Web-enabled knowledge-based analysis of genetic data

We present a web-based implementation of GenePath, an intelligent assistant tool for data analysis in functional genomics. GenePath considers mutant data and uses expert-defined patterns to find gene-to-gene or gene-to-outcome relations. It presents the results of analysis as genetic networks, wherein a set of genes has various influence on one another and on a biological outcome. In the paper, we particularly focus on its web-based interface and explanation mechanisms

Surveillance and Elimination of Bacteriophage Contamination in an Industrial Fermentation Process

Commercial fermentation processes are often vulnerable to bacteriophage due to the lack of genetic diversity and use of high cell density cultures. Bacteriophage infections in these fermentations can have adverse impacts on operability of the production facility and product quality and prevent recovery of valuable bioproducts in the downstream process. Prevention strategies have been developed and optimized through feedback from bacteriophage diagnostic tests, which inform improvements to process design for elimination of entry points, as well as modification of the biocatalyst to reduce or eliminate bacteriophage virulence. In this chapter, we provide case studies for successful elimination of bacteriophage virulence via host modifications, including bacteriophage binding-site modifications on the outer membrane of an Escherichia coli production host, used for commercial manufacture of 1,3-propanediol, as well as application of CRISPR-associated protein 9 (Cas9) for bacteriophage immunity. Finally, we report application of bacteriophage diagnostic methods to fully characterize and eliminate bacteriophage entry points in a commercial fermentation process

Cytoprotection and healing: Two unequal brethren

The promotion of the concept of cytoprotection has fostered hopes that the use of co-prescribed mucosal protective agents would revolutionize the prevention of NSAID-induced ulcers and supply the basis for novel ulcer therapy. Prostaglandins do not, however, accelerate ulcer healing when applied at doses that exert an unequivocal cytoprotective activity. Attempts have therefore been made in recent years to create new less-toxic NSAIDs, such as combined lipoxygenase/cyclo-oxygenase inhibitors, NSAIDs coupled to an NO donor and so-called COX-2 inhibitors. All these preparations do in fact exert a diminished gastrointestinal toxicity. There is however increasing evidence accumulating from studies performed in and outside our laboratories that in chromic ulcer models their increased gastrointestinal tolerance is not necessarily reflected by non-interference with ulcer healing. It is thus mandatory to distinguish between cytoprotective and healing properties of drugs interfering with the cyclo-oxygenase pathwa

Mitochondrion to endoplasmic reticulum apposition length in zebrafish embryo spinal progenitors is unchanged in response to perturbations associated with Alzheimer’s disease

Published: June 21, 2017Mutations in the human genes PRESENILIN1 (PSEN1), PRESENILIN2 (PSEN2) and AMYLOID BETA A4 PRECURSOR PROTEIN (APP) have been identified in familial Alzheimer's disease (AD). The length of mitochondrion-endoplasmic reticulum (M-ER) appositions is increased in Psen1-/-/Psen2-/- double knockout murine embryonic fibroblasts and in fibroblasts from AD-affected individuals. Development of an easily accessible, genetically manipulable, in vivo system for studying M-ER appositions would be valuable so we attempted to manipulate M-ER apposition length in zebrafish (Danio rerio) embryos. We injected fertilized zebrafish eggs with antisense morpholino oligonucleotides (MOs) that inhibit expression of zebrafish familial AD gene orthologues psen1 and psen2. Furthermore, we treated zebrafish embryos with DAPT (a highly specific γ-secretase inhibitor) or with sodium azide (to mimic partially hypoxic conditions). We then analyzed M-ER apposition in an identified, presumably proliferative neural cell type using electron microscopy. Our analysis showed no significant differences in M-ER apposition lengths at 48 hours post fertilization (hpf) between psen1 & psen2 MO co-injected embryos, embryos treated with DAPT, or sodium azide, and control embryos. Instead, the distribution of M-ER apposition lengths into different length classes was close to identical. However, this indicates that it is feasible to reproducibly measure M-ER size distributions in zebrafish embryos. While our observations differ from those of murine and human studies, this may be due to differences in cellular differentiation and metabolic state, cell age, or species-specific responses. In particular, by focusing on a presumably proliferative embryonic cell type, we may have selected a cell heavily already reliant on anaerobic glycolysis and less responsive to factors affecting M-ER apposition. Future examination of more differentiated, more secretory cell types may reveal measurable responses of M-ER apposition to environmental and genetic manipulation.Morgan Newman, Lena Halter, Anne Lim, Michael Lardell

ActivityAware: an App for Real-Time Daily Activity Level Monitoring on the Amulet Wrist-Worn Device

Physical activity helps reduce the risk of cardiovascular disease, hypertension and obesity. The ability to monitor a person\u27s daily activity level can inform self-management of physical activity and related interventions. For older adults with obesity, the importance of regular, physical activity is critical to reduce the risk of long-term disability. In this work, we present ActivityAware, an application on the Amulet wrist-worn device that measures daily activity levels (sedentary, moderate and vigorous) of individuals, continuously and in real-time. The app implements an activity-level detection model, continuously collects acceleration data on the Amulet, classifies the current activity level, updates the day\u27s accumulated time spent at that activity level, logs the data for later analysis, and displays the results on the screen. We developed an activity-level detection model using a Support Vector Machine (SVM). We trained our classifiers using data from a user study, where subjects performed the following physical activities: sit, stand, lay down, walk and run. With 10-fold cross validation and leave-one-subject-out (LOSO) cross validation, we obtained preliminary results that suggest accuracies up to 98%, for n=14 subjects. Testing the ActivityAware app revealed a projected battery life of up to 4 weeks before needing to recharge. The results are promising, indicating that the app may be used for activity-level monitoring, and eventually for the development of interventions that could improve the health of individuals

Death after smoking of fentanyl, 5F-ADB, 5F-MDMB-P7AICA and other synthetic cannabinoids with a bucket bong

Purpose: We report a case of a polydrug user who consumed various synthetic cannabinoids and fentanyl from a transdermal patch via a bucket bong. Toxicological results from postmortem matrices with special focus on synthetic cannabinoids are discussed in terms of their relevance to the death. Methods: The samples were analyzed by toxicological screening procedures involving immunoassays and gas chromatography–mass spectrometry (GC–MS) as well as quantitative analyses by means of GC–MS and high-performance liquid chromatography–tandem mass spectrometry (LC–MS/MS). Results: At the autopsy, coronary artery disease and signs of liver congestion were noted, in the absence of acute myocardial ischemic changes. Femoral blood concentrations of fentanyl and pregabalin were 14 ng/mL and 3,200 ng/mL, respectively. In addition, 2.7 ng/mL 5F-ADB and 13 ng/mL 5F-MDMB-P7AICA were detected together with relatively low amounts of 5 other synthetic cannabinoids in cardiac blood. A total number of up to 17 synthetic cannabinoids were detected in kidney, liver, urine and hair. Fentanyl and 5F-ADB were also detected in the water of the bucket bong. Conclusions: The cause of death could be attributed to an acute mixed intoxication by fentanyl and 5F-ADB (both Toxicological Significance Score (TSS) = 3) with a contribution of pregabalin and 5F-MDMB-P7AICA (TSS = 2), in a subject suffering from pre-existing heart damage. The most plausible mechanism of death consists in a respiratory depression. This case report demonstrates that use of opioids in combination with synthetic cannabinoids might be particularly dangerous

Development of a ‘Smart’ Resistance Exercise Band to Assess Strength

https://digitalcommons.dartmouth.edu/wetterhahnsymposium-2018/1004/thumbnail.jp

Geriatrics program development at the University of Michigan

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/31253/1/0000159.pd