Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 183
Filtrar
1.
Jpn Dent Sci Rev ; 59: 263-272, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37674898

RESUMO

Rheumatoid arthritis (RA) is characterized by chronic inflammatory destruction of joint tissue and is caused by an abnormal autoimmune response triggered by interactions between genetics, environmental factors, and epigenetic and posttranslational modifications. RA has been suggested to be interrelated with periodontitis, a serious form or stage of chronic inflammatory periodontal disease associated with periodontopathic bacterial infections, genetic predisposition, environmental factors, and epigenetic influences. Over the last decade, a number of animal and clinical studies have been conducted to assess whether or not periodontitis and associated periodontopathic bacteria constitute risk factors for RA. The present review introduces recent accumulating evidence to support the associations of periodontitis and periodontopathic bacteria with the risk of RA or the outcome of RA pharmacological treatment with disease-modifying antirheumatic drugs. In addition, the results from intervention studies have suggested an improvement in RA clinical parameters after nonsurgical periodontal treatment. Furthermore, the potential causal mechanisms underlying the link between periodontitis and periodontopathic bacteria and RA are summarized.

2.
Biochem Biophys Res Commun ; 666: 179-185, 2023 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-37199136

RESUMO

Hedgehog (Hh) signaling is involved in multiple biological events including development and cancers. It is processed through primary cilia, which are assembled from the mother centriole in most mammalian cells. Pancreatic ductal adenocarcinoma (PDAC) cells generally lose their primary cilia; thus, the Hh signaling pathway is postulated to be independent of the organelle in PDAC. We previously reported that the mother centriole-specific protein, centrosomal protein 164 (CEP164), is required for centriolar localization of the GLI2 transcription factor in Hh signaling and for suppressing the expression of Hh-target genes. In this study, we demonstrated the physical interaction between CEP164 and GLI2, and delineated their binding modes at the mother centriole. The ectopically expressed GLI2-binding region of CEP164 reduced the centriolar GLI2 localization and enhanced the expression of Hh-target genes in PDAC cells. Furthermore, similar phenotypes were observed in PDAC cells lacking primary cilia. These results suggest that the CEP164-GLI2 association at the mother centriole is responsible for controlling Hh signaling, independent of primary cilia in PDAC cells.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Animais , Proteínas Hedgehog/genética , Proteínas Hedgehog/metabolismo , Proteína Gli2 com Dedos de Zinco/genética , Proteína Gli2 com Dedos de Zinco/metabolismo , Cílios/metabolismo , Transdução de Sinais , Neoplasias Pancreáticas/patologia , Carcinoma Ductal Pancreático/patologia , Fatores de Transcrição Kruppel-Like/metabolismo , Mamíferos/metabolismo , Neoplasias Pancreáticas
3.
Mod Rheumatol ; 33(1): 81-87, 2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-34865087

RESUMO

OBJECTIVES: To assess whether periodontitis severity affects the clinical response to biological disease-modifying antirheumatic drugs (bDMARDs) for 1 year in rheumatoid arthritis (RA) patients. METHODS: Data were collected from 50 RA patients who had received corticosteroids, conventional synthetic DMARDs, or non-steroidal anti-inflammatory drugs before (baseline) and after 1 year of bDMARD therapy in a retrospective study. Rheumatologic conditions were compared between the two periodontitis severity groups according to the periodontal inflamed surface area (PISA) or Centers for Disease Control and Prevention (CDC)/American Academy of Periodontology (AAP) case definitions. RESULTS: Twenty-eight patients with no or mild periodontitis showed significantly greater decreases in changes in Clinical Disease Activity Index (CDAI) and tender and swollen joint count in comparison to 22 patients with moderate and severe periodontitis (p = .02, p = .01, and p = .03). Both bivariate and multivariate analyses revealed a significantly positive association between the baseline CDC/AAP definitions and CDAI changes (p = .005 and p = .0038). However, rheumatologic conditions were comparable between 25 patients each in the low and high PISA groups. CONCLUSIONS: Baseline periodontitis severity according to the CDC/AAP definitions is associated with the clinical response to bDMARDs for 1 year in RA patients.


Assuntos
Antirreumáticos , Artrite Reumatoide , Produtos Biológicos , Periodontite , Estados Unidos , Humanos , Antirreumáticos/uso terapêutico , Seguimentos , Estudos Retrospectivos , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/complicações , Periodontite/tratamento farmacológico , Periodontite/complicações , Produtos Biológicos/uso terapêutico
4.
Mod Rheumatol ; 33(5): 918-927, 2023 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-35962564

RESUMO

OBJECTIVES: The aim is to evaluate the relevance of serum immunoglobulin G (IgG) titres against periodontopathic bacteria to predict the clinical response to 1-year treatment with biological disease-modifying antirheumatic drugs (bDMARDs) in rheumatoid arthritis (RA) patients. METHODS: Data were collected from 50 RA patients who had received conventional synthetic DMARDs, corticosteroids, or non-steroidal anti-inflammatory drugs before (baseline) and after 1-year treatment with bDMARDs in a retrospective cohort study. Changes in rheumatologic conditions were compared between the two groups for low and high baseline IgG titres against Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans according to their median measurements. RESULTS: Twenty-five patients with low anti-P. gingivalis IgG titres showed significantly greater decreases in changes in the Clinical Disease Activity Index and swollen joint count than 25 patients with high anti-P. gingivalis IgG titres (p = .04 for both). Bivariate and multivariate analyses revealed a significantly positive association of baseline anti-P. gingivalis IgG titres with Clinical Disease Activity Index changes (p = .02 and p = .002). However, post-treatment rheumatologic conditions were comparable between 25 patients each in the low and high baseline anti-A. actinomycetemcomitans IgG titre groups. CONCLUSIONS: Baseline serum anti-P. gingivalis IgG titres are predictive of the clinical response to 1-year treatment with bDMARDs in RA patients.


Assuntos
Antirreumáticos , Artrite Reumatoide , Periodontite , Humanos , Porphyromonas gingivalis , Periodontite/tratamento farmacológico , Estudos Retrospectivos , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Imunoglobulina G
5.
AMB Express ; 12(1): 126, 2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-36183035

RESUMO

Carbon catabolite repression (CCR) enables preferential utilization of easily metabolizable carbon sources, implying the presence of mechanisms to ensure discriminatory gene repression depending on the ambient carbon sources. However, the mechanisms for such hierarchical repression are not precisely understood. In this report, we examined how deletion of pkaA and ganB, which encode cAMP signaling factors, and creA, which encodes a well-characterized repressor of CCR, affects CCR of hemicellulase genes in the filamentous fungus Aspergillus nidulans. ß-Xylanase production increased not only in ΔcreA but also in ΔpkaA and ΔganB, with the highest level observed in their double deletants, irrespective of the presence or absence of D-glucose. Expression of the ß-xylanase genes in the presence of D-glucose was de-repressed in all the deletion mutants, with significantly higher tolerance against D-glucose repression in ΔpkaA and ΔganB than in ΔcreA. In the presence of galactomannan and D-glucose, partial de-repression of ß-mannanase production was detected in ΔcreA, but not in ΔpkaA and ΔganB. The double deletion of creA/pkaA and creA/ganB led to earlier production. Release from D-glucose repression of the ß-mannanase genes was partial in the single deletants, while nearly full de-repression was observed in ΔcreAΔpkaA and ΔcreAΔganB. The contribution of PkaA and GanB to CCR by D-xylose of the ß-mannanase genes was very minor compared to that of CreA. Consequently, the present study revealed that cAMP signaling plays a major role in CCR of hemicellulase gene expression in a manner that is clearly independent from CreA.

6.
J Cell Sci ; 135(18)2022 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-36052645

RESUMO

Primary cilia are near-ubiquitously assembled on cells in the human body, and are broadly associated with genetic diseases and cancers. In the early stage of ciliogenesis, the ciliary vesicle (CV) is formed on the mother centriole, which nucleates the primary cilium. However, the regulatory mechanisms underlying CV formation have not yet been fully elucidated. Here, we found that the atypical small GTPase RAB-like 3 (RABL3) is necessary to assemble primary cilia in human cells. RABL3 directly interacts with RAB11 (herein referring to both RAB11A and RAB11B), which is involved in CV formation. RABL3 localizes around the centrosome during early ciliogenesis, reminiscent of RAB11 dynamics. Furthermore, RABL3 positively controls the CV formation like RAB11. These findings suggest that RABL3 plays an important role, in cooperation with RAB11, in CV formation during early ciliogenesis.


Assuntos
Cílios , Proteínas rab de Ligação ao GTP , Centríolos/metabolismo , Centrossomo/metabolismo , Cílios/metabolismo , Vesículas Citoplasmáticas/metabolismo , Humanos , Proteínas rab de Ligação ao GTP/genética , Proteínas rab de Ligação ao GTP/metabolismo
7.
J Magn Reson ; 343: 107280, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35998483

RESUMO

Among magnetic resonance imaging (MRI) techniques, ultra-low field (ULF) MRI has the potential to significantly lower the cost of implementation and maintenance, as well as the size of the scanning system. Due to the small amplitude of the signals produced by ULR-MRI, extremely sensitive magnetic sensors are required. Optically pumped magnetometers (OPMs) have been proposed for use in ULF-MRI as ultra-sensitive magnetic sensors capable of detecting very small signals. However, the cost of a ferromagnetic magnetic shield is often not affordable for many applications. By increasing the Larmor frequency, the influence of low-frequency magnetic noise can be mitigated, allowing OPM to be operated without the use of a magnetic shield chamber. This lowers the cost of the magnetic shield and further raises the signal strength, resulting in benefits such as non-prepolarization. We present a method for implementing the ULF-MRI using low-cost OPMs in this study. The Larmor frequency was adjusted to 300 kHz, and three-dimensional (3D) images of a phantom were acquired with a digital resolution of 3 × 3 × 3 mm3 using a static magnetic field of 7.05 mT without using a magnetic shield room or a prepolarization coil. Additionally, we corrected the frequency response to acquired images to consider the narrow bandwidth, and the SNR of 3D imaging was 18. The experimental results, we believe, establish a new guideline for higher-performance, lower-cost ULF-MRI that does not require expensive magnetic shielding.


Assuntos
Imageamento por Ressonância Magnética , Imageamento por Ressonância Magnética/métodos , Imagens de Fantasmas
8.
Life Sci Alliance ; 5(11)2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35803737

RESUMO

Clustering of supernumerary centrosomes, which potentially leads to cell survival and chromosomal instability, is frequently observed in cancers. However, the molecular mechanisms that control centrosome clustering remain largely unknown. The centrosomal kinesin KIF24 was previously shown to restrain the assembly of primary cilia in mammalian cells. Here, we revealed that KIF24 depletion suppresses multipolar spindle formation by clustering centrosomes in pancreatic ductal adenocarcinoma (PDAC) cells harboring supernumerary centrosomes. KIF24 depletion also induced hyper-proliferation and improved mitotic progression in PDAC cells. In contrast, disruption of primary cilia failed to affect the proliferation and spindle formation in KIF24-depleted cells. These results suggest a novel role for KIF24 in suppressing centrosome clustering independent of primary ciliation in centrosome-amplified PDAC cells.


Assuntos
Carcinoma Ductal Pancreático , Centrossomo/fisiologia , Cinesinas/metabolismo , Neoplasias Pancreáticas , Animais , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/patologia , Sobrevivência Celular/fisiologia , Análise por Conglomerados , Cinesinas/genética , Mamíferos , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Fuso Acromático/genética
9.
J Gen Appl Microbiol ; 68(1): 17-23, 2022 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-35387910

RESUMO

The His-Asp phosphorelay signal transduction from histidine kinase (HK) to the response regulator (RR) is an important mechanism for adaptation to environmental changes. Aspergillus nidulans expresses 15 different HKs, which may be involved in different types of adaptations. As reactive oxygen species (ROS) are a key signal of environmental changes, some HKs might be involved in ROS generation through transcriptional regulation. Previously, we identified 3 HK (NikA, FphA, and HysA) deletion strains that showed increased ROS production during growth. We also showed that the phosphorylation function of HysA is involved in ROS generation. Here, we investigated the role of HysA in ROS production in A. nidulans cells. HysA protein was detected in both the cytosol and mitochondria by biological fractionation of the vegetative cell lysate of A. nidulans. The subcellular localization analysis by expressing the the HysA-GFP fusion protein along with MitoTracker Red staining did not clearly reveal mitochondrial localization of HysA at the conidiophore during asexual development. However, mitochondrial ROS in hysA mutant strains were detected by MitoSOX Red staining, and their excess levels possibly caused morphological changes during asexual development.


Assuntos
Aspergillus nidulans , Aspergillus nidulans/genética , Aspergillus nidulans/metabolismo , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Histidina Quinase/genética , Histidina Quinase/metabolismo , Mitocôndrias/metabolismo , Proteínas Quinases/genética , Proteínas Quinases/metabolismo , Espécies Reativas de Oxigênio/metabolismo
10.
Enzyme Microb Technol ; 145: 109762, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33750542

RESUMO

Filamentous fungi belonging to the Aspergillus genus are one of the most favored microorganisms for industrial enzyme production because they can secrete large amounts of proteins into the culture medium. α-Amylase, an enzyme produced by Aspergillus species, is important for food and industrial applications. The production of α-amylase is induced by starch, mainly obtained from the edible biomass; however, the increasing demand for foods is limiting the application of the latter. Therefore, it is expected that using the non-edible biomass, such as rice straw, could improve the competition for industrial application starch containing resources. The transcription factor AmyR activates the transcription of amylolytic enzyme genes, while the transcription factor XlnR activates the transcription of xylanolytic enzyme genes in response to xylose. In this study, we aimed to construct an artificial AmyR::XlnR transcription factor (AXTF) by replacing the DNA-binding domain (1-159 amino acids) of XlnR with that (1-68 aa) of AmyR, which is capable of inducing amylolytic enzyme production in response to xylan-containing hemicellulosic biomass. The chimeric transcription factor AXTF was constructed and expressed using the gapA promoter in the amyR-deficient mutant strain SA1. When the AXTF strain was cultured in the minimal medium containing xylose as the carbon source, the amyB, amyF, agdB, and agdE transcription levels were 41.1-, 11.3-, 37.9-, and 23.7-fold higher, respectively, than those of the wild-type strain. The α-amylase and α-glucosidase activities in the culture supernatant of the AXTF strain grown with xylose for 48 h were 696.6 and 536.1 U/mL, respectively, while these activities were not detected in the culture supernatant of the wild-type and SA1 strains. When rice straw hydrolysate was used as a carbon source, the α-amylase and α-glucosidase activities were 590.2 and 362.7 U/mL, respectively. Thus, we successfully generated an Aspergillus nidulans strain showing amylolytic enzyme production in response to non-edible xylan-containing hemicellulosic biomass by transforming it with the chimeric transcription factor AXTF. Furthermore, the use of genes encoding engineered transcription factors is advantageous because introducing such genes into an industrial Aspergillus strain has similar simultaneous effects on multiple amylase genes controlled by AmyR.


Assuntos
Amilases , Fatores de Transcrição , Amilases/genética , Biomassa , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Regulação Fúngica da Expressão Gênica , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Xilanos
11.
J Periodontal Res ; 56(4): 702-709, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33641208

RESUMO

OBJECTIVE: The aim of the present study was to evaluate the association between the periodontal and serological parameters and the disease activity of rheumatoid arthritis (RA) and between the anti-agalactosyl immunoglobulin G (IgG) titer and periodontitis severity. The objective was also to assess the effect of supragingival scaling on the serological parameters in patients with RA. BACKGROUND: The periodontal and serological parameters in relation to the autoimmune inflammatory response have been linked to RA disease activity. However, the association of the anti-agalactosyl IgG titer with RA disease activity and periodontitis severity has not been elucidated. METHODS: The periodontal, rheumatologic, and serological data were collected from 127 patients with RA in a retrospective cohort study. Of the 127 patients, 21 had been randomly assigned to receive oral hygiene instruction and supragingival scaling. The anti-agalactosyl IgG titer was determined by an electrochemiluminescence immunoassay. RESULTS: The patients with a moderate to high RA disease activity showed significantly higher levels of probing depth (PD), clinical attachment level, anti-cyclic citrullinated peptide IgG, and anti-agalactosyl IgG titer and greater mean percentages of severe periodontitis than those with a low RA disease activity (p < .05 for all). Both univariate and multivariate analyses revealed a significantly positive correlation between the PD and RA disease activity (p = .009 and p = .001), between the anti-agalactosyl IgG titer and RA disease activity (p = .002 and p < .001), and between the anti-agalactosyl IgG titer and PD (p < .001 for both). Supragingival scaling significantly decreased the anti-agalactosyl IgG titer (p = 0.03). CONCLUSION: The PD and anti-agalactosyl IgG titer are positively interrelated, both of which are correlated positively with RA disease activity and influenced by supragingival scaling in patients with RA.


Assuntos
Artrite Reumatoide , Periodontite , Autoanticorpos , Humanos , Imunoglobulina G , Estudos Retrospectivos
12.
J Magn Reson ; 324: 106910, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33482529

RESUMO

Spin-lock preparation was studied to detect tiny oscillatory magnetic fields such as a neural magnetic field without the blood oxygen level-dependent effect. This approach is a direct measurement and independent of static magnetic field strength. Accordingly, it is anticipated as a feasible functional magnetic resonance imaging (fMRI) in low and ultra-low-field MRI. Several reports have been published on spin-lock preparation but reports on imaging simulation are rare. Research in this area can assist in investigating magnetic resonance signal changes and, accordingly, can help to develop new spin-lock methods. In this study, we propose an imaging simulation method with an analytical solution using the Bloch equation. To demonstrate the feasibility of our proposed method, we compared simulated images with experimental results in which the number of sub-voxels and the amplitude and phase of the target oscillatory magnetic fields varied. In addition, we also applied graphics processing unit parallel computing and investigated the feasibility of avoiding an impracticable calculation time by doing so.


Assuntos
Mapeamento Encefálico/métodos , Imageamento por Ressonância Magnética/métodos , Artefatos , Simulação por Computador , Imagens de Fantasmas
13.
Psychiatry Clin Neurosci ; 75(2): 46-56, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33090632

RESUMO

AIM: Several studies have reported altered age-associated changes in white matter integrity in bipolar disorder (BD). However, little is known as to whether these age-related changes are illness-specific. We assessed disease-specific effects by controlling for age and investigated age-associated changes and Group × Age interactions in white matter integrity among major depressive disorder (MDD) patients, BD patients, and healthy controls. METHODS: Healthy controls (n = 96; age range, 20-77 years), MDD patients (n = 101; age range, 25-78 years), and BD patients (n = 58; age range, 22-76 years) participated in this study. Fractional anisotropy (FA) derived from diffusion tensor imaging in 54 white matter tracts were compared after controlling for the linear and quadratic effect of age using a generalized linear model. Age-related effects and Age × Group interactions were also assessed in the model. RESULTS: The main effect of group was significant in the left column and body of the fornix after controlling for both linear and quadratic effects of age, and in the left body of the corpus callosum after controlling for the quadratic effect of age. BD patients exhibited significantly lower FA relative to other groups. There was no Age × Group interaction in the tracts. CONCLUSION: Significant FA reductions were found in BD patients after controlling for age, indicating that abnormal white matter integrity in BD may occur at a younger age rather than developing progressively with age.


Assuntos
Transtorno Bipolar/patologia , Transtorno Depressivo Maior/patologia , Substância Branca/patologia , Adulto , Fatores Etários , Idoso , Transtorno Bipolar/diagnóstico por imagem , Transtorno Depressivo Maior/diagnóstico por imagem , Imagem de Tensor de Difusão , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Substância Branca/diagnóstico por imagem , Adulto Jovem
14.
Magn Reson Med Sci ; 20(2): 166-174, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32389928

RESUMO

PURPOSE: To analyze subcortical brain volume more reliably, we propose a deep learning segmentation method of subcortical brain based on magnetic resonance imaging (MRI) having high generalization performance, accuracy, and robustness. METHODS: First, local images of three-dimensional (3D) bounding boxes were extracted for seven subcortical structures (thalamus, putamen, caudate, pallidum, hippocampus, amygdala, and accumbens) from a whole brain MR image as inputs to the neural network. Second, dilated convolution layers, which input information of variable scope, were introduced to the blocks that make up the neural network. These blocks were connected in parallel to simultaneously process global and local information obtained by the dilated convolution layers. To evaluate generalization performance, different datasets were used for training and testing sessions (cross-dataset evaluation) because subcortical brain segmentation in clinical analysis is assumed to be applied to unknown datasets. RESULTS: The proposed method showed better generalization performance that can obtain stable accuracy for all structures, whereas the state-of-the-art deep learning method obtained extremely low accuracy for some structures. The proposed method performed segmentation for all samples without failing with significantly higher accuracy (P < 0.005) than conventional methods such as 3D U-Net, FreeSurfer, and Functional Magnetic Resonance Imaging of the Brain's (FMRIB's) Integrated Registration and Segmentation Tool in the FMRIB Software Library (FSL-FIRST). Moreover, when applying this proposed method to larger datasets, segmentation was robustly performed for all samples without producing segmentation results on the areas that were apparently different from anatomically relevant areas. On the other hand, FSL-FIRST produced segmentation results on the area that were apparently and largely different from the anatomically relevant area for about one-third to one-fourth of the datasets. CONCLUSION: The cross-dataset evaluation showed that the proposed method is superior to existing methods in terms of generalization performance, accuracy, and robustness.


Assuntos
Encéfalo/anatomia & histologia , Encéfalo/diagnóstico por imagem , Processamento de Imagem Assistida por Computador/métodos , Processamento de Imagem Assistida por Computador/normas , Imageamento por Ressonância Magnética/métodos , Imageamento por Ressonância Magnética/normas , Reprodutibilidade dos Testes , Aprendizado Profundo , Humanos , Redes Neurais de Computação , Software
15.
Life Sci Alliance ; 4(3)2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33372037

RESUMO

G protein-coupled receptors (GPCRs) are the most common pharmacological target in human clinical practice. To perform their functions, many GPCRs must accumulate inside primary cilia, microtubule-based plasma membrane protrusions working as cellular antennae. Nevertheless, the molecular mechanisms underlying GPCR ciliary targeting remain poorly understood. Serotonin receptor 6 (HTR6) and somatostatin receptor 3 (SSTR3) are two brain-enriched ciliary GPCRs involved in cognition and pathologies such as Alzheimer's disease and cancer. Although the third intracellular loops (IC3) of HTR6 and SSTR3 suffice to target non-ciliary GPCRs to cilia, these IC3s are dispensable for ciliary targeting of HTR6 and SSTR3 themselves, suggesting these GPCRs contain additional ciliary targeting sequences (CTSs). Herein, we discover and characterize novel CTSs in HTR6 and SSTR3 C-terminal tails (CT). These CT-CTSs (CTS2) act redundantly with IC3-CTSs (CTS1), each being sufficient for ciliary targeting. In HTR6, RKQ and LPG motifs are critical for CTS1 and CTS2 function, respectively, whereas in SSTR3 these roles are mostly fulfilled by AP[AS]CQ motifs in IC3 and juxtamembrane residues in CT. Furthermore, we shed light on how these CTSs promote ciliary targeting by modulating binding to ciliary trafficking adapters TULP3 and RABL2.


Assuntos
Membrana Celular/metabolismo , Cílios/metabolismo , Receptores de Serotonina/química , Receptores de Serotonina/metabolismo , Receptores de Somatostatina/química , Receptores de Somatostatina/metabolismo , Transdução de Sinais/genética , Sequência de Aminoácidos , Animais , Técnicas de Silenciamento de Genes , Células HEK293 , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Camundongos , Domínios e Motivos de Interação entre Proteínas , Transporte Proteico/genética , Transfecção
16.
Heliyon ; 6(11): e05531, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33294679

RESUMO

BACKGROUND: Previous studies have reported associations between nonalcoholic fatty liver disease, periodontitis, and obesity. Serum immunoglobulin G (IgG) antibody titer against Porphyromonas gingivalis, a major pathogen of periodontitis, is an established indicator of periodontal infection. However, the relationship between the antibody titer and liver enzyme levels has not been clarified yet. A study in the elderly was needed to evaluate the effect of long-term persistent bacterial infection on liver function. The objective of this study was to investigate the association between liver function and infection by P. gingivalis, and the effect of obesity on the association. METHODS: A cross-sectional study was conducted in adult outpatients visiting Sado General Hospital, in Niigata Prefecture, Japan, from 2008 to 2010. The final participants included 192 men and 196 women (mean age 68.1 years). Multivariable logistic regression analyses were performed to assess the association between the serum IgG antibody titer and the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and γ-glutamine transferase (GGT) levels. RESULTS: In women, serum IgG antibody titers against P. gingivalis was associated with elevated ALT, but not with AST or GGT, independent of covariates (p = 0.015). No significant association was found between the antibody titer and the elevated liver enzymes in men. The effect of obesity on the relationship between antibody titer and liver enzyme levels was not statistically significant. CONCLUSIONS: A cross-sectional analysis of adult outpatients suggested an association between P. gingivalis infection and ALT levels in women. The effect of obesity on this association was not statistically significant.

17.
Front Cell Dev Biol ; 8: 587691, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33251215

RESUMO

Primary cilia are hair-like projections that protrude from most mammalian cells and mediate various extracellular signaling pathways. Pancreatic ductal adenocarcinoma (PDAC) cells are known to lose their primary cilia, but the relevance of this phenomenon remains unclear. In this study, we generated PDAC-originated Panc1 cells devoid of primary cilia by mutating a centriolar protein, centrosomal protein 164 (CEP164), which is required for ciliogenesis. CEP164 depletion enhanced the clonogenicity of Panc1 cells, along with chemically induced elimination of primary cilia, suggesting that a lack of these organelles promotes PDAC cells proliferation. In addition, the loss of CEP164 altered the cell cycle progression irrespective of absence of primary cilia. We found that CEP164 was co-localized with the GLI2 transcription factor at the mother centriole and controlled its activation, thus inducing Cyclin D-CDK6 expression. Furthermore, CEP164-mutated Panc1 cells were significantly tolerant to KRAS depletion-dependent growth inhibition. This study suggests that CEP164 deficiency is advantageous for PDAC cells proliferation due to not only lack of ciliation but also cilia-independent GLI2-Cyclin D/CDK6 activation, and that CEP164 is a potential therapeutic target for PDAC.

18.
J Magn Reson ; 321: 106849, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33128915

RESUMO

Several noninvasive techniques for the direct measurement of the neuronal activity using magnetic resonance imaging (MRI) have recently been reported. As a promising candidate, we focus on a spin-lock MRI sequence (i.e., stimulus-induced rotary saturation (SIRS)) directly measuring a tiny oscillating magnetic field. Previous phantom studies on SIRS have applied the target oscillating magnetic field parallel to the direction of the static magnetic field B0. However, in practice, the neuromagnetic fields are not always aligned in the same direction as in such a condition. This study investigates the MR signal changes during SIRS when the target magnetic field direction is not the same as that of the B0 field through both phantom experiments and Bloch simulations. The experimental results indicate that only the target magnetic field component along the B0 field affects the signal change, indicating that SIRS has partial sensitivity, even if the target magnetic fields are tilted from the B0 field. Furthermore, the simulation results show good agreements with the experimental results. These results clarify the sensitivity direction of SIRS-based fMRI and lead to the possibility that the direction of the generated neuromagnetic fields can be estimated, such that we can separate directional information from the other information contained in neuromagnetic fields (e.g., phase information).


Assuntos
Imageamento por Ressonância Magnética/métodos , Neuroimagem/métodos , Simulação por Computador , Humanos , Campos Magnéticos , Imagens de Fantasmas
19.
J Magn Reson ; 319: 106828, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33002769

RESUMO

We demonstrated the feasibility of the spin-lock preparation sequence using low-field magnetic resonance (MR) imaging that prevents interference from blood-oxygenation-level-dependent effects. We focused on two spin-lock preparations: spin-lock Mz (SL-Mz) and stimulus-induced rotary saturation (SIRS) and analyzed the magnetization dynamics during the sequences using the Bloch equation. Next, we performed phantom experiments using a loop coil to investigate the MR signal change as a function of the target signal strength and phase. Furthermore, we performed curve fittings to consider the radio frequency, which agreed with the experimental results. Then, we investigated the detectable strength of the magnetic field, and the SL-Mz detected a signal strength of 2.34 nT. In conclusion, our experimental results showed good agreement with the results obtained using the Bloch equation.

20.
Brain Behav ; 10(12): e01868, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33009714

RESUMO

OBJECTIVES: In recent years, a growing number of diffusion tensor imaging (DTI) studies have compared white matter integrity between patients with major depressive disorder (MDD) and bipolar disorder (BD). However, few studies have examined the pathophysiological significance of different degrees of white matter abnormalities between the two disorders. The present study comprehensively assessed white matter integrity among healthy controls (HC) and euthymic patients with MDD and BD using whole-brain tractography and examined associations between white matter integrity and cognitive functioning. METHODS: We performed neurocognitive examinations and DTI with 30 HCs, 30 patients with MDD, and 30 patients with BD. We statistically evaluated white matter integrity and cognitive function differences across the three groups, assessing associations between white matter integrities and cognitive function. RESULTS: The BD group showed lower fractional anisotropy (FA) for the corpus callosum body, as well as lower, sustained attention and set-shifting scores compared to the other groups. FA for the left body of the corpus callosum was correlated with sustained attention in patients with BD. CONCLUSIONS: The significant reduction of white matter integrity in the corpus callosum in BD, compared to MDD, was associated with an impairment of sustained attention. This result promotes the understanding of the significance of white matter integrity in mood disorders.


Assuntos
Transtorno Bipolar , Transtorno Depressivo Maior , Substância Branca , Transtorno Bipolar/diagnóstico por imagem , Estudos de Casos e Controles , Cognição , Corpo Caloso/diagnóstico por imagem , Transtorno Depressivo Maior/diagnóstico por imagem , Imagem de Tensor de Difusão , Humanos , Substância Branca/diagnóstico por imagem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...