Identifying factors that contribute to the transition to the dilated phase in cardiac ischemia is a critical challenge in heart failure treatment. Currently, no effective therapies exist for this ischemic complication, and the mechanisms driving left ventricular dilatation during chronic post-infarction remodeling remain poorly understood. One potential pathological process leading to ventricular dilatation involves specific compensatory rearrangements in the border zone adjacent to the infarct, which isolates the intact myocardium from inflammation at the scar edge.
View Article and Find Full Text PDFHere we explored new 1,5-disubstituted pyrrolidin-2-ones 1, 2 and 5-aryl-3,3,4,5-tetrahydropyrrolo[1,2-]quinoline-1(2)-ones 3 as inhibitors of tubulin polymerization. We evaluated their effects on microtubule dynamics and on the proliferation of A549 cells, using flow cytometry-based cell cycle analysis. The results were verified with phase-contrast microscopy in three cancer cell lines: A549, HeLa and MCF-7.
View Article and Find Full Text PDFHere, we present a new approach for the activation of donor-acceptor cyclopropanes in ring-opening reactions, which does not require the use of a Lewis or Brønsted acid as a catalyst. Donor-acceptor cyclopropanes containing a phenolic group as the donor undergo deprotonation and isomerization to form the corresponding quinone methides. This innovative strategy was applied to achieve (4 + 1)-annulation of cyclopropanes with sulfur ylides, affording functionalized dihydrobenzofurans.
View Article and Find Full Text PDFResident tissue macrophages (RTMs) encompass a highly diverse set of cells abundantly present in every tissue and organ. RTMs are recognized as central players in innate immune responses, and more recently their importance beyond host defense has started to be highlighted. Despite sharing a universal name and several canonical markers, RTMs perform remarkably specialized activities tailored to sustain critical homeostatic functions of the organs they reside in.
View Article and Find Full Text PDFγ-Aminobutyric acid (GABA) and GABA derivatives have attracted increased attention over the years in the fields of medicinal chemistry and chemical biology due to their interesting biological properties and synthetic relevance. Here, we report a short synthetic route to γ-(het)aryl- and γ-alkenyl-γ-aminobutyric acids, including the antiepileptic drug , from readily available donor-acceptor cyclopropanes and ammonia or methylamine. This protocol includes a facile synthesis of 2-oxopyrrolidine-3-carboxamides and their acid hydrolysis to γ-aryl- or γ-alkenyl-substituted GABAs, which can serve as perspective building blocks for the synthesis of various GABA-based N-heterocycles and bioactive compounds.
View Article and Find Full Text PDFA Lewis-acid-promoted domino ring-opening cyclization of readily available donor-acceptor cyclopropanes with a preinstalled electrophilic center, embedded in a donor group, to functionalized 1,2-dihydronaphthalenes is reported herein. The obtained compounds are transformed to pharmacologically attractive bridged tricyclic esters in a diastereospecific manner.
View Article and Find Full Text PDFUnderstanding the genetic causes of trait variation is a primary goal of genetic research. One way that individuals can vary genetically is through variable pangenomic genes: genes that are only present in some individuals in a population. The presence or absence of entire genes could have large effects on trait variation.
View Article and Find Full Text PDFSecreted protein toxins are widely used weapons in conflicts between organisms. Elucidating how organisms genetically adapt to defend themselves against these toxins is fundamental to understanding the coevolutionary dynamics of competing organisms. Within yeast communities, "killer" toxins are secreted to kill nearby sensitive yeast, providing a fitness advantage in competitive growth environments.
View Article and Find Full Text PDFBackground: Millions of workers experience work-related ill health every year. The loss of working days often accounts for poor well-being because of discomfort and stress caused by the workplace. The ongoing pandemic and postpandemic shift in socioeconomic and work culture can continue to contribute to adverse work-related sentiments.
View Article and Find Full Text PDFLewis acid-catalysed reactions of donor-acceptor cyclopropanes with 1,3-disubstituted 5-aminopyrazoles were investigated. Under catalysis with gallium(III) chloride, products of the three-membered ring opening a nucleophilic attack of the exocyclic amino group were obtained in a chemoselective manner. Oppositely, in the presence of scandium(III) triflate, products of either -alkylation or (4)-alkylation, or a mixture of both were formed.
View Article and Find Full Text PDFThe pilot batches of ThCl and RaCl were separated from Ас. Th was separated by anion exchange chromatography on the sorbent BioRad AG-1x8 100-200 mesh from 8 М HNO. After Th storage accumulated Ra was separated from Th using two chromatography columns: on sorbent BioRad AG-1x8 100-200 mesh from 8 М HNO followed by eluate evaporation, by dissolving of dry residue in 0.
View Article and Find Full Text PDFThe importance of intramolecular constraints in cyclic transition-state geometries is especially pronounced in -- cyclizations, where the usual backside approach of a nucleophile to the breaking bond is impossible for the rings containing less than eight atoms. Herein, we expand the limits of - cyclizations and show that donor-acceptor cyclopropanes can provide a seven-membered ring via a genuine 6-- process. Substrates containing a -alkyl--arylcarbamoyl moiety as an acceptor group undergo Lewis acid-induced cyclization to form tetrahydrobenz[]azepin-2-ones in high yields.
View Article and Find Full Text PDFWe report a study of the response function parameters (amplitude and rise/fall time) of a high-speed GaSb/GaInAsSb/GaAlAsSb photodiode operating at 1.9 µm as a function of optical input power and reverse bias voltage. The experimental measurement results yield the optimal pulse energy and optimal reverse bias voltage for the photodiode.
View Article and Find Full Text PDFWe propose a new concept of the triple role of protic ionic liquids with nucleophilic anions: a) a regenerable solvent, b) a Brønsted acid inducing diverse transformations via general acid catalysis, and c) a source of a nucleophile. The efficiency of this strategy was demonstrated using thiocyanate-based protic ionic liquids for the ring-opening of donor-acceptor cyclopropanes. A wide variety of activated cyclopropanes were found to react with 1-methylimidazolium thiocyanate under mild metal-free conditions via unusual nitrogen attack of the ambident thiocyanate ion on the electrophilic center of the three-membered ring affording pyrrolidine-2-thiones bearing donor and acceptor substituents at the C(5) and C(3) atoms, respectively, in a single time-efficient step.
View Article and Find Full Text PDFObesity is a widespread problem within modern society, serving to increase the risk of cardiovascular, metabolic, and neurodegenerative disorders. Peroxisome proliferator-activated receptor gamma (PPARγ) and PPARγ coactivator 1 α (PGC1α) play a key role in the regulation of cellular energy metabolism and is implicated in the pathology of these diseases. This study examined the association between polymorphisms of the PPARG and PPARGC1A genes and individual variability in weight loss in response to physical activity intervention.
View Article and Find Full Text PDFUsing the 'Korona' cava filter in a total of 1345 oncological patients revealed regularity of a change in the shape of the inferior vena cava at the level of implantation. This made it feasible to determine one of the causes of long-term complications following implantation of other models of cava filters. The absence of clinically significant complications in the remote period after using this model of cava filter made it possible to implant it for a longer period, which is of special importance in oncological patients.
View Article and Find Full Text PDFA straightforward method for ring opening of donor-acceptor cyclopropanes with trimethylsilyl cyanide as a surrogate of cyanide ion in the presence of B(CF) or trifluoromethanesulfonic acid as a catalyst has been developed. The methodology provides a short route to γ-cyanoesters that can be useful synthetic intermediates for the synthesis of diverse bioactive molecules such as glutaric and δ-aminovaleric acid derivatives, 3-arylpiperidines, or other substituted phenethylamines. Oppositely, the attempts to synthesize these γ-cyanoesters by direct reaction of cyclopropanes with sodium cyanide under typical S2 conditions led to the formation of 2-arylsuccinonitriles.
View Article and Find Full Text PDFSelf-incompatibility (SI) is genetically determined reproductive barrier preventing inbreeding and thereby providing the maintenance of plant species diversity. At present, active studies of molecular bases of SI mechanisms are underway. S-RNAse-based SI in Petunia hybrida L.
View Article and Find Full Text PDFOne of the urgent problems of gene therapy is the search for effective transfection methods. Synthetic cationic peptides (CPs) are considered to be one of the most promising approaches for intracellular transport of oligonucleotides. Almost unlimited possibilities of the architectural design of CPs (linear and cyclic structures with a variation of chirality as well as dendrimers) make CPs an effective tunable carrier in this field.
View Article and Find Full Text PDFThe formation of fertile male gametophyte is known to require timely degeneration of polyfunctional tapetum tissue. The last process caused by the programmed cell death (PCD) is a part of the anther program maturation which leads to sequential anther tissue destruction coordinated with pollen differentiation. In the present work, distribution of abscisic acid (ABA) and indole-3-acetic acid (IAA) in developing anthers of male-fertile and male-sterile lines of petunia (Petunia hybrida L.
View Article and Find Full Text PDFSymbiosomes are organelle-like compartments responsible for nitrogen fixation in infected nodule cells of legumes, which are formed as a result of symbiotic association of soil bacteria rhizobia with certain plant root cells. They are virtually the only source of reduced nitrogen in the Earth's biosphere, and consequently, are of great importance. It has been proven that the functioning of symbiosomes depends to a large extent on the transport of various metabolites and ions - most likely including Ca2+ - across the symbiosome membrane (SM).
View Article and Find Full Text PDFInto the fold: Prion diseases are neurodegenerative disorders characterized by the accumulation in the brain of a self-replicating, misfolded isoform (PrP ) of the cellular prion protein (PrP ). No therapies are available for these pathologies. We capitalized on previously described cell-based assays to screen a library of small molecules, and identified 55, a compound capable of counteracting both prion replication and toxicity.
View Article and Find Full Text PDFThe genus Deschampsia P. Beauv (Poaceae) involves a group of widespread polymorphic species. Some of them are highly tolerant to stressful and variable environmental conditions, and D.
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