Emerging Topics in Life Sciences最新文献

Asymmetric unilamellar vesicles are aqueous bodies surrounded by two dissimilar leaflets made from lipids, polymers, or both. They are great models for cell membranes and attractive vehicles in potential biomedicine applications. Despite their promise, asymmetric unilamellar vesicles are not widely studied or adopted in applications. This is largely due to the complexity in generating asymmetric membranes. Recent technical advances in microfluidics have opened doors to high throughput fabrication of asymmetric unilamellar vesicles. In this review, we focus on microfluidic methods for generating asymmetric lipid vesicles, with two dissimilar lipid leaflets, and asymmetric lipid-polymer vesicles, with one lipid leaflet and one polymer leaflet. We also review a few standard non-microfluidic methods for generating asymmetric vesicles. We hope to highlight the improved capability in obtaining asymmetric vesicles through a variety of methods and encourage the wider scientific community to adopt some of these for their own work.

The interaction between the actin cytoskeleton and the plasma membrane in eukaryotic cells is integral to a large number of functions such as shape change, mechanical reinforcement and contraction. These phenomena are driven by the architectural regulation of a thin actin network, directly beneath the membrane through interactions with a variety of binding proteins, membrane anchoring proteins and molecular motors. An increasingly common approach to understanding the mechanisms that drive these processes is to build model systems from reconstituted lipids, actin filaments and associated actin-binding proteins. Here we review recent progress in this field, with a particular emphasis on how the actin cytoskeleton provides mechanical reinforcement, drives shape change and induces contraction. Finally, we discuss potential future developments in the field, which would allow the extension of these techniques to more complex cellular processes.

This special issue of Emerging Topics in Life Sciences presents a selection of reviews that give insight into the vast array of research taking place in the fields of soft matter and biophysics, and where these two intersect. The reviews here cover the full range from the fundamentals of how biological systems may have assembled to how we can use this insight to develop and exploit new biomaterials for the future, all informed through the lens of the physical sciences. This issue has been both written and edited by early career researchers, highlighting the cutting-edge contributions that this generation of researchers is bringing to the field.

Compulsive behavior is observed in different neuropsychiatric disorders such as Obsessive-Compulsive Disorder (OCD), anxiety, phobia, schizophrenia and addiction. Compulsivity has been proposed as a transdiagnostic symptom, where the Research Domain Criteria (RDoC) strategy could help to understand its neuropsychological basis for a better understanding, and development of therapeutic and preventive strategies. However, research on compulsivity has been focused on the cognitive control domain, and the contribution of an altered negative valence system has been less considered. In this review, we collate the main findings in an animal model of compulsivity, the high drinker (HD) rats selected by Schedule-Induced Polydipsia (SIP) regarding these two research domains. This preclinical model of compulsivity has shown a phenotype characterized by a lack of behavioral inhibition, impulsive decision-making and cognitive inflexibility. Moreover, the results in compulsive HD rats, suggests that there is also a relevant alteration in the emotional dimension, linked to the negative valence system domain, as for example by: the increased perseverative responses in a withdrawal condition, associated with the behavioral construct of frustrative non-reward; and an inhibition or extinction deficit in memory retrieval associated with an alteration in the behavioral response to sustained threat. However, the precise nature of the link between these shared altered domains, cognitive control and negative valence system, remains unknown. These results point towards relevant behavioral aspects of the compulsive phenotype that should be taken into account when studying the vulnerability to compulsivity that could help in the development of a better transdiagnostic assessment, preventive and therapeutic strategies.

Activation of the fear system is adaptive, and protects individuals from impending harm; yet, exacerbation of the fear system is at the source of anxiety-related disorders. Here, we briefly review the 'why' and 'how' of fear, with an emphasis on models that encapsulate the elegant complexity of rodents' behavioral responding in the face of impending harm, and its relevance to developing treatment interventions.

Although the hey-day of motivation as an area of study is long past, the issues with which motivational theorists grappled have not grown less important: i.e. the development of deterministic explanations for the particular tuning of the nervous system to specific changes in the internal and external environment and the organisation of adaptive behavioural responses to those changes. Here, we briefly elaborate these issues in describing the structure and function of the 'positive valence system'. We describe the origins of adaptive behaviour in an ascending arousal system, sensitive to peripheral regulatory changes, that modulates and activates various central motivational states. Associations between these motivational states and sensory inputs underlie evaluative conditioning and generate the representation of the 'unconditioned' stimuli fundamental to Pavlovian conditioning. As a consequence, associations with these stimuli can generate Pavlovian conditioned responses through the motivational control of stimulus event associations with sensory and affective components of the valence system to elicit conditioned orienting, consummatory and preparatory responses, particularly the affective responses reflecting Pavlovian excitation and inhibition, arousal and reinforcement, the latter used to control the formation of habits. These affective processes also provoke emotional responses, allowing the externalisation of positive valence in hedonic experience to generate the goal or reward values that mediate goal-directed action. Together these processes form the positive valence system, ensure the maintenance of adaptive behaviour and, through the association of sensory events and emotional responses through consummatory experience, provide the origins of reward.

Behavioural reactivity to potential threat is used to experimentally refine models of anxiety symptoms in rodents. We present a short review of the literature tying the most commonly used tasks to model anxiety symptoms to functional recruitment of bed nucleus of the stria terminalis circuits (BNST). Using a review of studies that investigated the role of the BNST in anxiety-like behaviour in rodents, we flag the certain challenges for the field. These stem from inconsistent methods of reporting the neuroanatomical BNST subregions and the interpretations of specific behaviour across a wide variety of tasks as 'anxiety-like'. Finally, to assist in interpretation of the findings, we discuss the potential interactions between typically used 'anxiety' tasks of innate behaviour that are potentially modulated by the social and individual experience of the animal.

Cognitive dysfunction, particularly attentional impairment, is a core feature of many psychiatric disorders, yet is inadequately addressed by current treatments. Development of targeted therapeutics for the remediation of attentional deficits requires knowledge of underlying neurocircuit, cellular, and molecular mechanisms that cannot be directly assayed in the clinic. This level of detail can only be acquired by testing animals in cross-species translatable attentional paradigms, in combination with preclinical neuroscience techniques. The 5-choice continuous performance test (5C-CPT) and rodent continuous performance test (rCPT) represent the current state of the art of preclinical assessment of the most commonly studied subtype of attention: sustained attention, or vigilance. These tasks present animals with continuous streams of target stimuli to which they must respond (attention), in addition to non-target stimuli from which they must withhold responses (behavioral inhibition). The 5C-CPT and rCPT utilize the same measures as gold-standard clinical continuous performance tests and predict clinical efficacy of known pro-attentional drugs. They also engage common brain regions across species, although efforts to definitively establish neurophysiological construct validity are ongoing. The validity of these tasks as translational vigilance assessments enables their use in characterizing the neuropathology underlying attentional deficits of animal models of psychiatric disease, and in determining therapeutic potential of drugs ahead of clinical testing. Here, we briefly review the development and validation of such tests of attentional functioning, as well as the data they have generated pertaining to inattention, disinhibition, and impulsivity in psychiatric disorders.

This review describes the relationship between the National Institute of Mental Health (U.S.A.) Research Domain Criteria (RDoC) Negative Valence System related to responses to threat and the Predatory Imminence Continuum model of antipredator defensive behavior. While the original RDoC constructs of Potential Threat (anxiety) and Acute Threat (fear) fit well with the pre-encounter and post-encounter defense modes of the predatory imminence model, the Sustained Threat construct does not. Early research on the bed nuclei of the stria terminalis (BST) suggested that when fear responding needed to be sustained for a prolonged duration this region was important. However, follow-up studies indicated that the BST becomes critical not because responses needed to be sustained but rather when the stimuli triggering fear were more difficult to learn about, particularly when aversive stimuli were difficult to accurately predict. Instead, it is argued that the BST and the hippocampus act to expand the range of conditions that can trigger post-encounter defense (Acute Threat). It is further suggested that sustained threat refers to situations where the predatory imminence continuum becomes distorted causing defensive behavior to intrude into times when organisms should be engaging in other adaptive behaviors. Stress is seen as something that can cause a long-term disturbance of the continuum and this disturbance is a state of sustained threat.

Mental health disorders affect a substantial proportion of the worldwide population, and currently available treatments do not work for all affected individuals. Understanding the psychological and biological mechanisms that underlie mental health disorders will facilitate treatment development, and the use of translational animal models is potentially transformative for this. Structured around the US National Institute of Mental Health's 'Research Domain Criteria' (RDoC) approach, this special issue showcases reviews that consider how animal models can best be used to understand and treat the processes that go awry in mental health disorders.