Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “modification”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,423 records · Page 79Linked to original sources
PubMed1977

[Behavior modification and obesity (author's transl)].

Good results were obtained treating 49 obese patients with an elaborated selfcontrol behavior modification program. This program was an addition to the normal program of the obesity clinic of the 2. Medizinische Klinik der Universität Düsseldorf. The normal program contains some principles of behavior modification but less accentuated. After the initial 12 weeks of controlled training patients tried to reduce weight further decreasing external control. Only few patients were able to loose additional pounds during this period of 8 weeks. At the end of the initial 12 weeks patients had asked for another control before the vacational season, but only 10 out of 49 appeared at the control sessions 9 months after the program's start. If an additional behavior modification program is considered for incorporation into an already existing weight reduction clinic, additional costs and expected results have to be checked. Durative success of behavior modification techniques in weight loss programs has still to be submitted to proof.

Behavior Therapy↗
PubMed1997

Kinetics of grayanotoxin evoked modification of sodium channels in squid giant axons.

Kinetics of modification of the sodium channel by alpha-dihydrograyanotoxin II (GTX) were studied with voltage-clamped squid giant axons. GTX modified the channel to generate sustained inward current, only when the membrane was kept depolarized to levels more positive than -80mV, in a voltage-dependent manner, increasing the depolarization. Repetitive depolarizing pulses suppressed rather than increased the degree of GTX-evoked modification. GTX-evoked modification proceeded with a dual exponential time course, regardless of the presence or absence of the inactivation gate, but the elimination by pronase of the inactivation gate accelerated GTX-evoked modification. GTX unbound from the sodium channel with a time constant of 30 s at -150 mV in a manner independent of the concentration. The effective concentration that produced a half-maximal sustained sodium current (EC50), which represents GTX-modified channel activity, was estimated to be about 10 microM with one-to-one stoichiometry. The activation/voltage relationship for the sustained sodium current was shifted in the hyperpolarizing direction by as much as 63-94 mV compared with that of peak sodium current. At a GTX concentration of 100 microM and at +20mV, 64% of the sodium channel population was modified. A kinetics model is proposed to account for the behavior of GTX -modified sodium channels.

Animals↗
PubMed1997

Dietary modification of human macular pigment density.

PURPOSE: The retinal carotenoids lutein (L) and zeaxanthin (Z) that form the macular pigment (MP) may help to prevent neovascular age-related macular degeneration. The purpose of this study was to determine whether MP density in the retina could be raised by increasing dietary intake of L and Z from foods. METHODS: Macular pigment was measured psychophysically for 13 subjects. Serum concentrations of L, Z, and beta-carotene were measured by high-performance liquid chromatography. Eleven subjects modified their usual daily diets by adding 60 g of spinach (10.8 mg L, 0.3 mg Z, 5 mg beta-carotene) and ten also added 150 g of corn (0.3 mg Z, 0.4 mg L); two other subjects were given only corn. Dietary modification lasted up to 15 weeks. RESULTS: For the subjects fed spinach or spinach and corn, three types of responses to dietary modification were identified: Eight "retinal responders" had increases in serum L (mean, 33%; SD, 22%) and in MP density (mean, 19%; SD, 11%); two "retinal nonresponders" showed substantial increases in serum L (mean, 31%) but not in MP density (mean, -11%); one "serum and retinal nonresponder" showed no changes in serum L, Z, or beta-carotene and no change in MP density. For the two subjects given only corn, serum L changed little (+11%, -6%), but in one subject serum Z increased (70%) and MP density increased (25%). CONCLUSIONS: Increases in MP density were obtained within 4 weeks of dietary modification for most, but not all, subjects. When MP density increased with dietary modification, it remained elevated for at least several months after resuming an unmodified diet. Augmentation of MP for both experimental and clinical investigation appears to be feasible for many persons.

Adult↗
PubMed1998

Covalent modification of hemoglobin by carbon disulfide: III. A potential biomarker of effect.

Although the neurotoxicity of CS2 has been recognized for over a century, presently there is no accepted biomarker of effect for CS2 exposure. Previous investigations have supported covalent cross-linking of erythrocyte spectrin as a potential preneurotoxic marker reflective of the biochemical changes occurring within the axon. In the present investigation, the potential of using CS2 promoted modification of hemoglobin as a dosimeter for quantifying exposure to CS2 was evaluated. Liquid chromatography was used to isolate and measure alpha and beta chains of globin in blood obtained from rats exposed to CS2 by inhalation as a function of exposure level and duration. The degree of globin modification was compared to light microscopic and ultrastructural changes in the central and peripheral nervous systems to determine the temporal relationship of globin modification to the structural changes in the axon. Samples obtained from rats exposed to CS2 contained a globin chain not present in control samples. Analysis of the peak corresponding to the new chain using electrospray mass spectrometry was consistent with the generation of a single dithiocarbamate ester or thiourea intramolecular cross-link in the alpha 1 major chain. This altered globin chain was detectable both at the subneurotoxic level of exposure and prior to axonal structural changes at the neurotoxic levels of exposure used. The extent of modification was positively correlated to the exposure level and duration for all conditions examined. These findings support hemoglobin as a potential preneurotoxic biomarker of effect for CS2 possessing several practical advantages relative to the use of CS2-mediated spectrin cross-linking.

Administration, Inhalation↗
PubMed1998

[Interaction of derivatives of short oligonucleotides with nucleic acids. VIII. Characteristics of target DNA modification by alkylating oligonucleotide derivatives in tandem complexes].

The influence of effectors [octanucleotides and their 3',5'-di-N-(2-hydroxyethyl)phenazinium derivatives] on the modification of a target DNA by alkylating oligonucleotide derivatives forming duplexes of different stability with the target ws studied. It is shown that, being in tandem complexes immediately adjacent to the reactive group of an oligonucleotide reagent possessing a high hybridization capacity, the effector, on the one hand, enhances the stability of the reagent target duplex, and on the other hand, changes the site-specificity of alkylation and decreases the efficiency of the target modification at temperatures that provide a high extent of the target association with the reagent. Conversely, in the case of oligonucleotide reagents forming weak complexes with the target, effectors enhance both the stability of the target.reagent duplex and the extent of the target throughout the temperature range tested. The data indicate that the varying influence of effectors on the target modification by reagents with different hybridization capacities is due to conformational features of the target reagent duplexed regions. Increasing the rigidity of the target.reagent duplex reduces the efficiency of the target modification in tandem complexes.

Alkylating Agents↗
PubMed1976

Behavior modification: a perspective.

Behavior modification is an approach for changing behavior based on a preliminary study of the individual. Behavior change is attempted once the individual's learning characteristics and the identification of the optimal learning conditions for the learner have been analyzed. The ability to analyze systematically and to develop behavior-environment relationships also brings a responsibility to the user to understand and master the principles and procedures of behavior modification. This article basically ignores the issue of selecting broad treatment goals and the authority of clinicians or teachers to work actively toward achieving these goals. The principal focus is to provide a perspective on the evaluation and use of behavior modification programs based on their conceptual and procedural foundations. Criticisms and the misuse of behavior modification programs are included as well as a set of guidelines for evaluating and developing effective ones.

Behavior Therapy↗
PubMed1998

[Role of cervical modifications in threatened premature labor].

Uterine cervical modifications play a central role in preterm labor and are one of the main indicators for the clinical diagnosis of this syndrome. Modifications of the cervix are either isolated events "cervical incompetence" or associated with cervicovaginal infection, which is an important etiological factor. Furthermore, the extent of cervical modifications in preterm labor is probably related to the prognosis of preterm delivery. Certain developments in the treatment of preterm pregnancy have focused on the uterine cervix (e.g. cervical cerclage, treatment of cervicovaginal infections) and such strategies may facilitate the prevention of preterm delivery. The information currently available emphasizes an independent role for the uterine cervix in preterm labor. As a consequence, it should be realised that even though there is a direct association between cervical modifications and uterine contractions, management of preterm labour must not be directed exclusively at the control of uterine contractions and tocolysis.

Female↗
PubMed1998

Dietary modification of high density lipoprotein phospholipid and influence on cellular cholesterol efflux.

African green monkeys fed fat-specific diets served as a model to investigate the effect of phospholipid acyl chain modification on high density lipoprotein (HDL)-mediated cellular cholesterol efflux. Diets enriched in saturated, monounsaturated, n-6 polyunsaturated, or n-3 polyunsaturated fats were provided during both low cholesterol and cholesterol-enriched stages; sera and HDL3 samples were obtained at specific points during the treatment period. Analysis of the HDL phospholipid composition revealed significant acyl chain modification, consistent with the respective fat-specific diet. Cholesterol efflux from mouse L-cell fibroblasts to HDL3 isolated from the specific diet groups was measured and revealed no differences in the abilities of the particles to accept cellular cholesterol; determination of the bidirectional flux of cholesterol between the cells and HDL3 species further demonstrated no effect of phospholipid acyl chain modification on this process. The effects of dietary modification of phospholipid acyl chains on cellular cholesterol efflux were directly examined by isolating the HDL phospholipid and combining it with human apolipoprotein A-I to form well-defined reconstituted HDL particles. These complexes did not display any differences with respect to their ability to stimulate cellular cholesterol efflux. Incubations with 5% sera further confirmed that the fat-specific diets do not influence cholesterol efflux. These results suggest that the established influences of specific dietary fats on the progression of atherosclerosis are due to effects on cholesterol metabolism other than the efflux of cellular cholesterol in the first step of reverse cholesterol transport.

Animals↗
PubMed1998

Improving monoclonal antibody pharmacokinetics via chemical modification.

The aim of radioimmunotherapy in treating solid tumors is to target tumor sites while sparing normal tissues. This can best be achieved by using a monoclonal antibody (MAb) with high tumor uptake and rapid clearance. Because MAbs are basic, positively charged proteins, and mammalian cells are negatively charged, the electrostatic interactions between the two can create higher levels of background binding resulting in low tumor to normal organ ratios. To overcome this effect, investigators have attempted to improve MAb clearance by using various methods such as secondary agents as well as chemical and charge modifications of the MAb itself. The use of a second agent to remove the MAb involves using a biotinylated MAb followed by treatments with a molecule like avidin. Charge modification can be accomplished by conjugating a chemical moiety with a positive, negative or neutral charge to residues exposed on the surface of MAbs. Experimental results demonstrate that the lowering of the isoelectric point by this method correlates with a decreased clearance time and improved tumor targeting. Altering the pharmacokinetic characteristics of intact MAbs with charge modification can improve their clearance times to rates similar to those of MAb fragments. Several groups have reported on the effects of chemical modification using molecules such as dextran, PEG, lactose and biotin. Some of these modified MAbs retain the antigen binding specificity of the parent molecule and have improved clearance characteristics from blood and other organs. Hence, these methods can be used to improve both the diagnostic and therapeutic potential of MAbs by improving the signal to noise ratio and the absolute tumor accretion of MAb, respectively.

Animals↗
PubMed1999

Characterization of a CACAG pentanucleotide repeat in Pasteurella haemolytica and its possible role in modulation of a novel type III restriction-modification system.

In a previous study, a recombinant plasmid that contains a CACAG pentanucleotide repeat was isolated from a Pasteurella haemolytica A1 library. Southern hybridization analysis using a (CACAG)5probe indicated the presence of two loci that contain the pentanucleotide repeats on the genome of P.haemolytica A1. Additional hybridization analyses against genomic DNA from related microorganisms indicated that the repeats are only present in P.haemolytica and Pasteurella trehalosi T3. The various serotypes of P.haemolytica werefound to have either one or two of the CACAG repeat-containing loci. Examination of the locus designated Rpt2 by PCR and sequence analysis indicated that the number of CACAG repeats could change upon serial subculture which most likely occurs as a result of DNA slipped-strand mispairing. A plasmid carrying the Rpt2 locus was isolated and characterized. Sequenceanalysis indicated that the CACAG repeats are contained within the 5'-end of a gene that showed homology to mod genes of type III restriction-modification systems. A second open reading frame downstream was identified which showed homology to res genes of type III restriction-modification systems. Both the modification and restriction proteins could be expressed and polypeptides of the expected sizes were detected by SDS-PAGE. Restriction activity could also be detected in crude cytoplasmic extracts of Escherichia coli strains carrying the mod and res genes on recombinant plasmids.

Amino Acid Sequence↗
PubMed2026

Unveiling m7G modification patterns and causal drivers governing intracranial aneurysm rupture risk through multi-omics validation and m7G-MeRIP-seq profiling.

Intracranial aneurysm (IA) rupture causes severe brain hemorrhage with high mortality, yet its molecular drivers remain unclear and better risk prediction is urgently needed. Using transcriptomics, single-cell analysis, and genetic data, we investigated the role of N7-methylguanosine (m7G) RNA modification in IA. We identified distinct m7G modification patterns, validated their methylation features in patient samples, and incorporated these patterns into a machine learning-based rupture prediction model. The presence and characteristics of m7G patterns significantly improved model performance, achieving high predictive accuracy across three independent cohorts (AUC 0.91-0.95). Genetic analyses further identified three causal m7G-related genes (NSUN2, IFIT5, SNUPN), and laboratory experiments confirmed their altered expression and methylation in ruptured aneurysms. Overall, our findings demonstrate that m7G modifications play a key role in IA rupture. The validated prediction model offers strong clinical potential for rupture risk assessment, and the identified genes represent promising therapeutic targets.

Humans↗
PubMed2002

Chromatin remodeling, histone modifications, and DNA methylation-how does it all fit together?

DNA methylation is important in the control of gene transcription and chromatin structure. The complexities of this process are just beginning to be elucidated in relationship to other epigenetic mechanisms. Exciting new research in the areas of histone methylation and chromatin remodeling make it clear just how important the connections between these various mechanisms and DNA methylation are for the control of chromosome structure and gene expression. Emerging evidence suggests that chromatin remodeling enzymes and histone methylation are essential for proper DNA methylation patterns. Other histone modifications, such as acetylation and phosphorylation, in turn, affect histone methylation and histone methylation also appears to be highly reliant on chromatin remodeling enzymes. This review will summarize what is likely only the beginning of a flood of new information that will ultimately link all epigenetic modifications of the mammalian genome. A model will also be put forth to account for how chromatin modifications lead to genomic DNA methylation patterns.

Acetylation↗
PubMed2006

N-Terminal protein modifications in an insect cell-free protein synthesis system and their identification by mass spectrometry.

To evaluate the ability of an insect cell-free protein synthesis system to generate proper N-terminal cotranslational protein modifications such as removal of the initiating Met, N-acetylation, and N-myristoylation, several mutants were constructed using truncated human gelsolin (tGelsolin) as a model protein. Tryptic digests of these mutants were analyzed by MALDI-TOF MS and MALDI-quadrupole-IT-TOF MS. The wild-type tGelsolin, which is an N-myristoylated protein, was found to be N-myristoylated when myristoyl-CoA was added to the in vitro translation reaction mixture. N-myristoylation did not occur on the Gly-2 to Ala mutant, in which the N-myristoylation motif was disrupted, whereas this mutant was found to be N-acetylated after removal of the initiating Met. Analyses of Gly-2 to His and Leu-3 to Asp mutants revealed that the amino acids at positions 2 and 3 strongly affect the susceptibility of the nascent peptide chain to removal of the initiating Met and to N-acetylation, respectively. These results suggest that N-terminal modifications occurring in the insect cell-free protein synthesis system are quite similar to those observed in the mammalian protein synthesis system. Thus, a combination of the cell-free protein synthesis system with MS is an effective strategy to analyze protein modifications.

Acetylation↗
PubMedDate not supplied

Repair-modification and evolution of the eukaryotic genome organization.

For a complete reconstruction of the damaged unmethylated islands, in theory, the conventional excision-repair is sufficient. For a complete reconstruction of the damaged methylated domains, a coupling has to take place involving the excision-repair (able to reestablish their ATGC-language) plus the DNA-methylase (able to reestablish their modified ATGC5mC-language). This coupling, defined as "repair-modification," is essentially functioning during the S-phase, because the DNA-polymerase beta (pol beta) is active during the whole cell cycle, whereas the DNA-methylase (met) is active in S and appears to be repressed or inactive during the major part of G1 and during the phases G2 and M. Consequently, after damage, some silent genes might become expressed during these phases, if it is true that DNA methylation is inversely proportional to transcription. Repair-modification should, therefore, exert a continuous differential pressure on evolution of given parts of the genome, when they are methylated to a different extent. According to Darwinian concepts, repair-modification would lead to a high variability, especially of uncoding DNA sequences (if hypermethylated), whereas on the basis of this variability, selection might favor transposition of specific regulatory elements into given transcriptional units. In these, the conservative nature of the coding elements (if unmethylated) would obviously be ensured by the conventional excision-repair.

Animals↗
PubMed2006

Identifying novel proteins recognizing histone modifications using peptide pull-down assay.

Post-translational modifications of histones have been correlated with virtually all chromatin-templated processes, including gene expression regulation, DNA replication, mitosis and meiosis, and DNA repair. In order to better understand the mechanistic basis by which histone modifications participate in the control of cellular processes, it is essential to identify and characterize downstream effector proteins, or "readers", that are responsible for recognizing different marks and translating them into specific biological outcomes. Ideally, identification of potential histone-binding effectors should occur in an unbiased fashion. Although in the recent years much progress has been made in identifying readers of histone modifications, in particular methylation, recognition of the majority of known histone marks is still poorly understood. Here I describe a simple and unbiased biochemical pull-down assay that allows for the identification of novel histone effector proteins and utilizes biotinylated histone peptides modified at various residues. I provide detailed protocols and suggestions for troubleshooting.

Biotinylation↗
PubMed2026

tRNA m1A modification orchestrates STING translation in macrophages to enhance antitumor immunity and CAR-macrophage immunotherapy.

Tumor-associated macrophages (TAMs) play crucial roles in tumor progression. However, the mechanisms underlying the posttranscriptional regulation of TAMs remain largely unknown. Here, we demonstrated that Trmt61a, the "writer" enzyme of tRNA N1-methyladenosine (m1A) modification, is highly expressed in proinflammatory macrophages in tumor microenvironment. We generated conditional knockout (KO) mice for Trmt61a and observed that Trmt61a deletion in macrophages significantly promoted tumor growth. Mechanistically, we identified that m1A maintains the translation of STING, enhances STING-TBK1-IFN-β signaling in macrophages and therefore suppresses tumor cell growth. We further generated TRMT61A-overexpressing human iPSC-derived CAR-macrophage and demonstrated that human TRMT61A effectively promoted antitumor CAR-macrophage therapy in vivo. Collectively, our findings reveal a novel regulatory mechanism of tRNA m1A modification in macrophages, highlighting the antitumor therapeutic potential of targeting tRNA m1A modification in macrophages.

Animals↗
PubMed2001

Regulation of the HpyII restriction-modification system of Helicobacter pylori by gene deletion and horizontal reconstitution.

Helicobacter pylori, Gram-negative, curved bacteria colonizing the human stomach, possess strain-specific complements of functional restriction-modification (R-M) systems. Restriction-modification systems have been identified in most bacterial species studied and are believed to have evolved to protect the host genome from invasion by foreign DNA. The large number of R-Ms homologous to those in other bacterial species and their strain-specificity suggest that H. pylori may have horizontally acquired these genes. A type IIs restriction-modification system, hpyIIRM, was active in two out of the six H. pylori strains studied. We demonstrate now that in most strains lacking M.HpyII function, there is complete absence of the R-M system. Direct DNA repeats of 80 bp flanking the hpyIIRM system allow its deletion, resulting in an "empty-site" genotype. We show that strains possessing this empty-site genotype and strains with a full but inactive hpyIIRM can reacquire the hpyIIRM cassette and functional activity through natural transformation by DNA from the parental R-M+ strain. Identical isolates divergent for the presence of an active HpyII R-M pose different restriction barriers to transformation by foreign DNA. That H. pylori can lose HpyII R-M function through deletion or mutation, and can horizontally reacquire the hpyIIRM cassette, is, in composite, a novel mechanism for R-M regulation, supporting the general hypothesis that H. pylori populations use mutation and transformation to regulate gene function.

Base Sequence↗
PubMed1995

Restriction-modification systems as genomic parasites in competition for specific sequences.

Restriction-modification (RM) systems are believed to have evolved to protect cells from foreign DNA. However, this hypothesis may not be sufficient to explain the diversity and specificity in sequence recognition, as well as other properties, of these systems. We report that the EcoRI restriction endonuclease-modification methylase (rm) gene pair stabilizes plasmids that carry it and that this stabilization is blocked by an RM of the same sequence specificity (EcoRI or its isoschizomer, Rsr I) but not by an RM of a different specificity (PaeR7I) on another plasmid. The PaeR7I rm likewise stabilizes plasmids, unless an rm gene pair with identical sequence specificity is present. Our analysis supports the following model for stabilization and incompatibility: the descendants of cells that have lost an rm gene pair expose the recognition sites in their chromosomes to lethal attack by any remaining restriction enzymes unless modification by another RM system of the same specificity protects these sites. Competition for specific sequences among these selfish genes may have generated the great diversity and specificity in sequence recognition among RM systems. Such altruistic suicide strategies, similar to those found in virus-infected cells, may have allowed selfish RM systems to spread by effectively competing with other selfish genes.

Binding, Competitive↗