Nonhuman Research Articles

TAKE AN OLD DRUG AND STAY YOUNG? METFORMIN AS AN ANTI-AGING MEDICATION – A LITERATURE REVIEW.

AIMS: Metformin is the main drug used in the treatment of type 2 diabetes mellitus, and the most widely prescribed oral antihyperglycemic medication. Its mechanism of action is still not completely understood and research into new uses for the compound is still ongoing, with one possible novel application of the medication being to combat aging on both the cellular and the macroscopic level. The aim of the study is to evaluate the current state of knowledge on metformin’s potential as a lifespan-extending and anti-senescence drug, present evidence on the matter and assess possible lanes of further study into such effects. METHODS: The literature review was performed using Internet research paper databases (PubMed, Google Scholar, Medline), using articles available in English. RESULTS: Multiple papers suggest tentative support for the notion that metformin may contribute to slowing cellular senescence, as well as to extending the human lifespan. Theoretical knowledge exists that shows possible routes of action of metformin in this regard. CONCLUSIONS: There is ample evidence in the literature for metformin’s possible effects as an anti-aging drug. Numerous cellular pathways by which it could exert lifespan-extending effects have been elucidated, and in vivo studies on some non-human animals have shown a measurable decrease in their production of aging markers, as well as an increase in the lifespan. Studies on diabetic patients have also demonstrated a significant reduction in all-cause mortality in that particular group. However, there is a lack of data and a need for more research that would investigate metformin’s potential as a universal anti-senescence agent more directly. Two large-scale studies (MILES and TAME) in the area are currently underway.

Moral Future-Thinking: Does the Moral Circle Stand the Test of Time?

Humanity's long-term welfare may lie in the hands of those who are presently living, raising the question of whether people today hold the generations of tomorrow in their moral circles. Five studies (NTotal = 1652; Prolific) reveal present-oriented bias in the moral standing of future generations, with greater perceived moral obligation, moral concern, and prosocial intentions for proximal relative to distal future targets. Yet, present-oriented bias appears stronger for socially close compared with socially distant targets and for human targets relative to non-human animals and entities in nature. Individual differences, including longtermism beliefs and subjective imaginative vividness, predict greater concern for and obligation to the future. Likewise, concern and obligation predict greater future-oriented generosity. Our studies are among the first to explore moral considerations for targets across deep temporal expanses, reconcile conflicting evidence in the extant literature on moral judgment and future-thinking, and offer practical implications for bettering the shared societal future.

Zoographics in the Journal of the Experimental Analysis of Behavior: Increasing inclusion of female animals.

We examined the zoographics, or the characteristics of nonhuman animal subjects, reported for the entirety of the Journal of the Experimental Analysis of Behavior (JEAB) through the most recent complete year (1958-2023). Animal sex in particular was evaluated to determine whether the lack of inclusion of female subjects in other disciplines extends to JEAB. Through systematic coding of all nonhuman empirical articles, we found consistent underreporting of most zoographics and a disproportionate use of male subjects relative to female subjects. Additionally, animal sex was commonly unreported and the inclusion of both male and female subjects was sparse. Recent years show some improvement, but greater inclusion is required. Lack of female subjects in research as well as underreporting of zoographics can generate unrepresentative results and hamper replication, generalization, and translation. We provide resources to guide future research and reporting suggestions such as equal inclusion and disaggregation of data by sex. We also clarify misunderstandings about the use of both sexes in research such as beliefs that it necessarily increases the cost of research.

A multi-trait embodied framework for the evolution of brains and cognition across animal phyla.

Among non-human animals, crows, octopuses and honeybees are well-known for their complex brains and cognitive abilities. Widening the lens from the idiosyncratic abilities of exemplars like these to those of animals across the phylogenetic spectrum begins to reveal the ancient evolutionary process by which complex brains and cognition first arose in different lineages. The distribution of 35 phenotypic traits in 17 metazoan lineages reveals that brain and cognitive complexity in only three lineages (vertebrates, cephalopod mollusks, and euarthropods) can be attributed to the pivotal role played by body, sensory, brain and motor traits in active visual sensing and visuomotor skills. Together, these pivotal traits enabled animals to transition from largely reactive to more proactive behaviors, and from slow and two-dimensional motion to more rapid and complex three-dimensional motion. Among pivotal traits, high-resolution eyes and laminated visual regions of the brain stand out because they increased the processing demands on and the computational power of the brain by several orders of magnitude. The independent acquisition of pivotal traits in cognitively complex (CC) lineages can be explained as the completion of several multi-trait transitions over the course of evolutionary history, each resulting in an increasing level of complexity that arises from a distinct combination of traits. Whereas combined pivotal traits represent the highest level of complexity in CC lineages, combined traits at lower levels characterize many non-CC lineages, suggesting that certain body, sensory and brain traits may have been linked (the trait-linkage hypothesis) during the evolution of both CC and non-CC lineages.

From men's violence to an ethic of care: Ecofeminist contributions to green criminology

Green criminology has made important contributions to criminological inquiry by highlighting the destructive impact of humans on the more-than-human world. However, it often adopts a gender-neutral lens that overlooks the disproportionate role of men and masculinities in perpetrating green harms. This paper places green criminology into critical dialogue with ecofeminism, arguing that harms against the environment and nonhuman animals are inextricably gendered and should be understood as interconnected forms of men's violence. Ecofeminist insights reveal that violence against the more-than-human world is rooted in hierarchical dualisms, whereby humans are placed separate from and above nature, and the masculine is defined as superior to the feminine. This hierarchical logic enables men to view others in detached, instrumental ways and serves to legitimise acts of men's violence. But just as ecofeminism provides green criminologists with a productive framework for understanding men's violence against the environment and nonhuman animals, it also provides a means of moving beyond this violence. It does this by advocating for an ethic of care that unravels hierarchical modes of thinking and promotes more harmonious relationships between humans and the more-than-human world. By building caring, egalitarian relationships with other living beings (and with their own emotional selves), it is harder for men to act in violent, dominating ways towards others, providing the foundation for more sustainable, interdependent ways of being.

Security, ethics, and animals: towards a sentientist security discourse

ABSTRACT This article argues that it is high time for the (extra)ordinary violence and insecurity that nonhuman animals are subjected to in today’s world to be taken seriously in studies on security. Through a sympathetic yet critical engagement with how animals have appeared in recent posthuman security scholarship, the article insists on the need to differentiate between sentient beings on the one hand, and other beings as well as things on the other; the need to acknowledge and seek ways of eliminating the violence and insecurity internal to entangled human-animal relations; the feasibility of treating individual animals as direct subjects of security; and the feasibility of adopting a strong animal rights position grounded in sentience to supplement the relational or entanglement ethic dominant in posthuman security scholarship. The article proceeds by developing a tentative outline of a sentientist security discourse in terms of referent objects, nature of threats, security agents and security practices, and concludes by discussing some scholarly implications and the potential impact of securitising existential threats to animals.

When does metacognition evolve in the opt-out paradigm?

Metacognition (awareness of one's own knowledge) is taken for granted in humans, but its evolution in non-human animals is not well understood. While there is experimental evidence of seemingly metacognitive judgements across species, studies rarely focus on why metacognition may have evolved. To address this, I present an evolutionary model of the opt-out paradigm, a common experiment used to assess animal's metacognition. Individuals are repeatedly presented with a task or problem and must decide between opting-out and receiving a fixed payoff or opting-in and receiving a larger reward if they successfully solve the task. Two evolving traits - bias and metacognition - jointly determine whether individuals opt-in. The task's reward, the mean probability of success and the variability in success across trials, and the cost of metacognition were varied. Results identify two scenarios where metacognition evolves: (1) environments where success variability is high; and (2) environments where mean success is low, but rewards are high. Overall, the results support predictions implicating uncertainty in the evolution of metacognition but suggest metacognition may also evolve in conditions where metacognition can be used to identify cases where an otherwise inaccessible high payoff is easy to acquire.

Inflammation is associated with pain and fatigue in older adults

IntroductionIncreasing evidence suggests that inflammation may play a pivotal role in the development of chronic pain and fatigue in aging individuals. This study investigated the relationship between three inflammatory markers (IL-6, CRP, and TNFα) and pain and fatigue, both cross-sectionally and longitudinally, in a sample of older adults from the Saint Louis Personality and Aging (SPAN) study. MethodsSPAN study participants provided blood samples at two in-person sessions approximately 2 years apart for the analysis of the inflammatory biomarkers IL-6, CRP, and TNFα. Pain and fatigue were assessed using the RAND-36 Health Status Inventory. Correlations (with false discovery rate correction for multiple testing) and follow-up linear regressions including potentially confounding demographic (e.g., annual household income) and health (e.g., BMI, medication use) covariates were used to estimate cross sectional and longitudinal associations. Analytic ns ranged from 533 to 815. ResultsCross-sectional analyses revealed that higher IL-6 and CRP were associated with greater reported pain and fatigue, even after accounting for covariates (βs > .098, ps < .05). TNFα was associated with greater fatigue only (β = .100, p = .012). Longitudinally, CRP and IL-6 predicted future pain and fatigue, although only the relationship between CRP and future fatigue survived the inclusion of covariates (β = .104, p = .022). Both pain and fatigue predicted higher levels of IL-6 and CRP approximately 2 years later, although only the associations with IL-6 survived the inclusion of covariates (βs > .12, ps < .01). DiscussionOur study adds to a growing body of literature showing that inflammation is associated with greater pain and fatigue in older adults. Our longitudinal data showing temporal bidirectional associations is consistent with evidence from non-human animal models that heightened inflammation causally contributes to fatigue and also suggests that the experience of pain and fatigue may contribute to inflammation. It will be important for future work to identify how lifestyle factors associated with pain and fatigue (e.g., physical activity) may contribute to these associations.

To know or not to know? Curiosity and the value of prospective information in animals.

Humans and other animals often seek instrumental information to strategically improve their decisions in the present. Our curiosity also leads us to acquire non-instrumental information that is not immediately useful but can be encoded in memory and stored for use in the future by means of episodic recall. Despite its adaptive benefits and central role in human cognition, questions remain about the cognitive mechanisms and evolutionary origins that underpin curiosity. Here, we comparatively review recent empirical studies that some authors have suggested reflects curiosity in nonhuman animals. We focus on findings from laboratory tasks in which individuals can choose to gain advanced information about uncertain future outcomes, even though the information cannot be used to increase future rewards and is often costly. We explore the prevalence of preferences in these tasks across animals, discuss the theoretical advances that they have promoted, and outline some limitations in contemporary research. We also discuss several features of human curiosity that can guide future empirical research aimed at characterising and understanding curiosity in animals. Though the prevalence of curiosity in animals is actively debated, we surmise that investigating behavioural candidates for curiosity-motivated behaviour in a broader range of species and contexts, should help promote theoretical advances in our understanding of cognitive principles and evolutionary pressures that support curiosity-driven behaviour.

Friend or foe? Early life adversity to improve farmed animal welfare

Early life experiences can have lasting impacts on an animal’s development. Extensive research evidence aligns across both human and non-human rodent and primate laboratory animals showing negative impacts of early life adversity such as impairments in neurological and behavioural development. Farmed animals experience a range of adversities across their production lifetimes, often early in life, including species atypical social groupings, invasive husbandry procedures, and transport. Correspondingly, farmed animals also demonstrate a wide range of impairments such as stereotypic, injurious, and other abnormal behaviours. An individual, however, needs to experience adversity to be able to develop resilience and coping mechanisms that facilitate dealing with challenges later in life. Not all individuals will experience stress vulnerability following adversity, with some individuals instead developing stress resilience. This mini review collates evidence on the positive effects of early life adversity on improving adaptability in farmed species, both terrestrial and aquatic. While evidence across farmed animal species is currently much less than for humans, laboratory rodents or non-human primates, similar patterns emerge where mild adversity early in life, can improve the adaptability of the animal in the face of future stressors. Many views of optimised welfare posit that farmed animals should be housed in as natural environments as possible to limit many of the typical adversities they face. However, strategic mild exposure to early life adversity may facilitate improved animal welfare under intensive commercial farming conditions. Future research into this area could provide management tools to better predict and promote stress resilience over stress vulnerability.

A Systematic Review on Sex Differences in Prepulse Inhibition of Startle

Abstract: Prepulse inhibition of the startle response is defined as the inhibition of the startle reflex to an intense contextual stimulus (named pulse) when a weaker stimulus (named prepulse) precedes it and is considered a measure of sensorimotor gating. Consistent with recent research, it has been observed that this measure might exhibit sex differences in studies of both humans and rodents, although the results in the literature appear to be inconsistent. Therefore, this systematic review aims to analyze the sexual differences observed in human and nonhuman animal studies from a comparative perspective. A comprehensive search was conducted from the inception to the present in the Web of Science, PubMed, and PsycInfo databases. Following the search, 58 studies were included in the review. The average age in human studies ( n = 32) was 31.45 years (range = 4–69), while among nonhuman animal studies ( n = 26), the average age was 75.5 postnatal days (range = 7–360). The results indicated no clear sexual differences in the startle response magnitude. However, consistent sex differences in prepulse inhibition were found, revealing that males exhibited higher levels of sensorimotor gating compared to females in both humans (78.79% of the studies) and nonhuman animal studies (69.23% of the studies). Therefore, the findings corroborate the sex differences of prepulse inhibition and underscore the value of this paradigm in comparative science, emphasizing the importance of considering sex as an independent variable when studying this phenomenon.

Weapon of Assault: Combat, Protective Magic, and the Fatal Throat Bite in Icelandic Sagas

Abstract Icelandic sagas contain a literary motif little known in other pre-modern literary traditions: the throat bite. There are 10 scenes in the sagas in which one character bites, almost bites, or contemplates biting the throat of another character. The throat bite was used by saga authors strategically and purposefully, whether to resolve conflict, similar to a more conventional murder; to signify paranormal characteristics – or lack of paranormal characteristics; or to denote interpersonal power dynamics within a saga narrative. Due to the prevalence of the throat bite in extra-narrative contexts, including its use as hunting technique among non-human animals and the documented use of human teeth as a weapon among human populations, the saga writers of medieval Iceland accurately recognized that human teeth can serve as a weapon of assault and they craftily integrated the throat bite into the composition of select sagas.

Of Birds and Men in Rural Norway: Self, Place and Landscape in Vesaas and Lirhus

Abstract Agnar Lirhus’s Nå hogger de (2020) and Tarjei Vesaas’s Fuglane (1957) both feature a main character whose self-narrative is formed through interaction with nonhuman animals and grounded in attachment to place. These characters break with the dominant cultural ontology by attributing agency and intrinsic value to beings who are otherwise ignored or pursued for utilitarian purposes. I consider the ethical implications of their encounters with nonhumans, exploring whether these can be considered social interactions or are better understood as occurring on a spiritual plane. Finally, I show that the choice of outsiders as main characters can function as a literary strategy for questioning the dominant cultural ontology.

Two approaches to grounding moral standing: interests-first or value-first?

AbstractDo non-human animals have moral standing? Work on this question has focused on choosing the right grounding property (for example, personhood or sentience) while little attention has been paid to the various ways that the connection between grounding properties and moral standing has been explained. In this paper, I address that gap by offering a fresh way to approach the debate over the grounds of moral standing, including a novel taxonomy of positions, and argue that one kind of position, which takes a ‘value-first’ approach, is preferable to the other, which takes an ‘interests-first’ approach. According to value-first accounts, some individuals have moral standing because they have properties that make them valuable. According to interests-first accounts, some individuals have moral standing because they have interests, and any interest must always be taken into account. I argue that we should prefer value-first accounts because they engage directly with the problem the concept of moral standing is employed to solve, and because interests-first accounts cannot meet their explanatory burdens without begging the question against value-first accounts.

Emotional comorbidities in epilepsy result from seizure-induced corticosterone activity

People with epilepsy often have psychiatric comorbidities that can significantly impair their quality of life. We previously reported that repeated seizure activity persistently alters endocannabinoid (eCB) signaling in the amygdala which accounts for comorbid emotional dysregulation in rats, however, the mechanism by which these alterations in eCB signaling within the epileptic brain occur is unclear. Endocannabinoid signaling is influenced by corticosterone (CORT) to modulate cognitive and emotional processes and a hyperactive hypothalamic-pituitary-adrenal (HPA) axis occurs in both people with epilepsy and nonhuman animal models of epilepsy.We employed selective pharmacological tools and a variety of approaches including whole-cell patch-clamp electrophysiology, behavioural paradigms and biochemical assays in amygdala kindled adult male Long-Evans rats. We aimed to determine whether seizures induce hypersecretion of CORT and the role this plays in eCB system dysregulation, impaired fear memory, and anxiety-like behaviours associated with seizure activity.Plasma CORT levels were significantly and consistently elevated following seizures over the course of kindling. Pre-seizure administration with the CORT synthesis inhibitor metyrapone prevented this seizure-induced CORT increase, prevented amygdala anandamide downregulation, and synaptic alteration induced by seizure activity. Moreover, treatment with metyrapone or combined glucocorticoid receptor (GR)/mineralocorticoid receptor (MR) antagonists prior to each elicited seizure were equally effective in preventing chronically altered anxiety-like behaviour and fear memory responses.Inhibiting seizure-induced corticosterone synthesis, or directly blocking the effects of CORT at GR/MR prevents deleterious changes in emotional processing and could be a treatment option for emotional comorbidities in epilepsy.

Slimming shades: investigating the allure of black clothing on women's aesthetics

Colours play a significant role in sexual selection among nonhuman animals. As trichromatic primates, humans lack the pronounced skin colouration observed in certain primates. However, they expand their colour preferences by embracing various hues and styles through clothing and fashion. The attractiveness associated with black lacks a known biological basis but appears to derive from its perceived fashionable nature. One mechanism contributing to the allure of black is its slimming effect. Black absorbs visible light, creating shadows that obscure contours and the illusion of reduced distinctiveness in shapes. This visual effect can give a slimmer appearance than wearing lighter or brighter colours, which may accentuate curves or shapes more prominently. In Study 1, conducted by means of an online questionnaire, women wearing black clothing were perceived as slimmer than those wearing yellow and green clothing. However, the slimming effect was significant when comparing black with yellow and green but not significant when comparing black with white, red, and purple. Study 2 involved tracking the colours of the clothing worn by women for 30 days. The results revealed a significant positive correlation between wearing black clothes and the participants' body mass index (BMI). Our research suggests that the perceived attractiveness of the black colour is due in part to its slimming effect and that women with higher BMI may opt for black clothing to visually mitigate their weight.

Interdisciplinary Animal Research Ethics-Challenges, Opportunities, and Perspectives.

Can nonhuman animals be used for the benefit of humans in a scientifically and morally justified manner and, if yes, how? Based on our own experiences as scholars from various academic backgrounds, we argue that this question can only be answered as an interdisciplinary and international endeavor, considering insights from research ethics and animal ethics as well as scientific and legal aspects. The aim of this article is to contribute to the foundation of the emerging field of animal research ethics. In doing so, we describe the following seven phases of animal research experiments: ethical, legal and social presumptions (phase 0), planning (phase I), review (phase II), conduct of experiments (phase III), publication/dissemination (phase IV), further exploitation of results (phase V), and evaluation (phase VI). In total, 20 key ethical, legal, and practical challenges that an ethical framework for the use of animals in research needs to address are identified and analyzed. Finally, we characterize the following four meta-challenges and opportunities associated with animal research ethics as a field: (1) moral pluralism, (2) the integration of views and positions outside the laboratory, (3) international plurality of conduct, standards, and legal norms, and (4) interdisciplinary education.

Mice monitor their timing errors

Animals often engage in representationally guided goal-directed behaviors. These behaviors are thus also subjected to representational uncertainty (e.g. timing uncertainty during waiting), which has been previously shown to adaptively guide behaviors normatively. These observations raise the question of whether non-human animals can track the direction and magnitude of their timing errors (i.e. temporal error monitoring). Only a few studies have investigated this question without addressing the key components of temporal error monitoring (e.g. due to differential reinforcement of metacognitive judgments and primary task representation). We conducted the critical test of temporal error monitoring in mice by developing a novel behavioral task that involved temporal production that exponentially favored temporal accuracy and minimized the contribution of sensorimotor noise. The response rate for an upcoming probabilistic reward following the timing performance was used as a proxy for confidence. We found that mice exhibited high reward expectancy after accurate and low reward expectancy after inaccurate timing performance. The reward expectancy decreased as a function of deviations from the target interval for the short and long reproductions; pointing to the symmetrical sensitivity of metacognition to shorter/longer than target responses. These findings suggest a complete temporal error monitoring ability for mice with human-like metacognitive features.

The semiotic repertoire of dairy cows

Abstract This article moves from the familiar—the human—to the very different in sociolinguistics—the dairy cow. Based on multispecies ethnography, the aim of this article is to advocate the animal turn in sociolinguistics (Cornips 2019). The guiding question is how do non-human animals, that is, dairy cows—mutually and with humans—imbue their intraspecies and interspecies interaction with meaning that makes sense for the two species. The concept of semiotic repertoire is invoked in order to investigate how dairy cows draw on resources to make meaning, and the concept of material-semiotic assemblage is applied in order to account for the different effects generated by the resources that come together at particular moments. The assemblage perspective does not take a ‘cow’ or ‘human’ as discrete and fixed but focuses on the distributed and emergent agency as a relational effect of all elements involved: humans, non-humans, and other. (Intraspecies and interspecies interactions, the semiotic repertoire, assemblage, dairy cows, practices)*

Beyond Birth Control: The Neuroscience of Hormonal Contraceptives.

Hormonal contraceptives (HCs) are one of the most highly prescribed classes of drugs in the world used for both contraceptive and noncontraceptive purposes. Despite their prevalent use, the impact of HCs on the brain remains inadequately explored. This review synthesizes recent findings on the neuroscience of HCs, with a focus on human structural neuroimaging as well as translational, nonhuman animal studies investigating the cellular, molecular, and behavioral effects of HCs. Additionally, we consider data linking HCs to mood disorders and dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and stress response as a potential mediator. The review also addresses the unique sensitivity of the adolescent brain to HCs, noting significant changes in brain structure and function when HCs are used during this developmental period. Finally, we discuss potential effects of HCs in combination with smoking-derived nicotine on outcomes of ischemic brain damage. Methodological challenges, such as the variability in HC formulations and user-specific factors, are acknowledged, emphasizing the need for precise and individualized research approaches. Overall, this review underscores the necessity for continued interdisciplinary research to elucidate the neurobiological mechanisms of HCs, aiming to optimize their use and improve women's health.