Publications by authors named "Taylor Clinton"

Background: The Voices on Vax campaign was a collaborative effort that engaged youth to create an interactive website and social media presence to increase COVID vaccine confidence and uptake among African American families in Baltimore, Maryland.

Objectives: To describe lessons learned and offer recommendations for future health communication campaigns involving youth ambassadors and virtual platforms.

Methods: We collected website analytics and limited data from pop-up surveys on the Voices on Vax website, as well as reflections from the youth ambassadors about their experiences.

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Article Synopsis
  • The study investigates the WNK-OSR1/SPAK protein kinase signaling pathway, which is known to regulate ion homeostasis and cell volume, to discover its other potential signaling roles.
  • Researchers analyzed the binding specificity of the conserved C-terminal (CCT) domains of OSR1 and SPAK to identify possible interaction motifs in human proteins, highlighting key consensus sequences and ranking about 3,700 identified motifs.
  • The findings reveal not only that a significant portion of previously known motifs align with predicted ones but also introduce new variants lacking a previously essential arginine, showing an expanded functionality of CCT domains in linking WNK signaling to various cellular functions.
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Arc (also known as Arg3.1) is an activity-dependent immediate early gene product enriched in neuronal dendrites. Arc plays essential roles in long-term potentiation, long-term depression, and synaptic scaling.

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Certain areas of the brain involved in episodic memory and behavior, such as the hippocampus, express high levels of insulin receptors and glucose transporter-4 (GLUT4) and are responsive to insulin. Insulin and neuronal glucose metabolism improve cognitive functions and regulate mood in humans. Insulin-dependent GLUT4 trafficking has been extensively studied in muscle and adipose tissue, but little work has demonstrated either how it is controlled in insulin-responsive brain regions or its mechanistic connection to cognitive functions.

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Article Synopsis
  • - Activity-regulated cytoskeleton-associated protein (Arc) is crucial for various types of synaptic plasticity, such as long-term potentiation and depression, and can also form virus-like particles to facilitate mRNA transport between cells.
  • - Arc undergoes several post-translational modifications, particularly phosphorylation by protein kinase C (PKC), which occurs on specific serine residues, affecting its function.
  • - Mutating these serines to mimic phosphorylation leads to reduced palmitoylation, impaired nucleic acid binding, and instability of Arc oligomers, suggesting that PKC phosphorylation may restrict synaptic weakening and mRNA transport.
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The conserved p38 MAPK family is activated by phosphorylation during stress responses and inactivated by phosphatases. C. elegans PMK-1 p38 MAPK initiates innate immune responses and blocks development when hyperactivated.

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The most frequent ERK2 (MAPK1) mutation in cancers, E322K, lies in the common docking (CD) site, which binds short motifs made up of basic and hydrophobic residues present in the activators MEK1 (MAP2K1) and MEK2 (MAP2K2), in dual specificity phosphatases (DUSPs) that inactivate the kinases, and in many of their substrates. Also, part of the CD site, but mutated less often in cancers, is the preceding aspartate (D321N). These mutants were categorized as gain of function in a sensitized melanoma system.

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Calmodulin kinase-like vesicle-associated (CaMKv), a pseudokinase belonging to the Ca/calmodulin-dependent kinase family, is expressed predominantly in brain and neural tissue. It may function in synaptic strengthening during spatial learning by promoting the stabilization and enrichment of dendritic spines. At present, almost nothing is known regarding CaMKv structure and regulation.

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Article Synopsis
  • WNK kinases and their downstream effectors, OSR1 and SPAK, play crucial roles in regulating cell volume, ion balance, and various cellular functions, with mutations linked to inherited hypertension and neurological issues.
  • * Their interaction and activation depend on specific protein domains that bind to certain sequence motifs, indicating that understanding these interactions is essential for uncovering the complexity of WNK signaling pathways.
  • * Research into the structure and function of the CCT domains could reveal new insights into how these kinases affect cancer progression and other cellular processes.
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The most frequent extracellular signal-regulated kinase 2 (ERK2) mutation occurring in cancers is E322K (E-K). ERK2 E-K reverses a buried charge in the ERK2 common docking (CD) site, a region that binds activators, inhibitors, and substrates. Little is known about the cellular consequences associated with this mutation, other than apparent increases in tumor resistance to pathway inhibitors.

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An early step in signaling from activated receptor tyrosine kinases (RTKs) is the recruitment of cytosolic adaptor proteins to autophosphorylated tyrosines in the receptor cytoplasmic domains. Fibroblast growth factor receptor substrate 2α (FRS2α) associates via its phosphotyrosine-binding domain (PTB) to FGF receptors (FGFRs). Upon FGFR activation, FRS2α undergoes phosphorylation on multiple tyrosines, triggering recruitment of the adaptor Grb2 and the tyrosine phosphatase Shp2, resulting in stimulation of PI3K/AKT and MAPK signaling pathways.

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Article Synopsis
  • The WNK signaling pathway plays a crucial role in regulating cell volume and ion transport through kinases SPAK and OSR1.
  • SPAK and OSR1 interact with specific sequence motifs, including a variant that is present in some human inward rectifier K channels, which is essential for their activation.
  • The study shows that OSR1 activates certain K channels (Kir2.1 and Kir2.3) but not others (like Kir4.1), and highlights the importance of the WNK-OSR1 pathway in enhancing the plasma membrane localization of these channels.
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Article Synopsis
  • - Researchers, led by Herrero, discovered a small molecule that prevents the dimerization of ERK, which is important for cancer growth, without affecting its activity or MEK-induced phosphorylation.
  • - The study suggests that focusing on blocking protein dimerization is a promising new strategy for developing cancer treatments.
  • - This approach could help reduce drug resistance in kinases that are commonly involved in tumor signaling pathways.
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The related protein kinases SPAK and OSR1 regulate ion homeostasis in part by phosphorylating cation cotransporter family members. The structure of the kinase domain of OSR1 was determined in the unphosphorylated inactive form and, like some other Ste20 kinases, exhibited a domain-swapped activation loop. To further probe the role of domain swapping in SPAK and OSR1, we have determined the crystal structures of SPAK 63-403 at 3.

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Background: The Activity-regulated cytoskeleton-associated protein, Arc, is an immediate-early gene product implicated in various forms of synaptic plasticity. Arc promotes endocytosis of AMPA type glutamate receptors and regulates cytoskeletal assembly in neuronal dendrites. Its role in endocytosis may be mediated by its reported interaction with dynamin 2, a 100 kDa GTPase that polymerizes around the necks of budding vesicles and catalyzes membrane scission.

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The circadian clock in mammals is driven by an autoregulatory transcriptional feedback mechanism that takes approximately 24 hours to complete. A key component of this mechanism is a heterodimeric transcriptional activator consisting of two basic helix-loop-helix PER-ARNT-SIM (bHLH-PAS) domain protein subunits, CLOCK and BMAL1. Here, we report the crystal structure of a complex containing the mouse CLOCK:BMAL1 bHLH-PAS domains at 2.

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Geographic and temporal variations in the concentration and composition of particulate matter (PM) provide important insights into particle sources, atmospheric processes that influence particle formation, and PM management strategies. In the nonurban areas of California, annual-average PM2.5 and PM10 concentrations range from 3 to 10 microg/m3 and from 5 to 18 microg/m3, respectively.

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It will be many years before the recently deployed network of fine particulate matter with an aerodynamic diameter less than 2.5 microm (PM2.5) Federal Reference Method (FRM) samplers produces information on nonattainment areas, trends, and source impacts.

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