Developmental regulation of cohesin positioning on mammalian chromosome arms

Cohesin has a well-­established role in sister chromatid cohesion and postreplicative DNA repair. In addition, previous work in our laboratory suggested a positive correlation between cohesin binding and gene expression (Parelho et al. 2008). We decided to establish the ChIP-­seq technique to address the relationship between cohesin binding and gene expression at the genome-­wide level. However, in the meantime, several other groups reported genome-­wide binding maps of cohesin in embryonic stem (ES) cells, demonstrating cell-­type-­specific cohesin binding and its correlation with gene expression (Schmidt et al. 2010; Kagey et al. 2010; Nitzsche et al. 2011). Kagey and colleagues argue that cohesin is required for the expression of pluripotency-­associated genes, based on cohesin downregulation for an extended time period. We believe this method generates indirect effects such as cell stress, death and enrichment for slowly cycling differentiating cells, biasing the results towards differentiated cells. We have generated ES cells homozygous for conditional Rad21 alleles and have found that, unlike the Kagey approach, rapid 24-­hour cohesin depletion does not induce cell stress responses. We detect a stronger correlation between cohesin-­bound genes and gene expression changes, suggesting our approach is more accurate in understanding the role of cohesin in gene expression. We have expanded our analysis of cohesin binding by generating ES cells expressing epitope-­tagged BORIS, a paralogue of CTCF. We have mapped BORIS binding sites in ES cells and data suggest that BORIS, unlike CTCF, does not recruit cohesin. To study the specific involvement of cohesin in gene expression, two developmentally regulated models, T cell receptor α (Tcrα) rearrangement and X chromosome inactivation (XCI), have been used. Cohesin loss in non-­cycling developing thymocytes leads to impaired Tcrα rearrangement. Finally, we present evidence that cohesin contributes to creating chromatin boundaries that segregate facultative heterochromatin from active chromatin on the inactive X chromosome in differentiating female ES cells

Systemic Treatment Approaches in Breast Cancer

Breast cancer is the most conmlon malignant tumor among women, with an estimated 135,000 new cases and 58,000 recorded deaths per year in the Europeau Community in 1990. With respect to the Netherlands, the most recent data of The Netherlands Cancer Registry show an incidence of nearly 10.000 new cases of primary breast cancer and about 3500 breast cancer deaths per year. In women breast cancer comprises one-third (33,2%) of all types of cancer. Ultimately about one out of 10 women wiII get breast cancer during her life and one out of every 22 women wiII sooner or later die as a consequence of metastatic disease. Among the solid tumors breast cancer is one of the few types of cancers sensitive to different systemic treatment reginJens both with respect to endocrine- and chemotherapy. Both treatment modalities are nowadays standard practice in the treatment of breast cancer, either to achieve cure, or prolongation of (relapse-free) survival in the adjuvant setting, or to palliate metastatic disease. The efficacy of the different forms of systemic treatment is dependent on patients- and tumor characteristics

Clinical experience with venlafaxine in the treatment of hot flushes in women with a history of breast cancer

OBJECTIVE: To obtain practical experience with venlafaxine for hot flushes in breast cancer patients and incorporate this in a treatment protocol. METHOD: Twenty-two women with a history of breast cancer (mean age 49.2 years, range 35-65) were referred for consideration of treatment with venlafaxine for hot flushes. Patients received extensive information on treatment with venlafaxine and were advised to self-monitor the frequency of their hot flushes. RESULTS: Eight women did not start venlafaxine because they had no postmenopausal complaints, were lost to follow-up, had too low a frequency of hot flushes, or refused treatment. Eventually 14 women started venlafaxine. Two of them did not tolerate venlafaxine, four reported some effect but stopped because of side effects, two women had no effect whatsoever. Six women observed a clear ( > 50%) reduction in their hot flush frequency that was maintained at a median follow-up of 13 months. CONCLUSION: The group of patients referred for treatment was more heterogeneous and more patients dropped out because of side effects than expected. Extensive patient education, patient selection and evaluation of the treatment effect (by self-monitoring of hot flush frequency) are mandatory to avoid useless (continuation of) treatment and to prepare patients for side effects. Under these conditions, a substantial minority of patients benefit from venlafaxine

Кон'юнктурний аналіз розвитку ринку рекреаційних послуг АР Крим

Метою дослідження є кон’юнктурний аналіз розвитку ринку рекреаційних послуг АР Крим та порівняльна оцінка функціонування конкурентоспроможних рекреаційних районів

Rethinking the role of volunteering in the labour market inclusion of migrants

In this article we critically investigate the role that volunteering can have in the labour market inclusion of migrants. We consider how volunteering can both enhance and hinder inclusion through a comparison of two different contexts: Finland and the UK, where both welfare state and migration regimes are differently shaped. We also question whether volunteering to gain work experience can be defined as ‘volunteering’ or whether it corresponds more with a definition of unpaid labour. Our research is based on 104 interviews with migrants (including refugees and asylum seekers) from various nationalities. We find that volunteering is used in both countries as a way to gain work experience, in the absence of opportunities to enter regular employment. However, volunteering rarely directly leads to employment even though it may facilitate it indirectly, and thus risks trapping migrants in a vicious cycle that does not always lead to labour market inclusion.Output Status: Forthcomin

Negotiating autonomy in the public sector and nonprofits "collaborations" in politically contested fields

Nonprofits are increasingly involved in cross-sectoral collaborations with the public sector. However, we know little about the dynamics behind these collaborations and what happens to them in politically contested fields where actors may have divergent positions. In this article, a multi-country comparison of data gathered from semi-structured interviews (n = 68) with representatives of nonprofits involved in the labor market inclusion of newcomers is presented. Our findings indicate that, in politically contested fields, the possibility of participating in cross-sectoral collaborations (political autonomy) is influenced by nonprofits' financial and ideological autonomy. Welfare models and migration regimes play a fundamental role in shaping the inclusion of these organizations in collaborations, and in most cases, the collaborations are based on latent conflicts. Our article discusses that if the costs of autonomy associated with cross-sectoral collaborations are not offset, the collaboration in a politically contested field becomes a liability for nonprofits (and their beneficiaries)

Rethinking the role of volunteering in the labour market inclusion of migrants

In this article we critically investigate the role that volunteering can have in the labour market inclusion of migrants. We consider how volunteering can both enhance and hinder inclusion through a comparison of two different contexts: Finland and the UK, where both welfare state and migration regimes are differently shaped. We also question whether volunteering to gain work experience can be defined as ‘volunteering’ or whether it corresponds more with a definition of unpaid labour. Our research is based on 104 interviews with migrants (including refugees and asylum seekers) from various nationalities. We find that volunteering is used in both countries as a way to gain work experience, in the absence of opportunities to enter regular employment. However, volunteering rarely directly leads to employment even though it may facilitate it indirectly, and thus risks trapping migrants in a vicious cycle that does not always lead to labour market inclusion