Grid cells, found in the medial Entorhinal Cortex, are known for their regular spatial firing patterns. These cells have been proposed as the neural solution to a range of computational tasks, from performing path integration, to serving as a metric for space. Their exact function, however, remains fiercely debated. In this work, we explore the consequences of demanding distance preservation over ...

Native community resistance to plant invasion may reflect microbial effects on invader establishment. Here, we compared the effects of the aboveground and belowground microbes and leaf functional traits of 25 native plant species on the germination and survival of invader Ageratina adenophora. Results show that leaf physical and chemical traits vary among plant species and shape the aboveground mi...

The impact of the microenvironment on epigenetically plastic cancer cells underpins phenotypic heterogeneity, a major cause of metastatic dissemination and therapy resistance that together represent the primary cause of cancer-related death. Nutrient limitation is a key microenvironmental stress that can cause a phenotypic transition from proliferation to invasion via activation of the integrated ...

Self-incompatibility in flowering plants is a common mechanism that prevents self-fertilization and promotes outcrossing. In Brassicaceae, the self-incompatibility locus is highly diverse, with many alleles arranged in a complex dominance hierarchy and exhibiting monoallelic expression in heterozygote individuals. Monoallelic expression of the pollen self-incompatibility gene is achieved through t...

Understanding the dynamics and persistence of biodiversity patterns over short (contemporary) and long (thousands of years) time scales is crucial for predicting ecosystem changes under global climate and land-use changes. A key challenge is integrating currently scattered ecological data to assess complex vegetation dynamics over time. Here, we present VegVault, an interdisciplinary SQLite databa...

Host cells produce a vast network of antiviral factors in response to viral infection. The interferon-induced proteins with tetratricopeptide repeats (IFITs) are important effectors of a broad-spectrum antiviral response. In contrast to their canonical roles, we previously identified IFIT2 and IFIT3 as pro-viral host factors during influenza A virus (IAV) infection. During IAV infection, IFIT2 bin...

Background: Alzheimer's disease (AD) is characterized by the accumulation of amyloid beta-42 in the brain, causing various adverse effects. Thus, therapies that reduce amyloid beta-42 toxicity in AD are of great interest. One promising approach is to use extracellular vesicles from human induced pluripotent stem cell-derived neural stem cells (hiPSC-NSC-EVs) because they carry multiple therapeutic...

Spatial transcriptomics (ST) enables gene expression analysis within spatial context of tissues. Since most data are limited to multicellular resolution, current computational methods can only estimate cell proportions. To address this gap, we introduce SpatioCell, a framework that integrates imaging data-derived morphological features with transcriptomic measurements for precise single-cell annot...

Glutamine serves as a major fuel source for tumor cell proliferation while simultaneously playing an essential role in maintaining gastrointestinal health and immune function. Controversy exists regarding glutamine supplementation for cancer patients undergoing chemotherapy and radiation, with concerns that it may stimulate cancer growth. The present study is the first to examine the effects of di...

The efficacy of T cell-activating therapies against glioma is limited by an immunosuppressive tumor microenvironment and tumor-induced T cell sequestration. We investigated whether peripherally infused non-antigen specific autologous lymphocytes (ALT) could accumulate in intracranial tumors. We observed that non-specific autologous CD8+ ALT cells can indeed accumulate in this context, despite endo...

Exponential accumulation of cell size and highly expressed proteins is observed at the single-cell level in many bacterial species. While the exponential rates fluctuate from cycle to cycle, they remain stable on average over time and strongly correlated across different proteins and cell size. In this study, we investigate growth-rate variability at this state of \textit{balanced biosynthesis}, a...

Companion dogs (Canis lupus familiaris) offer a unique model for studying the gut microbiome and its relation to aging due to their cohabitation with humans, sharing similar environments, diets, and healthcare practices. Here, we present the Dog Aging Project (DAP) Precision cohort, the largest population-wide study of the canine gut microbiome to date. This cohort encompasses over 900 dogs of div...

Purine metabolism is a promising therapeutic target in cancer; however how cancer cells respond to purine shortage,particularly their adaptation and vulnerabilities, remains unclear. Using the recently developed purine shortage-inducing prodrug DRP-104 and genetic approaches, we investigated these responses in prostate, lung and glioma cancer models. We demonstrate that when de novo purine biosynt...

Tumor-infiltrating lymphocyte (TIL) therapy, recently approved by the FDA for melanoma, is an emerging modality for cell-based immunotherapy. However, its application in immunologically 'cold' tumors such as glioblastoma remains limited due to sparse T cell infiltration, antigenic heterogeneity, and a suppressive tumor microenvironment. To identify genomic and spatial determinants of TIL expandabi...

T cells exhibit high heterogeneity in both their gene expression profiles and antigen specificities, but the precise relationship between these two features remains largely unknown. Utilizing a large-scale single-cell immune-profiling dataset that includes both T cell receptor (TCR) sequences and gene expression profiles of individual cells, we systematically investigated how the transcriptional p...

The ketogenic diet (KD) is an established treatment for patients with medically intractable epilepsy and is chiefly characterized by high fat/low-carbohydrate intake and the production of ketone bodies (KB) such as {beta}-hydroxybutyrate (BHB). However, after more than a century of clinical use, the mechanisms underlying its efficacy remain unclear. While prior investigations have examined the eff...

The KRasG12D mutant is an attractive target in oncology and can now be drugged via the switch-II allosteric pocket. Non-covalent ligands typically bind in the presence of a conserved structural water, which interacts with Thr58 and Gly10. In this work, we use a dataset of published non-covalent KRasG12D inhibitors to evaluate free energy methods for the interaction with or displacement of this con...

Background: Autism spectrum disorder (ASD), a condition defined by deficits in social communication, restricted interests, and repetitive behaviors, is associated with early impairments in motor imitation that persist through childhood and into adulthood. Alterations in the mirror neuron system (MNS), crucial for interpreting and imitating actions, may underlie these ASD-associated differences in ...

Reinvigoration of tumor-reactive T-cells using co-stimulatory bispecific antibodies (bsAbs) targeting CD28 or CD137 is emerging as a promising therapeutic strategy. Conditional, tumor-specific recruitment can offer a necessary layer of control and specificity. We developed pH-selective CD28xVISTA bsAbs to act specifically within the acidic tumor microenvironment (TME), aiming for enhanced T-cell-m...

Protein domains are conserved structural and functional units that serve as building blocks of proteins. Through evolutionary expansion, domain families are represented by multiple members in diverse configurations with other domains, evolving new specificities for their interacting partners. Here, we develop a structure-based interface analysis to comprehensively map domain interfaces from experi...