UMaine holds virtual groundbreaking for $78 million Ferland Engineering Education and Design Center

A virtual groundbreaking ceremony for the $78 million Engineering Education and Design Center (EEDC) took place April 28, 2020 on the University of Maine campus. Click on the download link for a machine-generated English-language transcript

Mechanisms for Vascular Cell Adhesion Molecule-1 Activation of ERK1/2 during Leukocyte Transendothelial Migration

Background: During inflammation, adhesion molecules regulate recruitment of leukocytes to inflamed tissues. It is reported that vascular cell adhesion molecule-1 (VCAM-1) activates extracellular regulated kinases 1 and 2 (ERK1/2), but the mechanism for this activation is not known. Pharmacological inhibitors of ERK1/2 partially inhibit leukocyte transendothelial migration in a multi-receptor system but it is not known whether VCAM-1 activation of ERK1/2 is required for leukocyte transendothelial migration (TEM) on VCAM-1. Methodology/Principal Findings: In this study, we identified a mechanism for VCAM-1 activation of ERK1/2 in human and mouse endothelial cells. VCAM-1 signaling, which occurs through endothelial cell NADPH oxidase, protein kinase Ca (PKCa), and protein tyrosine phosphatase 1B (PTP1B), activates endothelial cell ERK1/2. Inhibition of these signals blocked VCAM-1 activation of ERK1/2, indicating that ERK1/2 is activated downstream of PTP1B during VCAM-1 signaling. Furthermore, VCAM-1-specific leukocyte migration under physiological laminar flow of 2 dynes/cm 2 was blocked by pretreatment of endothelial cells with dominant-negative ERK2 K52R or the MEK/ERK inhibitors, PD98059 and U0126, indicating for the first time that ERK regulates VCAM-1-dependent leukocyte transendothelial migration. Conclusions/Significance: VCAM-1 activation of endothelial cell NADPH oxidase/PKCa/PTP1B induces transient ERK1/2 activation that is necessary for VCAM-1-dependent leukocyte TEM

Mechanism for Initiation of Food Allergy: Dependence on skin barrier mutations and environmental allergen co-stimulation

Background Mechanisms for the development of food allergy in neonates are unknown but are clearly linked in patient populations to a genetic predisposition towards skin barrier defects. Whether skin barrier defects functionally contribute to development of food allergy is unknown. Objective The purpose of the study was to determine whether skin barrier mutations, that are primarily heterozygous in patient populations, contribute to the development of food allergy. Methods Mice heterozygous for the Flgft and Tmem79ma mutations were skin sensitized with environmental allergens and food allergens. After sensitization, mice received oral challenge with food allergen and then inflammation, inflammatory mediators, and anaphylaxis were measured. Results We define development of inflammation, inflammatory mediators, and food allergen-induced anaphylaxis in neonatal mice with skin barrier mutations following brief concurrent cutaneous exposure to food and environmental allergens. Moreover, neonates of allergic mothers have elevated responses to suboptimal sensitization with food allergens. Importantly, the responses to food allergens by these neonatal mice were dependent on genetic defects in skin barrier function and on exposure to environmental allergens. Blockade of ST2 during skin sensitization inhibited development of anaphylaxis, antigen-specific IgE and inflammatory mediators. The neonatal anaphylactic responses and antigen-specific IgE were also inhibited by oral pre-exposure to food allergen but, interestingly, this was blunted by concurrent pre-exposure of the skin to environmental allergen. Conclusion These studies uncover mechanisms for food allergy sensitization and anaphylaxis in neonatal mice that are consistent with features of human early life exposures and genetics in clinical food allergy and demonstrate that changes in barrier function drive development of anaphylaxis to food allergen

Ferland Engineering Education and Design Center (EEDC) Virtual Beam Topping Ceremony

Construction of the $78 million Engineering Education and Design Center (EEDC) on the University of Maine campus began in May 2020, with workers following state-mandated health and safety guidelines. Work on the 105,000-square-foot facility is expected to be completed in spring 2022. Design and construction of EEDC involved 78 graduates of the University of Maine, many from the College of Engineering. Over 500 alumni, friends, corporations, and foundations contributed to the fund-raising effort. Retired power industry executive and Skowhegan, Maine native, Jim Ferland and his wife Eileen provided a$10-million naming gift for the new Center. Jim Ferland earned a degree in Mechanical Engineering from the University of Maine in 1964. Click on the download link for a machine-generated English-language transcript

Media Theory, Public Relevance and the Propaganda Model

Since its initial formulation in 1988, the Herman-Chomsky Propaganda Model (PM) has become one of the most widely tested models of media performance in the social sciences. This is largely due to the combined efforts of a loose group of international scholars as well as an increasing number of students who have produced studies in the US, UK, Canadian, Australian, Japanese, Chinese, German, and Dutch contexts, amongst others. Yet, the PM has also been marginalised in media and communication scholarship, largely due to the fact that the PM‟s radical scholarly outlook challenges the liberal and conservative underpinnings of mainstream schools of thought in capitalist democracies. This paper brings together, for the first time, leading scholars to discuss important questions pertaining to the PM‟s origins, public relevance, connections to other approaches within Communication Studies and Cultural Studies, applicability in the social media age, as well as impact and influence. The paper aligns with the 30th anniversary of the PM and the publication of the collected volume, The Propaganda Model Today, and highlights the PM‟s continued relevance at a time of unprecedented corporate consolidation of the media, extreme levels of inequality and class conflict as well as emergence of new forms of authoritarianism

Caspase-11 regulates the tumour suppressor function of STAT1 in a murine model of colitis-associated carcinogenesis

Murine inflammatory caspase-11 has an important role in intestinal epithelial inflammation and barrier function. Activation of the non-canonical inflammasome, mediated by caspase-11, serves as a regulatory pathway for the production of the proinflammatory cytokines IL-1β and IL-18, and has a key role in pyroptotic cell death. We have previously demonstrated a protective role for caspase-11 during dextran sulphate sodium (DSS)-induced colitis, however the importance of caspase-11 during colorectal tumour development remains unclear. Here, we show that Casp11−/− mice are highly susceptible to the azoxymethane (AOM)-DSS model of colitis-associated cancer (CAC), compared to their wild type (WT) littermates. We show that deficient IL-18 production occurs at initial inflammation stages of disease, and that IL-1β production is more significantly impaired in Casp11−/− colons during established CAC. We identify defective STAT1 activation in Casp11−/− colons during disease progression, and show that IL-1β signalling induces caspase-11 expression and STAT1 activation in primary murine macrophages and intestinal epithelial cells. These findings uncover an anti-tumour role for the caspase-11 and the non-canonical inflammasome during CAC, and suggest a critical role for caspase-11, linking IL-1β and STAT1 signalling pathways

Serotonin transporter in the temporal lobe, hippocampus and amygdala in SUDEP

Several lines of evidence link deficient serotonin function and SUDEP. Chronic treatment with serotonin reuptake inhibitors (SRIs) reduces ictal central apnoea, a risk factor for SUDEP. Reduced medullary serotonergic neurones, modulators of respiration in response to hypercapnia, were reported in a SUDEP post-mortem series. The amygdala and hippocampus have high serotonergic innervation and are functionally implicated in seizure-related respiratory dysregulation. We explored serotonergic networks in mesial temporal lobe structures in a surgical and post-mortem epilepsy series in relation to SUDEP risk. We stratified 75 temporal lobe epilepsy patients with hippocampal sclerosis (TLE/HS) into high (N = 16), medium (N = 11) and low risk (N = 48) groups for SUDEP based on generalised seizure frequency. We also included the amygdala in 35 post-mortem cases, including SUDEP (N = 17), epilepsy controls (N = 10) and non-epilepsy controls (N = 8). The immunohistochemistry labelling index (LI) and axonal length (AL) of serotonin transporter (SERT)-positive axons were quantified in 13 regions of interest with image analysis. SERT LI was highest in amygdala and subiculum regions. In the surgical series, higher SERT LI was observed in high risk than low risk cases in the dentate gyrus, CA1 and subiculum (p < 0.05). In the post-mortem cases higher SERT LI and AL was observed in the basal and accessory basal nuclei of the amygdala and peri-amygdala cortex in SUDEP compared to epilepsy controls (p < 0.05). Patients on SRI showed higher SERT in the dentate gyrus (p < 0.005) and CA4 (p < 0.05) but there was no difference in patients with or without a psychiatric history. Higher SERT in hippocampal subfields in TLE/HS cases with SUDEP risk factors and higher amygdala SERT in post-mortem SUDEP cases than epilepsy controls supports a role for altered serotonergic networks involving limbic regions in SUDEP. This may be of functional relevance through reduced 5-HT availability