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Homophilous behaviour plays a central role in the formation of human friendships. Individuals form social ties with others that show similar phenotypic traits, independently of relatedness. Evidence of such homophily can be found in bottlenose dolphins ( Tursiops aduncus) in Shark Bay, Western Australia, where females that use marine sponges as foraging tools often associate with other females that use sponges. 'Sponging' is a socially learned, time-consuming behaviour, transmitted from mother to calf. Previous research illustrated a strong female bias in adopting this technique. The lower propensity for males to engage in sponging may be due to its incompatibility with adult male-specific behaviours, particularly the formation of multi-level alliances. However, the link between sponging and male behaviour has never been formally tested. Here, we show that male spongers associated significantly more often with other male spongers irrespective of their level of relatedness. Male spongers spent significantly more time foraging, and less time resting and travelling, than did male non-spongers. Interestingly, we found no difference in time spent socializing. Our study provides novel insights into the relationship between tool use and activity budgets of male dolphins, and indicates social homophily in the second-order alliance composition of tool-using bottlenose dolphins.

Objective: To determine whether typical road users appreciate the special optical properties of retroreflective materials., Background: Retroreflective surfaces reflect light back towards the source of the illumination. All drivers benefit from retroreflective materials, as they are required on road signs, on large trailers, in lane delineation, and other traffic control devices. Retroreflective markings can also greatly enhance the conspicuity of pedestrians at night, but pedestrians typically underuse retroreflective markings. One possible reason is that pedestrians may not appreciate the special optical properties of retroreflective materials., Method: Two experiments tested whether observers could correctly predict that retroreflective materials appear remarkably bright when illuminated by a source that is aligned with the observers' eyes. Observers used a magnitude estimation procedure to predict how bright retroreflective and non-retroreflective stimuli would appear during a demonstration designed to highlight retroreflectivity. They then judged the brightness again during the demonstration., Results: In general, observers underestimated how bright retroreflective stimuli would be and overestimated how bright diffuse reflective and fluorescent stimuli would be. The underestimates for retroreflective stimuli were particularly striking when the observers had not closely examined the stimuli in advance., Conclusion: The fact that road users do not appreciate retroreflectivity may help explain why pedestrians underuse retroreflective markings at night., Application: Educational interventions could prove useful in this domain.

For over a century, the evolution of animal play has sparked scientific curiosity. The prevalence of social play in juvenile mammals suggests that play is a beneficial behavior, potentially contributing to individual fitness. Yet evidence from wild animals supporting the long-hypothesized link between juvenile social play, adult behavior, and fitness remains limited. In Western Australia, adult male bottlenose dolphins ( Tursiops aduncus ) form multilevel alliances that are crucial for their reproductive success. A key adult mating behavior involves allied males using joint action to herd individual females. Juveniles of both sexes invest significant time in play that resembles adult herding-taking turns in mature male (actor) and female (receiver) roles. Using a 32-y dataset of individual-level association patterns, paternity success, and behavioral observations, we show that juvenile males with stronger social bonds are significantly more likely to engage in joint action when play-herding in actor roles. Juvenile males also monopolized the actor role and produced an adult male herding vocalization ("pops") when playing with females. Notably, males who spent more time playing in the actor role as juveniles achieved more paternities as adults. These findings not only reveal that play behavior provides male dolphins with mating skill practice years before they sexually mature but also demonstrate in a wild animal population that juvenile social play predicts adult reproductive success., Competing Interests: Competing interests statement:The authors declare no competing interest.

Vascular factors are known to be early and important players in Alzheimer's disease (AD) development, however the role of the ε4 allele of the Apolipoprotein (APOE) gene (a risk factor for developing AD) remains unclear. APOE4 genotype is associated with early and severe neocortical vascular deficits in anaesthetised mice, but in humans, vascular and cognitive dysfunction are focused on the hippocampal formation and appear later. How APOE4 might interact with the vasculature to confer AD risk during the preclinical phase represents a gap in existing knowledge. To avoid potential confounds of anaesthesia and to explore regions most relevant for human disease, we studied the visual cortex and hippocampus of awake APOE3 and APOE4-TR mice using 2-photon microscopy of neurons and blood vessels. We found mild vascular deficits: vascular density and functional hyperaemia were unaffected in APOE4 mice, and neuronal or vascular function did not decrease up to late middle-age. Instead, vascular responsiveness was lower, arteriole vasomotion was reduced and neuronal calcium signals during visual stimulation were increased. This suggests that, alone, APOE4 expression is not catastrophic but stably alters neurovascular physiology. We suggest this state makes APOE4 carriers more sensitive to subsequent insults such as injury or beta amyloid accumulation., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The social intelligence hypothesis holds that complex social relationships are the major selective force underlying the evolution of large brain size and intelligence. Complex social relationships are exemplified by coalitions and alliances that are mediated by affiliative behavior, resulting in differentiated but shifting relationships. Male Indo-Pacific bottlenose dolphins in Shark Bay, Australia, form three alliance levels or 'orders', primarily among non-relatives. Strategic alliance formation has been documented within both first- and second-order alliances and between second-order alliances ('third-order alliances'), revealing that the formation of strategic inter-group alliances is not limited to humans. Here we conducted a fine-scale study on 22 adult males over a 6-year period to determine if third-order alliance relationships are differentiated, and mediated by affiliative interactions. We found third-order alliance relationships were strongly differentiated, with key individuals playing a disproportionate role in maintaining alliances. Nonetheless, affiliative interactions occurred broadly between third-order allies, indicating males maintain bonds with third-order allies of varying strength. We also documented a shift in relationships and formation of a new third-order alliance. These findings further our understanding of dolphin alliance dynamics and provide evidence that strategic alliance formation is found in all three alliance levels, a phenomenon with no peer among non-human animals., (© 2023. The Author(s).)

Extrasynaptic GABA A receptors (GABA A Rs) composed of α4, β, and δ subunits mediate GABAergic tonic inhibition and are potential molecular targets in the modulation of behavioral responses to natural and drug rewards. These GABA A Rs are highly expressed within the nucleus accumbens (NAc), where they influence the excitability of the medium spiny neurons. Here, we explore their role in modulating behavioral responses to food-conditioned cues and the behavior-potentiating effects of cocaine. α4-Subunit constitutive knock-out mice (α4 -/- ) showed higher rates of instrumental responding for reward-paired stimuli in a test of conditioned reinforcement (CRf). A similar effect was seen following viral knockdown of GABA A R α4 subunits within the NAc. Local infusion of the α4βδ-GABA A R-preferring agonist THIP (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol; Gaboxadol) into the NAc had no effect on responding when given alone but reduced cocaine potentiation of responding for conditioned reinforcers in wild-type, but not α4 -/- mice. Finally, specific deletion of α4-subunits from dopamine D2, but not D1, receptor-expressing neurons (DRD2 and DRD1 neurons), mimicked the phenotype of the constitutive knockout, potentiating CRf responding, and blocking intra-accumbal THIP attenuation of cocaine-potentiated CRf responding. These data demonstrate that α4-GABA A R-mediated inhibition of DRD2 neurons reduces instrumental responding for a conditioned reinforcer and its potentiation by cocaine and emphasize the importance of GABAergic signaling within the NAc in mediating the effects of cocaine., Competing Interests: The authors declare no competing financial interests., (Copyright © 2023 Macpherson et al.)

The sea otter ( Enhydra lutris ) population of Southeast Alaska has been growing at a higher rate than other regions along the Pacific coast. While good for the recovery of this endangered species, rapid population growth of this apex predator can create a human-wildlife conflict, negatively impacting commercial and subsistence fishing. Previous foraging studies throughout the sea otter range have shown they will reduce invertebrate prey biomass when recolonizing an area. The goal of this study was to examine and quantify the energy content of sea otter diets through direct foraging observations and prey collection. Our study area, Prince of Wales Island in southern Southeast Alaska, exhibits a gradient of sea otter recolonization, thus providing a natural experiment to test diet change in regions with different recolonization histories. Sea otter prey items were collected in three seasons (spring, summer, and winter) to measure caloric value and lipid and protein content. We observed 3523 sea otter dives during the spring and summer. A majority of the sea otter diet consisted of clams. Sea otters in newly recolonized areas had lower diet diversity, higher energetic intake rates (EIR, kcal/min), and prey had higher energy content (kcal/g). Females with pups had the highest diet diversity and the lowest EIR. Sea otter EIR were higher in the fall and winter vs. spring and summer. Sea cucumber energy and lipid content appeared to correspond with times when sea otters consumed the highest proportion of sea cucumbers. These caloric variations are an important component of understanding ecosystem-level effects sea otters have in the nearshore environment., Competing Interests: None., (© 2023 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

Understanding the impact of human disturbance on wildlife populations is of societal importance, 1 with anthropogenic noise known to impact a range of taxa, including mammals, 2 birds, 3 fish, 4 and invertebrates. 5 While animals are known to use acoustic and other behavioral mechanisms to compensate for increasing noise at the individual level, our understanding of how noise impacts social animals working together remains limited. Here, we investigated the effect of noise on coordination between two bottlenose dolphins performing a cooperative task. We previously demonstrated that the dolphin dyad can use whistles to coordinate their behavior, working together with extreme precision. 6 By equipping each dolphin with a sound-and-movement recording tag (DTAG-3 7 ) and exposing them to increasing levels of anthropogenic noise, we show that both dolphins nearly doubled their whistle durations and increased whistle amplitude in response to increasing noise. While these acoustic compensatory mechanisms are the same as those frequently used by wild cetaceans, 8 , 9 , 10 , 11 , 12 , 13 they were insufficient to overcome the effect of noise on behavioral coordination. Indeed, cooperative task success decreased in the presence of noise, dropping from 85% during ambient noise control trials to 62.5% during the highest noise exposure. This is the first study to demonstrate in any non-human species that noise impairs communication between conspecifics performing a cooperative task. Cooperation facilitates vital functions across many taxa and our findings highlight the need to account for the impact of disturbance on functionally important group tasks in wild animal populations., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Knowledge of an animal's chronological age is crucial for understanding and predicting population demographics, survival and reproduction, but accurate age determination for many wild animals remains challenging. Previous methods to estimate age require invasive procedures, such as tooth extraction to analyse growth layers, which are difficult to carry out with large, mobile animals such as cetaceans. However, recent advances in epigenetic methods have opened new avenues for precise age determination. These 'epigenetic clocks' present a less invasive alternative and can provide age estimates with unprecedented accuracy. Here, we present a species-specific epigenetic clock based on skin tissue samples for a population of Indo-Pacific bottlenose dolphins ( Tursiops aduncus ) in Shark Bay, Western Australia. We measured methylation levels at 37,492 cytosine-guanine sites (CpG sites) in 165 samples using the mammalian methylation array. Chronological age estimates with an accuracy of ±1 year were available for 68 animals as part of a long-term behavioral study of this population. Using these samples with known age, we built an elastic net model with Leave-One-Out-Cross-Validation, which retained 43 CpG sites, providing an r  = 0.86 and median absolute age error (MAE) = 2.1 years (5% of maximum age). This model was more accurate for our data than the previously published methylation clock based on skin samples of common bottlenose dolphins ( T. truncatus : r  = 0.83, MAE = 2.2) and the multi-species odontocete methylation clock ( r  = 0.68, MAE = 6.8), highlighting that species-specific clocks can have superior performance over those of multi-species assemblages. We further developed an epigenetic sex estimator, predicting sex with 100% accuracy. As age and sex are critical parameters for the study of animal populations, this clock and sex estimator will provide a useful tool for extracting life history information from skin samples rather than long-term observational data for free-ranging Indo-Pacific bottlenose dolphins worldwide., Competing Interests: SH is a founder of the non‐profit Epigenetic Clock Development Foundation, which plans to license several of his patents from his employer UC Regents. The other authors declare no conflicts of interest., (© 2022 The Authors. Evolutionary Applications published by John Wiley & Sons Ltd.)

Objective: The purpose of this study was to investigate the immediate effects of cervical spine manipulation (SM) compared with muscle energy technique (MET) on neck muscle activity and range of motion in asymptomatic people., Methods: A randomized parallel-group study was conducted at a chiropractic teaching clinic in Durban, South Africa. Fifty asymptomatic participants between 18 and 35 years of age were randomly assigned into group 1 or group 2. Group 1 received cervical SM, and group 2 received MET. Participants were blinded to group allocation only. Baseline and post-test measurements consisted of resting upper trapezius and posterior cervical muscle activity and cervical spine range of motion (ROM) in lateral flexion and extension., Results: A significant difference was found in cervical ROM within groups ( P < .001), with no significant difference observed between the 2 groups. The right posterior cervical muscles showed a significant difference in group 1 only ( P  = .012). No significant muscle activity changes occurred in group 2. Resting muscle activity measures showed no statistically significant changes between groups., Conclusion: A single application of SM and MET to the cervical spine immediately increased cervical ROM. Neither cervical SM nor MET changed resting posterior cervical and upper trapezius muscle activity., (© 2022 by National University of Health Sciences.)

Efforts to understand human social evolution rely largely on comparisons with nonhuman primates. However, a population of bottlenose dolphins in Shark Bay, Western Australia, combines a chimpanzee-like fission-fusion grouping pattern, mating system, and life history with the only nonhuman example of strategic multilevel male alliances. Unrelated male dolphins form three alliance levels, or "orders", in competition over females: both within-group alliances (i.e., first- and second-order) and between-group alliances (third-order), based on cooperation between two or more second-order alliances against other groups. Both sexes navigate an open society with a continuous mosaic of overlapping home ranges. Here, we use comprehensive association and consortship data to examine fine-scale alliance relationships among 121 adult males. This analysis reveals the largest nonhuman alliance network known, with highly differentiated relationships among individuals. Each male is connected, directly or indirectly, to every other male, including direct connections with adult males outside of their three-level alliance network. We further show that the duration with which males consort females is dependent upon being well connected with third-order allies, independently of the effect of their second-order alliance connections, i.e., alliances between groups increase access to a contested resource, thereby increasing reproductive success. Models of human social evolution traditionally link intergroup alliances to other divergent human traits, such as pair bonds, but our study reveals that intergroup male alliances can arise directly from a chimpanzee-like, promiscuous mating system without one-male units, pair bonds, or male parental care.

Background: Limited access to mental health care services due to provider shortages, geographic limitations, and cost has driven the area of mobile health (mHealth) care to address these access gaps. Reports from the Cohen Veterans Network and National Council for Behavioral Health show that in states where mental health care is more accessible, 38% of people still do not receive the care they need. mHealth strategies help to provide care to individuals experiencing these barriers at lower cost and greater convenience, making mHealth a great resource to bridge the gaps., Objective: We present a mixed methods study to evaluate user experiences with the mental mHealth service, Cope Notes. Specifically, we aimed to investigate the following research questions: How do users perceive the service in relation to stigma, impact of the intervention, and perceived usefulness? How do users rate the Cope Notes service and SMS text messaging along various dimensions of acceptability? What is the relationship between Cope Notes SMS text message ratings, user personality, and coping strategies? What are user perspectives of leveraging ubiquitous sensing technologies to improve delivery and provide tailored content?, Methods: We performed qualitative interviews with Cope Notes users (N=14) who have used the service for at least 30 days to evaluate their experiences and usefulness of the service. These interviews were coded by 2 raters (SLK and JL), and the interrater reliability was calculated with SPSS (IBM Corp) at 61.8%. In addition, participants completed quantitative measures, including a user experiences survey, personality inventory (Big Five Inventory-10), and coping assessment (Brief Coping Orientation to Problems Experienced)., Results: We derived 7 themes from our qualitative interviews: Likes or Perceived Benefits, Dislikes or Limitations, Suggested Changes, Stigma or Help Seeking, Perceptions of Ubiquitous Sensing, Cultural Sensitivity, and Alternative mHealth Resources. Exploratory analyses between acceptability ratings of Cope Notes and personality factors showed statistically significant positive relationships between seeing oneself as someone who is generally trusting and acceptability items, the most significant being item 7 (I fully understood the sentiment behind Cope Notes Messages) with (r s(10) =0.82, P=.001). We also found statistically significant relationships between acceptability and Brief Coping Orientation to Problems Experienced items, with the strongest positive correlation between participants strongly endorsing coping by accepting the reality that an event has happened and acceptability item 7 (r s(8) =0.86, P=.001)., Conclusions: Our study found that Cope Notes subscribers appreciate the service for reframing their mental wellness with statistically significant correlations between personality and acceptability of the service. We found that some users prefer a more personalized experience with neutral to positive reactions to a potential companion app that continuously monitors user behavior via smartphone sensors to provide just-in-time interventions when users need it most., (©Sayde Leya King, Jana Lebert, Lacey Anne Karpisek, Amelia Phillips, Tempestt Neal, Kristin Kosyluk. Originally published in JMIR Formative Research (https://formative.jmir.org), 03.05.2022.)

Understanding determinants of differential reproductive success is at the core of evolutionary biology because of its connection to fitness. Early work has linked variation in reproductive success to differences in age, 1 rank, 2 or size, 3 , 4 as well as habitat characteristics. 5 More recently, studies in group-living taxa have revealed that social relationships also have measurable effects on fitness. 6-8 The influence of social bonds on fitness is particularly interesting in males who compete over reproductive opportunities. In Shark Bay, Western Australia, groups of 4-14 unrelated male bottlenose dolphins cooperate in second-order alliances to compete with rival alliances over access to females. 9-12 Nested within second-order alliances, pairs or trios of males, which can vary in composition, form first-order alliances to herd estrus females. Using 30 years of behavioral data, we examined how individual social factors, such as first-order alliance stability, social connectivity, and variation in social bond strength within second-order alliances, affect male fitness. Analyzing the reproductive careers of 85 males belonging to 10 second-order alliances, we found that the number of paternities a male achieved was positively correlated with his cumulative social bond strength but negatively correlated with his variation in bond strength. Thus, well-integrated males with more homogeneous social bonds to second-order allies obtained most paternities. Our findings provide novel insights into the fitness benefits of polyadic cooperation among unrelated males and highlight the adaptive value of social bonds in this context., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Vocal interactions are intrinsic features of social groups and can play a pivotal role in social bonding. 1 , 2 Dunbar's social bonding hypothesis posits that vocal exchanges evolved to "groom at a distance" when social groups became too large or complex for individuals to devote time to physical bonding activities. 1 , 3 Tests of this hypothesis in non-human primates, however, suggest that vocal exchanges occur between more strongly bonded individuals that engage in higher grooming rates 4-7 and thus do not provide evidence for replacement of physical bonding. Here, we combine data on social bond strength, whistle exchange frequency, and affiliative contact behavior rates to test this hypothesis in wild male Indo-Pacific bottlenose dolphins, who form multi-level alliances that cooperate over access to females. 8-10 We show that, although whistle exchanges are more likely to occur within the core alliance, they occur more frequently between those males that share weaker social bonds, i.e., between core allies that spend less time together, while the opposite occurs for affiliative physical contact behavior. This suggests that vocal exchanges function as a low-cost mechanism for male dolphins that spend less time in close proximity and engage in fewer affiliative contact behaviors to reinforce and maintain their valuable alliance relationships. Our findings provide new evidence outside of the primate lineage that vocal exchanges serve a bonding function and reveal that, as the social bonding hypothesis originally suggested, vocal exchanges can function as a replacement of physical bonding activities for individuals to maintain their important social relationships., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)

In Shark Bay, Western Australia, male bottlenose dolphins form a complex nested alliance hierarchy. At the first level, pairs or trios of unrelated males cooperate to herd individual females. Multiple first-order alliances cooperate in teams (second-order alliances) in the pursuit and defence of females, and multiple teams also work together (third-order alliances). Yet it remains unknown how dolphins classify these nested alliance relationships. We use 30 years of behavioural data combined with 40 contemporary sound playback experiments to 14 allied males, recording responses with drone-mounted video and a hydrophone array. We show that males form a first-person social concept of cooperative team membership at the second-order alliance level, independently of first-order alliance history and current relationship strength across all three alliance levels. Such associative concepts develop through experience and likely played an important role in the cooperative behaviour of early humans. These results provide evidence that cooperation-based concepts are not unique to humans, occurring in other animal societies with extensive cooperation between non-kin.

Investigations into cooperative partner choice should consider both potential and realised partners, allowing for the comparison of traits across all those available. Male bottlenose dolphins form persisting multi-level alliances. Second-order alliances of 4-14 males are the core social unit, within which 2-3 males form first-order alliances to sequester females during consortships. We compared social bond strength, relatedness and age similarity of potential and realised partners of individual males in two age periods: (i) adolescence, when second-order alliances are formed from all available associates, and (ii) adulthood, when first-order allies are selected from within second-order alliances. Social bond strength during adolescence predicted second-order alliance membership in adulthood. Moreover, males preferred same-aged or older males as second-order allies. Within second-order alliances, non-mating season social bond strength predicted first-order partner preferences during mating season consortships. Relatedness did not influence partner choice on either alliance level. There is thus a striking resemblance between male dolphins, chimpanzees and humans, where closely bonded non-relatives engage in higher-level, polyadic cooperative acts. To that end, our study extends the scope of taxa in which social bonds rather than kinship explain cooperation, providing the first evidence that such traits might have evolved independently in marine and terrestrial realms.

Cooperation experiments have long been used to explore the cognition underlying animals' coordination towards a shared goal. While the ability to understand the need for a partner in a cooperative task has been demonstrated in a number of species, there has been far less focus on cooperation experiments that address the role of communication. In humans, cooperative efforts can be enhanced by physical synchrony, and coordination problems can be solved using spoken language. Indeed, human children adapt to complex coordination problems by communicating with vocal signals. Here, we investigate whether bottlenose dolphins can use vocal signals to coordinate their behaviour in a cooperative button-pressing task. The two dolphin dyads used in this study were significantly more likely to cooperate successfully when they used whistles prior to pressing their buttons, with whistling leading to shorter button press intervals and more successful trials. Whistle timing was important as the dolphins were significantly more likely to succeed if they pushed their buttons together after the last whistle, rather than pushing independently of whistle production. Bottlenose dolphins are well known for cooperating extensively in the wild, and while it remains to be seen how wild dolphins use communication to coordinate cooperation, our results reveal that at least some dolphins are capable of using vocal signals to facilitate the successful execution of coordinated, cooperative actions., (© 2021 The Authors.)

Reliable scientific knowledge is crucial for informing legislative, regulatory, and policy decisions in a variety of areas. To that end, scientific reviews of topical issues can be invaluable tools for informing productive discourse and decision-making, assuming these reviews represent the target body of scientific knowledge as completely, accurately, and objectively as possible. Unfortunately, not all reviews live up to this standard. As a case in point, Marino et al.'s [1] review regarding the welfare of killer whales in captivity contains methodological flaws and misrepresentations of the scientific literature, including problematic referencing, overinterpretation of the data, misleading word choice, and biased argumentation. These errors and misrepresentations undermine the authors' conclusions and make it impossible to determine the true state of knowledge of the relevant issues. To achieve the goal of properly informing public discourse and policy on this and other issues, it is imperative that scientists and science communicators strive for higher standards of analysis, argumentation, and objectivity, in order to clearly communicate what is known, what is not known, what conclusions are supported by the data, and where we are lacking the data necessary to draw reliable conclusions., Competing Interests: The authors declare no conflict of interest.

Synchronous displays are hallmarks of many animal societies, ranging from the pulsing flashes of fireflies, to military marching in humans. Such displays are known to facilitate mate attraction or signal relationship quality. Across many taxa, synchronous male displays appear to be driven by competition, while synchronous displays in humans are thought to be unique in that they serve a cooperative function. Indeed, it is well established that human synchrony promotes cooperative endeavours and increases success in joint action tasks. We examine another system in which synchrony is tightly linked to cooperative behaviour. Male bottlenose dolphins form long-lasting, multi-level, cooperative alliances in which they engage in coordinated efforts to coerce single oestrus females. Previous work has revealed the importance of motor synchrony in dolphin alliance behaviour. Here, we demonstrate that allied dolphins also engage in acoustic coordination whereby males will actively match the tempo and, in some cases, synchronize the production of their threat vocalization when coercing females. This finding demonstrates that male dolphins are capable of acoustic coordination in a cooperative context and, moreover, suggests that both motor and acoustic coordination are features of coalitionary behaviour that are not limited to humans.

Male alliances are an intriguing phenomenon in the context of reproduction since, in most taxa, males compete over an indivisible resource, female fertilization. Adult male bottlenose dolphins ( Tursiops aduncus ) in Shark Bay, Western Australia, form long-term, multilevel alliances to sequester estrus females. These alliances are therefore critical to male reproductive success. Yet, the long-term processes leading to the formation of such complex social bonds are still poorly understood. To identify the criteria by which male dolphins form social bonds with other males, we adopted a long-term approach by investigating the ontogeny of alliance formation. We followed the individual careers of 59 males for 14 years while they transitioned from adolescence (8-14 years of age) to adulthood (15-21 years old). Analyzing their genetic relationships and social associations in both age groups, we found that the vast majority of social bonds present in adolescence persisted through time. Male associations in early life predict alliance partners as adults. Kinship patterns explained associations during adolescence but not during adulthood. Instead, adult males associated with males of similar age. Our findings suggest that social bonds among peers, rather than kinship, play a central role in the development of adult male polyadic cooperation in dolphins., (© The Author(s) 2019. Published by Oxford University Press on behalf of the International Society for Behavioral Ecology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Carriers of the APOE e4 allele are at higher risk of age-related cognitive decline and Alzheimer's disease (AD). The underlying neural mechanisms are uncertain, but genotype differences in medial temporal lobe (MTL) functional activity and structure at mid-age might contribute. We tested 16 non-e4 and 16 e4 carriers (aged 45-55) on a subsequent memory task in conjunction with MRI to assess how hippocampal volume (from T1 structural) and microstructure (neurite orientation-dispersion, from NODDI) differs by genotype and in relation to memory encoding. No previous study has investigated APOE effects on hippocampal microstructure using NODDI. Recall performance did not differ by genotype. A genotype by condition interaction in left parahippocampus indicated that in e4 carriers activity did not differentiate subsequently remembered from forgotten words. Hippocampal volumes and microstructure also did not differ by genotype but hippocampal volumes correlated positively with recognition performance in non-e4 carriers only. Similarly, greater hippocampal neurite orientation-dispersion was linked to better recall but only in non-e4s. Thus, we suggest that mid-age e4 carriers show a breakdown of normal MTL activation and structure-performance relationships. This could reflect an inability to utilise compensatory mechanisms, and contribute to higher risk of cognitive decline and AD in later life.

Coercive mate guarding, where males use aggression to control female movements, is a form of sexual coercion which functions to constrain female mate choice. Non-human primates, for example, herd females to keep them away from competing males, but male bottlenose dolphins (Tursiops aduncus) also herd females to keep them close to their alliance partners. Indeed, pairs and trios of male dolphins work together to sequester single estrus females and defend them from competing alliances. Yet how males facilitate such coordination remains unknown. Here, we investigate the vocal behaviour of allied male bottlenose dolphins during the herding of individual females, examining how the production of whistles and 'pops' (a threat vocalisation) varied with behavioural state and inter-animal distances. Allied males produced both whistles and pops significantly more often and at higher rates during social interactions, though they differed in function. Whistle rates increased significantly when new individuals joined the consorting group, consistent with previous work showing that whistles are part of a greeting sequence for this species. Whistle matching also appeared to play a role in within-alliance coordination. Pop vocalisations increased significantly when the nearest male to the female changed, likely inducing the female to remain close as the males coordinate a guard switch. Building upon prior research examining female movements in response to pops, we show that males approach the female and current guard whilst popping, leading to a guard switch. Our results provide new insights into the use of vocal signals during cooperative mate guarding between allied male dolphins.

Complex carbohydrates serve a wide range of biological functions in cells and tissues, and their biosynthesis involves more than 200 distinct glycosyltransferases (GTfs) in human cells. The kinetic properties, cellular expression patterns and subcellular topology of the GTfs direct the glycosylation capacity of a cell. Most GTfs are ER or Golgi resident enzymes, and their specific subcellular localization is believed to be distributed in the secretory pathway according to their sequential role in the glycosylation process, although detailed knowledge for individual enzymes is still highly fragmented. Progress in quantitative transcriptome and proteome analyses has greatly advanced our understanding of the cellular expression of this class of enzymes, but availability of appropriate antibodies for in situ monitoring of expression and subcellular topology have generally been limited. We have previously used catalytically active GTfs produced as recombinant truncated secreted proteins in insect cells for generation of mouse monoclonal antibodies (mAbs) to human enzymes primarily involved in mucin-type O-glycosylation. These mAbs can be used to probe subcellular topology of active GTfs in cells and tissues as well as their presence in body fluids. Here, we present several new mAbs to human GTfs and provide a summary of our entire collection of mAbs, available to the community. Moreover, we present validation of specificity for many of our mAbs using human cell lines with CRISPR/Cas9 or zinc finger nuclease (ZFN) knockout and knockin of relevant GTfs., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Behavioural differences among social groups can arise from differing ecological conditions, genetic predispositions and/or social learning. In the past, social learning has typically been inferred as responsible for the spread of behaviour by the exclusion of ecological and genetic factors. This 'method of exclusion' was used to infer that 'sponging', a foraging behaviour involving tool use in the bottlenose dolphin (Tursiops aduncus) population in Shark Bay, Western Australia, was socially transmitted. However, previous studies were limited in that they never fully accounted for alternative factors, and that social learning, ecology and genetics are not mutually exclusive in causing behavioural variation. Here, we quantified the importance of social learning on the diffusion of sponging, for the first time explicitly accounting for ecological and genetic factors, using a multi-network version of 'network-based diffusion analysis'. Our results provide compelling support for previous findings that sponging is vertically socially transmitted from mother to (primarily female) offspring. This research illustrates the utility of social network analysis in elucidating the explanatory mechanisms behind the transmission of behaviour in wild animal populations.

Homophilous behaviour plays a central role in the formation of human friendships. Individuals form social ties with others that show similar phenotypic traits, independently of relatedness. Evidence of such homophily can be found in bottlenose dolphins ( Tursiops aduncus) in Shark Bay, Western Australia, where females that use marine sponges as foraging tools often associate with other females that use sponges. 'Sponging' is a socially learned, time-consuming behaviour, transmitted from mother to calf. Previous research illustrated a strong female bias in adopting this technique. The lower propensity for males to engage in sponging may be due to its incompatibility with adult male-specific behaviours, particularly the formation of multi-level alliances. However, the link between sponging and male behaviour has never been formally tested. Here, we show that male spongers associated significantly more often with other male spongers irrespective of their level of relatedness. Male spongers spent significantly more time foraging, and less time resting and travelling, than did male non-spongers. Interestingly, we found no difference in time spent socializing. Our study provides novel insights into the relationship between tool use and activity budgets of male dolphins, and indicates social homophily in the second-order alliance composition of tool-using bottlenose dolphins.

The current review summarizes the research to date on social functioning for youth with attention-deficit/hyperactivity disorder (ADHD) with a focus on three key domains: peer rejection, friendship, and social information processing. The review extends past reviews by examining the research to date on how the presence of sluggish cognitive tempo (SCT) symptoms, a common correlate of ADHD, affects the social presentation of youth with ADHD. Overall, youth with ADHD show significant difficulty with peer rejection, forming and maintaining friendships, and abnormalities in how they process and respond to social information. Further, the presence of SCT symptoms results in great social withdrawal and isolation. Future studies are needed to better understand the social difficulties of youth with ADHD, particularly using experimental approaches that can manipulate and isolate mechanisms within the social information processing model. In addition, novel intervention approaches are needed to more effectively ameliorate the social difficulties of youth with ADHD and those with co-occurring SCT symptoms.

Germinal centers (GC) are microanatomical niches where B cells proliferate, undergo antibody affinity maturation, and differentiate to long-lived memory B cells and antibody-secreting plasma cells. For decades, GC B cells have been defined by their reactivity to the plant lectin peanut agglutinin (PNA), which binds serine/threonine (O-linked) glycans containing the asialylated disaccharide Gal-β1,3-GalNAc-Ser/Thr (also called T-antigen). In T cells, acquisition of PNA binding by activated T cells and thymocytes has been linked with altered tissue homing patterns, cell signaling, and survival. Yet, in GC B cells, the glycobiological basis and significance of PNA binding remains surprisingly unresolved. Here, we investigated the basis for PNA reactivity of GC B cells. We found that GC B cell binding to PNA is associated with downregulation of the α2,3 sialyltransferase, ST3GAL1 (ST3Gal1), and overexpression of ST3Gal1 was sufficient to reverse PNA binding in B cell lines. Moreover, we found that the primary scaffold for PNA-reactive O-glycans in B cells is the B cell receptor-associated receptor-type tyrosine phosphatase CD45, suggesting a role for altered O-glycosylation in antigen receptor signaling. Consistent with similar reports in T cells, ST3Gal1 overexpression in B cells in vitro induced drastic shortening in O-glycans, which we confirmed by both antibody staining and mass spectrometric O-glycomic analysis. Unexpectedly, ST3Gal1-induced changes in O-glycan length also correlated with altered binding of two glycosylation-sensitive CD45 antibodies, RA3-6B2 (more commonly called B220) and MEM55, which (in humans) have previously been reported to favor binding to naïve/GC subsets and memory/plasmablast subsets, respectively. Analysis of primary B cell binding to B220, MEM55, and several plant lectins suggested that B cell differentiation is accompanied by significant loss of O-glycan complexity, including loss of extended Core 2 O-glycans. To our surprise, decreased O-glycan length from naïve to post-GC fates best correlated not with ST3Gal1, but rather downregulation of the Core 2 branching enzyme GCNT1. Thus, our data suggest that O-glycan remodeling is a feature of B cell differentiation, dually regulated by ST3Gal1 and GCNT1, that ultimately results in expression of distinct O-glycosylation states/CD45 glycoforms at each stage of B cell differentiation.

In recent decades, a number of studies have examined whether various non-human animals understand their partner's role in cooperative situations. Yet the relatively tolerant timing requirements of these tasks make it theoretically possible for animals to succeed by using simple behavioural strategies rather than by jointly intended coordination. Here we investigated whether bottlenose dolphins could understand a cooperative partner's role by testing whether they could learn a button-pressing task requiring precise behavioural synchronization. Specifically, members of cooperative dyads were required to swim across a lagoon and each press their own underwater button simultaneously (within a 1 s time window), whether sent together or with a delay between partners of 1-20 s. We found that dolphins were able to work together with extreme precision even when they had to wait for their partner, and that their coordination improved over the course of the study, with the time between button presses in the latter trials averaging 370 ms. These findings show that bottlenose dolphins can learn to understand their partner's role in a cooperative situation, and suggest that the behavioural synchronization evident in wild dolphins' synchronous movement and coordinated alliance displays may be a generalized cognitive ability that can also be used to solve novel cooperative tasks., (© 2018 The Authors.)

Cancer cells often display altered cell-surface glycans compared to their nontransformed counterparts. However, functional contributions of glycans to cancer initiation and progression remain poorly understood. Here, from expression-based analyses across cancer lineages, we found that melanomas exhibit significant transcriptional changes in glycosylation-related genes. This gene signature revealed that, compared to normal melanocytes, melanomas downregulate I-branching glycosyltransferase, GCNT2, leading to a loss of cell-surface I-branched glycans. We found that GCNT2 inversely correlated with clinical progression and that loss of GCNT2 increased melanoma xenograft growth, promoted colony formation, and enhanced cell survival. Conversely, overexpression of GCNT2 decreased melanoma xenograft growth, inhibited colony formation, and increased cell death. More focused analyses revealed reduced signaling responses of two representative glycoprotein families modified by GCNT2, insulin-like growth factor receptor and integrins. Overall, these studies reveal how subtle changes in glycan structure can regulate several malignancy-associated pathways and alter melanoma signaling, growth, and survival.

Leukocytes are coated with a layer of heterogeneous carbohydrates (glycans) that modulate immune function, in part by governing specific interactions with glycan-binding proteins (lectins). Although nearly all membrane proteins bear glycans, the identity and function of most of these sugars on leukocytes remain unexplored. Here, we characterize the N-glycan repertoire (N-glycome) of human tonsillar B cells. We observe that naive and memory B cells express an N-glycan repertoire conferring strong binding to the immunoregulatory lectin galectin-9 (Gal-9). Germinal center B cells, by contrast, show sharply diminished binding to Gal-9 due to upregulation of I-branched N-glycans, catalyzed by the β1,6-N-acetylglucosaminyltransferase GCNT2. Functionally, we find that Gal-9 is autologously produced by naive B cells, binds CD45, suppresses calcium signaling via a Lyn-CD22-SHP-1 dependent mechanism, and blunts B cell activation. Thus, our findings suggest Gal-9 intrinsically regulates B cell activation and may differentially modulate BCR signaling at steady state and within germinal centers.

Cooperation between allied individuals and groups is ubiquitous in human societies, and vocal communication is known to play a key role in facilitating such complex human behaviors [1, 2]. In fact, complex communication may be a feature of the kind of social cognition required for the formation of social alliances, facilitating both partner choice and the execution of coordinated behaviors [3]. As such, a compelling avenue for investigation is what role flexible communication systems play in the formation and maintenance of cooperative partnerships in other alliance-forming animals. Male bottlenose dolphins in some populations form complex multi-level alliances, where individuals cooperate in the pursuit and defense of an important resource: access to females [4]. These strong relationships can last for decades and are critical to each male's reproductive success [4]. Convergent vocal accommodation is used to signal social proximity to a partner or social group in many taxa [5, 6], and it has long been thought that allied male dolphins also converge onto a shared signal to broadcast alliance identity [5-8]. Here, we combine a decade of data on social interactions with dyadic relatedness estimates to show that male dolphins that form multi-level alliances in an open social network retain individual vocal labels that are distinct from those of their allies. Our results differ from earlier reports of signature whistle convergence among males that form stable alliance pairs. Instead, they suggest that individual vocal labels play a central role in the maintenance of differentiated relationships within complex nested alliances., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

In this study we investigated effects of the APOE ε4 allele (which confers an enhanced risk of poorer cognitive ageing, and Alzheimer's Disease) on sustained attention (vigilance) performance in young adults using the Rapid Visual Information Processing (RVIP) task and event-related fMRI. Previous fMRI work with this task has used block designs: this study is the first to image an extended (6-minute) RVIP task. Participants were 26 carriers of the APOE ε4 allele, and 26 non carriers (aged 18-28). Pupil diameter was measured throughout, as an index of cognitive effort. We compared activity to RVIP task hits to hits on a control task (with similar visual parameters and response requirements but no working memory load): this contrast showed activity in medial frontal, inferior and superior parietal, temporal and visual cortices, consistent with previous work, demonstrating that meaningful neural data can be extracted from the RVIP task over an extended interval and using an event-related design. Behavioural performance was not affected by genotype; however, a genotype by condition (experimental task/control task) interaction on pupil diameter suggested that ε4 carriers deployed more effort to the experimental compared to the control task. fMRI results showed a condition by genotype interaction in the right hippocampal formation: only ε4 carriers showed downregulation of this region to experimental task hits versus control task hits. Experimental task beta values were correlated against hit rate: parietal correlations were seen in ε4 carriers only, frontal correlations in non-carriers only. The data indicate that, in the absence of behavioural differences, young adult ε4 carriers already show a different linkage between functional brain activity and behaviour, as well as aberrant hippocampal recruitment patterns. This may have relevance for genotype differences in cognitive ageing trajectories., Competing Interests: The authors have declared that no competing interests exist.

Proteolytic processing is an irreversible post-translational modification functioning as a ubiquitous regulator of cellular activity. Protease activity is tightly regulated via control of gene expression, enzyme and substrate compartmentalization, zymogen activation, enzyme inactivation, and substrate availability. Emerging evidence suggests that proteolysis can also be regulated by substrate glycosylation and that glycosylation of individual sites on a substrate can decrease or, in rare cases, increase its sensitivity to proteolysis. Here, we investigated the relationship between site-specific, mucin-type (or GalNAc-type) O -glycosylation and proteolytic cleavage of extracellular proteins. Using in silico analysis, we found that O -glycosylation and cleavage sites are significantly associated with each other. We then used a positional proteomic strategy, terminal amine isotopic labeling of substrates (TAILS), to map the in vivo cleavage sites in HepG2 SimpleCells with and without one of the key initiating GalNAc transferases, GalNAc-T2, and after treatment with exogenous matrix metalloproteinase 9 (MMP9) or neutrophil elastase. Surprisingly, we found that loss of GalNAc-T2 not only increased cleavage, but also decreased cleavage across a broad range of other substrates, including key regulators of the protease network. We also found altered processing of several central regulators of lipid homeostasis, including apolipoprotein B and the phospholipid transfer protein, providing new clues to the previously reported link between GALNT2 and lipid homeostasis. In summary, we show that loss of GalNAc-T2 O -glycosylation leads to a general decrease in cleavage and that GalNAc-T2 O -glycosylation affects key regulators of the cellular proteolytic network, including multiple members of the serpin family., (© 2018 King et al.)

Background: Basal ganglia hemorrhage (BG-ICH) and thalamic hemorrhage (TH-ICH) have been historically grouped into a single "deep" hemorrhage group in prior studies. We aimed to assess whether BG-ICH and TH-ICH have different optimal hematoma volume cut points in predicting functional outcome., Methods: Patients with BG-ICH and TH-ICH with no preexisting disabilities who were enrolled in a single-center intracerebral hemorrhage (ICH) cohort study were studied. The hematoma volume of patients who achieved modified Rankin Scale (mRS) of ≤2 and ≤3 at 3 months were compared between BG-ICH and TH-ICH groups. Receiver operating characteristic (ROC) curves were created to determine the optimal hematoma volume cut points in predicting 3-month mRS of ≤2 and ≤3 for BG-ICH and TH-ICH groups., Results: A total of 135 (81 BG-ICH and 54 TH-ICH) patients were studied. The hematoma volume among those with 3-month mRS ≤ 2 (BG-ICH: 9.5 ± 5.4 cm 3 vs. TH-ICH: 5.1 ± 4.9 cm 3 , p  = 0.01) and 3-month mRS ≤ 3 (BG-ICH: 14.2 ± 13.4 cm 3 vs. TH-ICH: 4.7 ± 4.1 cm 3 , p  = 0.001) were smaller in TH-ICH than BG-ICH. The area under the ROC curve in predicting mRS ≤ 2 was 0.838 for BG-ICH (optimal hematoma volume cut point: 18.0 cm 3 , sensitivity 72.1%, specificity 95.0%) and 0.802 for TH-ICH (optimal hematoma volume cut point: 4.6 cm 3 , sensitivity 83.8%, specificity 70.6%); and in predicting mRS ≤ 3 was 0.826 for BG-ICH (optimal hematoma volume cut point: 28.8 cm 3 , sensitivity 71.4%, specificity 93.8%) and 0.902 for TH-ICH (optimal hematoma volume cut point: 5.5 cm 3 , sensitivity 92.9%, specificity 76.9%)., Conclusion: TH-ICH have smaller optimal hematoma volume cut points than BG-ICH in predicting functional outcome.

Background: Disparities in outcome after intracerebral hemorrhage (ICH) among Asians, Native Hawaiians, and other Pacific Islanders (NHOPI) have been inadequately studied. We sought to assess differences in functional outcome between Asians and NHOPI after ICH., Methods: A multiracial prospective cohort study of ICH patients was conducted from 2011 to 2016 at a tertiary center in Honolulu, HI, USA to assess racial disparities in outcome after ICH. Favorable outcome was defined as 3-month modified Rankin Scale (mRS) score ≤2. Patients with no available 3-month functional outcome, race other than Asians and NHOPI, and baseline mRS > 0 were excluded. Multivariable analyses using logistic regression were performed to assess the impact of race on favorable outcome after adjusting for the ICH Score, early do-not-resuscitate (DNR) order and dementia/cognitive impairment., Results: A total of 220 patients (161 Asians, 59 NHOPI) were studied. Overall, 65 (29.5%) achieved favorable outcome at 3 months. NHOPI were younger than Asians ( p  < 0.0001) and had higher prevalence of diabetes ( p  = 0.007), obesity ( p  < 0.0001), and lower prevalence of dementia/cognitive impairment ( p  = 0.02), early DNR order ( p  = 0.0004), and advance directive presence ( p  = 0.0005). NHOPI race was a predictor of favorable outcome in the unadjusted model [odds ratio (OR) 2.47, 95% confidence interval (CI): 1.32-4.62] and after adjusting for the ICH Score (OR 2.30, 95% CI: 1.06-4.97) but not in the final model (OR 2.04, 95% CI: 0.94-4.42). In the final model, the ICH Score was the only independent negative predictor of outcome (OR 0.26, 95% CI: 0.17-0.41 per point)., Conclusion: NHOPI are more likely to achieve favorable functional outcome after ICH compared with Asians even after controlling for ICH severity. However, this association was attenuated by the DNR and dementia/cognitive impairment status.

Sexual displays enriched by object carrying serve to increase individual male fitness, yet are uncommon phenomena in the animal kingdom. While they have been documented in a variety of taxa, primarily birds, they are rare outside non-human mammals. Here, we document marine sponge presenting associated with visual and acoustic posturing found in several, geographically widespread populations of Australian humpback dolphins (Sousa sahulensis) over ten years of observation. Only adult males presented marine sponges, typically doing so in the presence of sexually mature females, although social groups predominantly consisted of mixed age and sex classes. Male humpback dolphins appear to be using sponges for signalling purposes in multi-modal sexual displays. Further, based on limited behavioural and genetic data, we hypothesise that pairs of adult male Sousa form at least temporary coalitions or alliances. The use of objects in sexual displays by non-human mammals is rare and, moreover, cooperation between males in the pursuit of an indivisible resource is an evolutionary hurdle relatively few species have overcome. These findings suggest a hitherto unrecognised level of social complexity in humpback dolphins.

Homeostatic programs balance immune protection and self-tolerance. Such mechanisms likely impact autoimmunity and tumor formation, respectively. How homeostasis is maintained and impacts tumor surveillance is unknown. Here, we find that different immune mononuclear phagocytes share a conserved steady-state program during differentiation and entry into healthy tissue. IFNγ is necessary and sufficient to induce this program, revealing a key instructive role. Remarkably, homeostatic and IFNγ-dependent programs enrich across primary human tumors, including melanoma, and stratify survival. Single-cell RNA sequencing (RNA-seq) reveals enrichment of homeostatic modules in monocytes and DCs from human metastatic melanoma. Suppressor-of-cytokine-2 (SOCS2) protein, a conserved program transcript, is expressed by mononuclear phagocytes infiltrating primary melanoma and is induced by IFNγ. SOCS2 limits adaptive anti-tumoral immunity and DC-based priming of T cells in vivo, indicating a critical regulatory role. These findings link immune homeostasis to key determinants of anti-tumoral immunity and escape, revealing co-opting of tissue-specific immune development in the tumor microenvironment., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The hemostatic system comprises platelet aggregation, coagulation, and fibrinolysis, and is critical to the maintenance of vascular integrity. Multiple studies indicate that glycans play important roles in the hemostatic system; however, most investigations have focused on N -glycans because of the complexity of O -glycan analysis. Here we performed the first systematic analysis of native- O -glycosylation using lectin affinity chromatography coupled to liquid chromatography mass spectrometry (LC-MS)/MS to determine the precise location of O -glycans in human plasma, platelets, and endothelial cells, which coordinately regulate hemostasis. We identified the hitherto largest O -glycoproteome from native tissue with a total of 649 glycoproteins and 1123 nonambiguous O -glycosites, demonstrating that O -glycosylation is a ubiquitous modification of extracellular proteins. Investigation of the general properties of O -glycosylation established that it is a heterogeneous modification, frequently occurring at low density within disordered regions in a cell-dependent manner. Using an unbiased screen to identify associations between O -glycosites and protein annotations we found that O -glycans were over-represented close (± 15 amino acids) to tandem repeat regions, protease cleavage sites, within propeptides, and located on a select group of protein domains. The importance of O -glycosites in proximity to proteolytic cleavage sites was further supported by in vitro peptide assays demonstrating that proteolysis of key hemostatic proteins can be inhibited by the presence of O -glycans. Collectively, these data illustrate the global properties of native O -glycosylation and provide the requisite roadmap for future biomarker and structure-function studies., Competing Interests: Conflict-of-interest disclosure: The authors declare no competing financial interests.

Variations in genes encoding several GABA A receptors have been associated with human drug and alcohol abuse. Among these, a number of human studies have suggested an association between GABRB1 , the gene encoding GABA A receptor β1 subunits, with Alcohol dependence (AD), both on its own and comorbid with other substance dependence and psychiatric illnesses. In the present study, we hypothesized that the GABRB1 genetically-associated increased risk for developing alcoholism may be associated with impaired behavioral control and altered sensitivity to reward, as a consequence of altered brain function. Exploiting the IMAGEN database (Schumann et al., 2010), we explored in a human adolescent population whether possession of the minor (T) variant of the single nucleotide polymorphism (SNP) rs2044081 is associated with performance of tasks measuring aspects of impulsivity, and reward sensitivity that are implicated in drug and alcohol abuse. Allelic variation did not associate with altered performance in either a stop-signal task (SST), measuring one aspect of impulsivity, or a monetary incentive delay (MID) task assessing reward anticipation. However, increased functional magnetic resonance imaging (fMRI) blood-oxygen-level dependent (BOLD) response in the right hemisphere inferior frontal gyrus (IFG), left hemisphere caudate/insula and left hemisphere inferior temporal gyrus (ITG) during MID performance was higher in the minor (T) allelic group. In contrast, during SST performance, the BOLD response found in the right hemisphere supramarginal gyrus, right hemisphere lingual and left hemisphere inferior parietal gyrus indicated reduced responses in the minor genotype. We suggest that β1-containing GABA A receptors may play a role in excitability of brain regions important in controlling reward-related behavior, which may contribute to susceptibility to addictive behavior.