Salivary testosterone and cortisol response in acute stress modulated by seven sessions of mindfulness meditation in young males.

Stress is an established risk factor for negative health outcomes. Salivary cortisol and testosterone concentrations increase in response to acute psychosocial stress. It's crucial to reduce stress for health and well-being through evidence-based interventions. Body-mind interventions such as meditation and Tai Chi have shown reduced cortisol levels but mixed results in testosterone concentration after stress. To address this research gap, we conducted a pilot randomized controlled trial to examine the modulating effects of a short-term (seven 20-minute sessions) mindfulness meditation on testosterone and cortisol in response to acute stress. Using one form of mindfulness meditation - Integrative Body-Mind Training (IBMT) and an active control-relaxation training (RT), we assessed salivary cortisol and testosterone concentrations at three stages of stress intervention - rest, stress, and an additional 20-min IBMT or RT practice. We found increased cortisol and testosterone concentrations after acute stress in both groups, but testosterone rise was not associated with cortisol rise. Moreover, an additional practice immediately after stress produced higher testosterone concentrations in the IBMT group than the RT group, whereas cortisol concentration increased in the RT group than in the IBMT group at the same time point. These findings indicate that brief mindfulness intervention modulates a dual-hormone profile of testosterone and cortisol in response to acute stress presumably via the co-regulation of hypothalamus-pituitary-adrenal and hypothalamus-pituitary-testicular axes.

Microbial transmission in the social microbiome and host health and disease.

Although social interactions are known to drive pathogen transmission, the contributions of socially transmissible host-associated mutualists and commensals to host health and disease remain poorly explored. We use the concept of the social microbiome-the microbial metacommunity of a social network of hosts-to analyze the implications of social microbial transmission for host health and disease. We investigate the contributions of socially transmissible microbes to both eco-evolutionary microbiome community processes (colonization resistance, the evolution of virulence, and reactions to ecological disturbance) and microbial transmission-based processes (transmission of microbes with metabolic and immune effects, inter-specific transmission, transmission of antibiotic-resistant microbes, and transmission of viruses). We consider the implications of social microbial transmission for communicable and non-communicable diseases and evaluate the importance of a socially transmissible component underlying canonically non-communicable diseases. The social transmission of mutualists and commensals may play a significant, under-appreciated role in the social determinants of health and may act as a hidden force in social evolution.

Evolutionary and neuroendocrine foundations of human aggression.

Humans present a behavioural paradox: they are peaceful in many circumstances, but they are also violent and kill conspecifics at high rates. We describe a social evolutionary theory to resolve this paradox. The theory interprets human aggression as a combination of low propensities for reactive aggression and coercive behaviour and high propensities for some forms of proactive aggression (especially coalitionary proactive aggression). These tendencies are associated with the evolution of groupishness, self-domestication, and social norms. This human aggression profile is expected to demand substantial plasticity in the evolved biological mechanisms responsible for aggression. We discuss the contributions of various social signalling molecules (testosterone, cortisol, oxytocin, vasopressin, serotonin, and dopamine) as the neuroendocrine foundation conferring such plasticity.

Generation of Proteins with Free N-Terminal Cysteine by Aminopeptidases.

Efficient, site-specific, and bio-orthogonal conjugation of chemical functionalities to proteins is of great utility in fundamental research as well as industrial processes (e.g., the production of antibody-drug conjugates and immobilization of enzymes for biocatalysis). A popular approach involves reacting a free N-terminal cysteine with a variety of electrophilic reagents. However, current methods for generating proteins with N-terminal cysteines have significant limitations. Herein we report a novel, efficient, and convenient method for producing recombinant proteins with free N-terminal cysteines by genetically fusing a Met-Pro-Cys sequence to the N-terminus of a protein of interest and subjecting the recombinant protein to the sequential action of methionine and proline aminopeptidases. The resulting protein was site-specifically labeled at the N-terminus with fluorescein and a cyclic cell-penetrating peptide through native chemical ligation and a 2-cyanobenzothiazole moiety, respectively. In addition, the optimal recognition sequence of Aeromonas sobria proline aminopeptidase was determined by screening a combinatorial peptide library and incorporated into the N-terminus of a protein of interest for most efficient N-terminal processing.

Discovery of a Cyclic Cell-Penetrating Peptide with Improved Endosomal Escape and Cytosolic Delivery Efficiency.

Cyclic cell-penetrating peptide 12 (CPP12) is highly efficient for the cytosolic delivery of a variety of cargo molecules into mammalian cells in vitro and in vivo. However, its cytosolic entry efficiency is substantially reduced at lower concentrations or in the presence of serum proteins. In this study, CPP12 analogs were prepared by replacing its hydrophobic residues with amino acids of varying hydrophobicity and evaluated for cellular entry. Substitution of l-3-benzothienylalanine (Bta) for l-2-naphthylalanine (Nal) resulted in CPP12-2, which exhibits up to 3.8-fold higher cytosolic entry efficiency than CPP12, especially at low CPP concentrations; thanks to improved endosomal escape efficiency. CPP12-2 is well suited for the cytosolic delivery of highly potent cargos to achieve biological activity at low concentrations.

Knowledge of wealth shapes social impressions.

Seven experiments conducted in India and the United States (N ∼7,000; 5 preregistered) examined the effects of wealth on warmth and competence, 2 fundamental dimensions of social impressions. Wealth causally influenced perceptions of a target's competence: high wealth increased perceived competence and low wealth decreased perceived competence (Experiments 1-3). Furthermore, both high and low wealth reduced perceived warmth compared with control conditions that provided no wealth-related information (Experiments 2 and 3). Attributing prosocial tendencies to the target in the form of charitable donations reversed wealth-induced reductions in warmth, while low levels of charitable donations lowered both perceived warmth and competence (Experiment 3). Reciprocally, information about the target's competence or warmth influenced how wealthy they were perceived to be (Experiment 4). Knowing the source of wealth (e.g., entrepreneurship, corporate fraud, inheritance) also affected perceptions of competence and warmth (Experiments 5 and 6). Moreover, participants expressed greater willingness to hire wealthier targets compared with poorer targets in hypothetical employment scenarios, a relationship mediated by perceived competence, suggesting that an individual's wealth may influence consequential assessments and decisions (Experiment 7). With rising economic inequality, it is crucial to understand how wealthy and poor individuals are perceived and the implications of these perceptions. The present experiments offer insight in this direction. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

The gut microbiome as a biomarker of differential susceptibility to SARS-CoV-2.

Coronavirus disease 2019 (COVID-19) continues to exact a devastating global toll. Ascertaining the factors underlying differential susceptibility and prognosis following viral exposure is critical to improving public health responses. We propose that gut microbes may contribute to variation in COVID-19 outcomes. We synthesise evidence for gut microbial contributions to immunity and inflammation, and associations with demographic factors affecting disease severity. We suggest mechanisms potentially underlying microbially mediated differential susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). These include gut microbiome-mediated priming of host inflammatory responses and regulation of endocrine signalling, with consequences for the cellular features exploited by SARS-CoV-2 virions. We argue that considering gut microbiome-mediated mechanisms may offer a lens for appreciating differential susceptibility to SARS-CoV-2, potentially contributing to clinical and epidemiological approaches to understanding and managing COVID-19.

Testosterone fluctuations in response to a democratic election predict partisan attitudes toward the elected leader.

Intergroup competitions such as democratic elections can intensify intergroup polarization and conflict. Partisan attitudes toward the elected leader can also shift from before to after an election, but the biology underlying these attitudinal shifts remains largely unknown. An important factor could be the hormone testosterone, which is theorized to fluctuate during competition and to influence status seeking. In a naturalistic study of 113 registered voters, we measured changes in testosterone levels and attitudes toward the winner of the 2012 US Presidential Election. We found that supporters of the losing candidate (Mitt Romney) showed acute increases in testosterone levels compared to supporters of the winner (Barack Obama) on the evening of Election Day. Supporters of the losing candidate also demonstrated flatter diurnal testosterone slopes on Election Day that persisted up to two days after the election. Furthermore, greater increases in acute testosterone levels and flatter diurnal slopes among supporters of the losing candidate were associated with less positive evaluations of the winning candidate. These testosterone-moderated attitudinal shifts observed in the days after the election showed a directionally similar pattern with a weaker effect size six months later. Finally, we confirmed that the main results were robust to alternative data analytic choices using multiverse specification curve analysis. The findings from this paper suggest that hormonal responses to large-scale intergroup competitions may shape how we perceive our elected leaders, shedding light on the biology of intergroup relations.

Discovery of a Bicyclic Peptidyl Pan-Ras Inhibitor.

The Ras subfamily of small GTPases is mutated in ∼30% of human cancers and represents compelling yet challenging anticancer drug targets owing to their flat protein surface. We previously reported a bicyclic peptidyl inhibitor, cyclorasin B3, which binds selectively to Ras-GTP with modest affinity and blocks its interaction with downstream effector proteins in vitro but lacks cell permeability or biological activity. In this study, optimization of B3 yielded a potent pan-Ras inhibitor, cyclorasin B4-27, which binds selectively to the GTP-bound forms of wild-type and mutant Ras isoforms (KD = 21 nM for KRasG12V-GppNHp) and is highly cell-permeable and metabolically stable (serum t1/2 > 24 h). B4-27 inhibits Ras signaling in vitro and in vivo by blocking Ras from interacting with downstream effector proteins and induces apoptosis of Ras-mutant cancer cells. When administered systemically (i.v.), B4-27 suppressed tumor growth in two different mouse xenograft models at 1-5 mg/kg of daily doses.

Microbial transmission in animal social networks and the social microbiome.

Host-associated microbiomes play an increasingly appreciated role in animal metabolism, immunity and health. The microbes in turn depend on their host for resources and can be transmitted across the host's social network. In this Perspective, we describe how animal social interactions and networks may provide channels for microbial transmission. We propose the 'social microbiome' as the microbial metacommunity of an animal social group. We then consider the various social and environmental forces that are likely to influence the social microbiome at multiple scales, including at the individual level, within social groups, between groups, within populations and species, and finally between species. Through our comprehensive discussion of the ways in which sociobiological and ecological factors may affect microbial transmission, we outline new research directions for the field.

The role of the microbiome in the neurobiology of social behaviour.

Microbes colonise all multicellular life, and the gut microbiome has been shown to influence a range of host physiological and behavioural phenotypes. One of the most intriguing and least understood of these influences lies in the domain of the microbiome's interactions with host social behaviour, with new evidence revealing that the gut microbiome makes important contributions to animal sociality. However, little is known about the biological processes through which the microbiome might influence host social behaviour. Here, we synthesise evidence of the gut microbiome's interactions with various aspects of host sociality, including sociability, social cognition, social stress, and autism. We discuss evidence of microbial associations with the most likely physiological mediators of animal social interaction. These include the structure and function of regions of the 'social' brain (the amygdala, the prefrontal cortex, and the hippocampus) and the regulation of 'social' signalling molecules (glucocorticoids including corticosterone and cortisol, sex hormones including testosterone, oestrogens, and progestogens, neuropeptide hormones such as oxytocin and arginine vasopressin, and monoamine neurotransmitters such as serotonin and dopamine). We also discuss microbiome-associated host genetic and epigenetic processes relevant to social behaviour. We then review research on microbial interactions with olfaction in insects and mammals, which contribute to social signalling and communication. Following these discussions, we examine evidence of microbial associations with emotion and social behaviour in humans, focussing on psychobiotic studies, microbe-depression correlations, early human development, autism, and issues of statistical power, replication, and causality. We analyse how the putative physiological mediators of the microbiome-sociality connection may be investigated, and discuss issues relating to the interpretation of results. We also suggest that other candidate molecules should be studied, insofar as they exert effects on social behaviour and are known to interact with the microbiome. Finally, we consider different models of the sequence of microbial effects on host physiological development, and how these may contribute to host social behaviour.

Peptidomimetics prepared by tail-to-side chain one component peptide stapling inhibit Alzheimer's amyloid-ß fibrillogenesis.

Alzheimer's disease (AD) is the most common form of dementia affecting the elderly population worldwide. Despite enormous efforts and considerable advancement in research, no therapeutic agents have come to light to date. However, many peptide-based and small molecule inhibitors interact efficiently with the amyloid-ß (Aß) peptide and alter its aggregation pathway. On the other hand, stapled peptides have been developed mainly to stabilize α-helix conformations and study protein-protein interactions. ß-Sheet stabilization or destabilization by stapled peptides has not been explored enough. Herein, we describe the generation of a library of "tail-to-side chain" stapled peptides via lactamization and their application for the first time as modulators of Aß1-40 self-association and fibrillogenesis. They also disrupt the preformed fibrillar aggregates into nontoxic species. Their stability in the presence of proteolytic enzymes is increased due to stapling. Therefore, the stapled peptides thus formed can be useful as potent amyloid aggregation inhibitors and pave a therapeutic pathway for combating amyloid-related diseases. Also, they may help in gaining insight into the process of aggregation.

Beyond the challenge hypothesis: The emergence of the dual-hormone hypothesis and recommendations for future research.

The challenge hypothesis makes specific predictions about the association between testosterone and status-seeking behaviors, but the findings linking testosterone to these behaviors are often inconsistent. The dual-hormone hypothesis was developed to help explain these inconsistencies. Specifically, according to this hypothesis, testosterone's association with status-seeking behavior depends on levels of cortisol. Here, we (1) describe the dual-hormone hypothesis in relation to the challenge hypothesis; (2) review recent studies that tested the dual-hormone hypothesis as well as meta-scientific evidence of heterogeneous dual-hormone findings across studies; (3) discuss potential explanations for this heterogeneity, including methodological considerations, contextual factors, and individual differences; and (4) provide recommendations for new work aimed at testing and extending the dual-hormone hypothesis.

Neuroenhancement of High-Level Cognition: Evidence for Homeostatic Constraints of Non-invasive Brain Stimulation.

Neuroenhancement aims to improve cognitive performance in typically and atypically functioning populations. However, it is currently debated whether it is also effective in exceptionally high-functioning individuals. Present theories suggest that homeostatic set points for learning and cortical plasticity limit the beneficial effects of neuroenhancement. To examine this possibility, we used transcranial random noise stimulation (tRNS) to non-invasively stimulate bilateral dorsolateral prefrontal cortices (DLPFC) of the world champion in mental calculation, G.M. TRNS did not change G.M.'s calculation performance compared to sham stimulation on an exceptionally complex arithmetic task. However, a sample of mathematicians who were not calculation prodigies (N = 6) showed reduced accuracy on a complex multiplication task in response to tRNS, relative to sham. Our findings suggest that there may be an upper limit for cognitive enhancement and that further attempts to enhance performance using tRNS (at least with the current parameters) may impair optimal functioning. The discussion of potential negative effects of brain stimulation for cognitive enhancement is critical, as it may lead to unintended impairments in different subgroups of the population.

The Microbiome in Psychology and Cognitive Neuroscience.

Psychology and microbiology make unlikely friends, but the past decade has witnessed striking bidirectional associations between intrinsic gut microbes and the brain, relationships with largely untested psychological implications. Although microbe-brain relationships are receiving a great deal of attention in biomedicine and neuroscience, psychologists have yet to join this journey. Here, we illustrate microbial associations with emotion, cognition, and social behavior. However, despite considerable enthusiasm and potential, technical and conceptual limitations including low statistical power and lack of mechanistic descriptions prevent a nuanced understanding of microbiome-brain-behavior relationships. Our goal is to describe microbial effects in domains of cognitive significance and the associated challenges to stimulate interdisciplinary research on the contribution of this hidden kingdom to psychological processes.

The Impact of Using Documented but Uncharged Offense Data on JSORRAT-II Predictive Validity.

Following the implementation of sexual offender notification laws, researchers have found a drop in the rate of prosecutions and an increase in plea bargains for sexual offenses committed by male juveniles. This type of prosecutorial hesitation has implications for the predictive validity of sexual recidivism risk assessments, such as the Juvenile Sexual Offender Recidivism Risk Assessment Tool-II (JSORRAT-II), that require data from officially adjudicated offenses in the scoring of several items. The present study sought to test the impact of including data from documented but uncharged (DBU) sexual offenses in the scoring of the JSORRAT-II on its predictive validity using an exhaustive sample of 1,095 juveniles who offended sexually from the states of Iowa and Utah. Although sexual recidivists had significantly more DBU data, the inclusion of those data did not improve the predictive validity of the tool. The authors discuss additional reasons why changes in prosecutorial practice might remain confound in risk assessment studies and suggest future research to investigate those hypotheses.

Psychobiotics and the Manipulation of Bacteria-Gut-Brain Signals.

Psychobiotics were previously defined as live bacteria (probiotics) which, when ingested, confer mental health benefits through interactions with commensal gut bacteria. We expand this definition to encompass prebiotics, which enhance the growth of beneficial gut bacteria. We review probiotic and prebiotic effects on emotional, cognitive, systemic, and neural variables relevant to health and disease. We discuss gut-brain signalling mechanisms enabling psychobiotic effects, such as metabolite production. Overall, knowledge of how the microbiome responds to exogenous influence remains limited. We tabulate several important research questions and issues, exploration of which will generate both mechanistic insights and facilitate future psychobiotic development. We suggest the definition of psychobiotics be expanded beyond probiotics and prebiotics to include other means of influencing the microbiome.

Mathematics Anxiety: What Have We Learned in 60 Years?

The construct of mathematics anxiety has been an important topic of study at least since the concept of "number anxiety" was introduced by Dreger and Aiken (1957), and has received increasing attention in recent years. This paper focuses on what research has revealed about mathematics anxiety in the last 60 years, and what still remains to be learned. We discuss what mathematics anxiety is; how distinct it is from other forms of anxiety; and how it relates to attitudes to mathematics. We discuss the relationships between mathematics anxiety and mathematics performance. We describe ways in which mathematics anxiety is measured, both by questionnaires, and by physiological measures. We discuss some possible factors in mathematics anxiety, including genetics, gender, age, and culture. Finally, we describe some research on treatment. We conclude with a brief discussion of what still needs to be learned.

Transcranial electrical stimulation and numerical cognition.

The effects of transcranial electrical stimulation (tES) have been documented for a variety of mental functions, including numerical cognition. This article first reviews 2 prominent forms of tES, transcranial direct current stimulation (tDCS) and transcranial random noise stimulation (tRNS). This is followed by an assessment of the applications of this technology in the enhancement of aspects of numerical cognition, including numerosity, magnitude representation, and more complex arithmetic operations. The review concludes with discussions of directions for future research. These include the need to take individual differences into account in experimental designs, extending research to individuals with difficulties and deficits in working with numbers, the need to consider potential cognitive costs that may offset cognitive benefits of tES. A recurring theme in this article is the need to move toward greater ecological validity of experimental findings.