Multicentre frozen elephant trunk technique experience as redo surgery to treat residual type A aortic dissections following ascending aortic replacement.

Objectives: The goal of this project was to assess the efficacy of a reoperative frozen elephant trunk (FET) operation for treating residual type A aortic dissections.

Methods: Between April 2015 and October 2023, a total of 237 patients underwent elective redo surgical aortic arch replacement via the FET technique to treat residual type A aortic dissection in 11 European aortic centres. Data were pooled and analysed retrospectively.

Circumferent dissection of the ascending aorta resulting in the occlusion of supra-aortic vessels repaired using the frozen elephant trunk technique - a case report.

Background: Our patient presented with acute back pain and dyspnea, without neurological symptoms. The computed tomography (CT) scan showed a circumferent rupture of the ascending aortic intima which was invaginated in the arch and descending aorta.

Case Presentation: A 54-year-old male patient was diagnosed with a Type A aortic dissection.

Rapid elucidation of agonist-driven regulation of the neurokinin 1 receptor using a GPCR phosphorylation immunoassay.

Agonist-induced phosphorylation is a crucial step in the activation/deactivation cycle of G protein-coupled receptors (GPCRs), but direct determination of individual phosphorylation events has remained a major challenge. We have recently developed a bead-based immunoassay for the quantitative assessment of agonist-induced GPCR phosphorylation that can be performed entirely in 96-well plates, thus eliminating the need for western blot analysis. In the present study, we adapted this assay to three novel phosphosite-specific antibodies directed against the neurokinin 1 (NK1) receptor, namely pS338/pT339-NK1, pT344/pS347-NK1, and pT356/pT357-NK1.

Bacteria employ lysine acetylation of transcriptional regulators to adapt gene expression to cellular metabolism.

The Escherichia coli TetR-related transcriptional regulator RutR is involved in the coordination of pyrimidine and purine metabolism. Here we report that lysine acetylation modulates RutR function. Applying the genetic code expansion concept, we produced site-specifically lysine-acetylated RutR proteins.

Phosphorylation bar-coding of free fatty acid receptor 2 is generated in a tissue-specific manner.

Free fatty acid receptor 2 (FFAR2) is activated by short-chain fatty acids and expressed widely, including in white adipocytes and various immune and enteroendocrine cells. Using both wild-type human FFAR2 and a designer receptor exclusively activated by designer drug (DREADD) variant we explored the activation and phosphorylation profile of the receptor, both in heterologous cell lines and in tissues from transgenic knock-in mouse lines expressing either human FFAR2 or the FFAR2-DREADD. FFAR2 phospho-site-specific antisera targeting either pSer/pSer or pThr/pThr provided sensitive biomarkers of both constitutive and agonist-mediated phosphorylation as well as an effective means to visualise agonist-activated receptors in situ.

Histological changes in retinal detachment: A systematic review for the clinician.

Although there have been numerous innovations in the management of retinal detachment (RD) over the past decades, there is still limited understanding of the pathophysiological processes that take place before and after repair. Summarizing key concepts using animal studies may allow for a better assessment of common pre- and postoperative microstructural abnormalities in RD. We performed a systematic literature review on Ovid MEDLINE, EMBASE, and Cochrane Controlled Register of Trials from January 1968 to January 2022, searching animal or human studies reporting retinal histologic changes following primary or induced RD.

GRK2 Kinases in the Primary Cilium Initiate SMOOTHENED-PKA Signaling in the Hedgehog Cascade.

During Hedgehog (Hh) signal transduction in development and disease, the atypical G protein-coupled receptor (GPCR) SMOOTHENED (SMO) communicates with GLI transcription factors by binding the protein kinase A catalytic subunit (PKA-C) and physically blocking its enzymatic activity. Here we show that GPCR kinase 2 (GRK2) orchestrates this process during endogenous Hh pathway activation in the vertebrate primary cilium. Upon SMO activation, GRK2 rapidly relocalizes from the ciliary base to the shaft, triggering SMO phosphorylation and PKA-C interaction.

Marine Bacteroidetes enzymatically digest xylans from terrestrial plants.

Marine Bacteroidetes that degrade polysaccharides contribute to carbon cycling in the ocean. Organic matter, including glycans from terrestrial plants, might enter the oceans through rivers. Whether marine bacteria degrade structurally related glycans from diverse sources including terrestrial plants and marine algae was previously unknown.

In situ visualization of opioid and cannabinoid drug effects using phosphosite-specific GPCR antibodies.

G protein-coupled receptors (GPCRs) are important signal transducers that are phosphorylated upon activation at intracellular serine and threonine residues. Although antibodies that specifically recognize the phosphorylation state of GPCRs have been available for many years, efficient immunolocalization of phosphorylated receptors in their tissues of origin has not been possible. Here, we show that phosphorylation of receptors is highly unstable during routine immunohistochemical procedures, requiring the use of appropriate phosphatase inhibitors particular during tissue perfusion, post-fixation, and cryoprotection but not during immunostaining of tissue sections.

Pathophysiology of outer retinal corrugations: Imaging dataset and mechanical models.

This article presents high-resolution swept-source optical coherence tomography (SS-OCT) imaging data used to elaborate a mechanical model that elucidates the formation of outer retinal corrugations (ORCs) in rhegmatogenous retinal detachments (RRD). The imaging data shared in the repository and presented in this article is related to the research paper entitled "Outer Retinal Corrugations in Rhegmatogenous Retinal Detachment: The Retinal Pigment Epithelium-Photoreceptor Dysregulation Theory" (Muni et al., AJO, 2022).

A Prototype Implantable Artificial Bronchus Reduces Lung Hyperinflation in Recently Deceased Patients with Emphysema.

Background: Several minimally invasive treatments have been offered to patients with severe emphysema over the last two decades. Currently, endobronchial valves (EBVs) are the only approved therapeutic option, but this method has drawbacks: only a few can undergo this therapy and the incidence of pneumothorax remains high. A minimally invasive technique, appropriate for a broader patient population and posing fewer risks, would represent a desirable alternative to improve lung function in these patients.

Identification of Kazal Inhibitor Scaffolds with Identical Canonical Binding Loops and Their Effects on Binding Properties.

Kazal inhibitors hold high potential as scaffolds for therapeutic molecules, taking advantage of the easily exchangeable canonical binding loop. Different Kazal inhibitor backbones have been suggested to be therapeutically useful, but the impact of different Kazal-like scaffolds on binding properties is still largely unknown. Here, we identified trypsin-targeting human serine protease inhibitor Kazal type 1 (SPINK1) homologues in different mammalian species that cluster in two P2-P1 combinations, implying the coevolution of these residues.

A bead-based GPCR phosphorylation immunoassay for high-throughput ligand profiling and GRK inhibitor screening.

Analysis of agonist-driven phosphorylation of G protein-coupled receptors (GPCRs) can provide valuable insights into the receptor activation state and ligand pharmacology. However, to date, assessment of GPCR phosphorylation using high-throughput applications has been challenging. We have developed and validated a bead-based immunoassay for the quantitative assessment of agonist-induced GPCR phosphorylation that can be performed entirely in multiwell cell culture plates.

Molecular interplay of ADAMTS13-MDTCS and von willebrand Factor-A2: deepened insights from extensive atomistic simulations.

Thrombotic thrombocytopenic purpura (TTP) is a rare and life-threatening disease. One hallmark is severe ADAMTS13 deficiency, causing ultra-large von Willebrand factor (VWF) multimers to accumulate, leading to microthrombi and lastly to microangiopathic hemolytic anemia and severe thrombocytopenia. Despite great success in recent decades, the molecular picture of the interaction between VWF and ADAMTS13 remains vague.

Outer Retinal Corrugations in Rhegmatogenous Retinal Detachment: The Retinal Pigment Epithelium-Photoreceptor Dysregulation Theory.

Purpose: Outer retinal folds occur when outer retinal corrugations (ORCs) persist after retinal reattachment with worse functional outcomes. We investigate the pathophysiology of ORCs in vivo.

Design: Prospective cohort study.

Structural Basis of the Pancreatitis-Associated Autoproteolytic Failsafe Mechanism in Human Anionic Trypsin.

Objective: The pathophysiological mechanisms underlying chronic pancreatitis (CP) are still poorly understood. Human cationic (TRY1) and anionic (TRY2) trypsins are the two major trypsin isoforms and their activities are tightly regulated within pancreatic acinar cells. Typically, they exist in a molar ratio of 2:1 (cationic:anionic).

The Role of Telocytes and Telocyte-Derived Exosomes in the Development of Thoracic Aortic Aneurysm.

A hallmark of thoracic aortic aneurysms (TAA) is the degenerative remodeling of aortic wall, which leads to progressive aortic dilatation and resulting in an increased risk for aortic dissection or rupture. Telocytes (TCs), a distinct type of interstitial cells described in many tissues and organs, were recently observed in the aortic wall, and studies showed the potential regulation of smooth muscle cell (SMC) homeostasis by TC-released shed vesicles. The purpose of the present work was to study the functions of TCs in medial degeneration of TAA.

Single Donor Infusion of S-Nitroso-Human-Serum-Albumin Attenuates Cardiac Isograft Fibrosis and Preserves Myocardial Micro-RNA-126-3p in a Murine Heterotopic Heart Transplant Model.

Cold ischemia and subsequent reperfusion injury are non-immunologic cornerstones in the development of graft injury after heart transplantation. The nitric oxide donor S-nitroso-human-serum-albumin (S-NO-HSA) is known to attenuate myocardial ischemia-reperfusion (I/R)-injury. We assessed whether donor preservation with S-NO-HSA affects isograft injury and myocardial expression of GATA2 as well as miR-126-3p, which are considered protective against vascular and endothelial injury.

Selective phosphorylation of threonine residues defines GPR84-arrestin interactions of biased ligands.

GPR84 is an immune cell-expressed, proinflammatory receptor currently being assessed as a therapeutic target in conditions including fibrosis and inflammatory bowel disease. Although it was previously shown that the orthosteric GPR84 activators 2-HTP and 6-OAU promoted its interactions with arrestin-3, a G protein-biased agonist DL-175 did not. Here, we show that replacement of all 21 serine and threonine residues within i-loop 3 of GPR84, but not the two serines in the C-terminal tail, eliminated the incorporation of [P] and greatly reduced receptor-arrestin-3 interactions promoted by 2-HTP.

Structural and Biophysical Insights into SPINK1 Bound to Human Cationic Trypsin.

(1) The serine protease inhibitor Kazal type 1 (SPINK1) inhibits trypsin activity in zymogen granules of pancreatic acinar cells. Several mutations in the gene are associated with acute recurrent pancreatitis (ARP) and chronic pancreatitis (CP). The most common variant is SPINK1 p.

The expression and role of tenascin C in abdominal aortic aneurysm formation and progression.

Objectives: Up-regulation of tenascin C (TNC), a matricellular protein, produced mainly by vascular smooth muscle cells (VSMC), is associated with the progression and dilation of abdominal aortic aneurysms (AAA). The aims of this study were (i) to evaluate whether serum levels of TNC in patients with AAA patients correlate with aortic diameter and (ii) to clarify the role of TNC in formation and progression of AAA in a murine model.

Methods: In 15 patients with AAA serum levels of TNC were measured and correlated with aortic diameters.

Easy Expression and Purification of Fluorescent N-Terminal BCL11B CCHC Zinc Finger Domain.

Zinc finger proteins play pivotal roles in health and disease and exert critical functions in various cellular processes. A majority of zinc finger proteins bind DNA and act as transcription factors. B-cell lymphoma/leukemia 11B (BCL11B) represents one member of the large family of zinc finger proteins.

A Hypothesized Mechanism for Chronic Pancreatitis Caused by the N34S Mutation of Serine Protease Inhibitor Kazal-Type 1 Based on Conformational Studies.

Purpose: Although strongly related, the pathophysiological effect of the N34S mutation in the serine protease inhibitor Kazal type 1 (SPINK1) in chronic pancreatitis is still unknown. In this study, we investigate the conformational space of the human cationic trypsin-serine protease inhibitor complex.

Methods: Simulations with molecular dynamics, replica exchange, and transition pathway methods are used.