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Biology subjects

Feng, Z.

Publications and source records attributed to Feng, Z..

At least 19 recordsLinked to original sources

MillionTrees: A global benchmark for tree detection across geography, sensor, and annotation geometry

Airborne tree monitoring using remotely sensed data, combined with the growth of computer vision models for object detection and segmentation, can facilitate broad scale assessment of tree health, ecology and ecosystem function. However, datasets for airborne tree detection have been largely limited to a single geography, resolution, or annotation approach, making it difficult to develop general models and benchmark their utility for broad applications. We compile existing and newly published annotation datasets to create a comprehensive dataset for training and evaluating airborne tree detection in RGB imagery. The MillionTrees dataset has over a million individual trees from a broad range of forest types, tree species, and geographic locations. In addition, it has six million weakly supervised annotations from a range of sources including airborne LiDAR and photogrammetry, arborist surveys, and simulated landscapes. An evaluation standard is provided to facilitate rapid model development. We benchmark several existing tree detection algorithms and demonstrate that while current open-source models do not generalize across the diverse datasets in the benchmark, training on MillionTrees improves both within-domain and out-of-domain performance. Held-out validation datasets using ground truth derived from terrestrial LiDAR paired with overhead RGB show that overfitting to test data is common and hyperparameter tuning is an underappreciated challenge towards a global zero shot tree detection method. We discuss the limitations of the currently available data for airborne RGB tree detection, how to create more robust evaluation data and the need for better understanding of the uncertainty and utility of tree detection from airborne remote sensing.

ecology↗

Panvascular-JEPA: Unseen-Structure Evaluation of Factorized Predictive States for Hemodynamic Networks

Predictive representations for vascular simulation should be tested on unseen network structures and compared with the governing equations before being interpreted as general-purpose world models. We constructed a new, dimensioned but uncalibrated nodal resistance-inertance-compliance benchmark containing all 38 connected, non-isomorphic six-node graphs with five to seven edges. Twenty-four structures supplied training, validation, and new-background testing; 14 structures were wholly withheld. Across 648 parameter backgrounds and two prescribed action programs, 1,296 trajectories contained 96 forecast steps over three cycles. Four graph predictors received equal six candidate optimization searches, followed by five fixed-seed fits. Selected configurations and analysis code were locked before test trajectories were generated. Comparators included known-equation numerical integrators, an inertia-free reduction, and a five-coefficient model fitted to training trajectories. Unseen-structure mean standardized RMSE was 8.46 x 109 for four-factor OPF, 329 for single factor OPF, and 1.83 x 1031 for supervised graph prediction, compared with 1.09 x 10-4 for foursubstep known-equation integration and 6.77 x 104 for the fitted mechanism. The primary OPF-4 minus OPF-1 difference was 8.46 x 109, with a paired stratified-graph 95% percentile interval of [2.23 x 105, 2.54 x 1010]. Neural errors were strongly dependent on training seed and network structure, with extreme forecasts dominating the means. All four neural means exceeded persistence; relative performance within this comparison did not establish a usable forecasting model. The study supplies a distinct numerical test of structure transfer, factor-count control, and recursive stability. Its conclusions concern the implemented models, optimization budget, and finite graph catalogue. It establishes neither patient-specific performance nor anatomical transfer, biological remodeling, device efficacy, or clinical readiness.

bioengineering↗

ALDH1B1 promotes mitochondrial γ-butyrobetaine biosynthesisand fatty acid oxidation in colorectal cancer

Metabolic reprogramming is a hallmark of cancer cells, and stem-like populations often upregulate aldehyde dehydrogenases (ALDHs). Functional studies have established essential roles for individual ALDH isoforms in tumor initiation, progression, and metastasis; however, the mechanisms by which these enzymes promote malignancy remain poorly understood. Here we show that aldehyde dehydrogenase 1B1 (ALDH1B1), a mitochondrial enzyme highly expressed in colorectal cancer (CRC) and pancreatic ductal adenocarcinoma (PDAC), generates {gamma}-butyrobetaine (GBB) and {gamma}-aminobutyric acid (GABA) in CRC cells. The biosynthesis of both aminocarboxylic acids has been attributed to the cytosolic enzyme ALDH9A1, and we demonstrate that mitochondrial GBB and GABA are functionally distinct from the cytosolic pools of these metabolites. We further demonstrate that mitochondrial GBB can function as an antiport substrate of carnitine-acylcarnitine translocase (CACT), the transporter that mediates fatty acid uptake into the mitochondrial inner matrix. This activity complements the role of cytosolic GBB as the biosynthetic precursor to carnitine. Accordingly, ALDH1B1 can markedly enhance mitochondrial fatty acid oxidation (FAO), a catabolic process that has been linked to CRC and PDAC stemness, progression, and metastasis. Our findings reveal an unexpected role for ALDH1B1 in carnitine metabolism, GABA biosynthesis, and FAO and illustrate how the compartmental reprogramming of metabolic pathways can promote tumor growth.

cancer biology↗

Spike Sorting with VanillaSort

Training spike detectors on real recordings is challenging because algorithmically generated labels can be noisy and incomplete. We propose VanillaSort, combining multichannel detection with spatially augmented, template-guided clustering. VanillaDet uses visibility-aware masking, truncated Gaussian targets and a temporally tolerant positive-bag loss, followed by conditional event-SNR gating. VanillaCluster combines HuiduRep embeddings with relative-amplitude features for Gaussian mixture clustering and refines assignments using cross-fitted waveform templates built from selected core events. VanillaDet improves detection accuracy over SimSort by two and three percentage points on the static and drift subsets of Hybrid Janelia, respectively. The complete pipeline also improves sorting performance over the corresponding HuiduRep baselines. These results support learning from imperfect real-data labels and incorporating waveform consistency into neuronal assignment.

neuroscience↗

Unifying physical and molecular coordinate systems across modalities in spatial biology

Establishing a unified physical and molecular coordinate system from fragmented multi-modal data is a longstanding challenge in biology. Here, we present MAPS, a modality-agnostic platform for spatial biology comprising (1) MAPS-alignment for ultrafast alignment of any modality, (2) MAPS-integration for both anchored and unanchored integration across orthogonal modalities for 3D multi-modal reconstruction, and (3) MAPS-Explorer for large-scale interactive 3D analysis. MAPS outperformed existing methods across extensive benchmarks on 34 datasets spanning 16 technology platforms and 6 modalities, while delineating fine-grained multi-modal tissue architectures across diverse biological systems in mouse and human. At cross-consortium scale, MAPS integrated 434 slices comprising 21 million cells from 18 atlases and 5 modalities to construct the most comprehensive 3D multi-modal mouse brain atlas. At individual laboratory scale, MAPS empowered routine 2D spatial assays to reconstruct continuous 3D multi-modal landscapes of human hepatocellular carcinoma, revealing the limitations of 2D spatial relationships and uncovering depth-dependent immune-state transitions.

bioinformatics↗

Protective pan-betacoronavirus neutralizing antibodies by vaccination

The continued emergence of betacoronaviruses underscores the urgent need for vaccines that provide broadly protective immunity. Here, we present an epitope-focused vaccine strategy targeting the conserved S2 stem-helix region of the spike fusion machinery, a broadly neutralizing antibody-(bnAb) epitope shared across betacoronaviruses yet partially occluded on the native spike. Immunization of non-human primates with engineered S2 stem-helix nanoparticle immunogens, alone or followed by a SARS-CoV-2 BA.1 spike mRNA boost, elicited broadly cross-reactive antibody responses against sarbecoviruses, merbecoviruses, and embecoviruses and neutralized SARS-CoV-2, multiple variants, other sarbecoviruses, and MERS-CoV. Vaccine-elicited monoclonal antibodies displayed broad in-vitro neutralizing activity and protected against both SARS-CoV-2 and MERS-CoV in-vivo. Structural analyses revealed conserved features between rhesus and human stem-helix bnAbs, supporting the translational potential. Overall, our findings provide proof-of-concept that epitope-focused nanoparticle immunogens can target partially occluded, immunoquiescent bnAb epitopes, laying the groundwork for pan-betacoronavirus vaccines that provide broad protection and strengthen pandemic preparedness. ONE SENTENCE SUMMARYEpitope-focused S2 stem-helix nanoparticle immunogens elicit protective broadly neutralizing antibodies (bnAbs) against diverse betacoronaviruses in non-human primates, establishing a framework for development of pan-betacoronavirus vaccines.

immunology↗

Hidden genetic diversity in 320 nearly-complete East Asian genome assemblies

East Asian populations, representing over 20% of the global population, remain critically underrepresented in human genomic studies, limiting our understanding of population-stratified genetic variation and its implications for health and disease. Here we present the first phase of the Asian Pan-Genome project (APG), comprising 320 nearly complete, fully phased haploid genome assemblies from 160 East Asian individuals. These assemblies achieve unprecedented quality, with an average contig N50 of 144.3 megabase pairs and an average quality value of 64.5. Leveraging these superior assemblies, we reveal previously uncharacterized diversity in human repeatome, including population-stratified patterns in centromere satellites and rDNA arrays. Compared to existing global human genome assemblies, the newly generated genomes supplement 152 million base pairs of novel sequences, 355 gene gains, 18,300 structural variation loci and 26 large euchromatic inversions missing from current human pangenomes. We perform population stratification analyses of structural variations, and further resolve the structural haplotypes of complex genomic regions such as Major Histocompatibility Complex and Survival Motor Neuron loci across global pangenomes, exemplifying tandem-duplicate and inversion-rich complex locus architectures in the human genome, respectively. This resource provides a critical foundation for human genetic studies, especially for East Asian populations, promoting more accurate variant discovery, reducing bias, and ultimately advancing the equity and efficacy of genomic medicine.

genomics↗

IntraTalker - Modelling Intracellular Signalling in1 Cellular Crosstalk

Single-cell sequencing has advanced the study of cell-cell communication, yet most methods focus on intercellular ligand-receptor interactions while neglecting downstream intracellular signalling cascades and the possibility that downstream target genes themselves encode ligands, thereby propagating communication across multiple cells. We present IntraTalker+CrossTalkeR that combines intracellular (IntraTalker) and intercellular (CrossTalkeR) signalling from multimodal single-cell data. IntraTalker infers cell-type-specific transcription factor activities and constructs receptomes that link receptors to downstream target genes, which are then integrated with ligand-receptor predictions in CrossTalkeR. To prioritize signalling receptors, the framework performs in silico receptor perturbation. In a murine bone marrow dataset, this recovered the known function of the Il1r1 receptor in driving myeloid progenitor cell-state changes. In a human myocardial infarction dataset, it predicted a novel role for IGF1R signalling in driving the differentiation of fibroblasts towards progenitor fibroblast states.

bioinformatics↗

Diaphragmatic EMG Uncovers Left-Right Diaphragmatic Imbalance After Ischemic Stroke with Implications for Motor Recovery

BackgroundStroke-associated respiratory dysfunction has been increasingly recognized, yet whether diaphragmatic impairment after stroke involves lateralized neuromuscular imbalance remains unclear. MethodsIn this controlled experimental study, transient left middle cerebral artery occlusion and reperfusion (tMCAO) was performed in mice, followed by multimodal assessment of treadmill-based peak oxygen uptake testing, diaphragm ultrasonography, bilateral diaphragmatic electromyography (dEMG) with simultaneous respiratory flow monitoring, behavioral assessment, and whole-mount immunofluorescence imaging of the diaphragm. ResultsIschemic stroke reduced exercise capacity and diaphragmatic excursion without detectable diaphragm thinning, indicating functional impairment rather than overt atrophy. Bilateral dEMG revealed a subacute left-right asymmetry in inspiratory activation, with the ipsilesional hemidiaphragm exhibiting reduced amplitude, decreased area under the curve, and altered burst duration, consistent with a relative contralateral-dominant pattern rather than frank hyperactivation. Whole-mount imaging demonstrated asymmetric nerve remodeling, characterized by a nadir in ipsilesional nerve fiber density at 1 week and partial recovery by 2 weeks after stroke. These structural changes closely paralleled the dEMG alterations, suggesting a neural substrate for lateralized dysfunction. Exploratory analyses further linked dEMG parameters with motor recovery. ConclusionsThese findings provide novel evidence that ischemic stroke induces a left-right diaphragmatic neuromuscular imbalance, with structural and functional correlates in diaphragmatic innervation. The study further supports the utility of bilateral dEMG as a functional marker for assessing diaphragmatic dysfunction and monitoring recovery after stroke. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=190 SRC="FIGDIR/small/737872v1_ufig1.gif" ALT="Figure 1"> View larger version (41K): org.highwire.dtl.DTLVardef@10001a4org.highwire.dtl.DTLVardef@16bc3d5org.highwire.dtl.DTLVardef@5e40aorg.highwire.dtl.DTLVardef@be53b7_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

Nuclear translocation of phosphorylated YB-1 via small extracellular vesicles contributes to the malignant phenotype of triple negative breast cancer

Despite continuous progress in diagnosis and therapy, breast carcinoma (BC) remains a major health problem. Triple-negative (Estrogen Receptor-/Progesterone Receptor-/HER2-) breast cancer (TNBC) is the most aggressive subtype due to its high metastatic potential and resistance to chemotherapy. The Y-box binding protein 1 (YB-1) transcription factor, a protein present in both cytoplasm and nucleus, is a driver of TNBC malignancy as it stimulates its cancer stem cell phenotype and disrupts cell cycle progression. Here, we hypothesized that YB-1-containing sEVs deliver YB-1 to the nuclear compartment of recipient cancer cells and play a major role in the activation of the metastatic process. We found a selective enrichment of YB-1 in sEVs from MDA and 4T1 cells, with [~]65% and 50% of all sEVs positive for YB-1 by d-STORM. Administration of sEVs from wild-type MDA and 4T1 to their YB-1 knockout counterparts resulted in nuclear translocation of sEV-associated YB-1 and increased tumorsphere formation. Pharmacological blockade of the nuclear transport machinery based on the inhibition of the formation of the "VOR" complex (VAP-A-ORP3-Rab7) by PRR851 impaired both nuclear translocation and the YB-1-induced increase in tumorsphere formation. YB-1 phosphorylation at S102 was required for nuclear localization. In fact, loss of YB-1 phosphorylation inhibited tumorsphere growth and stemness of cancer cells and YB-1-positive sEVs restored the oncogenic behavior of cancer cells expressing phospho-mutant YB-1. Moreover, PRR851 inhibited the nuclear translocation of the phosphorylated form of YB-1 and the oncogenic behavior of the TNBC cells. These data support the conclusion that the nuclear translocation of sEV-associated phosphorylated YB-1 is an important factor in the malignant behavior of TNBC and a potential therapeutic target.

cancer biology↗

HnRNPAB-targeted antisense oligonucleotides ameliorate tau pathology and cognitive deficits by modulating Alzheimers disease-associated alternative splicing

Aberrant alternative splicing alters multiple disease-associated splicing events, including MAPT exon 10 inclusion linked to tau pathology, and thereby impacts Alzheimers disease (AD) progression. Heterogeneous nuclear ribonucleoprotein AB (hnRNPAB) functions as a splicing regulator, yet its roles in AD remain poorly defined. Here, we identified AB332, the full-length isoform of hnRNPAB, as a novel repressor of MAPT exon 10 inclusion. AB332 binds a conserved AAUAU motif and recruits RBMX and RBMXL1 through its RRM and glycine-rich domains to assemble a complex. Beyond MAPT, AB332 modulates a network of splicing events in multiple AD-associated genes, including STAG2, ApoER2, MCL-1, PICALM, and zDHHC7. Importantly, the exon 7-skipping isoform AB285 lacks these activities. Transcriptomic analysis of post-mortem brain tissues from AD patients revealed reduced expression of hnRNPAB, while selective downregulation of AB332 was confirmed in the hippocampus of 3xTg AD mice. We performed a systematic antisense oligonucleotide-tiling screen targeting hnRNPAB exon 7 and its flanking intronic regions, identifying ASO30 that specifically upregulated AB332 expression. In 3xTg AD mice, ASO30 restored hippocampal AB332 levels, reduced pathological tau phosphorylation, and rescued cognitive deficits. These findings define a molecular mechanism by which AB332 regulates AD-associated splicing events, thereby providing a therapeutic strategy targeting hnRNPAB for AD. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=79 SRC="FIGDIR/small/736008v1_ufig1.gif" ALT="Figure 1"> View larger version (23K): org.highwire.dtl.DTLVardef@621096org.highwire.dtl.DTLVardef@2f01b1org.highwire.dtl.DTLVardef@182e6forg.highwire.dtl.DTLVardef@190afd3_HPS_FORMAT_FIGEXP M_FIG C_FIG

molecular biology↗

Singlet-states-mediated highly efficient two-photon fluorescence in organic dyes

This study reports a brand-new continuous-wave-excited (CW-excited) two-photon fluorescence emission mechanism in indocyanine green (ICG), an organic fluorescent dye widely used in clinical practice. This mechanism is based on the excited state absorption (ESA) process of the first singlet excited state. Intramolecular electrons sequentially absorb two photons to reach a high-energy singlet excited state, followed by direct radiative transition to the ground state to generate fluorescence. The entire process is exclusively mediated by singlet states. We further summarize the essential requirements for organic dyes to realize this luminescence mechanism. First, the dye must possess at least two well-separated singlet excited states with distinct energies, corresponding to two absorption peaks at different wavelengths in the absorption spectrum. The wavelength of the high-energy singlet excited state is about half that of the first singlet excited state. Second, the peak in the absorption spectrum corresponding to the transition from the ground state to the first singlet excited state has a sufficiently large molar extinction coefficient. Third, the first singlet excited state exhibits the capability of ESA. Fourth, electrons at the high-energy singlet excited state can directly transit to the ground state and emit fluorescence. We validated this mechanism in a variety of organic dyes satisfying the above conditions, confirming its universality. Using CW laser as the excitation source, we achieved two-photon fluorescence imaging of mouse cerebral blood vessels at a depth of 400 m, which clearly resolves three-dimensional vascular networks with high resolution. We also performed two-photon fluorescence imaging on human gastric cancer tissue samples at a depth of around 150 m, which provides a low-cost strategy for clinicians to rapidly acquire high-contrast tumor tissue images.

bioengineering↗

Green genetically encoded IP3 biosensor for hierarchical analysis of its signaling network

Inositol 1,4,5-trisphosphate (IP3) is a key second messenger that regulates diverse physiological processes. Visualization of IP3 dynamics in living cells is therefore important for understanding its signaling processes. In this study, we developed genetically encoded green fluorescent IP3 biosensors named Green iPenguins with distinct half-maximal effective concentrations (EC50) for IP3, enabling detection of IP3 signals over a range of concentrations. The biosensors displayed more than a 4-fold increase in fluorescence intensity upon IP3 and showed high specificity for IP3 over structurally related molecules. When expressed in HEK293T cells, the biosensors enabled visualization of IP3 dynamics involved in different signaling pathways. They were also compatible with dual-color imaging, allowing simultaneous monitoring of IP3 together with cAMP or Ca2+ signals. In addition, the hierarchical relationship between IP3 and Ca2+ signaling was visualized, providing insight into the temporal relationship between these two second messengers. The biosensors are expected to facilitate future studies of physiological processes involving IP3 signaling networks.

bioengineering↗

Cortical Stimulation Strength and sgACC Connectivity Shape Neuro-Cardiac Responses to Prefrontal TMS

Autonomic dysregulation is a core feature of major depressive disorder and a promising physiological readout for early signs of clinical effectiveness of therapeutic TMS targeting prefrontal regions. Yet the stimulation dose and network properties required to optimally engage autonomic circuits remain elusive. Here, we applied a cortex- and circuit-centered dosing framework combining resting-state fMRI, simulations of the TMS-induced electric field, and electrocardiography acquired during repetitive TMS of six left dorsolateral prefrontal cortex (DLPFC) targets in healthy adults. Heart-brain coupling (HBC), defined as spectral power in the cardiac response locked to the TMS onset frequency, was modeled as a function of either conventional motor-threshold-based dose or cortical electric-field strength, with and without DLPFC connectivity to the subgenual anterior cingulate cortex (sgACC). Across linear and nonlinear models, cortical electric-field dose explained substantially more variance in HBC, indicating that prefrontal TMS dosing is best assessed at the cortical level. Incorporating sgACC connectivity further improved model fit and revealed site-specific electric-field-by-connectivity interactions, with the strongest and most reliable HBC modulation at DLPFC regions anticorrelated with sgACC. Voxel-wise TMS mapping identified individualized cortical hotspots spatially overlapping with sgACC-anticorrelated tissue. Notably, whereas negative connectivity showed the most robust and monotonic effects, nonlinear dose-response analyses suggested a confined stimulation range over which positively connected sites also exhibited HBC modulation. Together, these findings position HBC as a network-sensitive physiological readout of DLPFC-sgACC-vagal engagement and offer a principled answer to where and how much to stimulate, supporting an electric-field- and connectivity-informed dosing framework for refining prefrontal TMS in depression-related autonomic dysregulation.

neuroscience↗

geneSync: Gene Symbol Harmonization for Large-scale RNA-seq Data Integration

Cross-cohort integration of transcriptomic data is a routine strategy for boosting statistical power and enhancing generalizability. However, gene nomenclature inconsistencies across datasets--arising from annotation version updates, historical renaming, and synonym reassignment--introduce silent mismatches during feature alignment, causing genes to be falsely classified as absent or split into duplicate features. Here, we present geneSync, an R package that performs gene symbol harmonization as a quality-control (QC) step prior to data integration. geneSync uses a hierarchical matching strategy, prioritizing exact matches to authoritative gene symbols, then exact matches to National Center for Biotechnology Information (NCBI) gene symbols, and finally synonym-based fallback. It includes built-in offline databases for human, mouse, and rat, and supports auditable conflict resolution, cross-species ortholog mapping, and native integration with Seurat and SingleCellExperiment objects. Benchmarking across six mouse hippocampus scRNA-seq datasets spanning 2020-2025 and five CellRanger versions shows that 1.41%-6.22% of features require synonym resolution, and harmonization improves pairwise gene overlap by up to 13.14 percentage points, rescuing 707-1,098 genes per dataset pair. Notably, CellRanger annotation version--rather than data collection year--was identified as the primary driver of nomenclature discrepancy. geneSync is freely available at https://github.com/xiaoqqjun/geneSync.

bioinformatics↗

Potent and Broad HIV-1 Neutralization by a Bispecific CD4-CD4i Fusion Protein based on Single-Domain CD4-D1 and X5 CD4i antibody

Human immunodeficiency virus (HIV) infection remains a global health threat. Although antiretroviral therapy (ART) has significantly transformed HIV into a manageable chronic disease, emergence of drug resistance to current ART is a continuing concern. Broadly neutralizing antibodies, as well as reagents containing both a soluble CD4 mimetic and an HIV co-receptor inhibitor--such as CD4-CD4i antibodies--are promising strategies for the prevention and treatment of HIV infection. We previously developed a CD4 D1mimetic (mD1.22) with enhanced neutralization potency, surpassing that of the clinically validated sCD4-D1D2 mimetic. We also previously identified a novel CD4i antibody (X5) that targets the conserved coreceptor binding site on the gp120 core and recognizes an epitope partially overlapping with 17b monoclonal antibody binding site. X5 binding to gp120 was augmented by CD4 and modestly enhanced by CCR5. To leverage these favorable interactions, we designed and optimized sCD4-X5 bispecific antibodies by computational structure-aided modification of antibody size and fusion linkers between the two binding moieties. The bispecific D1X5, with a (G4S)7 long linker between D1 and X5 (IgG1-LL D1X5), exhibited broad neutralization against 11 diverse HIV subtypes across B, C, G clades and AC, BC recombinants. The TZM-bl cell neutralization assay showed IgG1-LL D1X5 neutralization geometric mean IC50 and IC80 are 0.6 g/mL and 3.4 g/mL respectively, which are within the range of potent bnAbs. This work has identified a novel single domain soluble CD4 based CD4-CD4i bispecific antibody with broad HIV-1 neutralization.

molecular biology↗

Emergent frequency-dependent selection predicts mutation outcomes in complex ecological communities

Ecological interactions can dramatically alter evolutionary outcomes in complex communities. Yet, the framework of population genetics largely neglects interactions from a species-rich community. Here, we bridge this gap by using dynamical mean-field theory to integrate community ecology into classical population genetics models. We show that ecological interactions result in emergent frequency-dependent selection between parents and mutants, characterized by a single parameter measuring the strength of ecological feedbacks. This result generalizes classical population genetics models to highly diverse communities and enables predictions of mutation outcomes in these eco-evolutionary settings. We derive an analytic expression for fixation probability that extends Kimuras formula and reveals that ecological interactions strongly suppress the fixation of moderately beneficial mutations. This suppression arises because frequency-dependent selection leads to prolonged coexistence between parent and mutant lineages, which acts as a barrier to fixation. The strength of these effects increases with effective population size and the number of open niches in the ecosystem. Our study establishes a framework for integrating ecological interactions into population genetics, showing that evolutionary outcomes can be predicted using simple models even in the presence of complex community feedbacks.

evolutionary biology↗

Low-Intensity Focused Ultrasound Enhances Meningeal Lymphatic Drainage for Preventing Cognitive Decline in Alzheimer's Disease

Meningeal lymphatic vessels (mLVs) are vital for brain waste clearance, making them a promising therapeutic target. However, effective modulation strategies for mLVs with translational potential remain underdeveloped. Here, we develop a low-intensity focused ultrasound (LIFU) strategy that precisely targets the vault cranial meninges to non-invasively facilitate mLVs drainage. Using models of Alzheimers disease (AD) and aging, we demonstrate that this approach promotes CSF drainage, prevents cognitive decline, and reduces pathological biomarkers. Mechanistically, RNA sequencing combined with calcium imaging in vitro reveals that LIFU activates the Piezo1 ion channel in lymphatic endothelial cells, whereas pharmacological inhibition of Piezo1 abolishes LIFUs therapeutic effects. Compliant with FDA safety guidelines, this LIFU protocol demonstrates strong clinical translatability. If its efficacy is clinically confirmed, LIFU offers a promising therapy for neurodegenerative diseases triggered by waste accumulation.

neuroscience↗