Contingent Tunes of Neurochemical Ensembles in the Norm and Pathology: Can We See the Patterns?

BACKGROUND/AIMS: Progress in the development of DSM/ICD taxonomies has revealed limitations of both label-based and dimensionality approaches. These approaches fail to address the contingent, nonlinear, context-dependent, and transient nature of those biomarkers linked to specific symptoms of psychopathology or to specific biobehavioural traits of healthy people (temperament). The present review aims to highlight the benefits of a functional constructivism approach in the analysis of neurochemical biomarkers underlying temperament and psychopathology. METHOD: A review was performed. RESULTS: Eight systems are identified, and 7 neurochemical ensembles are described in detail. None of these systems is represented by a single neurotransmitter; all of them work in ensembles with each other. The functionality and relationships of these systems are presented here in association with their roles in action construction, with brief examples of psychopathology. The review introduces formal symbols for these systems to facilitate their more compact analysis in the future. CONCLUSION: This analysis demonstrates the possibility of constructivism-based unifying taxonomies of temperament (in the framework of the neurochemical model functional ensemble of temperament) and classifications of psychiatric disorders. Such taxonomies would present the biobehavioural individual differences as consistent behavioural patterns generated within a formally structured space of parameters related to the generation of behaviour.

Opium Effect in Pregnancy on the Dynamics of Maternal Behavior: Testing a Neurochemical Model.

BACKGROUND: Investigations into neurochemical mechanisms of opioid addiction are difficult due to the complexity of behavior and multiplicity of involved neurotransmitter and hormonal systems. The aim of this study was to examine the benefits of structured analysis of these mechanisms using the framework of the neurochemical model Functional Ensemble of Temperament (FET) and the example of maternal behavior under the condition of opium consumption in pregnancy. The FET differentiates between (a) endurance, (b) speed of integration, and (c) emotionality aspects of behavior suggesting that these systems are differentially regulated by (a) serotonin-neuropeptides-brain-derived neurotrophic factor (BDNF), (b) dopamine-GABA, and (c) opioid receptor systems, correspondingly. The FET also suggests that mu-opioid receptors (MORs) binding the endorphines (including opium's ingredient morphine) have a stronger association with regulation endurance, whereas delta-OR have a stronger association with integration of behavior and kappa-OR - with the perceptual mobilization seen in anxiety. To test the predictions of this model, we compared the impact of massive MOR dysregulation on 3 behavioral aspects of behavior and on serotonin, BDNF, and corticosterone levels. METHODS: The study used 24 female white Wistar rats which were randomly divided into (1) control group: pregnant rats without any intervention; (2) opium-exposed group: animals that were exposed to opium during pregnancy and after the delivery until the end of the study. At the end of the study, the levels of BDNF, serotonin (5-HT) in the hippocampus of the mother's brain, and serum corticosterone, as well as 12 aspects of the maternal behavior were evaluated. The differences between control and experimental groups were assessed using the t test for independent samples. RESULTS: The BDNF and serotonin concentrations in the hippocampus of the mother rats which were exposed to opium were lower than in the control group; the mean corticosterone in exposed mothers was higher than in the control group. Behaviorally, opium-consuming mothers showed lower endurance in 4 distinct behavioral categories (nesting, feeding, grooming, and retrieval) than the mothers in the control group. Ease of integration of behavior was affected to a lesser degree, showing a significant effect only in 1 out of 5 applied measures. Self-grooming, seen as an emotionality-related aspect of behavior, was not affected. CONCLUSION: Opium exposure during pregnancy in our experiment primarily reduced the endurance of rat's maternal behavior, but the speed of integration of behavioral acts was less affected. This negative impact of opium on endurance was associated with a decrease of BDNF and serotonin levels in the hippocampus and an increase in corticosterone level in opium-consuming mothers. There is no effect of opium exposure on self-grooming behavior. This pattern supports the FET hypothesis about the role of 5-HT and BDNF in endurance, differential regulation of endurance, integrative and emotionality aspects of behavior, and differential association of the MOR system with endurance aspects, in comparison with kappa- and delta opioid receptors.

There is more to mental illness than negative affect: comprehensive temperament profiles in depression and generalized anxiety.

BACKGROUND: Temperament and mental illness are thought to represent varying degrees along the same continuum of neurotransmitter imbalances. A taxonomy of temperament could provide the basis for a new taxonomy of mental illness. Most popular models of temperament, being based heavily on emotionality traits, show very poor ability to discriminate between mental disorders. The main goal of this study was to examine whether a temperament model based on modern neurophysiology and possessing an extensive set of non-emotionality traits provides better discrimination between Major Depression (MD), Generalized Anxiety (GAD) and Comorbid MD and GAD, in comparison to emotionality-based temperament models. METHODS: Using the Structure of Temperament Questionnaire, the temperament profiles of 687 individuals (396 clients of private psychiatric and psychological practice, and 291 control subjects) were compared across four adult age groups (18-24, 25-45, 46-65, 66-84). RESULTS: MD and GAD appear to be accurately distinguished by the traits of Motor Endurance and Motor Tempo (much lower values in depression), and Neuroticism (much higher value in anxiety). Comorbids can be distinguished based on a significant decrease in the traits of Plasticity, Intellectual Endurance, Sensitivity to Probabilities, and increased Impulsivity. These effects seemed independent of age and gender. CONCLUSIONS: The results suggest the benefits of including non-emotionality-related traits and the usefulness of a functional approach to both taxonomy of temperament and classification of mental disorders.

Functional Constructivism: In Search of Formal Descriptors.

The Functional Constructivism (FC) paradigm is an alternative to behaviorism and considers behavior as being generated every time anew, based on an individual's capacities, environmental resources and demands. Walter Freeman's work provided us with evidence supporting the FC principles. In this paper we make parallels between gradual construction processes leading to the formation of individual behavior and habits, and evolutionary processes leading to the establishment of biological systems. Referencing evolutionary theory, several formal descriptors of such processes are proposed. These FC descriptors refer to the most universal aspects for constructing consistent structures: expansion of degrees of freedom, integration processes based on internal and external compatibility between systems and maintenance processes, all given in four different classes of systems: (a) Zone of Proximate Development (poorly defined) systems; (b) peer systems with emerging reproduction of multiple siblings; (c) systems with internalized integration of behavioral elements ('cruise controls'); and (d) systems capable of handling low-probability, not yet present events. The recursive dynamics within this set of descriptors acting on (traditional) downward, upward and horizontal directions of evolution, is conceptualized as diagonal evolution, or di-evolution. Two examples applying these FC descriptors to taxonomy are given: classification of the functionality of neuro-transmitters and temperament traits; classification of mental disorders. The paper is an early step towards finding a formal language describing universal tendencies in highly diverse, complex and multi-level transient systems known in ecology and biology as 'contingency cycles.'

Transcription of highly repetitive tandemly organized DNA in amphibians and birds: A historical overview and modern concepts.

Tandemly organized highly repetitive DNA sequences are crucial structural and functional elements of eukaryotic genomes. Despite extensive evidence, satellite DNA remains an enigmatic part of the eukaryotic genome, with biological role and significance of tandem repeat transcripts remaining rather obscure. Data on tandem repeats transcription in amphibian and avian model organisms is fragmentary despite their genomes being thoroughly characterized. Review systematically covers historical and modern data on transcription of amphibian and avian satellite DNA in somatic cells and during meiosis when chromosomes acquire special lampbrush form. We highlight how transcription of tandemly repetitive DNA sequences is organized in interphase nucleus and on lampbrush chromosomes. We offer LTR-activation hypotheses of widespread satellite DNA transcription initiation during oogenesis. Recent explanations are provided for the significance of high-yield production of non-coding RNA derived from tandemly organized highly repetitive DNA. In many cases the data on the transcription of satellite DNA can be extrapolated from lampbrush chromosomes to interphase chromosomes. Lampbrush chromosomes with applied novel technical approaches such as superresolution imaging, chromosome microdissection followed by high-throughput sequencing, dynamic observation in life-like conditions provide amazing opportunities for investigation mechanisms of the satellite DNA transcription.

Transcription of subtelomere tandemly repetitive DNA in chicken embryogenesis.

Transcription of tandemly repetitive DNA in embryogenesis seems to be of special interest due to a crucial role of non-coding RNAs in many aspects of development. However, only a few data are available on tandem repeats transcription at subtelomere regions of chromosomes during vertebrate embryogenesis. To reduce this gap, we examined stage and tissue-specific pattern of subtelomeric PO41 (pattern of 41 bp) tandem repeat transcription during embryogenesis of chicken (Gallus gallus domesticus). Using whole-mount RNA fluorescent in situ hybridization and reverse transcription PCR with specific primers, we demonstrated that both strands of PO41 repeat are transcribed at each of the studied stages of chicken embryo development: from 7-8 HH to 20 HH stages. Subtelomere-derived transcripts localize in the nuclei of all cell types and throughout the all embryonic bodies: head, somites, tail, wings and buds. In embryo-dividing cells and cultured embryonic fibroblasts, PO41 RNAs envelop terminal regions of chromosomes. PO41-containing RNAs are predominantly single-stranded and can be polyadenylated, indicating appearance of non-nascent form of subtelomeric transcripts. PO41 repeat RNAs represent a rare example of ubiquitously transcribed non-coding RNAs, such as Xist/XIST RNA or telomere repeat-containing RNA. Distribution of PO41 repeat transcripts at different stages of embryo development and among cell types has extremely uniform pattern, indicating on possible universal functions of PO41 non-coding RNAs.

Do Psychological Sex Differences Reflect Evolutionary Bisexual Partitioning?

This article analyzes sex differences in communicative and exploratory abilities and mental disabilities from the rarely discussed perspective of sex differences in the shape of phenotypic distributions. The article reviews the most consistent findings related to such differences and compares them with the evolutionary theory of sex (ETS). The ETS considers sexual dimorphism as a functional specialization of a species into 2 partitions: variational and conservational. The analysis suggests that male superiority in risk and sensation seeking and physical abilities; higher rates of psychopathy, dyslexia, and autism; and higher birth and accidental death rates reflects the systemic variational function of the male sex. Female superiority in verbal abilities, lawfulness, socialization, empathy, and agreeableness is presented as a reflection of the systemic conservational function of the female sex. From this perspective psychological sex differences in communicative and exploratory abilities might not just be an accidental result of sexual selection or labor distribution in early humans. It might reflect a global functional differentiation tendency within a species to expand its phenotypic diversity and at the same time to conserve beneficial features in the species' behavior. The article also offers an addition to the ETS by suggesting that the male sex (variable partition) plays an evolutionary role in pruning of the redundant excesses in a species' bank of beneficial characteristics despite resistance from the conservational partition.

A study of the dynamics of sex differences in adulthood.

Studies of gender differences using primarily young individuals show that males, on average, perform better than females in physical activities but worse than females on tests of verbal abilities. There is however a controversy about the existence of these sex differences in adulthood. Our study used 1271 participants from four cultural backgrounds (Chinese, multi-generation Canadians, Indu-Canadians, and European-Canadians) divided in five age groups. We measured sex differences in the time required for participants to complete a lexical task experiment, and also assessed their verbal tempo and physical endurance using a validated temperament test (Structure of Temperament Questionnaire). We found a significant female advantage in time on the lexical task and on the temperament scale of social-verbal tempo, and a male advantage on the temperament scale of physical endurance. These sex differences, however, were more pronounced in young age groups (17-24), fading in older groups. This "middle age-middle sex" phenomenon suggests that sex differences in these two types of abilities observed in younger groups might be "a matter of age," and should not be attributed to gender in general. A one-dimensional approach to sex differences (common in meta-analytic studies) therefore overlooks a possible interaction of sex differences with age.

Anticipatory attractors, functional neurochemistry and "Throw & Catch" mechanisms as illustrations of constructivism.

This review explores several rarely discussed examples illustrating constructivism principles, generative and selective features of neuronal regulation of behaviour. First, the review highlights Walter Freeman's experiments and mathematical analysis that uncovered the existence of anticipatory attractors, i.e. non-random dynamical patterns in neurodynamics. Since Freeman's work did not extend to neurochemistry, this paper then points to the proposed earlier neurochemical framework summarizing the managerial roles of monoaminergic, cholinergic and opioid receptor systems likely contributing to anticipatory attractors in line with functional constructivism. As a third example, neurochemistry's evidence points to the "Throw & Catch" (T&C) principle in neurodynamics. This principle refers to the pro-active, neurochemically expensive, massive but topical increase of potentials ("Throw") within electrodynamics and neurotransmission in the brain whenever there is an uncertainty in selection of degrees of freedom (DFs). The T&C also underlines the relay-like processes during the selection of DFs. The "Throw" works as an internally generated "flashlight" that, contrarily to the expectations of entropy reduction, increases entropy and variance observed in processes related to orientation and action-formation. The discussed examples highlight the deficiency of structures-oriented projects and excitation-inhibition concepts in neuroscience. The neural regulation of behaviour appears to be a fluid, constructive process, constantly upgrading the choice of behavioural DFs, to ensure the compatibility between the environmental and individual's individuals' needs and capacities.

Analytic Background in the Neuroscience of the Potential Project "Hippocrates".

This paper reviews the principles identified in analytic neuroscience that could be used in the setup of an international project, "Hippocrates" (H-project), named after the author of the endocrine theory of temperaments. The H-project can aim to summarize the findings in functional neurochemistry of consistent behavioural patterns (CBPs) in health (such as temperament traits) and psychopathology (symptoms of psychiatric disorders); to have systematically structured neurochemical investigations; to have an analysis of CBPs that include all ranges of behavioural histories and to have these modules complemented by regional contrasts related to climate, diets and other bio-environmental factors. The review highlights the benefits of constructivism and illustrates the contrast between constructivism and current approaches in terms of analytic and methodological aspects. (1) "Where" the neurochemical biomarkers should be measured: the review expands the range of needed measurements to out-of-brain systems, including environmental factors, and explores the concept of Specialized Extended Phenotype. (2) "What" should be measured but is missing: the review points to the need for measurement of the "Throw & Catch" neurochemical relays; behavioural and neuronal events contributing to the consistency of the CBPs but not documented in measurements. (3) Structuring the H-project's setup: the paper briefly describes a proposed earlier neurochemical framework, Functional Ensemble of Temperament that that accommodates the neurochemical continuum between temperament and symptoms of psychiatric disorders. This framework is in line with documented "Throw & Catch" neurochemical relays and can also be used to organize data about the personal and professional history of an individual.

Functional Constructivism Approach to Multilevel Nature of Bio-Behavioral Diversity.

Attempts to revise the existing classifications of psychiatric disorders (DSM and ICD) continue and highlight a crucial need for the identification of biomarkers underlying symptoms of psychopathology. The present review highlights the benefits of using a Functional Constructivism approach in the analysis of the functionality of the main neurotransmitters. This approach explores the idea that behavior is neither reactive nor pro-active, but constructive and generative, being a transient selection of multiple degrees of freedom in perception and actions. This review briefly describes main consensus points in neuroscience related to the functionality of eight neurochemical ensembles, summarized as a part of the neurochemical model Functional Ensemble of Temperament (FET). None of the FET components is represented by a single neurotransmitter; all neurochemical teams have specific functionality in selection of behavioral degrees of freedom and stages of action construction. The review demonstrates the possibility of unifying taxonomies of temperament and classifications of psychiatric disorders and presenting these taxonomies formally and systematically. The paper also highlights the multi-level nature of regulation of consistent bio-behavioral individual differences, in line with the concepts of diagonal evolution (proposed earlier) and Specialized Extended Phenotype.

Emotionality vs. Other Biobehavioural Traits: A Look at Neurochemical Biomarkers for Their Differentiation.

This review highlights the differential contributions of multiple neurochemical systems to temperament traits related and those that are unrelated to emotionality, even though these systems have a significant overlap. The difference in neurochemical biomarkers of these traits is analysed from the perspective of the neurochemical model, Functional Ensemble of Temperament (FET) that uses multi-marker and constructivism principles. Special attention is given to a differential contribution of hypothalamic-pituitary hormones and opioid neuropeptides implicated in both emotional and non-emotional regulation. The review highlights the role of the mu-opioid receptor system in dispositional emotional valence and the role of the kappa-opioid system in dispositional perceptual and behavioural alertness. These opioid receptor (OR) systems, microbiota and cytokines are produced in three neuroanatomically distinct complexes in the brain and the body, which all together integrate dispositional emotionality. In contrast, hormones could be seen as neurochemical biomarkers of non-emotional aspects of behavioural regulation related to the construction of behaviour in fast-changing and current situations. As examples of the role of hormones, the review summarised their contribution to temperament traits of Sensation Seeking (SS) and Empathy (EMP), which FET considers as non-emotionality traits related to behavioural orientation. SS is presented here as based on (higher) testosterone (fluctuating), adrenaline and (low) cortisol systems, and EMP, as based on (higher) oxytocin, reciprocally coupled with vasopressin and (lower) testosterone. Due to the involvement of gonadal hormones, there are sex and age differences in these traits that could be explained by evolutionary theory. There are, therefore, specific neurochemical biomarkers differentiating (OR-based) dispositional emotionality and (hormones-based) body's regulation in fast-changing events. Here we propose to consider dispositional emotionality associated with OR systems as emotionality in a true sense, whereas to consider hormonal ensembles regulating SS and EMP as systems of behavioural orientation and not emotionality.

An investigation into differences between the structure of temperament and the structure of personality.

This article analyzes the differences between an activity-specific temperament model and the Big Five personality model using the Structure of Temperament Questionnaire--Compact (STQ-77). The STQ-77 has 3 emotionality scales and 9 scales assessing 3 dynamic aspects (arousal, lability, and sensory sensitivity) in 3 areas of activity (physical, verbal-social, and mental). The results of administration of the Russian STQ-77, NEO-FFI, and SSS-V to 174 Russian participants showed how components of temperament can represent the traits described in the Big Five model. The confirmatory factor analysis of the English STQ-77 and the results of a study involving a prolonged word classification task with 221 Canadian participants showed the benefits of the activity-specific approach, separating temperament traits in three areas of activity. Such specificity of temperament traits differentiates them from personality traits.

"Human status criteria: Sex differences and similarities across 14 nations": Correction to Buss et al. (2020).

Reports an error in "Human status criteria: Sex differences and similarities across 14 nations" by David M. Buss, Patrick K. Durkee, Todd K. Shackelford, Brian F. Bowdle, David P. Schmitt, Gary L. Brase, Jae C. Choe and Irina Trofimova (Journal of Personality and Social Psychology, Advanced Online Publication, May 28, 2020, np). In the article, the third sentence in the Content level subsection in the Status Criteria More Central to Women section of the Results should appear instead as Fidelity, chastity/purity, and long-term mating success increase women's status more than men's. A coding error in Figure 7 for Dishonoring Family appeared. The corrected Figure 7 now appears. (The following abstract of the original article appeared in record 2020-35662-001). Social status is a central and universal feature of our highly social species. Reproductively relevant resources, including food, territory, mating opportunities, powerful coalitional alliances, and group-provided health care, flow to those high in status and trickle only slowly to those low in status. Despite its importance and centrality to human social group living, the scientific understanding of status contains a large gap in knowledge-the precise criteria by which individuals are accorded high or low status in the eyes of their group members. It is not known whether there exist universal status criteria, nor the degree to which status criteria vary across cultures. Also unknown is whether status criteria are sex differentiated, and the degree of cross-cultural variability and consistency of sex-differentiated status criteria. The current article investigates status criteria across 14 countries (N = 2,751). Results provide the first systematic documentation of potentially universal and sex-differentiated status criteria. Discussion outlines important next steps in understanding the psychology of status. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Human status criteria: Sex differences and similarities across 14 nations.

[Correction Notice: An Erratum for this article was reported online in Journal of Personality and Social Psychology on Sep 7 2020 (see record 2020-68801-001). In the original article, the third sentence in the Content level subsection in the Status Criteria More Central to Women section of the Results should appear instead as Fidelity, chastity/purity, and long-term mating success increase women's status more than men's. A coding error in Figure 7 for Dishonoring Family appeared. The corrected Figure 7 now appears.] Social status is a central and universal feature of our highly social species. Reproductively relevant resources, including food, territory, mating opportunities, powerful coalitional alliances, and group-provided health care, flow to those high in status and trickle only slowly to those low in status. Despite its importance and centrality to human social group living, the scientific understanding of status contains a large gap in knowledge-the precise criteria by which individuals are accorded high or low status in the eyes of their group members. It is not known whether there exist universal status criteria, nor the degree to which status criteria vary across cultures. Also unknown is whether status criteria are sex differentiated, and the degree of cross-cultural variability and consistency of sex-differentiated status criteria. The current article investigates status criteria across 14 countries (N = 2,751). Results provide the first systematic documentation of potentially universal and sex-differentiated status criteria. Discussion outlines important next steps in understanding the psychology of status. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Adolescent feline heart contains a population of small, proliferative ventricular myocytes with immature physiological properties.

Recent studies suggest that rather than being terminally differentiated, the adult heart is a self-renewing organ with the capacity to generate new myocytes from cardiac stem/progenitor cells (CS/PCs). This study examined the hypotheses that new myocytes are generated during adolescent growth, to increase myocyte number, and these newly formed myocytes are initially small, mononucleated, proliferation competent, and have immature properties. Ventricular myocytes (VMs) and cKit(+) (stem cell receptor) CS/PCs were isolated from 11- and 22-week feline hearts. Bromodeoxyuridine incorporation (in vivo) and p16(INK4a) immunostaining were measured to assess myocyte cell cycle activity and senescence, respectively. Telomerase activity, contractions, Ca(2+) transients, and electrophysiology were compared in small mononucleated (SMMs) and large binucleated (LBMs) myocytes. Heart mass increased by 101% during adolescent growth, but left ventricular myocyte volume only increased by 77%. Most VMs were binucleated (87% versus 12% mononucleated) and larger than mononucleated myocytes. A greater percentage of SMMs was bromodeoxyuridine positive (SMMs versus LBMs: 3.1% versus 0.8%; P<0.05), and p16(INK4a) negative and small myocytes had greater telomerase activity than large myocytes. Contractions and Ca(2+) transients were prolonged in SMMs versus LBMs and Ca(2+) release was disorganized in SMMs with reduced transient outward current and T-tubule density. The T-type Ca(2+) current, usually seen in fetal/neonatal VMs, was found exclusively in SMMs and in myocytes derived from CS/PC. Myocyte number increases during adolescent cardiac growth. These new myocytes are initially small and functionally immature, with patterns of ion channel expression normally found in the fetal/neonatal period.

Exploration of the benefits of an activity-specific test of temperament.

The Structure of Temperament Questionnaire (STQ) was proposed by Rusalov in 1989 and subsequently tested in five languages. The questionnaire assesses four temperamental traits (Ergonicity, Plasticity, Tempo, and Emotionality) in three separate areas of activity: physical, verbal-social, and intellectual. The scales are all activity-specific. In 775 Canadian subjects, two temperament tests were compared, both developed on the basis of Pavlovian studies of the nervous system: the activity-specific approach (STQ) and the nonspecific Pavlovian Temperamental Survey (PTS). More significant sex differences were found on activity-specific scales of the STQ than on the nonspecific PTS scales. The pattern of correlations between the STQ scales and the time taken on an experimental task requiring a prolonged and intense word-assessment activity showed stronger correlations with the specific scales of the STQ measuring the dynamic aspects of social-verbal activity, and not with the PTS Strength of Excitation scale, which is based on a "general arousal" concept. The results supported the separation of temperament traits related to three different types of activities and opposed to "general arousal" theories of temperament.

Cyclooxygenase-1 is overexpressed in multiple genetically engineered mouse models of epithelial ovarian cancer.

Cyclooxygenases-1 and -2 (Cox-1 and Cox-2) are two distinct isoforms that catalyze the conversion of arachidonic acid to prostaglandins. The role of Cox-2 in a variety of cancers is well recognized, but the contribution of Cox-1 remains much less explored. We have previously shown that human epithelial ovarian tumors have increased levels of Cox-1, but not Cox-2. We also observed that Cox-1 is highly expressed in a mouse model of epithelial ovarian cancer (EOC), which lacks p53 but overexpresses c-myc and K-ras or c-myc and Akt. More importantly, a Cox-1-selective inhibitor, SC-560, attenuates EOC growth. In the present investigation, we used various genetically engineered mouse models of EOC to determine whether Cox-1 overexpression is unique to specific genetic and oncogenic alterations or is widespread. These models include: (a) deletion of both p53 and Rb, (b) induction of the transforming region of SV40 under the control of Mullerian inhibitory substance type II receptor, or (c) activation of K-Ras in the absence of Pten locally in the ovarian surface epithelium. We found that these three models, which produce spontaneous EOC, also show up-regulated expression of Cox-1, but not Cox-2. The results provide further evidence that Cox-1 overexpression is common in various models of EOC. Thus, Cox-1 serves as a potential marker of EOC and is a possible target for the prevention and/or treatment of this deadly disease.