Publications by authors named "Shane Cronin"

Seismic data recorded before volcanic eruptions provides important clues for forecasting. However, limited monitoring histories and infrequent eruptions restrict the data available for training forecasting models. We propose a transfer machine learning approach that identifies eruption precursors-signals that consistently change before eruptions-across multiple volcanoes.

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Article Synopsis
  • - During pregnancy and lactation, mammals experience significant changes in their intestinal epithelium, leading to an increase in intestinal surface area through the expansion of villi.
  • - The RANK-RANKL molecular pathway is crucial for this process, protecting gut cells from death and promoting intestinal stem cell activity, which results in villous elongation.
  • - Mice lacking RANK in their intestinal epithelium have offspring that are heavier and more prone to glucose intolerance, highlighting the importance of RANK-RANKL in both immediate and long-term health outcomes for offspring.
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Postoperative pain affects most patients after major surgery and can transition to chronic pain. The considerable side effects and limited efficacy of current treatments underline the need for new therapeutic options. We observed increased amounts of the metabolites BH4 and serotonin after skin injury.

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Unlabelled: On 15 January 2022, Hunga volcano erupted, creating an extensive and high-reaching umbrella cloud over the open ocean, hindering traditional isopach mapping and fallout volume estimation. In MODIS satellite imagery, ocean surface water was discolored around Hunga following the eruption, which we attribute to ash fallout from the umbrella cloud. By relating intensity of ocean discoloration to fall deposit thicknesses in the Kingdom of Tonga, we develop a methodology for estimating airfall volume over the open ocean.

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Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive, malignant, and lethal cancers, displaying strong resistance to immunotherapy. In this issue of Cell Metabolism, a study by Liu et al. identifies tetrahydrobiopterin metabolic dysregulation as a key driver for the immunosuppressive PDAC environment in mouse and human.

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Skeletal muscle plays a central role in the regulation of systemic metabolism during lifespan. With aging, this function is perturbed, initiating multiple chronic diseases. Our knowledge of mechanisms responsible for this decline is limited.

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One of the largest explosive eruptions instrumentally recorded occurred at Hunga volcano on 15 January 2022. The magma plumbing system under this volcano is unexplored because of inherent difficulties caused by its submarine setting. We use marine gravity data derived from satellite altimetry combined with multibeam bathymetry to model the architecture and dynamics of the magmatic system before and after the January 2022 eruption.

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Volcanic eruptions on land create hot and fast pyroclastic density currents, triggering tsunamis or surges that travel over water where they reach the ocean. However, no field study has documented what happens when large volumes of erupted volcanic material are instead delivered directly into the ocean. We show how the rapid emplacement of large volumes of erupted material onto steep submerged slopes triggered extremely fast (122 kilometers per hour) and long-runout (>100 kilometers) seafloor currents.

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Postoperative pain affects most patients after major surgery and can transition to chronic pain. Here, we discovered that postoperative pain hypersensitivity correlated with markedly increased local levels of the metabolite BH4. Gene transcription and reporter mouse analyses after skin injury identified neutrophils, macrophages and mast cells as primary postoperative sources of GTP cyclohydrolase-1 () expression, the rate-limiting enzyme in BH4 production.

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The development of novel analgesics for chronic pain in the last 2 decades has proven virtually intractable, typically failing due to lack of efficacy and dose-limiting side effects. Identified through unbiased gene expression profiling experiments in rats and confirmed by human genome-wide association studies, the role of excessive tetrahydrobiopterin (BH4) in chronic pain has been validated by numerous clinical and preclinical studies. BH4 is an essential cofactor for aromatic amino acid hydroxylases, nitric oxide synthases, and alkylglycerol monooxygenase so a lack of BH4 leads to a range of symptoms in the periphery and central nervous system (CNS).

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Infections with defined Herpesviruses, such as Pseudorabies virus (PRV) and Varicella zoster virus (VZV) can cause neuropathic itch, referred to as "mad itch" in multiple species. The underlying mechanisms involved in neuropathic "mad itch" are poorly understood. Here, we show that PRV infections hijack the RNA helicase DDX3X in sensory neurons to facilitate anterograde transport of the virus along axons.

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Article Synopsis
  • Dopa-responsive dystonia (DRD) and Parkinson's disease (PD) are linked to issues in dopaminergic neurons, and finding effective treatments is essential due to the impact these disorders have on quality of life.
  • Genetic studies have identified GCH1 variants linked to BH4 synthesis as key contributors to these movement disorders, with BH4 deficiency leading to more severe symptoms in models.
  • Enhancing BH4 levels shows protective effects against stressors related to PD, suggesting that targeting the BH4 pathway could be a promising therapeutic approach for managing these diseases.
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Management of neuropathic pain is notoriously difficult; current analgesics, including anti-inflammatory- and opioid-based medications, are generally ineffective and can pose serious side effects. There is a need to uncover non-addictive and safe analgesics to combat neuropathic pain. Here, we describe the setup of a phenotypic screen whereby the expression of an algesic gene,, is targeted.

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The Hunga Tonga-Hunga Ha'apai (HTHH) volcanic eruption in January 2022 generated catastrophic tsunami and contends for the largest natural explosion in more than a century. The main island, Tongatapu, suffered waves up to 17 m, and Tofua Island suffered waves up to 45 m, comfortably placing HTHH in the "megatsunami" league. We present a tsunami simulation of the Tongan Archipelago calibrated by field observations, drone, and satellite data.

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Muscle degeneration is the most prevalent cause for frailty and dependency in inherited diseases and ageing. Elucidation of pathophysiological mechanisms, as well as effective treatments for muscle diseases, represents an important goal in improving human health. Here, we show that the lipid synthesis enzyme phosphatidylethanolamine cytidyltransferase (PCYT2/ECT) is critical to muscle health.

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Unlabelled: On January 15th, 2022, at approximately 4:47 pm local time (0347 UTC), several weeks of heightened activity at the Hunga volcano 65 km northwest of Tongatapu, culminated in an 11-h long violent eruption which generated a significant near-field tsunami. Although the Kingdom of Tonga lies astride a large and tsunamigenic subduction zone, it has relatively few records of significant tsunami. Assessment activities took place both remotely and locally.

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Type 2 diabetes mellitus is one of the most prevalent metabolic diseases presenting with systemic pathologies, including reproductive disorders in male diabetic patients. However, the molecular mechanisms that contributing to spermatogenesis dysfunction in diabetic patients have not yet been fully elucidated. Here, we perform STRT-seq to examine the transcriptome of diabetic patients' testes at single-cell resolution including all major cell types of the testis.

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The HUSH (human silencing hub) complex contains the H3K9me3 binding protein M-phase phosphoprotein 8 (MPP8) and recruits the histone methyltransferase SETDB1 as well as Microrchidia CW-type zinc finger protein 2 (MORC2). Functional and mechanistic studies of the HUSH complex have hitherto been centered around SETDB1 while the in vivo functions of MPP8 and MORC2 remain elusive. Here, we show that genetic inactivation of or in the nervous system of mice leads to increased brain size, altered brain architecture, and behavioral changes.

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Article Synopsis
  • Increased tetrahydrobiopterin (BH4) levels in damaged sensory neurons are linked to heightened pain sensitivity, and the enzyme GTP cyclohydrolase 1 (GCH1) is crucial for BH4 production.
  • Research indicates that decreased GCH1 can lead to reduced pain and BH4 levels, though the regulation of GCH1 after nerve injury remains largely unexplored.
  • A study screening around 1000 FDA-approved drugs revealed that EGFR/KRAS signaling increases GCH1 expression and may contribute to neuropathic pain; inhibiting this pathway could offer a new angle for pain relief and potential cancer treatments.
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Neuromedin B (NMB) is a member of the neuromedin family of neuropeptides with a high level of region-specific expression in the brain. Several GWAS studies on non-obese and obese patients suggested that polymorphisms in NMB predispose to obesity by affecting appetite control and feeding preference. Furthermore, several studies proposed that NMB can act as an insulin releasing peptide.

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Volcanic eruptions that occur without warning can be deadly in touristic and populated areas. Even with real-time geophysical monitoring, forecasting sudden eruptions is difficult, because their precursors are hard to recognize and can vary between volcanoes. Here, we describe a general seismic precursor signal for gas-driven eruptions, identified through correlation analysis of 18 well-recorded eruptions in New Zealand, Alaska, and Kamchatka.

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Oncogenic mutations in the small GTPase RAS contribute to ~30% of human cancers. In a Drosophila genetic screen, we identified novel and evolutionary conserved cancer genes that affect Ras-driven tumorigenesis and metastasis in Drosophila including confirmation of the tetraspanin Tsp29Fb. However, it was not known whether the mammalian Tsp29Fb orthologue, TSPAN6, has any role in RAS-driven human epithelial tumors.

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