Tubulin tyrosination is a major factor affecting the recruitment of CAP-Gly proteins at microtubule plus ends

Tubulin-tyrosine ligase (TTL), the enzyme that catalyzes the addition of a C-terminal tyrosine residue to α-tubulin in the tubulin tyrosination cycle, is involved in tumor progression and has a vital role in neuronal organization. We show that in mammalian fibroblasts, cytoplasmic linker protein (CLIP) 170 and other microtubule plus-end tracking proteins comprising a cytoskeleton-associated protein glycine-rich (CAP-Gly) microtubule binding domain such as CLIP-115 and p150 Glued, localize to the ends of tyrosinated microtubules but not to the ends of detyrosinated microtubules. In vitro, the head domains of CLIP-170 and of p150 Glued bind more efficiently to tyrosinated microtubules than to detyrosinated polymers. In TTL-null fibroblasts, tubulin detyrosination and CAP-Gly protein mislocalization correlate with defects in both spindle positioning during mitosis and cell morphology during interphase. These results indicate that tubulin tyrosination regulates microtubule interactions with CAP-Gly microtubule plus-end tracking proteins and provide explanations for the involvement of TTL in tumor progression and in neuronal organization

ASO Visual Abstract: Functional Cerebral MRI Evaluation of the Integration of Breast Reconstruction into the Body Schema

International audienceNo abstract availabl

Functional Cerebral MRI Evaluation of Integration of Breast Reconstruction into the Body Schema

International audienceBackground: The objective of breast reconstruction (BR) is to erase the after-effects of total mastectomy by allowing patients to restore their breast shape. The aim of our study was to investigate the body map integration of different types of BR using functional magnetic resonance (fMRI). Patients and Methods: We prospectively enrolled all women undergoing BR for breast cancer to the Remasco study (NCT02553967). Participants were categorized into four groups according to the standard of care they required: immediate BR (IBR), delayed BR (DBR), flap (autologous), or implant BR. Each patient performed sensorimotor tasks during the fMRI acquisition. Results: Data of 38 patients were analyzed. We identified the cingulate region as the area of interest in the brain. In the case of DBR, the brain area activated during palpation of the total mastectomy scar (before BR) was different from the brain area activated during palpation of the reconstructed breast (Brodmann areas 31 versus 32). Palpation of the native breast and reconstructed breast activated the same Brodmann area 32. Comparing the brain activation signal during palpation of the native breast and the reconstructed breast did not reveal any significant difference in the overall population (P = 0.41) or in the groups: autologous (P = 0.32), implant (P = 0.10), IBR (P = 0.72), or DBR (P = 0.10). Conclusions: This experimental study allowed us to describe and understand the brain plasticity processes that accompany BR. The results suggest that the reconstructed breast is integrated into the body schema, regardless of the type of BR or the timing

Exploiting the superior protein resistance of polymer brushes to control single cell adhesion and polarisation at the micron scale

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Mimicking normal tissue architecture and perturbation in cancer with engineered micro-epidermis

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Severe perioperative morbidity after robot-assisted versus conventional laparoscopy in gynecologic oncology: Results of the randomized ROBOGYN-1004 trial

International audienceObjective: In gynecologic oncology, minimally invasive surgery using conventional laparoscopy (CL) decreases the incidence of severe morbidity compared to open surgery. In 2005, robot-assisted laparoscopy (RL) was approved for use in gynecology in the US. This study aimed to assess whether RL is superior to CL in terms of morbidity incidence. Methods: ROBOGYN-1004 (ClinicalTrials.gov, NCT01247779) was a multicenter, phase III, superiority randomized trial that compared RL and CL in patients with gynecologic cancer requiring minimally invasive surgery. Patients were recruited between 2010 and 2015. The primary endpoint was incidence of severe perioperative morbidity (severe complications during or 6 months after surgery). Results: Overall, 369 of 385 patients were included in the as-treated analysis: 176 and 193 underwent RL and CL, respectively. The median operating time for RL was 190 (range, 75–432) minutes and for CL was 145 (33–407) minutes (p < 0.001). The blood loss volumes for the corresponding procedures were 100 (0–2500) and 50 (0–1000) mL (p = 0.003), respectively. The overall rates of conversion to open surgery for the corresponding procedures were 7% (10/176) and 5% (10/193), respectively (p = 0.52). Severe perioperative morbidity occurred in 28% (49/176) and 21% (41/192) of patients who underwent RL and CL, respectively (p = 0.15). At a median follow-up of 25.1 months (range, 0.6–78.2), no significant differences in overall and disease-free survival were observed between the groups. Conclusions: RL was not found superior to CL with regard to the incidence of severe perioperative morbidity in patients with gynecologic cancer. In addition, RL involved a longer operating time than CL