The manuscript describes the “digital transcriptome atlas” of the developing mouse embryo, a powerful resource to determine co-expression of genes, to identify cell populations and lineages and to identify functional associations between genes relevant to development and disease.

Alzheimer's disease is a devastating neurodegenerative disease eventually leading to dementia. An effective treatment does not yet exist. Here we show that oral application of the compound anle138b restores hippocampal synaptic and transcriptional plasticity as well as spatial memory in a mouse model for Alzheimer's disease, when given orally before or after the onset of pathology. At the mechanistic level, we provide evidence that anle138b blocks the activity of conducting Aβ pores without changing the membrane embedded Aβ‐oligomer structure. In conclusion, our data suggest that anle138b is a novel and promising compound to treat AD‐related pathology that should be investigated further.

BackgroundIn situ hybridization (ISH) is a powerful method for visualizing gene expression patterns at the organismal level with cellular resolution. When automated, it is capable of determining the expression of a large number of genes.ResultsThe expression patterns of 662 genes that encode enzymes were determined by ISH in the mid-gestation mouse embryo, a stage that models the complexity of the adult organism. Forty-five percent of transcripts encoding metabolic enzymes (n = 297) showed a regional expression pattern. A similar percentage was found for the 190 kinases that were also analyzed. Many mRNAs encoding glycolytic and TCA cycle enzymes exhibited a characteristic expression pattern. The annotated expression patterns were deposited on the Genepaint database and are retrievable by user-defined queries including gene name and sites of expression.ConclusionThe 662 expression patterns discussed here comprised gene products with activities associated with catalysis. Preliminary analysis of these data revealed that a significant number of genes encoding housekeeping functions such as biosynthesis and catabolism were expressed regionally, so they could be used as tissue-specific gene markers. We found no difference in tissue specificity between mRNAs encoding housekeeping functions and those encoding components of signal transduction pathways, as exemplified by the kinases.

BackgroundThe disease modifying antirheumatic drugs (DMARD) impair the immune response of patients with immune-mediated inflammatory diseases (IMID).ObjectivesTo analyze the seroprevalence of SARS-CoV-2 in patients with IMID treated with biological disease modifying antirheumatic drugs (bDMARD) or targeted synthetic (tsDMARD).MethodsAn ambispective cross-sectional study was performed in patients with IMID treated with bDMARD or tsDMARD. Seroprevalence was compared by measuring IgG against SARS-CoV-2 between October 2020 and May 2021.ResultsA total of 550 patients with IMID were studied, all of them on bDMARD or tsDMARD therapy, none of them vaccinated at that time against SARS-CoV-2. Patients receiving anti-TNFα therapy had a higher seroprevalence than other biologic and synthetic targeted therapies (OR= 1.792; 95% CI 1.088-2.951; p= 0.021).Patients with bDMARD or tsDMARD treated concomitantly with some type of conventional synthetic DMARD (csDMARD) presented a lower seroprevalence compared to patients treated in monotherapy, 10.7 vs. 19.9% (p= 0.003). When analyzing the treatments with the different csDMARD separately (methotrexate, leflunomide, sulfasalazine, azathioprine, hydroxychloroquine and the others), methotrexate was determined to influence in a lower seroprevalence, compared to those who did not receive any csDMARD, 9.8 vs 19.9% (OR= 0.439, 95% CI 0.232-0.828; p= 0.011). When evaluating the influence of methotrexate on seroprevalence among the different groups of bDMARD or tsDMARD, a lower seroprevalence was demonstrated in the group of patients receiving anti-TNFα and methotrexate in combination, versus patients on this bDMARD in monotherapy, 10.1 vs 24.1% (OR= 0.355, 95% CI 0.165 - 0.764; p=0.006). No significant differences were identified with the other bDMARD.Regarding the patients’ IMIDs, no differences in seroprevalence were observed when compared by disease groups with each other.ConclusionSeroprevalence in the group of patients with IMID is influenced according to the therapy received, being higher in patients receiving anti-TNFα monotherapy, but significantly lower if concomitant to this drug they receive methotrexate. These differences are not seen with the other b/tsDMARD and csDMARD.References[1]Muñoz-Fernández S, Cebrian L, Thuissard IJ, Martina Steiner M, García-Yubero C, Esteban AV et al. Incidence of COVID-19 in 902 Patients With Immunomediated Inflammatory Diseases Treated With Biologics and Targeted Synthetic Disease-Modifying Antirheumatic Drugs-Findings From the BIOCOVID Study. J Clin Reumatol. 2022 Mar 1; 28(2): e348-e352.[2]Favalli EG, Gobbini A, Bombaci M, Maioli G, et al. The Impact of Anti-rheumatic Drugs on the Seroprevalence of Anti-SARS-CoV-2 Antibodies in a Cohort of Patients With Inflammatory Arthritis: The MAINSTREAM Study. Front Med (Lausana), March 2022.[3]Simon D, Tascilar K, Kleyer A, Fagni F, Krönke G, Médeet C et al. Impact of cytokine inhibitor therapy on the prevalence, seroconversion rate and longevity of the humoral immune response against SARSCoV- 2 in an unvaccinated cohort. Arthritis & Rheumatology Vol. 74, No. 5, May 2022, pp 783–790AcknowledgementsOlga Reillo from Hospital Universitario Infanta Sofía (Librarian - Documentalist)Disclosure of InterestsNone Declared.