Introduction to the Special Centennial Issue

This special issue of the Virginia Journal of Science (VJS) is dedicated to the 2023 Centennial of the Virginia Academy of Science (VAS). It includes congratulations from Commonwealth leaders, a proclamation by the Virginia General Assembly Senate, Academy members’ personal reflections, several historical papers and summaries, and portions of the program for the May 25-26, 2023 Annual Meeting in Williamsburg on the William & Mary campus

Gene Expression Under Combined Hypoxia And Acidosis In Chondrosarcoma

Chondrosarcomas are the second most common cause of bone cancer and are removed surgically with wide margins. On recurrence, they are resistant to chemo and radiation therapy and new treatment options are critically required. This tumor type produces hyaline cartilage, a cartilage normally formed under hypoxic and acidic environment due to lack of vasculature in cartilage. Paradoxically, chondrosarcomas arise in the well vascularized, oxygen rich environment of the bone. Hypoxia and acidosis are two stressors where the cellular effects are typically reported separately even though cells experience combined effects of hypoxia and acidosis. Given the mechanistic links between hypoxia and acidosis we hypothesized that gene expression profiles will be differentially changed when chondrosarcoma cells were exposed to individual compared to combined stressors. We investigated expression of four genes expressed during cartilage and cartilage tumor formation in primary chondrocytes and two grade II chondrosarcoma cell lines, SW1353 and JJ012. Two genes, PTH1R and SOX9 are known to respond to hypoxia and acidosis separately. Two genes, IDH1 and IDH2, are mutated in chondrosarcoma cell lines JJ012 and SW1353 respectively. These mutations confer a condition of false hypoxia on the cells through stabilization of HIF-1α. The result is chondrosarcoma cells metabolize glycolytically through aerobic glycolysis. How the cells respond to hypoxia and acidosis is of considerable interest as metabolically the cells are molecularly predisposed to these conditions. Our gene expression data found that combined hypoxia and extracellular acidosis alter gene expression compared to either stressor alone. Cells showed gene specific responses to stressors that were cell type specific likely indicating influence on gene expression regulatory sequences. The importance of this work is highlighting that conditions under which cells are investigated is crucial and should be considered when measuring cell response to in vitro treatment exposures

The Architecture of a Proteomic Network in the Yeast

We describe an approach to clustering the yeast protein-protein inter-action network in order to identify functional modules, groups of proteins forming multi-protein complexes accomplishing various functions in the cell. We have developed a clustering method that accounts for the small-world nature of the network. The algorithm makes use of the concept of k-cores in a graph, and employs recursive spectral clustering to compute the functional modules. The computed clusters are annotated using their protein memberships into known multi-protein complexes in the yeast. We also dissect the protein interaction network into a global subnetwork of hub proteins (connected to several clusters), and a local network consisting of cluster proteins

Selective Mutation Accumulation: A Computational Model of the Paternal Age Effect

Motivation: As the mean age of parenthood grows, the effect of parental age on genetic disease and child health becomes ever more important. A number of autosomal dominant disorders show a dramatic paternal age effect due to selfish mutations: substitutions that grant spermatogonial stem cells (SSCs) a selective advantage in the testes of the father, but have a deleterious effect in offspring. In this paper we present a computational technique to model the SSC niche in order to examine the phenomenon and draw conclusions across different genes and disorders. Results: We used a Markov chain to model the probabilities of mutation and positive selection with cell divisions. The model was fitted to available data on disease incidence and also mutation assays of sperm donors. Strength of selective advantage is presented for a range of disorders including Apert\u27s syndrome and achondroplasia. Incidence of the diseases was predicted closely for most disorders and was heavily influenced by the site-specific mutation rate and the number of mutable alleles. The model also successfully predicted a stronger selective advantage for more strongly activating gain-of-function mutations within the same gene. Both positive selection and the rate of copy-error mutations are important in adequately explaining the paternal age effect. Availability and Implementation: C++/R source codes and documentation including compilation instructions are available under GNU license at https://github.com/anwala/NicheSimulation. Contact: [email protected] Supplementary information: Supplementary data are available at Bioinformatics online

Interactions of Carboxylated Nanodiamonds With Mouse Macrophages Cell Line and Primary Cells

Nanodiamonds (ND) have attracted significant interest for their use in several biomedical applications. These applications can be very useful if the safety and compatibility of ND are proven. We assessed the effects of ND (100 nm, Carboxylated) on primary macrophages and a macrophage-like cell line and found that these particles are not toxic to these cells at lower concentrations but may interfere with cell functions and differentiation. Internalization of ND by these cells in a time- and dose-dependent manner was mostly via phagocytosis and clathrin-dependent endocytosis and localized to the cytoplasm but not into the nucleus. No significant induction of inflammatory cytokines or reduction in the ability of these cells to respond to lipopolysaccharides (LPS) was noted. However, the endocytic activity of these cells is significantly reduced. In addition, ND exposure reduced the ability of differentiating bone marrow cells to express macrophage surface markers. Measurement of the fluorescence and absorbance of ND-treated cells clearly showed the ability of these particles to produce a signal at different wavelengths. Therefore, it is important to consider interference of ND in different colorimetric and fluorometric assays when testing interactions or effects of ND on cells. Our findings suggest that ND are not cytotoxic to macrophages at the tested concentrations, but it can interfere with macrophage functions and differentiation and may interfere with assays’ result through the production of a signal at different wavelengths

Enhanced Killing Effect of Nanosecond Pulse Electric Fields on PANC1 and Jurkat Cell Lines in the Presence of Tween 80

We investigated the effects of nanosecond pulse electric fields (nsPEFs) on Jurkat and PANC1 cells, which are human carcinoma cell lines, in the presence of Tween 80 (T80) at a concentration of 0.18% and demonstarted an enhanced killing effect. We used two biological assays to determine cell viability after exposing cells to nsPEFs in the presence of T80 and observed a significant increase in the killing effect of nsPEFs. We did not see a toxic effect of T80 when cells were exposed to surfactant alone. However, we saw a synergistic effect when cells exposed to T80 were combined with the nsPEFs. Increasing the time of exposure for up to 8 h in T80 led to a significant decrease in cell viability when nsPEFs were applied to cells compared to control cells. We also observed cell type-specific swelling in the presence of T80. We suggest that T80 acts as an adjuvant in facilitating the effects of nsPEFs on the cell membrane; however, the limitations of the viability assays were addressed. We conclude that T80 may increase the fragility of the cell membrane, which makes it more susceptible to nsPEF-mediated killing

Investigating strength and range of motion of the hip complex in ice hockey athletes

CONTEXT: Ice hockey athletes frequently injure the hip complex via a non-contact mechanism. We investigated patterns of strength and range of motion (ROM) to establish major differences compared to soccer athletes. Soccer athletes were compared to ice hockey athletes due to similarities between the two sports with regards to the intermittent nature and high number of lower limb injuries. OBJECTIVE: To compare the differences in ROM and strength of the hip for both the dominant (Dom) and non-dominant (Ndom) limb in ice hockey and soccer athletes. DESIGN: Case control study. SETTING: Bilateral ROM in hip flexion in sitting (FS) and lying (FL), extension, abduction, adduction, and internal rotation (IR) and external rotation (ER) was measured using a goniometer and assessed for strength using a hand held dynamometer on both the Dom and Ndom limbs. Participants. Twenty four male, active, uninjured NCAA division III ice hockey (16) and soccer (8) athletes. MAIN OUTCOME MEASURE: ROM and strength for hip FS, FL extension, abduction, adduction, IR and ER. A mixed model ANOVA was used to investigate interactions and main effects. RESULTS: Ice hockey athletes exhibited greater hip adduction ROM compared to soccer athletes in the Dom leg (both p=0.002) and when both limbs were combined (p = 0.010). Ice hockey athletes had less ROM in ER (p = 0.042) than soccer athletes. Ice hockey athletes displayed less strength in adduction in their Ndom leg compared to their Dom leg (p=0.02) along with less adduction than soccer players in their Ndom leg (p=0.40). Ice hockey athletes displayed less strength in hip adduction (p=0.030), FS (p=0.023) and FL (p=0.030) than soccer athletes. CONCLUSIONS: Our findings suggest that ice hockey athletes may present an 'at risk' profile for non-contact hip injuries, in comparison with soccer athletes with regards to strength and ROM of the hip

In Vivo Imaging of Transport and Biocompatibility of Single Silver Nanoparticles in Early Development of Zebrafish Embryos

Real-time study of the transport and biocompatibility of nanomaterials in early embryonic development at single-nanoparticle resolution can offer new knowledge about the delivery and effects of nanomaterials in vivo, and provide new insights into molecular transport mechanisms in developing embryos. In this study, we directly characterized the transport of single silver nanoparticles into an in vivo model system (zebrafish embryos) and investigated their effects on early embryonic development at single-nanoparticle resolution in real time. We designed highly purified and stable (not aggregated and no photodecomposition) nanoparticles and developed single-nanoparticle optics and in vivo assays to enable the study. We found that single Ag nanoparticles (5- 46 nm) transport in and out of embryos through chorion pore canals (CPCs), and exhibit Brownian diffusion (not active transport), with ∼26 times lower diffusion coefficient (3×10-9 cm2/s) inside the chorionic space than that in egg water (7.7×10-8 cm2/s). In contrast, nanoparticles were trapped inside CPCs and the inner mass of the embryos, showing restricted diffusion. Individual Ag nanoparticles were observed inside embryos at each developmental stage and in normally developed, deformed, and dead zebrafish, showing that the biocompatibility and toxicity of Ag nanoparticles and types of abnormalities observed in zebrafish are highly dependent on the dose of Ag nanoparticles, with a critical concentration of 0.19 nM. Rates of passive diffusion and accumulation of nanoparticles in embryos are likely responsible for the dose-dependent abnormalities. Unlike other chemicals, single nanoparticles can be directly imaged inside developing embryos at nanometer (nm) spatial resolution, offering new opportunities to unravel the related pathways that lead to the abnormalities

Nanosecond Pulse Electrical Fields Used in Conjunction with Multi-Wall Carbon Nanotubes as a Potential Tumor Treatment

The objectives of this communication were to fabricate pure samples of multi-walled carbon nanotubes (MWCNTs) and to determine their toxicity in tumor cell lines. MWCNTs were dispersed in a concentration of the surfactant T80 that was minimally toxic. Cell-type variation in toxicity to MWCNTs was observed but was not significantly different to unexposed controls. Additionally, we investigated the increased cell killing of the pancreatic cancer cell line PANC1 when exposed to ultrashort (nanosecond) pulsed electrical fields (nsPEF) in the presence of MWCNTs as a potential form of cancer therapy. We hypothesized that the unique electronic properties of MWCNTs disrupt cell function, leading to cell death, when cells are exposed to nsPEF. We observed a 2.3-fold reduction in cell survival in cells pulsed in the presence of MWCNTs compared to pulsed controls. This study demonstrates that ultrashort pulse electrical field applications have enhanced killing effects when cells are previously grown in the presence of MWCNTs, suggesting that the electrical properties of MWCNTs play a vital role in this process and is suggestive of a synergistic interaction between these nanomaterials and electrical fields

STS-119 Safety and Mission Success Review

No abstract availabl