Objects Do Not Suffer: An Impact of Mechanistic Dehumanization on Perceptions of Women's Suffering and Lack of Justice in Domestic Assault.

Women constitute an overwhelming majority of those who experience domestic violence; furthermore, the vast majority of perpetrators of domestic violence go unsentenced. The objectification of women innately implies the denial of humanness, and dehumanization is known to play a role in willingness to engage in and acceptance of interpersonal harm. Yet, important questions remain. The current study examines the type of humanness objectified women are being denied, and how that denial implicates perceptions surrounding domestic assault. We predict that associating women with objects, and not animals, may be uniquely implicated in the lack of consequences for perpetrators-for objects cannot feel pain. In the current study (N = 319), we manipulated the presentation of a woman as sexualized or not and purported that she had been involved in a domestic violence incident. We found that when the target woman was sexualized (and thus objectified), participants associated her with an inert, non-human object (i.e., mechanistically dehumanized her) more than when she was not sexually objectified, but we found no effect of sexualization on animalistic dehumanization. Furthermore, mechanistic dehumanization mediated decreases in perceptions of the sexually objectified woman's suffering as a result of the domestic violence, which decreased the severity of the punishment participants recommended for the perpetrator, while also, increasing victim, and decreasing perpetrator, blame. We discuss critical considerations of the role of dehumanization in domestic violence directed toward women and the lack of consequences for perpetrators of these crimes.

Policies to prevent zoonotic spillover: a systematic scoping review of evaluative evidence.

BACKGROUND: Emerging infectious diseases of zoonotic origin present a critical threat to global population health. As accelerating globalisation makes epidemics and pandemics more difficult to contain, there is a need for effective preventive interventions that reduce the risk of zoonotic spillover events. Public policies can play a key role in preventing spillover events. The aim of this review is to identify and describe evaluations of public policies that target the determinants of zoonotic spillover. Our approach is informed by a One Health perspective, acknowledging the inter-connectedness of human, animal and environmental health. METHODS: In this systematic scoping review, we searched Medline, SCOPUS, Web of Science and Global Health in May 2021 using search terms combining animal health and the animal-human interface, public policy, prevention and zoonoses. We screened titles and abstracts, extracted data and reported our process in line with PRISMA-ScR guidelines. We also searched relevant organisations' websites for evaluations published in the grey literature. All evaluations of public policies aiming to prevent zoonotic spillover events were eligible for inclusion. We summarised key data from each study, mapping policies along the spillover pathway. RESULTS: Our review found 95 publications evaluating 111 policies. We identified 27 unique policy options including habitat protection; trade regulations; border control and quarantine procedures; farm and market biosecurity measures; public information campaigns; and vaccination programmes, as well as multi-component programmes. These were implemented by many sectors, highlighting the cross-sectoral nature of zoonotic spillover prevention. Reports emphasised the importance of surveillance data in both guiding prevention efforts and enabling policy evaluation, as well as the importance of industry and private sector actors in implementing many of these policies. Thoughtful engagement with stakeholders ranging from subsistence hunters and farmers to industrial animal agriculture operations is key for policy success in this area. CONCLUSION: This review outlines the state of the evaluative evidence around policies to prevent zoonotic spillover in order to guide policy decision-making and focus research efforts. Since we found that most of the existing policy evaluations target 'downstream' determinants, additional research could focus on evaluating policies targeting 'upstream' determinants of zoonotic spillover, such as land use change, and policies impacting infection intensity and pathogen shedding in animal populations, such as those targeting animal welfare.

Public awareness of One Health in China.

One Health is recognized as an increasingly important approach to global health. It has the potential to inform interventions and governance approaches to prevent future pandemics. Successfully implementing the One Health approach in policy will require active engagement from the public, which begs the question: how aware is the public of One Health? In this study, we examine the level and distribution of One Health awareness among the general public in China using a survey conducted in Beijing (n = 1820). We distinguish between awareness of the term of "One Health" versus awareness of the core set of ideas - the interconnection between the health of people, animals, and the environment. Our analysis shows that 40% of respondents reported that they have heard of the term, but more than double the number indicated that they recognize the core idea of interconnection between people, animals, and the environment. Specifically, about 83% of the respondents said that they believe people's health is closely connected to animal health and 86% believe people's health is closely connected to plant and environmental health. Multiple regression analysis indicates that women, younger people, and individuals with a higher level of education show higher levels of One Health awareness than their counterparts. Being aware of the term is associated with higher recognition of the core ideas. Policymakers and health practitioners should consider these findings when designing public awareness campaigns and educational initiatives to promote One Health principles.

Systems Thinking and Complexity Science Methods and the Policy Process in Non-communicable Disease Prevention: A Systematic Scoping Review.

BACKGROUND: Given the complex determinants of non-communicable diseases (NCDs), and the dynamic policy landscape, researchers and policymakers are exploring the use of systems thinking and complexity science (STCS) in developing effective policies. The aim of this review is to systematically identify and analyse existing applications of STCS-informed methods in NCD prevention policy. METHODS: Systematic scoping review: We searched academic databases (Medline, Scopus, Web of Science, EMBASE) for all publications indexed by 13 October 2020, screening titles, abstracts and full texts and extracting data according to published guidelines. We summarised key data from each study, mapping applications of methods informed by STCS to policy process domains. We conducted a thematic analysis to identify advantages, limitations, barriers and facilitators to using STCS. RESULTS: 4681 papers were screened and 112 papers were included in this review. The most common policy areas were tobacco control, obesity prevention and physical activity promotion. Methods applied included system dynamics modelling, agent-based modelling and concept mapping. Advantages included supporting evidence-informed decision-making; modelling complex systems and addressing multi-sectoral problems. Limitations included the abstraction of reality by STCS methods, despite aims of encompassing greater complexity. Challenges included resource-intensiveness; lack of stakeholder trust in models; and results that were too complex to be comprehensible to stakeholders. Ensuring stakeholder ownership and presenting findings in a user-friendly way facilitated STCS use. CONCLUSION: This review maps the proliferating applications of STCS methods in NCD prevention policy. STCS methods have the potential to generate tailored and dynamic evidence, adding robustness to evidence-informed policymaking, but must be accessible to policy stakeholders and have strong stakeholder ownership to build consensus and change stakeholder perspectives. Evaluations of whether, and under what circumstances, STCS methods lead to more effective policies compared to conventional methods are lacking, and would enable more targeted and constructive use of these methods.

Acceptability of an Online Module Addressing Weight Bias: Perspectives and Attitudes of Undergraduate Health Students and Instructors.

Weight bias and discrimination are highly pervasive and harmful to Canadians with higher weights. Researchers and practitioners who deliver, evaluate, and advise on dietary and weight-related interventions may inadvertently perpetuate weight bias through their work; however, trainees in these fields rarely have access to weight bias education within their applied health programs. This study evaluated the acceptability of an online educational weight bias module developed for undergraduate students enrolled in health courses. The intervention included a pre-recorded 20-minute online module with prompts for reflection or discussion, a self-assessment quiz, as well as a separate module and range of resources for instructors. Overall, 211 students from applied health courses and 4 instructors completed an online survey querying the module's delivery, impact, and relevance. Students agreed that the module provided useful information (82%), was easy to understand (97%), and was the right length (75%), but reported wanting more interactivity and engagement with the content. Instructors found the module engaging and useful and expressed interest in additional resources and support for weight bias education. Future research should explore the impact of weight bias education on students' weight-related attitudes and perceptions as well as feasibility and relevance of online features such as multimedia tools.

Policies to prevent zoonotic spillover: protocol for a systematic scoping review of evaluative evidence.

INTRODUCTION: The increasing incidence of pathogen transmission from animals to humans (zoonotic spillover events) has been attributed to behavioural practices and ecological and socioeconomic change. As these events sometimes involve pathogens with epidemic or pandemic potential, they pose a serious threat to population health. Public policies may play a key role in preventing these events. The aim of this review is to identify evaluations of public policies that target the determinants of zoonotic spillover, examining approaches taken to evaluation, choice of outcomes measures and evidence of effectiveness. Our approach to identifying and analysing this literature will be informed by a One Health lens, acknowledging the interconnectedness of human, animal and environmental health. METHODS AND ANALYSIS: A systematic scoping review methodology will be used. To identify articles, we will search Medline, SCOPUS, Web of Science and Global Health in May 2021 using search terms combining animal health and the animal-human interface, public policy, prevention and zoonoses. We will screen titles and abstracts and extract data according to published guidelines for scoping reviews. All evaluations of public policies aiming to prevent zoonotic spillover events will be eligible for inclusion. We will summarise key data from each study, mapping policies along the spillover pathway and outlining the range of policies, approaches to evaluation and outcome measures. Review findings will provide a useful reference for researchers and practitioners, outlining the state of the evaluative evidence around policies to prevent zoonotic spillover. ETHICS AND DISSEMINATION: Formal ethical approval is not required, because the study does not involve primary data collection. The findings of this study will be disseminated through a peer-reviewed publication, presentations and summaries for key stakeholders.

Fat-Secreted Ceramides Regulate Vascular Redox State and Influence Outcomes in Patients With Cardiovascular Disease.

BACKGROUND: Obesity is associated with increased cardiovascular risk; however, the potential role of dysregulations in the adipose tissue (AT) metabolome is unknown. OBJECTIVES: The aim of this study was to explore the role of dysregulation in the AT metabolome on vascular redox signaling and cardiovascular outcomes. METHODS: A screen was conducted for metabolites differentially secreted by thoracic AT (ThAT) and subcutaneous AT in obese patients with atherosclerosis (n = 48), and these metabolites were then linked with dysregulated vascular redox signaling in 633 patients undergoing coronary bypass surgery. The underlying mechanisms were explored in human aortic endothelial cells, and their clinical value was tested against hard clinical endpoints. RESULTS: Because ThAT volume was associated significantly with arterial oxidative stress, there were significant differences in sphingolipid secretion between ThAT and subcutaneous AT, with C16:0-ceramide and derivatives being the most abundant species released within adipocyte-derived extracellular vesicles. High ThAT sphingolipid secretion was significantly associated with reduced endothelial nitric oxide bioavailability and increased superoxide generated in human vessels. Circulating C16:0-ceramide correlated positively with ThAT ceramides, dysregulated vascular redox signaling, and increased systemic inflammation in 633 patients with atherosclerosis. Exogenous C16:0-ceramide directly increased superoxide via tetrahydrobiopterin-mediated endothelial nitric oxide synthase uncoupling and dysregulated protein phosphatase 2 in human aortic endothelial cells. High plasma C16:0-ceramide and its glycosylated derivative were independently related with increased risk for cardiac mortality (adjusted hazard ratios: 1.394; 95% confidence interval: 1.030 to 1.886; p = 0.031 for C16:0-ceramide and 1.595; 95% confidence interval: 1.042 to 2.442; p = 0.032 for C16:0-glycosylceramide per 1 SD). In a randomized controlled clinical trial, 1-year treatment of obese patients with the glucagon-like peptide-1 analog liraglutide suppressed plasma C16:0-ceramide and C16:0-glycosylceramide changes compared with control subjects. CONCLUSIONS: These results demonstrate for the first time in humans that AT-derived ceramides are modifiable regulators of vascular redox state in obesity, with a direct impact on cardiac mortality in advanced atherosclerosis. (The Interaction Between Appetite Hormones; NCT02094183).

Toward a Healthy and Environmentally Sustainable Campus Food Environment: A Scoping Review of Postsecondary Food Interventions.

Interventions are urgently needed to transform the food system and shift population eating patterns toward those consistent with human health and environmental sustainability. Postsecondary campuses offer a naturalistic setting to trial interventions to improve the health of students and provide insight into interventions that could be scaled up in other settings. However, the current state of the evidence on interventions to support healthy and environmentally sustainable eating within postsecondary settings is not well understood. A scoping review of food- and nutrition-related interventions implemented and evaluated on postsecondary campuses was conducted to determine the extent to which they integrate considerations related to human health and/or environmental sustainability, as well as to synthesize the nature and effectiveness of interventions and to identify knowledge gaps in the literature. MEDLINE (via PubMed), CINAHL, Scopus, and ERIC were searched to identify articles describing naturalistic campus food interventions published in English from January 2015 to December 2019. Data were extracted from 38 peer-reviewed articles, representing 37 unique interventions, and synthesized according to policy domains within the World Cancer Research Foundation's NOURISHING framework. Most interventions were focused on supporting human health, whereas considerations related to environmental sustainability were minimal. Interventions to support human health primarily sought to increase nutrition knowledge or to make complementary shifts in food environments, such as through nutrition labeling at point of purchase. Interventions to support environmental sustainability often focused on reducing food waste and few emphasized consumption patterns with lower environmental impacts. The implementation of integrated approaches considering the complexity and interconnectivity of human and planetary health is needed. Such approaches must go beyond the individual to alter the structural determinants that shape our food system and eating patterns.

Low-calorie sweeteners and human health: a rapid review of systematic reviews.

INTRODUCTION: Low-calorie sweeteners are increasingly prevalent in the food supply and their consumption has increased in recent decades. Although low-calorie sweeteners approved for use are considered safe from a toxicological perspective, their short- and long-term impacts on chronic disease risk remain uncertain. The aim of this review was to summarize the evidence from systematic reviews on low-calorie sweetener use and chronic conditions and risk factors in children and adults. METHODS: MEDLINE and the Cochrane Database of Systematic Reviews were searched to identify systematic reviews of randomized and nonrandomized studies that considered low-calorie sweeteners in relation to type 2 diabetes, cardiovascular disease, cancer, anthropometric measures, hypertension, hyperglycemia, hyperlipidemia, insulin resistance, and dental caries. Data were extracted from 9 reviews deemed of moderate or high quality on the basis of AMSTAR-2. RESULTS: Narrative synthesis suggested inconsistent evidence on low-calorie sweetener use in relation to chronic conditions and associated risk factors, with nonrandomized studies suggesting positive associations and randomized studies suggesting negative or no associations. CONCLUSION: Continued research on the long-term health impacts of low-calorie sweeteners across all life stages is warranted.

Testing the efficacy of and parents' preferences for nutrition labels on children's menus from a full-service chain restaurant: results of an online experiment.

OBJECTIVE: Test the efficacy and perceived effectiveness of nutrition labels on children's menus from a full-service chain restaurant in an online study. DESIGN: Using a between-groups experiment, parents were randomised to view children's menus displaying one of five children's nutrition labelling conditions: (i) No Nutrition Information (control); (ii) Calories Only; (iii) Calories + Contextual Statement (CS); (iv) Calories, Sodium + CS; or (v) Calories and Sodium in Traffic Lights + CS. Parents hypothetically ordered up to one entrée, side, beverage and dessert for their child, then rated and ranked all five labelling conditions on the level of perceived effectiveness. SETTING: Online survey. PARTICIPANTS: 998 parents with a 3-12 year old child. RESULTS: Parents exposed to menus displaying 'Calories, Sodium + CS' selected significantly fewer calories 'overall' (entrées + side + dessert + beverage) compared to parents exposed to the control condition (-53·1 calories, P < 0·05). Parents selected 'entrees' with significantly fewer calories and lower sodium when exposed to menus with 'Calories + CS' (-24·3 calories, P < 0·05); 'Calories, Sodium + CS' (-25·4 calories, -56·1 mg sodium, P < 0·05 for both); and 'Calories and Sodium in Traffic Lights + CS' (-29·1 calories, -58·6 mg sodium, P < 0·05 for both). Parents exposed to menus with 'Calories, Sodium + CS' and 'Calories and Sodium in Traffic Lights + CS' were more likely to notice and understand nutrition information compared to other nuntrition labelling conditions. Parents perceived the menu with 'Calories and Sodium in Traffic Lights + CS' as most effective (P < 0·05). CONCLUSIONS: Menus disclosing calories, sodium and a contextual statement increased the proportion of parents who noticed and understood nutrition information, and resulted in parents selecting lower calorie and sodium entrées for their children in the hypothetical purchase task.

The Healthfulness of Eateries at the University of Waterloo: A Comparison across 2 Time Points.

Purpose: The aim of this study was to assess the healthfulness of a sample of campus eateries at 2 time points, 2 years apart. Methods: Five eateries at the University of Waterloo were audited using the Nutrition Environment Measures Survey adapted for university campuses (NEMS-UC) in 2015 and late 2017-early 2018. Based on the availability of healthy options and facilitators of and barriers to healthy eating, possible NEMS-UC scores ranged from -5 to 23 points. Results: Scores were low, ranging from 7 to 14 (mean = 10.8, SD = 2.59) points in 2015 and 7 to 13 (mean = 9.6, SD = 2.19) points in 2017-2018. For all eateries except 1 residence cafeteria, scores at time 2 were the same or lower than scores at time 1. All venues carried whole fruit and vegetable options and lower-fat milks, and most offered whole-wheat options. However, healthier items were often located in low-traffic areas, priced higher than less healthy options, and sometimes limited to prepackaged items. Misleading health messaging was also evident. Conclusions: Increased availability, accessibility, and visibility of healthy offerings is needed to enhance campus food environments and support healthy eating patterns, while barriers such as contradictory messaging should be minimized.

Top dietary sources of energy, sodium, sugars, and saturated fats among Canadians: insights from the 2015 Canadian Community Health Survey.

Dietary factors are major contributors to morbidity and mortality, and significant attention is being paid to interventions to support healthy eating, including through the creation of a healthier food supply. The objective of this study was to inform interventions to support healthy eating by examining the top dietary sources of calories, sodium, sugars, and saturated fats among Canadians in relation to sex, age, and income. We drew upon data from the 2015 Canadian Community Health Survey, which collected interviewer-administered 24-h dietary recalls from Canadians who were 1 year of age and older (n = 20 176), residing in the 10 provinces. Foods and beverages were grouped into 91 mutually exclusive categories (e.g., 100% fruit juice, fruit drinks). On the basis of the average proportion contributed, the top 20 sources of each dietary component were identified for all individuals and by sex-age and income groups. The mean amount of each dietary component contributed by each category (per capita and per consumer) and the proportions of persons consuming items in each category were also examined. Top sources included commonly consumed items (e.g., breads and flatbreads as sources of sodium), as well as those high in a given dietary component (e.g., soda as a source of sugars). Several food and beverage categories were top contributors to more than one dietary component examined, suggesting possible priorities for intervention and future analyses. The identification of major sources of calories and nutrients of concern can inform population health efforts, such as reformulation, to improve the health of Canadians.

School-Age Children Can Recall Some Foods and Beverages Consumed the Prior Day Using the Automated Self-Administered 24-Hour Dietary Assessment Tool (ASA24) without Assistance.

BACKGROUND: Technological innovations allow for collection of 24-h recalls (24HRs) in a broader range of studies than previously possible. The web-based Automated Self-Administered 24-Hour Dietary Assessment Tool (ASA24) has been shown to be feasible and to perform well in capturing true intake among adults. However, data to inform use with children are limited. OBJECTIVE: This observational feeding study was conducted to evaluate children's ability to accurately report a lunchtime meal using ASA24 without assistance. METHODS: The study was conducted among children (n = 100) aged 10-13 y within a school setting. Students were served an individual cheese pizza, baby carrots, ranch dip, yogurt, a cookie, and 1 choice of water, juice, or milk. Plate waste was collected and weighed. The next day, participants completed ASA24 and a sociodemographic questionnaire. Descriptive statistics were generated to determine match rates by food item and age, and linear regression analyses were conducted to examine associations between sociodemographic characteristics and accuracy of reported energy and nutrient intake. Associations between true and reported energy and nutrient intakes and portion sizes were assessed with use of t tests. RESULTS: Just under half (49%) of children fully completed ASA24 (median time, 41 min). Children reported an exact, close, or far match for 58% of all foods and beverages consumed, ranging from 29% for dip to 76% for pizza, but also reported some items not consumed as part of the study meal. Older children completed the recall in a shorter time than younger children (mean 31 among 13 y compared with 52 min among 10 y). Intakes of energy (39%), protein (33%), and sodium (78%) were significantly overestimated, whereas portion sizes for cookies (53%) and juice (69%) were underestimated. CONCLUSIONS: Children can report some foods and drinks consumed using ASA24, but our findings suggest challenges with independent completion, necessitating research to examine strategies, such as training and resources, to support data quality.

Insights into the roles of CMK-1 and OGT-1 in interstimulus interval-dependent habituation in Caenorhabditis elegans.

Habituation is a ubiquitous form of non-associative learning observed as a decrement in responding to repeated stimulation that cannot be explained by sensory adaptation or motor fatigue. One of the defining characteristics of habituation is its sensitivity to the rate at which training stimuli are presented-animals habituate faster in response to more rapid stimulation. The molecular mechanisms underlying this interstimulus interval (ISI)-dependent characteristic of habituation remain unknown. In this article, we use behavioural neurogenetic and bioinformatic analyses in the nematode Caenorhabiditis elegans to identify the first molecules that modulate habituation in an ISI-dependent manner. We show that the Caenorhabditis elegans orthologues of Ca2+/calmodulin-dependent kinases CaMK1/4, CMK-1 and O-linked N-acetylglucosamine (O-GlcNAc) transferase, OGT-1, both function in primary sensory neurons to inhibit habituation at short ISIs and promote it at long ISIs. In addition, both cmk-1 and ogt-1 mutants display a rare mechanosensory hyper-responsive phenotype (i.e. larger mechanosensory responses than wild-type). Overall, our work identifies two conserved genes that function in sensory neurons to modulate habituation in an ISI-dependent manner, providing the first insights into the molecular mechanisms underlying the universally observed phenomenon that habituation has different properties when stimuli are delivered at different rates.

Gaps in the Evidence on Population Interventions to Reduce Consumption of Sugars: A Review of Reviews.

There is currently considerable attention directed to identifying promising interventions to reduce consumption of sugars among populations around the world. A review of systematic reviews was conducted to identify gaps in the evidence on such interventions. Medline, EMBASE CINAHL, and the Cochrane Database of Systematic Reviews were searched to identify systematic reviews published in English from January 2005 to May 2017 and considering research on interventions to reduce sugar intake. Twelve systematic reviews that considered price changes, interventions to alter the food available within specific environments, and health promotion and education programs were examined. Each of the identified reviews focused on sugar-sweetened beverages (SSBs). The existing literature provides some promising indications in terms of the potential of interventions to reduce SSB consumption among populations. However, a common thread is the limited scope of available evidence, combined with the heterogeneity of methods and measures used in existing studies, which limits conclusions that can be reached regarding the effectiveness of interventions. Reviewed studies typically had limited follow-up periods, making it difficult to assess the sustainability of effects. Further, there is a lack of studies that address the complex context within which interventions are implemented and evaluated, and little is known about the cost-effectiveness of interventions. Identified gaps speak to the need for a more holistic approach to sources of sugars beyond SSBs, consensus on measures and methods, attention to the implementation of interventions in relation to context, and careful monitoring to identify intended and unintended consequences.

Heteromeric acid-sensing ion channels (ASICs) composed of ASIC2b and ASIC1a display novel channel properties and contribute to acidosis-induced neuronal death.

Acid-sensing ion channel (ASIC) subunits associate to form homomeric or heteromeric proton-gated ion channels in neurons throughout the nervous system. The ASIC1a subunit plays an important role in establishing the kinetics of proton-gated currents in the CNS, and activation of ASIC1a homomeric channels induces neuronal death after local acidosis that accompanies cerebral ischemia. The ASIC2b subunit is expressed in the brain in a pattern that overlaps ASIC1a, yet the contribution of ASIC2b has remained elusive. We find that coexpression of ASIC2b with ASIC1a in Xenopus oocytes results in novel proton-gated currents with properties distinct from ASIC1a homomeric channels. In particular, ASIC2b/1a heteromeric channels are inhibited by the nonselective potassium channel blockers tetraethylammonium and barium. In addition, steady-state desensitization is induced at more basic pH values, and Big Dynorphin sensitivity is enhanced in these unique heteromeric channels. Cultured hippocampal neurons show proton-gated currents consistent with ASIC2b contribution, and these currents are lacking in neurons from mice with an ACCN1 (ASIC2) gene disruption. Finally, we find that these ASIC2b/1a heteromeric channels contribute to acidosis-induced neuronal death. Together, our results show that ASIC2b confers unique properties to heteromeric channels in central neurons. Furthermore, these data indicate that ASIC2, like ASIC1, plays a role in acidosis-induced neuronal death and implicate the ASIC2b/1a subtype as a novel pharmacological target to prevent neuronal injury after stroke.

Dopamine receptor 1 localizes to neuronal cilia in a dynamic process that requires the Bardet-Biedl syndrome proteins.

Primary cilia are nearly ubiquitous cellular appendages that provide important sensory and signaling functions. Ciliary dysfunction underlies numerous human diseases, collectively termed ciliopathies. Primary cilia have distinct functions on different cell types and these functions are defined by the signaling proteins that localize to the ciliary membrane. Neurons throughout the mammalian brain possess primary cilia upon which certain G protein-coupled receptors localize. Yet, the precise signaling proteins present on the vast majority of neuronal cilia are unknown. Here, we report that dopamine receptor 1 (D1) localizes to cilia on mouse central neurons, thereby implicating neuronal cilia in dopamine signaling. Interestingly, ciliary localization of D1 is dynamic, and the receptor rapidly translocates to and from cilia in response to environmental cues. Notably, the translocation of D1 from cilia requires proteins mutated in the ciliopathy Bardet-Biedl syndrome (BBS), and we find that one of the BBS proteins, Bbs5, specifically interacts with D1.

Identification of a calcium permeable human acid-sensing ion channel 1 transcript variant.

The acid-sensing ion channels (ASICs) are proton-gated cation channels activated when extracellular pH declines. In rodents, the Accn2 gene encodes transcript variants ASIC1a and ASIC1b, which differ in the first third of the protein and display distinct channel properties. In humans, ACCN2 transcript variant 2 (hVariant 2) is homologous to mouse ASIC1a. In this article, we study two other human ACCN2 transcript variants. Human ACCN2 transcript variant 1 (hVariant 1) is not present in rodents and contains an additional 46 amino acids directly preceding the proposed channel gate. We report that hVariant 1 does not produce proton-gated currents under normal conditions when expressed in heterologous systems. We also describe a third human ACCN2 transcript variant (hVariant 3) that is similar to rodent ASIC1b. hVariant 3 is more abundantly expressed in dorsal root ganglion compared with brain and shows basic channel properties analogous to rodent ASIC1b. Yet, proton-gated currents from hVariant 3 are significantly more permeable to calcium than either hVariant 2 or rodent ASIC1b, which shows negligible calcium permeability. hVariant 3 also displays a small acid-dependent sustained current. Such a sustained current is particularly intriguing as ASIC1b is thought to play a role in sensory transduction in rodents. In human DRG neurons, hVariant 3 could induce sustained calcium influx in response to acidic pH and make a major contribution to acid-dependent sensations, such as pain.

Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project.

We report the generation and analysis of functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a number of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in several major areas. First, our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another. Second, systematic examination of transcriptional regulation has yielded new understanding about transcription start sites, including their relationship to specific regulatory sequences and features of chromatin accessibility and histone modification. Third, a more sophisticated view of chromatin structure has emerged, including its inter-relationship with DNA replication and transcriptional regulation. Finally, integration of these new sources of information, in particular with respect to mammalian evolution based on inter- and intra-species sequence comparisons, has yielded new mechanistic and evolutionary insights concerning the functional landscape of the human genome. Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function.