Identifying substrate proteins for GAN1 and Keap1

Abstract only availableGAN1 and Keap1 are proteins characterized by a N-terminal BTB domain and a C-terminal Kelch repeat domain. Both of these domains are protein-protein interaction domains, suggesting that these BTB-Kelch proteins form signaling complexes in cells. Previous work has suggested that BTB-Kelch proteins function as substrate adaptor proteins for Cul3-dependent E3 ubiquitin ligase complexes. The goal of this project was to identify substrate proteins of GAN1 and Keap1. This information will be particularly useful when for understanding Giant Axonal Neuropathy, a sensorimotor disease characterized by excessive accumulation of neurofilaments in neurons that contain mutated GAN1 genes. We used an affinity purification approach to identify candidate substrate proteins for GAN1 and Keap1. Recombinant GAN1 and Keap1 genes containing a C-terminal chitin binding domain (CBD) were inserted into pBabe puro vectors. These vectors were used to generate virus stocks, which were used to infect a microglial cell line, BV-2. Stable cell lines were generated using puromycin selection. A mock-infected cell line was generated in parallel. When the cell lines were confluent, the cells were lysed using a 0.1% SDS RIPA solution and chitin beads were used to precipitate the CBD-tagged proteins. Western blot analyses were performed to determine if the purification of the CBD-tagged proteins was successful. No CBD-tagged proteins were identified in our first pull-down experiment. We are currently reexamining the precipitation protocol and preparing to lysate the same set of cells.Life Sciences Undergraduate Research Opportunity Progra

A healing journey with chronic pain – a meta-ethnography synthesising 195 qualitative studies

Objective There is a large body of research exploring what it means for a person to live with chronic pain. However, existing research does not help us understand what it means to recover. We aimed to identify qualitative research that explored the experience of living with chronic pain published since 2012 and to understand the process of recovery. Design A synthesis of qualitative research using meta-ethnography. Methods We used the seven stages of meta-ethnography. We systematically searched for qualitative research, published since 2012, that explored adults’ experiences of living with, and being treated for, chronic pain. We used constant comparison to distill the essence of ideas into themes and developed a conceptual model. Results We screened 1,328 titles and included 195 studies. Our conceptual model indicates that validation and reconnection can empower a person with chronic pain to embark on a journey of healing. To embark on this journey requires commitment, energy, and support. Conclusions The innovation of our study is to conceptualize healing as an ongoing and iterating journey rather than a destination. Health interventions for chronic pain would usefully focus on validating pain through meaningful and acceptable explanations; validating patients by listening to and valuing their stories; encouraging patients to connect with a meaningful sense of self, to be kind to themselves, and to explore new possibilities for the future; and facilitating safe reconnection with the social world. This could make a real difference to people living with chronic pain who are on their own healing journeys

NeuroSpeech

NeuroSpeech is a software for modeling pathological speech signals considering different speech dimensions: phonation, articulation, prosody, and intelligibility. Although it was developed to model dysarthric speech signals from Parkinson's patients, its structure allows other computer scientists or developers to include other pathologies and/or measures. Different tasks can be performed: (1) modeling of the signals considering the aforementioned speech dimensions, (2) automatic discrimination of Parkinson's vs. non-Parkinson's, and (3) prediction of the neurological state according to the Unified Parkinson's Disease Rating Scale (UPDRS) score. The prediction of the dysarthria level according to the Frenchay Dysarthria Assessment scale is also provided

Transformation Textures in Zirconia

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65433/1/j.1151-2916.1993.tb03696.x.pd

Multi-view representation learning via gcca for multimodal analysis of Parkinson's disease

Information from different bio-signals such as speech, handwriting, and gait have been used to monitor the state of Parkinson's disease (PD) patients, however, all the multimodal bio-signals may not always be available. We propose a method based on multi-view representation learning via generalized canonical correlation analysis (GCCA) for learning a representation of features extracted from handwriting and gait that can be used as a complement to speech-based features. Three different problems are addressed: classification of PD patients vs. healthy controls, prediction of the neurological state of PD patients according to the UPDRS score, and the prediction of a modified version of the Frenchay dysarthria assessment (m-FDA). According to the results, the proposed approach is suitable to improve the results in the addressed problems, specially in the prediction of the UPDRS, and m-FDA scores

Similar TKA designs with differences in clinical outcome: A randomized, controlled trial of 77 knees with a mean follow-up of 6 years

Contains fulltext : 96347.pdf (publisher's version ) (Open Access)Background and purpose To try to improve the outcome of our TKAs, we started to use the CKS prosthesis. However, in a retrospective analysis this design tended to give worse results. We therefore conducted a randomized, controlled trial comparing this CKS prosthesis and our standard PFC prosthesis. Because many randomized studies between different TKA concepts generally fail to show superiority of a particular design, we hypothesized that these seemingly similar designs would not lead to any difference in clinical outcome. Patients and methods 82 patients (90 knees) were randomly allocated to one or other prosthesis, and 39 CKS prostheses and 38 PFC prostheses could be followed for mean 5.6 years. No patients were lost to follow-up. At each follow-up, patients were evaluated clinically and radiographically, and the KSS, WOMAC, VAS patient satisfaction scores and VAS for pain were recorded. Results With total Knee Society score (KSS) as primary endpoint, there was a difference in favor of the PFC group at final follow-up (p = 0.04). Whereas there was one revision in the PFC group, there were 6 revisions in the CKS group (p = 0.1). The survival analysis with any reoperation as endpoint showed better survival in the PFC group (97% (95% CI: 92-100) for the PFC group vs. 79% (95% CI: 66-92) for the CKS group) (p = 0.02). Interpretation Our hypothesis that there would be no difference in clinical outcome was rejected in this study. The PFC system showed excellent results that were comparable to those in previous reports. The CKS design had differences that had considerable negative consequences clinically. The relatively poor results have discouraged us from using this design