Comparison of P-wave dispersion in healthy dogs,dogs with chronic valvular disease and dogs with disturbances of supraventricular conduction

Background  

P-wave dispersion (P_d) is a new ECG index used in human cardiology and veterinary medicine. It is defined as the difference between the maximum and the minimum P-wave duration recorded from multiple different ECG leads. So far no studies were performed assessing the importance of P-wave dispersion in dogs.     

Integration of additional copies of Trichoderma reesei gene encoding protein O-mannosyltransferase I results in a decrease of the enzyme activity and alteration of cell wall composition

In fungi, transfer of the first mannosyl residue to proteins during their O-glycosylation is catalyzed by protein O-mannosyltransferases. Integration of additional copies of the pmt1 gene into Trichoderma reesei genome unexpectedly resulted in the silencing of pmt1 expression. Strains carrying the additional copies of pmt1 gene exhibited lower total activity of protein O-mannosyltransferases, lower O- and N-glycosylation of secreted proteins and showed defects in their cell wall composition. Moreover, the strains grew slowly on solid medium and were hypersensitive to an antifungal reagent, Calcofluor white. These results indicate that protein O-mannosyltransferases are required for proper cell wall formation, and their decreased activity influences not only O- but also N-glycosylation.     

Microbiological and molecular assessment of bacteriophage ISP for the control of Staphylococcus aureus

The increasing antibiotic resistance in bacterial populations requires alternatives for classical treatment of infectious diseases and therefore drives the renewed interest in phage therapy. Methicillin resistant Staphylococcus aureus (MRSA) is a major problem in health care settings and live-stock breeding across the world. This research aims at a thorough microbiological, genomic, and proteomic characterization of S. aureus phage ISP, required for therapeutic applications. Host range screening of a large batch of S. aureus isolates and subsequent fingerprint and DNA microarray analysis of the isolates revealed a substantial activity of ISP against 86% of the isolates, including relevant MRSA strains. From a phage therapy perspective, the infection parameters and the frequency of bacterial mutations conferring ISP resistance were determined. Further, ISP was proven to be stable in relevant in vivo conditions and subcutaneous as well as nasal and oral ISP administration to rabbits appeared to cause no adverse effects. ISP encodes 215 gene products on its 138,339 bp genome, 22 of which were confirmed as structural proteins using tandem electrospray ionization-mass spectrometry (ESI-MS/MS), and shares strong sequence homology with the 'Twort-like viruses'. No toxic or virulence-associated proteins were observed. The microbiological and molecular characterization of ISP supports its application in a phage cocktail for therapeutic purposes.     

From genotype to phenotype in bovine functional genomics

In past 5 years, the promise that came with genome sequencing has revolutionized the functional genomics research field at unprecedented manner. It would soon know what all known genes do, particularly genes involved in genetic improvement of animal health and increase food animal production. With the availability of full bovine genomic sequence, yet we still have a lot of daunting tasks on 'genotype-to-phenotype problem' particularly about the phenotypic variations and trying to predict what genes are likely to be involved, and improved integrated interactive database. This article outlined and discussed about the current status of bovine functional genomics, recent development in bovine genome databases particularly in annotation of bovine genome, bovine quantitative trait loci database and its potential impact to unveil the from genotype-to-phenotype problem.     

Dynactin helps target Polo‐like kinase 1 to kinetochores via its left‐handed beta‐helical p27 subunit

Dynactin is a protein complex required for the in vivo function of cytoplasmic dynein, a microtubule (MT)‐based motor. Dynactin binds both dynein and MTs via its p150^Glued subunit, but little is known about the ‘pointed‐end complex’ that includes the protein subunits Arp11, p62 and the p27/p25 heterodimer. Here, we show that the p27/p25 heterodimer undergoes mitotic phosphorylation by cyclin‐dependent kinase 1 (Cdk1) at a single site, p27 Thr186, to generate an anchoring site for polo‐like kinase 1 (Plk1) at kinetochores. Removal of p27/p25 from dynactin results in reduced levels of Plk1 and its phosphorylated substrates at kinetochores in prometaphase, which correlates with aberrant kinetochore–MT interactions, improper chromosome alignment and abbreviated mitosis. To investigate the structural implications of p27 phosphorylation, we determined the structure of human p27. This revealed an unusual left‐handed β‐helix domain, with the phosphorylation site located within a disordered, C‐terminal segment. We conclude that dynactin plays a previously undescribed regulatory role in the spindle assembly checkpoint by recruiting Plk1 to kinetochores and facilitating phosphorylation of important downstream targets.     

Gene therapy on demand: Site specific regulation of gene therapy

Since 1990 when the first clinical gene therapy trial was conducted, much attention and considerable promise have been given to this form of treatment. Gene therapy has been used with success in patients suffering from severe combined immunodeficiency syndromes (X-SCID and ADA-deficiency), Leber's congenital amaurosis, hemophilia, β-thalassemia and adrenoleukodystrophy. Last year, the first therapeutic vector (Glybera) for treatment of lipoprotein lipase deficiency has been registered in the European Union. Nevertheless, there are still several numerous issues that need to be improved to make this technique more safe, effective and easily accessible for patients.     

Fenoterol did not enhance glucocorticoid-induced skeletal changes in male rats

Glucocorticoids and β(2)-adrenergic receptor agonists are the most commonly used drugs in the treatment of asthma. Both therapies are potentially dangerous to the skeletal system. The aim of the present study was to investigate the effects of fenoterol, a β(2)-receptor agonist, on the development of bone changes induced by glucocorticoid (prednisolone) administration in mature male rats. The experiments were carried out on 24-week-old male Wistar rats. The effects of prednisolone 21-hemisuccinate sodium salt (7 mg/kg s.c. daily) or/and fenoterol hydrobromide (1.4 mg/kg i.p. daily), administered for 4 weeks, on the skeletal system were studied. Bone turnover markers, geometric parameters, mass, mass of bone mineral in the tibia, femur and L-4 vertebra, bone histomorphometric parameters and mechanical properties of tibial metaphysis, femoral diaphysis and femoral neck were determined. Both prednisolone and fenoterol had damaging effects on the skeletal system of mature male rats. However, concurrent administration of fenoterol and prednisolone did not result in the intensification of the deleterious skeletal effect of either drug administered separately.     

Distribution of mitochondrial haplotypes (cytb) in Polish populations of Emys orbicularis (L., 1758)

The European pond turtle, Emys orbicularis, inhabits a wide distribution area in the western Palaearctic. Polish populations of pond turtle represent the nominotypical subspecies Emys orbicularis orbicularis. The mitochondrial DNA haplotype (cytb gene) variation among 131 turtles from 26 locations in five regions of Poland was investigated. Five haplotypes belonging to three distinct lineages were identified. Two clades (I and II) were represented by two haplotypes each, while the other clade (IV) was represented by one haplotype. Three haplotypes were reported for the first time in E. orbicularis. The eastern part of Poland is inhabited exclusively by turtles bearing haplotype Ia. The remaining four sequence variants were recorded in western Poland where only the IIb haplotype is considered endemic. The distribution of the other haplotypes in western Poland could thus reflect past introductions or accidental releases. The authors regarded the two locations (Drzeczkowo and Karpicko) that were first included in the western Poland populations as autochthonous catchment areas of haplotype Ia.