Contrasted Patterns of Selection on MHC-Linked Microsatellites in Natural Populations of the Malagasy Plague Reservoir

Plague (Yersinia pestis infection) is a highly virulent rodent disease that persists in many natural ecosystems. The black rat (Rattus rattus) is the main host involved in the plague focus of the central highlands of Madagascar. Black rat populations from this area are highly resistant to plague, whereas those from areas in which the disease is absent (low altitude zones of Madagascar) are susceptible. Various lines of evidence suggest a role for the Major Histocompatibility Complex (MHC) in plague resistance. We therefore used the MHC region as a candidate for detecting signatures of plague-mediated selection in Malagasy black rats, by comparing population genetic structures for five MHC-linked microsatellites and neutral markers in two sampling designs. We first compared four pairs of populations, each pair including one population from the plague focus and one from the disease-free zone. Plague-mediated selection was expected to result in greater genetic differentiation between the two zones than expected under neutrality and this was observed for one MHC-class I-linked locus (D20Img2). For this marker as well as for four other MHC-linked loci, a geographic pattern of genetic structure was found at local scale within the plague focus. This pattern would be expected if plague selection pressures were spatially variable. Finally, another MHC-class I-linked locus (D20Rat21) showed evidences of balancing selection, but it seems more likely that this selection would be related to unknown pathogens more widely distributed in Madagascar than plague

Plague Circulation and Population Genetics of the Reservoir Rattus rattus: The Influence of Topographic Relief on the Distribution of the Disease within the Madagascan Focus.

International audienceBACKGROUND: Landscape may affect the distribution of infectious diseases by influencing the population density and dispersal of hosts and vectors. Plague (Yersinia pestis infection) is a highly virulent, re-emerging disease, the ecology of which has been scarcely studied in Africa. Human seroprevalence data for the major plague focus of Madagascar suggest that plague spreads heterogeneously across the landscape as a function of the relief. Plague is primarily a disease of rodents. We therefore investigated the relationship between disease distribution and the population genetic structure of the black rat, Rattus rattus, the main reservoir of plague in Madagascar. METHODOLOGYPRINCIPAL FINDINGS: We conducted a comparative study of plague seroprevalence and genetic structure (15 microsatellite markers) in rat populations from four geographic areas differing in topology, each covering about 150-200 km(2) within the Madagascan plague focus. The seroprevalence levels in the rat populations mimicked those previously reported for humans. As expected, rat populations clearly displayed a more marked genetic structure with increasing relief. However, the relationship between seroprevalence data and genetic structure differs between areas, suggesting that plague distribution is not related everywhere to the effective dispersal of rats. CONCLUSIONSSIGNIFICANCE: Genetic diversity estimates suggested that plague epizootics had only a weak impact on rat population sizes. In the highlands of Madagascar, plague dissemination cannot be accounted for solely by the effective dispersal of the reservoir. Human social activities may also be involved in spreading the disease in rat and human populations

Towards the simplification of MHC typing protocols: targeting classical MHC class II genes in a passerine, the pied flycatcher Ficedula hypoleuca

<p>Abstract</p> <p>Background</p> <p>Major Histocompatibility Complex (MHC) has drawn the attention of evolutionary biologists due to its importance in crucial biological processes, such as sexual selection and immune response in jawed vertebrates. However, the characterization of classical MHC genes subjected to the effects of natural selection still remains elusive in many vertebrate groups. Here, we have tested the suitability of flanking intron sequences to guide the selective exploration of classical MHC genes driving the co-evolutionary dynamics between pathogens and their passerine (Aves, Order Passeriformes) hosts.</p> <p>Findings</p> <p>Intronic sequences flanking the usually polymorphic exon 2 were isolated from different species using primers sitting on conserved coding regions of MHC class II genes (β chain). Taking the pied flycatcher <it>Ficedula hypoleuca</it> as an example, we demonstrate that careful primer design can evade non-classical MHC gene and pseudogene amplification. At least four polymorphic and expressed loci were co-replicated using a single pair of primers in five non-related individuals (N = 28 alleles). The cross-amplification and preliminary inspection of similar MHC fragments in eight unrelated songbird taxa suggests that similar approaches can also be applied to other species.</p> <p>Conclusions</p> <p>Intron sequences flanking the usually polymorphic exon 2 may assist the specific investigation of classical MHC class II B genes in species characterized by extensive gene duplication and pseudogenization. Importantly, the evasion of non-classical MHC genes with a more specific function and non-functional pseudogenes may accelerate data collection and diminish lab costs. Comprehensive knowledge of gene structure, polymorphism and expression profiles may be useful not only for the selective examination of evolutionarily relevant genes but also to restrict chimera formation by minimizing the number of co-amplifying loci.</p

Scopolamine Administration Modulates Muscarinic, Nicotinic and NMDA Receptor Systems

Studies on the effect of scopolamine on memory are abundant but so far only regulation of the muscarinic receptor (M1) has been reported. We hypothesized that levels of other cholinergic brain receptors as the nicotinic receptors and the N-methyl-D-aspartate (NMDA) receptor, known to be involved in memory formation, would be modified by scopolamine administration

Organic-inorganic supramolecular solid catalyst boosts organic reactions in water

[EN] Coordination polymers and metal-organic frameworks are appealing as synthetic hosts for mediating chemical reactions. Here we report the preparation of a mesoscopic metal-organic structure based on single-layer assembly of aluminium chains and organic alkylaryl spacers. The material markedly accelerates condensation reactions in water in the absence of acid or base catalyst, as well as organocatalytic Michael-type reactions that also show superior enantioselectivity when comparing with the host-free transformation. The mesoscopic phase of the solid allows for easy diffusion of products and the catalytic solid is recycled and reused. Saturation transfer difference and two-dimensional H-1 nuclear Overhauser effect NOESY NMR spectroscopy show that non-covalent interactions are operative in these host-guest systems that account for substrate activation. The mesoscopic character of the host, its hydrophobicity and chemical stability in water, launch this material as a highly attractive supramolecular catalyst to facilitate (asymmetric) transformations under more environmentally friendly conditions.This work was funded by ERC-AdG-2014-671093-SynCatMatch and the Generalitat Valenciana (Prometeo). M.B. acknowledges the funding: CTQ2014-52633-P. The Severo Ochoa program (SEV-2012-0267) is thankfully acknowledged.García García, P.; Moreno Rodríguez, JM.; Díaz Morales, UM.; Bruix, M.; Corma Canós, A. (2016). Organic-inorganic supramolecular solid catalyst boosts organic reactions in water. Nature Communications. 7. https://doi.org/10.1038/ncomms10835S7Li, B. et al. A porous metal-organic framework with dynamic pyrimidine groups exhibiting record high methane storage working capacity. J. Am. Chem. Soc. 136, 6207–6210 (2014).Getman, R. B., Bae, Y.-S., Wilmer, C. E. & Snurr, R. Q. Review and analysis of molecular simulations of methane, hydrogen, and acetylene storage in metal–organic frameworks. Chem. Rev. 112, 703–723 (2012).Suh, M. P., Park, H. J., Prasad, T. K. & Lim, D.-W. Hydrogen storage in metal–organic frameworks. Chem. Rev. 112, 782–835 (2012).Li, B., Wen, H.-M., Zhou, W. & Chen, B. Porous metal-organic frameworks for gas storage and separation: what, how, and why? J. Phys. Chem. Lett. 5, 3468–3479 (2014).Li, J.-R., Sculley, J. & Zhou, H.-C. Metal–organic frameworks for separations. Chem. Rev. 112, 869–932 (2012).Cui, Y., Yue, Y., Qian, G. & Chen, B. Luminescent functional metal–organic frameworks. Chem. Rev. 112, 1126–1162 (2012).Yoon, M., Suh, K., Natarajan, S. & Kim, K. Proton conduction in metal–organic frameworks and related modularly built porous solids. Angew. Chem. Int. Ed. 52, 2688–2700 (2013).Kurmoo, M. Magnetic metal-organic frameworks. Chem. Soc. Rev. 38, 1353–1379 (2009).Horcajada, P. et al. Metal–organic frameworks in biomedicine. Chem. Rev. 112, 1232–1268 (2012).Liu, J. et al. Applications of metal-organic frameworks in heterogeneous supramolecular catalysis. Chem. Soc. Rev. 43, 6011–6061 (2014).Rowsell, J. L. C. & Yaghi, O. M. Metal–organic frameworks: a new class of porous materials. Micropor. Mesopor. Mat. 73, 3–14 (2004).Eubank, J. F. et al. The next chapter in MOF pillaring strategies: trigonal heterofunctional ligands to access targeted high-connected three dimensional nets, isoreticular platforms. J. Am. Chem. Soc. 133, 17532–17535 (2011).Rodenas, T. et al. Metal-organic framework nanosheets in polymer composite materials for gas separation. Nat. Mater. 14, 48–55 (2015).Chang, Z. et al. Rational construction of 3D pillared metal–organic frameworks: synthesis, structures, and hydrogen adsorption properties. Inorg. Chem. 50, 7555–7562 (2011).Cheetham, A. K., Rao, C. N. R. & Feller, R. K. Structural diversity and chemical trends in hybrid inorganic-organic framework materials. Chem. Commun. 4780–4795 (2006).Loiseau, T. et al. A rationale for the large breathing of the porous aluminum terephthalate (MIL-53) upon hydration. Chem. Eur. J. 10, 1373–1382 (2004).Senkovska, I. et al. New highly porous aluminium based metal-organic frameworks: Al(OH)(ndc) (ndc=2,6-naphthalene dicarboxylate) and Al (OH) (bpdc) (bpdc=4,4′-biphenyl dicarboxylate). Micropor. Mesopor. Mat. 122, 93–98 (2009).Klein, N. et al. Structural flexibility and intrinsic dynamics in the M2(2,6-ndc)2(dabco) (M=Ni, Cu, Co, Zn) metal-organic frameworks. J. Mater. Chem. 22, 10303–10312 (2012).Hoffmann, H. C. et al. High-pressure in situ 129Xe NMR spectroscopy and computer simulations of breathing transitions in the metal–organic framework Ni2(2,6-ndc)2(dabco) (DUT-8(Ni). J. Am. Chem. Soc. 133, 8681–8690 (2011).Gu, J.-M., Kim, W.-S. & Huh, S. Size-dependent catalysis by DABCO-functionalized Zn-MOF with one-dimensional channels. Dalton Trans. 40, 10826–10829 (2011).Carson, C. G. et al. Synthesis and structure characterization of copper terephthalate metal–organic frameworks. Eur. J. Inorg. Chem. 2009, 2338–2343 (2009).Yang, Q. et al. Probing the adsorption performance of the hybrid porous MIL-68(Al): a synergic combination of experimental and modelling tools. J. Mater. Chem. 22, 10210–10220 (2012).Li, H. et al. Visible light-driven water oxidation promoted by host-guest interaction between photosensitizer and catalyst with a high quantum efficiency. J. Am. Chem. Soc. 137, 4332–4335 (2015).Hapiot, F., Bricout, H., Menuel, S., Tilloy, S. & Monflier, E. Recent breakthroughs in aqueous cyclodextrin-assisted supramolecular catalysis. Catal. Sci. Technol. 4, 1899–1908 (2014).Harada, A., Takashima, Y. & Nakahata, M. Supramolecular polymeric materials via cyclodextrin-guest interactions. Acc. Chem. Res. 47, 2128–2140 (2014).Cong, H. et al. Substituent effect of substrates on cucurbit[8]uril-catalytic oxidation of aryl alcohols. J. Mol. Catal. A Chem. 374-375, 32–38 (2013).Masson, E., Ling, X., Joseph, R., Kyeremeh-Mensah, L. & Lu, X. Cucurbituril chemistry: a tale of supramolecular success. RSC Adv. 2, 1213–1247 (2012).Song, F.-T., Ouyang, G.-H., Li, Y., He, Y.-M. & Fan, Q.-H. Metallacrown ether catalysts containing phosphine-phosphite polyether ligands for Rh-catalyzed asymmetric hydrogenation—enhancements in activity and enantioselectivity. Eur. J. Org. Chem. 2014, 6713–6719 (2014).Rebilly, J.-N. & Reinaud, O. Calixarenes and resorcinarenes as scaffolds for supramolecular metallo-enzyme mimicry. Supramol. Chem. 26, 454–479 (2014).Ajami, D., Liu, L. & Rebek, J. Jr Soft templates in encapsulation complexes. Chem. Soc. Rev. 44, 490–499 (2015).Corma, A. & Garcia, H. Supramolecular host-guest systems in zeolites prepared by ship-in-a-bottle synthesis. Eur. J. Inorg. Chem. 2004, 1143–1164 (2004).Kemp, D. S., Cox, D. D. & Paul, K. G. Physical organic chemistry of benzisoxazoles. IV. Origins and catalytic nature of the solvent rate acceleration for the decarboxylation of 3-carboxybenzisoxazoles. J. Am. Chem. Soc. 97, 7312–7318 (1975).Thorn, S. N., Daniels, R. G., Auditor, M. T. & Hilvert, D. Large rate accelerations in antibody catalysis by strategic use of haptenic charge. Nature 373, 228–230 (1995).Yoshizawa, M., Klosterman, J. K. & Fujita, M. Functional molecular flasks: new properties and reactions within discrete, self-assembled hosts. Angew. Chem. Int. Ed. 48, 3418–3438 (2009).Yoshizawa, M., Tamura, M. & Fujita, M. Diels-Alder in aqueous molecular hosts: unusual regioselectivity and efficient catalysis. Science 312, 251–254 (2006).Murase, T., Nishijima, Y. & Fujita, M. Cage-catalyzed knoevenagel condensation under neutral conditions in water. J. Am. Chem. Soc. 134, 162–164 (2012).Zhao, C., Toste, F. D., Raymond, K. N. & Bergman, R. G. Nucleophilic substitution catalyzed by a supramolecular cavity proceeds with retention of absolute stereochemistry. J. Am. Chem. Soc. 136, 14409–14412 (2014).Choi, M. et al. Stable single-unit-cell nanosheets of zeolite MFI as active and long-lived catalysts. Nature 461, 246–249 (2009).Loiseau, T. et al. MIL-96, a porous aluminum trimesate 3D structure constructed from a hexagonal network of 18-membered rings and μ3-Oxo-centered trinuclear units. J. Am. Chem. Soc. 128, 10223–10230 (2006).Bezverkhyy, I. et al. MIL-53(Al) under reflux in water: formation of γ-AlO(OH) shell and H2BDC molecules intercalated into the pores. Micropor. Mesopor. Mat. 183, 156–161 (2014).Wang, L.-M. et al. Sodium stearate-catalyzed multicomponent reactions for efficient synthesis of spirooxindoles in aqueous micellar media. Tetrahedron 66, 339–343 (2010).List B. Science of Synthesis: Asymmetric Organocatalysis 1, Lewis Base and Acid Catalysts Georg Thieme Verlag (2012).He, T., Gu, Q. & Wu, X.-Y. Highly enantioselective Michael addition of isobutyraldehyde to nitroalkenes. Tetrahedron 66, 3195–3198 (2010).Avila, A., Chinchilla, R., Fiser, B., Gómez-Bengoa, E. & Nájera, C. Enantioselective Michael addition of isobutyraldehyde to nitroalkenes organocatalyzed by chiral primary amine-guanidines. Tetrahedron Asymmetry 25, 462–467 (2014).Meyer, B. & Peters, T. NMR spectroscopy techniques for screening and identifying ligand binding to protein receptors. Angew. Chem. Int. Ed. 42, 864–890 (2003).Szczygiel, A., Timmermans, L., Fritzinger, B. & Martins, J. C. Widening the view on dispersant−pigment interactions in colloidal dispersions with saturation transfer difference NMR spectroscopy. J. Am. Chem. Soc. 131, 17756–17758 (2009).Basilio, N., Martín-Pastor, M. & García-Río, L. Insights into the structure of the supramolecular amphiphile formed by a sulfonated calix[6]arene and alkyltrimethylammonium surfactants. Langmuir 28, 6561–6568 (2012).Mayer, M. & Meyer, B. Characterization of ligand binding by saturation transfer difference NMR spectroscopy. Angew. Chem. Int. Ed. 38, 1784–1788 (1999)

Cyclin D1 Expression in Patients with Multiple Myeloma

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