Long-range cooperative binding effects in a T cell receptor variable domain

Although cellular processes depend on protein-protein interactions, our understanding of molecular recognition between proteins remains far from comprehensive. Protein-protein interfaces are structural and energetic mosaics in which a subset of interfacial residues, called hot spots, contributes disproportionately to the affinity of the complex. These hot-spot residues can be further clustered into hot regions. It has been proposed that binding energetics between residues within a hot region are cooperative, whereas those between hot regions are strictly additive. If this idea held true for all protein-protein interactions, then energetically significant long-range conformational effects would be unlikely to occur. In the present study, we show cooperative binding energetics between distinct hot regions that are separated by >20 A. Using combinatorial mutagenesis and surface plasmon resonance binding analysis to dissect additivity and cooperativity in a complex formed between a variable domain of a T cell receptor and a bacterial superantigen, we find that combinations of mutations from each of two hot regions exhibited significant cooperative energetics. Their connecting sequence is composed primarily of a single beta-strand of the T cell receptor variable Ig domain, which has been observed to undergo a strand-switching event and does not form an integral part of the stabilizing core of this Ig domain. We propose that these cooperative effects are propagated through a dynamic structural network. Cooperativity between hot regions has significant implications for the prediction and inhibition of protein-protein interactions.     

Contributions to ecological chemistry CXV1 metabolism of 2,5,4,′—trichlorobiphenyl-14C and 2,4,6,2′,4′ — pentachlorobiphenyl-14C in the marsh plantVeronica Beccabunga

Conclusions Under the experimental conditions used, 2, 4, 6, 2, 4 -pentachlorobiphenyl is more persistent than2, 5, 4 -trichlorobiphenyl. 2, 5, 4 —Trichlorobiphenyl is metabolized to at least two monohydroxy derivatives which occur in free form as well as conjugated in the plant tissues (Fig. 2).CXIV. Communication: KAMAL, M., I. WEISGERBER, W. KLEIN, and F. KORTE, Arch. Environ. Health, submitted for publication.     

Successful Treatment of Novel H1N1 Influenza related Fulminant Myocarditis with Extracorporeal Life Support

The prevalence of myocardial involvement in influenza infection ranges from 0% to 12%. The 2009 pH1N1 influenza virus, formerly known as swine flu, first appeared in Mexico and the United States of America in March and April 2009 and has swept the globe with unprecedented speed. We report a case of fulminant myocarditis associated with this virus treated successfully using extra-corporal membrane oxygenator.     

Myotilin: a prominent marker of myofibrillar remodelling

Myofibrillar remodelling with insertion of sarcomeres is a typical feature of biopsies taken from persons suffering of exercise-induced delayed onset muscle soreness. Here we studied the presence of the sarcomeric protein myotilin in eccentric exercise related lesions. Myotilin is a component of sarcomeric Z-discs and it binds several other Z-disc proteins, i.e. alpha-actinin, filamin C, F-actin and FATZ. Myotilin has previously been shown to be present in nemaline rods and central cores and to be mutated in limb girdle muscular dystrophy 1A (LGMD1A) and in a subset of myofibrillar myopathies, indicating an important role in Z-disc maintenance. Our findings on non-diseased muscle affected by eccentric exercise give new information on how myotilin is associated to myofibrillar components upon remodelling. We show that myotilin was present in increased amount in lesions related to Z-disc streaming and events leading to insertion of new sarcomeres in pre-existing myofibrils and can therefore be used as a marker for myofibrillar remodelling. Interestingly, myotilin is preferentially associated with F-actin rather than with the core Z-disc protein alpha-actinin during these events. This suggests that myotilin has a key role in the dynamic molecular events mediating myofibrillar assembly in normal and diseased skeletal muscle.     

Prevention of sternal dehiscence with the Sternum External Fixation (Stern-E-Fix) corset -- a randomized trial in 750 patients

ABSTRACT: BACKGROUND: The main objective of this study will be to determine the effects of a new advanced sternum external fixation (Stern-E-Fix) corset on prevention of sternal instability and mediastinitis in high-risk patients. METHODS: This prospective, randomized study (January 2009 -- June 2011) comprised 750 male patients undergoing standard median sternotomy for cardiac procedures (78% CABG). Patients were divided in two randomized groups (A, n = 380: received a Stern-E-Fix corset postoperatively for 6 weeks and B, n = 370: control group received a standard elastic thorax bandage). In both groups, risk factors for sternal dehiscence and preoperative preparations were similar. RESULTS: Wound infections occurred in n = 13 (3.42%) pts. in group A vs. n = 35 (9.46%) in group B. In group A, only 1 patient presented with sternal dehiscence vs. 22 pts. in group B. In all 22 patients, sternal rewiring followed by antibiotic therapy was needed. Mediastinitis related mortality was none in A versus two in B. Treatment failure in group B was more than five times higher than in A (p = 0.01); the mean length of stay in hospital was 12.53 +/- 7.4 days (A) versus 17.9 +/- 15.1 days (B)(p = 0.02). Re-operation for sternal infection was 4 times higher in group B. Mean ventilation time was relatively longer in B (2.5 vs. 1.28 days) (p = 0.01). The mean follow-up period was 8 weeks (range 6 -- 12 weeks). CONCLUSIONS: We demonstrated that using an external supportive sternal corset (Stern-E-Fix) yields a significantly better and effective prevention against development of sternal dehiscence and secondary sternal infection in high-risk poststernotomy patients.     

Prevention of Sternal Wound Infections in Women Using an External Sternum Fixation Corset

Purpose: Deep sternal wound infection (DSWI) and mediastinitis are devastating complications after median sternotomy. Previous studies demonstrated an effective prevention of sternal wound infection (SWI) using an external sternal corset in high-risk cardiac surgery patients. The aim of this study is to assess the preventive effect of the Stern-E-Fix corset in high-risk poststernotomy female patients.Methods: A total of 145 high-risk female patients undergoing cardiac surgery through median sternotomy were retrospectively analyzed. Patients were divided into group A (n = 71), who received the Stern-E-Fix corset (Fendel & Keuchen GmbH, Aachen, Germany), and group B (n = 74), who received the elastic thorax bandage (SanThorax) postoperatively for 6 weeks. The mean follow-up period was 12 weeks.Results: Incidence of SWI was 7% in group A vs. 17.6% in group B (p = 0.025). One patient presented with DSWI in group A vs. seven patients in group B (p = 0.063). No patient developed mediastinitis in group A vs. four patients in group B (p = 0.121). In all, 4.2% of group A patients required operative wound therapy vs. 16.2% of group B patients (p = 0.026). The length of hospital stay was significantly longer in group B (p = 0.006).Conclusion: Using an external supportive sternal corset (Stern-E-Fix) yields a significantly better and effective prevention against development of sternal dehiscence, DSWI, and mediastinitis in high-risk poststernotomy female patients.