mRNA-LNPs induce immune activation and cytokine release in human whole blood assays across diverse health conditions.

RNA medicines have become a promising platform for therapeutic use in recent years. Understanding the immunomodulatory effects of novel mRNA-lipid nanoparticles (LNPs) is crucial for future therapeutic development. An in vitro whole blood assay was developed to assess the impact of mRNA-LNPs on immune cell function, cytokine release, and complement activation.

Radiative corrections: from medium to high energy experiments.

Radiative corrections are crucial for modern high-precision physics experiments, and are an area of active research in the experimental and theoretical community. Here we provide an overview of the state of the field of radiative corrections with a focus on several topics: lepton-proton scattering, QED corrections in deep-inelastic scattering, and in radiative light-hadron decays. Particular emphasis is placed on the two-photon exchange, believed to be responsible for the proton form-factor discrepancy, and associated Monte-Carlo codes.

Humoral correlates of protection against following intravenous BCG vaccination in rhesus macaques.

Altering Bacille Calmette-Guérin (BCG) immunization from low-dose intradermal (i.d.) to high-dose intravenous (i.

The energetic landscape of CH-π interactions in protein-carbohydrate binding.

CH-π interactions between carbohydrates and aromatic amino acids play an essential role in biological systems that span all domains of life. Quantifying the strength and importance of these CH-π interactions is challenging because these interactions involve several atoms and can exist in many distinct orientations. To identify an orientational landscape of CH-π interactions, we constructed a dataset of close contacts formed between β-d-galactose residues and the aromatic amino acids, tryptophan, tyrosine, and phenylalanine, across crystallographic structures deposited in the Protein Data Bank.

3D electron microscopy for analyzing nanoparticles in the tumor endothelium.

Delivering medical agents to diseased tissues has been challenging, leading researchers to study the in vivo transport process in the body for improving delivery. Many imaging techniques exist for mapping the distribution of medical agent-carrying nanoparticles in tissues, but they cannot capture the three-dimensional context of tissues with single nanoparticle resolution. Here, we developed 3DEM-NPD, a three-dimensional electron microscopy (3D EM) machine learning strategy to image and map single nanoparticle distributions (NPD) in tissues.

AI-Powered Multimodal Modeling of Personalized Hemodynamics in Aortic Stenosis.

Aortic stenosis (AS) is the most common valvular heart disease in developed countries. High-fidelity preclinical models can improve AS management by enabling therapeutic innovation, early diagnosis, and tailored treatment planning. However, their use is currently limited by complex workflows necessitating lengthy expert-driven manual operations.

Deep and dynamic metabolic and structural imaging in living tissues.

Label-free imaging through two-photon autofluorescence of NAD(P)H allows for nondestructive, high-resolution visualization of cellular activities in living systems. However, its application to thick tissues has been restricted by its limited penetration depth within 300 μm, largely due to light scattering. Here, we demonstrate that the imaging depth for NAD(P)H can be extended to more than 700 μm in living engineered human multicellular microtissues by adopting multimode fiber-based, low repetition rate, high peak power, three-photon excitation of NAD(P)H at 1100 nm.

Ongoing evolution of SARS-CoV-2 drives escape from mRNA vaccine-induced humoral immunity.

With the onset of the COVID-19 pandemic 4 years ago, viral sequencing continues to document numerous individual mutations in the viral spike protein across many variants. To determine the ability of vaccine-mediated humoral immunity to combat continued SARS-CoV-2 evolution, we construct a comprehensive panel of pseudoviruses harboring each individual mutation spanning 4 years of the pandemic to understand the fitness cost and resistance benefits of each. These efforts identify numerous mutations that escape from vaccine-induced humoral immunity.

Intracortical recordings reveal the neuronal selectivity for bodies and body parts in the human visual cortex.

Body perception plays a fundamental role in social cognition. Yet, the neural mechanisms underlying this process in humans remain elusive given the spatiotemporal constraints of functional imaging. Here, we present intracortical recordings of single- and multiunit spiking activity in two epilepsy surgery patients in or near the extrastriate body area, a critical region for body perception.

Cargo Quantification of Functionalized DNA Origami for Therapeutic Application.

In recent years, notable advances in nanotechnology-based drug delivery have emerged. A particularly promising platform in this field is DNA origami-based nanoparticles, which offer highly programmable surfaces, providing precise control over the nanoscale spacing and stoichiometry of various cargo. These versatile particles are finding diverse applications ranging from basic molecular biology to diagnostics and therapeutics.

Cognition is an emergent property.

Cognition relies on the flexible organization of neural activity. In this discussion, we explore how many aspects of this organization can be described as emergent properties, not reducible to their constituent parts. We discuss how electrical fields in the brain can serve as a medium for propagating activity nearly instantaneously, and how population-level patterns of neural activity can organize computations through subspace coding.

Saccharibacteria deploy two distinct Type IV pili, driving episymbiosis, host competition, and twitching motility.

All cultivated Patescibacteria, or CPR, exist as obligate episymbionts on other microbes. Despite being ubiquitous in mammals and environmentally, molecular mechanisms of host identification and binding amongst ultrasmall bacterial episymbionts are largely unknown. Type 4 pili (T4P) are well conserved in this group and predicted to facilitate symbiotic interactions.

Measurement of the electric potential and the magnetic field in the shifted analysing plane of the KATRIN experiment.

The projected sensitivity of the effective electron neutrino-mass measurement with the KATRIN experiment is below 0.3 eV (90 % CL) after 5 years of data acquisition. The sensitivity is affected by the increased rate of the background electrons from KATRIN's main spectrometer.

Obfuscation via pitch-shifting for balancing privacy and diagnostic utility in voice-based cognitive assessment.

Introduction: Digital voice analysis is gaining traction as a tool to differentiate cognitively normal from impaired individuals. However, voice data poses privacy risks due to the potential identification of speakers by automated systems.

Methods: We developed a framework that uses weighted linear interpolation of privacy and utility metrics to balance speaker obfuscation and cognitive integrity in cognitive assessments.

Quantitative analysis of the morphological variation within the tiger beetle Calomera littoralis (Fabricius, 1787) (Coleoptera: Cicindelidae) in Mongolia.

For the past couple of centuries, much of tiger beetle taxonomic work has been focused on explaining intraspecific variation. In the Northern Hemisphere, over a thousand subspecies have been described and many have since been relegated to synonymy. Generally, the phenotypic-based subspecies circumscription has been purely descriptive.

BCL11A +58/+55 enhancer-editing facilitates HSPC engraftment and HbF induction in rhesus macaques conditioned with a CD45 antibody-drug conjugate.

Editing the +58 region of the BCL11A erythroid enhancer has shown promise in treating β-globin disorders. To address variations in fetal hemoglobin (HbF) response, we investigated editing both +58 and +55 enhancers. Rhesus macaques transplanted with edited hematopoietic stem/progenitor cells (HSPCs) following busulfan conditioning exhibited durable, high-level (∼90%) editing frequencies post transplantation with sustained HbF reactivation over 4 years, without hematological perturbations.

Ecosystem stability relies on diversity difference between trophic levels.

The stability of ecological communities has a profound impact on humans, ranging from individual health influenced by the microbiome to ecosystem services provided by fisheries. A long-standing goal of ecology is the elucidation of the interplay between biodiversity and ecosystem stability, with some ecologists warning of instability due to loss of species diversity while others arguing that greater diversity will instead lead to instability. Here, by considering a minimal two-level ecosystem with multiple predator and prey species, we show that stability does not depend on absolute diversity but rather on diversity differences between levels.