The Development of a Viscoelastic Ellipsoidal Model for use in Measuring Plantar Tissue Material Properties during Walking

Introduction: The mechanical characteristics of the plantar tissues during walking is not well understood as most of the current research focuses on testing specific plantar regions in cadavers or while the feet of the participants are raised. In this work, it is hypothesized that a viscoelastic geometric ellipsoid model used to assess multiple structures of the foot would be accurate and robust. This model would be participant-specific and applicable to the entire stance phase of gait. Methods: The proposed viscoelastic ellipsoid model would represent several key anatomical areas: Heel, Posterior Midfoot, Anterior Midfoot, Metatarsals 1-2, Metatarsals 3-5, Toe 1, Toe 2, and Toes 3-5. The ellipsoid model required measurement of force and contact area simultaneously. This was done using pressure-measuring insoles (Medilogic ®, Schönefeld, Germany), worn by multiple, college-aged participants. The insole force and area data were used to optimize the model for each participant as the material properties and geometry of each participant’s foot will differ. Results: The results of the model application was able to show that the ellipsoid model was fairly successful in producing the ground reaction force during walking. Further, the ellipsoid model was able to characterize stiffness and damping results, that were different for all the plantar regions. These results were also different from previous research that used data from mechanical tests and experiments where the participant’s foot was static. Conclusion: The viscoelastic ellipsoidal model was able to reproduce ground reaction force and determine the unique mechanical characteristics for each plantar region. Future uses of the model will be with clinical data collected from persons with plantar diseases, which could lead to predictions and preventions of plantar disease

Understanding the Intersections between Metabolism and Cancer Biology

Transformed cells adapt metabolism to support tumor initiation and progression. Specific metabolic activities can participate directly in the process of transformation or support the biological processes that enable tumor growth. Exploiting cancer metabolism for clinical benefit requires defining the pathways that are limiting for cancer progression and understanding the context specificity of metabolic preferences and liabilities in malignant cells. Progress toward answering these questions is providing new insight into cancer biology and can guide the more effective targeting of metabolism to help patients.National Cancer Institute (U.S.) (CA168653)National Cancer Institute (U.S.) (CA201276)Lustgarten FoundationHoward Hughes Medical Institute (Faculty Scholars Award

Enhanced Laboratory X-ray Particle Tracking Velocimetry With Newly Developed Tungsten-Coated O(50 μ\mum) Tracers

Tracer particles designed specifically for X-ray particle tracking and imaging velocimetry (XPTV and XPIV) are necessary to widen the range of flows that can be studied with these techniques. In this study, we demonstrate in-lab XPTV using new, custom-designed $O$(50 $\mu$m) diameter tungsten-coated hollow carbon spheres and a single energy threshold photon counting detector. To explore the measurement quality enhancement enabled by the new tracer particles and photon counting detector, a well understood Poiseulle pipe flow is measured. The data show agreement with the analytical solution for the depth-averaged velocity profile. The experiment also shows that the tungsten-coated particles achieve higher contrast and are better localized than previously available silver-coated particles, making faster and more precise measurements attainable. The particles are manufactured with a readily scalable chemical vapor deposition process. We further show that laboratory XPTV is practical with currently available energy-resolving photon counting detectors (PCDs), despite their presently lower spatiotemporal resolution compared to scintillating detectors. This finding suggests that energy-thresholding identification of different classes of tracers is feasible, further motivating the exploration of the X-ray tracer particle design space. The latest generation of PCDs are incorporating multiple energy thresholds, and have higher count rate limits. In the near future one could potentially expand on the work presented and track multiple tracer species and scalar fields simultaneously.Comment: Submitted to Experiments in Fluids for consideration for publicatio

Nitrogen mass balance for spray fields fertilized with liquid swine waste

The swine industry has expanded rapidly in North Carolina over the last two decades. Animals are raised in confined facilities where waste is flushed into open-air lagoons and the liquid phase is land-applied to receiving fields as an organic fertilizer. The post-application fate has not been fully documented. Therefore, on three occasions I experimentally applied liquid swine waste at typical doses (40 to 130 kg N ha-2) to defined plots in an active spray field on a representative North Carolina swine production facility and constructed an N mass balance for a 14 to 18 d period. Most of the N (52%) was assimilated into plants, while surprisingly little (9%) was volatilized. Microbial immobilization accounted for 10% of the applied N, while 12% migrated below the active soil zone (surface 20 cm) and was presumably lost to groundwater. The soil storage term averaged 16%, while the denitrification sink was inconsequential (<1%)

The Gut Commensal Bacteroides thetaiotaomicron Exacerbates Enteric Infection through Modification of the Metabolic Landscape

SummaryThe enteric pathogen enterohemorrhagic Escherichia coli (EHEC) causes severe diarrhea, but the influence of the gut microbiota on EHEC infection is largely unknown. A predominant member of the microbiota, Bacteroides thetaiotaomicron (Bt), is resident at EHEC attachment sites. We show that Bt enhances EHEC virulence gene expression through the transcription factor Cra, which is functionally sensitive to sugar concentrations. This enhanced virulence accompanies increased formation of attaching and effacing (AE) lesions requisite for EHEC colonization. Infection with Citrobacter rodentium, a natural mouse pathogen homologous to EHEC, in Bt-reconstituted mice results in increased gut permeability along with exacerbated host pathology and mortality compared to mice deplete of microflora. Bt modifies the metabolite environment at infection sites, increasing metabolites involved in gluconeogenesis, with stark increases in succinate, which can be sensed by Cra. Our findings suggest that microbiota composition affects disease outcome and may explain links between microbiota composition and disease susceptibility

Regulation of mitochondrial biogenesis in erythropoiesis by mTORC1-mediated protein translation.

Advances in genomic profiling present new challenges of explaining how changes in DNA and RNA are translated into proteins linking genotype to phenotype. Here we compare the genome-scale proteomic and transcriptomic changes in human primary haematopoietic stem/progenitor cells and erythroid progenitors, and uncover pathways related to mitochondrial biogenesis enhanced through post-transcriptional regulation. Mitochondrial factors including TFAM and PHB2 are selectively regulated through protein translation during erythroid specification. Depletion of TFAM in erythroid cells alters intracellular metabolism, leading to elevated histone acetylation, deregulated gene expression, and defective mitochondria and erythropoiesis. Mechanistically, mTORC1 signalling is enhanced to promote translation of mitochondria-associated transcripts through TOP-like motifs. Genetic and pharmacological perturbation of mitochondria or mTORC1 specifically impairs erythropoiesis in vitro and in vivo. Our studies support a mechanism for post-transcriptional control of erythroid mitochondria and may have direct relevance to haematologic defects associated with mitochondrial diseases and ageing

Altered glutamine metabolism in breast cancer: subtype dependencies and alternative adaptations

Cancer cells must alter their metabolism in order to satisfy the demands of necessary energy and cellular building blocks. These metabolic alterations are mediated by many oncogenic changes that affect cellular signalling pathways, which result in sustained cell growth and proliferation. Recently, metabolomics, has received great attention in the field of cancer research and as the essential metabolic pathways that drive tumour growth and progression are determined, the possibilities of new targets for therapeutic intervention are opened. More specifically, as breast cancer is a heterogeneous disease there is growing evidence that differences in metabolic changes exist between molecular subtypes. In this review, the most recent findings in breast cancer cell metabolism are discussed, with particular emphasis on glutamine and its transporters which is considered one of the key amino acids fuelling cancer growth. Furthermore, the metabolic differences between the molecular subtypes of breast cancer are examined, highlighting the clinical utility for breast cancer diagnosis and treatment