A Chaperone Trap Contributes to the Onset of Cystic Fibrosis

Protein folding is the primary role of proteostasis network (PN) where chaperone interactions with client proteins determine the success or failure of the folding reaction in the cell. We now address how the Phe508 deletion in the NBD1 domain of the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) protein responsible for cystic fibrosis (CF) impacts the binding of CFTR with cellular chaperones. We applied single ion reaction monitoring mass spectrometry (SRM-MS) to quantitatively characterize the stoichiometry of the heat shock proteins (Hsps) in CFTR folding intermediates in vivo and mapped the sites of interaction of the NBD1 domain of CFTR with Hsp90 in vitro. Unlike folding of WT-CFTR, we now demonstrate the presence of ΔF508-CFTR in a stalled folding intermediate in stoichiometric association with the core Hsps 40, 70 and 90, referred to as a ‘chaperone trap’. Culturing cells at 30 C resulted in correction of ΔF508-CFTR trafficking and function, restoring the sub-stoichiometric association of core Hsps observed for WT-CFTR. These results support the interpretation that ΔF508-CFTR is restricted to a chaperone-bound folding intermediate, a state that may contribute to its loss of trafficking and increased targeting for degradation. We propose that stalled folding intermediates could define a critical proteostasis pathway branch-point(s) responsible for the loss of function in misfolding diseases as observed in CF

How Therapists Use Visualizations of Upper Limb Movement Information From Stroke Patients: A Qualitative Study With Simulated Information.

BACKGROUND: Stroke is a leading cause of disability worldwide, with upper limb deficits affecting an estimated 30% to 60% of survivors. The effectiveness of upper limb rehabilitation relies on numerous factors, particularly patient compliance to home programs and exercises set by therapists. However, therapists lack objective information about their patients' adherence to rehabilitation exercises as well as other uses of the affected arm and hand in everyday life outside the clinic. We developed a system that consists of wearable sensor technology to monitor a patient's arm movement and a Web-based dashboard to visualize this information for therapists. OBJECTIVE: The aim of our study was to evaluate how therapists use upper limb movement information visualized on a dashboard to support the rehabilitation process. METHODS: An interactive dashboard prototype with simulated movement information was created and evaluated through a user-centered design process with therapists (N=8) at a rehabilitation clinic. Data were collected through observations of therapists interacting with an interactive dashboard prototype, think-aloud data, and interviews. Data were analyzed qualitatively through thematic analysis. RESULTS: Therapists use visualizations of upper limb information in the following ways: (1) to obtain objective data of patients' activity levels, exercise, and neglect outside the clinic, (2) to engage patients in the rehabilitation process through education, motivation, and discussion of experiences with activities of daily living, and (3) to engage with other clinicians and researchers based on objective data. A major limitation is the lack of contextual data, which is needed by therapists to discern how movement data visualized on the dashboard relate to activities of daily living. CONCLUSIONS: Upper limb information captured through wearable devices provides novel insights for therapists and helps to engage patients and other clinicians in therapy. Consideration needs to be given to the collection and visualization of contextual information to provide meaningful insights into patient engagement in activities of daily living. These findings open the door for further work to develop a fully functioning system and to trial it with patients and clinicians during therapy

Estudio de la formación de contaminantes fotoquímicos mediante la modelación matemática y sus efectos en la salud en el Valle de Aburra

IP 1210-13-234-98PONENCIA(S) EN CONGRESO: Numeral investigation of meteorologicalconditions leading to elevated ozone;concentrations in Medellin, Colombia / P. Sahm ... [et al.]. --En: International Conference on Urban Air;Quality and Saturn Workshop (3, 5 : 2001 Mar. 19-23 : Loutraki,Grecia). -- [s.l. : s.n.], 2001. -- p. ; 28;cm. -- Emission inventory in Medellin (Colombia) city : anaproximation /M.V. Toro ... [et al.]. -- En:;contaminantes atmosfericos en la ciudad de Medellin mediante factores de emision Corinar / M. Victoria Toro G.;... [et al.] -- En: Acodal -- Vol. 191 (2002); p. -- ISSN120798 -- Diagnostico de la calidad del aire en el;ancon sur del valle de Aburra / Maria Victoria Toro ... [et al.]'-- en: Contaminacion ambiental. -- Vol. 17,;no. 30-31 (2000); p. 93-103. -- ISSN 01200674.;International Conference on Urban Air Quality and Saturn Workshop (3, 5 :2001 Mar. 19-23 : Loutraki, Grecia).; [s.l. : s.n.], 2001. -- p. ; 28 cm. -- ARTICULO(S) EN REVISTA: Calculode la emision vehicular d