Visualisation of tissue kallikrein, kininogen and kinin receptors in human skin following trauma and in dermal diseases

During dermal injury and inflammation the serine proteases kallikreins cleave endogenous, multifunctional substrates (kininogens) to form bradykinin and kallidin. The actions of kinins are mediated by preferential binding to constitutively expressed kinin-B2 receptors or inducible kinin-B1 receptors. A feature of the kinin-B1 receptors is that they show low levels of expression, but are distinctly upregulated following tissue injury and inflammation. Because recent evidence suggested that kinin-B1 receptors may perform a protective role during inflammation, we investigated the specific occurrence of the kallikrein-kinin components in skin biopsies obtained from normal skin, patients undergoing surgery, basalioma, lichenificated atopic eczema, and psoriasis. The tissue was immunolabelled in order to determine the localisation of tissue pro-kallikrein, kallikrein, kininogen and kinin receptors. The kinin components were visualised in normal, diseased and traumatised skin, except that no labelling was observed for kininogen in normal skin. Of the five types of tissue examined, upregulation of kinin-B1 receptors was observed only in skin biopsies obtained following surgery. In essence, the expression of kinin-B1 receptors did not appear to be enhanced in the other biopsies. Within the multiple steps of the inflammatory cascade in wound healing, our results suggest an important regulatory role for kinin-B1 receptors during the first phase of inflammation following injury

Reduction of myocardial infarction by calpain inhibitors A-705239 and A-705253 in isolated perfused rabbit hearts

Two novel calpain inhibitors (A-705239 and A-705253) were studied in isolated perfused rabbit hearts subjected to 60-min occlusion of the ramus interventricularis of the left coronary artery (below the origin of the first diagonal branch), followed by 120 min of reperfusion. The inhibitors were added to the perfusion fluid in various final concentrations from the beginning of the experiments before the coronary artery was blocked. Hemodynamic monitoring and biochemical analysis of perfusion fluid from the coronary outflow were carried out. Myocardial infarct size and the area at risk (transiently non-perfused myocardium) were determined from left ventricular slices after a special staining procedure with Evans blue and 2,3,5-triphenyltetrazolium chloride. The infarcted area (dead myocardium) was 77.9 +/- 2.3% of the area at risk in untreated controls (n=12). The infarct size was significantly reduced in the presence of both calpain inhibitors. The best effect was achieved with 10(-8) m A-705253 (n=8), which reduced (p<0.001) the infarcted area to 49.3 +/- 3.9% of the area at risk, corresponding to an infarct reduction of 61.8%. No statistical difference was observed between the experimental groups in coronary perfusion, left ventricular pressure, and in the release of lactate dehydrogenase and creatine kinase from heart muscle

Confident Feature Ranking

Interpretation of feature importance values often relies on the relative order of the features rather than on the value itself, referred to as ranking. However, the order may be unstable due to the small sample sizes used in calculating the importance values. We propose that post-hoc importance methods produce a ranking and simultaneous confident intervals for the rankings. Based on pairwise comparisons of the feature importance values, our method is guaranteed to include the ``true'' (infinite sample) ranking with high probability and allows for selecting top-k sets

Nördliche Badia, Jordanien: Aride Lebensräume im 5. bis frühen 3. Jahrtausend v. Chr.: Mobile Subsistenz, Kommunikation und Ressourcennutzung

The Northern Badia is part of the greater steppe desert Badiyat ash-Sham centrally located between the Middle Euphrates and the Southern Levant. In Jordanian territory this steppe desert is differentiated into a basalt steppe desert (al-harra) and the eastern adjacent limestone steppe desert (al-hamad). The chronological focus of the research project lies on the Late Chalcolithic and Early Bronze Age period (5th to early 3rd millennium BC). This is a crucial period in the late prehistory of southwest Asia due to the fact that the first complex and urban societies, which were embedded in supra-regional networks, developed in Mesopotamia, Syria and Southern Levant, which are neighbouring the Northern Badia. The aim of the project is to investigate the impact of these developments on the socio-economy of the centrally located but arid Northern Badia. From spring 2010 to autumn 2011 several archaeological survey campaigns have been carried out in this region. In spring 2012 and 2013 two further survey campaigns have been executed as well as an analysing season in autumn 2012

Hypofractionated helical intensity-modulated radiotherapy of the prostate bed after prostatectomy with or without the pelvic lymph nodes - the PRIAMOS trial

BACKGROUND: While evidence on safety and efficacy of primary hypofractionated radiotherapy in prostate cancer is accumulating, data on postoperative hypofractionated treatment of the prostate bed and of the pelvic lymph nodes is still scarce. This phase II trial was initiated to investigate safety and feasibility of hypofractionated treatment of the prostate bed alone or with the pelvic lymph nodes. METHODS/DESIGN: A total of 80 prostate cancer patients with the indication for adjuvant radiotherapy will be enrolled, where 40 patients with a low risk of lymph node involvement (arm 1) and another 40 patients with a high risk of lymph node involvement (arm 2) will each receive 54 Gy in 18 fractions to the prostate bed. Arm 2 will be given 45 Gy to the pelvic lymph nodes additionally. Helical Tomotherapy and daily image guidance will be used. DISCUSSION: This trial was initiated to substantiate data on hypofractionated treatment of the prostate bed and generate first data on adjuvant hypofractionated radiotherapy of the pelvic lymph nodes. TRIAL REGISTRATION: ClinicalTrials.gov; NCT0162071

Filamentous fungal characterizations by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry

Matrix-assisted laser desorption ⁄ ionization time-of-flight intact cell mass spectrometry (MALDI-TOF ICMS) is coming of age for the identification and characterization of fungi. The procedure has been used extensively with bacteria. UV-absorbing matrices function as energy mediators that transfer the absorbed photoenergy from an irradiation source to the surrounding sample molecules, resulting in minimum fragmentation. A surprisingly high number of fungal groups have been studied: (i) the terverticillate penicillia, (ii) aflatoxigenic, black and other aspergilli, (iii) Fusarium, (iv) Trichoderma, (iv) wood rotting fungi (e.g. Serpula lacrymans) and (v) dermatophytes. The technique has been suggested for optimizing quality control of fungal Chinese medicines (e.g. Cordyceps). MALDI-TOF ICMS offers advantages over PCR. The method is now used in taxonomic assessments (e.g. Trichoderma) as distinct from only strain characterization. Low and high molecular mass natural products (e.g. peptaibols) can be analysed. The procedure is rapid and requires minimal pretreatment. However, issues of reproducibility need to be addressed further in terms of strains of species tested and between run variability. More studies into the capabilities of MALDI-TOF ICMS to identify fungi are required.R.R.M. Paterson is grateful for FCT-Portugal Grant (SFRH/BPD/34879/2007) and IOI Professorial Chair, Malaysia where some of this review was first revised. C. Santos acknowledges FACEPE/CNPq-Brazil financial support. N. Lima appreciates the stay in the Biochemistry Department of UFPE-Brazil as Visiting Full Professor where this review was drafted. C. Santos and N. Lima acknowledge Laboratorio de Imunopatologia Keizo Asami (LIKA/UFPE) for the consent and support given to use their MALDI-TOF MS equipment

Genomic insights into the evolutionary origin of Myxozoa within Cnidaria

The Myxozoa comprise over 2,000 species of microscopic obligate parasites that use both invertebrate and vertebrate hosts as part of their life cycle. Although the evolutionary origin of myxozoans has been elusive, a close relationship with cnidarians, a group that includes corals, sea anemones, jellyfish, and hydroids, is supported by some phylogenetic studies and the observation that the distinctive myxozoan structure, the polar capsule, is remarkably similar to the stinging structures (nematocysts) in cnidarians. To gain insight into the extreme evolutionary transition from a free-living cnidarian to a microscopic endoparasite, we analyzed genomic and transcriptomic assemblies from two distantly related myxozoan species, Kudoa iwatai and Myxobolus cerebralis, and compared these to the transcriptome and genome of the less reduced cnidarian parasite, Polypodium hydriforme. A phylogenomic analysis, using for the first time to our knowledge, a taxonomic sampling that represents the breadth of myxozoan diversity, including four newly generated myxozoan assemblies, confirms that myxozoans are cnidarians and are a sister taxon to P. hydriforme. Estimations of genome size reveal that myxozoans have one of the smallest reported animal genomes. Gene enrichment analyses show depletion of expressed genes in categories related to development, cell differentiation, and cell–cell communication. In addition, a search for candidate genes indicates that myxozoans lack key elements of signaling pathways and transcriptional factors important for multicellular development. Our results suggest that the degeneration of the myxozoan body plan from a free-living cnidarian to a microscopic parasitic cnidarian was accompanied by extreme reduction in genome size and gene content

Quadripolar Left Ventricular Lead in a Patient with CRT-D Does Not Overcome Phrenic Nerve Stimulation

Effective cardiac resynchronization therapy (CRT) requires an accurate atrio-biventricular pacing system. The innovative Quartet lead is a quadripolar, over-the-wire left ventricular lead with four electrodes and has recently been designed to provide more options and greater control in pacing vector selection. A lead with multiple pacing electrodes is a potential alternative to physical adjustment of the lead and may help to overcome high thresholds and phrenic nerve stimulation (PNS)