Faculty Bibliography

L-Glutamic acid (L-Glu) is central to carbon-nitrogen metabolism, yet its ability to improve starch quality by regulating grain metabolism and by directly modulating starch structure remains unclear. In this study, we integrated a field experiment with an in vitro experiment and combined untargeted metabolomics, microscopy, structural characterization, physicochemical and processing property analyses, and molecular dynamics simulations. It was found that under drought, L-Glu spraying reprogrammed the grain metabolome, with pathway enrichment in aminoacyl-tRNA biosynthesis and starch/sucrose metabolism. In vitro, L-Glu increased the full width at half maximum of the Raman band at 480 cm^-1 and altered the FTIR absorbance ratio of 1047/1022 cm^-1. L-Glu enhanced in vitro digestibility and reduced swelling power and paste transparency, while decreasing setback viscosity, suggesting a potential inhibition of short-term starch retrogradation; however, freeze-thaw stability was reduced. Microscopy revealed a more disordered gel network after L-Glu addition. Simulations showed that L-Glu formed 1.47-2.18 persistent hydrogen bonds with amylose chain per system and extensive hydrogen bonds with water.

This study evaluated whether remediation at the Ringwood Mines/Landfill Superfund site in New Jersey reduced soil heavy metal exposure and associated health risks for the Ramapough Lunaape Turtle Clan, a Native American community whose traditional ties to the local land may increase exposure to legacy pollution. Soil heavy metal concentrations were measured in frequently visited areas in and around the Ringwood Superfund site, and evaluated against background levels using the geo-accumulation index (I_geo) and ecological risk index (E_r). I_geo results signaled anthropogenic enrichment of antimony, arsenic, cadmium, and lead, with cadmium showing E_r values denoting very high ecological risks. Receptor models (Positive Matrix Factorization [PMF] and UNMIX) identified source profiles consistent with iron mine tailings (arsenic, cobalt, iron, and vanadium) and automotive waste (cadmium, chromium, lead, and nickel), linking observed contamination to the sources responsible for the site's Superfund designation. Monte Carlo simulations of the hazard index (HI) and total cancer risk (TCR) indicated potential non-cancer and cancer risks for children and adults, primarily through soil ingestion, dermal contact, and game meat consumption-an oft-overlooked pathway in conventional risk assessments. Despite claims that the site is under control for human exposure, soil contamination from legacy sources persisted at levels associated with excess health risks. Findings from this study highlighted potential deficiencies in current remediation strategies in protecting the health of Native American communities with cultural and subsistence ties to their land, and contributed evidence that can inform future studies in similar settings.

PURPOSE/UNASSIGNED:To evaluate whether a non-invasive approach to treat keratoconus with corneal cross-linking (CXL) using oral riboflavin and natural sunlight could represent a cost-effective alternative. METHODS/UNASSIGNED:In a prospective, controlled study, 16 male New Zealand White rabbits (32 eyes) underwent a two-step protocol. Step 1 quantified stromal riboflavin in 4 rabbits (8 eyes) after 14 days of oral riboflavin (6 mg/kg/day). Step 2 randomized the remaining 12 rabbits (24 eyes) 1:1 to oral riboflavin plus natural sunlight or sunlight alone. After a 2,700 klux·h cumulative sunlight dose, corneal biomechanics were assessed by optical coherence tomography elastography and uniaxial stress-strain extensometry. RESULTS/UNASSIGNED:= .039), consistent with reduced apparent stiffness. CONCLUSIONS/UNASSIGNED:Oral riboflavin combined with ambient sunlight did not induce corneal stiffening under the tested conditions. Stromal riboflavin levels were nearly 500-fold lower than those achieved with standard CXL, indicating the tested approach is unlikely to serve as an effective standalone cross-linking strategy. The observed posterior corneal stiffness reduction may reflect ultraviolet-A-induced stromal degradation or subthreshold photochemical effects rather than true cross-linking.

Freezing during Pavlovian fear conditioning is the most commonly used indicator of learned fear in rodents. Although freezing and its neural underpinnings have been widely studied, the field has largely ignored other potential indicators of learned fear. Darting, an escape-like conditioned fear response, occurs more frequently in females and is reliably predicted by a distinct behavioral phenotype: heightened shock response and decreased freezing compared to rodents that do not engage in darting. The experiments in this study sought to expand the field's understanding of conditioned fear by investigating the neural correlates of conditioned darting, focusing on the infralimbic cortex (IL) and longitudinal columns of the periaqueductal gray (PAG) due to their known roles in modulating defensive responses, including conditioned freezing. We find that fear conditioning elicits greater neural activity (measured by quantification of cFos expression) in the IL of females compared to males, but that IL activation corresponds to freezing only in Darters. We next used chemogenetic tools to excite or inhibit either the IL alone or IL-PAG projections prior to fear conditioning. IL manipulations in either direction reduced freezing in both males and females, while IL inhibition increased darting and shock response in females only, and the effects of circuit-specific manipulations were minimal. Together, our findings suggest a novel, role for the IL in driving defensive responses during fear conditioning that is not dependent on IL-PAG connectivity.

BACKGROUND:: The glioblastoma (GBM) immunosuppressive tumor microenvironment is a clinical challenge. Oncolytic Zika virus (ZIKV) has emerged as a promising therapy, targeting treatment-resistant glioma stem cells, stimulating CD8+ T-cell-mediated immunity and extends survival in preclinical models but myeloid cell-driven immunosuppression persists. An antagonist of Siglec-15, a myeloid immune checkpoint molecule, is in a phase II trial for non-small cell lung cancer, but its role in CNS malignancies remains unclear. METHODS:: We evaluated Siglec-15 expression in human GBM samples using flow cytometry, mass cytometry, and immunofluorescence, as well as a public database. Using syngeneic glioma models, we tested a blocking antibody against Siglec-15, and Siglec-15 knock out mice, alongside ZIKV and anti-PD-1 therapies. We performed survival studies and analyzed immune responses, T-cell proliferation and phagocytosis, and tumor rechallenge. RESULTS:: Siglec-15 was expressed by human GBM myeloid (16-22%) and tumor (18-19%) cells, and higher expression was associated with shorter survival. In CT2A-bearing mice, ZIKV + anti-Siglec-15 increased long-term survival to 60% (vs. 40% with ZIKV alone), rising to 83% with anti-PD-1 treatment. Triple therapy in SB28 bearing mice yielded 76% long-term survivor rate with 1.7-fold higher CD8+ T-cell activation. Rechallenged mice showed 11-fold expansion of brain resident/effector memory CD8+ T-cells and 80% survival. Siglec-15 loss on myeloid cells enhanced phagocytosis (CT2A: 25%; SB28: 7%) and T-cell responses (activation: 81%; proliferation: 86.8%). CONCLUSION/CONCLUSIONS:: Targeting Siglec-15, combined with PD-1 blockade and ZIKV overcomes myeloid immunosuppression and enhances T-cell activation in GBM, promoting durable anti-tumor immunity. These findings support further investigation of this combination therapy.

Early life is characterized by heightened susceptibility to respiratory pathogens, yet the immune mechanisms that predispose infants to infection remain poorly defined. Using an infant mouse model of Streptococcus pneumoniae (Spn) colonization, we identify an age-dependent delay in IL-17 A production that was associated with prolonged bacterial colonization in infant mice. Consistent with a critical role for this pathway, IL-17 receptor A (IL-17RA)-deficient infant mice exhibited persistent Spn colonization of the upper respiratory tract (URT). Transcriptomic profiling of the URT from Spn-colonized IL-17RA-deficient infant mice revealed an enrichment of antiviral responses compared to WT controls and included increased expression of the interferon-stimulated gene Cxcl10, a chemokine whose expression is positively associated with Spn carriage in humans. These results suggested that IL-17RA signaling constrains the interferon response during URT Spn colonization. WT infant mice exhibited progressively increased expression of Cxcl10 during Spn colonization and was dependent on type 1 interferon (IFNAR1) signaling and the pore forming bacterial toxin, pneumolysin. Genetic deletion of Ifnar1 or Cxcl10, including myeloid cell-specific deletion of Ifnar1, accelerated bacterial clearance in infant mice. In contrast, adult mice exhibited earlier induction of IL-17 A, minimal induction of Cxcl10 expression, and no alteration in bacterial clearance rates following Ifnar1 or Cxcl10 deficiency. Taken together, our results reveal a developmental window in which delayed IL-17 A production postpones the IL-17RA-dependent restraint of the type I interferon/CXCL10 axis, thereby prolonging pneumococcal carriage through impaired myeloid cell-mediated bacterial clearance.

Developing dry antimicrobial delivery systems that combine bioactive protection with biofilm-matrix disruption remains a major challenge. Building on a previously established protease-modulated pea protein isolate (PPI)-carvacrol nanoemulsion system, this study developed protease-assisted microcapsules designed to preserve carvacrol and promote the removal of preformed biofilms. Carvacrol-loaded nanoemulsions were prepared at pH 3.5, 7.0, and 10.0 and supplemented with pepsin or trypsin before spray-drying or freeze-drying with maltodextrin. Protease-specific interfacial modification markedly affected emulsion stability, powder structure, and encapsulation performance. At pH 7.0 and 10.0, trypsin reduced droplet size from 284.60 to 232.52 nm and from 149.13 to 140.38 nm, respectively. The resulting spray-dried microcapsules exhibited high encapsulation efficiency (>96%) and low surface carvacrol contents (0.95-1.24 mg/g). In contrast, pepsin caused pronounced destabilization under acidic conditions, particularly after freeze-drying, yielding porous powders with an encapsulation efficiency of 48.18% and a surface carvacrol content of 69.51 mg/g. Trypsin-assisted microcapsules achieved 90-99% removal of preformed Listeria innocua biofilm biomass within 1 h, whereas enzyme-free and pepsin-containing formulations generally remained below 40%. Microscopic observations confirmed extensive disruption and detachment of the biofilm structure. After one year at 4 °C, trypsin-loaded formulations retained high biofilm biomass removal activity (85-99% after 2 h). These findings demonstrate that protease-assisted microencapsulation can couple interfacial regulation during particle formation with enzyme-mediated biofilm-matrix disruption after rehydration, providing a sustainable carvacrol delivery platform with durable antibiofilm functionality.

Children and youth seeking asylum encounter a range of unique experiences and obstacles in their efforts to secure protected immigration status. This study used a consensual qualitative research approach to analyze data that centered lived experience voice gathered from first-person interviews with 12 adults, six men, and six women aged 18-29 years, who entered the United States as minor asylum seekers. Results indicated that they experienced premigratory exposure to violence or harm, psychological distress, financial instability, and obstacles to health care. Participants also reported fear, adversity, and time spent in immigration detention centers as they sought asylum in the United States. Further, they disclosed current mental health concerns, as well as barriers to education, employment, and legal representation. Participants identified a series of effective internal and external supports they leveraged to adaptively respond to systemic challenges, described their aspirations for the future, and provided recommendations for guiding clinicians in service provision. The results of the study can inform psychologists and allied professionals about the impact of exposure to harm that asylum-seeking minors face, this population's resilience, and possible strengths-based strategies for responding to the needs of young people experiencing forced displacement and areas of potential advocacy. (PsycInfo Database Record (c) 2026 APA, all rights reserved).

Apicomplexan parasites, including Toxoplasma gondii and Plasmodium falciparum, reside within a specialized compartment known as the parasitophorous vacuole (PV) during their intracellular life cycle. The PV membrane (PVM), which derives from the host plasma membrane upon invasion, serves as a selective barrier that permits nutrient acquisition while shielding the parasite from host defense mechanisms. Although the protein composition of the PVM has been studied extensively, its lipid organization remains poorly understood. Using the quick-freeze, freeze-fracture replica labeling (QF-FRL) method, we quantitatively analyzed the transbilayer distribution of phosphatidylserine (PtdSer), phosphatidylethanolamine (PtdEtn), and GM3 ganglioside in the PVM of T. gondii and P. falciparum. Unlike host cell plasma membranes, where these lipids exhibit strict asymmetry-PtdSer and PtdEtn confined to the cytoplasmic leaflet and GM3 to the exoplasmic leaflet-we found that all three lipids were symmetrically distributed across both leaflets of the PVM. This striking loss of lipid asymmetry suggests that the PVM undergoes profound remodeling during infection. The presence of PtdSer and PtdEtn in the luminal leaflet may facilitate the binding of perforin-like proteins (PLP1s) during egress. These findings reveal a unique feature of the PVM that redefines our understanding of host-parasite membrane biology.

PURPOSE/UNASSIGNED:The high mortality associated with metastatic colorectal cancer (mCRC) illuminates an unmet need for innovative therapeutic modalities. Radiopharmaceutical therapy (RPT) offers a potent, molecular-scale approach for managing and treating cancers with distant micrometastases. However, its clinical use in mCRC remains an unrealized opportunity. We have therefore identified the transmembrane glycoprotein mucin 13 (MUC13) as a promising antigen for developing a targeted RPT and have undertaken preclinical evaluation of its potential by utilizing a monoclonal antibody tool representative of a future class of translatable therapeutics. EXPERIMENTAL DESIGN/UNASSIGNED:The immunoreactivity and transcriptome of patients with colorectal cancer (n = 72 primary, 100 liver metastases) were characterized using annotated clinical datasets. Preclinical assessment of MUC13 as an RPT target for mCRC was then performed in mice using a monoclonal MUC13-targeted antibody C14 labeled with either zirconium-89 for positron emission tomography (PET) measurement of mCRC-associated MUC13 density or terbium-161 for targeted RPT. RESULTS/UNASSIGNED:Strong MUC13 immunoreactivity was observed in ∼70% of mCRC and was inversely correlated with overall survival (P < 0.01). MUC13 levels were visualized by PET and agreed with immunohistochemically determined antigen presence. Furthermore, MUC13-targeted RPT exhibited in vivo proof-of-concept efficacy and enhanced survival in preclinical colorectal cancer models. Resulting imaging, therapeutic, and pathologic analyses elucidated relationships between target density, therapeutic outcome, and a potential genetic signature. CONCLUSIONS/UNASSIGNED:MUC13-targeted RPT response was not only associated with radiopharmaceutical accumulation but also seemed to be balanced by DNA damage repair gene expression, suggesting a potential sensitivity signature that could complement a future clinical theranostic approach in MUC13-positive mCRC.