Mediators of negative content and voice-related distress in a diverse sample of clinical and non-clinical voice-hearers.

OBJECTIVES: Negative content in hearing voices (i.e., auditory verbal hallucinations) has been associated with adverse clinical outcomes including voice-related distress. Voice appraisals and responding mindfully to voices are theorized to reduce voice-related distress. This study aimed in examine mediators of the negative content voice-related distress relationship in clinical (those who recently received input from mental health services) and non-clinical voice-hearers. METHODS: One hundred and twenty-one adults (71.9% female; 35.5% mixed or non-white ethnic background) who hear voices were recruited online and completed self-report measures of negative content of voices, voice-related distress, mindfulness of voices, interpretation of loss of control, thought suppression and intrusion. RESULTS: Clinical voice-hearers had significantly higher levels of negative content, voice-related distress and interpretation of loss of control than non-clinical voice-hearers. A mindful approach to voices and interpretation of loss of control mediated the relationship between negative content and voice-related distress across the whole sample. Thought suppression and intrusion did not mediate the relationship. CONCLUSIONS: The results support the use of mindfulness-based psychological intervention to reduce voice-related distress. Further development of valid and reliable measures specifically relating to constructs of voice content, voice-related distress and voice suppression will support further research in this area.

Long non-coding RNA Tug1 modulates mitochondrial and myogenic responses to exercise in skeletal muscle.

BACKGROUND: Mitochondria have an essential role in regulating metabolism and integrate environmental and physiological signals to affect processes such as cellular bioenergetics and response to stress. In the metabolically active skeletal muscle, mitochondrial biogenesis is one important component contributing to a broad set of mitochondrial adaptations occurring in response to signals, which converge on the biogenesis transcriptional regulator peroxisome proliferator-activated receptor coactivator 1-alpha (PGC-1α), and is central to the beneficial effects of exercise in skeletal muscle. We investigated the role of long non-coding RNA (lncRNA) taurine-upregulated gene 1 (TUG1), which interacts with PGC-1α in regulating transcriptional responses to exercise in skeletal muscle. RESULTS: In human skeletal muscle, TUG1 gene expression was upregulated post-exercise and was also positively correlated with the increase in PGC-1α gene expression (PPARGC1A). Tug1 knockdown (KD) in differentiating mouse myotubes led to decreased Ppargc1a gene expression, impaired mitochondrial respiration and morphology, and enhanced myosin heavy chain slow isoform protein expression. In response to a Ca2+-mediated stimulus, Tug1 KD prevented an increase in Ppargc1a expression. RNA sequencing revealed that Tug1 KD impacted mitochondrial Ca2+ transport genes and several downstream PGC-1α targets. Finally, Tug1 KD modulated the expression of ~300 genes that were upregulated in response to an in vitro model of exercise in myotubes, including genes involved in regulating myogenesis. CONCLUSIONS: We found that TUG1 is upregulated in human skeletal muscle after a single session of exercise, and mechanistically, Tug1 regulates transcriptional networks associated with mitochondrial calcium handling, muscle differentiation and myogenesis. These data demonstrate that lncRNA Tug1 exerts regulation over fundamental aspects of skeletal muscle biology and response to exercise stimuli.

Mitochondrial regulation in skeletal muscle: A role for non-coding RNAs?

NEW FINDINGS: What is the topic of this review? This article draws evidence from the current literature to support the hypothesis that non-coding RNA-mediated gene regulation takes place in the mitochondria. An emphasis is put on skeletal muscle. What advances does it highlight? This review highlights the potential role of microRNAs and long non-coding RNAs in mitochondrial gene regulation. The discovery of a new level of skeletal muscle mitochondria-controlled gene regulation presents exciting perspectives for our understanding of skeletal muscle physiology in health and disease. ABSTRACT: Skeletal muscle is a highly metabolic tissue characterized by high mitochondrial abundance. As such, skeletal muscle homeostasis relies on the tight control of mitochondrial gene expression to ensure efficient mitochondrial function. Mitochondria retain a conserved genome from prokaryotic ancestors, and mitochondrial gene regulation relies on communication between mitochondrial- and nuclear-encoded transcripts. Small and long non-coding RNAs (ncRNAs) have regulatory roles in the modulation of gene expression. Emerging evidence demonstrates that regulatory ncRNAs, particularly microRNAs (miRNAs) and long ncRNAs (lncRNAs), localize within the mitochondria in diverse physiological and pathological states. These molecules present intriguing possibilities for the regulation of mitochondrial gene expression. Current research suggests that all known miRNAs are encoded by the nuclear genome but can target mitochondrial genes. Initial investigations demonstrate direct interactions between the muscle-enriched miR-1 and miR-181c and mitochondrial transcripts, suggesting advanced roles of miRNAs in mitochondrial gene regulation. This review draws evidence from the current literature to discuss the hypothesis that a level of ncRNA-mediated gene regulation, in particular miRNA-mediated gene regulation, takes place in the mitochondria. Although ncRNA-mediated regulation of the mitochondrial genome is a relatively unexplored field, it presents exciting possibilities to further our understanding of mitochondrial metabolism and human muscle physiology.

Pharmacological and neurosurgical interventions for managing dystonia in cerebral palsy: a systematic review.

AIM: To systematically review evidence for pharmacological/neurosurgical interventions for managing dystonia in individuals with cerebral palsy (CP) to inform a care pathway. METHOD: Searches included studies with a minimum of five participants with dystonia in CP receiving oral baclofen, benzodiazepines (clonazepam, diazepam, lorazepam), clonidine, gabapentin, levodopa, trihexyphenidyl, botulinum toxin, intrathecal baclofen (ITB), or deep brain stimulation (DBS). Evidence was classified according to American Academy of Neurology guidelines. RESULTS: Twenty-eight articles underwent data extraction: one levodopa, five trihexyphenidyl, three botulinum toxin, six ITB, and 13 DBS studies. No articles for oral baclofen, benzodiazepines, clonidine, or gabapentin met the inclusion criteria. Evidence for reducing dystonia was level C (possibly effective) for ITB and DBS; level C (possibly ineffective) for trihexyphenidyl; and level U (inadequate data) for botulinum toxin. INTERPRETATION: For dystonia reduction, ITB and DBS are possibly effective, whereas trihexyphenidyl was possibly ineffective. There is insufficient evidence to support oral medications or botulinum toxin to reduce dystonia. There is insufficient evidence for pharmacological and neurosurgical interventions to improve motor function, decrease pain, and ease caregiving. The majority of the pharmacological and neurosurgical management of dystonia in CP is based on clinical expert opinion. WHAT THIS PAPER ADDS: Intrathecal baclofen and deep brain stimulation are possibly effective in reducing dystonia. Current evidence does not support effectiveness of oral medications or botulinum toxin to reduce dystonia. Evidence is inadequate for pharmacological/neurosurgical interventions impact on improving motor function, pain/comfort, and easing caregiving. The majority of the care pathway rests on expert opinion.

Embedding ecosystem services in coastal planning leads to better outcomes for people and nature.

Recent calls for ocean planning envision informed management of social and ecological systems to sustain delivery of ecosystem services to people. However, until now, no coastal and marine planning process has applied an ecosystem-services framework to understand how human activities affect the flow of benefits, to create scenarios, and to design a management plan. We developed models that quantify services provided by corals, mangroves, and seagrasses. We used these models within an extensive engagement process to design a national spatial plan for Belize's coastal zone. Through iteration of modeling and stakeholder engagement, we developed a preferred plan, currently under formal consideration by the Belizean government. Our results suggest that the preferred plan will lead to greater returns from coastal protection and tourism than outcomes from scenarios oriented toward achieving either conservation or development goals. The plan will also reduce impacts to coastal habitat and increase revenues from lobster fishing relative to current management. By accounting for spatial variation in the impacts of coastal and ocean activities on benefits that ecosystems provide to people, our models allowed stakeholders and policymakers to refine zones of human use. The final version of the preferred plan improved expected coastal protection by >25% and more than doubled the revenue from fishing, compared with earlier versions based on stakeholder preferences alone. Including outcomes in terms of ecosystem-service supply and value allowed for explicit consideration of multiple benefits from oceans and coasts that typically are evaluated separately in management decisions.

Research of visual attention networks in deaf individuals: a systematic review.

The impact of deafness on visual attention has been widely discussed in previous research. It has been noted that deficiencies and strengths of previous research can be attributed to temporal or spatial aspects of attention, as well as variations in development and clinical characteristics. Visual attention is categorized into three networks: orienting (exogenous and endogenous), alerting (phasic and tonic), and executive control. This study aims to contribute new neuroscientific evidence supporting this hypothesis. This paper presents a systematic review of the international literature from the past 15 years focused on visual attention in the deaf population. The final review included 24 articles. The function of the orienting network is found to be enhanced in deaf adults and children, primarily observed in native signers without cochlear implants, while endogenous orienting is observed only in the context of gaze cues in children, with no differences found in adults. Results regarding alerting and executive function vary depending on clinical characteristics and paradigms used. Implications for future research on visual attention in the deaf population are discussed.

The Effect of Palmitoylethanolamide (PEA) on Skeletal Muscle Hypertrophy, Strength, and Power in Response to Resistance Training in Healthy Active Adults: A Double-Blind Randomized Control Trial.

BACKGROUND: Palmitoylethanolamide (PEA) has analgesic/anti-inflammatory properties that may be a suitable alternative to over-the-counter (OTC) non-steroidal analgesics/anti-inflammatories. While OTC pain medications can impair strength training adaptations, the mechanism of action of PEA is distinct from these and it may not negatively affect skeletal muscle adaptations to strength training. METHODS: The primary aim of this study was to investigate the effects of daily PEA supplementation (350 mg Levagen + equivalent to 300 mg PEA) combined with 8-weeks of resistance training on lean body mass with secondary aims addressing strength, power, sleep, and wellbeing compared to placebo (PLA) in young, healthy, active adults. In a randomized, controlled, double-blinded trial, 52 untrained, recreationally active participants aged 18-35 y were allocated to either the PEA or PLA groups. Participants consumed either 2 × 175 mg Levagen + PEA or identically matched maltodextrin capsules during an 8-week period of whole-body resistance training. This trial assessed the pre- to post- changes in total and regional lean body mass, muscular strength (1-RM bench, isometric mid-thigh pull), muscular power [countermovement jump (CMJ), bench throw], pain associated with exercise training, sleep, and wellbeing compared with the PEA or PLA condition. RESULTS: 48 Participants were included in the final intention to treat (ITT) analysis and we also conducted per protocol (PP) analysis (n = 42). There were no significant between-group differences for total or regional lean muscle mass post-intervention. There was a significantly higher jump height (CMJ) at week 10 in the PEA group compared to the PLA (Adjusted mean difference [95% CI] p-value; ITT: - 2.94 cm [- 5.15, - 0.74] p = 0.010; PP: - 2.93 cm [- 5.31, - 0.55] p = 0.017). The PLA group had higher 1-RM bench press post-intervention compared with the PEA group (ITT: 2.24 kg [0.12, 4.37] p = 0.039; PP: 2.73 kg [0.40, 5.06] p = 0.023). No significant treatment effects were noted for any of the other outcomes. CONCLUSION: PEA supplementation, when combined with 8 weeks of strength training, did not impair lean mass gains and it resulted in significantly higher dynamic lower-body power when compared with the PLA condition. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR: ACTRN12621001726842p).

Amusic does not mean unmusical: beat perception and synchronization ability despite pitch deafness.

Pitch deafness, the most commonly known form of congenital amusia, refers to a severe deficit in musical pitch processing (i.e., melody discrimination and recognition) that can leave time processing--including rhythm, metre, and "feeling the beat"--preserved. In Experiment 1, we show that by presenting musical excerpts in nonpitched drum timbres, rather than pitched piano tones, amusics show normal metre recognition. Experiment 2 reveals that body movement influences amusics' interpretation of the beat of an ambiguous drum rhythm. Experiment 3 and a subsequent exploratory study show an ability to synchronize movement to the beat of popular dance music and potential for improvement when given a modest amount of practice. Together the present results are consistent with the idea that rhythm and beat processing are spared in pitch deafness--that is, being pitch-deaf does not mean one is beat-deaf. In the context of drum music especially, amusics can be musical.

Evidence-based target setting informs blue carbon strategies for nationally determined contributions.

The magnitude and pace of global climate change demand ambitious and effective implementation of nationally determined contributions (NDCs). Nature-based solutions present an efficient approach to achieving mitigation, adaptation and resilience goals. Yet few nations have quantified the diverse benefits of nature-based solutions to evaluate and select ecosystem targets for their NDCs. Here we report on Belize's pursuit of innovative, evidence-based target setting by accounting for multiple benefits of blue carbon strategies. Through quantification of carbon storage and sequestration and optimization of co-benefits, we explore time-bound targets and prioritize locations for mangrove protection and restoration. We find increases in carbon benefits with larger mangrove investments, while fisheries, tourism and coastal risk-reduction co-benefits grow initially and then plateau. We identify locations, currently lacking protected status, where prioritizing blue carbon strategies would provide the greatest delivery of co-benefits to communities. These findings informed Belize's updated NDCs to include an additional 12,000 ha of mangrove protection and 4,000 ha of mangrove restoration, respectively, by 2030. Our study serves as an example for the more than 150 other countries that have the opportunity to enhance greenhouse gas sequestration and climate adaptation by incorporating blue carbon strategies that provide multiple societal benefits into their NDCs.

A randomised controlled trial assessing the potential of palmitoylethanolamide (PEA) to act as an adjuvant to resistance training in healthy adults: a study protocol.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) and analgesics are used frequently by athletes either prophylactically for the prevention of pain, or to accelerate recovery following an injury. However, these types of pain management strategies have been shown to inhibit signalling pathways (e.g., cyclooxygenase-2) that may hinder muscular adaptations such as hypertrophy and strength. Nutraceuticals such as palmitoylethanolamide (PEA) have analgesic properties that act via different mechanisms to NSAIDS/analgesics. Furthermore, PEA has been shown to have a positive effect on sleep and may contribute positively to muscle hypertrophy via PKB activation. Although PEA has not been widely studied in the athletic or recreationally active population, it may provide an alternative solution for pain management if it is found not to interfere with, or enhance training adaptations. Therefore, the study aim is to investigate the effects of daily PEA supplementation (Levagen + ®) with resistance training on lean body mass, strength, power and physical performance and outcomes of recovery (e.g., sleep) compared to placebo. METHODS: This double-blind, randomised controlled study will take place over an 11-week period (including 8-weeks of progressive resistance training). Participants for this study will be 18-35 years old, healthy active adults that are not resistance trained. Participants will attend a familiarisation (week 0), pre-testing (week 1) and final-testing (week 11). At the pre-testing and final-testing weeks, total lean body mass (dual-energy X-ray absorptiometry; DXA), total mid-thigh cross sectional area (pQCT), maximal muscular strength (1 repetition maximum bench press, isometric mid-thigh pull) and power (countermovement jump and bench throw) will be assessed. Additionally, circulating inflammatory cytokines and anabolic hormones, sleep quality and quantity (ActiGraph), pain and subjective wellbeing (questionnaires) will also be examined. DISCUSSION: This study is designed to investigate the effects that PEA may have on pre-to post intervention changes in total body and regional lean muscle mass, strength, power, sleep, subjective wellbeing, and pain associated with resistance training and menstruation compared with the placebo condition. Unlike other NSAIDs and analgesics, which may inhibit muscle protein synthesis and training adaptations, PEA which provides analgesia via alternative mechanisms may provide an alternative pain management solution. It is therefore important to determine if this analgesic compound interferes with or enhances training adaptations so that athletes and active individuals can make an informed decision on their pain management strategies. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR: ACTRN12621001726842p).

Neuropsychological Development of Cool and Hot Executive Functions Between 6 and 12 Years of Age: A Systematic Review.

Previous studies on the development of executive functions (EFs) in middle childhood have traditionally focused on cognitive, or "cool," EFs: working memory, inhibitory control and cognitive flexibility. However, knowledge of the development of socio-emotional, or "hot," EFs, such as delay of gratification, decision-making and theory of mind, is more limited. The main aims of this systematic review were to characterize the typical development of both the primary cool and hot EFs in middle childhood, and to identify the main tools for evaluating EFs as a whole. We conducted a systematic search on studies of cognitive and socio-emotional EFs published in the last 5 years in Pubmed, PsycInfo, and WoS databases. Of 44 studies selected, we found a variety of tasks measuring cool EFs, while measures of hot EFs were limited. Nevertheless, the available data suggest that cool and hot components follow distinct, but related, developmental trajectories during middle childhood.

Inattention, Impulsivity, and Hyperactivity in Deaf Children Are Not Due to Deficits in Inhibitory Control, but May Reflect an Adaptive Strategy.

The present study had two main aims: (1) to determine whether deaf children show higher rates of key behaviors of ADHD (inattentive, hyperactive, and impulsive behaviors) and of Conduct Disorder-CD-(disruptive, aggressive, or antisocial behaviors) than hearing children, also examining whether the frequency of these behaviors in deaf children varied based on cochlear implant (CI) use, type of school (regular vs. specific for deaf) and level of receptive vocabulary; and (2) to determine whether any behavioral differences between deaf and hearing children could be explained by deficits in inhibitory control. We measured behaviors associated with ADHD and CD in 34 deaf and hearing children aged 9-10 years old, using the revised Spanish version of the Conners scale. We then assessed inhibitory control ability using a computerized Stroop task and a short version of the Attention Network Test for children. To obtain a measure of the level of receptive vocabulary of the deaf children we used a Spanish version of the Carolina Picture Vocabulary Test for Deaf and hearing-impaired children. Deaf children showed significantly higher rates of behaviors associated with ADHD and CD, and over 85% of cases detected with high risk of ADHD-inattentive type in the entire present sample were deaf children. Further, in the group of deaf children a negative correlation was found between receptive vocabulary and frequency of disruptive, aggressive, or antisocial behaviors associated with CD. However, inhibitory control scores did not differ between deaf and hearing children. Our results suggested that the ADHD-related behaviors seen in deaf children were not associated with a deficit in inhibitory control, at least in the interference suppression subcomponent. An alternative explanation could be that these behaviors are reflecting an adaptive strategy that permits deaf children to access information from their environment which is not available to them via audition.

Response to Staphylococcus aureus requires CD36-mediated phagocytosis triggered by the COOH-terminal cytoplasmic domain.

Phagocyte recognition and clearance of bacteria play essential roles in the host response to infection. In an on-going forward genetic screen, we identify the Drosophila melanogaster scavenger receptor Croquemort as a receptor for Staphylococcus aureus, implicating for the first time the CD36 family as phagocytic receptors for bacteria. In transfection assays, the mammalian Croquemort paralogue CD36 confers binding and internalization of Gram-positive and, to a lesser extent, Gram-negative bacteria. By mutational analysis, we show that internalization of S. aureus and its component lipoteichoic acid requires the COOH-terminal cytoplasmic portion of CD36, specifically Y463 and C464, which activates Toll-like receptor (TLR) 2/6 signaling. Macrophages lacking CD36 demonstrate reduced internalization of S. aureus and its component lipoteichoic acid, accompanied by a marked defect in tumor necrosis factor-alpha and IL-12 production. As a result, Cd36-/- mice fail to efficiently clear S. aureus in vivo resulting in profound bacteraemia. Thus, response to S. aureus requires CD36-mediated phagocytosis triggered by the COOH-terminal cytoplasmic domain, which initiates TLR2/6 signaling.

Singing proficiency in congenital amusia: imitation helps.

Singing out of tune characterizes congenital amusia. Here, we examine whether an aid to memory improves singing by studying vocal imitation in 11 amusic adults and 11 matched controls. Participants sang a highly familiar melody on the original lyrics and on the syllable /la/ in three conditions. First, they sang the melody from memory. Second, they sang it after hearing a model, and third, they sang in unison with the model. Results show that amusic individuals benefit from singing by imitation, whether singing after the model or in unison with the model. The amusics who were the most impaired in memory benefited most, particularly when singing on the syllable /la/. Nevertheless, singing remains poor on the pitch dimension; rhythm was intact and unaffected by imitation. These results point to memory as a source of impairment in poor singing, and to imitation as a possible aid for poor singers.

The ecology of entrainment: Foundations of coordinated rhythmic movement.

Entrainment has been studied in a variety of contexts including music perception, dance, verbal communication and motor coordination more generally. Here we seek to provide a unifying framework that incorporates the key aspects of entrainment as it has been studied in these varying domains. We propose that there are a number of types of entrainment that build upon pre-existing adaptations that allow organisms to perceive stimuli as rhythmic, to produce periodic stimuli, and to integrate the two using sensory feedback. We suggest that social entrainment is a special case of spatiotemporal coordination where the rhythmic signal originates from another individual. We use this framework to understand the function and evolutionary basis for coordinated rhythmic movement and to explore questions about the nature of entrainment in music and dance. The framework of entrainment presented here has a number of implications for the vocal learning hypothesis and other proposals for the evolution of coordinated rhythmic behavior across an array of species.

Extracellular vesicular miRNA expression is not a proxy for skeletal muscle miRNA expression in males and females following acute, moderate intensity exercise.

Skeletal muscle and extracellular vesicle (EV) miRNA expression increases following acute endurance exercise. However, research to date has only been performed in males. The aim of this study was to describe the expression levels of a subset of miRNAs in EVs following acute exercise and compare it to skeletal muscle miRNA expression. Twelve males (age 22.9 ± 2.6 years, mean ± SD) and eight females (age 23.0 ± 3.4 years) cycled for 60 min at 70% VO2 peak. Muscle biopsies and blood samples were collected at rest, immediately after and 3 hr after exercise. Acute exercise did not significantly alter the expression of miR-1, miR-16, miR-23b and miR-133a/b in EVs in males and females combined. There were no correlations between EV and skeletal muscle miRNA expression in any of the measured species at any time point. Exploratory analysis revealed differential miRNA responses to exercise between males and females. In males, a weak negative correlation was observed between skeletal muscle and EV miR-16 expression immediately following exercise; however, the physiological relevance of this correlation is unknown. Additionally, when compared with values at rest, male skeletal muscle miR-16 expression significantly increased immediately following exercise, whereas miR-133a expression significantly decreased 3 hr post exercise. Our findings suggest that miRNAs isolated from EVs are not a proxy for skeletal muscle miRNA content. Our exploratory data is the first known evidence of sex-specific differences in the miRNA response to an acute bout of endurance exercise, particularly for miRNA species implicated in mitochondrial metabolism and angiogenesis.

Advancing Brain-Computer Interface Applications for Severely Disabled Children Through a Multidisciplinary National Network: Summary of the Inaugural Pediatric BCI Canada Meeting.

Thousands of youth suffering from acquired brain injury or other early-life neurological disease live, mature, and learn with only limited communication and interaction with their world. Such cognitively capable children are ideal candidates for brain-computer interfaces (BCI). While BCI systems are rapidly evolving, a fundamental gap exists between technological innovators and the patients and families who stand to benefit. Forays into translating BCI systems to children in recent years have revealed that kids can learn to operate simple BCI with proficiency akin to adults. BCI could bring significant boons to the lives of many children with severe physical impairment, supporting their complex physical and social needs. However, children have been neglected in BCI research and a collaborative BCI research community is required to unite and push pediatric BCI development forward. To this end, the pediatric BCI Canada collaborative network (BCI-CAN) was formed, under a unified goal to cooperatively drive forward pediatric BCI innovation and impact. This article reflects on the topics and discussions raised in the foundational BCI-CAN meeting held in Toronto, ON, Canada in November 2019 and suggests the next steps required to see BCI impact the lives of children with severe neurological disease and their families.

Global modeling of nature's contributions to people.

The magnitude and pace of global change demand rapid assessment of nature and its contributions to people. We present a fine-scale global modeling of current status and future scenarios for several contributions: water quality regulation, coastal risk reduction, and crop pollination. We find that where people's needs for nature are now greatest, nature's ability to meet those needs is declining. Up to 5 billion people face higher water pollution and insufficient pollination for nutrition under future scenarios of land use and climate change, particularly in Africa and South Asia. Hundreds of millions of people face heightened coastal risk across Africa, Eurasia, and the Americas. Continued loss of nature poses severe threats, yet these can be reduced 3- to 10-fold under a sustainable development scenario.

Loss of receptor-mediated lipid uptake via scavenger receptor A or CD36 pathways does not ameliorate atherosclerosis in hyperlipidemic mice.

Macrophage internalization of modified lipoproteins is thought to play a critical role in the initiation of atherogenesis. Two scavenger receptors, scavenger receptor A (SR-A) and CD36, have been centrally implicated in this lipid uptake process. Previous studies showed that these receptors mediated the majority of cholesterol ester accumulation in macrophages exposed to oxidized LDL and that mice with deletions of either receptor exhibited marked reductions in atherosclerosis. This work has contributed to an atherosclerosis paradigm: scavenger receptor-mediated oxidized lipoprotein uptake is required for foam cell formation and atherogenesis. In this study, Apoe-/- mice lacking SR-A or CD36, backcrossed into the C57BL/6 strain for 7 generations, were fed an atherogenic diet for 8 weeks. Hyperlipidemic Cd36-/-Apoe-/- and Msr1-/-Apoe-/- mice showed significant reductions in peritoneal macrophage lipid accumulation in vivo; however, in contrast with previous reports, this was associated with increased aortic sinus lesion areas. Characterization of aortic sinus lesions by electron microscopy and immunohistochemistry showed abundant macrophage foam cells, indicating that lipid uptake by intimal macrophages occurs in the absence of CD36 or SR-A. These data show that alternative lipid uptake mechanisms may contribute to macrophage cholesterol ester accumulation in vivo and suggest that the roles of SR-A and CD36 as proatherosclerotic mediators of modified LDL uptake in vivo need to be reassessed.

Vestibular influence on auditory metrical interpretation.

When we move to music we feel the beat, and this feeling can shape the sound we hear. Previous studies have shown that when people listen to a metrically ambiguous rhythm pattern, moving the body on a certain beat--adults, by actively bouncing themselves in synchrony with the experimenter, and babies, by being bounced passively in the experimenter's arms--can bias their auditory metrical representation so that they interpret the pattern in a corresponding metrical form [Phillips-Silver, J., & Trainor, L. J. (2005). Feeling the beat: Movement influences infant rhythm perception. Science, 308, 1430; Phillips-Silver, J., & Trainor, L. J. (2007). Hearing what the body feels: Auditory encoding of rhythmic movement. Cognition, 105, 533-546]. The present studies show that in adults, as well as in infants, metrical encoding of rhythm can be biased by passive motion. Furthermore, because movement of the head alone affected auditory encoding whereas movement of the legs alone did not, we propose that vestibular input may play a key role in the effect of movement on auditory rhythm processing. We discuss possible cortical and subcortical sites for the integration of auditory and vestibular inputs that may underlie the interaction between movement and auditory metrical rhythm perception.