Background/objectives: The MHCII-dependent, CD4+ T-cell zwitterionic polysaccharide PS A1 has been investigated as a promising carrier for vaccine development because it can induce an MHCII-dependent CD4+ response towards a variety of tumor-associated carbohydrate antigens (TACAs). However, PS A1 cannot elicit cytotoxic T lymphocytes through MHCI, which may or may not hamper its potential clinical use in cancer, infectious and viral vaccine development. This paper addresses PS A1 MHCI independence through the introduction of an MHCI epitope, the poliovirus (PV) peptide, to establish an MHCI- and MHCII-dependent vaccine.
View Article and Find Full Text PDFNanoscale Fourier transform infrared (Nano-FTIR) imaging and spectroscopy correlated with photoluminescence measurements of lunar Apollo samples with different surface radiation exposure histories reveal distinct physical and chemical differences associated with space weathering effects. Analysis of two sample fragments: an ilmenite basalt (12016) and an impact melt breccia (15445) show evidence of intrinsic or delivered Nd and an amorphous silica glass component on exterior surfaces, whereas intrinsic Cr and/or trapped electron states are limited to interior surfaces. Spatially localized 1050 cm/935 cm band ratios in Nano-FTIR hyperspectral maps may further reflect impact-induced shock nanostructures, while shifts in silicate band positions indicate accumulated radiation damage at the nanoscale from prolonged space weathering due to micrometeorites, solar wind, energetic x-rays and cosmic ray bombardment.
View Article and Find Full Text PDFExtremity radiation exposure in nuclear medicine is a growing concern because it may surpass the maximum permissible dose of 500 mSv. This study aimed to assess the occupational finger dose received by technologists during the preparation and administration ofF-FDG radiopharmaceuticals in positron emission tomography-computed tomography (PET-CT) whole-body scan procedures. Fifty scans were selected, with one procedure excluded due to a high administered activity.
View Article and Find Full Text PDFG protein-coupled receptor kinase 5 (GRK5) has emerged as a potential drug development target against heart failure and cancer. A close homolog, GRK6 represents a therapeutic target for multiple myeloma. We have rationally designed a series of highly selective, potent, noncovalent, and drug-like GRK5 inhibitors.
View Article and Find Full Text PDFRibosomes are critical for cell function; their synthesis (known as ribosome biogenesis; "RiBi") is complex and energy-intensive. Surprisingly little is known about RiBi in differentiated cells in adult tissue. Here, we generated mice with conditional deletion of , an essential gene for RiBi and translation, to investigate effects of RiBi blockade We focused on RiBi in a long-lived, ribosome-rich cell population, pancreatic acinar cells, during homeostasis and tumorigenesis.
View Article and Find Full Text PDFTransfer RNA (tRNA) modifications are crucial for protein synthesis, but their position-specific physiological roles remain poorly understood. Here we investigate the impact of N4-acetylcytidine (acC), a highly conserved tRNA modification, using a Thumpd1 knockout mouse model. We find that loss of Thumpd1-dependent tRNA acetylation leads to reduced levels of tRNA, increased ribosome stalling, and activation of eIF2α phosphorylation.
View Article and Find Full Text PDFIn the Sri Lankan context, the lack of baseline studies to mitigate microplastic emissions through personal care and cosmetic products poses a huge problem. Hence this study serves as the first scientific investigation to analyze and characterize microplastics in selected personal care and cosmetic items available in the Sri Lankan markets. Fifteen brands representing five categories (face wash, facial scrubs, baby creams, shaving creams, and skin creams) of personal care and cosmetic items served as the basis for this investigation.
View Article and Find Full Text PDFThis study was set in the Greater Toronto and Hamilton Area (GTHA), where commercial vehicle movements were assigned across the road network. Implications for greenhouse gas (GHG) emissions, air quality, and health were examined through an environmental justice lens. Electrification of light-, medium-, and heavy-duty trucks was assessed to identify scenarios associated with the highest benefits for the most disadvantaged communities.
View Article and Find Full Text PDFHuman NAT10 acetylates the N4 position of cytidine in RNA, predominantly on rRNA and tRNA, to facilitate ribosome biogenesis and protein translation. NAT10 has been proposed as a therapeutic target in cancers as well as aging-associated pathologies such as Hutchinson-Gilford Progeria Syndrome (HGPS). The ∼120 kDa NAT10 protein uses its acetyl-CoA-dependent acetyltransferase, ATP-dependent helicase, and RNA binding domains in concert to mediate RNA-specific N4-cytidine acetylation.
View Article and Find Full Text PDFIn the search for much-needed new antibacterial chemical matter, a myriad of compounds have been reported in academic and pharmaceutical screening endeavors. Only a small fraction of these, however, are characterized with respect to mechanism of action (MOA). Here, we describe a pipeline that categorizes transcriptional responses to antibiotics and provides hypotheses for MOA.
View Article and Find Full Text PDFAcetylation of protein and RNA represent a critical event for development and cancer progression. NAT10 is the only known RNA acetylase that catalyzes the N4-actylcytidine (ac4C) modification of RNAs. Here, we show that the loss of NAT10 significantly decreases lung metastasis in allograft and genetically engineered mouse models of breast cancer.
View Article and Find Full Text PDFMaxillomandibular advancement surgery is a recognized technique for the management of obstructive sleep apnea. Complications for this surgery are not well-documented in the literature. The authors report an unusual case of mandibular plate bending following unplanned postoperative airway management using an oral endotracheal tube in a 65-year-old male.
View Article and Find Full Text PDFMetabolic reprogramming is a hallmark of cancer that facilitates changes in many adaptive biological processes. Mutations in the tricarboxylic acid cycle enzyme fumarate hydratase (FH) lead to fumarate accumulation and cause hereditary leiomyomatosis and renal cell cancer (HLRCC). HLRCC is a rare, inherited disease characterized by the development of non-cancerous smooth muscle tumors of the uterus and skin, and an increased risk of an aggressive form of kidney cancer.
View Article and Find Full Text PDFObjective: To assess and compare the diagnostic performance of Clinical Prediction Rules (CPRs) developed to detect group A Beta-haemolytic streptococci in people with acute pharyngitis (or sore throat).
Study Design: A systematic review.
Methods: We searched PubMed, Embase and Web of Science (inception-September 2022) for studies deriving and/or validating CPRs comprised of ≥2 predictors from an individual's history or physical examination.
Solid-state devices made from correlated oxides, such as perovskite nickelates, are promising for neuromorphic computing by mimicking biological synaptic function. However, comprehending dopant action at the nanoscale poses a formidable challenge to understanding the elementary mechanisms involved. Here, we perform infrared nanoimaging of hydrogen-doped correlated perovskite, neodymium nickel oxide (H-NdNiO, H-NNO), devices and reveal how an applied field perturbs dopant distribution at the nanoscale.
View Article and Find Full Text PDFBackground: Pain control is recognised as a crucial post-operative measure for patients undergoing oesophagectomy with a thoracotomy incision for oesophageal cancer, where ineffective breathing due to pain is directly correlated with increased morbidity. The analgesic benefits of negative pressure wound therapy (NPWT) appear to be a relatively new and emerging finding. This pilot study aims to investigate the effects of NPWT on post-operative pain control and determine the feasibility of a larger trial.
View Article and Find Full Text PDFCombination strategies of inhibition with immunotherapy in treating advanced or recurrent colorectal carcinoma (CRC) may need to be assessed in circulating tumour cells (CTCs) to achieve better clinical outcomes. This study aimed to investigate the genomic variations of in CTCs and matched CRC tissues and compared mRNA expression of and between wild-type and -mutated CTCs and CRC tissues. Clinicopathological correlations were also compared.
View Article and Find Full Text PDFWe report an in-plane extended nanopore Coulter counter (XnCC) chip fabricated in a thermoplastic via imprinting. The fabrication of the sensor utilized both photolithography and focused ion beam milling to make the microfluidic network and the in-plane pore sensor, respectively, in Si from which UV resin stamps were generated followed by thermal imprinting to produce the final device in the appropriate plastic (cyclic olefin polymer, COP). As an example of the utility of this in-plane extended nanopore sensor, we enumerated SARS-CoV-2 viral particles (VPs) affinity-selected from saliva and extracellular vesicles (EVs) affinity-selected from plasma samples secured from mouse models exposed to different ionizing radiation doses.
View Article and Find Full Text PDFFaysal Bin Hamid was not included as an author in the original publication [...
View Article and Find Full Text PDFOver the past two decades, the incidence of legionellosis has been steadily increasing in the United States though there is noclear explanation for the main factors driving the increase. While legionellosis is the leading cause of waterborne outbreaks in the US, most cases are sporadic and acquired in community settings where the environmental source is never identified. This scoping review aimed to summarise the drivers of infections in the USA and determine the magnitude of impact each potential driver may have.
View Article and Find Full Text PDFAust Dent J
September 2023
Background: Osteoradionecrosis (ORN) is an uncommon and debilitating consequence of head and neck radiotherapy and hyperbaric oxygen therapy (HBOT) has been advocated for prophylaxis prior to performing dentoalveolar procedures. The aim of this study was to evaluate a prophylactic HBOT protocol and describe the outcomes of susceptible individuals.
Methods: A retrospective audit of adults who attended the Oral and Maxillofacial Surgery department at the Royal Adelaide Hospital (South Australia) who received dental extractions with a history of radiotherapy to the jaws from 2008 to 2020.