Human SEL1L is an endoplasmic reticulum (ER) 3 resident protein (1-3) intensively expressed in neuroepithelial and pancreatic structures (4). Mouse SEL1L (mSEL-1L) was reported to be abundantly represented throughout the neural tube and dorsal root ganglia with higher abundance in the floor plate starting at embryonic day 10.5 (5). Recently, it has been shown that mSEL-1L gene trap mice were embryonic lethal and displayed growth and differentiation impairment of pancreatic epithelial cells (6). This is probably due to a systemic endoplasmic reticulum stress, which activated a defective unfolded protein response and impaired protein degradation (7).SEL1L, in association with HRD1 (E3 ligase), is a key component of the endoplasmic reticulum-associated degradation pathway, acting as a "gate keeper" in the control of newly synthesized soluble and membrane-bound proteins (1, 2). ER quality control mechanisms (8 -10) and proteasome degradation (11) are known to regulate proteins implicated in different cellular processes. Several reports have highlighted the role of ubiquitin ligases and proteasome in neural stem cell self-renewal, survival, and commitment (9, 10). The ubiquitin-proteasome-mediated degradation controls the availability of NSC fundamental proteins, such as Nestin (12), REST (repressor element 1-silencing transcription factor) (13-16), N-Myc (17), and components of the Notch/Delta/Numb pathway (18 -20). Actually, one of the most important goals in stem cell biology is to unravel the mechanisms that control stem cell self-renewal by modulating molecules with key roles in stemness or cell fate choice (21). The proteasomal degradation pathway is a very complicated regulatory network that integrates cell intrinsic and cell extrinsic signals and partially controls the balance between self-renewal and differentiation. In particularly, epigenetic modifiers, no-coding RNA regulators (microRNA: miR-9, let-7b, miR-137, and miR-124) (22), and specific signaling pathways (Notch, FGF, Wnt, Hedgehog, and ␤-catenin) (23) are emerging as a coordinated machinery that manages NSC fate by activating/repressing specific key regulators. In this study, we explored the possible involvement of mSEL-1L in this network. We found that mSEL-1L protein is selectively expressed in pluripotent embryonic stem cells and in multipotent NSCs, acting as a primitive marker of stemness. We also show that mSEL-1L protein expression is finely controlled by fine microRNA regulation both in vivo during mouse embryonic development and in vitro during NSC differentiation. However, its complete depletion heavily affects self-renewal capacity, by negatively regulating those important genes known to maintain the neural progenitor state. The results here presented reaffirm the previously published concept that mSEL-1L is a "multifaced" protein (4), affecting different biochemical pathways.

No abstract

This paper describes the formation of a civil society consortium, spurred to action by frustration over the Ebola crises, to facilitate the development of infrastructure and frameworks including policy development to support a harmonized, African approach to health crises on the continent. The Global Emerging Pathogens Treatment Consortium, or GET, is an important example of how African academics, scientists, clinicians and civil society have come together to initiate policy research, multilevel advocacy and implementation of initiatives aimed at building African capacity for timely and effective mitigations strategies against emerging infectious and neglected pathogens, with a focus on biobanking and biosecurity. The consortium has been able to establish it self as a leading voice, drawing attention to scientific infrastructure gaps, the importance of cultural sensitivities, and the power of community engagement. The GET consortium demonstrates how civil society can work together, encourage government engagement and strengthen national and regional efforts to build capacity.

No abstract