Publications by authors named "Gabriella Braun"

Mycosis fungoides (MF) is the most common form of cutaneous T-cell lymphoma (CTCL). Despite having a wide variety of therapeutic agents available for the treatment of MF, patients often suffer from a significant decrease in quality of life and rarely achieve long-term remission or complete cure, highlighting a need to develop novel therapeutic agents for this disease. The present study was undertaken to evaluate the efficacy of a novel anti-tumor agent, GZ17-6.

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The mechanisms that confer cognitive resilience to Alzheimer's Disease (AD) are not fully understood. Here, we describe a neural circuit mechanism underlying this resilience in a familial AD mouse model. In the prodromal disease stage, interictal epileptiform spikes (IESs) emerge during anesthesia in the CA1 and mPFC regions, leading to working memory disruptions.

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Article Synopsis
  • Actinic keratoses (AKs) are precancerous skin growths caused by UV exposure, and they can develop into cutaneous squamous cell carcinoma.
  • Recent research demonstrated that GZ21T, a topical formulation containing GZ17-6.02, effectively decreased both the number and size of AK lesions in a mouse model while also preventing progression to squamous cell carcinoma.
  • The treatment worked by suppressing multiple cellular signaling pathways and proteins linked to tumor growth and promoting autophagy, which aids in cellular cleanup.
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UV irradiation is commonly used in murine models of skin cancers. Despite the popularity of using UVB rays to model photocarcinogenesis in animals, there is a lack of standardization in the secondary enclosures used to administer radiation. An appraisal of the literature also shows a general lack of details regarding the materials and procedures utilized in the fabrication of such enclosures.

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Epidermal Growth Factor Receptor (EGFR) is amplified in over 50% of glioblastomas and promotes tumor formation and progression. However, attempts to treat glioblastoma with EGFR tyrosine kinase inhibitors have been unsuccessful thus far. The current standard of care is especially poor in patients with a constitutively active form of EGFR, EGFRvIII, which is associated with shorter survival time.

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Dysregulated homeostasis of neural activity has been hypothesized to drive Alzheimer's disease (AD) pathogenesis. AD begins with a decades-long presymptomatic phase, but whether homeostatic mechanisms already begin failing during this silent phase is unknown. We show that before the onset of memory decline and sleep disturbances, familial AD (fAD) model mice display no deficits in CA1 mean firing rate (MFR) during active wakefulness.

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Maintaining average activity within a set-point range constitutes a fundamental property of central neural circuits. However, whether and how activity set points are regulated remains unknown. Integrating genome-scale metabolic modeling and experimental study of neuronal homeostasis, we identified mitochondrial dihydroorotate dehydrogenase (DHODH) as a regulator of activity set points in hippocampal networks.

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Temperature compensation and period determination by casein kinase 1 (CK1) are conserved features of eukaryotic circadian rhythms, whereas the clock gene transcription factors that facilitate daily gene expression rhythms differ between phylogenetic kingdoms. Human red blood cells (RBCs) exhibit temperature-compensated circadian rhythms, which, because RBCs lack nuclei, must occur in the absence of a circadian transcription-translation feedback loop. We tested whether period determination and temperature compensation are dependent on CKs in RBCs.

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Circadian rhythms organize many aspects of cell biology and physiology to a daily temporal program that depends on clock gene expression cycles in most mammalian cell types. However, circadian rhythms are also observed in isolated mammalian red blood cells (RBCs), which lack nuclei, suggesting the existence of post-translational cellular clock mechanisms in these cells. Here we show using electrophysiological and pharmacological approaches that human RBCs display circadian regulation of membrane conductance and cytoplasmic conductivity that depends on the cycling of cytoplasmic K levels.

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The cytoplasmic loop between the second and third transmembrane segments is pivotal in the regulation of TRESK (TWIK-related spinal cord K+ channel, K2P18.1, KCNK18). Calcineurin binds to this region and activates the channel by dephosphorylation in response to the calcium signal.

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TRESK (TWIK-related spinal cord K(+) channel, KCNK18) is a major background K(+) channel of sensory neurons. Dominant-negative mutation of TRESK is linked to familial migraine. This important two-pore domain K(+) channel is uniquely activated by calcineurin.

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TRESK (TWIK-related spinal cord K(+) channel, KCNK18) belongs to the two-pore domain (K2P) background (leak) potassium channel family. Unlike other K2P channels, TRESK is activated by the calcium signal in heterologous expression systems. The activation is mediated by the calcium/calmodulin-dependent protein phosphatase, calcineurin.

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