Microglia response is proposed to be relevant in the neurogenerative process associated with alpha-synuclein (a-syn) pathology in Parkinson\'s disease (PD). STING is a protein related to the immune sensing of DNA and autophagy, and it has been proposed to be involved in PD neurodegeneration. To investigate this, we injected 10 g of murine pre-formed fibrils (PFFs) of a-syn (or monomeric and PBS as...

Prostate cancer (PCa) is an androgen receptor (AR) driven, high-incidence disease significantly contributing to cancer mortality. PCa is in need of better risk stratification at diagnosis and treatment outcomes in patients at high risk of metastasis. The unfolded protein response (UPR) is an AR-dependent process. However, the impact of the UPR transducer IRE1 on AR-dependent biology and treatment ...

Background. The association between plants and soil microbes is critical for both soil and plant health. Studies have shown that introducing beneficial microbial inoculants can shape the soil microbiome community for plant health. Among these microbes, mycorrhizal fungi play a well-documented role in enhancing nutrient uptake in plants. Ergothioneine (ERGO), a compound well-known for its anti-infl...

The rise and fall of motivational states may take place over timescales as long as many days. We used mouse mating behavior to model how the brain orchestrates slow-timescale changes in motivation. Male mice become sexually satiated after successful matings, and their motivation to mate gradually recovers over a week. Using deep-brain fluorescence-lifetime imaging in the medial preoptic area (MPOA...

Motivation: Antibodies possess high specificity toward target antigens, making them critical for therapeutic applications. However, experimental screening of antibody-antigen interactions is labor-intensive and costly. Existing structure-based computational methods often face significant challenges in modeling the dynamic conformational flexibility that governs antibody-antigen interactions, which...

Self-amplifying RNA (saRNA) has the potential to provide durable, non-integrating transgene expression for transient gene therapy. However, its auto-replicative nature mimics viral infection, triggering innate immune responses that shut down cap-dependent translation, degrade cellular mRNA, induce cell death, and release cytokines. In non-immunotherapy applications, this immune activation is undes...

High-Codon is a deep learning-based codon optimization tool designed to enhance the expression levels of heterologous proteins in Escherichia coli. This approach employs a BERT pre-trained model to construct a sequence labeling framework for predicting optimal codons. Additionally, an expression-level weighted loss function is introduced to strengthen the model's ability to learn from highly expre...

Complex biosystems exhibit ordered, functional, self-organized features. However, a universal framework for exploring their logical paradigms and dynamic characteristics remains lacking. Here we describe BioLogical, a user-friendly R package, designed for analyzing properties of biosystems. We demonstrate its versatile capacities of deciphering multi-valued logical paradigms, calculating order par...

Humans have the capacity to persist in behavioural policies, even in challenging environments that lack immediate reward. Persistence is the scaffold on which many higher executive functions are built. However, it remains unclear whether humans are uniquely persistent or, instead, if this capacity is widely conserved across species. To address this question, we compared humans with mice and monkey...

MicroRNAs (miRNA) are small non-coding RNAs that are key negative regulators of gene expression. Their roles include shaping the gene expression landscape during and after brain development by defining and maintaining levels of proteins that generate the distinct morphological and functional properties of neurons and other brain cell types. HT22, N2A, and SH-SY5Y are common immortalized neuronal c...

Mutations in the dystrophin (DMD) gene can cause a spectrum of muscle-wasting disorders ranging from the milder Becker muscular dystrophy (BMD) to the more severe Duchenne muscular dystrophy (DMD). Among these, exon 45 deletion is the most frequently reported single exon deletion in DMD patients worldwide. In this study, we generated a novel rat model with an exon 45 deletion using CRISPR/Cas9 tec...

Moore swabs have been used extensively for passive sampling in wastewater surveillance, typically yielding presence/absence information for targets of interest. Quantitative analysis of Moore swab data is only possible if target uptake is well characterized, specifically the relationship between quantity of the target in the liquid sample matrix and the quantity of target sorbing to the Moore swab...

Human chorionic gonadotropin beta (beta-hCG) is an oncofetal antigen expressed by trophoblast cells of the placenta, with minimal expression in adult somatic tissues. Numerous studies have demonstrated that beta-hCG-encoding genes are expressed in various cancers, but expression of these genes (CGB3, CGB5, CGB7, and CGB8) across diverse cancers has not been systematically evaluated. Here, we repor...

Achieving high binding strength and efficient delivery of molecular cargo to cells expressing biomarker targets is a significant challenge in drug delivery. Here, we investigated how altering the surface immobilization residue (i.e. anchor point) within a non-antibody binding scaffold called Anticalin can enhance particle adhesion to the immune checkpoint protein CTLA-4 on mammalian cells under sh...

Humans effortlessly relate what they see to what they know, drawing on existing knowledge of objects perceptual, conceptual, and contextual attributes while searching for and recognising objects. While prior studies have investigated the temporal dynamics of perceptual and conceptual object properties in the neural signal, it remains unclear whether and when contextual associations are uniquely re...

Cellular differentiation processes are largely orchestrated by variation in transcription factor (TF) abundance. Since these proteins are usually expressed at extremely low levels, studying TF-driven cellular processes using single-cell proteomics by mass spectrometry (scp-MS) has been challenging. Here we present informed DIA (iDIA), an acquisition method tailored towards low-input and scp-MS. iD...

Drosophila melanogaster serves as a powerful model for studying neurodegenerative diseases, often employing the GAL4-UAS system for targeted gene expression. Electroretinograms (ERGs) provide a robust in vivo functional readout of neuronal integrity and are increasingly used to assess disease progression and therapeutic interventions in these models. However, the genetic background upon which thes...

A quantitative measurement can have variation, referred to here as measurement variation, which is a probability distribution. Machine Learning models typically produce a prediction corresponding to the mode of the measurement variation. The Deviation Error is a novel metric, described here, to assess predictions that accounts for measurement variation. Measurement variations in genomics data were...

Tumor-associated macrophages (TAMs) represent a major immune population within the tumor microenvironment, influencing cancer progression and immune responses. Our group previously identified a subset of pro-inflammatory TAMs associated with poor prognosis in human melanoma. GM-CSF, a myeloid-priming cytokine, exhibits context-dependent effects on tumor growth and, despite its clinical use, its ro...

Background: Colonization with Staphylococcus aureus is a risk factor for subsequent infection. Decolonization with the topical antibiotic mupirocin is effective and reduces the risk of subsequent S. aureus infection for both methicillin-sensitive (MSSA) and methicillin-resistant (MRSA) strains but may select for mupirocin-resistant isolates. Methods: We characterized oxacillin and mupirocin suscep...