Protein glycosylation is implicated in a wide array of diseases, yet glycoprotein analysis remains elusive owing to the extreme heterogeneity of glycans, including microheterogeneity of some of the glycosites (amino acid residues). Various mass spectrometry (MS) strategies have proven tremendously successful for localizing and identifying glycans, typically utilizing a bottom-up workflow in which glycoproteins are digested to create glycopeptides to facilitate analysis. An emerging alternative is top-down MS that aims to characterize intact glycoproteins to allow precise identification and localization of glycans.
View Article and Find Full Text PDFIntroduction The goal of endodontic therapy is to completely eliminate the infection and stop microbes from infecting or reinfecting the root canal and the periradicular tissues. Amongst the primary microorganisms, (), a Gram-positive anaerobe, is the main cause of pulpal and periapical inflammation causing root canal failure. Literature evidence shows that the gold-standard calcium hydroxide is ineffective against due to its resistance to the alkaline pH and proton pump mechanism.
View Article and Find Full Text PDFHere we used native mass spectrometry (native MS) to probe a SARS-CoV protease, PLpro, which plays critical roles in coronavirus disease by affecting viral protein production and antagonizing host antiviral responses. Ultraviolet photodissociation (UVPD) and variable temperature electrospray ionization (vT ESI) were used to localize binding sites of PLpro inhibitors and revealed the stabilizing effects of inhibitors on protein tertiary structure. We compared PLpro from SARS-CoV-1 and SARS-CoV-2 in terms of inhibitor and ISG15 interactions to discern possible differences in protease function.
View Article and Find Full Text PDFPurpose: The blur introduced by breathing motion degrades the diagnostic accuracy of whole-body F-18 fluorodeoxyglucose positron emission tomography-computed tomography (F-FDG PET-CT) in lesions adjacent to the diaphragm by increasing the apparent size and by decreasing their metabolic activity. This study aims to evaluate the efficacy of motion correction by four-dimensional phase-based respiratory-gated (RG) F-FDG PET-CT in improving metabolic parameters of lesions adjacent to the diaphragm (especially in the lungs or liver).
Materials And Methods: Eighteen patients with known lung or liver lesions underwent conventional F-FDG PET-CT and respiratory-gated PET-CT acquisition of the desired region using a pressure-sensing, phase-based respiratory-gating system.
Gram-negative bacteria develop and exhibit resistance to antibiotics, owing to their highly asymmetric outer membrane maintained by a group of six proteins comprising the Mla (maintenance of lipid asymmetry) pathway. Here, we investigate the lipid binding preferences of one Mla protein, MlaC, which transports lipids through the periplasm. We used ultraviolet photodissociation (UVPD) to identify and characterize modifications of lipids endogenously bound to MlaC expressed in three different bacteria strains.
View Article and Find Full Text PDFBackground: Transcatheter renal denervation (RDN) has had inconsistent efficacy and concerns for durability of denervation. We aimed to investigate long-term safety and efficacy of transcatheter microwave RDN in vivo in normotensive sheep in comparison to conventional radiofrequency ablation.
Methods And Results: Sheep underwent bilateral RDN, receiving 1 to 2 microwave ablations (maximum power of 80-120 W for 240 s-480 s) and 12 to 16 radiofrequency ablations (180 s-240 s) in the main renal artery in a paired fashion, alternating the side of treatment, euthanized at 2 weeks (acute N=15) or 5.
Small nucleolar RNAs (snoRNAs) are emerging as important regulators of cardiovascular (patho)biology. Several roles of snoRNAs have recently been identified in heart development and congenital heart diseases, as well as their dynamic regulation in hypertrophic and dilated cardiomyopathies, coronary heart disease (CHD), myocardial infarction (MI), cardiac fibrosis, and heart failure. Furthermore, reports of changes in vesicular snoRNA expression and altered levels of circulating snoRNAs in response to cardiac stress suggest that snoRNAs also function in cardiac signaling and intercellular communication.
View Article and Find Full Text PDFProstate cancer (PCa) is a leading male malignancy worldwide, often progressing to bone metastasis, with limited curative options. Extracellular vesicles (EVs) have emerged as key players in cancer communication and metastasis, promoting the formation of supportive microenvironments in distant sites. Our previous studies have highlighted the role of PCa EVs in modulating osteoblasts and facilitating tumor progression.
View Article and Find Full Text PDFThe main objective of the study is the estimation of elemental impurities in selected packaged commercial fruit juices and fresh fruit juices available in Ahmedabad, Gujarat. Estimation of seventeen samples (9 commercial fruit juices and 8 fresh fruit juices) was carried out for elemental impurities which include lead, cadmium, arsenic, mercury, methyl mercury, nickel, chromium, tin, copper, and zinc. Inductively coupled plasma-mass spectroscopy (ICP-MS) with microwave-assisted sample digestion was used to determine the element content of samples.
View Article and Find Full Text PDFGM1 gangliosidosis is a neurodegenerative disorder caused by mutations in the GLB1 gene, which encodes lysosomal β-galactosidase. The enzyme deficiency blocks GM1 ganglioside catabolism, leading to accumulation of GM1 ganglioside and asialo-GM1 ganglioside (GA1 glycolipid) in brain. This disease can present in varying degrees of severity, with the level of residual β-galactosidase activity primarily determining the clinical course.
View Article and Find Full Text PDFExtracellular vesicles (EVs) contribute to osteoarthritis pathogenesis through their release into joint tissues and synovial fluid. Synovial fluid-derived EVs have the potential to be direct biomarkers in the causal pathway of disease but also enable understanding of their role in disease progression. Utilizing a temporal model of osteoarthritis, we defined the changes in matched synovial fluid and plasma-derived EV small non-coding RNA and protein cargo using sequencing and mass spectrometry.
View Article and Find Full Text PDFIt was recently suggested to end the usage of the term cell wall in microbiology (including prokaryotes and fungi) because it represented an inappropriate and potentially misleading metaphor (Casadevall and Gow, 2022). The analysis of the arguments for such a move from the viewpoint of the plant physiologist indicates that the suggestion is based on misunderstandings, first, of the early history of cell biology and its terminology; second, of the development of modern concepts of cell wall function since the late 19th century; and third, of the nature of metaphors and their role in scientific communication. We conclude that misconceptions concerning cell walls may arise due to pedagogical shortcomings in introducing students to our technical terminology rather than from the fact that part of this terminology originated from metaphors.
View Article and Find Full Text PDFIntroduction: Tumor lysis syndrome (TLS) is often diagnosed in children with hematological malignancies and can be life threatening due to metabolic disturbances. Continuous renal replacement therapy (CKRT) can reverse these disturbances relatively quickly when conventional medical management fails. Our objective was to investigate the benefit of CKRT in the management of TLS in children admitted to the intensive care unit with hematologic malignancies.
View Article and Find Full Text PDFThe measurement of collision cross sections (CCS, σ) offers supplemental information about sizes and conformations of ions beyond mass analysis alone. We have previously shown that CCSs can be determined directly from the time-domain transient decay of ions in an Orbitrap mass analyzer as ions oscillate around the central electrode and collide with neutral gas, thus removing them from the ion packet. Herein, we develop the modified hard collision model, thus deviating from the prior FT-MS hard sphere model, to determine CCSs as a function of center-of-mass collision energy in the Orbitrap analyzer.
View Article and Find Full Text PDFHematopoietic cell transplant (HCT), used for treatment of many malignant and non-malignant pediatric diseases, is associated with serious complications, limiting this therapy's benefit. Acute kidney injury (AKI), seen often after HCT, can occur at different stages of the transplant process and contributes to morbidity and mortality after HCT. The etiology of AKI is often multifactorial, including kidney hypoperfusion, nephrotoxicity from immunosuppressive and antimicrobial agents, and other transplant-related complications such as transplant-associated thrombotic microangiopathy and sinusoidal obstructive syndrome.
View Article and Find Full Text PDFExtracellular vesicles (EVs) function as mediators of intercellular communication and as such influence the recipient cell function. EVs derived from immune cells can carry out many of the same functions as their parental cells, as they carry costimulatory molecules, antigens, and antigen-MHC complexes. As a result, there is a strong interest in understanding the composition and origin of immune cell-derived EVs in order to understand their role in the pathogenesis of diseases.
View Article and Find Full Text PDFBrain cancer is a group of diverse and rapidly growing malignancies that originate in the central nervous system (CNS) and have a poor prognosis. The complexity of brain structure and function makes brain cancer modeling extremely difficult, limiting pathological studies and therapeutic developments. Advancements in human pluripotent stem cell technology have opened a window of opportunity for brain cancer modeling, providing a wealth of customizable methods to simulate the disease in vitro.
View Article and Find Full Text PDFAsian Spine J
April 2023
Study Design: Prospective randomized controlled study.
Purpose: This study aimed to assess the effects of a different combination of anesthetic techniques in lumbar and thoracolumbar spinal surgeries in terms of muscle relaxation and surgical field in addition to hemodynamic parameters.
Overview Of Literature: Adequate relaxation of the erector spinae muscle and good surgical fields are preferred in lumbar spine surgeries.
N-methyladenosine (mA) is the most abundant internal mRNA modification and is dynamically regulated through distinct protein complexes that methylate, demethylate, and/or interpret the mA modification. These proteins, and the mA modification, are involved in the regulation of gene expression, RNA stability, splicing and translation. Given its role in these crucial processes, mA has been implicated in many diseases, including in cancer development and progression.
View Article and Find Full Text PDFIntroduction: Equine osteoarthritis (OA) is a heterogeneous, degenerative disease of the musculoskeletal system with multifactorial causation, characterized by a joint metabolic imbalance. Extracellular vesicles are nanoparticles involved in intracellular communication. Mesenchymal stem cell (MSC) therapy is a form of regenerative medicine that utilizes their properties to repair damaged tissues.
View Article and Find Full Text PDFAmyotroph Lateral Scler Frontotemporal Degener
May 2023
Objective: To investigate clinically meaningful change for ROADS and ALSFRS-R using a patient-defined approach.
Methods: Data were reviewed from participants assessed at the Emory ALS Center from 2019-2022 with two assessments using both ROADS and ALSFRS-R and a completed patient-reported global impression of change scale at the second visit. Minimal important difference (MID), or the smallest amount of change that is clinically relevant, was assessed based on patient reported impression of change for ROADS and ALSFRS-R.
Measurement of collision cross section (CCS), a parameter reflecting an ion's size and shape, alongside high-resolution mass analysis extends the depth of molecular analysis by providing structural information beyond molecular mass alone. Although these measurements are most commonly undertaken using a dedicated ion mobility cell coupled to a mass spectrometer, alternative methods have emerged to extract CCSs directly by analysis of the decay rates of either time-domain transient signals or the FWHM of frequency domain peaks in FT mass analyzers. This information is also accessible from FTMS mass spectra obtained in commonly used workflows directly without the explicit access to transient or complex Fourier spectra.
View Article and Find Full Text PDFAndrogen deprivation therapies (ADTs) are important treatments which inhibit androgen-induced prostate cancer (PCa) progression by either preventing androgen biosynthesis (e.g. abiraterone) or by antagonizing androgen receptor (AR) function (e.
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