ARHGEF7 (BETA-PIX) Acts as Guanine Nucleotide Exchange Factor for Leucine-Rich Repeat Kinase 2

Background: Mutations within the leucine-rich repeat kinase 2 (LRRK2) gene are a common cause of familial and sporadic Parkinson’s disease. The multidomain protein LRRK2 exhibits overall low GTPase and kinase activity in vitro. Methodology/Principal Findings: Here, we show that the rho guanine nucleotide exchange factor ARHGEF7 and the small GTPase CDC42 are interacting with LRRK2 in vitro and in vivo. GTPase activity of full-length LRRK2 increases in the presence of recombinant ARHGEF7. Interestingly, LRRK2 phosphorylates ARHGEF7 in vitro at previously unknown phosphorylation sites. We provide evidence that ARHGEF7 might act as a guanine nucleotide exchange factor for LRRK2 and that R1441C mutant LRRK2 with reduced GTP hydrolysis activity also shows reduced binding to ARHGEF7. Conclusions/Significance: Downstream effects of phosphorylation of ARHGEF7 through LRRK2 could be (i) a feedback control mechanism for LRRK2 activity as well as (ii) an impact of LRRK2 on actin cytoskeleton regulation. A newly identified familial mutation N1437S, localized within the GTPase domain of LRRK2, further underlines the importance of the GTPas

Theoretical and unused potential for residual biomasses in the Emilia Romagna Region (Italy) through a revised and portable framework for their categorization

Global energy demand is lowering its growth, but it is still expected to increase by 30% between now and 2040. To decrease greenhouse gas emissions a shift to more sustainable renewable energy sources is fundamental. Among the renewable energy sources, biomasses already have the largest share in Europe and their future demand for biorefinery plants will increase at global level. This study provides a comprehensive and exportable categorization of the residual biomasses (RB) from different supply sectors. Thanks to the individual descriptive and quantitative parameters introduced in the paper, an estimate of the theoretical and techno-economic potential is presented for a well-industrialized, agricultural-oriented and environmentally advanced European Region. Results are presented as recoverable biogas or biomethane, considering also the seasonal availability. In a relatively small region like Emilia Romagna (Italy), 106 different types of residual biomasses belonging to 6 main groups have been characterized. Over half of the total residues come from the agro-industrial and food businesses (58) followed by the agricultural sector (33). The estimate reveals a theoretical potential of 3544\ub1291 Gg/year of total solids for thermochemical valorisation and 3460\ub1639 Gg/year of total solids suitable for biological treatment. In terms of unused potential, the quantities decrease respectively to 2120\ub1298 and 915\ub1167 Gg/year. The estimates indicate stable results over the years from 2014 to 2016. The seasonal availability shows two evident peaks from August to October, while a significant shortage is present from April to June for the residues suitable for thermochemical valorisation. The theoretical potential that can be obtained from the Region's residues corresponds to about 1.8-2.3 million TOE/year, corresponding to 13-17% of the total regional consumption. Unused residues contribute to 0.9-1.2 million TOE/year

Inhibition of the Exocyst Complex Attenuates the LRRK2 Pathological Effects

Pathological mutations in leucine-rich repeat kinase 2 (LRRK2) gene are the major genetic cause of Parkinson’s disease (PD). Multiple lines of evidence link LRRK2 to the control of vesicle dynamics through phosphorylation of a subset of RAB proteins. However, the molecular mechanisms underlying these processes are not fully elucidated. We have previously demonstrated that LRRK2 increases the exocyst complex assembly by Sec8 interaction, one of the eight members of the exocyst complex, and that Sec8 over-expression mitigates the LRRK2 pathological effect in PC12 cells. Here, we extend this analysis using LRRK2 drosophila models and show that the LRRK2-dependent exocyst complex assembly increase is downstream of RAB phosphorylation. Moreover, exocyst complex inhibition rescues mutant LRRK2 pathogenic phenotype in cellular and drosophila models. Finally, prolonged exocyst inhibition leads to a significant reduction in the LRRK2 protein level, overall supporting the role of the exocyst complex in the LRRK2 pathway. Taken together, our study suggests that modulation of the exocyst complex may represent a novel therapeutic target for PD

Parental presence in Italian pediatric intensive care units: a reappraisal of current visiting policies

Parental presence in Italian pediatric intensive care units: a reappraisal of current visiting policie