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Objective: To assess the repeatability and suitability for multicentre studies of MScanFit motor unit number estimation (MUNE), which involves modelling compound muscle action potential (CMAP) scans. Methods: Fifteen groups in 9 countries recorded CMAP scans twice, 1–2 weeks apart in healthy subjects from abductor pollicis brevis (APB), abductor digiti minimi (ADM) and tibialis anterior (TA) muscles. The original MScanFit program (MScanFit-1) was compared with a revised version (MScanFit-2), designed to accommodate different muscles and recording conditions by setting the minimal motor unit size as a function of maximum CMAP. Results: Complete sets of 6 recordings were obtained from 148 subjects. CMAP amplitudes differed significantly between centres for all muscles, and the same was true for MScanFit-1 MUNE. With MScanFit-2, MUNE differed less between centres but remained significantly different for APB. Coefficients of variation between repeats were 18.0% for ADM, 16.8% for APB, and 12.1% for TA. Conclusions: It is recommended for multicentre studies to use MScanFit-2 for analysis. TA provided the least variable MUNE values between subjects and the most repeatable within subjects. Significance: MScanFit was primarily devised to model the discontinuities in CMAP scans in patients and is less suitable for healthy subjects with smooth scans.

Animal modelling of arthritis is often associated with pain and suffering. Severity may be reduced with the use of analgesia which is, however, often withheld due to concerns of introducing a confounding variable. It is therefore important to design and validate pain relief protocols that reduce pain without compromising the scientific objectives. The present study evaluated the effect of buprenorphine analgesia in the immediate post-induction period of an adjuvant-induced monoarthritic rat model. The aim of this study was to extend previous work on refinement of the model by alleviating unnecessary pain

Item does not contain fulltext, Siglecs are a family of sialic acid-binding receptors expressed by cells of the immune system and a few other cell types capable of modulating immune cell functions upon recognition of sialoglycan ligands. While human Siglecs primarily bind to sialic acid residues on diverse types of glycoproteins and glycolipids that constitute the sialome, their fine binding specificities for elaborated complex glycan structures and the contribution of the glycoconjugate and protein context for recognition of sialoglycans at the cell surface are not fully elucidated. Here, we generated a library of isogenic human HEK293 cells with combinatorial loss/gain of individual sialyltransferase genes and the introduction of sulfotransferases for display of the human sialome and to dissect Siglec interactions in the natural context of glycoconjugates at the cell surface. We found that Siglec-4/7/15 all have distinct binding preferences for sialylated GalNAc-type O-glycans but exhibit selectivity for patterns of O-glycans as presented on distinct protein sequences. We discovered that the sulfotransferase CHST1 drives sialoglycan binding of Siglec-3/8/7/15 and that sulfation can impact the preferences for binding to O-glycan patterns. In particular, the branched Neu5Acα2-3(6-O-sulfo)Galβ1-4GlcNAc (6'-Su-SLacNAc) epitope was discovered as the binding epitope for Siglec-3 (CD33) implicated in late-onset Alzheimer's disease. The cell-based display of the human sialome provides a versatile discovery platform that enables dissection of the genetic and biosynthetic basis for the Siglec glycan interactome and other sialic acid-binding proteins.

In mouse (Mus musculus) models of diabetic nephropathy (DN), one of the most important read-outs is the 24-h urinary albumin excretion (UAE). The 24-h urine collection is usually performed by single housing mice in metabolic cages on wire mesh without enrichment. This is known to be stressful for the mice. Therefore, it was investigated if shorter urine collections would be sufficient to get reliable assessments of albuminuria. Twenty-one diabetic (C57BLKS-Leprdb/db) and ten non-diabetic mice (C57BLKS-Leprdb/+) were placed in metabolic cages at 15 and 20 weeks of age (WoA) for 24 h. Urine samples were taken at 4, 6, 18 and 24 h and albumin and creatinine concentration were measured. Four- and 6-h UAE was found to correlate significantly with 24-h UAE. Furthermore, a significant correlation was found between 24-h UAE and albumin:creatinine ratio (ACR) in the 4-h sample. However, the strength of the correlation between ACR and 24-h UAE was weaker than between the 4- and 24-h UAE. This suggests that normalising to creatinine may not provide additional value to the 4-h urine collection. In conclusion, the strong correlation between 4- and 6-h UAE and 24-h UAE indicates that the collection period can be considerably reduced. This refinement could reduce stress and increase welfare of the db/db model and potentially be applied to other DN models.