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31.
LC Rome DA Syme S Hollingworth SL Lindstedt SM Baylor 《Canadian Metallurgical Quarterly》1996,93(15):8095-8100
Vertebrate sound producing muscles often operate at frequencies exceeding 100 Hz, making them the fastest vertebrate muscles. Like other vertebrate muscle, these sonic muscles are "synchronous," necessitating that calcium be released and resequestered by the sarcoplasmic reticulum during each contraction cycle. Thus to operate at such high frequencies, vertebrate sonic muscles require extreme adaptations. We have found that to generate the "boatwhistle" mating call (approximately 200 Hz), the swimbladder muscle fibers of toadfish have evolved (i) a large and very fast calcium transient, (ii) a fast crossbridge detachment rate, and (iii) probably a fast kinetic off-rate of Ca2+ from troponin. The fibers of the shaker muscle of rattlesnakes have independently evolved similar traits, permitting tail rattling at approximately 90 Hz. 相似文献
32.
33.
Dougan DA; Malby RL; Gruen LC; Kortt AA; Hudson PJ 《Protein engineering, design & selection : PEDS》1998,11(1):65-74
The interactions between the Fab and single-chain Fv (scFv) fragments of an
antibody (NC10) and its antigen, influenza virus neuraminidase, were
analysed in the crystal structures of the Fab-neuraminidase and
scFv-neuraminidase complexes. To investigate the contribution to binding
made by cavities, salt links and hydrogen bonds in the antibody- antigen
interface, 14 single amino acid replacements were made at six contact
residues in the scFv fragment by site-directed mutagenesis. The binding
affinity of each mutant scFv antibody for neuraminidase was determined with
a BIAcore optical biosensor. Four of the mutations resulted in large
changes in the free energy of binding to neuraminidase (deltadeltaG > 1
kcal/mol) and together may account for approximately 70% of the free energy
of binding. Hence these data support the theory that a small number of
residues form the 'functional epitope' and are most important for binding
of NC10 to neuraminidase. The salt link between antibody residue (Asp)H56
and (Lys)N432 from neuraminidase was demonstrated to be important for
affinity, since substitution of (Asp)H56 with Asn caused a large reduction
in the free energy of binding (deltadeltaG = +2.8 kcal/mol). Hydrogen bonds
provided by (Tyr)L32 and (Asp)H56 were also important for binding: mutation
of (Tyr)L32 to Phe resulted in a significant reduction in binding affinity
(deltadeltaG = +1.7 kcal/mol). Disruption of hydrophobic interactions (van
der Waals contacts) led to significant reductions in affinity also
((Tyr)H99 to Ala, deltadeltaG = +1.5 kcal/mol; (Leu)L94 to Ala, deltadeltaG
> +3.0 kcal/mol). An attempt to increase binding affinity by filling a
cavity in the interface with a larger antibody side chain was unsuccessful,
as the free energy gained by new antibody-antigen interactions did not
compensate for the removal of cavity-bound water molecules.
相似文献
34.
Alessandro Marchioni Roberto Tonelli Alessandro Andreani Gaia Francesca Cappiello Matteo Fermi Fabiana Trentacosti Ivana Castaniere Riccardo Fantini Luca Tabbì Dario Andrisani Filippo Gozzi Giulia Bruzzi Linda Manicardi Antonio Moretti Serena Baroncini Anna Valeria Samarelli Massimo Pinelli Giorgio De Santis Alessandro Stefani Daniele Marchioni Francesco Mattioli Enrico Clini 《International journal of molecular sciences》2022,23(5)
Laryngotracheal stenosis (LTS) is a complex and heterogeneous disease whose pathogenesis remains unclear. LTS is considered to be the result of aberrant wound-healing process that leads to fibrotic scarring, originating from different aetiology. Although iatrogenic aetiology is the main cause of subglottic or tracheal stenosis, also autoimmune and infectious diseases may be involved in causing LTS. Furthermore, fibrotic obstruction in the anatomic region under the glottis can also be diagnosed without apparent aetiology after a comprehensive workup; in this case, the pathological process is called idiopathic subglottic stenosis (iSGS). So far, the laryngotracheal scar resulting from airway injury due to different diseases was considered as inert tissue requiring surgical removal to restore airway patency. However, this assumption has recently been revised by regarding the tracheal scarring process as a fibroinflammatory event due to immunological alteration, similar to other fibrotic diseases. Recent acquisitions suggest that different factors, such as growth factors, cytokines, altered fibroblast function and genetic susceptibility, can all interact in a complex way leading to aberrant and fibrotic wound healing after an insult that acts as a trigger. However, also physiological derangement due to LTS could play a role in promoting dysregulated response to laryngo-tracheal mucosal injury, through biomechanical stress and mechanotransduction activation. The aim of this narrative review is to present the state-of-the-art knowledge regarding molecular mechanisms, as well as mechanical and physio-pathological features behind LTS. 相似文献
35.
Studies in our laboratory have shown that as early as day 8.5 of development, mouse yolk sac cells can generate T cells when placed in a thymic microenvironment. At this stage, yolk sac cells can also differentiate into myeloid cells in vitro. B cell differentiation in vitro was achieved with day 9 yolk sac by providing a bone marrow stromal feeder layer. We have now established endothelial cell lines and clones from yolk sacs of day 8-12 mouse embryos. These vary in their ability to support stem cell maintenance and differentiation. Our principal work has been carried out with day 12 cloned endothelial cell lines. One clone supported the > 100 fold expansion of yolk sac hematopoietic stem cells that subsequently could generate B cells, T cells and myeloid cells both in vitro and in vivo. Preliminary experiments with endothelial cells from younger embryos are also described. 相似文献
36.
R Ameratunga JA Winkelstein L Brody M Binns LC Cork P Colombani D Valle 《Canadian Metallurgical Quarterly》1998,160(6):2824-2830
Genetically determined deficiency of the third component of complement (C3) in the dog is characterized by a predisposition to recurrent bacterial infections and to type 1 membranoproliferative glomerulonephritis. The current studies were undertaken to characterize the cDNA for wild-type canine C3 and identify the molecular basis for hereditary canine C3 deficiency. Amplification, cloning, and sequence analysis indicated that canine C3 is highly conserved in comparison with human, mouse, and guinea pig C3. Southern blot analysis failed to show any gross deletions or rearrangements of DNA from C3-deficient animals. Northern blot analysis indicated that the livers of these animals contain markedly reduced quantities of a normal length C3 mRNA. The full-length 5.1-kb canine C3 cDNA was amplified in overlapping PCR fragments. Sequence analysis of these fragments has shown a deletion of a cytosine at position 2136 (codon 712), leading to a frameshift that generates a stop codon 11 amino acids downstream. The deletion has been confirmed in genomic DNA, and its inheritance has been demonstrated by allele-specific oligonucleotide hybridization. 相似文献
37.
LC Maroto Y Carrascal MJ López A Forteza A Pérez C Zavanella 《Canadian Metallurgical Quarterly》1998,66(6):2110-2111
An asymptomatic cardiac cyst located in the interventricular septum was diagnosed in a 3.5-year-old child by echocardiographic findings. Surgical ablation was done and histopathologic analysis confirmed a hydatid cyst. The patient was discharged without symptoms. 相似文献
38.
N Raskin A Jakubowski ID Sizing DL Olson SL Kalled CA Hession CD Benjamin DP Baker LC Burkly 《Canadian Metallurgical Quarterly》1998,161(7):3474-3483
The IL receptor common gamma (gamma c) chain is required for the formation of high affinity cytokine receptor complexes for IL-2, IL-4, IL-7, IL-9, and IL-15, and for signals regulating cell survival, growth, and differentiation. Our current understanding of how gamma c chain associates with multiple ligands and receptor subunits is drawn largely from its structural homology to the human growth hormone (hGH) receptor and known structure of the hGH/hGH receptor complex. These receptors share distinct features in their extracellular portions and are believed to function by a mechanism of ligand-induced association of receptor subunits. Here, we report the first directed mutational analysis of the human gamma c chain by alanine scanning conducted across seven regions likely to contain residues required for intermolecular contact. Functionally distinct, neutralizing anti-gamma c mAbs were employed to define critical residues. One particular mAb, CP.B8, unique in its ability to inhibit IL-2-, IL-4-, IL-7-, and IL-15-induced proliferation and high affinity cytokine binding of normal T cells as an intact mAb and as a Fab fragment, localized critical residues to four noncontinuous stretches, namely residues in loops AB and EF of domain 1, in the interdomain segment, and in loop FG of domain 2. Notably, these residues form a contiguous patch on the gamma c chain surface in a three-dimensional structural model. These results provide functional evidence for the location of contact points on gamma c chain required for its association with multiple ligands. 相似文献
39.
U Pastorino G Muscolino M Valente S Andreani L Tavecchio M Infante G Terno G Ravasi 《Canadian Metallurgical Quarterly》1994,107(2):596-599
The reliability of polyglyconate monofilament (Maxon) suture for sternal closure was tested on 216 consecutive sternotomies, performed on 208 patients in our department from January 1986 to December 1990. The reason of sternotomy was primary lung cancer in 34 cases (16%), lung metastases in 127 (59%), and disorders of the thymus in 55 (25%). Mean age was 38 years (range 3 to 78 years); multiple lung resections were performed in 102 patients (average 7 lesions, range 2 to 30); maximum extent of the operation was pneumonectomy in 2 cases, lobectomy in 53, segmentectomy in 27, and wedge resection in 74. Prior chemotherapy had been administered in 75 cases (35%). A second sternotomy was performed in 8 cases. No cases of sternal dehiscence, sternal infection, or empyema were observed, after a median follow-up of 27 months. Overall perioperative mortality was 0.9% (2/216). Our series demonstrates the safety of polyglyconate monofilament (Maxon) suture for sternal closure. Absorbable sutures appear to be a safe alternative to steel wire closure in patients undergoing extended pulmonary or mediastinal resection. 相似文献
40.