Dengue virus has four distinct serotypes and the genetic diversity within each of the four serotypes contribute to its complexity. An important aspect of dengue molecular evolutionary studies has been the dissection of the extent and structure of genetic variation among major genotypes within each serotype. It is important to understand the role of dengue genetic variability and its potential role and impact in the effectiveness of the dengue vaccine.
View Article and Find Full Text PDFThe interplay of RNA modifications - deposited by "writers", removed by "erasers" and identified by RNA binding proteins known as "readers" - forms the basis of the epitranscriptomic gene regulation hypothesis. Recent studies have identified the oncofetal RNA-binding protein IGF2BP3 as a "reader" of the N6-methyladenosine (mA) modification and crucial for regulating gene expression. Yet, how its function as a reader overlaps with its critical oncogenic function in leukemia remains an open question.
View Article and Find Full Text PDFAm J Ophthalmol Case Rep
December 2024
Purpose: The authors report three separate cases of type 1 retinopathy of prematurity (ROP) treated with intravitreal bevacizumab before, or at 34 weeks postmenstrual age (PMA), with subsequent development of secondary glaucoma.
Observations: All three cases involve patients born ≤24 weeks and meeting the American Academy of Pediatrics criteria for ROP screening. Prior to treatment, each patient was noted to have normal anterior chamber structures with no signs of glaucoma.
Pro-inflammatory macrophage activation is a hallmark example of how mitochondria serve as signaling organelles. Upon classical macrophage activation, oxidative phosphorylation sharply decreases and mitochondria are repurposed to accumulate signals that amplify effector function. However, evidence is conflicting as to whether this collapse in respiration is essential or largely dispensable.
View Article and Find Full Text PDFAn upregulation of angiotensin-converting enzyme (ACE) expression strengthens the immune activity of myeloid lineage cells as a natural functional regulation mechanism in our immunity. ACE10/10 mice, possessing increased ACE expression in macrophages, exhibit enhanced anti-tumor immunity and anti-bactericidal effects compared to those of wild type (WT) mice, while the detailed molecular mechanism has not been elucidated yet. In this report, we demonstrate that peroxisome proliferator-activated receptor alpha (PPARα) is a key molecule in the functional upregulation of macrophages induced by ACE.
View Article and Find Full Text PDFObjective: To investigate preclinical data regarding the efficacy and biocompatibility of a bispecific protein, RO-101, with effects on VEGF-A and angiopoietin-2 (Ang-2) for use in retinal diseases.
Design: Experimental study.
Subjects: Brown Norway rats and New Zealand White Cross rabbits.
Metabolites and metabolic co-factors can shape the innate immune response, though the pathways by which these molecules adjust inflammation remain incompletely understood. Here we show that the metabolic cofactor Coenzyme A (CoA) enhances IL-4 driven alternative macrophage activation [m(IL-4)] and . Unexpectedly, we found that perturbations in intracellular CoA metabolism did not influence m(IL-4) differentiation.
View Article and Find Full Text PDFAstrocytes are heterogeneous glial cells of the central nervous system. However, the physiological relevance of astrocyte diversity for neural circuits and behaviour remains unclear. Here we show that a specific population of astrocytes in the central striatum expresses μ-crystallin (encoded by Crym in mice and CRYM in humans) that is associated with several human diseases, including neuropsychiatric disorders.
View Article and Find Full Text PDFElevated levels of branched chain amino acids (BCAAs) and branched-chain α-ketoacids are associated with cardiovascular and metabolic disease, but the molecular mechanisms underlying a putative causal relationship remain unclear. The branched-chain ketoacid dehydrogenase kinase (BCKDK) inhibitor BT2 (3,6-dichlorobenzo[b]thiophene-2-carboxylic acid) is often used in preclinical models to increase BCAA oxidation and restore steady-state BCAA and branched-chain α-ketoacid levels. BT2 administration is protective in various rodent models of heart failure and metabolic disease, but confoundingly, targeted ablation of Bckdk in specific tissues does not reproduce the beneficial effects conferred by pharmacologic inhibition.
View Article and Find Full Text PDFBackground: There is inter-individual variability in the influence of different components (e.g. nociception and expectations) on pain perception.
View Article and Find Full Text PDFAdvanced prostate cancers are treated with therapies targeting the androgen receptor (AR) signaling pathway. While many tumors initially respond to AR inhibition, nearly all develop resistance. It is critical to understand how prostate tumor cells respond to AR inhibition in order to exploit therapy-induced phenotypes prior to the outgrowth of treatment-resistant disease.
View Article and Find Full Text PDFFront Pain Res (Lausanne)
September 2023
Background: Although chronic pain and obesity are global health crises with substantial healthcare costs, little is known about the relationship between pain perception and eating behaviours. Food consumption has been reported to provide an analgesic effect by the release of neurotransmitters modulating the pain network. However, whether short-term (acute) fasting affects pain perception remains unclear.
View Article and Find Full Text PDFIdentifying biopsychosocial factors underlying chronic pain vulnerability is essential for the design of preventative efforts. Multiple chronic pain vulnerability models exist, however, there is a lack of comprehensive evaluation of these models in the literature, potentially due to the lack of guidelines that specify the criteria by which these types of work should be assessed. In this work, we created evaluation criteria (based on the general goals of conceptual models), and we then used them to critically review the chronic pain vulnerability models available in the current peer-reviewed literature (identified through a systematic search).
View Article and Find Full Text PDFElevated levels of branched chain amino acids (BCAAs) and branched-chain α-ketoacids (BCKAs) are associated with cardiovascular and metabolic disease, but the molecular mechanisms underlying a putative causal relationship remain unclear. The branched-chain ketoacid dehydrogenase kinase (BCKDK) inhibitor BT2 is often used in preclinical models to increase BCAA oxidation and restore steady-state BCAA and BCKA levels. BT2 administration is protective in various rodent models of heart failure and metabolic disease, but confoundingly, targeted ablation of in specific tissues does not reproduce the beneficial effects conferred by pharmacologic inhibition.
View Article and Find Full Text PDFPurpose: The authors describe a case of a retinal capillary hemangioblastoma (RCH) in a pediatric patient with von Hippel-Lindau (VHL) syndrome that was successfully treated with systemic belzutifan.
Methods: The clinical course was documented with serial fundus examinations and multimodal imaging, including Optos widefield fundus photography and optical coherence tomography. A literature review was conducted to look for similar cases and/or discussion.
To explore the user experiences of pre-sleep alpha entrainment via a smartphone-enabled audio or visual stimulation program for people with chronic pain and sleep disturbance. Semi-structured interviews were held with 27 participants completing a feasibility study of pre-sleep entrainment use for 4 weeks. Transcriptions were subject to template analysis.
View Article and Find Full Text PDFProteinaceous cysteines function as essential sensors of cellular redox state. Consequently, defining the cysteine redoxome is a key challenge for functional proteomic studies. While proteome-wide inventories of cysteine oxidation state are readily achieved using established, widely adopted proteomic methods such as OxICAT, Biotin Switch, and SP3-Rox, these methods typically assay bulk proteomes and therefore fail to capture protein localization-dependent oxidative modifications.
View Article and Find Full Text PDFIntroduction: Adverse life experiences have been identified as a possible vulnerability factor for chronic pain. This association could result from the effect of trauma on the psychological state of individuals. Previous studies found childhood trauma to be associated with pain catastrophizing and anxiety sensitivity, both of which have been associated with an increased risk of chronic pain.
View Article and Find Full Text PDFSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19). RT-PCR detection of viral RNA represents the gold standard method for diagnosis of COVID-19. However, multiple diagnostic tests are needed for acute disease diagnosis and assessing immunity during the COVID-19 outbreak.
View Article and Find Full Text PDFMalignant tumors exhibit heterogeneous metabolic reprogramming, hindering the identification of translatable vulnerabilities for metabolism-targeted therapy. How molecular alterations in tumors promote metabolic diversity and distinct targetable dependencies remains poorly defined. Here we create a resource consisting of lipidomic, transcriptomic, and genomic data from 156 molecularly diverse glioblastoma (GBM) tumors and derivative models.
View Article and Find Full Text PDFare a leading cause of healthcare-associated infections worldwide. In particular, strains expressing extended-spectrum β-lactamases (ESBLs) and carbapenemases pose serious treatment challenges, leading the World Health Organization (WHO) to designate ESBL and carbapenem-resistant Enterobacteriaceae as 'critical' threats to human health. Research efforts to combat these pathogens can be supported by accessibility to diverse and clinically relevant isolates for testing novel therapeutics.
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