The Rat Genome Database curation tool suite: a set of optimized software tools enabling efficient acquisition, organization, and presentation of biological data

The Rat Genome Database (RGD) is the premier repository of rat genomic and genetic data and currently houses over 40 000 rat gene records as well as human and mouse orthologs, 1771 rat and 1911 human quantitative trait loci (QTLs) and 2209 rat strains. Biological information curated for these data objects includes disease associations, phenotypes, pathways, molecular functions, biological processes and cellular components. A suite of tools has been developed to aid curators in acquiring and validating data objects, assigning nomenclature, attaching biological information to objects and making connections among data types. The software used to assign nomenclature, to create and edit objects and to make annotations to the data objects has been specifically designed to make the curation process as fast and efficient as possible. The user interfaces have been adapted to the work routines of the curators, creating a suite of tools that is intuitive and powerful

The Gene Ontology knowledgebase in 2023

The Gene Ontology (GO) knowledgebase (http://geneontology.org) is a comprehensive resource concerning the functions of genes and gene products (proteins and noncoding RNAs). GO annotations cover genes from organisms across the tree of life as well as viruses, though most gene function knowledge currently derives from experiments carried out in a relatively small number of model organisms. Here, we provide an updated overview of the GO knowledgebase, as well as the efforts of the broad, international consortium of scientists that develops, maintains, and updates the GO knowledgebase. The GO knowledgebase consists of three components: (1) the GO-a computational knowledge structure describing the functional characteristics of genes; (2) GO annotations-evidence-supported statements asserting that a specific gene product has a particular functional characteristic; and (3) GO Causal Activity Models (GO-CAMs)-mechanistic models of molecular "pathways" (GO biological processes) created by linking multiple GO annotations using defined relations. Each of these components is continually expanded, revised, and updated in response to newly published discoveries and receives extensive QA checks, reviews, and user feedback. For each of these components, we provide a description of the current contents, recent developments to keep the knowledgebase up to date with new discoveries, and guidance on how users can best make use of the data that we provide. We conclude with future directions for the project

The Gene Ontology knowledgebase in 2023

The Gene Ontology (GO) knowledgebase (http://geneontology.org) is a comprehensive resource concerning the functions of genes and gene products (proteins and noncoding RNAs). GO annotations cover genes from organisms across the tree of life as well as viruses, though most gene function knowledge currently derives from experiments carried out in a relatively small number of model organisms. Here, we provide an updated overview of the GO knowledgebase, as well as the efforts of the broad, international consortium of scientists that develops, maintains, and updates the GO knowledgebase. The GO knowledgebase consists of three components: (1) the GO-a computational knowledge structure describing the functional characteristics of genes; (2) GO annotations-evidence-supported statements asserting that a specific gene product has a particular functional characteristic; and (3) GO Causal Activity Models (GO-CAMs)-mechanistic models of molecular "pathways" (GO biological processes) created by linking multiple GO annotations using defined relations. Each of these components is continually expanded, revised, and updated in response to newly published discoveries and receives extensive QA checks, reviews, and user feedback. For each of these components, we provide a description of the current contents, recent developments to keep the knowledgebase up to date with new discoveries, and guidance on how users can best make use of the data that we provide. We conclude with future directions for the project

Fusarium-Arten auf den Samen von Pinus taeda und Pinus elliottii Engelm. in Argentinien

The quality of planted seeds has a critical influence on the ability of crops to become established and to realize their full potential of yield. Loblolly pine (Pinus taeda L.) and slash pine (Pinus elliottii Engelm.) are forest trees species, both native to the southern United States of America, mostly planted in Northeastern Argentina for site restoration and forest management due to their fast growth on diverse sites. Numerous diseases attack these two pine species in forest nurseries: damping-off and root rot. Many Fusarium species present on seeds were found to be associated with damping-off and root diseases in loblolly and slash pine seedlings. Seed of Pinus elliottii and P. taeda were collected from Northeastern Argentina and analyzed for seed-borne Fusarium. Seed treatments as running water for 24 and 48 h were tested for effectiveness in changing Fusarium populations on seeds. Seven different species of Fusarium were isolated from the seed lots assayed: F. solani, F. verticillioides (= F. moniliforme), F. oxysporum, F. proliferatum, F. incarnatum (= F. pallidoroseum = F. semitectum), F. equiseti and F. acuminatum. Fusarium populations detected on seeds changed after running water treatments for 24 and 48 h but this changes varied among seedlots. This is the first report on Fusarium species associated with P. elliottii and P. taeda seeds in Argentina.Die Qualität ausgesäter Samen hat einen entscheidenden Einfluss auf die Fähigkeit der Pflanzen, sich zu etablieren und ihr volles Ertragspotential zu realisieren. Sumpfkiefer (Pinus taeda) und Karibische Kiefer (Pinus elliottii Engelm.) sind Arten von Forstbäumen, die beide im Süden der USA heimisch sind. Wegen ihres schnellen Wachstums werden sie im Nordosten Argentiniens zur Aufforstung und in der Forstwirtschaft angepflanzt. Zahlreiche Krankheiten befallen diese Kiefern in der Baumschule, z. B. Umfallkrankheit und Wurzelfäule. Für viele auf den Samen vorhandene Fusarium-Arten wurde eine Assoziation mit der Umfallkrankheit und den Wurzelkrankheiten an den Jungpflanzen der Sumpf- und Karibischen Kiefer festgestellt. An Samen von Pinus elliottii und P. taeda aus dem Nordwesten Argentiniens erfolgte eine Untersuchung auf samenbürtige Fusarien. Dabei sollte auch festgestellt werden, ob eine 24- bzw. 48-stündige Behandlung mit fließendem Wasser zu Veränderungen der Populationen von Fusarium-Arten auf den Samen führte. Sieben verschiedene Fusarium-Arten konnten von den untersuchten Samenproben isoliert werden: F. solani, F. verticillioides (= F. moniliforme), F. oxysporum, F. proliferatum, F. incarnatum (= F. pallidoroseum = F. semitectum), F. equiseti und F. acuminatum. Die auf den Samen gefundenen Fusarium-Populationen veränderten sich nach 24- bzw. 48-stündiger Behandlung mit fließendem Wasser, aber zwischen den Samenproben traten Unterschiede auf. Hiermit wird zum ersten Mal über das Vorkommen von Fusarium-Arten auf Samen von P. elliottii und P. taeda in Argentinien berichtet.Facultad de Ciencias Agrarias y Forestale

Targeting PIM1-Mediated Metabolism in Myeloid Suppressor Cells to Treat Cancer.

There is a strong correlation between myeloid-derived suppressor cells (MDSC) and resistance to immune checkpoint blockade (ICB), but the detailed mechanisms underlying this correlation are largely unknown. Using single-cell RNA sequencing analysis in a bilateral tumor model, we found that immunosuppressive myeloid cells with characteristics of fatty acid oxidative metabolism dominate the immune-cell landscape in ICB-resistant subjects. In addition, we uncovered a previously underappreciated role of a serine/threonine kinase, PIM1, in regulating lipid oxidative metabolism via PPARγ-mediated activities. Enforced PPARγ expression sufficiently rescued metabolic and functional defects of Pim1 <sup>-/-</sup> MDSCs. Consistent with this, pharmacologic inhibition of PIM kinase by AZD1208 treatment significantly disrupted the myeloid cell-mediated immunosuppressive microenvironment and unleashed CD8 <sup>+</sup> T-cell-mediated antitumor immunity, which enhanced PD-L1 blockade in preclinical cancer models. PIM kinase inhibition also sensitized nonresponders to PD-L1 blockade by selectively targeting suppressive myeloid cells. Overall, we have identified PIM1 as a metabolic modulator in MDSCs that is associated with ICB resistance and can be therapeutically targeted to overcome ICB resistance