Acquired resistance to targeted therapies remains an inevitable outcome in EGFR-mutant non-small cell lung cancer, yet the spatiotemporal dynamics through which resistant clones emerge and evolve in vivo remain incompletely understood. In particular, how distinct oncogenic EGFR alleles shape evolutionary trajectories under therapeutic pressure within native tumor microenvironments remains unclear. Here, we establish a longitudinal […]
Suitable seasons: Global monthly habitat suitability for the arbovirus vectors Aedes aegypti and Aedes albopictus in 1975-2024
The mosquito species Aedes aegypti and Aedes albopictus are the primary vectors of the arboviruses dengue, Zika, and chikungunya. Expansion of these vectors into previously non-endemic regions due to climate and environmental changes has accelerated global burden from arboviral diseases. To combat this, predictive models accurately mapping Aedes habitats are essential for epidemiological modelling, effective […]
Defining the DNA Binding Specificity of GRHL2
Grainyhead-like 2 (GRHL2) is an epithelial transcription factor with context-dependent regulatory roles, yet the sequence rules governing its DNA recognition remain incompletely defined. In this study, a high-density genomic Specificity and Affinity for Protein (SNAP) DNA-binding array containing 772,732 tiled probes derived from GRHL2 ChIP-seq regions was used to resolve GRHL2 binding specificity at 6 […]
Hornbill abundance and habitat correlates in Kali Tiger Reserve, Western Ghats, India-Insights from collaborative monitoring
The future of species, particularly large-bodied birds, under climate threats, is increasingly unclear. Protected areas (PAs) can mitigate the impacts of global change but are not completely immune. This makes it imperative to monitor populations even inside PAs. In the forests of the Western Ghats, three hornbill species are found: Malabar Grey Hornbill, Malabar Pied […]
SIRPA suppresses integrin-dependent virus endocytosis
New World arenaviruses (NWAs) that cause viral hemorrhagic fever, such as Junin virus, have few therapeutic options. Entry of these viruses into cells is mediated by binding to cell surface receptors, followed by endocytosis and trafficking to a low pH compartment. We showed previously that Signal Regulatory Protein Alpha (SIRPA), a critical cell surface receptor […]
Droplet-compatible single-cell DNA methylation sequencing with PreTIC
Single-cell DNA methylation sequencing has remained technically specialized due to challenges of interfacing conversion chemistry with droplet microfluidics. We introduce pre-tagmentation in situ conversion (PreTIC), which enables whole-methylome profiling on a commercial droplet platform using off-the-shelf reagents. With PreTIC, we produce over 13,000 single-cell methylomes from fixed frozen cells in two days and resolve cell-specific […]
Conjugation-based genome engineering enables rapid prototyping and bioproduction in non-model bacteria
Non-model bacteria offer unique metabolic capabilities for sustainable bioproduction, yet their limited genetic accessibility hinders systematic strain development. Here we present conjugation-based serine recombinase-assisted genome engineering (cSAGE), a broad-host-range platform that enables predictable, iterative genomic integration in transformation-resistant bacteria. cSAGE combines conjugative DNA delivery, standardized low-copy vectors, orthogonal recombinases, and modular genetic parts to support […]
Resolving in vitro heterogeneity of host functional responses to HCoV-229E via single-cell analyses
Understanding host-pathogen interactions at the molecular level is essential to elucidating the mechanisms that govern immunity and pathogenesis. While diverse responses to viral infection have been documented, it remains unclear if this variability arises from the complex host milieu or represents an intrinsic property of the infection itself. To investigate this, we performed single-cell (sc) […]
Ocular findings in Northern Gannets following an outbreak of high pathogenicity avian influenza (H5N1)
During 2021-2022, high pathogenicity avian influenza (HPAI) caused mass mortality in wild birds across Europe, with Northern Gannets (Morus bassanus) among the most affected. Following the outbreak, unusual alterations in the species’ characteristic pale iris were observed in some individuals. Opportunistically captured gannets on Bass Rock (n=52), selected to represent a range of iris pigmentation, […]
Methods for evaluating bacterial dispersal on hyphal networks
In heterogeneous environments, the hyphae of filamentous fungi and oomycetes can facilitate the dispersal of other microorganisms. The use of these fungal highways (FH) is regulated by both physical and biological factors with their interplay resulting in variable capabilities of different microbes to establish FH. Several devices have been developed to test the movement of […]
How Functional Variants Reconfigure the Rac2 Conformational Landscape
Rac2, a member of the Rho family of small GTPases, is a fundamental regulator of essential cellular processes. Pathogenic substitutions near and within the Switch II region, specifically D57N and E62K, have been implicated in oncogenesis and immunodeficiency. Despite their proximity, D57N is characterized as a loss-of-function mutation, while E62K is a constitutively active, gain-of-function […]
Combination of engineered cell type-specific promoters and a high-efficiency AAV capsid restores hearing in adult DFNB1 mice model with demonstrated safety in nonhuman primate
A major challenge in gene therapy for GJB2-related hearing loss (DFNB1), the most common form of hereditary deafness, is achieving efficient and precise connexin 26 delivery. Herein, we engineered two cell type-specific promoters (GJB2-1 and WFS1-2274) and developed an AAV capsid, AAV-MAS012, with enhanced transduction efficiency in mature cochlear cells. Our AAV-mediated gene therapy systems […]