Structure of the imine reductase from Ajellomyces dermatitidis in three crystal forms.

The NADPH-dependent imine reductase from Ajellomyces dermatitidis (AdRedAm) catalyzes the reductive amination of certain ketones with amine donors supplied in an equimolar ratio. The structure of AdRedAm has been determined in three forms. The first form, which belongs to space group P3121 and was refined to 2.01 Šresolution, features two molecules (one dimer) in the asymmetric unit in complex with the redox-inactive cofactor NADPH4. The second form, which belongs to space group C21 and was refined to 1.73 Šresolution, has nine molecules (four and a half dimers) in the asymmetric unit, each complexed with NADP+. The third form, which belongs to space group P3121 and was refined to 1.52 Šresolution, has one molecule (one half-dimer) in the asymmetric unit. This structure was again complexed with NADP+ and also with the substrate 2,2-difluoroacetophenone. The different data sets permit the analysis of AdRedAm in different conformational states and also reveal the molecular basis of stereoselectivity in the transformation of fluorinated acetophenone substrates by the enzyme.

The complete chloroplast genome of the threatened Napa False Indigo Amorpha californica var. napensis Jeps. 1925 (Fabaceae) from Northern California, USA.

Amorpha californica var. napensis Jeps. 1925, the Napa false indigo, is a threatened shrub endemic to northern California. Here the complete chloroplast genome of topotype material of var. napensis was assembled and characterized to contribute to the bioinformatics, systematics, and conservation of this variety. The chloroplast genome (GenBank accession OK274088) is 158,294 base pairs (bp) in length, encodes 130 genes including 85 protein-coding, 37 tRNA, 8 rRNA, and shows a high-level of gene synteny to other Papilionoideae. Phylogenetic analysis fully resolved var. napensis in a clade with A. fruticosa L. and A. roemeriana Scheele, sister to the Dalbergieae. The newly sequenced chloroplast genome shows that the genetic differences between var. napensis and Amorpha californica Nutt. var. californica are greater than the variation observed between var. napensis and many other Amorpha spp. sequences deposited in GenBank. These data suggest that var. napensis should be elevated to full species rank.

Pancitopenia inducida por bajas dosis de metotrexato / Low dose methotrexate induced pancytopenia

Resumen El metotrexato es un agente que antagoniza el metabolismo del ácido fólico reduciendo los niveles de tetrahidrofolato en las células, inhibiendo su replicación y la síntesis de proteínas. Actualmente, se emplea en el tratamiento de diversas enfermedades malignas o inflamatorias. Tiene descritos numerosos efectos tóxicos, tanto a dosis altas en esquemas quimioterapéuticos como bajas de larga duración para inmunosupresión, los cuales incluyen compromiso hepático, neurológico, cutáneo, gastrointestinal y, con menor frecuencia, afección pulmonar y hematológica. Se reporta el caso de un paciente de edad avanzada quien se encontraba en tratamiento con metotrexato por más de cuatro años y acudió al servicio de urgencias con toxicidad severa resaltándose pancitopenia y concomitantemente choque séptico, quien, a pesar del manejo establecido, presentó evolución clínica desfavorable. Se resalta la importancia de tener en cuenta esta toxicidad dado su subregistro en Colombia y la repercusión que puede tener en un paciente incluso al establecer el manejo adecuado.

Abstract Methotrexate is an agent that antagonizes the metabolism of folic acid by reducing the levels of tetrahydrofolate in cells, which inhibits cellular replication and protein synthesis. It is currently used in the treatment of various malignancies and some inflammatory diseases such as rheumatoid arthritis. It has described numerous toxic effects both at high doses in chemotherapeutic schemes and long-term low doses for immunosuppression; these include renal, hepatic, neurological, cutaneous, gastrointestinal, and much less frequently pulmonary and hematological involvement. This article reports the case of an elderly patient who was in treatment with methotrexate for more than four years and went to the emergency department with severe toxicity highlighting pancytopenia and concomitant septic shock, whom despite the established management presented a poor response. The importance of taking into account this toxicity is highlighted given the underreporting in Colombia and the impact it can have on a patient even when establishing the appropriate management.