Environmental Enrichment Cage for Laboratory Mice: A Downloadable Alternative.

Environmentally enriched housing (EE) provides a stimulating and species-typical environment that enhances brain plasticity and cognition, while reducing disease severity in laboratory animals. However, standardizing EE protocols has been challenging due to issues such as variability, high pricing, or limited laboratory space. To address these challenges, we present a replicable and cost-efficient cage protocol that is accessible to researchers with limited resources and space constraints. The protocol is designed to provide a stimulating and species-typical environment for the animals. It incorporates elements such as social interaction, physical exercise, cognitive stimulation, manipulable objects, environmental variability, and sensory stimulation. As evidenced in our previous studies using our protocol, users can expect to observe similar neuroplastic and health-wise benefits that accompany EE experimental paradigms. These included straightforward step-by-step guide, which allows for construction of functional EE cages in under 8 hr. Basic knowledge of 3D printing and laser cutting is required, but no advanced skills are necessary. The protocol enables researchers to create stimulating and replicable environments that promote animal welfare, enhance brain plasticity, and yield valuable experimental results for low cost. © 2024 Wiley Periodicals LLC. Basic Protocol: An effective and cost-efficient environmental enrichment cage designed to encourage standardization amongst laboratory protocols.

Basin scale coherence of Kauai-Beacon m-sequence transmissions received at Wake Island and Monterey, CA.

The 75 Hz Kauai-Beacon source is well-situated for observing the North Pacific Ocean acoustically, and ongoing efforts enable transmissions and analysis of broadband signals in 2023 and beyond. This is the first demonstration of acoustic receiving along paths to Wake Island (∼3500 km) and Monterey Bay (∼4000 km). The 44 received m-sequence waveforms exhibit excellent phase stability with processing gain approaching the maximum theoretical gain evaluated over the 20 min signal transmission duration. The article concludes with a discussion on the future source utility and highlights research topics of interest, including observed Doppler (waveform dilation), thermometry, and tomography.

The sex-dependent and enduring impact of pubertal stress on health and disease.

Illness is often predicated long before the manifestation of its symptoms. Exposure to stressful experiences particularly during critical periods of development, such as puberty and adolescence, can induce various physical and mental illnesses. Puberty is a critical period of maturation for neuroendocrine systems, such as the hypothalamic-pituitary-gonadal (HPG) and hypothalamic-pituitary-adrenal (HPA) axes. Exposure to adverse experiences during puberty can impede normal brain reorganizing and remodelling and result in enduring consequences on brain functioning and behaviour. Stress responsivity differs between the sexes during the pubertal period. This sex difference is partly due to differences in circulating sex hormones between males and females, impacting stress and immune responses differently. The effects of stress during puberty on physical and mental health remains under-examined. The purpose of this review is to summarize the most recent findings pertaining to age and sex differences in HPA axis, HPG axis, and immune system development, and describe how disruption in the functioning of these systems can propagate disease. Lastly, we delve into the notable neuroimmune contributions, sex differences, and the mediating role of the gut microbiome on stress and health outcomes. Understanding the enduring consequences of adverse experiences during puberty on physical and mental health will allow a greater proficiency in treating and preventing stress-related diseases early in development.

Enduring sex-dependent effects of lipopolysaccharide treatment on the hypothalamic-pituitary-gonadal axis in mice.

Pubertal stress causes enduring sexual behavior dysfunction in males and females, but the underlying mechanism remains unknown. These changes may arise from pubertal programming of the hypothalamic-pituitary-gonadal axis. Previous findings show that stress exposure downregulates the hypothalamic-pituitary-gonadal axis, particularly through the reduction of the neuropeptide kisspeptin (Kiss1) and its receptor (Kiss1R). Although acute changes in kiss1 and Kiss1r genes have been observed following pubertal immune stress, it is unclear whether immune stress-induced downregulation of kiss1 and kiss1r persists beyond puberty. The current study investigated the enduring sex-specific consequences of lipopolysaccharide on the expression of Kiss1 and Kiss1r in 160 pubertal or adult mice at multiple time points. Six-week and 10-week-old male and female mice were treated with either saline or with lipopolysaccharide. Mice were euthanized either 8 h or 4 weeks following treatment. Although we did not identify any sex differences, our results revealed that lipopolysaccharide treatment decreases hypothalamic Kiss1 and Kiss1r in both pubertal and adult mice within 8 h of treatment. The decreased hypothalamic Kiss1 expression persists 4 weeks later only in mice treated with lipopolysaccharide during puberty. Our findings highlight the age-dependent vulnerability of the hypothalamic-pituitary-gonadal axis to immune stress, providing a better understanding of the mechanisms implicated in allostatic shift during immune stress. Finally, our findings also show the effects of immune stress on various components of the hypothalamic-pituitary-gonadal axis, which could have implications for sexual and fertility-related dysfunctions.

Environmental enrichment alters LPS-induced changes in BDNF and PSD-95 expressions during puberty.

Puberty is a critical period of cortical reorganization and increased synaptogenesis. Healthy cortical reorganization and synaptic growth require sufficient environmental stimuli and minimalized stress exposure during pubertal development. Exposure to impoverished environments or immune challenges impact cortical reorganization and reduce the expression of proteins associated with neuronal plasticity (BDNF) and synaptogenesis (PSD-95). Environmentally enriched (EE) housing includes improved social-, physical-, and cognitive stimulation. We hypothesized that enriched housing environment would mitigate pubertal stress-induced decreases in BDNF and PSD-95 expressions. Three-week-old male and female CD-1 mice (n = 10 per group) were housed for three weeks in either EE, social or deprived housing conditions. At 6 weeks of age, mice were treated with either lipopolysaccharide (LPS) or saline eight hours prior to tissue collection. Male and female EE mice displayed greater BDNF and PSD-95 expressions in the medial prefrontal cortex and hippocampus compared to socially housed and deprived housed mice. LPS treatment decreased BDNF expression in all the brain regions examined in EE mice, except for the CA3 region of the hippocampus, where EE housing successfully mitigated the pubertal LPS-induced decrease in BDNF expression. Interestingly, LPS-treated mice housed in deprived conditions displayed unexpected increases in BDNF and PSD-95 expressions throughout the medial prefrontal cortex and hippocampus. Both enriched and deprived housing conditions moderate how an immune challenge influences BDNF and PSD-95 expressions in a region-specific manner. These findings also emphasize the vulnerability of brain plasticity during puberty to various environmental factors.

Oceanic giants dance to atmospheric rhythms: Ephemeral wind-driven resource tracking by blue whales.

Trophic transfer of energy through marine food webs is strongly influenced by prey aggregation and its exploitation by predators. Rapid aggregation of some marine fish and crustacean forage species during wind-driven coastal upwelling has recently been discovered, motivating the hypothesis that predators of these forage species track the upwelling circulation in which prey aggregation occurs. We examine this hypothesis in the central California Current Ecosystem using integrative observations of upwelling dynamics, forage species' aggregation, and blue whale movement. Directional origins of blue whale calls repeatedly tracked upwelling plume circulation when wind-driven upwelling intensified and aggregation of forage species was heightened. Our findings illustrate a resource tracking strategy by which blue whales may maximize energy gain amid ephemeral foraging opportunities. These findings have implications for the ecology and conservation of diverse predators that are sustained by forage populations whose behaviour is responsive to episodic environmental dynamics.

The effects of antimicrobials and lipopolysaccharide on acute immune responsivity in pubertal male and female CD1 mice.

Exposure to stress during critical periods of development-such as puberty-is associated with long-term disruptions in brain function and neuro-immune responsivity. However, the mechanisms underlying the effect of stress on the pubertal neuro-immune response has yet to be elucidated. Therefore, the objective of the current study was to investigate the effect antimicrobial and lipopolysaccharide (LPS) treatments on acute immune responsivity in pubertal male and female mice. Moreover, the potential for probiotic supplementation to mitigate these effects was also examined. 240 male and female CD1 mice were treated with one week of antimicrobial treatment (mixed antimicrobials or water) and probiotic treatment (L. rhamnosis R0011 and L. helveticus R0052 or L. helveticus R0052 and B. longum R0175) or placebo at five weeks of age. At six weeks of age (pubertal stress-sensitive period), the mice received a single injection of LPS or saline. Sickness behaviours were assessed, and mice were euthanized 8 h post-injection. Brain, blood, and intestinal samples were collected. The results indicated that the antimicrobial treatment reduced sickness behaviours, and potentiated LPS-induced plasma cytokine concentrations and pro-inflammatory markers in the pre-frontal cortex (PFC) and hippocampus, in a sex-dependent manner. However, probiotics reduced LPS-induced plasma cytokine concentrations along with hippocampal and PFC pro-inflammatory markers in a sex-dependent manner. L. rhamnosis R0011 and L. helveticus R0052 treatment also mitigated antimicrobial-induced plasma cytokine concentrations and sickness behaviours. These findings suggest that the microbiome is an important modulator of the pro-inflammatory immune response during puberty.

Pretransplant survival of patients with end-stage heart failure under competing risks.

Heart transplantation is the gold standard of care for end-stage heart failure in the United States. Donor hearts are a scarce resource, however the current allocation policy-proposed in 2016 and implemented in 2018-has not addressed certain disparities. Between 2005 and 2016, the number of active candidates increased 127%, whereas transplant rates decreased 27.8%. Pretransplant mortality rates declined steadily for that period from 14.6 to 9.7, especially for candidates with mechanical circulatory assistive devices (MCSDs). This study reports survival analyses of candidates for heart transplantation list under competing events of transplantation and MCSD implantation. We queried the transplant data for a cohort of adult patients (age ≥ 16) without MCSDs prior to listing for transplantation between 2005 and 2014 (n = 23,373). We used cause-specific and subdistribution hazards models as multivariate regressions for all competing events. Patients listed as low priority for transplantation are less likely to require implantation but less likely to survive after 1,000 days of listing than patients listed at higher priorities. The current policy does not address this disparity as it focuses on stratifying patients with different types of MCSD. Clinical characteristics must be considered in prioritization.

Acoustic vector sensor analysis of the Monterey Bay region soundscape and the impact of COVID-19.

From February 2019 through January 2021, data were collected by an acoustic vector sensor moored on the seafloor at a depth of approximately 900 m just outside of Monterey Bay, California, near a major shipping lane off the California coast. Analysis of the vector sensor data has shown the ability to accurately determine bearings to merchant vessels at ranges up to 60 km. This paper examines the features of the low-frequency soundscape using spectral probability densities and evaluates directional features through vector intensity processing as well as coherent linear and adaptive processing of the vector sensor channels. Merchant vessel acoustic data were analyzed using the 1/3 octave band centered at 63 Hz. Over the period analyzed, a reduction in merchant vessel noise was observed between February and June 2020 relative to the same period in 2019, consistent with a reduction in vessel traffic due to the worldwide response to COVID-19. The directional features of the data evaluated through adaptive processing methods also suggest this reduction can be most clearly distinguished towards the south, where the shipping lane is limited to transiting vessels, rather to the north-northwest, where merchant vessels tend to congregate on approach into the San Francisco Bay area.

Politics is making us sick: The negative impact of political engagement on public health during the Trump administration.

OBJECTIVES: To quantify the effect of politics on the physical, psychological, and social health of American adults during the four-year span of the Trump administration. METHODS: A previously validated politics and health scale was used to compare health markers in nationally representative surveys administered to separate samples in March 2017 (N = 800) and October 2020 (N = 700). Participants in the 2020 survey were re-sampled approximately two weeks after the 2020 election and health markers were compared to their pre-election baselines. RESULTS: Large numbers of Americans reported politics takes a significant toll on a range of health markers-everything from stress, loss of sleep, or suicidal thoughts to an inability to stop thinking about politics and making intemperate social media posts. The proportion of Americans reporting these effects stayed stable or slightly increased between the spring of 2017 and the fall of 2020 prior to the presidential election. Deterioration in measures of physical health became detectably worse in the wake of the 2020 election. Those who were young, politically interested, politically engaged, or on the political left were more likely to report negative effects. CONCLUSIONS: Politics is a pervasive and largely unavoidable source of chronic stress that exacted significant health costs for large numbers of American adults between 2017 and 2020. The 2020 election did little to alleviate those effects and quite likely exacerbated them.

Pubertal probiotics mitigate lipopolysaccharide-induced programming of the hypothalamic-pituitary-adrenal axis in male mice only.

Puberty is a period of rapid cortical and neuronal development. Stress exposure during puberty programs the hypothalamic-pituitary-adrenal (HPA) axis responsiveness to future stressors. However, programming can result in an enduring maladaptation of the HPA axis activity and can be associated with long-term anxiety- and depression-like behaviours. Probiotic treatment mitigates the effect of stress on mental health, suggesting that the gut microbiome may mediate the programming of the HPA axis. However, the mechanism underlying this effect remains elusive. Thus, we investigated the effect of probiotic exposure on lipopolysaccharide (LPS)-induced programming of the HPA axis and glucocorticoid receptor (GR) expression in the paraventricular (PVN), basolateral amygdala (BLA), piriform cortex (PIR), and medial prefrontal cortex (mPFC). Male and female mice were exposed to either probiotics or control skim milk and were treated with either saline or LPS during puberty. Prior to euthanasia in adulthood, mice were restrained for 30 min. The results showed that pubertal LPS treatment permanently decreased GR expression in the PVN in milk fed control males. However, pubertal probiotic treatment blocked the LPS-induced decrease in GR expression in males. Given that this effect is limited to males, further research is required to better understand sex differences in the interactions between the gut microbiome and the programming of the HPA axis during puberty. Nevertheless, our findings suggest that the gut microbiome influences the neurophysiology of the HPA axis and mediates its programming in pubertal males. The prevention of GR reduction in the male PVN and PIR using probiotics illustrates the complexity of the gut-brain communication and compels continued investigation.

Pubertal immune challenge suppresses the hypothalamic-pituitary-gonadal axis in male and female mice.

Kisspeptin is a neuropeptide responsible for propagating the hypothalamic-pituitary-gonadal (HPG) axis and initiating puberty. Pubertal exposure to an immune challenge causes enduring sexual behavior dysfunction in males and females, but the mechanism underlying this stress-induced sexual dysfunction remains unknown. Previous findings show that stress exposure can downregulate the HPG axis in adult females. However, it is unclear whether stress induced HPG axis suppression is limited to adult females or also extends to males and to pubertal animal models. The current study was designed to investigate the sex-specific consequences of a pubertal immune challenge on specific components of the HPG axis. Six-week old pubertal male and female mice were treated with saline or with lipopolysaccharide, a bacterial endotoxin. Expression of hypothalamic Kiss1 and Kiss1R as well as serum concentrations of luteinizing hormone, follicle-stimulating hormone, and growth hormone were examined. Pubertal lipopolysaccharide treatment decreased hypothalamic Kiss1, but not Kiss1R, expression in both males and females. Furthermore, only males showed decreases in circulating luteinizing and follicle-stimulating hormones. These results show that pubertal immune challenge suppresses the HPG axis by inhibiting Kiss1 production and decreasing serum gonadotropin concentrations in pubertal males, but points to a different mechanism in pubertal females.

Chronic sleep disruption induces depression-like behavior in adolescent male and female mice and sensitization of the hypothalamic-pituitary-adrenal axis in adolescent female mice.

Depression is a prevalent mood disorder responsible for reduced quality of life for over 264 million people. Depression commonly develops during adolescence and becomes twice as prevalent in females than in males. However, the mechanisms underlying adolescent depression onset and sex differences in the prevalence rate remain unclear. Adolescent exposure to stress and subsequent sensitization of the hypothalamic-pituitary-adrenal (HPA) axis contributes to mood disorder development, and females are particularly vulnerable to HPA sensitization. Repeated exposure to stressors common to adolescent development, like sleep disruption, could partially be responsible for adolescent female susceptibility to depression. To address this possibility, 80 adolescent and adult CD-1 mice (Male, n = 40; Female, n = 40) were manually sleep disrupted for the first four hours of each rest cycle or allowed normal rest for eight consecutive days. Depression-like behavior was assessed with the forced swim test. 5-HT1A and glucocorticoid receptor expression and concurrent cellular activation via glucocorticoid receptor/c-Fos colocalization were examined in various brain regions to assess cellular correlates of depression and HPA-axis activation. Both adolescent male and female mice displayed significantly greater depression-like behavior and prelimbic c-Fos expression after chronic sleep disruption than non-sleep disrupted adolescent and sleep disrupted adult counterparts. However, sleep disrupted adolescent females demonstrated greater dorsal raphe 5-HT1A expression than sleep disrupted adolescent males. Adolescent females and males had decreased medial prefrontal 5-HT1A expression after chronic sleep disruption, but only adolescent females expressed decreased hippocampal 5-HT1A expression compared to controls. Chronic sleep disruption significantly increased corticosterone release, glucocorticoid expression in the CA1, and activation of glucocorticoid immunoreactive cells in the prelimbic cortex of adolescent females but not in adolescent males. These findings suggest that chronic sleep disruption during adolescence could give rise to depressive symptoms in male and female adolescents through differing signaling mechanisms.

Political attitudes vary with detection of androstenone.

Building on a growing body of research suggesting that political attitudes are part of broader individual and biological orientations, we test whether the detection of the hormone androstenone is predictive of political attitudes. The particular social chemical analyzed in this study is androstenone, a nonandrogenic steroid found in the sweat and saliva of many mammals, including humans. A primary reason for scholarly interest in odor detection is that it varies so dramatically from person to person. Using participants' self-reported perceptions of androstenone intensity, together with a battery of survey items testing social and political preferences and orientations, this research supports the idea that perceptions of androstenone intensity relate to political orientations-most notably, preferences for social order-lending further support to theories positing the influence of underlying biological traits on sociopolitical attitudes and behaviors.

Regioselective Arylboration of 1,3-Butadiene.

A method for the regioselective 1,2-arylboration of 1,3-butadiene, a feedstock chemical, is reported. The reactions result in the formation of products that can be easily elaborated to other structures. The mechanistic details of this process are also discussed.

Genetic capitalism and stabilizing selection of antimicrobial resistance genotypes in Escherichia coli.

Antimicrobial resistance (AMR) in pathogenic strains of bacteria, such as Escherichia coli (E. coli), adversely impacts personal and public health. In this study, we examine competing hypotheses for the evolution of AMR including (i) 'genetic capitalism' in which genotypes that confer antibiotic resistance are gained and not often lost in lineages, and (ii) 'stabilizing selection' in which genotypes that confer antibiotic resistance are gained and lost often. To test these hypotheses, we assembled a dataset that includes annotations for 409 AMR genotypes and a phylogenetic tree based on genome-wide single nucleotide polymorphisms from 29 255 isolates of E. coli collected over the past 134 years. We used phylogenetic methods to count the times each AMR genotype was gained and lost across the tree and used model-based clustering of the genotypes with respect to their gain and loss rates. We demonstrate that many genotypes cluster to support the hypothesis for genetic capitalism while a few genotypes cluster to support the hypothesis for stabilizing selection. Comparing the sets of genotypes that fall under each of the hypotheses, we found a statistically significant difference in the breakdown of resistance mechanisms through which the AMR genotypes function. The result that many AMR genotypes cluster under genetic capitalism reflects that strong positive selective forces, primarily induced by human industrialization of antibiotics, outweigh the potential fitness costs to the bacterial lineages for carrying the AMR genotypes. We expect genetic capitalism to further drive bacterial lineages to resist antibiotics. We find that antibiotics that function via replacement and efflux tend to behave under stabilizing selection and thus may be valuable in an antibiotic cycling strategy.

Pubertal probiotic blocks LPS-induced anxiety and the associated neurochemical and microbial outcomes, in a sex dependent manner.

Puberty is a critical period of neural development, and exposure to stress and inflammation during this period is thought to increase vulnerability to mental illness. The gut microbiome influences brain functioning and behavior and impacts mental health. Yet, the role of the gut microbiome during puberty, a period during which mental health conditions tend to onset, remains largely uninvestigated. We first examined age and sex differences in gut microbial changes among CD-1 mice exposed to an immune challenge (lipopolysaccharide; LPS) at 6 weeks of age (during the pubertal stress-sensitive period) or at 10 weeks of age (in adulthood) (Experiment 1). Compared to their adult counterparts, pubertal males and females showed more significant changes in gut microbial composition following LPS treatment, including the depletion of numerous bacterial genera such as Lactobacillus. Given the beneficial effects of Lactobacillus strains on stress and behaviour, we next investigated whether replenishment of the gut with the probiotic Lactobacillus reuteri (L. reuteri) throughout pubertal development would modulate LPS-induced sickness and enduring effects on memory dysfunction, anxiety-like behaviour and stress reactivity in adulthood (Experiment 2). LPS treatment at 6 weeks of age created enduring changes in anxiety-like behaviors among males only. Similarly, only males showed the protective effects of L. reuteri supplementation during puberty in preventing longstanding LPS-induced changes in anxiety-like behavior and stress-induced brain activation. These findings demonstrate that colonizing the gut with L. reuteri during puberty modulates sickness responses and enduring behavioural and neurochemical outcomes in a sex-specific manner. Therefore, colonizing the gut with beneficial microbes may protect against the development of mental illnesses in adulthood.

Underwater acoustic energy fluctuations during strong internal wave activity using a three-dimensional parabolic equation model.

The three-dimensional Monterey-Miami parabolic equation model is used to simulate a nonlinear internal wave (NIW) crossing the sound field in a shallow water environment. The impetus for this research stems from acoustic measurements taken during the Shallow Water '06 (SW06) field experiment, where a NIW traversed the water column such that soliton wavecrests were nearly parallel to the source-receiver path. Horizontal refraction effects are important in this scenario. A sound speed profile adapted from experimental SW06 data is used to simulate the NIW, assuming variations along the wavecrests (e.g., curvature) are negligible. Broadband and modal energy metrics show acoustic fluctuations due to internal wave activity. Repeated model runs simulate the NIW crossing the parabolic equation (PE) field over space and time. Statistical analysis shows the PE data are best fit by a lognormal distribution but tends to an exponential distribution during certain scenarios. Small angle differences between the acoustic track and the propagating NIW cause substantial differences in energy distribution throughout the PE field. While refraction effects due to the leading edge of the NIW's arrival are important in all cases, the impacts of focusing and defocusing in the perfectly parallel case dominate the field fluctuations. In the non-parallel case, the strong fluctuations introduced by the passage of the NIW are of similar order to the refraction off the leading edge.

Friends, relatives, sanity, and health: The costs of politics.

Political scientists have long known that political involvement exacts costs but they have typically defined these costs in relatively narrow, largely economic terms. Though anecdotal evidence suggests that the costs of politics may in fact extend beyond economics to frayed personal relationships, compromised emotional stability, and even physical problems, no systematic evidence on these broader costs exists. We construct and validate batteries of survey items that delineate the physical, social, and emotional costs of political engagement and administer these items to a demographically representative sample of U.S. adults. The results suggest that a large number of Americans believe their physical health has been harmed by their exposure to politics and even more report that politics has resulted in emotional costs and lost friendships.

Probiotic consumption during puberty mitigates LPS-induced immune responses and protects against stress-induced depression- and anxiety-like behaviors in adulthood in a sex-specific manner.

Puberty/adolescence is a significant period of development and a time with a high emergence of psychiatric disorders. During this period, there is increased neuroplasticity and heightened vulnerability to stress and inflammation. The gut microbiome regulates stress and inflammatory responses and can alter brain chemistry and behaviour. However, the role of the gut microbiota during pubertal development remains largely uninvestigated. The current study examined gut manipulation with probiotics during puberty in CD1 mice on lipopolysaccharide (LPS)-induced immune responses and enduring effects on anxiety- and depression-like behaviours and stress-reactivity in adulthood. Probiotics reduced LPS-induced sickness behaviour at 12 h in females and at 48 h following LPS treatment in males. Probiotics also reduced LPS-induced changes in body weight at 48 h post-treatment in females. Probiotic treatment also prevented LPS-induced increases in pro- and anti-inflammatory peripheral cytokines at 8 h following LPS treatment, reduced central cytokine mRNA expression in the hypothalamus, hippocampus and PFC, and prevented LPS-induced changes to in the gut microbiota. A single exposure to LPS during puberty resulted in enduring depression-like behaviour in female mice, and anxiety-like behaviour in male mice in adulthood. However, pubertal exposure to probiotics prevented enduring LPS-induced depression-like behaviour in females and anxiety-like behaviors in males. Moreover, probiotics altered toll-like receptor-4 activity in the paraventricular nucleus of the hypothalamus (PVN) in males in response to a novel stressor in adulthood. Our results suggest that the gut microbiome plays an important role in pubertal neurodevelopment. These findings indicate that exposure to probiotics during puberty mitigates inflammation and decreases stress-induced vulnerabilities to emotional behaviours later in life, in a sex-specific manner.