The Story of Here: A Graphic Guide to Holy Cross and College Hill

This illustrated guide captures the history of the section of Worcester where the College of the Holy Cross is located. Historical sources and imaginative interpretations based on historical research are combined to create a unique then and now approach and experience of double vision to tell the story of College Hill. This guide was a project of Montserrat Seminar 111N, taught by Prof. Sarah Luria in Spring 2020.https://crossworks.holycross.edu/hc_books/1051/thumbnail.jp

Medial prefrontal cortex serotonin 1A and 2A receptor binding interacts to predict threat-related amygdala reactivity

Background\ud The amygdala and medial prefrontal cortex (mPFC) comprise a key corticolimbic circuit that helps shape individual differences in sensitivity to threat and the related risk for psychopathology. Although serotonin (5-HT) is known to be a key modulator of this circuit, the specific receptors mediating this modulation are unclear. The colocalization of 5-HT1A and 5-HT2A receptors on mPFC glutamatergic neurons suggests that their functional interactions may mediate 5-HT effects on this circuit through top-down regulation of amygdala reactivity. Using a multimodal neuroimaging strategy in 39 healthy volunteers, we determined whether threat-related amygdala reactivity, assessed with blood oxygen level-dependent functional magnetic resonance imaging, was significantly predicted by the interaction between mPFC 5-HT1A and 5-HT2A receptor levels, assessed by positron emission tomography.\ud \ud Results\ud 5-HT1A binding in the mPFC significantly moderated an inverse correlation between mPFC 5-HT2A binding and threat-related amygdala reactivity. Specifically, mPFC 5-HT2A binding was significantly inversely correlated with amygdala reactivity only when mPFC 5-HT1A binding was relatively low.\ud \ud Conclusions\ud Our findings provide evidence that 5-HT1A and 5-HT2A receptors interact to shape serotonergic modulation of a functional circuit between the amygdala and mPFC. The effect of the interaction between mPFC 5-HT1A and 5-HT2A binding and amygdala reactivity is consistent with the colocalization of these receptors on glutamatergic neurons in the mPFC

Screening for glucose intolerance and development of a lifestyle education programme for prevention of Type 2 diabetes in a population with intellectual disabilities

Background: The prevalence of type 2 diabetes mellitus (T2DM) and of cardiovascular disease (CVD) is believed to be higher among people with intellectual disability (ID) than in the general population. However, research on prevalence and prevention in this population is limited. Objectives: The objectives of this programme of work were to establish a programme of research that would significantly enhance the knowledge and understanding of impaired glucose regulation (IGR) and T2DM in people with ID; to test strategies for the early identification of IGR and T2DM in people with ID; and to develop a lifestyle education programme and educator training protocol to promote behaviour change in a population with ID and IGR (or at a high risk of T2DM/CVD). Setting: Leicestershire, UK. Participants: Adults with ID were recruited from community settings, including residential homes and family homes. Adults with mild to moderate ID who had an elevated body mass index (BMI) of ≥ 25 kg/m2 and/or IGR were invited to take part in the education programme. Main outcome measures: The primary outcome of the screening programme was the prevalence of screen-detected T2DM and IGR. The uptake, feasibility and acceptability of the intervention were assessed. Data sources: Participants were recruited from general practices, specialist ID services and clinics, and through direct contact. Results: A total of 930 people with ID were recruited to the screening programme: 58% were male, 80% were white and 68% were overweight or obese. The mean age of participants was 43.3 years (standard deviation 14.2 years). Bloods were obtained for 675 participants (73%). The prevalence of previously undiagnosed T2DM was 1.3% [95% confidence interval (CI) 0.5% to 2%] and of IGR was 5% (95% CI 4% to 7%). Abnormal IGR was more common in those of non-white ethnicity; those with a first-degree family history of diabetes; those with increasing weight, waist circumference, BMI, diastolic blood pressure or triglycerides; and those with lower high-density lipoprotein cholesterol. We developed a lifestyle educational programme for people with ID, informed by findings from qualitative stakeholder interviews (health-care professionals, n = 14; people with ID, n = 7) and evidence reviews. Subsequently, 11 people with ID (and carers) participated in pilot education sessions (two groups) and five people attended education for the feasibility stage (one group). We found that it was feasible to collect primary outcome measures on physical activity and sedentary behaviour using wrist-worn accelerometers. We found that the programme was relatively costly, meaning that large changes in activity or diet (or a reduction in programme costs) would be necessary for the programme to be cost-effective. We also developed a quality development process for assessing intervention fidelity. Limitations: We were able to screen only around 30% of the population and involved only a small number in the piloting and feasibility work. Conclusions: The results from this programme of work have significantly enhanced the existing knowledge and understanding of T2DM and IGR in people with ID. We have developed a lifestyle education programme and educator training protocol to promote behaviour change in this population. Future work: Further work is needed to evaluate the STOP Diabetes intervention to identify cost-effective strategies for its implementation

Modifications of myosin-regulatory light chain correlate with function of stunned myocardium

The precise molecular basis for myocardial stunning remains unresolved, but protein damage within the myofibril is a likely mechanism. We used two-dimensional gel electrophoresis (2-DE) and mass spectrometry (MS) to identify protein modifications in stunned myocardium. In isolated, perfused rabbit hearts, low-flow ischemia (1 ml/min) and reperfusion resulted in impaired left-ventricular function (rate-pressure product (RPP) after 15-min ischemia: 65 ± 5% pre-ischemia). We have characterised the sequence of ventricular myosin-regulatory light chain (MLC-2, 18 kDa) in rabbit myocardium and identified two non-phosphorylated (P1 and P2) and two phosphorylated (P3 and P4 at Ser-14) isoelectric point variants. MS revealed that the acidic isoelectric point post-translational modification of P1 and P3, resulting in P2 and P4 respectively, was due to deamidation of asparagine to aspartate at residue 13, adjacent to Ser-14 phosphorylation site. After 15-min ischemia and reperfusion, a 15-kDa MLC-2 fragment was detected (MLC-214-165), resulting from N-terminal cleavage between Asn/Asp-13 and Ser-14 of non-phosphorylated MLC-2, which accounted for 9.8% of visible non-phosphorylated MLC-2. Subsequent 2-DE of subcellular fractions showed that the fragment was lost from the myofilament. Treatment with an OH radical scavenger, N-(2-mercaptopropionyl) glycine (MPG, 3 mmol/l), preserved contractile function (RPP: 106 ± 9% pre-ischemia) and prevented cleavage of MLC-2. Proteolytic damage to MLC-2, related to presence of OH radicals during reperfusion, correlates with myocardial stunning and may contribute to impaired contractility.8 page(s