PSC-derived neuronal co-cultures to model corticostriatal connectivity loss and associated phenotypes observed in Huntington's disease

Huntington's disease (HD) is a genetic neurodegenerative disease caused by an expanded CAG-repeat mutation in exon 1 of the gene encoding huntingtin (HTT) which results in an elongated polyglutamine (polyQ) tract. A triad of symptoms encompassing cognitive, motor and psychiatric features are evident in mutant gene carriers, with typical symptom manifestation in adult life; the degeneration of the corticostriatal (CS) pathway and disruption to its connectivity partially underlie the manifestation of these symptoms. The CS pathway is composed of cortical layer V projection neurons (CPNs) and striatal medium spiny neurons (MSNs), which are the principle neuronal subtypes targeted in HD pathology. The aim of this thesis was to recapitulate the CS pathway in vitro using human cells in co-culture, in order to better understand the early pathological events that lead to its disruption in HD. Using human pluripotent stem cells (PSC) derived from an HD family and an isogenic HTT allelic series, MSN- and CPN-containing cultures expressing various HTT polyQ lengths were generated using validated methods that were then adapted and optimised for use in this thesis. HD-associated phenotypes were revealed in both cell types by using a thorough approach to phenotypical profiling. Alterations in cell viability at baseline and after stress were documented, as well as changes to neuronal morphology and adhesive function. Novel investigations into axonal projection revealed a HTT polyQ-length dependent deficiency in HD CPNs, as well as altered neurotrophin production and release. Using microfluidic chambers (MFC), a co-culture system was created to recapitulate the CS pathway. Their use showed that it is possible to culture PSC-derived neurons in MFCs, with evidence of neuronal connectivity as shown by the formation of synapses within the devices. Differences in the level of synapse maintenance suggest that this platform could be useful in further assessing the development of early CS pathology in an HD context

Managing Uncertainty and Risk in Access to the Solicitors’ Profession in England : Classed Pathways?

Despite decades of diversity and widening participation initiatives, access to elite professions for those from lower socio-economic backgrounds remains a troublingly persistent issue. Degree apprenticeships present an alternative to the traditional university pathway and an opportunity to increase social mobility into professional occupations. Yet, uptake of this pathway has so far been from more advantaged individuals. This article explores the dispositions of key stakeholders towards alternative pathways. It asks whether professional apprenticeships are perceived as legitimate and, if not, what are the likely consequences? Using the solicitors’ profession in England as a pertinent case, interviews with 23 participants on the degree apprenticeship and university pathways were asked about their social and educational backgrounds, exploring the influences on their career and pathway decision making. The analysis demonstrates differing perceptions of risk and legitimacy among those from different social and educational backgrounds, with implications for equity, inequality and social mobility

Nutritional Evaluation of Food Bank Services in Chittenden and Addison Counties, Vermont

Background: Feeding Chittenden and Addison Food Shelf are programs that alleviate hunger in Vermont utilizing the Food Access Network. This Network allows customers to select food and have it delivered to a location of their choice, with an aim of providing healthier foods while reducing barriers and stigma. Methods: Using nutritional standards adapted from a BMC Public Health study [1], food items delivered from March- May 2023 were scored based on category, amount of saturated fat, sodium, and added sugar. Scores included ‘1,’ recommended often, ‘2,’ recommended sometimes, and ‘3,’ recommended rarely. Analysis was conducted on total offerings, total orders, and order pickup/drop-off locations in the two counties. Results: The average score for the food offered in Chittenden v. Addison County was 1.69 v. 1.60 with Chittenden being 45.9% foods scored ‘1,’ 39.3% ‘2,’ and 14.8% ‘3,’ and Addison being 51.7% ‘1,’ 36.3% ‘2,’ and 12.1% ‘3.’Although Addison offered more food options scored as ‘1’ it demonstrated a higher average order score (1.83) compared to Chittenden (1.62). This trend continued when analyzing pick-up/drop-off locations as 71% of Addison sites versus 7.7% of Chittenden sites had foods scored ‘2’ as their highest percentage of items ordered. Conclusion: While at baseline one may consider a direct correlation between the food choices offered and the ordering habits of an individual, it is evident from this data that there are factors beyond ordering options that are impacting ordering habits. Previous research suggests an unexplained difference between rural and urban counties when it comes to dietary intake (Euler 2019). When considering the limitations of previous studies and the robust data available through this study in combination with Rural Urban Commuting Area (RUCA) Code, future research will be able to further explore the differences in nutritional habits by county, allowing more targeted interventions to address these differences. Future Directions: Going forward, there are many directions future research could pursue with CVOEO. Our initial research was a descriptive study of Chittenden and Addison counties stocked and outgoing foods. A metric we used in our data analysis was the selected drop-off locations. Additional metrics that could be used to analyze the data are the age of the registrant, the home zip code, and the referral source. Each of these metrics could allow for more information to be gathered about specific populations that utilize the Food Access Network. Additionally, an interventional study could be done. At the current moment, Chittenden, and Addison County list their produce and meats differently. Addison County lists the specific produce and meat, while Chittenden County offers “assorted” categories of each. Standardizing the listing and then studying potential changes in ordering trends is a potential direction for future stud

University or Degree Apprenticeship? Stratification and Uncertainty in Routes to the Solicitors’ Profession

This article considers whether degree apprenticeships could disrupt traditional university routes to professional careers and redress longstanding inequalities in access between individuals from different social backgrounds. Using the solicitors’ profession as a pertinent case, issues of access and choice are explored, utilising Breen and Goldthorpe’s theory of Relative Risk Aversion (1997) to understand variation across social background. Drawing on 23 in-depth interviews with law students, trainee solicitors and solicitor degree apprentices from four universities and five law firms across England, the analysis illuminates the decision-making approaches of aspiring solicitors through both the university and the degree apprenticeship routes. Contrary to expectation, the degree apprenticeship route appears to be discounted as unfamiliar and risky by many of those from disadvantaged backgrounds. Instead it is tactically adopted as an alternative by some middle-class students. As such, the degree apprenticeship is not likely to disrupt existing patterns in access to the solicitors’ profession

Why is speech language pathology considered a gendered profession amongst male college students in health related majors?

A gender disparity exists in the field of speech-language pathology, and it is recognized in the American Speech and Hearing Association’s demographic report. In Mississippi, 98.4% of SLPs are female and 1.6% are male (ASHA, 2022). Given the numbers presented by ASHA, awareness of speech-language pathology amongst male college students comes into question. According to ASHA’s Strategic Pathway to Excellence, objective #6 is to increase diversity/equity/inclusion within the Association and the discipline (ASHA, 2023). A goal of this research study is to identify the barriers and awareness level of males in health-related undergraduate majors. This information would better facilitate how recruitment and stereotypes should be addressed in speech-language pathology. An online survey will be used for this study to gather information from male college students who are enrolled in health related majors at The Mississippi University for Women to gain more insight on why the ratio of men to women in the speech-language pathology department is so vast and what may deter males from majoring in speech-language pathology. We will reach out to the head of the department of each of these health related majors to get permission to give the survey using the website “Qualtrics” as our method. This method is easy to use and is customizable because there are different themes, images, and other features to choose from. The questionnaire will be made prior to January 2024 and will be passed out and collected over a two-week period at the beginning of spring semester

Gender patterns in dress and outward appearance: an individual choice or fulfillment of cultural expectations?

This study examines the extent to which males and females conform to gender schemas regarding outward appearance and clothing styles. Participants were observed from a distance in various natural settings and were coded based on estimated age, hair length, certain clothing choices, and certain jewelry and accessory choices. We found statistically significant gender differences (with p \u3c.0001) for all characteristics, with the codes for hair length, earrings, and dresses showing the strongest discrepancies. These data showed a pattern of males being more confined to strict gender displays than were females, which can be seen particularly clearly in the wearing of earrings and dresses, as males rarely deviated from the socially acceptable gender signals. These findings imply that the feminist movement loosened feminine standards for dress and appearance; lacking a similar social movement, men remain more strictly confined to traditional displays of gender

Species information in whistle frequency modulation patterns of common dolphins

Funding for this project was generously provided by the Office of Naval Research Marine Mammals and Biology program.The most flexible communication systems are those of open-ended vocal learners that can acquire new signals throughout their lifetimes. While acoustic signals carry information in general voice features that affect all of an individual's vocalizations, vocal learners can also introduce novel call types to their repertoires. Delphinids are known for using such learned call types in individual recognition, but their role in other contexts is less clear. We investigated the whistles of two closely related, sympatric common dolphin species, Delphinus delphis and Delphinus bairdii, to evaluate species differences in whistle contours. Acoustic recordings of single-species groups were obtained from the Southern California Bight. We used an unsupervised neural network to categorize whistles and compared the resulting whistle types between species. Of the whistle types recorded in more than one encounter, 169 were shared between species and 60 were species-specific (32 D. delphis types, 28 D. bairdii types). Delphinus delphis used 15 whistle types with an oscillatory frequency contour while only one such type was found in D. bairdii. Given the role of vocal learning in delphinid vocalizations, we argue that these differences in whistle production are probably culturally driven and could help facilitate species recognition between Delphinus species.Publisher PDFPeer reviewe