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Critical review of RDoC approaches to the study of motivation with animal models: effort valuation/willingness to work. 用动物模型研究动机的RDoC方法的批判性回顾:努力评估/工作意愿。
IF 3.8 Q1 Medicine Pub Date : 2022-12-09 DOI: 10.1042/ETLS20220008
John D Salamone, Merce Correa

The NIMH research domain criteria (RDoC) approach was instigated to refocus mental health research on the neural circuits that mediate psychological functions, with the idea that this would foster an understanding of the neural basis of specific psychiatric dysfunctions (i.e. 'symptoms and circuits') and ultimately facilitate treatment. As a general idea, this attempt to go beyond traditional diagnostic categories and focus on neural circuit dysfunctions related to specific symptoms spanning multiple disorders has many advantages. For example, motivational dysfunctions are present in multiple disorders, including depression, schizophrenia, Parkinson's disease, and other conditions. A critical aspect of motivation is effort valuation/willingness to work, and several clinical studies have identified alterations in effort-based decision making in various patient groups. In parallel, formal animal models focusing on the exertion of effort and effort-based decision making have been developed. This paper reviews the literature on models of effort-based motivational function in the context of a discussion of the RDoC approach, with an emphasis on the dissociable nature of distinct aspects of motivation. For example, conditions associated with depression and schizophrenia blunt the selection of high-effort activities as measured by several tasks in animal models (e.g. lever pressing, barrier climbing, wheel running). Nevertheless, these manipulations also leave fundamental aspects of hedonic reactivity, food motivation, and reinforcement intact. This pattern of effects demonstrates that the general emphasis of the RDoC on the specificity of the neural circuits mediating behavioral pathologies, and the dissociative nature of these dysfunctions, is a valid concept. Nevertheless, the specific placement of effort-related processes as simply a 'sub-construct' of 'reward processing' is empirically and conceptually problematic. Thus, while the RDoC is an excellent general framework for new ways to approach research and therapeutics, it still needs further refinement.

NIMH研究领域标准(RDoC)方法是为了将精神健康研究的重点重新集中在调节心理功能的神经回路上,其理念是这将促进对特定精神功能障碍的神经基础的理解。“症状和回路”),并最终促进治疗。总的来说,这种尝试超越传统的诊断类别,专注于与多种疾病的特定症状相关的神经回路功能障碍,具有许多优势。例如,动机功能障碍存在于多种疾病中,包括抑郁症、精神分裂症、帕金森病和其他疾病。动机的一个关键方面是努力评估/工作意愿,一些临床研究已经确定了不同患者群体中基于努力的决策的变化。与此同时,研究努力和基于努力的决策的正式动物模型也得到了发展。本文在讨论RDoC方法的背景下,回顾了基于努力的动机功能模型的文献,重点介绍了动机不同方面的可分离性。例如,与抑郁症和精神分裂症相关的条件削弱了对高强度活动的选择,这是通过动物模型中的几个任务(如按杠杆、爬障碍、跑轮子)来衡量的。然而,这些操作也保留了享乐反应、食物动机和强化的基本方面。这种效应模式表明,RDoC普遍强调神经回路介导行为病理的特异性,以及这些功能障碍的解离性,是一个有效的概念。然而,将与努力相关的过程简单地定位为“奖励处理”的“子结构”,在经验和概念上都存在问题。因此,尽管RDoC是研究和治疗新方法的优秀通用框架,但它仍需要进一步完善。
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引用次数: 5
The importance of a multidimensional approach to the preclinical study of major depressive disorder and apathy. 重性抑郁障碍和冷漠的临床前研究的多维方法的重要性。
IF 3.8 Q1 Medicine Pub Date : 2022-12-09 DOI: 10.1042/ETLS20220004
Megan G Jackson, Emma S J Robinson

Both the neuropsychiatric syndrome of apathy and major depressive disorder comprise a heterogenous cluster of symptoms which span multiple behavioural domains. Despite this heterogeneity, there is a tendency in the preclinical literature to conclude a MDD or apathy-like phenotype from a single dimensional behavioural task used in isolation, which may lead to inaccurate phenotypic interpretation. This is significant, as apathy and major depressive disorder are clinically distinct with different underlying mechanisms and treatment approaches. At the clinical level, apathy and major depressive disorder can be dissociated in the negative valence (loss) domain of the Research Domain Criteria. Symptoms of MDD in the negative valence (loss) domain can include an exaggerated response to emotionally salient stimuli and low mood, while in contrast apathy is characterised by an emotionally blunted state. In this article, we highlight how using a single dimensional approach can limit psychiatric model interpretation. We discuss how integrating behavioural findings from both the positive and negative (loss) valence domains of the Research Domain Criteria can benefit interpretation of findings. We focus particularly on behaviours relating to the negative valence (loss) domain, which may be used to distinguish between apathy and major depressive disorder at the preclinical level. Finally, we consider how future approaches using home cage monitoring may offer a new opportunity to detect distinct behavioural profiles and benefit the overall translatability of findings.

两种神经精神综合症的冷漠和重度抑郁症包括一个异质集群的症状跨越多个行为领域。尽管存在这种异质性,但在临床前文献中有一种倾向,即从孤立使用的单一维度行为任务中得出重度抑郁症或冷漠样表型,这可能导致不准确的表型解释。这是很重要的,因为冷漠和重度抑郁症在临床上是不同的,有不同的潜在机制和治疗方法。在临床水平上,冷漠和重性抑郁症可以在研究领域标准的负效价(损失)领域中分离。MDD在负效价(丧失)域的症状包括对情绪显著刺激的夸张反应和情绪低落,而相反,冷漠的特征是情绪迟钝状态。在这篇文章中,我们强调如何使用单一维度的方法可以限制精神病学模型的解释。我们讨论了如何整合来自研究领域标准的正价域和负价域(损失)的行为发现有助于解释研究结果。我们特别关注与负效价(损失)域相关的行为,这可能用于区分冷漠和临床前水平的重度抑郁症。最后,我们考虑了使用家庭笼监测的未来方法如何提供新的机会来检测不同的行为特征,并有利于研究结果的整体可翻译性。
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引用次数: 1
Assessing episodic memory in rodents using spontaneous object recognition tasks. 利用自发物体识别任务评估啮齿动物的外显记忆。
IF 3.8 Q1 Medicine Pub Date : 2022-12-07 DOI: 10.1042/ETLS20220010
Flávio Freitas Barbosa, Rochele Castelo-Branco

Models of episodic memory are successfully established using spontaneous object recognition tasks in rodents. In this review, we present behavioral techniques devised to investigate this type of memory, emphasizing methods based on associations of places and temporal order of items explored by rats and mice. We also provide a review on the areas and circuitry of the medial temporal lobe underlying episodic-like memory, considering that a large number of neurobiology data derived from these protocols. Although spontaneous recognition tasks are commonplace in this field, there is need for careful evaluation of factors affecting animal performance. Such as the ongoing development of tools for investigating the neural basis of memory, efforts should be put in the refinement of experimental designs, in order to provide reliable behavioral evidence of this complex mnemonic system.

利用啮齿动物的自发物体识别任务成功建立了外显记忆模型。在这篇综述中,我们介绍了为研究这类记忆而设计的行为学技术,强调了基于大鼠和小鼠探索的地点关联和项目时间顺序的方法。考虑到大量的神经生物学数据都来自于这些方案,我们还对内侧颞叶的区域和电路进行了综述,这些区域和电路是类似外显记忆的基础。虽然自发识别任务在这一领域很常见,但仍需要仔细评估影响动物表现的因素。在不断开发用于研究记忆神经基础的工具的同时,还应努力完善实验设计,以便为这一复杂的记忆系统提供可靠的行为证据。
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引用次数: 0
Pathogens transported by plastic debris: does this vector pose a risk to aquatic organisms? 塑料碎片传播的病原体:这种媒介是否对水生生物构成风险?
IF 3.8 Q1 Medicine Pub Date : 2022-12-01 DOI: 10.1042/ETLS20220022
Jake Bowley, Craig Baker-Austin, Steve Michell, Ceri Lewis

Microplastics are small (<5 mm) plastic particles of varying shapes and polymer types that are now widespread global contaminants of marine and freshwater ecosystems. Various estimates suggest that several trillions of microplastic particles are present in our global oceanic system, and that these are readily ingested by a wide range of marine and freshwater species across feeding modes and ecological niches. Here, we present some of the key and pressing issues associated with these globally important contaminants from a microbiological perspective. We discuss the potential mechanisms of pathogen attachment to plastic surfaces. We then describe the ability of pathogens (both human and animal) to form biofilms on microplastics, as well as dispersal of these bacteria, which might lead to their uptake into aquatic species ingesting microplastic particles. Finally, we discuss the role of a changing oceanic system on the potential of microplastic-associated pathogens to cause various disease outcomes using numerous case studies. We set out some key and imperative research questions regarding this globally important issue and present a methodological framework to study how and why plastic-associated pathogens should be addressed.

微塑料很小(
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引用次数: 4
Plastic pollution requires an integrative systems approach to understand and mitigate risk. 塑料污染需要一个综合系统的方法来理解和减轻风险。
IF 3.8 Q1 Medicine Pub Date : 2022-12-01 DOI: 10.1042/ETLS20220018
Winnie Courtene-Jones, Nathaniel J Clark, Richard C Thompson

To date, much effort has been placed on quantifying plastic pollution and understanding its negative environmental effects, arguably to the detriment of research and evaluation of potential interventions. This has led to piecemeal progress in interventions to reduce plastic pollution, which do not correspond to the pace of emissions. For substances that are used on a global scale and identified as hazardous, there is a need to act before irreversible damage is done. For example, the history of dichlorodiphenyltrichloethane's (DDT) use has demonstrated that legacy chemicals with properties of persistence can still be found in the environment despite being first prohibited 50 years ago. Despite the growing evidence of harm, evidence to inform actions to abate plastic pollution lag behind. In part, this is because of the multifaceted nature of plastic pollution and understanding the connections between social, economic and environmental dimensions are complex. As such we highlight the utility of integrative systems approaches for addressing such complex issues, which unites a diversity of stakeholders (including policy, industry, academia and society), and provides a framework to identify to develop specific, measurable and time-bound international policies on plastic pollution and meet the ambitious yet necessary goals of the UN Plastic Treaty.

迄今为止,人们在量化塑料污染和了解其对环境的负面影响方面付出了很多努力,这可能会损害对潜在干预措施的研究和评估。这导致在减少塑料污染的干预措施方面取得了零星的进展,这与排放的速度不相符。对于在全球范围内使用并被确定为危险的物质,有必要在造成不可逆转的损害之前采取行动。例如,使用二氯二苯三氯乙烷(滴滴涕)的历史表明,尽管在50年前首次被禁止,但具有持久性的遗留化学品仍然可以在环境中找到。尽管危害的证据越来越多,但减少塑料污染行动的证据却滞后。在某种程度上,这是因为塑料污染的多面性,以及理解社会、经济和环境层面之间的联系是复杂的。因此,我们强调综合系统方法在解决此类复杂问题方面的效用,它将各种利益相关者(包括政策、行业、学术界和社会)联合起来,并提供一个框架,以确定制定具体、可衡量和有时限的塑料污染国际政策,并实现《联合国塑料条约》雄心勃勃但必要的目标。
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引用次数: 2
From microbes to ecosystems: a review of the ecological effects of biodegradable plastics. 从微生物到生态系统:可生物降解塑料的生态效应综述。
IF 3.8 Q1 Medicine Pub Date : 2022-12-01 DOI: 10.1042/ETLS20220015
Winnie Courtene-Jones, Ana Martínez Rodríguez, Richard D Handy

Biodegradable plastics have been proposed as a potential solution to plastic pollution, as they can be biodegraded into their elemental components by microbial action. However, the degradation rate of biodegradable plastics is highly variable across environments, leading to the potential for accumulation of plastic particles, chemical co-contaminants and/or degradation products. This paper reviews the toxicological effects of biodegradable plastics on species and ecosystems, and contextualises these impacts with those previously reported for conventional polymers. While the impacts of biodegradable plastics and their co-contaminants across levels of biological organisation are poorly researched compared with conventional plastics, evidence suggests that individual-level effects could be broadly similar. Where differences in the associated toxicity may arise is due to the chemical structure of biodegradable polymers which should facilitate enzymatic depolymerisation and the utilisation of the polymer carbon by the microbial community. The input of carbon can alter microbial composition, causing an enrichment of carbon-degrading bacteria and fungi, which can have wider implications for carbon and nitrogen dynamics. Furthermore, there is the potential for toxic degradation products to form during biodegradation, however understanding the environmental concentration and effects of degradation products are lacking. As global production of biodegradable polymers continues to increase, further evaluation of their ecotoxicological effects on organisms and ecosystem function are required.

可生物降解塑料被认为是一种潜在的塑料污染解决方案,因为它们可以通过微生物作用生物降解成它们的基本成分。然而,可生物降解塑料的降解率在不同环境下变化很大,导致塑料颗粒、化学共污染物和/或降解产物积累的可能性。本文综述了生物降解塑料对物种和生态系统的毒理学影响,并将这些影响与先前报道的传统聚合物的影响进行了比较。虽然与传统塑料相比,可生物降解塑料及其共污染物对生物组织各个层面的影响研究很少,但有证据表明,个人层面的影响可能大致相似。相关毒性的差异可能是由于可生物降解聚合物的化学结构,它应该促进酶解聚合和微生物群落对聚合物碳的利用。碳的输入可以改变微生物组成,导致碳降解细菌和真菌的富集,这可能对碳和氮动力学有更广泛的影响。此外,在生物降解过程中有可能形成有毒降解产物,但对降解产物的环境浓度和影响缺乏了解。随着全球可生物降解聚合物产量的不断增加,需要进一步评估其对生物和生态系统功能的生态毒理学影响。
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引用次数: 4
Plastic pollution: the science we need for the planet we want. 塑料污染:我们想要的地球所需要的科学。
IF 3.8 Q1 Medicine Pub Date : 2022-12-01 DOI: 10.1042/ETLS20220019
Winnie Courtene-Jones, Nathaniel J Clark, Richard C Thompson

Plastics are incredibly versatile materials that can bring diverse societal and environmental benefit, yet current practices of production, use and disposal have negative effects on wildlife, the environment and human health leading to growing concern across public, policy makers and industry. This Special Issue in Emerging Topics in Life Sciences describes recent advances in our understanding of the consequences of plastic pollution. In particular, it examines their potential to act as vectors for chemicals and pathogens in the environment; evaluates the effects of plastic pollution on biogeochemical cycling, ecosystem functioning and highlights the potential for enhanced effects in environments that are already subject to substantive changes in their climate. The impacts plastics pose to terrestrial ecosystems including soil communities are described and evaluated, along with evidence of potential issues for human health. With an increase in the production of plastics labelled as 'biodegradable' their context and ecological impacts are reviewed. Finally, we discuss the need to take an integrative, system approach when developing and evaluating solutions to plastic pollution, to achieve the ambitious yet necessary aims of the UN Plastics Treaty.

塑料是一种用途广泛的材料,可以带来各种各样的社会和环境效益,但目前的生产、使用和处置做法对野生动物、环境和人类健康产生了负面影响,导致公众、政策制定者和行业日益关注。本期《生命科学新兴话题》特刊描述了我们对塑料污染后果的理解的最新进展。它特别审查了它们作为环境中化学品和病原体媒介的潜力;评估了塑料污染对生物地球化学循环、生态系统功能的影响,并强调了塑料污染对已经受到气候实质性变化影响的环境的潜在增强影响。对塑料对包括土壤群落在内的陆地生态系统造成的影响进行了描述和评估,并提供了人类健康潜在问题的证据。随着标记为“可生物降解”的塑料生产的增加,他们的背景和生态影响进行了审查。最后,我们讨论了在制定和评估塑料污染解决方案时采取综合系统方法的必要性,以实现《联合国塑料条约》雄心勃勃但必要的目标。
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引用次数: 1
The ecotoxicological consequences of microplastics and co-contaminants in aquatic organisms: a mini-review. 微塑料和共污染物对水生生物的生态毒理学影响:微型综述。
IF 3.4 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2022-12-01 DOI: 10.1042/ETLS20220014
Farhan R Khan, Ana I Catarino, Nathaniel J Clark

Microplastics (MPs, <5 mm in size) are a grave environmental concern. They are a ubiquitous persistent pollutant group that has reached into all parts of the environment - from the highest mountain tops to the depths of the ocean. During their production, plastics have added to them numerous chemicals in the form of plasticizers, colorants, fillers and stabilizers, some of which have known toxicity to biota. When released into the environments, MPs are also likely to encounter chemical contaminants, including hydrophobic organic contaminants, trace metals and pharmaceuticals, which can sorb to plastic surfaces. Additionally, MPs have been shown to be ingested by a wide range of organisms and it is this combination of ingestion and chemical association that gives weight to the notion that MPs may impact the bioavailability and toxicity of both endogenous and exogenous co-contaminants. In this mini-review, we set the recent literature within what has been previously published about MPs as chemical carriers to biota, with particular focus on aquatic invertebrates and fish. We then present a critical viewpoint on the validity of laboratory-to-field extrapolations in this area. Lastly, we highlight the expanding 'microplastic universe' with the addition of anthropogenic particles that have gained recent attention, namely, tire wear particles, nanoplastics and, bio-based or biodegradable MPs, and highlight the need for future research in their potential roles as vehicles of co-contaminant transfer.

微塑料(MPs、
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引用次数: 0
Micro and nano-plastics, a threat to human health? 微塑料和纳米塑料,对人类健康的威胁?
IF 3.8 Q1 Medicine Pub Date : 2022-12-01 DOI: 10.1042/ETLS20220024
Sarah Bastyans, Simon Jackson, Gyorgy Fejer

Micro and nanosize plastic polymers degrading from large plastic compounds are accumulating in the natural environment and expose potential biological threats to human health. These particles are largely persistent and consequently accumulate in the exposed individuals. The presence of microplastics has already been demonstrated in various human organs including the lung, the gastrointestinal system and the blood raising concerns about their possible harmful effects. The chemical composition, size and shape of microplastics as well as their weathering status represent important factors influencing the potential impact of microplastics on tissues. In addition, microplastics can function as vectors for adsorbed chemical compounds and may harbour and deliver live microbial pathogens or their ligands. In vitro and in vivo animal studies demonstrated that microplastics are taken up to cells in a size and cell type dependent manner. Once inside the targeted cell they activate oxidative processes, mitochondrial dysfunction and ER-stress. These molecular processes result in the activation or repression of cell type specific functions and potentially in the induction of cytotoxicity. The microplastic elicited events may result in inflammation, organ damage and fibrosis of the targeted organs as well as in systemic immunological and metabolic conditions. In addition, microplastics may impact on the gut microbiota which may exert further gastrointestinal and systemic metabolic and immunological effects. In this minireview, we evaluate the factors and mechanisms that influence potential microplastic induced cellular and organ pathologies in humans and discuss limitations of current understanding regarding microplastic elicited conditions as well as future perspectives for research.

由大型塑料化合物降解而成的微纳米级塑料聚合物在自然环境中不断积累,对人类健康构成潜在的生物威胁。这些颗粒大部分是持久性的,因此在接触者体内积累。微塑料的存在已经被证明存在于包括肺、胃肠道系统和血液在内的各种人体器官中,这引起了人们对其可能有害影响的担忧。微塑料的化学成分、尺寸和形状及其风化状态是影响微塑料对组织潜在影响的重要因素。此外,微塑料可以作为吸附化合物的载体,并可能窝藏和运送活的微生物病原体或其配体。体外和体内动物研究表明,微塑料以大小和细胞类型依赖的方式被吸收到细胞中。一旦进入目标细胞,它们就会激活氧化过程、线粒体功能障碍和内质网应激。这些分子过程导致细胞类型特异性功能的激活或抑制,并可能诱导细胞毒性。微塑性引发的事件可能导致炎症、器官损伤和靶器官纤维化,以及全身免疫和代谢状况。此外,微塑料还可能影响肠道微生物群,从而进一步发挥胃肠道和全身代谢和免疫作用。在这篇综述中,我们评估了影响潜在微塑料诱导的人类细胞和器官病理的因素和机制,并讨论了目前对微塑料诱发条件的理解的局限性以及未来研究的前景。
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引用次数: 5
Implication of microplastics on soil faunal communities - identifying gaps of knowledge. 微塑料对土壤动物群落的影响——识别知识空白。
IF 3.8 Q1 Medicine Pub Date : 2022-12-01 DOI: 10.1042/ETLS20220023
Bas Boots

There is mounting evidence that plastic and microplastic contamination of soils can affect physico-chemical processes and soil fauna, as has been excellently summarised in many recently published meta-analyses and systematic reviews elsewhere. It has become clear that impacts are highly context dependent on, e.g. polymer type, shape, dose and the soil itself. Most published studies are based on experimental approaches using (semi-)controlled laboratory conditions. They typically focus on one or several representative animal species and their behaviour and/or physiological response - for example, earthworms, but rarely on whole communities of animals. Nevertheless, soil animals are rarely found in isolation and form part of intricate foodwebs. Soil faunal biodiversity is complex, and species diversity and interactions within the soil are very challenging to unravel, which may explain why there is still a dearth of information on this. Research needs to focus on soil animals from a holistic viewpoint, moving away from studies on animals in isolation and consider different trophic levels including their interactions. Furthermore, as evidence obtained from laboratory studies is complemented by relatively few studies done in field conditions, more research is needed to fully understand the mechanisms by which plastic pollution affects soil animals under realistic field conditions. However, field-based studies are typically more challenging logistically, requiring relatively large research teams, ideally of an interdisciplinary nature to maintain long-term field experiments. Lastly, with more alternative, (bio)degradable and/or compostable plastics being developed and used, their effects on soil animals will need to be further researched.

越来越多的证据表明,塑料和微塑料污染会影响土壤的物理化学过程和土壤动物,这在其他地方最近发表的许多荟萃分析和系统综述中得到了很好的总结。很明显,影响高度取决于具体情况,例如聚合物类型、形状、剂量和土壤本身。大多数发表的研究是基于使用(半)控制的实验室条件的实验方法。它们通常关注一种或几种具有代表性的动物物种及其行为和/或生理反应——例如蚯蚓,但很少关注整个动物群落。然而,土壤动物很少被孤立地发现,它们是复杂食物网的一部分。土壤动物多样性是复杂的,土壤中的物种多样性和相互作用是非常具有挑战性的,这可能解释了为什么在这方面仍然缺乏信息。研究需要从整体的角度关注土壤动物,而不是孤立地研究动物,而是考虑不同的营养水平,包括它们之间的相互作用。此外,由于从实验室研究中获得的证据与在实地条件下进行的相对较少的研究相辅相成,因此需要更多的研究来充分了解塑料污染在实际实地条件下影响土壤动物的机制。然而,实地研究通常在后勤上更具挑战性,需要相对较大的研究团队,最好是跨学科性质的团队,以维持长期的实地实验。最后,随着更多可替代的(生物)可降解和/或可堆肥塑料的开发和使用,它们对土壤动物的影响将需要进一步研究。
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引用次数: 4
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