Biology subjects

Lewis, C. L.

Publications and source records attributed to Lewis, C. L..

5 recordsLinked to original sources

bioRxiv2026

The Influence of Obesity and Body Shape on Sagittal Plane Knee Kinematics and Kinetics during Obstacle Crossing

Altered walking mechanics in individuals with obesity can contribute to knee osteoarthritis. The gait deviations may become more pronounced during obstacle crossing. In women, body fat distribution may further influence knee load, especially when excess fat accumulates in the thighs and hips. However, relatively little is known about how regional fat distribution affects gait in women with obesity. This study investigated how obesity and, among women, different fat distributions (Apple: more abdominal fat; Pear: more lower-limb fat) influence knee biomechanics during walking with and without obstacle crossing. Participants were 15 controls without obesity (NB) and 27 with obesity (OB). Within female participants, 10 without obesity (fNB) were compared with 20 with obesity, stratified by waist-hip ratio (Apple:10, Pear:10). Speed-adjusted statistical parametric mapping applied a general linear model (NB vs. OB) and an analysis of covariance (fNB vs. Apple vs. Pear). OB exhibited a significantly greater late-stance knee extension moment than NB across all tasks, and this difference persisted among fNB, Apple, and Pear in obstacle tasks (p<0.05). OB walked with reduced knee flexion during the early-stance leading limb after crossing a medium-height obstacle (p=0.048) and a high-height obstacle (p=0.008) compared to NB. There were significant body-shape effects (p<0.05), and post-hoc comparisons confirmed that Pear had lower knee angles than fNB in both leading-limb conditions after crossing medium- and high-height obstacles (p=0.008 and p=0.001, respectively). These findings suggest that obstacle crossing helps illuminate how excess weight influences knee biomechanics, and how regional fat distribution modulates the degree of this alteration.

bioengineering↗

bioRxiv2026

TMEM119+ microglia MHC class I restricted antigen presentation impacts CD8 T cell memory, effector status, and blood-brain barrier disruption during neurotropic virus infection

The impact of microglia antigen presentation on CNS infiltrating CD8 T cells responses during neurotropic virus infection has been difficult to define. Using Theilers murine encephalomyelitis virus (TMEV) infection of neurons as a model system, our laboratory has previously determined that H-2Db restricted, but not H-2Kb restricted CD8 T cells are required for viral clearance, demonstrating the role of discrete MHC class I alleles. To determine the extent microglia antigen presentation impacts brain-infiltrating CD8 T cells, our laboratory generated novel single MHC class I conditional knockout mice in which H-2Kb or H-2Db can be specifically deactivated in TMEM119+ microglia with tamoxifen administration. During TMEV infection, conditional knockout of H-2Kb in microglia reduced antigen-specific CD8 T cell proliferation in the brain. Meanwhile, mice with deletion of Db in microglia had reduced levels of perforin in antigen-specific CD8 T cells. Furthermore, microglia specific deletion of H-2Db reduced CD8 T cell numbers in the brain and preserved blood-brain barrier (BBB) integrity. Microglial Db restricted antigen presentation was also essential for the reactivation of CD8 tissue resident memory (TRM) cells and BBB integrity during memory recall responses. These findings further our understanding of how brain infiltrating antiviral CD8 T cell responses are impacted by microglia, as well as define how this cellular interaction contributes to BBB disruption during neuroinflammation. These findings also have high significance to our understanding of how microglia impact CD8 TRM cell populations that reside in the brain long after virus infection is cleared. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=111 SRC="FIGDIR/small/722741v1_ufig1.gif" ALT="Figure 1"> View larger version (42K): org.highwire.dtl.DTLVardef@1f53d89org.highwire.dtl.DTLVardef@19af9a8org.highwire.dtl.DTLVardef@17cb8b5org.highwire.dtl.DTLVardef@1428440_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2026

pamiR: INVESTIGATING PLANT CELLS ONE ORGANELLE AT A TIME

Functional genetic redundancy (FGR) within gene families limits the discovery of gene function in plants because single-gene perturbations often fail to produce informative phenotypes. Artificial microRNAs (amiRNAs) provide a strategy to silence multiple related genes simultaneously. However, the existing amiRNA-based libraries used for genetic gene function discovery in plants do not account for the subcellular localization of gene products, which can lead to pleiotropic or difficult-to-interpret phenotypes. Plastids are essential plant cell organelles that integrate central metabolic and signaling processes, including photosynthesis, hormone biosynthesis, and environmental responses. Here we introduce pamiR, a plastid-targeted amiRNA library designed to enable organelle-specific gene function discovery in Arabidopsis thaliana. Using plastid proteomic datasets, we identified high-confidence plastid-localized proteins and designed amiRNAs to target their gene(s) (families) minimizing FGR. This amiRNA library was introduced in a vector with fluorescence-accumulating seed technology enabling rapid, herbicide-free selection and screening in the first generation. Validation by next-generation sequencing, confirmed high representation and uniform distribution of amiRNAs within pamiR. Proof-of-concept screens recovered mutants affecting known and additional candidate genes involved in photosynthesis and abscisic acid biosynthesis. Therefore, the pamiR library provides a fast platform for plastid-focused genetic screens that is compatible with existing mutant collections. One-sentence summaryThe plastid amiRNA (pamiR) library enables organelle-specific forward genetics without functional genetic redundancy.

plant biology↗

bioRxiv2025

Development and Characterization of a Tunable PDMS Substrate Model for Investigating Elastic Properties and Mechanical Stretching in Intervertebral Disc Mechanobiology

BackgroundAberrant mechanical loading and altered extracellular matrix (ECM) composition favor catabolic cell responses, contributing to intervertebral disc (IVD) degeneration and ultimately impairing the integrity of the annulus fibrosus (AF). This highlights the need for new in vitro models to investigate the interplay of mechanical loading and cell-substrate interactions. Therefore, this study introduces a tunable stretching chamber platform to simultaneously study both factors in AF degeneration. MethodsTunable PDMS substrates were fabricated by adjusting ratios of Sylgard 184 and Sylgard 527, enabling molding into stretching chambers or well plates. Substrates underwent mechanical, optical and chemical characterization. Bovine AF cells were seeded onto the substrates and cultured under static conditions or subjected to cyclic strain (8% strain at 1 Hz). Substrate biocompatibility and cell morphology were assessed over 72 h in static cultures. Dynamic responses were assessed by cell viability and alignment. Digital Image Correlation (DIC) was employed to assess surface strain in custom-designed and commercial (STREX) stretching chambers at strains between 8 to 20%. ResultsPDMS formulations resulted in a stiffness (E modulus) range of 8.72 - 238.00 kPa, demonstrating distinct viscoelastic profiles. All substrate formulations supported AF cell adhesion and viability. DIC analysis revealed non-uniform axial and transverse strain distributions on membrane surfaces. Cyclic stretching showed that cells maintained viability up to 14 h. Additionally, cells responded to the applied strain by perpendicular alignment to the stretch axis at 6 h. ConclusionsThe PDMS based stretching platform offers a biocompatible and tunable mechanical environment that mimics physiological and pathophysiological elastic properties. It enables systematic investigations on how elastic properties and mechanical strain modulate AF cell behavior in IVD disease progression. Finally, this study raises the awareness of non-uniform and transverse strain components within the stretching chambers and highlights the discrepancy of effective strain transfer to the cell interaction surface.

bioengineering↗

bioRxiv2018

Fallen Pillars: The Past, Present, and Future Population Dynamics of a Rare, Specialist Coral-Algal Symbiosis

Rare and ecologically specialized species are at greater risk of extinction. Rarity in terms of low genotypic diversity may be obscured in sessile foundation species that can reproduce asexually. Asexual propagules are often only distinguishable from sexual recruits through molecular tools. Thus, molecular markers are necessary to assess genotypic variation and population structure in clonal organisms such as corals. The global decline of corals has necessitated marker development for improved conservation of rare coral species. We infer past demographic changes, describe modern population structure, and quantify asexual reproduction of the uncommon Caribbean pillar coral, Dendrogyra cylindrus and its endosymbiotic dinoflagellate, Symbiodinium dendrogyrum using de novo microsatellite markers. Results show that D. cylindrus comprises three distinct populations in the Caribbean whereas the symbiont was differentiated into four populations. Thus, barriers to gene flow differ between host and symbiont. In Florida, host and symbiont reproduced mainly asexually, yielding lower genotypic diversity than predicted from census size. Models of past demographic events revealed no evidence of historical changes in population size, consistent with the geological record of D. cylindrus indicating it has been rare for hundreds of thousands of years. The most recent global thermal stress event triggered a severe disease outbreak among D. cylindrus in Florida, resulting in a precipitous population decline. Projections indicate a high likelihood that this species may become locally extinct within the coming decades. The ecosystem consequences of losing rare coral species and their symbionts with increasingly frequent extreme warming events are not known but require urgent study.

genetics↗