Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “looping”

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 631 records · Page 35Linked to original sources

Effects of nicks on repair of single-stranded loops in heteroduplex DNA in mammalian cells.

Heteroduplexes that contain single-stranded loops are repaired very efficiently in mammalian cells. The strand that does not contain the loop is used as the template strand for repair nearly twice as often as the looped strand. In this study we tested the influence of nearby nicks on the choice of template strand. We find that strand selection in repair of heteroduplexes with single-stranded loops is influenced by the presence of a nick located 71 or 125 base pairs from the loop, but only to a minor degree. Thus the loop itself is a stronger signal for repair than is a nearby nick. On the other hand, if a break is introduced into the single strand that forms the loop, the looped strand is marked for excision and rarely, if ever, is used as the template for repair.

Animals↗

Limitations of the open loop gain concept in studies of respiratory control.

A steady state mathematical model was used to study the limitations of applying the open loop gain concept to the ventilatory control system. Open loop gain is a term used in the study of linear control systems and is an indicator of how well the controlled variable is regulated. The model contained descriptions of the O2 and CO2 control systems as well as their interactions. Disturbances to the system were modelled as occurring via inspired air, metabolic rate and ventilation. The ventilatory response to hypoxia was simulated for (a) hypocapnic hypoxia, (b) normocapnic hypoxia (PaCO2 = 40 torr) and (c) hypercapnic hypoxia (PaCO2 = 45 torr). The open loop gains of the O2 and CO2 loops were calculated at each operating point. In addition, the sensitivity of the controlled variable to disturbances to the loop were also compared. It was observed that open loop gain did not completely describe the characteristics of the ventilatory control system. This was due to the fact that the ventilatory system is nonlinear and the regulatory ability of the ventilatory system depends on the route of the disturbance, and (2) open loop gain ignores the interactions of the CO2 and O2 loops, which can be substantial.

Animals↗

Association of RB97D, an RRM protein required for male fertility, with a Y chromosome lampbrush loop in Drosophila spermatocytes.

The Y chromosome of Drosophila melanogaster, which is required only for male fertility, contains six loci that are essential for spermatogenesis. In primary spermatocytes, three of these loci form large lampbrush loops containing RNA transcripts and associated proteins. The identities and functions of these Y chromosome loop-binding proteins are largely unknown. This report demonstrates that the RB97D protein, which is essential for spermatogenesis, bound to a specific lampbrush loop. RB97D contains two copies of a well-characterized RNA binding domain, the RNA recognition motif, followed by a proline-glutamine rich domain. Immunohistochemical and immunofluorescence experiments showed that in the testis, RB97D was found only in primary spermatocyte nuclei and associated with the C loop from the ks-1 fertility locus in an RNAse-sensitive manner. The anti-RB97D antibodies also bound a single Y chromosome loop in D. hydei, suggesting that the protein and its loop-binding function have been evolutionarily conserved. These results demonstrate that the proteins that bind lampbrush loops can be essential for fertility. Since RB97D was present only premeiotically, its function is likely to be directly related to the metabolism of the C loop transcripts.

Animals↗

Effects of diazepam on closed- and open-loop optokinetic nystagmus (OKN) in humans.

The effects of diazepam on optokinetic nystagmus (OKN) eye movements were studied under closed-loop and open-loop conditions in healthy humans. The open-loop condition was achieved by adding the eye-movement velocity signal of OKN to the computer-generated signal controlling the moving stimulus grating. Each of four subjects received a single oral dose of 5 mg diazepam or a placebo on two separate days in a double-blind randomized fashion. OKN eye movements were measured 90 min after administration of the treatments. As compared to placebo, diazepam significantly reduced the gain of open-loop OKN, but did not modify the gain of closed-loop OKN. The results indicate that the OKN gain under the open-loop condition is a more sensitive detector of the parameter changes of the OKN system than under the closed-loop condition. Thus, open-loop OKN gain can provide an objective, quantitative measure of benzodiazepine agonist effects.

Adult↗

[Rotational stability in intraocular lenses with C-loop haptics versus Z haptics in cataract surgery. A prospective randomised comparison].

The aim of the study was to compare the rotational stability of intraocular lenses (IOLs) with C-loop haptics and those with Z haptics. A total of 50 patients with cataracts were prospectively randomised in equal numbers using a design equivalent to IOL MS 612 S (C-loop haptic) and MS 6120 (Z haptic, both HumanOptics, Erlangen). Complete ophthalmological examinations were performed including assessment of the IOL rotation after 1 day, 1 month and 3 months postoperatively. The significances between the groups were evaluated using the Wilcoxon test. The Fisher exact test was used for the primary finding of the study (rotation of at least 10 degrees ). The IOL group with the C-loop haptics showed a median lens rotation of 0 degrees on the first day and 2 degrees clockwise after 1 month and 3 months. In the Z haptic group, there was no median rotation in the IOL group. Moreover, the range of IOL rotation of the C-loop haptics was broader (3 months postoperatively: maximum in the C-loop haptics: 21 degrees with 15.5 degrees in the Z haptics). There was no significant difference at any time. At 3 months postoperatively, 32% of the C-loop haptic IOL and 16% of the Z haptic IOL rotated at least 10 degrees (P=0.32). In 59% of the IOL with C-loop haptics, the direction of the rotation was clockwise. This was 40% for the IOL with Z haptics (P=0.33). At 3 months postoperatively, both IOLs demonstrated good rotational stability with a low mean deviation from the target axis. IOLs with Z haptics showed a tendency to greater rotational stability than C-loop haptics but without any significant difference. There was no significant difference in visual rehabilitation.

Cataract Extraction↗

Quantifying the strength of the linear causal coupling in closed loop interacting cardiovascular variability signals.

The coherence function measures the amount of correlation between two signals x and y as a function of the frequency, independently of their causal relationships. Therefore, the coherence function is not useful in deciding whether an open-loop relationship between x and y is set (x acts on y, but the reverse relationship is prevented) or x and y interact in a closed loop (x affects y, and vice versa). This study proposes a method based on a bivariate autoregressive model to derive the strength of the causal coupling on both arms of a closed loop. The method exploits the definition of causal coherence. After the closed-loop identification of the model coefficients, the causal coherence is calculated by switching off separately the feedback or the feedforward path, thus opening the closed loop and fixing causality. The method was tested in simulations and applied to evaluate the degree of the causal coupling between two variables known to interact in a closed loop mainly at a low frequency (LF, around 0.1 Hz) and at a high frequency (HF, at the respiratory rate): the heart period (RR interval) and systolic arterial pressure (SAP). In dogs at control, the RR interval and the SAP are highly correlated at HF. This coupling occurs in the causal direction from the RR interval to the SAP (the mechanical path), while the coupling on the reverse causal direction (the baroreflex path) is not significant, thus pointing out the importance of the direct effects of respiration on the RR interval. Total baroreceptive denervation, by opening the closed loop at the level of the influences of SAP on RR interval, does not change these results. In elderly healthy men at rest, the RR interval and SAP are highly correlated at the LF and the HF. At the HF, a significant coupling in both causal directions is found, even though closed-loop interactions are detected in few cases. At the LF, the link on the baroreflex pathway is negligible with respect to that on the reverse mechanical one. In heart transplant recipients, in which SAP variations do not cause RR interval changes as a result of the cardiac denervation, the method correctly detects a significant coupling only on the pathway from the RR interval to the SAP.

Animals↗

Loop electrosurgical excision procedures for cervical dysplasia: experience in a community hospital.

OBJECTIVE: The study was undertaken to evaluate the use of the loop electrosurgical excision procedure as an outpatient hospital or surgicenter procedure. STUDY DESIGN: The records of 358 patients treated for cervical intraepithelial neoplasia at a large community hospital over a 1-year period were reviewed. RESULTS: The specimens obtained by loop electrosurgical excision procedure and laser cone excision were comparable in size but smaller than those by means of cold-knife conization. Seventy-two percent of loop electrosurgical excision procedure specimens consisted of two to eight tissue fragments (mean 3.4). In addition, 48% of the loop electrosurgical excision procedure specimens and 38% of laser cones had moderate or severe thermal artifacts. Fragmentation and cautery damage precluded orientation of tissue and evaluation of margins in 19% of the cases. CONCLUSIONS: The advent of the loop electrosurgical excision procedure has shifted the management of cervical intraepithelial neoplasia from the office to the outpatient surgery centers. This negates and, in fact, reverses the advantage of loop electrosurgical excision procedure over other methods in regard to cost and convenience through evaluating and treating a patient with cervical intraepithelial neoplasia in one office visit. Loop electrosurgical excision procedures provide specimens that are inferior compared with cold-knife cones; therefore the role of loop electrosurgical excision procedure for the management of cervical intraepithelial neoplasia outside the office appears limited.

Adolescent↗

Structural modifications of the omega loop in human acetylcholinesterase.

Conformational mobility of the surface omega loop (Cys-69-Cys-96) in human acetylcholinesterase (HuAChE) was recently implicated in substrate accessibility to the active center and in the mechanism of allosteric modulation of enzymatic activity. We therefore generated and kinetically evaluated the following modifications or replacements in HuAChE: (a) residues at the loop ends, (b) residues involved in putative hydrogen-bond interactions within the loop and between the loop and the protein core, (c) ChEs conserved proline residues within the loop and (d) a deletion of a conserved segment of 5 residues. All the residue replacements, including those of the prolines, had either limited or no effect on enzyme reactivity. These results suggest that unlike the case of lipase, the omega loop in the HuAChE is not involved in large lid-like displacements. In cases where modifications of the loop sequence had some effect on reactivity, the effects could be attributed to an altered position of residue Trp-86 supporting the proposed coupling between the structure of the omega loop and the positioning of the Trp-86 indole moiety, in catalytic activity and in allosterism.

Acetylcholinesterase↗

Analysis of protein loop closure. Two types of hinges produce one motion in lactate dehydrogenase.

As shown in previous crystallographic investigations, upon binding lactate and NAD, lactate dehydrogenase undergoes a large conformational change that results in a surface loop moving roughly 10 A to cover the active site. In addition, there are appreciable movements (approximately 2 A) of five helices and three other loops. We demonstrate by a new fitting procedure that the loop moves on two hinges separated by a relatively rigid type II turn. The first hinge has few steric constraints on it, and its motion can be well accounted for by large changes in two torsion angles, i.e. as in a classic hinge motion. In contrast, the second hinge, which is part of a helix connected to the end of the loop, has many more constraints on it and distributes its deformation over more torsion angles. This novel motion involves the helix stretching and splitting into alpha-helical and 3(10)-helical components and substantial side-chain repacking in the sense of "cogs hopping between grooves" at its interface with the end of a neighboring helix. The loop is stabilized by five transverse (across loop) hydrogen bonds. These are preserved, through the conformational change and through 17 lactate dehydrogenase sequences, more than the longitudinal hydrogen bonds down the sides of the loop. Through a network of contacts, many of them conserved hydrophobic residues, the motion of the loop is propagated outward to structures that have no direct contact with the ligands. These moving structures are on the surface of the protein, and the whole protein can be subdivided into concentric shells of increasing mobility.

Amino Acid Sequence↗

DNA looping induced by bacteriophage lambda O protein: implications for formation of higher order structures at the lambda origin of replication.

A plasmid has been constructed, pOri2, which contains two lambda replication origin sequences separated by 1068 bp; both lambda sequences having the same orientation. When lambda initiation protein O is reacted with linearized pOri2 and examined by electron microscopy it is found to contain a looped area in which two parts of the plasmid are bound together by the O protein complex. Length measurements show that the O protein binds at the expected positions of the lambda origin sequences and that the looped area represents the DNA segment between the two O protein binding domains. Similar looping occurs in reactions with supercoiled pOri2 or if an amino-terminal fragment of O protein is used. When looped molecules are reacted with psoralen, crosslinked by irradiation with uv light, and then denatured, it is found that the looped area is more thermostable than the rest of the molecule. This indicates that the DNA within the looped segment is torsionally constrained while that outside the loop is free to rotate and suggests that simultaneous binding of O to two origins fixes the linkage number of the intervening DNA. The double origin binding ability of O may be diagnostic of the details of the reaction of O with a single origin sequence. A model is presented that rests on the assumption that O can produce microscopic looping between O protein binding sites within a single ori sequence.

Bacteriophage lambda↗

DNA clones and RNA transcripts of four lampbrush loops from the Y chromosome of Drosophila hydei.

Drosophila hydei clones representing transcribed middle-repetitive sequences from four of six major lampbrush loops of the Y chromosome were isolated. Sequences homologous to each clone are clustered in a particular locus on the Y chromosome, but additional euchromatic sites were found for one of the transcribed clones. In situ hybridization to lampbrush-loops RNA permitted the identification of clones homologous with the two "nooses" loops on YS and with the "clubs" and "tubular ribbons" on the YL arm. Loop-specific nuclear RNA molecules range in size from 10S to 60S. Loop RNA is accumulated in the nucleus and remains attached to the loops during the course of primary spermatocyte growth. It disappears, however, along with the loop structures, during the first meiotic prophase. The structure and function of the Y chromosome and its lampbrush loops are briefly considered in the light of these findings.

Animals↗

Intraaortic spring coil loops: early and late results.

OBJECTIVES: Our aim was to determine the late fate of intraaortic spring coil loops after embolization of aortopulmonary vessels. BACKGROUND: In some aortopulmonary collateral vessels and patent ductus arteriosi, the narrowest segment is close to the aorta; coils used to close such vessels will "straddle" the lesion, allowing one or more coil loops to protrude into the aortic lumen. The consequences of this procedure are unknown. METHODS: We reviewed the cineangiograms of all patients who had at least one aortopulmonary collateral vessel or patent ductus arteriosus closure between January 1, 1988 and August 31, 1993. From this group, 53 patients had multiple-plane angiographic evidence of intraaortic coil loops. All subsequent cineangiograms were reviewed to determine coil position or movement and evidence of recanalization or endothelial coverage of the coil loop. We also reviewed each hospital record or communicated directly with referring physicians to identify any subsequent complications such as emboli or endocarditis. RESULTS: Of the 53 patients with intraaortic coil loops, 49 patients had closure of one or more aortopulmonary collateral vessels (59 vessels), and 4 had closure of a patient ductus arteriosus (4 vessels). Patient follow-up ranged from 1 day to 66 months (median 20 months); follow-up was not available in 6 patients. Five of the 53 patients (9.3%; 95% confidence limits [CL] 3.1% to 20.7%) died at operation or of end-stage heart failure. Patients with late angiography had no residual flow in 31 of 35 aortopulmonary collateral vessels (88.6%; 95% CL 73.3% to 96.8%), and 0.5 mm separated the coil and aortic contrast column in all 12 coils with adequate angiography, suggesting endothelial coverage of the intraaortic coil loop. No episodes of stroke, embolic events, endocarditis or coil migration were reported. CONCLUSIONS: Although coil occlusion of aortopulmonary collateral vessels or patent ductus arteriosi may produce intraaortic coil loops, endothelialization appears routine. No late complications associated with intraaortic coil loops were observed.

Aorta, Thoracic↗

The central loop of Escherichia coli glutamine synthetase is flexible and functionally passive.

Bacterial glutamine synthetases (GSs) are dodecameric aggregates comprised of two face-to-face hexameric rings, which form a cylindrical aqueous channel. Available crystal structures indicate that each subunit provides a 'central loop' that protrudes into this channel. Residues on either side of this loop contribute directly to substrate or metal ion cofactor binding. Although it has been suggested that this conspicuous structural feature may be functionally important, a systematic structure-function analysis of this loop has not been done. Here, we examine the behavior of a cysteine mutant, E165C, which yields inter-subunit disulfide bonds connecting the central loops. The inter-subunit disulfide bonds are readily detected by electrospray ionization mass spectrometry. Based on molecular models, the disulfide bonds would form only if the engineered cysteines on adjacent subunits moved approximately 5 A. Surprisingly, inter-subunit disulfide bonds between the central loops caused no detectable changes in the KMs for glutamate or ATP, nor the KD for either ATP or the transition state analog (L)-methionine sulfoximine (MSOX). Furthermore, covalent and quantitative adduction of the E165C mutant with iodo-acetamido-pyrene yielded nearly fully active enzyme bearing fluorescent pyrene excimers. The relative contribution of pyrene monomers to excimers in the steady state fluorescence is temperature dependent, suggesting thermal equilibrium between loop conformational states. However, the monomer-excimer ratio is independent of ligands such as MSOX, glutamate, or Mn2+. These results validate the suspected flexibility of the central loop, but raise significant doubt about its direct functional role in GS catalysis via conformational switching, including the proposed regulation of GS via ADP-ribosylation within this loop.

Adenosine Diphosphate↗

Characterization of the VP1 loop mutations widespread among JC polyomavirus isolates associated with progressive multifocal leukoencephalopathy.

Recently, we found that JC polyomavirus (JCPyV) associated with progressive multifocal leukoencephalopathy (PML) frequently undergoes amino acid substitutions (designated VP1 loop mutations) in the outer loops of the major capsid protein, VP1. To further characterize the mutations, we analyzed the VP1 region of the JCPyV genome in brain-tissue or cerebrospinal fluid samples from 20 PML patients. VP1 loop mutations occurred far more frequently than silent mutations. Polymorphic residues were essentially restricted to three positions (55, 60, and 66) within the BC loop, one (123) within the DE loop, and three (265, 267, and 269) within the HI loop. The mutations at most polymorphic residues showed a trend toward a change to specific amino acids. Finally, we presented evidence that the VP1 loop mutations were associated with the progression of PML. These findings should form the basis for elucidating the biological significance of the VP1 loop mutations.

Autopsy↗

Catalytic loop motion in human glutathione synthetase: A molecular modeling approach.

Conformational changes of three flexible loops (G, A, and S) in human glutathione synthetase (hGS) arise to accommodate the substrates inside the active site. The crystal structure of hGS, a member of the ATP-grasp superfamily, has been reported only for the product-enzyme complex. To study the function of the hGS loops, molecular dynamics simulations are performed on three different conformational models: unbound enzyme, reactant-enzyme, and product-enzyme complex of hGS. The conformational changes among the three models are analyzed and the roles of the loops during the catalytic process are described. The modeled structures of hGS show that the central portions of the G- and A-loop have a double role in the reactant complex conformation: they bind the substrates and simultaneously interact with each other through an extensive network of hydrogen bonds. The present study proposes that these favorable loop-ligand and loop-loop interactions are required for opening and closing of the active site of hGS. Additionally, this research identifies important amino acid residues and explains their function within the catalytic loops of hGS.

Amino Acid Sequence↗

The relevance of free fluid between intestinal loops detected by sonography in the clinical assessment of small bowel obstruction in adults.

INTRODUCTION: The main role of the radiologist in the management of patients with suspicion of small bowel obstruction is to help triage patients into those that need immediate surgical intervention from those that require medical therapy or delayed surgery. Ultrasound examination is usually considered not helpful in bowel obstruction because of air in the intestinal lumen that interferes the evaluation of the intestinal loops, however recently some Authors attested the increasing important role of sonography in the acute abdominal disease. Aim of our report is to demonstrate the value of free fluid detected by US in differentiating between low and high-grade small bowel obstruction. MATERIALS AND METHODS: The study is based on 742 consecutive patients who presented symptoms of the acute abdomen; all patients had undergone initial serial abdominal plain film and US examinations prior to any medical intervention. We reviewed the imaging findings of 150 cases in whom small bowel obstruction was clinically suspected and confirmed at surgery. We consider the following radiographic and US findings: dilatation of small bowel loops; bowel wall thickness; presence of air-fluid levels; thickness of valvulae conniventes; evidence of peristalsis; presence and echogenicity of extraluminal fluid. We looked at the value of extraluminal peritoneal fluid at US examination in differentiating low and high-grade small bowel obstruction based on the surgical outcome. RESULTS: In 46 patients altered peristaltic activity, thin bowel walls, fluid filled loops with hyperechoic spots in the bowel segment proximal to obstruction were noted at US, whereas radiographic features were: moderate dilatation of small bowel loops, with thin bowel wall and evidence of numerous and subtle valvulae conniventes; presence of air-fluid levels was also noted. In 70 other patients, US examination revealed all the findings described in the precedent cases and also the presence of free extraluminal fluid; abdominal plain film showed an increased dilatation of small bowel loops with moderate thickened wall and air-fluid levels. In 34 other patients US examination revealed the presence of thick-walled loops, hypoperistalsis and a larger amount of free extraluminal fluid. Radiographic findings in these patients were: horizontal featured and markedly dilated small bowel loops presenting parietal thickness, presence of intraluminal fluid stasis and evidence of thickened, sparse and incomplete valvulae conniventes. At surgery etiology of small bowel obstructions was various, but most of cases related to adhesions (70 cases). The presence of extraluminal fluid were confirmed at surgery in 104 patients. CONCLUSIONS: Our experience using sonography in suspicion of SBO (small bowel obstruction) suggests the usefulness of this imaging modality to differentiate a functional or obstructive ileus, demonstrating the evidence of intestinal peristalsis. Furthermore, the presence of a large amount of fluid between dilated small bowel loops suggests worsening mechanical small bowel obstruction, that requires not a medical therapy but immediate surgery.

Abdomen, Acute↗

Conformational analysis of DNA-trinucleotide-hairpin-loop structures using a continuum solvent model.

A number of trinucleotide sequences in DNA can form compact and stable hairpin loops that may have significance for DNA replication and transcription. The conformational analysis of these motifs is important for an understanding of the function and design of nucleic acid structures. Extensive conformational searches have been performed on three experimentally known trinucleotide hairpin loops (AGC, AAA, and GCA) closed by a four-base-pair stem. An implicit solvation model based on the generalized Born method has been employed during energy minimization and conformational search. In addition, energy-minimized conformers were evaluated using a finite-difference Poisson-Boltzmann approach. For all three loop sequences, conformations close to experiment were found as lowest-energy structures among several thousand alternative energy minima. The inclusion of reaction-field contributions was found to be important for a realistic conformer ranking. Most generated hairpin loop structures within approximately 5 kcal x mol(-1) of the lowest-energy structure have a similar topology. Structures within approximately 10 kcal x mol(-1) could be classified into about five structural families representing distinct arrangements of loop nucleotides. Although a large number of backbone torsion angle combinations were compatible with each structural class, some specific patterns could be identified. Harmonic mode analysis was used to account for differences in conformational flexibility of low-energy sub-states. Class-specific differences in the pattern of atomic fluctuations along the sequence were observed; however, inclusion of conformational entropy contributions did not change ranking of structural classes. For an additional loop sequence (AAG) with no available experimental structure, the approach suggests a lowest-energy loop topology overall similar to the other three loop sequences but closed by a different non-canonical base-pairing scheme.

Biophysical Phenomena↗

Non-Watson-Crick basepairing and hydration in RNA motifs: molecular dynamics of 5S rRNA loop E.

Explicit solvent and counterion molecular dynamics simulations have been carried out for a total of >80 ns on the bacterial and spinach chloroplast 5S rRNA Loop E motifs. The Loop E sequences form unique duplex architectures composed of seven consecutive non-Watson-Crick basepairs. The starting structure of spinach chloroplast Loop E was modeled using isostericity principles, and the simulations refined the geometries of the three non-Watson-Crick basepairs that differ from the consensus bacterial sequence. The deep groove of Loop E motifs provides unique sites for cation binding. Binding of Mg(2+) rigidifies Loop E and stabilizes its major groove at an intermediate width. In the absence of Mg(2+), the Loop E motifs show an unprecedented degree of inner-shell binding of monovalent cations that, in contrast to Mg(2+), penetrate into the most negative regions inside the deep groove. The spinach chloroplast Loop E shows a marked tendency to compress its deep groove compared with the bacterial consensus. Structures with a narrow deep groove essentially collapse around a string of Na(+) cations with long coordination times. The Loop E non-Watson-Crick basepairing is complemented by highly specific hydration sites ranging from water bridges to hydration pockets hosting 2 to 3 long-residing waters. The ordered hydration is intimately connected with RNA local conformational variations.

Base Pair Mismatch↗