Telomere-to-telomere (T2T) and haplotype-resolved assembly are crucial for understanding eukaryotic genomes. For diploid species, this resolution is critical to uncover allelic variations, inheritance patterns, and functional genomic traits. Current scaffolding methods typically employ either sequence-based or graph-based strategies.Sequence-based approaches rely on proximity signals to yield high contiguity, but underutilize assembly graph information, resulting in more […]

Synthetic receptors are powerful tools for cellular engineering, yet their utility is often constrained by constitutive activity and the absence of natural feedback mechanisms that maintain cellular homeostasis. To address this, we engineered an autonomous regulatory circuit for synthetic Notch (synNotch) receptor activation using an orthogonal microRNA (miRNA)-mediated negative feedback mechanism in mammalian cells. Specifically, […]

Our understanding of how ganglioside species are spatially and quantitatively distributed within regions in mammalian remains limited. Studies are typically translated from rodents, assuming that gangliosides species contents within brain regions reflect the human condition. Herein, we provide a rich spatial ganglioside brain atlas describing the content, compositional differences, and concentrations of 48 ganglioside species […]

Rapid expansion into new territory is fundamental to population persistence, ecological dominance, and evolutionary success. Every race for space is initiated by founding populations, yet how their initial spatiotemporal conditions shape the outcome remains unclear. Here, by combining nonlinear theory with quantitative microbial experiments, we show that collective motility can overturn the classical logic of […]

Control of arboviruses remains heavily reliant on insecticide-based vector control targeting adult Aedes aegypti, especially during outbreaks, but the effectiveness of these tools can be compromised by insecticide resistance. While the mechanisms underlying resistance have been widely studied in Latin American and South East Asian Ae. aegypti, knowledge from African populations is limited, particularly regarding […]

Photosynthetic membranes undergo structural remodeling in response to environmental stress by altering fatty acid composition and desaturation levels. These changes, mediated by fatty acid desaturases (FADs), are essential for maintaining photosynthetic performance and adaptation. In this study, we demonstrate that copper-deficient Chlamydomonas reinhardtii cells upregulate the expression of the gene encoding stearoyl-ACP desaturase (SAD/FAB2). We […]

CDP-ribitol serves as an essential donor for D-ribitol-5-phosphate incorporation into bacterial and mammalian glycoconjugates. Here, we demonstrate the one-pot enzymatic synthesis of CDP-ribitol from the readily available precursor ribitol. We also explore the synthesis of bioorthogonally tagged derivatives and other CDP conjugates, thereby providing valuable new tools for glycoscience research.

Recent chromosomal rearrangements and divergence in large falcon species make them excellent foci for studies on evolution and genomic architecture. Here, we use high-coverage (44-74X) whole genome resequencing with 10X Genomics Linked-Reads to assess patterns of genomic divergence in peregrine, saker, and gyrfalcons and we link these to chromosomal type and chromosomal rearrangements. We first […]

The cerebellar nuclei form the main output structures of the cerebellum and are composed of a deeply conserved set of cell types. Two excitatory cell classes, Class-A and -B, are present in each cerebellar nucleus and mediate all excitatory output of the cerebellum. To provide genetic access to these cell types, here we identified Acan […]

Neurodegenerative diseases such as Parkinson disease (PD) result from complex interactions between neuronal stress and the surrounding tissue environment, yet the determinants that govern this interplay remain incompletely understood. While neuronal responses to mitochondrial dysfunction and proteotoxic stress have been extensively characterized, the contribution of microglial state to disease progression remains unclear. Here, we identify […]

Therapeutics fused to brain shuttles that exploit endogenous receptor-mediated transport at the blood brain barrier (BBB) offer a promising strategy to deliver large molecule drugs and biologics to the CNS. A fundamental but untested assumption underlying their clinical development is that their endothelial receptor targets are consistently expressed between individuals and between patient populations. Here, […]

Somatic copy-number alterations (CNAs) accumulate with age and contribute to age-related pathologies, but their systematic characterization at single-cell resolution has been limited by the throughput-resolution trade-off in single-cell whole-genome sequencing. Here, we developed ultra-CNA, a high-resolution single-cell analysis pipeline that extends CNA detection to 10-kb bin resolution and jointly profiles copy-number and single-nucleotide variation (SNV). […]