RESUMO
Eukaryotic cells divide and separate all their components after chromosome segregation by a process called cytokinesis to complete cell division. Cytokinesis is highly regulated by the recruitment of the components to the division site and through post-translational modifications such as phosphorylations. The budding yeast mitotic kinases Cdc28-Clb2, Cdc5, and Dbf2-Mob1 phosphorylate several cytokinetic proteins contributing to the regulation of cytokinesis. The PP2A-Cdc55 phosphatase regulates mitosis counteracting Cdk1- and Cdc5-dependent phosphorylation. This prompted us to propose that PP2A-Cdc55 could also be counteracting the mitotic kinases during cytokinesis. Here we show that in the absence of Cdc55, AMR contraction and the primary septum formation occur asymmetrically to one side of the bud neck supporting a role for PP2A-Cdc55 in cytokinesis regulation. In addition, by in vivo and in vitro assays, we show that PP2A-Cdc55 dephosphorylates the chitin synthase II (Chs2 in budding yeast) a component of the Ingression Progression Complexes (IPCs) involved in cytokinesis. Interestingly, the non-phosphorylable version of Chs2 rescues the asymmetric AMR contraction and the defective septa formation observed in cdc55∆ mutant cells. Therefore, timely dephosphorylation of the Chs2 by PP2A-Cdc55 is crucial for proper actomyosin ring contraction. These findings reveal a new mechanism of cytokinesis regulation by the PP2A-Cdc55 phosphatase and extend our knowledge of the involvement of multiple phosphatases during cytokinesis.
Assuntos
Actomiosina/metabolismo , Citocinese/fisiologia , Quitina Sintase/metabolismo , Segregação de Cromossomos/fisiologia , Fosforilação/fisiologia , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomycetales/metabolismoRESUMO
Lipophorin, the main Drosophila lipoprotein, circulates in the hemolymph transporting lipids between organs following routes that must adapt to changing physiological requirements. Lipophorin receptors expressed in developmentally dynamic patterns in tissues such as imaginal discs, oenocytes and ovaries control the timing and tissular distribution of lipid uptake. Using an affinity purification strategy, we identified a novel ligand for the lipophorin receptors, the circulating lipoprotein Lipid Transfer Particle (LTP). We show that specific isoforms of the lipophorin receptors mediate the extracellular accumulation of LTP in imaginal discs and ovaries. The interaction requires the LA-1 module in the lipophorin receptors and is strengthened by a contiguous region of 16 conserved amino acids. Lipophorin receptor variants that do not interact with LTP cannot mediate lipid uptake, revealing an essential role of LTP in the process. In addition, we show that lipophorin associates with the lipophorin receptors and with the extracellular matrix through weak interactions. However, during lipophorin receptor-mediated lipid uptake, LTP is required for a transient stabilization of lipophorin in the basolateral plasma membrane of imaginal disc cells. Together, our data suggests a molecular mechanism by which the lipophorin receptors tether LTP to the plasma membrane in lipid acceptor tissues. LTP would interact with lipophorin particles adsorbed to the extracellular matrix and with the plasma membrane, catalyzing the exchange of lipids between them.
Assuntos
Apolipoproteínas/metabolismo , Proteínas de Transporte/metabolismo , Membrana Celular/metabolismo , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/metabolismo , Metabolismo dos Lipídeos , Receptores Citoplasmáticos e Nucleares/genética , Animais , Animais Geneticamente Modificados , Apolipoproteínas/genética , Proteínas de Transporte/genética , Drosophila melanogaster/embriologia , Drosophila melanogaster/genética , Embrião não Mamífero/metabolismo , Feminino , Hemolinfa/metabolismo , Lipoproteínas/sangue , Lipoproteínas/genética , Ovário/metabolismo , Isoformas de Proteínas , Estrutura Terciária de Proteína , Receptores Citoplasmáticos e Nucleares/metabolismoRESUMO
This randomized clinical trial was designed to determine whether glutamine administration was effective in reducing the incidence and severity of mucositis and dermatitis induced by radiotherapy (RT) or chemoradiotherapy (CHRT) in patients with head and neck cancer (HNC). Fifty patients were randomized to receive orally either L-Glutamine or placebo (25 patients in each arm). In the glutamine-treated group, 10 g of oral glutamine was administered three times daily. The primary endpoint was to compare the appearance of clinical mucositis between groups at the 6th week, according to the Common Terminology Criteria for Adverse Events. Secondary endpoints were: Functional mucositis, mucositis onset, cervicofacial dermatitis, pain, weight loss and assessment of quality of life (according to the M.D. Anderson Symptom Inventory-Head and Neck). In total, 76 and 87.5% developed clinical mucositis in the glutamine and placebo group, respectively. The incidence and severity grade of mucositis at the 6th week did not exhibit statistically significantly differences between the two groups, although it had a higher value in the placebo group. Significant reduction of dermatitis incidence (P=0.038) and severity (P=0.032) was found in the glutamine group. There were no differences in other outcomes such as pain, weight loss and mucositis onset, in treatment parameters including concomitant chemotherapy, radiation dose and previous surgery, or in quality of life. The present study revealed that glutamine provided slight clinical effects compared with placebo in terms of reducing oral mucositis induced by RT or CHRT in patients with HNC at the 6th week; however, the results were not statistically significant. Although the findings suggested a significant benefit in reducing the incidence and severity of dermatitis, further confirmatory studies are required.
RESUMO
Mastitis is an inflammation of one or several mammal lobes accompanied or not by a mammary gland infection (WHO 2000). The most frequent etiology is infectious, and the highest prevalence period in women is breast-feeding time. The incidence varies from 2 to 33% according to different authors, being more frequent in primiparous women and during the early postpartum weeks. There are other breast inflammatory processes related etiologies, unrelated to breastfeeding, such as neoplasms or trauma to which no reference is made at this time, since the primary objective of this work is focused on infectious etiology which is caused almost exclusively in relation to postpartum and lactation factors.
La mastitis es la inflamación de uno o varios lóbulos de la glándula mamaria acompañada o no de infección1. La etiología más frecuente es la infecciosa y el periodo de mayor prevalencia es durante la lactancia. La incidencia varía del 2 al 33% según los diferentes autores, siendo más frecuente en primíparas y durante las primeras semanas postparto. Existen otros procesos inflamatorios mamarios relacionados con etiologías que no guardan relación con la lactancia, como pueden ser neoplasias o traumatismos a los cuales no vamos a hacer referencia, dado que el objetivo primordial de este trabajo está orientado a la etiología infecciosa y casi exclusivamente en relación con el puerperio y lactancia.
Assuntos
Infecções Bacterianas/tratamento farmacológico , Mastite/tratamento farmacológico , Probióticos/uso terapêutico , Adulto , Infecções Bacterianas/microbiologia , Infecções Bacterianas/prevenção & controle , Aleitamento Materno , Humanos , Lactente , Recém-Nascido , Masculino , Mastite/microbiologia , Mastite/prevenção & controleRESUMO
Tumours of the temporomandibular joint (TMJ) often mimic common conditions of the TMJ, such as TMJ dysfunction syndrome, leading to a delay in the diagnosis. Chondrosarcoma of the TMJ is a rare tumour, with only 18 cases described in the literature. The initial surgical attempt at removal is of important, as aggressive excision offers the best chance for successful treatment. Chondrosarcoma present at the surgical resection margins has a poor prognosis. We present a case of chondrosarcoma of the right TMJ. In our case, combined diagnostic techniques consisting of a panoramic radiograph, computed tomography (CT) and magnetic resonance imaging (MRI) made an accurate preoperative assessment possible and significantly influenced the treatment provided.