Transplantation of canine olfactory ensheathing cells producing chondroitinase ABC promotes chondroitin sulphate proteoglycan digestion and axonal sprouting following spinal cord injury

Olfactory ensheathing cell (OEC) transplantation is a promising strategy for treating spinal cord injury (SCI), as has been demonstrated in experimental SCI models and naturally occurring SCI in dogs. However, the presence of chondroitin sulphate proteoglycans within the extracellular matrix of the glial scar can inhibit efficient axonal repair and limit the therapeutic potential of OECs. Here we have used lentiviral vectors to genetically modify canine OECs to continuously deliver mammalian chondroitinase ABC at the lesion site in order to degrade the inhibitory chondroitin sulphate proteoglycans in a rodent model of spinal cord injury. We demonstrate that these chondroitinase producing canine OECs survived at 4 weeks following transplantation into the spinal cord lesion and effectively digested chondroitin sulphate proteoglycans at the site of injury. There was evidence of sprouting within the corticospinal tract rostral to the lesion and an increase in the number of corticospinal axons caudal to the lesion, suggestive of axonal regeneration. Our results indicate that delivery of the chondroitinase enzyme can be achieved with the genetically modified OECs to increase axon growth following SCI. The combination of these two promising approaches is a potential strategy for promoting neural regeneration following SCI in veterinary practice and human patients

FAT1 mutations cause a glomerulotubular nephropathy

Steroid-resistant nephrotic syndrome (SRNS) causes 15% of chronic kidney disease (CKD). Here we show that recessive mutations in FAT1 cause a distinct renal disease entity in four families with a combination of SRNS, tubular ectasia, haematuria and facultative neurological involvement. Loss of FAT1 results in decreased cell adhesion and migration in fibroblasts and podocytes and the decreased migration is partially reversed by a RAC1/CDC42 activator. Podocyte-specific deletion of Fat1 in mice induces abnormal glomerular filtration barrier development, leading to podocyte foot process effacement. Knockdown of Fat1 in renal tubular cells reduces migration, decreases active RAC1 and CDC42, and induces defects in lumen formation. Knockdown of fat1 in zebrafish causes pronephric cysts, which is partially rescued by RAC1/CDC42 activators, confirming a role of the two small GTPases in the pathogenesis. These findings provide new insights into the pathogenesis of SRNS and tubulopathy, linking FAT1 and RAC1/CDC42 to podocyte and tubular cell function

Cheese yield, casein fractions and major components of milk of Saanen and Anglo-Nubian dairy goats Rendimento de produção de queijos, frações de caseína e principais componentes do leite de cabras Saanen e Anglo-Nubiana

<abstract language="por">Avaliaram-se os componentes, as frações de caseína e o rendimento na produção de queijo do leite de cabras das raças Saanen e Anglo-Nubiana, principais raças criadas no Uruguai. O estudo foi realizado em uma fazenda com sistema de criação semi-intensiva. O leite das cabras Anglo-Nubianas apresentou teores mais elevados de gordura (4,65 vs 3,59%), proteína total (3,48 vs 2,84%), caseína total (2,82 vs 2,23%), e maior rendimento na produção de queijos (22,00 vs 15,03kg/100l) que o leite das cabras Saanen. As fraçoes de &#945;s1-caseína (6,99 vs 2,37g/l), &#946;-caseína (13,95 vs 12,75g/l) e &#954;-caseína (4,24 vs 3,64g/l) também foram mais elevadas no leite das cabras Anglo-Nubianas, porém no teor de &#945;s2-caseína (3,02 vs 3,60g/l) não se observaram diferenças. O rendimento na produção de queijos foi significativamente correlacionado com os teores de gordura, proteína, caseína total e com as frações de caseína. A &#945;s1-caseína representou a fração com maior correlação com os teores de proteína total, caseína, gordura e produção de queijo. Demonstrou-se, neste estudo, que o leite de cabras Anglo-Nubianas é mais indicado para a produção de queijo e o de cabras Saanen para utilização como leite fluido

Myelin-associated proteins block the migration of olfactory ensheathing cells: an in vitro study using single cell tracking and traction force microscopy

Newly generated olfactory receptor axons grow from the peripheral to the central nervous system aided by olfactory ensheathing cells (OECs). Thus, OEC transplantation has emerged as a promising therapy for spinal cord injuries and for other neural diseases. However, these cells do not present a uniform population, but, instead, a functionally heterogeneous population that exhibits a variety of responses including adhesion, repulsion and crossover during cell-cell and cell-matrix interactions. Some studies report that the migratory properties of OECs are compromised by inhibitory molecules and potentiated by chemical gradients. Here, we demonstrated that rodent OECs express all the components of the Nogo Receptor complex and that their migration is blocked by Myelin. Next, we used cell tracking and traction force microscopy to analyze OEC migration and its mechanical properties over Myelin. Our data relate the absence of traction force of OEC with lower migratory capacity, which correlates with changes in the F-Actin cytoskeleton and focal adhesion distribution. Lastly, OEC traction force and migratory capacity is enhanced after cell incubation with the Nogo Receptor inhibitor NEP1-40