Isolation of Intermediate Filament Proteins from Multiple Mouse Tissues to Study Aging-associated Post-translational Modifications

In this method we present biochemical procedures for rapid and efficient isolation of intermediate filament (IF) proteins from multiple mouse tissues. Isolated IFs can be used to study changes in post-translational modifications by mass spectrometry and other biochemical assays

Uncertain R&D Outcomes and Cooperation in R&D

The present paper provides a brief survey of some of the papers dealing with R&D uncertainty. This helps us identify which factors are more favorable for cooperative R&D and which factors are not. The paper provides the analysis under a unified framework. We take the classic paper by Marjit (1991) as the benchmark case, and then proceeds to examine whether, or to what extent, Marjit result will undergo a change with respect to different assumptions related to R&D investment

A microscopic complex potential description of elastic, inelastic cross section in the Coulomb nuclear interference region in the 28Si on 28Si system

Elastic and inelastic angular distribution and excitation functions were measured for the 28Si + 28Si system in the vicinity of the Coulomb barrier. While the elastic data could be described very well by using fully microscopic complex potential, the inelastic cross sections were found to be more sensitive to small variations in the potential. In particular the Coulomb nuclear interference dip observed in the inelastic excitation functions could not be fitted satisfactorily with calculation. Inclusion of an energy dependent term of Gaussian shape to the associated matrix element with the reorientation coupling in the phenomenological calculations leads to a better fit the inelastic excitation functions. © 1998 Elsevier Science B.V

Site-specific phosphorylation and caspase cleavage of GFAP are new markers of Alexander Disease severity

Alexander Disease (AxD) is a fatal neurodegenerative disorder caused by mutations in glial fibrillary acidic protein (GFAP), which supports the structural integrity of astrocytes. Over 70 GFAP missense mutations cause AxD, but the mechanism linking different mutations to disease-relevant phenotypes remains unknown. We used AxD patient brain tissue and induced pluripotent stem cell (iPSC)-derived astrocytes to investigate the hypothesis that AxD-causing mutations perturb key post-translational modifications (PTMs) on GFAP. Our findings reveal selective phosphorylation of GFAP-Ser13 in patients who died young, independently of the mutation they carried. AxD iPSC-astrocytes accumulated pSer13-GFAP in cytoplasmic aggregates within deep nuclear invaginations, resembling the hallmark Rosenthal fibers observed in vivo. Ser13 phosphorylation facilitated GFAP aggregation and was associated with increased GFAP proteolysis by caspase-6. Furthermore, caspase-6 was selectively expressed in young AxD patients, and correlated with the presence of cleaved GFAP. We reveal a novel PTM signature linking different GFAP mutations in infantile AxD

How to increase technology transfers to developing countries: a synthesis of the evidence

The existing United Nations Framework Convention on Climate Change (UNFCCC) has failed to deliver the rate of low-carbon technology transfer (TT) required to curb GHG emissions in developing countries. This failure has exposed the limitations of universalism and renewed interest in bilateral approaches to TT. Gaps are identified in the UNFCCC approach to climate change TT: missing links between international institutions and the national enabling environments that encourage private investment; a non-differentiated approach for (developing) country and technology characteristics; and a lack of clear measurements of the volume and effectiveness of TTs. Evidence from econometric literature and business experience on climate change TT is reviewed, so as to address the identified pitfalls of the UNFCCC process. Strengths and weaknesses of different methodological approaches are highlighted. International policy recommendations are offered aimed at improving the level of emission reductions achieved through TT

SLC25A22 is a novel gene for migrating partial seizures in infancy

Objective To identify a genetic cause for migrating partial seizures in infancy (MPSI). Methods We characterized a consanguineous pedigree with MPSI and obtained DNA from affected and unaffected family members. We analyzed single nucleotide polymorphism 500K data to identify regions with evidence of linkage. We performed whole exome sequencing and analyzed homozygous variants in regions of linkage to identify a candidate gene and performed functional studies of the candidate gene SLC25A22. Results In a consanguineous pedigree with 2 individuals with MPSI, we identified 2 regions of linkage, chromosome 4p16.1-p16.3 and chromosome 11p15.4-pter. Using whole exome sequencing, we identified 8 novel homozygous variants in genes in these regions. Only 1 variant, SLC25A22 c.G328C, results in a change of a highly conserved amino acid (p.G110R) and was not present in control samples. SLC25A22 encodes a glutamate transporter with strong expression in the developing brain. We show that the specific G110R mutation, located in a transmembrane domain of the protein, disrupts mitochondrial glutamate transport. Interpretation We have shown that MPSI can be inherited and have identified a novel homozygous mutation in SLC25A22 in the affected individuals. Our data strongly suggest that SLC25A22 is responsible for MPSI, a severe condition with few known etiologies. We have demonstrated that a combination of linkage analysis and whole exome sequencing can be used for disease gene discovery. Finally, as SLC25A22 had been implicated in the distinct syndrome of neonatal epilepsy with suppression bursts on electroencephalogram, we have expanded the phenotypic spectrum associated with SLC25A22. Ann Neurol 2013;74:873-882 © 2013 American Neurological Association