Geography, environment, and colonization history interact with morph type to shape genomic variation in an Arctic fish

Funding Information: Thanks go to our editor and three anonymous reviewers whose suggestions greatly improved this study. We thank S. Avery, J. Callahan, S. Duffy, S. Hann, L. Pike, R. Solomon, A. Walsh, for assistance with sample collection and fieldwork. We are grateful to X. Dallaire and J.S. Moore for providing samples from Ungava, Bay (HAB) and to L. Bernatchez for his valuable comments on an earlier version of this manuscript. Thanks to Parks Canada for allowing us access to the Torngat Mountains National Park and the Nunatsiavut government for allowing us to collect samples from their lands. Thanks to A. Belay at Mount Sinai Hospital for her help with sequencing, A. Mesmer for help with genotyping, and S. Lehnert for insightful data analysis suggestions. We also thank the Institute for Biodiversity, Ecosystem Science, and Sustainability of the Department of Environment and Conservation of the Government of Labrador and Newfoundland for funding for this project; NSERC for the Strategic Grant STPGP 430198 and Discovery Grant awarded to DER, for the CGS‐D awarded to SJS; the Killam Trust for the Level 2 Izaak awarded to SJS; and the Government of Nova Scotia for the Graduate Scholarship awarded to SJS. Publisher Copyright: © 2023 The Authors. Molecular Ecology published by John Wiley & Sons Ltd.Peer reviewedPublisher PD

Adaptive Immune Response to Model Antigens Is Impaired in Murine Leukocyte-Adhesion Deficiency-1 Revealing Elevated Activation Thresholds In Vivo

Absence of β2 integrins (CD11/CD18) leads to leukocyte-adhesion deficiency-1 (LAD1), a rare primary immunodeficiency syndrome. Although extensive in vitro work has established an essential function of β2 integrins in adhesive and signaling properties for cells of the innate and adaptive immune system, their respective participation in an altered adaptive immunity in LAD1 patients are complex and only partly understood in vivo. Therefore, we investigated adaptive immune responses towards different T-dependent antigens in a murine LAD1 model of β2 integrin-deficiency (CD18−/−). CD18−/− mice generated only weak IgG responses after immunization with tetanus toxoid (TT). In contrast, robust hapten- and protein-specific immune responses were observed after immunization with highly haptenated antigens such as (4-hydroxy-3-nitrophenyl)21 acetyl chicken γ globulin (NP21-CG), even though regularly structured germinal centers with specificity for the defined antigens/haptens in CD18−/− mice remained absent. However, a decrease in the hapten/protein ratio lowered the efficacy of immune responses in CD18−/− mice, whereas a mere reduction of the antigen dose was less crucial. Importantly, haptenation of TT with NP (NP-TT) efficiently restored a robust IgG response also to TT. Our findings may stimulate further studies on a modification of vaccination strategies using highly haptenated antigens in individuals suffering from LAD1

Genomic evidence of past and future climate-linked loss in a migratory Arctic fish

Acknowledgements We thank staff of the Newfoundland DFO Salmonids section, Parks Canada, the Nunatsiavut Government, the NunatuKavut Community Council, the Sivunivut Inuit Community Corporation, the Innu Nation, the Labrador Hunting and Fishing Association and fishers for their support, participation and tissue collections and the staff of the Aquatic Biotechnology Lab at the Bedford Institute of Oceanography for DNA extractions. This study was supported by the Ocean Frontier Institute, a Genomics Research and Development Initiative (GRDI) Grant, a Natural Sciences and Engineering Research Council (NSERC) Discovery Grant and Strategic Project Grant to I.R.B., the Weston Family Award for research at the Torngat Mountains Base Camp and an Atlantic Canada Opportunities Agency and Department of Tourism, Culture, Industry and Innovation grant allocated to the Labrador Institute. Author Correction: Layton, K.K.S., Snelgrove, P.V.R., Dempson, J.B. et al. Author Correction: Genomic evidence of past and future climate-linked loss in a migratory Arctic fish. Nat. Clim. Chang. 11, 551 (2021). https://doi.org/10.1038/s41558-021-01023-8Peer reviewedPostprin

Resolving fine-scale population structure and fishery exploitation using sequenced microsatellites in a northern fish

Funding Information Natural Sciences and Engineering Research Council of Canada (NSERC) Strategic Project Atlantic Canada Opportunities Agency and Department of Tourism, Culture, Industry and Innovation grants allocated to the Labrador Institute (MC) Natural Sciences and Engineering Research Council of Canada (NSERC) Discovery Genomics Research and Development Initiative (GRDI) Weston Family AwardPeer reviewedPublisher PD

Impact of aversive affect on neural mechanisms of categorization decisions

Abstract Introduction Many theories contend that evidence accumulation is a critical component of decision‐making. Cognitive accumulation models typically interpret two main parameters: a drift rate and decision threshold. The former is the rate of accumulation, based on the quality of evidence, and the latter is the amount of evidence required for a decision. Some studies have found neural signals that mimic evidence accumulators and can be described by the two parameters. However, few studies have related these neural parameters to experimental manipulations of sensory data or memory representations. Here, we investigated the influence of affective salience on neural accumulation parameters. High affective salience has been repeatedly shown to influence decision‐making, yet its effect on neural evidence accumulation has been unexamined. Methods The current study used a two‐choice object categorization task of body images (feet or hands). Half the images in each category were high in affective salience because they contained highly aversive features (gore and mutilation). To study such quick categorization decisions with a relatively slow technique like functional magnetic resonance imaging, we used a gradual reveal paradigm to lengthen cognitive processing time through the gradual “unmasking” of stimuli. Results Because the aversive features were task‐irrelevant, high affective salience produced a distractor effect, slowing decision time. In visual accumulation regions of interest, high affective salience produced a longer time to peak activation. Unexpectedly, the later peak appeared to be the product of changes to both drift rate and decision threshold. The drift rate for high affective salience was shallower, and the decision threshold was greater. To our knowledge, this is the first demonstration of an experimental manipulation of sensory data or memory representations that changed the neural decision threshold. Conclusion These findings advance our knowledge of the neural mechanisms underlying affective responses in general and the influence of high affective salience on object representations and categorization decisions

The Genomic Consistency of the Loss of Anadromy in an Arctic Fish (Salvelinus alpinus)

We thank our editor, J. A. Lau, associate editor K. E. Lotterhos, as well as two anonymous reviewers whose suggestions greatly improved this work. We greatly appreciate S. Avery, J. Callahan, S. Duffy, S. Hann, L. Pike, R. Solomon, and A. Walsh for their indispensable help with fieldwork. We thank Parks Canada for allowing us access to the Torngat Mountains National Park and the Nunatsiavut Government for allowing us to collect samples from their lands. We thank A. Belay at Mount Sinai Hospital for help with sequencing, A. Messmer for help with genotyping, and S. Lehnert for insightful data analysis suggestions. We also thank the Institute for Biodiversity, Ecosystem Science, and Sustainability of the Department of Environment and Conservation of the Government of Labrador and Newfoundland for funding for this project; the Natural Sciences and Engineering Research Council of Canada for the Strategic Grant STPGP 430198 and Discovery Grant awarded to D.E.R. and for the Canada Graduate Scholarships–Doctoral awarded to S.J.S.; the Killam Trust for the Level 2 Izaak awarded to S.J.S.; and the Government of Nova Scotia for the graduate scholarship awarded to S.J.S.Peer reviewedPostprintPublisher PD

A 9-centimorgan interval of chromosome 10 controls the T cell-dependent psoriasiform skin disease and arthritis in a murine psoriasis model

Psoriasis is a complex genetic disease of unresolved pathogenesis with both heritable and environmental factors contributing to onset and severity. In addition to a disfiguring skin inflammation, approximately 10-40% of psoriasis patients suffer from destructive joint involvement. Previously, we reported that the CD18 hypomorphic PL/J mouse carrying a mutation resulting in reduced expression of the common chain of beta(2) integrins (CD11/CD18) spontaneously develops a skin disease that closely resembles human psoriasis. In contrast, the same mutation on C57BL/6J background did not demonstrate this phenotype. By a genome-wide linkage analysis, two major loci were identified as contributing to the development of psoriasiform dermatitis under the condition of low CD18 expression. Using a congenic approach, we now demonstrate that the introduction of a 9-centimorgan fragment of chromosome 10 derived from the PL/J strain into the disease-resistant CD18 hypomorphic C57BL/6J was promoting the development of psoriasiform skin disease and notably also arthritis. We therefore designated this locus psoriasiform skin disease-associated locus 1 (PSD1). High numbers of CD4(+) T cells and TNF-alpha producing macrophages were detected both in inflamed skin and joints in these congenic mice, with a complete resolution upon TNF-alpha inhibitor therapy or depletion of CD4(+) T cells. For the first time, we have identified a distinct genetic element that contributes to the T cell-dependent development of both psoriasiform skin disease and associated arthritis. This congenic model will be suitable to further investigations of genetic and molecular pathways that cause psoriasiform dermatitis and arthritis, and it may also be relevant for other autoimmune diseases