Novel Identification of Ankyrin-R in Cardiac Fibroblasts and a Potential Role in Heart Failure.

Altered ankyrin-R (AnkR; encoded by ) expression is associated with diastolic function, left ventricular remodeling, and heart failure with preserved ejection fraction (HFpEF). First identified in erythrocytes, the role of AnkR in other tissues, particularly the heart, is less studied. Here, we identified the expression of both canonical and small isoforms of AnkR in the mouse myocardium.

Pathogenomes of Shiga Toxin Positive and Negative O157:H7 Strains TT12A and TT12B: Comprehensive Phylogenomic Analysis Using Closed Genomes.

Shiga toxin-producing are zoonotic pathogens that cause food-borne human disease. Among these, the O157:H7 serotype has evolved from an enteropathogenic O55:H7 ancestor through the displacement of the somatic gene cluster and recurrent toxigenic conversion by Shiga toxin-converting bacteriophages. However, atypical strains that lack the Shiga toxin, the characteristic virulence hallmark, are circulating in this lineage.

Pathogenomes and virulence profiles of representative big six non-O157 serogroup Shiga toxin-producing .

Shiga toxin (Stx)-producing (STEC) of non-O157:H7 serotypes are responsible for global and widespread human food-borne disease. Among these serogroups, O26, O45, O103, O111, O121, and O145 account for the majority of clinical infections and are colloquially referred to as the "Big Six." The "Big Six" strain panel we sequenced and analyzed in this study are reference type cultures comprised of six strains representing each of the non-O157 STEC serogroups curated and distributed by the American Type Culture Collection (ATCC) as a resource to the research community under panel number ATCC MP-9.

Acute mitral regurgitation with and without acute heart failure.

Acute severe mitral regurgitation (MR) is rare, but often leads to cardiogenic shock, pulmonary edema, or both. Most common causes of acute severe MR are chordae tendineae (CT) rupture, papillary muscle (PM) rupture, and infective endocarditis (IE). Mild to moderate MR is often seen in patients with acute myocardial infarction (AMI).

Isolation and characterization of a SARS-CoV-2 variant with a Q677H mutation in the spike protein.

We isolated 20 SARS-CoV-2 strains from positive clinical samples collected in Columbus, Ohio, and investigated the replication of one pair of isolates: a clade 20G strain and a variant of this strain carrying a Q677H mutation in the spike protein and six other amino acid mutations. The OSU.20G variant replicated to a higher peak infectious titer than the 20G base strain in Vero-E6 cells, but the titers were similar when both strains were grown in Calu-3 cells.

Pathogenome comparison and global phylogeny of Escherichia coli ST1485 strains.

Escherichia coli ST1485 strains belong to the clinically important phylogroup F and have disseminated worldwide in humans, animals, and the environment. Here, we elucidated the pathogenome of a global collection of E. coli ST1485 isolates from diverse sources retrieved from public databases and a high-quality sequenced complete genome of colistin-resistant E.

Humanized ACM Mouse Model Displays Stress-Induced Cardiac Electrical and Structural Phenotypes.

Arrhythmogenic cardiomyopathy (ACM) is an inherited disorder characterized by fibro-fatty infiltration with an increased propensity for ventricular arrhythmias and sudden death. Genetic variants in desmosomal genes are associated with ACM. Incomplete penetrance is a common feature in ACM families, complicating the understanding of how external stressors contribute towards disease development.

Pathogenomes and variations in Shiga toxin production among geographically distinct clones of O113:H21.

Infections with globally disseminated Shiga toxin-producing (STEC) of the O113:H21 serotype can progress to severe clinical complications, such as hemolytic uremic syndrome (HUS). Two phylogeographically distinct clonal complexes have been established by multi locus sequence typing (MLST). Infections with ST-820 isolates circulating exclusively in Australia have caused severe human disease, such as HUS.

New mechanistic insights to PLOD1-mediated human vascular disease.

Heritable thoracic aortic disease and familial thoracic aortic aneurysm/dissection are important causes of human morbidity/mortality, most without identifiable genetic cause. In a family with familial thoracic aortic aneurysm/dissection, we identified a missense p. (Ser178Arg) variant in PLOD1 segregating with disease, and evaluated PLOD1 enzymatic activity, collagen characteristics and in human aortic vascular smooth muscle cells, studied the effect on function.

Inherited Variants in Cause Severe Early-Onset Coronary Artery Disease.

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Giant ankyrin-G regulates cardiac function.

Cardiovascular disease (CVD) remains the most common cause of adult morbidity and mortality in developed nations. As a result, predisposition for CVD is increasingly important to understand. Ankyrins are intracellular proteins required for the maintenance of membrane domains.

Arrhythmogenic Cardiomyopathy: Molecular Insights for Improved Therapeutic Design.

Arrhythmogenic cardiomyopathy (ACM) is an inherited disorder characterized by structural and electrical cardiac abnormalities, including myocardial fibro-fatty replacement. Its pathological ventricular substrate predisposes subjects to an increased risk of sudden cardiac death (SCD). ACM is a notorious cause of SCD in young athletes, and exercise has been documented to accelerate its progression.

Pathogenomes of Atypical Non-shigatoxigenic NSF/SF O157:H7/NM: Comprehensive Phylogenomic Analysis Using Closed Genomes.

The toxigenic conversion of strains by Shiga toxin-converting (Stx) bacteriophages were prominent and recurring events in the stepwise evolution of enterohemorrhagic (EHEC) O157:H7 from an enteropathogenic (EPEC) O55:H7 ancestor. Atypical, attenuated isolates have been described for both non-sorbitol fermenting (NSF) O157:H7 and SF O157:NM serotypes, which are distinguished by the absence of Stx, the characteristic virulence hallmark of Stx-producing (STEC). Such atypical isolates either never acquired Stx-phages or may have secondarily lost during the course of infection, isolation, or routine subculture; the latter are commonly referred to as LST (Lost Shiga Toxin)-isolates.

Aberrant Expression of a Non-muscle RBFOX2 Isoform Triggers Cardiac Conduction Defects in Myotonic Dystrophy.

Myotonic dystrophy type 1 (DM1) is a multisystemic genetic disorder caused by the CTG repeat expansion in the 3'-untranslated region of DMPK gene. Heart dysfunctions occur in ∼80% of DM1 patients and are the second leading cause of DM1-related deaths. Herein, we report that upregulation of a non-muscle splice isoform of RNA-binding protein RBFOX2 in DM1 heart tissue-due to altered splicing factor and microRNA activities-induces cardiac conduction defects in DM1 individuals.

Mechanisms and Alterations of Cardiac Ion Channels Leading to Disease: Role of Ankyrin-B in Cardiac Function.

Ankyrin-B (encoded by ), originally identified as a key cytoskeletal-associated protein in the brain, is highly expressed in the heart and plays critical roles in cardiac physiology and cell biology. In the heart, ankyrin-B plays key roles in the targeting and localization of key ion channels and transporters, structural proteins, and signaling molecules. The role of ankyrin-B in normal cardiac function is illustrated in animal models lacking ankyrin-B expression, which display significant electrical and structural phenotypes and life-threatening arrhythmias.

Ankyrin-B dysfunction predisposes to arrhythmogenic cardiomyopathy and is amenable to therapy.

Arrhythmogenic cardiomyopathy (ACM) is an inherited arrhythmia syndrome characterized by severe structural and electrical cardiac phenotypes, including myocardial fibrofatty replacement and sudden cardiac death. Clinical management of ACM is largely palliative, owing to an absence of therapies that target its underlying pathophysiology, which stems partially from our limited insight into the condition. Following identification of deceased ACM probands possessing ANK2 rare variants and evidence of ankyrin-B loss of function on cardiac tissue analysis, an ANK2 mouse model was found to develop dramatic structural abnormalities reflective of human ACM, including biventricular dilation, reduced ejection fraction, cardiac fibrosis, and premature death.

Developmental origins for semilunar valve stenosis identified in mice harboring congenital heart disease-associated mutation.

Congenital heart defects affect ∼2% of live births and often involve malformations of the semilunar (aortic and pulmonic) valves. We previously reported a highly penetrant p.Gly296Ser mutation in familial, congenital atrial septal defects and pulmonic valve stenosis and showed that mice harboring the orthologous G295S disease-causing mutation display not only atrial septal defects, but also semilunar valve stenosis.

Defining new mechanistic roles for αII spectrin in cardiac function.

Spectrins are cytoskeletal proteins essential for membrane biogenesis and regulation and serve critical roles in protein targeting and cellular signaling. αII spectrin () is one of two α spectrin genes and αII spectrin dysfunction is linked to alterations in axon initial segment formation, cortical lamination, and neuronal excitability. Furthermore, human αII spectrin loss-of-function variants cause neurological disease.

Genomic features of colistin resistant Escherichia coli ST69 strain harboring mcr-1 on IncHI2 plasmid from raw milk cheese in Egypt.

There is emerging evidence that food of animal origin may be responsible for the spread of multidrug resistant extraintestinal pathogenic Escherichia coli in the community. Here, we describe the emergence of colistin resistance gene, mcr-1, in a strain belonging to the dominant uropathogenic E. coli ST69 lineage.

MG 53 Protein Protects Aortic Valve Interstitial Cells From Membrane Injury and Fibrocalcific Remodeling.

Background The aortic valve of the heart experiences constant mechanical stress under physiological conditions. Maladaptive valve injury responses contribute to the development of valvular heart disease. Here, we test the hypothesis that MG 53 (mitsugumin 53), an essential cell membrane repair protein, can protect valvular cells from injury and fibrocalcific remodeling processes associated with valvular heart disease.

Closed Genome Sequence of Escherichia coli K-12 Group Strain C600.

Escherichia coli strain C600 is a prototypical K-12 derived laboratory strain which has been broadly used for molecular microbiology and bacterial physiology studies since its isolation in 1954. Here, we present the closed genome sequence of E. coli strain C600, retrieved from the American Type Culture Collection (ATCC 23724).