LOESS-based normalization workflow for targeted HDL glycoproteomics in an Alzheimer's disease cohort

RSC Advances · 2026-01-01

LOESS-based normalization with internal standards improves analytical stability in HDL glycoproteomics, enabling detection of APOE genotype-associated differences in peptide abundance in an Alzheimer's disease cohort.

Neonatal Enteric Infection Disrupts the Microbiota-Gut-Brain Axis Through Pattern Recognition Receptors and Altered Neuroimmune Signaling

bioRxiv (Cold Spring Harbor Laboratory) · 2026-01-15

ABSTRACT Early-life enteric infection can have long-lasting effects on the microbiota–gut–brain (MGB) axis. Using a neonatal Enteropathogenic Escherichia coli (EPEC) model, we show that intestinal epithelial cell (IEC) NOD1 signaling coordinates mucosal immunity, barrier repair, and neuroimmune outcomes throughout early development and into adulthood. Neonates infected at postnatal day (P) 7 exhibited ileal inflammation, as demonstrated by increased expression of inflammatory cytokines ( Il1β , Il6 , Il12 , Il22 ), chemokines/chemokine receptors ( Ccl2 , Cxcl1 , Ccr2 ), and barrier-repair genes ( Muc2 , Slc26a3 ), with increased monocyte/macrophage infiltration and reduced epithelial proliferation in WT mice that was blunted in Nod1 ΔIEC mice. Neonatal infection of WT mice induced persistent defects into adulthood (P56), including increased intestinal permeability, sustained inflammatory/repair signatures, hippocampal inflammation, altered neurogenesis, and impaired recognition memory, which were largely absent in Nod1 ΔIEC mice, establishing a crucial role for IEC NOD1 as a determinant of long-term MGB remodeling. Microbially derived ligands of NOD2, muropeptides, isolated from probiotic Lactobacillus species attenuated EPEC-induced mucosal inflammation and chemokine induction without altering bacterial burden, demonstrating NOD2 host-directed immunomodulation. Together, these findings identify an important role for NOD-dependent signaling axis in the gastrointestinal tract that links early-life infection to enduring gut-brain dysfunction and reveals probiotic-derived muropeptides as candidate microbial therapeutics.

A Multi-Glycomic Method for Resistant Starch Structural Characterization

SSRN Electronic Journal · 2026-01-01

A multi-glycomic tool for characterization of resistant starch

Carbohydrate Polymers · 2026-04-09

Selective Human-Milk-Inspired Antimicrobial Peptides for the Treatment of Bacterial Vaginosis

Pharmaceutics · 2026-03-17

Background: Antimicrobial resistance (AMR) is a global healthcare threat. Traditional largely non-selective antibiotics produce side effects due to the natural host microbiome being modified creating a loss in homeostasis. In women, AMR is a cause of acute generational impact. For example, bacterial vaginosis (BV), the most common gynecological infection in reproductive-age women, is a serious public health concern due to its high rates of recurrence, secondary infections, and reproductive issues; and two currently prescribed antibiotics for BV do not fully resolve the symptoms. Objective: The strong need for innovative, potent, safe, and selective therapeutics has prompted a search for such bioactive molecules in milk. Resulting from 200 million years of evolutionary pressure, mammalian lactation not only nourishes infants, but it has also been under relentless Darwinian selective pressure to provide protection from a variety of infections. Methods: Computationally designed human-milk-inspired peptides (AMPs) were tested in standard microbicidal assays for activity against BV pathogens, and evaluated for stability and safety. Results: Several AMPs are bactericidal towards Gardnerella vaginalis, a major BV-associated pathogen, and other BV-associated pathogens. Some novel AMPs do not impact the viability of key lactobacilli linked to a healthy vaginal microbiome. These stable, membrane-acting cationic AMPs reduce inflammation during an infection assay and are safe in EpiVag organoid tissues. Conclusions: AMPs can address concerns like non-selectivity and antibiotic resistance—thereby addressing AMR. Lead AMPs from this study offer a promising solution for the development of novel therapeutics for the treatment of BV, which may reduce the burden of AMR.

Author response for "Comparative glycomic analysis of hawk (<i>Rupornis magnirostris</i>), caiman (<i>Caiman latirostris</i>) and sea turtle (<i>Caretta caretta</i>) tear films"

2025-07-25

Simultaneous Isolation and Characterization of Lipoprotein Classes in Plasma, Including HDL Subclasses and the Uncharacterized Dense HDL

bioRxiv (Cold Spring Harbor Laboratory) · 2025-09-30

Summary Lipoproteins (LPP) and extracellular vesicles are carriers of extracellular small RNA, with potential applications both in the areas of diagnostics and therapeutics. Lipid nanoparticles overlap across a range of densities and sizes in plasma, making them difficult to isolate intact and without contamination from other plasma components. Accurate characterization of their cargo through efficient isolation from other plasma components is required to understand their function. Here we describe the simultaneous separation of LPP classes using sequential flotation ultracentrifugation followed by size exclusion chromatography from 500µL of starting plasma. Using western blot, denaturing and non-denaturing gel electrophoresis, nuclear magnetic resonance, and electron microscopy, we demonstrate separation of the LPP classes with minimal contamination. We also show unique lipidomic, proteomic and small RNA signatures for each LPP class, including, for the first time, very high density high density lipoprotein particles in the density range of 1.21–1.25 g/mL. Motivation In plasma, lipid nanoparticles overlap in size and density, making it difficult to separate and isolate intact particles. Additionally, currently available methods do not allow for simultaneous characterization and isolation of these particles. This method resolves both challenges. The results presented also analyze and describe the presence of known lipoprotein particles, as well as those that have been previously under-characterized.

Corrigendum to “Development of a comprehensive food glycomic database and its application: Associations between dietary carbohydrates and insulin resistance” [Food Chemistry 473 (2025) 142977]

Food Chemistry · 2025-04-03

Expression and characterization of SARS-CoV-2 spike protein in Thermothelomyces heterothallica C1

Vaccine · 2025-09-30

The COVID-19 pandemic demonstrated a pressing need for rapid, adaptive, and scalable manufacturing of vaccines and reagents. With the transition into an endemic disease and rising threats of other emerging pandemics, production of these biologicals requires a stable and sustainable supply chain and accessible distribution methods. In this study, we demonstrate the strength of an engineered filamentous fungal platform, Thermothelomyces heterothallica C1, for high volumetric productivity of the full-length spike glycoprotein. Spike protein produced in this system is highly thermostable and immunization of mice with spike made in C1 or mammalian platforms resulted in a similar humoral response. Additionally, it was shown that the native N-glycan profile can be redecorated with complex sialylated structures, if necessary, resulting in a more human-like glycan profile, without impacting binding characteristics as shown experimentally and in simulations. Through extensive physicochemical analysis, the C1-produced spike performs similarly to spike proteins produced in other commercially available systems. The data presented is evidence that C1 can be a strong platform for production of complex glycosylated recombinant proteins such as subunit antigen vaccines. • Engineered filamentous fungal platform, Thermothelomyces heterothallica C1 is suitable for high volumetric productivity of the full-length spike glycoprotein. • Spike protein produced in this system is highly thermostable and immunization of mice with spike made in C1 or mammalian platforms resulted in a similar humoral response. • The native N-glycan profile can be redecorated with complex sialylated structures, if necessary, resulting in a more human-like glycan profile. • C1 produced spike performs similarly to spike proteins produced in other commercially available systems. • This can be a useful platform for production of complex glycosylated recombinant proteins such as subunit antigen vaccines.

Author response for "Comparative glycomic analysis of hawk (<i>Rupornis magnirostris</i>), caiman (<i>Caiman latirostris</i>) and sea turtle (<i>Caretta caretta</i>) tear films"

2025-07-08