Eukaryotic cell size regulation and its implications for cellular function and dysfunction.

Depending on cell type, environmental inputs, and disease, the cells in the human body can have widely different sizes. In recent years, it became clear that cell size is a major regulator of cell function. However, we are only beginning to understand how optimization of cell function determines a given cell's optimal size. Here, we review currently known size control strategies of eukaryotic cells, and the intricate link of cell size to intracellular biomolecular scaling, organelle homeostasis and cell cycle progression. We detail the cell size dependent regulation of early development and the impact of cell size on cell differentiation. Given the importance of cell size for normal cellular physiology, cell size control must account for changing environmental conditions. We describe how cells sense environmental stimuli, such as nutrient availability, and accordingly adapt their size by regulating cell growth and cell cycle progression. Moreover, we discuss the correlation of pathological states with misregulation of cell size, and how for a long time, this was considered a downstream consequence of cellular dysfunction. We review newer studies that reveal a reversed causality, with misregulated cell size leading to pathophysiological phenotypes such as senescence and aging. In summary, we highlight important roles of cell size in cellular function and dysfunction, which could have major implications for both diagnostics and treatment in the clinic.

Neighbourhood inequities in the availability of retailers selling tobacco products: a systematic review.

OBJECTIVE: To examine inequities in tobacco retailer availability by neighbourhood-level socioeconomic, racial/ethnic and same-sex couple composition. DATA SOURCES: We conducted a 10 November 2022 search of PubMed, PsycINFO, Global Health, LILACS, Embase, ABI/Inform, CINAHL, Business Source Complete, Web of Science and Scopus. STUDY SELECTION: We included records from Organisation for Economic Co-operation and Development member countries that tested associations of area-level measures of tobacco retailer availability and neighbourhood-level sociodemographic characteristics. Two coders reviewed the full text of eligible records (n=58), including 41 records and 205 effect sizes for synthesis. DATA EXTRACTION: We used dual independent screening of titles, abstracts and full texts. One author abstracted and a second author confirmed the study design, location, unit of analysis, sample size, retailer data source, availability measure, statistical approach, sociodemographic characteristic and unadjusted effect sizes. DATA SYNTHESIS: Of the 124 effect sizes related to socioeconomic inequities (60.5% of all effect sizes), 101 (81.5%) indicated evidence of inequities. Of 205 effect sizes, 69 (33.7%) tested associations between retailer availability and neighbourhood composition of racially and ethnically minoritised people, and 57/69 (82.6%) documented inequities. Tobacco availability was greater in neighbourhoods with more Black, Hispanic/Latine and Asian residents (82.8%, 90.3% and 40.0% of effect sizes, respectively). Two effect sizes found greater availability with more same-sex households. CONCLUSIONS: There are stark inequities in tobacco retailer availability. Moving beyond documenting inequities to partnering with communities to design, implement, and evaluate interventions that reduce and eliminate inequities in retail availability is needed to promote an equitable retail environment. PROSPERO REGISTRATION NUMBER: CRD42019124984.

Super-Obesity is Associated With an Increased Risk of Complications Following Primary Total Knee Arthroplasty.

BACKGROUND: Obesity, defined as a body mass index (BMI) ≥ 30, is an ever-growing epidemic, with > 35% of adults in the United States currently classified as obese. Super-obese individuals, defined as those who have a BMI ≥ 50, are the fastest-growing portion of this group. This study sought to quantify the infection risk as well as the incidence of surgical, medical, and thromboembolic complications among super-obese patients undergoing total knee arthroplasty (TKA). METHODS: An all-payer claims database was used to identify patients who underwent elective, primary TKA between 2016 and 2021. Patients who had a BMI ≥ 50 were compared to those who had a normal BMI of 18 to 25. Demographics and the incidence of 90-days postoperative complications were compared between the 2 groups. Univariate analysis and multivariable regression were used to assess differences between groups. RESULTS: In total, 3,376 super-obese TKA patients were identified and compared to 17,659 patients who had a normal BMI. Multivariable analysis indicated that the super-obese cohort was at an increased postoperative risk of periprosthetic joint infection (adjusted odds ratio [aOR] 3.7, 95% confidence interval [CI]: 2.1 to 6.4, P < .001), pulmonary embolism (aOR 2.2, 95%-CI: 1.0 to 5.0, P = .047), acute respiratory failure (aOR 4.1, 95%-CI: 2.7 to 6.1, P < .001), myocardial infarction (aOR 2.5, 95%-CI: 1.1 to 5.8, P = .026), wound dehiscence (aOR 2.3, 95%-CI: 1.4 to 3.8, P = .001), and acute renal failure (aOR 3.2, 95%-CI: 2.4 to 4.2, P < .001) relative to patients who have normal BMI. CONCLUSIONS: Super-obese TKA patients are at an elevated risk of postoperative infectious, surgical, medical, and thromboembolic complications. As such, risk stratification, as well as appropriate medical management and optimization, is of utmost importance for this high-risk group.

Reversible male contraception by targeted inhibition of serine/threonine kinase 33.

Men or mice with homozygous serine/threonine kinase 33 (STK33) mutations are sterile owing to defective sperm morphology and motility. To chemically evaluate STK33 for male contraception with STK33-specific inhibitors, we screened our multibillion-compound collection of DNA-encoded chemical libraries, uncovered potent STK33-specific inhibitors, determined the STK33 kinase domain structure bound with a truncated hit CDD-2211, and generated an optimized hit CDD-2807 that demonstrates nanomolar cellular potency (half-maximal inhibitory concentration = 9.2 nanomolar) and favorable metabolic stability. In mice, CDD-2807 exhibited no toxicity, efficiently crossed the blood-testis barrier, did not accumulate in brain, and induced a reversible contraceptive effect that phenocopied genetic STK33 perturbations without altering testis size. Thus, STK33 is a chemically validated, nonhormonal contraceptive target, and CDD-2807 is an effective tool compound.

Comparison of Tobacco Product Prices at Fort Liberty Army Installation and Surrounding Community Areas, 2021.

INTRODUCTION: High rates of tobacco use persist in the U.S. military, with 18.4% of service members smoking cigarettes in 2018. The Department of Defense's (DoD) 2017 policy required that tobacco retailers on military installations set tobacco product prices equal to the most common community price, including tax, but there is limited evidence confirming whether local retailers are adhering to this policy. We examined tobacco product pricing in tobacco retailers on- and off-post at the largest U.S. Army installation, Fort Liberty, and Cumberland County, North Carolina. METHODS: Between June-August 2021, we collected data on tobacco product availability, price, and promotions from retailers on Fort Liberty (n=14) and a random sample of off-post retailers within 10-miles of installation gates (n=52). We calculated the mode, mean, and median price of each product, plus the difference in these prices at on- and off-post retailers. We used Welch's t-test to test differences in mean prices between on- vs. off-post retailers. RESULTS: The mode, mean, and median prices of cigarette packs and cartons were lower on-post than off-post (e.g., $0.51-$0.55 cheaper for Marlboro cigarette packs on-post). However, the mode, mean, and median prices of smokeless tobacco products and little cigars were higher on-post than off-post (e.g., $0.82-$0.89 more costly for Swisher Sweets 2-packs on-post). CONCLUSION: Results highlight the need for continued enforcement to ensure compliance with the 2017 DoD policy. Comprehensive policy action to reduce tobacco price disparities on- and off-post is critical to reducing high rates of tobacco use among service members. IMPLICATIONS: Despite the implementation of the 2017 DoD pricing policy, some tobacco products remain cheaper at tobacco retailers on-post compared to off-post retailers. Our results highlight the need for greater routine surveillance to increase implementation of the policy-particularly for cigarettes-to reduce high rates of tobacco use among service members.

Identification of potent pan-ephrin receptor kinase inhibitors using DNA-encoded chemistry technology.

EPH receptors (EPHs), the largest family of tyrosine kinases, phosphorylate downstream substrates upon binding of ephrin cell surface-associated ligands. In a large cohort of endometriotic lesions from individuals with endometriosis, we found that EPHA2 and EPHA4 expressions are increased in endometriotic lesions relative to normal eutopic endometrium. Because signaling through EPHs is associated with increased cell migration and invasion, we hypothesized that chemical inhibition of EPHA2/4 could have therapeutic value. We screened DNA-encoded chemical libraries (DECL) to rapidly identify EPHA2/4 kinase inhibitors. Hit compound, CDD-2693, exhibited picomolar/nanomolar kinase activity against EPHA2 (Ki: 4.0 nM) and EPHA4 (Ki: 0.81 nM). Kinome profiling revealed that CDD-2693 bound to most EPH family and SRC family kinases. Using NanoBRET target engagement assays, CDD-2693 had nanomolar activity versus EPHA2 (IC50: 461 nM) and EPHA4 (IC50: 40 nM) but was a micromolar inhibitor of SRC, YES, and FGR. Chemical optimization produced CDD-3167, having picomolar biochemical activity toward EPHA2 (Ki: 0.13 nM) and EPHA4 (Ki: 0.38 nM) with excellent cell-based potency EPHA2 (IC50: 8.0 nM) and EPHA4 (IC50: 2.3 nM). Moreover, CDD-3167 maintained superior off-target cellular selectivity. In 12Z endometriotic epithelial cells, CDD-2693 and CDD-3167 significantly decreased EFNA5 (ligand) induced phosphorylation of EPHA2/4, decreased 12Z cell viability, and decreased IL-1ß-mediated expression of prostaglandin synthase 2 (PTGS2). CDD-2693 and CDD-3167 decreased expansion of primary endometrial epithelial organoids from patients with endometriosis and decreased Ewing's sarcoma viability. Thus, using DECL, we identified potent pan-EPH inhibitors that show specificity and activity in cellular models of endometriosis and cancer.

Neighborhood Inequities in Tobacco Product Descriptors, Washington, DC, 2018-2019.

BACKGROUND: The tobacco industry uses product descriptors to communicate reduced harm and increase appeal. This cross-sectional study assessed store-level racial, ethnic, and socioeconomic inequities in the distribution of retail tobacco product descriptors in a convenience sample of retailers in Washington, DC. METHODS: Young adults (n = 146) who did not currently use tobacco reported real-time store visits over 14 days. Trained data collectors took high-resolution photographs of all tobacco (including e-cigarette) marketing in each store (n = 96) participants visited. We coded text descriptors on tobacco product advertisements and displays into descriptor categories (eg, fruit, sweet, concept). We fit multilevel models to examine relationships between store neighborhood census tract-level racial, ethnic, and socioeconomic characteristics and tobacco product descriptors in stores. As a supplementary analysis, we used geospatial methods to model predicted patterns of descriptors at the census tract level. RESULTS: Stores located in census tracts with the highest versus lowest percentage of Black residents had a greater count of fruit, sweet or dessert, alcohol, and concept descriptors (p < .05), similar to findings from the geospatial approach. Adjusted models also indicated some inequities in stores in census tracts with higher percentages of Hispanic or Latino residents for fruit, alcohol, and concept descriptors; however, tract-level models showed opposite results for concept flavors. CONCLUSIONS: In this convenience sample, fruit, alcohol, sweet/dessert, and concept FTP descriptors were prevalent in stores in neighborhoods with more Black residents demonstrated through two analytic approaches. Surveillance using representative samples of tobacco retailers could improve the ability to track the extent of this inequity. IMPLICATIONS: We document inequities in the amount of fruit, sweet or dessert, alcohol, and concept flavor descriptors in stores across neighborhoods in Washington, DC. Federal, state, and local regulatory action is needed to reduce inequities in flavored tobacco product availability and marketing, including for concept flavors.

Corrigendum: What can the common fruit fly teach us about stroke?: lessons learned from the hypoxic tolerant Drosophila melanogaster.

[This corrects the article DOI: 10.3389/fncel.2024.1347980.].

Encoding and context-dependent control of reward consumption within the central nucleus of the amygdala.

Dysregulation of the central amygdala is thought to underlie aberrant choice in alcohol use disorder, but the role of central amygdala neural activity during reward choice and consumption is unclear. We recorded central amygdala neurons in male rats as they consumed alcohol or sucrose. We observed activity changes at the time of reward approach, as well as lick-entrained activity during ongoing consumption of both rewards. In choice scenarios where rats could drink sucrose, alcohol, or quinine-adulterated alcohol with or without central amygdala optogenetic stimulation, rats drank more of stimulation-paired options when the two bottles contained identical options. Given a choice among different options, central amygdala stimulation usually enhanced consumption of stimulation-paired rewards. However, optogenetic stimulation during consumption of the less-preferred option, alcohol, was unable to enhance alcohol intake while sucrose was available. These findings indicate that the central amygdala contributes to refining motivated pursuit toward the preferred available option.

Uncontrolled vaping and restraint strategies: A qualitative study.

INTRODUCTION: Little is known about uncontrolled vaping, defined as vaping more than the user prefers. We sought to understand e-cigarette users' experiences with uncontrolled vaping and how they restrain their vaping. METHODS: Participants were 24 US adult e-cigarette users recruited in 2021. We conducted semi-structured qualitative interviews about uncontrolled vaping and restraint strategies and analyzed findings based on behavioral categories described in the Process Model of Self-Control. RESULTS: While most participants (21 of 24) described experiences of uncontrolled vaping, some expressed ambivalence about how much they vaped. To restrain vaping, willpower was rarely used and was not perceived as effective. Distraction, deployment of attention away from the urge to vape, and reappraisal, thinking differently about vaping such as reminding oneself of health consequences, were common and helped some participants limit use in the moment of wanting to vape. Participants described using both situation selection, choosing to be in situations where e-cigarette use was less possible, and situation modification, modifying their circumstances to restrict opportunities to vape. DISCUSSION: Uncontrolled vaping is not yet a well-defined concept for many e-cigarette users. E-cigarette users employed proactive situational strategies that required planning ahead to restrain use and found these strategies more effective compared to reactive strategies. Tobacco control programs and interventions should consider leveraging restraint strategies that people who vape are naturally using and perceive to be effective.

What can the common fruit fly teach us about stroke?: lessons learned from the hypoxic tolerant Drosophila melanogaster.

Stroke, resulting in hypoxia and glucose deprivation, is a leading cause of death and disability worldwide. Presently, there are no treatments that reduce neuronal damage and preserve function aside from tissue plasminogen activator administration and rehabilitation therapy. Interestingly, Drosophila melanogaster, the common fruit fly, demonstrates robust hypoxic tolerance, characterized by minimal effects on survival and motor function following systemic hypoxia. Due to its organized brain, conserved neurotransmitter systems, and genetic similarity to humans and other mammals, uncovering the mechanisms of Drosophila's tolerance could be a promising approach for the development of new therapeutics. Interestingly, a key facet of hypoxic tolerance in Drosophila is organism-wide metabolic suppression, a response involving multiple genes and pathways. Specifically, studies have demonstrated that pathways associated with oxidative stress, insulin, hypoxia-inducible factors, NFκB, Wnt, Hippo, and Notch, all potentially contribute to Drosophila hypoxic tolerance. While manipulating the oxidative stress response and insulin signaling pathway has similar outcomes in Drosophila hypoxia and the mammalian middle cerebral artery occlusion (MCAO) model of ischemia, effects of Notch pathway manipulation differ between Drosophila and mammals. Additional research is warranted to further explore how other pathways implicated in hypoxic tolerance in Drosophila, such as NFκB, and Hippo, may be utilized to benefit mammalian response to ischemia. Together, these studies demonstrate that exploration of the hypoxic response in Drosophila may lead to new avenues of research for stroke treatment in humans.

Cullin-RING ligases employ geometrically optimized catalytic partners for substrate targeting.

Cullin-RING ligases (CRLs) ubiquitylate specific substrates selected from other cellular proteins. Substrate discrimination and ubiquitin transferase activity were thought to be strictly separated. Substrates are recognized by substrate receptors, such as Fbox or BCbox proteins. Meanwhile, CRLs employ assorted ubiquitin-carrying enzymes (UCEs, which are a collection of E2 and ARIH-family E3s) specialized for either initial substrate ubiquitylation (priming) or forging poly-ubiquitin chains. We discovered specific human CRL-UCE pairings governing substrate priming. The results reveal pairing of CUL2-based CRLs and UBE2R-family UCEs in cells, essential for efficient PROTAC-induced neo-substrate degradation. Despite UBE2R2's intrinsic programming to catalyze poly-ubiquitylation, CUL2 employs this UCE for geometrically precise PROTAC-dependent ubiquitylation of a neo-substrate and for rapid priming of substrates recruited to diverse receptors. Cryo-EM structures illuminate how CUL2-based CRLs engage UBE2R2 to activate substrate ubiquitylation. Thus, pairing with a specific UCE overcomes E2 catalytic limitations to drive substrate ubiquitylation and targeted protein degradation.

The Impact of Menthol Cigarette Bans: A Systematic Review and Meta-Analysis.

INTRODUCTION: This review investigates the impacts of banning the sale of menthol cigarettes at stores. METHODS: A systematic search of studies published in English up to November 2022 was conducted. The following databases were searched: PubMed/Medline, CINAHL, PsycINFO, Web of Science, and Embase, as well as a non-indexed journal. Studies evaluating either the impact of real-world or hypothesized menthol cigarette bans were included. Primary outcomes include tobacco use behaviors. Secondary outcomes include cigarette sales, retailer compliance, and the tobacco industry's response to a menthol ban. Data on tobacco use behavior after a menthol ban were pooled using random-effects models. Two pairs of reviewers independently extracted data and assessed study quality. RESULTS: Of the 964 articles that were identified during the initial search, 78 were included in the review and 16 were included in the meta-analysis. Cessation rates among menthol cigarette smokers were high after a menthol ban. Pooled results show that 24% (95% confidence interval [95% CI]: 20%, 28%) of menthol cigarette smokers quit smoking after a menthol ban, 50% (95% CI: 31%, 68%) switched to non-menthol cigarettes, 12% (95% CI: 3%, 20%) switched to other flavored tobacco products, and 24% (95% CI: 17%, 31%) continued smoking menthol cigarettes. Hypothesized quitting and switching rates were fairly close to real-world rates. Studies found the tobacco industry attempts to undermine menthol bans. National menthol bans appear more effective than local or state menthol bans. CONCLUSIONS: Menthol cigarette bans promote smoking cessation suggesting their potential to improve public health. IMPLICATIONS: Findings from this review suggest that menthol cigarette bans promote smoking cessation among menthol cigarette smokers and have the potential to improve public health.

Morpho-molecular and environmental evidence of the ocurrence of Karenia longicanalis (Dinophyceae: Kareniaceae) as a bloom former in the Eastern Pacific Ocean.

Karenia longicanalis, an athecate dinoflagellate, was first described during a bloom in Victoria Harbour (Hong Kong, China). This study confirms the presence of K. longicanalis as a bloom former in the eastern Pacific Ocean. Specimens were collected in March 2019 at three sampling stations in Acapulco Bay, Mexico. Water temperature, salinity, dissolved oxygen, and pH were measured in situ at the time of sample collection. Cell morphology was examined by optical and scanning electron microscopy. A molecular analysis based on the amplification of the large subunit (LSU) rDNA region revealed that the LSU sequences formed a monophyletic group with other GenBank sequences belonging to K. longicanalis. The resulting phylogeny demonstrates that Karenia is closely related to Asterodinium, Gertia, and Shimiella. The morphology of the specimens was consistent with previous descriptions.

Concussion-Related Decision-Making by Certified Athletic Trainers: Implications for Concussion Prevention and Care.

Concussions are a common sport-related injury that require appropriate initial care. Athletic trainers, often a primary source of healthcare for student-athletes, are key individuals involved in initial concussion diagnostic and management decisions. Challenges exist within the athletic environment that may hinder the consistency, efficacy, and/or effectiveness of concussion-related decision-making by athletic trainers, thereby impacting secondary concussion prevention and patient health. The purpose of this study was to identify factors that impact the intentions of athletic trainers to make appropriate concussion-related decisions under various circumstances. Overall, 1029 participants completed a survey examining educational precursors (quantity and quality of healthcare communication educational focus), demographic precursors (age, gender, educational degree, and employment setting), theory-based mediators (attitudes, perceived norms, and personal agency), and external mediators (knowledge, salience, and communication/collaboration practices) on appropriate concussion-related decision-making intentions. Data were analyzed using a two-step structural equation modeling approach. Quality of healthcare communication educational focus indirectly impacted appropriate concussion-related decision-making intentions via perceived behavioral control and communication/collaboration practices. Additionally, several factors impacted intentions to make appropriate concussion-related decisions directly including employment setting, self-efficacy, and general attitudes towards decision-making and concussions. Concussion prevention is aided by the initial and appropriate action taken by a healthcare professional to reduce immediate consequences; however, this action may be influenced by stakeholder relationships. These influential factors of decision-making may place athletes at further injury risk and negatively impact overall athlete health. As such, a sound theoretical framework incorporating the complexity of factors that may influence decision-making is needed.

The Use of Social Media to Express and Manage Medical Uncertainty in Dyskeratosis Congenita: Content Analysis.

BACKGROUND: Social media has the potential to provide social support for rare disease communities; however, little is known about the use of social media for the expression of medical uncertainty, a common feature of rare diseases. OBJECTIVE: This study aims to evaluate the expression of medical uncertainty on social media in the context of dyskeratosis congenita, a rare cancer-prone inherited bone marrow failure and telomere biology disorder (TBD). METHODS: We performed a content analysis of uncertainty-related posts on Facebook and Twitter managed by Team Telomere, a patient advocacy group for this rare disease. We assessed the frequency of uncertainty-related posts, uncertainty sources, issues, and management and associations between uncertainty and social support. RESULTS: Across all TBD social media platforms, 45.98% (1269/2760) of posts were uncertainty related. Uncertainty-related posts authored by Team Telomere on Twitter focused on scientific (306/434, 70.5%) or personal (230/434, 53%) issues and reflected uncertainty arising from probability, ambiguity, or complexity. Uncertainty-related posts in conversations among patients and caregivers in the Facebook community group focused on scientific (429/511, 84%), personal (157/511, 30.7%), and practical (114/511, 22.3%) issues, many of which were related to prognostic unknowns. Both platforms suggested uncertainty management strategies that focused on information sharing and community building. Posts reflecting response-focused uncertainty management strategies (eg, emotional regulation) were more frequent on Twitter compared with the Facebook community group (χ21=3.9; P=.05), whereas posts reflecting uncertainty-focused management strategies (eg, ordering information) were more frequent in the Facebook community group compared with Twitter (χ21=55.1; P<.001). In the Facebook community group, only 36% (184/511) of members created posts during the study period, and those who created posts did so with a low frequency (median 3, IQR 1-7 posts). Analysis of post creator characteristics suggested that most users of TBD social media are White, female, and parents of patients with dyskeratosis congenita. CONCLUSIONS: Although uncertainty is a pervasive and multifactorial issue in TBDs, our findings suggest that the discussion of medical uncertainty on TBD social media is largely limited to brief exchanges about scientific, personal, or practical issues rather than ongoing supportive conversation. The nature of uncertainty-related conversations also varied by user group: patients and caregivers used social media primarily to discuss scientific uncertainties (eg, regarding prognosis), form social connections, or exchange advice on accessing and organizing medical care, whereas Team Telomere used social media to express scientific and personal issues of uncertainty and to address the emotional impact of uncertainty. The higher involvement of female parents on TBD social media suggests a potentially greater burden of uncertainty management among mothers compared with other groups. Further research is needed to understand the dynamics of social media engagement to manage medical uncertainty in the TBD community.

State and rate-of-change encoding in parallel mesoaccumbal dopamine pathways.

The nervous system uses fast- and slow-adapting sensory detectors in parallel to enable neuronal representations of external states and their temporal dynamics. It is unknown whether this dichotomy also applies to internal representations that have no direct correlation in the physical world. Here we find that two distinct dopamine (DA) neuron subtypes encode either a state or its rate-of-change. In mice performing a reward-seeking task, we found that the animal's behavioral state and rate-of-change were encoded by the sustained activity of DA neurons in medial ventral tegmental area (VTA) DA neurons and transient activity in lateral VTA DA neurons, respectively. The neural activity patterns of VTA DA cell bodies matched DA release patterns within anatomically defined mesoaccumbal pathways. Based on these results, we propose a model in which the DA system uses two parallel lines for proportional-differential encoding of a state variable and its temporal dynamics.

Highly active fish in low oxygen environments: vertical movements and behavioural responses of bigeye and yellowfin tunas to oxygen minimum zones in the eastern Pacific Ocean.

Oxygen minimum zones in the open ocean are predicted to significantly increase in volume over the coming decades as a result of anthropogenic climatic warming. The resulting reduction in dissolved oxygen (DO) in the pelagic realm is likely to have detrimental impacts on water-breathing organisms, particularly those with higher metabolic rates, such as billfish, tunas, and sharks. However, little is known about how free-living fish respond to low DO environments, and therefore, the effect increasing OMZs will have cannot be predicted reliably. Here, we compare the responses of two active predators (bigeye tuna Thunnus obesus and yellowfin tuna Thunnus albacares) to DO at depth throughout the eastern Pacific Ocean. Using time-series data from 267 tagged tunas (59,910 days) and 3D maps of modelled DO, we find that yellowfin tuna respond to low DO at depth by spending more time in shallower, more oxygenated waters. By contrast, bigeye tuna, which forage at deeper depths well below the thermocline, show fewer changes in their use of the water column. However, we find that bigeye tuna increased the frequency of brief upward vertical excursions they performed by four times when DO at depth was lower, but with no concomitant significant difference in temperature, suggesting that this behaviour is driven in part by the need to re-oxygenate following time spent in hypoxic waters. These findings suggest that increasing OMZs will impact the behaviour of these commercially important species, and it is therefore likely that other water-breathing predators with higher metabolic rates will face similar pressures. A more comprehensive understanding of the effect of shoaling OMZs on pelagic fish vertical habitat use, which may increase their vulnerability to surface fisheries, will be important to obtain if these effects are to be mitigated by future management actions. Supplementary Information: The online version contains supplementary material available at 10.1007/s00227-023-04366-2.

Spatial Clustering of Tobacco Retailers Near US Public Schools.

INTRODUCTION: Previous studies have found that tobacco retailers cluster near schools. However, all retail outlets may be located near each other and near schools due to existing infrastructure and zoning policies. We assessed whether tobacco retailers cluster near schools in the United States more than expected when accounting for existing retail locations. AIMS AND METHODS: We identified 322 056 probable tobacco retailers, 95 110 public schools, and more than 3.8 million businesses comparable to tobacco retailers in land use and business type. We created 500 simulated tobacco retailer datasets by randomly selecting from the larger list of businesses. For each simulated dataset, we calculated the distance from schools to the nearest tobacco retailer (proximity) and the count of tobacco retailers within 800 m of schools (density). Observed proximity and density values were compared to 95% coverage intervals from the 500 simulations. We stratified analyses by urbanicity, percentage of students in the free and reduced-priced lunch program (FRLP), and percentage of Hispanic/Latino, non-Hispanic Black, and non-Hispanic white students. RESULTS: Tobacco retailers were closer to schools in rural areas, cities, and towns and more dense around schools in rural areas, cities, and suburbs compared to random locations in potential retail space. Schools with more students receiving FRLP had higher density than expected while schools with fewer students receiving FRLP had lower density than expected. Within rural areas, clustering did not vary across sociodemographic groups. Within non-rural areas, there were inequities in clustering by racial, ethnic, and socioeconomic school composition. CONCLUSIONS: Tobacco retailers cluster near schools after accounting for existing business patterns. There are inequities in clustering by sociodemographic school composition. IMPLICATIONS: This study provides compelling evidence that tobacco retailers cluster near US public schools and that there are racial, ethnic, and socioeconomic inequities in clustering, even when accounting for overall retail location patterns. Given that public schools tend to reflect neighborhood demographics, policies to limit tobacco retailers near schools may reduce both school-based and neighborhood-based inequities.

Nucleus accumbens and dorsal medial striatal dopamine and neural activity are essential for action sequence performance.

Separable striatal circuits have unique functions in Pavlovian and instrumental behaviors but how these roles relate to performance of sequences of actions with and without associated cues are less clear. Here, we tested whether dopamine transmission and neural activity more generally in three striatal subdomains are necessary for performance of an action chain leading to reward delivery. Male and female Long-Evans rats were trained to press a series of three spatially distinct levers to receive reward. We assessed the contribution of neural activity or dopamine transmission within each striatal subdomain when progression through the action sequence was explicitly cued and in the absence of cues. Behavior in both task variations was substantially impacted following microinfusion of the dopamine antagonist, flupenthixol, into nucleus accumbens core (NAc) or dorsomedial striatum (DMS), with impairments in sequence timing and numbers of rewards earned after NAc flupenthixol. In contrast, after pharmacological inactivation to suppress overall activity, there was minimal impact on total rewards earned. Instead, inactivation of both NAc and DMS impaired sequence timing and led to sequence errors in the uncued, but not cued task. There was no impact of dopamine antagonism or reversible inactivation of dorsolateral striatum on either cued or uncued action sequence completion. These results highlight an essential contribution of NAc and DMS dopamine systems in motivational and performance aspects of chains of actions, whether cued or internally generated, as well as the impact of intact NAc and DMS function for correct sequence performance.