RESUMO
The highly structured, cis-encoded RNA elements known as riboswitches modify gene expression upon binding a wide range of molecules. The yybP-ykoY motif was one of the most broadly distributed and numerous bacterial riboswitches for which the cognate ligand was unknown. Using a combination of in vivo reporter and in vitro expression assays, equilibrium dialysis, and northern analysis, we show that the yybP-ykoY motif responds directly to manganese ions in both Escherichia coli and Bacillus subtilis. The identification of the yybP-ykoY motif as a manganese ion sensor suggests that the genes that are preceded by this motif and encode a diverse set of poorly characterized membrane proteins have roles in metal homeostasis.
Assuntos
Bacillus subtilis/genética , Proteínas de Escherichia coli/genética , Escherichia coli/genética , Manganês/metabolismo , Proteínas de Membrana Transportadoras/genética , Sequências Reguladoras de Ácido Ribonucleico , Riboswitch/genética , Regiões 5' não Traduzidas , Bacillus subtilis/efeitos dos fármacos , Bacillus subtilis/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Sequência de Bases , Escherichia coli/efeitos dos fármacos , Escherichia coli/metabolismo , Proteínas de Escherichia coli/metabolismo , Proteínas de Fímbrias/genética , Proteínas de Fímbrias/metabolismo , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Manganês/farmacologia , Proteínas de Membrana Transportadoras/metabolismo , Dados de Sequência Molecular , Mutação , Regiões Promotoras Genéticas/efeitos dos fármacos , RNA Bacteriano/metabolismo , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismoRESUMO
Repeatable, convergent outcomes are prima facie evidence for determinism in evolutionary processes. Among fishes, well-known examples include microevolutionary habitat transitions into the water column, where freshwater populations (e.g., sticklebacks, cichlids, and whitefishes) recurrently diverge toward slender-bodied pelagic forms and deep-bodied benthic forms. However, the consequences of such processes at deeper macroevolutionary scales in the marine environment are less clear. We applied a phylogenomics-based integrative, comparative approach to test hypotheses about the scope and strength of convergence in a marine fish clade with a worldwide distribution (snappers and fusiliers, family Lutjanidae) featuring multiple water-column transitions over the past 45 million years. We collected genome-wide exon data for 110 (â¼80%) species in the group and aggregated data layers for body shape, habitat occupancy, geographic distribution, and paleontological and geological information. We also implemented approaches using genomic subsets to account for phylogenetic uncertainty in comparative analyses. Our results show independent incursions into the water column by ancestral benthic lineages in all major oceanic basins. These evolutionary transitions are persistently associated with convergent phenotypes, where deep-bodied benthic forms with truncate caudal fins repeatedly evolve into slender midwater species with furcate caudal fins. Lineage diversification and transition dynamics vary asymmetrically between habitats, with benthic lineages diversifying faster and colonizing midwater habitats more often than the reverse. Convergent ecological and functional phenotypes along the benthic-pelagic axis are pervasive among different lineages and across vastly different evolutionary scales, achieving predictable high-fitness solutions for similar environmental challenges, ultimately demonstrating strong determinism in fish body-shape evolution.
Assuntos
Organismos Aquáticos/fisiologia , Evolução Biológica , Peixes/fisiologia , Água , Animais , Ecossistema , Modelos Teóricos , Filogenia , Filogeografia , IncertezaRESUMO
The Neotropical region represents one of the greatest biodiversity hot spots on earth. Despite its unparalleled biodiversity, regional comparative phylogeographic studies are still scarce, with most focusing on model clades (e.g. birds) and typically examining a handful of loci. Here, we apply a genome-wide comparative phylogeographic approach to test hypotheses of codiversification of freshwater fishes in the trans-Andean region. Using target capture methods, we examined exon data for over 1,000 loci combined with complete mitochondrial genomes to study the phylogeographic history of five primary fish species (>150 individuals) collected from eight major river basins in Northwestern South America and Lower Central America. To assess their patterns of genetic structure, we inferred genealogical concordance taking into account all major aspects of phylogeography (within loci, across multiple genes, across species and among biogeographic provinces). Based on phylogeographic concordance factors, we tested four a priori biogeographic hypotheses, finding support for three of them and uncovering a novel, unexpected pattern of codiversification. The four emerging inter-riverine patterns are as follows: (a) Tuira + Atrato, (b) Ranchería + Catatumbo, (c) Magdalena system and (d) Sinú + Atrato. These patterns are interpreted as shared responses to the complex uplifting and orogenic processes that modified or sundered watersheds, allowing codiversification and speciation over geological time. We also find evidence of cryptic speciation in one of the species examined and instances of mitochondrial introgression in others. These results help further our knowledge of the historical geographic factors shaping the outstanding biodiversity of the Neotropics.
Assuntos
Biodiversidade , DNA Mitocondrial/genética , Peixes/genética , Marcadores Genéticos , Animais , Núcleo Celular/genética , América Central , Água Doce , Genoma , Filogeografia , Rios , América do SulRESUMO
We present genome sequences of 63 species of catfish from the Ariidae family. Illumina sequencing was performed on tissue from wild-collected museum specimens. The reads were assembled using a de novo method followed by a finishing step. The raw and assembled data are publicly available via Genbank.
RESUMO
Childhood cancer patients experience emotional hardship associated with their life-threatening diagnoses. Interdisciplinary team members working in pediatric cancer care can help alleviate physical pain and psychological suffering of children by facilitating collaborative legacy-building activities with patients and families. The contents of this article aim to support legacy building as a medium for emotional healing prior to the end of life. The authors use a case review to contextualize legacy-building projects and provide a comprehensive overview of methods and considerations for these initiatives.
RESUMO
Manganese is a critical micronutrient for cells, serving as an enzyme cofactor and protecting against oxidative stress. Yet, manganese is toxic in excess and little is known about its distribution in cells. Bacteria control intracellular manganese levels by the transcription regulator MntR. When this work began, the only Escherichia coli K-12 gene known to respond to manganese via MntR repression was mntH, which encodes a manganese importer. We show that mntS (formerly the small RNA gene rybA) is repressed by manganese through MntR and encodes an unannotated 42-amino-acid protein. Overproduction of MntS causes manganese sensitivity, while a lack of MntS perturbs proper manganese-dependent repression of mntH. We also provide evidence that mntP (formerly yebN), which encodes a putative efflux pump, is positively regulated by MntR. Deletion of mntP leads to profound manganese sensitivity and to elevated intracellular manganese levels. This work thus defines two new proteins involved in manganese homeostasis and suggests mechanisms for their action.
Assuntos
Escherichia coli K12/genética , Proteínas de Escherichia coli/metabolismo , Regulação Bacteriana da Expressão Gênica , Manganês/metabolismo , Proteínas de Membrana Transportadoras/metabolismo , Proteínas Repressoras/metabolismo , Proteínas de Escherichia coli/genética , Deleção de Genes , Homeostase , Proteínas de Membrana Transportadoras/genética , Proteínas Repressoras/genéticaRESUMO
Particularly interesting cysteine histidine-rich (PINCH) protein functions as a shuttling protein in Schwann cells after peripheral nerve damage, during repair and remodeling, and in maintaining neuronal polarity. However, the presence of PINCH in the human CNS during disease has not been addressed. Because HIV-associated damage to cells of the CNS involves dysregulation of neuronal signaling and white matter damage, we hypothesized that PINCH may play a role in neuropathological processes during the course of HIV infection. To determine the expression of PINCH in the CNS, brain, and cerebrospinal fluid (CSF) obtained at autopsy from HIV patients with no CNS alterations, HIV encephalitic (HIVE) patients, and HIV-negative individuals with no CNS alterations were examined for PINCH immunoreactivity. Our results show that PINCH is expressed robustly in the brains and CSF of HIV patients, but is nearly undetectable in HIV-negative individuals. However, HIVE patients' CSF contained significantly less PINCH than HIV patients with no CNS alterations. PINCH immunolabeling was significantly more intense in the white matter than in the grey matter and was associated exclusively with neuronal cell bodies or processes, or with the extracellular matrix. Given the recently discovered importance of PINCH in maintaining neuronal fitness, our observations that PINCH is robustly expressed in the CNS of HIV patients suggests an important role for PINCH in HIV-associated neurodegenerative processes. Understanding mechanisms by which PINCH functions during HIV-associated CNS alterations will provide new insight into potential treatments to limit neurological alterations in HIV.
Assuntos
Complexo AIDS Demência/metabolismo , Biomarcadores/metabolismo , Encéfalo/metabolismo , Proteínas de Ligação a DNA/biossíntese , Infecções por HIV/metabolismo , Complexo AIDS Demência/líquido cefalorraquidiano , Complexo AIDS Demência/patologia , Proteínas Adaptadoras de Transdução de Sinal , Idoso , Western Blotting , Encéfalo/patologia , Encéfalo/virologia , Proteínas de Ligação a DNA/líquido cefalorraquidiano , Imunofluorescência , Infecções por HIV/líquido cefalorraquidiano , Infecções por HIV/patologia , Humanos , Imuno-Histoquímica , Proteínas com Domínio LIM , Proteínas de Membrana , Pessoa de Meia-Idade , Neurônios/metabolismo , Neurônios/patologiaRESUMO
We report four mitochondrial genomes of South American electric knifefishes, derived from target capture and Illumina sequencing (HiSeq 2500 PE100). Two trans-Andean species Eigenmannia humboldtii (mitochondrial consensus genome of 25 individuals) and Sternopygus aequilabiatus (mitochondrial consensus genome of 30 individuals) from Colombia and two cis-Andean species Eigenmannia limbata from Suriname and Sternopygus macrurus from Argentina. Regarding Eigenmannia humboldtii, Eigenmannia limbata, and Sternopygus macrurus mitochondrial genomes have 13 protein-coding genes, 1 D-loop, 2 ribosomal RNAs, 22 transfer RNAs, and are 13,394 bp, 10,921 bp, and 13,013 bp in length respectively, for Sternopygus aequilabiatus mitochondrial genomes have 13 protein-coding genes, 2 ribosomal RNAs, 22 transfer RNAs, and is 14,270 bp in length.
RESUMO
We report two mitochondrial genomes of headstanders, derived from target capture and Illumina sequencing (HiSeq 2500 PE100). One trans-Andean species Megaleporinus muyscorum (mitochondrial consensus genome of 25 individuals) from Colombia and one cis-Andean species M. obtusidens from Argentina. Regarding M. muyscorum, mitochondrial genome has 13 protein-coding genes, 1 D-loop, 2 ribosomal RNAs, 21 transfer RNAs, and is 14,434 bp in length, for M. obtusidens mitochondrial genome has 13 protein-coding genes, 2 ribosomal RNAs, 22 transfer RNAs, and is 15,546 bp in length.
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The transforming growth factor-ß (TGF-ß) and bone morphogenetic protein (BMP) family of cytokines critically regulates vascular morphogenesis and homeostasis. Impairment of TGF-ß or BMP signaling leads to heritable vascular disorders, including hereditary hemorrhagic telangiectasia (HHT). Drosha, a key enzyme for microRNA (miRNA) biogenesis, also regulates the TGF-ß and BMP pathway through interaction with Smads and their joint control of gene expression through miRNAs. We report that mice lacking Drosha in the vascular endothelium developed a vascular phenotype resembling HHT that included dilated and disorganized vasculature, arteriovenous fistulae, and hemorrhages. Exome sequencing of HHT patients who lacked known pathogenic mutations revealed an overrepresentation of rare nonsynonymous variants of DROSHA Two of these DROSHA variants (P100L and R279L) did not interact with Smads and were partially catalytically active. In zebrafish, expression of these mutants or morpholino-directed knockdown of Drosha resulted in angiogenesis defects and abnormal vascular permeability. Together, our studies point to an essential role of Drosha in vascular development and the maintenance of vascular integrity, and reveal a previously unappreciated link between Drosha dysfunction and HHT.
Assuntos
Regulação da Expressão Gênica , Mutação , Neovascularização Patológica , Ribonuclease III/genética , Ribonuclease III/fisiologia , Telangiectasia Hemorrágica Hereditária/genética , Animais , Estudos de Casos e Controles , Células Cultivadas , Criança , Estudos de Coortes , Endotélio Vascular/metabolismo , Endotélio Vascular/patologia , Feminino , Humanos , Masculino , Camundongos , Camundongos Knockout , Morfogênese , Linhagem , Fenótipo , Ribonuclease III/metabolismo , Transdução de Sinais , Telangiectasia Hemorrágica Hereditária/metabolismo , Telangiectasia Hemorrágica Hereditária/patologia , Peixe-Zebra/embriologia , Peixe-Zebra/fisiologiaRESUMO
Assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) is a useful method to map genome-wide chromatin accessibility and nucleosome positioning. Genome-wide sequencing is performed utilizing adapter sequences inserted by a prokaryotic transposase, Tn5, into the accessible regions of chromatin. Here we describe the use of ATAC-seq in the zebrafish embryo and thereby the applicability of this approach in whole vertebrate embryos.
Assuntos
Sequenciamento de Nucleotídeos em Larga Escala , Peixe-Zebra/genética , Animais , Cromatina/isolamento & purificação , Embrião não Mamífero , Genoma , Reação em Cadeia da Polimerase , Análise de Sequência de DNA , Transposases/químicaRESUMO
Eigenmannia is one of the more taxonomically complex genera within the Gymnotiformes. Here we adopt an integrative taxonomic approach, combining osteology, COI gene sequences, and geometric morphometrics to describe three new species belonging to the E. trilineata species group from Colombian trans-Andean region. These new species increase the number of species in the E. trilineata complex to 18 and the number of species in the genus to 25. The distribution range of the E. trilineata species group is expanded to include parts of northwestern South America and southern Central America.(AU)
Eigenmannia es uno de los géneros taxonómicamente más complejos dentro de los Gymnotiformes. En este artículo adoptamos un enfoque taxonómico integrador, que combina osteología, secuencias del gene COI y morfometría geométrica, para describir tres nuevas especies que pertenecen al grupo de especies de E. trilineata de la región transandina de Colombia. Estas nuevas especies aumentan el número de especies en el complejo E. trilineata a 18 y el número de especies en el género a 25. El rango de distribución del grupo de especies de E. trilineata se ha expandido al noroeste de Sudamérica y el sur de América Central.(AU)
Assuntos
Animais , Peixe Elétrico/classificação , Gimnotiformes/anatomia & histologia , Gimnotiformes/classificaçãoRESUMO
In Ethiopia, like many developing countries, autopsy is rare unless conducted in the medico-legal arena, making vital statistics that include pathological diagnoses sparse. To determine the most common factors contributing to death among individuals who died from natural or injury-related events in Ethiopia 200 consecutive autopsies were conducted in 2006 at the Forensic Medico-legal Pathology Department, Menelik II Hospital, Addis Ababa, Ethiopia. The results describe significant pathological observations, putative cause of death, age distribution, and gender ratios. Eighty-one percent of the cases were male, and the mean age was 38.9 (+/-15.5 years). Fifty-two percent of the individuals died from natural causes, including infections, and 48% died from injury-related events. In the natural deaths group, as determined by gross examination at autopsy pulmonary complications were the most commonly reported cause of death, with suspected tuberculosis accounting for 12%. Tuberculosis (21, 8%) and liver disease (14, 5%) were the most common histopathological findings in the natural and injury-related causes groups, respectively. In the injury-related group, automobile accident was the most common cause of accidental death (80%), and homicide by beating was the most common cause of death in the intentional injury group (31%). These data provide valuable unbiased analyses of causes of death among individuals in Addis Ababa, Ethiopia.