Search

Some people are exceptional at reading emotional expressions, while others struggle. Here we ask whether the way we experience emotion "on the inside" influences the way we expect emotions to be expressed in the "outside world" and subsequently our ability to read others' emotional expressions. Across multiple experiments, incorporating discovery and replication samples, we develop EmoMap (N = 20; N = 271) and ExpressionMap (N = 98; replication N = 193) to map adults' experiences of emotions and visual representations of others' emotions. Some individuals have modular maps, wherein emotional experiences and visual representations are consistent and distinct—anger looks and feels different from happiness, which looks and feels different from sadness. In contrast, others have experiences and representations that are variable and overlapping—anger, happiness, and sadness look and feel similar and are easily confused for one another. Here we illustrate an association between these maps: those with consistent and distinct experiences of emotion also have consistent and distinct visual representations of emotion. Finally (N = 193), we construct the Inside Out Model of Emotion Recognition, which explains 60.8% of the variance in emotion recognition and illuminates multiple pathways to emotion recognition difficulties. These findings have important implications for understanding the emotion recognition difficulties documented in numerous clinical populations. [ABSTRACT FROM AUTHOR]

To date, studies have not yet established the mechanisms underpinning differences in autistic and non-autistic emotion recognition. The current study first investigated whether autistic and non-autistic adults differed in terms of the precision and/or differentiation of their visual emotion representations and their general matching abilities, and second, explored whether differences therein were related to challenges in accurately recognizing emotional expressions. To fulfil these aims, 45 autistic and 45 non-autistic individuals completed three tasks employing dynamic point light displays of emotional facial expressions. We identified that autistic individuals had more precise visual emotion representations than their non-autistic counterparts, however, this did not confer any benefit for their emotion recognition. Whilst for non-autistic people, non-verbal reasoning and the interaction between precision of emotion representations and matching ability predicted emotion recognition, no variables contributed to autistic emotion recognition. These findings raise the possibility that autistic individuals are less guided by their emotion representations, thus lending support to Bayesian accounts of autism. [ABSTRACT FROM AUTHOR]

Bacterial Chondronecrosis with Osteomyelitis (BCO) is a specific cause of lameness in commercial fast-growing broiler (meat-type) chickens and represents significant economic, health, and wellbeing burdens. However, the molecular mechanisms underlying the pathogenesis remain poorly understood. This study represents the first comprehensive characterization of the proximal tibia proteome from healthy and BCO chickens. Among a total of 547 proteins identified, 222 were differentially expressed (DE) with 158 up- and 64 down-regulated proteins in tibia of BCO vs. normal chickens. Biological function analysis using Ingenuity Pathways showed that the DE proteins were associated with a variety of diseases including cell death, organismal injury, skeletal and muscular disorder, immunological and inflammatory diseases. Canonical pathway and protein–protein interaction network analysis indicated that these DE proteins were involved in stress response, unfolded protein response, ribosomal protein dysfunction, and actin cytoskeleton signaling. Further, we identified proteins involved in bone resorption (osteoclast-stimulating factor 1, OSFT1) and bone structural integrity (collagen alpha-2 (I) chain, COL2A1), as potential key proteins involved in bone attrition. These results provide new insights by identifying key protein candidates involved in BCO and will have significant impact in understanding BCO pathogenesis. [ABSTRACT FROM AUTHOR]

To date, studies have not established whether autistic and non-autistic individuals differ in emotion recognition from facial motion cues when matched in terms of alexithymia. Here, autistic and non-autistic adults (N = 60) matched on age, gender, non-verbal reasoning ability and alexithymia, completed an emotion recognition task, which employed dynamic point light displays of emotional facial expressions manipulated in terms of speed and spatial exaggeration. Autistic participants exhibited significantly lower accuracy for angry, but not happy or sad, facial motion with unmanipulated speed and spatial exaggeration. Autistic, and not alexithymic, traits were predictive of accuracy for angry facial motion with unmanipulated speed and spatial exaggeration. Alexithymic traits, in contrast, were predictive of the magnitude of both correct and incorrect emotion ratings. [ABSTRACT FROM AUTHOR]

Rationale: Brain catecholamines have long been implicated in reinforcement learning, exemplified by catecholamine drug and genetic effects on probabilistic reversal learning. However, the mechanisms underlying such effects are unclear. Objectives and methods: Here we investigated effects of an acute catecholamine challenge with methylphenidate (20 mg, oral) on a novel probabilistic reversal learning paradigm in a within-subject, double-blind randomised design. The paradigm was designed to disentangle effects on punishment avoidance from effects on reward perseveration. Given the known large individual variability in methylphenidate's effects, we stratified our effects by working memory capacity and trait impulsivity, putatively modulating the effects of methylphenidate, in a large sample (n = 102) of healthy volunteers. Results: Contrary to our prediction, methylphenidate did not alter performance in the reversal phase of the task. Our key finding is that methylphenidate altered learning of choice-outcome contingencies in a manner that depended on individual variability in working memory span. Specifically, methylphenidate improved performance by adaptively reducing the effective learning rate in participants with higher working memory capacity. Conclusions: This finding emphasises the important role of working memory in reinforcement learning, as reported in influential recent computational modelling and behavioural work, and highlights the dependence of this interplay on catecholaminergic function. [ABSTRACT FROM AUTHOR]

The ability to ascribe mental states, such as beliefs or desires to oneself and other individuals forms an integral part of everyday social interaction. Animations tasks, in which observers watch videos of interacting triangles, have been extensively used to test mental state attribution in a variety of clinical populations. Compared to control participants, individuals with clinical conditions such as autism typically offer less appropriate mental state descriptions of such videos. Recent research suggests that stimulus kinematics and movement similarity (between the video and the observer) may contribute to mental state attribution difficulties. Here we present a novel adaptation of the animations task, suitable to track and compare animation generator and -observer kinematics. Using this task and a population-derived stimulus database, we confirmed the hypotheses that an animation's jerk and jerk similarity between observer and animator significantly contribute to the correct identification of an animation. By employing random forest analysis to explore other stimulus characteristics, we reveal that other indices of movement similarity, including acceleration- and rotation-based similarity, also predict performance. Our results highlight the importance of movement similarity between observer and animator and raise new questions about reasons why some clinical populations exhibit difficulties with this task. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study is to determine whether a school-based program that allows middle school students to actively take responsibility of their learning can act as an effective intervention to promote stroke awareness and healthy lifestyle. Methods: Middle school students in grades 6, 7, and 8 (ages 11–14) were divided into small groups and participated in a series of interactive learning activities, centered on motivating middle school kids to learn and recognize signs and symptoms of stroke and to learn healthy lifestyle choices. Results: A total of 127 sixth, 113 seventh, and 98 eighth grade students participated in the intervention program. ANOVA found a significant difference in the baseline knowledge of all stroke and healthy life parameters evaluated in the pre-and post-intervention between the 6th, 7th, and 8th grades. Post-hoc analysis revealed a significant change in the performance (P < 0.001) from pre to the post-intervention for all grade levels. Conclusions: A school-based intervention program that allows middle school students to actively learn how to recognize the signs of a stroke and to identify healthy lifestyle choices can significantly change knowledge from baseline and act as an effective tool to promote stroke and healthy lifestyle education. [ABSTRACT FROM AUTHOR]

A subset of colorectal cancer (CRC) cases are attributable to Lynch syndrome (LS), a hereditary form of CRC. Effective evaluation for LS can be done on CRC tumors to guide diagnostic testing. Increased diagnosis of LS allows for surveillance and risk reduction, which can mitigate CRC-related burden and prevent cancer-related deaths. We evaluated participation in LS screening among newly diagnosed adult CRC patients. Some cases were referred for genetics evaluation prior to study recruitment (selective screening). Those not referred directly were randomized to the intervention or control (usual care) arms. Control cases were observed for one year, then given information about LS screening. Patients who declined participation were followed through the medical record. Of 601 cases of CRC, 194 (32%) enrolled in our study and were offered LS screening, 43 (7%) were followed as a control group, 148 (25%) declined participation and 216 (36%) were ineligible [63 (10%) of which received prior selective screening]. Six and nine cases of LS were identified through the intervention and selective screening groups, respectively. Overall, a higher proportion of PMS2 variants were identified in the intervention (3/6, 50%) versus selective screening groups (2/9, 22%) (not statistically significant). Eighty-eight percent and 23% of intervention and control patients, respectively, received LS screening. No control patients were found to have LS. Systems-based approaches are needed to ensure we fully identify LS cases. The proportion of LS cases from this program was 4% of newly diagnosed cases of CRC, similar to other programs. [ABSTRACT FROM AUTHOR]

Purpose of Review: Heart failure is a complex and expensive disease that represents an increasing burden to the healthcare system. Regulatory changes that affect payments for inpatient care have influenced the way we practice medicine. Recent Findings: Hospitals have struggled to employ strategies to improve publically reported metrics. Resources are available yet there is no clear recommendation on best practice. There is a debate whether the 30-day readmission metric represents favorable patient outcomes. Summary: There will be continued debate on how to best define quality for heart failure care; provider engagement is necessary as pressures on healthcare value will certainly remain. [ABSTRACT FROM AUTHOR]

Universal screening for Lynch syndrome (LS) among all cases of colorectal cancer (CRC) could increase the diagnosis of LS and reduce morbidity and mortality of LS-associated cancers. Given universal screening includes all patients, irrespective of high risk factors such early age at onset or family history of CRC, it is important to understand perspectives of all patients and not just those at high risk. As part of a study to assess the feasibility and implementation of universal screening, 189 patients newly diagnosed with CRC were surveyed about their interest in screening for LS and communication of results with at-risk family members. Overall, participants responded positively regarding screening for LS, with most wanting to know their genetic risks in general (86%) and risk of hereditary CRC (93%). Prior to receiving screening results, most participants stated they intended to share their screening results with parents (89%), siblings (96%), and children (96%). Of the 28 participants who received a positive LS screening result, 26 (93%) reported sharing their result with at least one first-degree family member. Interest in screening for LS and communication of screening results with family members was not associated with high risk factors. This study indicates that patients are interested in being screened for LS and that sharing information on the risk of LS with at-risk family members is not a significant barrier. These findings provide novel insight into patient perspectives about screening for LS and can guide successful implementation of universal screening programs. [ABSTRACT FROM AUTHOR]

The efficiency of drug research and development has paradoxically declined over the last decades despite major scientific and technological advances, promoting new cost-effective strategies such as drug repositioning by systematic screening for new actions of known drugs. Here, we performed a screening for positive allosteric modulators (PAMs) at melanocortin (MC) receptors. The non-steroidal anti-inflammatory drug fenoprofen, but not the similar compound ibuprofen, presented PAM activity at MC, MC, and MC receptors. In a model of inflammatory arthritis, fenoprofen afforded potent inhibition while ibuprofen was nearly inactive. Fenoprofen presented anti-arthritic actions on cartilage integrity and synovitis, effects markedly attenuated in Mc3r−/− mice. Fenoprofen displayed pro-resolving properties promoting macrophage phagocytosis and efferocytosis, independently of cyclooxygenase inhibition. In conclusion, combining repositioning with advances in G-protein coupled receptor biology ( allosterism) may lead to potential new therapeutics. In addition, MC PAMs emerged as a viable approach to the development of innovative therapeutics for joint diseases. [ABSTRACT FROM AUTHOR]

Master transcription factors interact with DNA to establish cell type identity and to regulate gene expression in mammalian cells. The genome-wide map of these transcription factor binding sites has been termed the cistrome. Here we show that the androgen receptor (AR) cistrome undergoes extensive reprogramming during prostate epithelial transformation in man. Using human prostate tissue, we observed a core set of AR binding sites that are consistently reprogrammed in tumors. FOXA1 and HOXB13 colocalized at the reprogrammed AR binding sites in human tumor tissue. Introduction of FOXA1 and HOXB13 into an immortalized prostate cell line reprogrammed the AR cistrome to resemble that of a prostate tumor, functionally linking these specific factors to AR cistrome reprogramming. These findings offer mechanistic insights into a key set of events that drive normal prostate epithelium toward transformation and establish the centrality of epigenetic reprogramming in human prostate tumorigenesis. [ABSTRACT FROM AUTHOR]

Trastuzumab is effective in the treatment of HER2/neu over-expressing breast cancer, but not all patients benefit from it. In vitro data suggest a role for HER3 in the initiation of signaling activity involving the AKT-mTOR pathway leading to trastuzumab insensitivity. We sought to investigate the potential of HER3 alone and in the context of p95HER2 (p95), a trastuzumab resistance marker, as biomarkers of trastuzumab escape. Using the VeraTag assay platform, we developed a dual antibody proximity-based assay for the precise quantitation of HER3 total protein (H3T) from formalin-fixed paraffin-embedded (FFPE) breast tumors. We then measured H3T in 89 patients with metastatic breast cancer treated with trastuzumab-based therapy, and correlated the results with progression-free survival and overall survival using Kaplan-Meier and decision tree analyses that also included HER2 total (H2T) and p95 expression levels. Within the sub-population of patients that over-expressed HER2, high levels of HER3 and/or p95 protein expression were significantly associated with poor clinical outcomes on trastuzumab-based therapy. Based on quantitative H3T, p95, and H2T measurements, multiple subtypes of HER2-positive breast cancer were identified that differ in their outcome following trastuzumab therapy. These data suggest that HER3 and p95 are informative biomarkers of clinical outcomes on trastuzumab therapy, and that multiple subtypes of HER2-positive breast cancer may be defined by quantitative measurements of H3T, p95, and H2T. [ABSTRACT FROM AUTHOR]

Appropriate modulation of imitation according to social context is important for successful social interaction. In the present study we subliminally primed high-functioning adults with ASC and age- and IQ-matched controls with either a pro- or non- social attitude. Following priming, an automatic imitation paradigm was used to acquire an index of imitation. Whereas imitation levels were higher for pro-socially primed relative to non-socially primed control participants, there was no difference between pro- and non- socially primed individuals with ASC. We conclude that high-functioning adults with ASC demonstrate atypical social modulation of imitation. Given the importance of imitation in social interaction we speculate that difficulties with the modulation of imitation may contribute to the social problems characteristic of ASC. [ABSTRACT FROM AUTHOR]

Previous studies have demonstrated a bidirectional relationship between social attitudes and imitation in adults: pro-social attitudes promote imitation, and imitation further increases positive social attitudes. Social attitudes and the social brain are developing throughout the adolescent years. Thus, the aim of this study was to test whether pro-social attitudes promote imitation in an Adolescent Group to the same extent as in an Adult Group. Participants were primed with pro-social or non-social words in a Scrambled Sentence Priming task. They then completed an Imitation task wherein participants were required to perform a lift action with either the index or middle finger, whilst observing either a compatible action (e.g. index finger response and observed index finger lift) or an incompatible action (e.g. index finger response and observed middle finger lift). In an Effector Priming control condition, observed fingers remained stationary but a semi-transparent green mask was added to either the compatible or incompatible finger. The magnitude of the Imitation Effect and Effector Priming Effect was calculated by subtracting reaction times on compatible trials from those on incompatible trials. In the Adult Group, social priming specifically modulated the Imitation Effect: pro-social priming produced a larger Imitation Effect but did not modulate the Effector Priming Effect. In adolescents, however, no effect of social priming was seen on either the Imitation or Effector Priming measures. We consider possible explanations for these results including the immature development of social brain regions and reduced experience of the relationship between social attitudes and imitation in adolescence. [ABSTRACT FROM AUTHOR]

Continued gambling to recover losses-'loss chasing'-is a prominent feature of social and pathological gambling. However, little is known about the neuromodulators that influence this behavior. In three separate experiments, we investigated the role of serotonin activity, D2/D3 receptor activity, and beta-adrenoceptor activity on the loss chasing of age and IQ-matched healthy adults randomized to treatment or an appropriate control/placebo. In Experiment 1, participants consumed amino-acid drinks that did or did not contain the serotonin precursor, tryptophan. In Experiment 2, participants received a single 176 μg dose of the D2/D3 receptor agonist, pramipexole, or placebo. In Experiment 3, participants received a single 80 mg dose of the beta-adrenoceptor blocker, propranolol, or placebo. Following treatment, participants completed a computerized loss-chasing game. Mood and heart rate were measured at baseline and following treatment. Tryptophan depletion significantly reduced the number of decisions made to chase losses, and the number of consecutive decisions to chase, in the absence of marked changes in mood. By contrast, pramipexole significantly increased the value of losses chased and diminished the value of losses surrendered. Propranolol markedly reduced heart rate, but produced no significant changes in loss-chasing behavior. Loss chasing can be thought of as an aversively motivated escape behavior controlled, in part, by the marginal value of continued gambling relative to the value of already accumulated losses. Serotonin and dopamine appear to play dissociable roles in the tendency of individuals to gamble to recover, or to seek to 'escape' from, previous losses. Serotonergic activity seems to promote the availability of loss chasing as a behavioral option, whereas D2/D3 receptor activity produces complex changes in the value of losses judged worth chasing. Sympathetic arousal, at least as mediated by beta-adrenoceptors, does not play a major role in laboratory-based loss-chasing choices. [ABSTRACT FROM AUTHOR]

Epidemiological and experimental animal studies have shown that exposure to xenoestrogens during reproductive tract development reprograms target tissues, leading to increased disease risk later in adult life. To understand what defines the critical risk period for this effect, termed developmental programming, the authors assess the sensitivity of the female reproductive tract to developmental programming during various stages of neonatal development. Eker rats, which are predisposed to develop uterine leiomyoma because of a germ-line defect in the tuberous sclerosis complex 2 (Tsc-2) tumor suppressor gene, were exposed to the xenoestrogen diethylstilbestrol (DES) on either posnatal days 3 to 5, 10 to 12, or 17 to 19, 3 important periods of reproductive tract development and differentiation. Developmental programming was observed in both carrier (Tsc-2ek/+) and wild-type (Tsc-2+/+) rats exposed to DES at days 3 to 5 and days 10 to 12 but not in rats exposed at days 17 to 19. Developmental programming resulted in increased tumor suppressor gene penetrance in Tsc-2Ek/+ females relative to vehicle controls. In contrast, DES exposure at days 17 to 19 did not significantly increase the incidence of uterine leiomyoma in carrier females, indicating that the window of susceptibility had closed by this time. Gene expression analysis to determine what defined the susceptible (days 3-5 and days 10-12) versus resistant (days 17-19) periods revealed that in adult myometrium, expression of the estrogen-responsive genes calbindin D9K and progesterone receptor had been reprogrammed in females exposed to DES at days 3 to 5 and days 10 to 12 but not in those exposed at days 17 to 19. Reprogramming in response to DES exposure resulted in a hyperresponsiveness to ovarian hormones and could be prevented by ovariectomy prior to sexual maturity. Furthermore, in the neonatal uterus, DES was equally effective at inducing transcription of estrogen-responsive genes during both sensitive and resistant periods, indicating that resistance to developmental programming was not due to an inability of the estrogen receptor to transactivate gene expression. Interestingly, the resistant period coincided with the time at which reproductive tract tissues are exposed to endogenous estrogen, suggesting that target tissues are most vulnerable to developmental programming during the period in which they would normally be maintained in an estrogen-naïve state. [ABSTRACT FROM AUTHOR]

The severe combined immunodeficient (SCID) mouse model of human immunodeficiency virus (HIV) encephalitis exhibits many of the histopathological and pathophysiological features of human HIV-associated dementia (HAD). Although deficits that may resemble HAD in humans have been reported for HIV-infected SCID mice, the cognitive deficit aspect of the model has very limited empirical support. Here, the authors report that HIV-infected SCID mice display cognitive deficits on a task requiring the animal to learn and remember the spatial relationship of cues in its environment in order to locate a submerged platform in a Morris water maze. The cognitive deficits manifest as longer latencies to locate the platform on the last day of the maze acquisition period and during a retention test 8 days later. Control experiments indicated that the poor performance by HIV-infected mice in comparison to controls was not due to impaired motor function or swimming ability, impaired visual acuity, or increased susceptibility to fatigue. Thus, the increased times required for HIV-infected mice to locate the submerged platform during the acquisition and memory tests likely reflect a cognitive deficit, rather than sensorimotor or emotional abnormalities. These behavioral deficits are associated with significant increases in astrogliosis and microgliosis in the HIV-infected mice. The results of this study strengthen the SCID mouse model of HIV encephalitis by definitively establishing cognitive deficits for the model in addition to its previously reported neuropathological features. [ABSTRACT FROM AUTHOR]

CATECHOLLISION is an arcade-style computer game that teaches catecholamine synthesis. Tyrosine and the enzymes involved in the synthesis fall from the top of the screen. The player must combine them to produce DOPA and the catecholamines. An accumulation of unused chemicals ends the game. The game includes features such as music and sound effects, several levels of difficulty, a hint option for beginning students, and saved high scores. [ABSTRACT FROM AUTHOR]