Interaction of the DYNLT (TCTEX1/RP3) light chains and the intermediate chains reveals novel intersubunit regulation during assembly of the dynein complex

The cytoplasmic dynein 1 cargo binding domain is formed by five subunits including the intermediate chain and the DYNLT, DYNLL, and DYNLRB light chain families. Six isoforms of the intermediate chain and two isoforms of each of the light chain families have been identified in mammals. There is evidence that different subunit isoforms are involved in regulating dynein function, in particular linking dynein to different cargoes. However, it is unclear how the subunit isoforms are assembled or if there is any specificity to their interactions. Co-immunoprecipitation using DYNLT-specific antibodies reveals that dynein complexes with DYNLT light chains also contain the DYNLL and DYNLRB light chains. The DYNLT light chains, but not DYNLL light chains, associate exclusively with the dynein complex. Yeast two-hybrid and co-immunoprecipitation assays demonstrate that both members of the DYNLT family are capable of forming homodimers and heterodimers. In addition, both homodimers of the DYNLT family bind all six intermediate chain isoforms. However, DYNLT heterodimers do not bind to the intermediate chain. Thus, whereas all combinations of DYNLT light chain dimers can be made, not all of the possible combinations of the isoforms are utilized during the assembly of the dynein complex.     

Circumflex artery-related acute myocardial infarction: limited ECG abnormalities but poor outcome

Background. Circumflex (CX) artery-related myocardial infarction (MI) is less well represented in trials on ST-elevation acute myocardial infarction (STEMI), most often due to the absence of significant ST-segment elevation, and therefore the outcome of these patients is less well known. We aimed to compare the outcome of patients with CX versus right coronary artery (RCA) related STEMI in a large cohort of patients treated with primary angioplasty. Methods. A total of 1683 consecutive patients with STEMI were studied. Patients who lacked STsegment elevation were also included if they had persistent chest pain with signs of ischaemia or regional wall motion abnormalities on echocardiography. Coronary angioplasty was performed according to standard procedures. After the intervention, all patients received aspirin and clopidogrel or ticlopidine. Results. The infarct-related vessel was the CX in 229 patients (14%) and the RCA in 600 patients (36%). No differences in baseline characteristics were present. Mean extent of ST-segment elevation or deviation was significantly higher in patients with the RCA as infarct-related vessel. Enzymatic infarct size was significantly higher in the CXrelated MI (1338±1117 IU/l vs. 1806±1498 IU/l, p<0.001). Left ventricular ejection fraction <45% was more often present in patients with CXrelated MI (37 vs. 26%, p<0.01). Both short- and long-term mortality were significantly higher in the CX-related MI. Conclusion. This study emphasises the fact that CX-related infarction has a worse prognosis compared with RCA-related infarction. (Neth Heart J 2007;15:286-90.)     

Fundamental studies of the cytochrome c immobilization by the potential cycling method on nanometer-scale nickel oxide surfaces

This work describes the performance of cytochrome c/nickel oxide nanoparticles/glassy carbon electrode, prepared by the electrochemical deposition of the nickel oxide nanoparticles (NiO NPs) on the glassy carbon (GC) electrode surface and the cytochrome c immobilization on the nickel oxide nanoparticle surfaces. An extensive sample examination with the help of the SEM and AFM presented the existence of different geometrical shapes of the nickel oxide particles. These geometrical structures could lead to the better immobilization of proteins on their surfaces. The resulting electrode displayed an excellent behavior for the redox of the cytochrome c. Also, the resulting heme protein exhibited a direct electrical contact with the electrode because of the structural alignment of the heme protein on the nanometer-scale nickel oxide surfaces. This method could be suitable for applications to nanofabricated devices. In the end, it was concluded that the cytochrome c could be tethered to the nanometer-scale nickel oxide surfaces.     

Are patients with non-ST elevation myocardial infarction undertreated?

Background

We have previously documented significant differences in orthogonal P wave morphology between patients with and without paroxysmal atrial fibrillation (PAF). However, there exists little data concerning normal P wave morphology. This study was aimed at exploring orthogonal P wave morphology and its variations in healthy subjects.

Methods

120 healthy volunteers were included, evenly distributed in decades from 20–80 years of age; 60 men (age 50+/-17) and 60 women (50+/-16). Six-minute long 12-lead ECG registrations were acquired and transformed into orthogonal leads. Using a previously described P wave triggered P wave signal averaging method we were able to compare similarities and differences in P wave morphologies.

Results

Orthogonal P wave morphology in healthy individuals was predominately positive in Leads X and Y. In Lead Z, one third had negative morphology and two-thirds a biphasic one with a transition from negative to positive. The latter P wave morphology type was significantly more common after the age of 50 (P < 0.01). P wave duration (PWD) increased with age being slightly longer in subjects older than 50 (121+/-13 ms vs. 128+/-12 ms, P < 0.005). Minimal intraindividual variation of P wave morphology was observed.

Conclusion

Changes of signal averaged orthogonal P wave morphology (biphasic signal in Lead Z), earlier reported in PAF patients, are common in healthy subjects and appear predominantly after the age of 50. Subtle age-related prolongation of PWD is unlikely to be sufficient as a sole explanation of this finding that is thought to represent interatrial conduction disturbances. To serve as future reference, P wave morphology parameters of the healthy subjects are provided.     

Improving the performance of an acid-labile 4-hydroxymethyl phenoxyacetic acid (HMP) linker on resin and SynPhase grafted solid-supports.

A replacement of the acetic acid moiety by valeric acid within the 4-hydroxymethylphenoxyacetic acid (HMP) linker (Sheppard RC, Williams BJ. Acid-labile resin linkage agents for use in solid phase peptide synthesis. Int. J. Peptide Protein Res. 1982; 20: 451-454) significantly improved its performance in terms of loading capacity, yield and purity of the final products. The results indicated the spacer-linker combination and type of solid supports are important factors for solid-phase synthesis.