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Article ; Online: Multiscale modeling in the framework of biological systems and its potential for spaceflight biology studies

Andrew Millar-Wilson / Órla Ward / Eolann Duffy / Gary Hardiman

iScience, Vol 25, Iss 11, Pp 105421- (2022)

2022

Abstract: Summary: A central tenet of systems biology is that biological systems are greater than the sum of their component parts. Spaceflight is associated with hazards including radiation exposure and microgravity which impact different echelons of biological ... ...

Abstract	Summary: A central tenet of systems biology is that biological systems are greater than the sum of their component parts. Spaceflight is associated with hazards including radiation exposure and microgravity which impact different echelons of biological organizations spanning molecular, cellular, organ, and organismal levels. These insults lead to physical damage, including muscle and bone loss, neurological damage, and impaired immunity. Mitochondrial dysfunction and biological alterations occurring during spaceflight have been reported. The health challenges presented by long-term space travel must be addressed and appropriate countermeasures developed to protect astronauts. Increasing quantity of multiomics data are being generated from cells and model organisms flown in space, with physiological data from astronauts. Systems biology approaches leveraging mathematical reasoning and computational modeling are required to characterize these components in a holistic fashion. In this review, we provide an historic perspective on multiscale biological systems modeling, followed by a discussion on its utility for spaceflight biology research.
Keywords	systems biology ; in silico biology ; space sciences ; Science ; Q
Language	English
Publishing date	2022-11-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Integrated Genomic and Bioinformatics Approaches to Identify Molecular Links between Endocrine Disruptors and Adverse Outcomes

Jacopo Umberto Verga / Matthew Huff / Diarmuid Owens / Bethany J. Wolf / Gary Hardiman

International Journal of Environmental Research and Public Health, Vol 19, Iss 574, p

2022 Volume 574

Abstract: Exposure to Endocrine Disrupting Chemicals (EDC) has been linked with several adverse outcomes. In this review, we examine EDCs that are pervasive in the environment and are of concern in the context of human, animal, and environmental health. We explore ...

Abstract	Exposure to Endocrine Disrupting Chemicals (EDC) has been linked with several adverse outcomes. In this review, we examine EDCs that are pervasive in the environment and are of concern in the context of human, animal, and environmental health. We explore the consequences of EDC exposure on aquatic life, terrestrial animals, and humans. We focus on the exploitation of genomics technologies and in particular whole transcriptome sequencing. Genome-wide analyses using RNAseq provides snap shots of cellular, tissue and whole organism transcriptomes under normal physiological and EDC perturbed conditions. A global view of gene expression provides highly valuable information as it uncovers gene families or more specifically, pathways that are affected by EDC exposures, but also reveals those that are unaffected. Hypotheses about genes with unknown functions can also be formed by comparison of their expression levels with genes of known function. Risk assessment strategies leveraging genomic technologies and the development of toxicology databases are explored. Finally, we review how the Adverse Outcome Pathway (AOP) has exploited this high throughput data to provide a framework for toxicology studies.
Keywords	Endocrine Disrupting Chemicals (EDC) ; DNA microarrays ; RNA sequencing ; Adverse Outcome Pathway (AOP) ; Molecular Initiating Event (MIE) ; Key Events (KE) ; Medicine ; R
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Study on Anti-Constipation Effects of Hemerocallis citrina Baroni through a Novel Strategy of Network Pharmacology Screening

Yuxuan Liang / Xiaoyi Wei / Rui Ren / Xuebin Zhang / Xiyao Tang / Jinglan Yang / Xiaoqun Wei / Riming Huang / Gary Hardiman / Yuanming Sun / Hong Wang

International Journal of Molecular Sciences, Vol 24, Iss 4844, p

2023 Volume 4844

Abstract: Daylily ( Hemerocallis citrina Baroni) is an edible plant widely distributed worldwide, especially in Asia. It has traditionally been considered a potential anti-constipation vegetable. This study aimed to investigate the anti-constipation effects of ... ...

Abstract	Daylily ( Hemerocallis citrina Baroni) is an edible plant widely distributed worldwide, especially in Asia. It has traditionally been considered a potential anti-constipation vegetable. This study aimed to investigate the anti-constipation effects of daylily from the perspective of gastro-intestinal transit, defecation parameters, short-chain organic acids, gut microbiome, transcriptomes and network pharmacology. The results show that dried daylily (DHC) intake accelerated the defecation frequency of mice, while it did not significantly alter the levels of short-chain organic acids in the cecum. The 16S rRNA sequencing showed that DHC elevated the abundance of Akkermansia , Bifidobacterium and Flavonifractor , while it reduced the level of pathogens (such as Helicobacter and Vibrio ). Furthermore, a transcriptomics analysis revealed 736 differentially expressed genes (DEGs) after DHC treatment, which are mainly enriched in the olfactory transduction pathway. The integration of transcriptomes and network pharmacology revealed seven overlapping targets ( Alb , Drd2 , Igf2 , Pon1 , Tshr , Mc2r and Nalcn ). A qPCR analysis further showed that DHC reduced the expression of Alb, Pon1 and Cnr1 in the colon of constipated mice. Our findings provide a novel insight into the anti-constipation effects of DHC.
Keywords	daylily ; constipation ; 16S rRNA ; transcriptomes ; network pharmacology ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Language	English
Publishing date	2023-03-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Fusion Genes in Prostate Cancer

Rebecca Morgan / Dulcie Keeley / E. Starr Hazard / Emma H. Allott / Bethany Wolf / Stephen J. Savage / Chanita Hughes Halbert / Sebastiano Gattoni-Celli / Gary Hardiman

Biology, Vol 11, Iss 625, p

A Comparison in Men of African and European Descent

2022 Volume 625

Abstract: Prostate cancer is one of the most prevalent cancers worldwide, particularly affecting men living a western lifestyle and of African descent, suggesting risk factors that are genetic, environmental, and socioeconomic in nature. In the USA, African ... ...

Abstract	Prostate cancer is one of the most prevalent cancers worldwide, particularly affecting men living a western lifestyle and of African descent, suggesting risk factors that are genetic, environmental, and socioeconomic in nature. In the USA, African American (AA) men are disproportionately affected, on average suffering from a higher grade of the disease and at a younger age compared to men of European descent (EA). Fusion genes are chimeric products formed by the merging of two separate genes occurring as a result of chromosomal structural changes, for example, inversion or trans/cis-splicing of neighboring genes. They are known drivers of cancer and have been identified in 20% of cancers. Improvements in genomics technologies such as RNA-sequencing coupled with better algorithms for prediction of fusion genes has added to our knowledge of specific gene fusions in cancers. At present AA are underrepresented in genomic studies of prostate cancer. The primary goal of this study was to examine molecular differences in predicted fusion genes in a cohort of AA and EA men in the context of prostate cancer using computational approaches. RNA was purified from prostate tissue specimens obtained at surgery from subjects enrolled in the study. Fusion gene predictions were performed using four different fusion gene detection programs. This identified novel putative gene fusions unique to AA and suggested that the fusion gene burden was higher in AA compared to EA men.
Keywords	prostate cancer ; fusion genes ; African American ; African descent ; European American ; RNA-sequencing ; Biology (General) ; QH301-705.5
Subject code	570
Language	English
Publishing date	2022-04-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Systems Analysis of the Liver Transcriptome in Adult Male Zebrafish Exposed to the Plasticizer (2-Ethylhexyl) Phthalate (DEHP)

Matthew Huff / Willian A. da Silveira / Oliana Carnevali / Ludivine Renaud / Gary Hardiman

Scientific Reports, Vol 8, Iss 1, Pp 1-

2018 Volume 17

Abstract: Abstract The organic compound diethylhexyl phthalate (DEHP) represents a high production volume chemical found in cosmetics, personal care products, laundry detergents, and household items. DEHP, along with other phthalates causes endocrine disruption in ...

Abstract	Abstract The organic compound diethylhexyl phthalate (DEHP) represents a high production volume chemical found in cosmetics, personal care products, laundry detergents, and household items. DEHP, along with other phthalates causes endocrine disruption in males. Exposure to endocrine disrupting chemicals has been linked to the development of several adverse health outcomes with apical end points including Non-Alcoholic Fatty Liver Disease (NAFLD). This study examined the adult male zebrafish (Danio rerio) transcriptome after exposure to environmental levels of DEHP and 17α-ethinylestradiol (EE2) using both DNA microarray and RNA-sequencing technologies. Our results show that exposure to DEHP is associated with differentially expressed (DE) transcripts associated with the disruption of metabolic processes in the liver, including perturbation of five biological pathways: ‘FOXA2 and FOXA3 transcription factor networks’, ‘Metabolic pathways’, ‘metabolism of amino acids and derivatives’, ‘metabolism of lipids and lipoproteins’, and ‘fatty acid, triacylglycerol, and ketone body metabolism’. DE transcripts unique to DEHP exposure, not observed with EE2 (i.e. non-estrogenic effects) exhibited a signature related to the regulation of transcription and translation, and ruffle assembly and organization. Collectively our results indicate that exposure to low DEHP levels modulates the expression of liver genes related to fatty acid metabolism and the development of NAFLD.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2018-02-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: A de novo transcriptome assembly approach elucidates the dynamics of ovarian maturation in the swordfish (Xiphias gladius)

Giorgia Gioacchini / Luca Marisaldi / Danilo Basili / Michela Candelma / Paolo Pignalosa / Riccardo Aiese Cigliano / Walter Sanseverino / Gary Hardiman / Oliana Carnevali

Scientific Reports, Vol 9, Iss 1, Pp 1-

2019 Volume 12

Abstract: Abstract The Mediterranean swordfish (Xiphias gladius) has been recently classified as overfished and in 2016, the International Commission for the Conservation of the Atlantic Tunas (ICCAT) established a multi-annual management plan to recover this ... ...

Abstract	Abstract The Mediterranean swordfish (Xiphias gladius) has been recently classified as overfished and in 2016, the International Commission for the Conservation of the Atlantic Tunas (ICCAT) established a multi-annual management plan to recover this stock. To successfully achieve this goal, knowledge about swordfish biology is needed. To date, few studies on swordfish have been performed and none of them has provided useful insights into the reproductive biology at molecular level. Here we set to characterise the molecular dynamics underlying ovarian maturation by employing a de novo transcriptome assembly approach. Differential gene expression analysis in mature and immature ovaries identified a number of differentially expressed genes associated with biological processes driving ovarian maturation. Focusing on ovarian steroidogenesis and vitellogenin uptake, we depict the molecular dynamics characterizing these processes while a phylogenetic analysis let us identify a candidate vitellogenin receptor. This is the first swordfish transcriptome assembly and these findings provide in-depth understanding of molecular processes describing ovarian maturation. Moreover, the establishment of a publicly available database containing information on the swordfish transcriptome aims to boost research on this species with the long-term of developing more comprehensive and successful stock management plans.
Keywords	Medicine ; R ; Science ; Q
Subject code	612
Language	English
Publishing date	2019-05-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Induced Torpor as a Countermeasure for Low Dose Radiation Exposure in a Zebrafish Model

Thomas Cahill / Willian Abraham da Silveira / Ludivine Renaud / Tucker Williamson / Hao Wang / Dongjun Chung / Ian Overton / Sherine S. L. Chan / Gary Hardiman

Cells, Vol 10, Iss 906, p

2021 Volume 906

Abstract: The development of the Artemis programme with the goal of returning to the moon is spurring technology advances that will eventually take humans to Mars and herald a new era of interplanetary space travel. However, long-term space travel poses unique ... ...

Abstract	The development of the Artemis programme with the goal of returning to the moon is spurring technology advances that will eventually take humans to Mars and herald a new era of interplanetary space travel. However, long-term space travel poses unique challenges including exposure to ionising radiation from galactic cosmic rays and potential solar particle events, exposure to microgravity and specific nutritional challenges arising from earth independent exploration. Ionising radiation is one of the major obstacles facing future space travel as it can generate oxidative stress and directly damage cellular structures such as DNA, in turn causing genomic instability, telomere shortening, extracellular-matrix remodelling and persistent inflammation. In the gastrointestinal tract (GIT) this can lead to leaky gut syndrome, perforations and motility issues, which impact GIT functionality and affect nutritional status. While current countermeasures such as shielding from the spacecraft can attenuate harmful biological effects, they produce harmful secondary particles that contribute to radiation exposure. We hypothesised that induction of a torpor-like state would confer a radioprotective effect given the evidence that hibernation extends survival times in irradiated squirrels compared to active controls. To test this hypothesis, a torpor-like state was induced in zebrafish using melatonin treatment and reduced temperature, and radiation exposure was administered twice over the course of 10 days. The protective effects of induced-torpor were assessed via RNA sequencing and qPCR of mRNA extracted from the GIT. Pathway and network analysis were performed on the transcriptomic data to characterise the genomic signatures in radiation, torpor and torpor + radiation groups. Phenotypic analyses revealed that melatonin and reduced temperature successfully induced a torpor-like state in zebrafish as shown by decreased metabolism and activity levels. Genomic analyses indicated that low dose radiation caused DNA damage and oxidative stress triggering a stress response, including steroidal signalling and changes to metabolism, and cell cycle arrest. Torpor attenuated the stress response through an increase in pro-survival signals, reduced oxidative stress via the oxygen effect and detection and removal of misfolded proteins. This proof-of-concept model provides compelling initial evidence for utilizing an induced torpor-like state as a potential countermeasure for radiation exposure.
Keywords	torpor ; countermeasure ; space ; radiation ; zebrafish ; metabolism ; Biology (General) ; QH301-705.5
Subject code	600
Language	English
Publishing date	2021-04-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Transcriptomic analysis of short-term 17α-ethynylestradiol exposure in two Californian sentinel fish species sardine (Sardinops sagax) and mackerel (Scomber japonicus)

Renaud, Ludivine / Nisha Agarwal / Dylan J. Richards / Silvia Falcinelli / E. Starr Hazard / Oliana Carnevali / John Hyde / Gary Hardiman

Elsevier Ltd Environmental pollution. 2019 Jan., v. 244

2019

Abstract: Endocrine disrupting chemicals (EDCs) are substances which disrupt normal functioning of the endocrine system by interfering with hormone regulated physiological pathways. Aquatic environments provide the ultimate reservoir for many EDCs as they enter ... ...

Abstract	Endocrine disrupting chemicals (EDCs) are substances which disrupt normal functioning of the endocrine system by interfering with hormone regulated physiological pathways. Aquatic environments provide the ultimate reservoir for many EDCs as they enter rivers and the ocean via effluent discharges and accumulate in sediments. One EDC widely dispersed in municipal wastewater effluent discharges is 17α-ethynylestradiol (EE2), which is one of the most widely prescribed medicines. EE2 is a bio-active estrogen employed in the majority of oral contraceptive pill formulations. As evidence of the health risks posed by EDCs mount, there is an urgent need to improve diagnostic tools for monitoring the effects of pollutants. As the cost of high throughput sequencing (HTS) diminishes, transcriptional profiling of an organism in response to EDC perturbation presents a cost-effective way of screening a wide range of endocrine responses. Coastal pelagic filter feeding fish species analyzed using HTS provide an excellent tool for EDC risk assessment in the marine environment. Unfortunately, there are limited genome sequence data and annotation for many of these species including Pacific sardine (Sardinops sagax) and chub mackerel (Scomber japonicus), which limits the utility of molecular tools such as HTS to interrogate the effects of endocrine disruption. In this study, we carried out RNA sequencing (RNAseq) of liver RNA harvested from wild sardine and mackerel exposed for 5 h under laboratory conditions to a concentration of 12.5 pM EE2 in the tank water. We developed an analytical framework for transcriptomic analyses of species with limited genomic information. EE2 exposure altered expression patterns of key genes involved in important metabolic and physiological processes. The systems approach presented here provides a powerful tool for obtaining a comprehensive picture of endocrine disruption in aquatic organisms.
Keywords	RNA ; Sardinops sagax ; Scomber japonicus ; cost effectiveness ; diagnostic techniques ; endocrine system ; endocrine-disrupting chemicals ; estrogens ; fish feeding ; genes ; genomics ; high-throughput nucleotide sequencing ; laboratory experimentation ; liver ; mackerel ; marine environment ; monitoring ; municipal wastewater ; nucleotide sequences ; pollutants ; risk ; risk assessment ; rivers ; sardines ; screening ; sediments ; transcription (genetics) ; transcriptomics
Language	English
Dates of publication	2019-01
Size	p. 926-937.
Publishing place	Elsevier Ltd
Document type	Article
ZDB-ID	280652-6
ISSN	1873-6424 ; 0013-9327 ; 0269-7491
ISSN (online)	1873-6424
ISSN	0013-9327 ; 0269-7491
DOI	10.1016/j.envpol.2018.10.058
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: ShinyGPA

Emma Kortemeier / Paula S Ramos / Kelly J Hunt / Hang J Kim / Gary Hardiman / Dongjun Chung

PLoS ONE, Vol 13, Iss 1, p e

An interactive visualization toolkit for investigating pleiotropic architecture using GWAS datasets.

2018 Volume 0190949

Abstract: In spite of accumulating evidence suggesting that different complex traits share a common risk basis, namely pleiotropy, effective investigation of pleiotropic architecture still remains challenging. In order to address this challenge, we developed ... ...

Abstract	In spite of accumulating evidence suggesting that different complex traits share a common risk basis, namely pleiotropy, effective investigation of pleiotropic architecture still remains challenging. In order to address this challenge, we developed ShinyGPA, an interactive and dynamic visualization toolkit to investigate pleiotropic structure. ShinyGPA requires only the summary statistics from genome-wide association studies (GWAS), which reduces the burden on researchers using this tool. ShinyGPA allows users to effectively investigate genetic relationships among phenotypes using a flexible low-dimensional visualization and an intuitive user interface. In addition, ShinyGPA provides joint association mapping functionality that can facilitate biological understanding of the pleiotropic architecture. We analyzed GWAS summary statistics for 12 phenotypes using ShinyGPA and obtained visualization results and joint association mapping results that are well supported by the literature. The visualization produced by ShinyGPA can also be used as a hypothesis generating tool for relationships between phenotypes, which might also be used to improve the design of future genetic studies. ShinyGPA is currently available at https://dongjunchung.github.io/GPA/.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2018-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Author Correction

Afshin Beheshti / Kaushik Chakravarty / Homer Fogle / Hossein Fazelinia / Willian A. da Silveira / Valery Boyko / San-Huei Lai Polo / Amanda M. Saravia-Butler / Gary Hardiman / Deanne Taylor / Jonathan M. Galazka / Sylvain V. Costes

Scientific Reports, Vol 10, Iss 1, Pp 1-

Multi-omics analysis of multiple missions to space reveal a theme of lipid dysregulation in mouse liver

2020 Volume 1

Abstract: An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...

Abstract	An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2020-01-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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