Adaptive Feedback Control in Human Reaching Adaptation to Force Fields

Sensorimotor adaptation is a central function of the nervous system, as it allows humans and other animals to flexibly anticipate their interaction with the environment. In the context of human reaching adaptation to force fields, studies have traditionally separated feedforward (FF) and feedback (FB) processes involved in the improvement of behavior. Here, we review computational models of FF adaptation to force fields and discuss them in light of recent evidence highlighting a clear involvement of feedback control. Instead of a model in which FF and FB mechanisms adapt in parallel, we discuss how online adaptation in the feedback control system can explain both trial-by-trial adaptation and improvements in online motor corrections. Importantly, this computational model combines sensorimotor control and short-term adaptation in a single framework, offering novel perspectives for our understanding of human reaching adaptation and control.

Sustainability and Finance: Environment, Social, and Governance (ESG)

Finance plays a central function in the business world. From being included in small and specialized funds, Environment, Social, and Governance (ESG) and socially responsible investment (SRI) have become part of the mainstream for investors and analysts. In this chapter, I will address what ESG, SRI, environmental and social risk assessment, and ethical investment are about, as well as different investment strategies taking these into account. Further, dilemmas that arise are introduced such as what is a sustainable sector or product and how this differs based on the values of individuals. The move from addressing sustainability issues as a risk reduction activity to a business opportunity is discussed. Finally, the Norwegian Pension Fund, the world’s largest fund, is used as an example to illustrate product-based and conduct-based exclusions in practice.

‘It is unbelievable how many come to us’:

In advanced, digitalized democratic communities the demands for literacy are a prerequisite for engagement and inclusion, at the same time different forms of divides are omnipresent. By providing access and qualified support to all citizens, public libraries play a central function in the building of democratic and inclusive local communities, being increasingly relied upon by governments to deliver access and support for e-services. Based on a case study of community library services in Sweden, Östergötland, this paper aims to study digital inclusion as reflected in daily practices through the perspective of librarians. In this paper we argue that while advancing digitalisation involves opening of new access and engagement opportunities through empowering digital tools and Internet, it also involves different challenges of exclusion for those who cannot use, choose not to use or have other needs

Outrage and the Bounds of Empathy

Often, when we are angry, we are angry at someone who has hurt us. Our anger is a protest against a perceived mistreatment, and its function is to hold the person accountable for their offense. The anger involves a demand for some sort of change or response: that the hurt be acknowledged, that the relationship be repaired, that the offending party reform in some way. Call this “reform” anger. A different sort of attitude, often contrasted with reform anger, is hatred. Hatred is also a response to a perceived mistreatment, and it also demands some sort of change. Unlike reform anger, however, its goal is not to repair the relationship. Instead, its goal is destruction, to remove the offending party. In this paper, I develop and defend an account of a third sort of attitude, which I call “outrage” anger, that is distinct from both reform anger and hatred. I argue that outrage anger has an important role to play in the context of political injustice, but that it also comes with significant costs. In §1, I introduce outrage anger, and contrast it with reform anger. In §2, drawing on the work of Maria Lugones, I develop an account of outrage anger as a second-order attitude directed at the state of affairs in which a violation is not fully intelligible as the violation it is. I argue its central function is a kind of psychological boundary setting: it closes off the victim’s ability to feel empathy for their abuser. In §3, I show that the benefits of outrage come with serious costs, both epistemic and prudential. In §4, I make some suggestions about when, and for whom, the benefits of outrage outweigh the costs.

Religious Rituals and Logical Thought in Durkheim

In The Elementary Forms of Religious Life, ritual has a central function in Durkheim’s argument. It is on its redefinition that the constitution of sacred things rests, in relation to the constitution of the group itself and to the formation of categories of thought. In this study, we restore the basis of this conception: the interpretation of the ritual of the intichiuma, and more particularly its mimetic dimension, which prevails over its sacrificial dimension. The relationship between practice and objective thought then turns out to be the touchstone of the concept of the sacred developed by Durkheim.

Angiotensin-converting enzyme governs endogenous opioid signaling and synaptic plasticity in nucleus accumbens

Angiotensin-converting enzyme (ACE) regulates blood pressure by cleaving angiotensin I to produce angiotensin II. In the brain, ACE is expressed at uniquely high levels in the striatonigral pathway, but its central function remains poorly understood. We find that ACE degrades an unconventional enkephalin heptapeptide, Met-enkephalin-Arg-Phe, in the nucleus accumbens of mice. ACE inhibition enhanced mu opioid receptor activation by Met-enkephalin-Arg-Phe, causing a cell type-specific long-term depression of glutamate release onto medium spiny projection neurons expressing the Drd1 dopamine receptor. Systemic ACE inhibition was not intrinsically rewarding, but decreased the conditioned place preference caused by fentanyl administration, and enhanced reciprocal social interaction. Our results raise the enticing prospect that central ACE inhibition can boost endogenous opioid signaling for clinical benefit, while mitigating risk of addiction.

Resident vascular endothelial progenitor definition and function: the age of reckoning

The cardiovascular system is composed around the central function of the endothelium that lines the inner surfaces of its vessels. In recent years, the existence of a progenitor population within the endothelium has been validated through the study of endothelial colony-forming cells (ECFCs) in human peripheral blood and certain vascular beds. However, our knowledge on endothelial populations in vivo that can give rise to ECFCs in culture has been limited. In this review we report and analyse recent attempts at describing progenitor populations in vivo from murine studies that reflect the self-renewal and stemness capacity observed in ECFCs. We pinpoint seminal discoveries within the field, which have phenotypically defined, and functionally scrutinised these endothelial progenitors. Furthermore, we review recent publications utilising single-cell sequencing technologies to better understand the endothelium in homeostasis and pathology.

RNA-bound PGC-1α controls gene expression in liquid-like nuclear condensates

Plasticity of cells, tissues, and organs is controlled by the coordinated transcription of biological programs. However, the mechanisms orchestrating such context-specific transcriptional networks mediated by the dynamic interplay of transcription factors and coregulators are poorly understood. The peroxisome proliferator–activated receptor γ coactivator 1α (PGC-1α) is a prototypical master regulator of adaptive transcription in various cell types. We now uncovered a central function of the C-terminal domain of PGC-1α to bind RNAs and assemble multiprotein complexes including proteins that control gene transcription and RNA processing. These interactions are important for PGC-1α recruitment to chromatin in transcriptionally active liquid-like nuclear condensates. Notably, such a compartmentalization of active transcription mediated by liquid–liquid phase separation was observed in mouse and human skeletal muscle, revealing a mechanism by which PGC-1α regulates complex transcriptional networks. These findings provide a broad conceptual framework for context-dependent transcriptional control of phenotypic adaptations in metabolically active tissues.

Stuttering: A Disorder of Energy Supply to Neurons?

Stuttering is a disorder characterized by intermittent loss of volitional control of speech movements. This hypothesis and theory article focuses on the proposal that stuttering may be related to an impairment of the energy supply to neurons. Findings from electroencephalography (EEG), brain imaging, genetics, and biochemistry are reviewed: (1) Analyses of the EEG spectra at rest have repeatedly reported reduced power in the beta band, which is compatible with indications of reduced metabolism. (2) Studies of the absolute level of regional cerebral blood flow (rCBF) show conflicting findings, with two studies reporting reduced rCBF in the frontal lobe, and two studies, based on a different method, reporting no group differences. This contradiction has not yet been resolved. (3) The pattern of reduction in the studies reporting reduced rCBF corresponds to the regional pattern of the glycolytic index (GI; Vaishnavi et al., 2010). High regional GI indicates high reliance on non-oxidative metabolism, i.e., glycolysis. (4) Variants of the gene ARNT2 have been associated with stuttering. This gene is primarily expressed in the brain, with a pattern roughly corresponding to the pattern of regional GI. A central function of the ARNT2 protein is to act as one part of a sensor system indicating low levels of oxygen in brain tissue and to activate appropriate responses, including activation of glycolysis. (5) It has been established that genes related to the functions of the lysosomes are implicated in some cases of stuttering. It is possible that these gene variants result in a reduced peak rate of energy supply to neurons. (6) Lastly, there are indications of interactions between the metabolic system and the dopamine system: for example, it is known that acute hypoxia results in an elevated tonic level of dopamine in the synapses. Will mild chronic limitations of energy supply also result in elevated levels of dopamine? The indications of such interaction effects suggest that the metabolic theory of stuttering should be explored in parallel with the exploration of the dopaminergic theory.

The Role of Post-Translational Modifications of Chemokines by CD26 in Cancer

Chemokines are a large family of small chemotactic cytokines that fulfill a central function in cancer. Both tumor-promoting and -impeding roles have been ascribed to chemokines, which they exert in a direct or indirect manner. An important post-translational modification that regulates chemokine activity is the NH2-terminal truncation by peptidases. CD26 is a dipeptidyl peptidase (DPPIV), which typically clips a NH2-terminal dipeptide from the chemokine. With a certain degree of selectivity in terms of chemokine substrate, CD26 only recognizes chemokines with a penultimate proline or alanine. Chemokines can be protected against CD26 recognition by specific amino acid residues within the chemokine structure, by oligomerization or by binding to cellular glycosaminoglycans (GAGs). Upon truncation, the binding affinity for receptors and GAGs is altered, which influences chemokine function. The consequences of CD26-mediated clipping vary, as unchanged, enhanced, and reduced activities are reported. In tumors, CD26 most likely has the most profound effect on CXCL12 and the interferon (IFN)-inducible CXCR3 ligands, which are converted into receptor antagonists upon truncation. Depending on the tumor type, expression of CD26 is upregulated or downregulated and often results in the preferential generation of the chemokine isoform most favorable for tumor progression. Considering the tight relationship between chemokine sequence and chemokine binding specificity, molecules with the appropriate characteristics can be chemically engineered to provide innovative therapeutic strategies in a cancer setting.