Comparative local analysis of metabolites, lipids and proteins in intact fish tissues by LAESI mass spectrometry

Direct mass spectrometric analysis of animal tissues is an emerging field enabled by recent developments in ambient ion sources. Label-free in situ analysis of metabolites, lipids, and peptides/proteins from intact tissues in whole fish specimens of different gender and age were performed by laser ablation electrospray ionization (LAESI) mass spectrometry (MS). Hypertrophied glandular tissue (gill gland) of adult male Aphyocharax anisitsi (bloodfin tetra) was compared with gill tissues in females of the same species. Comparison of a large number of sample-specific ions was aided by a multivariate statistical method based on orthogonal projections to latent structures discriminant analysis. More than 200 different ions were detected in the mass spectra corresponding to primary metabolites, hormones, lipids and peptides/proteins. The gill tissues of the sexually mature males exhibited multiply charged ions in the 6+ to 10+ charge states corresponding to a protein with a molecular weight of 11 380 Da. This protein was present only in the mature male gill glands but absent in the corresponding area of the female and immature male specimens. An additional nine proteins were detected by LAESI-MS in both the male and female gill tissues

The Abca7V1613M variant reduces Aβ generation, plaque load, and neuronal damage

BackgroundVariants in ABCA7, a member of the ABC transporter superfamily, have been associated with increased risk for developing late onset Alzheimer's disease (LOAD).MethodsCRISPR-Cas9 was used to generate an Abca7V1613M variant in mice, modeling the homologous human ABCA7V1599M variant, and extensive characterization was performed.ResultsAbca7V1613M microglia show differential gene expression profiles upon lipopolysaccharide challenge and increased phagocytic capacity. Homozygous Abca7V1613M mice display elevated circulating cholesterol and altered brain lipid composition. When crossed with 5xFAD mice, homozygous Abca7V1613M mice display fewer Thioflavin S-positive plaques, decreased amyloid beta (Aβ) peptides, and altered amyloid precursor protein processing and trafficking. They also exhibit reduced Aβ-associated inflammation, gliosis, and neuronal damage.DiscussionOverall, homozygosity for the Abca7V1613M variant influences phagocytosis, response to inflammation, lipid metabolism, Aβ pathology, and neuronal damage in mice. This variant may confer a gain of function and offer a protective effect against Alzheimer's disease-related pathology.HighlightsABCA7 recognized as a top 10 risk gene for developing Alzheimer's disease. Loss of function mutations result in increased risk for LOAD. V1613M variant reduces amyloid beta plaque burden in 5xFAD mice. V1613M variant modulates APP processing and trafficking in 5xFAD mice. V1613M variant reduces amyloid beta-associated damage in 5xFAD mice

Molecular phylogeny of the subfamily Stevardiinae Gill, 1858 (Characiformes: Characidae): classification and the evolution of reproductive traits

Abstract Background The subfamily Stevardiinae is a diverse and widely distributed clade of freshwater fishes from South and Central America, commonly known as “tetras” (Characidae). The group was named “clade A” when first proposed as a monophyletic unit of Characidae and later designated as a subfamily. Stevardiinae includes 48 genera and around 310 valid species with many species presenting inseminating reproductive strategy. No global hypothesis of relationships is available for this group and currently many genera are listed as incertae sedis or are suspected to be non-monophyletic. Results We present a molecular phylogeny with the largest number of stevardiine species analyzed so far, including 355 samples representing 153 putative species distributed in 32 genera, to test the group’s monophyly and internal relationships. The phylogeny was inferred using DNA sequence data from seven gene fragments (mtDNA: 12S, 16S and COI; nuclear: RAG1, RAG2, MYH6 and PTR). The results support the Stevardiinae as a monophyletic group and a detailed hypothesis of the internal relationships for this subfamily. Conclusions A revised classification based on the molecular phylogeny is proposed that includes seven tribes and also defines monophyletic genera, including a resurrected genus Eretmobrycon, and new definitions for Diapoma, Hemibrycon, Bryconamericus sensu stricto, and Knodus sensu stricto, placing some small genera as junior synonyms. Inseminating species are distributed in several clades suggesting that reproductive strategy is evolutionarily labile in this group of fishes.http://deepblue.lib.umich.edu/bitstream/2027.42/134621/1/12862_2015_Article_403.pd

A review of the Cis-Andean species of Hemibrycon Günther (Teleostei: Characiformes: Characidae: Stevardiinae), with description of two new species

As espécies de Hemibrycon que ocorrem a leste das Cordilheiras dos Andes são revisadas com base na análise do material tipo e exemplares adicionais. Nove espécies são redescritas: H. beni da bacia do río Beni, Bolívia; H. helleri do alto río Ucayali, Peru; H. huambonicus para as bacias dos ríos Huallaga e Marañon, Peru; H. jeslkii para as porções superiores das bacias dos rios Marañon, Ucayali e Madeira, Bolívia, Brasil e Peru; H. metae para a bacia do río Orinoco, Colômbia e Venezuela, e bacias costeiras do Caribe na Venezuela; H. polyodon (espécie-tipo) para a bacia do río Pastaza, Equador; H. surinamensis para as bacia costeiras da Guiana Francesa e Suriname, e porção inferior das bacias dos rios Tapajós, Tocantins e Xingu, Brasil; H. taeniurus para os rios da ilha de Trinidad, Trinidad and Tobago; H. tridens para a bacia do alto río Ucayali, Peru. Duas espécies novas são descritas: H. inambari para a bacia do alto río Madre de Dios, Peru e H. mikrostiktos para a bacia do río Ucayali, Peru. Estas espécies distinguem-se principalmente pelo padrão de colorido e caracteres merísticos. A área de distribuição do gênero é ampliada para as porções inferiores das bacias do Tapajós, Tocantins e Xingu, Brasil, com o primeiro registro de H. surinamensis para este país. Uma nova diagnose e descrição são fornecidas para a espécie-tipo do gênero, apesar de ter sido recentemente redescrita. A série-tipo de H. helleri previamente considerada questionável é encontrada e descrita. Hemibrycon coxeyi e H. pautensis são considerados sinônimos juniores de H. polyodon. Tetragonopterus (Hemibrycon) trinitatis, anteriormente considerada como species inquirenda em Characidae, e Hemibrycon guppyi são sinônimos juniores de H. taeniurus. Hemibrycon orcesi é transferida para Boehlkea. É apresentada uma chave taxonômica para as espécies do gênero a leste das Cordilheiras dos Andes.The species of Hemibrycon occurring in the east of the Andean Cordilleras are reviewed based on their type series and additional specimens. Nine species are redescribed: H. beni from río Beni basin, Bolivia; H. helleri from the upper rio Ucayali, Peru; H. huambonicus from the ríos Huallaga and Marañon basins, Peru; H. jeslkii from the upper portions of ríos Marañon, Ucayali and Madeira basins, Bolivia, Brazil, and Peru; H. metae from río Orinoco basin, Colombia and Venezuela, and Caribbean coastal basins of Venezuela; H. polyodon (type species) from río Pastaza basin, Ecuador; H. surinamensis from coastal basins of French Guiana and Suriname, and from lower rios Tapajós, Tocantins and Xingu basins, Brazil; H. taeniurus from river basins from Trinidad Island, Trinidad and Tobago, and H. tridens from upper río Ucayali basin, Peru. Two new species are described: H. inambari from the upper río Madre de Dios basin, Peru and H. mikrostiktos from río Ucayali basin, Peru. These species are distinguished among themselves mainly by the color pattern, and meristic characters. The distribution area of the genus is enlarged reaching the lower Tapajós, Tocantins and Xingu river basins, Brazil, with the first record of the occurrence of H. surinamensis in this country. A new description and diagnosis is provided for the type species of the genus, regardless its recent redescription. The type series of H. helleri that was previously considered dubious is found and described. Hemibrycon coxeyi and H. pautensis are considered junior synonyms of H. polyodon. Tetragonopterus (Hemibrycon) trinitatis, previously considered species inquirenda in Characidae, and Hemibrycon guppyi are junior synonyms of H. taeniurus. Hemibrycon orcesi is transferred to Boehlkea. A taxonomic key for the species of the genus to the east of the Andean Cordilleras is presented

Generation of a humanized Aβ expressing mouse demonstrating aspects of Alzheimer's disease-like pathology.

The majority of Alzheimer’s disease (AD) cases are late-onset and occur sporadically, however most mouse models of the disease harbor pathogenic mutations, rendering them better representations of familial autosomal-dominant forms of the disease. Here, we generated knock-in mice that express wildtype human Aβ under control of the mouse App locus. Remarkably, changing 3 amino acids in the mouse Aβ sequence to its wild-type human counterpart leads to age-dependent impairments in cognition and synaptic plasticity, brain volumetric changes, inflammatory alterations, the appearance of Periodic Acid-Schiff (PAS) granules and changes in gene expression. In addition, when exon 14 encoding the Aβ sequence was flanked by loxP sites we show that Cre-mediated excision of exon 14 ablates hAβ expression, rescues cognition and reduces the formation of PAS granules