Results
- Showing results for:
- Reset all filters
Search results
-
Journal articleTregoning J, Tillotson R, 2024,
‘That’s funny’: creative solutions for time-starved researchers
, Nature, ISSN: 0028-0836 -
Journal articleStolarczyk E, Vong CT, Garrido-Mesa N, et al., 2024,
Global deletion of the immune cell transcription factor, T-bet, alters gut microbiota and insulin sensitivity in mice
, FRONTIERS IN GENETICS, Vol: 15 -
Journal articleHarper KL, Harrington EM, Hayward C, et al., 2024,
Virus-modified paraspeckle-like condensates are hubs for viral RNA processing and their formation drives genomic instability
, Nature Communications, Vol: 15, ISSN: 2041-1723The nucleus is a highly organised yet dynamic environment containing distinct membraneless nuclear bodies. This spatial separation enables a subset of components to be concentrated within biomolecular condensates, allowing efficient and discrete processes to occur which regulate cellular function. One such nuclear body, paraspeckles, are comprised of multiple paraspeckle proteins (PSPs) built around the architectural RNA, NEAT1_2. Paraspeckle function is yet to be fully elucidated but has been implicated in a variety of developmental and disease scenarios. We demonstrate that Kaposi’s sarcoma-associated herpesvirus (KSHV) drives formation of structurally distinct paraspeckles with a dramatically increased size and altered protein composition that are required for productive lytic replication. We highlight these virus-modified paraspeckles form adjacent to virus replication centres, potentially functioning as RNA processing hubs for viral transcripts during infection. Notably, we reveal that PSP sequestration into virus-modified paraspeckles result in increased genome instability during both KSHV and Epstein Barr virus (EBV) infection, implicating their formation in virus-mediated tumourigenesis.
-
Journal articleLee JH, Reischl S, Walter RL, et al., 2024,
Orally delivered biodegradable targeted inflammation resolving pectin-coated nanoparticles induce anastomotic healing post intestinal surgery
, Scientific Reports, Vol: 14, ISSN: 2045-2322Targeted perioperative therapeutics supporting anastomotic healing during colitis are an urgent medical need. This study aimed to develop and evaluate a novel nanoparticle (NP)-based drug delivery system for improving anastomotic healing in Inflammatory bowel disease (IBD) patients following surgery. We developed pectin-coated polymeric NPs encapsulating the inflammation-resolving peptide Ac2-26. These NPs are designed to survive gastric passage, facilitate localized release in the colon via microbial pectinase degradation, and bind to the intestinal wound through collagen IV targeting. We investigated these NPs in a murine surgical model combining intestinal anastomosis with preoperative colitis induction. Perioperative administration of pectin-chitosan coated NPs containing Ac2-26 (P-C-Col IV-Ac2-26-NP) reduced colitis activity postoperatively. Macroscopic wound closure improved, as evaluated by endoscopy and intraabdominal adhesion scoring. Microscopic analysis revealed an improved semiquantitative healing score in the treatment group. This proof-of-concept study demonstrates that novel P-C-Col IV-Ac2-26-NP could be a promising and clinically feasible perioperative treatment strategy for IBD patients undergoing intestinal surgery. The targeted delivery system shows potential for enhancing anastomotic healing and reducing postoperative complications in this IBD patient population.
-
Journal articleScheiner B, Kang B, Balcar L, et al., 2024,
Outcome and management of patients with hepatocellular carcinoma who achieved a complete response to immunotherapy-based systemic therapy
, HEPATOLOGY, ISSN: 0270-9139 -
Journal articleCochran D, Takis PG, Alexander JL, et al., 2024,
Evaluating protocols for reproducible targeted metabolomics by NMR
, The Analyst, Vol: 149, Pages: 5423-5432, ISSN: 0003-2654Metabolomics aims to study the downstream effects of variables like diet, environment, or disease on a given biological system. However, inconsistencies in sample preparation, data acquisition/processing protocols lead to reproducibility and accuracy concerns. A systematic study was conducted to assess how sample preparation methods and data analysis platforms affect metabolite susceptibility. A targeted panel of 25 metabolites was evaluated in 69 clinical metabolomics samples prepared following three different protocols: intact, ultrafiltration, and protein precipitation. The resulting metabolic profiles were characterized by 1D 1H nuclear magnetic resonance (NMR) spectroscopy and analyzed with Chenomx v8.3 and SMolESY software packages. Greater than 90% of the metabolites were extracted more efficiently using protein precipitation than filtration, which aligns with previously reported results. Additionally, analysis of data processing software suggests that metabolite concentrations were overestimated by Chenomx batch-fitting, which only appears reliable for determining relative fold changes rather than absolute quantification. However, an assisted-fit method provided sufficient guidance to achieve accurate results while avoiding a time-consuming fully manual-fitting approach. By combining our results with previous studies, we can now provide a list of 5 common metabolites [2-hydroxybutyrate (2-HB), choline, dimethylamine (DMA), glutamate, lactate] with a high degree of variability in reported fold changes and standard deviations that need careful consideration before being annotated as potential biomarkers. Our results show that sample preparation and data processing package critically impact clinical metabolomics study success. There is a clear need for an increased degree of standardization and harmonization of methods across the metabolomics community to ensure reliable outcomes.
-
Journal articleFinney L, Fenwick P, Kemp S, et al., 2024,
Impaired anti-viral immunity in frequent exacerbators of chronic obstructive pulmonary disease
, American Journal of Physiology: Lung Cellular and Molecular Physiology, ISSN: 1040-0605 -
Journal articleSampson HA, Arasi S, Bahnson HT, et al., 2024,
AAAAI-EAACI PRACTALL: Standardizing oral food challenges-2024 Update
, Pediatric Allergy and Immunology, Vol: 35, ISSN: 0905-6157This common statement of the American Academy of Allergy, Asthma and Immunology (AAAAI) and The European Academy of Allergy and Clinical Immunology (EAACI) provides an update of the 2012 published guidelines on food challenges. The guidelines equally address food challenges in the research and the clinical settings. They first address the diagnostic tests which can guide the decision to conduct a challenge. Safety of food challenges is prime, and the various procedures and safety issues as well as medications potentially involved in challenges are extensively discussed. Challenges are suggested to be conducted with semi-logarithmic incremental doses based on the protein content, typically for IgE-mediated food allergy with intervals of 20–30 min between doses. Specific protocols for other types of reactions such atopic dermatitis or gastrointestinal food allergy are detailed separately. Proper stopping criteria are essential in order to reduce the risk of false-positive diagnoses, but also severe reactions. The guidelines recommend criteria based on “go on,” “stop,” or “observation.” These revised guidelines will clearly provide much needed guidance for food challenges in the research and clinical settings. They will continue to evolve with new diagnostic tests or new needs in the field of food allergy.
-
OtherSpear S, Le Saux O, Mirza HB, et al., 2024,
Table S3 HMOX1-hi gene expression from <i>PTEN</i> Loss Shapes Macrophage Dynamics in High-Grade Serous Ovarian Carcinoma
<jats:p><p>Up- and down-regulated differentially expressed genes in HMOX1-hi human macrophages</p></jats:p>
-
Journal articleAntariksa NF, Di Antonio M, 2024,
The emerging roles of multimolecular G-quadruplexes in transcriptional regulation and chromatin organization
, Accounts of Chemical Research, Vol: 57, Pages: 3397-3406, ISSN: 0001-4842ConspectusThe ability of genomic DNA to adopt non-canonical secondary structures known as G-quadruplexes (G4s) under physiological conditions has been recognized for its potential regulatory function of various biological processes. Among those, transcription has recently emerged as a key process that can be heavily affected by G4 formation, particularly when these structures form at gene promoters. While the presence of G4s within gene promoters has been traditionally associated with transcriptional inhibition, in a model whereby G4s act as roadblocks to polymerase elongation, recent genomics experiments have revealed that the regulatory role of G4s in transcription is more complex than initially anticipated. Indeed, earlier studies linking G4-formation and transcription mainly relied on small-molecule ligands to stabilize and promote G4s, which might lead to disruption of protein–DNA interactions and local environments and, therefore, does not necessarily reflect the endogenous function of G4s at gene promoters. There is now strong evidence pointing toward G4s being associated with transcriptional enhancement, rather than repression, through multifaceted mechanisms such as recruitment of key transcriptional proteins, molding of chromatin architecture, and mode of phase separation.In this Account, we explore pivotal findings from our research on a particular subset of G4s, namely, those formed through interactions between distant genomic locations or independent nucleic acid strands, referred to as multimolecular G4s (mG4s), and discuss their active role in transcriptional regulation. We present our recent studies suggesting that the formation of mG4s may positively regulate transcription by inducing phase-separation and selectively recruiting chromatin-remodeling proteins. Our work highlighted how mG4-forming DNA and RNA sequences can lead to liquid–liquid phase separation (LLPS) in the absence of any protein. This discovery provided new insights into
This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.