Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “MACROMOLECULAR SYSTEMS”

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 235 records · Page 13Linked to original sources
PubMed1987

Autoantibodies against RNA polymerase I in scleroderma and Sjögren's syndrome sera.

Anti-RNA polymerase I antibodies were detected by radioimmunoassay in the sera of 8 out of 9 Sjögren's syndrome patients, 11 out of 19 individuals with scleroderma, and 19 out of 19 systemic lupus erythematosus patients. The results of the radioimmunoassay were confirmed by demonstrating the ability of the patients' IgG to inhibit RNA polymerase I activity in vitro. Sera from four patients in each category were also tested for reaction with individual subunits of RNA polymerase I. All 4 SLE sera, 3 out of 4 scleroderma sera and 1 out of 4 Sjögren's syndrome sera contained antibodies against the 65 kDa (S3) subunit of RNA polymerase I in addition to antibodies against one other subunit. Sera from the remaining scleroderma and Sjögren's syndrome patients tested in this assay contained only anti-S3 antibodies. These results demonstrate that anti-RNA polymerase I antibodies are characteristic of a variety of rheumatic autoimmune sera.

Autoantibodies↗
PubMed2001

alpha-Synuclein forms a complex with transcription factor Elk-1.

alpha-Synuclein has been identified as a component of Lewy bodies in Parkinson's disease and diffuse Lewy body disease, and glial cytoplasmic inclusions (GCIs) in multiple system atrophy (MSA). To explore the role of alpha-synuclein in the pathogenesis, we searched for molecules interacting with alpha-synuclein and discovered that GCIs are stained by anti-Elk-1 antibody. To seek the role of Elk-1 in synucleinopathies, we cotransfected alpha-synuclein and Elk-1 to cultured cells, and found small granular structure complexes where the two molecules colocalized. Moreover, alpha-synuclein and Elk-1 were co-immunoprecipitated from the cell lysates. For formation of the complex, the presence of both ETS and B-box domains of Elk-1 was required. Although there was no evidence of direct binding between alpha-synuclein and Elk-1, we discovered that alpha-synuclein and Elk-1 both bind to ERK-2, a MAP kinase. The effect of alpha-synuclein on the MAP kinase pathway was assessed using the Pathdetect system, which showed prominent attenuation of Elk-1 phosphorylation with alpha-synuclein, and especially A53T mutant. Our results suggest that alpha-synuclein reacts with the MAP kinase pathway, which might cause dysfunction of neurons and oligodendrocytes and lead to neurodegeneration in Parkinson's disease and MSA.

Amino Acid Motifs↗
PubMed1981

Urinary macromolecular substances as natural inhibitors of calcium oxalate crystal aggregation.

We studied the inhibitory effect of urinary macromolecular substances (UMM), more than 10,000 mol. wt., on aggregation of calcium oxalate crystals in a crystal-seed system and a non-crystal-seed system. In both assay systems, UMM from non-stone-farmers showed a marked inhibitory activity on crystal aggregation, whereas UMM from recurrent stone-formers showed a weak inhibitory activity. The distinction between the two types of UMM was greater in the non-crystal-seed system. The macromolecular inhibitors seemed to be composed of proteins or protein-complexes inasmuch as approximately 70 to 90 per cent of the macromolecular inhibitory activity was destroyed by protein digestion with pronase. Urinary acid glycosaminoglycans, which have been considered possible inhibitors, played a small role in the inhibition of crystal aggregation.

Adult↗
PubMedDate not supplied

Decreasing resistance during fast infusion of a subcutaneous tumor.

High interstitial pressure limits the uptake of systemically-administered macromolecular agents. Fast infusion, which has been found to spread by convection macromolecules in the brain, was examined in a xenograft tumor system. Subcutaneous human U251 glioblastoma tumors (0.3-1.3 cm3) were infused for up to 40 minutes starting at 20 microliters/minutes while line pressure was recorded. The spread of blue dextran (molecular weight 2 x 10(6) was examined in excised tumors. Resistance to infusion decreased with time so that the infusion rate could be increased without an increase in line pressure. Blue dextran was spread up to the length of the tumor (maximum of 1.5 cm), but the spreading appeared to be asymmetric. The results suggest the pressures produced by the infusion dilated the tumor tissue, thus producing increased hydraulic conductivity. Although this produces rapid convective spread, the spread is asymmetric. Possible methods for obtaining a more uniform or controlled convective spread of macromolecular agents are discussed.

Animals↗
PubMed1987

Poly(I).poly(C), a potential drug carrier for the antitumor agent mitoxantrone: in vitro drug binding study.

Coupling of mitoxantrone, a new antitumor agent, to a macromolecular carrier system may improve the drug's selectivity of action and pharmacokinetic properties. We have studied in vitro binding of mitoxantrone to poly(I).poly(C), a macromolecular, double-stranded homoribopolymer, by equilibrium dialysis and high-performance liquid chromatography (HPLC). Results showed high binding affinity for mitoxantrone to poly(I).poly(C) (Kd = 1.05 X 10(-6) M), the calculated number of mitoxantrone-binding sites is 60 per molecule poly(I).poly(C). In view of the good tolerance in clinical studies, poly(I).poly(C) may thus be a useful drug carrier for mitoxantrone. A mitoxantrone:poly(I).poly(C) ratio of 1:30 (w/w) is recommended for therapeutic studies.

Binding Sites↗
PubMed1979

Bootstrapping on the adaptive landscape.

Different versions of a gene or of a multigenic system may be essentially equivalent so far as the specific function of the structures which they code for or control is concerned, but very different with respect to their amenability to evolution. The structural features which increase evolutionary amenability are a disadvantage to the organism in terms of energy. Nevertheless, they accumulate in the course of evolution as a consequence of hitchhiking along with the desirable traits whose evolution they make possible. This is the bootstrap principle of evolutionary adaptability. In terms of the adaptive landscape bootstrapping corresponds to populations evolving in such a way that they occupy regions of the landscape which are more amenable to evolutionary hill climbing. The bootstrapping idea has implications for structure-function relations in a number of complex biological information processing systems, including biochemical systems, the immune system, and the brain. Bootstrapping is also discussed in connection with the origin of information processing (the origin of life) and in connection with possible designs for macromolecular computing systems.

Adaptation, Biological↗
PubMed2005

A hybrid systems framework for cellular processes.

With the availability of technologies that allow us to obtain stimulus-response time series data for modeling and system identification, there is going to be an increasing need for conceptual frameworks in which to formulate and test hypotheses about intra- and inter-cellular dynamics, in general and not just dependent on a particular cell line, cell type, organism, or technology. While the semantics can be quite different, biologists and systems scientists use in many cases a similar language (notion of feedback, regulation, etc.). A more abstract system-theoretic framework for signals, systems, and control could provide the biologist with an interface between the domains. Apart from recent examples to identify functional elements and describing them in engineering terms, there have been various more abstract developments to describe dynamics at the cell level in the past. This includes Rosen's (M,R)-systems. This paper presents an abstract and general compact mathematical framework of intracellular dynamics, regulation and regime switching inspired by (M,R)-theory and based on hybrid automata.

Algorithms↗
PubMed1999

Development of blood-labyrinth barrier in the semicircular canal ampulla of the rat.

Cationic polyethyleneimine (PEI) administered intravenously was transported to anionic sites on the capillary and subepithelial basal laminae (BL) in the vestibular labyrinth. Therefore, changes in the PEI distribution on the BL reflect changes in the transport system in the vestibular labyrinth. A 0.1% PEI solution was administered intravenously (7.5 ml/kg) to developing (1, 4, 7, 14 days after birth) and adult rats in order to investigate the development of the macromolecular transport in the ampulla of the semicircular canal as a function of age. After 1 h, the bony labyrinth was removed and embedded in Epoxy resin. Ultrathin sections of the ampulla were then examined with a transmission electron microscope. In the subepithelial BL in the dark cell area and capillary BL in the crista ampullaris, the PEI distribution in both 1- and 4-day-old rats was markedly increased compared to that in either 7-, 14-day or adult rats. In the sensory cells in 1-, 4-day or 7-day-old rats, PEI density and area was significantly greater than in the adult rats. These findings suggest that the macromolecular transport system in the developing rat ampulla becomes mature by 14 days after birth and that the maturation of its transport system in the ampulla is strongly associated with that in the stria vascularis.

Animals↗
PubMed1993

Molecular cloning and characterization of 13 out genes from Erwinia carotovora subspecies carotovora: genes encoding members of a general secretion pathway (GSP) widespread in gram-negative bacteria.

The chemical mutagen ethylmethanesulphonate (EMS) has been used to generate mutants of Erwinia carotovora subspecies carotovora which are defective in the secretion of pectinases (Pel) and cellulases (Cel) but unaltered for protease (Prt) secretion. Such mutants, called Out-, still synthesize Pel and Cel but these enzymes accumulate within the periplasm. Cosmid clones carrying wild-type E. carotovora ssp. carotovora DNA, identified by their ability to restore the Out+ phenotype when transferred to some Out- mutants, were classified into six complementation groups using cosmids and cosmid derivatives. Analysis of the nucleotide sequence of a 12.7 kb DNA fragment, encompassing complementing cosmid inserts, revealed a coding capacity for 13 potential open reading frames (ORFs), and these were designated outC-outO. Some of the out gene products were visualized using a T7 gene 10 expression system. The predicted Out proteins are highly similar to components of extracellular enzyme secretion systems from a diverse range of eubacteria including Erwinia chrysanthemi, Klebsiella oxytoca, Aeromonas hydrophila, Pseudomonas aeruginosa and Xanthomonas campestris. Lower levels of similarity exist between Ecc Out proteins and components of macromolecular trafficking systems from Bacillus subtilis, Haemophilus influenzae, Agrobacterium tumefaciens, Yersinia pestis and a protein involved in the morphogenesis of filamentous bacteriophages such as M13.

Amino Acid Sequence↗
PubMed1975

Free energy and the kinetics of biochemical diagrams, including active transport.

In earlier papers on muscle contraction it was found very useful to relate the actual (not standard) free energy levels of the different states in the biochemical diagram of the myosin cross-bridge to the first-order rate constants governing transitions between these states and to the details of the conversion of ATP free energy into mechanical work. This same approach is applied here to other macromolecular biochemical systems, for example, carriers in active transport, and simple enzyme reactions. With the definition of free energy changes between states of diagram used here (and in the muscle papers), the rate constants of the diagram are firat order, the macromolecular transitions are effectively isomeric, the equilibrium constants are dimensionless, the free energy changes are directly related to first-order rate constant ratios, and the ratio of products of forward and backward rate constants around any cycle of the diagram is related to operational free energy changes (e.g. the in vivo free energy of ADP HYDROLYSIS). These general points are illustrated by means of particular arbitrary models, especially transport models. In contrast to the muscle case, the free energy conversion question in other biochemical systems can be handled at the less detailed, complete-cycle level rather than at the elementary transition level. There is a corresponding complete-cycle kinetics, with composite first-order rate constants for the different possible cycles (in both directions). An introductory stochastic treatment of cycle kinetics is included.

Adenosine Triphosphatases↗
PubMedDate not supplied

The suitability of Ta6Br12(2+) for phasing in protein crystallography.

The title compound Ta6Br12(2+) is of interest for the analysis of biological structures as a heavy metal derivative with great potential for the structure determination of large protein systems. In macromolecular crystallography the phases of the measured structure factor amplitudes have to be determined by compounds that produce measurable changes of the diffraction intensities. Ta6Br12(2+) uniquely meets the demands of a heavy metal derivative and is an important tool for phase determination, especially considering the structure determination of large protein systems.

Bromides↗
PubMed2001

Regulation of the transcriptional coactivator PGC-1 via MAPK-sensitive interaction with a repressor.

Mechanisms and signals that regulate transcriptional coactivators are still largely unknown. Here we provide genetic evidence for a repressor that interacts with and regulates the nuclear receptor coactivator PGC-1. Association with the repressor requires a PGC-1 protein interface that is similar to the one used by nuclear receptors. Removal of the repressor enhances PGC-1 coactivation of steroid hormone responses. We also provide evidence that interaction of the repressor with PGC-1 is regulated by mitogen-activated protein kinase (MAPK) signaling. Activation of the MAPK p38 enhances the activity of wild-type PGC-1 but not of a PGC-1 variant that no longer interacts with the repressor. Finally, p38 activation enhances steroid hormone response in a PGC-1-dependent manner. Our data suggest a model where the repressor and nuclear receptors compete for recruiting PGC-1 to an inactive and active state, respectively. Extracellular signals such as nuclear receptor ligands or activators of the MAPK p38 can shift the equilibrium between the two states.

Amino Acid Motifs↗
PubMed2003

p27Kip1 inhibition of GRB2-SOS formation can regulate Ras activation.

p27(Kip1) (p27) is often inappropriately downregulated in aggressive human cancers. Although p27 can inhibit cyclin-dependent kinases (CDKs), low p27 does not always correlate with increased CDK activity. Furthermore, cells derived from p27(-/-) mice respond to antimitogens, maintain restriction point control, and do not deregulate CDKs. Thus, disruption of a p27 function other than CDK inhibition may contribute to the disease state. A yeast two-hybrid screen identified growth factor receptor-bound protein 2 (GRB2) as a p27 binding partner. We now demonstrate that p27 can inhibit GRB2 function by blocking its association with the guanine nucleotide exchange factor SOS. Endogenous p27 is rapidly exported from the nucleus to the cytoplasm in response to mitogen stimulation, where it binds GRB2 concomitant with a decrease in GRB2-associated SOS. As predicted, mitogen-stimulated p27(-/-) cells maintained their GRB2-SOS complexes for significantly longer. The Ras/mitogen-activated protein kinase pathway does not appear to be deregulated in cells lacking p27 despite excess GRB2-SOS, suggesting that additional control mechanisms are present. A transient-transfection approach was employed to show that p27 can inhibit Ras activation by targeting GRB2 and further revealed that the CDK and GRB2 inhibitory functions of p27 are separable and distinct. Thus, p27 downregulation may compromise control of Ras, one of the most common oncogenic events in human cancer.

Adaptor Proteins, Signal Transducing↗
PubMed2003

1H,15N,13C-triple resonance NMR of very large systems at 900 MHz.

We provide quantitative signal to noise data and feasibility study at 900 MHz for 1H-15N-13C triple resonance backbone assignment pulse sequences obtained from a medium sized 2H, 13C, 15N labeled protein slowed down in glycerol-water solution to mimic relaxation and spectroscopic properties of a much larger protein system with macromolecular tumbling correlation time of 52 and 80 ns, respectively, at 296 and 283 K (corresponding to molecular weights of 130 and 250 kDa). Comparisons of several different schemes for transferring magnetization from proton to nitrogen and back to proton confirms Yang and Kay's 1999 prediction that avoiding the unfavorable relaxation properties of 1H-15N multiple quantum coherence in the TROSY phase cycle of the final 15N-1H transfer before acquisition is crucial for maximal sensitivity from these very large molecular weight systems. We also show results which confirm some predictions regarding the superiority of TROSY at 900 MHz vs. 800 MHz especially as the molecular weights become very large.

Carbon Isotopes↗