Publications by authors named "Joshua Snyder"

The faradaic efficiency (FE) of the electrochemical hydrogenation (ECH) of phenol and other biomass-derived model compounds could potentially be improved by operating in alkaline electrolytes, where the parasitic hydrogen evolution reaction rate is significantly slower due to a higher Volmer step barrier. However, this approach is potentially limited by the impact of the higher barrier for adsorbed hydrogen (H) formation, as hydrocarbon ECH is expected to be limited by a hydrogen atom transfer, progressing through a Langmuir-Hinshelwood-type (LH) mechanism. In this work, we show that there are contrasting pH trends for phenol ECH between Pt and Rh, two common catalysts for ECH reactions.

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Article Synopsis
  • - A new approach to cancer treatment is emerging, focusing on developing therapies throughout all stages of cancer, using various preclinical models to test these treatments.
  • - The research emphasizes the complexity of cancer, which includes genetic mutations and changes in cell behavior, and involves collaborations among experts at the National Cancer Institute to share insights on preclinical modeling.
  • - The authors outline the strengths and weaknesses of different cancer models, proposing a roadmap and initial suggestions for using advanced preclinical models to improve strategies for cancer prevention and treatment.
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Cancer screening is based upon a linear model of neoplastic growth and malignant progression. Yet, historical observations suggest that malignant progression is uncoupled from growth which may explain the paradoxical increase in early-stage breast cancer detection without a dramatic reduction in metastatic burden. Here we lineage trace millions of genetically transformed field cells and thousands of screen detectable and symptomatic tumors using a cancer rainbow mouse model of HER2+ breast cancer.

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Unlabelled: The ability to temporally regulate gene expression and track labeled cells makes animal models powerful biomedical tools. However, sudden expression of xenobiotic genes [e.g.

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Epidemiological and histopathological findings have raised the possibility that misfolded α-synuclein protein might spread from the gut to the brain and increase the risk of Parkinson's disease. Although past experimental studies in mouse models have relied on gut injections of exogenous recombinant α-synuclein fibrils to study gut-to-brain α-synuclein transfer, the possible origins of misfolded α-synuclein within the gut have remained elusive. We recently demonstrated that sensory cells of intestinal mucosa express α-synuclein.

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Article Synopsis
  • Mechanical high-intensity focused ultrasound (M-HIFU) is a new cancer treatment that uses sound waves instead of heat to destroy tumors, making it less damaging than traditional methods.
  • Early trials show that M-HIFU might help the body's immune system attack cancer while also treating liver tumors effectively.
  • Researchers are exploring ways to combine M-HIFU with other cancer treatments and need to study how these treatments work together to improve results for patients.
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Epidemiological and histopathological findings have raised the possibility that misfolded α-synuclein protein might spread from the gut to the brain and increase the risk of Parkinson's disease (PD). While past experimental studies in mouse models have relied on gut injections of exogenous recombinant α-synuclein fibrils to study gut to brain α-synuclein transfer, the possible origins of misfolded α-synuclein within the gut have remained elusive. We recently demonstrated that sensory cells of the gut mucosa express α-synuclein.

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Human Flower (hFWE) isoforms hFWE1-4 are putative transmembrane (TM) proteins that reportedly mediate fitness comparisons during cell competition through extracellular display of their C-terminal tails. Isoform topology, subcellular localization, and duration of plasma membrane presentation are essential to this function. However, disagreement persists regarding the structure of orthologous fly and mouse FWEs, and experimental evidence for hFWE isoform subcellular localization or membrane structure is lacking.

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Intestinal epithelial stem cells (ISCs) are responsible for intestinal epithelial barrier renewal; thereby, ISCs play a critical role in intestinal pathophysiology research. While transgenic ISC reporter mice are available, advanced translational studies lack a large animal model. This study validates ISC isolation in a new porcine Leucine Rich Repeat Containing G Protein-Coupled Receptor 5 (LGR5) reporter line and demonstrates the use of these pigs as a novel colorectal cancer (CRC) model.

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Collective cell behavior contributes to all stages of cancer progression. Understanding how collective behavior emerges through cell-cell interactions and decision-making will advance our understanding of cancer biology and provide new therapeutic approaches. Here, we summarize an interdisciplinary discussion on multicellular behavior in cancer, draw lessons from other scientific disciplines, and identify future directions.

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A Cancer Rainbow mouse line that expresses 3 fluorescently labeled isoforms of the tumor-driver gene (HER2BOW) was developed recently for the study of tumorigenesis in the mammary gland. The expression of 1 of the 3 HER2 isoforms in HER2BOW mice is induced through the Cre/ system. However, in addition to developing palpable mammary tumors, HER2BOW mice developed orbital tumors, specifically of the Harderian gland.

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The protease caspase-3 is a key mediator of apoptotic programmed cell death. But weak or transient caspase activity can contribute to neuronal differentiation, axonal pathfinding, and synaptic long-term depression. Despite the importance of sublethal, or nonapoptotic, caspase activity in neurodevelopment and neural plasticity, there has been no simple method for mapping and quantifying nonapoptotic caspase activity (NACA) in rodent brains.

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Background: Despite multimodal adjuvant management with radiotherapy, chemotherapy and hormonal therapies, most surgically resected primary breast cancers relapse or metastasize. A potential solution to late and distant recurrence is to augment systemic antitumor immunity, in part by appropriately presenting tumor antigens, but also by modulating the immunosuppressive tumor microenvironment (TME). We previously validated this concept in models of murine carcinoma treated with a novel predominately microcavitating version of high-intensity focused ultrasound (HIFU), mechanical high-intensity focused ultrasound (M-HIFU).

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A noninvasive test to discriminate indolent prostate cancers from lethal ones would focus treatment where necessary while reducing overtreatment. We exploited the known activity of heat shock protein 90 (Hsp90) as a chaperone critical for the function of numerous oncogenic drivers, including the androgen receptor and its variants, to detect aggressive prostate cancer. We linked a near-infrared fluorescing molecule to an HSP90 binding drug and demonstrated that this probe (designated HS196) was highly sensitive and specific for detecting implanted prostate cancer cell lines with greater uptake by more aggressive subtypes.

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Practical stellar interferometry for space domain awareness is challenged by the relative motions of orbital objects and telescope arrays that require array phasing using guide stars. An orbital object's image sensitivity to the location and brightness of the guide star is problematic, possibly resulting in a degraded resolution or loss of image content when both objects fall within the interferometer's field of view. We characterized an orbital object's visibility using visibility contrast to noise ratios () as a performance metric for orbital object image quality.

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HER2-positive breast cancers are among the most heterogeneous breast cancer subtypes. The early amplification of HER2 and its known oncogenic isoforms provide a plausible mechanism in which distinct programs of tumor heterogeneity could be traced to the initial oncogenic event. Here a Cancer rainbow mouse simultaneously expressing fluorescently barcoded wildtype (HER2), exon-16 null (HER2), and N-terminally truncated (HER2) HER2 isoforms is used to trace tumorigenesis from initiation to invasion.

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Heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors (GPCRs) are common drug targets and canonically couple to specific G protein subtypes and β-arrestin adaptor proteins. G protein-mediated signaling and β-arrestin-mediated signaling have been considered separable. We show here that GPCRs promote a direct interaction between G protein subtype family members and β-arrestins regardless of their canonical G protein subtype coupling.

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Purpose: Despite promising advances in breast cancer immunotherapy, augmenting T-cell infiltration has remained a significant challenge. Although neither individual vaccines nor immune checkpoint blockade (ICB) have had broad success as monotherapies, we hypothesized that targeted vaccination against an oncogenic driver in combination with ICB could direct and enable antitumor immunity in advanced cancers.

Experimental Design: Our models of HER2 breast cancer exhibit molecular signatures that are reflective of advanced human HER2 breast cancer, with a small numbers of neoepitopes and elevated immunosuppressive markers.

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A remaining challenge for the deployment of proton-exchange membrane fuel cells is the limited durability of platinum (Pt) nanoscale materials that operate at high voltages during the cathodic oxygen reduction reaction. In this work, atomic-scale insight into well-defined single-crystalline, thin-film and nanoscale surfaces exposed Pt dissolution trends that governed the design and synthesis of durable materials. A newly defined metric, intrinsic dissolution, is essential to understanding the correlation between the measured Pt loss, surface structure, size and ratio of Pt nanoparticles in a carbon (C) support.

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Photodynamic therapy (PDT) ablates malignancies by applying focused near-infrared (nIR) light onto a lesion of interest after systemic administration of a photosensitizer (PS); however, the accumulation of existing PS is not tumor-exclusive. We developed a tumor-localizing strategy for PDT, exploiting the high expression of heat shock protein 90 (Hsp90) in cancer cells to retain high concentrations of PS by tethering a small molecule Hsp90 inhibitor to a PS (verteporfin, VP) to create an Hsp90-targeted PS (HS201). HS201 accumulates to a greater extent than VP in breast cancer cells both in vitro and in vivo, resulting in increased treatment efficacy of HS201-PDT in various human breast cancer xenografts regardless of molecular and clinical subtypes.

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Polymer electrolyte membrane fuel cell (PEMFC) electrodes with a 0.07 mg cm Pt/Vulcan electrocatalyst loading, containing only a sulfonated poly(ionic liquid) block copolymer (SPILBCP) ionomer, were fabricated and achieved a ca. 2× enhancement of kinetic performance through the suppression of Pt surface oxidation.

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The pH-dependent kinetics of the hydrogen oxidation and evolution reactions (HERs and HORs) remain a fundamental conundrum in modern electrochemistry. Recent efforts have focused on the impact of the interfacial water network on the reaction kinetics. In this work, we quantify the importance of interfacial water dynamics on the overall hydrogen reaction kinetics with kinetic isotope effect (KIE) voltammetry experiments on single-crystal Pt(111) and Pt(110).

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Field cancerization is a premalignant process marked by clones of oncogenic mutations spreading through the epithelium. The timescales of intestinal field cancerization can be variable and the mechanisms driving the rapid spread of oncogenic clones are unknown. Here we use a Cancer rainbow (Crainbow) modelling system for fluorescently barcoding somatic mutations and directly visualizing the clonal expansion and spread of oncogenes.

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