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Objective: The present study developed a measure assessing the emotional responses, "Displacement Imposition," of cigarette and e-cigarette users on a college campus with a smoking/vaping ban. It also examined the relationship between "Displacement Imposition" and readiness to quit smoking/ vaping, and how this relationship differed between cigarette and e-cigarette users. Participants: Participants (N=297) were from a large, Midwestern university. Methods: Participants completed online questionnaires assessing demographics, cigarette and e-cigarette use, "Displacement Imposition," and readiness to quit. Results: All six "Displacement Imposition" items loaded onto a single factor. A significant interaction emerged between "Displacement Imposition" and product use in predicting readiness to quit. At high levels of "Displacement Imposition," cigarette users were less ready to quit than e-cigarette users. Conclusions: Findings suggest restrictions imposed on cigarette and e-cigarette users were associated with reduced readiness to quit. Findings inform tobacco control policies as tobacco denormalization may increase the burden placed on tobacco users.

Objectives: Sexual Strategies Theory suggests people fall on a continuum between having short-term mating orientation (STMO) and long-term mating orientation. One way STMO individuals signal mating goals is via risky drinking. The current study therefore aims to investigate drinks per week (DPW) as a mediator between STMO and risky sexual behavior (RSB), with gender as a moderator between STMO and DPW. Participants: Undergraduate students (N = 300) from a Midwestern university during Fall 2019. Method: Participants completed questionnaires assessing STMO, DPW, and RSB frequency. Results: A moderated-mediation model indicated DPW significantly mediated the relationship between STMO and RSB. Positive associations were found among all three variables. Gender was not a moderator between STMO and DPW. Conclusions: Mating orientation was a correlate of alcohol use and RSB for women and men, contributing to the literature identifying STMO as an indicator of those in need of substance use and RSB intervention.

The article delves into the confusion with the interpretations and enforcement of the Migratory Bird Treaty Act (MBTA) regarding avian interactions with the built environment, particularly the intentional taking or killing of protected bird species. Topics discussed include sustainable development and voluntary initiatives for the protection of plants and animal species, provisions of the Lacey Act and MBTA on wildlife protection, and building modifications to prevent bird collisions.

BACKGROUND: Bowel dilation and bowel wall thickness are common prenatal ultrasound measurements for fetuses with gastroschisis. Data regarding antenatal sonographic bowel findings and postnatal outcomes are conflicting. Our objective was to evaluate the impact of in utero bowel measurements on perinatal outcomes in gastroschisis pregnancies. METHODS: Retrospective cohort study of 116 pregnancies complicated by gastroschisis between 2011 and 2020. We reviewed ultrasounds documenting fetal bowel measurements. To evaluate the association of these measurements with antepartum and delivery outcomes, we ran logistic and linear models using generalized estimating equations. RESULTS: Eleven perinatal outcomes reached statistical significance, although with minimal clinical impact given small magnitude of effect. Intra-abdominal bowel dilation was associated with a 0.5 week decrease in delivery gestational age (GA) (95% CI –0.07, –0.03) and a 6.93 g increase in birth weight (95% CI 1.54, 28.73). Intra-abdominal bowel wall thickness was associated with later GA of non-stress test (NST) start of 0.22 weeks (95% CI 0.07, 0.37), increased delivery GA of 0.08 weeks (95% CI 0.02, 0.15), 0.006 decrease in umbilical artery (UA) pH (95% CI –0.009, –0.003), 0.26 increase in UA base deficit (95% CI 0.09, 0.43), and decreased odds of cesarean delivery (OR = 0.83, 95% CI 0.70, 0.99). Extra-abdominal bowel wall thickness was associated with a 0.1 increase in UA base deficit (95% CI 0.02, 0.19) and a 0.05 increase in 5-min APGAR score (95% CI 0.01, 0.09). Stomach cross-section was associated with a 0.01 week decrease in delivery GA (95% CI –0.02, –0.001) and increased odds of receiving betamethasone (OR = 1.02, 95% CI 1.01, 1.04). CONCLUSIONS: In utero bowel characteristics reached statistical significance for several outcomes, but with minimal meaningful clinical differences in outcomes. [ABSTRACT FROM AUTHOR]

Sexual Strategies Theory suggests people fall on a continuum between having short-term mating orientation (STMO) and long-term mating orientation. One way STMO individuals signal mating goals is via risky drinking. The current study therefore aims to investigate drinks per week (DPW) as a mediator between STMO and risky sexual behavior (RSB), with gender as a moderator between STMO and DPW. Undergraduate students (N = 300) from a Midwestern university during Fall 2019. Participants completed questionnaires assessing STMO, DPW, and RSB frequency. A moderated-mediation model indicated DPW significantly mediated the relationship between STMO and RSB. Positive associations were found among all three variables. Gender was not a moderator between STMO and DPW. Mating orientation was a correlate of alcohol use and RSB for women and men, contributing to the literature identifying STMO as an indicator of those in need of substance use and RSB intervention. [ABSTRACT FROM AUTHOR]

The present study developed a measure assessing the emotional responses, "Displacement Imposition," of cigarette and e-cigarette users on a college campus with a smoking/vaping ban. It also examined the relationship between Displacement Imposition and readiness to quit smoking/vaping, and how this relationship differed between cigarette and e-cigarette users. Participants (N = 297) were from a large, Midwestern university. Participants completed online questionnaires assessing demographics, cigarette and e-cigarette use, Displacement Imposition, and readiness to quit. All six Displacement Imposition items loaded onto a single factor. A significant interaction emerged between Displacement Imposition and product use in predicting readiness to quit. At high levels of Displacement Imposition, cigarette users were less ready to quit than e-cigarette users. Findings suggest restrictions imposed on cigarette and e-cigarette users were associated with reduced readiness to quit. Findings inform tobacco control policies as tobacco denormalization may increase the burden placed on tobacco users. [ABSTRACT FROM AUTHOR]

Child labour is the most common form of child abuse in the world today, with almost half of child workers employed in hazardous industries. The large-scale employment of children during the rapid industrialisation of the late 18th and early 19th centuries in England is well documented. During this period, the removal of pauper children from workhouses in cities to work as apprentices in rural mills in the North of England was commonplace. Whilst the experiences of some of these children have been recorded historically, this study provides the first direct evidence of their lives through bioarchaeological analysis. The excavation of a rural churchyard cemetery in the village of Fewston, North Yorkshire, yielded the skeletal remains of 154 individuals, including an unusually large proportion of children aged between 8 to 20 years. A multi-method approach was undertaken, including osteological and palaeopathological examination, stable isotope and amelogenin peptide analysis. The bioarchaeological results were integrated with historical data regarding a local textile mill in operation during the 18th-19th centuries. The results for the children were compared to those obtained from contemporaneous individuals of known identity (from coffin plates) of comparable date. Most of the children exhibited distinctive 'non-local' isotope signatures and a diet low in animal protein when compared to the named local individuals. These children also showed severe growth delays and pathological lesions indicative of early life adversity, as well as respiratory disease, which is a known occupational hazard of mill work. This study has provided unique insights into the harrowing lives of these children; born into poverty and forced to work long hours in dangerous conditions. This analysis provides a stark testimony of the impacts of industrial labour on the health, growth and mortality risk of children, with implications for the present as well as our understanding of the past. [ABSTRACT FROM AUTHOR]

Lithium’s role in the global green energy transition provides an engaging context to visualize the interconnectedness of chemistry to seismic shifts taking place in society. Lithium has seen a dramatic increase in utilization, but given lithium’s current low rates of recyclability, this development is exacerbating the e-waste problem. Equally important, we posit that lithium extraction, from either brine or ore, and the associated impacts on the environment and local communities should not be so easily decoupled from the shift in human behaviors causing its demand. Presented here is a mapping activity that was trialed in professional learning workshops organized in New Zealand for secondary/high school chemistry teachers. In their mapping activity response, the teachers were able to connect typical school chemistry content (batteries, chemical processes) with environmental (planetary systems) and social, economic, and ethical considerations (useful products, unintended consequences, inequity in access to water) of the ongoing electrification of society. The teachers indicated a positive intention to utilize the activity, or one similar with a different chemical process or product, in their own classrooms. A school-ready version of the activity is provided in the supplementary information, which was revised based on feedback from the teachers attending the workshops.

The primary aim of the current study is to determine the incremental efficacy of adding a novel values component to a personalized feedback intervention for young adult drinking. Undergraduate students (N = 254) were randomized to receive either traditional, traditional with values assessment, or values enhanced feedback. Results showed significant decreases in drinks per week (p <.01) and alcohol-related consequences (p <.05) across all feedback conditions. Further research is needed to determine whether using values-based feedback could enhance intervention effects and how best to incorporate feedback in a way that is feasible and acceptable to recipients. [ABSTRACT FROM AUTHOR]

Administration of oxygen microbubbles (OMBs) has been shown to increase oxygen and decrease carbon dioxide in systemic circulation, as well as reduce lung inflammation and promote survival in preclinical models of hypoxia caused by lung injury. However, their impact on microenvironmental oxygenation remains unexplored. Herein, we investigated the effects of intraperitoneal administration of OMBs in anesthetized rats exposed to hypoxic ventilation (FiO2 = 0.14). Blood oxygenation and hemodynamics were evaluated over a 2 h time frame, and then organ and tissue samples were collected for hypoxic and metabolic analyses. Data showed that OMBs improved blood SaO2 (~14%) and alleviated tissue hypoxia within the microenvironment of the kidney and intestine at 2 h of hypoxia. Metabolomic analysis revealed OMBs induced metabolic differences in the cecum, liver, kidney, heart, red blood cells and plasma. Within the spleen and lung, principal component analysis showed a metabolic phenotype more comparable to the normoxic group than the hypoxic group. In the spleen, this shift was characterized by reduced levels of fatty acids and 2-hydroxygluterate, alongside increased expression of antioxidant enzymes such as glutathione and hypoxanthine. Interestingly, there was also a shuttle effect within the metabolism of the spleen from the tricarboxylic acid cycle to the glycolysis and pentose phosphate pathways. In the lung, metabolomic analysis revealed upregulation of phosphatidylethanolamine and phosphatidylcholine synthesis, indicating a potential indirect mechanism through which OMB administration may improve lung surfactant secretion and prevent alveolar collapse. In addition, cell-protective purine salvage was increased within the lung. In summary, oxygenation with intraperitoneal OMBs improves systemic blood and local tissue oxygenation, thereby shifting metabolomic profiles of the lung and spleen toward a healthier normoxic state.

Political polarization, fueled by conflicting meta-perceptions, presents a critical obstacle to constructive discourse and collaboration. These meta-perceptions-how one group perceives another group's views of them-are often inaccurate and can lead to detrimental outcomes such as increased hostility and dehumanization. Across two studies, we introduce and experimentally test a novel approach that exposes participants to atypical, counter-stereotypical members of an opposing group who either confirm or disrupt their existing meta-perceptions. We find that disrupting meta-perceptions decreases dehumanization of the partner, increases interest in wanting to learn more about them, but fails to increase willingness to interact in the future with the partner. We conduct an exploratory text analysis to uncover differences in word choice by condition. Our research adds a new dimension to the existing body of work by examining the efficacy of alternative intervention strategies to improve intergroup relations in politically polarized settings.

Deep learning (DL) models for medical image classification frequently struggle to generalize to data from outside institutions. Additional clinical data are also rarely collected to comprehensively assess and understand model performance amongst subgroups. Following the development of a single-center model to identify the lung sliding artifact on lung ultrasound (LUS), we pursued a validation strategy using external LUS data. As annotated LUS data are relatively scarce—compared to other medical imaging data—we adopted a novel technique to optimize the use of limited external data to improve model generalizability. Externally acquired LUS data from three tertiary care centers, totaling 641 clips from 238 patients, were used to assess the baseline generalizability of our lung sliding model. We then employed our novel Threshold-Aware Accumulative Fine-Tuning (TAAFT) method to fine-tune the baseline model and determine the minimum amount of data required to achieve predefined performance goals. A subgroup analysis was also performed and Grad-CAM++ explanations were examined. The final model was fine-tuned on one-third of the external dataset to achieve 0.917 sensitivity, 0.817 specificity, and 0.920 area under the receiver operator characteristic curve (AUC) on the external validation dataset, exceeding our predefined performance goals. Subgroup analyses identified LUS characteristics that most greatly challenged the model’s performance. Grad-CAM++ saliency maps highlighted clinically relevant regions on M-mode images. We report a multicenter study that exploits limited available external data to improve the generalizability and performance of our lung sliding model while identifying poorly performing subgroups to inform future iterative improvements. This approach may contribute to efficiencies for DL researchers working with smaller quantities of external validation data.

This observational pilot study examined the association between diet, meal pattern and glucose over a 2-week period under free-living conditions in 26 adults with dysglycemia (D-GLYC) and 14 with normoglycemia (N-GLYC). We hypothesized that a prolonged eating window and late eating occasions (EOs), along with a higher dietary carbohydrate intake, would result in higher glucose levels and glucose variability (GV). General linear models were run with meal timing with time-stamped photographs in real time, and diet composition by dietary recalls, and their variability (SD), as predictors and glucose variables (mean glucose, mean amplitude of glucose excursions [MAGE], largest amplitude of glucose excursions [LAGE] and GV) as dependent variables. After adjusting for calories and nutrients, a later eating midpoint predicted a lower GV (β = −2.3, SE = 1.0, p = 0.03) in D-GLYC, while a later last EO predicted a higher GV (β = 1.5, SE = 0.6, p = 0.04) in N-GLYC. A higher carbohydrate intake predicted a higher MAGE (β = 0.9, SE = 0.4, p = 0.02) and GV (β = 0.4, SE = 0.2, p = 0.04) in N-GLYC, but not D-GLYC. In summary, our data suggest that meal patterns interact with dietary composition and should be evaluated as potential modifiable determinants of glucose in adults with and without dysglycemia. Future research should evaluate causality with controlled diets.

Aberrant coagulation in sickle cell disease (SCD) is linked to extracellular vesicle (EV) exposure. However, there is no consensus on the contributions of small EVs (SEVs) and large EVs (LEVs) toward underlying coagulopathy or on their molecular cargo. The present observational study compared the thrombin potential of SEVs and LEVs isolated from the plasma of stable pediatric and adult SCD patients. Further, EV lipid and protein contents were analyzed to define markers consistent with activation of thrombin and markers of underlying coagulopathy. Results suggested that LEVs—but not SEVs—from pediatrics and adults similarly enhanced phosphatidylserine (PS)-dependent thrombin generation, and cell membrane procoagulant PS (18:0;20:4 and 18:0;18:1) were the most abundant lipids found in LEVs. Further, LEVs showed activated coagulation in protein pathway analyses, while SEVs demonstrated high levels of cholesterol esters and a protein pathway analysis that identified complement factors and inflammation. We suggest that thrombin potential of EVs from both stable pediatric and adult SCD patients is similarly dependent on size and show lipid and protein contents that identify underlying markers of coagulation and inflammation.

IntroductionHuman and murine sickle cell disease (SCD) associated pulmonary hypertension (PH) is defined by hemolysis, nitric oxide depletion, inflammation, and thrombosis. Further, hemoglobin (Hb), heme, and iron accumulation are consistently observed in pulmonary adventitial macrophages at autopsy and in hypoxia driven rodent models of SCD, which show distribution of ferric and ferrous Hb as well as HO-1 and ferritin heavy chain. The anatomic localization of these macrophages is consistent with areas of significant vascular remodeling. However, their contributions toward progressive disease may include unique, but also common mechanisms, that overlap with idiopathic and other forms of pulmonary hypertension. These processes likely extend to the vasculature of other organs that are consistently impaired in advanced SCD.MethodsTo date, limited information is available on the metabolism of macrophages or monocytes isolated from lung, spleen, and peripheral blood in humans or murine models of SCD.ResultsHere we hypothesize that metabolism of macrophages and monocytes isolated from this triad of tissue differs between Berkley SCD mice exposed for ten weeks to moderate hypobaric hypoxia (simulated 8,000 ft, 15.4% O2) or normoxia (Denver altitude, 5000 ft) with normoxia exposed wild type mice evaluated as controls.DiscussionThis study represents an initial set of data that describes the metabolism in monocytes and macrophages isolated from moderately hypoxic SCD mice peripheral lung, spleen, and blood mononuclear cells.

An experimental design was used to examine the effects of interviewer gender and (mis)understanding on physiological stress (i.e., cortisol). A total of 103 undergraduate students wrote about a recent social conflict and then discussed that conflict with either a male or a female interviewer. During these discussions, the interviewer displayed verbal and nonverbal cues of (mis)understanding toward the participants. Participants' cortisol was assessed four times throughout the study. Results from a 2 × 2 × 4 mixed‐model analysis of variance demonstrated an interaction between the gender of the interviewer, understanding condition, and time such that cortisol decreased the most over time when the interviewer used cues of understanding that matched stereotypical expectations for the interviewers' gender (i.e., when women were understanding and men were misunderstanding). [ABSTRACT FROM AUTHOR]

Sickle cell anemia and β‐thalassemia intermedia are very different genetically determined hemoglobinopathies predisposing to pulmonary hypertension. The etiologies responsible for the associated development of pulmonary hypertension in both diseases are multi‐factorial with extensive mechanistic contributors described. Both sickle cell anemia and β‐thalassemia intermedia present with intra and extravascular hemolysis. And because sickle cell anemia and β‐thalassemia intermedia share features of extravascular hemolysis, macrophage iron excess and anemia we sought to characterize the common features of the pulmonary hypertension phenotype, cardiac mechanics, and function as well as lung and right ventricular metabolism. Within the concept of iron, we have defined a unique pulmonary vascular iron accumulation in lungs of sickle cell anemia pulmonary hypertension patients at autopsy. This observation is unlike findings in idiopathic or other forms of pulmonary arterial hypertension. In this study, we hypothesized that a common pathophysiology would characterize the pulmonary hypertension phenotype in sickle cell anemia and β‐thalassemia intermedia murine models. However, unlike sickle cell anemia, β‐thalassemia is also a disease of dyserythropoiesis, with increased iron absorption and cellular iron extrusion. This process is mediated by high erythroferrone and low hepcidin levels as well as dysregulated iron transport due transferrin saturation, so there may be differences as well. Herein we describe common and divergent features of pulmonary hypertension in aged Berk‐ss (sickle cell anemia) and Hbbth/3+ (intermediate β‐thalassemia) mice and suggest translational utility as proof‐of‐concept models to study pulmonary hypertension therapeutics specific to genetic anemias.

Macrophages are a heterogeneous population with both pro‐ and anti‐inflammatory functions play an essential role in maintaining tissue homeostasis, promoting inflammation under pathological conditions, and tissue repair after injury. In pulmonary hypertension, the M1 phenotype is more pro‐inflammatory compared to the M2 phenotype, which is involved in tissue repair. The role of macrophages in the initiation and progression of pulmonary hypertension is well studied. However, their role in the regression of established pulmonary hypertension is not well known. Rats chronically exposed to hemoglobin (Hb) plus hypoxia (HX) share similarities to humans with pulmonary hypertension associated with hemolytic disease, including the presence of a unique macrophage phenotype surrounding distal vessels that are associated with vascular remodeling. These lung macrophages are characterized by high iron content, HO‐1, ET‐1, and IL‐6, and are recruited from the circulation. Depletion of macrophages in this model prevents the development of pulmonary hypertension and vascular remodeling. In this study, we specifically investigate the regression of pulmonary hypertension over a four‐week duration after rats were removed from Hb + HX exposure with and without gadolinium chloride administration. Withdrawal of Hb + HX reversed systolic pressures and right ventricular function after Hb + Hx exposure in four weeks. Our data show that depleting circulating monocytes/macrophages during reversal prevents complete recovery of right ventricular systolic pressure and vascular remodeling in this rat model of pulmonary hypertension at four weeks post exposure. The data presented offer a novel insight into the role of macrophages in the processes of pulmonary hypertension regression in a rodent model of Hb + Hx‐driven disease.

3D scaffold-based in vitro cell culturing is a recent technological advancement in cancer research bridging the gap between conventional 2D culture and in vivo tumours. The main challenge in treating neuroblastoma, a paediatric cancer of the sympathetic nervous system, is to combat tumour metastasis and resistance to multiple chemotherapeutic drugs. The aim of this study was to establish a physiologically relevant 3D neuroblastoma tissue-engineered system and explore its therapeutic relevance. Two neuroblastoma cell lines, chemotherapeutic sensitive Kelly and chemotherapeutic resistant KellyCis83 were cultured in a 3D in vitro model on two collagen-based scaffolds containing either glycosaminoglycan (Coll-GAG) or nanohydroxyapatite (Coll-nHA) and compared to 2D cell culture and an orthotopic murine model. Both neuroblastoma cell lines actively infiltrated the scaffolds and proliferated displaying >100-fold increased resistance to cisplatin treatment when compared to 2D cultures, exhibiting chemosensitivity similar to orthotopic xenograft in vivo models. This model demonstrated its applicability to validate miRNA-based gene delivery. The efficacy of liposomes bearing miRNA mimics uptake and gene knockdown was similar in both 2D and 3D in vitro culturing models highlighting the proof-of-principle for the applicability of 3D collagen-based scaffolds cell system for validation of miRNA function. Collectively, this data shows the successful development and characterisation of a physiologically relevant, scaffold-based 3D tissue-engineered neuroblastoma cell model, strongly supporting its value in the evaluation of chemotherapeutics, targeted therapies and investigation of neuroblastoma pathogenesis. While neuroblastoma is the specific disease being focused upon, the platform may have multi-functionality beyond this tumour type. Statement of Significance Traditional 2D cell cultures do not completely capture the 3D architecture of cells and extracellular matrix contributing to a gap in our understanding of mammalian biology at the tissue level and may explain some of the discrepancies between in vitro and in vivo results. Here, we demonstrated the successful development and characterisation of a physiologically relevant, scaffold-based 3D tissue-engineered neuroblastoma cell model, strongly supporting its value in the evaluation of chemotherapeutics, targeted therapies and investigation of neuroblastoma pathogenesis. The ability to test drugs in this reproducible and controllable tissue-engineered model system will help reduce the attrition rate of the drug development process and lead to more effective and tailored therapies. Importantly, such 3D cell models help to reduce and replace animals for pre-clinical research addressing the principles of the 3Rs. [ABSTRACT FROM AUTHOR]

When creating any new anti-parasitic interventions, it is important to evaluate their effects across all life stages. This study had three objectives, which were to evaluate the effect of feeding cranberry vine pellet (CVP) on (1) ewes’ body weights and BCS during late gestation and lactation; (2) ewes’ milk quality during lactation; and (3) lambs’ body weight and growth parameters from birth to 65 days of age. Across two years, 41 Dorset ewes were fed either a 50% CVP or a matching control pellet (CON) from 104 ± 1.60 days of gestation for 62.8 ± 0.68 days of lactation. Measurements were collected from ewes (BW, BCS, and milk) and lambs (BW and body size). Milk from CVP ewes exhibited reduced milk fat and solids (p < 0.01) and increased concentrations of milk urea nitrogen (p = 0.02) when evaluated for the treatment–time. There was no significant difference in the BCS, protein, lamb BW, or growth measurements for treatment–time (p ≥ 0.05). Additional research that targets blood biochemistry and metabolic assessments is needed to fully determine the impact of this pellet on ewes and lambs.

Background: Annotating large medical imaging datasets is an arduous and expensive task, especially when the datasets in question are not organized according to deep learning goals. Here, we propose a method that exploits the hierarchical organization of annotating tasks to optimize efficiency. Methods: We trained a machine learning model to accurately distinguish between one of two classes of lung ultrasound (LUS) views using 2908 clips from a larger dataset. Partitioning the remaining dataset by view would reduce downstream labelling efforts by enabling annotators to focus on annotating pathological features specific to each view. Results: In a sample view-specific annotation task, we found that automatically partitioning a 780-clip dataset by view saved 42 min of manual annotation time and resulted in 55±6 additional relevant labels per hour. Conclusions: Automatic partitioning of a LUS dataset by view significantly increases annotator efficiency, resulting in higher throughput relevant to the annotating task at hand. The strategy described in this work can be applied to other hierarchical annotation schemes.

Previous studies (1) support a role of circadian genes in regulating alcohol intake, and (2) reveal that harmful alcohol use alters circadian rhythms. However, there is minimal knowledge of the effects of chronic alcohol processes on rhythmic circadian gene expression across brain regions important for circadian biology and alcohol intake. Therefore, the present study sought to test the effects of chronic binge-like drinking on diurnal circadian gene expression patterns in the master circadian pacemaker (SCN), the ventral tegmental area (VTA), and the nucleus accumbens (NAc) in High Drinking in the Dark-1 (HDID-1) mice, a unique genetic risk model for drinking to intoxication. Consistent with earlier findings, we found that 8 weeks of binge-like drinking reduced the amplitude of several core circadian clock genes in the NAc and SCN, but not the VTA. To better inform the use of circadian-relevant pharmacotherapies in reducing harmful drinking and ameliorating alcohol’s effects on circadian gene expression, we tested whether the casein kinase-1 inhibitor, PF-67046, or the phosphodiesterase type-4 (an upstream regulator of circadian signalling) inhibitor, apremilast, would reduce binge-like intake and mitigate circadian gene suppression. PF-67046 did not reduce intake but did have circadian gene effects. In contrast, apremilast reduced drinking, but had no effect on circadian expression patterns.

Accurate chromosome segregation depends on bipolar chromosome–microtubule attachment and tension generation on chromosomes. Incorrect chromosome attachment results in chromosome missegregation, which contributes to genome instability. The kinetochore is a protein complex that localizes at the centromere region of a chromosome and mediates chromosome–microtubule interaction. Incorrect chromosome attachment leads to checkpoint activation to prevent anaphase onset. Kinetochore detachment activates the spindle assembly checkpoint (SAC), while tensionless kinetochore attachment relies on both the SAC and tension checkpoint. In budding yeast Saccharomyces cerevisiae, kinesin-5 motor proteins Cin8 and Kip1 are needed to separate spindle pole bodies for spindle assembly, and deletion of CIN8 causes lethality in the absence of SAC. To study the function of Cin8 and Kip1 in chromosome segregation, we constructed an auxin-inducible degron (AID) mutant, cin8-AID. With this conditional mutant, we first confirmed that cin8-AID kip1∆ double mutants were lethal when Cin8 is depleted in the presence of auxin. These cells arrested in metaphase with unseparated spindle pole bodies and kinetochores. We further showed that the absence of either the SAC or tension checkpoint was sufficient to abolish the cell-cycle delay in cin8-AID mutants, causing chromosome missegregation and viability loss. The tension checkpoint-dependent phenotype in cells with depleted Cin8 suggests the presence of tensionless chromosome attachment. We speculate that the failed spindle pole body separation in cin8 mutants could increase the chance of tensionless syntelic chromosome attachments, which depends on functional tension checkpoint for survival.