University of Portland

Historically, neural variability observed during task was interpreted as “noise,” assumed to obscure meaningful signal and thus something to be minimized both analytically by researchers and functionally by the brain. Changes to this signal-to-noise ratio have been proposed as a possible neural mechanism behind the increased reaction-time variability (RTV) in attention deficit hyperactivity disorder (ADHD). However, not all variability is the same – in some cases, variability can have some underlying “statistical structure” that can be beneficial to information processing. The challenge lies in distinguishing meaningful variability from random noise. The edge-of-synchrony critical point, which describes a system poised between synchronous and asynchronous regimes, could be a good theoretical framework to study these different types of neural variability. In this study, we investigate whether changes in criticality and oscillatory dynamics preceded slower behavioral responses during a bimodal continuous performance task in ADHD. We find evidence that, prior to slower responses, neural dynamics shift toward criticality in both ADHD and control groups, suggesting that increase variability in ADHD and during attention lapses are related to structured variability and not necessarily random noise. Notably, these findings run counter predictions based on the proposed model and previous literature on neural noise in this population, challenging predictions of edge-of-synchrony criticality as a unifying account of neural variability and behavioral performance. Furthermore, this effect did not emerge at the between-subject level, underscoring the limitations of relying on between-subject correlations to infer neural mechanisms.

Copper (Cu) is essential for innate immunity; however, how neutrophils regulate Cu homeostasis to support their functions remains unclear. We found that myeloid progenitors express abundant Cu-transporter ATP7B targeted to distinct vesicles and store Cu in vesicles. During neutrophil differentiation, ATP7B is downregulated, whereas ATP7A, LOXL2, and SLC31A2 are induced, suggesting a coordinated switch from Cu storage to utilization. As mature neutrophils exit the bone marrow, cellular Cu levels drop markedly, indicating Cu release during late maturation or egress. Myeloid-specific deletion of Atp7b in mice uncouples lineage commitment from functional maturation: Atp7b-deficient cells differentiate into neutrophils but fail to mature fully, showing more mitochondria, fewer lysosome-like structures, lower abundance of Cebp-ε and Ngal, reduced tubulin levels, and disrupted microtubules. Following lipopolysaccharide injection, Atp7b-deficient bone marrow releases fewer neutrophils into the bloodstream. Together, these findings reveal a previously unrecognized role of the Cu-transport network in neutrophil maturation and egress.

Background: Triple-negative breast cancer (TNBC) is an aggressive subtype of cancer with poor clinical outcomes. There is a critical need to identify novel, druggable targets for TNBC to improve therapy response and patient outcomes. Due to their roles in critical processes driving cancer progression, kinases have been a major focus of drug discovery efforts. The role of extracellular signal-regulated kinase 5 (ERK5) in mediating TNBC extracellular matrix (ECM) has previously been described in 2D culture and in vivo. Here, we characterized the impact of ERK5 on breast cancer biology in 2D culture, 3D spheroids, and our 3D breast adipose-macrophysiological system (BA-MaPS). Methods: We assessed migration changes in MDA-MB-231 parental and ERK5-knockout (ERK5-ko) cells cultured in the three in vitro models using transwell, scratch, and spheroid pseudo-migration assays. Differential gene expression among these cell lines in the three platforms was assessed by RNA sequencing and pathway analysis. Stromal remodeling of adipocytes and matrix was evaluated by H&E and Masson's Trichrome. Results: Across the in vitro models, ERK5 deletion impaired TNBC cell migration. ERK5-mediated transcriptomic changes included genes associated with epithelial-to-mesenchymal transition (EMT) and migration, with further analysis showing significant alterations in core and associated matrisome. Histological staining corroborated the downregulation of collagen with ERK5 depletion in the BA-MaPS. The NFκB pathway was significantly upregulated only in the ERK5-ko 2D-cultured cells, not in 3D spheroids nor the BA-MaPS model. Conclusions: These results indicate a link between ERK5 and TNBC progression through regulation of TME remodeling, EMT, and cell motility. Differences in 2D culture, 3D spheroid, and BA-MaPS underscore the importance of using physiologically relevant models in breast cancer research.

The genusStreptococcuscontains some of the most important commensals and pathogens of the human microbiome. To obtain the fatty acids required for cell membranes,Streptococcuseither produce fatty acidsde novothrough the fatty acid biosynthesis (fab) pathway or uptake host fatty acids through the fatty acid kinase (fak) pathway. Although both thefabandfakpathways represent potential therapeutic targets to prevent or treat infection, progress is limited because of an incomplete understanding of taxon-to-taxon variability in streptococcal lipid metabolism. Here, we examined the role ofde novomonounsaturated fatty acid (MUFA) synthesis in physiology and virulence-associated traits inStreptococcus mutans, Streptococcus pyogenes,andStreptococcus pneumoniae,three major pathogens that cause disease at distinct body sites. In all three species, deletion offabMabolished MUFA production and caused severe growth defects, decreased stress tolerance, increased antibiotic susceptibility, and defects in cell viability, morphology, and division. InS. mutans,loss offabMalso markedly reduced competence signaling and production of the mutacin IV bacteriocin. Deletion offabMincreased susceptibility to killing by human neutrophils inS. mutansandS. pneumoniae,but notS. pyogenes. Together, these findings illustrate that MUFA synthesis is broadly important for streptococcal physiology and cell membrane homeostasis, while its contribution to pathogenesis is strongly species- and context-dependent, providing leads to guide development of novel therapeutic and/or preventative strategies.

Fire whirls, a combustion-intensifying phenomenon, offer potential for cleaner, more efficient burns with reduced emissions in environmental applications like oil spill remediation. While most knowledge of fire whirls stems from laboratory-scale experiments, and only a limited subset of these experiments has captured emissions, this study addresses a critical research gap by conducting one of the largest controlled fire whirl experiments to date, focusing on enhancing in-situ burning. Using a 1.5-meter diameter crude oil pool with 15 mm and 40 mm slick thicknesses on an open water surface, fire whirls were successfully generated within a 5-meter-tall three-wall structure under the influence of various wind conditions. Measurements of flame geometry, flow velocity, temperature profiles, heat flux, mass consumption, and emissions were compared to pool fires. Results revealed that fire whirls, with mean flame heights nearly double those of pool fires, increased burning rates by 40% and reduced soot emissions by 40%. The highest fuel consumption efficiency of 95% was achieved in a 15 mm slick thickness fire whirl experiment, while in other fire whirl experiments, especially those with 40 mm slick thickness, premature extinguishment was observed lowering ultimate fuel consumption efficiencies. Enhanced performance compared to traditional pool fires suggests that fire whirls might be more effective for in-situ burning, however this efficiency is currently only achieved under calm ambient conditions. This study discusses the potential interactive effects of ambient conditions, configuration sizing, and boilover phenomenon on fire whirl dynamics, highlighting the need of continued research across scales to optimize configurations and mitigate detrimental emissions, thereby enhancing the efficacy of in-situ burning in large-scale oil spill scenarios.