IL-6 trans-signalling is elevated in ALS models and drives TDP-43 induced inflammatory responses in microglia.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by chronic inflammation in both the central nervous system (CNS) and peripheral tissues. Interleukin-6 (IL-6) has been implicated in ALS pathology; however, IL-6 exhibits both anti-inflammatory and pro-inflammatory functions. Notably, IL-6 trans-signalling possesses pro-inflammatory properties and is emerging as a key contributor to neuroinflammation during neurodegeneration.

Molecular fingerprints of a convergent mechanism orchestrating diverse ligand recognition and species-specific pharmacology at the complement anaphylatoxin receptors.

Complement anaphylatoxin receptors (C3aR and C5aR1) are prototypical G protein-coupled receptors (GPCRs) playing crucial physiological roles in innate immunity by combating pathogenic infections and orchestrating inflammatory responses. They continue to be important therapeutic targets for multiple disorders including autoimmune diseases, acute and chronic inflammation, and allergy-related conditions. Recent structural coverage has provided important insights into their activation and signaling, however, confounding observations in the literature related to ligand efficacy and functional responses, especially in different model systems, present a major challenge for drug discovery efforts.

Ischaemic endothelial necroptosis induces haemolysis and COVID-19 angiopathy.

Microangiopathy is a major complication of SARS-CoV-2 infection and contributes to the acute and chronic complications of the disease. Endotheliopathy and dysregulated blood coagulation are prominent in COVID-19 and are considered to be major causes of microvascular obstruction. Here we demonstrate extensive endothelial cell (EC) death in the microvasculature of COVID-19 organs.

Are humans still necessary? Expanding the discussion.

The rise of automation, artificial intelligence (AI), and autonomous systems raises important questions about the future role of humans and the field of human factors/ergonomics in workplaces. This paper builds on Dr. Peter Hancock's 2023 'Are Humans Still Necessary?' article published in the journal.

Colon-targeted complement C5a receptor inhibition using pH-sensitive nanoparticles ameliorates experimental colitis.

Background And Purpose: The complement system is associated with inflammatory bowel disease (IBD) pathology. Complement activation induces C5a production, which signals through the C5a receptor (C5aR1) to drive inflammatory responses that may underlie IBD.

Experimental Approach: We examined mucosal biopsies from ulcerative colitis patients and identified C5a receptor up-regulated in active lesions, supporting the C5a receptor as a target for therapeutic intervention.

Metabolic rate and insulin-independent glucose uptake increase in a TDP-43 mouse model of amyotrophic lateral sclerosis.

Impaired glucose regulation is increasingly recognised in amyotrophic lateral sclerosis (ALS), yet the precise mechanisms remain unclear. Here, we investigated energy balance and glucose control in TAR DNA-binding protein 43 (TDP-43) mice, a model of ALS, at both the early and late symptomatic stages of disease. Mutant TDP-43 mice and non-transgenic controls underwent indirect calorimetry, as well as intraperitoneal glucose, insulin, and glucagon tolerance testing.

The Effects of Presenting AI Uncertainty Information on Pharmacists' Trust in Automated Pill Recognition Technology: Exploratory Mixed Subjects Study.

Background: Dispensing errors significantly contribute to adverse drug events, resulting in substantial health care costs and patient harm. Automated pill verification technologies have been developed to aid pharmacists with medication dispensing. However, pharmacists' trust in such automated technologies remains unexplored.

Peripheral and central elevation of IL-8 in patients with Huntington's disease.

Objectives: Huntington's Disease (HD) is a debilitating neurodegenerative condition characterized by motor, cognitive and psychiatric abnormalities. Immune hyperactivity and dysregulation are common in HD. In addition to the central nervous system, HD patients exhibit systemic innate immune activation and inflammation, which has been shown to contribute to the pathogenic effects of the Huntingtin gene mutation.

Complement(ing) long-COVID thromboinflammation and pathogenesis.

The persistence or recurrence of symptoms after acute SARS-CoV-2 infection, termed 'long COVID', presents a formidable challenge to global healthcare systems. Recent research by Cervia-Hasler and colleagues delves into the intricate immunological landscape in patients with long COVID, demonstrating an interplay between complement and coagulation, driven by antiviral antibodies and tissue damage.

Complement C5a Receptor Signaling Alters Stress Responsiveness and Modulates Microglia Following Chronic Stress Exposure.

Background: Accumulating evidence underscores the pivotal role of heightened inflammation in the pathophysiology of stress-related diseases, but the underlying mechanisms remain elusive. The complement system, a key effector of the innate immune system, produces the C5-cleaved activation product C5a upon activation, initiating inflammatory responses through the canonical C5a receptor 1 (C5aR1). While C5aR1 is expressed in stress-responsive brain regions, its role in stress responsiveness remains unknown.

A probabilistic neural twin for treatment planning in peripheral pulmonary artery stenosis.

The substantial computational cost of high-fidelity models in numerical hemodynamics has, so far, relegated their use mainly to offline treatment planning. New breakthroughs in data-driven architectures and optimization techniques for fast surrogate modeling provide an exciting opportunity to overcome these limitations, enabling the use of such technology for time-critical decisions. We discuss an application to the repair of multiple stenosis in peripheral pulmonary artery disease through either transcatheter pulmonary artery rehabilitation or surgery, where it is of interest to achieve desired pressures and flows at specific locations in the pulmonary artery tree, while minimizing the risk for the patient.

Cell-intrinsic C5a synergizes with Dectin-1 in macrophages to mediate fungal killing.

The complement factor C5a is a core effector product of complement activation. C5a, acting through its receptors C5aR1 and C5aR2, exerts pleiotropic immunomodulatory functions in myeloid cells, which is vital for host defense against pathogens. Pattern-recognition receptors (PRRs) are similarly expressed by immune cells as detectors of pathogen-associated molecular patterns.

A Panel of miRNA Biomarkers Common to Serum and Brain-Derived Extracellular Vesicles Identified in Mouse Model of Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron disease characterised by the deposition of aggregated proteins including TAR DNA-binding protein 43 (TDP-43) in vulnerable motor neurons and the brain. Extracellular vesicles (EVs) facilitate the spread of neurodegenerative diseases and can be easily accessed in the bloodstream. This study aimed to identify a panel of EV miRNAs that can capture the pathology occurring in the brain and peripheral circulation.

Measuring trust: a text analysis approach to compare, contrast, and select trust questionnaires.

Introduction: Trust has emerged as a prevalent construct to describe relationships between people and between people and technology in myriad domains. Across disciplines, researchers have relied on many different questionnaires to measure trust. The degree to which these questionnaires differ has not been systematically explored.

Trust and trustworthy artificial intelligence: A research agenda for AI in the environmental sciences.

Demands to manage the risks of artificial intelligence (AI) are growing. These demands and the government standards arising from them both call for trustworthy AI. In response, we adopt a convergent approach to review, evaluate, and synthesize research on the trust and trustworthiness of AI in the environmental sciences and propose a research agenda.

It's Not Only What You Say, But Also How You Say It: Machine Learning Approach to Estimate Trust from Conversation.

Objective: The objective of this study was to estimate trust from conversations using both lexical and acoustic data.

Background: As NASA moves to long-duration space exploration operations, the increasing need for cooperation between humans and virtual agents requires real-time trust estimation by virtual agents. Measuring trust through conversation is a novel and unintrusive approach.

(Mis-)use of standard Autopilot and Full Self-Driving (FSD) Beta: Results from interviews with users of Tesla's FSD Beta.

Tesla's Full Self-Driving Beta (FSD) program introduces technology that extends the operational design domain of standard Autopilot from highways to urban roads. This research conducted 103 in-depth semi-structured interviews with users of Tesla's FSD Beta and standard Autopilot to evaluate the impact on user behavior and perception. It was found that drivers became complacent over time with Autopilot engaged, failing to monitor the system, and engaging in safety-critical behaviors, such as hands-free driving, enabled by weights placed on the steering wheel, mind wandering, or sleeping behind the wheel.

TLQP-21 is a low potency partial C3aR activator on human primary macrophages.

TLQP-21 is a 21-amino acid neuropeptide derived from the VGF precursor protein. TLQP-21 is expressed in the nervous system and neuroendocrine glands, and demonstrates pleiotropic roles including regulating metabolism, nociception and microglial functions. Several possible receptors for TLQP-21 have been identified, with complement C3a receptor (C3aR) being the most commonly reported.

On the relationship between occlusion times and in-car glance durations in simulated driving.

Drivers have spare visual capacity in driving, and often this capacity is used for engaging in secondary in-car tasks. Previous research has suggested that the spare visual capacity could be estimated with the occlusion method. However, the relationship between drivers' occlusion times and in-car glance duration preferences has not been sufficiently investigated for granting occlusion times the role of an estimate of spare visual capacity.

Comparing Subjective Similarity of Automated Driving Styles to Objective Distance-Based Similarity.

Objective: This study explores subjective and objective driving style similarity to identify how similarity can be used to develop driver-compatible vehicle automation.

Background: Similarity in the ways that interaction partners perform tasks can be measured subjectively, through questionnaires, or objectively by characterizing each agent's actions. Although subjective measures have advantages in prediction, objective measures are more useful when operationalizing interventions based on these measures.

SARS-CoV-2 drives NLRP3 inflammasome activation in human microglia through spike protein.

Coronavirus disease-2019 (COVID-19) is primarily a respiratory disease, however, an increasing number of reports indicate that SARS-CoV-2 infection can also cause severe neurological manifestations, including precipitating cases of probable Parkinson's disease. As microglial NLRP3 inflammasome activation is a major driver of neurodegeneration, here we interrogated whether SARS-CoV-2 can promote microglial NLRP3 inflammasome activation. Using SARS-CoV-2 infection of transgenic mice expressing human angiotensin-converting enzyme 2 (hACE2) as a COVID-19 pre-clinical model, we established the presence of virus in the brain together with microglial activation and NLRP3 inflammasome upregulation in comparison to uninfected mice.