Anti-herpetic tau preserves neurons via the cGAS-STING-TBK1 pathway in Alzheimer's disease.

Alzheimer's disease (AD) diagnosis relies on the presence of extracellular β-amyloid (Aβ) and intracellular hyperphosphorylated tau (p-tau). Emerging evidence suggests a potential link between AD pathologies and infectious agents, with herpes simplex virus 1 (HSV-1) being a leading candidate. Our investigation, using metagenomics, mass spectrometry, western blotting, and decrowding expansion pathology, detects HSV-1-associated proteins in human brain samples.

Basic Science and Pathogenesis.

Background: The failure of amyloid plaque-reducing drugs to reverse cognitive decline in Alzheimer's disease (AD) has suggested that treatments might be more effective in early or prodromal stages of the disease. However, the progression of synaptic and circuit changes associated with Aβ overexpression, particularly at very early ages, have not been well-characterized. Indeed, evidence from both human and animal studies indicates that brain structure and function might be altered months to years before plaques can be detected.

Clinical Manifestations.

Background: There is growing evidence that discourse (i.e., connected speech) could serve as a cost-effective and ecologically valid means of identifying individuals with prodromal Alzheimer's disease.

Spin Waves and Three Dimensionality in the High-Pressure Antiferromagnetic Phase of SrCu_{2}(BO_{3})_{2}.

Quantum magnetic materials can provide explicit realizations of paradigm models in quantum many-body physics. In this context, SrCu_{2}(BO_{3})_{2} is a faithful realization of the Shastry-Sutherland model for ideally frustrated spin dimers, even displaying several of its quantum magnetic phases as a function of pressure. We perform inelastic neutron scattering measurements on SrCu_{2}(BO_{3})_{2} at 5.

R(3780) Resonance Interpreted as the 1^{3}D_{1}-Wave Dominant State of Charmonium from Precise Measurements of the Cross Section of e^{+}e^{-}→Hadrons.

We report the precise measurements of the cross section of e^{+}e^{-}→hadrons at center-of-mass energies from 3.645 to 3.871 GeV.

The Detrimental Effect of Stroke on Motor Adaptation.

Background: While it is evident that stroke impairs motor control, it remains unclear whether stroke impacts motor adaptation-the ability to flexibly modify movements in response to changes in the body and the environment. The mixed results in the literature may be due to differences in participants' brain lesions, sensorimotor tasks, or a combination of both.

Objective: We first sought to better understand the overall impact of stroke on motor adaptation and then to delineate the impact of lesion hemisphere and sensorimotor task on adaptation poststroke.

Cardiorespiratory fitness, hippocampal subfield morphology, and episodic memory in older adults.

Objective: Age-related hippocampal atrophy is associated with memory loss in older adults, and certain hippocampal subfields are more vulnerable to age-related atrophy than others. Cardiorespiratory fitness (CRF) may be an important protective factor for preserving hippocampal volume, but little is known about how CRF relates to the volume of specific hippocampal subfields, and whether associations between CRF and hippocampal subfield volumes are related to episodic memory performance. To address these gaps, the current study evaluates the associations among baseline CRF, hippocampal subfield volumes, and episodic memory performance in cognitively unimpaired older adults from the Investigating Gains in Neurocognition Trial of Exercise (IGNITE) (NCT02875301).

Functional dynamics of G protein-coupled receptors reveal new routes for drug discovery.

G protein-coupled receptors (GPCRs) are the largest human membrane protein family that transduce extracellular signals into cellular responses. They are major pharmacological targets, with approximately 26% of marketed drugs targeting GPCRs, primarily at their orthosteric binding site. Despite their prominence, predicting the pharmacological effects of novel GPCR-targeting drugs remains challenging due to the complex functional dynamics of these receptors.

Fine-mapping causal tissues and genes at disease-associated loci.

Complex diseases often have distinct mechanisms spanning multiple tissues. We propose tissue-gene fine-mapping (TGFM), which infers the posterior inclusion probability (PIP) for each gene-tissue pair to mediate a disease locus by analyzing summary statistics and expression quantitative trait loci (eQTL) data; TGFM also assigns PIPs to non-mediated variants. TGFM accounts for co-regulation across genes and tissues and models uncertainty in cis-predicted expression models, enabling correct calibration.

Dynamics of visual object coding within and across the hemispheres: Objects in the periphery.

The human brain continuously integrates information across its two hemispheres to construct a coherent representation of the perceptual world. Characterizing how visual information is represented in each hemisphere over time is crucial for understanding how hemispheric transfer contributes to perception. Here, we investigated information processing within each hemisphere over time and the degree to which it is distinct or duplicated across hemispheres.

PMAIP1-mediated glucose metabolism and its impact on the tumor microenvironment in breast cancer: Integration of multi-omics analysis and experimental validation.

Background: Glucose metabolism in breast cancer has a potential effect on tumor progression and is related to the immune microenvironment. Thus, this study aimed to develop a glucose metabolism-tumor microenvironment score to provide new perspectives on breast cancer treatment.

Method: Data were acquired from the Gene Expression Omnibus and UCSC Xena databases, and glucose-metabolism-related genes were acquired from the Gene Set Enrichment Analysis database.

Synergistic Combination of Living Ring-Opening Metathesis Polymerization and Atom Transfer Radical Polymerization to Synthesize Structurally Tailored and Engineered Macromolecular Networks.

Structurally tailored and engineered macromolecular (STEM) networks are attractive materials for soft robotics, stretchable electronics, tissue engineering, and 3D printing due to their tunable properties. To date, STEM networks have been synthesized by atom transfer radical polymerization (ATRP) or the combination of reversible addition-fragmentation chain-transfer (RAFT) polymerization and ATRP. RAFT polymerization could have limited selectivity with ATRP inimer sites that can participate in radical-transfer processes.

Generative design-enabled exploration of wireframe DNA origami nanostructures.

Recent advances in computer-aided design tools have helped rapidly advance the development of wireframe DNA origami nanostructures. Specifically, automated tools now exist that can convert an input polyhedral mesh into a DNA origami nanostructure, greatly reducing the design difficulty for wireframe DNA origami nanostructures. However, one limitation of these automated tools is that they require a designer to fully conceptualize their intended nanostructure, which may be limited by their own preconceptions.

Comparison of Alternative Approaches to Using Race-and-Ethnicity Data in Estimating Differences in Health Care and Social Determinants of Health.

Objective: The objective of this study was to compare 2 approaches for representing self-reported race-and-ethnicity, additive modeling (AM), in which every race or ethnicity a person endorses counts toward measurement of that category, and a commonly used mutually exclusive categorization (MEC) approach. The benchmark was a gold-standard, but often impractical approach that analyzes all combinations of race-and-ethnicity as distinct groups.

Methods: Data came from 313,739 respondents to the 2021 Medicare Consumer Assessment of Healthcare Providers and Systems (CAHPS) surveys who self-reported race-and-ethnicity.

Experimental assessment and analysis of mass transport limiting current density in water vapor-fed polymer electrolyte membrane electrolyzers.

Polymer electrolyte membrane water electrolyzers (PEMWEs) are a critical technology for efficient hydrogen production to decarbonize fuels and industrial feedstocks. To make hydrogen cost-effective, the overpotentials across the cell need to be decreased and platinum-group metal loading reduced. One overpotential that needs to be better understood is due to mass transport limitations from bubble formation within the porous transport layer (PTL) and anode catalyst layer (ACL), which can lead to a reduction in performance at typical operating current densities.

PharmRL: pharmacophore elucidation with deep geometric reinforcement learning.

Background: Molecular interactions between proteins and their ligands are important for drug design. A pharmacophore consists of favorable molecular interactions in a protein binding site and can be utilized for virtual screening. Pharmacophores are easiest to identify from co-crystal structures of a bound protein-ligand complex.

Functional resilience of the neural visual recognition system post-pediatric occipitotemporal resection.

Neural representations for visual stimuli typically emerge with a bilateral distribution across occipitotemporal cortex (OTC)? Pediatric patients undergoing unilateral OTC resection offer an opportunity to evaluate whether representations for visual stimulus individuation can sufficiently develop in a single OTC. Here, we assessed the non-resected hemisphere of patients with pediatric resection within ( = 9) and outside ( = 12) OTC, as well as healthy controls' two hemispheres ( = 21). Using functional magnetic resonance imaging, we mapped category selectivity (CS), and representations for visual stimulus individuation (for faces, objects, and words) with repetition suppression (RS).

North Atlantic Heat Transport Convergence Derived from a Regional Energy Budget Using Different Ocean Heat Content Estimates.

This study uses an oceanic energy budget to estimate the ocean heat transport convergence in the North Atlantic during 2005-2018. The horizontal convergence of the ocean heat transport is estimated using ocean heat content tendency primarily derived from satellite altimetry combined with space gravimetry. The net surface energy fluxes are inferred from mass-corrected divergence of atmospheric energy transport and tendency of the ECMWF ERA5 reanalysis combined with top-of-the-atmosphere radiative fluxes from the clouds and the Earth's radiant energy system project.

Does high perceived stress over the past month alter cortisol reactivity to the Trier Social Stress Test?

Background: Theories highlight the important role of chronic stress in remodeling HPA-axis responsivity under stress. The Perceived Stress Scale (PSS) is one of the most widely used measures of enduring stress perceptions, and no previous studies have evaluated whether greater perceptions of stress on the PSS are associated with cortisol hypo- or hyperactivity responses to the Trier Social Stress Test (TSST).

Objective: To examine if high perceived stress over the past month, as measured by the PSS, alters cortisol and subjective acute stress reactivity to the TSST in healthy young adults.

A randomized controlled trial on anonymizing reviewers to each other in peer review discussions.

Many peer-review processes involve reviewers submitting their independent reviews, followed by a discussion between the reviewers of each paper. A common question among policymakers is whether the reviewers of a paper should be anonymous to each other during the discussion. We shed light on this question by conducting a randomized controlled trial at the Conference on Uncertainty in Artificial Intelligence (UAI) 2022 conference where reviewer discussions were conducted over a typed forum.

The Topology of Poly(2-methyl-2-oxazine) Shells on Nanoparticles Determines Their Interaction with Serum and Uptake by Immune Cells.

Cyclic poly(2-methyl-2-oxazine) (-PMOZI) brush shells on Au nanoparticles (NPs) exhibit enhanced stealth properties toward serum and different cell lines compared to their linear PMOZI (-PMOZI) counterparts. While selectively recruiting immunoglobulins, -PMOZI shells reduce overall human serum (HS) protein binding and alter the processing of complement factor 3 (C3) compared to chemically identical linear shells. Polymer cyclization significantly decreases NP uptake by nonphagocytic cells and macrophages in both complement-deficient fetal bovine serum (FBS) and complement-expressing HS, indicating ineffective functional opsonization.

A Roadmap for Implanting Electrode Arrays to Evoke Tactile Sensations Through Intracortical Stimulation.

Intracortical microstimulation (ICMS) is a method for restoring sensation to people with paralysis as part of a bidirectional brain-computer interface (BCI) to restore upper limb function. Evoking tactile sensations of the hand through ICMS requires precise targeting of implanted electrodes. Here we describe the presurgical imaging procedures used to generate functional maps of the hand area of the somatosensory cortex and subsequent planning that guided the implantation of intracortical microelectrode arrays.