Searching for specific binding sites of the secretory glycoproteins of the subcommissural organ

The molecular organization of Reissner's fiber (RF), the structure of its proteins, and the permanent turnover of these proteins are all facts supporting the possibility that RF may perform multiple functions. There is evidence that CSF-soluble RF-glycoproteins may occur under physiological conditions. The present investigation was designed to investigate the probable existence within the CNS of specific binding sites for RF-glycoproteins. Three experimental protocols were used: (1) immunocytochemistry of the CNS of bovine fetuses using anti-idiotypic antibodies, raised against monoclonal antibodies developed against bovine RF-glycoproteins; (2) in vivo binding of the RF glycoproteins, perfusing into the rat CSF 125I-labeled RF-glycoproteins, or grafting SCO into a lateral ventricle of the rat; (3) in vitro binding of unlabeled RF-glycoproteins to rat and bovine choroid plexuses maintained in culture. One of the anti-idiotypic antibody generated by a Mab raised against RF-glycoproteins binds to choroidal cells. Furthermore, binding of RF-glycoproteins to the rat choroid plexus was obtained when: (1) the choroid plexus was cultured in the presence of unlabeled RF-glycoproteins; (2) the concentration of soluble RF-glycoproteins in the CSF was increased by isografting SCOs into a lateral ventricle; (3) radiolabeled glycoproteins were perfused into the ventricular CSF. This evidence suggests that the apical plasma membrane of the ependymal cells of the choroid plexus has specific binding sites for RF-glycoproteins, of unknown functional significance. The radiolabeled RF-glycoproteins perfused into the rat CSF also bound to the paraventricular thalamic nucleus, the floor of the Sylvian aqueduct and of the rostral half of the fourth ventricle, and title meninges of the brain and spinal cord. The labeling of the paraventricular thalamic nucleus points to a functional relationship between this nucleus and the SCO. The possibility that; the SCO may be a component of the circadian timing system is discussed. Microsc. Res. Tech. 52:541-551, 2001. (C) 2001 Wiley-Liss, Inc

Interspecific Genetic Differences and Historical Demography in South American Arowanas (Osteoglossiformes, Osteoglossidae, Osteoglossum)

The South American arowanas (Osteoglossiformes, Osteoglossidae, Osteoglossum) are emblematic species widely distributed in the Amazon and surrounding basins. Arowana species are under strong anthropogenic pressure as they are extensively exploited for ornamental and food purposes. Until now, limited genetic and cytogenetic information has been available, with only a few studies reporting to their genetic diversity and population structure. In the present study, cytogenetic and DArTseq-derived single nucleotide polymorphism (SNP) data were used to investigate the genetic diversity of the two Osteoglossum species, the silver arowana O. bicirrhosum, and the black arowana O. ferreirai. Both species differ in their 2n (with 2n = 54 and 56 for O. ferreirai and O. bicirrhosum, respectively) and in the composition and distribution of their repetitive DNA content, consistent with their taxonomic status as different species. Our genetic dataset was coupled with contemporary and paleogeographic niche modeling, to develop concurrent demographic models that were tested against each other with a deep learning approach in O. bicirrhosum. Our genetic results reveal that O. bicirrhosum colonized the Tocantins-Araguaia basin from the Amazon basin about one million years ago. In addition, we highlighted a higher genetic diversity of O. bicirrhosum in the Amazon populations in comparison to those from the Tocantins-Araguaia basin. © 2019 by the authors. Licensee MDPI, Basel, Switzerland

Estudo de estrutura genética da espécie de Cactácea colunar Pilosocereus machrisii utilizando DNA microssatélite

Pilosocereus machrisii is a columnar cacti with natural fragmented distribution; restrict to campos rupestres vegetation patches or rocky outcrops on the Cerrado domain; in Central and eastern Brazil. These features makes P. machrisii an appropriate biological model for population genetic studies aiming to gather information on population structure; since small and isolated populations are often vulnerable to genetic drift and high levels of inbreeding. Genetic diversity and population structure were assessed for ten microsatellite loci in 12 P. machrisii populations; covering the majority of the species distribution. Genetic diversity levels were relatively similar on sampled populations; except for Brotas-SP samples; that showed lower levels than those observed for other locations. Significant Hardy Weinberg Equilibrium departures were detected in eight different populations; for one or two loci. High levels of genetic differentiation and private alleles with elevated frequencies were detected; with total FST value of 0.357. The genetic structure of P. machrisii was analyzed with STRUCTURE and SAMOVA softwares; and populations were grouped in four main clusters; with secondary structure on two of these clusters. Significative levels of correlation between genetic and geographic distances were observed for the whole dataset; however; when the genetic groups were analyzed separately; no correlation was verified. Furthermore; the genetic relationship between the populations was observed with a principal coordinate analysis (PCA) and an UPGMA dendrogram. The genetic structure observed in P. machrisii suggests that historical factors caused populations fragmentation; with subsequent geographic isolation and high genetic differentiation between them.Universidade Federal de Minas GeraisPilosocereus machrisii é um cacto colunar com distribuição naturalmente fragmentada no centro e leste do Brasil; restrito aos enclaves de vegetação de campos rupestres ou de afloramentos rochosos no domínio Cerrado. Essas características tornam a espécie um modelo biológico apropriado para a realização de estudos de estrutura populacional; uma vez que suas populações pequenas e isoladas podem estar altamente vulneráveis a efeitos de deriva genética e endogamia. Foram estimados os níveis de diversidade genética e estruturação populacional a partir de dez locos marcadores microssatélite em doze populações de ocorrência natural de P. machrisii; cobrindo a maior parte de sua distribuição. Os níveis de diversidade genética dentro das populações apresentaram resultados relativamente similares nas localidades amostradas; exceto pelas amostras do município de Brotas-SP; com índices menores que os observados em outras populações. Desvios significativos em relação às proporções do Equilíbrio de Hardy-Weinberg foram detectados para um ou dois locos em oito populações diferentes. Alelos privados em alta frequência foram detectados; assim como altos níveis de diferenciação genética; com um valor de FST total de 0;357. A estrutura genética das populações; verificada a partir da análise com os programas STRUCTURE e SAMOVA apresentou uma estruturação mais provável em quatro grupos principais e níveis secundários de estruturação dentro desses grupos. Níveis significativos de correlação entre as distâncias genéticas e geográficas entre pares de populações foram detectados para o conjunto total de dados; no entanto não houve correlação quando os agrupamentos genéticos foram analisados separadamente. Além disso; foi possível verificar as relações genéticas entre as diferentes populações a partir de uma análise de coordenadas principais (PCA) e de um dendrograma construído a partir do método UPGMA. A estrutura genética observada em P. machrisii aponta para um importante efeito de eventos históricos que causaram a fragmentação das populações; com posterior isolamento geográfico e aquisição de elevada diferenciação genética

Deciphering the Evolutionary History of Arowana Fishes (Teleostei, Osteoglossiformes, Osteoglossidae):Insight from Comparative Cytogenomics

Arowanas (Osteoglossinae) are charismatic freshwater fishes with six species and two genera (Osteoglossum and Scleropages) distributed in South America, Asia, and Australia. In an attempt to provide a better assessment of the processes shaping their evolution, we employed a set of cytogenetic and genomic approaches, including i) molecular cytogenetic analyses using C-and CMA3/DAPI staining, repetitive DNA mapping, comparative genomic hybridization (CGH), and Zoo-FISH, along with ii) the genotypic analyses of single nucleotide polymorphisms (SNPs) generated by diversity array technology sequencing (DArTseq). We observed diploid chromosome numbers of 2n = 56 and 54 in O. bicirrhosum and O. ferreirai, respectively, and 2n = 50 in S. formosus, while S. jardinii and S. leichardti presented 2n = 48 and 44, respectively. A time-calibrated phylogenetic tree revealed that Osteoglossum and Scleropages divergence occurred approximately 50 million years ago (MYA), at the time of the final separation of Australia and South America (with Antarctica). Asian S. formosus and Australian Scleropages diverged about 35.5 MYA, substantially after the latest terrestrial connection between Australia and Southeast Asia through the Indian plate movement. Our combined data provided a comprehensive perspective of the cytogenomic diversity and evolution of arowana species on a timescale. © 2019 by the authors. Licensee MDPI, Basel, Switzerland

The Genetic Architecture of Parkinson Disease in Spain: Characterizing Population-Specific Risk, Differential Haplotype Structures, and Providing Etiologic Insight

Background: The Iberian Peninsula stands out as having variable levels of population admixture and isolation, making Spain an interesting setting for studying the genetic architecture of neurodegenerative diseases. Objectives: To perform the largest PD genome-wide association study restricted to a single country. Methods: We performed a GWAS for both risk of PD and age at onset in 7,849 Spanish individuals. Further analyses included population-specific risk haplotype assessments, polygenic risk scoring through machine learning, Mendelian randomization of expression, and methylation data to gain insight into disease-associated loci, heritability estimates, genetic correlations, and burden analyses. Results: We identified a novel population-specific genome-wide association study signal at PARK2 associated with age at onset, which was likely dependent on the c.155delA mutation. We replicated four genome-wide independent signals associated with PD risk, including SNCA, LRRK2, KANSL1/MAPT, and HLA-DQB1. A significant trend for smaller risk haplotypes at known loci was found compared to similar studies of non-Spanish origin. Seventeen PD-related genes showed functional consequence by two-sample Mendelian randomization in expression and methylation data sets. Long runs of homozygosity at 28 known genes/loci were found to be enriched in cases versus controls. Conclusions: Our data demonstrate the utility of the Spanish risk haplotype substructure for future fine-mapping efforts, showing how leveraging unique and diverse population histories can benefit genetic studies of complex diseases. The present study points to PARK2 as a major hallmark of PD etiology in Spain.This research was supported, in part, by the Intramural Research Program of the National Institutes of Health (National Institute on Aging, National Institute of Neurological Disorders and Stroke; project numbers: 1ZIA‐NS003154‐03, Z01‐AG000949‐02, and Z01‐ES101986). In addition, this work was supported by the Department of Defense (award W81XWH‐09‐2‐0128), The Michael J Fox Foundation for Parkinson's Research, and the ISCIII Grants PI 15/0878 (Fondos Feder) to V.A. and PI 15/01013 to J,H. This study was supported by grants from the Spanish Ministry of Economy and Competitiveness (PI14/01823, PI16/01575, PI18/01898, [SAF2006‐10126 (2006‐2009), SAF2010‐22329‐C02‐01 (2010‐2012), and SAF2013‐47939‐R (2013‐2018)]), co‐founded by ISCIII (Subdirección General de Evaluación y Fomento de la Investigación) and by Fondo Europeo de Desarrollo Regional (FEDER), the Consejería de Economía, Innovación, Ciencia y Empleo de la Junta de Andalucía (CVI‐02526, CTS‐7685), the Consejería de Salud y Bienestar Social de la Junta de Andalucía (PI‐0437‐2012, PI‐0471‐2013), the Sociedad Andaluza de Neurología, the Jacques and Gloria Gossweiler Foundation, the Fundación Alicia Koplowitz, and the Fundación Mutua Madrileña. Pilar Gómez‐Garre was supported by the “Miguel Servet” (from ISCIII16 FEDER) and “Nicolás Monardes” (from Andalusian Ministry of Health) programmes. Silvia Jesús Maestre was supported by the “Juan Rodés” programme, and Daniel Macías‐García was supported by the “Río Hortega” programme (both from ISCIII‐FEDER). Cristina Tejera Parrado was supported by VPPI‐US from the Universidad de Sevilla. This research has been conducted using samples from the HUVR‐IBiS Biobank (Andalusian Public Health System Biobank and ISCIII‐Red de Biobancos PT13/0010/0056). This work was also supported by the grant PSI2014‐57643 from the Junta de Andalucía to the CTS‐438 group and a research award from the Andalusian Society of Neurology