12 research outputs found
Predicting university performance in psychology: the role of previous performance and discipline-specific knowledge
Recent initiatives to enhance retention and widen participation ensure it is crucial to understand the factors that predict students' performance during their undergraduate degree. The present research used Structural Equation Modeling (SEM) to test three separate models that examined the extent to which British Psychology students' A-level entry qualifications predicted: (1) their performance in years 1-3 of their Psychology degree, and (2) their overall degree performance. Students' overall A-level entry qualifications positively predicted performance during their first year and overall degree performance, but negatively predicted their performance during their third year. Additionally, and more specifically, students' A-level entry qualifications in Psychology positively predicted performance in the first year only. Such findings have implications for admissions tutors, as well as for students who have not studied Psychology before but who are considering applying to do so at university
African and European local ancestry surrounding Apolipoprotein E has a differential biological effect upon acute amyloid beta exposure in iPSC‐differentiated astrocytes
Background
Studies have shown that the lower risk associated with the ε4 allele for African ancestry is associated with the local ancestry (LA) surrounding the ApoE gene. Previous studies have shown differences between ApoE3 and ApoE4 alleles in isogenic induced pluripotent stem cell (iPSC) models when exposed to Aβ. We hypothesized that ApoE4 individuals with African LA would respond differently to Aβ compared to European ApoE3 and European ApoE4 LA lines. However, as we cannot produce isogenic lines to test LA, we used RNA expression changes to Aβ exposure to increase our sensitivity to potential differences.
Method
We differentiated European LA ε4/ε4 and African LA ε4/ε4 allele astrocytes from iPSC lines. Astrocytes were exposed to exogenous Aβ and RNA was obtained at 0 and 24 hours. We performed bioinformatic analyses with the STAR algorithm and differential expression calculation using linear models implemented in edgeR. Pathway enrichment analysis for Gene Ontology Biological Processes, KEGG and Reactome pathways was performed using Metascape.
Result
Twenty‐four hours following Aβ exposure, 524 and 671 genes were deferentially expressed from baseline in African and European LA lines respectively. Analysis of the unregulated genes in the two different ancestries revealed markedly different pathways. The unregulated genes in African LA astrocytes were enriched for Ribosome Biogenesis and RNA modification processes while the upregulated genes in the European LA astrocytes were enriched for Cell Cycle and DNA modification processes. In the European LA astrocytes, downregulated genes were enriched for Synaptic Assembly and Kainate Receptor Activity while in the African LA astrocytes downregulated genes enriched for Extracellular Matrix‐related processes.
Conclusion
Our initial results suggest that the two ancestries respond differently to Aβ exposure. Whether this is due to global or local ancestry differences is unclear. Further studies including astrocytes bearing African LA ε3/ε3 are needed to clarify that question. Both ribosomal dysfunction and astrocyte‐neuronal and astrocyte‐microglia synaptic assembly have been implicated in Aβ clearance and/or AD. A potential link between LA and the regulation of these processes due to Aβ exposure could pave the path to a better understanding of LOAD pathology
The Behavioural Response to Intrathecal Serotonin is Changed by Acute but not by Repeated Treatment with Zimelidine or Metergoline
Efficacy and immunogenicity of MultiTEP-based DNA vaccines targeting human α-synuclein: prelude for IND enabling studies.
Accumulation of misfolded proteins such as amyloid-β (Aβ), tau, and α-synuclein (α-Syn) in the brain leads to synaptic dysfunction, neuronal damage, and the onset of relevant neurodegenerative disorder/s. Dementia with Lewy bodies (DLB) and Parkinson's disease (PD) are characterized by the aberrant accumulation of α-Syn intracytoplasmic Lewy body inclusions and dystrophic Lewy neurites resulting in neurodegeneration associated with inflammation. Cell to cell propagation of α-Syn aggregates is implicated in the progression of PD/DLB, and high concentrations of anti-α-Syn antibodies could inhibit/reduce the spreading of this pathological molecule in the brain. To ensure sufficient therapeutic concentrations of anti-α-Syn antibodies in the periphery and CNS, we developed four α-Syn DNA vaccines based on the universal MultiTEP platform technology designed especially for the elderly with immunosenescence. Here, we are reporting on the efficacy and immunogenicity of these vaccines targeting three B-cell epitopes of hα-Syn aa85-99 (PV-1947D), aa109-126 (PV-1948D), aa126-140 (PV-1949D) separately or simultaneously (PV-1950D) in a mouse model of synucleinopathies mimicking PD/DLB. All vaccines induced high titers of antibodies specific to hα-Syn that significantly reduced PD/DLB-like pathology in hα-Syn D line mice. The most significant reduction of the total and protein kinase resistant hα-Syn, as well as neurodegeneration, were observed in various brain regions of mice vaccinated with PV-1949D and PV-1950D in a sex-dependent manner. Based on these preclinical data, we selected the PV-1950D vaccine for future IND enabling preclinical studies and clinical development