c-Maf-positive spinal cord neurons are critical elements of a dorsal horn circuit for mechanical hypersensitivity in neuropathy

Corticospinal tract (CST) neurons innervate the deep spinal dorsal horn to sustain chronic neuropathic pain. The majority of neurons targeted by the CST are interneurons expressing the transcription factor c-Maf. Here, we used intersectional genetics to decipher the function of these neurons in dorsal horn sensory circuits. We find that excitatory c-Maf (c-Maf(EX)) neurons receive sensory input mainly from myelinated fibers and target deep dorsal horn parabrachial projection neurons and superficial dorsal horn neurons, thereby connecting non-nociceptive input to nociceptive output structures. Silencing c-Maf(EX) neurons has little effect in healthy mice but alleviates mechanical hypersensitivity in neuropathic mice. c-Maf(EX) neurons also receive input from inhibitory c-Maf and parvalbumin neurons, and compromising inhibition by these neurons caused mechanical hypersensitivity and spontaneous aversive behaviors reminiscent of c-Maf(EX) neuron activation. Our study identifies c-Maf(EX) neurons as normally silent second-order nociceptors that become engaged in pathological pain signaling upon loss of inhibitory control

The Genomes of the Fungal Plant Pathogens Cladosporium fulvum and Dothistroma septosporum Reveal Adaptation to Different Hosts and Lifestyles But Also Signatures of Common Ancestry

We sequenced and compared the genomes of the Dothideomycete fungal plant pathogens Cladosporium fulvum (Cfu) (syn. Passalora fulva) and Dothistroma septosporum (Dse) that are closely related phylogenetically, but have different lifestyles and hosts. Although both fungi grow extracellularly in close contact with host mesophyll cells, Cfu is a biotroph infecting tomato, while Dse is a hemibiotroph infecting pine. The genomes of these fungi have a similar set of genes (70% of gene content in both genomes are homologs), but differ significantly in size (Cfu >61.1-Mb; Dse 31.2-Mb), which is mainly due to the difference in repeat content (47.2% in Cfu versus 3.2% in Dse). Recent adaptation to different lifestyles and hosts is suggested by diverged sets of genes. Cfu contains an a-tomatinase gene that we predict might be required for detoxification of tomatine, while this gene is absent in Dse. Many genes encoding secreted proteins are unique to each species and the repeat-rich areas in Cfu are enriched for these species-specific genes. In contrast, conserved genes suggest common host ancestry. Homologs of Cfu effector genes, including Ecp2 and Avr4, are present in Dse and induce a Cf-Ecp2- and Cf-4-mediated hypersensitive response, respectively. Strikingly, genes involved in production of the toxin dothistromin, a likely virulence factor for Dse, are conserved in Cfu, but their expression differs markedly with essentially no expression by Cfu in planta. Likewise, Cfu has a carbohydrate-degrading enzyme catalog that is more similar to that of necrotrophs or hemibiotrophs and a larger pectinolytic gene arsenal than Dse, but many of these genes are not expressed in planta or are pseudogenized. Overall, comparison of their genomes suggests that these closely related plant pathogens had a common ancestral host but since adapted to different hosts and lifestyles by a combination of differentiated gene content, pseudogenization, and gene regulatio

The Genomes of the Fungal Plant Pathogens Cladosporium fulvum and Dothistroma septosporum Reveal Adaptation to Different Hosts and Lifestyles But Also Signatures of Common Ancestry

We sequenced and compared the genomes of the Dothideomycete fungal plant pathogens Cladosporium fulvum (Cfu) (syn. Passalora fulva) and Dothistroma septosporum (Dse) that are closely related phylogenetically, but have different lifestyles and hosts. Although both fungi grow extracellularly in close contact with host mesophyll cells, Cfu is a biotroph infecting tomato, while Dse is a hemibiotroph infecting pine. The genomes of these fungi have a similar set of genes (70% of gene content in both genomes are homologs), but differ significantly in size (Cfu >61.1-Mb; Dse 31.2-Mb), which is mainly due to the difference in repeat content (47.2% in Cfu versus 3.2% in Dse). Recent adaptation to different lifestyles and hosts is suggested by diverged sets of genes. Cfu contains an alpha-tomatinase gene that we predict might be required for detoxification of tomatine, while this gene is absent in Dse. Many genes encoding secreted proteins are unique to each species and the repeat-rich areas in Cfu are enriched for these species-specific genes. In contrast, conserved genes suggest common host ancestry. Homologs of Cfu effector genes, including Ecp2 and Avr4, are present in Dse and induce a Cf-Ecp2- and Cf-4-mediated hypersensitive response, respectively. Strikingly, genes involved in production of the toxin dothistromin, a likely virulence factor for Dse, are conserved in Cfu, but their expression differs markedly with essentially no expression by Cfu in planta. Likewise, Cfu has a carbohydrate-degrading enzyme catalog that is more similar to that of necrotrophs or hemibiotrophs and a larger pectinolytic gene arsenal than Dse, but many of these genes are not expressed in planta or are pseudogenized. Overall, comparison of their genomes suggests that these closely related plant pathogens had a common ancestral host but since adapted to different hosts and lifestyles by a combination of differentiated gene content, pseudogenization, and gene regulation

Preserving accuracy in GenBank

GenBank, the public repository for nucleotide and protein sequences, is a critical resource for molecular biology, evolutionary biology, and ecology. While some attention has been drawn to sequence errors, common annotation errors also reduce the value of this database. In fact, for organisms such as fungi, which are notoriously difficult to identify, up to 20% of DNA sequence records may have erroneous lineage designations in GenBank. Gene function annotation in protein sequence databases is similarly error-prone. Because identity and function of new sequences are often determined by bioinformatic analyses, both types of errors are propagated into new accessions, leading to long-term degradation of the quality of the database. Currently, primary sequence data are annotated by the authors of those data, and can only be reannotated by the same authors. This is inefficient and unsustainable over the long term as authors eventually leave the field. Although it is possible to link third-party databases to GenBank records, this is a short-term solution that has little guarantee of permanence. Similarly, the current third-party annotation option in GenBank (TPA) complicates rather than solves the problem by creating an identical record with a new annotation, while leaving the original record unflagged and unlinked to the new record. Since the origin of public zoological and botanical specimen collections, an open system of cumulative annotation has evolved, whereby the original name is retained, but additional opinion is directly appended and used for filing and retrieval. This was needed as new specimens and analyses allowed for reevaluation of older specimens and the original depositors became unavailable. The time has come for the public sequence database to incorporate a community-curated, cumulative annotation process that allows third parties to improve the annotations of sequences when warranted by published peer-reviewed analyses.Fil: Bidartondo, Martin I.. Imperial College London; Reino Unido. Royal Botanic Gardens; Reino UnidoFil: Bruns, Thomas D.. University of California at Berkeley; Estados UnidosFil: Blackwell, Meredith. Louisiana State University; Estados UnidosFil: Edwards, Ivan. University of Michigan; Estados UnidosFil: Taylor, Andy F. S.. Swedish University of Agricultural Sciences; SueciaFil: Bianchinotti, Maria Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Centro de Recursos Naturales Renovables de la Zona Semiárida. Universidad Nacional del Sur. Centro de Recursos Naturales Renovables de la Zona Semiárida; Argentina. Universidad Nacional del Sur; ArgentinaFil: Padamsee, Mahajabeen. University of Minnesota; Estados UnidosFil: Callac, Philippe. Institut National de la Recherche Agronomique; FranciaFil: Lima, Nelson. Universidade do Minho; PortugalFil: White, Merlin M.. Boise State University; Estados UnidosFil: Barreau Daly, Camila. Centre National de la Recherche Scientifique; Francia. Institut National de la Recherche Agronomique; FranciaFil: Juncai, M. A.. Chinese Academy of Sciences; República de ChinaFil: Buyck, Bart. Museum National d'Histoire Naturelle; FranciaFil: Rabeler, Richard K.. University of Michigan; Estados UnidosFil: Liles, Mark R.. Auburn University; Estados UnidosFil: Estes, Dwayne. Austin Peay State University; Estados UnidosFil: Carter, Richard. Valdosta State University; Estados UnidosFil: Herr Jr., J. M.. University of South Carolina; Estados UnidosFil: Chandler, Gregory. University of North Carolina; Estados UnidosFil: Kerekes, Jennifer. University of California at Berkeley; Estados UnidosFil: Cruse Sanders, Jennifer. Salem College Herbarium; Estados UnidosFil: Galán Marquez, R.. Universidad de Alcalá; EspañaFil: Horak, Egon. Zurich Herbarium; SuizaFil: Fitzsimons, Michael. University of Chicago; Estados UnidosFil: Döering, Heidi. Royal Botanic Gardens; Reino UnidoFil: Yao, Su. China Center of Industrial Culture Collection; ChinaFil: Hynson, Nicole. University of California at Berkeley; Estados UnidosFil: Ryberg, Martin. University Goteborg; SueciaFil: Arnold, A. E.. University of Arizona; Estados UnidosFil: Hughes, Karen. University of Tennessee; Estados Unido