Multimodal Analysis Reveals New Genetic Effectors in Parkinson'S Disease-Related Gene LRRK2 Gly2019Ser Mutation

BackgroundMutations in the LRRK2 gene, which encodes leucine-rich repeat kinase 2 (LRRK2), generate one of the most prevalent monogenic forms of Parkinson's disease (PD). Patients with autosomal dominant PD and apparent sporadic PD, who are clinically indistinguishable from those with idiopathic PD, are found to have LRRK2 mutations, particularly the most prevalent variant Gly2019Ser. Nonetheless, potential effectors of Gly2019Ser remain unknown.MethodsWe used the GEO database to undertake and evaluate a multitiered bioinformatic investigation to look into the gene expression implicated in the development of Parkinson's disease. Individual differences in gene expression were then confirmed in whole blood samples collected in the clinic. These genetic factors were also subjected to an interaction analysis and prediction. ResultsIn total, 607 genes in the LRRK2 Gly2019Ser mutation group expressed differently from those in the wild group. The following 10 top hub genes were discovered in protein-protein interaction (PPI) networks: CD44, CTGF, THBS1, VEGFA, SPP1, EGF, VCAM1, MMP3, CXCR4, and LOX. The gene expression of CD44, CTGF, THBS1, SPP1, EGF, and LOX was considerably higher in the LRRK2 Gly2019Ser mutant group than in the LRRK2 wild group. Meanwhile, CXCR4 gene expression in the LRRK2 Gly2019Ser mutant group was significantly lower than in the LRRK2 wild group. We then confirmed the expression of the hub genes in LRRK2 Gly2019Ser mutated iPSC-induced DA cells. As a result, the levels of CD44, CTGF, THBS1, VEGFA, SPP1 were positively correlated to the mutation of LRRK2, displayed promising effectors for discriminating the pathogenesis of PD. ConclusionsWe identified CD44, CTGF, THBS1, VEGFA, and SPP1 as the potential genetic effectors responding to the mutation of LRRK2. They could be a promising mechanism for discriminating the PD and potential factors contributing to the disease's development.

Differences in personality / temperament in the endangered tortoise Testudo hermanni and their implications on dispersal and conservation

Behavioural studies are more an more implicated in species conservation. Determining individuals personality in the case of reintroduction operations may be very useful. Actually, indiviuals temperament may be associated to their dispersal capacities and their habilities to adapt to novel environments. Considered as asociable species, few studies have been conducted on reptiles and this is even worse in the case of endangered species. Hermann tortoise, Testudo hermanni, an endemic species from Mediterranean region is endangered because of the lost and modification of its habitats. Before conducting reintroduction actions it is important to have more information on individuals personality traits. We have tested the reaction of three groups of tortoises (domestic, wild and from the SOPTOM center) when confronted to a novel environment and to human presence. The aim was to discriminate individuals with bold and shy behaviours. Behavioural profiles are different between the three groups of tortoises, the domestic group appeared to be bolder than the wild one. Moreover, for the wild group, bold individuals travel longer distances in the field, sometimes outside the protected areas. Thus, it is important to take into account the personality of individuals choosen for translocation projects.

Unreciprocated allogrooming hierarchies in a population of wild group-living mammals

Allogrooming can relate to social status in mammalian societies, and thus, be used to infer social structure. This relationship has previously been investigated by examining an individual’s dominance rank and their total amount of allogrooming. This, however, does not account for the identity of allogrooming partners. We applied a novel approach, calculating the linearity and steepness of unreciprocated allogrooming hierarchies using actor–receiver matrices in European badgers (Meles meles) groups. Badgers have relatively unstructured social groups compared to most group-living carnivores and allogrooming in badgers is currently hypothesized to have a hygiene function. We examine whether allogrooming is linked to social status by investigating: 1) the presence, linearity, and steepness of unreciprocated allogrooming hierarchies; 2) the trading of unreciprocated allogrooming for the potential benefit of receiving reduced aggression from dominant individuals; and, 3) whether unreciprocated allogrooming is associated with relatedness. We found weak unreciprocated allogrooming hierarchies, with marginal linearity, steepness overall, and variation between social-group-years. Unreciprocated allogrooming was positively correlated with directed aggression, potentially providing evidence for the trading of allogrooming for reduced aggression. Allogrooming was not correlated with relatedness, possibly due to high relatedness within social groups. Our findings reaffirm that European badgers have a relatively unstructured social system; likely reflecting a relatively simple state of sociality in Carnivores, with little need for hierarchical order. Using actor–receiver unreciprocated allogrooming matrices to test for linearity and steepness of unreciprocated allogrooming hierarchies in other social species will improve knowledge of group social structure.

CDKN2A or CDKN2B homozygous deletion with high-immune infiltration as a favorable prognostic factor for lung adenocarcinoma.

e20543 Background: CDKN2A and CDKN2B both acted as tumor suppressor genes by regulating the cell cycle, which in humans were located at chromosome 9, band p21.3. The frequencies of homozygous deletion (HomDel) in CDKN2A and CDKN2B in lung adenocarcinoma (LUAD) were 12.5% and 12.1%, respectively. However, the genomic, immunogenomic features and impact on the prognosis of LUAD patients with CDKN2A/B HomDel were still unclear. Methods: The cohort of this study was from The Cancer Genome Atlas (TCGA). A total of 508 LUAD patients, including 99 CDKN2A/B HomDel (homdel) and 509 CDKN2A/B wild (wild). This study explored the difference of genomic and immunogenomic landscape between homdel and wild by analysis of whole-exome sequencing (WES) and RNA sequencing data. Results: The most frequently mutated genes were TP53, TTN, MUC16, and CSMD3. Their frequencies in homdel and wild are 46% and 48%, 43% and 46%, 35% and 41%, 33% and 38%, respectively. There was no significant difference of tumor mutational burden (TMB) between homdel and wild (median TMB, 133 in homdel vs 177 in wild; Wilcoxon test, p = 0.11), and clinical characteristics including age, gender, smoking history, and tumor stage were not significantly different between homdel and wild. Homdel had a shorter overall survival (OS) than wild (Log-rank test, p = 0.04, Hazard Ratio: 0.7, 95% CI: 0.49-1.02), but there was no significant difference in progression-free survival (PFS) (Log-rank test, p = 0.05, Hazard Ratio: 0.73, 95% CI: 0.51-1.04). We used single sample gene set enrichment analysis (ssGSEA) to calculate the enrichment score (ES) of 25 immune-related pathways such as antigen presentation and T cell-mediated immunity, and then used the consensus clustering algorithm (ConsensusClusterPlus) to cluster homdel and wild respectively, and both clustered into low and high immune infiltration groups. For the high immune infiltration and low immune infiltration in homdel and wild, high immune infiltration had a longer OS (Log-rank test, p = 0.009, Hazard Ratio: 2.19, 95% CI: 1.22-3.94) and PFS (Log-rank test, p = 0.044, Hazard Ratio: 1.8, 95% CI: 1.01-3.2) than low immune infiltration in homdel. However, there was no significant heterogeneity between high and immune infiltration in terms of PFS (Log-rank test, p = 0.28, Hazard Ratio: 1.21, 95% CI: 0.87-1.68) and OS (Log-rank test, p = 0.96, Hazard Ratio: 1.01, 95% CI: 0.71-1.44) in the wild group, the wild group had longer OS than homdel group with low immune infiltration (Log-rank test, p = 0.003, Hazard Ratio: 0.5, 95% CI: 0.29-0.88), while had the same OS with homdel with high immune infiltration, irrespective of immune infiltration. And so was PFS (Log-rank test, p = 0.005, Hazard Ratio: 0.48, 95% CI: 0.27-0.82). Conclusions: CDKN2A/B homdel was an unfavorable prognostic factor for LUAD, but which with high immune infiltration might improve patient survival time.

Wild and farmed burbot Lota lota: differences in energy consumption and behavior during the spawning season

Farmed fish released in a native environment can display different spawning behaviour compared to their wild conspecifics. In our study, farmed and wild burbot, a species recently introduced for aquacultural production, were equipped with electromyogram (EMG) radio tags. EMG biotelemetry allows a description of the spatial distribution of fish together with simultaneous measurements of individual energy consumption. Farmed burbot were released into the wild to simulate stocking or hatchery escape and were observed over a nocturnal phase during November to January. The observational period was assumed to cover the whole spawning season, including an expected peak of spawning activity determined according to egg production by naturally spawning burbot in an experimental seminatural river channel. We detected increased energy consumption and lower movement activity at the time of expected peak spawning for wild burbot only. Across the whole spawning season, farmed females showed lower movement activity and energy consumption than wild females, whereas the opposite results were found for farmed males. Farmed and wild fish kept larger distances between each other than the individuals within a group (farmed and wild) across the whole spawning season. The closest positions occurred between males and females in the wild group, while for farmed fish, the closest position was found within the same sex. Sexually conditioned energy consumption and spatial distribution differed between wild and farmed fish.

Effect of Dietary Carotenoids on Reproducers of Amazon River Prawn Macrobrachium amazonicum. Part 2: External Coloration, Accumulation of Astaxanthin in Body Tissues and Pigment Stability in Feed

The color is an important factor to distinguish the commercialized Amazon river prawns. The accumulation of pigments in the body can vary according to the prawn’s diet. In this work, ethanolic extracts of “buriti” and annatto rich in pigments were obtained and tested comparatively with synthetic astaxanthin in the feeding of adults of Macrobrachium amazonicum, together with a control group without pigments and a newly captured wild group. Levels of body pigments were measured using UV reflective spectroscopy and external staining by colorimetry. Differences were observed in the accumulation of astaxanthin in body tissues, differences in saturation between genders and that annatto extract has greater stability in the feed after water immersion (P˂0.05). Further studies are recommended to verify the ideal dosage of natural pigments in relation to synthetic astaxanthin that benefits the productive development of prawns.

Effect of -55C/T Polymorphism of Uncoupling Protein 3 Gene on Risk for New-Onset Diabetes in Chinese Peritoneal Dialysis Patients: A Prospective Cohort Study

<b><i>Background:</i></b> A high-glucose load in therapy can cause new-onset diabetes (NOD) in peritoneal dialysis (PD) patients. Genetic variability may result in risk modulation. <b><i>Objectives:</i></b> This study aims to investigate the association between −55C/T polymorphism of uncoupling protein 3 (UCP3) gene and the risk of NOD in PD patients. <b><i>Methods:</i></b> Nondiabetic incident PD patients between May 2005 and January 2017 were recruited (<i>n</i> = 154). −55C/T polymorphism of the UCP3 was genotyped in all participants at baseline. The cohort of wild group (−55CC) and mutant group (−55CT or −55TT) was built based on the genotypic difference. Insulin resistance was evaluated by the homeostasis model assessment method (HOMA-IR) during the follow-up. Binary logistic regression was performed to explore the association between HOMA-IR and genotypes. Competitive risk analysis was used to analyze the impact of −55C/T polymorphism of UCP3 on risk for NOD. <b><i>Results:</i></b> The cohort was followed for up to 164.6 months (median: 58.3 months; interquartile range: 30.7 months). During the follow-up, 14 NODs occurred in the mutant group, while only 3 occurred in the wild group. Patients in the mutant group had higher HOMA-IR (Odd ratio: 2.210; 95% CI: 1.043–4.680; <i>p</i> = 0.038). Genotype with the variant T allele turned out to be an independent predictor for NOD morbidity (HR: 7.639; 95% CI: 1.798–32.451; <i>p</i> = 0.006). <b><i>Conclusions:</i></b> The variant of T allele of UCP3 −55C/T polymorphism was an independent predictor for NOD in PD patients. Early identification of the genotype may provide scientific basis for patients’ clinic management.

A poor substitute for the real thing: captive-reared monarch butterflies are weaker, paler and have less elongated wings than wild migrants

For many animals and insects that are experiencing dramatic population declines, the only recourse for conservationists is captive rearing. To ensure success, reared individuals should be biologically indistinct from those in the wild. We tested if this is true with monarch butterflies, Danaus plexippus , which are increasingly being reared for release by citizens and commercial breeders. Since late-summer monarchs should be as migration capable as possible for surviving the arduous long-distance migration, we evaluated four migration-relevant traits across two groups of captive-reared monarchs ( n = 41 and 42) and one group of wild-caught migrants ( n = 41). Monarchs (descendants of wild individuals) were reared from eggs to adulthood either in a warm indoor room next to a window, or in an incubator that mimicked late-summer conditions. Using an apparatus consisting of a perch mounted to an electronic force gauge, we assessed ‘grip strength' of all groups, then used image analysis to measure forewing size, pigmentation and elongation. In three of the four traits, reared monarchs underperformed compared to wild ones, even those reared under conditions that should have produced migration-ready individuals. The average strength of reared monarchs combined was 56% less than the wild group, even when accounting for size. Their orange wing colour was paler (an indicator of poor condition and flight ability) and their forewings were less elongated (elongation is associated with migration propensity) than wild monarchs. The reason(s) behind these effects is unknown but could stem from the frequent disturbance and/or handling of reared monarchs, or the fact that rearing removes the element of natural selection from all stages. Regardless, these results explain prior tagging studies that showed reared monarchs have lower migratory success compared to wild.