Gene expression asymmetry in Parkinson's Disease; variation of and gene expression levels are correlated with hemisphere specific severity.

Parkinson's Disease (PD) develops unilaterally, which may be related to brain hemispheric differences in gene expression. Here we measured bulk RNA-seq levels in neuronal nuclei obtained from prefrontal cortex postmortem brain samples from males and females with PD and from healthy controls. Left and right hemispheres from each brain were related the side of symptom onset and compared.

Evaluation of different glycerol fed-batch strategies in a lab-scale bioreactor for the improved production of a novel engineered β-fructofuranosidase enzyme in Pichia pastoris.

The β-fructofuranosidase enzyme from Aspergillus niger has been extensively used to commercially produce fructooligosaccharides from sucrose. In this study, the native and an engineered version of the β-fructofuranosidase enzyme were expressed in Pichia pastoris under control of the glyceraldehyde-3-phosphate dehydrogenase promoter, and production was evaluated in bioreactors using either dissolved oxygen (DO-stat) or constant feed fed-batch feeding strategies. The DO-stat cultivations produced lower biomass concentrations but this resulted in higher volumetric activity for both strains.

Fine-mapping analysis including over 254,000 East Asian and European descendants identifies 136 putative colorectal cancer susceptibility genes.

Genome-wide association studies (GWAS) have identified more than 200 common genetic variants independently associated with colorectal cancer (CRC) risk, but the causal variants and target genes are mostly unknown. We sought to fine-map all known CRC risk loci using GWAS data from 100,204 cases and 154,587 controls of East Asian and European ancestry. Our stepwise conditional analyses revealed 238 independent association signals of CRC risk, each with a set of credible causal variants (CCVs), of which 28 signals had a single CCV.

Parkinson's disease risk enhancers in microglia.

Genome-wide association studies have identified thousands of single nucleotide polymorphisms that associate with increased risk for Parkinson's disease (PD), but the functions of most of them are unknown. Using assay for transposase-accessible chromatin (ATAC) and H3K27ac chromatin immunoprecipitation (ChIP) sequencing data, we identified 73 regulatory elements in microglia that overlap PD risk SNPs. To determine the target genes of a "risk enhancer" within intron two of , we used CRISPR-Cas9 to delete the open chromatin region where two PD risk SNPs reside.

Deciphering colorectal cancer genetics through multi-omic analysis of 100,204 cases and 154,587 controls of European and east Asian ancestries.

Colorectal cancer (CRC) is a leading cause of mortality worldwide. We conducted a genome-wide association study meta-analysis of 100,204 CRC cases and 154,587 controls of European and east Asian ancestry, identifying 205 independent risk associations, of which 50 were unreported. We performed integrative genomic, transcriptomic and methylomic analyses across large bowel mucosa and other tissues.

Genetic Elements at the Alpha-Synuclein Locus.

Genome-wide association studies have consistently shown that the alpha-synuclein locus is significantly associated with Parkinson's disease. The mechanism by which this locus modulates the disease pathology and etiology remains largely under-investigated. This is due to the assumption that is the only driver of the functional aspects of several single nucleotide polymorphism (SNP) risk-signals at this locus.

The Parkinson's disease variant rs356182 regulates neuronal differentiation independently from alpha-synuclein.

One of the most significant risk variants for Parkinson's disease (PD), rs356182, is located at the PD-associated locus near the alpha-synuclein (α-syn) encoding gene, SNCA. SNCA-proximal variants, including rs356182, are thought to function in PD risk through enhancers via allele-specific regulatory effects on SNCA expression. However, this interpretation discounts the complex activity of genetic enhancers and possible non-conical functions of α-syn.

Influence of codon optimization, promoter, and strain selection on the heterologous production of a β-fructofuranosidase from Aspergillus fijiensis ATCC 20611 in Pichia pastoris.

Fructooligosaccharides (FOS) are compounds possessing various health properties and are added to functional foods as prebiotics. The commercial production of FOS is done through the enzymatic transfructolysation of sucrose by β-fructofuranosidases which is found in various organisms of which Aureobasidium pullulans and Aspergillus niger are the most well known. This study overexpressed two differently codon-optimized variations of the Aspergillus fijiensis β-fructofuranosidase-encoding gene (fopA) under the transcriptional control of either the alcohol oxidase (AOX1) or glyceraldehyde-3-phosphate dehydrogenase (GAP) promoters.

Alpha-synuclein negatively controls cell proliferation in dopaminergic neurons.

As researchers grapple with the mechanisms and implications of alpha-synuclein (α-syn) in neuropathology, it is often forgotten that the function(s) of α-syn in healthy cells remain largely elusive. Previous work has relied on observing α-syn localization in the cell or using knockout mouse models. Here, we address the specific role of α-syn in human dopaminergic neurons by disrupting its gene (SNCA) in the human dopaminergic neuron cell line, LUHMES.

Functions of Intracellular Alpha-Synuclein in Microglia: Implications for Parkinson's Disease Risk.

Alpha-synuclein accumulation in dopaminergic neurons is one of the primary features of Parkinson's disease (PD). Despite its toxic properties during PD, alpha-synuclein has some important physiological functions. Although the activity of the protein has been extensively studied in neurons, the protein is also expressed in other cell types including immune cells and glia.

The enigma and implications of brain hemispheric asymmetry in neurodegenerative diseases.

The lateralization of the human brain may provide clues into the pathogenesis and progression of neurodegenerative diseases. Though differing in their presentation and underlying pathologies, neurodegenerative diseases are all devastating and share an intriguing theme of asymmetrical pathology and clinical symptoms. Parkinson's disease, with its distinctive onset of motor symptoms on one side of the body, stands out in this regard, but a review of the literature reveals asymmetries in several other neurodegenerative diseases.

The effect of growth rate on the production and vitality of non-Saccharomyces wine yeast in aerobic fed-batch culture.

Non-Saccharomyces wine yeasts are of increasing importance due to their influence on the organoleptic properties of wine and thus the factors influencing the biomass production of these yeasts, as starter cultures, are of commercial value. Therefore, the effects of growth rates on the biomass yield (Y) and fermentation performance of non-Saccharomyces yeasts at bench and pilot scale were examined. The fermentative performance and (Y) were optimised, in aerobic fed-batch cultivations, to produce commercial wine seed cultures of Lachancea thermotolerans Y1240, Issatchenkia orientalis Y1161 and Metschnikowia pulcherrima Y1337.

Discovery and fine-mapping of height loci via high-density imputation of GWASs in individuals of African ancestry.

Although many loci have been associated with height in European ancestry populations, very few have been identified in African ancestry individuals. Furthermore, many of the known loci have yet to be generalized to and fine-mapped within a large-scale African ancestry sample. We performed sex-combined and sex-stratified meta-analyses in up to 52,764 individuals with height and genome-wide genotyping data from the African Ancestry Anthropometry Genetics Consortium (AAAGC).

Post-GWAS knowledge gap: the how, where, and when.

Genetic risk for complex diseases very rarely reflects only Mendelian-inherited phenotypes where single-gene mutations can be followed in families by linkage analysis. More commonly, a large set of low-penetrance, small effect-size variants combine to confer risk; they are normally revealed in genome-wide association studies (GWAS), which compare large population groups. Whereas Mendelian inheritance points toward disease mechanisms arising from the mutated genes, in the case of GWAS signals, the effector proteins and even general risk mechanism are mostly unknown.

Epigenomic analysis of Parkinson's disease neurons identifies Tet2 loss as neuroprotective.

Parkinson's disease (PD) pathogenesis may involve the epigenetic control of enhancers that modify neuronal functions. Here, we comprehensively examine DNA methylation at enhancers, genome-wide, in neurons of patients with PD and of control individuals. We find a widespread increase in cytosine modifications at enhancers in PD neurons, which is partly explained by elevated hydroxymethylation levels.

Understanding Non-Mendelian Genetic Risk.

This opinion paper highlights strategies for a better understanding of non-Mendelian genetic risk that was revealed by genome-wide association studies (GWAS) of complex diseases. The genetic risk resides predominantly in non-coding regulatory DNA, such as in enhancers. The identification of mechanisms, the causal variants (mainly SNPs), and their target genes are, however, not always apparent but are likely involved in a network of risk determinants; the identification presents a bottle-neck in the full understanding of the genetics of complex phenotypes.

Scalable methanol-free production of recombinant glucuronoyl esterase in Pichia pastoris.

Objective: Glucuronoyl esterase (GE) is an emerging enzyme that improves fractionation of lignin-carbohydrate complexes. However, the commercial availability of GE is limited, which hinders the research of GE-based bioprocesses for its industrial application in lignocellulose biorefineries. This study evaluated a workable, cost-effective, and commercially scalable production strategy to improve the ease of GE-based research.

MCF-7 as a Model for Functional Analysis of Breast Cancer Risk Variants.

Background: Breast cancer genetic predisposition is governed by more than 142 loci as revealed by genome-wide association studies (GWAS). The functional contribution of these risk loci to breast cancer remains unclear, and additional post-GWAS analyses are required.

Methods: We identified active regulatory elements (enhancers, promoters, and chromatin organizing elements) by histone H3K27 acetylation and CTCF occupancy and determined the enrichment of risk variants at these sites.

Amberlite IRA 900 versus calcium alginate in immobilization of a novel, engineered β-fructofuranosidase for short-chain fructooligosaccharide synthesis from sucrose.

The immobilization of β-fructofuranosidase for short-chain fructooligosaccharide (scFOS) synthesis holds the potential for a more efficient use of the biocatalyst. However, the choice of carrier and immobilization technique is a key to achieving that efficiency. In this study, calcium alginate (CA), Amberlite IRA 900 (AI900) and Dowex Marathon MSA (DMM) were tested as supports for immobilizing a novel engineered β-fructofuranosidase from Aspergillus japonicus for scFOS synthesis.

Ozonesonde Quality Assurance: The JOSIE-SHADOZ (2017) Experience.

The ozonesonde is a small balloon-borne instrument that is attached to a standard radiosonde to measure profiles of ozone from the surface to 35 km with ~100-m vertical resolution. Ozonesonde data constitute a mainstay of satellite calibration and are used for climatologies and analysis of trends, especially in the lower stratosphere where satellites are most uncertain. The electrochemical-concentration cell (ECC) ozonesonde has been deployed at ~100 stations worldwide since the 1960s, with changes over time in manufacture and procedures, including details of the cell chemical solution and data processing.

Corrective wedge ostectomy for an atypical femoral procurvatum deformity stabilised with a supracondylar bone plate.

Physeal fractures of the distal femur are among the most commonly encountered fractures in skeletally immature dogs. These fractures respond poorly to conservative management and thus early surgical reduction and stabilisation are recommended. A 7-month-old intact male Border collie presented with a history of chronic lameness.

Functional Analysis and Fine Mapping of the 9p22.2 Ovarian Cancer Susceptibility Locus.

Genome-wide association studies have identified 40 ovarian cancer risk loci. However, the mechanisms underlying these associations remain elusive. In this study, we conducted a two-pronged approach to identify candidate causal SNPs and assess underlying biological mechanisms at chromosome 9p22.

CRISPR-mediated deletion of prostate cancer risk-associated CTCF loop anchors identifies repressive chromatin loops.

Background: Recent genome-wide association studies (GWAS) have identified more than 100 loci associated with increased risk of prostate cancer, most of which are in non-coding regions of the genome. Understanding the function of these non-coding risk loci is critical to elucidate the genetic susceptibility to prostate cancer.

Results: We generate genome-wide regulatory element maps and performed genome-wide chromosome confirmation capture assays (in situ Hi-C) in normal and tumorigenic prostate cells.