RhoH is a negative regulator of eosinophilopoiesis

Eosinophils are frequently elevated in pathological conditions and can cause tissue damage and disease exacerbation. The number of eosinophils in the blood is largely regulated by factors controlling their production in the bone marrow. While several exogenous factors, such as interleukin-5, have been described to promote eosinophil differentiation, comparatively little is known about eosinophil-intrinsic factors that control their de novo generation. Here, we report that the small atypical GTPase RhoH is induced during human eosinophil differentiation, highly expressed in mature blood eosinophils and further upregulated in patients suffering from a hypereosinophilic syndrome. Overexpression of RhoH increases, in a Rho-associated protein kinase-dependent manner, the expression of GATA-2, a transcription factor involved in regulating eosinophil differentiation. In RhoH(-/-) mice, we observed reduced GATA-2 expression as well as accelerated eosinophil differentiation both in vitro and in vivo. Conversely, RhoH overexpression in bone marrow progenitors reduces eosinophil development in mixed bone marrow chimeras. These results highlight a novel negative regulatory role for RhoH in eosinophil differentiation, most likely in consequence of altered GATA-2 levels

Academic freedom: a lawyer's perspective

Academic freedom is central to ideas of higher education, yet in the United Kingdom it is facing challenges from changing managerial approaches within some universities and changing governmental expectations. Universities are increasingly expected to focus upon knowledge which can be shown to have value and to exploit the results of academic enterprise. Resulting constraints on teaching and research by incessant market-driven demands have the potential to compromise academic freedom. This article considers aspects of academic freedom in an increasingly market-driven environment from a lawyer’s perspective. The legal protections for academic freedom in the UK are minimal, and consideration of the intellectual property policies of a significant number of UK universities suggests that, in many, academic outputs, especially those relating to teaching, have become subject to more entrepreneurial models of higher education, becoming potentially saleable products to be owned and exploited by universities as they see fit. The position is exacerbated by increasing developments in the use of technology as part of the teaching process. Academics who lose ownership of aspects of their intellectual output risk the undermining of their position and academic freedom with a current employer and limiting their opportunities to change employer

EVER2 Deficiency is Associated with Mild T-cell Abnormalities

Epidermodysplasia verruciformis (EV) is a rare genodermatosis characterized by persistent flat warts or pityriasis versicolor-like lesions caused by betapapillomaviruses (EV-HPVs). Autosomal recessive EVER1 and EVER2 deficiencies account for EV in most patients. The mechanisms by which mutations in these partners of the Zinc transporter ZnT1 impair host defense against EV-HPVs are still poorly understood. Keratinocytes of EVER-deficient patients display an alteration of zinc homeostasis and an enhanced proliferative activity. Since EVER proteins are highly expressed in T lymphocytes, we aimed to assess the impact of EVER2 deficiency on T-cell development and function. We studied circulating lymphocyte populations in three adult EV patients sharing the same EVER2 mutation (T150fsX3). We found a normal count of CD4(+) and CD8(+) T cells and a normal proliferative capacity in response to anti-CD3 stimulation. However, we observed a significant increase of memory CD4(+) and effector memory CD8(+) T cells, a bias of the TCR Vαβ and Vγδ repertoires and an increase of skin-homing CD4(+) T-cell subsets. Our findings suggest that EVER2-deficient patients display mild T-cell abnormalities. It remains unclear whether these abnormalities result from EVER deficiency, chronic EV-HPV infection, or both