTS: Elders living alone were significantly older and tended to have the following characteristics: women, lower household income, lower educational level, poor perceived health status, non-smokers, non-drinkers and lack of physical activity. Elders living alone had a poorer perceived oral health status, had not received an oral examination in the past year, had chewing problems and had fewer existing teeth (P < .05). Elders living with family showed better oral health and nutrient intake status. Participants who had many existing teeth had higher nutrient intake than the participants who had fewer existing teeth. CONCLUSIONS: For healthy lives at old age, family support or additional social support for elders living alone should be considered.


Subject(s)
Family Characteristics , Nutritional Status , Oral Health/statistics & numerical data , Aged , Aged, 80 and over , Diet/statistics & numerical data , Female , Health Status , Humans , Male , Nutrition Surveys , Republic of Korea/epidemiology , Socioeconomic Factors , Surveys and Questionnaires
19.
Plant J ; 85(2): 258-68, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26686836

ABSTRACT

MicroRNAs (miRNAs) play important roles in diverse biological processes in eukaryotes, generally through degradation and/or inhibition of the translation of target mRNAs. MicroRNAs are loaded into Argonaute (AGO) proteins to form the RNA-induced silencing complex (RISC) and used as guides to identify complementary transcripts. The distinct functions and features, such as associated small RNA classes and modes of silencing, of individual AGO paralogs have been well documented in multicellular eukaryotes. However, this aspect of miRNA function remains poorly understood in the unicellular green alga Chlamydomonas reinhardtii, which contains three AGO paralogs. In this study, we isolated AGO2 and AGO3 insertional mutants and confirmed that AGO3 is more abundantly expressed than AGO2. MicroRNA-directed target transcript cleavage and translational repression were impaired in the AGO3 mutant background, indicating that AGO3 can mediate both modes of silencing. In contrast, although the AGO2 mutant is not a null, the involvement of AGO2 in miRNA-directed silencing appears to be more limited. Our results strongly suggest that miRNA-mediated post-transcriptional gene silencing relies primarily on AGO3 in Chlamydomonas.


Subject(s)
Argonaute Proteins/genetics , Argonaute Proteins/metabolism , Chlamydomonas/genetics , Gene Expression Regulation/genetics , MicroRNAs/genetics , Mutagenesis/genetics , Mutagenesis/physiology
20.
Am Heart J ; 177: 138-44, 2016 07.
Article in English | MEDLINE | ID: mdl-27297859

ABSTRACT

BACKGROUND: The epidemiology of atrial fibrillation (AF) without comorbidities, known as 'lone AF', is uncertain. Although it has been considered a benign condition, we hypothesized that it confers a worse prognosis compared with a matched sample without AF. METHODS: We described the proportion of AF without comorbidities (clinical, subclinical cardiovascular disease and triggers) among the entire AF sample in Framingham Heart Study (FHS). We compared AF without comorbidities with typical AF, and age-, sex- and cohort-matched individuals without AF, using Cox proportional hazards analysis in relation to combined cardiovascular events (stroke, heart failure, myocardial infarction), and mortality. RESULTS: Of 10,311 FHS participants, 1,961 were diagnosed with incident AF, among which 173 individuals had AF without comorbidities (47% women, mean age 71±12 years). AF without comorbidities had a prevalence of 1.7% of the entire cohort, and an annual incidence of 0.5 per 1000 person-years. During a median follow-up of 9.7 years after initial AF, 137 individuals with AF without comorbidities (79.2%) died and 141 individuals developed cardiovascular events (81.5%). AF without comorbidities had significantly lower mortality (HR 0.67, 95%CI 0.55-0.81, P < .001) and total cardiovascular events (HR 0.66, 95% CI 0.55-0.80, P < .001) compared with typical AF. However, mortality (HR1.43, 95% CI 1.18-1.75, P < .001) and risk of total cardiovascular events (HR 1.73, 95% CI 1.39-2.16, P < .001) were higher than age-, sex-, and cohort-matched individuals without AF. CONCLUSIONS: The risk of cardiovascular outcomes and mortality among individuals with AF without comorbidities is lower than typical AF, but is significantly elevated compared with matched individuals without AF.


Subject(s)
Atrial Fibrillation/epidemiology , Heart Failure/epidemiology , Mortality , Myocardial Infarction/epidemiology , Stroke/epidemiology , Aged , Aged, 80 and over , Comorbidity , Female , Follow-Up Studies , Humans , Incidence , Male , Massachusetts/epidemiology , Middle Aged , Prevalence , Prognosis , Proportional Hazards Models
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