Mayo Clinic Tapestry Study: A Large-Scale Decentralized Whole Exome Sequencing Study for Clinical Practice, Research Discovery, and Genomic Education.

Objective: To execute a large-scale, decentralized, clinical-grade whole exome sequencing study, coined Tapestry, for clinical practice, research discovery, and genomic education.

Patients And Methods: Between July 1, 2020, and May 31, 2024, we invited 1,287,608 adult Mayo Clinic patients to participate in Tapestry. Of those contacted, 114,673 patients were consented and 98,222 (65.

Piezo2 interacts with E-cadherin in specialized gastrointestinal epithelial mechanoreceptors.

Piezo2 is a mechanically gated ion channel most commonly expressed by specialized mechanoreceptors, such as the enteroendocrine cells (EECs) of the gastrointestinal epithelium. A subpopulation of EECs expresses Piezo2 and functionally resembles the skin's touch sensors, called Merkel cells. Low-magnitude mechanical stimuli delivered to the mucosal layer are primarily sensed by mechanosensitive EECs in a process we term "gut touch.

Protocol for isolating immune cells from human gastric muscularis propria for single-cell analysis.

Understanding the diversity of gastrointestinal (GI) immune cells, especially in the muscularis propria, is crucial for understanding their role in the maintenance of enteric neurons and smooth muscle and their contribution to GI motility. Here, we present a detailed protocol for isolating single immune cells from the human gastric muscularis propria. We describe steps for tissue preservation, dissection, and dissociation of the muscularis propria.

Low Vitamin D Levels in Patients with Symptoms of Gastroparesis: Relationships with Nausea and Vomiting, Gastric Emptying and Gastric Myoelectrical Activity.

Unlabelled: Patients with gastroparesis (Gp) often have diets deficient in calories, electrolytes, and vitamins. Vitamin D levels have been reported to be low in some patients with Gp but has not been systematically studied.

Aims: To determine vitamin D levels and relationships among symptoms, gastric emptying and gastric myoelectrical activity (GMA) in patients with symptoms of Gp.

Circadian rhythm and whole gut transit in mice.

Background: In preclinical studies whole gut transit (WGT) in mice is a gold-standard "leading-edge" approach that measures the time between orogastric gavage of carmine red and defecation of the first carmine red pellet. Transit studies in humans are performed during the active day because GI motility and transit are suppressed during the night. Since mice are nocturnal, WGT studies traditionally done during the day occur during their rest phase.

Single cell atlas of human gastric muscle immune cells and macrophage-driven changes in idiopathic gastroparesis.

Gastrointestinal immune cells, particularly muscularis macrophages (MM) interact with the enteric nervous system and influence gastrointestinal motility. Here we determine the human gastric muscle immunome and its changes in patients with idiopathic gastroparesis (IG). Single cell sequencing was performed on 26,000 CD45 cells obtained from the gastric tissue of 20 subjects.

Preliminary study on the dynamic positron emission tomography imaging with C-ER176 to delineate macrophage activation in diabetic gastroparesis.

Background: Animal models and human data have suggested macrophage-driven immune dysregulation in diabetic gastroparesis (DG). Translocator protein (TSPO) upregulation has been suggested to indicate activated state of macrophages and ER176 is a high affinity third generation TSPO-specific radioligand. The aim of this study was to determine feasibility of dynamic C-ER 176 PET to identify macrophage activation in DG.

Stretch response of the mechano-gated channel TMEM63A in membrane patches and single cells.

The recently discovered ion channel TMEM63A has biophysical features distinctive for mechano-gated cation channels, activating at high pressures with slow kinetics while not inactivating. However, some biophysical properties are less clear, including no information on its function in whole cells. The aim of this study is to expand the TMEM63A biophysical characterization and examine the function in whole cells.

Mapping the cellular and molecular landscape of cardiac non-myocytes in murine diabetic cardiomyopathy.

Diabetes is associated with a significantly elevated risk of heart failure. However, despite extensive efforts to characterize the phenotype of the diabetic heart, the molecular and cellular protagonists that underpin cardiac pathological remodeling in diabetes remain unclear, with a notable paucity of data regarding the impact of diabetes on non-myocytes within the heart. Here we aimed to define key differences in cardiac non-myocytes between spontaneously type-2 diabetic () and healthy control mouse hearts.

Adeno-associated virus-9 reverses delayed gastric emptying of solids in diabetic mice.

Background: Gastroparesis is defined by delayed gastric emptying (GE) without obstruction. Studies suggest targeting heme oxygenase-1 (HO1) may ameliorate diabetic gastroparesis. Upregulation of HO1 expression via interleukin-10 (IL-10) in the gastric muscularis propria is associated with reversal of delayed GE in diabetic NOD mice.

Relationships among intragastric meal distribution during gastric emptying scintigraphy, water consumption during water load satiety testing, and symptoms of gastroparesis.

Gastric emptying scintigraphy (GES) measures total gastric retention after a solid meal and can assess intragastric meal distribution (IMD). Water load satiety test (WLST) measures gastric capacity. Both IMD immediately after meal ingestion [ratio of proximal gastric counts after meal ingestion to total gastric counts at (IMD)] and WLST (volume of water ingested over 5 min) are indirect measures of gastric accommodation.

Buspirone for early satiety and symptoms of gastroparesis: A multi-centre, randomised, placebo-controlled, double-masked trial (BESST).

Background: Patients with gastroparesis and related disorders have symptoms including early satiety, postprandial fullness and bloating. Buspirone, a 5-HT receptor agonist, may improve fundic accommodation.

Aim: To determine if buspirone treatment improves early satiety and postprandial fullness in patients with symptoms of gastroparesis.

Titration-based normalization of antibody amount improves consistency of ChIP-seq experiments.

Chromatin immunoprecipitation (ChIP) is an antibody-based approach that is frequently utilized in chromatin biology and epigenetics. The challenge in experimental variability by unpredictable nature of usable input amounts from samples and undefined antibody titer in ChIP reaction still remains to be addressed. Here, we introduce a simple and quick method to quantify chromatin inputs and demonstrate its utility for normalizing antibody amounts to the optimal titer in individual ChIP reactions.

Mechanosensitive pore opening of a prokaryotic voltage-gated sodium channel.

Voltage-gated ion channels (VGICs) orchestrate electrical activities that drive mechanical functions in contractile tissues such as the heart and gut. In turn, contractions change membrane tension and impact ion channels. VGICs are mechanosensitive, but the mechanisms of mechanosensitivity remain poorly understood.

Characteristics and outcomes of patients with gastroparesis using enteral and/or exclusive parenteral nutrition.

Background: Patients with gastroparesis (Gp) may need enteral nutrition (EN) or exclusive parenteral nutrition (PN). Among patients with Gp, we aimed to (1) identify the frequency of EN and exclusive PN use and (2) explore characteristics of patients using EN and/or exclusive PN compared with those using oral nutrition (ON), including changes over 48 weeks.

Methods: Patients with Gp underwent history and physical examination, gastric emptying scintigraphy, water load satiety testing (WLST), and questionnaires assessing gastrointestinal symptoms and quality of life (QOL).

Clinical and Pathological Features of Severe Gut Dysmotility.

Severe gut motility disorders are characterized by ineffective propulsion of intestinal contents. As a result, patients often develop extremely uncomfortable symptoms, ranging from nausea and vomiting along with alterations of bowel habits, up to radiologically confirmed subobstructive episodes. Chronic intestinal pseudo-obstruction (CIPO) is a typical clinical phenotype of severe gut dysmotility due to morphological and functional alterations of the intrinsic (enteric) innervation and extrinsic nerve supply (hence neuropathy), interstitial cells of Cajal (ICCs) (mesenchymopathy), and smooth muscle cells (myopathy).

Intestinal enteroendocrine cells rely on ryanodine and IP calcium store receptors for mechanotransduction.

Enteroendocrine cells (EECs) are specialized sensors of luminal forces and chemicals in the gastrointestinal (GI) epithelium that respond to stimulation with a release of signalling molecules such as serotonin (5-HT). For mechanosensitive EECs, force activates Piezo2 channels, which generate a very rapidly activating and inactivating (∼10 ms) cationic (Na , K , Ca ) receptor current. Piezo2 receptor currents lead to a large and persistent increase in intracellular calcium (Ca ) that lasts many seconds to sometimes minutes, suggesting signal amplification.

Teleparallel gravity: from theory to cosmology.

Teleparallel gravity (TG) has significantly increased in popularity in recent decades, bringing attention to Einstein's other theory of gravity. In this Review, we give a comprehensive introduction to how teleparallel geometry is developed as a gauge theory of translations together with all the other properties of gauge field theory. This relates the geometry to the broader metric-affine approach to forming gravitational theories where we describe a systematic way of constructing consistent teleparallel theories that respect certain physical conditions such as local Lorentz invariance.