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At least 19 recordsLinked to original sources
PubMed2026

When Homing Endonuclease Meets Transposon: The OMEGA System.

Sequence-specific DNA endonucleases have made significant contributions to biology, biotechnology, and medicine; restriction enzymes and homing endonucleases are among classic examples. The demonstration of programmable genome editing using Cas9 in the CRISPR-Cas system, in which the target DNA sequence is recognized by base pairing with a guide RNA, revolutionized the field of genome engineering, making target selection more flexible and convenient. The OMEGA (Obligate Mobile Element-Guided Activity) system, considered a precursor to Cas12, and likely to Cas9, in the CRISPR-Cas system, is an RNA-guided DNA endonuclease composed of a TnpB, IscB, IsrB, or Fanzor protein, and a structural RNA designated reRNA or ωRNA. The OMEGA system is present in the three domains of life as an auxiliary component of transposons. The OMEGA system cuts DNA in an allele from which a transposon is excised and triggers recombination to reinstate the transposon at the same position. This "transposon restorative homing" redefines the OMEGA system as a homing endonuclease. In this review, the selfish aspects of the OMEGA system are discussed in the historical context of homing endonuclease research.

Cas12↗
PubMed2025

Engineer the eukaryotic OMEGA-Fanzor systems for genome editing in plants.

The activity of the eukaryotic OMEGA-Fanzor genome editing system remains limited in plants. We engineered the Fanzor nucleases SpuFz1, GtFz1, NlovFz2, and MmeFz2 in plants, with NlovFz2 being the most efficient, achieving up to 50.0% editing in regenerated rice plants, making it a promising tool for plant genome editing.

Oryza↗
PubMed1975

Omega-1, Omega-2 and Omega-3 hydroxylation of long-chain fatty acids, amides and alcohols by a soluble enzyme system from Bacillus megaterium.

A soluble enzyme preparation from Bacillus megaterium, previously shown to hydroxylate free fatty acids to isomeric mixtures of Omega-1, Omega-2 and Omega-3 monohydroxy fatty acids in the presence of NADPH and O2, has now been shown to act also on fatty amides but not only hydrocarbons or fatty acid methyl esters. Using 14-C-labelled substrates, both the chain-length specificity and the positional specificity of hydroxylation was determined for fatty acids, alcohols and amides. The most active saturated fatty acid (pentadecanoic) was hydroxylated at a rate 10 times greater than the most active amide (myristamide) and 14 times faster than the most active alcohol (1-tetradecanol). Among the saturated fatty acids, the order of activity as hydroxylation substrates was C15 greater than C16 greater than C14 greater than C17 greater than C13 greater than C18 = C12. For amides the order was C14 greater than C12 greater than C15 greater than C16 while for alcohols it was C14 greater than C13 = C15 greater than C12 greater than C15. Four cis-monounsaturated fatty acids were also tested. Oleic, palmitoleic and cis-12-octadecenoic acids were more active than their saturated analogs but cis-5-tetradecenoate was less active than myristate. For all of the substrates mentioned above, with the possible exception of several unsaturated acids, the alkyl chains were monohydroxylated to give isomeric mixtures of the Omega-1, Omega-2 and Omega-3 derivatives. The distribution of these three isomers varied with chain-length and type of substrate but generally, the Omega-2 position was favored. The terminal methyl (Omega) group of these substrates was never hydroxylated and there did not appear to be significant hydroxylation of methylene carbons beyond the Omega-3 position. Based on the data presented here and in a previous paper, a model is proposed for the enzyme-substrate complex which involves hydrophobic binding and sequestering of the terminal methyl group of the substrate and electrostatic binding of the substrate's polar functional group.

Amides↗
PubMed1977

Selective inhibition of tRNATyr transcription by guanosine 3'-diphosphate 5'-diphosphate.

Guanosine 3'-diphosphate 5'-diphosphate (ppGpp) selectively reduces the synthesis of su+III tRNA from omega 80 psu+III DNA relative to the synthesis of omega 80 RNA in a system in vitro containing DNA and Escherichia coli RNA polymerase holoenzyme as the sole macromolecular components. The response of su+III tRNA synthesis to increasing salt and to temperature in the presence of ppGpp suggests that the nucleotide may reduce the affinity of the enzyme for su+III promoters. The Ki for the selective inhibition of tRNA synthesis by ppGpp is 4 muM in contrast to the value of 150 muM for the inhibition of rRNA synthesis.

Ammonium Chloride↗
PubMed1977

Effect of metabolites on epsilon-N-hydroxylysine formation in cell-free extracts of Aerobacter aerogenes 62-1.

The conversion of L-lysine to its corresponding epsilon-N-hydroxy derivative has been achieved for the first time by cell-free extracts of Aerobacter aerogenes 62-1. Partial fractionation by differential centrifugation (at 12 000 X g) revealed that both supernatant and pellet are essential for maximum enzymatic activity. The omega-N-hydroxylase (EC 1.14.99) was found to function optimally at pH 7-7.5 and exhibited an apparent Km of about 75 muM for L-lysine. L(+)-Lactate or DL-lactate and pyruvate greatly stimulate the omega-N-hydroxylase activity. The system is strongly inhibited by arsenite and sulfite.

Arsenic↗
PubMed2025

Immunomodulatory Effects of Omega-3 Fatty Acids: Mechanistic Insights and Health Implications.

Omega-3 fatty acids play a significant role in immunomodulation, with nutrigenomic approaches highlighting their impact on gene expression related to immune responses. Research indicates that omega-3 fatty acids can modulate inflammatory pathways, potentially reducing chronic inflammation and enhancing immune function. This review discusses the intersection of nutrigenomics and nutriepigenomics, focusing on how omega-3 fatty acids influence gene expression, immune function, and overall health. The immune system is a complex network responsible for defending the body against pathogens and maintaining internal balance. Comprised of innate and adaptive immunity, the system involves various cells, tissues, and organs working together to combat infections and prevent diseases. Omega-3 polyunsaturated fatty acids (PUFAs), particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), play a significant role in modulating the immune system. These fatty acids influence immune cell function, membrane fluidity, and signaling processes, enhancing immune responses and reducing inflammation. Furthermore, EPA and DHA affect several signaling pathways, reducing the expression of proinflammatory cytokines and inhibiting nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation, a critical transcription factor in the inflammatory response. Additionally, they activate PPAR-γ, further diminishing inflammatory gene expression. As precursors to specialized proresolving lipid mediators, EPA and DHA help shift the lipid mediator profile from proinflammatory to antiinflammatory derivatives, thus aiding in the resolution of inflammation.

Humans↗
PubMed2026

Lysine iminylation derived from ω-3 polyunsaturated fatty acids.

Protein posttranslational modifications (PTMs) play a central role for regulating protein function and cellular processes, with many PTMs arising from reactions with electrophilic metabolites. Here we extend the known landscape of PTMs with the identification of "lysine C3-iminylation," the conjugation of protein lysine residues with propionaldehyde. To stabilize iminylation for mass spectrometric analyses and distinguish it from other isomeric PTMs, we developed a fixation and stable-isotope labeling approach based on parallel reduction of proteome with sodium borohydride and borodeuteride. Analyses of protein hydrolysates confirmed the presence of C3-iminylation in Caenorhabditis elegans and mouse. Additionally, proteomics results demonstrated specificity of this PTM in vitro and in vivo and revealed C3-iminylation in proteins related to critical metabolic pathways. Importantly, collective evidence from isotope tracing as well as genetic, dietary, and pharmacological manipulation experiments uncovered that C3-iminylation originates from cytochrome P450 (CYP)-mediated oxidation of omega-3 fatty acids. Correspondingly, C3-iminylation levels were elevated in C. elegans daf-2(e1370) mutants, an aging model, in which CYP activity is generally increased. These findings not only expand our understanding of the biochemical diversity of PTMs but also underscore the complex interplay between lipid metabolism and protein modifications, enabling further exploration of their biological and clinical implications.

Animals↗
PubMed1979

Vasodilation and inhibition of platelet aggregation by prostacyclins with modified omega-side chain.

Prostacyclin analogs with modified omega-side chain were synthetized in search of therapeutically useful agents. To characterize the vasodilator and platelet-antiaggregating properties, prostacyclin analogs were tested on systemic blood pressure in anesthetized rats, relaxation of bovine coronary artery and inhibition of arachidonic acid induced human platelet aggregation. The sodium salt of prostacyclin induced a dose dependent decrease of blood pressure with an ED25 of 0.23 microgram/kg i.v., a marked relaxation of bovine coronary artery with an IC50 of 5.9 ng/ml and a strong inhibition of platelet aggregation with an ED50 of 3x10(-9) M. Similar results were obtained with prostacyclin-methylester. Replacement of the n-pentyl moiety attached to C-15 of prostacyclin by cyclohexyl, 2-(2-furyl)ethyl, 2-(3-thienyl)ethyl and especially by 3-thienyl-oxymethyl yielded analogs with comparable prostacyclin properties, while substitution by 1,1-dimethyloxaalkyl residues was followed by a marked loss of activity. The order of potency among the analogs of the sodium salt and methylester of prostacyclin with strong vasodepressor and antiaggregatory properties was identical in all three models used. The three test systems used for evaluation have demonstrated that suitable modifications of the omega-side chain of prostacyclin result in potent vasodilator and platelet-antiaggregating agents.

Animals↗
PubMed1978

Properties of internally perfused, voltage-clamped, isolated nerve cell bodies.

The membrane properties of isolated neurons from Helix aspersa were examined by using a new suction pipette method. The method combines internal perfusion with voltage clamp of nerve cell bodies separated from their axons. Pretreatment with enzymes such as trypsin that alter membrane function is not required. A platinized platinum wire which ruptures the soma membrane allows low resistance access directly to the cell's interior improving the time resolution under voltage clamp by two orders of magnitude. The shunt resistance of the suction pipette was 10-50 times the neuronal membrane resistance, and the series resistance of the system, which was largely due to the tip diameter, was about 10(5) omega. However, the peak clamp currents were only about 20 nA for a 60-mV voltage step so that measurements of membrane voltage were accurate to within at least 3%. Spatial control of voltage was achieved only after somal separation, and nerve cell bodies isolated in this way do not generate all-or-none action potentials. Measurements of membrane potential, membrane resistance, and membrane time constant are equivalent to those obtained using intracellular micropipettes, the customary method. With the axon attached, comparable all-or-none action potentials were also measured by either method. Complete exchange of Cs+ for K+ was accomplished by internal perfusion and allowed K+ currents to be blocked. Na+ currents could then be blocked by TTX or suppressed by Tris-substituted snail Ringer solution. Ca2+ currents could be blocked using Ni2+ and other divalent cations as well as organic Ca2+ blockers. The most favorable intracellular anion was aspartate-, and the sequence of favorability was inverted from that found in squid axon.

Animals↗
PubMed1978

Mutagenicity of alkyl-(omega-hydroxyalkyl) nitrosamines related to dibutylnitrosamine.

Various alkyl-(omega-hydroxyalkyl) derivatives related to dibutylnitrosamine (DBN) were investigated for mutagenicity in the absence of liver-activation system. Butyl-(4-hydroxybutyl)-, butyl-(3-hydroxypropyl)-, and butyl-(2-hydroxyethyl)-nitrosamines were so tested and found to be mutagenic for TA 1535 strain of Salmonella typhimurium. In all cases, a simple dose-response relationship was observed. Furthermore, no significant (p less than 0.05) differences in the mutagenicity of the various test compounds were observed as the alkyl sidechain possessing the OH group increased in length. From these results it is siggested that mutagenesis in S. typhimurium by the higher dialkylnitrosamines is partially due to the formation of omega-hydroxylated derivatives in addition to the major mutagenic metabolite derived from alpha-carbon dealkylation.

Dose-Response Relationship, Drug↗
PubMedDate not supplied

[Phenomenon of w-reactivation in plasmids].

An analysis of the action of the bacterial repair system on the UV-irradiated pMB9 plasmid has been carried out. It has been shown that the UV-irradiated plasmid is repaired in the bacteria similarly to the DNA of bacteriophage (lambda): the effectiveness of the UVR-system is lowered two-three times, and the postreplicativing REC system acts only at low doses of the UV-light. The phenomenon of omega-reactivation is observed both with plasmid and phage DNAs.

Coliphages↗
PubMed1978

Fibrinolytic activity in blood and cerebrospinal fluid in subarachnoid hemorrhage from ruptured intracranial saccular aneurysm before and during EACA treatment.

10 patients suffering from intracranial aneurysm causing subarachnoid hemorrhage (SAH) have been treated during the acute pre-and postoperatory phase with omega-aminocaproic acid. The blood and the cerebrospinal fluid of the treated patients have been analyzed in order to study fibrin(ogen) degradation products (FDP) and fibrinolytic activity (FA). The results so obtained show only an alteration of local fibrinolytic processes either inside or around the aneurysmatic clot: there were no alterations of the systemic FA. Furthermore, monitoring of FDP and FA was a very useful tool in those patients who took advantage of the treatment with omega-aminocaproic acid which protected them from rebleeding.

Aminocaproates↗
PubMed1975

Fatty acid hydroxylation in rat kidney cortex microsomes.

Rat kidney microsomes have been found to catalyze the hydroxylation of medium-chained fatty acids to the omega- and (omego-1)-hydroxy derivatives. This reaction, which requires NADPH and molecular oxygen, is a function of monooxygenase system present in the kidney microsomes, containing NADPH-cytochrome c reductase and cytochrome P-450K. NADH is about half as effective as an electron donor as NADPH and there is an additive effect in the presence of both nucleotides. Cytochrome P-450K absorbs light maximally at 452-3 nm, when it is reduced and bound to carbon monoxide. The extinction coefficient of this complex is 91 mM(-1) cm(-1). Electrons from NADPH are transferred to cytochrome P-450K via the NADPH-cytochrome c reductase. The reduction rate of cytochrome P-450K is stimulated by added fatty acids and the reduction kinetics reveal the presence of endogenous substrates bound to cytochrome P-450K. Both cytochrome P-450K concentration and fatty acid hydroxylation activity in kidney microsomes are increased by starvation. On the other hand, phenobarbital treatment of the rats has no effect on either the hemoprotein or the overall hydroxylation reaction and 3,4-benzpyrene administration induces a new species of cytochrome P-450K not involved in fatty acid hydroxylation. Cytochrome P-450K shows, in contrast to liver P-450, high substrate specificity. The only substances forming enzyme-substrate complexes with cytochrome P-450K are the medium-chained fatty acids and certain derivatives of these acids. The chemical requirements for substrate binding include a carbon chain of medium length and at the end of the chain a carbonyl group and a free electron pair on a neighbouring atom. The distance between the binding site for the carbonyl group and the active oxygen is suggested to be in the order of 16 A. This distance fixes the ratio of omega- and (omega-1)-hydroxylated products formed from a certain fatty acid by the single species of cytochrome P-450K involved. The membrane microenvironment seems also to be of importance for the substrate specificity of cytochrome P-450K, since removal of the cytochrome from the membrane lowers its binding specificity to some extent. A comparison between the liver and kidney cytochrome P-450 systems suggests that the kidney cytochrome P-450K system is specialized for fatty acid hydroxylation.

Animals↗
PubMed1975

The microbial metabolism of acetophenone. Metabolism of acetophenone and some chloroacetophenones by an Arthrobacter species.

1. An organism that utilizes acetophenone as sole source of carbon and energy was isolated in pure culture and tentatively identified as an Arthrobacter sp. 2. Cell-free extracts of the acetophenone-grown organism contained an enzyme, acetophenone oxygenase, that catalysed an NADPH-dependent consumption of O(2) in the presence of the growth substrate; approx. 1mol of O(2) and 1mol of NADPH were consumed per mol of acetophenone oxidized. 3. Cell-free extracts also contained an enzyme capable of the hydrolysis of phenyl acetate to phenol and acetate. The amount of this esterase was increased markedly by growth on acetophenone. 4. The observed products of the acetophenone oxygenase reaction by crude cell-free extracts were phenol and acetate. However, inhibition of the phenyl acetate esterase by paraoxon resulted in the formation of phenyl acetate from acetophenone. 5. A degradative sequence is proposed in which acetophenone is metabolized by an oxygen-insertion reaction to form phenyl acetate. Further metabolism occurs by hydrolysis of this ester. 6. The organism and extracts were shown to metabolize chlorinated acetophenones. The environmental implications of this observation are discussed.

Acetophenones↗
PubMed2016

Toxin-Antitoxin Systems of Staphylococcus aureus.

Toxin-antitoxin (TA) systems are small genetic elements found in the majority of prokaryotes. They encode toxin proteins that interfere with vital cellular functions and are counteracted by antitoxins. Dependent on the chemical nature of the antitoxins (protein or RNA) and how they control the activity of the toxin, TA systems are currently divided into six different types. Genes comprising the TA types I, II and III have been identified in Staphylococcus aureus. MazF, the toxin of the mazEF locus is a sequence-specific RNase that cleaves a number of transcripts, including those encoding pathogenicity factors. Two yefM-yoeB paralogs represent two independent, but auto-regulated TA systems that give rise to ribosome-dependent RNases. In addition, omega/epsilon/zeta constitutes a tripartite TA system that supposedly plays a role in the stabilization of resistance factors. The SprA1/SprA1AS and SprF1/SprG1 systems are post-transcriptionally regulated by RNA antitoxins and encode small membrane damaging proteins. TA systems controlled by interaction between toxin protein and antitoxin RNA have been identified in S. aureus in silico, but not yet experimentally proven. A closer inspection of possible links between TA systems and S. aureus pathophysiology will reveal, if these genetic loci may represent druggable targets. The modification of a staphylococcal TA toxin to a cyclopeptide antibiotic highlights the potential of TA systems as rather untapped sources of drug discovery.

Antitoxins↗