F-actin mechanics control spindle centring in the mouse zygote

International audienceMitotic spindle position relies on interactions between astral microtubules nucleated by centrosomes and a rigid cortex. Some cells, such as mouse oocytes, do not possess centrosomes and astral microtubules. These cells rely only on actin and on a soft cortex to position their spindle off-centre and undergo asymmetric divisions. While the first mouse embryonic division also occurs in the absence of centrosomes, it is symmetric and not much is known on how the spindle is positioned at the exact cell centre. Using interdisciplinary approaches, we demonstrate that zygotic spindle positioning follows a three-step process: (1) coarse centring of pronuclei relying on the dynamics of an F-actin/Myosin-Vb meshwork; (2) fine centring of the metaphase plate depending on a high cortical tension; (3) passive maintenance at the cell centre. Altogether, we show that F-actin-dependent mechanics operate the switch between asymmetric to symmetric division required at the oocyte to embryo transition

Negotiations of minority ethnic rugby league players in the Cathar country of France

This article is based on new empirical, qualitative research with minority ethnic rugby league players in the southwest of France. Drawing on similar research on rugby league in the north and the south of England, the article examines how rugby league, traditionally viewed as a white, working-class male game (Collins, 2006; Denham, 2004; Spracklen, 1995, 2001) has had to re-imagine its symbolic boundaries as they are constituted globally and locally to accommodate the needs of players from minority ethnic backgrounds. In particular, the article examines the sense in which experiences of minority ethnic rugby league players in France compare with those of their counterparts in England (Spracklen, 2001, 2007), how rugby league is used in France to construct identity, and in what sense the norms associated with the imaginary community of rugby league are replicated or challenged by the involvement of minority ethnic rugby league players in France. Questions about what it means to be (provincial, national) French (Kumar, 2006) are posed, questions that relate to the role of sport in the construction of Frenchness, and in particular the role of rugby league (and union). © Copyright ISSA and SAGE Publications

Artificially decreasing cortical tension generates aneuploidy in mouse oocytes

Human and mouse oocytes’ developmental potential can be predicted by their mechanical properties. Their development into blastocysts requires a specific stiffness window. In this study, we combine live-cell and computational imaging, laser ablation, and biophysical measurements to investigate how deregulation of cortex tension in the oocyte contributes to early developmental failure. We focus on extra-soft cells, the most common defect in a natural population. Using two independent tools to artificially decrease cortical tension, we show that chromosome alignment is impaired in extra-soft mouse oocytes, despite normal spindle morphogenesis and dynamics, inducing aneuploidy. The main cause is a cytoplasmic increase in myosin-II activity that could sterically hinder chromosome capture. We describe here an original mode of generation of aneuploidies that could be very common in oocytes and could contribute to the high aneuploidy rate observed during female meiosis, a leading cause of infertility and congenital disorders

Geriatric oncology: comparing health related quality of life in head and neck cancer patients

Background: Population ageing is increasing the number of people annually diagnosed with cancer worldwide, once most types of tumours are age-dependent. High-quality healthcare in geriatric oncology requires a multimodal approach and should take into account stratified patient outcomes based on factors other than chronological age in order to develop interventions able to optimize oncology care. This study aims to evaluate the Health Related Quality of Life in head and neck cancer patients and compare the scores in geriatric and younger patients. Methods. Two hundred and eighty nine head and neck cancer patients from the Oncology Portuguese Institute participated in the Health Related Quality of Life assessment. Two patient groups were considered: the geriatric ( 65 years old, n = 115) and the younger (45-60 years old, n= 174). The EORTC QLQ-C30 and EORTC QLQ-H&N35 questionnaires were used. Results: Head and neck cancer patients were mostly males, 77.4% within geriatric group and 91.4% among younger patients group. The most frequent tumour locations were similar in both groups: larynx, oral cavity and oropharynx - base of the tongue. At the time of diagnosis, most of younger male patients were at disease stage III/IV (55.9%) whereas the majority of younger female patients were at disease stage I/II (83.4%). The geriatric patient distribution was found to be similar in any of the four disease stages and no gender differences were observed. We found that age (geriatrics scored generally worse), gender (females scored generally worse), and tumour site (larynx tumours denounce more significant problems between age groups) clearly influences Health Related Quality of Life perceptions. Conclusions: Geriatric oncology assessments signalize age-independent indicators that might guide oncologic geriatric care optimization. Decision-making in geriatric oncology must be based on tumour characteristics and chronological age but also on performance status evaluation, co-morbidity, and patient reported outcomes assessment.info:eu-repo/semantics/publishedVersio

Phase I study of docetaxel in combination with cyclophosphamide as first-line chemotherapy for metastatic breast cancer

This phase I was study conducted to establish the maximum tolerated dose, dose-limiting toxicity, and recommended dose of docetaxel in combination with cyclophosphamide as first-line chemotherapy for metastatic breast cancer. Twenty-six patients were treated with cyclophosphamide (600 mg m−2, intravenous bolus) followed by docetaxel (60, 75 or 85 mg m−2, 1-h intravenous infusion) every 3 weeks. The maximum tolerated dose was docetaxel 85 mg m−2 with cyclophosphamide 600 mg m−2, the dose-limiting toxicity being febrile neutropenia. Grade 4 neutropenia was experienced by all patients, but was generally brief. Otherwise, the combination was well tolerated with few acute and no chronic non-haematological toxicities of grade 3/4. Activity was observed at all dose levels and disease sites, and the overall response rate was 42% (95% confidence interval 22–61%). The pharmacokinetics of docetaxel were not modified by cyclophosphamide coadministration. These findings establish a recommended dose of docetaxel 75 mg m−2 in combination with cyclophosphamide 600 mg m−2 every three weeks for phase II evaluation

The need for multidisciplinarity in specialist training to optimize future patient care

Harmonious interactions between radiation, medical, interventional and surgical oncologists, as well as other members of multidisciplinary teams, are essential for the optimization of patient care in oncology. This multidisciplinary approach is particularly important in the current landscape, in which standard-of-care approaches to cancer treatment are evolving towards highly targeted treatments, precise image guidance and personalized cancer therapy. Herein, we highlight the importance of multidisciplinarity and interdisciplinarity at all levels of clinical oncology training. Potential deficits in the current career development pathways and suggested strategies to broaden clinical training and research are presented, with specific emphasis on the merits of trainee involvement in functional multidisciplinary teams. Finally, the importance of training in multidisciplinary research is discussed, with the expectation that this awareness will yield the most fertile ground for future discoveries. Our key message is for cancer professionals to fulfil their duty in ensuring that trainees appreciate the importance of multidisciplinary research and practice

Meiotic Regulation of TPX2 Protein Levels Governs Cell Cycle Progression in Mouse Oocytes

Formation of female gametes requires acentriolar spindle assembly during meiosis. Mitotic spindles organize from centrosomes and via local activation of the RanGTPase on chromosomes. Vertebrate oocytes present a RanGTP gradient centred on chromatin at all stages of meiotic maturation. However, this gradient is dispensable for assembly of the first meiotic spindle. To understand this meiosis I peculiarity, we studied TPX2, a Ran target, in mouse oocytes. Strikingly, TPX2 activity is controlled at the protein level through its accumulation from meiosis I to II. By RNAi depletion and live imaging, we show that TPX2 is required for spindle assembly via two distinct functions. It controls microtubule assembly and spindle pole integrity via the phosphorylation of TACC3, a regulator of MTOCs activity. We show that meiotic spindle formation in vivo depends on the regulation of at least a target of Ran, TPX2, rather than on the regulation of the RanGTP gradient itself

Screening for Vulnerability in Older Cancer Patients: The ONCODAGE Prospective Multicenter Cohort Study:

Background: Geriatric Assessment is an appropriate method for identifying older cancer patients at risk of life-threatening events during therapy. Yet, it is underused in practice, mainly because it is time- and resource-consuming. This study aims to identify the best screening tool to identify older cancer patients requiring geriatric assessment by comparing the performance of two short assessment tools the G8 and the Vulnerable Elders Survey (VES-13). Patients and Methods: The diagnostic accuracy of the G8 and the (VES-13) were evaluated in a prospective cohort study of 1674 cancer patients accrued before treatment in 23 health care facilities. 1435 were eligible and evaluable. Outcome measures were multidimensional geriatric assessment (MGA), sensitivity (primary), specificity, negative and positive predictive values and likelihood ratios of the G8 and VES-13, and predictive factors of 1-year survival rate. Results: Patient median age was 78.2 years (70-98) with a majority of females (69.8%), various types of cancer including 53.9% breast, and 75.8% Performance Status 0-1. Impaired MGA, G8, and VES-13 were 80.2%, 68.4%, and 60.2%, respectively. Mean time to complete G8 or VES-13 was about five minutes. Reproducibility of the two questionnaires was good. G8 appeared more sensitive (76.5% versus 68.7%, P5 0.0046) whereas VES-13 was more specific (74.3% versus 64.4%, P<0.0001). Abnormal G8 score (HR = 2.72), advanced stage (HR = 3.30), male sex (HR = 2.69) and poor Performance Status (HR = 3.28) were independent prognostic factors of 1-year survival. Conclusion: With good sensitivity and independent prognostic value on 1-year survival, the G8 questionnaire is currently one of the best screening tools available to identify older cancer patients requiring geriatric assessment, and we believe it should be implemented broadly in daily practice. Continuous research efforts should be pursued to refine the selection process of older cancer patients before potentially life-threatening therapy