Emotion regulation skills develop substantially across adolescence, a period characterized by emotional challenges and developing regulatory neural circuitry. Adolescence is also a risk period for ...the new onset of anxiety and depressive disorders, psychopathologies which have long been associated with disruptions in regulation of positive and negative emotions. This paper reviews the current understanding of the role of disrupted emotion regulation in adolescent anxiety and depression, describing findings from self-report, behavioral, peripheral psychophysiological, and neural measures. Self-report studies robustly identified associations between emotion dysregulation and adolescent anxiety and depression. Findings from behavioral and psychophysiological studies are mixed, with some suggestion of specific impairments in reappraisal in anxiety. Results from neuroimaging studies broadly implicate altered functioning of amygdala-prefrontal cortical circuitries, although again, findings are mixed regarding specific patterns of altered neural functioning. Future work may benefit from focusing on designs that contrast effects of specific regulatory strategies, and isolate changes in emotional regulation from emotional reactivity. Approaches to improve treatments based on empirical evidence of disrupted emotion regulation in adolescents are also discussed. Future intervention studies might consider training and measurement of specific strategies in adolescents to better understand the role of emotion regulation as a treatment mechanism.
Triggering receptor expressed on myeloid cells 2 (TREM2) is a microglial surface receptor that triggers intracellular protein tyrosine phosphorylation. Recent genome-wide association studies have ...shown that a rare R47H mutation of TREM2 correlates with a substantial increase in the risk of developing Alzheimer’s disease (AD). To address the basis for this genetic association, we studied TREM2 deficiency in the 5XFAD mouse model of AD. We found that TREM2 deficiency and haploinsufficiency augment β-amyloid (Aβ) accumulation due to a dysfunctional response of microglia, which fail to cluster around Aβ plaques and become apoptotic. We further demonstrate that TREM2 senses a broad array of anionic and zwitterionic lipids known to associate with fibrillar Aβ in lipid membranes and to be exposed on the surface of damaged neurons. Remarkably, the R47H mutation impairs TREM2 detection of lipid ligands. Thus, TREM2 detects damage-associated lipid patterns associated with neurodegeneration, sustaining the microglial response to Aβ accumulation.
Display omitted
•TREM2 deficiency augments Aβ accumulation and neuronal loss in a mouse model of AD•TREM2 sustains the microglial response to Aβ plaques by promoting microglial survival•TREM2 senses anionic lipids that have been found to interact with fibrillar Aβ•TREM2 R47H mutation linked to Alzheimer’s disease impairs lipid recognition
TREM2 acts in microglia as a sensor for a wide array of lipids that are associated with β-amyloid accumulation and neuronal loss. The TREM2 mutation that has recently been identified as a risk factor for Alzheimer’s disease attenuates microglial detection of damage-associated lipids, providing a mechanistic basis for the genetic association.
The field of lung transplant has made significant advances over the last several decades. Despite these advances, morbidity and mortality remain high when compared with other solid organ transplants. ...As the field moves forward, the speed by which progress can be made will in part be determined by our ability to overcome several stumbling blocks, including donor shortage, proper selection of candidates, primary graft dysfunction, and chronic lung allograft dysfunction. The advances and developments surrounding these factors will have a significant impact on shaping the field within the coming years. In this review, we look at the current climate (ripe for expanding the donor pool), new technology (ex vivo lung perfusion and bioengineered lungs), cutting-edge innovation (novel biomarkers and new ways to treat infected donors), and evidence-based medicine to discuss current trends and predict future developments for what we hope is a bright future for the field of lung transplantation.
The mechanisms by which cells sense their mechanical environment and transduce the signal through focal adhesions and signaling pathways to the nucleus is an area of key focus for the field of ...mechanobiology. In the past two years, there has been expansion of our knowledge of commonly studied pathways, such as YAP/TAZ, FAK/Src, RhoA/ROCK, and Piezo1 signaling, as well as the discovery of new interactions, such as the effect of matrix rigidity of cell mitochondrial function and metabolism, which represent a new and exciting direction for the field as a whole. This review covers the most recent advances in the field of substrate stiffness sensing as well as perspective on future directions.
Display omitted
Insomnia is prevalent and debilitating, comprising sustained difficulties initiating or maintaining sleep. Cognitive-behavioural therapy for insomnia (CBT-I) is a multicomponent intervention ...recommended as the first-line treatment, but the mediators of change remain unclear. This systematic review and meta-analysis aimed to synthesise and evaluate the evidence for potential mediators of CBT-I. Searches were performed for studies published until February 2021, reporting on mediation analyses with CBT-I. Seventeen unique samples of adults with insomnia (20 studies, N = 3125) were included. Two-stage structural equation modelling was applied to the available data, where 7 studies examined the cognitive mediator, ‘dysfunctional beliefs about sleep’, 5 studies examined a hyperarousal mediator, and 3 studies examined the behavioural mediator, ‘time in bed’. There was evidence in support of changes in dysfunctional beliefs as a cognitive mediator of insomnia symptom improvement following CBT-I. There was more limited evidence in support of changes in hyperarousal-related mediators, and no significant effect of time in bed as a mediator. Numerous studies recorded diary-based measures of potential behavioural mediators, but analyses of these variables were not typically conducted. The most serious limitation of the evidence base is that the temporal precedence of mediator changes cannot be established. Future studies should consider: i) using mid-treatment measurements of mediator changes; ii) reporting on mediator psychometric properties; and iii) explicitly stating analyses as pre-specified or exploratory.
Summarising the mediators synthesised using two-stage structural equation modelling. Display omitted
•Most mediation studies of CBT for Insomnia have tested cognitive mediators.•There has been more limited assessment of arousal and behavioural mediators.•No studies have established the timing of mediator and outcome changes.•There is most evidence for a reduction in dysfunctional beliefs about sleep.•Fewer studies have provided evidence for arousal reduction in CBT-I.
Display omitted
An ideal antibiotic is an antibacterial agent that kills or inhibits the growth of all harmful bacteria in a host, regardless of site of infection without affecting beneficial gut ...microbes (gut flora) or causing undue toxicity to the host. Sadly, no such antibiotics exist. What exist are many effective Gram-positive antibacterial agents as well as broad-spectrum agents that provide treatment of certain Gram-negative bacteria but not holistic treatment of all bacteria. However effectiveness of all antibacterial agents is being rapidly eroded due to resistance. This viewpoint provides an overview of today’s antibiotics, challenges and potential path forward of discovery and development of new (ideal) antibiotics.
•Systematic review of the impact of mindfulness based interventions on brain activity.•We found changes in insula reactivity following 8 week interventions.•Included studies were with heterogeneous ...populations and tasks.
Mindfulness-based interventions are increasingly used in the treatment and prevention of mental health conditions. Despite this, the mechanisms of change for such interventions are only beginning to be understood, with a number of recent studies assessing changes in brain activity. The aim of this systematic review was to assess changes in brain functioning associated with manualised 8-session mindfulness interventions. Searches of PubMed and Scopus databases resulted in 39 papers, 7 of which were eligible for inclusion. The most consistent longitudinal effect observed was increased insular cortex activity following mindfulness-based interventions. In contrast to previous reviews, we did not find robust evidence for increased activity in specific prefrontal cortex sub-regions. These findings suggest that mindfulness interventions are associated with changes in functioning of the insula, plausibly impacting awareness of internal reactions ‘in-the-moment’. The studies reviewed here demonstrated a variety of effects across populations and tasks, pointing to the need for greater consistency in future study design.
Adhesive structures between cells and with the surrounding matrix are essential for the development of multicellular organisms. In addition to providing mechanical integrity, they are key signalling ...centres providing feedback on the extracellular environment to the cell interior, and vice versa. During development, mitosis and repair, cell adhesions must undergo extensive remodelling. Post-translational modifications of proteins within these complexes serve as switches for activity. Tyrosine phosphorylation is an important modification in cell adhesion that is dynamically regulated by the protein tyrosine phosphatases (PTPs) and protein tyrosine kinases. Several PTPs are implicated in the assembly and maintenance of cell adhesions, however, their signalling functions remain poorly defined. The PTPs can act by directly dephosphorylating adhesive complex components or function as scaffolds. In this review, we will focus on human PTPs and discuss their individual roles in major adhesion complexes, as well as Hippo signalling. We have collated PTP interactome and cell adhesome datasets, which reveal extensive connections between PTPs and cell adhesions that are relatively unexplored. Finally, we reflect on the dysregulation of PTPs and cell adhesions in disease.
Using a case study of Arvind Sharma’s thinking on
striyaḥ
(women), a subject he claims he has not written about aside from the topic of
sati
, this essay analyzes the epigrams and prefaces found in ...his fifteen edited books on women as a point of departure to tease out his larger scholarly project: not only to understand why India became colonized and Hinduism moribund, but also how to overcome their lingering effects without alienation from past culture. Toward this end, the essay focuses on how Sharma tackles stereotypes by restoring complexities to the historical record, using the multiple methods of religious studies, taking on the mantle of engaged scholar as a “threshold response,” and entering the public sphere on issues of justice and affirmative action. Juxtaposition of pivotal events recorded in his autobiography with these scholarly discussions suggests that his cryptic insights on women’s history and liberation is core to his thought, a case of “reciprocal illumination” as it were. All this raises the question of whether Sharma is a Hindu apologist or a reformer.
Dimensional models of anxiety and depression highlight common and distinct symptom clusters that are thought to reflect disruptions in underlying functional processes. The current study investigated ...how functioning of threat neurocircuitry relates to symptom dimensions of anxiety and depression. Participants were aged 18-19 years (n = 229, 158 female) and were selected to ensure a range of scores on symptom measures. Symptom dimensions of "General Distress" (common to anxiety disorders and depression), "Fears" (more specific to anxiety disorders), and "Anhedonia-apprehension" (more specific to depression) were evaluated. Participants underwent functional magnetic resonance imaging during a Pavlovian fear conditioning paradigm. Multilevel modeling analyses estimated relationships between symptom dimensions and activation in threat neural circuitry. Exploratory whole brain analyses were also conducted. Threat-related neural activity was not associated with General Distress or Fears. Anhedonia-apprehension was associated with activation of bilateral amygdala, anterior insula and dACC during late extinction. We found no evidence to support an association between symptom dimensions of General Distress or Fears with threat circuitry activation in a large sample of young adults. We did, however, find that the symptom dimension of Anhedonia-apprehension was significantly associated with threat-related neural activation during fear extinction. This effect requires replication in future work but may reflect anhedonic impairments in learning when contingencies are altered, possibly linked to the rewarding relief of an unexpectedly absent threat.
PDF
