Four and a half LIM protein 1 binds myosin-binding protein C and regulates myosin filament formation and sarcomere assembly

Four and a half LIM protein 1 (FHL1/SLIM1) is highly expressed in skeletal and cardiac muscle; however, the function of FHL1 remains unknown. Yeast two-hybrid screening identified slow type skeletal myosin-binding protein C as an FHL1 binding partner. Myosin-binding protein C is the major myosin-associated protein in striated muscle that enhances the lateral association and stabilization of myosin thick filaments and regulates actomyosin interactions. The interaction between FHL1 and myosin-binding protein C was confirmed using co-immunoprecipitation of recombinant and endogenous proteins. Recombinant FHL2 and FHL3 also bound myosin-binding protein C. FHL1 impaired co-sedimentation of myosin-binding protein C with reconstituted myosin filaments, suggesting FHL1 may compete with myosin for binding to myosin-binding protein C. In intact skeletal muscle and isolated myofibrils, FHL1 localized to the I-band, M-line, and sarcolemma, co-localizing with myosin-binding protein C at the sarcolemma in intact skeletal muscle. Furthermore, in isolated myofibrils FHL1 staining at the M-line appeared to extend partially into the C-zone of the A-band, where it co-localized with myosin-binding protein C. Overexpression of FHL1 in differentiating C2C12 cells induced "sac-like" myotube formation (myosac), associated with impaired Z-line and myosin thick filament assembly. This phenotype was rescued by co-expression of myosin-binding protein C. FHL1 knockdown using RNAi resulted in impaired myosin thick filament formation associated with reduced incorporation of myosin-binding protein C into the sarcomere. This study identified FHL1 as a novel regulator of myosin-binding protein C activity and indicates a role for FHL1 in sarcomere assembly.     

The CD11a partner in Sus scrofa lymphocyte function-associated antigen-1 (LFA-1): mRNA cloning, structure analysis and comparison with mammalian homologues

Background  

Lymphocyte function-associated antigen-1 (LFA-1, CD11a/CD18, alphaLbeta2), the most abundant and widely expressed beta2-integrin, is required for many cellular adhesive interactions during the immune response. Many studies have shown that LFA-1 is centrally involved in the pathogenesis of several diseases caused by Repeats-in-toxin (RTX) -producing bacteria.     

The Effect of Transdermal Delivery of Fentanyl on Activity in Growing Pigs

Recently, decreased activity levels have been observed in pigs treated postoperatively with transdermal delivery of fentanyl (TD-fentanyl) after isoflurane anaesthesia. Whether the change in behaviour is related to opioid-induced sedation or to insufficient pain relief remains to be investigated. This study was therefore undertaken to evaluate the effect of TD-fentanyl 50 μg h^-1 on the activity level with and without isoflurane anaesthesia. Eight pigs (25.4 ± 5.2 kg) were submitted to a cross-over study and given two treatments; 1) fentanyl patch applied after 30 minutes of anaesthesia (treatment A/F) and 2) fentanyl patch without anaesthesia (treatment F). The pigs' behaviour was observed from a video recording instantaneously every 10 minutes for 24 h before treatments and up to 72 h after the patch attachment. Venous blood samples were taken 1, 6, 12, 24, 48 and 72 h after the patch application. The behaviour recordings showed that TD-fentanyl did not produce sedation in any pig. No differences were found between the two treatments in activity level, weight gain or serum fentanyl concentration. This concentration measured after 24 h was 0.27 ± 0.11 ng ml^-1 and 0.47 ± 0.40 ng ml^-1 in the A/F and F group, respectively.     

Phase II protocol for the evaluation of new treatments in patients with advanced gastric carcinoma: results of ECOG 5282

The study was a Phase II randomized study to evaluate the efficacy of new agents for the treatment of advanced gastric carcinoma. Patients were randomized to receive single agent chemotherapy with mitoxantrone, etoposide, aclacinomycin-A or spirogermanium. The patients were stratified by prior use of chemotherapy, prior doxorubicin use and ECOG performance status. Patients with a history of cardiac disease or prior doxorubicin exceeding a dose of 400 mg/m² were restrictively randomized to sopirogermanium or etoposide only. One hundred and fourteen patients were registered for the study. Among 98 evaluable patients there were only two partial responses (both in the etoposide arm), and one complete response in the mitoxantrone arm. The median survival on the study was 3.3 months. One hundred and six patients were analyzable for toxicity. There were four treatment-related deaths and four life-threatening toxicities. Because of low response rates and relatively high toxicities the studied compounds were not deemed worth further investigation for advanced gastric cancer.     

Host habitat assessment by a parasitoid using fungal volatiles

Background

The genus Mantella, endemic poison frogs of Madagascar with 16 described species, are known in the field of international pet trade and entered under the CITES control for the last four years. The phylogeny and phylogeography of this genus have been recently subject of study for conservation purposes. Here we report on the studies of the phylogeography of the Mantella cowani group using a fragment of 453 bp of the mitochondrial cytochrome b gene from 195 individuals from 21 localities. This group is represented by five forms: M. cowani, a critically endangered species, a vulnerable species, M. haraldmeieri, and the non-threatened M. baroni, M. aff. baroni, and M. nigricans.

Results

The Bayesian phylogenetic and haplotype network analyses revealed the presence of three separated haplotype clades: (1) M. baroni, M. aff. baroni, M. nigricans, and putative hybrids of M. cowani and M. baroni, (2) M. cowani and putative hybrids of M. cowani and M. baroni, and (3) M. haraldmeieri. The putative hybrids were collected from sites where M. cowani and M. baroni live in sympatry.

Conclusion

These results suggest (a) a probable hybridization between M. cowani and M. baroni, (b) a lack of genetic differentiation between M. baroni/M. aff. baroni and M. nigricans, (c) evidence of recent gene-flow between the northern (M. nigricans), eastern (M. baroni), and south-eastern (M. aff. baroni) forms of distinct coloration, and (d) the existence of at least three units for conservation in the Mantella cowani group.     

Hepatitis B Antigen in Viral Hepatitis in West London

During the first 12 months of a total population survey 249 patients were seen with viral hepatitis. A total of 215 of these were tested for hepatitis B antigen (HB Ag) by radioimmunoassay and 32 (15%) were positive.More than five times as many men (27) as women (5) were HBAg positive and 19 of the men were between the ages of 20 and 39 years. There were only four drug addicts among those tested, two of whom were positive, as were two of the four patients who were tattooed.Sixty out of 86 children (under 15 years) were tested for HBAg and none was positive.     

Cell-mediated Immunity to Intrinsic Factor in Autoimmune Disorders

Evidence of cell-mediated immunity to gastric intrinsic factor was present in 86% of patients with pernicious anaemia and in at least 13% of patients with hyperthyroidism, 21% of patients with atrophic gastritis, and four out of nine (46%) patients with hypogammaglobulinaemia. Controls gave negative results. The four patients with hypogammaglobulinaemia and cell-mediated immunity to intrinsic factor had evidence of impaired gastric function.