Cataloging University Research Resources to Create DMPTool Templates and a LibGuide Research Portal

Objective Research data management plans require information about the resources used to create, store, and analyze the data. A table of resources in and outside the university was compiled for use when writing DMPTool templates for grants. The table was also used to create a LibGuide to help researchers learn about all the available resources. Methods Initially, resources directly related to data management such as storage availability, sharing options, and database programs available at the university were investigated to find boilerplate language to use in DMPTool data management plan templates. As the data librarian worked on more plans for grant applications, it became apparent that information about research resources related to the creation of data, and resources outside of the university would help provide more comprehensive data management plans, so further resources were investigated. Interviews with researchers had highlighted the lack of a centralized research resource catalogue at the university, so the information collected in spreadsheets by a graduate assistant was used to create a research portal LibGuide for all the documented resources. Plans are also underway to collaborate with the Coordinator for Research Development Services to create a boilerplate library for grants citing university resources

Foxo3a induces motoneuron death through the Fas pathway in cooperation with JNK

BACKGROUND: Programmed cell death of motoneurons in the developing spinal cord is thought to be regulated through the availability of target-derived neurotrophic factors. When deprived of trophic support, embryonic spinal motoneurons in vitro over-express FasL, a ligand activating a Fas-mediated death pathway. How trophic factors regulate the expression of FasL is presently unclear, but two regulators of FasL, FOXO3a (FKHRL1) and JNK have been described to play a role in other cell types. Thus, their potential function in motoneurons was investigated in this study. RESULTS: We show here that as a result of removal of neurotrophic factors and the consequent reduction in signalling through the PI3K/Akt pathway, Foxo3a translocates from the cytoplasm to the nucleus where it triggers cell death. Death is reduced in Fas and FasL mutant motoneurons and in the presence of JNK inhibitors indicating that a significant part of it requires activation of the Fas/FasL pathway through JNK. CONCLUSIONS: Therefore, in motoneurons as in other cell types, FOXO transcriptional regulators provide an important link between other signalling pathways and the cell death machinery

Functional anatomy of the masking level difference, an fMRI study

Introduction: Masking level differences (MLDs) are differences in the hearing threshold for the detection of a signal presented in a noise background, where either the phase of the signal or noise is reversed between ears. We use N0/Nπ to denote noise presented in-phase/out-of-phase between ears and S0/Sπ to denote a 500 Hz sine wave signal as in/out-of-phase. Signal detection level for the noise/signal combinations N0Sπ and NπS0 is typically 10-20 dB better than for N0S0. All combinations have the same spectrum, level, and duration of both the signal and the noise. Methods: Ten participants (5 female), age: 22-43, with N0Sπ-N0S0 MLDs greater than 10 dB, were imaged using a sparse BOLD fMRI sequence, with a 9 second gap (1 second quiet preceding stimuli). Band-pass (400-600 Hz) noise and an enveloped signal (.25 second tone burst, 50% duty-cycle) were used to create the stimuli. Brain maps of statistically significant regions were formed from a second-level analysis using SPM5. Results: The contrast NπS0- N0Sπ had significant regions of activation in the right pulvinar, corpus callosum, and insula bilaterally. The left inferior frontal gyrus had significant activation for contrasts N0Sπ-N0S0 and NπS0-N0S0. The contrast N0S0-N0Sπ revealed a region in the right insula, and the contrast N0S0-NπS0 had a region of significance in the left insula. Conclusion: Our results extend the view that the thalamus acts as a gating mechanism to enable dichotic listening, and suggest that MLD processing is accomplished through thalamic communication with the insula, which communicate across the corpus callosum to either enhance or diminish the binaural signal (depending on the MLD condition). The audibility improvement of the signal with both MLD conditions is likely reflected by activation in the left inferior frontal gyrus, a late stage in the what/where model of auditory processing. © 2012 Wack et al

Exploring the Fate of Nitrogen Heterocycles in Complex Prebiotic Mixtures

A long standing question in the field of prebiotic chemistry is the origin of the genetic macromolecules DNA and RNA. DNA and RNA have very complex structures with repeating subunits of nucleotides, which are composed of nucleobases (nitrogen heterocycles) connected to sugar-phosphate. Due to the instability of some nucleobases (e.g. cytosine), difficulty of synthesis and instability of D-ribose, and the likely scarcity of polyphosphates necessary for the modern nucleotides, alternative nucleotides have been proposed for constructing the first genetic material. Thus, we have begun to investigate the chemistry of nitrogen heterocycles in plausible, complex prebiotic mixtures in an effort to identify robust reactions and potential alternative nucleotides. We have taken a complex prebiotic mixture produced by a spark discharge acting on a gas mixture of N2, CO2, CH4, and H2, and reacted it with four nitrogen heterocycles: uracil, 5-hydroxymethyluracil, guanine, and isoxanthopterin (2-amino-4,7-dihydroxypteridine). The products of the reaction between the spark mixture and each nitrogen heterocycle were characterized by liquid chromatography coupled to UV spectroscopy and Orbitrap mass spectrometry. We found that the reaction between the spark mixtUl'e and isoxanthopterin formed one major product, which was a cyanide adduct. 5-hydroxymethyluracil also reacted with the spark mixture to form a cyanide adduct, uracil-5-acetonitrile, which has been synthesized previously by reacting HCN with S-hydroxymethyluracil. Unlike isoxanthopterin, the chromatogram of the 5-hydroxymethyluracil reaction was much more complex with multiple products including spark-modified dimers. Additionally, we observed that HMU readily self-polymerizes in solution to a variety of oligomers consistent with those suggested by Cleaves. Guanine and uracil, the biological nucleobases, did not react with the spark mixture, even at high temperature (100 C). This suggests that there are alternative nucleobases which are more reactive under prebiotic conditions and may have been involved in producing precursor nucleotides

Stem Cells in the Nervous System

Given their capacity to regenerate cells lost through injury or disease, stem cells offer new vistas into possible treatments for degenerative diseases and their underlying causes. As such, stem cell biology is emerging as a driving force behind many studies in regenerative medicine. This review focuses on the current understanding of the applications of stem cells in treating ailments of the human brain, with an emphasis on neurodegenerative diseases. Two types of neural stem cells are discussed: endogenous neural stem cells residing within the adult brain and pluripotent stem cells capable of forming neural cells in culture. Endogenous neural stem cells give rise to neurons throughout life, but they are restricted to specialized regions in the brain. Elucidating the molecular mechanisms regulating these cells is key in determining their therapeutic potential as well as finding mechanisms to activate dormant stem cells outside these specialized microdomains. In parallel, patient-derived stem cells can be used to generate neural cells in culture, providing new tools for disease modeling, drug testing, and cell-based therapies. Turning these technologies into viable treatments will require the integration of basic science with clinical skills in rehabilitation

Improved walking function in laboratory does not guarantee increased community walking in stroke survivors: Potential role of gait biomechanics

Reduced daily stepping in stroke survivors may contribute to decreased functional capacity and increased mortality. We investigated the relationships between clinical and biomechanical walking measures that may contribute to changes in daily stepping activity following physical interventions provided to participants with subacute stroke. Following ≤40 rehabilitation sessions, 39 participants were categorized into three groups: responders/retainers increased daily stepping >500 steps/day post-training (POST) without decreases in stepping at 2-6 month follow-up (F/U); responders/non-retainers increased stepping at POST but declined >500 steps/day at F/U; and, non-responders did not change daily stepping from baseline testing (BSL). Gait kinematics and kinetics were evaluated during graded treadmill assessments at BSL and POST. Clinical measures of gait speed, timed walking distance, balance and balance confidence were measured at BSL, POST and F/U. Between-group comparisons and regression analyses were conducted to predict stepping activity from BSL and POST measurements. Baseline and changes in clinical measures of walking demonstrated selective associations with stepping, although kinematic measures appeared to better discriminate responders. Specific measures suggest greater paretic vs non-paretic kinematic changes in responders with training, although greater non-paretic changes predicted greater gains (i.e., smaller declines) in stepping in retainers at F/U. No kinetic variables were primary predictors of changes in stepping activity at POST or F/U. The combined findings indicate specific biomechanical assessments may help differentiate changes in daily stepping activity post-stroke

Dose Effect of Whey Protein on Gut Hormone Responses in Pre-Diabetics and Type 2 Diabetics

GLP-1 and GIP have been shown to increase following a 50 g dose of whey protein prior to a high glycemic load in type 2 diabetics. However, this increase is reduced in diabetics compared to healthy individuals. Pancreatic polypeptide (PP) and peptide tyrosine tyrosine (PYY) also increase, while ghrelin decreases after the consumption of whey protein; however, it is not known if a similar hormone response occurs with a lower dose of whey protein prior to a glycemic load or if there is a dose effect. Our hypothesis was that 20 g and 30 g of whey protein would increase GLP-1, GIP, PP, and PYY and decrease ghrelin in a dose dependent manner. PURPOSE: The purpose of this study was to examine the effect of two different doses of whey protein ingested 30 min prior to a 50 g OGTT on gut hormone and incretin response. METHODS: Nine diabetic and pre-diabetic participants (n=9, mean ± SD; age: 64.3 + 8.1 yrs.; BMI: 29.4 + 6.0 kg/m2; HbA1c: 6.4 + 0.6%) completed three trials. The randomly assigned trials consisted of: ingestion of 250ml of water (CON); 250 ml of water + 20 g whey (20g); 250ml of water + 30 g whey (30g), prior to completing a 50 g OGTT. Blood was collected at -30, 0, 15, 30, 60, 90, 120, and 150 min for the measurement of GIP, GLP-1, ghrelin, PP, and PYY. The whey protein was administered immediately following the -30 min and the 50 g OGTT began immediately after the 0 min blood draw. Metabolites were measured using multiplex fluorescent detection. One-way repeated measure ANOVA was used for statistical analysis for each dependent variable (P \u3c 0.05). RESULTS: 20g and 30g of whey protein significantly increased incremental area under the curve (AUC) of GIP 32% and 38% compared to CON. 30g significantly decreased ghrelin AUC -13.9% and -20% compared to 20g and CON. 30g significantly increased PP AUC 28% compared to CON only. There were no differences in ghrelin and PP AUC between 20g and CON. There were no significant differences for GLP-1 and PYY between all trials. CONCLUSION: 30 g of whey protein prior to a glucose challenge increased secretion of GIP and PP and decreased ghrelin in type 2 and pre-diabetics. There seems to be a dose effect relationship between whey, ghrelin, and PP. 30 g of whey preload may induce insulinotropic and satiety effects from GIP, PP, and ghrelin responses in type 2 and pre-diabetics

A High-Density Admixture Scan in 1,670 African Americans with Hypertension

Hypertension (HTN) is a devastating disease with a higher incidence in African Americans than European Americans, inspiring searches for genetic variants that contribute to this difference. We report the results of a large-scale admixture scan for genes contributing HTN risk, in which we screened 1,670 African Americans with HTN and 387 control individuals for regions of the genome with elevated proportion of African or European ancestry. No loci were identified that were significantly associated with HTN. We also searched for evidence of an admixture signal at 40 candidate genes and eight previously reported linkage peaks, but none appears to contribute substantially to the differential HTN risk between African and European Americans. Finally, we observed nominal association at one of the loci detected in the admixture scan of Zhu et al. 2005 (p = 0.016 at 6q24.3 correcting for four hypotheses tested), although we caution that the significance is marginal and the estimated odds ratio of 1.19 per African allele is less than what would be expected from the original report; thus, further work is needed to follow up this locus