Framing Outcomes and Program Assessment for Digital Scholarship Services: A Logic Model Approach

This is an Accepted Manuscript of an article published by the Association of College and Research Libraries in College and Research Libraries in March 2021, available online: https://doi.org/10.5860/crl.82.2.142Assessing digital scholarship services offered either through academic libraries or elsewhere on campuses is important for both program development and service refinement. Digital scholarship support is influenced by fluid campus priorities and limited resources, including staffing, service models, infrastructure, and partnership opportunities available at a university. Digital scholarship support is built upon deep, ongoing relationships and there is an intrinsic need to balance these time-intensive collaborations with scalable service offerings. Therefore, typical library assessment methods do not adequately capture the sustained engagement and impacts to research support and collaboration that come from digital scholarship services. This article discusses the creation of a logic model as one approach to frame assessment of digital scholarship services in the university environment.Publisher allows immediate open acces

Itaconate modulates tricarboxylic acid and redox metabolism to mitigate reperfusion injury.

ObjectivesCerebral ischemia/reperfusion (IR) drives oxidative stress and injurious metabolic processes that lead to redox imbalance, inflammation, and tissue damage. However, the key mediators of reperfusion injury remain unclear, and therefore, there is considerable interest in therapeutically targeting metabolism and the cellular response to oxidative stress.MethodsThe objective of this study was to investigate the molecular, metabolic, and physiological impact of itaconate treatment to mitigate reperfusion injuries in in vitro and in vivo model systems. We conducted metabolic flux and bioenergetic studies in response to exogenous itaconate treatment in cultures of primary rat cortical neurons and astrocytes. In addition, we administered itaconate to mouse models of cerebral reperfusion injury with ischemia or traumatic brain injury followed by hemorrhagic shock resuscitation. We quantitatively characterized the metabolite levels, neurological behavior, markers of redox stress, leukocyte adhesion, arterial blood flow, and arteriolar diameter in the brains of the treated/untreated mice.ResultsWe demonstrate that the "immunometabolite" itaconate slowed tricarboxylic acid (TCA) cycle metabolism and buffered redox imbalance via succinate dehydrogenase (SDH) inhibition and induction of anti-oxidative stress response in primary cultures of astrocytes and neurons. The addition of itaconate to reperfusion fluids after mouse cerebral IR injury increased glutathione levels and reduced reactive oxygen/nitrogen species (ROS/RNS) to improve neurological function. Plasma organic acids increased post-reperfusion injury, while administration of itaconate normalized these metabolites. In mouse cranial window models, itaconate significantly improved hemodynamics while reducing leukocyte adhesion. Further, itaconate supplementation increased survival in mice experiencing traumatic brain injury (TBI) and hemorrhagic shock.ConclusionsWe hypothesize that itaconate transiently inhibits SDH to gradually "awaken" mitochondrial function upon reperfusion that minimizes ROS and tissue damage. Collectively, our data indicate that itaconate acts as a mitochondrial regulator that controls redox metabolism to improve physiological outcomes associated with IR injury

The relation of perceptual factors and speed of handwriting to spelling ability.

Thesis (Ed.M.)--Boston Universit

Morphine Preferentially Activates the Periaqueductal Gray – Rostral Ventromedial Medullary Pathway in the Male Rat: A Potential Mechanism for Sex Differences in Antinociception

The midbrain periaqueductal gray (PAG), and its descending projections to the rostral ventromedial medulla (RVM), provide an essential neural circuit for opioid-produced antinociception. Recent anatomical studies have reported that the projections from the PAG to the RVM are sexually dimorphic and that systemic administration of morphine significantly suppresses pain-induced activation of the PAG in male but not female rats. Given that morphine antinociception is produced in part by disinhibition of PAG output neurons, it is hypothesized that a differential activation of PAG output neurons mediates the sexually dimorphic actions of morphine. The present study examined systemic morphine-induced activation of PAG-RVM neurons in the absence of pain. The retrograde tracer Fluorogold (FG) was injected into the RVM to label PAG-RVM output neurons. Activation of PAG neurons was determined by quantifying the number of Fos-positive neurons 1 h following systemic morphine administration (4.5 mg/kg). Morphine produced comparable activation of the PAG in both male and female rats, with no significant differences in either the quantitative or qualitative distribution of Fos. While microinjection of FG into the RVM labeled significantly more PAG output neurons in female rats than male rats, very few of these neurons (20%) were activated by systemic morphine administration in comparison to males (50%). The absolute number of PAG-RVM neurons activated by morphine was also greater in males. These data demonstrate widespread disinhibition of PAG neurons following morphine administration. The greater morphine-induced activation of PAG output neurons in male compared with female rats is consistent with the greater morphine-induced antinociception observed in males

Sexually Dimorphic Activation of the Periaqueductal Gray – Rostral Ventromedial Medullary Circuit during the Development of Morphine Tolerance in the Rat

Previous studies have shown that tolerance develops to a greater degree in male compared to female rats. The midbrain periaqueductal gray (PAG), and its descending projections to the rostral ventromedial medulla (RVM), provides an essential neural circuit for the antinociceptive effects of opiates and has been implicated in the development of tolerance to morphine. We have previously reported that systemic morphine administration activates a greater proportion of PAG-RVM neurons in male versus female rats; our hypothesis is that if the PAG-RVM pathway is essential for the development of morphine tolerance, then (1) morphine activation of the PAG-RVM pathway should decline as tolerance develops, and (2) sex differences should be reflected as a greater decline in males. These hypotheses were tested using behavioral and neuroanatomical techniques to map the activation of the PAG-RVM pathway during the development of tolerance to repeated morphine administration (4.5 mg/kg; s.c.). We found that as male rats develop tolerance (D50 increased from 3.0 to 6.3 mg/kg), there was no significant decline in the overall activation of the PAG, however, there was a steady decline in the percentage of PAG-RVM output neurons activated by morphine. This reduction occurred in males only; there was no significant decline in the activity of PAG-RVM output neurons in females. These data demonstrate that the greater development of tolerance to morphine administration in male rats corresponds with a significant reduction in the activation of the PAG-RVM circuit. Our results provide additional data demonstrating a central role for the PAG in morphine tolerance

Detection of a Tyrosine Phosphatase LAR on Intestinal Epithelial Cells and Intraepithelial Lymphocytes in the Human Duodenum

Studies of tyrosine phosphorylation in the human duodenum have indicated that proliferating cells in the middle portion of the duodenal crypt were devoid of this feature, suggesting that tyrosine kinase activation is not a dominant factor in crypt cell proliferation, and that consequently tyrosine phosphatase activity may be a more critical factor in crypt cell development. We investigated the expression of the leukocyte common antigen-related receptor (LAR) family of tyrosine phosphatases. A flow cytometry system was used to examine cells from the surface, mid-portion, and lower part of the crypt. Individual cell populations were immunostained with anti-LAR antibodies using phycoerythrin-conjugated anti-CD3 to discriminate between epithelial cells (CD3(−)) and intraepithelial lymphocytes (CD3(+)). Epithelial cells expressed LAR throughout the crypt. Expression of LAR was maximal in the mid-portion of the crypt with lower expression at the top of the villi. Intraepithelial lymphocytes expressed low levels of LAR at the tips of the villi with stronger expression extending towards the base of the crypt. These findings were confirmed by immunohistochemistry on paraffin-fixed sections. Of note, peripheral blood lymphocytes expressed less LAR than IEL. These observations suggest the possibility that tyrosine phosphatase LAR may be of importance in the regulation of crypt cell proliferation. Moreover, as the extracellular domain of LAR has homology with adhesion molecules, the finding of this molecule on IEL could suggest a possible functional role in homing of this unique lymphocyte