Exceptional Uptake, Limited Protein Expression: Liver Macrophages Lost in Translation of Synthetic mRNA.

Most gene therapies exert their actions via manipulation of hepatocytes (parenchymal cells) and the reasons behind the suboptimal performance of synthetic mRNA in non-parenchymal cells (NPC) such as Kupffer cells (KC), and liver macrophages, remain unclear. Here, the spatio-temporal distribution of mRNA encoding enhanced green fluorescent protein (Egfp), siRNA, or both co-encapsulated into lipid nanoparticles (LNP) in the liver in vivo using real-time intravital imaging is investigated. Although both KC and hepatocytes demonstrate comparable high and rapid uptake of mRNA-LNP and siRNA-LNP in vivo, the translation of Egfp mRNA occurs exclusively in hepatocytes during intravital imaging.

Beyond Routine Maintenance: Current Trends in Working Memory Research.

Working memory (WM) is an evolving concept. Our understanding of the neural functions that support WM develops iteratively alongside the approaches used to study it, and both can be profoundly shaped by available tools and prevailing theoretical paradigms. Here, the organizers of the 2024 Working Memory Symposium-inspired by this year's meeting-highlight current trends and looming questions in WM research.

Transcranial direct current stimulation improves time perception in children with ADHD.

Individuals with ADHD struggle with time perception. The ventromedial prefrontal cortex (vmPFC) and dorsolateral prefrontal cortex (dlPFC) are two distinct cortical areas that are involved in the psychopathology of ADHD, including time perception. In the present study, we aimed to explore if modulation of the excitability of these areas with non-invasive brain stimulation alters time perception in ADHD.

Translation and validation of the Nature Relatedness Scale to German.

Over the recent past, tools have been developed to asses people's connection to and attitudes towards nature due to increasing interest in this topic in society and research. We translated one such questionnaire, the Nature Relatedness Scale, consisting of three subscales (NR-Self, NR-Perspective, NR-Experience) to German. We collected 251 data sets and performed a confirmatory factor analysis, followed by an exploratory factor analysis.

A study of long-term GABA and high-energy phosphate alterations in the primary motor cortex using anodal tDCS and H/P MR spectroscopy.

Introduction: Anodal transcranial direct current stimulation (tDCS) has been reported to modulate gamma-aminobutyric acid levels and cerebral energy consumption in the brain. This study aims to investigate long-term GABA and cerebral energy modulation following anodal tDCS over the primary motor cortex.

Method: To assess GABA and energy level changes, proton and phosphorus magnetic resonance spectroscopy data were acquired before and after anodal or sham tDCS.

The association between hair cortisol and burnout is moderated by age, psychosocial, and immunological markers.

Background: Exhaustion and depersonalization are the core symptoms of the occupational burnout. However, burnout is not an all-or-nothing phenomenon, but can occur in a milder to moderate form in otherwise healthy employees. In the last two decades hair cortisol concentrations (HCC) were increasingly related to the cumulative effect of psychosocial stress at work.

Neuronavigated Focalized Transcranial Direct Current Stimulation Administered During Functional Magnetic Resonance Imaging.

Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique that allows the modulation of the excitability and plasticity of the human brain. Focalized tDCS setups use specific electrode arrangements to constrain the current flow to circumscribed brain regions. However, the effectiveness of focalized tDCS can be compromised by electrode positioning errors on the scalp, resulting in significant reductions of the current dose reaching the target brain regions for tDCS.

Randomized Controlled Trial of Transcranial Direct Current Stimulation over the Supplementary Motor Area in Tourette Syndrome.

Background: Transcranial direct current stimulation (tDCS) over the supplementary motor area (SMA) has shown promise in Tourette syndrome (TS), but previous studies were limited in size and stimulation duration.

Objective: The aim was to explore the efficacy and safety of multiple sessions of cathodal tDCS over the bilateral SMA on tic severity in TS.

Methods: A double-blind, randomized, sham-controlled trial 1 mA cathodal tDCS over bilateral SMA was performed in participants with TS older than 16 years.

Prospective heat stress risk assessment for professional soccer players in the context of the 2026 FIFA World Cup.

This study investigates the risk of severe heat stress and associated potential water losses in professional soccer players, considering as well the oxygen content of the inhaled air in the context of the 2026 FIFA World Cup. For the 16 stadiums, hourly values of biometeorological indices (adjusted Universal Thermal Climate Index - UTCI, Water loss - SW and Oxygen volume - Ov) were calculated. UTCI adjustments included modifications to activity levels, movement speeds and clothing configurations to better reflect the level of thermal stress on soccer player during a match.

Simultaneous Stimulation of Peripheral Blood Mononuclear Cells with CpG ODN2006 and α-IgM Antibodies Leads to Strong Immune Responses in Monocytes Independent of B Cell Activation.

CpG ODN2006 is widely used both in vitro and in vivo to achieve B cell activation and has been previously applied in clinical trials as an adjuvant and anti-cancer agent. Recent studies have demonstrated the benefit of combining CpG ODN2006 with α-IgM antibodies to obtain optimal B cell activation in vitro. In this study, we expanded the knowledge of how both agents affect other types of peripheral blood mononuclear cells (PBMCs), thereby highlighting beneficial and potentially unfavorable properties of the combination of CpG ODN2006 and α-IgM when applied beyond isolated B cells.

Validation of NBD-coupled taurocholic acid for intravital analysis of bile acid transport in liver and kidney of mice.

Fluorophore-coupled bile acids (BA) represent an important tool for intravital analysis of BA flux in animal models of cholestatic diseases. However, addition of a fluorophore to a BA may alter transport properties. We developed and validated a 4-chloro-7-nitrobenzo-2-oxa-1,3-diazole-coupled taurocholic acid (3β-NBD-TCA) as a probe for intravital analysis of BA homeostasis.

You Are as Old as the Connectivity You Keep: Distinct Neurophysiological Mechanisms Underlying Age-Related Changes in Hand Dexterity and Strength.

Background: Aging can lead to a decline in motor control. While age-related motor impairments have been documented, the underlying changes in cortico-cortical interactions remain poorly understood.

Methods: We took advantage of the high temporal resolution of dual-site transcranial magnetic stimulation (dsTMS) to investigate how communication between higher-order rostral premotor regions and the primary motor cortex (M1) influences motor control in young and elderly adults.

Design of optimal concentrations for in vitro cytotoxicity experiments.

Concentration-dependent cytotoxicity experiments are frequently used in toxicology. Although it has been reported that an adequate choice of concentrations improves the quality of the statistical inference substantially, a recent literature review of three major toxicological journals has shown that the corresponding methods are rarely used in toxicological practice. In this study the performance of different sets of concentrations, also called designs, are analyzed, while the overall goal is to promote the advantages of optimal design procedures and to present a user-friendly guideline for planning new cytotoxicity concentration-response experiments.

Synchronization-based fusion of EEG and eye blink signals for enhanced decoding accuracy.

Decoding locomotor tasks is crucial in cognitive neuroscience for understanding brain responses to physical tasks. Traditional methods like EEG offer brain activity insights but may require additional modalities for enhanced interpretative precision and depth. The integration of EEG with ocular metrics, particularly eye blinks, presents a promising avenue for understanding cognitive processes by combining neural and ocular behaviors.

Longitudinal Evaluation of Individuals With Severe Alpha-1 Antitrypsin Deficiency (Pi∗ZZ Genotype).

Background & Aims: Homozygous Pi∗Z mutation in alpha-1 antitrypsin (Pi∗ZZ genotype) predisposes to pulmonary loss-of-function and hepatic gain-of-function injury. To facilitate selection into clinical trials typically targeting only 1 organ, we systematically evaluated an international, multicenter, longitudinal, Pi∗ZZ cohort to uncover natural disease course and surrogates for future liver- and lung-related endpoints.

Methods: Cohort 1 recruited 737 Pi∗ZZ individuals from 25 different centers without known liver comorbidities who received a baseline clinical and laboratory assessment as well as liver stiffness measurement (LSM).

Role of WISP1 in Stellate Cell Migration and Liver Fibrosis.

The mechanisms underlying the remarkable capacity of the liver to regenerate are still not completely understood. Particularly, the cross-talk between cytokines and cellular components of the process is of utmost importance because they represent potential avenues for diagnostics and therapeutics. WNT1-inducible-signaling pathway protein 1 (WISP1) is a cytokine member of the CCN family, a family of proteins that play many different roles in liver pathophysiology.

Frontal midline theta power during the cue-target-interval reflects increased cognitive effort in rewarded task-switching.

Cognitive performance largely depends on how much effort is invested during task-execution. This also means that we rarely perform as good as we could. Cognitive effort is adjusted to the expected outcome of performance, meaning that it is driven by motivation.

A meta-analysis of the effects of transcranial direct current stimulation combined with cognitive training on working memory in healthy older adults.

Background: Working memory (WM) loss, which can lead to a loss of independence, and declines in the quality of life of older adults, is becoming an increasingly prominent issue affecting the ageing population. Transcranial direct current stimulation (tDCS), a non-invasive brain stimulation technique, is emerging as a potential alternative to pharmacological treatments that shows promise for enhancing WM capacity and May enhance the effects of cognitive training (CT) interventions.

Objective: The purpose of this meta-analysis was to explore how different tDCS protocols in combination with CT enhanced WM in healthy older adults.