Quantification of DNA of and Trichothecene Genotypes 3ADON and NIV in the Grain of Winter Wheat.

Fusarium head blight (FHB) is a wheat disease caused by fungi of the genus . The aim of the study was to find relationships between the weather conditions in the experimental years and the locations and the amount of DNA and trichothecene genotypes, as well as the proportions between them. A three-year field experiment (2017, 2018 and 2019) was established in two locations (Poznań, Radzików).

Discovery of Ervogastat (PF-06865571): A Potent and Selective Inhibitor of Diacylglycerol Acyltransferase 2 for the Treatment of Non-alcoholic Steatohepatitis.

Discovery efforts leading to the identification of ervogastat (PF-06865571), a systemically acting diacylglycerol acyltransferase (DGAT2) inhibitor that has advanced into clinical trials for the treatment of non-alcoholic steatohepatitis (NASH) with liver fibrosis, are described herein. Ervogastat is a first-in-class DGAT2 inhibitor that addressed potential development risks of the prototype liver-targeted DGAT2 inhibitor PF-06427878. Key design elements that culminated in the discovery of ervogastat are (1) replacement of the metabolically labile motif with a 3,5-disubstituted pyridine system, which addressed potential safety risks arising from a cytochrome P450-mediated -dearylation of PF-06427878 to a reactive quinone metabolite precursor, and (2) modifications of the amide group to a 3-THF group, guided by metabolite identification studies coupled with property-based drug design.

Pharmacological, Pharmacokinetic, Pharmacodynamic and Physicochemical Characterization of FE 205030: A Potent, Fast Acting, Injectable CGRP Receptor Antagonist for the Treatment of Acute Episodic Migraine.

The neuropeptide calcitonin gene-related peptide (CGRP) is known to play a central role in the underlying pathophysiology of migraine. In comparison to the effective triptan class of antimigraine treatments, the CGRP antagonists possess a comparable efficacy but a superior cardiovascular safety profile in patients. This paper describes the development of selective and potent peptidic CGRP antagonist, FE 205030, that has a fast onset of action and an optimal half-life (subcutaneous T ~ 60 min, and t ~ 4.

Molecular identification of triticale introgression lines carrying leaf rust resistance genes transferred from Aegilops kotschyi Boiss. and Ae. tauschii Coss.

Triticale (× Triticosecale Wittmack) is a commercial hybrid harboring wheat (Triticum sp.) and rye (Secale cereale L.) genomes.

Hepatotropic Properties of SARS-CoV-2-Preliminary Results of Cross-Sectional Observational Study from the First Wave COVID-19 Pandemic.

Liver injury-expressed as elevated liver enzymes-is common in patients with COVID-19. Little is known about the potential mechanisms of liver damage by SARS-CoV-2. A direct cytopathic effect on hepatocytes as well as injury related to hypoxia or hepatotoxicity are being considered.

Development and Cytomolecular Identification of Monosomic Alien Addition and Substitution Lines of Triticale (× Wittmack) With 2S Chromosome Conferring Leaf Rust Resistance Derived From Boiss.

Alien chromosome introgression has become a valuable tool to broaden the genetic variability of crop plants via chromosome engineering. This study details the procedure to obtain monosomic addition and monosomic substitution lines of the triticale carrying 2S chromosome from Boiss., which harbors + leaf and stripe rust-resistant gene loci, respectively.

Nosocomial COVID-19 Infection and Severe COVID-19 Pneumonia in Patients Hospitalized for Alcoholic Liver Disease: A Case Report.

BACKGROUND COVID-19 is an infectious disease caused by SARS-CoV-2. It has spread rapidly through the world, endangering human life. The main target of COVID-19 is the lungs; however, it can involve other organs, including the liver.

Discovery of PF-06835919: A Potent Inhibitor of Ketohexokinase (KHK) for the Treatment of Metabolic Disorders Driven by the Overconsumption of Fructose.

Increased fructose consumption and its subsequent metabolism have been implicated in metabolic disorders such as nonalcoholic fatty liver disease and steatohepatitis (NAFLD/NASH) and insulin resistance. Ketohexokinase (KHK) converts fructose to fructose-1-phosphate (F1P) in the first step of the metabolic cascade. Herein we report the discovery of a first-in-class KHK inhibitor, PF-06835919 (), currently in phase 2 clinical trials.

Pharmacological Characterization of Apraglutide, a Novel Long-Acting Peptidic Glucagon-Like Peptide-2 Agonist, for the Treatment of Short Bowel Syndrome.

Glucagon-like peptide-2 (GLP-2) agonists have therapeutic potential in clinical indications in which the integrity or absorptive function of the intestinal mucosa is compromised, such as in short bowel syndrome (SBS). Native hGLP-2, a 33-amino acid peptide secreted from the small intestine, contributes to nutritional absorption but has a very short half-life because of enzymatic cleavage and renal clearance and thus is of limited therapeutic value. The GLP-2 analog teduglutide (Revestive/Gattex; Shire Inc.

Identification of Proteomic Components Associated with Resistance to Head Blight in Rye.

Rye was used here to dissect molecular mechanisms of resistance to head blight (FHB) and to go deeper with our understanding of that process in cereals. -damaged kernels of two lines different in their potential of resistance to FHB were analyzed using two-dimensional gel electrophoresis and mass spectrometry to identify resistance markers. The proteome profiling was accompanied by measurements of α- and β-amylase activities and mycotoxin content.

Discovery of Potent, Selective, and Short-Acting Peptidic V Receptor Agonists.

The vasopressin analogue desmopressin (desamino-d-arginine vasopressin, dDAVP, 1) is a potent vasopressin 2 (V) receptor (VR) agonist approved in many countries for the treatment of diabetes insipidus, primary nocturnal enuresis, nocturia, and coagulation disorders. Since 1 is primarily excreted via the kidneys, an age-related decline in kidney function leads to slower elimination, prolonged antidiuresis, and hyponatremia. In search of novel, potent, selective, and short-acting peptidic VR agonists, we synthesized a series of C-terminally truncated analogues of [Val]dDAVP, 2, modified in positions 2, 3, and 7 and/or at the disulfide bridge.

Relationship between Fusarium Head Blight, Kernel Damage, Concentration of Biomass, and Toxins in Grain of Winter Wheat Inoculated with .

Winter wheat lines were evaluated for their reaction to Fusarium head blight (FHB) after inoculation with in two field experiments. A mixture of two chemotypes was applied (3ADON-deoxynivalenol producing, NIV-nivalenol producing). Different types of resistance were evaluated, including head infection, kernel damage, biomass content and trichothecenes B (deoxynivalenol (DON), and nivalenol (NIV)) accumulation in grain.

Resistance of ( × ) × Hybrids to Leaf Rust () Determined on the Macroscopic and Microscopic Level.

Leaf rust caused by Eriks belongs to the most important fungal pathogens of wheat ( L.) and triticale (× ). Effective resistance to leaf rust is both, cost-effective and environmentally safe.

Correction: Chromosomal distribution of pTa-535, pTa-86, pTa-713, 35S rDNA repetitive sequences in interspecific hexaploid hybrids of common wheat (Triticum aestivum L.) and spelt (Triticum spelta L.).

[This corrects the article DOI: 10.1371/journal.pone.

Selective and non-selective OT receptor agonists induce different locomotor behaviors in male rats via central OT receptors and peripheral V1a receptors.

Oxytocin (OT) continues to inspire much research due to its diverse physiological effects. While the best-understood actions of OT are uterine contraction and milk ejection, OT is also implicated in maternal and bonding behaviors, and potentially in CNS disorders such as autism, schizophrenia, and pain. The dissection of the mechanism of action of OT is complicated by the fact that this peptide activates not only its cognate receptor but also vasopressin type 1a (V1a) receptors.

A Modular Approach to the Synthesis of gem-Disubstituted Cyclopropanes.

A diastereoselective, Pd-catalyzed Suzuki-Miyaura coupling reaction of geminal bis(boryl)cyclopropanes has been developed. The reaction offers a highly modular approach to the synthesis of tertiary cyclopropylboronic esters. The resulting boronic esters may be further functionalized to afford a range of gem-disubstituted cyclopropanes, which represent an important structural motif in the pharmaceutical industry.

Chromosomal distribution of pTa-535, pTa-86, pTa-713, 35S rDNA repetitive sequences in interspecific hexaploid hybrids of common wheat (Triticum aestivum L.) and spelt (Triticum spelta L.).

Fluorescent in situ hybridization (FISH) relies on fluorescent-labeled probes to detect specific DNA sequences in the genome, and it is widely used in cytogenetic analyses. The aim of this study was to determine the karyotype of T. aestivum and T.

Alcohol Relapse After Liver Transplantation: Younger Women Are at Greatest Risk.

Background: Alcoholic cirrhosis is an indication for 40% of liver transplantations (LT) in Europe. In most centers, 6 months of abstinence is required before listing. However, alcohol recidivism is quite high after LT, and approximately 20–25% of recipients with ALD resume harmful drinking, resulting in liver insufficiency, which casts doubt on the 6-months rule as a reliable marker of abstinence maintenance after LT.

Accessions with Geographically Diverse Origin Show Differences in Chromosome Organization and Polymorphism of Molecular Markers Linked to Leaf Rust and Powdery Mildew Resistance Genes.

(2n = 2x = 14) is a diploid wild species which is reported as a donor of the D-genome of cultivated bread wheat. The main goal of this study was to examine the differences and similarities in chromosomes organization among accessions of with geographically diversed origin, which is believed as a potential source of genes, especially determining resistance to fungal diseases (i.e.

Gametocidal Factor Transferred from Roth Can Be Adapted for Large-Scale Chromosome Manipulations in Cereals.

Segregation distorters are curious, evolutionarily selfish genetic elements, which distort Mendelian segregation in their favor at the expense of others. Those agents include gametocidal factors (Gc), which ensure their preferential transmission by triggering damages in cells lacking them via chromosome break induction. Hence, we hypothesized that the gametocidal system can be adapted for chromosome manipulations between and chromosomes in hexaploid triticale (× Wittmack).

Higher Fusarium Toxin Accumulation in Grain of Winter Triticale Lines Inoculated with Fusarium culmorum as Compared with Wheat.

Resistance to head blight in 32 winter triticale and 34 winter wheat accessions was evaluated. Triticale and wheat were sown in field experiments in two locations. At the time of flowering, heads were inoculated with three isolates.

Similarities and differences in the nuclear genome organization within Pooideae species revealed by comparative genomic in situ hybridization (GISH).

In this paper, we highlight the affinity between the genomes of key representatives of the Pooideae subfamily, revealed at the chromosomal level by genomic in situ hybridization (GISH). The analyses were conducted using labeled probes from each species to hybridize with chromosomes of every species used in this study based on a "round robin" rule. As a result, the whole chromosomes or chromosome regions were distinguished or variable types of signals were visualized to prove the different levels of the relationships between genomes used in this study.

Alterations in Kernel Proteome after Infection with Fusarium culmorum in Two Triticale Cultivars with Contrasting Resistance to Fusarium Head Blight.

Highlight: The level of pathogen alpha-amylase and plant beta-amylase activities could be components of plant-pathogen interaction associated with the resistance of triticale to Fusarium head blight. Triticale was used here as a model to recognize new components of molecular mechanism of resistance to Fusarium head blight (FHB) in cereals. Fusarium-damaged kernels (FDK) of two lines distinct in levels of resistance to FHB were applied into a proteome profiling using two-dimensional gel electrophoresis (2-DE) to create protein maps and mass spectrometry (MS) to identify the proteins differentially accumulated between the analyzed lines.