RESUMEN
The early branching eukaryote Trypanosoma brucei divides uni-directionally along the longitudinal cell axis from the cell anterior toward the cell posterior, and the cleavage furrow ingresses along the cell division plane between the new and the old flagella of a dividing bi-flagellated cell. Regulation of cytokinesis in T. brucei involves actomyosin-independent machineries and trypanosome-specific signaling pathways, but the molecular mechanisms underlying cell division plane positioning remain poorly understood. Here we report a kinesin-13 family protein, KIN13-5, that functions downstream of FPRC in the cytokinesis regulatory pathway and determines cell division plane placement. KIN13-5 localizes to multiple cytoskeletal structures, interacts with FPRC, and depends on FPRC for localization to the site of cytokinesis initiation. Knockdown of KIN13-5 causes loss of microtubule bundling at both ends of the cell division plane, leading to mis-placement of the cleavage furrow and unequal cytokinesis, and at the posterior cell tip, causing the formation of a blunt posterior. In vitro biochemical assays demonstrate that KIN13-5 bundles microtubules, providing mechanistic insights into the role of KIN13-5 in cytokinesis and posterior morphogenesis. Altogether, KIN13-5 promotes microtubule bundle formation to ensure cleavage furrow placement and to maintain posterior cytoskeleton morphology in T. brucei.
Asunto(s)
Citocinesis , Trypanosoma brucei brucei , Citocinesis/fisiología , Trypanosoma brucei brucei/metabolismo , Cinesinas/genética , Cinesinas/metabolismo , Citoesqueleto/metabolismo , Microtúbulos/metabolismo , Morfogénesis , Proteínas Protozoarias/metabolismoRESUMEN
The relationship between postoperative morphological changes in the inferior nasal cavity and inferior turbinate after Le Fort I osteotomy remains unclear. This study aimed to investigate how the bone volume of the inferior turbinate affects contact with the inferior nasal cavity of patients who underwent superior repositioning. We evaluated the 3-dimensional relationship between the anatomical changes in the inferior nasal passage before and after surgery in 51 patients who underwent Le Fort I osteotomy with an elevation of >4.0 mm in the first molar. The soft tissue and bone volumes of the inferior turbinate and airway volume of the inferior nasal passage were calculated using Proplan CMF 3.0 and compared according to the size of the bone volume of the inferior turbinate. In addition, we reclassified the maxillary movements in the pitch direction and compared the results. The contact rates of the postoperative inferior nasal airway and the inferior turbinate in the large-bone group was 72.3% and that in the small-bone group was 40.0% in the χ2 test. The reduction in the inferior nasal passage volume was significantly greater in the large-bone group (pitch+) than in the small-bone group (pitch+). For patients with well-developed bony tissue of the inferior turbinate, caution is advised if the maxillary elevation is ≥4.0 mm, because the possibility of postoperative obstruction of the inferior nasal passages exist, which may lead to deterioration of nasal ventilation.
Asunto(s)
Cavidad Nasal , Osteotomía Le Fort , Humanos , Cavidad Nasal/cirugía , Osteotomía Le Fort/métodos , Cornetes Nasales/diagnóstico por imagen , Cornetes Nasales/cirugía , Maxilar/diagnóstico por imagen , Maxilar/cirugía , CraneotomíaRESUMEN
PURPOSE: To retrospectively evaluate skeletal stability after Le Fort I maxillary impaction surgery and mandibular autorotation without bilateral sagittal split osteotomy (BSSO) in high-angle class II patients. MATERIALS AND METHODS: Seven female high-angle class II patients who underwent maxillary impaction surgery and mandibular autorotation without bilateral sagittal split osteotomy were included in this study. Surgical changes and relapse were measured on lateral cephalograms taken preoperatively and at 1âmonth, 6âmonths and 1âyear postoperatively. RESULTS: The horizontal movement of the maxilla at point A was 5.8â±â3.3âmm backward, and the upward movement at the posterior nasal spine was 3.3â±â1.4âmm. The mean horizontal change at point A during the 1-year follow-up period was 0.1â±â0.2âmm, and the vertical change at posterior nasal spine was 0.2â±â1.3âmm, which were not statistically significant. The horizontal surgical change at point B was 4.0â±â1.8âmm forward and the vertical surgical change at point B was 4.7â±â1.8âmm upward. Postoperative relapse was 10.9% and 13.7% in the horizontal and vertical directions, respectively. CONCLUSIONS: Le Fort I maxillary impaction surgery with mandibular autorotation may be 1 of the suitable procedures for high-angle class II patients.
Asunto(s)
Maloclusión de Angle Clase III , Maloclusión Clase II de Angle , Diente Impactado , Cefalometría/métodos , Femenino , Estudios de Seguimiento , Humanos , Maloclusión Clase II de Angle/diagnóstico por imagen , Maloclusión Clase II de Angle/cirugía , Maloclusión de Angle Clase III/cirugía , Mandíbula/diagnóstico por imagen , Mandíbula/cirugía , Maxilar/diagnóstico por imagen , Maxilar/cirugía , Osteotomía Le Fort/métodos , Recurrencia , Estudios RetrospectivosRESUMEN
OBJECTIVE: There are cases in which patients complain of nasal obstruction after Le Fort I osteotomy, but the relationship with postoperative morphological changes in the nasal cavity, including the septum and inferior turbinate, is not clear. STUDY DESIGN: The authors evaluated the three-dimensional relationship of the morphological changes in the inferior turbinate before and after surgery in 84 patients who underwent Le Fort I osteotomy. Three classifications were made according to superior amount of maxillary movement at the base of nasal cavity. RESULTS: The high elevation group (4.0 mm or more) had 31 sides, the moderate elevation group had 93 sides, and the low elevation group (less than 2.0 mm) had 44 sides. The volume of inferior turbinate was 76.9 ± 12.8% of that before surgery in the high elevation group. The high- and moderate-elevation groups had significantly higher changes than the low elevation group, and the rate of contact between inferior turbinate and nasal cavity floor was 67.7%. CONCLUSIONS: After Le Fort I osteotomy, the volume of inferior turbinate tissue decreased in proportion to the amount of elevation of the maxilla. Although the soft tissue volume may be reduced due to adaptation of respiratory function, the inferior nasal passage was not completely ventilated in the high elevation group. If the elevation exceeds 4.0 mm counterclockwise with maxillary movement, it is necessary to consider the concomitant inferior turbinate resection because it may lead to nasal obstruction.
Asunto(s)
Obstrucción Nasal , Cornetes Nasales , Humanos , Maxilar/diagnóstico por imagen , Maxilar/cirugía , Cavidad Nasal , Obstrucción Nasal/cirugía , Osteotomía Le Fort/métodos , Cornetes Nasales/cirugíaRESUMEN
Trypanosoma brucei possesses a motile flagellum that determines cell morphology and the cell division plane. Inheritance of the newly assembled flagellum during the cell cycle is controlled by the Polo-like kinase homolog TbPLK, which also regulates cytokinesis initiation. How TbPLK is targeted to its subcellular locations remains poorly understood. Here we report the trypanosome-specific protein BOH1 that cooperates with TbPLK to regulate flagellum inheritance and cytokinesis initiation in the procyclic form of T. brucei BOH1 localizes to an unusual sub-domain in the flagellum-associated hook complex, bridging the hook complex, the centrin arm and the flagellum attachment zone. Depletion of BOH1 disrupts hook-complex morphology, inhibits centrin-arm elongation and abolishes flagellum attachment zone assembly, leading to flagellum mis-positioning and detachment. Further, BOH1 deficiency impairs the localization of TbPLK and the cytokinesis regulator CIF1 to the cytokinesis initiation site, providing a molecular mechanism for its role in cytokinesis initiation. These findings reveal the roles of BOH1 in maintaining hook-complex morphology and regulating flagellum inheritance, and establish BOH1 as an upstream regulator of the TbPLK-mediated cytokinesis regulatory pathway.
Asunto(s)
Proteínas de Ciclo Celular/metabolismo , Citocinesis , Flagelos/metabolismo , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Proto-Oncogénicas/metabolismo , Proteínas Protozoarias/metabolismo , Trypanosoma brucei brucei/metabolismo , Flagelos/ultraestructura , Técnicas de Silenciamiento del Gen , Unión Proteica , Dominios Proteicos , Proteínas Protozoarias/química , Trypanosoma brucei brucei/ultraestructura , Quinasa Tipo Polo 1RESUMEN
DNA damage-induced cell cycle checkpoints serve as surveillance mechanisms to maintain genomic stability, and are regulated by ATM/ATR-mediated signaling pathways that are conserved from yeast to humans. Trypanosoma brucei, an early divergent microbial eukaryote, lacks key components of the conventional DNA damage-induced G2/M cell cycle checkpoint and the spindle assembly checkpoint, and nothing is known about how T. brucei controls its cell cycle checkpoints. Here we discover a kinetochore-based, DNA damage-induced metaphase checkpoint in T. brucei. MMS-induced DNA damage triggers a metaphase arrest by modulating the abundance of the outer kinetochore protein KKIP5 in an Aurora B kinase- and kinetochore-dependent, but ATM/ATR-independent manner. Overexpression of KKIP5 arrests cells at metaphase through stabilizing the mitotic cyclin CYC6 and the cohesin subunit SCC1, mimicking DNA damage-induced metaphase arrest, whereas depletion of KKIP5 alleviates the DNA damage-induced metaphase arrest and causes chromosome mis-segregation and aneuploidy. These findings suggest that trypanosomes employ a novel DNA damage-induced metaphase checkpoint to maintain genomic integrity.
Asunto(s)
Puntos de Control del Ciclo Celular/genética , Daño del ADN , Genoma de Protozoos/genética , Inestabilidad Genómica , Cinetocoros/metabolismo , Trypanosoma/genética , Proteínas de la Ataxia Telangiectasia Mutada/genética , Proteínas de la Ataxia Telangiectasia Mutada/metabolismo , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Proteínas Cromosómicas no Histona/genética , Proteínas Cromosómicas no Histona/metabolismo , Ciclinas/genética , Ciclinas/metabolismo , Humanos , Metafase , Proteínas Protozoarias/genética , Proteínas Protozoarias/metabolismo , Trypanosoma/metabolismo , Trypanosoma brucei brucei/genética , Trypanosoma brucei brucei/metabolismo , CohesinasRESUMEN
The evolutionarily early divergent human parasite Trypanosoma brucei proliferates through binary cell fission in both its tsetse fly vector and mammalian host. The parasite divides unidirectionally along the longitudinal cell axis from the anterior cell tip toward the posterior cell tip through a mechanism distinct from that in the cells of its human host. Initiation of cytokinesis in T. brucei is regulated by two evolutionarily conserved protein kinases, the Polo-like kinase TbPLK and the Aurora B kinase TbAUK1, and a cohort of trypanosome-specific proteins, including the three cytokinesis initiation factors CIF1, CIF2, and CIF3. Here, using RNAi, in situ epitope tagging of proteins, GST pulldown, and coimmunoprecipitation assays, and immunofluorescence and scanning electron microscopy analyses, we report the identification and functional characterization of two trypanosome-specific proteins, flagellum attachment zone tip-localizing protein required for cytokinesis (FPRC) and CIF4. We found that the two proteins colocalize to the distal tips of the new and the old flagellum attachment zones and are required for cytokinesis initiation. Knockdown of FPRC or CIF4 disrupted the localization of CIF1, suggesting that they function upstream of CIF1. Moreover, depletion of CIF4 abolished FPRC localization, indicating that CIF4 acts upstream of FPRC. Together, these results identify two new cytokinesis regulators in T. brucei and integrate them into the CIF1-mediated cytokinesis regulatory pathway. These findings highlight the existence of a cytokinesis pathway in T. brucei that is different from that of its mammalian host and therefore suggest that cytokinesis in T. brucei could potentially be exploited as a new drug target.
Asunto(s)
Citocinesis/fisiología , Proteínas Protozoarias/metabolismo , Trypanosoma brucei brucei/metabolismo , Ciclo Celular , Complejos Multiproteicos/química , Complejos Multiproteicos/metabolismo , Plásmidos/genética , Plásmidos/metabolismo , Unión Proteica , Proteínas Protozoarias/antagonistas & inhibidores , Proteínas Protozoarias/genética , Interferencia de ARNRESUMEN
Faithful chromosome segregation depends on correct spindle microtubule-kinetochore attachment and requires certain spindle-associated proteins (SAPs) involved in regulating spindle dynamics and chromosome segregation. Little is known about the spindle-associated proteome in the early divergent Trypanosoma brucei and its roles in chromosome segregation. Here we report the identification of a cohort of divergent SAPs through localization-based screening and proximity-dependent biotin identification. We identified seven new SAPs and seventeen new nucleolar proteins that associate with the spindle, and demonstrated that the kinetochore protein KKIP4 also associates with the spindle. These SAPs localize to distinct subdomains of the spindle during mitosis, and all but one localize to nucleus during interphase and post-mitotic phases. Functional analyses of three nucleus- and spindle-associated proteins (NuSAPs) revealed distinct functions in chromosome segregation. NuSAP1 is a kinetoplastid-specific protein required for equal chromosome segregation and for maintaining the stability of the kinetochore proteins KKIP1 and KKT1. NuSAP2 is a highly divergent ASE1/PRC1/MAP65 homolog playing an essential role in promoting the G2/M transition. NuSAP3 is a kinetoplastid-specific Kif13-1-binding protein maintaining Kif13-1 protein stability and regulating the G2/M transition. Together, our work suggests that chromosome segregation in T. brucei requires a cohort of kinetoplastid-specific and divergent SAPs with distinct functions.
Asunto(s)
Segregación Cromosómica , Cinetocoros/metabolismo , Proteínas Asociadas a Microtúbulos/metabolismo , Proteínas Protozoarias/metabolismo , Huso Acromático/metabolismo , Trypanosoma brucei brucei/metabolismo , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Línea Celular , Hibridación Fluorescente in Situ , Microscopía Fluorescente , Proteínas Asociadas a Microtúbulos/genética , Microtúbulos/metabolismo , Mitosis , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Proteínas Protozoarias/genética , Interferencia de ARN , Trypanosoma brucei brucei/citología , Trypanosoma brucei brucei/genéticaRESUMEN
Cytokinesis, the terminal step in cell division, in the protist human pathogen Trypanosoma brucei occurs along the longitudinal axis from the anterior tip of the new flagellum attachment zone (FAZ) toward the posterior cell tip. This process is regulated by a signaling cascade composed of the Polo-like kinase homolog TbPLK, the Aurora B kinase homolog TbAUK1, and the trypanosome-specific CIF1-CIF2 protein complex. However, the regulatory mechanism and the signaling pathway for this unusual mode of cytokinesis remain poorly understood. Here, we report another trypanosome-specific protein assembly, the CIF1-CIF3 complex, and its essential role in cytokinesis initiation. Through biochemical and genetic approaches, we demonstrate that CIF3 interacts with CIF1 in a TbPLK-dependent manner and maintains CIF1 localization at the new FAZ tip. Conversely, CIF1 maintains CIF3 stability at the new FAZ tip. We further show that TbPLK is required for CIF3 localization and that CIF3 is necessary for targeting TbAUK1 to the new FAZ tip during anaphase. These results suggest that two trypanosome-specific CIF1-containing protein complexes cooperate with the evolutionarily conserved Polo-like kinase and Aurora B kinase to promote cytokinesis in T. brucei.
Asunto(s)
Citocinesis , Proteínas Protozoarias/metabolismo , Trypanosoma brucei brucei/citología , Trypanosoma brucei brucei/metabolismo , Estabilidad Proteica , Transporte de Proteínas , Proteínas Protozoarias/química , Especificidad de la Especie , Dedos de ZincRESUMEN
Cytokinesis in trypanosomes occurs uni-directionally along the longitudinal axis from the cell anterior towards the cell posterior and requires a trypanosome-specific CIF1-CIF2 protein complex. However, little is known about the contribution of the structural motifs in CIF1 and CIF2 to complex assembly and cytokinesis. Here, we demonstrate that the two zinc-finger motifs but not the coiled-coil motif in CIF1 are required for interaction with the EF-hand motifs in CIF2. We further show that localization of CIF1 depends on the coiled-coil motif and the first zinc-finger motif and that localization of CIF2 depends on the EF-hand motifs. Deletion of the coiled-coil motif and mutation of either zinc-finger motif in CIF1 disrupts cytokinesis. Furthermore, mutation of either zinc-finger motif in CIF1 mislocalizes CIF2 to the cytosol and destabilizes CIF2, whereas deletion of the coiled-coil motif in CIF1 spreads CIF2 over to the new flagellum attachment zone and stabilizes CIF2. Together, these results uncover the requirement of the coiled-coil and zinc-finger motifs for CIF1 function in cytokinesis and for CIF2 localization and stability, providing structural insights into the functional interplay between the two cytokinesis regulators.
Asunto(s)
Citocinesis/genética , Proteínas Protozoarias/genética , Trypanosoma brucei brucei/genética , Dedos de Zinc/genética , Secuencia de Aminoácidos/genética , Desarrollo Embrionario/genética , Humanos , Complejos Multiproteicos/química , Unión Proteica , Proteínas Protozoarias/química , Trypanosoma brucei brucei/química , Trypanosoma brucei brucei/patogenicidadRESUMEN
Transcriptional mechanisms governing hematopoietic stem cell (HSC) quiescence, self-renewal, and differentiation are not fully understood. Sequence-specific ssDNA-binding protein 2 (SSBP2) is a candidate acute myelogenous leukemia (AML) suppressor gene located at chromosome 5q14. SSBP2 binds the transcriptional adaptor protein Lim domain-binding protein 1 (LDB1) and enhances LDB1 stability to regulate gene expression. Notably, Ldb1 is essential for HSC specification during early development and maintenance in adults. We previously reported shortened lifespan and greater susceptibility to B cell lymphomas and carcinomas in Ssbp2(-/-) mice. However, whether Ssbp2 plays a regulatory role in normal HSC function and leukemogenesis is unknown. In this study, we provide several lines of evidence to demonstrate a requirement for Ssbp2 in the function and transcriptional program of hematopoietic stem and progenitor cells (HSPCs) in vivo. We found that hematopoietic tissues were hypoplastic in Ssbp2(-/-) mice, and the frequency of lymphoid-primed multipotent progenitor cells in bone marrow was reduced. Other significant features of these mice were delayed recovery from 5-fluorouracil treatment and diminished multilineage reconstitution in lethally irradiated bone marrow recipients. Dramatic reduction of Notch1 transcripts and increased expression of transcripts encoding the transcription factor E2a and its downstream target Cdkn1a also distinguished Ssbp2(-/-) HSPCs from wild-type HSPCs. Finally, a tendency toward coordinated expression of SSBP2 and the AML suppressor NOTCH1 in a subset of the Cancer Genome Atlas AML cases suggested a role for SSBP2 in AML pathogenesis. Collectively, our results uncovered a critical regulatory function for SSBP2 in HSPC gene expression and function.
Asunto(s)
Diferenciación Celular , Proteínas de Unión al ADN/metabolismo , Células Madre Hematopoyéticas/citología , Células Madre Hematopoyéticas/metabolismo , Estrés Fisiológico , Animales , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Médula Ósea/metabolismo , Médula Ósea/patología , Trasplante de Médula Ósea , Diferenciación Celular/genética , Proteínas de Unión al ADN/genética , Expresión Génica , Hematopoyesis/genética , Homeostasis/genética , Inmunofenotipificación , Ratones , Ratones Noqueados , Fenotipo , Receptor Notch1/genética , Receptor Notch1/metabolismoRESUMEN
The master regulators of the cell cycle are cyclin-dependent kinases (Cdks), which influence the function of a myriad of proteins via phosphorylation. Mitotic Cdk1 is activated by A-type, as well as B1- and B2-type, cyclins. However, the role of a third, conserved cyclin B family member, cyclin B3, is less well defined. Here, we show that Caenorhabditis elegans CYB-3 has essential and distinct functions from cyclin B1 and B2 in the early embryo. CYB-3 is required for the timely execution of a number of cell cycle events including completion of the MII meiotic division of the oocyte nucleus, pronuclear migration, centrosome maturation, mitotic chromosome condensation and congression, and, most strikingly, progression through the metaphase-to-anaphase transition. Our experiments reveal that the extended metaphase delay in CYB-3-depleted embryos is dependent on an intact spindle assembly checkpoint (SAC) and results in salient defects in the architecture of holocentric metaphase chromosomes. Furthermore, genetically increasing or decreasing dynein activity results in the respective suppression or enhancement of CYB-3-dependent defects in cell cycle progression. Altogether, these data reveal that CYB-3 plays a unique, essential role in the cell cycle including promoting mitotic dynein functionality and alleviation of a SAC-dependent block in anaphase chromosome segregation.
Asunto(s)
Anafase , Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/citología , Caenorhabditis elegans/metabolismo , Segregación Cromosómica , Ciclina B/metabolismo , Huso Acromático/metabolismo , Animales , Caenorhabditis elegans/embriología , Núcleo Celular/metabolismo , Dineínas Citoplasmáticas/metabolismo , Embrión no Mamífero/citología , Embrión no Mamífero/metabolismo , Eliminación de Gen , Cinetocoros/metabolismo , Metafase , Interferencia de ARN , Factores de TiempoRESUMEN
OBJECTIVE: Recently, RapidSorb plates (DePuy Synthes) made of 85.15 poly (L-lactide-co-glycolide) have been used for orthognathic surgery; however, reports regarding their effectiveness are limited. We aimed to compare the postoperative stability of RapidSorb plates, RapidSorb combined with titanium (MOJ plates), and MOJ plates in patients who underwent Le Fort I osteotomy at Tokyo Medical and Dental University Hospital. STUDY DESIGN: The use of RapidSorb in the maxilla is a load-sharing application and therefore constitutes an approved indication. Discrepancies in the maxillary positions were measured using postoperative computed tomography data at 1 week and 1 year using the centroid method 3-dimensionally. Treatment with RapidSorb alone showed a more vertical discrepancy in the maxilla treatment with MOJ and RapidSorb+MOJ. The RapidSorb4 group was subdivided into 2 groups (under and over 1.0-mm) based on the change in the maxillary centroid. RESULTS: The bone gap at the lateral border of the piriform aperture was significantly larger in the over-1.0-mm group than in the 1.0-mm group. CONCLUSIONS: The fixation of RapidSorb alone is not appropriate in load-bearing and unstable applications but is not contraindicated for load-sharing indications. Fixation with RapidSorb combined with MOJ was clinically effective, with results similar to titanium plate-only fixation regarding postoperative stability.
Asunto(s)
Osteotomía Le Fort , Titanio , Humanos , Osteotomía Le Fort/métodos , Implantes Absorbibles , Dioxanos , Maxilar/diagnóstico por imagen , Maxilar/cirugía , Placas Óseas , Cefalometría/métodosRESUMEN
OBJECTIVE: To quantify facial swelling at 1 week after Le Fort I osteotomy and bilateral sagittal splitting ramus osteotomy in Class III patients and to identify factors contributing to the swelling based on clinical, morphologic, and surgical variables. STUDY DESIGN: Data from 63 patients were examined in this single-center, retrospective study. Facial swelling was quantitatively measured by superimposing computed tomography data taken in the supine position at 1 week and 1 year postoperatively and extracting the area of maximum intersurface distance. Age, sex, body mass index, thickness of subcutaneous tissue, and of masseter muscle, maxillary length (A-VRP), mandibular length (B-VRP), and posterior maxillary height (U6-HRP), surgical movement (ΔA-VRP, ΔB-VRP, ΔU6-HRP), drainage method, and usage of facial bandages were examined. Multiple regression analysis was performed using the above factors. RESULTS: The median swelling at 1 week postoperatively was 8.35 IQR (5.99-11.47) mm. Multiple regression analysis revealed three factors that were significantly associated with facial swelling: Use of postoperative facial bandages (P=0.03), masseter muscle thickness (P=0.03), and ΔB-VRP (P=0.04). CONCLUSION: Absence of a facial bandage, thin masseter muscle, and large horizontal mandibular movement are risk factors for facial swelling at 1 week postoperatively.
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Angioedema , Cirugía Ortognática , Humanos , Estudios Retrospectivos , Cara/cirugía , Factores de RiesgoRESUMEN
Cytokinesis in Trypanosoma brucei occurs unidirectionally from the anterior toward the posterior through mechanisms distinct from those of its human host and is controlled by a signaling pathway comprising evolutionarily conserved and trypanosome-specific regulatory proteins. The mechanistic roles and the functional interplay of these cytokinesis regulators remain poorly understood. Here, we investigate the requirement of the structural motifs in the trypanosome-specific cytokinesis regulator CIF3 for the initiation of cytokinesis, the interaction with other cytokinesis regulators, and the recruitment of CIF3-interacting proteins to the cytokinesis initiation site. We demonstrate that the internal and C-terminal coiled-coil motifs, but not the N-terminal coiled-coil motif, of CIF3 play essential roles in cytokinesis and interact with distinct cytokinesis regulators. CIF3 interacts with TbPLK, CIF1, CIF4, and FPRC through the N-terminal and C-terminal coiled-coil motifs and with KAT80 through all three coiled-coil motifs. The C-terminal coiled-coil motif of CIF3 is required for the localization of CIF3 and all of its interacting proteins, and additionally, the internal coiled-coil motif of CIF3 is required for KAT80 localization. Conversely, all the CIF3-interacting proteins are required to maintain CIF3 at the cytokinesis initiation site at different cell cycle stages. These results demonstrate that CIF3 cooperates with multiple interacting partner proteins to promote cytokinesis in T. brucei. IMPORTANCE Cytokinesis is the final stage of cell division and is regulated by a signaling pathway conserved from yeast to humans. Cytokinesis in Trypanosoma brucei, an early-branching protozoan parasite causing human sleeping sickness, is regulated by mechanisms that are distinct from those of its human host, employing a number of trypanosome-specific regulatory proteins to cooperate with evolutionarily conserved regulators. The functional interplay of these cytokinesis regulators is still poorly understood. In this work, we investigated the structural requirement of the trypanosome-specific cytokinesis regulator CIF3 for the initiation of cytokinesis, the interaction with other cytokinesis regulatory proteins, and the recruitment of CIF3-interacting proteins. We demonstrated that different structural motifs of CIF3 played distinct roles in cytokinesis, interacted with distinct cytokinesis regulatory proteins, and were required for the recruitment of distinct cytokinesis regulatory proteins. These findings provided novel insights into the cooperative roles of cytokinesis regulators in promoting cytokinesis in T. brucei.
Asunto(s)
Trypanosoma brucei brucei , División Celular , Citocinesis , Humanos , Dominios Proteicos , Proteínas Protozoarias/metabolismo , Factores de Transcripción/metabolismo , Trypanosoma brucei brucei/metabolismoRESUMEN
Oral care is defined in a narrow sense as cleaning of the teeth, oral cavity, and dentures, and in a broad sense as the maintenance of oral functions (feeding, swallowing, chewing, speech, aesthetics, etc.), dental treatment, feeding and swallowing training, and articulation training. In the past, it was recognized as simply cleaning the mouth, but the concept of oral care has gradually expanded, and many studies and surveys have been conducted in cooperation with various other professions. As a result, oral health care is involved not only in the prevention of pneumonia, but also in the onset and suppression for severity of diabetes, cardiovascular diseases, some malignant tumors, cerebrovascular diseases, rheumatoid arthritis, dementia, etc. It is also a powerful supportive therapy in cancer treatment. In the terminal stages of life, oral health care can help people to maintain their dignity by continuing to consume food orally until the end of their lives, and in times of disaster, oral health care has been found to be as important as attention to deep vein thrombosis. It has also been found to be effective in preventing severe diseases such as COVID-19. And, although it has not been discussed much, it has been found to have medical and economic benefits such as reducing the duration of hospitalization and treatment costs. This article reviews the results of research to date.
Asunto(s)
COVID-19 , Humanos , Salud Bucal , SARS-CoV-2 , Sociedades , Encuestas y CuestionariosRESUMEN
OBJECTIVE: To evaluate the relationship between the changes in condylar volume and maxillofacial skeletal morphology according to sex as well as the relationship between condylar volume reduction and skeletal relapse in patients who underwent orthognathic surgery. METHODS: Ninety-five patients were categorized into skeletal Class III, Class II, and facial asymmetry groups. Computed tomography scans taken preoperatively and at 1 year postoperatively were used for quantitative measurement. RESULTS: Postoperative condylar volume was reduced in both the Class II group and the deviated side of the asymmetry group. Both female and Class II deformity were significant predictors of postoperative reduction in the condylar volume. There was a significant correlation between skeletal relapse and postoperative change in condylar volume in the Class II group. CONCLUSION: Postoperative condylar resorption may be associated with preoperative maxillofacial skeletal morphology and sex and also with skeletal relapse in the Class II group.
RESUMEN
Perioperative oral management (POM) is used to prevent pneumonia in patients with cancer. However, the factors that expose hospitalized patients to increased risk of developing pneumonia remain unclear. For example, no study to date has compared the incidence of pneumonia in hospitalized patients by cancer primary lesion, or POM implementation, or not. We determined which patients were most likely to benefit from POM and examined the effects of POM on pneumonia prevention and mortality. In a total of 9441 patients with cancer who underwent surgery during hospitalization, there were 8208 patients in the No POM group, and 1233 in the POM group. We examined between-group differences in the incidence of pneumonia and associated outcomes during hospitalization. There was no significant between-group difference in the incidence of pneumonitis, however, patients with lung, or head and neck cancers, demonstrated a lower incidence of postoperative pneumonia. Among patients with lung and pancreatic cancers, mortality was significantly lower in the POM group. POM appears effective at reducing the risk of postoperative pneumonia in patients with certain cancers. Further, mortality was significantly lower in patients with lung and pancreatic cancers who received POM; hence, POM may be an effective adjuvant therapy for patients with cancer.
RESUMEN
Cytokinesis in eukaryotes is regulated by a Polo-like kinase-mediated and Aurora B kinase-mediated signalling pathway that promotes the assembly of the actomyosin contractile ring, a cytokinesis machinery conserved across evolution from yeast to humans. Trypanosoma brucei, an early divergent parasitic protozoan, employs an actomyosin-independent mechanism for its unusual cytokinesis that is controlled by a regulatory pathway comprising the Polo-like kinase TbPLK, the Aurora B kinase TbAUK1 and multiple trypanosomatid-specific regulators. However, whether any of these trypanosomatid-specific regulators function as substrates of TbPLK and/or TbAUK1 and how they cooperate with TbPLK and TbAUK1 to promote cytokinesis remain unknown. Here, we demonstrate that TbPLK and TbAUK1 phosphorylate the cytokinesis regulators CIF1 and CIF2 on multiple sites within their intrinsically disordered regions. We further show that TbPLK localization depends on its interaction with CIF1 from S/G2 phases, that TbPLK maintains CIF1 and CIF2 localization from G2 phase until early mitosis, and that TbAUK1 maintains CIF1 and CIF2 localization from late mitosis. Finally, we demonstrate that the cytokinesis regulators CIF4 and FPRC are not substrates of TbPLK and TbAUK1, and that they function upstream of TbPLK and TbAUK1 in the cytokinesis regulatory pathway. Together, these results provide insights into the functional interplay and the order of actions between the two protein kinases and the trypanosomatid-specific cytokinesis regulators in T. brucei.
Asunto(s)
Trypanosoma brucei brucei , Actomiosina/metabolismo , Aurora Quinasa B/genética , Aurora Quinasa B/metabolismo , Citocinesis/fisiología , Humanos , Proteínas Protozoarias/genética , Proteínas Protozoarias/metabolismo , Trypanosoma brucei brucei/metabolismoRESUMEN
OBJECTIVE: To investigate morphologic and surgical risk factors causing neurosensory disturbances (NSDs) after bilateral sagittal split osteotomy (BSSO). STUDY DESIGN: A total of 237 patients (with 474 sides) who underwent BSSO were followed up for 1 year. Parameters examined included age, sex, asymmetry, mandibular movement direction, mandible cutting devices, split type, intraoperative exposure of the inferior alveolar nerve (IAN), contact between the IAN and screw, distance between mandibular canal and inner surface of the cortical bone (distance A), distance from lateral osteotomy to mental foramen (distance B), and NSD at 1 year postoperatively. RESULTS: NSD was observed in 62 (13.1%) sides of 51 patients. Exploratory factor analysis determined 4 factors (factor 1: distance A; factor 2: direction of mandibular movement; factor 3: distance B and cutting devices; factor 4: IAN exposure). Logistic regression analysis was performed using the above factors and age, sex, and asymmetry, making a total of 7 variables. Age, factor 1, and factor 4 were significant predictors of NSD. CONCLUSIONS: Advanced age, close distance between mandibular canal and inner surface of the cortical bone, and IAN intraoperative exposure are risk factors for NSD 1 year postoperatively. Cases at high risk for NSD must be treated with great care.