Endosomolytic peptides enable the cellular delivery of peptide nucleic acids.

Precision genetic medicine enlists antisense oligonucleotides (ASOs) to bind to nucleic acid targets important for human disease. Peptide nucleic acids (PNAs) have many desirable attributes as ASOs but lack cellular permeability. Here, we use an assay based on the corrective splicing of an mRNA to assess the ability of synthetic peptides to deliver a functional PNA into a human cell.

piRNA Defense Against Endogenous Retroviruses.

Infection by retroviruses and the mobilization of transposable elements cause DNA damage that can be catastrophic for a cell. If the cell survives, the mutations generated by retrotransposition may confer a selective advantage, although, more commonly, the effect of new integrants is neutral or detrimental. If retrotransposition occurs in gametes or in the early embryo, it introduces genetic modifications that can be transmitted to the progeny and may become fixed in the germline of that species.

Mechanistic and Therapeutic Implications of Protein and Lipid Sialylation in Human Diseases.

Glycan structures of glycoproteins and glycolipids on the surface glycocalyx and luminal sugar layers of intracellular membrane compartments in human cells constitute a key interface between intracellular biological processes and external environments. Sialic acids, a class of alpha-keto acid sugars with a nine-carbon backbone, are frequently found as the terminal residues of these glycoconjugates, forming the critical components of these sugar layers. Changes in the status and content of cellular sialic acids are closely linked to many human diseases such as cancer, cardiovascular, neurological, inflammatory, infectious, and lysosomal storage diseases.

How Do Transformers Model Physics? Investigating the Simple Harmonic Oscillator.

How do transformers model physics? Do transformers model systems with interpretable analytical solutions or do they create an "alien physics" that is difficult for humans to decipher? We have taken a step towards demystifying this larger puzzle by investigating the simple harmonic oscillator (SHO), x¨+2γx˙+ω02x=0, one of the most fundamental systems in physics. Our goal was to identify the methods transformers use to model the SHO, and to do so we hypothesized and evaluated possible methods by analyzing the encoding of these methods' intermediates. We developed four criteria for the use of a method within the simple test bed of linear regression, where our method was y=wx and our intermediate was : (1) Can the intermediate be predicted from hidden states? (2) Is the intermediate's encoding quality correlated with the model performance? (3) Can the majority of variance in hidden states be explained by the intermediate? (4) Can we intervene on hidden states to produce predictable outcomes? Armed with these two correlational (1,2), weak causal (3), and strong causal (4) criteria, we determined that transformers use known numerical methods to model the trajectories of the simple harmonic oscillator, specifically, the matrix exponential method.

Glycoconjugate vaccines: platforms and adjuvants for directed immunity.

Central to immune recognition is the glycocalyx, a glycan-rich coat on all cells that plays a crucial role in interactions that enable pathogen detection and activation of immune defenses. Pathogens and cancerous cells often display distinct glycans on their surfaces, making these saccharide antigens prime targets for vaccine development. However, carbohydrates alone generally serve as poor immunogens due to their often weak binding affinities, inability to effectively recruit T cell help, and reliance on adjuvants to iboost immune activation.

Renewing Our Focus on Vulnerable Populations Among People Living with HIV.

The global HIV landscape has changed over the past few decades, with great milestones achieved in both HIV treatment and prevention [...

The Role of Chemerin in Upper Gastrointestinal Cancer.

: Chemerin, which is a multifunctional cytokine and adipokine, has been implicated in inflammatory and metabolic processes and might play a role in upper gastrointestinal (GI) malignancies, particularly gastric and esophageal cancer. The aim of this review is to explore the role of chemerin in the pathophysiology of upper GI cancers, as well as its potential as a biomarker for early detection and as a therapeutic target. : A comprehensive review of recent studies about chemerin's biochemical properties and interaction with its receptors, as well as its effects on inflammatory responses, immune regulation, and metabolic processes, was conducted.

Fast Autograft Generation Using Transferable 3D Keratinocyte Cell Sheet on PEDOT:PSS Composite PDMS Membrane for Enhancing Wound Healing.

The application of cell sheet technology for wound healing preserves dense cell tissue and the natural extracellular matrix (ECM), contributing to disease prevention. Despite the effectiveness of autologous and allograft cell sheets for wound healing, conventional cell sheets, although stable, may experience necrosis in their middle layers due to a lack of nutrients or oxygen. To address these issues, a novel approach is proposed to create cell sheets using mechanical and electrical stimulation.

Permeability-selectivity trade-off for a universal leaky channel inspired by mobula filters.

Mobula rays have evolved leaf-shaped filter structures to separate food particles from seawater, which function similarly to industrial cross-flow filters. Unlike cross-flow filtration, where permeability and selectivity are rationally designed following trade-off analyses, the driving forces underlying the evolution of mobula filter geometry have remained elusive. To bridge the principles of cross-flow and mobula filtration, we establish a universal framework for the permeability-selectivity trade-off in a leaky channel inspired by mobula filters, where permeability and selectivity are characterized by the pore-scale leaking rate and the cut-off particle size, respectively.

Use of Basket Trials to Solve Sleep Problems in Patients with Rare Diseases.

The need for sleep is universal, and the ability to meet this need impacts the quality of life for patients, families, and caregivers. Although substantial progress has been made in treating rare diseases, many patients have unmet medical sleep needs, and current regulatory policy makes it prohibitively difficult to address those needs medically. This opinion reviews the rare disease experience with sleep disorders and explores potential solutions.

Modulating the immunodominance hierarchy of immunoglobulin germline-encoded structural motifs targeting the influenza hemagglutinin stem.

Antibodies targeting epitopes through germline-encoded motifs can be found in different individuals. While these public antibodies are often beneficial, they also pose hurdles for subdominant antibodies to emerge. Here, we use transgenic mice that reproduce the human IGHV1-6901 germline-encoded antibody response to the conserved stem epitope on group 1 hemagglutinin (HA) of influenza A virus to show that this germline-endowed response can be overridden by a subdominant yet cross-group reactive public antibody response.

CalDAG-GEFI acts as a guanine nucleotide exchange factor for LRRK2 to regulate LRRK2 function and neurodegeneration.

Mutations in are the most common genetic cause of Parkinson's disease (PD). LRRK2 protein contains two enzymatic domains: a GTPase (Roc-COR) and a kinase domain. Disease-causing mutations are found in both domains.

Microbes display broad diversity in cobamide preferences.

Cobamides, the vitamin B (cobalamin) family of cofactors, are used by most organisms but produced by only a fraction of prokaryotes, and are thus considered key shared nutrients among microbes. Cobamides are structurally diverse, with multiple different cobamides found in most microbial communities. The ability to use different cobamides has been tested for several bacteria and microalgae, and nearly all show preferences for certain cobamides.

Streamlined miRNA loading of surface protein-specific extracellular vesicle subpopulations through electroporation.

Background: Extracellular vesicles (EVs) have emerged as an exciting tool for targeted delivery of therapeutics for a wide range of diseases. As nano-scale membrane-bound particles derived from living cells, EVs possess inherent capabilities as carriers of biomolecules. However, the translation of EVs into viable therapeutic delivery vehicles is challenged by lengthy and inefficient processes for cargo loading and pre- and post-loading purification of EVs, resulting in limited quantity and consistency of engineered EVs.

Width-dependent continuous growth of atomically thin quantum nanoribbons from nanoalloy seeds in chalcogen vapor.

Nanoribbons (NRs) of atomic layer transition metal dichalcogenides (TMDs) can boost the rapidly emerging field of quantum materials owing to their width-dependent phases and electronic properties. However, the controllable downscaling of width by direct growth and the underlying mechanism remain elusive. Here, we demonstrate the vapor-liquid-solid growth of single crystal of single layer NRs of a series of TMDs (MeX: Me = Mo, W; X = S, Se) under chalcogen vapor atmosphere, seeded by pre-deposited and respective transition metal-alloyed nanoparticles that also control the NR width.

Revisiting the correlation between simulated and field-observed conflicts using large-scale traffic reconstruction.

Safety is a critical aspect of traffic systems. However, traditional crash data-based methods suffer from scalability and generalization issues. Although SSMs offer a proactive alternative for safety evaluation, their validation in simulated settings remains inconsistent, especially with emerging mobility technologies like autonomous driving.

VONet: A deep learning network for 3D reconstruction of organoid structures with a minimal number of confocal images.

Organoids and 3D imaging techniques are crucial for studying human tissue structure and function, but traditional 3D reconstruction methods are expensive and time consuming, relying on complete z stack confocal microscopy data. This paper introduces VONet, a deep learning-based system for 3D organoid rendering that uses a fully convolutional neural network to reconstruct entire 3D structures from a minimal number of z stack images. VONet was trained on a library of over 39,000 virtual organoids (VOs) with diverse structural features and achieved an average intersection over union of 0.

Proton hyperfine couplings and Overhauser DNP.

We have prepared trityl radicals with protons at the positions of the -COOH group in the phenyl rings and examined their EPR spectra, which show large - hyperfine couplings, and their dynamic nuclear polarization (DNP) Zeeman field profiles . By assessing these polarizing agents for high-field and Overhauser effect DNP, we gain insight into the roles that these hyperfine couplings and other molecular properties play in the DNP performance of these radicals. Interestingly, we do not observe OE DNP in any of the three molecules we examined.

GENCODE 2025: reference gene annotation for human and mouse.

GENCODE produces comprehensive reference gene annotation for human and mouse. Entering its twentieth year, the project remains highly active as new technologies and methodologies allow us to catalog the genome at ever-increasing granularity. In particular, long-read transcriptome sequencing enables us to identify large numbers of missing transcripts and to substantially improve existing models, and our long non-coding RNA catalogs have undergone a dramatic expansion and reconfiguration as a result.

Accuracy prompts protect professional content moderators from the illusory truth effect.

Content moderators review problematic content for technology companies. One concern is that repeated exposure to false claims could cause moderators to come to believe the very claims they are supposed to moderate, via the "illusory truth effect." In a first lab-in-field experiment ( = 199) with a global content moderation company, we found that exposure to false claims while working as moderators increased subsequent belief among (mostly Indian and Philippine) employees by 7.