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31.
The genetic origin of human skin pigmentation remains an open question in biology. Several skin disorders and diseases originate from mutations in conserved pigmentation genes, including albinism, vitiligo, and melanoma. Teleosts possess the capacity to modify their pigmentation to adapt to their environmental background to avoid predators. This background adaptation occurs through melanosome aggregation (white background) or dispersion (black background) in melanocytes. These mechanisms are largely regulated by melanin-concentrating hormone (MCH) and α-melanocyte–stimulating hormone (α-MSH), two hypothalamic neuropeptides also involved in mammalian skin pigmentation. Despite evidence that the exogenous application of MCH peptides induces melanosome aggregation, it is not known if the MCH system is physiologically responsible for background adaptation. In zebrafish, we identify that MCH neurons target the pituitary gland-blood vessel portal and that endogenous MCH peptide expression regulates melanin concentration for background adaptation. We demonstrate that this effect is mediated by MCH receptor 2 (Mchr2) but not Mchr1a/b. mchr2 knock-out fish cannot adapt to a white background, providing the first genetic demonstration that MCH signaling is physiologically required to control skin pigmentation. mchr2 phenotype can be rescued in adult fish by knocking-out pomc, the gene coding for the precursor of α-MSH, demonstrating the relevance of the antagonistic activity between MCH and α-MSH in the control of melanosome organization. Interestingly, MCH receptor is also expressed in human melanocytes, thus a similar antagonistic activity regulating skin pigmentation may be conserved during evolution, and the dysregulation of these pathways is significant to our understanding of human skin disorders and cancers. 相似文献
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Romain Benoist Claire Capdevielle‐Dulac Clina Chantre Rmi Jeannette Paul‐Andr Calatayud Jean‐Michel Drezen Stphane Dupas Arnaud Le Rouzic Bruno Le Ru Laurence Moreau Erwin Van Dijk Laure Kaiser Florence Mougel 《Molecular ecology》2020,29(18):3476-3493
Dissecting the genetic basis of intraspecific variations in life history traits is essential to understand their evolution, notably for potential biocontrol agents. Such variations are observed in the endoparasitoid Cotesia typhae (Hymenoptera: Braconidae), specialized on the pest Sesamia nonagrioides (Lepidoptera: Noctuidae). Previously, we identified two strains of C. typhae that differed significantly for life history traits on an allopatric host population. To investigate the genetic basis underlying these phenotypic differences, we used a quantitative trait locus (QTL) approach based on restriction site‐associated DNA markers. The characteristic of C. typhae reproduction allowed us generating sisters sharing almost the same genetic content, named clonal sibship. Crosses between individuals from the two strains were performed to generate F2 and F8 recombinant CSS. The genotypes of 181 clonal sibships were determined as well as the phenotypes of the corresponding 4,000 females. Informative markers were then used to build a high‐quality genetic map. These 465 markers spanned a total length of 1,300 cM and were organized in 10 linkage groups which corresponded to the number of C. typhae chromosomes. Three QTLs were detected for parasitism success and two for offspring number, while none were identified for sex ratio. The QTLs explained, respectively, 27.7% and 24.5% of the phenotypic variation observed. The gene content of the genomic intervals was investigated based on the genome of C. congregata and revealed 67 interesting candidates, as potentially involved in the studied traits, including components of the venom and of the symbiotic virus (bracovirus) shown to be necessary for parasitism success in related wasps. 相似文献
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Engelhardt Ilonka C. Niklaus Pascal A. Bizouard Florian Breuil Marie-Christine Rouard Nadine Deau Florence Philippot Laurent Barnard Romain L. 《Plant and Soil》2021,461(1-2):151-162
Plant and Soil - Contrasting nutrient-acquisition strategies would explain why species differ in their distribution in relation to soil phosphorus (P) availability, promoting diversity. However,... 相似文献
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Jolivet Raphaël Clavreul Julie Brière Raphaël Besseau Romain Prieur Vernat Anne Sauze Marie Blanc Isabelle Douziech Mélanie Pérez-López Paula 《The International Journal of Life Cycle Assessment》2021,26(12):2457-2471
The International Journal of Life Cycle Assessment - In this paper, we present new tools to ease the analysis of the effect of variability and uncertainty on life cycle assessment (LCA) results.... 相似文献
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Nomi Kreif Oleg Sofrygin Julie A. Schmittdiel Alyce S. Adams Richard W. Grant Zheng Zhu Mark J. van der Laan Romain Neugebauer 《Biometrics》2021,77(1):329-342
In studies based on electronic health records (EHR), the frequency of covariate monitoring can vary by covariate type, across patients, and over time, which can limit the generalizability of inferences about the effects of adaptive treatment strategies. In addition, monitoring is a health intervention in itself with costs and benefits, and stakeholders may be interested in the effect of monitoring when adopting adaptive treatment strategies. This paper demonstrates how to exploit nonsystematic covariate monitoring in EHR‐based studies to both improve the generalizability of causal inferences and to evaluate the health impact of monitoring when evaluating adaptive treatment strategies. Using a real world, EHR‐based, comparative effectiveness research (CER) study of patients with type II diabetes mellitus, we illustrate how the evaluation of joint dynamic treatment and static monitoring interventions can improve CER evidence and describe two alternate estimation approaches based on inverse probability weighting (IPW). First, we demonstrate the poor performance of the standard estimator of the effects of joint treatment‐monitoring interventions, due to a large decrease in data support and concerns over finite‐sample bias from near‐violations of the positivity assumption (PA) for the monitoring process. Second, we detail an alternate IPW estimator using a no direct effect assumption. We demonstrate that this estimator can improve efficiency but at the potential cost of increase in bias from violations of the PA for the treatment process. 相似文献
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Florian Wilfling Huajin Wang Joel T. Haas Natalie Krahmer Travis J. Gould Aki Uchida Ji-Xin Cheng Morven Graham Romain Christiano Florian Fröhlich Xinran Liu Kimberly K. Buhman Rosalind A. Coleman Joerg Bewersdorf Robert V. Farese Tobias C. Walther 《Developmental cell》2013,24(4):384-399
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Joseph A. Webb Christopher P. Jones Leslie J. Parent Ioulia Rouzina Karin Musier-Forsyth 《RNA (New York, N.Y.)》2013,19(8):1078-1088
Despite the vast excess of cellular RNAs, precisely two copies of viral genomic RNA (gRNA) are selectively packaged into new human immunodeficiency type 1 (HIV-1) particles via specific interactions between the HIV-1 Gag and the gRNA psi (ψ) packaging signal. Gag consists of the matrix (MA), capsid, nucleocapsid (NC), and p6 domains. Binding of the Gag NC domain to ψ is necessary for gRNA packaging, but the mechanism by which Gag selectively interacts with ψ is unclear. Here, we investigate the binding of NC and Gag variants to an RNA derived from ψ (Psi RNA), as well as to a non-ψ region (TARPolyA). Binding was measured as a function of salt to obtain the effective charge (Zeff) and nonelectrostatic (i.e., specific) component of binding, Kd(1M). Gag binds to Psi RNA with a dramatically reduced Kd(1M) and lower Zeff relative to TARPolyA. NC, GagΔMA, and a dimerization mutant of Gag bind TARPolyA with reduced Zeff relative to WT Gag. Mutations involving the NC zinc finger motifs of Gag or changes to the G-rich NC-binding regions of Psi RNA significantly reduce the nonelectrostatic component of binding, leading to an increase in Zeff. These results show that Gag interacts with gRNA using different binding modes; both the NC and MA domains are bound to RNA in the case of TARPolyA, whereas binding to Psi RNA involves only the NC domain. Taken together, these results suggest a novel mechanism for selective gRNA encapsidation. 相似文献