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Biology subjects

Parker, S. R.

Publications and source records attributed to Parker, S. R..

5 recordsLinked to original sources

A historical specimen of False Lingzhi (Ganoderma lucidum) resolves a 245-year-old confusion within an important medicinal mushroom group

O_LIPlants and fungi are major sources of natural products beneficial to society, making the study of distinct species essential for discovering new drugs and bioactive compounds. The medicinal mushroom "Lingzhi" or "Reishi" (Ganoderma lingzhi) is widely used in traditional medicine and extensively studied for its bioactive triterpenoids, yet it is commonly identified as Ganoderma lucidum, the type species of the genus, which lacks a type specimen. C_LIO_LIWe sequenced a G. lucidum specimen preserved in the Kew fungarium, which agreed with the original description and was collected from wood of Corylus avellana in southern England. Using this reference specimen, we compiled genomic and ITS barcoding datasets to explore the genetic and geographic variation within this species. C_LIO_LIWe showed that G. lingzhi and G. lucidum diverged more than 12 million years ago and that all seven "G. lucidum" genomes deposited in public databases belong to other species. More than 1000 barcoding sequences showed that the widely used homology-based ITS barcoding is not working in this group, which can be mitigated by a phylogenetic placement approach. The 149 sequences assigned to G. lucidum with high confidence showed a Eurasian distribution and introductions to North and South America and Africa. C_LIO_LIOur study underscores the importance of accurate species identification and provides guidance for a group of pharmaceutical and socially significant species. To further support future studies and the wider public in differentiating between G. lingzhi and G. lucidum, we propose using "False Lingzhi" as the English name for G. lucidum. C_LI Societal Impact StatementTraditional Chinese Medicine has expanded far beyond Asia, with growing markets in North America and Europe for supplements and functional foods. Lingzhi or Reishi (Ganoderma lingzhi), a well-known medicinal mushroom, is valued for its anti-inflammatory and anticancer properties. However, it is often misidentified with species that may not provide the same health benefits. This confusion poses risks to consumer safety, product regulation, and research. Here, we establish a reference using morphological and molecular tools for the most commonly misidentified species (Ganoderma lucidum) and propose the name "False Lingzhi" to distinguish it, supporting accurate identification, safer product development, and reliable research.

evolutionary biology↗

A modular, high-bandwidth, bidirectional implantable device for neural interrogation

Modern neuroelectronic interfaces have shown great potential to diagnose conditions, address neurological dysfunction, and advance neuroscientific knowledge. However, neural interface systems today require tethered connections that restrict mobility, prevent testing across ecological contexts, and inhibit clinical translation to at-home use. Fully implantable commercial systems have previously been developed, but exhibit significant constraints, including a bulky design, limited modularity, low bandwidth, or unidirectional communication (e.g. deep brain stimulation systems, DBS; spinal cord stimulation systems, SCS). Here, we have developed the Modular Bionic Interface (MBI), a system composed of a fully implantable device and a worn unit for high-bandwidth, bidirectional interfacing with the nervous system. The MBI can record high fidelity electrophysiological signals and deliver spatiotemporally modulated electrical stimulation for clinical and research purposes through flexible interaction with third party implantable devices. We performed benchtop evaluation to validate the recording and stimulation capabilities of the MBI across a diverse range of inputs and outputs. We then evaluated the MBI system in vivo through chronic implantation within a sheep, where results were stable for the length of evaluation, over three months. While connected to an actively powered, third-party high-resolution spinal cord stimulation electrode array, the MBI system was able to deliver stimulation to evoke lower extremity motor responses and record spinal compound action potentials evoked by peripheral nerve and spinal stimulation. Through rigorous evaluation, we demonstrate a fully implantable system with a small footprint capable of high-resolution, bi-directional communication with the nervous system via modular connections to third-party devices. We expect that modular devices will further our ability to treat complex neurological disease and injury.

neuroscience↗

Triple-Negative Breast Cancer Cells Activate Sensory Neurons via TRPV1 to Drive Nerve Outgrowth and Tumor Progression

The tumor microenvironment in triple-negative breast cancer (TNBC) is characterized by increased sensory nerve density, which contributes to cancer progression by promoting migration and metastasis. However, the origin of tumor-innervating nerves and the mechanisms driving sensory innervation into tumors remain poorly understood. Using in vivo retrograde labeling techniques, we show that mammary tumors are associated with an increase in nerves originating from the dorsal root ganglia. Additionally, we find that TNBC cells trigger stress and activation markers and induce neuronal firing in a transient receptor potential anilloid subtype 1 (TRPV1)-dependent manner. In both 2D and 3D cell culture models, TNBC cells promote outgrowth of sensory nerves that is abrogated with Trpv1 knockout. We identified c-Jun and IL-6 as an effector of neurite outgrowth that acts downstream of TRPV1 to promote outgrowth in vitro. Finally, in Trpv1 knockout mice, TNBC tumors exhibit delayed growth and reduced lung metastasis. These findings suggest that a critical role for TRPV1 in tumor-nerve crosstalk, offering a potential target to reduce metastatic disease.

cancer biology↗

An active electronic bidirectional interface for high resolution interrogation of the spinal cord

ObjectiveEpidural electrical stimulation (EES) has shown promise as both a clinical therapy and research tool for studying nervous system function. However, available clinical EES paddles are limited to using a small number of contacts due to the burden of wires necessary to connect each contact to the therapeutic delivery device, limiting the treatment area or density of epidural electrode arrays. We aimed to eliminate this burden using advanced on-paddle electronics. ApproachWe developed a smart EES paddle with a 60-electrode programmable array, addressable using an active electronic multiplexer embedded within the electrode paddle body. The electronics are sealed in novel, ultra-low profile hermetic packaging. We conducted extensive reliability testing on the novel array, including a battery of ISO 10993-1 biocompatibility tests and determination of the hermetic package leak rate. We then evaluated the EES device in vivo, placed on the epidural surface of the ovine lumbosacral spinal cord for 15 months. Main resultsThe active paddle array performed nominally when implanted in sheep for over 15 months and no device-related malfunctions were observed. The onboard multiplexer enabled bespoke electrode arrangements across, and within, experimental sessions. We identified stereotyped responses to stimulation in lower extremity musculature, and examined local field potential responses to EES using high-density recording bipoles. Finally, spatial electrode encoding enabled machine learning models to accurately perform EES parameter inference for unseen stimulation electrodes, reducing the need for extensive training data in future deep models. SignificanceWe report the development and chronic large animal in vivo evaluation of a high-density EES paddle array containing active electronics. Our results provide a foundation for more advanced computation and processing to be integrated directly into devices implanted at the neural interface, opening new avenues for the study of nervous system function and new therapies to treat neural injury and dysfunction.

bioengineering↗

Cell morphology best predicts tumorigenicity and metastasis in vivo across multiple TNBC cell lines of different metastatic potential

BackgroundMetastasis is the leading cause of death in breast cancer patients. For metastasis to occur, tumor cells must invade locally, intravasate, and colonize distant tissues and organs, all steps that require tumor cell migration. The majority of studies on invasion and metastasis rely on human breast cancer cell lines. While it is known that these cells have different properties and abilities for growth and metastasis, the in vitro morphological, proliferative, migratory, and invasive behavior of these cell lines and their correlation to in vivo behavior is poorly understood. Thus, we sought to classify each cell line as poorly or highly metastatic by characterizing tumor growth and metastasis in a murine model of six commonly used human triple-negative breast cancer xenografts, as well as determine which in vitro assays commonly used to study cell motility best predict in vivo metastasis. MethodsWe evaluated the liver and lung metastasis of human TNBC cell lines MDA-MB-231, MDA-MB-468, BT549, Hs578T, BT20, and SUM159 in immunocompromised mice. We characterized each cell lines cell morphology, proliferation, and motility in 2D and 3D to determine the variation in these parameters between cell lines. ResultsWe identified MDA-MB-231, MDA-MB-468, and BT549 cells as highly tumorigenic and metastatic, Hs578T as poorly tumorigenic and metastatic, BT20 as intermediate tumorigenic with poor metastasis to the lungs but highly metastatic to the livers, and SUM159 as intermediate tumorigenic but poorly metastatic to the lungs and livers. We showed that metrics that characterize cell morphology are the most predictive of tumor growth and metastatic potential to the lungs and liver. Further, we found that no single in vitro motility assay in 2D or 3D significantly correlated with metastasis in vivo. ConclusionsOur results provide an important resource for the TNBC research community, identifying the metastatic potential of 6 commonly used cell lines. Our findings also support the use of cell morphological analysis to investigate the metastatic potential and emphasize the need for multiple in vitro motility metrics using multiple cell lines to represent the heterogeneity of metastasis in vivo.

cancer biology↗