TREM2 macrophages mediate the beneficial effects of bariatric surgery against MASH.

Background And Aims: For patients with obesity and metabolic syndrome, bariatric procedures such as vertical sleeve gastrectomy (VSG) have a clear benefit in ameliorating metabolic dysfunction-associated steatohepatitis (MASH). While the effects of bariatric surgeries have been mainly attributed to nutrient restriction and malabsorption, whether immuno-modulatory mechanisms are involved remains unclear.

Approach And Result: Using murine models, we report that VSG ameliorates MASH progression in a weight loss-independent manner.

Hepatic lipid-associated macrophages mediate the beneficial effects of bariatric surgery against MASH.

For patients with obesity and metabolic syndrome, bariatric procedures such as vertical sleeve gastrectomy (VSG) have a clear benefit in ameliorating metabolic dysfunction-associated steatohepatitis (MASH). While the effects of bariatric surgeries have been mainly attributed to nutrient restriction and malabsorption, whether immuno-modulatory mechanisms are involved remains unclear. Here we report that VSG ameliorates MASH progression in a weight loss-independent manner.

Dysfunctional T Follicular Helper Cells Cause Intestinal and Hepatic Inflammation in NASH.

Nonalcoholic steatohepatitis (NASH), characterized by hepatic inflammation and cellular damage, is the most severe form of nonalcoholic fatty liver disease and the fastest-growing indication for a liver transplant. The intestinal immune system is a central modulator of local and systemic inflammation. In particular, Peyer's patches (PPs) contain T follicular helper (Tfh) cells that support germinal center (GC) responses required for the generation of high-affinity intestinal IgA and the maintenance of intestinal homeostasis.

Genetic variations in idiopathic pulmonary fibrosis and patient response to pirfenidone.

Background: Genetic variations in Idiopathic Pulmonary Fibrosis (IPF) affect survival and outcomes. Current antifibrotic agents are managed based on the patient's reported side effects, although certain single nucleotide polymorphisms (SNPs) might alter treatment response and survival depending on the antifibrotic administered. This study investigated variations in response and outcomes to pirfenidone based on patients-specific genetic profiles.

Immune tolerance of food is mediated by layers of CD4 T cell dysfunction.

Gastrointestinal health depends on the adaptive immune system tolerating the foreign proteins in food. This tolerance is paradoxical because the immune system normally attacks foreign substances by generating inflammation. Here we addressed this conundrum by using a sensitive cell enrichment method to show that polyclonal CD4 T cells responded to food peptides, including a natural one from gliadin, by proliferating weakly in secondary lymphoid organs of the gut-liver axis owing to the action of regulatory T cells.

The genome of the zebra mussel, Dreissena polymorpha: a resource for comparative genomics, invasion genetics, and biocontrol.

The zebra mussel, Dreissena polymorpha, continues to spread from its native range in Eurasia to Europe and North America, causing billions of dollars in damage and dramatically altering invaded aquatic ecosystems. Despite these impacts, there are few genomic resources for Dreissena or related bivalves. Although the D.

Discovery of clinically relevant fusions in pediatric cancer.

Background: Pediatric cancers typically have a distinct genomic landscape when compared to adult cancers and frequently carry somatic gene fusion events that alter gene expression and drive tumorigenesis. Sensitive and specific detection of gene fusions through the analysis of next-generation-based RNA sequencing (RNA-Seq) data is computationally challenging and may be confounded by low tumor cellularity or underlying genomic complexity. Furthermore, numerous computational tools are available to identify fusions from supporting RNA-Seq reads, yet each algorithm demonstrates unique variability in sensitivity and precision, and no clearly superior approach currently exists.

Cardiac Resident Macrophages Prevent Fibrosis and Stimulate Angiogenesis.

Rationale: The initial hypertrophy response to cardiac pressure overload is considered compensatory, but with sustained stress, it eventually leads to heart failure. Recently, a role for recruited macrophages in determining the transition from compensated to decompensated hypertrophy has been established. However, whether cardiac resident immune cells influence the early phase of hypertrophy development has not been established.

Patterns of genetic variation in a prairie wildflower, Silphium integrifolium, suggest a non-prairie origin and locally adaptive variation.

Premise: Understanding the relationship between genetic structure and geography provides information about a species' history and can be used for breeding and conservation goals. The North American prairie is interesting because of its recent origin and subsequent fragmentation. Silphium integrifolium, an iconic perennial American prairie wildflower, is targeted for domestication, having undergone a few generations of improvement.

RNA sequencing of whole blood in dogs with primary immune-mediated hemolytic anemia (IMHA) reveals novel insights into disease pathogenesis.

Immune-mediated hemolytic anemia (IMHA) is a life-threatening autoimmune disorder characterized by a self-mediated attack on circulating red blood cells. The disease occurs naturally in both dogs and humans, but is significantly more prevalent in dogs. Because of its shared features across species, dogs offer a naturally occurring model for studying IMHA in people.

A negative reciprocal regulatory axis between cyclin D1 and HNF4α modulates cell cycle progression and metabolism in the liver.

Hepatocyte nuclear factor 4α (HNF4α) is a master regulator of liver function and a tumor suppressor in hepatocellular carcinoma (HCC). In this study, we explore the reciprocal negative regulation of HNF4α and cyclin D1, a key cell cycle protein in the liver. Transcriptomic analysis of cultured hepatocyte and HCC cells found that cyclin D1 knockdown induced the expression of a large network of HNF4α-regulated genes.

An alpha-defensin gene single nucleotide polymorphism modulates the gut microbiota and may alter the risk of acute graft-versus-host disease.

We previously reported a protective association between single nucleotide polymorphisms (SNPs; rs4415345G and rs4610776A alleles) of Paneth cell α-defensin-5 against acute graft-versus-host disease (aGVHD). Because dysbiosis has been associated with aGVHD, we hypothesized that these SNPs may have a gut microbiota signature. In Lasso regression analysis of 248 healthy individuals, rs4415345G was associated with a higher abundance of Odoribacter splanchnicus, an anaerobic butyrogenic commensal.

The role of gene flow in rapid and repeated evolution of cave-related traits in Mexican tetra, Astyanax mexicanus.

Understanding the molecular basis of repeatedly evolved phenotypes can yield key insights into the evolutionary process. Quantifying gene flow between populations is especially important in interpreting mechanisms of repeated phenotypic evolution, and genomic analyses have revealed that admixture occurs more frequently between diverging lineages than previously thought. In this study, we resequenced 47 whole genomes of the Mexican tetra from three cave populations, two surface populations and outgroup samples.

Neo-Domestication of an Interspecific Tetraploid × Population That Segregates for Perennial Habit.

Perennial agriculture has been proposed as an option to improve the sustainability of cropping systems, by increasing the efficiency of resource use, while also providing ecosystem services. Neo-domestication, the contemporary domestication of plants that have not previously been used in agriculture, can be used to generate new crops for these systems. Here we explore the potential of a tetraploid (2n = 4x = 68) interspecific hybrid sunflower as a perennial oilseed for use in multifunctional agricultural systems.

Pre-clinical Safety and Off-Target Studies to Support Translation of AAV-Mediated RNAi Therapy for FSHD.

RNAi emerged as a prospective molecular therapy nearly 15 years ago. Since then, two major RNAi platforms have been under development: oligonucleotides and gene therapy. Oligonucleotide-based approaches have seen more advancement, with some promising therapies that may soon reach market.

The unusual S locus of Leavenworthia is composed of two sets of paralogous loci.

The Leavenworthia self-incompatibility locus (S locus) consists of paralogs (Lal2, SCRL) of the canonical Brassicaceae S locus genes (SRK, SCR), and is situated in a genomic position that differs from the ancestral one in the Brassicaceae. Unexpectedly, in a small number of Leavenworthia alabamica plants examined, sequences closely resembling exon 1 of SRK have been found, but the function of these has remained unclear. BAC cloning and expression analyses were employed to characterize these SRK-like sequences.

Long-term right ventricular implantable cardioverter-defibrillator lead performance in arrhythmogenic right ventricular cardiomyopathy.

Background: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a progressive disease characterized by replacement of normal myocardium by fibrofatty tissue. The right ventricular (RV) apex is the typical target for implantable cardioverter-defibrillator (ICD) lead placement, raising concerns for suboptimal lead performance in medium- to long-term follow-up.

Objective: The purpose of this study was to determine whether placement of ICD leads at the RV apex was associated with performance deterioration of medium-term leads in ARVC patients compared to non-ARVC patients.

Recent selection for self-compatibility in a population of Leavenworthia alabamica.

The evolution of self-compatibility (SC) is the first step in the evolutionary transition in plants from outcrossing enforced by self-incompatibility (SI) to self-fertilization. In the Brassicaceae, SI is controlled by alleles of two tightly linked genes at the S-locus. Despite permitting inbreeding, mutations at the S-locus leading to SC may be selected if they provide reproductive assurance and/or gain a transmission advantage in a population when SC plants self- and outcross.

Outcome of Apparently Unexplained Cardiac Arrest: Results From Investigation and Follow-Up of the Prospective Cardiac Arrest Survivors With Preserved Ejection Fraction Registry.

Background: The Cardiac Arrest Survivors with Preserved Ejection Fraction Registry (CASPER) enrolls patients with apparently unexplained cardiac arrest and no evident cardiac disease to identify the pathogenesis of cardiac arrest through systematic clinical testing. Exercise testing, drug provocation, advanced cardiac imaging, and genetic testing may be useful when a cause is not apparent.

Methods And Results: The first 200 survivors of unexplained cardiac arrest from 14 centers across Canada were evaluated to determine the results of investigation and follow-up (age, 48.

Life threatening causes of syncope: channelopathies and cardiomyopathies.

Syncope is common, has a high recurrence rate and carries a risk of morbidity and, dependent on the cause, mortality. Although the majority of patients with syncope have a benign prognosis, syncope as a result of cardiomyopathy or channelopathy carries a poor prognosis. In addition, the identification of these disorders allows for the institution of treatments, which are effective at reducing the risk of both syncope and mortality.

Portal for Families Overcoming Neurodevelopmental Disorders (PFOND): Implementation of a Software Framework for Facilitated Community Website Creation by Nontechnical Volunteers.

Background: The Portal for Families Overcoming Neurodevelopmental Disorders (PFOND) provides a structured Internet interface for the sharing of information with individuals struggling with the consequences of rare developmental disorders. Large disease-impacted communities can support fundraising organizations that disseminate Web-based information through elegant websites run by professional staff. Such quality resources for families challenged by rare disorders are infrequently produced and, when available, are often dependent upon the continued efforts of a single individual.

Secondary evolution of a self-incompatibility locus in the Brassicaceae genus Leavenworthia.

Self-incompatibility (SI) is the flowering plant reproductive system in which self pollen tube growth is inhibited, thereby preventing self-fertilization. SI has evolved independently in several different flowering plant lineages. In all Brassicaceae species in which the molecular basis of SI has been investigated in detail, the product of the S-locus receptor kinase (SRK) gene functions as receptor in the initial step of the self pollen-rejection pathway, while that of the S-locus cysteine-rich (SCR) gene functions as ligand.

Phylogeny of Leavenworthia S-alleles suggests unidirectional mating system evolution and enhanced positive selection following an ancient population bottleneck.

The adoption of self-fertilization from an ancestral outcrossing state is one of the most common evolutionary transitions in the flowering plants. In the mustard family, outcrossing is typically enforced by sporophytic self-incompatibility (SI), but there are also many self-compatible species. The genus Leavenworthia contains taxa that either possess or lack SI.