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

Validation of close‐kin mark–recapture (CKMR) methods for estimating population abundance

Under embargo until: 2020-06-181. Knowing how many individuals there are in a population is a fundamental problem in the management and conservation of freshwater and marine fish. We compare abundance estimates (census size, Nc) in seven brook trout Salvelinus fontinalis populations using standard mark–recapture (MR) and the close‐kin mark–recapture (CKMR) method. Our purpose is to validate CKMR as a method for estimating population size. 2. Close‐kin mark–recapture is based on the principle that an individual's genotype can be considered a “recapture” of the genotypes of each of its parents. Assuming offspring and parents are sampled independently, the number of parent–offspring pairs (POPs) genetically identified in these samples can be used to estimate abundance. We genotyped (33 microsatellites) and aged c. 2,400 brook trout individuals collected over 5 consecutive years (2014–2018). 3. We provide an alternative interpretation of CKMR in terms of the Lincoln– Petersen estimator in which the parents are considered as tagging the offspring rather than the offspring “recapturing” the parents. 4. Despite various sources of uncertainty, we find close agreement between standard MR abundance estimates obtained through double‐pass electrofishing and CKMR estimates, which require information on age‐specific fecundity, and population‐ and age‐specific survival rates. Population sizes (N) are estimated to range between 300 and 6,000 adult individuals. Our study constitutes the first in situ validation of CKMR and establishes it as a useful method for estimating population size in aquatic systems where assumptions of random sampling and thorough mixing of individuals can be met.acceptedVersio

Monomeric IgA Antagonizes IgG-Mediated Enhancement of DENV Infection

Dengue virus (DENV) is a prevalent human pathogen, infecting approximately 400 million individuals per year and causing symptomatic disease in approximately 100 million. A distinct feature of dengue is the increased risk for severe disease in some individuals with preexisting DENV-specific immunity. One proposed mechanism for this phenomenon is antibody-dependent enhancement (ADE), in which poorly-neutralizing IgG antibodies from a prior infection opsonize DENV to increase infection of Fc gamma receptor-bearing cells. While IgM and IgG are the most commonly studied DENV-reactive antibody isotypes, our group and others have described the induction of DENV-specific serum IgA responses during dengue. We hypothesized that monomeric IgA would be able to neutralize DENV without the possibility of ADE. To test this, we synthesized IgG and IgA versions of two different DENV-reactive monoclonal antibodies. We demonstrate that isotype-switching does not affect the antigen binding and neutralization properties of the two mAbs. We show that DENV-reactive IgG, but not IgA, mediates ADE in Fc gamma receptor-positive K562 cells. Furthermore, we show that IgA potently antagonizes the ADE activity of IgG. These results suggest that levels of DENV-reactive IgA induced by DENV infection might regulate the overall IgG mediated ADE activity of DENV-immune plasma in vivo, and may serve as a predictor of disease risk

Temporally Integrated Single Cell RNA Sequencing Analysis of PBMC from Experimental and Natural Primary Human DENV-1 Infections

Dengue human infection studies present an opportunity to address many longstanding questions in the field of flavivirus biology. However, limited data are available on how the immunological and transcriptional response elicited by an attenuated challenge virus compares to that associated with a wild-type DENV infection. To determine the kinetic transcriptional signature associated with experimental primary DENV-1 infection and to assess how closely this profile correlates with the transcriptional signature accompanying natural primary DENV-1 infection, we utilized scRNAseq to analyze PBMC from individuals enrolled in a DENV-1 human challenge study and from individuals experiencing a natural primary DENV-1 infection. While both experimental and natural primary DENV-1 infection resulted in overlapping patterns of inflammatory gene upregulation, natural primary DENV-1 infection was accompanied with a more pronounced suppression in gene products associated with protein translation and mitochondrial function, principally in monocytes. This suggests that the immune response elicited by experimental and natural primary DENV infection are similar, but that natural primary DENV-1 infection has a more pronounced impact on basic cellular processes to induce a multi-layered anti-viral state

The effects of meteorological factors on the occurrence of Ganoderma sp. spores in the air

Ganoderma sp. is an airborne fungal spore type known to trigger respiratory allergy symptoms in sensitive patients. Aiming to reduce the risk for allergic individuals, we analysed fungal spore circulation in Szczecin, Poland, and its dependence on meteorological conditions. Statistical models for the airborne spore concentrations of Ganoderma sp.—one of the most abundant fungal taxa in the area—were developed. Aerobiological sampling was conducted over 2004–2008 using a volumetric Lanzoni trap. Simultaneously, the following meteorological parameters were recorded: daily level of precipitation, maximum and average wind speed, relative humidity and maximum, minimum, average and dew point temperatures. These data were used as the explaining variables. Due to the non-linearity and non-normality of the data set, the applied modelling techniques were artificial neural networks (ANN) and mutlivariate regression trees (MRT). The obtained classification and MRT models predicted threshold conditions above which Ganoderma sp. appeared in the air. It turned out that dew point temperature was the main factor influencing the presence or absence of Ganoderma sp. spores. Further analysis of spore seasons revealed that the airborne fungal spore concentration depended only slightly on meteorological factors

Experimental Demonstration of Attosecond Pump-Probe Spectroscopy with an X-ray Free-Electron Laser

Pump-probe experiments with sub-femtosecond resolution are the key to understanding electronic dynamics in quantum systems. Here we demonstrate the generation and control of sub-femtosecond pulse pairs from a two-colour X-ray free-electron laser (XFEL). By measuring the delay between the two pulses with an angular streaking diagnostic, we characterise the group velocity of the XFEL and demonstrate control of the pulse delay down to 270 as. We demonstrate the application of this technique to a pump-probe measurement in core-excited para-aminophenol. These results demonstrate the ability to perform pump-probe experiments with sub-femtosecond resolution and atomic site specificity.Comment: 55 pages, main manuscript (5 figures) + supplementary materials (25 figures), 30 figures total. Submitted to Nature Photonic

Rifampin pharmacokinetics in children, with and without human immunodeficiency virus infection, hospitalized for the management of severe forms of tuberculosis

<p>Abstract</p> <p>Background</p> <p>Rifampin is a key drug in antituberculosis chemotherapy because it rapidly kills the majority of bacilli in tuberculosis lesions, prevents relapse and thus enables 6-month short-course chemotherapy. Little is known about the pharmacokinetics of rifampin in children. The objective of this study was to evaluate the pharmacokinetics of rifampin in children with tuberculosis, both human immunodeficiency virus type-1-infected and human immunodeficiency virus-uninfected.</p> <p>Methods</p> <p>Fifty-four children, 21 human immunodeficiency virus-infected and 33 human immunodeficiency virus-uninfected, mean ages 3.73 and 4.05 years (<it>P </it>= 0.68), respectively, admitted to a tuberculosis hospital in Cape Town, South Africa with severe forms of tuberculosis were studied approximately 1 month and 4 months after commencing antituberculosis treatment. Blood specimens for analysis were drawn in the morning, 45 minutes, 1.5, 3.0, 4.0 and 6.0 hours after dosing. Rifampin concentrations were determined by liquid chromatography tandem mass spectrometry. For two sample comparisons of means, the Welch version of the t-test was used; associations between variables were examined by Pearson correlation and by multiple linear regression.</p> <p>Results</p> <p>The children received a mean rifampin dosage of 9.61 mg/kg (6.47 to 15.58) body weight at 1 month and 9.63 mg/kg (4.63 to 17.8) at 4 months after commencing treatment administered as part of a fixed-dose formulation designed for paediatric use. The mean rifampin area under the curve 0 to 6 hours after dosing was 14.9 and 18.1 μg/hour/ml (<it>P </it>= 0.25) 1 month after starting treatment in human immunodeficiency virus-infected and human immunodeficiency virus-uninfected children, respectively, and 16.52 and 17.94 μg/hour/ml (<it>P </it>= 0.59) after 4 months of treatment. The mean calculated 2-hour rifampin concentrations in these human immunodeficiency virus-infected and human immunodeficiency virus-uninfected children were 3.9 and 4.8 μg/ml (<it>P </it>= 0.20) at 1 month after the start of treatment and 4.0 and 4.6 μg/ml (<it>P </it>= 0.33) after 4 months of treatment. These values are considerably less than the suggested lower limit for 2-hour rifampin concentrations in adults of 8.0 μg/ml and even 4 μg/ml</p> <p>Conclusion</p> <p>Both human immunodeficiency virus-infected and human immunodeficiency virus-uninfected children with tuberculosis have very low rifampin serum concentrations after receiving standard rifampin dosages similar to those used in adults. Pharmacokinetic studies of higher dosages of rifampin are urgently needed in children to assist in placing the dosage of rifampin used in childhood on a more scientific foundation.</p

One-Off Subsidies and Long-Run Adoption Experimental Evidence on Improved Cooking Stoves in Senegal

Free technology distribution can be an effective development policy instrument if adoption is socially inefficient and hampered by affordability constraints. Yet, policy makers often oppose free distribution, arguing that reference dependence spoils the willingness to pay and thus market potentials in the long run. For improved cookstoves, this paper studies the willingness to pay six years after a randomized one-time free distribution. Using a real-purchase offer procedure, we find that households who received a free stove in the past do not reveal a lower willingness to pay to repurchase the stove. Furthermore, we provide exploratory evidence that learning and reference-dependence effects do not spill over from the treatment to the control group. The policy implication is that one-time free distribution does not disturb future market establishment and might even facilitate it.JEL Codes: D03, D12, O12, O13, Q4

Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders

Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed analyses of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyper-activity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders, identifying three groups of inter-related disorders. Meta-analysis across these eight disorders detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning prenatally in the second trimester, and play prominent roles in neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.Peer reviewe