Endothelial identity not found - Beyond passage 38, commercial cardiac microvascular endothelial cells do not express CD31 and VE-cadherin.

Few immortalized cardiac microvascular endothelial cell (CMEC) lines are available, particularly mouse lines. We purchased the CLU510 mCMEC line (Cedarlane), isolated by fluorescence-activated cell sorting for CD31 and VE-cadherin. The cell line has been used in previous studies, although none report CD31 or VE-cadherin expression.

Western diet triggers cardiac dysfunction in heterozygous -targeted knock-in mice: A two-hit model of hypertrophic cardiomyopathy.

Background And Aim: Phenotypic expression of hypertrophic cardiomyopathy (HCM) and disease course are associated with unfavorable metabolic health. We investigated if Western diet (WD) feeding is sufficient to trigger cardiac hypertrophy and dysfunction in heterozygous (HET) knock-in mice.

Methods And Results: Wild-type (WT) and HET mice (3-months-old) were fed a WD or normal chow (NC) for 8 weeks.

Prolonged corticosteroid therapy and lung abnormalities in patients after severe COVID-19 pneumonia.

Background: Some of the hospitalized patients after severe COVID-19 pneumonia experience significant fall in peripheral saturation despite optimal treatment. Because of immune dysregulation in COVID-19 there are indications that prolonged corticosteroids could be considered in treating patients for persistent radiological sequelae and respiratory symptoms.

Objectives: to investigate lung function and lung sequelae on high-resolution CT (HRCT) im COVID-19 patients who were treated with glucocorticoid therapy in two dose regimens with a control group of patients who did not receive additional glucocorticoid therapy.

Glycogen synthase kinase-3 inhibition and insulin enhance proliferation and inhibit maturation of human iPSC-derived cardiomyocytes via TCF and FOXO signaling.

Embryonic signaling pathways exert stage-specific effects during cardiac development, yet the precise signals for proliferation or maturation remain elusive. To uncover the cues for proliferation, we performed a combinatory cell-cycle screen for insulin and glycogen synthase kinase-3 (GSK3) inhibition in spontaneously beating human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). Our analysis for proliferation, and subsequential downstream sarcomere development, gene expression analysis, and molecular interventions identified a temporal interplay between insulin/Akt/FOXO and CHIR99021/Wnt/GSK3/TCF signaling.

Translating myosin-binding protein C and titin abnormalities to whole-heart function using a novel calcium-contraction coupling model.

Mutations in cardiac myosin-binding protein C (cMyBP-C) or titin may respectively lead to hypertrophic (HCM) or dilated (DCM) cardiomyopathies. The mechanisms leading to these phenotypes remain unclear because of the challenge of translating cellular abnormalities to whole-heart and system function. We developed and validated a novel computer model of calcium-contraction coupling incorporating the role of cMyBP-C and titin based on the key assumptions: 1) tension in the thick filament promotes cross-bridge attachment mechanochemically, 2) with increasing titin tension, more myosin heads are unlocked for attachment, and 3) cMyBP-C suppresses cross-bridge attachment.

Intra-condensate demixing of TDP-43 inside stress granules generates pathological aggregates.

Cytosolic aggregation of the nuclear protein TDP-43 is associated with many neurodegenerative diseases, but the triggers for TDP-43 aggregation are still debated. Here, we demonstrate that TDP-43 aggregation requires a double event. One is up-concentration in stress granules beyond a threshold, and the other is oxidative stress.

Hypertrophic cardiomyopathy dysfunction mimicked in human engineered heart tissue and improved by sodium-glucose cotransporter 2 inhibitors.

Aims: Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiomyopathy, often caused by pathogenic sarcomere mutations. Early characteristics of HCM are diastolic dysfunction and hypercontractility. Treatment to prevent mutation-induced cardiac dysfunction is lacking.

Understanding Naturalistic Facial Expressions with Deep Learning and Multimodal Large Language Models.

This paper provides a comprehensive overview of affective computing systems for facial expression recognition (FER) research in naturalistic contexts. The first section presents an updated account of user-friendly FER toolboxes incorporating state-of-the-art deep learning models and elaborates on their neural architectures, datasets, and performances across domains. These sophisticated FER toolboxes can robustly address a variety of challenges encountered in the wild such as variations in illumination and head pose, which may otherwise impact recognition accuracy.

Nuclear actin polymerization rapidly mediates replication fork remodeling upon stress by limiting PrimPol activity.

Cells rapidly respond to replication stress actively slowing fork progression and inducing fork reversal. How replication fork plasticity is achieved in the context of nuclear organization is currently unknown. Using nuclear actin probes in living and fixed cells, we visualized nuclear actin filaments in unperturbed S phase and observed their rapid extension in number and length upon genotoxic treatments, frequently taking contact with replication factories.

Geranylgeranylacetone reduces cardiomyocyte stiffness and attenuates diastolic dysfunction in a rat model of cardiometabolic syndrome.

Titin-dependent stiffening of cardiomyocytes is a significant contributor to left ventricular (LV) diastolic dysfunction in heart failure with preserved LV ejection fraction (HFpEF). Small heat shock proteins (HSPs), such as HSPB5 and HSPB1, protect titin and administration of HSPB5 in vitro lowers cardiomyocyte stiffness in pressure-overload hypertrophy. In humans, oral treatment with geranylgeranylacetone (GGA) increases myocardial HSP expression, but the functional implications are unknown.

DWORF Extends Life Span in a PLN-R14del Cardiomyopathy Mouse Model by Reducing Abnormal Sarcoplasmic Reticulum Clusters.

Background: The p.Arg14del variant of the (phospholamban) gene causes cardiomyopathy, leading to severe heart failure. Calcium handling defects and perinuclear PLN aggregation have both been suggested as pathological drivers of this disease.

Longitudinal analysis of chest Q-SPECT/CT in patients with severe COVID-19.

Introduction: Patients with COVID-19 have an increased risk for microvascular lung thrombosis. In order to evaluate the type and prevalence of perfusion defects, we performed a longitudinal analysis of combined perfusion single-photon emission and low-dose computed tomography (Q-SPECT/CT scan) in patients with COVID-19 pneumonia.

Methods: Consecutive patients with severe COVID-19 (B.

Characterization of heterozygous and homozygous mouse models with the most common hypertrophic cardiomyopathy mutation MYBPC3 in the Netherlands.

Hypertrophic cardiomyopathy (HCM) is frequently caused by mutations in the cardiac myosin binding protein-C (cMyBP-C) encoding gene MYBPC3. In the Netherlands, approximately 25% of patients carry the MYBPC3 founder mutation. Most patients are heterozygous (MYBPC3) and have highly variable phenotypic expression, whereas homozygous (MYBPC3) patients have severe HCM at a young age.

Human and machine recognition of dynamic and static facial expressions: prototypicality, ambiguity, and complexity.

A growing body of research suggests that movement aids facial expression recognition. However, less is known about the conditions under which the dynamic advantage occurs. The aim of this research was to test emotion recognition in static and dynamic facial expressions, thereby exploring the role of three featural parameters (prototypicality, ambiguity, and complexity) in human and machine analysis.

The microtubule signature in cardiac disease: etiology, disease stage, and age dependency.

Employing animal models to study heart failure (HF) has become indispensable to discover and test novel therapies, but their translatability remains challenging. Although cytoskeletal alterations are linked to HF, the tubulin signature of common experimental models has been incompletely defined. Here, we assessed the tubulin signature in a large set of human cardiac samples and myocardium of animal models with cardiac remodeling caused by pressure overload, myocardial infarction or a gene defect.

Psychophysiological responses to eye contact with a humanoid robot: Impact of perceived intentionality.

Eye contact with a social robot has been shown to elicit similar psychophysiological responses to eye contact with another human. However, it is becoming increasingly clear that the attention- and affect-related psychophysiological responses differentiate between direct (toward the observer) and averted gaze mainly when viewing embodied faces that are capable of social interaction, whereas pictorial or pre-recorded stimuli have no such capability. It has been suggested that genuine eye contact, as indicated by the differential psychophysiological responses to direct and averted gaze, requires a feeling of being watched by another mind.

EGFR/IGF1R Signaling Modulates Relaxation in Hypertrophic Cardiomyopathy.

Background: Diastolic dysfunction is central to diseases such as heart failure with preserved ejection fraction and hypertrophic cardiomyopathy (HCM). However, therapies that improve cardiac relaxation are scarce, partly due to a limited understanding of modulators of cardiomyocyte relaxation. We hypothesized that cardiac relaxation is regulated by multiple unidentified proteins and that dysregulation of kinases contributes to impaired relaxation in patients with HCM.

Emergence of sense of body ownership but not agency during virtual tool-use training is associated with an altered body schema.

In this study we examined if training with a virtual tool in augmented reality (AR) affects the emergence of ownership and agency over the tool and whether this relates to changes in body schema (BS). 34 young adults learned controlling a virtual gripper to grasp a virtual object. In the visuo-tactile (VT) but not the vision-only (V) condition, vibro-tactile feedback was applied to the palm, thumb and index fingers through a CyberTouch II glove when the tool touched the object.

Tool-use training in augmented reality: plasticity of forearm body schema does not predict sense of ownership or agency in older adults.

In young adults (YA) who practised controlling a virtual tool in augmented reality (AR), the emergence of a sense of body ownership over the tool was associated with the integration of the virtual tool into the body schema (BS). Agency emerged independent of BS plasticity. Here we aimed to replicate these findings in older adults (OA).

Real-Time Measurements of Calcium and Contractility Parameters in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes.

Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) represent a powerful tool for studying mutation-mediated changes in cardiomyocyte function and defining the effects of stressors and drug interventions. In this study, it is demonstrated that this optics-based system is a powerful tool to assess the functional parameters of hiPSC-CMs in 2D. By using this platform, it is possible to perform paired measurements in a well-preserved temperature environment on different plate layouts.

Effects of Early Emollient Use in Children at High Risk of Atopic Dermatitis: A German Pilot Study.

Several small studies have indicated that daily emollient use from birth might delay, suppress or prevent atopic dermatitis (AD). Two larger trials did not confirm this; however, a recent smaller study indicated a protective effect if daily emollient use is used in the first 2 months of life. Further research is needed to evaluate the effect of emollient use on development of AD.

Direct visualization of transcription-replication conflicts reveals post-replicative DNA:RNA hybrids.

Transcription-replication collisions (TRCs) are crucial determinants of genome instability. R-loops were linked to head-on TRCs and proposed to obstruct replication fork progression. The underlying mechanisms, however, remained elusive due to the lack of direct visualization and of non-ambiguous research tools.