Objectives: The mechanism by which mitral valve (MV) disease leads to atrial fibrillation (AF) remains poorly understood. Delayed-enhancement cardiac magnetic resonance imaging (DE-MRI) has been used to assess left atrial (LA) fibrosis in patients with lone AF before catheter ablation; however, few studies have used DE-MRI to assess MV-induced LA fibrosis in patients with or without AF undergoing MV surgery.
Methods: Between March 2018 and September 2022, 38 subjects were enrolled; 15 age-matched controls, 14 patients with lone mitral regurgitation (MR), and 9 patients with MR and AF (MR + AF).
Objective: A right minithoracotomy (RMT) is a minimally invasive surgical approach that has been increasingly performed for the concomitant Cox maze IV procedure (CMP) and mitral valve surgery (MVS). Little is known regarding whether long-term rhythm and survival outcomes are affected by the RMT as compared with the traditional median sternotomy (MS) approach.
Methods: Between April 2004 and April 2021, 377 patients underwent the concomitant CMP and MVS, of whom 38% had RMT.
Protein glycosylation, a complex and heterogeneous post-translational modification that is frequently dysregulated in disease, has been difficult to analyse at scale. Here we report a data-independent acquisition technique for the large-scale mass-spectrometric quantification of glycopeptides in plasma samples. The technique, which we named 'OxoScan-MS', identifies oxonium ions as glycopeptide fragments and exploits a sliding-quadrupole dimension to generate comprehensive and untargeted oxonium ion maps of precursor masses assigned to fragment ions from non-enriched plasma samples.
View Article and Find Full Text PDFJ Thorac Cardiovasc Surg
February 2024
Objective: The Cox-Maze IV procedure (CMP-IV) is the most effective treatment for atrial fibrillation. Increased left atrial (LA) size has been identified as a risk factor for failure to restore sinus rhythm. This has biased many surgeons against ablation in patients with giant left atrium (GLA), defined as LA diameter >6.
View Article and Find Full Text PDFIon-mobility spectrometry shows great promise to tackle analytically challenging research questions by adding another separation dimension to liquid chromatography-mass spectrometry. The understanding of how analyte properties influence ion mobility has increased through recent studies, but no clear rationale for the design of customized experimental settings has emerged. Here, we leverage machine learning to deepen our understanding of field asymmetric waveform ion-mobility spectrometry for the analysis of cross-linked peptides.
View Article and Find Full Text PDFViruses have evolved means to manipulate the host's ubiquitin-proteasome system, in order to down-regulate antiviral host factors. The Vpx/Vpr family of lentiviral accessory proteins usurp the substrate receptor DCAF1 of host Cullin4-RING ligases (CRL4), a family of modular ubiquitin ligases involved in DNA replication, DNA repair and cell cycle regulation. CRL4DCAF1 specificity modulation by Vpx and Vpr from certain simian immunodeficiency viruses (SIV) leads to recruitment, poly-ubiquitylation and subsequent proteasomal degradation of the host restriction factor SAMHD1, resulting in enhanced virus replication in differentiated cells.
View Article and Find Full Text PDFProtein-protein interactions govern most cellular pathways and processes, and multiple technologies have emerged to systematically map them. Assessing the error of interaction networks has been a challenge. Crosslinking mass spectrometry is currently widening its scope from structural analyses of purified multi-protein complexes towards systems-wide analyses of protein-protein interactions (PPIs).
View Article and Find Full Text PDFCrosslinking mass spectrometry has developed into a robust technique that is increasingly used to investigate the interactomes of organelles and cells. However, the incomplete and noisy information in the mass spectra of crosslinked peptides limits the numbers of protein-protein interactions that can be confidently identified. Here, we leverage chromatographic retention time information to aid the identification of crosslinked peptides from mass spectra.
View Article and Find Full Text PDFJ Thorac Cardiovasc Surg
November 2022
Objectives: Stand-alone surgical ablation of atrial fibrillation is indicated in patients with refractory atrial fibrillation who have failed medical or catheter-based ablation. Few reports of late outcomes after stand-alone surgical ablation exist using comprehensive follow-up with strict definitions of success. This study examined our late outcomes of the stand-alone Cox-Maze IV procedure.
View Article and Find Full Text PDFIntroduction: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, and results in significant morbidity and mortality. The Cox-Maze IV procedure (CMP-IV) has been shown to have excellent efficacy in returning patients to sinus rhythm, but there have been few reports of late follow-up in sizable cohorts of patients with longstanding persistent AF, the most difficult type of AF to treat.
Methods And Results: Between May 2003 and March 2020, 174 consecutive patients underwent a stand-alone CMP-IV for longstanding persistent AF.
Background: Acute kidney injury (AKI) after cardiac surgery remains a common complication that has been associated with increased morbidity and mortality. This study implemented Kidney Disease Improving Global Outcomes criteria to evaluate renal outcomes after concomitant surgical ablation for atrial fibrillation.
Methods: Patients with a history of atrial fibrillation who underwent elective cardiac surgery at our institution from 2008 to 2018 were retrospectively reviewed.
Organofluorine compounds are known to be toxic to a broad variety of living beings in different habitats, and chemical fluorination has been historically exploited by mankind for the development of therapeutic drugs or agricultural pesticides. On the other hand, several studies so far have demonstrated that, under appropriate conditions, living systems (in particular bacteria) can tolerate the presence of fluorinated molecules (e.g.
View Article and Find Full Text PDFStructural biology studies performed inside cells can capture molecular machines in action within their native context. In this work, we developed an integrative in-cell structural approach using the genome-reduced human pathogen We combined whole-cell cross-linking mass spectrometry, cellular cryo-electron tomography, and integrative modeling to determine an in-cell architecture of a transcribing and translating expressome at subnanometer resolution. The expressome comprises RNA polymerase (RNAP), the ribosome, and the transcription elongation factors NusG and NusA.
View Article and Find Full Text PDFComplexes containing a pair of structural maintenance of chromosomes (SMC) family proteins are fundamental for the three-dimensional (3D) organization of genomes in all domains of life. The eukaryotic SMC complexes cohesin and condensin are thought to fold interphase and mitotic chromosomes, respectively, into large loop domains, although the underlying molecular mechanisms have remained unknown. We used cryo-EM to investigate the nucleotide-driven reaction cycle of condensin from the budding yeast Saccharomyces cerevisiae.
View Article and Find Full Text PDFJ Thorac Cardiovasc Surg
February 2022
Objective: Surgical ablation of atrial fibrillation (AF) is indicated both in patients with AF undergoing concomitant cardiac surgery and in those who have not responded to medical and/or catheter-based ablation therapy. This study examined our long-term outcomes following the Cox-Maze IV procedure (CMP-IV).
Methods: Between May 2003 and March 2018, 853 patients underwent either biatrial CMP-IV (n = 765) or a left-sided CMP-IV (n = 88) lesion set with complete isolation of the posterior left atrium.
J Thorac Cardiovasc Surg
November 2021
Objectives: The incidence of atrial fibrillation (AF) in patients older than 75 years of age is expected to increase, and its treatment remains challenging. This study evaluated the impact of age on the outcomes of surgical ablation of AF.
Methods: A retrospective review was performed of patients who underwent the Cox-maze IV procedure at a single institution between 2005 and 2017.
Thyroglobulin (TG) is the protein precursor of thyroid hormones, which are essential for growth, development and the control of metabolism in vertebrates. Hormone synthesis from TG occurs in the thyroid gland via the iodination and coupling of pairs of tyrosines, and is completed by TG proteolysis. Tyrosine proximity within TG is thought to enable the coupling reaction but hormonogenic tyrosines have not been clearly identified, and the lack of a three-dimensional structure of TG has prevented mechanistic understanding.
View Article and Find Full Text PDFThe field of structural biology is increasingly focusing on studying proteins in situ, i.e., in their greater biological context.
View Article and Find Full Text PDFPurpose: Secondary usage of patient data has recently become of increasing interest for the development and application of computer analytic techniques. Strict oversight of these data is required and the individual patients themselves are integral to providing guidance. We sought to understand patients' attitudes to sharing their imaging data for research purposes.
View Article and Find Full Text PDFBackground: Atrial fibrillation (AF) is a common cause of tachycardia-induced cardiomyopathy (TIC). This study evaluated the outcomes of the Cox-Maze IV procedure in patients with TIC and significant left ventricular dysfunction.
Methods: Between January 2002 and January 2017, 37 consecutive patients with a left ventricular ejection fraction (LVEF) of 0.
Structural maintenance of chromosomes (SMC)-kleisin complexes organize chromosomal DNAs in all domains of life, with key roles in chromosome segregation, DNA repair and regulation of gene expression. They function through the entrapment and active translocation of DNA, but the underlying conformational changes are largely unclear. Using structural biology, mass spectrometry and cross-linking, we investigated the architecture of two evolutionarily distant SMC-kleisin complexes: MukBEF from Escherichia coli, and cohesin from Saccharomyces cerevisiae.
View Article and Find Full Text PDFCross-linking mass spectrometry draws structural information from covalently linked peptide pairs. When these links do not match to previous structural models, they may indicate changes in protein conformation. Unfortunately, such links can also be the result of experimental error or artifacts.
View Article and Find Full Text PDFAirborne transmission of porcine reproductive and respiratory syndrome virus (PRRSV) has been known for a long time. Most experiments were performed using PRRSV-2 strains and fairly little information is available on the airborne spread of PRRSV-1. The aim of this study was to assess three different air samplers for their ability to detect PRRSV-1 under experimental and field conditions.
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