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"Carr, M."
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Multiple mitogenomes indicate Things Fall Apart with Out of Africa or Asia hypotheses for the phylogeographic evolution of Honey Bees (Apis mellifera)
Previous morpho-molecular studies of evolutionary relationships within the economically important genus of honey bees (
Apis
), including the Western Honey Bee (
A. mellifera
L.), have suggested Out of Africa or Asia origins and subsequent spread to Europe. I test these hypotheses by a meta-analysis of complete mitochondrial DNA coding regions (11.0 kbp) from 22 nominal subspecies represented by 78 individual sequences in
A. mellifera
. Parsimony, distance, and likelihood analyses identify six nested clades: Things Fall Apart with Out of Africa or Asia hypotheses. Molecular clock-calibrated phylogeographic analysis shows instead a basal origin of
A. m. mellifera
in Europe ~ 780 Kya, and expansion to Southeast Europe and Asia Minor ~ 720 Kya. Eurasian bees spread southward via a Levantine/Nilotic/Arabian corridor into Africa ~ 540 Kya. An African clade re-established in Iberia ~ 100 Kya spread thereafter to westerly Mediterranean islands and back into North Africa. Nominal subspecies within the Asia Minor and Mediterranean clades are less differentiated than are individuals within other subspecies. Names matter: paraphyletic anomalies are artefacts of mis-referral in GenBank of sequences to the wrong subspecies, or use of faulty sequences, which are clarified by inclusion of multiple sequences from available subspecies.
Journal Article
Clay work and body image in art therapy : using metaphor and symbolism to heal
\"Clay Work and Body Image in Art Therapy provides an important addition to resources available in the field of clay work and art therapy, highlighting the unique sensory aspects of the medium and its ability to provide a therapeutic resource for women who experience body image issues. Chapters offer a comprehensive distillation of current knowledge in the field of body image, clay work, neuroscience, and art therapy, building a theoretical framework around personal narratives. Case studies examine the benefits of exploring body image through clay work within art therapy practice, providing a positive and contained way to find personal acceptance and featuring photographs of clay body image sculptures created by research participants that highlight their individual stories and experiences. As well as offering both clinical and practical implications, the text provides a full protocol for the research and evaluation methods carried out, enabling further replication of the intervention and research methods by other therapists. This book highlights clay work as a significant resource for art therapists, arts in health practitioners, and counsellors, providing an emotive yet contained approach to the development of personal body image acceptance and self-compassion\"-- Provided by publisher.
Book
Long non-coding RNA-derived peptides are immunogenic and drive a potent anti-tumour response
Protein arginine methyltransferase (PRMT) 5 is over-expressed in a variety of cancers and the master transcription regulator E2F1 is an important methylation target. We have explored the role of PRMT5 and E2F1 in regulating the non-coding genome and report here a striking effect on long non-coding (lnc) RNA gene expression. Moreover, many MHC class I protein-associated peptides were derived from small open reading frames in the lncRNA genes. Pharmacological inhibition of PRMT5 or adjusting E2F1 levels qualitatively altered the repertoire of lncRNA-derived peptide antigens displayed by tumour cells. When presented to the immune system as either ex vivo-loaded dendritic cells or expressed from a viral vector, lncRNA-derived peptides drove a potent antigen-specific CD8 T lymphocyte response, which translated into a significant delay in tumour growth. Thus, lncRNA genes encode immunogenic peptides that can be deployed as a cancer vaccine.
Long noncoding RNA molecules are RNA transcripts long thought to remain untranslated. In this study, the authors demonstrate that certain lncRNA can be translated into peptides that are immunogenic to CD8
+
T cells and promote anti-tumour responses when delivered as vaccine vectors in mice.
Journal Article
A Tri-Oceanic Perspective: DNA Barcoding Reveals Geographic Structure and Cryptic Diversity in Canadian Polychaetes
Although polychaetes are one of the dominant taxa in marine communities, their distributions and taxonomic diversity are poorly understood. Recent studies have shown that many species thought to have broad distributions are actually a complex of allied species. In Canada, 12% of polychaete species are thought to occur in Atlantic, Arctic, and Pacific Oceans, but the extent of gene flow among their populations has not been tested.
Sequence variation in a segment of the mitochondrial cytochrome c oxidase I (COI) gene was employed to compare morphological versus molecular diversity estimates, to examine gene flow among populations of widespread species, and to explore connectivity patterns among Canada's three oceans. Analysis of 1876 specimens, representing 333 provisional species, revealed 40 times more sequence divergence between than within species (16.5% versus 0.38%). Genetic data suggest that one quarter of previously recognized species actually include two or more divergent lineages, indicating that richness in this region is currently underestimated. Few species with a tri-oceanic distribution showed genetic cohesion. Instead, large genetic breaks occur between Pacific and Atlantic-Arctic lineages, suggesting their long-term separation. High connectivity among Arctic and Atlantic regions and low connectivity with the Pacific further supports the conclusion that Canadian polychaetes are partitioned into two distinct faunas.
Results of this study confirm that COI sequences are an effective tool for species identification in polychaetes, and suggest that DNA barcoding will aid the recognition of species overlooked by the current taxonomic system. The consistent geographic structuring within presumed widespread species suggests that historical range fragmentation during the Pleistocene ultimately increased Canadian polychaete diversity and that the coastal British Columbia fauna played a minor role in Arctic recolonization following deglaciation. This study highlights the value of DNA barcoding for providing rapid insights into species distributions and biogeographic patterns in understudied groups.
Journal Article
Intracellular lipid droplet accumulation occurs early following viral infection and is required for an efficient interferon response
Lipid droplets (LDs) are increasingly recognized as critical organelles in signalling events, transient protein sequestration and inter-organelle interactions. However, the role LDs play in antiviral innate immune pathways remains unknown. Here we demonstrate that induction of LDs occurs as early as 2 h post-viral infection, is transient and returns to basal levels by 72 h. This phenomenon occurs following viral infections, both in vitro and in vivo. Virally driven in vitro LD induction is type-I interferon (IFN) independent, and dependent on Epidermal Growth Factor Receptor (EGFR) engagement, offering an alternate mechanism of LD induction in comparison to our traditional understanding of their biogenesis. Additionally, LD induction corresponds with enhanced cellular type-I and -III IFN production in infected cells, with enhanced LD accumulation decreasing viral replication of both Herpes Simplex virus 1 (HSV-1) and Zika virus (ZIKV). Here, we demonstrate, that LDs play vital roles in facilitating the magnitude of the early antiviral immune response specifically through the enhanced modulation of IFN following viral infection, and control of viral replication. By identifying LDs as a critical signalling organelle, this data represents a paradigm shift in our understanding of the molecular mechanisms which coordinate an effective antiviral response.
Lipid droplets (LDs) are recognized as dynamic organelles and scaffolding platforms to regulate signalling cascades. Here, Monson et al. provide evidence that LDs are involved in regulation of an early antiviral immune response specifically through the enhanced modulation of IFN following viral infection in vitro and in vivo.
Journal Article
Metabolic dysfunction–associated steatotic liver disease and the gut microbiome: pathogenic insights and therapeutic innovations
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a major cause of liver disease worldwide, and our understanding of its pathogenesis continues to evolve. MASLD progresses from steatosis to steatohepatitis, fibrosis, and cirrhosis, and this Review explores how the gut microbiome and their metabolites contribute to MASLD pathogenesis. We explore the complexity and importance of the intestinal barrier function and how disruptions of the intestinal barrier and dysbiosis work in concert to promote the onset and progression of MASLD. The Review focuses on specific bacterial, viral, and fungal communities that impact the trajectory of MASLD and how specific metabolites (including ethanol, bile acids, short chain fatty acids, and other metabolites) contribute to disease pathogenesis. Finally, we underscore how knowledge of the interaction between gut microbes and the intestinal barrier may be leveraged for MASLD microbial-based therapeutics. Here, we include a discussion of the therapeutic potential of prebiotics, probiotics, postbiotics, and microbial-derived metabolites.
Journal Article
Absence of Perilipin 2 Prevents Hepatic Steatosis, Glucose Intolerance and Ceramide Accumulation in Alcohol-Fed Mice
Perilipin 2 (Plin2) is a lipid droplet protein that has roles in both lipid and glucose homeostasis. An increase in Plin2 in liver is associated with the development of steatosis, glucose intolerance, and ceramide accumulation in alcoholic liver disease. We investigated the role of Plin2 on energy balance and glucose and lipid homeostasis in wildtype and Plin2 knockout (Plin2KO) mice chronically fed a Lieber-DeCarli liquid ethanol or control diet for six weeks.
We performed in vivo measurements of energy intake and expenditure; body composition; and glucose tolerance. After sacrifice, liver was dissected for histology and lipid analysis.
We found that neither genotype nor diet had a significant effect on final weight, body composition, or energy intake between WT and Plin2KO mice fed alcohol or control diets. Additionally, alcohol feeding did not affect oxygen consumption or carbon dioxide production in Plin2KO mice. We performed glucose tolerance testing and observed that alcohol feeding failed to impair glucose tolerance in Plin2KO mice. Most notably, absence of Plin2 prevented hepatic steatosis and ceramide accumulation in alcohol-fed mice. These changes were related to downregulation of genes involved in lipogenesis and triglyceride synthesis.
Plin2KO mice chronically fed alcohol are protected from hepatic steatosis, glucose intolerance, and hepatic ceramide accumulation, suggesting a critical pathogenic role of Plin2 in experimental alcoholic liver disease.
Journal Article
Functionally impaired plasmacytoid dendritic cells and non-haematopoietic sources of type I interferon characterize human autoimmunity
Autoimmune connective tissue diseases arise in a stepwise fashion from asymptomatic preclinical autoimmunity. Type I interferons have a crucial role in the progression to established autoimmune diseases. The cellular source and regulation in disease initiation of these cytokines is not clear, but plasmacytoid dendritic cells have been thought to contribute to excessive type I interferon production. Here, we show that in preclinical autoimmunity and established systemic lupus erythematosus, plasmacytoid dendritic cells are not effector cells, have lost capacity for Toll-like-receptor-mediated cytokine production and do not induce T cell activation, independent of disease activity and the blood interferon signature. In addition, plasmacytoid dendritic cells have a transcriptional signature indicative of cellular stress and senescence accompanied by increased telomere erosion. In preclinical autoimmunity, we show a marked enrichment of an interferon signature in the skin without infiltrating immune cells, but with interferon-κ production by keratinocytes. In conclusion, non-hematopoietic cellular sources, rather than plasmacytoid dendritic cells, are responsible for interferon production prior to clinical autoimmunity.
Type I interferon drives autoimmune pathology in SLE and has been assumed to come predominantly from plasmacytoid dendritic cells (pDCs). Here, the authors show that prior to the onset of SLE, pDCs lose multiple immunogenic functions and, instead, non-hematopoietic cells such as keratinocytes are a major source of type I interferons.
Journal Article