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BackgroundAdvances in in vivo fluorescent imaging have exploded with the recent developments of genetically encoded calcium indicators (GECIs) and fluorescent biosensors. Their use with a bulk imaging technique such as fiber photometry (FP) can be highly beneficial in identifying neuronal signatures in behavioral neuroscience experiments.Popularity of FP has grown rapidly. Initially applied to classical conditioning, its integration into operant behavior paradigms is progressing. However, in operant behavior, protocols can be complex including numerous scheduled events, while behavioral responses can occur in diverse and non-predictable manners. To optimize data processing and analysis, there is a need for a flexible tool to extract and relate behavioral and fiber photometry data occurring over operant sessions.New MethodApplied to cocaine intravenous self-administration (using ImetronicⓇ polymodal apparati) and FP recordings in the prelimbic cortex (using Doric Lenses photometry system) in the rat, we established Pyfiber, an outline and open source data analysis python library that facilitates the merge of fiber photometry (using Doric Lenses) with operant behavior (using ImetronicⓇ). It allows relating activity changes within a neuronal population to the various behavioral responses and events occurring during operant behavior.ResultsWe show some of the possibilities and benefits of the analytical tool Pyfiber, which helps to: 1. Extract the different types of events that occur in an operant session, 2. Extract and process the fiber photometry signals, 3. Select events of interest and align them to the corresponding fiber photometry signals, 4. Apply the most appropriate type of FP signal normalization and signal analysis according to the studied type of event or behavioral response, 5. Run data extraction and analysis on multiple individuals and sessions at the same time, 6. Collect results in an easily readable format for statistical analysis.From our data and through the use of Pyfiber, we show that we can successfully record and easily analyze calcium transients surrounding events occurring during a cocaine self-administration paradigm in the rat.Comparison with Existing Method(s)While other analytical tools can be used for streamlined fiber photometry analysis, they are either too rigid and specific or too flexible, requiring extensive coding to properly fit the data sets. Additionally, current tools do not permit easy exploration of multiple types of events in parallel- something that is possible with Pyfiber.ConclusionsThis work established an open source resource that facilitates the pairing of fiber photometry recordings (using Doric Lenses photometry system) with operant behavior (using ImetronicⓇ polymodal apparati), setting a solid foundation in analyzing the relationship between different dimensions of operant behavior with fluorescent signals from brain regions of interest.

Family and twin studies demonstrate that genetic factors determine 20-60% of the vulnerability to opioid use disorder. However, the genes/alleles that mediate the risk of developing addiction-related behaviors, including the sensitivity to the analgesic efficacy of opioids, the development of tolerance, dependence, and escalation of oxycodone taking and seeking, have been ill-defined, thus hindering efforts to design pharmacological interventions to enable precision medicine strategies. Here we characterized oxycodone addiction-like behaviors in heterogeneous stock (HS) rats, that show high genetic diversity that mimics the high genetic variability in humans. HS rats were allowed to self-administer oxycodone for two h/daily for four days (ShA) and then moved to 12h/daily (LgA) for 14 days. Animals were screened for motivation to self-administer oxycodone using a progressive-ratio (PR) schedule of reinforcement and for the development of withdrawal-induced hyperalgesia and tolerance to the analgesic effects of oxycodone using the von-Frey and tail immersion tests, respectively. To reduce cohort-specific effects, we used cohorts of 46-60 rats and normalized the response level within cohorts using a Z-score. To take advantage of the four opioid-related behaviors and further identify subjects that are consistently vulnerable vs. resilient to compulsive oxycodone use, we computed an Addiction Index by averaging normalized responding (Z-scores) for the four behavioral tests. Results showed high individual variability between vulnerable and resilient rats, likely to facilitate the detection of gene variants associated with vulnerable vs. resilient individuals. Such data will have considerable translational value for designing follow-up studies in humans.

RationaleCurrent medications for opioid use disorder include buprenorphine, methadone, and naltrexone. While these medications show significant efficacy in reducing craving and opioid use, there are substantial individual differences in response to these treatments in humans. The reason for such difference is poorly known.ObjectivesHere, we tested the hypothesis that similar individual differences may be observed in a large population of heterogenous stock rats, that have been bred to maximize genetic diversity, using a behavioral paradigm relevant to opioid use disorder.MethodsOver 500 rats were given intermittent (4d/week) and extended access (12h/day) to oxycodone self-administration for 14 sessions to establish oxycodone dependence and escalation of intake. We then measured the effect of buprenorphine (0.5mg/kg), methadone (3mg/kg) and naltrexone (3mg/kg) on the motivation to self-administer oxycodone by using a progressive ratio schedule of reinforcement.ResultsWe found that naltrexone and buprenorphine significantly decreased motivation to oxycodone rewards. While naltrexone reduced oxycodone intake in both males and females, systemic administration with buprenorphine reduced progressive ratio responses only in males. Methadone reduced motivation to oxycodone self-administration in nearly 25% of the population, without reaching statical significance. Our results showed that the efficacy of these medications depends on the severity of addiction like behaviors, indicated by the addiction index.ConclusionsThese results demonstrate individual differences in response to medications to treat opioid use disorder in a genetically diverse population of rats.

Fire is an integral component of ecosystems globally and a tool that humans have harnessed for millennia. Altered fire regimes are a fundamental cause and consequence of global change, impacting people and the biophysical systems on which they depend. As part of the newly emerging Anthropocene, marked by human-caused climate change and radical changes to ecosystems, fire danger is increasing, and fires are having increasingly devastating impacts on human health, infrastructure, and ecosystem services. Increasing fire danger is a vexing problem that requires deep transdisciplinary, trans-sector, and inclusive partnerships to address. Here, we outline barriers and opportunities in the next generation of fire science and provide guidance for investment in future research. We synthesize insights needed to better address the long-standing challenges of innovation across disciplines to (i) promote coordinated research efforts; (ii) embrace different ways of knowing and knowledge generation; (iii) promote exploration of fundamental science; (iv) capitalize on the “firehose” of data for societal benefit; and (v) integrate human and natural systems into models across multiple scales. Fire science is thus at a critical transitional moment. We need to shift from observation and modeled representations of varying components of climate, people, vegetation, and fire to more integrative and predictive approaches that support pathways toward mitigating and adapting to our increasingly flammable world, including the utilization of fire for human safety and benefit. Only through overcoming institutional silos and accessing knowledge across diverse communities can we effectively undertake research that improves outcomes in our more fiery future.

This essay documents forms in which repressed supremacy—with the purpose to ultimately push out and exclude people of color professors—is enacted. My endurance within toxic spaces is the result of channeling Tlazolteotl and putting my Coyolxauhqui together, referring to the act of constantly reinventing myself by turning excrement into life and rejoining the pieces of my experience. I also share a successful teaching, research, and service agenda of resistance that fulfills requirements as it is simultaneously defiant. By referring to covert acts of violence as the methodology of the repressed, my goal is to expose and promote their collective eradication.

A large body of work suggests that trade affects workers unevenly. By shifting economic activity across occupations, industries, or regions, freer trade can generate gains for some workers and losses for others.

Global geopolitical risks have soared since Russia's invasion of Ukraine. Investors, market participants, and policymakers expect that the war will exert a drag on the global economy while pushing up inflation, with a sharp increase in uncertainty and risks of severe adverse outcomes. As an example of these concerns, the April 2022 edition of the International Monetary Fund's World Economic Outlook contains more than 200 mentions of the word "war."

ObjectivesImproved methods of rupture prediction are a priority in abdominal aortic aneurysm (AAA). Biomechanical analysis of risk in AAA has major clinical potential but lacks robust evidence that it adds clinical value. We aimed to test if the aneurysm biomechanical ratio (ABR, a dimensionless ratio of wall stress and wall strength) can predict aneurysm-related events.Methods In a prospective multicentre clinical study of 295 patients with AAA (diameter ≥ 40 mm), we used three-dimensional reconstruction and computational biomechanical analyses to compute ABR at baseline. Participants were followed for at least two years and the primary endpoint was the composite of aneurysm rupture or repair. Results The majority were male (87%) current or former smokers (86%), most (72%) had hypertension (mean systolic blood pressure of 140±22 mmHg) and mean baseline diameter was 49.0±6.9 mm. Mean ABR was 0.49±0.27. Participants were followed up for a mean of 848±379 days and rupture (n=13) or repair (n=102) occurred in 115 (39%) cases. The number of repairs increased across tertiles of ABR; low (n=24), medium (n=34), high ABR (n=44) (p=0.010). Rupture or repair occurred more frequently in those with higher ABR (log rank p=0.009) and ABR was independently predictive of this outcome after adjusting for diameter and other clinical risk factors, including gender and smoking (hazard ratio, 1.41; 95% confidence interval, 1.09-1.83; p=0.010). Conclusions We have shown that the biomechanical ABR is a strong independent predictor of AAA rupture or repair in a model incorporating known risk factors, including diameter. Determining ABR at baseline could help guide the management of patients with AAA.

Aims Metaphyseal tritanium cones can be used to manage the tibial bone loss commonly encountered at revision total knee arthroplasty (rTKA). Tibial stems provide additional fixation and are generally used in combination with cones. The aim of this study was to examine the role of the stems in the overall stability of tibial implants when metaphyseal cones are used for rTKA. Methods This computational study investigates whether stems are required to augment metaphyseal cones at rTKA. Three cemented stem scenarios (no stem, 50 mm stem, and 100 mm stem) were investigated with 10 mm-deep uncontained posterior and medial tibial defects using four loading scenarios designed to mimic activities of daily living. Results Small micromotions (mean < 12 µm) were found to occur at the bone-implant interface for all loading cases with or without a stem. Stem inclusion was associated with lower micromotion, however these reductions were too small to have any clinical significance. Peak interface micromotion, even when the cone is used without a stem, was too small to effect osseointegration. The maximum difference occurred with stair descent loading. Stress concentrations in the bone occurred around the inferior aspect of each implant, with the largest occurring at the end of the long stem; these may lead to end-of-stem pain. Stem use is also found to result in stress shielding in the bone along the stem. Conclusion When a metaphyseal cone is used at rTKA to manage uncontained posterior or medial defects of up to 10 mm depth, stem use may not be necessary. Cite this article: Bone Joint Res. 2020;9(4):162–172.

Predators impact preyscapes (3-D distribution of forage species) by consuming prey according to their abilities or by altering prey behavior as they avoid being consumed. We elucidate prey (Antarctic silverfish[Pleuragramma antarctica] and crystal krill[Euphausia chrystallorophias]) responses to predation associated with the marginal ice zone (MIZ) of the McMurdo Sound, Antarctica, polynya. Prey abundance and habitat was sampled across a 30 × 15 km area by remotely-operated vehicle, and included locations that were accessible (ice edge) or inaccessible (solid fast ice) to air-breathing predators. Prey and habitat sampling coincided with bio-logging of Adélie penguins and observations of other air-breathing predators (penguins, seals, and whales), all of which were competing for the same prey. Adélie penguins dived deeper, and more frequently, near the ice edge. Lowered abundance of krill at the ice edge indicated they were depleted or were responding to increased predation and/or higher light levels along the ice edge. Penguin diet shifted increasingly to silverfish from krill during sampling, and was correlated with the arrival of krill-eating whales. Behaviorally-mediated, high trophic transfer characterizes the McMurdo Sound MIZ, and likely other MIZs, warranting more specific consideration in food web models and conservation efforts.

A major limitation of the most widely used current animal models of alcohol dependence is that they use forced exposure to ethanol including ethanol-containing liquid diet and chronic intermittent ethanol (CIE) vapor to produce clinically relevant blood alcohol levels (BAL) and addiction-like behaviors. We recently developed a novel animal model of voluntary induction of alcohol dependence using ethanol vapor self-administration (EVSA). In this model, naive outbred rats given intermittent access to alcohol vapor self-administration exhibit BAL in the 150-300 mg% range and develop somatic signs of withdrawal during acute abstinence. However, it is unknown whether EVSA leads to an escalation of alcohol drinking per se, and whether such escalation is associated with neuroadaptations in brain regions related to stress, reward, and habit. To address these issues, we compared the levels of alcohol drinking during withdrawal between rats passively exposed to alcohol (CIE) or voluntarily exposed to EVSA and measured the number of Fos+ neurons during acute withdrawal (16 h) in the central nucleus of the amygdala (CeA), dorsomedial striatum (DMS), dorsolateral striatum (DLS), nucleus accumbens core (Nacc), periaqueducal grey area (PAG), lateral Habenula (HbL), and the paraventricular nucleus of the thalamus (PVT). The rats were first trained to orally self-administer alcohol in standard operant chambers and then divided in 4 groups (CIE, CI-Air, EVSA and Air-SA) and exposed to intermittent ethanol vapor (passive or active) or intermittent air (passive or active) for 8 h/day, 3 days a week. CIE and EVSA rats exhibited similar BAL (150-300 mg% range) and similar escalation of alcohol drinking during withdrawal, while no changes in terms of drinking were observed in the air exposed rats. CIE and EVSA also increased the motivation for alcohol compared to their respective air control groups under a progressive ratio schedule of reinforcement. Acute withdrawal from EVSA and CIE recruited a similar number of Fos+ neurons in the CeA, however, acute withdrawal from EVSA recruited a higher number of Fos+ neurons in every other brain region analyzed compared to acute withdrawal from CIE. Moreover, acute withdrawal from EVSA specifically recruited the DMS and PVT, a pattern not observed in CIE rats.In summary, these results demonstrate that EVSA produces similar escalation of alcohol drinking, motivation to drink, and blood-alcohol levels than the CIE model, while letting animals voluntary initiate alcohol exposure and maintain alcohol dependence. Moreover, while the behavioral measures of alcohol dependence between the voluntary (EVSA) and passive (CIE) model was similar, the recruitment of neuronal ensembles during acute withdrawal was very different with a higher recruitment of Fos+ neurons in key brain regions important for stress, reward and habit-related processes. The EVSA model may be particularly useful to unveil the neuronal networks and pharmacology responsible for the voluntary induction and maintenance of alcohol dependence and may improve translational studies by providing preclinical researchers with an animal model with better face validity for alcohol use disorder.

From a conservation perspective, quantifying potential refugial capacity has been predominantly focused on climate refugia, which is critical for maintaining the persistence of species and ecosystems. However, protection from other stressors, such as human-induced changes in fire and hydrology, that cause habitat loss, degradation, and fragmentation is also necessary to ensure that conservation efforts focused on climate are not undermined by other threats. Thus, conceptual and methodological advances for quantifying potential refugia from multiple anthropogenic stressors are important to support conservation efforts. We devised a new conceptual approach, the domains of refugia, for assessing refugial capacity that identifies areas where exposure to multiple stressors is low. In our framework, patterns of environmental variability (e.g., increased frequency of warm summers), thresholds of resilience, and extent and intensity of stressors are used to identify areas of potential refugia from a suite of ongoing anthropogenic stressors (e.g., changes in fire regime). To demonstrate its utility, we applied the framework to a Southern California landscape. Sites with high refugial capacity (super-refugia sites) had on average 30% fewer extremely warm summers, 20% fewer fire events, 10% less exposure to altered river channels and riparian areas, and 50% fewer recreational trails than the surrounding landscape. Our results suggest that super-refugia sites (∼8200 kmMarco Conceptual a para Identificar Refugios de Múltiples Amenazas a Escala de Paisaje Resumen Desde la perspectiva de la conservación, la cuantificación de la capacidad potencial de refugio se ha enfocado principalmente en los refugios climáticos, los cuales son críticos para mantener la persistencia de las especies y los ecosistemas. Sin embargo, la protección ante otros factores estresantes, como los cambios inducidos por los humanos en los incendios y la hidrología, que causan la pérdida, degradación y fragmentación del hábitat, también son necesarios para asegurar que los esfuerzos de conservación enfocados en el clima no sean afectados por otras amenazas. Por lo tanto, los avances conceptuales y metodológicos para cuantificar los refugios potenciales ante múltiples factores estresantes causados por el humano son importantes para asegurar que los esfuerzos de conservación logren sus objetivos. Diseñamos una nueva estrategia conceptual, los dominios de los refugios, para evaluar la capacidad de refugio de un paisaje donde la exposición a múltiples factores estresantes es baja. En nuestro marco conceptual usamos los patrones de variabilidad ambiental (p. ej.: incremento en la frecuencia de veranos cálidos), los umbrales de resiliencia y la extensión e intensidad de los factores estresantes para identificar las áreas de refugios potenciales a partir de un conjunto de factores antropogénicos persistentes (p. ej.: cambios en el régimen de incendios). Para demostrar su utilidad, aplicamos el marco conceptual a un paisaje del sur de California. Los sitios con una alta capacidad de refugio (sitios de súper-refugios) tuvieron en promedio un 30% menos veranos extremadamente cálidos, 20% menos eventos de incendios y 50% menos senderos recreativos que el paisaje circundante. Nuestros resultados sugieren que los sitios de súper-refugios (∼ 8,200 km从保护的角度来看, 目前对潜在避难能力的量化主要关注的是气候避难所, 它们对于维持物种和生态系统续存至关重要。然而, 为了确保关注气候的保护工作不受其它威胁因素破坏, 还需要考虑针对其它压力因素的保护, 包括人类引起的火灾和水文变化, 因为它们会导致栖息地丧失、退化和破碎化。因此, 在概念和方法上推动量化多种人为压力因素的潜在避难所的研究进展, 对支持保护工作十分重要。本研究设计了一个新的概念性方法 (即避难所领域) 用于评估避难能力, 以识别受多种压力因素影响较小的地区。我们的框架利用环境变异性格局 (如暖夏出现频率增加) 、恢复力阈值, 以及压力因素的范围和强度来识别一系列持续的人为压力因素 (如火灾变化) 影响下的潜在避难所。为了证明该框架的有效性, 我们将其应用于南加州的一处景观之中。结果表明, 与周围景观相比, 具有高避难能力的位点 (超级避难所) 极端暖夏出现的概率平均低 30%, 火灾出现概率平均低 20%, 河道和河岸地区被改变的风险低 10%, 且存在的休闲步道少 50%。我们的结果指出, 一些自然群落的超级避难所 (约 8,200 平方公里) 在现有的保护区网络中的代表性不足, 这一发现可以指导扩大保护区的工作。我们的案例研究还强调了考虑多种压力因素的暴露情况将如何为规划和实践提供信息, 从而在不断变化的世界中保护生物多样性。 【翻译: 胡怡思; 审校: 聂永刚】.

Twin studies suggest that approximately 50% of the vulnerability to cocaine use disorder is determined by genetic factors, but genome-wide association studies (GWAS) in humans have only begun to identify specific genes that confer this risk. The identification of a set of single nucleotide polymorphisms (SNPs) associated with increased vulnerability to develop compulsive cocaine use represents a major goal for understanding of the genetic risk factors to cocaine use disorder and facilitating the identification of novel druggable targets.Here we characterized addiction-like behaviors in heterogeneous stock (HS) rats, a unique outbred strain of rats characterized by high genetic variability that has been developed to mimic genetic variability in humans. HS rats were allowed to self-administer cocaine 6h/daily for 14 days. Animals were also screened for compulsive cocaine use, using progressive-ratio (PR) and responding despite adverse consequences (contingent foot shocks). To minimize cohort-specific effects, we used large cohorts (n = 46-60) and normalized the level of responding within cohorts using a Z-score. To take advantage of the three behaviors related to compulsive intake and further identify subjects that are consistently vulnerable vs. resilient to compulsive cocaine use we computed an Addiction index by averaging normalized responding (Z-scores) for the three behavioral tests. Results showed high individual variability between vulnerable and resilient rats that is likely to facilitate detection of gene variants associated with vulnerable vs. resilient individuals. Such data will have considerable translational value for designing pharmacogenetic studies in humans.

The gut-brain axis is a bi-directional communication system through which microbial communities in the gut interact with the nervous system, perhaps influencing neuropsychiatric disorders such as drug abuse. This study used behavioral data and biological samples from the Cocaine Biobank to test the hypothesis that the gut microbiota can predict and reflect susceptibility to cocaine reinforcement. Adult male heterogenous rats were catheterized and allowed to self-administer cocaine in short-access sessions (2 hr/day, 10 days, 0.5 mg/kg per intravenous infusion), followed by progressive ratio (PR) tests, long-access sessions (6 hr/day, 14 days), and alternating blocks of PR, long-access, and footshock testing. Fecal samples were collected at three time points and bacterial 16s rRNA genes were sequenced to profile the microbiota. As expected, cocaine-related behavior varied among subjects, such that a quartile split identified low and high responders on each measure, as well as an overall addiction index. Although beta diversity in the microbiota at baseline and after short access did not predict membership in high or low addiction quartiles, linear discriminant analysis (LDA) identified taxa that were more robustly represented in low or high responders. Beta diversity after long access was different among quartiles, as were several specific taxa. Investigation of baseline differences revealed that high relative abundance of Akkermansia muciniphila predicted future low response rates, whereas Ruminococcaceae predicted high response. This study is the first to report that microbiota variability reflects levels of cocaine intake and that microbial profiles might facilitate diagnosis and identify risk factors predictive of drug vulnerability.Significance StatementMicrobial organisms inhabiting the gut of animals appear to influence organismal function through various signaling pathways, ultimately affecting behavior and disease vulnerability. This experiment investigates links between gut bacteria and vulnerability to addiction-related behaviors in adult male rats. Not only did gut bacterial profiles change as a result of cocaine intake but also gut bacterial profiles before any exposure to cocaine predicted which animals would be high or low addiction-prone individuals. These results suggest that microbial profiles might facilitate diagnosis and identify risk factors predictive of drug addiction.

In early 2020, the novel coronavirus (COVID-19) spread to the United States and upended normal life. Using trip-level data on over 17 million taxi rides taken in Chicago from 2018-2021, I document how tipping behavior changed during the COVID-19 pandemic. I find that the average non-zero tip increased by almost 2 percentage points, from roughly 26% to 28% of the taxi fare. Meanwhile, the likelihood that a passenger left a tip at all declined by roughly 5 percentage points, down from a pre-pandemic likelihood of 95%. My preferred specification suggests that the effect on the intensive margin dominates that in the extensive margin, leading to an aggregate increase in tipping generosity during the pandemic. I leverage granularity in the data to explore the mechanisms behind these trends and offer two explanations consistent with thedata. First, passengers responded to the two economic shocks of the pandemic – unemployment and savingsoverhangs – by varying their tipping rates accordingly. Second, passengers internalized the increased risk of COVID-19 infection as an additional cost for taxi drivers and increased their tips as compensation. My analysis testifies to the sustainability of tipping in times of crises and offers theoretical insight into what drives tipping behavior.

Climate and land use patterns are expected to change dramatically in the coming century, raising concern about their effects on wildfire patterns and subsequent impacts to human communities. The relative influence of climate versus land use on fires and their impacts, however, remains unclear, particularly given the substantial geographical variability in fire-prone places like California. We developed a modeling framework to compare the importance of climatic and human variables for explaining fire patterns and structure loss for three diverse California landscapes, then projected future large fire and structure loss probability under two different climate (hot-dry or warm-wet) and two different land use (rural or urban residential growth) scenarios. The relative importance of climate and housing pattern varied across regions and according to fire size or whether the model was for large fires or structure loss. The differing strengths of these relationships, in addition to differences in the nature and magnitude of projected climate or land use change, dictated the extent to which large fires or structure loss were projected to change in the future. Despite this variability, housing and human infrastructure were consistently more responsible for explaining fire ignitions and structure loss probability, whereas climate, topography, and fuel variables were more important for explaining large fire patterns. For all study areas, most structure loss occurred in areas with low housing density (from 0.08 to 2.01 units/ha), and expansion of rural residential land use increased structure loss probability in the future. Regardless of future climate scenario, large fire probability was only projected to increase in the northern and interior parts of the state, whereas climate change had no projected impact on fire probability in southern California. Given the variation in fire-climate relationships and land use effects, policy and management decision-making should be customized for specific geographical regions.

Highly mobile species, such as migratory birds, respond to seasonal and interannual variability in resource availability by moving to better habitats. Despite the recognized importance of resource thresholds, species-distribution models typically rely on long-term average habitat conditions, mostly because large-extent, temporally resolved, environmental data are difficult to obtain. Recent advances in remote sensing make it possible to incorporate more frequent measurements of changing landscapes; however, there is often a cost in terms of model building and processing and the added value of such efforts is unknown. Our study tests whether incorporating real-time environmental data increases the predictive ability of distribution models, relative to using long-term average data. We developed and compared distribution models for shorebirds in California's Central Valley based on high temporal resolution (every 16 days), and 17-year long-term average surface water data. Using abundance-weighted boosted regression trees, we modeled monthly shorebird occurrence as a function of surface water availability, crop type, wetland type, road density, temperature, and bird data source. Although modeling with both real-time and long-term average data provided good fit to withheld validation data (the area under the receiver operating characteristic curve, or AUC, averaged between 0.79 and 0.89 for all taxa), there were small differences in model performance. The best models incorporated long-term average conditions and spatial pattern information for real-time flooding (e.g., perimeter-area ratio of real-time water bodies). There was not a substantial difference in the performance of real-time and long-term average data models within time periods when real-time surface water differed substantially from the long-term average (specifically during drought years 2013-2016) and in intermittently flooded months or locations. Spatial predictions resulting from the models differed most in the southern region of the study area where there is lower water availability, fewer birds, and lower sampling density. Prediction uncertainty in the southern region of the study area highlights the need for increased sampling in this area. Because both sets of data performed similarly, the choice of which data to use may depend on the management context. Real-time data may ultimately be best for guiding dynamic, adaptive conservation actions, whereas models based on long-term averages may be more helpful for guiding permanent wetland protection and restoration.

Visual Abstract, The rat oxycodone and cocaine biobanks contain samples that vary by genotypes (by using genetically diverse genotyped HS rats), phenotypes (by measuring addiction-like behaviors in an advanced SA model), timepoints (samples are collected longitudinally before, during, and after SA, and terminally at three different timepoints in the addiction cycle: intoxication, withdrawal, and abstinence or without exposure to drugs through age-matched naive rats), samples collected (organs, cells, biofluids, feces), preservation (paraformaldehyde-fixed, snap-frozen, or cryopreserved) and application (proteomics, transcriptomics, microbiomics, metabolomics, epigenetics, anatomy, circuitry analysis, biomarker discovery, etc. Substance use disorders (SUDs) are pervasive in our society and have substantial personal and socioeconomical costs. A critical hurdle in identifying biomarkers and novel targets for medication development is the lack of resources for obtaining biological samples with a detailed behavioral characterization of SUD. Moreover, it is nearly impossible to find longitudinal samples. As part of two ongoing large-scale behavioral genetic studies in heterogeneous stock (HS) rats, we have created two preclinical biobanks using well-validated long access (LgA) models of intravenous cocaine and oxycodone self-administration (SA) and comprehensive characterization of addiction-related behaviors. The genetic diversity in HS rats mimics diversity in the human population and includes individuals that are vulnerable or resilient to compulsive-like responding for cocaine or oxycodone. Longitudinal samples are collected throughout the experiment, before exposure to the drug, during intoxication, acute withdrawal, and protracted abstinence, and include naive, age-matched controls. Samples include, but are not limited to, blood plasma, feces and urine, whole brains, brain slices and punches, kidney, liver, spleen, ovary, testis, and adrenal glands. Three preservation methods (fixed in formaldehyde, snap-frozen, or cryopreserved) are used to facilitate diverse downstream applications such as proteomics, metabolomics, transcriptomics, epigenomics, microbiomics, neuroanatomy, biomarker discovery, and other cellular and molecular approaches. To date, >20,000 samples have been collected from over 1000 unique animals and made available free of charge to non-profit institutions through https://www.cocainebiobank.org/ and https://www.oxycodonebiobank.org/.

In early 2020, the novel coronavirus (COVID-19) spread to America and upended normal life for over a year. Using trip-level data on 17 million taxi rides taken in Chicago from 2018-2021, I explore how tipping patterns changed during the COVID-19 pandemic. I find that the average non-zero tip left by passengers increased by almost 2 percentage points, from roughly 26\% to 28\% of the taxi fare. Meanwhile, the likelihood that a passenger leaves a tip at all declined by roughly 5 percentage points, down from a pre-pandemic average of 95\%. I interpret these opposing effects on aggregate tipping generosity as evidence of the disparate economic effects of the pandemic and use a crude proxy of passenger's income to provide evidence for a "K-shaped" trends in tipping generosity. I offer a secondary hypothesis, that elevated tipping rates reflect an effort to compensate essential workers for the increased risk of COVID-19 infection, and test this theory of hazard pay by exploiting variation in trip lengths and daily hospitalizations at the time of trip. Given the numerous reasons one might expect tipping rates to decrease during the pandemic, I consider the aggregate increase in tip generosity during the pandemic as evidence that crises and broad negative shocks increase preferences for altruism and reciprocity in tipping.

Preserving landscape connectivity is one of the most frequently recommended strategies to address the synergistic threats of climate change, habitat fragmentation, and intensifying disturbances. Although assessments to develop plans for linked and connected landscapes in response to climate and land-use change have been increasingly employed in the last decade, efforts to operationalize and implement these plans have been limited. Here, we present a framework using existing, available biological data to design an implementable, comprehensive multispecies connectivity plan. This framework uses a scenario-based approach to consider how ecosystems, habitats, and species may need to adapt to future conditions with an ensemble of connectivity models. We use the south coast ecoregion of California as an example to evaluate and prioritize linkages by combining linked metapopulation models and key landscape features (e.g., conservation planning status and implementation feasibility) to identify and prioritize a multispecies linkage network. Our analyses identified approximately 30,000 km2 of land, roughly one-fifth of our study area, where actions to preserve or enhance connectivity may support climate adaptation, nearly half of which is already conserved. By developing and implementing a dynamic connectivity assessment with an eye towards projected changes, our analysis demonstrates how dynamic connectivity can be integrated into feasible regional conservation and management plans that account for demographic as well as landscape change. We observed overlap across multiple models, reinforcing the importance of areas that appeared across methods. We also identified unique areas important for connectivity captured by our complementary models. By integrating multiple approaches, the resultant linkage network is robust, building on the strengths of a variety of methods to identify model consensus and reduce uncertainty. By linking quantitative connectivity metrics with prioritized areas for conservation, our approach supports transparent and robust decision-making for landscape planning, despite uncertainties of climate and land-use change.

Background: In the UK around 10% of hip and knee arthroplasties are revision operations. At revision total knee arthroplasty (rTKA), bone loss management is critical to achieving a stable bone-implant construct. Though tritanium cones have been used to manage bone defects in rTKA, their biomechanical performance with varying defects remains unknown. Methods: Uncontained tibial bone defects at four anatomic locations, with varying depths and widths (Type T2A and T2B) were investigated computationally in a composite tibia which was subjected to four loading scenarios. The ability of the tritanium cone to replace the tibial bone defect was examined using the outcome 24 measures of bone strain distribution and interface micromotions. Results: It was found that anterior and lateral defects do not significantly alter the strain distribution compared with intact bone. For medial defects, strain distribution is sensitive to defect width; while strain distributions for posterior defects are associated with defect width and depth. In general, micromotions at the bone-implant interface are small and are primarily influenced by defect depth. Conclusions: Our models show that the cone is an acceptable choice for bone defect management in rTKA. Since all observed micromotions were small, successful osteointegration would be expected in all types of uncontained defects considered in this study. Tritanium cones safely accommodate uncontained tibial defects up to 10mm deep and extending up to 9mm from the centre of the cone. Medial and posteriorly based defects managed with symmetric cones display the greatest bone strains and asymmetric cones may be useful in this context.

RATIONALE: Over the last decade, oxycodone has become one of the most widely abused drugs in the USA. Oxycodone use disorder (OUD) is a serious health problem that has prompted a need to develop animal models of OUD that have both face and predictive validity. Oxycodone use in humans is more prevalent in women and leads to pronounced hyperalgesia and irritability during withdrawal. However, unclear is whether current animal models of oxycodone self-administration recapitulate these characteristics in humans. OBJECTIVES: We assessed the face validity of a model of extended-access oxycodone self-administration in rats by examining the escalation of oxycodone intake and behavioral symptoms of withdrawal, including irritability-like behavior and mechanical nociception, in male and female Wistar rats. RESULTS: Both male and female rats escalated their oxycodone intake over fourteen 12-h self-administration sessions. After escalation, female rats administered more drug than male rats. No differences in plasma oxycodone levels were identified, but males had a significantly higher level of oxycodone in the brain at 30 min. Extended access to oxycodone significantly decreased aggressive-like behavior and increased defensive-like behaviors when tested immediately after a 12-h self-administration session, followed by a rebound increase in aggressive-like behavior 12 h into withdrawal. Tests of mechanical nociception thresholds during withdrawal indicated pronounced hyperalgesia. No sex differences in irritability-like behavior or pain sensitivity were observed. CONCLUSIONS: The present study demonstrated the face validity of the extended access model of oxycodone self-administration by identifying sex differences in the escalation of oxycodone intake and pronounced changes in pain and affective states.

Aims Metaphyseal tritanium cones can be used to manage the tibial bone loss commonly encountered at revision total knee arthroplasty (rTKA). Tibial stems provide additional fixation and are generally used in combination with cones. The aim of this study was to examine the role of the stems in the overall stability of tibial implants when metaphyseal cones are used for rTKA. Methods This computational study investigates whether stems are required to augment metaphyseal cones at rTKA. Three cemented stem scenarios (no stem, 50 mm stem, and 100 mm stem) were investigated with 10 mm-deep uncontained posterior and medial tibial defects using four loading scenarios designed to mimic activities of daily living. Results Small micromotions (mean < 12 µm) were found to occur at the bone-implant interface for all loading cases with or without a stem. Stem inclusion was associated with lower micromotion, however these reductions were too small to have any clinical significance. Peak interface micromotion, even when the cone is used without a stem, was too small to effect osseointegration. The maximum difference occurred with stair descent loading. Stress concentrations in the bone occurred around the inferior aspect of each implant, with the largest occurring at the end of the long stem; these may lead to end-of-stem pain. Stem use is also found to result in stress shielding in the bone along the stem. Conclusion When a metaphyseal cone is used at rTKA to manage uncontained posterior or medial defects of up to 10 mm depth, stem use may not be necessary. Cite this article: Bone Joint Res. 2020;9(4):162–172.

This chapter is intended primarily for engineers and designers whose experience with vessels is primarily with metal equipment. Those having experience with fiberglass equipment but not with Section X or RTP-1 will also find this chapter useful. Section X is part of the ASME Boiler and Pressure Vessel Code and governs vessels constructed of thermosetting resin reinforced with glass fibers and vessels reinforced with carbon or aramid fibers. The chapter is intended to serve as a manual on the use of Section X and RTP-1. The pressure scope of Section X is 15 psig to 15,000 psig internal pressure. RTP-1 covers tanks and vessels with design pressures of 0–5 psig. The chapter begins with a discussion on the basics of fiber-reinforced plastic (FRP) technology used in RTP-1 and Section X that may not be familiar to engineers and designers of metal vessels. It describes the resins and reinforcing fibers included in RTP-1 and Section X. The chapter then discusses the following processes used to manufacture RTP-1 and Section X vessels: contact molding, bag molding, centrifugal casting, and filament winding. The joining of vessel parts made by these methods is also discussed. The chapter describes ways to treat the two factors that complicate the stress analysis of FRP vessels. The scope of Section X and RTP-1 is covered next. It then looks at the design qualification of Section X, Class I, Class II, Class III, and RTP-1 vessels. In addition, it presents an example of a Section X Design Specification and its calculations as well as RTP-1 design examples. The chapter closes with a discussion on the quality assurance requirements of Section X and RTP-1.

The “Rainbow Journalism” (RJ) course was a way to proactively channel the devastating effects 45 had on the CSUSB community. This article focuses on the decolonial tactics of RJ, which are simultan...

Selective permeation of water vapor over liquid phase water through hydrophobic conduits finds broad use in separation processes, including desalination and membrane distillation. The tangential momentum accommodation coefficient (TMAC), a fundamental parameter that dictates momentum changes to a molecule colliding with a wall remains unknown for water vapor at room temperature and pressure conditions. Here, a nanofluidic platform with tunable hydrophobic regions that selectively barricaded flow of liquid water was patterned within glass nanochannels. The surface functionalization with an alkyltrichlorosilane led to either a fluoride or a methyl terminal group generating partially hydrophobic regions along the length of the nanochannels. Differential osmotic pressure solutions on either side of the hydrophobic region cause an isothermal evaporation-condensation process, which drives net water vapor transport from higher to lower vapor pressure solution, similar to osmotic distillation. Water vapor transport under such conditions for the 80 nm deep nanochannels was in the transitional regime with the Knudsen number ∼O(1). The TMAC was estimated experimentally to be of the order of 10-4-10-3 for both the hydrophobic coatings leading to a near-elastic collision of H2O molecules with the nanochannel walls. Use of the low TMAC surfaces was evaluated in two proof-of-concept technology demonstrations: (1) osmotic distillation using hyper-saline (brine) 3 M Utica shale flowback water as both the feed and draw and (2) separation of trace amounts of toluene and chloroform from water at high flux and selectivity. The results reported here likely provide new insights in designing hydrophilic-hydrophobic junctions for nanoscale liquid/vapor fluid transport with enhanced flux and selectivity.

Supplemental Digital Content is available in the text., Background: Ultrasmall superparamagnetic particles of iron oxide (USPIO) detect cellular inflammation on magnetic resonance imaging (MRI). In patients with abdominal aortic aneurysm, we assessed whether USPIO-enhanced MRI can predict aneurysm growth rates and clinical outcomes. Methods In a prospective multicenter open-label cohort study, 342 patients with abdominal aortic aneurysm (diameter ≥40 mm) were classified by the presence of USPIO enhancement and were monitored with serial ultrasound and clinical follow-up for ≥2 years. The primary end point was the composite of aneurysm rupture or repair. Results Participants (85% male, 73.1±7.2 years) had a baseline aneurysm diameter of 49.6±7.7 mm, and USPIO enhancement was identified in 146 (42.7%) participants, absent in 191 (55.8%), and indeterminant in 5 (1.5%). During follow-up (1005±280 days), 17 (5.0%) abdominal aortic aneurysm ruptures, 126 (36.8%) abdominal aortic aneurysm repairs, and 48 (14.0%) deaths occurred. Compared with those without uptake, patients with USPIO enhancement have increased rates of aneurysm expansion (3.1±2.5 versus 2.5±2.4 mm/year, P=0.0424), although this was not independent of current smoking habit (P=0.1993). Patients with USPIO enhancement had higher rates of aneurysm rupture or repair (47.3% versus 35.6%; 95% confidence intervals, 1.1–22.2; P=0.0308). This finding was similar for each component of rupture (6.8% versus 3.7%, P=0.1857) or repair (41.8% versus 32.5%, P=0.0782). USPIO enhancement was associated with reduced event-free survival for aneurysm rupture or repair (P=0.0275), all-cause mortality (P=0.0635), and aneurysm-related mortality (P=0.0590). Baseline abdominal aortic aneurysm diameter (P

Inflammation detected through the uptake of ultrasmall superparamagnetic particles of iron oxide (USPIO) on magnetic resonance imaging (MRI) and finite element (FE) modelling of tissue stress both hold potential in the assessment of abdominal aortic aneurysm (AAA) rupture risk. This study aimed to examine the spatial relationship between these two biomarkers. Patients (n = 50) > 40 years with AAA maximum diameters > = 40 mm underwent USPIO-enhanced MRI and computed tomography angiogram (CTA). USPIO uptake was compared with wall stress predictions from CTA-based patient-specific FE models of each aneurysm. Elevated stress was commonly observed in areas vulnerable to rupture (e.g. posterior wall and shoulder). Only 16% of aneurysms exhibited co-localisation of elevated stress and mural USPIO enhancement. Globally, no correlation was observed between stress and other measures of USPIO uptake (i.e. mean or peak). It is suggested that cellular inflammation and stress may represent different but complimentary aspects of AAA disease progression. Electronic supplementary material The online version of this article (doi:10.1007/s12265-017-9766-9) contains supplementary material, which is available to authorized users.

Objective To establish the feasibility and acceptability of home-based HPV self-sampling among women who did not attend screening appointments in rural El Salvador. Methods In a cross-sectional study, data were collected from May 2015 to January 2016 among 60 women aged 30–59 years who were not pregnant, provided informed consent, had not been screened in 2 years, had no history of pre-cancer treatment, and did not attend a scheduled HPV screening. Participants completed questionnaires and received educational information before being given an opportunity to self-sample with the Hybrid Capture 2 High Risk HPV DNA Test. Results Self-sampling was accepted by 41 (68%) participants. Almost all women chose to self-sample because the process was easy (40/41, 98%), could be performed at home (40/41, 98%), and saved time (38/41, 93%), and because they felt less embarrassed (33/41, 80%). The most common reason for declining the test was not wanting to be screened (8/19, 42%). The prevalence of high-risk HPV types among women who accepted self-sampling was 17% (7/41). Conclusion For most women, community-based self-sampling was an acceptable way to participate in a cervical cancer screening program. In low-resource countries, incorporating community-based self-sampling into screening programs might improve coverage of high-risk women.

Author(s): Conlisk, Erin; Cristina Castanha; Matthew J. Germino; Thomas T. Veblen; Jeremy M. Smith; Lara M. Kueppers | Abstract: Species distribution shifts in response to climate change require that recruitment increase beyond current range boundaries. For trees with long life spans, the importance of climateâsensitive seedling establishment to the pace of range shifts has not been demonstrated quantitatively. Using spatially explicit, stochastic population models combined with data from longâterm forest surveys, we explored whether the climateâsensitivity of recruitment observed in climate manipulation experiments was sufficient to alter populations and elevation ranges of two widely distributed, highâelevation North American conifers. Empirically observed, warmingâdriven declines in recruitment led to rapid modelled population declines at the lowâelevation, âwarm edgeâ of subalpine forest and slow emergence of populations beyond the highâelevation, âcool edgeâ. Because population declines in the forest occurred much faster than population emergence in the alpine, we observed range contraction for both species. For Engelmann spruce, this contraction was permanent over the modelled time horizon, even in the presence of increased moisture. For limber pine, lower sensitivity to warming may facilitate persistence at low elevations â especially in the presence of increased moisture â and rapid establishment above tree line, and, ultimately, expansion into the alpine. Synthesis. Assuming 21st century warming and no additional moisture, population dynamics in highâelevation forests led to transient range contractions for limber pine and potentially permanent range contractions for Engelmann spruce. Thus, limitations to seedling recruitment with warming can constrain the pace of subalpine tree range shifts.

Surface charge governs nanoscale aqueous electrolyte transport, both in engineered analytical systems and in biological entities such as ion channels and ion pumps as a function of ion type and concentration. Embedded electrodes in a nanofluidic channel, isolated from the fluid in the channel by a dielectric layer, act as active, tunable gates to systematically modify local surface charge density at the interface between the nanochannel surface and the aqueous electrolyte solution, causing significant changes in measured nanochannel conductance. A systematic comparison of transport of monovalent electrolytes [potassium chloride (KCl), sodium chloride (NaCl)], 2:1 electrolytes [magnesium chloride (MgCl2), calcium chloride (CaCl2)], and electrolyte mixtures (KCl + CaCl2) through a gated nanofluidic device was performed. Ion–surface interactions between divalent Ca2+ and Mg2+ ions and the nanochannel walls reduced the native surface charge density by up to ∼4–5 times compared to the monovalent cations. In el...

Because they are intuitive and mathematically straight-forward, colonization rules are often used to model spatial patterns in ecology. Colonization rules assign individuals to categories according to the locations of previous colonists. In this note, a compact introduction to colonization rules in ecology is presented with implications for autocorrelation and spatial distributions. I use the colonization rule approach to unify a diverse set of spatial and species diversity analyses, exploring future extensions to incorporate greater realism.

Dynamics of charged sub-micron or colloidal particles in a microfluidic device through cross-stream migration under combined pressure gradients and electric potential gradients was demonstrated using confocal microscopy. The microfluidic device was a rectangular cross-section poly(dimethylsiloxane) or PDMS microchannel sealed with a borosilicate glass lid to form a hybrid PDMS-glass device. We postulate that the reported particle migration may arise in response to electrophoretic particle slip, i.e., the difference between the particle and fluid velocities, due to the applied electric potential gradient across the microchannel. Colloidal particle migration was observed either towards or away from the microchannel walls depending on the relative directions for the applied potential and pressure gradients. When pressure gradient driving the fluid flow and potential gradient were applied in the same direction, colloidal particles migrate away from the microchannel walls. In the case of opposite directions for the pressure and potential gradients, colloidal particles migrate towards the microchannel walls and subsequently assemble into distinct bands next to both the bottom glass and top PDMS walls. The results reported here demonstrate that the particle dynamics due to electrophoresis in Poiseuille flow within a microchannel result in non-uniform spatial distributions of colloidal particles via cross-stream migration, with the ability to assemble particles into distinct band structures at channel walls. Such manipulation, once fully realized, could lead to several microfluidics applications in material synthesis, particle separation, and biosensing.

Climate and land use patterns are expected to change dramatically in the coming century, raising concern about their effects on wildfire patterns and subsequent impacts to human communities. The relative influence of climate versus land use on fires and their impacts, however, remains unclear, particularly given the substantial geographical variability in fire-prone places like California. We developed a modeling framework to compare the importance of climatic and human variables for explaining fire patterns and structure loss for three diverse California landscapes, then projected future large fire and structure loss probability under two different climate (hot-dry or warm-wet) and two different land use (rural or urban residential growth) scenarios. The relative importance of climate and housing pattern varied across regions and according to fire size or whether the model was for large fires or structure loss. The differing strengths of these relationships, in addition to differences in the nature and magnitude of projected climate or land use change, dictated the extent to which large fires or structure loss were projected to change in the future. Despite this variability, housing and human infrastructure were consistently more responsible for explaining fire ignitions and structure loss probability, whereas climate, topography, and fuel variables were more important for explaining large fire patterns. For all study areas, most structure loss occurred in areas with low housing density (from 0.08 to 2.01 units/ha), and expansion of rural residential land use increased structure loss probability in the future. Regardless of future climate scenario, large fire probability was only projected to increase in the northern and interior parts of the state, whereas climate change had no projected impact on fire probability in southern California. Given the variation in fire-climate relationships and land use effects, policy and management decision-making should be customized for specific geographical regions.

Although most conservation efforts address the direct, local causes of biodiversity loss, effective long‐term conservation will require complementary efforts to reduce the upstream economic pressures, such as demands for food and forest products, which ultimately drive these downstream losses. Here, we present a wildlife footprint analysis that links global losses of wild birds to consumer purchases across 57 economic sectors in 129 regions. The United States, India, China, and Brazil have the largest regional wildlife footprints, while per‐person footprints are highest in Mongolia, Australia, Botswana, and the United Arab Emirates. A US$100 purchase of bovine meat or rice products occupies approximately 0.1 km2 of wild bird ranges, displacing 1–2 individual birds, for 1 year. Globally significant importer regions, including Japan, the United Kingdom, Germany, Italy, and France, have large footprints that drive wildlife losses elsewhere in the world and represent important targets for consumption‐focused conservation attention.

PurposeDue to age-related changes to the material properties and thinning of the cortical bone structure, older patients with osteoporosis may be at greater risk of femoral fracture following total knee arthroplasty. This study investigates whether there is a potential role for stemmed prostheses in such scenarios to help mitigate peri-implant fracture risk, and if so what should the optimum stem length be to balance surgical bone loss with reduced fracture risk.MethodsFinite element models of the distal femur implanted with four different implant types: a posterior stabilising implant, a total stabilising implant with short stem (12 mm × 50 mm), a TS implant with medium stem (12 mm × 75 mm), and a TS implant with long stem (12 mm × 100 mm), were developed and analysed in this study. Osteoporotic properties were applied to the implanted femurs and the periprosthetic stresses and strains of each were recorded.ResultsAll stem lengths examined were found to lead to a reduction in periprosthetic stress in comparison with a primary stemless implant, with short-, medium-, and long-stemmed implants leading to an 11, 26, and 29% reduction in stress, respectively.ConclusionThe results of this study show that periprosthetic stress and therefore fracture risk in old osteoporotic patients may be reduced through the use of stemmed femoral components. Of the three stems investigated, a medium-length stem is found to represent the best balance between bone preservation at the time of surgery and reduction in periprosthetic stress following implantation.

Rupture of abdominal aortic aneurysms (AAAs) is linked to aneurysm morphology. This study investigates the influence of patient-specific (PS) AAA wall thickness on predicted clinical outcomes. Eight patients under surveillance for AAAs were selected from the MA(3)RS clinical trial based on the complete absence of intraluminal thrombus. Two finite element (FE) models per patient were constructed; the first incorporated variable wall thickness from CT (PS_wall), and the second employed a 1.9mm uniform wall (Uni_wall). Mean PS wall thickness across all patients was 1.77±0.42mm. Peak wall stress (PWS) for PS_wall and Uni_wall models was 0.6761±0.3406N/mm(2) and 0.4905±0.0850N/mm(2), respectively. In 4 out of 8 patients the Uni_wall underestimated stress by as much as 55%; in the remaining cases it overestimated stress by up to 40%. Rupture risk more than doubled in 3 out of 8 patients when PS_wall was considered. Wall thickness influenced the location and magnitude of PWS as well as its correlation with curvature. Furthermore, the volume of the AAA under elevated stress increased significantly in AAAs with higher rupture risk indices. This highlights the sensitivity of standard rupture risk markers to the specific wall thickness strategy employed.

Motor proteins, like kinesin, transport cargo within biological cells by transforming chemical energy into mechanical energy through the hydrolysis of adenosine triphosphate (ATP). Kinesins walk across small tracks called microtubules. Recent studies have found that these concepts can be applied in vitro by attaching the motors to a glass substrate, on which microtubules can then glide across. These systems could be useful for many applications, such as targeted drug delivery and efficient, easy medical diagnosis. However, the motion of traveling microtubules is randomly ordered, and methods for controlling it are often hard to implement and recreate. One promising approach is to use depletants, or unreactive macromolecules, that can align microtubules in the same direction by forcing them to move together. This study aims to improve control of microtubule collective motion by using DNA as a signal to increase the effect that depletants have on the microtubule system. This is done by attaching bulky DNA molecules to the filaments, thus increasing their volumes. By comparing the organization of the system before and after the modification of the microtubules, the effects can be analyzed at many concentrations. This study provides an assessment of the relationship between the use of altered microtubules and the concentration of depletants within a gliding assay to induce an ordered collective motion.

GPR139 is an orphan G protein-coupled receptor (GPCR) that is expressed mainly in the brain, with the highest expression in the medial habenula. The modulation of GPR139 receptor function has been hypothesized to be beneficial in the treatment of some mental disorders, but behavioral studies have not yet provided causal evidence of the role of GPR139 in brain dysfunction. Because of the high expression of GPR139 in the habenula, a critical brain region in addiction, we hypothesized that GPR139 may play role in alcohol dependence. Thus, we tested the effect of GPR139 receptor activation using the selective, brain-penetrant receptor agonist JNJ-63533054 on addiction-like behaviors in alcohol-dependent male rats. Systemic administration of JNJ-63533054 (30 mg/kg but not 10 mg/kg, p.o.) reversed the escalation of alcohol self-administration in alcohol-dependent rats, without affecting water or saccharin intake in dependent rats or alcohol intake in nondependent rats. Moreover, systemic JNJ-63533054 administration decreased withdrawal-induced hyperalgesia, without affecting somatic signs of alcohol withdrawal. Further analysis demonstrated that JNJ-63533054 was effective only in a subgroup of dependent rats that exhibited compulsive-like alcohol drinking. Finally, site-specific microinjection of JNJ-63533054 in the habenula but not interpeduncular nucleus (IPN) reduced both alcohol self-administration and withdrawal-induced hyperalgesia in dependent rats. These results provide robust preclinical evidence that GPR139 receptor activation reverses key addiction-like behaviors in dependent animals, suggest that GPR139 may be a novel target for the treatment of alcohol use disorder, and demonstrate that GPR139 is functionally relevant in regulating mammalian behavior.