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At least 163 records · Page 9Linked to original sources
PubMed1996

Mapping of genomic DNA loop organization in a 500-kilobase region of the Drosophila X chromosome by the topoisomerase II-mediated DNA loop excision protocol.

The recently developed procedure of chromosomal DNA loop excision by topoisomerase II-mediated DNA cleavage at matrix attachment sites (S. V. Razin, R. Hancock, O. Iarovaia, O. Westergaard, I. Gromova, and G. P. Georgiev, Cold Spring Harbor Symp. Quant. Biol. 58:25-35, 1993; I. I. Gromova, B. Thompsen, and S. V. Razin, Proc. Natl. Acad. Sci. USA 92:102-106, 1995) has been employed for mapping the DNA loop anchorage sites in a 500-kb region of the Drosophila melanogaster X chromosome. Eleven anchorage sites delimiting 10 DNA loops ranging in size from 20 to 90 kb were found within this region. Ten of these 11 anchorage sites colocalize with previously mapped scaffold attachment regions. However, a number of other scaffold attachment regions are found to be located in loop DNA.

Animals↗
PubMed2003

Detection of BCR-ABL mutations in patients with CML treated with imatinib is virtually always accompanied by clinical resistance, and mutations in the ATP phosphate-binding loop (P-loop) are associated with a poor prognosis.

Imatinib-treated chronic myeloid leukemia (CML) patients with acquired resistance commonly have detectable BCR-ABL kinase domain mutations. It is unclear whether patients who remain sensitive to imatinib also have a significant incidence of mutations. We evaluated 144 patients treated with imatinib for BCR-ABL kinase domain mutations by direct sequencing of 40 accelerated phase (AP), 64 late chronic phase (> or = 12 months from diagnosis, late-CP), and 40 early-CP patients. Mutations were detected in 27 patients at 17 different residues, 13 (33%) of 40 in AP, 14 (22%) of 64 in late-CP, and 0 of 40 in early-CP. Acquired resistance was evident in 24 (89%) of 27 patients with mutations. Twelve (92%) of 13 patients with mutations in the adenosine triphosphate (ATP) binding loop (P-loop) died (median survival of 4.5 months after the mutation was detected). In contrast, only 3 (21%) of 14 patients with mutations outside the P-loop died (median follow-up of 11 months). As the detection of mutations was strongly associated with imatinib resistance, we analyzed features that predicted for their detection. Patients who commenced imatinib more than 4 years from diagnosis had a significantly higher incidence of mutations (18 [41%] of 44) compared with those treated within 4 years (9 [9%] of 100), P <.0001. Lack of a major cytogenetic response (MCR) was also associated with a higher likelihood of detecting a mutation; 19 (38%) of 50 patients without a MCR had mutations compared with 8 (8.5%) of 94 with an MCR, P <.0001. In conclusion, the detection of kinase domain mutations using a direct sequencing technique was almost always associated with imatinib resistance, and patients with mutations in the P-loop had a particularly poor prognosis.

Adenosine Triphosphate↗
PubMed1980

[Enteric dysentery vaccines and their effectiveness in a rabbit intestinal loop model. I. The residual virulence of attenuated vaccinal strains of Shigella administered into the intestinal loops].

Virulent Sh. flexneri strain 2a, Sh. sonnei strain, attenuated Sh. flexneri vaccine strain 2a 516M, and Sh. sonnei vaccine strain 6S (isolated by Yu. A. Belaya), as well as streptomycin-dependent Sh. flexneri strain 2a 1605/3 (isolated by V. V. Sergeev) were introduced into the ligated loops of the rabbit ileum. The use of light and immunofluorescent microscopy, the measurement of the volume of the fluid in the intestinal loops and the quantitative inoculation of their contents resulted in revealing the differences in the properties of the virulent and vaccine strains. The vaccine strains, in contrast to the virulent strains, did not proliferate in the lumen and did not cause the accumulation of fluid in the intestinal loops. They retained sharply limited, especially in the streptomycin-dependent bacteria, ability to penetrate into enterocytes and, via their cytoplasm, into the basement membrane, but lost their ability to proliferate in the cytoplasm of enterocytes (and probably even deteriorated there) and to cause plurulent ulcerous inflammation. This indicates that vaccine strains have insignificant residual virulence and suggests that the intestinal loop models, together with other models, may be used for testing the safety of vaccines prepared from Shigella strains.

Animals↗
PubMed1986

De-functioning stomas: a prospective controlled trial comparing loop ileostomy with loop transverse colostomy.

Patients undergoing colorectal surgery who required a defunctioning stoma were randomly allocated to receive either a loop ileostomy (n = 23) or transverse loop colostomy (n = 24). Assessment was made during construction, immediately postoperatively, during the period of outpatient supervision and before and after stoma closure. The ileostomy was associated with significantly less odour than the colostomy (P less than 0.01) and required significantly less appliance changes (P less than 0.05). Furthermore eleven patients (58 per cent) with a colostomy experienced three or more problems with stoma management compared with only three patients (18 per cent) with an ileostomy (P less than 0.05). Wound infection was also significantly more common after closure of the colostomy compared with the ileostomy. Both types of stoma were demonstrated objectively to defunction the distal bowel almost completely. These results indicate that a loop ileostomy is the procedure of first choice when a stoma is needed to defunction the distal colorectum.

Adult↗
PubMed1987

Structural features of the terminal loop region of frog retinal rod outer segment disk membranes: III. Implications of the terminal loop complex for disk morphogenesis, membrane fusion, and cell surface interactions.

The perimeter of rod outer segment (ROS) disks displays a two-dimensional lattice of components referred to as the terminal loop complex (Corless, Fetter, Zampighi, Costello, and Wall-Buford: J. Comp. Neurol. 257:9-23, '87b). We take the view that this pattern of structural organization reflects the mechanism(s) whereby the disk perimeter is defined and constructed. Herein we develop and partially evaluate a generalized template mechanism of disk perimeter development, to account for the structure and the axial alignment of both marginal and incisural domains. Components of the terminal loop complex are conceived as the morphogens that determine the location and guide the differentiation of the disk perimeter. Briefly, we postulate that transmembranous components of the terminal loop complex are present within the reflection of plasmalemma that forms the base of the rod outer segment. These components interact with the cytoplasmic template provided by the perimeter lattice present along the lower surface of the most basal disk, thereby propagating the lattice and creating an extracellular template. The latter is then available to interact with corresponding elements distributed within the apical surface of the adjacent disk precursor evagination. The progressive interaction and alignment of these extracellular domains form the scaffolding that guides the restructuring of the plasmalemma, to form the mature disk margin topology. Successive repetitions of this process are seen to produce an axial stacking of disks whose perimeters are aligned and ensheathed by a two-dimensional net.

Animals↗
PubMed2000

The effect of a pictorial illusion on closed-loop and open-loop prehension.

It has been proposed that movements to visible and remembered targets are sensitive to qualitatively different types of visual information. When the target is continuously visible, prehensile movements are thought to reflect veridical object size, whereas memory-dependent prehension is sensitive to the perceived size of the object. This hypothesis was explored by assessing the influence of illusory target width on prehension kinematics in three visual conditions: closed-loop (CL; full vision during the response), open-loop brief-delay (OL; visual occlusion coincident with the movement initiation cue) and open-loop 3-s delay (OL3; visual occlusion 3 s prior to movement initiation). To modulate illusory target width, objects were placed on backgrounds consisting of three forms of the Müller-Lyer (ML) figure. Peak grip aperture was sensitive to the ML figure in the OL and OL3, but not CL conditions, suggesting that perceptual information is used to modulate this grasping parameter when the movement is programmed and executed on the basis of visual memory. Peak-aperture velocity was affected by the ML illusion in all three visual conditions, suggesting that perceived object size might be important for modulating this aspect of prehension, independent of memory requirements. The different sensitivity of grip aperture and aperture velocity to illusory target width in the CL condition suggests that grasp preshaping might reflect multiple visuomotor processes. The results of this study are consistent with the tenets of the two-stream model of visual processing.

Adult↗
PubMed1994

Amino acid substitutions within the analogous nucleotide binding loop (P-loop) of aminoglycoside 3'-phosphotransferase-II.

1. Oligonucleotide-directed mutagenesis of APH(3')-II was used to investigate the functions of key amino acids in the P-loop analogous motif of the enzyme. 2. The mutations of Gly205-->Glu, Gly210-->Ala and Arg211-->Pro considerably reduced the resistance of the resulting strains to KM and to related drugs, e.g. G418. 3. Similarly, enzyme activity in the crude extracts of these mutants was substantially reduced as well as the enzyme's affinity for Mg2+ ATP. 4. Alternatively substitutions at a highly conserved basic residue (Arg211-->Lys and Arg211-->His) were not sufficient for the enzyme to sustain the activity at a level comparable to that of the wildtype. 5. Moreover, an Arg211-->His mutation drastically reduced affinity of the enzyme for Mg2+ ATP. 6. This argues the importance of Arg211 residue in contributing to the formation of the P-loop structure in addition to its involvement in phosphoryl transfer reaction. 7. Computer analysis of the secondary structure predicted that the APH(3')-II loop connects a beta-strand to an alpha-helix and that the above mutations caused varying degrees of structural distortions at the corresponding regions of the protein.

Amino Acid Sequence↗
PubMed1992

Blood flow in the uterine loop artery and loop vein is bidirectional in the mouse: implications for transport of steroids between fetuses.

In rodents, steroids are able to pass between fetuses. Although not previously examined in mice, we have provided evidence that blood flow in the uterine loop artery in rats is bidirectional and that steroids are transported between fetuses by diffusion via the uterine lumen, not via the uterine blood vessels of the mother. The direction of blood flow in the uterine loop artery and vein feeding each uterine horn in house mice was examined on day 17 of pregnancy. Dye was injected into the heart to determine the direction of blood flow in the uterine artery while injection of dye into individual placentae was used to determine the direction of blood flow in the uterine vein. Blood entered the loop artery from both the dorsal and caudal ends and was thus bidirectional. Venus blood flow from placentae was in a rostral direction from placentae in the rostral portion of a uterine horn and in a caudal direction from placentae in the caudal portion of a uterine horn. Comparison of anogenital distance and body weight at birth using a variety of classification schemes, based on different assumptions about the mechanism and direction of transport of steroids between fetuses, showed that the only scheme which accounted for variation in anogenital distance at birth in female mice was that which was based on the number of directly adjacent male siblings in utero. Taken together with recent findings in rats reported elsewhere, we conclude that blood flow in the uterine blood vessels is bidirectional, and steroids are transported between fetuses by diffusing through the amniotic fluid and across the fetal membranes of adjacent fetuses.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2000

Cystatin inhibition of cathepsin B requires dislocation of the proteinase occluding loop. Demonstration By release of loop anchoring through mutation of his110.

Cystatins A and C were both shown to inhibit cathepsin B by a two-step mechanism, involving an initial weak interaction followed by a conformational change. Disruption of the major salt bridge anchoring the occluding loop of cathepsin B to the main body of the enzyme by mutation of His110 to Ala converted the binding to an apparent one-step reaction. The second step of cystatin binding to cathepsin B must therefore be due to the inhibitor having to alter the conformation of the enzyme by displacing the occluding loop to allow a tight complex to be formed. Cystatin A was appreciably less effective in displacing the loop than cystatin C, resulting in a considerably lower overall inhibition rate constant.

Alanine↗
PubMed1997

Differences between locking loops and grasping loops: effects on 2-strand core suture.

The differences between locking and grasping configurations used to suture lacerated flexor tendons were evaluated using a 2-strand core model in human cadaver tendon. Locking suture configurations tighten around bundles of tendon fibers with tension, while grasping loops do not tighten around but pull through tendon fibers and distract with tension. The greatest tensile strength was found in 1-locking, 2-locking, and 2-grasping suture loop configurations per suture strand. The 2-grasping loops per suture strand, however, had the greatest distraction (gapping) as the suture material pulled through the tendon. A single locking configuration per strand yielded the maximum tensile strength with reduced distraction (gapping) at the repair site.

Cadaver↗
PubMed2002

2'-O-methyl-RNA hairpins generate loop-loop complexes and selectively inhibit HIV-1 Tat-mediated transcription.

The interaction of the TAR RNA element of human immunodeficiency virus type 1 (HIV-1) with a 2'-O-methyl analogue of an RNA hairpin aptamer previously identified by in vitro selection [Ducongé, F., and Toulmé, J. J. (1999) RNA 5, 1605-1614] was characterized by UV-monitored thermal denaturation and surface plasmon resonance experiments. The complex between TAR and this aptamer derivative displays stability (K(d) = 9.9 +/- 1.0 nM) and kinetic properties [k(on) = 9.0 +/- 0.3 M(-1) s(-1), k(off) = (8.9 +/- 0.6) x 10(-4) s(-1)] close to those of the parent RNA aptamer. The modified aptamer forms a "kissing" complex with TAR driven by the same key elements as the TAR-RNA aptamer one. In particular, the G and A residues closing the aptamer loop remain crucial for TAR-2'-O-methyl aptamer complexes. Moreover, the 2'-O-methyl aptamer analogue specifically inhibits Tat-mediated transcription in an in vitro assay more efficiently than the RNA aptamer. This is likely due to the increased lifetime of the former oligonucleotide in the cell-free extract. The 2'-O-methyl modification extends the range of molecules that can be used to target viral hairpin RNA through loop-loop interactions. More generally, this demonstrates the interest of SELEX for targeting RNA hairpins and understanding nucleic acid interactions.

Gene Expression Regulation, Viral↗
PubMed2003

Active peptidic mimics of the second intracellular loop of the V(1A) vasopressin receptor are structurally related to the second intracellular rhodopsin loop: a combined 1H NMR and biochemical study.

Vasopressin (VP) receptors belong to the widespread G protein-coupled receptor family. The crucial role of VP receptor intracellular loops in the coupling with the heterotrimeric G proteins was previously demonstrated by construction of a vasopressin receptor chimera. Yet, no fine structural data are available concerning the receptor molecular determinants involved in their interactions with G proteins. In this study, we synthesized both a linear and a cyclic form of the second intracellular loop (i2) of the human V(1a) vasopressin receptor isoform that is important for the interaction between the alphaq/alpha11 G protein and the receptor. These two peptides are biologically active. They specifically inhibit vasopressin binding to the V(1a) receptor, suggesting that the corresponding endogenous peptides contribute to the structure of the vasopressin binding site via intra- or intermolecular interactions with the core of the V(1a) receptor. The i2 peptide structures were determined by (1)H NMR. Both exhibit a helix and helical elements in their N- and C-terminal parts, respectively, separated by a turn imposed by a proline residue. More interestingly, the central Pro-Leu motif conserved in many GPCRs and thought to be important for coupling to G proteins can adopt different conformations. The "U" shape structure of the i2 loop is compatible with its anchoring to transmembrane domains III and IV and is very similar to the shape of bovine rhodopsin i2. Altogether, these data contribute to a better understanding of the structure of a not yet crystallized GPCR using the mimetic peptide approach.

Amino Acid Sequence↗
PubMed1997

Structure of an RNA hairpin loop with a 5'-CGUUUCG-3' loop motif by heteronuclear NMR spectroscopy and distance geometry.

Structural features of a 19-nucleotide RNA hairpin loop (5'-GGCGUACGUUUCGUACGCC-3'), a loop motif which occurs in eukaryotic 18S rRNA, have been derived using multidimensional heteronuclear NMR spectroscopy in combination with local conformational analysis and torsion angle distance geometry followed by restrained energy minimization. A method to obtain both the 3JC4'P3' and 3JC4'P5' coupling constants from a set of spin-echo difference constant time HSQC spectra is introduced, and it is shown how these couplings can be assigned to the backbone angles beta and epsilon. A total of 280 distance constraints as well as 132 homo- and heteronuclear three-bond scalar coupling constants were derived from the NMR data. The structure which has been determined is a pentaloop rather than a triloop with no base pairing between G8 and C12. G8 is pointed to the minor groove where it forms a base triplet with C7-G13 that is further stabilized by hydrogen bonding to the 2'-hydroxyl group of C7. C12 is directed to the major groove where its conformation is stabilized by hydrogen bonding between O2 and HO2'. The NMR data suggest two possible, interconverting conformations with stacking of bases U10-G8 or U11-C7. Overall, the loop provides a variety of interaction sites for RNA or protein interactions.

Carbon Isotopes↗
PubMed1998

Dimerization of MoMuLV genomic RNA: redefinition of the role of the palindromic stem-loop H1 (278-303) and new roles for stem-loops H2 (310-352) and H3 (355-374).

Genomic RNAs from retroviruses are packaged as dimers of two identical RNA molecules. In Moloney murine leukemia virus, a stem-loop structure (H1) located in the encapsidation domain Psi (nucleotides 215-564) was postulated to trigger RNA dimerization through base pairing between auto complementary sequences. The Psi domain also contains two other stem-loop structures (H2 and H3) that are essential for RNA packaging. Since it was suspected than H1 is not the only element involved in RNA dimerization, we systematically investigated the dimerization capacity of several subdomains of the first 725 nucleotides of genomic RNA. The efficiency of dimerization of the various RNAs was estimated by measuring their apparent dissociation constants, and the specificity was tested by competition experiments. Our results indicate that the specificity of dimerization of RNA nucleotides 1-725 is driven by motifs H1-H3 in domain Psi. To define the relative contributions of these elements, RNA deletion mutants containing different combinations of H1-H3 were constructed and further analyzed in competition and kinetic experiments. Our results confirm the importance of H1 in triggering dimerization and shed new light on the mechanism of dimerization. H1 is required to provide a stable dimer, probably through the formation of extended intermolecular interactions. However, H1-mediated association is a slow process that is kinetically enhanced by H3, and to a lesser extent by H2. We suggest that they facilitate the recognition between the two RNAs, most likely through their conserved GACG loops. Our results reinforce the idea that dimerization and packaging are two closely related processes.

Animals↗
PubMed2006

Self-condensation of a thiazole-peptide bearing a 21-membered loop into a library of giant macrocycles with multiple orthogonal loops.

[reaction: see text] Tetrapeptide analogue H-[Glu-Ser-Lys(Thz)]-OH, containing a turn-inducing thiazole constraint, was used as a template to produce a 21-membered structurally characterized loop by linking Glu and Lys side chains with a Val-Ile dipeptide. This template was oligomerized in one pot to a library (cyclo-[1](n)(), n = 2-10) of giant symmetrical macrocycles (up to 120-membered rings), fused to 2-10 appended loops that were carried intact through multiple oligomerization (chain extension) and cyclization (chain terminating) reactions of the template. A three-dimensional solution structure for cyclo-[1](3) shows all three appended loops projecting from the same face of the macrocycle. This is a promising approach to separating peptide motifs over large distances.

Cyclization↗
PubMed1997

Involvement of the M7/M8 extracellular loop of the sodium pump alpha subunit in ion transport. Structural and functional homology to P-loops of ion channels.

Mutations were introduced in the motif 884DDRW887 from an extracellular peptide of the sodium pump alpha subunit localized between M7 and M8 membrane spans to investigate a possible role of this structure in ion recognition. A homologous sequence 399QDCW402 that occurs in the P-loops of Na+ channels was shown earlier to be important for ion gating. Mutant sodium pumps were expressed in yeast and subsequently investigated for their behavior toward ouabain, Na+, K+, and ATP. Native enzyme and D884A, D884R, D885A, D885E, or D885R mutants all bind ouabain in the presence of phosphate and Mg2+. The KD values determined from Scatchard analysis are in the range 5-8 nM for the native enzyme and the D884A, D885E, or D885A mutants, and 15.7 +/- 2.04 and 30.1 +/- 4.32 nM for mutants D884R and D885R, respectively. This ouabain binding is reduced in the presence of K+ in a similar way for both native or mutant sodium pumps with relative affinities (K0.5) for K+ ranging from 1.4 to 3.7 mM. Ouabain binding in the presence of 100 microM ATP is promoted by Na+ with K0.5 = 1.64 +/- 0.01 mM for the native enzyme and K0.5 = 8. 6 +/- 1.35 mM for the D884R mutant. The K0.5 values of the two enzymes for ATP are 0.66 +/- 0.16 microM and 1.1 +/- 0.12 microM, respectively. Ouabain binding as a function of Na+ concentration, on the other hand, is very low for the D885R mutant, even at an ATP concentration of 2 mM. Phosphate or eosin, however, are recognized by this mutant enzyme, so that a major conformational change within the ATP-binding site appears unlikely. The inability of the D885R mutant to bind ouabain in the presence of Na+ and ATP could be explained by assuming that the M7/M8 connecting extracellular loop, which also contains the mutated amino acids, is invaginated within the plane of the plasma membrane and possibly involved in acceptance and/or release of Na+ ions coming from cytosolic areas of the protein. In this case, the placement of an additional positive charge might repel Na+ ions and interrupt their flow, thus not allowing the enzyme to assume the proper conformational state for ouabain binding. Such invaginated hydrophilic protein structures, such as the P-loops of Na+ and K+ channels, are already known and have been shown to participate in ion conduction.

Adenosine Triphosphate↗
PubMed2005

The Q-loop disengages from the first intracellular loop during the catalytic cycle of the multidrug ABC transporter BmrA.

The ATP-binding cassette is the most abundant family of transporters including many medically relevant members and gathers both importers and exporters involved in the transport of a wide variety of substrates. Although three high resolution three-dimensional structures have been obtained for a prototypic exporter, MsbA, two have been subjected to much criticism. Here, conformational changes of BmrA, a multidrug bacterial transporter structurally related to MsbA, have been studied. A three-dimensional model of BmrA, based on the "open" conformation of Escherichia coli MsbA, was probed by simultaneously introducing two cysteine residues, one in the first intracellular loop of the transmembrane domain and the other in the Q-loop of the nucleotide-binding domain (NBD). Intramolecular disulfide bonds could be created in the absence of any effectors, which prevented both drug transport and ATPase activity. Interestingly, addition of ATP/Mg plus vanadate strongly prevented this bond formation in a cysteine double mutant, whereas ATP/Mg alone was sufficient when the ATPase-inactive E504Q mutation was also introduced, in agreement with additional BmrA models where the ATP-binding sites are positioned at the NBD/NBD interface. Furthermore, cross-linking between the two cysteine residues could still be achieved in the presence of ATP/Mg plus vanadate when homobifunctional cross-linkers separated by more than 13 Angstrom were added. Altogether, these results give support to the existence, in the resting state, of a monomeric conformation of BmrA similar to that found within the open MsbA dimer and show that a large motion is required between intracellular loop 1 and the nucleotide-binding domain for the proper functioning of a multidrug ATP-binding cassette transporter.

ATP-Binding Cassette Transporters↗