Dysregulation of oxygen hemodynamic responses to synaptic train stimulation in a rat hippocampal model of subarachnoid hemorrhage

We investigated microvascular reactivity to synaptic train stimulation after induction of subarachnoid hemorrhage in adult rats, analyzing tissue oxygen levels [pO₂] in intact hippocampus. In control rats, hippocampal pO₂ averaged 11.4 mm Hg whereas hemodynamic responses averaged 13.1 mm Hg (to a 25 s train). After subarachnoid hemorrhage (at 2 days), we recorded a dramatic elevation in baseline pO₂ in the hippocampus (to 68.4 mm Hg) accompanied by inverted pO₂ responses to synaptic train stimulation (−9.46 mm Hg). These significant changes in baseline hippocampal pO₂ and inverted pO₂ responses after subarachnoid hemorrhage indicate severe alterations of neurovascular coupling and neuronal viability.     

MZB1 is a GRP94 cochaperone that enables proper immunoglobulin heavy chain biosynthesis upon ER stress

MZB1 (pERp1) is a B-cell-specific and endoplasmic reticulum (ER)-localized protein implicated in antibody secretion and integrin-mediated cell adhesion. Here, we examine the role of MZB1 in vivo by conditional gene inactivation in the mouse germline and at different stages of B lymphopoiesis. Deletion of MZB1 impairs humoral immune responses and antibody secretion in plasma cells that naturally undergo ER stress. In addition, we found that experimental induction of ER stress by tunicamycin injections in mice results in a block of pro-B-cell to pre-B-cell differentiation specifically in Mzb1^−/− mice. A similar developmental block was observed in Mzb1^fl/flmb1^Cre mice, whereby a Cre recombinase-induced genotoxic stress unmasks a role for MZB1 in the surface expression of immunoglobulin µ heavy chains (µHCs). MZB1 associates directly with the substrate-specific chaperone GRP94 (also called HSP90B1 or gp96) in an ATP-sensitive manner and is required for the interaction of GRP94 with µHCs upon ER stress. Thus, MZB1 seems to act as a substrate-specific cochaperone of GRP94 that enables proper biosynthesis of µHCs under conditions of ER stress.     

Value-based design for the elderly: An application in the field of mobility aids

In the aging society, the need for the elderly to remain mobile and independent is higher than ever. However, many aids supporting mobility often fail to target real needs and lack acceptance. The aim of this study is to demonstrate how value-based design can contribute to the design of mobility aids that address real needs and thus, lead to high acceptance. We elicited values, facilitators, and barriers of mobility of older adults via ten in-depth interviews. Next, we held co-creation sessions, resulting in several designs of innovative mobility aids, which were evaluated for acceptance via nine in-depth interviews. The interviews resulted in a myriad of key values, such as “independence from family” and “doing their own groceries.” Design sessions resulted in three designs for a wheeled walker. Their acceptance was rather low. Current mobility device users were more eager to accept the designs than non-users. The value-based approach offers designers a close look into the lives of the elderly, thereby opening up a wide range of innovation possibilities that better fit their actual needs. Product service systems seem to be a promising focus for targeting human needs in mobility device design.