Systemic Acrolein Elevations in Mice With Experimental Autoimmune Encephalomyelitis and Patients With Multiple Sclerosis

Demyelination and axonal injury are the key pathological processes in multiple sclerosis (MS), driven by inflammation and oxidative stress. Acrolein, a byproduct and instigator of oxidative stress, has been demonstrated as a neurotoxin in experimental autoimmune encephalomyelitis (EAE), an animal model of MS. However, due to the invasive nature of acrolein detection using immunoblotting techniques, the investigation of acrolein in MS has been limited to animal models. Recently, detection of a specific acrolein-glutathione metabolite, 3-HPMA, has been demonstrated in urine, enabling the noninvasive quantification of acrolein for the first time in humans with neurological disorders. In this study, we have demonstrated similar elevated levels of acrolein in both urine (3-HPMA) and in spinal cord tissue (acrolein-lysine adduct) in mice with EAE, which can be reduced through systemic application of acrolein scavenger hydralazine. Furthermore, using this approach we have demonstrated an increase of 3-HPMA in both the urine and serum of MS patients relative to controls. It is expected that this noninvasive acrolein detection could facilitate the investigation of the role of acrolein in the pathology of MS in human. It may also be used to monitor putative therapies aimed at suppressing acrolein levels, reducing severity of symptoms, and slowing progression as previously demonstrated in animal studies

Software Metrics and Dashboard

Software metrics are a critical tool which provide continuous insight to products and processes and help build reliable software in mission critical environments. Using software metrics we can perform calculations that help assess the effectiveness of the underlying software or process. The two types of metrics relevant to our work is complexity metrics and in-process metrics. Complexity metrics tend to focus on intrinsic code properties like code complexity. In-process metrics focus on a higher-level view of software quality, measuring information that can provide insight into the underlying software development process. Our aim is to develop and evaluate a metrics dashboard to support Computational Science and Engineering (CSE) software development projects. This task requires us to perform the following activities: Assess how metrics are used and which general classes/types of metrics will be useful in CSE projects. Develop a metrics dashboard that will work for teams using sites like Github, Bitbucket etc. Assess the effectiveness of the dashboard in terms of project success and developer attitude towards metrics and process. Our current focus is on identifying requirements for the metrics dashboard which include the types of metrics that will help understand and improve the software quality. We have also started the development on the metrics dashboard based on the currently identified metrics types. We plan to provide a reliable metrics dashboard which could be used by the CSE development teams to improve their software quality, this will be done by instrumenting the metrics dashboard to gather usage statistics. In this way the dashboard evolves continuously

Phase Angle Adaptation to Exercise Training in Cancer Patients Undergoing Treatment

Phase angle is a measure of cellular resistance and reactance to bioelectrical impedance analysis. This measurement is useful as a marker of cell membrane integrity and is used as a prognostic marker in several clinical populations. Cancer and its related treatments impact cell membrane integrity, leading to poor cell function. Exercise is shown to increase phase angle, resulting in lowered risk of hospitalization and cardiovascular events. However, the effect of chronic exercise training on phase angle in the cancer population is unclear. Purpose: To assess the effect of chronic exercise on phase angle in cancer patients who are actively undergoing chemotherapy and/or radiation. Methods: A total of 56 cancer patients who were actively undergoing chemotherapy and/or radiotherapy were recruited to participate in a 12 week exercise-based rehabilitation program at the University of Northern Colorado Cancer Rehabilitation Institute. Each participant underwent an initial assessment of physiological parameters, including body composition and phase angle analysis. Results of this assessment were used to develop an individualized exercise prescription. Each participant received prescribed, supervised, one-on-one training from a Clinical Cancer Exercise Specialist, three times per week for one hour each session. After 12 weeks, each participant underwent a follow-up assessment of physiological parameters. Results: After 12 weeks of exercise training, significant increases in whole body (Initial: 4.55 ± 0.72, Follow-up: 4.68 ± 0.68; p = 0.02), right arm (Initial: 4.45 ± 0.76, Follow-up: 4.57 ± 0.72; p = 0.03), and left arm (Initial: 4.28 ± 0.79, Follow-up: 4.39 ± 0.75; p = 0.03) phase angle was observed. Conclusion: This study demonstrates that prescribed exercise training can increase phase angle in cancer survivors even while undergoing chemotherapy and/or radiation treatments. These changes may provide insight into the protective and rehabilitative benefits (e.g., cellular health, membrane integrity, disease risk) that exercise may have in this population

Nutrient Content and Physical Properties of Scottish Hemp Oil and Oil By-products : Data to support the revalorisation of hemp by-products and promote a circular nutrition

This research was funded by the Scottish Government’s Rural and Environment Science and Analytical Services Division (RESAS) Strategic Research Programme; Theme B, Hemp: a climate resilient crop for the future of Scottish agriculture; Project Reference: RI-B1-01

Individual differences in search and monitoring for color targets in dynamic visual displays

Many jobs now involve the monitoring visual representations of data that change over time. Monitoring dynamically changing displays for the onset of targets can be done in two ways: detecting targets directly post their onset or predicting their onset from the prior state of distractors. In the present study, participants? eye movements were measured as they monitored arrays of 108 colored squares whose colors changed systematically over time. Across three experiments, the data show that participants detected the onset of targets both directly and predictively. Experiments 1 and 2 showed that predictive detection was only possible when supported by sequential color changes that followed a scale ordered in color space. Experiment 3 included measures of individual differences in working memory capacity (WMC) and anxious affect and a manipulation of target prevalence in the search task. It found that predictive monitoring for targets, and decisions about target onsets, were influenced by interactions between individual differences in verbal and spatial WMC and intolerance of uncertainty, a characteristic that reflects worry about uncertain future events. The results have implications for the selection of individuals tasked with monitoring dynamic visual displays for target onsets

Association between hospital case volume and the use of bronchoscopy and esophagoscopy during head and neck cancer diagnostic evaluation

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/102212/1/cncr28379.pd

Genome-wide association study identifies _FUT8_ and _ESR2_ as co-regulators of a bi-antennary N-linked glycan A2 (GlcNAc~2~Man~3~GlcNAc~2~) in human plasma proteins

HPLC analysis of N-glycans quantified levels of the biantennary glycan (A2) in plasma proteins of 924 individuals. Subsequent genome-wide association study (GWAS) using 317,503 single nucleotide polymorphysms (SNP) identified two genetic loci influencing variation in A2: FUT 8 and ESR2. We demonstrate that human glycans are amenable to GWAS and their genetic regulation shows sex-specific effects with _FUT 8_ variants explaining 17.3% of the variance in pre-menopausal women, while _ESR2_ variants explained 6.0% of the variance in post-menopausal women

SUMOylation of DISC1: a potential role in neural progenitor proliferation in the developing cortex

DISC1 is a multifunctional, intracellular scaffold protein. At the cellular level, DISC1 plays a pivotal role in neural progenitor proliferation, migration, and synaptic maturation. Perturbation of the biological pathways involving DISC1 is known to lead to behavioral changes in rodents, which supports a clinical report of a Scottish pedigree in which the majority of family members with disruption of the DISC1 gene manifest depression, schizophrenia, and related mental conditions. The discrepancy between modest evidence in genetics and strong biological support for the role of DISC1 in mental conditions suggests a working hypothesis that regulation of DISC1 at the protein level, such as posttranslational modification, may play a role in the pathology of mental conditions. In this study, we report on the SUMOylation of DISC1. This posttranslational modification occurs on lysine residues where the small ubiquitin-related modifier (SUMO) and its homologs are conjugated to a large number of cellular proteins, which in turn regulates their subcellular distribution and protein stability. By using in silico, biochemical, and cell-biological approaches, we now demonstrate that human DISC1 is SUMOylated at one specific lysine 643 (K643). We also show that this residue is crucial for proper neural progenitor proliferation in the developing cortex

High Resolution mid-Infrared Imaging of SN 1987A

Using the Thermal-Region Camera and Spectrograph (T-ReCS) attached to the Gemini South 8m telescope, we have detected and resolved 10 micron emission at the position of the inner equatorial ring (ER) of supernova SN 1987A at day 6067. ``Hot spots'' similar to those found in the optical and near-IR are clearly present. The morphology of the 10 micron emission is globally similar to the morphology at other wavelengths from X-rays to radio. The observed mid-IR flux in the region of SN1987A is probably dominated by emission from dust in the ER. We have also detected the ER at 20 micron at a 4 sigma level. Assuming that thermal dust radiation is the origin of the mid-IR emission, we derive a dust temperature of 180^{+20}_{-10} K, and a dust mass of 1.- 8. 10^{-5} Mo for the ER. Our observations also show a weak detection of the central ejecta at 10 micron. We show that previous bolometric flux estimates (through day 2100) were not significantly contaminated by this newly discovered emission from the ER. If we assume that the energy input comes from radioactive decays only, our measurements together with the current theoretical models set a temperature of 90 leq T leq 100 K and a mass range of 10^{-4} - 2. 10^{-3} Mo for the dust in the ejecta. With such dust temperatures the estimated thermal emission is 9(+/-3) 10^{35} erg s^{-1} from the inner ring, and 1.5 (+/-0.5) 10^{36} erg s^{-1} from the ejecta. Finally, using SN 1987A as a template, we discuss the possible role of supernovae as major sources of dust in the Universe.Comment: aastex502, 14 pages, 4 figures; Accepted for publication in ApJ Content changed: new observations, Referee's comments and suggestion