scholarly journals Epigenome and phenome study reveals circulating markers pertinent to brain health

2021 ◽  
Author(s):  
Danni A Gadd ◽  
Robert F Hillary ◽  
Daniel L. McCartney ◽  
Liu Shi ◽  
Robert I McGeachan ◽  
...  
Keyword(s):  
Association Study ◽  
Quantitative Trait ◽  
Plasma Proteins ◽  
Multiple Testing ◽  
Current Knowledge ◽  
Protein Markers ◽  
Brain Health ◽  
Circulating Markers ◽  
Epigenetic Signatures ◽  
Insight Into

Characterising associations between the epigenome, proteome and phenome may provide insight into molecular regulation of biological pathways governing health. However, epigenetic signatures for many neurologically-associated plasma protein markers remain uncharacterised. Here, we report an epigenome and phenome-wide association study of the circulating proteome in relation to brain health. We perform epigenome-wide studies of 4,235 plasma proteins (n=778), identifying 2,895 CpG-protein associations (protein quantitative trait methylation loci; pQTMs) after stringent correction for multiple testing. These were independent of known genetic protein quantitative trait loci (pQTL) and common lifestyle effects, extending current knowledge by analysing a further 3,286 protein measurements with 2,854 novel pQTMs. We then perform a phenome-wide study of each protein in relation to neurological traits in 1,065 individuals, identifying 644 proteins related to cognitive, brain imaging phenotypes or APOE status. By integrating our pQTM dataset with our phenome association study, we uncovered 88 epigenetic associations for protein markers of neurological traits, 83 of which were previously unreported. These data are pertinent to understanding heterogeneity in brain health.

Analysis of plasma protein biomarkers from the phase 3 CONCUR study of regorafenib in Asian patients with metastatic colorectal cancer (mCRC).

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 672-672 ◽  
Author(s):  
Michael Teufel ◽  
Joachim Kalmus ◽  
Mark Daniel Rutstein ◽  
Karl Koechert ◽  
Henrik Seidel ◽  
...  
Keyword(s):  
Plasma Proteins ◽  
Multiple Testing ◽  
Statistical Significance ◽  
Protein Markers ◽  
Correct Trial ◽  
Phase 3 ◽  
Treatment Benefit ◽  
Protein Biomarker ◽  
Asian Patients ◽  
Biomarker Analysis

672 Background: In the randomized phase 3 CONCUR trial (NCT01584830), regorafenib significantly improved overall survival (OS) and progression-free survival (PFS) vs placebo (PBO) in Asian patients (n = 136 regorafenib; n = 68 PBO) with treatment-refractory mCRC (HR [95% CI]: OS 0.55 [0.40‒0.77]; PFS 0.31 (0.22‒0.44]). Protein biomarker data from the phase 3 CORRECT trial of mostly Western patients with mCRC identified TIE-1 as a potential predictor of clinical response to regorafenib; however, this association was not significant in multivariable analyses. We present an exploratory protein biomarker analysis of patients in CONCUR. Methods: Sixteen proteins of interest, many of which are involved in angiogenesis, were quantified by multiplex immunoassay or ELISA in plasma samples collected at study entry from 121/204 (59%) patients (n = 83 regorafenib; n = 38 PBO). Potential predictive and prognostic effects were evaluated. Results: The biomarker cohort was representative of the overall study population in major baseline demographic factors, OS (HR 0.61; 95% CI 0.40‒0.93), and PFS (HR 0.25; 95% CI 0.16‒0.39). Elevated levels of ANG-2 (HR 2.46; p = 0.0016) and VEGF-A (HR 1.38; p = 0.03) were associated with poor OS prognosis; however, no significant association with treatment OS benefit for regorafenib vs PBO was observed for either marker (ANG-2: HR 0.76; p = 0.3307; VEGF-A: HR 0.83; p = 0.20). Elevated levels of five plasma proteins were associated with poor PFS prognosis: ANG-2 (HR 1.73; p = 0.0085), VEGF-A (HR 1.30; p = 0.0308), IL-8 (HR 1.67; p = 0.0014), VWF (HR 2.39; p = 0.0029), and IGF-BP2 (HR 1.71; p = 0.0384). Elevated levels of IL-8 (HR 0.70; p = 0.019), VWF (HR 0.53; p = 0.0312), and IGF-BP2 (HR 0.60; p = 0.0336) showed a modest interaction with regorafenib PFS; however, these results did not reach statistical significance after adjustment for multiple testing (p = 0.0045). Conclusions: None of the plasma proteins analyzed were predictive of regorafenib clinical benefit as measured by both OS and PFS in Asian patients with mCRC. These results, as well as those in CORRECT, suggest that rationally selected protein markers are not suitable to predict treatment benefit of regorafenib. Clinical trial information: NCT01584830.

Nucleosome dynamics

2006 ◽  
Vol 73 ◽  
pp. 109-119 ◽  
Author(s):  
Chris Stockdale ◽  
Michael Bruno ◽  
Helder Ferreira ◽  
Elisa Garcia-Wilson ◽  
Nicola Wiechens ◽  
...  
Keyword(s):  
High Resolution ◽  
Chromatin Structure ◽  
Current Knowledge ◽  
Dynamic Properties ◽  
Structure And Dynamics ◽  
Nucleosome Dynamics ◽  
Sharp Focus ◽  
Recent Advances ◽  
Insight Into ◽  
Chromatin Structure And Dynamics

In the 30 years since the discovery of the nucleosome, our picture of it has come into sharp focus. The recent high-resolution structures have provided a wealth of insight into the function of the nucleosome, but they are inherently static. Our current knowledge of how nucleosomes can be reconfigured dynamically is at a much earlier stage. Here, recent advances in the understanding of chromatin structure and dynamics are highlighted. The ways in which different modes of nucleosome reconfiguration are likely to influence each other are discussed, and some of the factors likely to regulate the dynamic properties of nucleosomes are considered.

Lactobacillus plantarum DR7 improved brain health in aging rats via the serotonin, inflammatory and apoptosis pathways

2020 ◽  
Vol 11 (8) ◽  
pp. 753-766
Author(s):  
A.I. Zaydi ◽  
L.-C. Lew ◽  
Y.-Y. Hor ◽  
M.H. Jaafar ◽  
L.-O. Chuah ◽  
...  
Keyword(s):  
Lactobacillus Plantarum ◽  
Cognitive Functions ◽  
High Fat Diet ◽  
Normal Diet ◽  
Sprague Dawley ◽  
Brain Health ◽  
High Fat ◽  
Dietary Strategy ◽  
Apoptosis Pathways ◽  
Insight Into

Aging processes affect the brain in many ways, ranging from cellular to functional levels which lead to cognitive decline and increased oxidative stress. The aim of this study was to investigate the potentials of Lactobacillus plantarum DR7 on brain health including cognitive and memory functions during aging and the impacts of high fat diet during a 12-week period. Male Sprague-Dawley rats were separated into six groups: (1) young animals on normal diet (ND, (2) young animals on a high fat diet (HFD), (3) aged animals on ND, (4) aged animals on HFD, (5) aged animals on HFD and L. plantarum DR7 (109 cfu/day) and (6) aged animals receiving HFD and lovastatin. To induce ageing, all rats in group 3 to 6 were injected sub-cutaneously at 600 mg/kg/day of D-galactose daily. The administration of DR7 has reduced anxiety accompanied by enhanced memory during behavioural assessments in aged-HFD rats (P<0.05). Hippocampal concentration of all three pro-inflammatory cytokines were increased during aging but reduced upon administration of both statin and DR7. Expressions of hippocampal neurotransmitters and apoptosis genes showed reduced expressions of indoleamine dioxygenase and P53 accompanied by increased expression of TPH1 in aged- HFD rats administered with DR7, indicating potential effects of DR7 along the pathways of serotonin and oxidative senescence. This study provided an insight into potentials of L. plantarum DR7 as a prospective dietary strategy to improve cognitive functions during aging. This study provided an insight into potentials of L. plantarum DR7 as a prospective dietary strategy to improve cognitive functions during aging.

scholarly journals Effects of Glucosinolate-Derived Isothiocyanates on Fungi: A Comprehensive Review on Direct Effects, Mechanisms, Structure-Activity Relationship Data and Possible Agricultural Applications

2021 ◽  
Vol 7 (7) ◽  
pp. 539
Author(s):  
Tamás Plaszkó ◽  
Zsolt Szűcs ◽  
Gábor Vasas ◽  
Sándor Gonda
Keyword(s):  
Mycorrhizal Fungi ◽  
Current Knowledge ◽  
Synergistic Activity ◽  
Microbial Composition ◽  
Soil Microbial ◽  
Structure Activity ◽  
Agricultural Applications ◽  
Antifungal Action ◽  
Insight Into ◽  
Soil Microbial Composition

Plants heavily rely on chemical defense systems against a variety of stressors. The glucosinolates in the Brassicaceae and some allies are the core molecules of one of the most researched such pathways. These natural products are enzymatically converted into isothiocyanates (ITCs) and occasionally other defensive volatile organic constituents (VOCs) upon fungal challenge or tissue disruption to protect the host against the stressor. The current review provides a comprehensive insight on the effects of the isothiocyanates on fungi, including, but not limited to mycorrhizal fungi and pathogens of Brassicaceae. In the review, our current knowledge on the following topics are summarized: direct antifungal activity and the proposed mechanisms of antifungal action, QSAR (quantitative structure-activity relationships), synergistic activity of ITCs with other agents, effects of ITCs on soil microbial composition and allelopathic activity. A detailed insight into the possible applications is also provided: the literature of biofumigation studies, inhibition of post-harvest pathogenesis and protection of various products including grains and fruits is also reviewed herein.

scholarly journals Interplay between cofactors and transcription factors in hematopoiesis and hematological malignancies

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Zi Wang ◽  
Pan Wang ◽  
Yanan Li ◽  
Hongling Peng ◽  
Yu Zhu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Hematological Malignancies ◽  
Current Knowledge ◽  
Regulation Of Gene Expression ◽  
Hematologic Disorders ◽  
Cell Lineages ◽  
Stage Of Development ◽  
Transcription Complexes ◽  
Insight Into

AbstractHematopoiesis requires finely tuned regulation of gene expression at each stage of development. The regulation of gene transcription involves not only individual transcription factors (TFs) but also transcription complexes (TCs) composed of transcription factor(s) and multisubunit cofactors. In their normal compositions, TCs orchestrate lineage-specific patterns of gene expression and ensure the production of the correct proportions of individual cell lineages during hematopoiesis. The integration of posttranslational and conformational modifications in the chromatin landscape, nucleosomes, histones and interacting components via the cofactor–TF interplay is critical to optimal TF activity. Mutations or translocations of cofactor genes are expected to alter cofactor–TF interactions, which may be causative for the pathogenesis of various hematologic disorders. Blocking TF oncogenic activity in hematologic disorders through targeting cofactors in aberrant complexes has been an exciting therapeutic strategy. In this review, we summarize the current knowledge regarding the models and functions of cofactor–TF interplay in physiological hematopoiesis and highlight their implications in the etiology of hematological malignancies. This review presents a deep insight into the physiological and pathological implications of transcription machinery in the blood system.

Genetic dissection of 2-heptenal content in soybean (Glycine max) seed through genome-wide association study

2020 ◽  
Vol 71 (10) ◽  
pp. 884
Author(s):  
Zhikun Wang ◽  
Mingming Yang ◽  
Yuanzhuo Wang ◽  
Chao Yang ◽  
Xue Zhao ◽  
...  
Keyword(s):  
Glycine Max ◽  
Association Study ◽  
Quantitative Trait ◽  
Genome Wide Association Study ◽  
Fatty Acid Content ◽  
Soybean Seed ◽  
Genome Wide Association ◽  
Quality Characteristic ◽  
Genome Wide ◽  
A Genome

Association analysis is an alternative to conventional, family-based methods for detecting the location of gene(s) or quantitative trait loci (QTLs), and provides relatively high resolution in terms of defining the genome position of a gene or QTL. Flavour is an essential quality characteristic of soymilk; however, soymilk contains volatile compounds unacceptable to consumers. One of main constituents in the volatiles of normal soymilk is 2-heptenal, which is thought to be a degradative oxidation product of polyunsaturated acids. In this study, a genome-wide association study using 24651 single-nucleotide polymorphisms (SNPs) was performed to identify quantitative trait nucleotides (QTNs) controlling 2-heptenal content in soybean (Glycine max (L.) Merr.) seed from a natural population of 110 soybean germplasm accessions. We detected 62 significant QTNs located on 18 different chromosomes that are significantly associated with 2-heptenal content in soybean seed. Among these, 17 QTNs co-localised with QTLs previously found to be related to protein, oil and/or fatty acid content in soybean seed. We also identified some candidate genes involved in lipid metabolism. These findings further our understanding of the genetic basis of 2-heptenal content in soybean seed and the improvement of marker-assisted breeding efficiency, which will be important for breeding soybean cultivars with low 2-heptenal content.

scholarly journals A Genome-Wide Association Study Identifies Protein Quantitative Trait Loci (pQTLs)

PLoS Genetics ◽  
2008 ◽  
Vol 4 (5) ◽  
pp. e1000072 ◽  
Author(s):  
David Melzer ◽  
John R. B. Perry ◽  
Dena Hernandez ◽  
Anna-Maria Corsi ◽  
Kara Stevens ◽  
...  
Keyword(s):  
Quantitative Trait Loci ◽  
Association Study ◽  
Quantitative Trait ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Genome Wide ◽  
A Genome ◽  
Trait Loci

A Proteome-Wide Association Study Identified Candidate Human Brain Proteins Associated with Coffee Consumption

2021 ◽  
Author(s):  
Chun'e Li ◽  
Xiao Liang ◽  
Yumeng Jia ◽  
Yan Wen ◽  
Huijie Zhang ◽  
...  
Keyword(s):  
Human Brain ◽  
Association Study ◽  
Plasma Proteins ◽  
Genome Wide Association Study ◽  
Genetic Correlations ◽  
Coffee Consumption ◽  
Genetic Associations ◽  
Brain Proteins ◽  
Genome Wide ◽  
Brain Proteome

Abstract Background Increasing evidence suggests the association between caffeine and the brain and nervous system. However, there is limited research on the genetic associations between coffee consumption subtypes and brain proteome, plasma proteomes, and peripheral metabolites. Methods First, proteome-wide association study (PWAS) of coffee consumption subtypes was performed by integrating two independent genome-wide association study (GWAS) datasets (91,462–502,650 subjects) with two reference human brain proteomes (ROS/MAP and Banner), by using the FUSION pipeline. Second, transcriptome-wide association study (TWAS) analysis of coffee consumption subtypes was conducted by integrating the two gene expression weight references (RNAseq and splicing) of brain RNA-seq and the two GWAS datasets (91,462–502,650 subjects) of coffee consumption subtypes. Finally, we used the LD Score Regression (LDSC) analysis to evaluate the genetic correlations of coffee consumption subtypes with plasma proteomes and peripheral metabolites. Results For the traits related to coffee consumption, we identified 3 common PWAS proteins, such as MADD (P PWAS−Banner−dis=0.0114, P PWAS−ROS/MAP−rep =0.0489). In addition, 11 common TWAS genes were found in two cohorts, such as ARPC2 (P TWAS−splicing−dis =2063×10− 12, P TWAS−splicing−dis =1.25×10− 10, P TWAS−splicing−dis =1.24e-08, P TWAS−splicing−rep =3.25×10− 9 and P TWAS−splicing−rep =3.42×10− 13). Importantly, we have identified 8 common genes between PWAS and TWAS, such as ALDH2 (P PWAS−banner−rep =1.22×10− 22, PTWAS− splicing−dis = 4.54×10− 92). For the LDSC analysis of human plasma proteome, we identified 11 plasma proteins, such as CHL1 (P dis = 0.0151, P rep =0.0438). For the LDSC analysis of blood metabolites, 5 metabolites have been found, such as myo-inositol (P dis = 0.0073, P dis = 0.0152, P dis =0.0414, P rep =0.0216). Conclusions We identified several brain proteins and genes associated with coffee consumption subtypes. In addition, we also detected several candidate plasma proteins and metabolites related to these subtypes.

scholarly journals High-Performance Computing of BEAST/BEAGLE in Bayesian Phylogenetics using SDumont Hybrid Resources

2020 ◽  
Author(s):  
Kary Ocaña ◽  
Micaella Coelho ◽  
Guilherme Freire ◽  
Carla Osthoff
Keyword(s):  
High Performance Computing ◽  
High Performance ◽  
Current Knowledge ◽  
Data Sets ◽  
Length Estimation ◽  
Computationally Intensive ◽  
Mcmc Chain ◽  
Performance Computing ◽  
Insight Into

Bayesian phylogenetic algorithms are computationally intensive. BEAST 1.10 inferences made use of the BEAGLE 3 high-performance library for efficient likelihood computations. The strategy allows phylogenetic inference and dating in current knowledge for SARS-CoV-2 transmission. Follow-up simulations on hybrid resources of Santos Dumont supercomputer using four phylogenomic data sets, we characterize the scaling performance behavior of BEAST 1.10. Our results provide insight into the species tree and MCMC chain length estimation, identifying preferable requirements to improve the use of high-performance computing resources. Ongoing steps involve analyzes of SARS-CoV-2 using BEAST 1.8 in multi-GPUs.

scholarly journals Vaccinium gaultherioides: Another insight into water relations of alpine dwarf shrubs

2015 ◽  
Vol 2 ◽  
pp. e004 ◽  
Author(s):  
Andrea Ganthaler ◽  
S. Mayr
Keyword(s):  
Growth Form ◽  
Current Knowledge ◽  
European Alps ◽  
Hydraulic Parameters ◽  
Turgor Loss Point ◽  
Dwarf Shrubs ◽  
Hydraulic Safety ◽  
Conductivity Cell ◽  
Osmotic Properties ◽  
Insight Into

Dwarf shrubs exhibit different requirements for a safe and efficient water supply compared to trees due their basitonic branching and low growth height. Though, only few studies dealt with the hydraulics of this growth form. Here we report key hydraulic parameters (vulnerability to drought-induced embolism, xylem hydraulic conductivity, cell osmotic potential, potential at turgor loss point) and related wood anatomical traits for Vaccinium gaultherioides, a wide-spread species in the European Alps. The results affirm the current knowledge, by indicating a relatively risky hydraulic strategy with low hydraulic safety compared to alpine trees and osmotic properties connected to the species’ soil humidity requirements.

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