Isolation of microplastics in biota-rich seawater samples and marine organisms.

notes: PMCID: PMC3970126types: Journal Article; Research Support, Non-U.S. Gov'tThis is an open access article that is freely available in ORE or from the publisher's web site. Please cite the published version.Microplastic litter is a pervasive pollutant present in aquatic systems across the globe. A range of marine organisms have the capacity to ingest microplastics, resulting in adverse health effects. Developing methods to accurately quantify microplastics in productive marine waters, and those internalized by marine organisms, is of growing importance. Here we investigate the efficacy of using acid, alkaline and enzymatic digestion techniques in mineralizing biological material from marine surface trawls to reveal any microplastics present. Our optimized enzymatic protocol can digest >97% (by weight) of the material present in plankton-rich seawater samples without destroying any microplastic debris present. In applying the method to replicate marine samples from the western English Channel, we identified 0.27 microplastics m(-3). The protocol was further used to extract microplastics ingested by marine zooplankton under laboratory conditions. Our findings illustrate that enzymatic digestion can aid the detection of microplastic debris within seawater samples and marine biota.Natural Environment Research Council (NERC

Sources, Distribution, and Fate of Microscopic Plastics in Marine Environments

Microplastics are pieces of plastic debris <5 mm in diameter. They enter the environment from a variety of sources including the direct input of small pieces such as exfoliating beads used in cosmetics and as a consequence of the fragmentation of larger items of debris. A range of common polymers, including polyethylene, polypropylene, polystyrene, and polyvinyl chloride, are present in the environment as microplastic particles. Microplastics are widely distributed in marine and freshwater habitats. They have been reported on shorelines from the poles to the equator; they are present at the sea surface and have accumulated in ocean systems far from land. Microplastics are also present in substantial quantities on the seabed. A wide range of organisms including birds, fish, and invertebrates are known to ingest microplastics and for some species it is clear that a substantial proportion of the population have microplastic in their digestive tract. The extent to which this might have harmful effects is not clear; however, the widespread encounter rate indicates that substantial quantities of microplastic may be distributed within living organisms themselves as well as in the habitats in which they live. Our understanding about the long-term fate of microplastics is relatively limited. Some habitats such as the deep sea may be an ultimate sink for the accumulation of plastic debris at sea; indeed, some recent evidence indicates quantities in the deep sea can be greater than at the sea surface. It has also been suggested that microplastics might be susceptible to biodegradation by microorganisms; however, this is yet to be established and the prevailing view is that even if emissions of debris to the environment are substantially reduced, the abundance of microplastics will increase over the next few decades. However, it is also clear that the benefits which plastics bring to society can be realized without the need for emissions of end-of-life plastics to the ocean. To some extent the accumulation of microplastic debris in the environment is a symptom of an outdated business model. There are solutions at hand and many synergistic benefits can be achieved in terms of both waste reduction and sustainable use of resources by moving toward a circular economy

Mitochondria function associated genes contribute to Parkinson's Disease risk and later age at onset

Mitochondrial dysfunction has been implicated in the etiology of monogenic Parkinson’s disease (PD). Yet the role that mitochondrial processes play in the most common form of the disease; sporadic PD, is yet to be fully established. Here, we comprehensively assessed the role of mitochondrial function-associated genes in sporadic PD by leveraging improvements in the scale and analysis of PD GWAS data with recent advances in our understanding of the genetics of mitochondrial disease. We calculated a mitochondrial-specific polygenic risk score (PRS) and showed that cumulative small effect variants within both our primary and secondary gene lists are significantly associated with increased PD risk. We further reported that the PRS of the secondary mitochondrial gene list was significantly associated with later age at onset. Finally, to identify possible functional genomic associations we implemented Mendelian randomization, which showed that 14 of these mitochondrial functionassociated genes showed functional consequence associated with PD risk. Further analysis suggested that the 14 identified genes are not only involved in mitophagy, but implicate new mitochondrial processes. Our data suggests that therapeutics targeting mitochondrial bioenergetics and proteostasis pathways distinct from mitophagy could be beneficial to treating the early stage of PD

Identification of sixteen novel candidate genes for late onset Parkinson’s disease

Background Parkinson’s disease (PD) is a neurodegenerative movement disorder affecting 1–5% of the general population for which neither effective cure nor early diagnostic tools are available that could tackle the pathology in the early phase. Here we report a multi-stage procedure to identify candidate genes likely involved in the etiopathogenesis of PD. Methods The study includes a discovery stage based on the analysis of whole exome data from 26 dominant late onset PD families, a validation analysis performed on 1542 independent PD patients and 706 controls from different cohorts and the assessment of polygenic variants load in the Italian cohort (394 unrelated patients and 203 controls). Results Family-based approach identified 28 disrupting variants in 26 candidate genes for PD including PARK2, PINK1, DJ-1(PARK7), LRRK2, HTRA2, FBXO7, EIF4G1, DNAJC6, DNAJC13, SNCAIP, AIMP2, CHMP1A, GIPC1, HMOX2, HSPA8, IMMT, KIF21B, KIF24, MAN2C1, RHOT2, SLC25A39, SPTBN1, TMEM175, TOMM22, TVP23A and ZSCAN21. Sixteen of them have not been associated to PD before, were expressed in mesencephalon and were involved in pathways potentially deregulated in PD. Mutation analysis in independent cohorts disclosed a significant excess of highly deleterious variants in cases (p = 0.0001), supporting their role in PD. Moreover, we demonstrated that the co-inheritance of multiple rare variants (≥ 2) in the 26 genes may predict PD occurrence in about 20% of patients, both familial and sporadic cases, with high specificity (> 93%; p = 4.4 × 10− 5). Moreover, our data highlight the fact that the genetic landmarks of late onset PD does not systematically differ between sporadic and familial forms, especially in the case of small nuclear families and underline the importance of rare variants in the genetics of sporadic PD. Furthermore, patients carrying multiple rare variants showed higher risk of manifesting dyskinesia induced by levodopa treatment. Conclusions Besides confirming the extreme genetic heterogeneity of PD, these data provide novel insights into the genetic of the disease and may be relevant for its prediction, diagnosis and treatment

Moving beyond neurons: the role of cell type-specific gene regulation in Parkinson's disease heritability

Parkinson’s disease (PD), with its characteristic loss of nigrostriatal dopaminergic neurons and deposition of α-synuclein in neurons, is often considered a neuronal disorder. However, in recent years substantial evidence has emerged to implicate glial cell types, such as astrocytes and microglia. In this study, we used stratified LD score regression and expression-weighted cell-type enrichment together with several brain-related and cell-type-specific genomic annotations to connect human genomic PD findings to specific brain cell types. We found that PD heritability attributable to common variation does not enrich in global and regional brain annotations or brain-related cell-type-specific annotations. Likewise, we found no enrichment of PD susceptibility genes in brain-related cell types. In contrast, we demonstrated a significant enrichment of PD heritability in a curated lysosomal gene set highly expressed in astrocytic, microglial, and oligodendrocyte subtypes, and in LoF-intolerant genes, which were found highly expressed in almost all tested cellular subtypes. Our results suggest that PD risk loci do not lie in specific cell types or individual brain regions, but rather in global cellular processes detectable across several cell types