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Article ; Online: Overexpression of Lox in triple-negative breast cancer.

Leo, Cornelia / Cotic, Christine / Pomp, Victoria / Fink, Daniel / Varga, Zsuzsanna

2018 Volume 34, Page(s) 98–102

Abstract: Background: Triple negative breast cancer (TNBC) accounts for approximately 15% of breast cancers. It is associated with a poor prognosis and typically earlier onset of metastasis in comparison with other breast cancer subtypes. Since TNBC lacks the ... ...

Abstract	Background: Triple negative breast cancer (TNBC) accounts for approximately 15% of breast cancers. It is associated with a poor prognosis and typically earlier onset of metastasis in comparison with other breast cancer subtypes. Since TNBC lacks the expression of estrogen and progesterone receptors and Her2 status is also negative, there is currently no target that can be used for systemic therapy. Epithelial-mesenchymal transition (EMT) plays an important role in tumor progression and metastasis. In this study, we examined a subset of EMT markers consisting of Snail, Twist-1 and Lox in TNBC and non-TNBC breast cancer subtypes and analyzed their expression pattern in regard to subtype, clinico-pathological parameters and prognosis. Experimental design: We analyzed 659 breast cancer samples from two tissue microarrays. Breast cancer samples were categorized into two groups according to hormone receptor expression and Her2 status (n = 146 were triple negative, n = 513 were non triple-negative). Immunohistochemical expression of Snail, Twist-1 and Lox was semi-quantitatively analyzed using a three-tiered (weak-moderate-strong) scoring system. Results were statistically analyzed and correlated to clinico-pathological parameters and overall survival. Results: Strong overexpression of Lox was significantly higher in triple negative breast cancers when compared to non triple-negative breast cancers (p < 0.001). No difference was seen between the groups regarding Snail and Twist expression (p > 0.05). In addition, Lox expression was significantly stronger in poorly differentiated (G3) breast cancers (p < 0.001 for Lox). Conclusions: The EMT marker Lox has a differential expression pattern in breast cancer, being significantly overexpressed in triple negative breast cancers. We could not link this expression to prognosis, however, this marker might be explored in future studies as possible target for systemic therapy of TNBC.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Cohort Studies ; Epithelial-Mesenchymal Transition ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Prognosis ; Protein-Lysine 6-Oxidase/metabolism ; Receptor, ErbB-2/metabolism ; Receptors, Progesterone/metabolism ; Tissue Array Analysis ; Triple Negative Breast Neoplasms/metabolism ; Young Adult
Chemical Substances	Receptors, Progesterone ; LOX protein, human (EC 1.4.3.13) ; Protein-Lysine 6-Oxidase (EC 1.4.3.13) ; ERBB2 protein, human (EC 2.7.10.1) ; Receptor, ErbB-2 (EC 2.7.10.1)
Language	English
Publishing date	2018-03-27
Publishing country	United States
Document type	Journal Article
ZDB-ID	1440011-x
ISSN	1532-8198 ; 1092-9134
ISSN (online)	1532-8198
ISSN	1092-9134
DOI	10.1016/j.anndiagpath.2018.03.009
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Zs.A 5463: Show issues

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Article: Genetic determinants of voluntary exercise.

Kelly, Scott A / Pomp, Daniel

Trends in genetics : TIG

2013 Volume 29, Issue 6, Page(s) 348–357

Abstract: Variation in voluntary exercise behavior is an important determinant of long-term human health. Increased physical activity is used as a preventative measure or therapeutic intervention for disease, and a sedentary lifestyle has generally been viewed as ... ...

Abstract	Variation in voluntary exercise behavior is an important determinant of long-term human health. Increased physical activity is used as a preventative measure or therapeutic intervention for disease, and a sedentary lifestyle has generally been viewed as unhealthy. Predisposition to engage in voluntary activity is heritable and induces protective metabolic changes, but its complex genetic/genomic architecture has only recently begun to emerge. We first present a brief historical perspective and summary of the known benefits of voluntary exercise. Second, we describe human and mouse model studies using genomic and transcriptomic approaches to reveal the genetic architecture of exercise. Third, we discuss the merging of genomic information and physiological observations, revealing systems and networks that lead to a more complete mechanistic understanding of how exercise protects against disease pathogenesis. Finally, we explore potential regulation of physical activity through epigenetic mechanisms, including those that persist across multiple generations.
MeSH term(s)	Animals ; Epigenesis, Genetic ; Exercise ; Gene Expression ; Gene Regulatory Networks ; Genetic Determinism ; Genome-Wide Association Study ; Humans ; Quantitative Trait Loci
Language	English
Publishing date	2013-01-23
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	619240-3
ISSN	1362-4555 ; 0168-9525 ; 0168-9479
ISSN (online)	1362-4555
ISSN	0168-9525 ; 0168-9479
DOI	10.1016/j.tig.2012.12.007
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Zs.A 2272: Show issues

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Article ; Online: The 'Omics' of Voluntary Exercise: Systems Approaches to a Complex Phenotype.

Kelly, Scott A / Villena, Fernando Pardo-Manuel de / Pomp, Daniel

Trends in endocrinology and metabolism: TEM

2015 Volume 26, Issue 12, Page(s) 673–675

Abstract: Predisposition to engage in exercise is highly variable and simultaneously influenced by the environment, complex genomics, and their interactions. Given the importance of exercise to health, understanding the underlying influences of variability is ... ...

Abstract	Predisposition to engage in exercise is highly variable and simultaneously influenced by the environment, complex genomics, and their interactions. Given the importance of exercise to health, understanding the underlying influences of variability is crucial. Here, we discuss murine systems approaches, focusing on 'omics', relevant to revealing the architecture of voluntary activity.
MeSH term(s)	Animals ; Environment ; Exercise/physiology ; Genomics ; Humans ; Phenotype ; Physical Conditioning, Animal/physiology ; Proteomics
Language	English
Publishing date	2015-12
Publishing country	United States
Document type	Journal Article
ZDB-ID	1042384-9
ISSN	1879-3061 ; 1043-2760
ISSN (online)	1879-3061
ISSN	1043-2760
DOI	10.1016/j.tem.2015.10.002
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Zs.A 2999: Show issues

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Article: Incidental or Intentional? Different Brain Responses to One's Own Action Sounds in Hurdling vs. Tap Dancing.

Heins, Nina / Pomp, Jennifer / Kluger, Daniel S / Trempler, Ima / Zentgraf, Karen / Raab, Markus / Schubotz, Ricarda I

Frontiers in neuroscience

2020 Volume 14, Page(s) 483

Abstract: Most human actions produce concomitant sounds. Action sounds can be either part of the action goal (GAS, goal-related action sounds), as for instance in tap dancing, or a mere by-product of the action (BAS, by-product action sounds), as for instance in ... ...

Abstract	Most human actions produce concomitant sounds. Action sounds can be either part of the action goal (GAS, goal-related action sounds), as for instance in tap dancing, or a mere by-product of the action (BAS, by-product action sounds), as for instance in hurdling. It is currently unclear whether these two types of action sounds-incidental or intentional-differ in their neural representation and whether the impact on the performance evaluation of an action diverges between the two. We here examined whether during the observation of tap dancing compared to hurdling, auditory information is a more important factor for positive action quality ratings. Moreover, we tested whether observation of tap dancing vs. hurdling led to stronger attenuation in primary auditory cortex, and a stronger mismatch signal when sounds do not match our expectations. We recorded individual point-light videos of newly trained participants performing tap dancing and hurdling. In the subsequent functional magnetic resonance imaging (fMRI) session, participants were presented with the videos that displayed their own actions, including corresponding action sounds, and were asked to rate the quality of their performance. Videos were either in their original form or scrambled regarding the visual modality, the auditory modality, or both. As hypothesized, behavioral results showed significantly lower rating scores in the GAS condition compared to the BAS condition when the auditory modality was scrambled. Functional MRI contrasts between BAS and GAS actions revealed higher activation of primary auditory cortex in the BAS condition, speaking in favor of stronger attenuation in GAS, as well as stronger activation of posterior superior temporal gyri and the supplementary motor area in GAS. Results suggest that the processing of self-generated action sounds depends on whether we have the intention to produce a sound with our action or not, and action sounds may be more prone to be used as sensory feedback when they are part of the explicit action goal. Our findings contribute to a better understanding of the function of action sounds for learning and controlling sound-producing actions.
Language	English
Publishing date	2020-05-13
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2411902-7
ISSN	1662-453X ; 1662-4548
ISSN (online)	1662-453X
ISSN	1662-4548
DOI	10.3389/fnins.2020.00483
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Article ; Online: Correction to: Quantitative trait mapping in Diversity Outbred mice identifies two genomic regions associated with heart size.

Shorter, John R / Huang, Wei / Beak, Ju Youn / Hua, Kunjie / Gatti, Daniel M / de Villena, Fernando Pardo-Manuel / Pomp, Daniel / Jensen, Brian C

Mammalian genome : official journal of the International Mammalian Genome Society

2018 Volume 30, Issue 1-2, Page(s) 42

Abstract: The original article has been published with an incorrect text in Materials and Methods section. The corrected text should read as. ...

Abstract	The original article has been published with an incorrect text in Materials and Methods section. The corrected text should read as.
Language	English
Publishing date	2018-10-31
Publishing country	United States
Document type	Journal Article ; Published Erratum
ZDB-ID	1058547-3
ISSN	1432-1777 ; 0938-8990
ISSN (online)	1432-1777
ISSN	0938-8990
DOI	10.1007/s00335-018-9789-9
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Zs.A 3489: Show issues

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Article: Epistatic Control of Mammary Cancer Susceptibility in Mice may Depend on the Dietary Environment.

Leamy, Larry J / Gordon, Ryan R / Pomp, Daniel

Hereditary genetics : current research

2014 Volume 1, Issue 2, Page(s) 108

Abstract: Recent studies have linked a high fat diet to the development of breast cancer, but any genetic basis for this association is poorly understood. We investigated this association with an epistatic analysis of seven cancer traits in a segregating ... ...

Abstract	Recent studies have linked a high fat diet to the development of breast cancer, but any genetic basis for this association is poorly understood. We investigated this association with an epistatic analysis of seven cancer traits in a segregating population of mice with metastatic mammary cancer that were fed either a control or a high-fat diet. We used an interval mapping approach with single nucleotide polymorphisms to scan all 19 autosomes, and discovered a number of diet-independent epistatic interactions of quantitative trait loci (QTLs) affecting these traits. More importantly, we also discovered significant epistatic by diet interactions affecting some of the traits that suggested these epistatic effects varied depending on the dietary environment. An analysis of these interactions showed some were due to epistasis that occurred in mice fed only the control diet or only the high-fat diet whereas other interactions were generated by differential effects of epistasis in the two dietary environments. Some of the epistatic QTLs appeared to colocalize with cancer QTLs mapped in other mouse populations and with candidate genes identified from eQTLs previously mapped in this population, but others represented novel modifying loci affecting these cancer traits. It was concluded that these diet-dependent epistatic QTLs contribute to a genetic susceptibility of dietary effects on breast cancer, and their identification may eventually lead to a better understanding that will be needed for the design of more effective treatments for this disease.
Language	English
Publishing date	2014-02-18
Publishing country	United States
Document type	Journal Article
ISSN	2161-1041
ISSN	2161-1041
DOI	10.4172/2161-1041.1000108
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Article ; Online: Genetic architecture modulates diet-induced hepatic mRNA and miRNA expression profiles in Diversity Outbred mice.

Que, Excel / James, Kristen L / Coffey, Alisha R / Smallwood, Tangi L / Albright, Jody / Huda, M Nazmul / Pomp, Daniel / Sethupathy, Praveen / Bennett, Brian J

Genetics

2021 Volume 218, Issue 3

Abstract: Genetic approaches in model organisms have consistently demonstrated that molecular traits such as gene expression are under genetic regulation, similar to clinical traits. The resulting expression quantitative trait loci (eQTL) have revolutionized our ... ...

Abstract	Genetic approaches in model organisms have consistently demonstrated that molecular traits such as gene expression are under genetic regulation, similar to clinical traits. The resulting expression quantitative trait loci (eQTL) have revolutionized our understanding of genetic regulation and identified numerous candidate genes for clinically relevant traits. More recently, these analyses have been extended to other molecular traits such as protein abundance, metabolite levels, and miRNA expression. Here, we performed global hepatic eQTL and microRNA expression quantitative trait loci (mirQTL) analysis in a population of Diversity Outbred mice fed two different diets. We identified several key features of eQTL and mirQTL, namely differences in the mode of genetic regulation (cis or trans) between mRNA and miRNA. Approximately 50% of mirQTL are regulated by a trans-acting factor, compared to ∼25% of eQTL. We note differences in the heritability of mRNA and miRNA expression and variance explained by each eQTL or mirQTL. In general, cis-acting variants affecting mRNA or miRNA expression explain more phenotypic variance than trans-acting variants. Finally, we investigated the effect of diet on the genetic architecture of eQTL and mirQTL, highlighting the critical effects of environment on both eQTL and mirQTL. Overall, these data underscore the complex genetic regulation of two well-characterized RNA classes (mRNA and miRNA) that have critical roles in the regulation of clinical traits and disease susceptibility.
MeSH term(s)	Animals ; Diet ; Genotype ; Hybridization, Genetic ; Liver/metabolism ; Mice ; MicroRNAs/genetics ; MicroRNAs/metabolism ; Multifactorial Inheritance ; Quantitative Trait Loci ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Transcriptome
Chemical Substances	MicroRNAs ; RNA, Messenger
Language	English
Publishing date	2021-11-27
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2167-2
ISSN	1943-2631 ; 0016-6731
ISSN (online)	1943-2631
ISSN	0016-6731
DOI	10.1093/genetics/iyab068
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Zs.B 767: Show issues

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Article ; Online: Image of the month-quiz. Cystadenoma of the cystic duct.

Marcotte, Eric / Afaneh, Cheguevara / Pomp, Alfons / Cherqui, Daniel

JAMA surgery

2013 Volume 148, Issue 4, Page(s) 395–396

MeSH term(s)	Bile Duct Neoplasms/diagnosis ; Bile Duct Neoplasms/pathology ; Bile Duct Neoplasms/surgery ; Cystadenoma/diagnosis ; Cystadenoma/pathology ; Cystadenoma/surgery ; Cystic Duct/pathology ; Diagnosis, Differential ; Female ; Humans ; Middle Aged
Language	English
Publishing date	2013-04
Publishing country	United States
Document type	Case Reports ; Journal Article
ZDB-ID	2701841-6
ISSN	2168-6262 ; 2168-6254
ISSN (online)	2168-6262
ISSN	2168-6254
DOI	10.1001/jamasurg.2013.317a
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Article ; Online: Systems genetics in diversity outbred mice inform BMD GWAS and identify determinants of bone strength.

Al-Barghouthi, Basel M / Mesner, Larry D / Calabrese, Gina M / Brooks, Daniel / Tommasini, Steven M / Bouxsein, Mary L / Horowitz, Mark C / Rosen, Clifford J / Nguyen, Kevin / Haddox, Samuel / Farber, Emily A / Onengut-Gumuscu, Suna / Pomp, Daniel / Farber, Charles R

Nature communications

2021 Volume 12, Issue 1, Page(s) 3408

Abstract: Genome-wide association studies (GWASs) for osteoporotic traits have identified over 1000 associations; however, their impact has been limited by the difficulties of causal gene identification and a strict focus on bone mineral density (BMD). Here, we ... ...

Abstract	Genome-wide association studies (GWASs) for osteoporotic traits have identified over 1000 associations; however, their impact has been limited by the difficulties of causal gene identification and a strict focus on bone mineral density (BMD). Here, we use Diversity Outbred (DO) mice to directly address these limitations by performing a systems genetics analysis of 55 complex skeletal phenotypes. We apply a network approach to cortical bone RNA-seq data to discover 66 genes likely to be causal for human BMD GWAS associations, including the genes SERTAD4 and GLT8D2. We also perform GWAS in the DO for a wide-range of bone traits and identify Qsox1 as a gene influencing cortical bone accrual and bone strength. In this work, we advance our understanding of the genetics of osteoporosis and highlight the ability of the mouse to inform human genetics.
MeSH term(s)	Animals ; Bone Density/genetics ; Cell Differentiation/genetics ; Collaborative Cross Mice ; Datasets as Topic ; Female ; Femur/physiology ; Fluoresceins/administration & dosage ; Fluorescent Dyes/administration & dosage ; Genome-Wide Association Study ; Glycosyltransferases/genetics ; Humans ; Male ; Mesenchymal Stem Cells ; Mice ; Mice, Knockout ; Osteoblasts ; Osteogenesis/genetics ; Osteoporosis/genetics ; Oxidoreductases Acting on Sulfur Group Donors/genetics ; RNA-Seq ; Single-Cell Analysis
Chemical Substances	Fluoresceins ; Fluorescent Dyes ; Oxidoreductases Acting on Sulfur Group Donors (EC 1.8.-) ; QSOX1 protein, mouse (EC 1.8.3.2) ; Glycosyltransferases (EC 2.4.-) ; fluorexon (V0YM2B16TS)
Language	English
Publishing date	2021-06-07
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-021-23649-0
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Article ; Online: Surmising synchrony of sound and sight: Factors explaining variance of audiovisual integration in hurdling, tap dancing and drumming.

Heins, Nina / Pomp, Jennifer / Kluger, Daniel S / Vinbrüx, Stefan / Trempler, Ima / Kohler, Axel / Kornysheva, Katja / Zentgraf, Karen / Raab, Markus / Schubotz, Ricarda I

PloS one

2021 Volume 16, Issue 7, Page(s) e0253130

Abstract: Auditory and visual percepts are integrated even when they are not perfectly temporally aligned with each other, especially when the visual signal precedes the auditory signal. This window of temporal integration for asynchronous audiovisual stimuli is ... ...

Abstract	Auditory and visual percepts are integrated even when they are not perfectly temporally aligned with each other, especially when the visual signal precedes the auditory signal. This window of temporal integration for asynchronous audiovisual stimuli is relatively well examined in the case of speech, while other natural action-induced sounds have been widely neglected. Here, we studied the detection of audiovisual asynchrony in three different whole-body actions with natural action-induced sounds-hurdling, tap dancing and drumming. In Study 1, we examined whether audiovisual asynchrony detection, assessed by a simultaneity judgment task, differs as a function of sound production intentionality. Based on previous findings, we expected that auditory and visual signals should be integrated over a wider temporal window for actions creating sounds intentionally (tap dancing), compared to actions creating sounds incidentally (hurdling). While percentages of perceived synchrony differed in the expected way, we identified two further factors, namely high event density and low rhythmicity, to induce higher synchrony ratings as well. Therefore, we systematically varied event density and rhythmicity in Study 2, this time using drumming stimuli to exert full control over these variables, and the same simultaneity judgment tasks. Results suggest that high event density leads to a bias to integrate rather than segregate auditory and visual signals, even at relatively large asynchronies. Rhythmicity had a similar, albeit weaker effect, when event density was low. Our findings demonstrate that shorter asynchronies and visual-first asynchronies lead to higher synchrony ratings of whole-body action, pointing to clear parallels with audiovisual integration in speech perception. Overconfidence in the naturally expected, that is, synchrony of sound and sight, was stronger for intentional (vs. incidental) sound production and for movements with high (vs. low) rhythmicity, presumably because both encourage predictive processes. In contrast, high event density appears to increase synchronicity judgments simply because it makes the detection of audiovisual asynchrony more difficult. More studies using real-life audiovisual stimuli with varying event densities and rhythmicities are needed to fully uncover the general mechanisms of audiovisual integration.
MeSH term(s)	Acoustic Stimulation ; Adult ; Auditory Perception ; Dancing/physiology ; Dancing/psychology ; Female ; Humans ; Male ; Music/psychology ; Photic Stimulation ; Sound ; Track and Field/physiology ; Track and Field/psychology ; Visual Perception/physiology ; Young Adult
Language	English
Publishing date	2021-07-22
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0253130
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