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PLOS Papers on Role of LRRK2 in Parkinson's Disease, Visceral Leishmaniasis Survey, Pink Salmon Genome

Researchers led by Mark Cookson at the US National Institute on Aging investigate the role of the leucine-rich repeat kinase 2 (LRRK2) gene — variants in which have been implicated in Parkinson's disease — in vesicular trafficking. In their PLOS Biology paper, they focus on LRRK2 and its substrate Rab8a, a small GTPase that is involved in the trafficking of transferrin, to find that gain-of-function mutations in LRRK2 leads to the sequestration of Rab8a in lysosomes, though the effect can be reversed by pharmacological inhibition. The researchers further find that microglia derived from patients with a common LRRK2 mutation mis-traffic transferrin in a model of inflammation. "Deciphering the protein trafficking pathways around LRRK2 will help us understand the mechanistic underpinnings of neurodegeneration and the biological implications of blocking LRRK2 kinase in the clinic, while highlighting signaling avenues that can be targeted as therapeutic means," Cookson and colleagues write in their paper.

A team from Sun Yat-Sen University has conducted an 11-year survey of visceral leishmaniasis in western China. They collected 20 isolates of Leishmania species that cause visceral leishmaniasis, also known as black fever, from patients, sand-fly vectors, and Tarim hares. Following PCR analysis of key diagnostic genes like ITS1, hsp70 and nagt, the researchers conducted a phylogenetic analysis that found that isolates causing anthroponotic visceral leishmaniasis fell into a separate clade from those behind zoonotic visceral leishmaniasis. Their analysis further revealed a likely zoonotic transmission cycle involving the Tarim hares as reservoir of desert type zoonotic visceral leishmaniasis. "Further control measures targeting these wild animals may be needed for the effective control of this disease," the team notes in its PLOS Neglected Tropical Diseases paper.

Finally, researchers from University of Victoria in British Columbia and elsewhere report in PLOS One that they have sequenced the pink salmon genome. Pink salmon, they note, have a two-year life cycle that has led some populations to be temporally isolated, with some spawning in odd years and others in even years. By analyzing both odd- and even-year populations, the researchers found little gene flow between the temporally isolated populations and in particular noticed differences between genes involved in the immune system, organ development, and behavior as well as divergence at the centromere. However, they did note some shared variants and shared mitochondrial lineages that suggest there is some gene flow. "These … differences offer us a glimpse into the evolutionary landscape and the selective pressures or demographic histories of pink salmon," the researchers write.