Levels of Ycg1 Limit Condensin Function during the Cell Cycle

During mitosis chromosomes are condensed to facilitate their segregation, through a process mediated by the condensin complex. Although several factors that promote maximal condensin activity during mitosis have been identified, the mechanisms that downregulate condensin activity during interphase are largely unknown. Here, we demonstrate that Ycg1, the Cap-G subunit of budding yeast condensin, is cell cycle-regulated with levels peaking in mitosis and decreasing as cells enter G1 phase. This cyclical expression pattern is established by a combination of cell cycle-regulated transcription and constitutive degradation. Interestingly, overexpression of YCG1 and mutations that stabilize Ycg1 each result in delayed cell-cycle entry and an overall proliferation defect. Overexpression of no other condensin subunit impacts the cell cycle, suggesting that Ycg1 is limiting for condensin complex formation. Consistent with this possibility, we find that levels of intact condensin complex are reduced in G1 phase compared to mitosis, and that increased Ycg1 expression leads to increases in both levels of condensin complex and binding to chromatin in G1. Together, these results demonstrate that Ycg1 levels limit condensin function in interphase cells, and suggest that the association of condensin with chromosomes must be reduced following mitosis to enable efficient progression through the cell cycle

Upper limb traumatic injuries: A concise overview of reconstructive options

Different options for upper limb reconstruction are described in literature: advancement or rotation flaps, regional flaps and free flaps are the most common. Local and regional flaps can represent the reconstructive options for small defects while large wounds require the use of free flaps or distant pedicled flaps. In case of large wound, the use of free flaps rather than distant pedicle flaps is usually preferred. To choose the best reconstructive option, it is essential for the surgeon to have a general overview about the different methods. In this review the Authors will refer to the most commonly used methods to cover soft tissues injuries affecting the dorsum and the palm of the hand and the forearm (excluding fingers). The aim is to show all flap reconstructive options so as to support the inexperienced surgeon during the management of traumatic injuries of the upper limb

Objective Selection Criteria between ALT and Radial Forearm Flap in Oral Soft Tissues Reconstruction

Different locoregional and free flaps were described for oral soft tissues reconstruction after oncological resections; however, free flaps remain the first choice. Among free flaps, the radial forearm flap (RFF) and the anterolateral thigh perforator flap (ALT) are preferred the most. The lack of standardization of the flap choice leaves the selection to the surgeon's experience. The purpose of our observational study is to provide an algorithm to support the flap choice for the reconstruction of oral soft tissues. Sixty patients with squamous cell carcinoma of oral soft tissues were enrolled in our study. All the patients underwent preoperative magnetic resonance imaging (MRI) to measure the three-dimensional size of the tumor. During the follow-up, the patients were evaluated by using the University of Washington-Quality of Life Questionnaire. The questionnaire score was better for small tumors and worse for large tumors in both functional and relational fields. We observed that most of the overlapping results were obtained for small defects and the choice of RFF, as well as for large defects and the use of ALT. We observed that in the preoperative time, it is possible to select which flap between radial forearm and ALT is more appropriate for oral soft tissues defects reconstruction, according to the size of the tumor evaluated by MRI. We propose a decisional algorithm that suggests the type of flap to use between ALT and RFF

Hcm1 integrates signals from Cdk1 and calcineurin to control cell proliferation

Cyclin-dependent kinase (Cdk1) orchestrates progression through the cell cycle by coordinating the activities of cell-cycle regulators. Although phosphatases that oppose Cdk1 are likely to be necessary to establish dynamic phosphorylation, specific phosphatases that target most Cdk1 substrates have not been identified. In budding yeast, the transcription factor Hcm1 activates expression of genes that regulate chromosome segregation and is critical for maintaining genome stability. Previously we found that Hcm1 activity and degradation are stimulated by Cdk1 phosphorylation of distinct clusters of sites. Here we show that, upon exposure to environmental stress, the phosphatase calcineurin inhibits Hcm1 by specifically removing activating phosphorylations and that this regulation is important for cells to delay proliferation when they encounter stress. Our work identifies a mechanism by which proliferative signals from Cdk1 are removed in response to stress and suggests that Hcm1 functions as a rheostat that integrates stimulatory and inhibitory signals to control cell proliferation

Failure by congestion of pedicled and free flaps for reconstruction of lower limbs after trauma: the role of negative-pressure wound therapy

Lower limb reconstruction with pedicled or free flaps can be commonly compromised by venous insufficiency. This complication often leads to partial/complete flap necrosis and increases the risk of superinfection. Negative-pressure wound therapy (NPWT) is known to increase local blood flow, decrease edema, promote tissue granulation, and reduce the likelihood of soft tissue infection. This study aims to evaluate the effectiveness of NPWT in the treatment of congested pedicled and free flaps of the lower limb after reconstructions in lower limb traumas. A retrospective analysis was performed on four congested (pedicled and free) flaps on the lower limbs. NPWT was applied in all cases after partial flap debridement. NPWT was able to improve and resolve tissue edema and venous insufficiency, avoid further flap necrosis, and promote granulation. On NPWT removal, a split-thickness skin graft was applied on the wound, achieving complete and uneventful healing. NPWT is a useful instrument in managing flaps affected by venous insufficiency in lower limb reconstruction, although larger studies are necessary to better define the effectiveness and indications of NPWT in this setting

Obturator nerve split for gracilis free-flap double reinnervation in facial paralysis

The use of a double-powered free muscle transfer for facial reanimation has been reported by several authors with different types of nerve coaptation. A new nerve coaptation strategy is presented herein. We performed a 1-stage double-powered free gracilis muscle flap transfer in a patient with long-standing facial paralysis by splitting the obturator nerve and anastomosing the 2 free ends to the contralateral facial nerve (through a sural graft) and to the masseteric nerve. Voluntary movement of the transferred muscle with teeth clenching was observed at 6 months after the operation and a symmetric smile with bilateral elevation of the mouth angle at 10 months. Our limited experience suggests that in case of a large cross-section of the obturator nerve, the latter can be split and sutured to the ipsilateral masseteric nerve and to the contralateral facial nerve with a sural graft by double end-to-end anastomosis

A Potent and Effective Suicidal Listeria Vaccine Platform.

Live-attenuated Listeria monocytogenes has shown encouraging potential as an immunotherapy platform in preclinical and clinical settings. However, additional safety measures will enable application across malignant and infectious diseases. Here, we describe a new vaccine platform, termed Lm-RIID (L. monocytogenes recombinase-induced intracellular death), that induces the deletion of genes required for bacterial viability yet maintains potent T cell responses to encoded antigens. Lm-RIID grows normally in broth but commits suicide inside host cells by inducing Cre recombinase and deleting essential genes flanked by loxP sites, resulting in a self-limiting infection even in immunocompromised mice. Lm-RIID vaccination of mice induces potent CD8+ T cells and protects against virulent challenges, similar to live L. monocytogenes vaccines. When combined with α-PD-1, Lm-RIID is as effective as live-attenuated L. monocytogenes in a therapeutic tumor model. This impressive efficacy, together with the increased clearance rate, makes Lm-RIID ideal for prophylactic immunization against diseases that require T cells for protection

The coordinate actions of calcineurin and Hog1 mediate the stress response through multiple nodes of the cell cycle network

Upon exposure to environmental stressors, cells transiently arrest the cell cycle while they adapt and restore homeostasis. A challenge for all cells is to distinguish between stress signals and coordinate the appropriate adaptive response with cell cycle arrest. Here we investigate the role of the phosphatase calcineurin (CN) in the stress response and demonstrate that CN activates the Hog1/p38 pathway in both yeast and human cells. In yeast, the MAPK Hog1 is transiently activated in response to several well-studied osmostressors. We show that when a stressor simultaneously activates CN and Hog1, CN disrupts Hog1-stimulated negative feedback to prolong Hog1 activation and the period of cell cycle arrest. Regulation of Hog1 by CN also contributes to inactivation of multiple cell cycle-regulatory transcription factors (TFs) and the decreased expression of cell cycle-regulated genes. CN-dependent downregulation of G1/S genes is dependent upon Hog1 activation, whereas CN inactivates G2/M TFs through a combination of Hog1-dependent and -independent mechanisms. These findings demonstrate that CN and Hog1 act in a coordinated manner to inhibit multiple nodes of the cell cycle-regulatory network. Our results suggest that crosstalk between CN and stress-activated MAPKs helps cells tailor their adaptive responses to specific stressors

A proposito di un caso di ricostruzione della mano mediante uso di sostituto dermico

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Surgical excision of Infantile Haemangiomas: a technical refinement to prevent bleeding complications

Purpose: The aim of the study is to improve operative speed and precision of haemangiomas excision. Methods: Case-report: haemangioma is a common affection of the 8% of the population during the neonatal period. In complicated cases and involution sequelae surgical treatment is the first choice. The Authors propose a surgical refinement to prevent intraoperative bleeding. Methods: several suture stitches were placed around the hemangioma. The edges of the lesion became more defined, thus allowing accurate excision. Results and Conclusions: Haemangiomas are characterized by rich blood supply. Surgery is often hindered by massive bleeding and Temporary placement of full-thickness sutures, surrounding the hemangioma, allowed a noticeable improvement in hemostasis precision and greater definition of the margins of the hemangioma