Increased Flexibility (increased + flexibility)

Distribution by Scientific Domains


Selected Abstracts


Probing residue-specific interactions in the stabilization of proteins using high-resolution NMR: A study of disulfide bond compensation

JOURNAL OF PHARMACEUTICAL SCIENCES, Issue 6 2010
Andria L. Skinner
Abstract It is well established that the oxidation state of cysteine residues in proteins is critical to overall physical stability. Disulfide bonds most often impart thermodynamic stability, but in some cases, diminish it. Predicting the circumstances that lead to each outcome is difficult because mechanistic information is lacking. Because the techniques typically used to study protein stability do not provide sufficient detail, high-resolution NMR was used in combination with low-resolution analysis to obtain mechanistic information regarding disulfide bond formation in a model protein. Tm (CD) and Tonset (SLS) for the reduced and oxidized wild type and C104S and C49S mutants were measured. The mutant proteins have altered Tms and Tonsets compared to the reduced wild type, indicating that differences in local interactions of the Cys side chains are important for stability. The NMR spectra clearly show distinct differences in the chemical environment surrounding these Cys residues and the overall tertiary structure. The C49S protein, which is less stable and more aggregation prone than reduced wild type, lacks a hydrogen bond between Y53 and H103. Increased flexibility of the Y53-containing loop is correlated with increased dynamics and unraveling of ,2, which likely leads to edge strand initiated aggregation of the central ,-sheet. © 2010 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99: 2643,2654, 2010 [source]


Data structures in Java for matrix computations

CONCURRENCY AND COMPUTATION: PRACTICE & EXPERIENCE, Issue 8 2004
Geir Gundersen
Abstract In this paper we show how to utilize Java's native arrays for matrix computations. The disadvantages of Java arrays used as a 2D array for dense matrix computation are discussed and ways to improve the performance are examined. We show how to create efficient dynamic data structures for sparse matrix computations using Java's native arrays. This data structure is unique for Java and shown to be more dynamic and efficient than the traditional storage schemes for large sparse matrices. Numerical testing indicates that this new data structure, called Java Sparse Array, is competitive with the traditional Compressed Row Storage scheme on matrix computation routines. Java gives increased flexibility without losing efficiency. Compared with other object-oriented data structures Java Sparse Array is shown to have the same flexibility. Copyright © 2004 John Wiley & Sons, Ltd. [source]


Similarity of permeabilities for Ficoll, pullulan, charge-modified albumin and native albumin across the rat peritoneal membrane

ACTA PHYSIOLOGICA, Issue 4 2009
D. Asgeirsson
Abstract Aim:, Compared to neutral globular proteins, neutral polysaccharides, such as dextran, pullulan and Ficoll, appear hyperpermeable across the glomerular filtration barrier. This has been attributed to an increased flexibility and/or asymmetry of polysaccharides. The present study investigates whether polysaccharides are hyperpermeable also across the continuous capillaries in the rat peritoneum. Methods:, In anaesthetized Wistar rats, FITC,Ficoll or FITC,pullulan together with 125I-human serum albumin (RISA) or neutralized 125I-bovine serum albumin (nBSA) were given intravenously, after which peritoneal dialysis (PD) using conventional PD fluid (Gambrosol 1.5%) was performed for 120 min. Concentrations of FITC-polysaccharides and radioactive albumin species in plasma and dialysis fluid were analysed with high-performance size exclusion chromatography and a gamma counter respectively. Transperitoneal clearance values were calculated for polysaccharides in the molecular radius range 36,150 Å, and for RISA and nBSA. Results:, Ficoll and pullulan showed more or less identical permeabilities, compared to RISA and nBSA, across the peritoneal membrane. Although RISA-clearance, 5.50 ± 0.28 (,L min,1; ±SEM), tended to be lower than the clearances of Ficoll36Å (6.55 ± 0.25), pullulan36Å (6.08 ± 0.22) and nBSA (6.56 ± 0.23), the difference was not statistically significant. This is in contrast to the hyperpermeability exhibited by polysaccharides across the glomerular filtration barrier and also contrasts with the charge selectivity of the latter. Conclusion:, The phenomenon of molecular flexibility is more important for a macromolecule's permeability through the glomerular filter than across the continuous peritoneal capillary endothelium. Furthermore, it seems that charge plays a subordinate role in the steady-state transport across the combined peritoneal capillary,interstitial barrier. [source]


Insect silk contains both a Kunitz-type and a unique Kazal-type proteinase inhibitor

FEBS JOURNAL, Issue 7 2001
Xavier Nirmala
Insect silk is made up of structural fibrous (fibroins) and sticky (sericins) proteins, and contains a few small peptides of hitherto unknown functions. We demonstrate that two of these peptides inhibit bacterial and fungal proteinases (subtilisin, proteinase K and pronase). These ,silk proteinase inhibitors' 1 and 2 (SPI 1 and 2) are produced in the middle section of the silk-secreting glands prior to cocoon spinning and their production is controlled at transcription level. The full length cDNA of pre-SPI 1 contains 443 nucleotides and encodes a peptide of 76 amino-acid residues, of which 20 make up a signal sequence. The mature SPI 1 (6056.7 Da, 56 residues) is a typical thermostable Kunitz-type proteinase inhibitor with Arg in P1 position. The cDNA of pre-SPI 2 consists of 260 nucleotides and yields a putative secretory peptide of 58 amino-acid residues. The functional SPI 2 (3993 Da, 36 residues) is a single-domain Kazal-type proteinase inhibitor with unique structural features: free segment of the N-terminus is reduced to a single amino-acid residue, lack of CysI and CysV precludes formation of the A-ring and provides increased flexibility to the C-ring, and absence of several residues around the normal position of CysV shortens and changes the , helix segment of the protein. The structure reveals that the length and arrangement of the B-ring, including exposure of the P1 residue, and the position of the C-terminus relative to the B-loop, are essential for the activity of the Kazal-type inhibitors. [source]


Figulla ASD Occluder versus Amplatzer Septal Occluder: A Comparative Study on Validation of a Novel Device for Percutaneous Closure of Atrial Septal Defects

JOURNAL OF INTERVENTIONAL CARDIOLOGY, Issue 6 2009
AYSENUR PAC M.D.
Objectives: Occlutech Figulla ASD Occluder (FSO) is an alternative device to Amplatzer Septal Occluder (ASO) with some structural innovations including increased flexibility, minimizing the amount of material implanted, and absence of the left atrial clamp. We aimed to report our experiences with FSO and compare the outcomes of this novel device versus ASO. Interventions: Between December 2005 and February 2009, 75 patients diagnosed with secundum atrial septal defects underwent transcatheter closure. The FSO device was used in 33 patients, and the ASO was used in 42. Results: Patient characteristics, stretch size of the defect, device left disc size, procedure, and fluoroscopy time were similar between the groups. However, the difference between device waist size and stretched diameter of the defect was significantly higher, and device delivery sheath was significantly larger in FSO group and device left disc size was significantly lower in the FSO group. In all subjects, the residual shunt was small to trivial during follow-up and the reduction in prevalence of residual shunt with time was similar in both groups (P = 0.68). We found no differences in complication rate between the two devices; however, device embolization to the pulmonary bifurcation in one patient was recorded as major complication in FSO device group. Conclusions: Both devices are clinically safe and effective in ASD closure. FSO device has similar outcomes when compared to ASO device. Difficulties in selecting the correct device size in larger defects and larger venous sheath requirement need to be evaluated in further studies. [source]


Novel, cell-penetrating molecular transporters with flexible backbones and permanently charged side-chains

JOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 8 2007
N. Bodor
Various cell-penetrating peptides have been discovered recently that can translocate across plasma membranes and can even carry large cargo molecules into the cells. Because under physiological conditions most of these peptides carry considerable positive charges due to the presence of basic amino acids such as arginine, we decided to investigate whether molecular transporters composed of permanently charged side-chains also possess such cell penetrating ability. Arginine-rich oligomers that have a backbone with increased flexibility due to incorporation of non-,-amino acids (,-aminocaproic acid) have been found to be effective molecular transporters. Here, we report the preparation of analogue structures by replacing the arginine residues with the quaternary form of a novel redox amino acid (Nys+) that contain a trigonelline moiety; it has already been shown possible to replace the original basic amino acid side-chain of neuropeptides without significant activity-loss due to the sufficiently close steric and electronic analogy between the new Nys+ and the original side-chains (in their protonated form, e.g., Arg+, Lys+). A nonamer analogue showed transporter activity resulting in increased cellular uptake in human carcinoma (HeLa) cells. [source]


Flexibility, friendship, and family

PERSONAL RELATIONSHIPS, Issue 1 2008
GRAHAM ALLAN
This article is concerned with the impact of late modernity on patterns of solidarity in friend and family relationships. It takes as its starting point the transformations in partnership, family, and household formation and dissolution that have been occurring in Western societies since the 1970s. Accepting these shifts as indicative of the greater freedoms people now have over the construction of their personal relationships and social networks, the article examines the degree to which the domains of family and friendship are merging. Its principal argument is that despite increased flexibility in the construction of personal life, including diversity in the prioritization of different relationships, at a cultural level clear boundaries exist between family and friendship ties. [source]