The antibacterial threaded-lasso peptide capistruin inhibits bacterial RNA polymerase

Capistruin, a ribosomally synthesized, post-translationally modified peptide produced by Burkholderia thailandensis E264, efficiently inhibits growth of Burkholderia and closely related Pseudomonas strains. The functional target of capistruin is not known. Capistruin is a threaded-lasso peptide (lariat peptide) consisting of an N-terminal ring of nine amino acids and a C-terminal tail of 10 amino acids threaded through the ring. The structure of capistruin is similar to that of microcin J25 (MccJ25), a threaded-lasso antibacterial peptide that is produced by some strains of Escherichia coli and targets DNA-dependent RNA polymerase (RNAP). Here, we show that capistruin, like MccJ25, inhibits wild type E. coli RNAP but not mutant, MccJ25-resistant, E. coli RNAP. We show further that an E. coli strain resistant to MccJ25, as a result of a mutation in an RNAP subunit gene, exhibits resistance to capistruin. The results indicate that the structural similarity of capistruin and MccJ25 reflects functional similarity and suggest that the functional target of capistruin, and possibly other threaded-lasso peptides, is bacterial RNAP.     

Decomposition of tensiomyogram and comparison with torque twitch responses after post-activation potentiation

Objectives:This study evaluates the effect of post-activation potentiation (PAP) after 5x5s maximal voluntary isometric contractions (activation stimulus, AS) on tensiomyography (TMG) and torque twitch contractile parameters of vastus lateralis (VL) and medialis (VM), respectively. Further, we validated the decomposition of TMG response to separate responses of three fiber types.Methods:15 healthy individuals participated in this study (40% women; age 19±2.3 years). A decomposition of VL TMG response was done after optimal fitting of three exponential curves.Results:We found main effects in contraction time (Tc) for muscle, method and time. Furthermore, we found interactions between muscle*method, method*time and muscle*method*time. Compared to PRE AS, we found shorter TMG Tc in VL and VM during the first two minutes after AS. Torque Tc remained unchanged in VL, while it increased in VM within 30 seconds after AS. A decomposition of VL TMG response confirmed PAP effects being present only in decomposed type IIb muscle fibers.Conclusion:The TMG is a sensitive method to detect PAP effects with a sensor mounted directly above the muscle belly. After the decomposition of the TMG signal to three separate muscle fiber phenotypes, we provided a non-invasive insight in the contribution of each muscle fiber phenotype to the PAP of the whole muscle.     

Ovarian cancer: PCD and brain metastases

Paraneoplastic cerebellar degeneration (PCD), the one of the most common paraneoplastic syndromes, refer to clinical disorders associated mostly with lung, ovarian and breast cancer, but not directly caused by the cancer or its metastases. Pathologic finding is an extensive loss of Purkinje cells in the cerebellum. Immunohistochemically, the auto-antibodies on the Purkinje cells had been detected. Clinically, PCD is characterized by sub-acutely evolving pancerebellar symptoms. Neurological dysfunction may appear before the detection of the underlying cancer. Therefore, the surgical exploration is necessary for the final diagnosis. The patient undergoes specific therapy. Soon, neurological status of the patient gets irreparable worse. Death come usually 2-3 years after the first symptoms of the PCD occurs. Case of a 63-years old woman with PCD as the first evidence of her cancer is reported. The patient developed brain metastases and died almost 3 years after the first symptoms of PCD occur     

The prevalence of cardiovascular disease risk factors in patients from Croatian Zagorje County treated at Department of Medicine, Zabok General Hospital from 2000 to 2006

The aim of the study was to assess the prevalence of risk factors for cardiovascular disease in patients treated for coronary heart disease (CHD) at Department of Medicine, Zabok General Hospital during the 2000-2006 period. Cardiovascular diseases are a group of diseases that occur due to arterial. The risk factors that lead to the development and occurrence of cardiovascular disease are hypertension, cigarette smoking, hyperholesterolemia, hypertriglyceridemia, diabetes mellitus and positive family history. Additional factors favoring the occurrence of cardiovascular disease include overweight, inadequate physical activity, and emotional stress. Data on all patients hospitalized and diagnosed with CHD at Department of Medicine, Zabok General Hospital during the 2000-2006 period were analyzed for the prevalence of risk factors for CHD, i.e. hypertension, cigarette smoking, hypercholesterolemia, hypertriglyceridemia, diabetes mellitus and positive family history of cardiovascular disease. Hypercholesterolemia was defined by a cholesterol level higher than 5.1 mmol/L, hypertension from history data and blood pressure measurement on admission greater than 140/90 mmHg, diabetes mellitus from history data, and hypertriglyceridemia by a triglyceride level greater than 1.7 mmol/L. Information on heredity and cigarette smoking was collected from history and a questionnaire filled out on admission. All laboratory values were determined on patient admission to the hospital. Analysis of the risk factors for CHD recorded in patients from Zagorje County during the 2000-2006 period revealed hypertension to be the most common risk factor in our patients. According to sex, CHD was found to show a male preponderance. According to age at admission, CHD predominated in the > 70 age group, which accounted for one third of all patients, followed by a comparable proportion of the 50-60 and 60-70 age groups, i.e. still active population groups. As CHD is one of the leading health threats worldwide, estimated to remain so at least by 2020, it is fully justified to invest all efforts in the study of cardiovascular disease. New research projects should be focused on the prevention and early detection of the disease, improvement of diagnosis procedures, introduction of novel therapeutic options, use of new concepts, and due survey of the measures taken. CHD poses great socioeconomic burden upon every community in industrialized societies because of the ever younger age at onset. Actions should be taken to improve awareness of the CHD risks and morbidity in the population at large, stimulating favorable lifestyle and dietary modifications, and one's own health awareness, in order to upgrade the control of risk factors for and morbidity of cardiovascular disease.     

Sunshine on holidays--eye risks

Ultraviolet (UV) light is the most common cause of radiation injury to the eye which in acute exposure causes photokeratitis and photoconjunctivitis. After a whole day exposure to the sun on the Mediteranian coast patient presented with mixed conjunctival injection, chemosis, edematous corneal epithelium with superficially present fluoresceine positive small pinpoint defects. Epithelial bullous changes, circular stromal infiltration in the middle stromal perifery and reduction of corneal transparency were more pronounced on the left eye. After treatment moderate conjunctival injection remained together with circular stromal infiltration in the middle perifery, corneas were transparent, epithelialised and fluorescein negative. Anterior chambers and lenses were clear. One month after patient regained bilateral visual acuity of 1.0. To our kownledge, this case shows for the first time connection between acute ultraviolet radiation exposure and persistent circular stromal infiltration in the middle corneal perifery in humans.     

DNA end resection controls the balance between homologous and illegitimate recombination in Escherichia coli

Even a partial loss of function of human RecQ helicase analogs causes adverse effects such as a cancer-prone Werner, Bloom or Rothmund-Thompson syndrome, whereas a complete RecQ deficiency in Escherichia coli is not deleterious for a cell. We show that this puzzling difference is due to different mechanisms of DNA double strand break (DSB) resection in E. coli and humans. Coupled helicase and RecA loading activities of RecBCD enzyme, which is found exclusively in bacteria, are shown to be responsible for channeling recombinogenic 3' ending tails toward productive, homologous and away from nonproductive, aberrant recombination events. On the other hand, in recB1080/recB1067 mutants, lacking RecBCD's RecA loading activity while preserving its helicase activity, DSB resection is mechanistically more alike that in eukaryotes (by its uncoupling from a recombinase polymerization step), and remarkably, the role of RecQ also becomes akin of its eukaryotic counterparts in a way of promoting homologous and suppressing illegitimate recombination. The sickly phenotype of recB1080 recQ mutant was further exacerbated by inactivation of an exonuclease I, which degrades the unwound 3' tail. The respective recB1080 recQ xonA mutant showed poor viability, DNA repair and homologous recombination deficiency, and very increased illegitimate recombination. These findings demonstrate that the metabolism of the 3' ending overhang is a decisive factor in tuning the balance of homologous and illegitimate recombination in E. coli, thus highlighting the importance of regulating DSB resection for preserving genome integrity. recB mutants used in this study, showing pronounced RecQ helicase and exonuclease I dependence, make up a suitable model system for studying mechanisms of DSB resection in bacteria. Also, these mutants might be useful for investigating functions of the conserved RecQ helicase family members, and congruently serve as a simpler, more defined model system for human oncogenesis.