10 th Annual Conference of the International FES Society

Abstract This was a randomized pilot study in which FES was applied as a therapeutic tool to help patients improve voluntary grasp and release movements. The goal of the treatment was to increase hand function, independence in activities of daily living and quality of life. In the treatment group (N=13), daily FES was applied to stimulate weak and non-functional muscles in a sequence of movements to coordinate a hand grasp for manipulating everyday objects. In the control group (N=9), patients received conventional occupational therapy of equal intensity to the treatment group. The following tests were used to measure change: Rehabilitation Engineering Laboratory Hand Function Test, Functional Independence Measure, Spinal Cord Independence Measure and a Qualitative Interview. Preliminary results suggest: 1) the proposed treatment has a positive impact on voluntary hand grasp when used in combination with occupational therapy; 2) greater improvement was expected with incomplete participants, but was also seen with our patients with complete injuries; 3) stimulation programs need to be adjusted by an occupational therapist regularly; and 4) patients report improved voluntary hand function, greater independence and quality of life as a result of the neuroprosthesis treatment

A succinate/SUCNR1-brush cell defense program in the tracheal epithelium

Host-derived succinate accumulates in the airways during bacterial infection. Here, we show that luminal succinate activates murine tracheal brush (tuft) cells through a signaling cascade involving the succinate receptor 1 (SUCNR1), phospholipase Cβ2, and the cation channel transient receptor potential channel subfamily M member 5 (TRPM5). Stimulated brush cells then trigger a long-range Ca2+ wave spreading radially over the tracheal epithelium through a sequential signaling process. First, brush cells release acetylcholine, which excites nearby cells via muscarinic acetylcholine receptors. From there, the Ca2+ wave propagates through gap junction signaling, reaching also distant ciliated and secretory cells. These effector cells translate activation into enhanced ciliary activity and Cl− secretion, which are synergistic in boosting mucociliary clearance, the major innate defense mechanism of the airways. Our data establish tracheal brush cells as a central hub in triggering a global epithelial defense program in response to a danger-associated metabolite

A systematic analysis of the effects of increasing degrees of serum immunodepletion in terms of depth of coverage and other key aspects in top-down and bottom-up proteomic analyses

Immunodepletion of clinical fluids to overcome the dominance by a few very abundant proteins has been explored but studies are few, commonly examining only limited aspects with one analytical platform. We have systematically compared immunodepletion of 6, 14, or 20 proteins using serum from renal transplant patients, analysing reproducibility, depth of coverage, efficiency, and specificity using 2-D DIGE (‘top-down’) and LC-MS/MS (‘bottom-up’). A progressive increase in protein number (≥2 unique peptides) was found from 159 in unfractionated serum to 301 following 20 protein depletion using a relatively high-throughput 1-D-LC-MS/MS approach, including known biomarkers and moderate–lower abundance proteins such as NGAL and cytokine/growth factor receptors. On the contrary, readout by 2-D DIGE demonstrated good reproducibility of immunodepletion, but additional proteins seen tended to be isoforms of existing proteins. Depletion of 14 or 20 proteins followed by LC-MS/MS showed excellent reproducibility of proteins detected and a significant overlap between columns. Using label-free analysis, greater run-to-run variability was seen with the Prot20 column compared with the MARS14 column (median %CVs of 30.9 versus 18.2%, respectively) and a corresponding wider precision profile for the Prot20. These results illustrate the potential of immunodepletion followed by 1-D nano-LC-LTQ Orbitrap Velos analysis in a moderate through-put biomarker discovery process

Keratins regulate protein biosynthesis through localization of GLUT1 and -3 upstream of AMP kinase and Raptor

Removal of the entire keratin family of intermediate filament proteins from embryonic epithelia has surprising implications for mTOR signaling

iTRAQ Identification of Candidate Serum Biomarkers Associated with Metastatic Progression of Human Prostate Cancer

A major challenge in the management of patients with prostate cancer is identifying those individuals at risk of developing metastatic disease, as in most cases the disease will remain indolent. We analyzed pooled serum samples from 4 groups of patients (n = 5 samples/group), collected prospectively and actively monitored for a minimum of 5 yrs. Patients groups were (i) histological diagnosis of benign prostatic hyperplasia with no evidence of cancer ‘BPH’, (ii) localised cancer with no evidence of progression, ‘non-progressing’ (iii) localised cancer with evidence of biochemical progression, ‘progressing’, and (iv) bone metastasis at presentation ‘metastatic’. Pooled samples were immuno-depleted of the 14 most highly abundant proteins and analysed using a 4-plex iTRAQ approach. Overall 122 proteins were identified and relatively quantified. Comparisons of progressing versus non-progressing groups identified the significant differential expression of 25 proteins (p<0.001). Comparisons of metastatic versus progressing groups identified the significant differential expression of 23 proteins. Mapping the differentially expressed proteins onto the prostate cancer progression pathway revealed the dysregulated expression of individual proteins, pairs of proteins and ‘panels’ of proteins to be associated with particular stages of disease development and progression. The median immunostaining intensity of eukaryotic translation elongation factor 1 alpha 1 (eEF1A1), one of the candidates identified, was significantly higher in osteoblasts in close proximity to metastatic tumour cells compared with osteoblasts in control bone (p = 0.0353, Mann Whitney U). Our proteomic approach has identified leads for potentially useful serum biomarkers associated with the metastatic progression of prostate cancer. The panels identified, including eEF1A1 warrant further investigation and validation

Effects of environmental pollutants on the reproduction and welfare of ruminants

Anthropogenic pollutants comprise a wide range of synthetic organic compounds and heavy metals, which are dispersed throughout the environment, usually at low concentrations. Exposure of ruminants, as for all other animals, is unavoidable and while the levels of exposure to most chemicals are usually too low to induce any physiological effects, combinations of pollutants can act additively or synergistically to perturb multiple physiological systems at all ages but particularly in the developing foetus. In sheep, organs affected by pollutant exposure include the ovary, testis, hypothalamus and pituitary gland and bone. Reported effects of exposure include changes in organ weight and gross structure, histology and gene and protein expression but these changes are not reflected in changes in reproductive performance under the conditions tested. These results illustrate the complexity of the effects of endocrine disrupting compounds on the reproductive axis, which make it difficult to extrapolate between, or even within, species. Effects of pollutant exposure on the thyroid gland, immune, cardiovascular and obesogenic systems have not been shown explicitly, in ruminants, but work on other species suggests that these systems can also be perturbed. It is concluded that exposure to a mixture of anthropogenic pollutants has significant effects on a wide variety of physiological systems, including the reproductive system. Although this physiological insult has not yet been shown to lead to a reduction in ruminant gross performance, there are already reports indicating that anthropogenic pollutant exposure can compromise several physiological systems and may pose a significant threat to both reproductive performance and welfare in the longer term. At present, many potential mechanisms of action for individual chemicals have been identified but knowledge of factors affecting the rate of tissue exposure and of the effects of combinations of chemicals on physiological systems is poor. Nevertheless, both are vital for the identification of risks to animal productivity and welfare

Metabolites of Purine Nucleoside Phosphorylase (NP) in Serum Have the Potential to Delineate Pancreatic Adenocarcinoma

Pancreatic Adenocarcinoma (PDAC), the fourth highest cause of cancer related deaths in the United States, has the most aggressive presentation resulting in a very short median survival time for the affected patients. Early detection of PDAC is confounded by lack of specific markers that has motivated the use of high throughput molecular approaches to delineate potential biomarkers. To pursue identification of a distinct marker, this study profiled the secretory proteome in 16 PDAC, 2 carcinoma in situ (CIS) and 7 benign patients using label-free mass spectrometry coupled to 1D-SDS-PAGE and Strong Cation-Exchange Chromatography (SCX). A total of 431 proteins were detected of which 56 were found to be significantly elevated in PDAC. Included in this differential set were Parkinson disease autosomal recessive, early onset 7 (PARK 7) and Alpha Synuclein (aSyn), both of which are known to be pathognomonic to Parkinson's disease as well as metabolic enzymes like Purine Nucleoside Phosphorylase (NP) which has been exploited as therapeutic target in cancers. Tissue Microarray analysis confirmed higher expression of aSyn and NP in ductal epithelia of pancreatic tumors compared to benign ducts. Furthermore, extent of both aSyn and NP staining positively correlated with tumor stage and perineural invasion while their intensity of staining correlated with the existence of metastatic lesions in the PDAC tissues. From the biomarker perspective, NP protein levels were higher in PDAC sera and furthermore serum levels of its downstream metabolites guanosine and adenosine were able to distinguish PDAC from benign in an unsupervised hierarchical classification model. Overall, this study for the first time describes elevated levels of aSyn in PDAC as well as highlights the potential of evaluating NP protein expression and levels of its downstream metabolites to develop a multiplex panel for non-invasive detection of PDAC

Action research: A qualitative study of educators in a collaborative inquiry process

Critics of educational reform efforts accuse educators of reinventing the pedagogical wheel of education rather than creating, implementing and modifying new theories and structures for instruction. Teachers are often credited with having the essential power to instigate that change and discredited for not having done so. Visions are present but implementation vehicles appear lacking. This is an investigation of a process called action research and its potential to instigate teacher change in practice and insights into practice. Specifically, this is a study of twenty-two teachers from two different midwestern school sites as they conducted research investigations of self-identified issues during the second semester of the school year. Most of the teacher-researchers grouped themselves into collaborative teams and all participants at each site met periodically to support and assist each other in their efforts. One site involved a teaming of novice and veteran teachers. While researching the project, the dissertation researcher also acted as facilitator of the process. The findings of this study supported many of the acclamations given to action research by advocates from the United States, Britain, and Australia. Teachers and students became empowered and excited by the relevance, ownership, and practicality of the process and results. The same principles of learning that educators understand to be important in instructing students--constructivism, learning by doing, and relevance--surfaced as key components of action research and reinforcers of the process. Challenges exist in the action research process conducted by teachers. Practitioner research is sometimes discounted for lacking rigor and quality. Teachers are also confronted with dual and possibly conflicting roles of teacher and researcher. Time and expectations are other factors influencing the potential of action research as a change agent. Questions continuously before advocates and opponents of the process include the purpose, the direction, and the institutionalization of the process

The localization of the United States sugar beet seed industry with emphasis on the Willamette Valley

This investigation has analyzed and described the impact of place on one of man's activities -- the production of sugar beet seed. It is apparent that in this activity man's relationship to the earth is especially close and dependent upon a number of factors. These are localizing factors. Sugar beets grown for seed are sensitive to a number of environmental elements, particularly to the physical element of temperature. Relative compatibility with certain established farming systems and the establishment of seed producing organizations in places favorable for sugar beet seed production are other localizing factors. Since the market for sugar beet seed is tightly controlled by contracting, and since the seed producing agencies have been established in certain favorable areas, and since quantity needs are rather static, it is probable that sugar beet seed production will continue to be localized in the present production areas. Furthermore, no great increase in quantity of production can be expected. The long, relatively mild winters with temperatures favorable to development of the reproductive phase of growth in the sugar beet have made the Willamette Valley of Oregon one of the two chief sugar beet seed producing areas of the United States. Because it is the place offering the best opportunity for total or complete reproduction in all varieties, the Willamette Valley is the foremost producer of seed of bolting resistant varieties of sugar beets. For the same reason, it is the most prominent place for producing seed breeders' elite and stock seed for increase. It is probable that these aspects of the United States sugar beet seed industry will remain localized to the Willamette Valley. The Willamette Valley has ample land on which sugar beets for seed could be raised should demand for seed ever warrant expansion. Sugar beets for seed compete favorably with other crops grown on the Valley's best soils; the present situation indicates that the same kind of competition could be carried to any suitable part of the Valley. With the only slight expansion now taking place, localization within the Willamette Valley will likely remain within a radius of 30 to 40 miles of Salem, and principally on a north -south axis on the more suitable alluvial soils