73 research outputs found
The endogenous anti-angiogenic VEGF isoform, VEGF165b inhibits human tumour growth in mice
Vascular endothelial growth factor-A is widely regarded as the principal stimulator of angiogenesis required for tumour growth. VEGF is generated as multiple isoforms of two families, the pro-angiogenic family generated by proximal splice site selection in the terminal exon, termed VEGFxxx, and the anti-angiogenic family formed by distal splice site selection in the terminal exon, termed VEGFxxxb, where xxx is the amino acid number. The most studied isoforms, VEGF165 and VEGF165b have been shown to be present in tumour and normal tissues respectively. VEGF165b has been shown to inhibit VEGF- and hypoxia-induced angiogenesis, and VEGF-induced cell migration and proliferation in vitro. Here we show that overexpression of VEGF165b by tumour cells inhibits the growth of prostate carcinoma, Ewing's sarcoma and renal cell carcinoma in xenografted mouse tumour models. Moreover, VEGF165b overexpression inhibited tumour cell-mediated migration and proliferation of endothelial cells. These data show that overexpression of VEGF165b can inhibit growth of multiple tumour types in vivo indicating that VEGF165b has potential as an anti-angiogenic, anti-tumour strategy in a number of different tumour types, either by control of VEGF165b expression by regulation of splicing, overexpression of VEGF165b, or therapeutic delivery of VEGF165b to tumours
Generation of a Convalescent Model of Virulent Francisella tularensis Infection for Assessment of Host Requirements for Survival of Tularemia
Francisella tularensis is a facultative intracellular bacterium and the causative agent of tularemia. Development of novel vaccines and therapeutics for tularemia has been hampered by the lack of understanding of which immune components are required to survive infection. Defining these requirements for protection against virulent F. tularensis, such as strain SchuS4, has been difficult since experimentally infected animals typically die within 5 days after exposure to as few as 10 bacteria. Such a short mean time to death typically precludes development, and therefore assessment, of immune responses directed against virulent F. tularensis. To enable identification of the components of the immune system that are required for survival of virulent F. tularensis, we developed a convalescent model of tularemia in C57Bl/6 mice using low dose antibiotic therapy in which the host immune response is ultimately responsible for clearance of the bacterium. Using this model we demonstrate αβTCR+ cells, γδTCR+ cells, and B cells are necessary to survive primary SchuS4 infection. Analysis of mice deficient in specific soluble mediators shows that IL-12p40 and IL-12p35 are essential for survival of SchuS4 infection. We also show that IFN-γ is required for survival of SchuS4 infection since mice lacking IFN-γR succumb to disease during the course of antibiotic therapy. Finally, we found that both CD4+ and CD8+ cells are the primary producers of IFN-γand that γδTCR+ cells and NK cells make a minimal contribution toward production of this cytokine throughout infection. Together these data provide a novel model that identifies key cells and cytokines required for survival or exacerbation of infection with virulent F. tularensis and provides evidence that this model will be a useful tool for better understanding the dynamics of tularemia infection
Vascular endothelial growth factor as a survival factor for human islets: effect of immunosuppressive drugs
The balance of proangiogenic and antiangiogenic VEGFA isoforms regulate follicle development
Understanding the vocational functioning of autistic employees: the role of disability and mental health
PURPOSE:
Employment rates for autistic people are low, despite increasing employment-focused programmes. Given the reported complexities for autistic people in finding and keeping work and flourishing there, further exploration is needed to understand how best to help employers accommodate autistic employees.
MATERIAL AND METHODS:
We assessed 88 employed autistic adults, without comorbid intellectual disability and examined whether self-reported disability and mental health symptoms were associated with two measures of vocational functioning: disability days off work and vocational disability.
RESULTS:
Nearly half (47%) reported at least one disability day absence in the previous month. Autism severity and IQ were not associated with either measure of vocational functioning. Greater disability and higher mental health symptoms were associated with both types of vocational functioning. However, the associations of anxiety and stress with both vocational outcomes were attenuated to null in a multivariable model. Disability (B = 6.74, p = 0.009; B = 1.18, p < 0.001) and depression (B = 4.46, p = 0.035; B = 1.01, p = 0.049) remained independently associated with both outcomes.
CONCLUSIONS:
Clinicians and vocational support programmes addressing modifiable factors may need to focus on addressing mental health comorbidities, specifically depression rather than anxiety, or core features of autism to improve vocational outcomes for autistic people.
IMPLICATIONS FOR REHABILITATION:
- Individual-level interventions that reduce disablement, particularly in social areas, and depressive symptoms as a way of reducing days off work and improving workplace activities in autistic employees are recommended.
- Organisations can accommodate autistic employees by encouraging use of mental health programmes or looking at how the workplace environment can be adapted to limit social disability
Language Ideologies and the Experiences of International Students
Through their language policies, universities favour particular languages in the process of learning and this challenges the value, inclusion and power of other languages. This chapter explores this issue from the perspective of international students through a series of task-based focus group interviews that concentrate on the University of Helsinki language policy and which have been analysed using discourse analysis methodology. The findings suggest that while the university is supportive of the development of language proficiency and values languages in general, many languages which are present in the international student body are not used actively for study purposes.Peer reviewe
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