Plasmons and Interband Transitions of Ca11_{11}Sr3_3Cu24_{24}O41_{41} investigated by Electron Energy-Loss Spectroscopy

Electron energy-loss spectroscopy studies have been performed in order to get a deeper insight into the electronic structure and elementary excitations of the two-leg ladder system Ca$_{11}$Sr$_3$Cu$_{24}$O$_{41}$. We find a strong anisotropy of the loss function for momentum transfers along the a and c-crystallographic axis, and a remarkable linear plasmon dispersion for a momentum transfer parallel to the legs of the ladders. The investigated spectral features are attributed to localized and delocalized charge-transfer excitations and the charge carrier plasmon. The charge carrier plasmon position and dispersion in the long wave-length limit agree well with expectations based upon the band structure of the two-leg ladder, while the observed quasi-linear plasmon dispersion might be related to the peculiar properties of underdoped cuprates in general.Comment: 16 pages, 8 figure

Phenotypic and molecular characterization of Staphylococcus aureus isolates expressing low- and high-level mupirocin resistance in Nigeria and South Africa

<p>Abstract</p> <p>Background</p> <p>Mupirocin is a topical antimicrobial agent which is used for the treatment of skin and postoperative wound infections, and the prevention of nasal carriage of methicillin-resistant <it>Staphylococcus aureus </it>(MRSA). However, the prevalence of mupirocin resistance in <it>S. aureus</it>, particularly in MRSA, has increased with the extensive and widespread use of this agent in hospital settings. This study characterized low- and high-level mupirocin-resistant <it>S. aureus </it>isolates obtained from Nigeria and South Africa.</p> <p>Methods</p> <p>A total of 17 mupirocin-resistant <it>S. aureus </it>isolates obtained from two previous studies in Nigeria and South Africa, were characterized by antibiogram, PCR-RFLP of the coagulase gene and PFGE. High-level mupirocin resistant isolates were confirmed by PCR detection of the <it>mupA </it>gene. The genetic location of the resistance determinants was established by curing and transfer experiments.</p> <p>Results</p> <p>All the low-level mupirocin resistant isolates were MRSA and resistant to gentamicin, tetracycline and trimethoprim. PFGE identified a major clone in two health care institutions located in Durban and a health care facility in Pietermaritzburg, Greytown and Empangeni. Curing and transfer experiments indicated that high-level mupirocin resistance was located on a 41.1 kb plasmid in the South African strain (A15). Furthermore, the transfer of high-level mupirocin resistance was demonstrated by the conjugative transfer of the 41.1 kb plasmid alone or with the co-transfer of a plasmid encoding resistance to cadmium. The size of the mupirocin-resistance encoding plasmid in the Nigerian strain (35 IBA) was approximately 35 kb.</p> <p>Conclusion</p> <p>The emergence of mupirocin-resistant <it>S. aureus </it>isolates in Nigeria and South Africa should be of great concern to medical personnel in these countries. It is recommended that methicillin-susceptible <it>S. aureus </it>(MSSA) and MRSA should be routinely tested for mupirocin resistance even in facilities where the agent is not administered. Urgent measures, including judicious use of mupirocin, need to be taken to prevent clonal dissemination of the mupirocin/methicillin resistant <it>S. aureus </it>in KZN, South Africa and the transfer of the conjugative plasmid encoding high-level mupirocin resistance identified in this study.</p

Analytical performance of the Roche Lightcycler® Mycobacterium Detection Kit for the diagnosis of clinically important mycobacterial species

BACKGROUND: The LightCyclerH Mycobacterium Detection Kit based on real-time PCR technology for the detection of Mycobacterium tuberculosis, Mycobacterium avium and Mycobacterium kansasii was recently developed. This study evaluated its analytical sensitivity, specificity and reproducibility. METHODOLOGY/PRINCIPAL FINDINGS: Plasmid standards were prepared and used to determine the limit of detection. The assay was also performed against organisms other than mycobacteria, other mycobacterial strains and interfering substances to exclude cross-reactivity and interference. Reference standards were prepared and tested to assess the assay’s reproducibility. All PCR assays were performed using the LightCyclerH 2.0 Instrument. The detection limit for M. tuberculosis was 28 copies per microlitre. Neither cross-reactivity nor interference occurred with non-mycobacterial organisms and substances tested. Overall reproducibility for consecutive measurements, run-to-run, lot-to-lot, day-to-day and laboratory-to-laboratory achieved a coefficient of variance of less than two percent. SIGNIFICANCE: The LightCyclerH Mycobacterium Detection kit has shown to be a robust and accurate assay with the potential to be used as a rapid TB diagnostic test.http://www.plosone.or

K(2P)18.1 translates T cell receptor signals into thymic regulatory T cell development

It remains largely unclear how thymocytes translate relative differences in T cell receptor (TCR) signal strength into distinct developmental programs that drive the cell fate decisions towards conventional (Tconv) or regulatory T cells (Treg). Following TCR activation, intracellular calcium (Ca2+) is the most important second messenger, for which the potassium channel K(2P)18.1 is a relevant regulator. Here, we identify K(2P)18.1 as a central translator of the TCR signal into the thymus-derived Treg (tTreg) selection process. TCR signal was coupled to NF-kappa B-mediated K(2P)18.1 upregulation in tTreg progenitors. K(2P)18.1 provided the driving force for sustained Ca2+ influx that facilitated NF-kappa B- and NFAT-dependent expression of FoxP3, the master transcription factor for Treg development and function. Loss of K(2P)18.1 ion-current function induced a mild lymphoproliferative phenotype in mice, with reduced Treg numbers that led to aggravated experimental autoimmune encephalomyelitis, while a gain-of-function mutation in K(2P)18.1 resulted in increased Treg numbers in mice. Our findings in human thymus, recent thymic emigrants and multiple sclerosis patients with a dominant-negative missense K(2P)18.1 variant that is associated with poor clinical outcomes indicate that K(2P)18.1 also plays a role in human Treg development. Pharmacological modulation of K(2P)18.1 specifically modulated Treg numbers in vitro and in vivo. Finally, we identified nitroxoline as a K(2P)18.1 activator that led to rapid and reversible Treg increase in patients with urinary tract infections. Conclusively, our findings reveal how K(2P)18.1 translates TCR signals into thymic T cell fate decisions and Treg development, and provide a basis for the therapeutic utilization of Treg in several human disorders.Peer reviewe

A New Approach for Determining Phase Response Curves Reveals that Purkinje Cells Can Act as Perfect Integrators

Cerebellar Purkinje cells display complex intrinsic dynamics. They fire spontaneously, exhibit bistability, and via mutual network interactions are involved in the generation of high frequency oscillations and travelling waves of activity. To probe the dynamical properties of Purkinje cells we measured their phase response curves (PRCs). PRCs quantify the change in spike phase caused by a stimulus as a function of its temporal position within the interspike interval, and are widely used to predict neuronal responses to more complex stimulus patterns. Significant variability in the interspike interval during spontaneous firing can lead to PRCs with a low signal-to-noise ratio, requiring averaging over thousands of trials. We show using electrophysiological experiments and simulations that the PRC calculated in the traditional way by sampling the interspike interval with brief current pulses is biased. We introduce a corrected approach for calculating PRCs which eliminates this bias. Using our new approach, we show that Purkinje cell PRCs change qualitatively depending on the firing frequency of the cell. At high firing rates, Purkinje cells exhibit single-peaked, or monophasic PRCs. Surprisingly, at low firing rates, Purkinje cell PRCs are largely independent of phase, resembling PRCs of ideal non-leaky integrate-and-fire neurons. These results indicate that Purkinje cells can act as perfect integrators at low firing rates, and that the integration mode of Purkinje cells depends on their firing rate

Early continence in patients with localized prostate cancer. A comparison between open retropubic (RRPE) and endoscopic extraperitoneal radical prostatectomy (EERPE) ଁ

Abstract Objective: The study examined and compared continence rates in prostate cancer patients who had undergone either open retropubic prostatectomy (RRPE) or endoscopic extraperitoneal radical prostatectomy (EERPE). The core question was whether the surgical approach had an effect on the patients&apos; continence status 3 months after surgery. Methods: We conducted a multicentric, longitudinal study in 7 German hospitals. Three hundred fifty prostate cancer patients (166 EERPE, 184 RRPE) were asked to self-assess symptoms associated with urinary incontinence (UI) 1 day before and 3 months after prostatectomy. Symptoms of UI were assessed using the EORTC QLQ-PR25 questionnaire. Urinary continence was defined according to (1) the use of no protective pad, (2) the use of up to a single protective pad in a 24-hour period, and (3) according to the patient&apos;s self-assessment. A binary regression model was employed to predict early continence status. Results: Three months after prostatectomy, 44% of patients who underwent EERPE and 40% of patients who underwent RRPE were completely continent. Patients who underwent nerve-sparing prostatectomy and patients younger than 65 years had a better chance of regaining urinary continence earlier. The surgical approach had no significant impact on the patients&apos; continence status. Limitations of the study are a drop-out rate of 39% and sociodemographic and clinical differences between both treatment groups. Conclusions: Three months after prostatectomy, there were no significant differences between both treatment groups regarding urinary continence. The surgical approach had no significant effect on the patients&apos; continence status. Higher age and non-nerve-sparing surgery are associated with a longer period of convalescence

Pathological consequences of VCP mutations on human striated muscle

*These authors have contributed equally to this work. Mutations in the valosin-containing protein (VCP, p97) gene on chromosome 9p13-p12 cause a late-onset form of autosomal dominant inclusion body myopathy associated with Paget disease of the bone and frontotemporal dementia (IBMPFD). We report on the pathological consequences of three heterozygous VCP (R93C, R155H, R155C) mutations on human striated muscle. IBMPFD skeletal muscle pathology is characterized by degenerative changes and filamentous VCP-and ubiquitin-positive cytoplasmic and nuclear protein aggregates. Furthermore, this is the first report demonstrating that mutant VCP leads to a novel form of dilatative cardiomyopathy with inclusion bodies. In contrast to post-mitotic striated muscle cells and neurons of IBMPFD patients, evidence of protein aggregate pathology was not detected in primary IBMPFD myoblasts or in transient and stable transfected cells using wild-type-VCP and R93C-, R155H-, R155C-VCP mutants. Glutathione S-transferase pull-down experiments showed that all three VCP mutations do not affect the binding to Ufd1, Npl4 and ataxin-3. Structural analysis demonstrated that R93 and R155 are both surface-accessible residues located in the centre of cavities that may enable ligand-binding. Mutations at R93 and R155 are predicted to induce changes in the tertiary structure of the VCP protein. The search for putative ligands to the R93 and R155 cavities resulted in the identification of cyclic sugar compounds with high binding scores. The latter findings provide a novel link to VCP carbohydrate interactions in the complex pathology of IBMPFD. Keywords: VCP; p97; myopathy; cardiomyopathy; IBMPFD Abbreviations: GST = glutathione S-transferase; IBMPFD = inclusion body myopathy associated with Paget disease of the bone and frontotemporal dementia; PBS = phosphate-buffered saline; SDS = sodium dodecyl sulphate; VCP = valosin-containing protei

Gelingendes Leben - Krise als Chance für Person & Gesellschaft. Band II

• Peter Antes, Rel.wiss. • Petra Bahr, Theol. / Journ. • Matthias Beck Med./JS, AT • Gottfried Biewer, Bildungswiss., AT • Aladin El-Mafaalani, Pol.wiss.• Johannes Eurich, Diak.wiss. • Mario Feigel, Med. CH • Heike Gramkow, Manag.Dir. • Heinrich Greving, Heilpäd. • Udo Hahn, Theol.• Maria-C. Hallwachs, Stud., Beratg. schon betroffen • Walter Hirche, Min. a.D./Präs. Dt. UNESCO • Wolfgang Jantzen †, Soz. • Jochen-C. Kaiser, Hist. • Karl-J. Kemmelmeyer, Präs. Musikrat • Hermes Kick, Med.-Ethik • Waldemar Kippes Redemptorist JN • Ferdinand Klein, SoPäd., SK • Berthold Krüger, bpb • Christian Larsen, Arzt, CH • Ulrich Lilie Präs. Diak.W • Christian Lindmeier, SoPäd., DGfE • Ralf Meister, Bischof • Bertolt Meyer, Org.- u. Wirtschaftspsych, schon betroffen, CH • Peter Neher, Präs. Caritas • Ekkehard Nuissl, Dir. Dt. Inst. EB, DIE • Ulrich Pohl, Vorst. Bethel • Hartmann Römer, Physiker • David Roth, Lt. Hospiz • Hartmut Schlegel SoPäd. • Joachim Schoss, Unternehmer, schon betroffen, CH • Walter Surböck Med., AT• Karl-H. Steinmetz, Trad. Europ. Med., AT • Rudolf Tippelt, Bildg. Forschg. • Inge Wasserberg, Inklu.Beratg. • Walter Thirring †, Phys. CERN, C