Explaining informal payments for health services in Central and Eastern Europe: an institutional asymmetry perspective

The aim of this paper is to propose and evaluate a new institutional theory explanation for patients making informal payments for health services in Central and Eastern Europe. This views informal payments by patients to healthcare professionals as arising when formal institutional failures lead to an asymmetry between the laws and regulations of formal institutions and the unwritten rules of informal institutions. Reporting a 2013 Eurobarometer survey of the prevalence of informal payments by patients in Central and Eastern European countries, a strong association is revealed between the level of asymmetry between the formal and informal institutions, and the propensity to make informal payments. The association between informal payments and various formal institutional imperfections is then explored to evaluate which structural conditions might reduce this institutional asymmetry, and thus the propensity to make informal payments. The paper concludes by exploring the implications for tackling such informal practices

LRRK2 Biology from structure to dysfunction: research progresses, but the themes remain the same

Since the discovery of leucine-rich repeat kinase 2 (LRRK2) as a protein that is likely central to the aetiology of Parkinson's disease, a considerable amount of work has gone into uncovering its basic cellular function. This effort has led to the implication of LRRK2 in a bewildering range of cell biological processes and pathways, and probable roles in a number of seemingly unrelated medical conditions. In this review we summarise current knowledge of the basic biochemistry and cellular function of LRRK2. Topics covered include the identification of phosphorylation substrates of LRRK2 kinase activity, in particular Rab proteins, and advances in understanding the activation of LRRK2 kinase activity via dimerisation and association with membranes, especially via interaction with Rab29. We also discuss biochemical studies that shed light on the complex LRRK2 GTPase activity, evidence of roles for LRRK2 in a range of cell signalling pathways that are likely cell type specific, and studies linking LRRK2 to the cell biology of organelles. The latter includes the involvement of LRRK2 in autophagy, endocytosis, and processes at the trans-Golgi network, the endoplasmic reticulum and also key microtubule-based cellular structures. We further propose a mechanism linking LRRK2 dimerisation, GTPase function and membrane recruitment with LRRK2 kinase activation by Rab29. Together these data paint a picture of a research field that in many ways is moving forward with great momentum, but in other ways has not changed fundamentally. Many key advances have been made, but very often they seem to lead back to the same places

Multi-ancestry genome-wide association meta-analysis of Parkinson’s disease

\ua9 2023, This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply. Although over 90 independent risk variants have been identified for Parkinson’s disease using genome-wide association studies, most studies have been performed in just one population at a time. Here we performed a large-scale multi-ancestry meta-analysis of Parkinson’s disease with 49,049 cases, 18,785 proxy cases and 2,458,063 controls including individuals of European, East Asian, Latin American and African ancestry. In a meta-analysis, we identified 78 independent genome-wide significant loci, including 12 potentially novel loci (MTF2, PIK3CA, ADD1, SYBU, IRS2, USP8, PIGL, FASN, MYLK2, USP25, EP300 and PPP6R2) and fine-mapped 6 putative causal variants at 6 known PD loci. By combining our results with publicly available eQTL data, we identified 25 putative risk genes in these novel loci whose expression is associated with PD risk. This work lays the groundwork for future efforts aimed at identifying PD loci in non-European populations

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

Author Correction: Elucidating causative gene variants in hereditary Parkinson’s disease in the Global Parkinson’s Genetics Program (GP2)

Correction to: s41531-023-00526-9 npj Parkinson’s Disease, published online 27 June 2023 In this article the Global Parkinson’s Genetics Program (GP2) members names and affiliations were missing in the main author list of the Original article which are listed in the below

Defining the causes of sporadic Parkinson's disease in the global Parkinson's genetics program (GP2)

The Global Parkinson’s Genetics Program (GP2) will genotype over 150,000 participants from around the world, and integrate genetic and clinical data for use in large-scale analyses to dramatically expand our understanding of the genetic architecture of PD. This report details the workflow for cohort integration into the complex arm of GP2, and together with our outline of the monogenic hub in a companion paper, provides a generalizable blueprint for establishing large scale collaborative research consortia

Multi-ancestry genome-wide association meta-analysis of Parkinson?s disease

Although over 90 independent risk variants have been identified for Parkinson’s disease using genome-wide association studies, most studies have been performed in just one population at a time. Here we performed a large-scale multi-ancestry meta-analysis of Parkinson’s disease with 49,049 cases, 18,785 proxy cases and 2,458,063 controls including individuals of European, East Asian, Latin American and African ancestry. In a meta-analysis, we identified 78 independent genome-wide significant loci, including 12 potentially novel loci (MTF2, PIK3CA, ADD1, SYBU, IRS2, USP8, PIGL, FASN, MYLK2, USP25, EP300 and PPP6R2) and fine-mapped 6 putative causal variants at 6 known PD loci. By combining our results with publicly available eQTL data, we identified 25 putative risk genes in these novel loci whose expression is associated with PD risk. This work lays the groundwork for future efforts aimed at identifying PD loci in non-European populations