Contractile and Genetic Characterization of Cardiac Constructs Engineered from Human Induced Pluripotent Stem Cells: Modeling of Tuberous Sclerosis Complex and the Effects of Rapamycin.

The implementation of three-dimensional tissue engineering concurrently with stem cell technology holds great promise for in vitro research in pharmacology and toxicology and modeling cardiac diseases, particularly for rare genetic and pediatric diseases for which animal models, immortal cell lines, and biopsy samples are unavailable. It also allows for a rapid assessment of phenotype-genotype relationships and tissue response to pharmacological manipulation. Mutations in the and genes lead to dysfunctional mTOR signaling and cause tuberous sclerosis complex (TSC), a genetic disorder that affects multiple organ systems, principally the brain, heart, skin, and kidneys.

New Pseudomonas Bacterial Strains: Biological Activity and Characteristic Properties of Metabolites.

This paper investigates the antagonistic and plant growth promotion activity of the new indigenous bacteria antagonist strains BZR 245-F and sp. BZR 523-2. It was found that on the 10th day of cultivation, BZR 245-F and BZR 523-2 exhibit an antagonistic activity against at the level of 59.

[A study of the mechanisms of action of Fertiwell in vivo].

Aim: To investigate the specific mechanisms of action of Fertiwell in a mouse model of D-galactose-induced aging of the reproductive system.

Materials And Methods: C57BL/6J mice were randomized into four groups: intact mice (control group), a group of mice with artificial accelerated aging treated with D-galactose alone (Gal), D-galactose followed by Fertiwell (PP), and D-galactose followed by a combination of L-carnitine and acetyl-L-carnitine (LC). The artificial accelerated aging of reproductive system was induced by daily intraperitoneal administration of D-galactose at a dose of 100 mg/kg for 8 weeks.

Polycystic Ovary Syndrome and Gut Microbiota: Phenotype Matters.

Abnormalities in gut microbiota diversity are considered important mechanisms in metabolic disorders in polycystic ovarian syndrome (PCOS). However, the data on the association of these disorders with the PCOS phenotype remain controversial. The objectives of this study were to estimate the alpha diversity of the gut microbiota of healthy women and PCOS patients depending on phenotype.

CRISPR/Cas9-induced modification of the conservative promoter region of alters the heading time of hexaploid bread wheat.

In cereals, the vernalization-related gene network plays an important role in regulating the transition from the vegetative to the reproductive phase to ensure optimal reproduction in a temperate climate. In hexaploid bread wheat ( L.), the spring growth habit is associated with the presence of at least one dominant locus of gene (), which usually differs from recessive alleles due to mutations in the regulatory sequences of the promoter or/and the first intron.

Comparative transcriptomic analysis of the larval and adult stages of Dibothriocephalus dendriticus (Cestoda: Diphyllobothriidea).

Tapeworms of the genus Dibothriocephalus are widely distributed throughout the world, some of which are agents of human diphyllobothriasis, one of the most important fish-borne zoonoses caused by a cestode parasite. Genomic and transcriptomic data can be used to develop future diagnostic tools and epidemiological studies. The present work focuses on a comparative analysis of the transcriptomes of adult and plerocercoid D.

Blocking P2X7 receptor with AZ 10606120 exacerbates vascular hyperpermeability and inflammation in murine polymicrobial sepsis.

Sepsis is a devastating disease with high morbidity and mortality and no specific treatments. The pathophysiology of sepsis involves a hyperinflammatory response and release of damage-associated molecular patterns (DAMPs), including adenosine triphosphate (ATP), from activated and dying cells. Purinergic receptors activated by ATP have gained attention for their roles in sepsis, which can be pro- or anti-inflammatory depending on the context.

Effect of Grafting on Viral Resistance of Non-transgenic Plum Scion Combined With Transgenic PPV-Resistant Rootstock.

In stone fruit trees, resistance to (PPV) can be achieved through the specific degradation of viral RNA by the mechanism of RNA interference (RNAi). Transgenic virus-resistant plants, however, raise serious biosafety concerns due to the insertion and expression of hairpin constructs that usually contain various selective foreign genes. Since a mature stone tree represents a combination of scion and rootstock, grafting commercial varieties onto transgenic virus-tolerant rootstocks is a possible approach to mitigate biosafety problems.

Complete mitochondrial genomes of Baikal endemic coregonids: omul and lacustrine whitefish (Salmonidae: sp.).

Coregonid fishes are among the most successful groups in the subarctic, boreal, and subalpine fresh waters of the northern hemisphere. Limnetic-benthic sympatric species-pairs from two different evolutionary lineages, the North American lake whitefish ( species complex), and the European whitefish ( species complex), are becoming the subject of close attention to explore the role of natural selection during the ecological speciation. Baikal endemic coregonids, limnetic omul (), and benthic lacustrine whitefish () are the only representatives of another unique lineage that has not left the lake since the divergence from the two above.

Post-Soviet shifts in grazing and fire regimes changed the functional plant community composition on the Eurasian steppe.

Globally, grasslands are shaped by grazing and fire, and grassland plants are adapted to these disturbances. However, temperate grasslands have been hotspots of land-use change, and how such changes affect interrelations between herbivory, fire and vegetation are poorly understood. Such land-use changes are widespread on the Eurasian steppe, where the dissolution of the Soviet Union in 1991 triggered the abandonment of cropland and pasture on globally relevant scales.

GROWTH AND CHARACTERIZATION OF A TISSUE-ENGINEERED CONSTRUCT FROM HUMAN CORONARY ARTERY SMOOTH MUSCLE CELLS.

Objective: To optimize a bioengineered «I-Wire» platform to grow tissue-engineered constructs (TCs) derived from coronary artery smooth muscle cells and characterize the mechano-elastic properties of the grown TCs.

Materials And Methods: A fibrinogen-based cell mixture was pipetted in a casting mold having two parallel titanium anchoring wires inserted in the grooves on opposite ends of the mold to support the TC. The casting mold was 3 mm in depth, 2 mm in width and 12 mm in length.

Highly Reactive Isolevuglandins Promote Atrial Fibrillation Caused by Hypertension.

Oxidative damage is implicated in atrial fibrillation (AF), but antioxidants are ineffective therapeutically. The authors tested the hypothesis that highly reactive lipid dicarbonyl metabolites, or isolevuglandins (IsoLGs), are principal drivers of AF during hypertension. In a hypertensive murine model and stretched atriomyocytes, the dicarbonyl scavenger 2-hydroxybenzylamine (2-HOBA) prevented IsoLG adducts and preamyloid oligomers (PAOs), and AF susceptibility, whereas the ineffective analog 4-hydroxybenzylamine (4-HOBA) had minimal effect.

Optimization of laboratory cultivation conditions for the synthesis of antifungal metabolites by bacillus subtilis strains.

In order to achieve the optimal number of colony forming units and a high level of antifungal metabolites synthesis, we carried out the periodic cultivation of the BZR 336 g and BZR 517 strains at various pH and temperature levels. In the experiment for determining the optimal temperature, the maximum titer of BZR 336 g bacterium (1.6-1.

Mitochondrial Deacetylase Sirt3 Reduces Vascular Dysfunction and Hypertension While Sirt3 Depletion in Essential Hypertension Is Linked to Vascular Inflammation and Oxidative Stress.

Rationale: Hypertension represents a major risk factor for stroke, myocardial infarction, and heart failure and affects 30% of the adult population. Mitochondrial dysfunction contributes to hypertension, but specific mechanisms are unclear. The mitochondrial deacetylase Sirt3 (Sirtuin 3) is critical in the regulation of metabolic and antioxidant functions which are associated with hypertension, and cardiovascular disease risk factors diminish Sirt3 level.

Haptoglobin-2 variant increases susceptibility to acute respiratory distress syndrome during sepsis.

Acute respiratory distress syndrome (ARDS) is an inflammatory lung disorder that frequently complicates critical illness and commonly occurs in sepsis. Although numerous clinical and environmental risk factors exist, not all patients with risk factors develop ARDS, raising the possibility of genetic underpinnings for ARDS susceptibility. We have previously reported that circulating cell-free hemoglobin (CFH) is elevated during sepsis, and higher levels predict worse outcomes.

-Mediated Transformation of Russian Commercial Plum cv. "Startovaya" ( L.) With Virus-Derived Hairpin RNA Construct Confers Durable Resistance to PPV Infection in Mature Plants.

In modern horticulture (PPV) imposes serious threats to commercial plantations of a wide range of fruit species belonging to genera . Given the lack of natural genetic resources, which display reliable resistance to PPV infection, there has been considerable interest in using genetic engineering methods for targeted genome modification of stone fruit trees to control Sharka disease caused by PPV. Among the many virus defense mechanisms, RNA interference is shown to be the most promising transgenic disease-control strategy in plant biotechnology.

Azithromycin Causes a Novel Proarrhythmic Syndrome.

Background: The widely used macrolide antibiotic azithromycin increases risk of cardiovascular and sudden cardiac death, although the underlying mechanisms are unclear. Case reports, including the one we document here, demonstrate that azithromycin can cause rapid, polymorphic ventricular tachycardia in the absence of QT prolongation, indicating a novel proarrhythmic syndrome. We investigated the electrophysiological effects of azithromycin in vivo and in vitro using mice, cardiomyocytes, and human ion channels heterologously expressed in human embryonic kidney (HEK 293) and Chinese hamster ovary (CHO) cells.

I-Wire Heart-on-a-Chip I: Three-dimensional cardiac tissue constructs for physiology and pharmacology.

Unlabelled: Engineered 3D cardiac tissue constructs (ECTCs) can replicate complex cardiac physiology under normal and pathological conditions. Currently, most measurements of ECTC contractility are either made isometrically, with fixed length and without control of the applied force, or auxotonically against a variable force, with the length changing during the contraction. The "I-Wire" platform addresses the unmet need to control the force applied to ECTCs while interrogating their passive and active mechanical and electrical characteristics.

Cardiomyocyte-Specific Human Bcl2-Associated Anthanogene 3 P209L Expression Induces Mitochondrial Fragmentation, Bcl2-Associated Anthanogene 3 Haploinsufficiency, and Activates p38 Signaling.

The Bcl2-associated anthanogene (BAG) 3 protein is a member of the BAG family of cochaperones, which supports multiple critical cellular processes, including critical structural roles supporting desmin and interactions with heat shock proteins and ubiquitin ligases intimately involved in protein quality control. The missense mutation P209L in exon 3 results in a primarily cardiac phenotype leading to skeletal muscle and cardiac complications. At least 10 other Bag3 mutations have been reported, nine resulting in a dilated cardiomyopathy for which no specific therapy is available.

BRG1 and BRM SWI/SNF ATPases redundantly maintain cardiomyocyte homeostasis by regulating cardiomyocyte mitophagy and mitochondrial dynamics in vivo.

There has been an increasing recognition that mitochondrial perturbations play a central role in human heart failure. Mitochondrial networks, whose function is to maintain the regulation of mitochondrial biogenesis, autophagy ('mitophagy') and mitochondrial fusion/fission, are new potential therapeutic targets. Yet our understanding of the molecular underpinning of these processes is just emerging.

Activation of transient receptor potential vanilloid-1 (TRPV1) influences how retinal ganglion cell neurons respond to pressure-related stress.

Our recent studies implicate the transient receptor potential vanilloid-1 (TRPV1) channel as a mediator of retinal ganglion cell (RGC) function and survival. With elevated pressure in the eye, TRPV1 increases in RGCs, supporting enhanced excitability, while Trpv1 -/- accelerates RGC degeneration in mice. Here we find TRPV1 localized in monkey and human RGCs, similar to rodents.

Hypertension is associated with preamyloid oligomers in human atrium: a missing link in atrial pathophysiology?

Background: Increasing evidence indicates that proteotoxicity plays a pathophysiologic role in experimental and human cardiomyopathy. In organ-specific amyloidoses, soluble protein oligomers are the primary cytotoxic species in the process of protein aggregation. While isolated atrial amyloidosis can develop with aging, the presence of preamyloid oligomers (PAOs) in atrial tissue has not been previously investigated.