Background: Spinal muscular atrophy (SMA) is a children’s neuromuscular disorder. Although motor neuron loss is a major feature of the disease, we have identified fatty acid abnormalities in SMA patients and in preclinical animal models, suggesting metabolic perturbation is also an important component of SMA. Methods: Biochemical, histological, proteomic, and high resolution respirometry were used. Results: SMA patients are more susceptible to dyslipidemia than the average population as determined by a standard lipid profile in a cohort of 72 pediatric patients. As well, we observed a non-alcoholic liver disease phenotype in apreclinical mouse model. Denervation alone was not sufficient to induce liver steatosis, as a mouse model of ALS, did not develop fatty liver. Hyperglucagonemia in Smn2B/-mice could explain the hepatic steatosis by increasing plasma substrate availability via glycogen depletion and peripheral lipolysis. Proteomic analysis identified mitochondrion and lipid metabolism as major clusters. Alterations in mitochondrial function were revealed by high-resolution respirometry. Finally, low-fat diets led to increased survival in Smn2B/-mice. Conclusions: These results provide strong evidence for lipid metabolism defects in SMA. Further investigation will be required to establish the primary mechanism of these alterations and understand how they lead to additional co-morbidities in SMA patients.

This article addresses the metallurgical and mechanical properties of Nd:YAG laser welded Inconel 625 and duplex stainless steel SAF 2205. Keyhole plasma mode laser welding was adopted to obtain the joints. Microstructure studies showed slight grain coarsening at the heat affected zone of Inconel 625. Line mapping and elemental mapping analysis were carried out at the weld interface and in the fusion zone to examine the elemental migration as well as the composition of the phases present in these regions. The fusion zone microstructure showed the presence of Nb, Mo rich Laves phase segregated at the interdendritic arms. Tensile studies corroborated that an average joint strength of 820 MPa has been displayed by these weldments, which was almost equal to one of the parent metals, SAF 2205. It is evident from the charpy v-notch studies that the impact toughness of these laser weldments was found to be 10 J and this low toughness could be reasoned out to the formation of Mo rich phases. The structure–property relationships of these weldments have been addressed in detail and the outcomes of the study will be highly useful for marine and geothermal applications.

In this study, cDNA microarray analysis of a closely related species, Leishmania major, was used as a screening tool to compare antimonial-resistant and susceptible clinical isolates of Leishmania donovani in order to to identify candidate genes on the basis of antimony resistance. Clinically confirmed resistant isolate 39 and sensitive isolate 2001 were used in this study. Many differentially regulated genes were identified whose expression levels differ in sodium antimony gluconate (SAG)-treated patients. Interestingly, genes on the array, showing changes in expression of over 2-fold revealed the identity of ABC transporters, which are known determinants of drug resistance in laboratory mutants. The functionality of the transporters was validated by flow cytometry which, being biologically informative, provides direct clues to gene function. The results suggest that isolate 39 could have developed resistance by an increased multidrug resistance protein (MRP)-like pump. This study provides preliminary clues to the role of a thiol-dependent efflux system in antimonial resistant clinical isolates of Leishmania donovani.