Chronic activation of Toll-like receptor 2 induces an ichthyotic skin phenotype

BACKGROUND: Ichthyosis defines a group of chronic conditions that manifest phenotypically as a thick layer of scales and often affects the entire skin. While the gene mutations that lead to ichthyosis are well documented, the actual signalling mechanisms that lead to scaling are poorly characterised, however recent publications suggest that there are common mechanisms active in ichthyotic tissue, and in analogous models of ichthyosis. OBJECTIVE: To determine common mechanisms of hyperkeratosis that may be easily targeted with small molecule inhibitors. METHODS: We combined gene expression analysis of gene-specific shRNA knockdowns in rat epidermal keratinocytes of two genes mutated in autosomal recessive congenital ichthyosis (ARCI), Transglutaminase 1 (TGM1) and arachidonate 12-lipoxygenase, 12R type (ALOX12B), and proteomic analysis of skin scale from ARCI patients.as well as RNAseq data from rat epidermal keratinocytes treated with the Toll-like receptor-2 agonist PAM3CSK. RESULTS: we identified a common activation of the Toll-like receptor (TLR) 2 pathway. Exogenous TLR2 activation led to increased expression of important cornified envelope genes and in organotypic culture caused hyperkeratosis. Conversely, blockade of TLR2 signalling in ichthyosis patient keratinocytes and our shRNA models reduced the expression of keratin 1, a structural protein over-expressed in ichthyosis scale. A time-course of Tlr2 activation in rat epidermal keratinocytes revealed that although there was rapid initial activation of innate immune pathways, this was rapidly superseded by widespread up-regulation of epidermal differentiation related proteins. Both NFκβ phosphorylation and Gata3 up-regulation was associated with this switch and Gata3 overexpression was sufficient to increase Keratin 1 expression. CONCLUSION: Taken together, these data define a dual role for Toll-like receptor 2 activation during epidermal barrier repair, that may be a useful therapeutic modality in treating diseases of epidermal barrier dysfunction

A 2022 Assessment of Food Security and Health Outcomes during the COVID-19 Pandemic

We conducted a Northern New England survey to understand the impacts of the COVID-19 pandemic on food security, food access, home food production, health behaviors, and health outcomes. The surveys were conducted in the spring of 2022 (April-May) with a total of 1,013 adults (598 in Maine and 415 in Vermont) responding to the survey. Key findings include:1. The prevalence of food insecurity remains similarly high to early points in the pandemic, likely driven by inflation and food prices, and long-term impacts from the pandemic. 2. The majority (62%) indicated the recent rise in food prices affected their food purchasing, this was significantly higher (90%) for food insecure respondents. 3. 1/3 of respondents utilized food assistance programs in the last 12 months. They reported difficulty traveling to food program offices to apply or recertify as a key challenge. 4. 2/3 of respondents engaged in some kind of home food production (HFP) and half of those did HFP activities for the first time or did existing HFP activities more in the last 12 months. 5. Nearly 1/3 reported weight gain during the COVID-19 pandemic. Food insecure respondents were significantly more likely to report weight gain. 6. Nearly 40% of food insecure respondents ate fewer fruits and vegetables and certain animal products in the last 12 months. These changes are significantly higher than for food secure respondents. 7. Half of the respondents faced a health care challenge in the last 12 months, with canceled appointments and trouble finding a timely appointment being the most commonly reported challenges. 8. More than 50% of respondents indicated anxiety and/or depression, with 17% of those with a diagnosis newly diagnosed in the last 12 months. 9. Compared to food secure respondents, food insecure respondents were significantly more likely to face a variety of health challenges in the last 12 months, including difficulty accessing healthcare, being diagnosed with anxiety and depression, stopping and skipping medications due to cost, and using habit-forming substances

Home Food Production and Food Security Since the COVID-19 Pandemic

We conducted a Northern New England survey to understand the initial and continued impacts of the COVID-19 pandemic on food security, food access, and home food production (HFP) (i.e. gardening, fishing, harvesting shellfish, foraging, hunting, trapping, raising animals for meat, dairy, or eggs, and food preservation such as canning, drying or freezing). The surveys were conducted in the Spring and Summer of 2021 (March – June). The survey was conducted in Maine (n = 562) and Vermont (n = 426). The cohort of respondents was representative of racial and ethnic identities of Vermont and Maine state populations. The data presented in this research brief were weighted to be representative of income in both states. Here, we summarize our findings related to changes in food security, food sourcing, and HFP before and since the COVID-19 pandemic. When data are referred to as “significant” it indicates a statistical significance at p\u3c 0.05

Change in Food Security and Health Outcomes Since the COVID-19 Pandemic in Northern New England

We conducted a Northern New England survey in March-June of 2021 to understand the initial and continued impacts of the COVID-19 pandemic on food security, health behaviors, and health outcomes. A total of 988 adults (562 in Maine and 426 in Vermont) responded regarding food access and availability, health behaviors such as diet composition and exercise, and use of habit-forming substances (e.g. alcohol, tobacco, etc.) before and in the year following the onset of the COVID-19 pandemic. Key findings include: 1. 39.1% of Maine and 43.2% of Vermont respondents indicated weight gain since the start of the COVID-19 pandemic. 2. Individuals with food insecurity were significantly less likely to consume fruits and vegetables and engage in physical activity than those who report being food secure. 3. Nearly half of respondents indicated anxiety or depression during the COVID-19 pandemic. 4. Those with persistent food insecurity (i.e. food insecure before and during the COVID-19 pandemic) were 8.8 times more likely to experience higher levels of stress, 2.6 times more likely to experience anxiety and be diagnosed with diabetes type 2 and hypertension during the COVID-19 pandemic. 5. Individuals who identify as LGBTQ+ were more likely to be food insecure, 4 times more likely to report anxiety or depression, and also experienced higher levels of stress than individuals who did not identify as LGBTQ+ during the COVID-19 pandemic. 6. Individuals with food insecurity were up to 7 times more likely to skip or stop their medication for anxiety, depression, and/or hypertension, as compared to food secure respondents. 7. Individuals reporting the use of substances prior to the onset of the pandemic (e.g., tobacco, alcohol, and drugs) were more likely to have increased their use of additional habit-forming substances during the COVID-19 pandemic. Substance use was also associated with a higher prevalence of stress

The fiber knob protein of human adenovirus type 49 mediates highly efficient and promiscuous infection of cancer cell lines using a novel cell entry mechanism

The human adenovirus (HAdV) phylogenetic tree is diverse, divided across seven species and comprising over 100 individual types. Species D HAdV are rarely isolated with low rates of pre-existing immunity, making them appealing for therapeutic applications. Several species D vectors have been developed as vaccines against infectious diseases where they induce robust immunity in pre-clinical models and early phase clinical trials. However, many aspects of the basic virology of species D HAdV, including their basic receptor usage and means of cell entry, remain understudied. Here, we investigated HAdV-D49, which previously has been studied for vaccine and vascular gene transfer applications. We generated a pseudotyped HAdV-C5 presenting the HAdV-D49 fiber knob protein (HAdV-C5/D49K). This pseudotyped vector was efficient at infecting cells devoid of all known HAdV receptors, indicating HAdV-D49 uses an unidentified cellular receptor. Conversely, a pseudotyped vector presenting the fiber knob protein of the closely related HAdV-D30 (HAdV-C5/D30K), differing in four amino acids to HAdV-D49, failed to demonstrate the same tropism. These four amino acid changes resulted in a change in isoelectric point of the knob protein, with HAdV-D49K possessing a basic apical region compared to a more acidic region in HAdV-D30K. Structurally and biologically we demonstrate that HAdV-D49 knob protein is unable to engage CD46, while potential interaction with CAR is extremely limited by extension of the DG loop. HAdV-C5/49K efficiently transduced cancer cell lines of pancreatic, breast, lung, oesophageal and ovarian origin, indicating it may have potential for oncolytic virotherapy applications, especially for difficult to transduce tumor types

Considerations on Genre and Gender Conventions in Translating from Old English

The Old English poem The Wife's Lament is an extremely conventional and, at the same time, original text. It portrays a female character suffering for the absence of her loved one, through the framework of the so-called 'elegiac' style and a mainly heroic vocabulary. The traditional exile theme is, thus, interwoven with the uncommon motif of love sickness. While this appraisal of the poem is the most widely accepted one, disagreement still remains about the translation of some keywords, strictly related to the exile theme, such as sīþ or wræcsīþ. The aim of this paper is to examine diverging readings and glosses of the above mentioned 'exilic/elegiac' keywords, and to show that an accurate translation should not neglect a thorough appraisal of the text in its complexity and the association with related literary patterns and imagery in other poetic and prose texts

Effect of Electron Withdrawing and Electron Donating Substituents on the Synthesis of 1,3,4-Oxadiazoles using Dibromotriphenylphosphorane

The goal of this project was to determine the effects that electron withdrawing and electron donating substituents have on the synthesis of 1,3,4-oxadiazoles using a hydrazide starting material and dibromotriphenylphosphorane. This investigation involved the synthesis of hydrazide starting material followed by the synthesis of the oxadiazole with electron donating, withdrawing, or neutral substituents. Through this study, one neutral, three electron donating, two electron withdrawing substituents were investigated. Reactions were analyzed through nuclear magnetic resonance spectroscopy. Neutral electronegative substituents were deemed to be more successful through their percent yield and nuclear magnetic resonance spectroscopy data than both electron donating and withdrawing groups. Electron donating groups also produced more consistent and higher yields than electron donating substituents. Neither electron donating nor neutral substituents have enough statistical evidence to declare an affirmative trend, however, evidence from this study supports the hypothesis that electron withdrawing and neutral substituents are more ideal than electron donating substituents

Transformescense

Senior Project submitted to The Division of Arts of Bard Colleg