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"Miller, Justin"
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Teaching Note—Teaching Self-Care and Wellness as a Professional Practice Skill
Educating for human rights and justice requires attention to the well-being of those being prepared to pursue these aims. This article describes an MSW program’s implementation of teaching self-care as a core practice skill. This curricular innovation stems from the increasing literature documenting the deleterious effects of burnout in professional helping and the need to address this concern in educational curricula. Further, this curricular change is a result of increased student exhaustion affecting academic performance and professional preparedness, and the ethical imperative to address this phenomenon. We describe specific components, strategies, and assignments in the curriculum as well as assessment of the curricular innovation. This curricular example is readily adaptable for other programs.
Journal Article
Bad news for Labour : antisemitism, the party and public belief
During the summer of 2018, numerous members of the Labour Party were accused of anti-Semitic behaviour by their detractors. The controversy reached fever pitch amid claims that the Labour Party had become 'institutionally racist' under the leadership of Jeremy Corbyn, and that the prospect of a Corbyn-led government posed an 'existential threat' to Jewish life in Britain. Shrouded in confusion, hyped by the media, whether these accusations were true or not got lost in the mix. This book clears the confusion by drawing on deep and original research on public beliefs and media representation of antisemitism and the Labour Party, revealing shocking findings of misinformation spread by the press, including the supposedly impartial BBC, and the liberal Guardian.
Book
The Combined Effect of Copper Nanoparticles and Microplastics on Transcripts Involved in Oxidative Stress Pathway in Rainbow Trout (Oncorhynchus Mykiss) Hepatocytes
Copper nanoparticles (CuNPs) and microplastics (MPs) are two emerging contaminants of freshwater systems. Despite their co-occurrence in many water bodies, the combined effects of CuNPs and MPs on aquatic organisms are not well-investigated. In this study, primary cultures of rainbow trout hepatocytes were exposed to dissolved Cu, CuNPs, MPs, or a combination of MPs and CuNPs for 48 h, and the transcript abundances of oxidative stress-related genes were investigated. Exposure to CuNPs or dissolved Cu resulted in a significant increase in the transcript abundances of two antioxidant enzymes, catalase (
CAT
) and superoxide dismutase (
SOD
). Exposure to CuNPs also led to an upregulation in the expression of Na
+
/K
+
ATPase alpha 1 subunit (
ATP1A1
). Microplastics alone or in combination with CuNPs did not have a significant effect on abundances of the target gene transcripts. Overall, our findings suggested acute exposure to CuNPs or dissolved ions may induce oxidative stress in hepatocytes, and the Cu-induced effect on target gene transcripts was not associated with MPs.
Journal Article
Apolipoprotein E4 has extensive conformational heterogeneity in lipid-free and lipid-bound forms
The ε4-allele variant of apolipoprotein E (ApoE4) is the strongest genetic risk factor for Alzheimer’s disease, although it only differs from its neutral counterpart ApoE3 by a single amino acid substitution. While ApoE4 influences the formation of plaques and neurofibrillary tangles, the structural determinants of pathogenicity remain undetermined due to limited structural information. Previous studies have led to conflicting models of the C-terminal region positioning with respect to the N-terminal domain across isoforms largely because the data are potentially confounded by the presence of heterogeneous oligomers. Here, we apply a combination of single-molecule spectroscopy and molecular dynamics simulations to construct an atomically detailed model of monomeric ApoE4 and probe the effect of lipid association. Importantly, our approach overcomes previous limitations by allowing us to work at picomolar concentrations where only the monomer is present. Our data reveal that ApoE4 is far more disordered and extended than previously thought and retains significant conformational heterogeneity after binding lipids. Comparing the proximity of the N- and C-terminal domains across the three major isoforms (ApoE4, ApoE3, and ApoE2) suggests that all maintain heterogeneous conformations in their monomeric form, with ApoE2 adopting a slightly more compact ensemble. Overall, these data provide a foundation for understanding how ApoE4 differs from nonpathogenic and protective variants of the protein.
Journal Article
Human-interpretable clustering of short text using large language models
Clustering short text is a difficult problem, owing to the low word co-occurrence between short text documents. This work shows that large language models (LLMs) can overcome the limitations of traditional clustering approaches by generating embeddings that capture the semantic nuances of short text. In this study, clusters are found in the embedding space using Gaussian mixture modelling. The resulting clusters are found to be more distinctive and more human-interpretable than clusters produced using the popular methods of doc2vec and latent Dirichlet allocation. The success of the clustering approach is quantified using human reviewers and through the use of a generative LLM. The generative LLM shows good agreement with the human reviewers and is suggested as a means to bridge the ‘validation gap’ which often exists between cluster production and cluster interpretation. The comparison between LLM coding and human coding reveals intrinsic biases in each, challenging the conventional reliance on human coding as the definitive standard for cluster validation.
Journal Article
Codon Pairs are Phylogenetically Conserved: A comprehensive analysis of codon pairing conservation across the Tree of Life
Identical codon pairing and co-tRNA codon pairing increase translational efficiency within genes when two codons that encode the same amino acid are translated by the same tRNA before it diffuses from the ribosome. We examine the phylogenetic signal in both identical and co-tRNA codon pairing across 23 428 species using alignment-free and parsimony methods. We determined that conserved codon pairing typically has a smaller window size than the length of a ribosome, and codon pairing tracks phylogenies across various taxonomic groups. We report a comprehensive analysis of codon pairing, including the extent to which each codon pairs. Our parsimony method generally recovers phylogenies that are more congruent with the established phylogenies than our alignment-free method. However, four of the ten taxonomic groups did not have sufficient orthologous codon pairings and were therefore analyzed using only the alignment-free methods. Since the recovered phylogenies using only codon pairing largely match phylogenies from the Open Tree of Life and the NCBI taxonomy, and are comparable to trees recovered by other algorithms, we propose that codon pairing biases are phylogenetically conserved and should be considered in conjunction with other phylogenomic techniques.
Journal Article
Fundamental Characteristics of AAA+ Protein Family Structure and Function
Many complex cellular events depend on multiprotein complexes known as molecular machines to efficiently couple the energy derived from adenosine triphosphate hydrolysis to the generation of mechanical force. Members of the AAA+ ATPase superfamily (ATPases Associated with various cellular Activities) are critical components of many molecular machines. AAA+ proteins are defined by conserved modules that precisely position the active site elements of two adjacent subunits to catalyze ATP hydrolysis. In many cases, AAA+ proteins form a ring structure that translocates a polymeric substrate through the central channel using specialized loops that project into the central channel. We discuss the major features of AAA+ protein structure and function with an emphasis on pivotal aspects elucidated with archaeal proteins.
Journal Article
Mycobacterium tuberculosis ClpC1 N-Terminal Domain Is Dispensable for Adaptor Protein-Dependent Allosteric Regulation
ClpC1 hexamers couple the energy of ATP hydrolysis to unfold and, subsequently, translocate specific protein substrates into the associated ClpP protease. Substrate recognition by ATPases associated with various cellular activities (AAA+) proteases is driven by the ATPase component, which selectively determines protein substrates to be degraded. The specificity of these unfoldases for protein substrates is often controlled by an adaptor protein with examples that include MecA regulation of Bacillus subtilis ClpC or ClpS-mediated control of Escherichia coli ClpA. No adaptor protein-mediated control has been reported for mycobacterial ClpC1. Using pulldown and stopped-flow fluorescence methods, we report data demonstrating that Mycobacterium tuberculosis ClpC1 catalyzed unfolding of an SsrA-tagged protein is negatively impacted by association with the ClpS adaptor protein. Our data indicate that ClpS-dependent inhibition of ClpC1 catalyzed SsrA-dependent protein unfolding does not require the ClpC1 N-terminal domain but instead requires the presence of an interaction surface located in the ClpC1 Middle Domain. Taken together, our results demonstrate for the first time that mycobacterial ClpC1 is subject to adaptor protein-mediated regulation in vitro.
Journal Article