Sedentary Behavior and College Students: Why It Matters Now

A growing body of research demonstrates the accumulation of sedentary behavior and its negative health effects, especially in middle-aged and older adults (Dunstan, Howard, Healy, & Owen, 2012; Owen, Sparling, Healy, Dunstan, & Matthews, 2010; Teychenne, Ball, & Salmon, 2010; Teychenne, Costigan, & Parker, 2015). However, little is known about sedentary time in younger individuals. The primary purpose of this research was to characterize sedentary behavior in college-aged men and women. A secondary purpose was to examine the relationship between sedentary time and physical activity. Participants included full-time students over the age of 18 (N=72). Sedentary behavior was measured by an ActiGraph accelerometer worn during waking hours for one week. On average, subjects spent 72% of the day sedentary (639.76 + 80.09 minutes/day) and accumulated a large portion of this time (72%) on weekdays between 5:00 and 9:00pm. Further, subjects accumulated an average of 52% of their sedentary time in bouts greater than 30 minutes and 25% in bouts greater than 60 minutes. Sedentary time did not differ between individuals who met physical activity recommendations versus those who did not, whereas an inverse correlation was found between sedentary behavior and light intensity activity. Future research should explore the feasibility and outcome of reducing and breaking up sedentary time in this population due to the potential for health benefits

Reconciling Moral Dissonance: A Framework for Re-Integrating Moral Orientation with Life Agency During Warfighters’ Struggles with Military Moral Injury

This dissertation uses case studies to critically examine the Three Mirror Model (TMM) as a framework for understanding the formation and healing of Military Moral Injury (MMI). I adapt the work of Stephen Brookfield and Neal Krause to evaluate using the TMM as a methodology for dealing with the complex issues of MMI within a military deployment cycle (training, warfighting, and healing) (Brookfield 2012, 2017; Krause 2022). Specifically, I use theorists, researchers, healers, and warfighters as key stakeholders to identify and critically examine the intersections of disciplines and the subsets of models where warfighters’ moral orientations and moral agency form and reconcile the moral dissonance that results in MMI. A warfighter’s moral orienting system is a composite of core values used to “guide individual[s] along preferred pathways to significant destinations” (Pargament and Exline 2022, 29-30, 243-ff). These destinations include the moral agency that individuals use to: 1) regulate their cognitions and reactions, and 2) process their emotions and life narratives. Within the military ethos, moral orienting systems are driven by warrior codes that define the moral standards that direct warfighters’ identity and ethical agency. Therefore, the content and processes of warfighters’ moral orientations need to be considered when defining and treating MMI. During military training, warfighters integrate military values and professional competencies into the moral orienting systems that drive the moral agency they perform during combat. Specific events in warfighting can dis-integrate relationships between moral orientation and moral agency, causing levels of moral dissonance (Litz et al. 2009; Shay 2014; Maguen et al. 2011; Tick 2005). Moral dissonance can be examined as struggles that 1) disorient the nature of individuals’ moral orienting systems, 2) disrupt their formations of life purpose and meaning, and 3) result in a spectrum of maladaptive behaviors (Pargament and Exline 2022, 32-34). Following combat, warfighters need to reconcile their moral dissonance. Their inability to do this results in MMI. Multiple treatment modalities and programs support warfighters’ reconciliation of moral dissonance through the creation of adaptive post-traumatic meanings (Park et al. 2017). The TMM is a framework that explains this process. It provides a multi-discipline, research-based approach for understanding, mitigating, and healing moral dissonance from warfighting

Empirical Approach for Modelling Tree Phenology in Mixed Forests Using Remote Sensing

Phenological events are good indicators of the effects of climate change, since phenological phases are sensitive to changes in environmental conditions. Although several national phenological networks monitor the phenology of different plant species, direct observations can only be conducted on individual trees, which cannot be easily extended over large and continuous areas. Remote sensing has often been applied to model phenology for large areas, focusing mostly on pure forests in which it is relatively easier to match vegetation indices with ground observations. In mixed forests, phenology modelling from remote sensing is often limited to land surface phenology, which consists of an overall phenology of all tree species present in a pixel. The potential of remote sensing for modelling the phenology of individual tree species in mixed forests remains underexplored. In this study, we applied the seasonal midpoint (SM) method with MODIS GPP to model the start of season (SOS) and the end of season (EOS) of six different tree species in Slovenian mixed forests. First, substitute locations were identified for each combination of observation station and plant species based on similar environmental conditions (aspect, slope, and altitude) and tree species of interest, and used to retrieve the remote sensing information used in the SM method after fitting the best of a Gaussian and two double logistic functions to each year of GPP time series. Then, the best thresholds were identified for SOS and EOS, and the results were validated using cross-validation. The results show clearly that the usual threshold of 0.5 is not best in most cases, especially for estimating the EOS. Despite the difficulty in modelling the phenology of different tree species in a mixed forest using remote sensing, it was possible to estimate SOS and EOS with moderate errors as low as <8 days (Fagus sylvatica and Tilia sp.) and <10 days (Fagus sylvatica and Populus tremula), respectively

Structure-based identification of functional residues in the nucleoside-2'-O-methylase domain of Bluetongue virus VP4 capping enzyme.

Bluetongue virus (BTV) encodes a single capping protein, VP4, which catalyzes all reactions required to generate cap1 structures on nascent viral transcripts. Further, structural analysis by X-ray crystallography indicated each catalytic reaction is arranged as a discrete domain, including a nucleoside-2'-O-methyltransferase (2'-O MTase). In this study, we have exploited the structural information to identify the residues that are important for the catalytic activity of 2'-O MTase of VP4 and their influence on BTV replication. The effect of these mutations on GMP binding, guanylyltransferase (GTase) and methylase activities were analysed by a series of in vitro biochemical assays using recombinant mutant proteins; subsequently their effects on virus replication were assessed by introducing the same mutations in replicating viral genome using a reverse genetics system. Our data showed that single substitution mutations in the catalytic tetrad K-D-K-E were sufficient to abolish 2'-O MTase activity in vitro and to completely abrogate BTV replication in cells; although these mutants retained the upstream GMP binding, GTase and guanine-N7-methyltransferase activities. Mutations of the surrounding substrate-binding pocket (predicted to recruit cap0) had variable effects on in vitro VP4 capping activity. Only triple but not single substitution mutations of these residues in genome resulted in reduced virus replication kinetics. This is the first report investigating the importance of 2'-O MTase function for any member of the Reoviridae and highlights the significance of K-D-K-E tetrad and surrounding residues for the efficiency of 2'-O MTase activity and in turn, for virus fitness

Evading innate immunity in nonviral mRNA delivery : don't shoot the messenger

In de field of non-viral gene therapy, in vitro transcribed (IVT) mRNA has emerged as a promising tool for the delivery of genetic information. Over the past few years it has become widely known the introduction of IVT mRNA into mammalian cells elicits an innate immune response which has favored mRNA use towards immunotherapeutic vaccination strategies. However, for non-immunotherapy related applications this intrinsic immune-stimulatory activity directly interferes with the aimed therapeutic outcome, as it can seriously compromise the expression of the desired protein. This review presents an overview of the immune-related obstacles that limit mRNA advance for non-immunotherapy related applications

Nucleoside modifications in RNA limit activation of 2′-5′-oligoadenylate synthetase and increase resistance to cleavage by RNase L

The interferon-induced enzymes 2′-5′-oligoadenylate synthetase (OAS) and RNase L are key components of innate immunity involved in sensory and effector functions following viral infections. Upon binding target RNA, OAS is activated to produce 2′-5′-linked oligoadenylates (2-5A) that activate RNase L, which then cleaves single-stranded self and non-self RNA. Modified nucleosides that are present in cellular transcripts have been shown to suppress activation of several RNA sensors. Here, we demonstrate that in vitro transcribed, unmodified RNA activates OAS, induces RNase L-mediated ribosomal RNA (rRNA) cleavage and is rapidly cleaved by RNase L. In contrast, RNA containing modified nucleosides activates OAS less efficiently and induces limited rRNA cleavage. Nucleoside modifications also make RNA resistant to cleavage by RNase L. Examining translation in RNase L−/− cells and mice confirmed that RNase L activity reduces translation of unmodified mRNA, which is not observed with modified mRNA. Additionally, mRNA containing the nucleoside modification pseudouridine is translated longer and has an extended half-life. The observation that modified nucleosides in RNA reduce 2-5A pathway activation joins OAS and RNase L to the list of RNA sensors and effectors whose functions are limited when RNA is modified, confirming the role of nucleoside modifications in suppressing immune recognition of RNA

The Replicase Gene of Avian Coronavirus Infectious Bronchitis Virus Is a Determinant of Pathogenicity

We have previously demonstrated that the replacement of the S gene from an avirulent strain (Beaudette) of infectious bronchitis virus (IBV) with an S gene from a virulent strain (M41) resulted in a recombinant virus (BeauR-M41(S)) with the in vitro cell tropism of the virulent virus but that was still avirulent. In order to investigate whether any of the other structural or accessory genes played a role in pathogenicity we have now replaced these from the Beaudette strain with those from M41. The recombinant IBV was in effect a chimaeric virus with the replicase gene derived from Beaudette and the rest of the genome from M41. This demonstrated that it is possible to exchange a large region of the IBV genome, approximately 8.4 kb, using our transient dominant selection method. Recovery of a viable recombinant IBV also demonstrated that it is possible to interchange a complete replicase gene as we had in effect replaced the M41 replicase gene with the Beaudette derived gene. Analysis of the chimaeric virus showed that it was avirulent indicating that none of the structural or accessory genes derived from a virulent isolate of IBV were able to restore virulence and that therefore, the loss of virulence associated with the Beaudette strain resides in the replicase gene