Biology subjects

Goldman, E.

Publications and source records attributed to Goldman, E..

6 recordsLinked to original sources

bioRxiv2026

Novel 3D Mature Osteocyte Perfusion Platform Reveals Subtype-Dependent and Radiation-Sensitive Disruption of Mechanotransduction by Breast Cancer Secretomes

Osteocytes (OCys) coordinate bone remodeling by transducing mechanical signals into anabolic cues, primarily through suppressing sclerostin and RANKL. In breast cancer (BCa) bone metastasis, mechanical loading fails to restore lost bone, pointing to tumor-induced OCy mechanosensory dysfunction. Here, we investigate how BCa molecular subtype heterogeneity and frontline therapies like radiation influence OCy mechanobiology. We leveraged a 3D mineralized scaffold paired with a forced perfusion bioreactor to establish a physiologically relevant model of mature, dendrite-bearing OCys. After optimizing perfusion parameters, 3D mature OCys were exposed to conditioned media (CM) from estrogen receptor-positive (ER+; ZR-75-1) or triple-negative (TN; MDA-MB-231) BCa cells generated 24 h post-irradiation (0 vs. 2 Gy). Downstream OCy gene expression (Sost, Tnfsf11, Tnfrsf11b) and tumor CM proteomic profiles (84 oncology targets) were evaluated. Differentiated 3D MPC-2s exhibited interconnected dendritic networks, classical responsiveness to parathyroid hormone, and robust flow-induced Sost suppression. Non-irradiated ER+ BCa CM preserved canonical OCy mechanoresponsiveness (Sost downregulation post-flow), but this response was eliminated when ER+ cells received 2 Gy radiation. Conversely, TN CM blunted flow-induced Sost suppression regardless of irradiation status. Proteomic profiling revealed that BCa subtype was the primary driver of secretome composition, whereas 2 Gy radiation induced distinct directional secretome shifts between subtypes. These findings demonstrate that BCa-induced impairment of OCy mechanosensing is subtype-dependent and that low-dose radiation further exacerbates secretome-mediated mechanosensory loss in ER+ disease, highlighting key tumor-derived targets for restoring skeletal health.

bioengineering↗

bioRxiv2025

Inactivation of Airborne Pathogen Surrogates by Triethylene Glycol

The COVID-19 outbreak brought to the fore the importance of airborne transmission in spreading human infectious diseases and highlighted the need for sustainable mitigation strategies. Triethylene glycol (TEG) has been documented as having microbicidal capabilities and has been proposed as one such mitigation strategy. Aerosolized TEG exhibits antimicrobial activity against airborne microorganisms; Grignard Pure Technology was developed to safely aerosolize TEG for decontamination of enclosed spaces. Here we show that this TEG formulation effectively inactivates airborne microorganisms, resulting in 2 to 4.5 net log reduction in concentration of viable bacteria, viruses, and mycobacteria within 30-60 minutes at TEG concentration (aerosol + vapor) of [~]0.7 mg/m3, which is well within the range considered safe for humans. Our data also demonstrate that aerosolizing both the test organisms and the antimicrobial product provides a more accurate and relevant measure of the products efficacy for indoor usage than traditional surface - or solution - based disinfection assays. Accurate evaluation of antimicrobial efficacy is a crucial step in adopting novel interventions and tools to control airborne pathogens that pose a public health risk. Our findings argue that testing protocols must match the intended use of any intervention. Given the safety concerns of aerosolizing human pathogens for direct testing of airborne infectious burden, we also advance an approach for selecting suitable surrogate microorganisms based on their phenotypic and biophysical similarity to corresponding pathogenic species. ImportanceDuring the COVID-19 pandemic, personal protective equipment, social distancing, and even vaccinations proved sub-optimal in controlling the spread of COVID-19. Public health practice and the hierarchy of controls emphasize primary prevention, whereby the pathogen is removed or destroyed before exposure to the public. Triethylene glycol (TEG) has the potential to inactivate airborne pathogens and limit their spread. TEG is designated a "safer chemical" by the US EPA and has been used for decades in aerosol deodorizers and theatrical special effects. This study shows that aerosolized TEG is highly effective at eliminating a wide spectrum of viable airborne pathogen surrogates at concentrations well below the threshold of safety concern. Thus, it may afford significant protection against the transmission of infectious agents with pandemic potential.

microbiology↗

bioRxiv2024

The maternal microbiome modifies adverse effects of protein undernutrition on offspring neurobehavioral impairment in mice

Protein undernutrition is a global risk factor for impaired growth and neurobehavioral development in children. However, the critical periods, environmental interactions, and maternal versus neonatal influences on programming lasting behavioral abnormalities are poorly understood. In a mouse model of fetal growth restriction, limiting maternal protein intake particularly during pregnancy leads to cognitive and anxiety-like behavioral abnormalities in adult offspring, indicating a critical role for the gestational period. By cross-fostering newborn mice to dams previously exposed to either low protein or standard diet, we find that the adult behavioral impairments require diet-induced conditioning of both fetal development and maternal peripartum physiology, rather than either alone. This suggests that protein undernutrition during pregnancy directly disrupts fetal neurodevelopment and indirectly alters maternal state in ways that interact postnatally to precipitate behavioral deficits. Consistent with this, maternal protein restriction during pregnancy reduces the diversity of the maternal gut microbiome, modulates maternal serum metabolomic profiles, and yields widespread alterations in fetal brain transcriptomic and metabolomic profiles, including subsets of microbiome-dependent metabolites. Depletion of the maternal microbiome in protein-restricted dams further alters fetal brain gene expression and exacerbates neurocognitive behavior in adult offspring, suggesting that the maternal microbiome modifies the impact of gestational protein undernutrition on risk for neurobehavioral impairment in the offspring. To explore the potential for microbiome-targeted interventions, we find that maternal treatment with short chain fatty acids or a cocktail of 10 diet- and microbiome-dependent metabolites each yield differential effects on fetal development and/or postnatal behavior. Results from this study highlight impactful prenatal influences of maternal protein undernutrition on fetal neurodevelopment and adverse neurobehavioral trajectories in offspring, which are mitigated by microbiome-targeted interventions during pregnancy.

animal behavior and cognition↗

bioRxiv2022

The efficiency of Grignard Pure™ to inactivate airborne SARS-CoV-2 surrogate

Grignard Pure (GP) is a unique and proprietary blend of Triethylene Glycol (TEG) and inert ingredients designed for continuous antimicrobial treatment of air. GP received approval from the US EPA under its Section 18 Public Health Emergency Exemption program for use in seven states. This study characterizes the efficacy of GP for inactivating MS2 bacteriophage - a non-enveloped virus widely used as a surrogate for SARs-CoV-2. Experiments measured the decrease in the airborne viable MS2 concentration in the presence of different concentrations of GP from 60 to 90 minutes, accounting for both natural die-off and settling of MS2. Experiments were conducted both by introducing GP aerosol into air containing MS2 and by introducing airborne MS2 into air containing GP aerosol. GP is consistently able to rapidly reduce viable MS2 bacteriophage concentration by 2-3 logs at GP concentrations of 0.02 mg/m3 to 0.5 mg/m3 (corresponding to TEG concentrations of 0.012 mg/m3 to 0.287 mg/m3). Related GP efficacy experiments by the US EPA, as well as GP (TEG) safety and toxicology, are also discussed. SynopsisLimited research on the germicidal properties of triethylene glycol against airborne pathogens was conducted during the 1940s and 50s. This paper investigates the inactivation rate of airborne bacteriophage MS2 by Grignard Pure product, containing a unique and proprietary blend of Triethylene Glycol (TEG) and inert ingredients.

microbiology↗

bioRxiv2021

Higher concentrations of bacterial enveloped virus Phi6 can protect the virus from environmental decay

Phage Phi6 is an enveloped virus considered as a possible non-pathogenic surrogate for SARS-CoV-2 and other viral pathogens in transmission studies. Higher input amounts of bacteriophage Phi6 are shown to delay and protect the phage from environmental decay, both when the phage are dried in plastic tubes, and when they are stored in saline solution at 4{degrees}C. When bacteriophage Phi6 are placed in LB (Luria-Bertani) growth medium prior to placement on the plastic surface, viral recovery is not influenced by the starting concentration. The protection is reflected in longer half-lives of the phage at higher concentrations compared to lower. Because experiments supporting the possibility of fomite transmission of SARS-CoV-2 and other viruses rely upon survival of infectious virus following inoculation of various surfaces, high initial amounts of input virus on a surface may generate artificially inflated survival times compared to realistic lower levels of virus that a subject would normally encounter. This is not only because there are extra half-lives to go through at the higher concentrations, but also because the half-lives themselves are extended at the higher virus concentrations. It is important to design surface drying experiments for pathogens with realistic levels of input virus, and to consider the role of the carrier and matrix if the results are to be clinically relevant. IMPORTANCEDuring the COVID-19 pandemic, a lot of attention has been paid to the environmental decay of SARS-CoV-2 due to proposed transmission of the virus via fomites. However, published experiments have commenced with very high virus titer inoculums, an experimental design not representative of real-life conditions. The study described here evaluated the impact of initial virus titer on environmental decay of an enveloped virus, using a non-pathogenic surrogate for SARS-CoV-2, enveloped bacteriophage Phi6. We establish that higher concentrations of virus can protect the virus from environmental decay, depending on conditions. This has important implications for stability studies of SARS-CoV-2 and other viruses. Our results point to a limitation in the fundamental methodology that has been used to attribute fomite transmission for almost all respiratory viruses.

microbiology↗

bioRxiv2020

Only 40% of the world's forests are in good health

Many global environmental agendas, including halting biodiversity loss, reversing land degradation, and limiting climate change, depend upon retaining forests with high ecological integrity, yet the scale and degree of forest modification remains poorly quantified and mapped. By integrating data on observed and inferred human pressures and an index of lost connectivity, we generate the first globally-consistent, continuous index of forest condition as determined by degree of anthropogenic modification. Globally, only 17.4 million km2 of forest (40.5%) have high landscape level integrity (mostly found in Canada, Russia, the Amazon, Central Africa and New Guinea) and only 27% of this area is found in nationally-designated protected areas. Of the forest in protected areas, only 56% has high landscape level integrity. Ambitious policies that prioritize the retention of forest integrity, especially in the most intact areas, are now urgently needed alongside current efforts aimed at halting deforestation and restoring the integrity of forests globally.

ecology↗