Spatial transcriptomics reveal markers of histopathological changes in Duchenne muscular dystrophy mouse models.

Duchenne muscular dystrophy is caused by mutations in the DMD gene, leading to lack of dystrophin. Chronic muscle damage eventually leads to histological alterations in skeletal muscles. The identification of genes and cell types driving tissue remodeling is a key step to developing effective therapies. Here we use spatial transcriptomics in two Duchenne muscular dystrophy mouse models differing in disease severity to identify gene expression signatures underlying skeletal muscle pathology and to directly link gene expression to muscle histology. We perform deconvolution analysis to identify cell types contributing to histological alterations. We show increased expression of specific genes in areas of muscle regeneration (Myl4, Sparc, Hspg2), fibrosis (Vim, Fn1, Thbs4) and calcification (Bgn, Ctsk, Spp1). These findings are confirmed by smFISH. Finally, we use differentiation dynamic analysis in the D2-mdx muscle to identify muscle fibers in the present state that are predicted to become affected in the future state.

Targeting myelin lipid metabolism as a potential therapeutic strategy in a model of CMT1A neuropathy.

In patients with Charcot-Marie-Tooth disease 1A (CMT1A), peripheral nerves display aberrant myelination during postnatal development, followed by slowly progressive demyelination and axonal loss during adult life. Here, we show that myelinating Schwann cells in a rat model of CMT1A exhibit a developmental defect that includes reduced transcription of genes required for myelin lipid biosynthesis. Consequently, lipid incorporation into myelin is reduced, leading to an overall distorted stoichiometry of myelin proteins and lipids with ultrastructural changes of the myelin sheath. Substitution of phosphatidylcholine and phosphatidylethanolamine in the diet is sufficient to overcome the myelination deficit of affected Schwann cells in vivo. This treatment rescues the number of myelinated axons in the peripheral nerves of the CMT rats and leads to a marked amelioration of neuropathic symptoms. We propose that lipid supplementation is an easily translatable potential therapeutic approach in CMT1A and possibly other dysmyelinating neuropathies.

Sensitivity of crude and purified Fasciola antigens in immunological diagnosis of human fascioliasis.

A study has been done to find the effect of purification of crude antigens, extracted from adult Fasciola gigantica and Fasciola hepatica worms on the sensitivity of some serological techniques in diagnosis of fascioliasis. Using C.I.E.P. test, the partially purified antigens of both Fasciola species were less sensitive than their corresponding crude ones. Using I.H.A., the difference between results of crude and partially purified antigens for the two species were statistically insignificant, both (P greater than 0.05). So in applying this test, there is no need for the partially purification of antigen. On using E.L.I.S.A. the partially purified antigens showed higher sensitivities for detection of fascioliasis than their corresponding crude ones. Partially purified F. gigantica and F. hepatica antigens gave nearly the same results whether using C.I.E.P., I.H.A. or E.L.I.S.A. However, E.L.I.S.A. was the most sensitive technique followed by I.H.A. then C.I.E.P.