Form-function relationships underlie rapid dietary changes in a lizard.

Macroevolutionary changes such as variation in habitat use or diet are often associated with convergent, adaptive changes in morphology. However, it is still unclear how small-scale morphological variation at the population level can drive shifts in ecology such as observed at a macroevolutionary scale. Here, we address this question by investigating how variation in cranial form and feeding mechanics relate to rapid changes in diet in an insular lizard (Podarcis siculus) after experimental introduction into a new environment. We first quantified differences in the skull shape and jaw muscle architecture between the source and introduced population using three-dimensional geometric morphometrics and dissections. Next, we tested the impact of the observed variation in morphology on the mechanical performance of the masticatory system using computer-based biomechanical simulation techniques. Our results show that small differences in shape, combined with variation in muscle architecture, can result in significant differences in performance allowing access to novel trophic resources. The confrontation of these data with the already described macroevolutionary relationships between cranial form and function in these insular lizards provides insights into how selection can, over relatively short time scales, drive major changes in ecology through its impact on mechanical performance.

Investigating habits in humans with a symmetrical outcome-revaluation task.

The translation of the outcome-devaluation paradigm to study habit in humans has yielded interesting insights but proven to be challenging. We present a novel, outcome-revaluation task with a symmetrical design, in the sense that half of the available outcomes are always valuable and the other half not-valuable. In the present studies, during the instrumental learning phase, participants learned to respond (Go) to certain stimuli to collect valuable outcomes (and points) while refraining to respond (NoGo) to stimuli signaling not-valuable outcomes. Half of the stimuli were short-trained, while the other half were long-trained. Subsequently, in the test phase, the signaled outcomes were either value-congruent with training (still-valuable and still-not-valuable), or value-incongruent (devalued and upvalued). The change in outcome value on value-incongruent trials meant that participants had to flexibly adjust their behavior. At the end of the training phase, participants completed the self-report behavioral automaticity index - providing an automaticity score for each stimulus-response association. We conducted two experiments using this task, that both provided evidence for stimulus-driven habits as reflected in poorer performance on devalued and upvalued trials relative to still-not-valuable trials and still-valuable trials, respectively. While self-reported automaticity increased with longer training, behavioral flexibility was not affected. After extended training (Experiment 2), higher levels of self-reported automaticity when responding to stimuli signaling valuable outcomes were related to more 'slips of action' when the associated outcome was subsequently devalued. We conclude that the symmetrical outcome-revaluation task provides a promising paradigm for the experimental investigation of habits in humans.

New Synthetic Lethality Re-Sensitizing Platinum-Refractory Cancer Cells to Cisplatin In Vitro: The Rationale to Co-Use PARP and ATM Inhibitors.

The pro-apoptotic tumor suppressor BIN1 inhibits the activities of the neoplastic transcription factor MYC, poly (ADP-ribose) polymerase-1 (PARP1), and ATM Ser/Thr kinase (ATM) by separate mechanisms. Although BIN1 deficits increase cancer-cell resistance to DNA-damaging chemotherapeutics, such as cisplatin, it is not fully understood when BIN1 deficiency occurs and how it provokes cisplatin resistance. Here, we report that the coordinated actions of MYC, PARP1, and ATM assist cancer cells in acquiring cisplatin resistance by BIN1 deficits. Forced BIN1 depletion compromised cisplatin sensitivity irrespective of Ser15-phosphorylated, pro-apoptotic TP53 tumor suppressor. The BIN1 deficit facilitated ATM to phosphorylate the DNA-damage-response (DDR) effectors, including MDC1. Consequently, another DDR protein, RNF8, bound to ATM-phosphorylated MDC1 and protected MDC1 from caspase-3-dependent proteolytic cleavage to hinder cisplatin sensitivity. Of note, long-term and repeated exposure to cisplatin naturally recapitulated the BIN1 loss and accompanying RNF8-dependent cisplatin resistance. Simultaneously, endogenous MYC was remarkably activated by PARP1, thereby repressing the BIN1 promoter, whereas PARP inhibition abolished the hyperactivated MYC-dependent BIN1 suppression and restored cisplatin sensitivity. Since the BIN1 gene rarely mutates in human cancers, our results suggest that simultaneous inhibition of PARP1 and ATM provokes a new BRCAness-independent synthetic lethal effect and ultimately re-establishes cisplatin sensitivity even in platinum-refractory cancer cells.

Recollections of Childhood Sexual Abuse: Complexities of Religious Coping and Muslim Religious and Psychological Adjustment in Afghanistan.

Religious coping is a double-edged sword. Clarification of the psychological benefits for positive religious coping requires statistical controls for negative religious coping and vice versa. This study sought to further explore the complexities of Muslim religious coping by extending the analysis to Afghans who coped with the sufferings associated with recollections of childhood and adolescent sexual abuse. Two hundred Dari Persian-speaking Afghan university students (122 identified having experience of childhood sexual abuse) self-reported on variables that measure religious orientation, religious coping, Muslim experiential religiousness, mental health, and child abuse. Results showed that negative religious coping interfered with the possibly beneficial effects of positive religious coping on mental health and child abuse. After controlling for negative religious coping, the associations of positive religious coping became obvious. In addition, Muslim spirituality moderated the associations of religious coping with mental health outcomes and child abuse: for people with higher Muslim spirituality, positive religious coping associated with better mental health, and negative religious coping associated with less child abuse. Implications for religious coping and combating trauma in a religious context are discussed.

Loss of the tumor suppressor BIN1 enables ATM Ser/Thr kinase activation by the nuclear protein E2F1 and renders cancer cells resistant to cisplatin.

The tumor suppressor bridging integrator 1 (BIN1) is a corepressor of the transcription factor E2F1 and inhibits cell-cycle progression. BIN1 also curbs cellular poly(ADP-ribosyl)ation (PARylation) and increases sensitivity of cancer cells to DNA-damaging therapeutic agents such as cisplatin. However, how BIN1 deficiency, a hallmark of advanced cancer cells, increases cisplatin resistance remains elusive. Here, we report that BIN1 inactivates ataxia telangiectasia-mutated (ATM) serine/threonine kinase, particularly when BIN1 binds E2F1. BIN1 + 12A (a cancer-associated BIN1 splicing variant) also inhibited cellular PARylation, but only BIN1 increased cisplatin sensitivity. BIN1 prevented E2F1 from transcriptionally activating the human ATM promoter, whereas BIN1 + 12A did not physically interact with E2F1. Conversely, BIN1 loss significantly increased E2F1-dependent formation of MRE11A/RAD50/NBS1 DNA end-binding protein complex and efficiently promoted ATM autophosphorylation. Even in the absence of dsDNA breaks (DSBs), BIN1 loss promoted ATM-dependent phosphorylation of histone H2A family member X (forming γH2AX, a DSB biomarker) and mediator of DNA damage checkpoint 1 (MDC1, a γH2AX-binding adaptor protein for DSB repair). Of note, even in the presence of transcriptionally active (i.e. proapoptotic) TP53 tumor suppressor, BIN1 loss generally increased cisplatin resistance, which was conversely alleviated by ATM inactivation or E2F1 reduction. However, E2F2 or E2F3 depletion did not recapitulate the cisplatin sensitivity elicited by E2F1 elimination. Our study unveils an E2F1-specific signaling circuit that constitutively activates ATM and provokes cisplatin resistance in BIN1-deficient cancer cells and further reveals that γH2AX emergence may not always reflect DSBs if BIN1 is absent.

Amanah and Muslim Identity: Relationships with Religious and Psychological Adjustment in Malaysia.

Amanah refers to the accountability of Muslims to their community. In Malaysian Muslim university students (N = 209), an Amanah Scale predicted a stronger sense of identity along with more adaptive religious and psychosocial functioning. Multiple regression analyses identified Accountability to Society as especially influential, but Accountability to Allah exhibited at least some problematic implications. Amanah mediated Identity linkages with some measures of religious and psychological adjustment, but also suppressed Identity relationships with greater self-knowledge and lower anxiety. These data confirmed the importance of communal commitments in Muslim mental health, suggested that accountability may have limited liabilities as well as more obvious psychosocial advantages, and identified possible complexities in the assessment of Accountability to Allah.

Preventing intrusive memories after trauma via a brief intervention involving Tetris computer game play in the emergency department: a proof-of-concept randomized controlled trial.

After psychological trauma, recurrent intrusive visual memories may be distressing and disruptive. Preventive interventions post trauma are lacking. Here we test a behavioural intervention after real-life trauma derived from cognitive neuroscience. We hypothesized that intrusive memories would be significantly reduced in number by an intervention involving a computer game with high visuospatial demands (Tetris), via disrupting consolidation of sensory elements of trauma memory. The Tetris-based intervention (trauma memory reminder cue plus c. 20 min game play) vs attention-placebo control (written activity log for same duration) were both delivered in an emergency department within 6 h of a motor vehicle accident. The randomized controlled trial compared the impact on the number of intrusive trauma memories in the subsequent week (primary outcome). Results vindicated the efficacy of the Tetris-based intervention compared with the control condition: there were fewer intrusive memories overall, and time-series analyses showed that intrusion incidence declined more quickly. There were convergent findings on a measure of clinical post-trauma intrusion symptoms at 1 week, but not on other symptom clusters or at 1 month. Results of this proof-of-concept study suggest that a larger trial, powered to detect differences at 1 month, is warranted. Participants found the intervention easy, helpful and minimally distressing. By translating emerging neuroscientific insights and experimental research into the real world, we offer a promising new low-intensity psychiatric intervention that could prevent debilitating intrusive memories following trauma.

Factors influencing patient uptake of an exercise referral scheme: a qualitative study.

Exercise referral schemes aim to increase physical activity amongst inactive individuals with or at risk of long-term health conditions. Yet many patients referred to these schemes (by health professionals) fail to take up the exercise opportunities on offer. Understanding factors influencing uptake to exercise referral schemes may help improve future attendance. Using the Socio-Ecological Model as a framework, this qualitative study aimed to explore factors influencing uptake to an exercise referral scheme based in the North West of England. Semi-structured interviews were conducted with referred patients (n = 38) about their reasons for referral, interactions with referring health professionals, events following referral and ideas to improve future uptake. Data were analysed thematically and mapped onto the constructs of the Socio-Ecological Model. Factors reported to influence uptake included intrapersonal (past PA experiences, motivation, competing priorities), interpersonal (scheme explanations, support) and organizational influences (scheme promotion, communication between service, cost). Whilst several intrapersonal-level factors influenced patient decisions to uptake the exercise referral scheme, modifiable interpersonal and organizational factors were identified as potential targets for intervention. Recommendations are made for improving awareness of exercise referral schemes and for enhancing communication between referring practitioners, patients and referral scheme staff.

A biomechanical analysis of prognathous and orthognathous insect head capsules: evidence for a many-to-one mapping of form to function.

Insect head shapes are remarkably variable, but the influences of these changes on biomechanical performance are unclear. Among 'basal' winged insects, such as dragonflies, mayflies, earwigs and stoneflies, some of the most prominent anatomical changes are the general mouthpart orientation, eye size and the connection of the endoskeleton to the head. Here, we assess these variations as well as differing ridge and sclerite configurations using modern engineering methods including multibody dynamics modelling and finite element analysis in order to quantify and compare the influence of anatomical changes on strain in particular head regions and the whole head. We show that a range of peculiar structures such as the genal/subgenal, epistomal and circumocular areas are consistently highly loaded in all species, despite drastically differing morphologies in species with forward-projecting (prognathous) and downward-projecting (orthognathous) mouthparts. Sensitivity analyses show that the presence of eyes has a negligible influence on head capsule strain if a circumocular ridge is present. In contrast, the connection of the dorsal endoskeletal arms to the head capsule especially affects overall head loading in species with downward-projecting mouthparts. Analysis of the relative strains between species for each head region reveals that concerted changes in head substructures such as the subgenal area, the endoskeleton and the epistomal area lead to a consistent relative loading for the whole head capsule and vulnerable structures such as the eyes. It appears that biting-chewing loads are managed by a system of strengthening ridges on the head capsule irrespective of the general mouthpart and head orientation. Concerted changes in ridge and endoskeleton configuration might allow for more radical anatomical changes such as the general mouthpart orientation, which could be an explanation for the variability of this trait among insects. In an evolutionary context, many-to-one mapping of strain patterns onto a relatively similar overall head loading indeed could have fostered the dynamic diversification processes seen in insects.

Making a move in exercise referral: co-development of a physical activity referral scheme.

Background: Translational research is required to ensure exercise referral schemes (ERSs) are evidence-based and reflect local needs. This article reports process data from the co-development phase of an ERS, providing an insight into (i) factors that must be considered when translating evidence to practice in an ERS setting, and (ii) challenges and facilitators of conducting participatory research involving multiple stakeholders. Methods: An ERS was iteratively co-developed by a multidisciplinary stakeholder group (commissioners, managers, practitioners, patients and academics) via five participatory meetings and an online survey. Audio data (e.g. group discussions) and visual data (e.g. whiteboard notes) were recorded and analysed using NVivo-10 electronic software. Results: Factors to consider when translating evidence to practice in an ERS setting included (i) current ERS culture; (ii) skills, safety and accountability; and (iii) resources and capacity. The co-development process was facilitated by needs-analysis, open questions, multidisciplinary debate and reflective practice. Challenges included contrasting views, irregular attendance and (mis)perceptions of evaluation. Conclusion: The multidisciplinary co-development process highlighted cultural and pragmatic issues related to exercise referral provision, resulting in an evidence-based intervention framework designed to be implemented within existing infrastructures. Further work is required to establish the feasibility and effectiveness of the co-developed intervention in practice.

Surgery alters parameters of vitamin D status and other laboratory results.

Fracture liaison services often perform laboratory testing, but these results may be altered by surgery. In 40 hip arthroplasty patients, many laboratory parameters of bone health relevance were reduced by 8-22% on the first post-operative day. Laboratory results obtained in the immediate post-surgery interval do not reliably ascertain baseline status. INTRODUCTION: As secondary causes of osteoporosis are common, fracture liaison services often perform laboratory testing in the immediate post-fracture interval. We hypothesized that laboratory results obtained shortly after surgery may not accurately ascertain baseline status. If true, such alterations might confound subsequent fracture prevention efforts. METHODS: Patients undergoing elective total hip arthroplasty were studied as a surrogate for hip fracture patients. Blood and urine were obtained 2 weeks before surgery, before anesthetic induction, on post-operative day one, and 6 weeks after surgery. Serum total and free 25-hydroxyvitamin D (25(OH)D), vitamin D-binding protein (DBP), calcium, creatinine, albumin (Alb), alkaline phosphatase (ALP), plasma hemoglobin (Hgb) and urinary DBP/creatinine ratio (UDBP/Cr) were measured. RESULTS: Forty volunteers (28 women; 12 men) with mean age of 65.7 [8.7] years were studied. Laboratory results were stable from 2 weeks before to the day of surgery. On the first day after surgery, total 25(OH)D, DBP, calcium, creatinine, ALP, and Alb declined 8-22% (p < 0.0001); free 25(OH)D and Hgb declined by 8 and 15% (p < 0.01), respectively; and UDBP/Cr increased 32% (p < 0.01). Using a 25(OH)D <30 ng/mL threshold, vitamin D inadequacy prevalence increased from 38% before surgery to 68% the day after (p < 0.001). All laboratory values returned to baseline at 6 weeks after surgery. CONCLUSIONS: Laboratory values are reduced immediately following elective total hip arthroplasty. Testing at that time does not accurately ascertain baseline status and may lead to elevated estimates of vitamin D inadequacy, incorrect interventions, and misallocation of healthcare resources.

Dopamine/noradrenaline reuptake inhibition in women improves endurance exercise performance in the heat.

Catecholamine reuptake inhibition improves the performance of male volunteers exercising in warm conditions, but sex differences in thermoregulation, circulating hormones, and central neurotransmission may alter this response. With local ethics committee approval, nine physically active women (mean ± SD age 21 ± 2 years; height 1.68 ± 0.08 m; body mass 64.1 ± 6.0 kg; VO2peak 51 ± 7 mL/kg/min) were recruited to examine the effect of pre-exercise administration of Bupropion (BUP; 4 × 150 mg) on prolonged exercise performance in a warm environment. Participants completed a VO2peak test, two familiarization trials, and two randomized, double-blind experimental trials. All trials took place during the first 10 days of the follicular phase of the menstrual cycle. Participants cycled for 1 h at 60% VO2peak followed by a 30-min performance test. Total work done was greater during the BUP trial (291 ± 48 kJ) than the placebo trial (269 ± 46 kJ, P = 0.042, d = 0.497). At the end of the performance test, core temperature was higher on the BUP trial (39.5 ± 0.4 °C) than on the placebo trial (39.2 ± 0.6 °C, P = 0.021; d = 0.588), as was heart rate (185 ± 9 vs 179 ± 13, P = 0.043; d = 0.537). The results indicate that during the follicular phase of the menstrual cycle, an acute dosing protocol of BUP can improve self-regulated performance in warm conditions.

Religious and Psychological Implications of Positive and Negative Religious Coping in Iran.

This study examined the religious and psychological implications of religious coping in Iran. University students (N = 224) responded to the Brief Positive and Negative Religious Coping Scales along with measures of Religious Orientation, Integrative Self-Knowledge, Self-Control, Mindfulness, Self-Compassion, Self-Esteem, Guilt, Shame, and Self-Criticism. As in previous research elsewhere, Positive Religious Coping was stronger on average than Negative Religious Coping, and Positive and Negative Religious Coping predicted adjustment and maladjustment, respectively, In addition, this study demonstrated that direct relationships between Positive and Negative Religious Coping appeared to be reliable in Iran; that Positive Religious Copings was broadly compatible with, and Negative Religious Coping was largely irrelevant to, Iranian religious motivations; and that Negative Religious Coping obscured linkages of Positive Religious Coping with religious and psychological adjustment.

Underlying sources of cognitive-anatomical variation in multi-modal neuroimaging and cognitive testing.

Healthy adults have robust individual differences in neuroanatomy and cognitive ability not captured by demographics or gross morphology (Luders, Narr, Thompson, & Toga, 2009). We used a hierarchical independent component analysis (hICA) to create novel characterizations of individual differences in our participants (N=190). These components fused data across multiple cognitive tests and neuroanatomical variables. The first level contained four independent, underlying sources of phenotypic variance that predominately modeled broad relationships within types of data (e.g., "white matter," or "subcortical gray matter"), but were not reflective of traditional individual difference measures such as sex, age, or intracranial volume. After accounting for the novel individual difference measures, a second level analysis identified two underlying sources of phenotypic variation. One of these made strong, joint contributions to both the anatomical structures associated with the core fronto-parietal "rich club" network (van den Heuvel & Sporns, 2011), and to cognitive factors. These findings suggest that a hierarchical, data-driven approach is able to identify underlying sources of individual difference that contribute to cognitive-anatomical variation in healthy young adults.

An associative account of how the obesogenic environment biases adolescents' food choices.

Adolescents and children are the targets of much food advertising, the majority of which is for unhealthy snacks. Although the effects of advertising on food preferences and consummatory behavior are well documented, our understanding of the underlying mechanisms is still limited. The present study investigates an associative (ideomotor) mechanism by which exposure to rewarding (snack) outcomes may activate behavior that previously resulted in these rewards. Specifically, we used a computerized task to investigate whether exposing adolescents to food pictures directly, or to Pavlovian cues predictive of those food pictures, would bias their subsequent responses towards the presented/signaled food. Furthermore, we assessed whether this effect was particularly pronounced with palatable, high-calorie snacks (crisps and chocolate) relative to low-calorie snacks (tomatoes and cucumber). In two experiments, adolescents learnt that certain key presses would yield particular food pictures - some high calorie and others low calorie - before learning Pavlovian associations between cues (cartoon monsters) and these same food pictures. Subsequently, in a response-priming test, we examined the extent to which the food pictures and Pavlovian cues spontaneously primed the previously associated response. The results show that we replicated, in adolescents, previous demonstrations of ideomotor response priming in adults: food pictures biased responding towards the response that previously yielded them, and this effect transferred to the Pavlovian cues. Furthermore, the priming effect was significantly stronger for high-calorie rewards than for low-calorie. These findings indicate that the ideomotor mechanism plays an important role in the detrimental effect of our obesogenic environment, with its plethora of unhealthy food reminders, on adolescents' food-related choices.

A Phase-Locked Loop Epilepsy Network Emulator.

Most seizure forecasting employs statistical learning techniques that lack a representation of the network interactions that give rise to seizures. We present an epilepsy network emulator (ENE) that uses a network of interconnected phase-locked loops (PLLs) to model synchronous, circuit-level oscillations between electrocorticography (ECoG) electrodes. Using ECoG data from a canine-epilepsy model (Davis et al. 2011) and a physiological entropy measure (approximate entropy or ApEn, Pincus 1995), we demonstrate the entropy of the emulator phases increases dramatically during ictal periods across all ECoG recording sites and across all animals in the sample. Further, this increase precedes the observable voltage spikes that characterize seizure activity in the ECoG data. These results suggest that the ENE is sensitive to phase-domain information in the neural circuits measured by ECoG and that an increase in the entropy of this measure coincides with increasing likelihood of seizure activity. Understanding this unpredictable phase-domain electrical activity present in ECoG recordings may provide a target for seizure detection and feedback control.

Muslim Spirituality, Religious Coping, and Reactions to Terrorism Among Pakistani University Students.

Pakistani Muslim university students (N = 207) displayed Personal Distress, Public Distress, and Personal Defeat Reactions to Terrorism. All three reactions predicted poorer mental health with Personal Defeat being especially disturbed in its adjustment implications. In line with the assumptions of coping theory, scores on the Negative Religious Coping Scale correlated positively with Personal Distress and with Personal Defeat. However, Positive Religious Coping, the spirituality of Muslim Experiential Religiousness, and the Intrinsic and Extrinsic Personal Religious Orientations exhibited positive rather than the expected negative linkages with Personal Distress and Public Distress. Muslim Experiential Religiousness moderated associations of Positive and Negative Religious Coping with Public Distress. When spirituality was high, these relationships were negative. When spirituality was low, they became positive. These data documented the negative impacts that terrorism can have on Pakistanis and suggested that Muslim religious commitments may have an important role to play in resisting those influences.

Integrative self-knowledge and marital satisfaction.

Married Iranian couples (N = 210) responded to the Integrative Self-Knowledge Scale along with a measure of marital satisfaction, the International Personality Item Pool (IPIP) Big Five, and an index of interpersonal problems. Integrative self-knowledge correlated positively with marital satisfaction, positively with all but the extraversion Big Five traits, and negatively with three indices of interpersonal problems. Integrative self-knowledge also mediated a number of personality relationships with marital satisfaction. Spouse-ratings of personality confirmed the adaptive implications of integrative self-knowledge for marriage. Linkages with questionnaire response styles supported the description of integrative self-knowledge as a measure of both self-insight and self-development. Results confirmed the potential of integrative self-knowledge for studying self-regulatory processes and suggested that the enhancement of self-knowledge may be a useful goal in efforts to strengthen marriages.

Canine hepacivirus is not associated with chronic liver disease in dogs.

Canine hepacivirus (CHV) has recently been identified in liver and respiratory tract samples from dogs, and comparative phylogenetic analysis has confirmed it to be the closest genetic relative of hepatitis C virus (HCV) described to date. CHV offers great potential as a model system for HCV, but only if the underlying processes of infection and pathogenesis are similar for both viruses. However, it is not yet clear if CHV is hepatotrophic. Canine chronic hepatitis (CH) is a common and usually idiopathic disease that shares similar histological features to that of HCV infection of humans. To date, no study has attempted to determine whether CHV is involved in the aetiology of liver disease in dogs. We employed two nested PCR assays, using primers targeting regions of the helicase domain of CHV NS3, to identify viral nucleic acids in liver samples from 100 dogs with CH of unknown cause in the UK. We also used a sensitive luciferase immunoprecipitation system (LIPS) assay to screen serum samples from these dogs for the presence of anti-CHV antibodies. Surprisingly, there was no evidence of exposure to, or a carrier state of, CHV in this large cohort, suggesting that the virus is not associated with CH in UK dogs. Future work, including transmission studies, is required to understand the pathogenesis of CHV in canids before it can be proposed as a surrogate model for HCV-induced liver disease in man.