CD14 is a coreceptor of Toll-like receptors 7 and 9

CD14 interacts with and is essential for the functions of endosomal TLR7 and TLR9 in mice

Crop rotational diversity increases disease suppressive capacity of soil microbiomes

Microbiomes can aid in the protection of hosts from infection and disease, but the mechanisms underpinning these functions in complex environmental systems remain unresolved. Soils contain microbiomes that influence plant performance, including their susceptibility to disease. For example, some soil microorganisms produce antimicrobial compounds that suppress the growth of plant pathogens, which can provide benefits for sustainable agricultural management. Evidence shows that crop rotations increase soil fertility and tend to promote microbial diversity, and it has been hypothesized that crop rotations can enhance disease suppressive capacity, either through the influence of plant diversity impacting soil bacterial composition or through the increased abundance of disease suppressive microorganisms. In this study, we used a long�term field experiment to test the effects of crop diversity through time (i.e., rotations) on soil microbial diversity and disease suppressive capacity. We sampled soil from seven treatments along a crop diversity gradient (from monoculture to five crop species rotation) and a spring fallow (non�crop) treatment to examine crop diversity influence on soil microbiomes including bacteria that are capable of producing antifungal compounds. Crop diversity significantly influenced bacterial community composition, where the most diverse cropping systems with cover crops and fallow differed from bacterial communities in the 1–3 crop species diversity treatments. While soil bacterial diversity was about 4% lower in the most diverse crop rotation (corn–soybean–wheat + 2 cover crops) compared to monoculture corn, crop diversity increased disease suppressive functional group prnD gene abundance in the more diverse rotation by about 9% compared to monocultures. In addition, disease suppressive potential was significantly diminished in the (non�crop) fallow treatment compared to the most diverse crop rotation treatments. The composition of the microbial community could be more important than diversity to disease suppressive function in our study. Identifying patterns in microbial diversity and ecosystem function relationships can provide insight into microbiome management, which will require manipulating soil nutrients and resources mediated through plant diversity

Закономерности формирования угольных бассейнов Южно-Гобийской провинции Монголии и содержание в них редких элементов

Background— Ion channels are key determinants for the function of excitable cells, but little is known about their role and involvement during cardiac development. Earlier work identified Ca 2+ -activated potassium channels of small and intermediate conductance (SKCas) as important regulators of neural stem cell fate. Here we have investigated their impact on the differentiation of pluripotent cells toward the cardiac lineage. Methods and Results— We have applied the SKCa activator 1-ethyl-2-benzimidazolinone on embryonic stem cells and identified this particular ion channel family as a new critical target involved in the generation of cardiac pacemaker-like cells: SKCa activation led to rapid remodeling of the actin cytoskeleton, inhibition of proliferation, induction of differentiation, and diminished teratoma formation. Time-restricted SKCa activation induced cardiac mesoderm and commitment to the cardiac lineage as shown by gene regulation, protein, and functional electrophysiological studies. In addition, the differentiation into cardiomyocytes was modulated in a qualitative fashion, resulting in a strong enrichment of pacemaker-like cells. This was accompanied by induction of the sino-atrial gene program and in parallel by a loss of the chamber-specific myocardium. In addition, SKCa activity induced activation of the Ras-Mek-Erk signaling cascade, a signaling pathway involved in the 1-ethyl-2-benzimidazolinone–induced effects. Conclusions— SKCa activation drives the fate of pluripotent cells toward mesoderm commitment and cardiomyocyte specification, preferentially into nodal-like cardiomyocytes. This provides a novel strategy for the enrichment of cardiomyocytes and in particular, the generation of a specific subtype of cardiomyocytes, pacemaker-like cells, without genetic modification. </jats:sec

Impact of PPARγ on cardiomyogenesis in vitro in the murine embryonic stem cell model embryoid body

In dieser Arbeit wurde der Einfluss des orphanen Kernrezeptors Peroxisom-Proliferatoraktivierte Rezeptor des Subtyps Gamma (PPARγ) auf die kardiale Differenzierung in vitro untersucht. Hierfür wurde die murinen embryonale Stammzelllinie CGR8 und das Modellsystems Embryoid Body verwendet. Zur Beantwortung der Fragestellung wurden einerseits pharmakologische Inkubationsexperimente mit spezifischen Agonisten sowie Antagonisten realisiert. Andererseits wurde das Differenzierungsverhalten vergleichend in einer PPARγ-Knockdown-Zelllinie betrachtet, welche durch eine stabile Herunterregulation des Rezeptorsubtyps gekennzeichnet ist

Cholesterol Crystal Dissolution Rate of Serum Predicts Outcomes in Patients With Aortic Stenosis Undergoing Transcatheter Aortic Valve Replacement

Background Aortic stenosis has pathophysiological similarities with atherosclerosis, including the deposition of cholesterol‐containing lipoproteins. The resulting cholesterol crystals activate the NLRP3 (NOD‐like receptor protein 3) inflammasome, leading to inflammation and cardiovascular diseases. We aimed to investigate the cholesterol crystal dissolution rate (CCDR) of serum in patients with aortic stenosis and to assess the prognostic value of this biomarker. Methods and Results The study included 348 patients with aortic stenosis undergoing transcatheter aortic valve replacement. The CCDR was measured using flow cytometry to enumerate cholesterol crystals that were added to a serum solution, at baseline and after 2 hours of incubation. Based on the median CCDR, the cohort was stratified into high and low cholesterol crystal dissolvers. The incidence of the primary end point, a composite of 1‐year all‐cause mortality and major vascular complication, was significantly lower in the high CCDR group (7.3 per 100 person‐years) compared with the low CCDR group (17.0 per 100 person‐years, P=0.01). This was mainly driven by a lower 1‐year mortality rate in patients with a high CCDR (7.3 versus 15.1 per 100 person‐years, P=0.04). Unplanned endovascular interventions were significantly less frequent in high cholesterol crystal dissolvers (12.8 versus 22.6 per 100 person‐years, P=0.04). Although low‐density lipoprotein cholesterol levels were comparable in both groups (101.8±37.3 mg/dL versus 97.9±37.6 mg/dL, P=0.35), only patients with a low CCDR showed a benefit from statin treatment. In multivariate analysis, low CCDR (hazard ratio, 2.21 [95% CI, 0.99–4.92], P=0.04) was significantly associated with 1‐year mortality. Conclusions The CCDR is a novel biomarker associated with outcome in patients with aortic stenosis undergoing transcatheter aortic valve replacement. It may provide new insights into patients' anti‐inflammatory capacity and additional prognostic information beyond classic risk assessment

Pet Rats as the Likely Reservoir for Human SeoulOrthohantavirus Infection.

Seoul orthohantavirus (SEOV) is a rat-associated zoonotic pathogen with an almost worldwide distribution. In 2019, the first autochthonous human case of SEOV-induced hemorrhagic fever with renal syndrome was reported in Germany, and a pet rat was identified as the source of the zoonotic infection. To further investigate the SEOV reservoir, additional rats from the patient and another owner, all of which were purchased from the same vendor, were tested. SEOV RNA and anti-SEOV antibodies were found in both of the patient's rats and in two of the three rats belonging to the other owner. The complete coding sequences of the small (S), medium (M), and large (L) segments obtained from one rat per owner exhibited a high sequence similarity to SEOV strains of breeder rat or human origin from the Netherlands, France, the USA, and Great Britain. Serological screening of 490 rats from breeding facilities and 563 wild rats from Germany (2007-2020) as well as 594 wild rats from the Netherlands (2013-2021) revealed 1 and 6 seropositive individuals, respectively. However, SEOV RNA was not detected in any of these animals. Increased surveillance of pet, breeder, and wild rats is needed to identify the origin of the SEOV strain in Europe and to develop measures to prevent transmission to the human population

Pet Rats as the Likely Reservoir for Human SeoulOrthohantavirus Infection

Seoul orthohantavirus (SEOV) is a rat-associated zoonotic pathogen with an almost worldwide distribution. In 2019, the first autochthonous human case of SEOV-induced hemorrhagic fever with renal syndrome was reported in Germany, and a pet rat was identified as the source of the zoonotic infection. To further investigate the SEOV reservoir, additional rats from the patient and another owner, all of which were purchased from the same vendor, were tested. SEOV RNA and anti-SEOV antibodies were found in both of the patient’s rats and in two of the three rats belonging to the other owner. The complete coding sequences of the small (S), medium (M), and large (L) segments obtained from one rat per owner exhibited a high sequence similarity to SEOV strains of breeder rat or human origin from the Netherlands, France, the USA, and Great Britain. Serological screening of 490 rats from breeding facilities and 563 wild rats from Germany (2007–2020) as well as 594 wild rats from the Netherlands (2013–2021) revealed 1 and 6 seropositive individuals, respectively. However, SEOV RNA was not detected in any of these animals. Increased surveillance of pet, breeder, and wild rats is needed to identify the origin of the SEOV strain in Europe and to develop measures to prevent transmission to the human population