Publications by authors named "THORN G"

Article Synopsis
  • Cordycepin, a compound being studied for cancer therapy, has various proposed mechanisms of action, but recent research suggests its active form is cordycepin triphosphate which inhibits gene expression triggered by growth factors.
  • The compound was found to block critical cell signaling pathways (PI3K/AKT/mTOR and MEK/ERK) in multiple cell lines, without needing to activate AMPK.
  • The action of cordycepin on the mTOR pathway occurs rapidly, within just 30 minutes, indicating a universal effect on growth factor signaling through a currently unidentified target molecule.
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Background: Nucleosome repositioning in cancer is believed to cause many changes in genome organisation and gene expression. Understanding these changes is important to elucidate fundamental aspects of cancer. It is also important for medical diagnostics based on cell-free DNA (cfDNA), which originates from genomic DNA regions protected from digestion by nucleosomes.

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With only 13.75% of the identified Aboriginal and Torres Strait Islander population of northern Queensland accessing a billed 715 Health Assessment over a 12-month period, Northern Queensland Primary Health Network (NQPHN) is embarking on an ambitious 12-month program to dramatically improve access to health assessments, and integrated and coordinated care for First Nations' people within its region. By supporting primary care providers with targeted education, training, and digital health literacy bundles and tools, NQPHN aims to facilitate quality and culturally safe 715 Health Assessments to manage chronic conditions.

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Background: The utility of circulating tumour DNA (ctDNA) for longitudinal tumour monitoring in pancreatic ductal adenocarcinoma (PDAC) has not been explored beyond mutations in the KRAS proto-oncogene. Here, we aimed to characterise and track patient-specific somatic ctDNA variants, to assess longitudinal changes in disease burden and explore the landscape of actionable alterations.

Methods: We followed 3 patients with resectable disease and 4 patients with unresectable disease, including 4 patients with ≥ 3 serial follow-up samples, of whom 2 were rare long survivors (> 5 years).

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The mammalian epigenome contains thousands of heterochromatin nanodomains (HNDs) marked by di- and trimethylation of histone H3 at lysine 9 (H3K9me2/3), which have a typical size of 3-10 nucleosomes. However, what governs HND location and extension is only partly understood. Here, we address this issue by introducing the chromatin hierarchical lattice framework (ChromHL) that predicts chromatin state patterns with single-nucleotide resolution.

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Article Synopsis
  • - Breast cancer is a significant health issue for women, impacting one in seven globally; early detection through mammographic screenings has improved outcomes, yet up to 15% of patients experience recurrence within 10 years post-surgery.
  • - Traditional treatment methods primarily focus on the primary tumor using pathological and genomic evaluations, but recent advancements have identified unique changes in peri-tumoral tissues that might contribute to local recurrence.
  • - The field cancerization theory suggests that tumors develop from a region of altered cells rather than solely from the primary tumor site, highlighting the need for integrated pathological and molecular evaluations to better assess recurrence risk and improve patient management strategies.
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Widespread mammographic screening programs and improved self-monitoring allow for breast cancer to be detected earlier than ever before. Breast-conserving surgery is a successful treatment for select women. However, up to 40% of women develop local recurrence after surgery despite apparently tumor-free margins.

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Primary HPV screening for cervical cancer by HPV mRNA testing (Aptima) was implemented in January 2017, for women ≥30 through 70 years, in the Region of Skåne, Sweden. HPV positive samples underwent cytology assessment, and women with any degree of abnormal cytology were referred for colposcopy. The aim was to audit the primary HPV screening program, by comparing the cytology results to those of corresponding women (aged ≥30 through 65 years) screened with conventional cytology during 2016.

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Coordinated changes of DNA (de)methylation, nucleosome positioning, and chromatin binding of the architectural protein CTCF play an important role for establishing cell-type-specific chromatin states during differentiation. To elucidate molecular mechanisms that link these processes, we studied the perturbed DNA modification landscape in mouse embryonic stem cells (ESCs) carrying a double knockout (DKO) of the and dioxygenases. These enzymes are responsible for the conversion of 5-methylcytosine (5mC) into its hydroxymethylated (5hmC), formylated (5fC), or carboxylated (5caC) forms.

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Clinically, osteoarthritis (OA) pain is significantly associated with synovial inflammation. Identification of the mechanisms driving inflammation could reveal new targets to relieve this prevalent pain state. Herein, a role of polyadenylation in OA synovial samples was investigated, and the potential of the polyadenylation inhibitor cordycepin (3' deoxyadenosine) to inhibit inflammation as well as to reduce pain and structural OA progression were studied.

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Like other positive-strand RNA viruses, plant potyviruses assemble viral replication complexes (VRCs) on modified cellular membranes. Potyviruses encode two membrane proteins, 6K2 and P3. The former is known to play pivotal roles in the formation of membrane-associated VRCs.

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In continuous phosphate-limited conditions, under pH control from high pH (pH ≳ 5.2) to low pH (pH ≲ 5.2), the metabolism of the Gram-positive bacterium Clostridium acetobutylicum,switches from acid to solvent production.

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The Gram-positive bacterium Clostridium acetobutylicum is an anaerobic endospore-forming species which produces acetone, butanol and ethanol via the acetone-butanol (AB) fermentation process, leading to biofuels including butanol. In previous work we looked to estimate the parameters in an ordinary differential equation model of the glucose metabolism network using data from pH-controlled continuous culture experiments. Here we combine two approaches, namely the approximate Bayesian computation via an existing sequential Monte Carlo (ABC-SMC) method (to compute credible intervals for the parameters), and the profile likelihood estimation (PLE) (to improve the calculation of confidence intervals for the same parameters), the parameters in both cases being derived from experimental data from forward shift experiments.

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Background: Quality of life (QoL) studies are well established when accompanying trials in head and neck cancer, but studies on long-term survivors are rare.

Aims: The aim was to evaluate long-term follow-up patients treated with an intensified multi-modality therapy.

Setting And Design: Cross-sectional study, tertiary care center.

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Histone acetylation is one of the vital reversible modifications of chromatin structure that regulates gene expression in eukaryotes. Histone acetyltransferases (HATs) and histone deacetylases (HDACs) maintain the homeostasis of histone acetylation. Studies in Arabidopsis have revealed that HATs are involved in plant responses to various stresses including light, temperature, salt and ABA.

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In response to changing extracellular pH levels, phosphate-limited continuous cultures of Clostridium acetobutylicum reversibly switches its metabolism from the dominant formation of acids to the prevalent production of solvents. Previous experimental and theoretical studies have revealed that this pH-induced metabolic switch involves a rearrangement of the intracellular transcriptomic, proteomic and metabolomic composition of the clostridial cells. However, the influence of the population dynamics on the observations reported has so far been neglected.

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The acetone-butanol (AB) fermentation process in the anaerobic endospore-forming Gram-positive bacterium Clostridium acetobutylicum is useful as a producer of biofuels, particularly butanol. Recent work has concentrated on trying to improve the efficiency of the fermentation method, either through changes in the environmental conditions or by modifying the genome to selectively favour the production of one particular solvent over others. Fermentation of glucose by C.

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A BOD:N:P ratio of 100:5:1 is often used as a benchmark for nutrient addition in nutrient limited wastewaters. The impact of varying nitrogen levels, whilst maintaining phosphorus constant, was studied in a simulated aerated lagoon (BOD:N of 100:0; 100:1.3; 100:1.

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Random walks are used to model movement in a wide variety of contexts: from the movement of cells undergoing chemotaxis to the migration of animals. In a two-dimensional biased random walk, the diffusion about the mean drift position is entirely dependent on the moments of the angular distribution used to determine the movement direction at each step. Here we consider biased random walks using several different angular distributions and derive expressions for the diffusion coefficients in each direction based on either a fixed or variable movement speed, and we use these to generate a probability density function for the long-time spatial distribution.

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A photoreactive quinolinemethanol analog, N-[4-[1-hydroxy-2-(dibutylamino)ethyl]quinolin-8yl]-4- azido-2-salicylamide (ASA-MQ) has been synthesized which closely mimics the action of mefloquine. ASA-MQ possesses potent antimalarial activity against a mefloquine-sensitive strain of Plasmodium falciparum and shows decreased activity against a mefloquine-resistant parasite strain. Radioiodinated ASA-MQ has been used in photoaffinity labeling studies to identify mefloquine-interacting proteins in serum, uninfected erythrocytes and Plasmodium falciparum-infected erythrocytes.

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