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Article ; Online: Deconvoluting Wavelengths Leading to Fluorescent Light Induced Inflammation and Cellular Stress in Zebrafish (Danio rerio)

Mikki Boswell / William Boswell / Yuan Lu / Markita Savage / Ronald B. Walter

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

2020 Volume 13

Abstract: Abstract Fluorescent light (FL) has been shown to induce a cellular immune and inflammatory response that is conserved over 450 MY of evolutionary divergence and among vertebrates having drastically different lifestyles such as Mus musculus, Danio rerio, ...

Abstract	Abstract Fluorescent light (FL) has been shown to induce a cellular immune and inflammatory response that is conserved over 450 MY of evolutionary divergence and among vertebrates having drastically different lifestyles such as Mus musculus, Danio rerio, Oryzias latipes and Xiphophorus maculatus. This surprising finding of an inflammation and immune response to FL not only holds for direct light receiving organs (skin) but is also observed within internal organs (brain and liver). Light responsive genetic circuitry initiated by the IL1B regulator induces a highly conserved acute phase response in each organ assessed for all of biological models surveyed to date; however, the specific light wavelengths triggering this response have yet to be determined so investigation of mechanisms and/or light specific molecule(s) leading to this response are difficult to assess. To understand how specific light wavelengths are received in both external and internal organs, zebrafish were exposed to specific 50 nm light wavebands spanning the visible spectrum from 300–600 nm and the genetic responses to each waveband exposure were assessed. Surprisingly, the induced cellular stress response previously observed following FL exposure is not triggered by the lower “damaging” wavelengths of light (UVB and UVA from 300–400 nm) but instead is maximally induced by higher wavelengths ranging from 450–500 nm in skin to 500–600 nm in both brain and liver).
Keywords	Medicine ; R ; Science ; Q
Subject code	535
Language	English
Publishing date	2020-02-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Deconvoluting Wavelengths Leading to Fluorescent Light Induced Inflammation and Cellular Stress in Zebrafish (Danio rerio)

Mikki Boswell / William Boswell / Yuan Lu / Markita Savage / Ronald B. Walter

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

2020 Volume 13

Abstract	Abstract Fluorescent light (FL) has been shown to induce a cellular immune and inflammatory response that is conserved over 450 MY of evolutionary divergence and among vertebrates having drastically different lifestyles such as Mus musculus, Danio rerio, Oryzias latipes and Xiphophorus maculatus. This surprising finding of an inflammation and immune response to FL not only holds for direct light receiving organs (skin) but is also observed within internal organs (brain and liver). Light responsive genetic circuitry initiated by the IL1B regulator induces a highly conserved acute phase response in each organ assessed for all of biological models surveyed to date; however, the specific light wavelengths triggering this response have yet to be determined so investigation of mechanisms and/or light specific molecule(s) leading to this response are difficult to assess. To understand how specific light wavelengths are received in both external and internal organs, zebrafish were exposed to specific 50 nm light wavebands spanning the visible spectrum from 300–600 nm and the genetic responses to each waveband exposure were assessed. Surprisingly, the induced cellular stress response previously observed following FL exposure is not triggered by the lower “damaging” wavelengths of light (UVB and UVA from 300–400 nm) but instead is maximally induced by higher wavelengths ranging from 450–500 nm in skin to 500–600 nm in both brain and liver).
Keywords	Medicine ; R ; Science ; Q
Subject code	535
Language	English
Publishing date	2020-02-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Transcriptome assembly and candidate genes involved in nutritional programming in the swordtail fish Xiphophorus multilineatus

Yuan Lu / Charlotte M. Klimovich / Kalen Z. Robeson / William Boswell / Oscar Ríos-Cardenas / Ronald B. Walter / Molly R. Morris

PeerJ, Vol 5, p e

2017 Volume 3275

Abstract: Background Nutritional programming takes place in early development. Variation in the quality and/or quantity of nutrients in early development can influence long-term health and viability. However, little is known about the mechanisms of nutritional ... ...

Abstract	Background Nutritional programming takes place in early development. Variation in the quality and/or quantity of nutrients in early development can influence long-term health and viability. However, little is known about the mechanisms of nutritional programming. The live-bearing fish Xiphophorus multilineatus has the potential to be a new model for understanding these mechanisms, given prior evidence of nutritional programming influencing behavior and juvenile growth rate. We tested the hypotheses that nutritional programming would influence behaviors involved in energy homeostasis as well gene expression in X. multilineatus. Methods We first examined the influence of both juvenile environment (varied in nutrition and density) and adult environment (varied in nutrition) on behaviors involved in energy acquisition and energy expenditure in adult male X. multilineatus. We also compared the behavioral responses across the genetically influenced size classes of males. Males stop growing at sexual maturity, and the size classes of can be identified based on phenotypes (adult size and pigment patterns). To study the molecular signatures of nutritional programming, we assembled a de novo transcriptome for X. multilineatus using RNA from brain, liver, skin, testis and gonad tissues, and used RNA-Seq to profile gene expression in the brains of males reared in low quality (reduced food, increased density) and high quality (increased food, decreased density) juvenile environments. Results We found that both the juvenile and adult environments influenced the energy intake behavior, while only the adult environment influenced energy expenditure. In addition, there were significant interactions between the genetically influenced size classes and the environments that influenced energy intake and energy expenditure, with males from one of the four size classes (Y-II) responding in the opposite direction as compared to the other males examined. When we compared the brains of males of the Y-II size class reared in a low quality ...
Keywords	RNA-Seq ; Xiphophorus multilineatus ; Transcriptome ; Energy homeostasis ; Medicine ; R
Subject code	590
Language	English
Publishing date	2017-05-01T00:00:00Z
Publisher	PeerJ Inc.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Molecular genetic response of Xiphophorus maculatus–X. couchianus interspecies hybrid skin to UVB exposure

Lu, Yuan / Kuan Yang / Manfred Schartl / Mikki Bowswell / Ronald B. Walter / William Bowswell

Comparative biochemistry and physiology. 2015 Dec., v. 178

2015

Abstract: The phenotypic and genetic similarities between Xiphophorus and human melanoma render Xiphophorus a useful animal model for studying the genetic basis of melanoma etiology. In the Xiphophorus model, melanoma has been shown to be inducible by ultraviolet ... ...

Abstract	The phenotypic and genetic similarities between Xiphophorus and human melanoma render Xiphophorus a useful animal model for studying the genetic basis of melanoma etiology. In the Xiphophorus model, melanoma has been shown to be inducible by ultraviolet light (UVB) exposure among interspecies hybrids, but not in parental line fish similarly treated. This leads to questions of what genes are responsive to UVB exposure in the skin of the interspecies hybrids, as well as how parental alleles in hybrids may be differentially regulated and the potential roles they may play in induced melanomagenesis. To address these questions, we produced X. maculatus Jp 163 B×X. couchianus (Sp-Couch) F1 hybrid fish, exposed both hybrid and parental fish to UVB, and performed gene expression profiling of the skin using RNA-Seq methodology. We characterized a group of unique UVB-responsive genes in Sp-Couch hybrid including dct, pmela, tyr, tyrp1a, slc2a11b, rab38a, rab27, tspan10, slc45a2, oca2, slc24a5, ptn and mitfa. These genes are associated with melanin production and melanocyte proliferation. They were also up-regulated in Sp-Couch hybrid, indicating that their UVB response is hybridization initiated. In the hybrid, several melanin production and pigmentation related genes, including slc45a2, tspan10, dct, slc2a11b and ptn showed either X. couchianus or X. maculatus allele specific expression. The finding that these genes exhibit allele specific expression regulatory mechanisms in Sp-Couch hybrids, but do not exhibit a corresponding UVB response in either one of the parental fishes, may suggest UVB targets and imply mechanisms regarding the susceptibility of Sp-Couch to induced melanomagenesis.
Keywords	alleles ; animal models ; dermal exposure ; etiology ; fish ; gene expression regulation ; genetic similarity ; humans ; hybridization ; hybrids ; melanin ; melanocytes ; melanoma ; phenotype ; pigmentation ; sequence analysis ; ultraviolet radiation ; Xiphophorus
Language	English
Dates of publication	2015-12
Size	p. 86-92.
Publishing place	Elsevier Inc.
Document type	Article
ZDB-ID	189285-x
ISSN	0306-4492 ; 0742-8413 ; 1532-0456
ISSN	0306-4492 ; 0742-8413 ; 1532-0456
DOI	10.1016/j.cbpc.2015.07.011
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Application of the Transcriptional Disease Signature (TDSs) to Screen Melanoma-Effective Compounds in a Small Fish Model

Yuan Lu / William Boswell / Mikki Boswell / Barbara Klotz / Susanne Kneitz / Janine Regneri / Markita Savage / Cristina Mendoza / John Postlethwait / Wesley C. Warren / Manfred Schartl / Ronald B. Walter

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

2019 Volume 13

Abstract: Abstract Cell culture and protein target-based compound screening strategies, though broadly utilized in selecting candidate compounds, often fail to eliminate candidate compounds with non-target effects and/or safety concerns until late in the drug ... ...

Abstract	Abstract Cell culture and protein target-based compound screening strategies, though broadly utilized in selecting candidate compounds, often fail to eliminate candidate compounds with non-target effects and/or safety concerns until late in the drug developmental process. Phenotype screening using intact research animals is attractive because it can help identify small molecule candidate compounds that have a high probability of proceeding to clinical use. Most FDA approved, first-in-class small molecules were identified from phenotypic screening. However, phenotypic screening using rodent models is labor intensive, low-throughput, and very expensive. As a novel alternative for small molecule screening, we have been developing gene expression disease profiles, termed the Transcriptional Disease Signature (TDS), as readout of small molecule screens for therapeutic molecules. In this concept, compounds that can reverse, or otherwise affect known disease-associated gene expression patterns in whole animals may be rapidly identified for more detailed downstream direct testing of their efficacy and mode of action. To establish proof of concept for this screening strategy, we employed a transgenic strain of a small aquarium fish, medaka (Oryzias latipes), that overexpresses the malignant melanoma driver gene xmrk, a mutant egfr gene, that is driven by a pigment cell-specific mitf promoter. In this model, melanoma develops with 100% penetrance. Using the transgenic medaka malignant melanoma model, we established a screening system that employs the NanoString nCounter platform to quantify gene expression within custom sets of TDS gene targets that we had previously shown to exhibit differential transcription among xmrk-transgenic and wild-type medaka. Compound-modulated gene expression was identified using an internet-accessible custom-built data processing pipeline. The effect of a given drug on the entire TDS profile was estimated by comparing compound-modulated genes in the TDS using an activation Z-score and Kolmogorov-Smirnov statistics. TDS gene probes were designed that target common signaling pathways that include proliferation, development, toxicity, immune function, metabolism and detoxification. These pathways may be utilized to evaluate candidate compounds for potential favorable, or unfavorable, effects on melanoma-associated gene expression. Here we present the logistics of using medaka to screen compounds, as well as, the development of a user-friendly NanoString data analysis pipeline to support feasibility of this novel TDS drug-screening strategy.
Keywords	Medicine ; R ; Science ; Q
Subject code	570
Language	English
Publishing date	2019-01-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Cortisol release in response to UVB exposure in Xiphophorus fish

Contreras, Adam J / Amanda Pasquali / Kevin P. Downs / Mikki Boswell / Ronald B. Walter

Comparative Biochemistry and Physiology, Part C. 2014 June, v. 163

2014

Abstract: Xiphophorus fishes are comprised of 26 known species. Interspecies hybridization between select species has been utilized to produce experimental models to study melanoma development. Xiphophorus melanoma induction protocols utilize ultraviolet light ( ... ...

Abstract	Xiphophorus fishes are comprised of 26 known species. Interspecies hybridization between select species has been utilized to produce experimental models to study melanoma development. Xiphophorus melanoma induction protocols utilize ultraviolet light (UVB) to induce DNA damage and associated downstream tumorigenesis. However, the impact of induced stress caused by the UVB treatment of the experimental animals undergoing tumor induction protocols has not been assessed. Stress is an adaptive physiological response to excessive or unpredictable environmental stimuli. The stress response in fishes may be measured by an assay of cortisol released into the water. Here, we present results from investigations of stress response during an experimental treatment and UVB exposure in Xiphophorus maculatus Jp 163 B, Xiphophorus couchianus, and F1 interspecies hybrids produced from the mating X. maculatus Jp 163 BÃX. couchianus. Overall, cortisol release rates for males and females after UVB exposure showed no statistical differences. At lower UVB doses (8 and 16kJ/m2), X. couchianus exhibited 2 fold higher levels of DNA damage then either X. maculatus or the F1 hybrid. However, based on the cortisol release rates, none of the fish types tested induced a primary stress response at the UVB lower doses (8 and 16kJ/m2). In contrast, at a very high UVB dose (32kJ/m2) both X. maculatus and the F1 hybrid showed a 5 fold increase in the cortisol release rate. To determine the effect of pigmentation on UVB induced stress, wild type and albino Xiphophorus hellerii were exposed to UVB (32kJ/m2). Albino X. hellerii exhibited 3.7 fold increase in the cortisol release while wild type X. hellerii did not exhibit a significant cortisol response to UVB. Overall, the data suggest the rather low UVB doses often employed in tumor induction protocols do not induce a primary stress response in Xiphophorus fishes.
Keywords	albino ; carcinogenesis ; cortisol ; DNA damage ; females ; fish ; hybrids ; interspecific hybridization ; laboratory animals ; males ; melanoma ; models ; pigmentation ; stress response ; ultraviolet radiation ; Xiphophorus maculatus
Language	English
Dates of publication	2014-06
Size	p. 95-101.
Publishing place	Elsevier Inc.
Document type	Article
ZDB-ID	189285-x
ISSN	0306-4492 ; 0742-8413 ; 1532-0456
ISSN	0306-4492 ; 0742-8413 ; 1532-0456
DOI	10.1016/j.cbpc.2014.02.004
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Long-term experimental hybridisation results in the evolution of a new sex chromosome in swordtail fish

Paolo Franchini / Julia C. Jones / Peiwen Xiong / Susanne Kneitz / Zachariah Gompert / Wesley C. Warren / Ronald B. Walter / Axel Meyer / Manfred Schartl

Nature Communications, Vol 9, Iss 1, Pp 1-

2018 Volume 11

Abstract: Fish have a high diversity of sex-determining systems, but the mechanisms responsible for this are not well understood. Here, Franchini et al. show how hybridization and backcrossing have led to the evolution of a new sex chromosome in swordtail fish ... ...

Abstract	Fish have a high diversity of sex-determining systems, but the mechanisms responsible for this are not well understood. Here, Franchini et al. show how hybridization and backcrossing have led to the evolution of a new sex chromosome in swordtail fish during 30 years of experimental evolution.
Keywords	Science ; Q
Language	English
Publishing date	2018-12-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Long-term experimental hybridisation results in the evolution of a new sex chromosome in swordtail fish

Paolo Franchini / Julia C. Jones / Peiwen Xiong / Susanne Kneitz / Zachariah Gompert / Wesley C. Warren / Ronald B. Walter / Axel Meyer / Manfred Schartl

Nature Communications, Vol 9, Iss 1, Pp 1-

2018 Volume 11

Abstract	Fish have a high diversity of sex-determining systems, but the mechanisms responsible for this are not well understood. Here, Franchini et al. show how hybridization and backcrossing have led to the evolution of a new sex chromosome in swordtail fish during 30 years of experimental evolution.
Keywords	Science ; Q
Language	English
Publishing date	2018-12-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Molecular genetic response to varied wavelengths of light in Xiphophorus maculatus skin

Chang, Jordan / Kaela L. Caballero / Mikki Boswell / Ronald B. Walter / William T. Boswell / Yuan Lu

Comparative biochemistry and physiology. 2015 Dec., v. 178

2015

Abstract: Xiphophorus fishes represent a model often utilized to study UVB induced tumorigenesis. Recently, varied genetic responses to UVB exposure have been documented in the skin of female and male Xiphophorus, as have differences in UVB response in the skin of ...

Abstract	Xiphophorus fishes represent a model often utilized to study UVB induced tumorigenesis. Recently, varied genetic responses to UVB exposure have been documented in the skin of female and male Xiphophorus, as have differences in UVB response in the skin of different parental species and for interspecies hybrids produced from crossing them. Additionally, it has been shown that exposure to “cool white” fluorescent light induces a shift in the genetic profiles of Xiphophorus skin that is nearly as robust as the UVB response, but involves a fundamentally different set of genes. Given these results and the use of Xiphophorus interspecies hybrids as an experimental model for UVB inducible melanoma, it is of interest to characterize genes that may be transcriptionally modulated in a wavelength specific manner.The global molecular genetic response of skin upon exposure of the intact animal to specific wavelengths of light has not been investigated. Herein, we report results of RNA-Seq experiments from the skin of male Xiphophorus maculatus Jp 163 B following exposure to varied 50nm wavelengths of light ranging from 300–600nm. We identify two specific wavelength regions, 350–400nm (88 genes) and 500–550nm (276 genes), that exhibit transcriptional modulation of a significantly greater number of transcripts than any of the other 50nm regions in the 300–600nm range. Observed functional sets of genes modulated within these two transcriptionally active light regions suggest different mechanisms of gene modulation.
Keywords	carcinogenesis ; crossing ; females ; fish ; fluorescent lighting ; genes ; hybrids ; males ; melanoma ; models ; sequence analysis ; transcription (genetics) ; wavelengths ; Xiphophorus maculatus
Language	English
Dates of publication	2015-12
Size	p. 104-115.
Publishing place	Elsevier Inc.
Document type	Article
ZDB-ID	189285-x
ISSN	0306-4492 ; 0742-8413 ; 1532-0456
ISSN	0306-4492 ; 0742-8413 ; 1532-0456
DOI	10.1016/j.cbpc.2015.10.002
Database	NAL-Catalogue (AGRICOLA)

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Article: Sex-specific molecular genetic response to UVB exposure in Xiphophorus maculatus skin

Boswell, William / James Titus / Jianjun Shen / Markita Savage / Mikki Boswell / Ronald B. Walter / Yuan Lu

Comparative biochemistry and physiology. 2015 Dec., v. 178

2015

Abstract: In both Xiphophorus fishes and humans, males are reported to have a higher incidence of melanoma than females. To better understand sex-specific differences in the molecular genetic response to UVB, we performed RNA-Seq experiments in skin of female and ... ...

Abstract	In both Xiphophorus fishes and humans, males are reported to have a higher incidence of melanoma than females. To better understand sex-specific differences in the molecular genetic response to UVB, we performed RNA-Seq experiments in skin of female and male Xiphophorus maculatus Jp 163 B following UVB doses of 8 or 16kJ/m2 exposure. Male X. maculatus differentially express a significantly larger number of transcripts following exposure to 16kJ/m2 UVB (1293 genes) compared to 8kJ/m2 UVB (324 genes). Female skin showed differential gene expression in a larger number of transcripts following 8kJ/m2 UVB (765) than did males; however, both females and males showed similar numbers of differentially expressed genes at 16kJ/m2 UVB (1167 and1293, respectively).Although most modulated transcripts after UVB exposure represented the same dominant pathways in both females and males (e.g., DNA repair, circadian rhythm, and fatty acid biosynthesis), we identified genes in several pathways that exhibited opposite modulation in female vs. male skin (e.g., synaptic development, cell differentiation, wound healing, and glucose metabolism). The oppositely modulated genes appear related through uncoupling protein 3 (UCP3) that is involved with the regulation of fatty acid oxidation and serves to balance glucose and lipid metabolism. Overall, these results identify gender-specific differences in UVB-induced genetic profiles in the skin of females and males and show female and male X. maculatus respond to UVB differently through pathways involved in reactive oxygen species, wound healing, and energy homeostasis.
Keywords	beta oxidation ; biosynthesis ; cell differentiation ; circadian rhythm ; DNA repair ; energy ; fatty acids ; females ; fish ; gene expression ; gene expression regulation ; genes ; glucose ; homeostasis ; humans ; males ; melanoma ; reactive oxygen species ; sequence analysis ; tissue repair ; Xiphophorus maculatus
Language	English
Dates of publication	2015-12
Size	p. 76-85.
Publishing place	Elsevier Inc.
Document type	Article
ZDB-ID	189285-x
ISSN	0306-4492 ; 0742-8413 ; 1532-0456
ISSN	0306-4492 ; 0742-8413 ; 1532-0456
DOI	10.1016/j.cbpc.2015.07.007
Database	NAL-Catalogue (AGRICOLA)

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