Reversal of C9orf72 mutation-induced transcriptional dysregulation and pathology in cultured human neurons by allele-specific excision.

Efforts to genetically reverse C9orf72 pathology have been hampered by our incomplete understanding of the regulation of this complex locus. We generated five different genomic excisions at the C9orf72 locus in a patient-derived induced pluripotent stem cell (iPSC) line and a non-diseased wild-type (WT) line (11 total isogenic lines), and examined gene expression and pathological hallmarks of C9 frontotemporal dementia/amyotrophic lateral sclerosis in motor neurons differentiated from these lines. Comparing the excisions in these isogenic series removed the confounding effects of different genomic backgrounds and allowed us to probe the effects of specific genomic changes. A coding single nucleotide polymorphism in the patient cell line allowed us to distinguish transcripts from the normal vs. mutant allele. Using digital droplet PCR (ddPCR), we determined that transcription from the mutant allele is upregulated at least 10-fold, and that sense transcription is independently regulated from each allele. Surprisingly, excision of the WT allele increased pathologic dipeptide repeat poly-GP expression from the mutant allele. Importantly, a single allele was sufficient to supply a normal amount of protein, suggesting that the C9orf72 gene is haplo-sufficient in induced motor neurons. Excision of the mutant repeat expansion reverted all pathology (RNA abnormalities, dipeptide repeat production, and TDP-43 pathology) and improved electrophysiological function, whereas silencing sense expression did not eliminate all dipeptide repeat proteins, presumably because of the antisense expression. These data increase our understanding of C9orf72 gene regulation and inform gene therapy approaches, including antisense oligonucleotides (ASOs) and CRISPR gene editing

Efficient Assessment:Streamlining online assessment and developing tools to improve student feedback

With growing student numbers and a limited staff, the Fashion with Business Studies team has had to re-think our approach to marking large volumes of assignments. At the Curriculum Development Review in 2019, assessment choices for students were expanded, introducing the option to give a live presentation to staff members instead of submitting a written report. In this presentation we will explore how this has helped students to develop key employability skills and offer a useful alternative for those who have traditionally struggled with written assessments. As a staff team, the presentation format has allowed us to explore more efficient models of assessment including marking during the live presentation itself using a paper-based marking matrix (developed by Senior Lecturer in Professional Practice Joanna Zara). We will discuss how we have moved from the initial pilot in 2019-2020 using a paper-based system which proved cumbersome to digitise to an online assessment method in 2020-2021.The online assessment coincided with the shift to remote teaching due to the pandemic. With an online course the live presentations were not possible. Instead, students pre-recorded their presentations. We will discuss how the flexibility for creating rubrics in Grade Centre, has allowed the team (with Learning Technologist Robin Englebright) to develop the paper-based marking matrix into a digital assessment tool which we have piloted again for module AGP491 in 2020-2021 and how this could be rolled out across all of our business modules in 2021-2022.This pre-recorded presentation charts the development of the digital assessment tool and our reflections on how it has streamlined assessing times and, in doing so, enabled us to provide improved feedback to students

Improving the assessment process for students:Reflections on using audio feedback in assessment as a tool improve the student learning experience for large student cohorts

In 2021 we piloted the use of audio feedback in Grade Centre and Turnitin during 2021/22 to assess the 106 Level 6 Business Plan assignments. This presentation will reflect on the responses from Level 6 students to receiving feedback in an audio format. We will discuss how audio feedback as a digital assessment tool has enabled the Business Studies team within the Fashion, Textiles & Fashion Communication programme to provide coherent and engaging feedback which is more accessible and useful to students. We will also explore how audio feedback can enhance formative assessment by minimising the misunderstandings which can happen with written assessments. The use of audio feedback enhances the digital assessment tool we implemented in 2020 which uses rubrics to streamline the assessment process and improve feedback for large student cohorts and represents a process of continual improvement

Plasma Proteomic Profiling: Search for Lung Cancer Diagnostic and Early Detection Markers

Environmental and occupational exposure to asbestos is among the established risk factors for lung cancer, the leading cause of cancer-related deaths in the United States. This link between exposure to asbestos and the excessive death rate from lung cancer was evident in a study of former workers of an asbestos pipe insulation manufacturing plant in Tyler, TX. We performed comparative proteomic profiling of plasma samples that were collected from nine patients within 12 months before death and their age-, race- and exposure-matched disease-free controls on strong anion exchange chips using surface-enhanced laser desorption ionization time-of-flight mass spectrometry. A distance-dependent K-nearest neighbor (KNN) classification algorithm identified spectral features of m/z values 7558.9 and 15103.0 that were able to distinguish lung cancer patients from disease-free individuals with high sensitivity and specificity. The high correlation between the intensities of these two peaks (r=0.987) strongly suggests that they are the doubly and singly charged ions of the same protein product. Examination of these proteomic markers in the plasma samples of subjects from \u3e5 years before death from lung cancer suggested that they are related to the early development of lung cancer. Validation of these biomarkers would have significant implications for the early detection of lung cancer and better management of high-risk patients

Immune Response Dynamics and Biomarkers in COVID-19 Patients

Background: The immune response dynamics in COVID-19 patients remain a subject of intense investigation due to their implications for disease severity and treatment outcomes. We examined changes in leukocyte levels, eosinophil activity, and cytokine profiles in patients hospitalized with COVID-19. Methods: Serum samples were collected within the first 10 days of hospitalization/confirmed infection and analyzed for eosinophil granule proteins (EGP) and cytokines. Information from medical records including comorbidities, clinical symptoms, medications, and complete blood counts were collected at the time of admission, during hospitalization and at follow up approximately 3 months later. Results: Serum levels of eotaxin, type 1 and type 2 cytokines, and alarmin cytokines were elevated in COVID-19 patients, highlighting the heightened immune response (p p < 0.05). Leukocyte counts increased consistently from admission to follow-up, indicative of recovery. Conclusion: Attenuated eosinophil activity alongside elevated chemokine and cytokine levels during active infection, highlights the complex interplay of immune mediators in the pathogenesis COVID-19 and underscores the need for further investigation into immune biomarkers and treatment strategies