APOE
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Lipidated ApoE is found in nanoscale proximity to Aβ aggregates in human Alzheimer brains.
Apolipoprotein E (APOE) associates with amyloid plaques A{beta} in Alzheimer disease (AD). The {epsilon}4 allele of apolipoprotein E (APOE{epsilon}4) is the strongest genetic risk factor for sporadic AD and exacerbates A{beta} plaque burden relative to APOE{epsilon}3 and APOE{epsilon}2. The majority of ApoE associates with multiple lipid classes to form lipoproteins both in the brain and the periphery.
Reflection in the Dark: Exposing and Escaping the Black Box in Reflective Prompt Optimization
arXiv:2603.18388v2 Announce Type: replace Abstract: Automatic prompt optimization (APO) has emerged as a powerful paradigm for improving LLM performance without manual prompt engineering. Reflective APO methods such as GEPA iteratively refine prompts by diagnosing failure cases, but the optimization process remains black-box and label-free, leading to uninterpretable trajectories and systematic failure. We identify and empirically demonstrate four limitations: on GSM8K with a defective seed,...
Beta-Adrenergic Stimulation and MYH7 G256E Mutant Gene Dosage Drive Hypertrophic Cardiomyopathy Phenotype Penetrance
Aims Hypertrophic cardiomyopathy (HCM) is the most prevalent genetic heart disorder, characterized by significant phenotypic variability even among individuals with identical MYH7 mutations. This study aims to elucidate factors contributing to this variability and identify drivers of phenotype penetrance. We compared the baseline phenotypes of a highly penetrant MYH7 H251N mutation and the variably penetrant MYH7 G256E mutation and investigated the impact of adding beta-adrenergic...
Structure of a dopamine-binding RNA aptamer reveals metal-mediated ligand recognition
The selection of small-molecule binding RNA aptamers enables the creation of ligand-responsive RNA tools, yet most aptamers fail to operate reliably across diverse environments. Scaffolded selection addresses this limitation by preserving the tertiary architecture of a riboswitch scaffold while driving the evolution of a new ligand-binding pocket. Using the xpt purine riboswitch aptamer, we previously generated dopamine-binding aptamers.
Huge study of Alzheimer’s genetics identifies new drug targets
The biggest genetic study of Alzheimer’s disease so far has identified 127 gene locations that are associated with the condition, of which 48 are new. The study also pinpoints several genes that could be prioritised as drug targets and cell types linked to a higher genetic risk of the condition. “It’s an exciting time for Alzheimer’s genetics,” says Rudolph Tanzi at Massachusetts General Hospital, who provided evidence of the first Alzheimer’s-linked gene, APP, in 1987.
AlloGen: Conformation-Selective Binder Generation with Differential State Scoring
arXiv:2606.05474v1 Announce Type: cross Abstract: Protein binder design has largely optimized for affinity alone, leaving conformational selectivity unaddressed: for allosteric targets such as kinases, nuclear receptors, and GPCRs, a binder that engages both active and inactive states provides no functional specificity regardless of how tightly it binds. We introduce AlloGen, a modular framework that decouples backbone generation from a learned state-selectivity scorer $Q_\theta$, an...
Sleep apnea’s hidden heart disease trigger found in the gut
Sleep apnea’s hidden heart disease trigger found in the gut - Date: - June 9, 2026 - Source: - American Society for Microbiology - Summary: - A surprising gut-heart connection may help explain why sleep apnea increases the risk of cardiovascular disease. In mice, disabling a bile acid receptor called FXR sharply reduced plaque buildup, opening the door to potential new treatments based on gut microbes and their chemical signals. - Share: Millions of people worldwide live with obstructive...