Effectiveness of methotrexate and leflunomide as corticoid-sparing drugs in patients with polymyalgia rheumatica.

Objectives: The need for glucocorticoid-sparing drugs (GCSD) remains an important issue and is an unmet need in the treatment of polymyalgia rheumatica (PMR). We therefore aimed to assess the effectiveness and safety of methotrexate (MTX) and of leflunomide (LEF) in daily clinical practice in PMR patients from Argentina.

Methods: A multicentre and observational study (medical records review) of PMR patients seen between 2007 and 2023, who had at least three months of follow-up after starting a GCSD, either MTX or LEF, was performed.

Sociodemographic and clinical factors associated with poor COVID-19 outcomes in patients with rheumatic diseases: data from the SAR-COVID Registry.

Background/objective: This study aims to describe the course and to identify poor prognostic factors of SARS-CoV-2 infection in patients with rheumatic diseases.

Methods: Patients ≥ 18 years of age, with a rheumatic disease, who had confirmed SARS-CoV-2 infection were consecutively included by major rheumatology centers from Argentina, in the national, observational SAR-COVID registry between August 13, 2020 and July 31, 2021. Hospitalization, oxygen requirement, and death were considered poor COVID-19 outcomes.

Comparing demographics, clinical presentation, treatments and outcome between systemic lupus erythematosus patients treated in a public and private health system in Santa Fe, Argentina.

The study includes 159 SLE patients seen between 1987 and 2011, of whom 116 were treated in the public health system and 43 in private practice. In the comparison between both groups, it was shown that patients in the public health system were younger at first consultation and at the onset of SLE, and that the mean duration of their disease prior to nephropathy was statistically significantly shorter. They also presented with more SLE activity (measured by Systemic Lupus Erythematosus Activity Index) such as fever, lower levels of C4, and elevated erythrocyte sedimentation rate.

Association of the yeast RNA-binding protein She2p with the tubular endoplasmic reticulum depends on membrane curvature.

Localization of mRNAs contributes to the generation and maintenance of cellular asymmetry in a wide range of organisms. In Saccharomyces cerevisiae, the so-called locasome complex with its core components Myo4p, She2p, and She3p localizes more than 30 mRNAs to the yeast bud tip. A significant fraction of these mRNAs encodes membrane or secreted proteins.

A cytoplasmic complex mediates specific mRNA recognition and localization in yeast.

In eukaryotes, hundreds of mRNAs are localized by specialized transport complexes. For localization, transcripts are recognized by RNA-binding proteins and incorporated into motor-containing messenger ribonucleoprotein particles (mRNPs). To date, the molecular assembly of such mRNPs is not well understood and most details on cargo specificity remain unresolved.

Nuclear transit of the RNA-binding protein She2 is required for translational control of localized ASH1 mRNA.

Cytoplasmic localization and localized translation of messenger RNAs contribute to asymmetrical protein distribution. Recognition of localized mRNAs by RNA-binding proteins can occur in the cytoplasm or, alternatively, co- or post-transcriptionally in the nucleus. In budding yeast, mRNAs destined for localization are bound by the She2 protein before their nuclear export.

Simultaneous transport of different localized mRNA species revealed by live-cell imaging.

Intracellular mRNA localization is a common mechanism to achieve asymmetric distributions of proteins. Previous studies have revealed that in a number of cell types, different mRNA species are localized by the same transport machinery. However, it has been unclear if these individual mRNA species are specifically sorted into separate or common ribonucleoprotein (RNP) particles before or during transport.

Membrane association is a determinant for substrate recognition by PMT4 protein O-mannosyltransferases.

Protein O-mannosylation represents an evolutionarily conserved, essential posttranslational modification with immense impact on a variety of cellular processes. In humans, O-mannosylation defects result in Walker-Warburg syndrome, a severe recessive congenital muscular dystrophy associated with defects in neuronal migration that produce complex brain and eye abnormalities. In mouse and yeasts, loss of O-mannosylation causes lethality.

Why cells move messages: the biological functions of mRNA localization.

RNA localization is a widespread mechanism that allows cells to spatially control protein function by determining their sites of synthesis. In embryos, localized mRNAs are involved in morphogen gradient formation or the asymmetric distribution of cell fate determinants. In somatic cell types, mRNA localization contributes to local assembly of protein complexes or facilitates protein targeting to organelles.

Coordination of endoplasmic reticulum and mRNA localization to the yeast bud.

Localization of messenger RNAs and local protein synthesis contribute to asymmetric protein distribution not only of cytoplasmic but also of membrane or secreted proteins. Since synthesis of the latter protein classes occurs at the rough endoplasmic reticulum (ER), mRNA localization and distribution of ER should be coordinated. However, this coordination is not yet understood.