Voluntary exercise in the C57B1/6J mouse: phenotypic effects of varying dietary fat levels and hippocampal gene expression differences between high-level and low-level exercisers

The drive to exercise voluntarily likely results from complex interactions between genes in many organ systems and various psychological parameters, such as motivation and the perception of fatigue. Reproducible variations in exercise intensity and duration are well established in laboratory rodents, but the genes responsible remain largely unknown. Also, to date, studies addressing the adaptive changes to exercise that might prevent dietary-induced obesity have focused primarily on energy intake and nutrient oxidation/partitioning, as opposed to genetics. We hypothesize that increased voluntary physical activity may be a normal mechanism in certain rodent strains to deter dietary-induced obesity and that in an inbred strain of mice, environmentally sensitive genes must be responsible for observed differences in individual voluntary exercise performance. To study this theory, we have designed a set of experiments that establish an animal model to address whether different gene expression profiles can be detected using microarrays and confirmed with quantitative real-time PCR (qRT-PCR) in distinct exercise phenotypes. We also used the model to address whether dietary manipulations affect voluntary exercise performance in a single strain of inbred mice susceptible to dietary-induced obesity. We determined that animals weaned onto high fat diet exercise at levels significantly higher than those weaned onto low fat diet. These animals were able to maintain body weight and decrease body fat after three weeks of exercise. We also report the results and validation of three microarray comparisons using pooled RNA from the hippocampi of exercising animals. These data suggest that several genes from the HSP 70 family, specifically several molecular chaperones localized to the endoplasmic reticulum, are differentially regulated in running versus sedentary animals at several exercise time points. We suggest that increased voluntary physical activity may be an adaptive response in male C57Bl/6J mice that prevents dietary-induced obesity on high fat diets, and we demonstrate that differential gene expression profiles related to exercise could be identified in the brain using microarrays and qRT-PCR. We conclude that genes from the molecular chaperone family, a well-described environmentally sensitive gene family, are differentially regulated in response to voluntary exercise in an inbred mouse strain

Local History Unbridled: Anecdotal Reflection in Bringing Digitized Microfilm to Digital Commons

When vinegar syndrome threatened to destroy microfilm containing a vast trove of history, Murray State University Libraries quickly responded. The microfilm--which included one of the broadest collections of local and regional newspapers in the Jackson Purchase area, as well as birth, marriage, and death certificates from Calloway and surrounding counties--was sent to a commercial vendor for digitization with the intention of archiving and making the contents accessible through the institutional repository, Digital Commons. Today, that microfilm is transitioning from moldering in closed stacks to becoming widely accessible to a global pool of researchers. Presenters will examine the history and logistics of our digitization process; delineate the staffing, workflow, progress and setbacks relating to creating and ingesting the metadata for each issue; and explore how collaboration across departments was key to the successful implementation of the project. Discussions will conclude with some of the unexpected benefits of the project, including classroom applications, the accessibility of the collection to historians and genealogists, and how the project might encourage deeper dives into other collections

ResearchFanshawe Magazine Issue 5

https://first.fanshawec.ca/researchfanshawemag/1004/thumbnail.jp

The biopsychosocial model of stress in adolescence: self-awareness of performance versus stress reactivity

Extensive research among adults supports the biopsychosocial (BPS) model of challenge and threat, which describes relationships among stress appraisals, physiological stress reactivity, and performance; however, no previous studies have examined these relationships in adolescents. Perceptions of stressors as well as physiological reactivity to stress increase during adolescence, highlighting the importance of understanding the relationships among stress appraisals, physiological reactivity, and performance during this developmental period. In this study, 79 adolescent participants reported on stress appraisals before and after a Trier Social Stress Test in which they performed a speech task. Physiological stress reactivity was defined by changes in cardiac output and total peripheral resistance from a baseline rest period to the speech task, and performance on the speech was coded using an objective rating system. We observed in adolescents only two relationships found in past adult research on the BPS model variables: (1) pre-task stress appraisal predicted post-task stress appraisal and (2) performance predicted post-task stress appraisal. Physiological reactivity during the speech was unrelated to pre- and post-task stress appraisals and to performance. We conclude that the lack of association between post-task stress appraisal and physiological stress reactivity suggests that adolescents might have low self-awareness of physiological emotional arousal. Our findings further suggest that adolescent stress appraisals are based largely on their performance during stressful situations. Developmental implications of this potential lack of awareness of one’s physiological and emotional state during adolescence are discussed.Psycholog

Novel verbal fluency scores and structural brain imaging for prediction of cognitive outcome in mild cognitive impairment

AbstractIntroductionThe objective of this study was to assess the utility of novel verbal fluency scores for predicting conversion from mild cognitive impairment (MCI) to clinical Alzheimer's disease (AD).MethodVerbal fluency lists (animals, vegetables, F, A, and S) from 107 MCI patients and 51 cognitively normal controls were transcribed into electronic text files and automatically scored with traditional raw scores and five types of novel scores computed using methods from machine learning and natural language processing. Additional scores were derived from structural MRI scans: region of interest measures of hippocampal and ventricular volumes and gray matter scores derived from performing ICA on measures of cortical thickness. Over 4 years of follow-up, 24 MCI patients converted to AD. Using conversion as the outcome variable, ensemble classifiers were constructed by training classifiers on the individual groups of scores and then entering predictions from the primary classifiers into regularized logistic regression models. Receiver operating characteristic curves were plotted, and the area under the curve (AUC) was measured for classifiers trained with five groups of available variables.ResultsClassifiers trained with novel scores outperformed those trained with raw scores (AUC 0.872 vs 0.735; P < .05 by DeLong test). Addition of structural brain measurements did not improve performance based on novel scores alone.ConclusionThe brevity and cost profile of verbal fluency tasks recommends their use for clinical decision making. The word lists generated are a rich source of information for predicting outcomes in MCI. Further work is needed to assess the utility of verbal fluency for early AD

Water Use in the Eagle Ford Shale: An Economic and Policy Analysis of Water Supply and Demand

The Eagle Ford Shale is a massive geologic formation located in South Texas spanning 30 Texas counties from Brazos County in the north east to Webb County in the southwest . With the advent of hydraulic fracturing (HF) and horizontal drilling, over 200 operators have been able to tap into previously inaccessible shale reserves to p roduce abundant amounts of oil and gas. The oil and gas proliferation in the Eagle Ford has seen exponential growth , and production is not anticipated to decline until 2025. In addition, a typical HF well in the Eagle Ford is estimated to consume about 13 acre - feet of water for a standard 5000 foot lateral . Approximately 90% of water for HF comes from fresh groundwater aquifers. This interaction of HF and water consumption is of primary importance from a poli tical and economic perspective. This s erves as t he focal point of our report. Using the tools of statistics, our research considered the groundwater consumption trends within the Eagle Ford counties using water consumption data of municipal, irrigation, mining (oil and gas) and other categories over a span of four years . This analysis showed that fresh groundwater is being consumed at about 2.5 times the groundwater recharge rates . Furthermore, irrigation is using more water than all other water - consuming categories combined. Thus, the water problem reaches well beyond the use of fresh grou ndwater for mining . With respect to likely requirements of water for HF, we posited this question: “ W ill technology bail us out?” Retrofitting learning curves to our data for water uses and the length of the well la teral , we find that after i nitial improvements in water us age, the technology appears to have stabilized. This, coupled with massi ve irrigation water consumption suggests that technology will not be a major source of water savings in the long run. Instead, we must look to better public policies . From a policy perspective, the status quo for groundwater u se is governed by the Rule of Capture and the oversight of groundwater conservation districts (GCDs) . T here exists a real conflict as large - scale water users are competing for a diminishing aquifer resource with no market signals of increasing scarcity. In addition, groundwater wells drilled in connection with oil and gas exploration are exempt from GCD per mitting requirements and receive a de facto “free pass” to water for HF. Likewise, limita tions imposed on irrigation users by the GCDs are rarely binding, so these users usually get a free pass as well. Our analysis leads us to three basic policy recommend ations . The first involves mandatory reporting of all groundwater uses by all classes of water use r s. Currently, government agencies and the public lack basic information on actual water consumption; t his policy seeks to relax that knowledge gap and bring transparency. Second , we propose incentivizing oil and gas companies to substitute brackish groundwater for fresh ground water. Our proposal calls for a severance tax reduction for tho se companies limiting fresh groundwater use for HF in the Eagle Ford. In addition to a temporary reduction in the severance tax, these companies c ould be recognized by the RRC and possibly the TCEQ for their environmental stewardship with a “ Green Star ” designation. Our t hird , most heterodox and long - term recommendation is to define ground water property rights on a per - acre ownership basis, which would attach to the surface owner’s real property. Under this system, the owner s of the water rights would be able to sell their water as they would any other resource, and the market would adjust the price of water to an economically efficient level. Most importantly, it would remove the incentive to use all you can today , leaving more water for the future at a lower future price.Commissioner Christi Craddick, Texas Railroad Commissio

Harnessing radiotherapy-induced NK-cell activity by combining DNA damage-response inhibition and immune checkpoint blockade.

BackgroundDespite therapeutic gains from immune checkpoint inhibitors (ICI) in many tumor types, new strategies are needed to extend treatment benefits, especially in patients failing to mount effective antitumor T-cell responses. Radiation and drug therapies can profoundly affect the tumor immune microenvironment. Here, we aimed to identify immunotherapies to increase the antitumor response conferred by combined ataxia telangiectasia and Rad3-related kinase inhibition and radiotherapy.MethodsUsing the human papillomavirus (HPV)-negative murine oral squamous cell carcinoma model, MOC2, we assessed the nature of the antitumor response following ataxia telangiectasia and Rad3-related inhibitor (ATRi)/radiotherapy (RT) by performing RNA sequencing and detailed flow cytometry analyses in tumors. The benefit of immunotherapies based on T cell immunoreceptor with Ig and ITIM domains (TIGIT) and Programmed cell death protein 1 (PD-1) immune checkpoint blockade following ATRi/RT treatment was assessed in the MOC2 model and confirmed in another HPV-negative murine oral squamous cell carcinoma model called SCC7. Finally, immune profiling was performed by flow cytometry on blood samples in patients with head and neck squamous cell carcinoma enrolled in the PATRIOT clinical trial of combined ATRi/RT.ResultsATRi enhances radiotherapy-induced inflammation in the tumor microenvironment, with natural killer (NK) cells playing a central role in maximizing treatment efficacy. We demonstrated that antitumor activity of NK cells can be further boosted with ICI targeting TIGIT and PD-1. Analyses of clinical samples from patients receiving ATRi (ceralasertib) confirm the translational potential of our preclinical studies.ConclusionThis work delineates a previously unrecognized role for NK cells in the antitumor immune response to radiotherapy that can be augmented by small-molecule DNA damage-response inhibitors and immune checkpoint blockade

Exile Vol. XL No. 1

38th Year Title Page by Carrie Horner \u2797 i Epigraph by Ezra Pound ii Table of Contents iii-iv Vertigo by Lisa Stillman \u2795 1 Departing Flight by Morgan Roper \u2794 2 Untitled by Lizzie Loud \u2795 3 Marietta by Craig McDonough \u2794 4 Interlaken by Kira A . Pollack \u2794 5 Why Nature Surprises Us by Josh Endicott \u2796 6-7 Untitled by Colin Mack \u2794 7 My Father by Matt Wanat \u2795 8 Legs In The Dust by Alison Stevens \u2795 9-11 Untitled by Lilly Streett \u2794 12 of cigarettes, saltwater and death... by Tricia B. Swearingen \u2794 13 Serendipity by Lizzie Lout \u2795 14 Untitled by Lilly Streett \u2794 15 Summer by Allison Lemieux \u2795 16 And the Rain Fell by Jeremy Aufrance \u2795 17-18 Main Street by Elise Gargarella \u2795 19 Füssen by Morgan Roper \u2794 20 Lightning on the Snow by Matt Wanat \u2795 21 A discussion of 12 year-old murders, of course by Jeremy Aufrance \u2795 22 Get your hands off my hat by Jamie Oliver \u2794 23 The Hero by Sara Sterling Ely \u2796 24-26 Punker Dave by Trevett Allen \u2795 27 still looking for the perfect line by ryan shafer \u2794 28-29 Untitled by Lizzie Loud \u2795 30 Civil War by Katherine Anne Campo \u2794 31 Disposable belief by ryan shafer \u2794 32-33 Schizophrenic Sylvia by Maria Mohiuddin \u2795 34 Excerpts from Revolutions, a novel by Marcu McLaughlin \u2794 35-36 Untitled by Keith Chapman \u2795 37 The Survivors by Kira A. Pollack \u2794 38 Days of Prophecy by Trey Dunham \u2794 39 Untitled by Carrie Horner \u2797 40 What to do by Christopher Harnish \u2794 41 Familiar Stranger by Lisa Stillman \u2795 42-46 Untitled by John Salter \u2797 47 On Meeting Emma by Allison Lemieux \u2795 48 Nude Figure by James Oliver \u2794 49 Tathagata by Leslie Dana Wells \u2794 50 On Fences and My Dogs by Christopher Harnish \u2794 51 Editorial Board 52 Cover, Kira Pollack \u2794 -iv Editorial decision is shared equally among the Editorial Board. -5