Drug-resistant organisms (DROs) necessitate the development of new therapies. Antimicrobial blue light (ABL) is a promising option, utilizing photoexcitation of endogenous bacterial components to generate reactive oxygen species, leading to bacterial death. The aim of this study is to investigate the effects of a novel isotropic optical fiber under in-vitro conditions on multidrug-resistant gram-negative Pseudomonas aeruginosa (MDR-Pa) and methicillin-resistant Staphylococcus aureus (MRSA).
View Article and Find Full Text PDFProc Natl Acad Sci U S A
December 2024
Oxidation of the sub-arc mantle driven by slab-derived fluids has been hypothesized to contribute to the formation of gold deposits in magmatic arc environments that host the majority of metal resources on Earth. However, the mechanism by which the infiltration of slab-derived fluids into the mantle wedge changes its oxidation state and affects Au enrichment remains poorly understood. Here, we present the results of a numerical model that demonstrates that slab-derived fluids introduce large amounts of sulfate (S) into the overlying mantle wedge that increase its oxygen fugacity by up to 3 to 4 log units relative to the pristine mantle.
View Article and Find Full Text PDFSpecialized or secondary metabolites are small molecules of biological origin, often showing potent biological activities with applications in agriculture, engineering and medicine. Usually, the biosynthesis of these natural products is governed by sets of co-regulated and physically clustered genes known as biosynthetic gene clusters (BGCs). To share information about BGCs in a standardized and machine-readable way, the Minimum Information about a Biosynthetic Gene cluster (MIBiG) data standard and repository was initiated in 2015.
View Article and Find Full Text PDFPhotodynamic implants are an increasingly popular minimally invasive option for the surgical treatment of metastatic bone disease. Following surgery, adjuvant radiation therapy (RT) is frequently administered to achieve better disease control and improve patient quality of life, but the role of RT in implant failures associated with photodynamic implants remains unclear. The aim of this study is to determine if the therapeutic RT range of 10-50 Gy affects the biomechanical properties of photodynamic implants.
View Article and Find Full Text PDFVaping cannabinoids in electronic (e)-cigarette devices is rapidly increasing in popularity, particularly among adolescents, although the chemistry affecting the composition of the vape aerosol is not well understood. This work investigates the formation of aerosol mass, bioactive hydroxyquinones, and harmful or potentially harmful carbonyls from the e-cigarette vaping of natural and synthetic cannabinoids e-liquids in propylene glycol and vegetable glycerin (PG/VG) solvent at a 50 mg/mL concentration in a commercial fourth-generation vaping device. The following cannabinoids were studied: cannabidiol (CBD), 8,9-dihydrocannabidiol (H2CBD), 1,2,8,9-tetrahydrocannabidiol (H4CBD), cannabigerol (CBG), and cannabidiolic acid (CBDA).
View Article and Find Full Text PDFThe small ubiquitin-like modifier (SUMO) protein pathway governs a panoply of vital biological processes including cell death, proliferation, differentiation, metabolism, and signal transduction by diversifying the functions, half-lives, and partnerships of target proteins in situ. More recently, SUMOylation has emerged as a key regulator of ion homeostasis and excitability across multiple tissues due to the regulation of a plethora of ion channels expressed in a range of tissue subtypes. Altogether, the balance of SUMOylation states among relevant ion channels can result in graded biophysical effects that tune excitability and contribute to a range of disease states including cardiac arrhythmia, epilepsy, pain transmission, and inflammation.
View Article and Find Full Text PDFApproximately 50% of patients with surgically resected early-stage lung cancer develop distant metastasis. At present, there is no in vivo metastasis model to investigate the biology of human lung cancer metastases. Using well-characterized lung adenocarcinoma (LUAD) patient-derived organoids (PDOs), we establish an in vivo metastasis model that preserves the biologic features of human metastases.
View Article and Find Full Text PDFTrauma Violence Abuse
January 2025
We are grateful to the Editors of TVA for the opportunity to respond to the commentary on our systematic review of the sex trafficking of minors, specifically regarding the initial recruitment location. Upon revisiting the 7 out of 23 reviewed studies that address recruitment locations, we find that the discrepancy with the commentators' views stems from differing interpretations of the term "initial." We affirm that these seven studies, which include the internet as a prominent initial recruitment site, are valid and appropriate for inclusion.
View Article and Find Full Text PDFThe platypus () is an amphibious, egg-laying mammal of high conservation value that is found only in Australia. The zoonotic bacterium serovar Hardjo was discovered in platypuses in prior studies, but little is known about its epidemiology. Samples in the Platypus Serum Bank were tested in 2023 and the results were combined with historical records.
View Article and Find Full Text PDFThe ability of the attaching and effacing pathogens enterohaemorrhagic Escherichia coli (EHEC) and Citrobacter rodentium to overcome colonisation resistance is reliant on a type 3 secretion system used to intimately attach to the colonic epithelium. This crucial virulence factor is encoded on a pathogenicity island known as the Locus of Enterocyte Effacement (LEE) but its expression is regulated by several core-genome encoded transcription factors. Here, we unveil that the core transcription factor PdhR, traditionally known as a regulator of central metabolism in response to cellular pyruvate levels, is a key activator of the LEE.
View Article and Find Full Text PDFBackground: is a species of the insect pathogenic genus that has been isolated as an etiological agent in human infections. Since then, multiple isolates have been identified worldwide; however, actual clinical infections have so far only been identified in North America, Australia, and Nepal. Previous research on the clinical isolates had shown that the strains differed in their behaviour when infecting cultured human cells.
View Article and Find Full Text PDFUpland habitats provide vital ecological services, yet they are highly threatened by natural and anthropogenic stressors. Monitoring these vulnerable habitats is fundamental for conservation and involves determining information about their spatial locations and conditions. Remote sensing has evolved as a promising tool to map the distribution of upland habitats in space and time.
View Article and Find Full Text PDFAdvances in genome engineering and associated technologies have reinvigorated natural products research. Here we highlight the latest developments in the field across the discover-design-build-test-learn cycle of bioengineering, from recent progress in computational tools for AI-supported genome mining, enzyme and pathway engineering, and compound identification to novel host systems and new techniques for improving production levels, and place these trends in the context of responsible research and innovation, emphasizing the importance of anticipatory analysis at the early stages of process development.
View Article and Find Full Text PDFEpidemiologic studies frequently use risk ratios to quantify associations between exposures and binary outcomes. When the data are physically stored at multiple data partners, it can be challenging to perform individual-level analysis if data cannot be pooled centrally due to privacy constraints. Existing methods either require multiple file transfers between each data partner and an analysis center (e.
View Article and Find Full Text PDFBackground: Transcatheter aortic valve replacement (TAVR) is accepted as an alternative to surgical aortic valve replacement (SAVR) in patients with severe symptomatic aortic valve stenosis. Prior studies have shown that TAVR has comparable or superior outcomes to SAVR in intermediate and high-risk patients. However, there is paucity of data about outcome of TAVR vs SAVR in low-surgical-risk patients evaluated at 4 or more years post-procedure.
View Article and Find Full Text PDFObjective: Partially observed confounder data pose challenges to the statistical analysis of electronic health records (EHR) and systematic assessments of potentially underlying missingness mechanisms are lacking. We aimed to provide a principled approach to empirically characterize missing data processes and investigate performance of analytic methods.
Methods: Three empirical sub-cohorts of diabetic SGLT2 or DPP4-inhibitor initiators with complete information on HbA1c, BMI and smoking as confounders of interest (COI) formed the basis of data simulation under a plasmode framework.
Virulence and metabolism are often interlinked to control the expression of essential colonisation factors in response to host-associated signals. Here, we identified an uncharacterised transporter of the dietary monosaccharide ʟ-arabinose that is widely encoded by the zoonotic pathogen enterohaemorrhagic Escherichia coli (EHEC), required for full competitive fitness in the mouse gut and highly expressed during human infection. Discovery of this transporter suggested that EHEC strains have an enhanced ability to scavenge ʟ-arabinose and therefore prompted us to investigate the impact of this nutrient on pathogenesis.
View Article and Find Full Text PDFSustainable reductions in African malaria transmission require innovative tools for mosquito control. One proposal involves the use of low-threshold gene drive in Anopheles vector species, where a 'causal pathway' would be initiated by (i) the release of a gene drive system in target mosquito vector species, leading to (ii) its transmission to subsequent generations, (iii) its increase in frequency and spread in target mosquito populations, (iv) its simultaneous propagation of a linked genetic trait aimed at reducing vectorial capacity for Plasmodium, and (v) reduced vectorial capacity for parasites in target mosquito populations as the gene drive system reaches fixation in target mosquito populations, causing (vi) decreased malaria incidence and prevalence. Here the scope, objectives, trial design elements, and approaches to monitoring for initial field releases of such gene dive systems are considered, informed by the successful implementation of field trials of biological control agents, as well as other vector control tools, including insecticides, Wolbachia, larvicides, and attractive-toxic sugar bait systems.
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