Zobrazení zdroje stránky Yangjuarez8451

Collective migration of cohesive tissues is a fundamental process in morphogenesis and is particularly well illustrated during gastrulation by the rapid and massive internalization of the mesoderm, which contrasts with the much more modest movements of the ectoderm. In the Xenopus embryo, the differences in morphogenetic capabilities of ectoderm and mesoderm can be connected to the intrinsic motility of individual cells, very low for ectoderm, high for mesoderm. Surprisingly, we find that these seemingly deep differences can be accounted for simply by differences in Rho-kinases (Rock)-dependent actomyosin contractility. We show that Rock inhibition is sufficient to rapidly unleash motility in the ectoderm and confer it with mesoderm-like properties. In the mesoderm, this motility is dependent on two negative regulators of RhoA, the small GTPase Rnd1 and the RhoGAP Shirin/Dlc2/ArhGAP37. Both are absolutely essential for gastrulation. At the cellular and tissue level, the two regulators show overlapping yet distinct functions. They both contribute to decrease cortical tension and confer motility, but Shirin tends to increase tissue fluidity and stimulate dispersion, while Rnd1 tends to favor more compact collective migration. Thus, each is able to contribute to a specific property of the migratory behavior of the mesoderm. We propose that the "ectoderm to mesoderm transition" is a prototypic case of collective migration driven by a down-regulation of cellular tension, without the need for the complex changes traditionally associated with the epithelial-to-mesenchymal transition.To ensure genome stability, sexually reproducing organisms require that mating brings together exactly 2 haploid gametes and that meiosis occurs only in diploid zygotes. In the fission yeast Schizosaccharomyces pombe, fertilization triggers the Mei3-Pat1-Mei2 signaling cascade, which represses subsequent mating and initiates meiosis. Here, we establish a degron system to specifically degrade proteins postfusion and demonstrate that mating blocks not only safeguard zygote ploidy but also prevent lysis caused by aberrant fusion attempts. Using long-term imaging and flow-cytometry approaches, we identify previously unrecognized and independent roles for Mei3 and Mei2 in zygotes. We show that Mei3 promotes premeiotic S-phase independently of Mei2 and that cell cycle progression is both necessary and sufficient to reduce zygotic mating behaviors. Mei2 not only imposes the meiotic program and promotes the meiotic cycle, but also blocks mating behaviors independently of Mei3 and cell cycle progression. Thus, we find that fungi preserve zygote ploidy and survival by at least 2 mechanisms where the zygotic fate imposed by Mei2 and the cell cycle reentry triggered by Mei3 synergize to prevent zygotic mating.Despite continued and considerable progress following the introduction of proteasome inhibitors and immunomodulatory agents, multiple myeloma (MM) remains an incurable disease, and new therapeutic strategies are urgently needed. Monoclonal antibodies represent a well-established targeted approach to the treatment of MM, with selective killing properties and limited off-target toxicity. Since their approval, the anti-CD38 agent daratumumab, the anti-SLAMF7 agent elotuzumab, and most recently the anti-CD38 agent isatuximab have led to pivotal improvements in the treatment of double-refractory MM; currently, they are on their way to becoming integral parts in the up-front care of patients who have newly diagnosed MM, with daratumumab already approved in this setting. Several other antibody-based strategies are undergoing clinical assessment in MM. Although the investigation of checkpoint inhibitors in MM has been halted, bispecific T-cell engagers and especially antibody-drug conjugates demonstrate encouraging efficacy and manageable toxicity in triple class-refractory MM. The accelerated approval of belantamab mafodotin represents an important milestone in antibody development; its ability to target B-cell maturation antigen (BCMA) in advanced disease is now established. Here, we present an overview of the currently available monoclonal antibody treatments in MM and discuss the clinical value, significant potential, and possible limitations of these immunotherapeutic approaches to driving deeper responses and achieving longer overall survival among patients with a challenging disease.Surgical cytoreduction and platinum/taxane-based chemotherapy are the cornerstones of the management of advanced ovarian cancer; however, the optimal timing and order of these interventions remain a topic of debate. Interpreting the available data, specifically regarding the role of neoadjuvant chemotherapy in the primary setting and surgical cytoreduction in the recurrent setting, requires careful evaluation of surgical quality and patient selection. One tenet that has persisted throughout the historical and modern literature is the prognostic effect of the volume of residual disease after cytoreductive surgery. The goal of debulking surgery has appropriately evolved to that of the complete gross resection of all visible disease, and the repertoire of the gynecologic cancer surgeon has grown to include radical pelvic, upper abdominal, and thoracic procedures. Novel surgical techniques are under investigation, such as minimally invasive cytoreductive procedures and the intraoperative utilization of heated intraperitoneal chemotherapy. Of equal importance is a recent refocusing of attention on patient preferences and the patient's experience during treatment and recovery. In this review article, we examine the literature supporting the role of surgery in the management of advanced ovarian cancer.The use of blood transfusions is a mainstay of modern medical practice. Jehovah's Witnesses decline the use of blood transfusions as a matter of faith, however, and other patients do so for personal reasons. In all cases, it is important to document what blood products can or cannot be used. [https://www.selleckchem.com/products/nec-1s-7-cl-o-nec1.html Nec-1s] It is also essential to test all patients for iron deficiency, and to address any correctable factors in those who are anemic. This article reviews a variety of options that are available to aid in caring for patients who refuse blood transfusions, ranging from tranexamic acid to erythropoiesis-stimulating agents. With the use of these treatments, patients who decline blood transfusion can be safely managed in situations ranging from elective surgery to stem cell transplant to pregnancy.