Brown Fat Paucity Due to Impaired BMP Signaling Induces Compensatory Browning of White Fat

Summary Maintenance of body temperature is essential for survival of homeotherms. Brown adipose tissue (BAT) is a specialized fat tissue that is dedicated to thermoregulation1. Due to its remarkable capacity to dissipate stored energy and its demonstrated presence in adult humans2-5, BAT holds great promise for the treatment of obesity and metabolic syndrome1. Rodent data suggest the existence of two types of brown fat cells: the constitutive BAT (cBAT), which is of embryonic origin and anatomically located in the interscapular region of mice, and the recruitable BAT (rBAT) that resides within white adipose tissue (WAT)6 and skeletal muscle7, that has alternatively been called beige8, brite9, or inducible BAT10. Bone morphogenetic proteins (BMPs) regulate the formation and thermogenic activity of BAT10-12. We here provide evidence for a systemically active regulatory mechanism that serves to control whole body BAT-activity for thermoregulation and energy homeostasis. Genetic ablation of type 1A BMP-receptor (Bmpr1A) in brown adipogenic progenitor cells leads to a severe paucity of cBAT. This in turn increases sympathetic input to WAT, thereby promoting the formation of rBAT within white fat depots. This previously unknown compensatory mechanism, aimed at restoring total brown fat-mediated thermogenic capacity in the body, is sufficient to maintain normal temperature homeostasis and resistance to diet-induced obesity. These data suggest an important physiological cross-talk between the constitutive and recruitable brown fat cells. This sophisticated regulatory mechanism of body temperature may participate in the control of energy balance and metabolic disease

Think globally, measure locally: The MIREN standardized protocol for monitoring plant species distributions along elevation gradients

Climate change and other global change drivers threaten plant diversity in mountains worldwide. A widely documented response to such environmental modifications is for plant species to change their elevational ranges. Range shifts are often idiosyncratic and difficult to generalize, partly due to variation in sampling methods. There is thus a need for a standardized monitoring strategy that can be applied across mountain regions to assess distribution changes and community turnover of native and non-native plant species over space and time. Here, we present a conceptually intuitive and standardized protocol developed by the Mountain Invasion Research Network (MIREN) to systematically quantify global patterns of native and non-native species distributions along elevation gradients and shifts arising from interactive effects of climate change and human disturbance. Usually repeated every five years, surveys consist of 20 sample sites located at equal elevation increments along three replicate roads per sampling region. At each site, three plots extend from the side of a mountain road into surrounding natural vegetation. The protocol has been successfully used in 18 regions worldwide from 2007 to present. Analyses of one point in time already generated some salient results, and revealed region-specific elevational patterns of native plant species richness, but a globally consistent elevational decline in non-native species richness. Non-native plants were also more abundant directly adjacent to road edges, suggesting that disturbed roadsides serve as a vector for invasions into mountains. From the upcoming analyses of time series, even more exciting results can be expected, especially about range shifts. Implementing the protocol in more mountain regions globally would help to generate a more complete picture of how global change alters species distributions. This would inform conservation policy in mountain ecosystems, where some conservation policies remain poorly implemented.EEA BarilocheFil: Haider, Sylvia. German Centre for Integrative Biodiversity Research; AlemaniaFil: Haider, Sylvia. Martin Luther University. Institute of Biology. Geobotany and Botanical Garden; AlemaniaFil: Lembrechts, Jonas Johan. University of Antwerp. Centre of Excellence Plants and Ecosystems (PLECO); BélgicaFil: McDougall, Keith. Department of Planning, Industry and Environment; AustraliaFil: Pauchard, Aníbal. Universidad de Concepción. Facultad de Ciencias Forestales. Laboratorio de Invasiones Biológicas; ChileFil: Pauchard, Aníbal. Institute of Ecology and Biodiversity (IEB); ChileFil: Alexander, Jake M. Institute of Integrative Biology; SuizaFil: Barros, Agustina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico. Instituto Argentino de Nivología y Glaciología y Ciencias Ambientales (IANIGLA); ArgentinaFil: Cavieres, Lohengrin A. Universidad de Concepción. Facultad de Ciencias Naturales y Oceanográficas. Departamento de Botánica; ChileFil: Cavieres, Lohengrin A. Institute of Ecology and Biodiversity (IEB); ChileFil: Rashid, Irfan. University of Kashmir. Department of Botany; IndiaFil: Rew, Lisa J. Montana State University. Department of Land Resource and Environmental Sciences; Estados UnidosFil: Aleksanyan, Alla. Institute of Botany aft. A.L. Takhtajyan NAS RA. Department of Geobotany and Plant Ecophysiology; ArmeniaFil: Aleksanyan, Alla. Armenian National Agrarian University. Chair of Biology and Biotechnologies; ArmeniaFil: Dimarco, Romina Daniela. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Bariloche. Instituto de Investigaciones Forestales y Agropecuarias Bariloche. Grupo de Ecología de Poblaciones de Insectos; ArgentinaFil: Dimarco, Romina Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones Forestales y Agropecuarias Bariloche. Grupo de Ecología de Poblaciones de Insectos; ArgentinaFil: Dimarco, Romina Daniela. University of Houston. Department of Biology and Biochemistry; Estados UnidosFil: Seipel, Tim. Montana State University. Department of Land Resource and Environmental Sciences; Estados Unido

Mapping review of interventions to reduce the use of restrictive practices in children and young people's institutional settings: The CONTRAST study

Restrictive practices are often used harmfully with children in institutional settings. Interventions to reduce their use do not appear to have been mapped systematically. Using environmental scanning, we conducted a broad-scope mapping review of English language academic databases, websites and social media, using systematic methods. Included records (N = 121) were mostly from the United States and contained details of 82 different interventions. Children's participation was limited. Reporting quality was inconsistent, which undermined claims of effectiveness. Overall, despite a multitude of interventions, evidence is limited. Leaders should consider the evidence, including children's perspectives, before introducing poorly understood interventions into children's settings

Components of interventions to reduce restrictive practices with children and young people in institutional settings: the Contrast systematic mapping review

Background Incidents in which children or young people experience severe distress or harm or cause distress or harm to others occur frequently in children and young people’s institutional settings. These incidents are often managed using restrictive practices, such as restraint, seclusion, sedation or constant observation; however, these also present significant risks of physical and psychological harm to children and young people as well as staff. Numerous interventions aim to reduce the use of restrictive techniques, but research is hampered by limited attention to specific intervention components. The behavior change technique taxonomy may improve reporting by providing a common language for specifying the content and mechanisms of behaviour change. This study aimed to identify, standardise and report the effectiveness of components of interventions to reduce restrictive practices in children and young people’s institutional settings. Objectives To map interventions aimed at reducing restrictive practices in children and young people’s institutional settings internationally, to conduct behaviour change technique analysis of intervention components, to identify process elements, and to explore effectiveness evidence to identify promising behaviour change techniques and compare the results with those found in adult psychiatric inpatient settings in a companion review. Design Systematic mapping review with programme content coding using the behavior change technique taxonomy. Review methods Eleven relevant English-language health and social care research databases 1989–2019 [including Applied Social Sciences Index (ASSIA), Criminal Justice Abstracts, Educational Resources Information Center (ERIC), MEDLINE and PsycInfo®], grey literature and social media were searched during 2019 (updated January 2020). Data extraction, guided by Workgroup for Intervention Development and Evaluation Research (WIDER), Cochrane Library and theory coding scheme recommendations, included intervention characteristics and study design and reporting. Screening and quality appraisal used the Mixed Methods Appraisal Tool. The behavior change technique taxonomy was applied systematically, and interventions were coded for behaviour change technique components. Outcomes data were then related back to these components. Results There were 121 records, including 76 evaluations. Eighty-two interventions, mostly multicomponent, were identified. Evaluation approaches commonly used a non-randomised design. There were no randomised controlled trials. Behaviour change techniques from 14 out of a possible 16 clusters were detected. Four clusters (i.e. goals and planning, antecedents, shaping knowledge, and feedback and monitoring) contained the majority of identified behaviour change techniques and were detected in over half of all interventions. Two clusters (i.e. self-belief and covert learning) contained no identified behaviour change techniques. The most common setting in which behaviour change techniques were found was ‘mental health’. The most common procedure focused on staff training. The two most common behaviour change techniques were instruction on how to perform the behaviour and restructuring the social environment. Promising behaviour change techniques included instruction on how to perform the behaviour, restructuring the social environment, feedback on outcomes of behaviour and problem-solving. Compared with the companion review, service user perspectives were more sparse and there was more interest in trauma-informed approaches. Effectiveness evidence, range of interventions and reporting were broadly similar. Limitations Poor reporting may have prevented detection of some behaviour change techniques. The finding that the evidence was weak restricted the feasibility of examining behaviour change technique effectiveness. Literature searches were restricted to English-language sources. Conclusions This study generated, to our knowledge, the first review of evidence on the content and effectiveness of interventions to reduce restrictive practices in children and young people’s institutional settings. Interventions tend to be complex, reporting is inconsistent and robust evaluation data are limited, but some behaviour change techniques seem promising. Future work Promising behaviour change techniques could be further explored. Better evidence could help address the urgent need for effective strategies. Study registration This study is registered as PROSPERO CRD42019124730. Funding This project was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme and will be published in full in Health and Social Care Delivery Research; Vol. 10, No. 8. See the NIHR Journals Library website for further project information. </jats:sec

A collaboratively produced model of service design for children and young people with common mental health problems

Background: Little is known about the effectiveness of, and implementation complexities associated with, service delivery models for children and young people (CYP) experiencing ‘common’ mental health problems such as anxiety, depression, behavioural difficulties and self-harm. This paper outlines how a model for high-quality service design for this population group was developed by identifying available services, their effectiveness, cost-effectiveness and acceptability, and the barriers and enablers to access. Methods: Sequential, mixed-methods design, combining evidence syntheses (scoping and integrative reviews of the international literature) with primary research (a collective case study in England and Wales). Data from these two elements were collaboratively synthesised in a subsequent model-building phase. Results: The scoping review yielded a service model typology. The integrative review found effectiveness evidence only for four models: collaborative care (the only service model to also have cost-effectiveness evidence), outreach approaches, brief intervention services and an organisational framework called ‘Availability, Responsiveness and Continuity’. No service model seemed more acceptable than others. Three case study themes were identified: pathways to support; service engagement; and learning and understanding. The model-building phase identified rapid access, learning self-care skills, individualised support, clear information, compassionate and competent staff and aftercare planning as core characteristics of high-quality services. These characteristics were underpinned by four organisational qualities: values that respect confidentiality; engagement and involvement; collaborative relationships; and a learning culture. Conclusions: A consistent organisational evidence-base for service design and delivery in CYP’s mental health spanning many years appears to have had little impact on service provision in England and Wales. Rather than impose – often inflexible and untested – specific local or national models or frameworks, those commissioning, designing and delivering mental health services for CYP should (re)focus on already known, fundamental components necessary for high-quality services. These fundamental components have been integrated into a collaboratively produced general model of service design for CYP with common mental health problems. While this general model is primarily focused on British service provision, it is broad enough to have utility for international audiences

Democratization and foreign policy in Southeast Asia: the case of the ASEAN Inter-Parliamentary Myanmar Caucus

This is an Author's Accepted Manuscript of an article published in Cambridge Review of International Affairs Vol. 22, Iss. 3, 2009 as published in the CAMBRIDGE REVIEW OF INTERNATIONAL AFFAIRS, 2009, copyright Taylor & Francis, available online at: http://www.tandfonline.com/10.1080/09557570903104008

Think globally, measure locally: The MIREN standardized protocol for monitoring plant species distributions along elevation gradients

Climate change and other global change drivers threaten plant diversity in mountains worldwide. A widely documented response to such environmental modifications is for plant species to change their elevational ranges. Range shifts are often idiosyncratic and difficult to generalize, partly due to variation in sampling methods. There is thus a need for a standardized monitoring strategy that can be applied across mountain regions to assess distribution changes and community turnover of native and non-native plant species over space and time. Here, we present a conceptually intuitive and standardized protocol developed by the Mountain Invasion Research Network (MIREN) to systematically quantify global patterns of native and non-native species distributions along elevation gradients and shifts arising from interactive effects of climate change and human disturbance. Usually repeated every five years, surveys consist of 20 sample sites located at equal elevation increments along three replicate roads per sampling region. At each site, three plots extend from the side of a mountain road into surrounding natural vegetation. The protocol has been successfully used in 18 regions worldwide from 2007 to present. Analyses of one point in time already generated some salient results, and revealed region-specific elevational patterns of native plant species richness, but a globally consistent elevational decline in non-native species richness. Non-native plants were also more abundant directly adjacent to road edges, suggesting that disturbed roadsides serve as a vector for invasions into mountains. From the upcoming analyses of time series, even more exciting results can be expected, especially about range shifts. Implementing the protocol in more mountain regions globally would help to generate a more complete picture of how global change alters species distributions. This would inform conservation policy in mountain ecosystems, where some conservation policies remain poorly implemented

Ten people‐centered rules for socially sustainable ecosystem restoration

As the UN Decade on Ecosystem Restoration begins, there remains insufficient emphasis on the human and social dimensions of restoration. The potential that restoration holds for achieving both ecological and social goals can only be met through a shift toward people-centered restoration strategies. Toward this end, this paper synthesizes critical insights from a special issue on “Restoration for whom, by whom” to propose actionable ways to center humans and social dimensions in ecosystem restoration, with the aim of generating fair and sustainable initiatives. These rules respond to a relative silence on socio-political issues in di Sacco et al.'s “Ten golden rules for reforestation to optimize carbon sequestration, biodiversity recovery and livelihood benefits” on socio-political issues and offer complementary guidance to their piece. Arranged roughly in order from pre-intervention, design/initiation, implementation, through the monitoring, evaluation and learning phases, the 10 people-centered rules are: (1) Recognize diversity and interrelations among stakeholders and rightsholders'; (2) Actively engage communities as agents of change; (3) Address socio-historical contexts; (4) Unpack and strengthen resource tenure for marginalized groups; (5) Advance equity across its multiple dimensions and scales; (6) Generate multiple benefits; (7) Promote an equitable distribution of costs, risks, and benefits; (8) Draw on different types of evidence and knowledge; (9) Question dominant discourses; and (10) Practice inclusive and holistic monitoring, evaluation, and learning. We contend that restoration initiatives are only tenable when the issues raised in these rules are respectfully addressed

Automated Equivalence Checking of Switch Level Circuits

A chip that is required to meet strict operating criteria in terms of speed, power, or area is commonly custom designed at the switch level. Traditional techniques for verifying these designs, based on simulation, are expensive in terms of resources and cannot completely guarantee correct operation. Formal verification methods, on the other hand, provide for a complete proof of correctness, and require less effort to setup. This paper presents Motorola&apos;s Switch Level Verification (SLV) tool, which employs detailed switch level analysis to model the behavior of MOS transistors and obtain an equivalent RTL model. This tool has been used for equivalence checking at the switch level for several years within Motorola for the PowerPC, M*Core and DSP custom blocks. We focus on the novel techniques employed in SLV, particularly in the areas of pre-charged and sequential logic analysis, and provide details on the automated and integrated equivalence checking flow in which the tool is used

Remnants of ancestral larval eyes in an eyeless mollusk?:Molecular characterization of photoreceptors in the scaphopod Antalis entalis

BACKGROUND: Eyes have evolved and been lost multiple times during animal evolution, however, the process of eye loss has only been reconstructed in a few cases. Mollusks exhibit eyes as varied as the octopod camera eye or the gastropod cup eye and are ideal systems for studying the evolution of eyes, photoreceptors, and opsins.RESULTS: Here, we identify genes related to photoreceptor formation and function in an eyeless conchiferan mollusk, the scaphopod Antalis entalis, and investigate their spatial and temporal expression patterns during development. Our study reveals that the scaphopod early mid-stage trochophore larva has putative photoreceptors in a similar location and with a similar gene expression profile as the trochophore of polyplacophoran mollusks. The apical and post-trochal putative photoreceptors appear to co-express go-opsin, six1/2, myoV, and eya, while expression domains in the posterior foot and pavilion (posterior mantle opening) show co-expression of several other candidate genes but not go-opsin. Sequence analysis reveals that the scaphopod Go-opsin amino acid sequence lacks the functionally important lysine (K296; Schiff base) in the retinal-binding domain, but has not accumulated nonsense mutations and still exhibits the canonical G-protein activation domain.CONCLUSIONS: The scaphopod Go-opsin sequence reported here is the only known example of a bilaterian opsin that lacks lysine K296 in the retinal-binding domain. Although this may render the Go-opsin unable to detect light, the protein may still perform sensory functions. The location, innervation, development, and gene expression profiles of the scaphopod and polyplacophoran apical and post-trochal photoreceptors suggest that they are homologous, even though the scaphopod post-trochal photoreceptors have degenerated. This indicates that post-trochal eyes are not a polyplacophoran apomorphy but likely a molluscan synapomorphy lost in other mollusks. Scaphopod eye degeneration is probably a result of the transition to an infaunal life history and is reflected in the likely functional degeneration of Go-opsin, the loss of photoreceptor shielding pigments, and the scarce expression of genes involved in phototransduction and eye development. Our results emphasize the importance of studying a phylogenetically broad range of taxa to infer the mechanisms and direction of body plan evolution.</p