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Biology subjects

McCormick, R.

Publications and source records attributed to McCormick, R..

4 recordsLinked to original sources

A hierarchical Bayesian model for dynamic phenotypes in multi-environment trials with genotype by environment interaction

New phenotyping tools produce longitudinal phenotypes that describe plant growth and development. Estimates for the parameters that describe the dynamics of such longitudinal phenotypes can be incorporated as predictors in models for static target traits like yield and biomass. Within a hierarchical Bayesian context, we present a differential equation (DE) model for log-logistic growth in longitudinal traits for sets of genotypes across multiple environments. The DE parameters coincide with a midpoint, a slope, and an asymptote at the end of growth and development, i.e., final biomass. Each DE parameter in our hierarchical model results from contributions of genotype, environment, and G x E. This formulation allows one to assess and quantify the genotype-specificity of the DE parameters. When none of the DE parameters in our model requires a G x E term, the dynamic parameters characterizing the particular trait will be useful features for inclusion in prediction models for yield or biomass. We fitted a DE model to APSIM-simulated longitudinal wheat biomass data and quantified the contribution of genotype, environment and G x E to the phenotypic variation in the DE parameters. Only the upper asymptote showed clear G x E. Estimates for genotypic and G x E parameters within the DE parameters were used to characterize genotypes. Estimates for environmental and G x E effects formed inputs for environmental characterization.

plant biology↗

Biological Drivers of Early Childhood Caries in Preschool Children of Northern Arizona and Hawaii

Early childhood caries (ECC) is the most prevalent chronic childhood disease, disproportionately affecting children from specific racial/ethnic groups. While ECC is a multifactorial disease influenced by demographic, behavioral, and environmental factors, it is also widely associated with the presence of Streptococcus mutans in the oral microbiome. To better understand the interplay between demographic and microbial factors and ECC risk, we collected saliva samples from 408 preschool children aged 1-6 years, including 266 from northern Arizona and 142 from Hawaii, representing racially and geographically diverse populations. Logistic regression showed that the odds of developing ECC increased 80.09% with each year of age, and that compared to White children, the odds were significantly higher for Native Hawaiian/Pacific Islander (330.94%), Native American (282.35%), and Hispanic (245.22%) children. Oral S. mutans colonization increased odds by 360.49%. The S. mutans-positive samples were genotyped using a multiplexed targeted amplicon sequencing assay. Phylogenetic analysis showed high genetic diversity in S. mutans between and within populations, with no geographic clustering. Some S. mutans clades were associated with up to a 33-fold increase in ECC odds. Only Native Hawaiian/Pacific Islander children were more likely to carry S. mutans strains from higher-risk clades. Markers associated with high risk S. mutans strains were identified in genes involved in carbohydrate metabolism, pH regulation, and biofilm formation. This study underscores the multifaceted nature of ECC, linking demographic disparities with strain-specific features of S. mutans and identifies new genetic markers that may play a role in S. mutans virulence.

microbiology↗

Optimisation of a Novel Bio-Substrate as a Treatment for Atrophic Age-Related Macular Degeneration.

Atrophic age-related macular degeneration (AMD) is the most common form of AMD accounting for 90% of patients. During atrophic AMD the waste/exchange pathway between the blood supply (choroid) and the retinal pigment epithelium (RPE) is compromised. This results in atrophy and death of the RPE cells and subsequently the photoreceptors leading to central blindness. Although the mechanisms behind AMD are unknown, the growth of fatty deposits known as drusen, have been shown to play a role in the disease. There is currently no treatment or cure for atrophic AMD. Much research focuses on developing a synthetic substrate in order to transplant healthy cells to the native Bruchs membrane (BM), however, the diseased native BM and related structures still leave the potential for transplanted cells to succumb to disease. In this work we electrospun poly(ethylene terephthalate) (PET) to fabricate a nanofibrous cytocompatible synthetic BM. The apical surface of the membrane was cultured with ARPE-19 cells and the basal surface was decorated with poly(lactic acid-co-glycolic acid) (PLGA) or poly(glycolic acid) (PGA) degradable nanoparticles by electrospraying. The membrane exhibited hydrophilicity, high tensile strength and structurally resembled the native BM. ARPE-19 cells were able to form a monolayer on the surface of the membrane and no cell invasion into the membrane was seen. The presence of both PLGA and PGA nanoparticles increased ARPE-19 cell metabolism but had no effect on cell viability. There was a decrease in pH of ARPE-19 cell culture media 7 days following culturing with the PLGA nanoparticles but this change was eliminated by 2 weeks; PGA nanoparticles had no effect on cell culture media pH. The fluorescent dye FITC was encapsulated into nanoparticles and showed sustained release from PLGA nanoparticles for two weeks and PGA nanoparticles for 1 day. Future work will focus on encapsulating biologically active moieties to target drusen. This would allow this novel bioactive substrate to be a potential treatment for atrophic AMD that would function two-fold: deliver the required monolayer of healthy RPE cells to the macula on a synthetic BM and remove diseased structures within the retina, restoring the waste/exchange pathway and preventing vision loss.

bioengineering↗

miR-181a Regulates p62/SQSTM1, Parkin and Protein DJ-1 Promoting Mitochondrial Dynamics in Skeletal Muscle Ageing

One of the key mechanisms underlying skeletal muscle functional deterioration during ageing is disrupted mitochondrial dynamics. Regulation of mitochondrial dynamics is essential to maintain a healthy mitochondrial population and prevent the accumulation of damaged mitochondria, however the regulatory mechanisms are poorly understood. We demonstrated loss of mitochondrial content and disrupted mitochondrial dynamics in muscle during ageing concomitant with dysregulation of miR-181a target interactions. Using functional approaches and mitoQc assay, we have established that miR-181a is an endogenous regulator of mitochondrial dynamics through concerted regulation of Park2, p62/SQSTM1 and DJ-1 in vitro. Downregulation of miR-181a with age was associated with an accumulation of autophagy-related proteins and abnormal mitochondria. Restoring miR-181a levels in old mice prevented accumulation of p62, DJ-1 and PARK2, improved mitochondrial quality and muscle function. These results provide physiological evidence for the potential of microRNA-based interventions for age-related muscle atrophy and of wider significance for diseases with disrupted mitochondrial dynamics.\n\n\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=107 SRC=\"FIGDIR/small/805176v1_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (54K):\norg.highwire.dtl.DTLVardef@1d6d4c7org.highwire.dtl.DTLVardef@12b6940org.highwire.dtl.DTLVardef@10aed74org.highwire.dtl.DTLVardef@6b5b34_HPS_FORMAT_FIGEXP M_FIG C_FIG

physiology↗