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1.
PLoS Genet ; 16(12): e1009232, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33347437

RESUMO

Motile cilia can beat with distinct patterns, but how motility variations are regulated remain obscure. Here, we have studied the role of the coiled-coil protein CFAP53 in the motility of different cilia-types in the mouse. While node (9+0) cilia of Cfap53 mutants were immotile, tracheal and ependymal (9+2) cilia retained motility, albeit with an altered beat pattern. In node cilia, CFAP53 mainly localized at the base (centriolar satellites), whereas it was also present along the entire axoneme in tracheal cilia. CFAP53 associated tightly with microtubules and interacted with axonemal dyneins and TTC25, a dynein docking complex component. TTC25 and outer dynein arms (ODAs) were lost from node cilia, but were largely maintained in tracheal cilia of Cfap53-/- mice. Thus, CFAP53 at the base of node cilia facilitates axonemal transport of TTC25 and dyneins, while axonemal CFAP53 in 9+2 cilia stabilizes dynein binding to microtubules. Our study establishes how differential localization and function of CFAP53 contributes to the unique motion patterns of two important mammalian cilia-types.

2.
J Anesth ; 34(6): 963, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33135148

RESUMO

The authors have retracted this article because they did not have permission to use the data in Tables 1 and 2.

3.
Dev Cell ; 55(4): 383-384, 2020 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-33232672

RESUMO

The developing heart begins as a seemingly straight tube, but it soon undergoes rightward looping. In this issue of Developmental Cell, Desgrange et al. report how left-right asymmetric Nodal signaling regulates heart looping.

4.
Nat Commun ; 11(1): 5520, 2020 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-33139725

RESUMO

Axonemal dynein ATPases direct ciliary and flagellar beating via adenosine triphosphate (ATP) hydrolysis. The modulatory effect of adenosine monophosphate (AMP) and adenosine diphosphate (ADP) on flagellar beating is not fully understood. Here, we describe a deficiency of cilia and flagella associated protein 45 (CFAP45) in humans and mice that presents a motile ciliopathy featuring situs inversus totalis and asthenospermia. CFAP45-deficient cilia and flagella show normal morphology and axonemal ultrastructure. Proteomic profiling links CFAP45 to an axonemal module including dynein ATPases and adenylate kinase as well as CFAP52, whose mutations cause a similar ciliopathy. CFAP45 binds AMP in vitro, consistent with structural modelling that identifies an AMP-binding interface between CFAP45 and AK8. Microtubule sliding of dyskinetic sperm from Cfap45-/- mice is rescued with the addition of either AMP or ADP with ATP, compared to ATP alone. We propose that CFAP45 supports mammalian ciliary and flagellar beating via an adenine nucleotide homeostasis module.


Assuntos
Nucleotídeos de Adenina/metabolismo , Astenozoospermia/genética , Proteínas do Citoesqueleto/deficiência , Situs Inversus/genética , Adolescente , Adulto , Animais , Astenozoospermia/patologia , Axonema/ultraestrutura , Sistemas CRISPR-Cas/genética , Cílios/metabolismo , Cílios/ultraestrutura , Proteínas do Citoesqueleto/genética , Análise Mutacional de DNA , Modelos Animais de Doenças , Epididimo/patologia , Feminino , Flagelos/metabolismo , Flagelos/ultraestrutura , Humanos , Mutação com Perda de Função , Masculino , Camundongos , Camundongos Knockout , Pessoa de Meia-Idade , Planárias/citologia , Planárias/genética , Planárias/metabolismo , Mucosa Respiratória/citologia , Mucosa Respiratória/patologia , Situs Inversus/diagnóstico por imagem , Situs Inversus/patologia , Motilidade Espermática/genética , Tomografia Computadorizada por Raios X , Sequenciamento Completo do Exoma
5.
Sci Adv ; 6(30): eaba1195, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32743070

RESUMO

Immotile cilia sense extracellular signals such as fluid flow, but whether Ca2+ plays a role in flow sensing has been unclear. Here, we examined the role of ciliary Ca2+ in the flow sensing that initiates the breaking of left-right (L-R) symmetry in the mouse embryo. Intraciliary and cytoplasmic Ca2+ transients were detected in the crown cells at the node. These Ca2+ transients showed L-R asymmetry, which was lost in the absence of fluid flow or the PKD2 channel. Further characterization allowed classification of the Ca2+ transients into two types: cilium-derived, L-R-asymmetric transients (type 1) and cilium-independent transients without an L-R bias (type 2). Type 1 intraciliary transients occurred preferentially at the left posterior region of the node, where L-R symmetry breaking takes place. Suppression of intraciliary Ca2+ transients delayed L-R symmetry breaking. Our results implicate cilium-derived Ca2+ transients in crown cells in initiation of L-R symmetry breaking in the mouse embryo.

6.
Proc Jpn Acad Ser B Phys Biol Sci ; 96(7): 273-296, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32788551

RESUMO

Although the human body appears superficially symmetrical with regard to the left-right (L-R) axis, most visceral organs are asymmetric in terms of their size, shape, or position. Such morphological asymmetries of visceral organs, which are essential for their proper function, are under the control of a genetic pathway that operates in the developing embryo. In many vertebrates including mammals, the breaking of L-R symmetry occurs at a structure known as the L-R organizer (LRO) located at the midline of the developing embryo. This symmetry breaking is followed by transfer of an active form of the signaling molecule Nodal from the LRO to the lateral plate mesoderm (LPM) on the left side, which results in asymmetric expression of Nodal (a left-side determinant) in the left LPM. Finally, L-R asymmetric morphogenesis of visceral organs is induced by Nodal-Pitx2 signaling. This review will describe our current understanding of the mechanisms that underlie the generation of L-R asymmetry in vertebrates, with a focus on mice.

7.
Cell Rep ; 31(10): 107733, 2020 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-32521258

RESUMO

Endocytosis has been proposed to modulate cell signaling activities. However, the role of endocytosis in embryogenesis, which requires coordination of multiple signaling inputs, has remained less understood. We previously showed that mouse embryos lacking a small guanosine triphosphate (GTP)-binding protein Rab7 implicated in endocytic flow are defective in gastrulation. Here, we investigate how subcellular defects associated with Rab7 deficiency are related to the observed developmental defects. Rab7-deficient embryos fail to organize mesodermal tissues due to defects in Wnt-ß-catenin signaling. Visceral endoderm (VE)-specific ablation of Rab7 results in patterning defects similar to systemic Rab7 deletion. Rab7 mutants accumulate the Wnt antagonist Dkk1 in the extracellular space and in intracellular compartments throughout the VE epithelium. These data indicate that Rab7-dependent endocytosis regulates the concentration and availability of extracellular Dkk1, thereby relieving the epiblast of antagonism. This intercellular mechanism therefore organizes distinct spatiotemporal patterns of canonical Wnt activity during the peri-gastrulation stages of embryonic development.

8.
J Anesth ; 34(5): 658-665, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32535660

RESUMO

PURPOSE: This study aimed to evaluate whether the three ryanodine receptor type 1 (RYR1) variants (p.Ser2345Thr, p.Ser2345Arg, and p.Lys3367Arg) which we identified in Japanese malignant hyperthermia (MH) patients with a clinical grading scale rank of 6 were causative for MH. METHODS: We prepared human embryonic kidney (HEK)-293 cells transfected with wild-type RYR1 or one of the RYR1 variants, along with myotubes cultured from muscle pieces. Calcium kinetics were examined by calculating the 340/380-nm ratio under various caffeine and 4-chloro-m-cresol (4CmC) concentrations with the ratiometric dye Fura-2 AM. Half-maximal effective concentration (EC50) values were calculated from dose-response curves. Statistical analysis was based on one-way analysis of variance with a Dunnett's multiple comparison test, using a P value < 0.05 as evidence of statistical significance. RESULTS: In functional analysis using HEK-293 cells, we found significant reductions in the EC50 of p.Ser2345Thr and p.Ser2345Arg in comparison with wild-type RYR1 (P < 0.001), while the EC50 of p.Lys3367Arg was not significantly different (P = 0.062 for caffeine and P > 0.999 for 4CmC). On the other hand, functional analysis using myotubes showed significant differences in the EC50 values for all variants (P < 0.001 for all comparisons). CONCLUSIONS: p.Ser2345Thr and p.Ser2345Arg appear capable of causing a calcium metabolism disorder that leads to the onset of MH, and p.Ser2345Arg can be considered as a diagnostic mutation, because it meets the European Malignant Hyperthermia Group criteria. However, patients with p.Lys3367Arg might have mutations in genes other than RYR1 that are capable of causing MH.

9.
Dev Biol ; 464(2): 161-175, 2020 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-32579954

RESUMO

The Dishevelled proteins transduce both canonical Wnt/ß-catenin and non-canonical Wnt/planar cell polarity (PCP) signaling pathways to regulate many key developmental processes during embryogenesis. Here, we disrupt both canonical and non-canonical Wnt pathways by targeting the entire Dishevelled family of genes (Dvl1, Dvl2, and Dvl3) to investigate their functional roles in the early embryo. We identified several defects in anterior-posterior axis specification and mesoderm patterning in Dvl1+/-; Dvl2-/-; Dvl3-/- embryos. Homozygous deletions in all three Dvl genes (Dvl TKO) resulted in defects in distal visceral endoderm migration and a complete failure to induce mesoderm formation. To identify potential mechanisms that lead to the defects in the developmental processes preceding gastrulation, we generated Dvl TKO mouse embryonic stem cells (mESCs) and compared the transcriptional profile of these cells with wild-type (WT) mESCs during germ lineage differentiation into 3D embryoid bodies (EBs). While the Dvl TKO mESCs displayed similar morphology, self-renewal properties, and minor transcriptional variation from WT mESCs, we identified major transcriptional dysregulation in the Dvl TKO EBs during differentiation in a number of genes involved in anterior-posterior pattern specification, gastrulation induction, mesenchyme morphogenesis, and mesoderm-derived tissue development. The absence of the Dvls leads to specific down-regulation of BMP signaling genes. Furthermore, exogenous activation of canonical Wnt, BMP, and Nodal signaling all fail to rescue the mesodermal defects in the Dvl TKO EBs. Moreover, endoderm differentiation was promoted in the absence of mesoderm in the Dvl TKO EBs, while the suppression of ectoderm differentiation was delayed. Overall, we demonstrate that the Dvls are dispensable for maintaining self-renewal in mESCs but are critical during differentiation to regulate key developmental signaling pathways to promote proper axis specification and mesoderm formation.

10.
Neuron ; 107(1): 82-94.e6, 2020 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-32330411

RESUMO

Patients lacking PYCR2, a mitochondrial enzyme that synthesizes proline, display postnatal degenerative microcephaly with hypomyelination. Here we report the crystal structure of the PYCR2 apo-enzyme and show that a novel germline p.Gly249Val mutation lies at the dimer interface and lowers its enzymatic activity. We find that knocking out Pycr2 in mice phenocopies the human disorder and depletes PYCR1 levels in neural lineages. In situ quantification of neurotransmitters in the brains of PYCR2 mutant mice and patients revealed a signature of encephalopathy driven by excessive cerebral glycine. Mechanistically, we demonstrate that loss of PYCR2 upregulates SHMT2, which is responsible for glycine synthesis. This hyperglycemia could be partially reversed by SHMT2 knockdown, which rescued the axonal beading and neurite lengths of cultured Pycr2 knockout neurons. Our findings identify the glycine metabolic pathway as a possible intervention point to alleviate the neurological symptoms of PYCR2-mutant patients.


Assuntos
Córtex Cerebral/metabolismo , Glicina Hidroximetiltransferase/metabolismo , Glicina/metabolismo , Doenças Desmielinizantes Hereditárias do Sistema Nervoso Central/patologia , Pirrolina Carboxilato Redutases/genética , Adolescente , Animais , Córtex Cerebral/patologia , Pré-Escolar , Feminino , Doenças Desmielinizantes Hereditárias do Sistema Nervoso Central/genética , Doenças Desmielinizantes Hereditárias do Sistema Nervoso Central/metabolismo , Humanos , Lactente , Masculino , Camundongos , Camundongos Knockout , Degeneração Neural/genética , Degeneração Neural/metabolismo , Degeneração Neural/patologia , Linhagem , Pirrolina Carboxilato Redutases/deficiência
11.
PLoS Genet ; 16(3): e1008664, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32203505

RESUMO

Motile cilia/flagella are essential for swimming and generating extracellular fluid flow in eukaryotes. Motile cilia harbor a 9+2 arrangement consisting of nine doublet microtubules with dynein arms at the periphery and a pair of singlet microtubules at the center (central pair). In the central system, the radial spoke has a T-shaped architecture and regulates the motility and motion pattern of cilia. Recent cryoelectron tomography data reveal three types of radial spokes (RS1, RS2, and RS3) in the 96 nm axoneme repeat unit; however, the molecular composition of the third radial spoke, RS3 is unknown. In human pathology, it is well known mutation of the radial spoke head-related genes causes primary ciliary dyskinesia (PCD) including respiratory defect and infertility. Here, we describe the role of the primary ciliary dyskinesia protein Rsph4a in the mouse motile cilia. Cryoelectron tomography reveals that the mouse trachea cilia harbor three types of radial spoke as with the other vertebrates and that all triplet spoke heads are lacking in the trachea cilia of Rsph4a-deficient mice. Furthermore, observation of ciliary movement and immunofluorescence analysis indicates that Rsph4a contributes to the generation of the planar beating of motile cilia by building the distal architecture of radial spokes in the trachea, the ependymal tissues, and the oviduct. Although detailed mechanism of RSs assembly remains unknown, our results suggest Rsph4a is a generic component of radial spoke heads, and could explain the severe phenotype of human PCD patients with RSPH4A mutation.


Assuntos
Cílios/metabolismo , Proteínas do Citoesqueleto/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Animais , Axonema/genética , Axonema/metabolismo , Cílios/genética , Transtornos da Motilidade Ciliar/genética , Transtornos da Motilidade Ciliar/metabolismo , Proteínas do Citoesqueleto/genética , Dineínas/metabolismo , Feminino , Flagelos/genética , Flagelos/metabolismo , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Microtúbulos/metabolismo , Mutação , Proteínas do Tecido Nervoso/genética
12.
F1000Res ; 92020.
Artigo em Inglês | MEDLINE | ID: mdl-32148774

RESUMO

Left-right (L-R) asymmetry of visceral organs in animals is established during embryonic development via a stepwise process. While some steps are conserved, different strategies are employed among animals for initiating the breaking of body symmetry. In zebrafish (teleost), Xenopus (amphibian), and mice (mammal), symmetry breaking is elicited by directional fluid flow at the L-R organizer, which is generated by motile cilia and sensed by mechanoresponsive cells. In contrast, birds and reptiles do not rely on the cilia-driven fluid flow. Invertebrates such as Drosophila and snails employ another distinct mechanism, where the symmetry breaking process is underpinned by cellular chirality acquired downstream of the molecular interaction of myosin and actin. Here, we highlight the convergent entry point of actomyosin interaction and planar cell polarity to the diverse L-R symmetry breaking mechanisms among animals.


Assuntos
Actomiosina/fisiologia , Padronização Corporal , Polaridade Celular , Cílios , Desenvolvimento Embrionário , Animais , Aves , Embrião de Mamíferos , Embrião não Mamífero , Camundongos , Répteis , Xenopus , Peixe-Zebra
13.
Nat Ecol Evol ; 4(2): 261-269, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31907383

RESUMO

Unidirectional fluid flow generated by motile cilia at the left-right organizer (LRO) breaks left-right (L-R) symmetry during early embryogenesis in mouse, frog and zebrafish. The chick embryo, however, does not require motile cilia for L-R symmetry breaking. The diversity of mechanisms for L-R symmetry breaking among vertebrates and the trigger for such symmetry breaking in non-mammalian amniotes have remained unknown. Here we examined how L-R asymmetry is established in two reptiles, Madagascar ground gecko and Chinese softshell turtle. Both of these reptiles appear to lack motile cilia at the LRO. The expression of the Nodal gene at the LRO in the reptilian embryos was found to be asymmetric, in contrast to that in vertebrates such as mouse that are dependent on cilia for L-R patterning. Two paralogues of the Nodal gene derived from an ancient gene duplication are retained and expressed differentially in cilia-dependent and cilia-independent vertebrates. The expression of these two Nodal paralogues is similarly controlled in the lateral plate mesoderm but regulated differently at the LRO. Our in-depth analysis of reptilian embryos thus suggests that mammals and non-mammalian amniotes deploy distinct strategies dependent on different Nodal paralogues for rendering Nodal activity asymmetric at the LRO.


Assuntos
Padronização Corporal , Cílios , Animais , Embrião de Galinha , Madagáscar , Camundongos , Répteis , Peixe-Zebra
14.
Genes Cells ; 24(11): 731-745, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31554018

RESUMO

Cluap1/IFT38 is a ciliary protein that belongs to the IFT-B complex and is required for ciliogenesis. In this study, we have examined the behaviors of Cluap1 protein in nonciliated and ciliated cells. In proliferating cells, Cluap1 is located at the distal appendage of the mother centriole. When cells are induced to form cilia, Cluap1 is found in a novel noncentriolar compartment, the cytoplasmic IFT spot, which mainly exists once in a cell. Other IFT-B proteins such as IFT46 and IFT88 are colocalized in this spot. The cytoplasmic IFT spot is present in mouse embryonic fibroblasts (MEFs) but is absent in ciliogenesis-defective MEFs lacking Cluap1, Kif3a or Odf2. The cytoplasmic IFT spot is also found in mouse embryos but is absent in the Cluap1 mutant embryo. When MEFs are induced to form cilia, the cytoplasmic IFT spot appears at an early step of ciliogenesis but starts to disappear when ciliogenesis is mostly completed. These results suggest that IFT-B proteins such as Cluap1 accumulate in a previously undescribed cytoplasmic compartment during ciliogenesis.


Assuntos
Cílios/metabolismo , Citoplasma/metabolismo , Proteínas do Citoesqueleto/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Animais , Cílios/ultraestrutura , Citoplasma/ultraestrutura , Fibroblastos , Proteínas de Choque Térmico , Peptídeos e Proteínas de Sinalização Intracelular/genética , Cinesina , Camundongos , Camundongos Knockout , Proteínas Supressoras de Tumor
15.
Int J Oncol ; 55(4): 896-904, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31432148

RESUMO

Human promyelocytic HL­60 cells can be differentiated into macrophage­like cells by treatment with 12­O­tetra decanoylphorbol­13­acetate (TPA). Certain 5' upstream regions of the zinc finger protein (ZNF)­encoding genes contain duplicated GGAA motifs, which are frequently found in the TPA­responding gene promoter regions. To examine transcriptional responses to TPA, 5'flanking regions of human zinc finger CCCH­type containing, antiviral, ZNF252, ZNF343, ZNF555, ZNF782 and zinc finger nfx­1­type containing 1 (ZNFX1) genes were isolated by polymerase chain reaction (PCR) and ligated into a multiple­cloning site of the pGL4.10[luc2] vector. Transient transfection and a luciferase assay revealed that the ZNFX1 promoter most prominently responded to the TPA treatment. Deletion and point mutation experiments indicated that the duplicated GGAA motif in the 100­bp region positively responded to TPA. In addition, reverse transcription­quantitative PCR and western blotting showed that the mRNA and protein of ZNFX1 accumulate during the differentiation of HL­60 cells. These results indicated that expression of the TPA­inducible ZNFX1 gene, which belongs to the group of interferon­responsive genes, is regulated by the cis­action of the duplicated GGAA motif.


Assuntos
Antígenos de Neoplasias/genética , Antígenos de Neoplasias/metabolismo , Regiões Promotoras Genéticas/efeitos dos fármacos , Acetato de Tetradecanoilforbol/farmacologia , Diferenciação Celular , Repetições de Dinucleotídeos/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células HL-60 , Humanos , Mutação Puntual , Deleção de Sequência , Ativação Transcricional
16.
J Biochem ; 2019 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-31199460

RESUMO

The E2F transcription factors (TFs), which control the progression of the cell cycle in response to DNA-damage and various stresses, are known to interact with a tumor suppressor, Retinoblastoma 1 (RB1). We previously showed that the response of the human RB1 promoter to a 12-O-tetradecanoylphorbol-13-acetate (TPA) in HL-60 cells is mediated by a duplicated GGAA-motif, which is also present in the 5'-upstream of the E2F family genes. The motifs are especially rich in the 5'-upstream of the E2F4 gene. In the present study, we constructed Luciferase (Luc) expression vectors containing a 466-bp of the 5'-upstream of the human E2F4 gene. The transfection of this plasmid and deletion/mutation-introduced derivatives into HL-60 cells and a Luc reporter assay showed that duplicated and triplicated GGAA (TTCC) motifs in the E2F4 promoter respond to TPA. As expected, electrophoretic mobility shift assay (EMSA) indicated that SPI1 (PU.1) binds to the GGAA-motif containing element. A quantitative RT-PCR and Western blotting showed that the E2F4 transcripts and its encoding proteins accumulate during the differentiation of HL-60 into macrophage-like cells. In contrast, the expression of the E2F1 gene and the protein, which possibly acts as a cell cycle accelerator, was greatly diminished.

17.
JA Clin Rep ; 5(1): 3, 2019 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-32026002

RESUMO

BACKGROUND: Changes in coagulability during the hyperacute phase within 24 h after transcatheter aortic valve implantation (TAVI) for Heyde's syndrome, or aortic stenosis complicated by gastrointestinal angiodysplasia and acquired coagulation dysfunction, have not been clarified. We evaluated perioperative changes in coagulability using rotational thromboelastometry (ROTEM). CASE PRESENTATION: A female patient with Heyde's syndrome in her 80s underwent TAVI. ROTEM showed coagulation dysfunction before and at 6 h after surgery. Improvements in coagulation function started at 12 h after surgery. Based on ROTEM findings, oral administration of antiplatelet agents was started on the day after surgery. No hemorrhagic complications were observed in the postoperative phase. CONCLUSIONS: Evaluation of coagulation function using ROTEM was useful for monitoring perioperative hemostasis and coagulation in this patient.

18.
J Anesth ; 33(1): 75-79, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30470896

RESUMO

BACKGROUND: We have noted that patients frequently complain of thoracic or low back pain after undergoing an endovascular aortic repair, which we speculated was caused by the indwelling stent. METHODS: We investigated the patients who underwent an elective thoracic or abdominal endovascular aortic repair (TEVAR or EVAR) and noted the location of stent, and postoperative pain. The incidence of either thoracic or low back pain at individual vertebra levels was determined, after which we fitted the sigmoidal function to the discrete data to obtain a cut-off line. The study patients were then divided into 2 groups using the cut-off line to compare the incidence of pain. RESULTS: We analyzed 96 patients (68 TEVAR, 28 EVAR). The incidence of thoracic pain was significantly higher in TEVAR as compared to EVAR (26.5% vs. 3.6%, P = 0.01), while that of low back pain was significantly higher in EVAR (35.7% vs. 16.2%, P = 0.04). With the cut-off line for thoracic pain set at the 12th thoracic vertebra, the incidence of thoracic pain was significantly higher in patients with the upper end of the stent above the cut-off as compared to at a lower point (26.5% vs. 3.6%, P = 0.01). As for low back pain, the cut-off line was set at the 9th thoracic vertebra, and the incidence of that pain was significantly higher in patients with the lower end of the stent below that line (30.9% vs. 0.0%, P < 0.01). CONCLUSION: Thoracic and low back pain after an endovascular aortic repair procedure were associated with stenting site.


Assuntos
Aneurisma da Aorta Torácica/cirurgia , Dor Lombar/etiologia , Complicações Pós-Operatórias/etnologia , Stents , Idoso , Idoso de 80 Anos ou mais , Procedimentos Endovasculares/métodos , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo
19.
Cell Physiol Biochem ; 51(6): 2843-2857, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30562762

RESUMO

BACKGROUND/AIMS: Nodal cilia that rotate in the ventral node play an important role in establishing left-right asymmetry during embryogenesis; however, inv mutant cilia present abnormal movement and induce laterality defects. The mechanism of their motility, which is regulated by dynein activation and microtubule arrangement, has not been fully understood. This study analyzed the dynein-triggered ciliary motion in the abnormal ultrastructure of the inv mutant, aiming to quantitatively evaluate the influence of microtubule mislocalization on the movement of the cilium. METHODS: We established a realistic 3-D model of an inv mutant cilium with an ultrastructure based on tomographic datasets generated by ultra-high voltage electron microscopy. The time-variant activation of the axonemal dynein force was simulated by pairs of point loads and embedded at dynein-mounted positions between adjacent microtubule doublets in this mathematical model. Utilizing the finite element method and deformable grid, the motility of the mutant cilium that is induced by various dynein activation hypotheses was investigated and compared to experimental observation. RESULTS: The results indicate that for the inv mutant, simulations of the ciliary movement with the engagement of dyneins based on the distance-controlled pattern in the partially activation scenario are broadly consistent with the observation; the shortening of the microtubules induces smaller movement amplitudes, while the angles of the mislocalized microtubules affect the pattern of the ciliary movement, and during the ciliary movement, the microtubules swing and twist in the mutant ciliary body. CONCLUSION: More generally, this study implies that dynein engagement is sensitive to subtle geometric changes in the axoneme, and thus, this geometry greatly influences the integrity of a well-formed ciliary rotation.


Assuntos
Cílios/fisiologia , Dineínas/metabolismo , Microtúbulos/metabolismo , Animais , Cílios/ultraestrutura , Simulação por Computador , Dineínas/ultraestrutura , Módulo de Elasticidade , Desenvolvimento Embrionário , Camundongos Endogâmicos ICR , Microtúbulos/ultraestrutura , Modelos Biológicos , Movimento
20.
Dev Cell ; 46(5): 525-526, 2018 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-30205033

RESUMO

The cellular basis of left-right asymmetric organogenesis remains largely unknown, but signaling events on the left side were thought to be dominant. In this issue of Developmental Cell, however, Sivakumar et al. (2018) suggest that covalent modification of hyaluronan on the right side initiates directional looping of the developing midgut.


Assuntos
Ácido Hialurônico , Organogênese , Padronização Corporal , Sistema Digestório , Endoderma , Coração
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