@article{SchmidtLiuLiuetal.2014, author = {Schmidt, Sebastian and Liu, Guoxing and Liu, Guilai and Yang, Wenting and Honisch, Sabina and Pantelakos, Stavros and Stournaras, Christos and H{\"o}nig, Arnd and Lang, Florian}, title = {Enhanced Orai1 and STIM1 expression as well as store operated \(Ca^{2+}\) entry in therapy resistant ovary carcinoma cells}, series = {Oncotarget}, volume = {5}, journal = {Oncotarget}, number = {13}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-121423}, pages = {4799-810}, year = {2014}, abstract = {Mechanisms underlying therapy resistance of tumor cells include protein kinase Akt. Putative Akt targets include store-operated \(Ca^{2+}\)-entry (SOCE) accomplished by pore forming ion channel unit Orai1 and its regulator STIM1. We explored whether therapy resistant (A2780cis) differ from therapy sensitive (A2780) ovary carcinoma cells in Akt, Orai1, and STIM1 expression, \(Ca^{2+}\)-signaling and cell survival following cisplatin (100µM) treatment. Transcript levels were quantified with RT-PCR, protein abundance with Western blotting, cytosolic \(Ca^{2+}\)-activity ([\(Ca^{2+}\)]i) with Fura-2-fluorescence, SOCE from increase of [\(Ca^{2+}\)]i following \(Ca^{2+}\)-readdition after Ca2+-store depletion, and apoptosis utilizing flow cytometry. Transcript levels of Orai1 and STIM1, protein expression of Orai1, STIM1, and phosphorylated Akt, as well as SOCE were significantly higher in A2780cis than A2780 cells. SOCE was decreased by Akt inhibitor III (SH-6, 10µM) in A2780cis but not A2780 cells and decreased in both cell lines by Orai1 inhibitor 2-aminoethoxydiphenyl borate (2-ABP, 50µM). Phosphatidylserine exposure and late apoptosis following cisplatin treatment were significantly lower in A2780cis than A2780 cells, a difference virtually abolished by SH-6 or 2-ABP. In conclusion, Orai1/STIM1 expression and function are increased in therapy resistant ovary carcinoma cells, a property at least in part due to enhanced Akt activity and contributing to therapy resistance in those cells.}, language = {en} } @article{VembarScherfSiegel2014, author = {Vembar, Shruti S. and Scherf, Artur and Siegel, T. Nicolai}, title = {Noncoding RNAs as emerging regulators of Plasmodium falciparum virulence gene expression}, series = {Current Opinion in Microbiology}, volume = {20}, journal = {Current Opinion in Microbiology}, number = {100}, issn = {1369-5274}, doi = {10.1016/j.mib.2014.06.013}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-121416}, pages = {153-61}, year = {2014}, abstract = {The eukaryotic unicellular pathogen Plasmodium falciparum tightly regulates gene expression, both during development and in adaptation to dynamic host environments. This regulation is evident in the mutually exclusive expression of members of clonally variant virulence multigene families. While epigenetic regulators have been selectively identified at active or repressed virulence genes, their specific recruitment remains a mystery. In recent years, noncoding RNAs (ncRNAs) have emerged as lynchpins of eukaryotic gene regulation; by binding to epigenetic regulators, they provide target specificity to otherwise non-specific enzyme complexes. Not surprisingly, there is great interest in understanding the role of ncRNA in P. falciparum, in particular, their contribution to the mutually exclusive expression of virulence genes. The current repertoire of P. falciparum ncRNAs includes, but is not limited to, subtelomeric ncRNAs, virulence gene-associated ncRNAs and natural antisense RNA transcripts. Continued improvement in high-throughput sequencing methods is sure to expand this repertoire. Here, we summarize recent advances in P. falciparum ncRNA biology, with an emphasis on ncRNA-mediated epigenetic modes of gene regulation.}, language = {en} } @article{PatelMurphyHaralmbievaetal.2014, author = {Patel, Suketu and Murphy, Derek and Haralmbieva, Eugenia and Abdulla, Zainalabideen A. and Wong, Kah Keng and Chen, Hong and Gould, Edith and Roncador, Giovanna and Hatton, Chris S. R. and Anderson, Amanda P. and Banham, Alison H. and Pulford, Karen}, title = {Increased Expression of Phosphorylated FADD in Anaplastic Large Cell and Other T-Cell Lymphomas}, series = {Biomarker Insights}, volume = {9}, journal = {Biomarker Insights}, issn = {1177-2719}, doi = {10.4137/bmi.s16553}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-121403}, pages = {77-84}, year = {2014}, abstract = {FAS-associated protein with death domain (FADD) is a major adaptor protein involved in extrinsic apoptosis, embryogenesis, and lymphocyte homeostasis. Although abnormalities of the FADD/death receptor apoptotic pathways have been established in tumorigenesis, fewer studies have analyzed the expression and role of phosphorylated FADD (pFADD). Our identification of FADD as a lymphoma-associated autoantigen in T-cell lymphoma patients raises the possibility that pFADD, with its correlation with cell cycle, may possess role(s) in human T-cell lymphoma development. This immunohistochemical study investigated pFADD protein expression in a range of normal tissues and lymphomas, particularly T-cell lymphomas that require improved therapies. Whereas pFADD was expressed only in scattered normal T cells, it was detected at high levels in T-cell lymphomas (eg, 84\% anaplastic large cell lymphoma and 65\% peripheral T cell lymphomas, not otherwise specified). The increased expression of pFADD supports further study of its clinical relevance and role in lymphomagenesis, highlighting phosphorylation of FADD as a potential therapeutic target.}, language = {en} } @article{NiklassStoyanovGarzetal.2014, author = {Niklass, Solveig and Stoyanov, Stoyan and Garz, Cornelia and Bueche, Celine Z. and Mencl, Stine and Reymann, Klaus and Heinze, Hans-Jochen and Carare, Roxana O. and Kleinschnitz, Christoph and Schreiber, Stefanie}, title = {Intravital imaging in spontaneously hypertensive stroke-prone rats-a pilot study}, series = {Experimental \& Translational Stroke Medicine}, volume = {6}, journal = {Experimental \& Translational Stroke Medicine}, doi = {10.1186/2040-7378-6-1}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-121353}, pages = {1}, year = {2014}, abstract = {Background There is growing evidence that endothelial failure and subsequent blood brain barrier (BBB) breakdown initiate cerebral small vessel disease (CSVD) pathology. In spontaneously hypertensive stroke-prone rats (SHRSP) endothelial damage is indicated by intraluminal accumulations of erythrocytes (erythrocyte thrombi) that are not observed with current magnetic resonance imaging techniques. Two-photon microscopy (2 PM) offers the potential for real-time direct detection of the small vasculature. Thus, within this pilot study we investigated the sensitivity of 2 PM to detect erythrocyte thrombi expressing initiating CSVD phenomena in vivo. Methods Eight SHRSP and 13 Wistar controls were used for in vivo imaging and subsequent histology with haematoxylin-eosin (HE). For 2 PM, cerebral blood vessels were labeled by fluorescent Dextran (70 kDa) applied intraorbitally. The correlation between vascular erythrocyte thrombi observed by 2 PM and HE-staining was assessed. Artificial surgical damage and parenchymal Dextran distribution were analyzed postmortem. Results Dextran was distributed within the small vessel walls and co-localized with IgG. Artificial surgical damage was comparable between SHRSP and Wistar controls and mainly affected the small vasculature. In fewer than 20\% of animals there was correlation between erythrocyte thrombi as observed with 2 PM and histologically with HE. Conclusions Contrary to our initial expectations, there was little agreement between intravital 2 PM imaging and histology for the detection of erythrocyte thrombi. Two-photon microscopy is a valuable technique that complements but does not replace the value of conventional histology.}, language = {en} } @article{MoussetBuchheidtHeinzetal.2014, author = {Mousset, Sabine and Buchheidt, Dieter and Heinz, Werner and Ruhnke, Markus and Cornely, Oliver A. and Egerer, Gerlinde and Kr{\"u}ger, William and Link, Hartmut and Neumann, Silke and Ostermann, Helmut and Panse, Jens and Penack, Olaf and Rieger, Christina and Schmidt-Hieber, Martin and Silling, Gerda and S{\"u}dhoff, Thomas and Ullmann, Andrew J. and Wolf, Hans-Heinrich and Maschmeyer, Georg and B{\"o}hme, Angelika}, title = {Treatment of invasive fungal infections in cancer patients—updated recommendations of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO)}, series = {Annals of Hematology}, volume = {96}, journal = {Annals of Hematology}, doi = {10.1007/s00277-013-1867-1}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-121340}, pages = {13-32}, year = {2014}, abstract = {Invasive fungal infections are a main cause of morbidity and mortality in cancer patients undergoing intensive chemotherapy regimens. Early antifungal treatment is mandatory to improve survival. Today, a number of effective and better-tolerated but more expensive antifungal agents compared to the former gold standard amphotericin B deoxycholate are available. Clinical decision-making must consider results from numerous studies and published guidelines, as well as licensing status and cost pressure. New developments in antifungal prophylaxis improving survival rates result in a continuous need for actualization. The treatment options for invasive Candida infections include fluconazole, voriconazole, and amphotericin B and its lipid formulations, as well as echinocandins. Voriconazole, amphotericin B, amphotericin B lipid formulations, caspofungin, itraconazole, and posaconazole are available for the treatment of invasive aspergillosis. Additional procedures, such as surgical interventions, immunoregulatory therapy, and granulocyte transfusions, have to be considered. The Infectious Diseases Working Party of the German Society of Hematology and Oncology here presents its 2008 recommendations discussing the dos and do-nots, as well as the problems and possible solutions, of evidence criteria selection.}, language = {en} } @article{LichteneggerBinaRoieretal.2014, author = {Lichtenegger, Sabine and Bina, Isabelle and Roier, Sandro and Bauernfeind, Stilla and Keidel, Kristina and Schild, Stefan and Anthony, Mark and Reidl, Joachim}, title = {Characterization of lactate utilization and its implication on the physiology of Haemophilus influenzae}, series = {International Journal of Medical Microbiology}, volume = {304}, journal = {International Journal of Medical Microbiology}, number = {3-4}, doi = {10.1016/j.ijmm.2014.02.010}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-121335}, pages = {490-8}, year = {2014}, abstract = {Haemophilus influenzae is a Gram-negative bacillus and a frequent commensal of the human nasopharynx. Earlier work demonstrated that in H. influenzae type b, l-lactate metabolism is associated with serum resistance and in vivo survival of the organism. To further gain insight into lactate utilization of the non-typeable (NTHi) isolate 2019 and laboratory prototype strain Rd KW20, deletion mutants of the l-lactate dehydrogenase (lctD) and permease (lctP) were generated and characterized. It is shown, that the apparent KM of l-lactate uptake is 20.1μM as determined for strain Rd KW20. Comparison of the COPD isolate NTHi 2019-R with the corresponding lctP knockout strain for survival in human serum revealed no lactate dependent serum resistance. In contrast, we observed a 4-fold attenuation of the mutant strain in a murine model of nasopharyngeal colonization. Characterization of lctP transcriptional control shows that the lactate utilization system in H. influenzae is not an inductor inducible system. Rather negative feedback regulation was observed in the presence of l-lactate and this is dependent on the ArcAB regulatory system. Additionally, for 2019 it was found that lactate may have signaling function leading to increased cell growth in late log phase under conditions where no l-lactate is metabolized. This effect seems to be ArcA independent and was not observed in strain Rd KW20. We conclude that l-lactate is an important carbon-source and may act as host specific signal substrate which fine tunes the globally acting ArcAB regulon and may additionally affect a yet unknown signaling system and thus may contribute to enhanced in vivo survival.}, language = {en} } @article{ChungGedeborgNicholasetal.2014, author = {Chung, Shen-Chia and Gedeborg, Rolf and Nicholas, Owen and James, Stefan and Jeppsson, Anders and Wolfe, Charles and Heuschmann, Peter and Wallentin, Lars and Deanfield, John and Timmis, Adam and Jernberg, Tomas and Hemingway, Harry}, title = {Acute myocardial infarction: a comparison of short-term survival in national outcome registries in Sweden and the UK}, series = {Lancet}, volume = {383}, journal = {Lancet}, number = {9925}, doi = {10.1016/s0140-6736(13)62070-x}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-121327}, pages = {1305-12}, year = {2014}, abstract = {Background International research for acute myocardial infarction lacks comparisons of whole health systems. We assessed time trends for care and outcomes in Sweden and the UK. Methods We used data from national registries on consecutive patients registered between 2004 and 2010 in all hospitals providing care for acute coronary syndrome in Sweden and the UK. The primary outcome was all-cause mortality 30 days after admission. We compared effectiveness of treatment by indirect casemix standardisation. This study is registered with ClinicalTrials.gov, number NCT01359033. Findings We assessed data for 119 786 patients in Sweden and 391 077 in the UK. 30-day mortality was 7·6\% (95\% CI 7·4-7·7) in Sweden and 10·5\% (10·4-10·6) in the UK. Mortality was higher in the UK in clinically relevant subgroups defined by troponin concentration, ST-segment elevation, age, sex, heart rate, systolic blood pressure, diabetes mellitus status, and smoking status. In Sweden, compared with the UK, there was earlier and more extensive uptake of primary percutaneous coronary intervention (59\% vs 22\%) and more frequent use of β blockers at discharge (89\% vs 78\%). After casemix standardisation the 30-day mortality ratio for UK versus Sweden was 1·37 (95\% CI 1·30-1·45), which corresponds to 11 263 (95\% CI 9620-12 827) excess deaths, but did decline over time (from 1·47, 95\% CI 1·38-1·58 in 2004 to 1·20, 1·12-1·29 in 2010; p=0·01). Interpretation We found clinically important differences between countries in acute myocardial infarction care and outcomes. International comparisons research might help to improve health systems and prevent deaths.}, language = {en} } @article{BremGruenblattDrechsleretal.2014, author = {Brem, Silvia and Gr{\"u}nblatt, Edna and Drechsler, Renate and Riederer, Peter and Walitza, Susanne}, title = {The neurobiological link between OCD and ADHD}, series = {Attention Deficit and Hyperactivity Disorders}, volume = {6}, journal = {Attention Deficit and Hyperactivity Disorders}, number = {3}, doi = {10.1007/s12402-014-0146-x}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-121312}, pages = {175-202}, year = {2014}, abstract = {Obsessive compulsive disorder (OCD) and attention deficit hyperactivity disorder (ADHD) are two of the most common neuropsychiatric diseases in paediatric populations. The high comorbidity of ADHD and OCD with each other, especially of ADHD in paediatric OCD, is well described. OCD and ADHD often follow a chronic course with persistent rates of at least 40-50 \%. Family studies showed high heritability in ADHD and OCD, and some genetic findings showed similar variants for both disorders of the same pathogenetic mechanisms, whereas other genetic findings may differentiate between ADHD and OCD. Neuropsychological and neuroimaging studies suggest that partly similar executive functions are affected in both disorders. The deficits in the corresponding brain networks may be responsible for the perseverative, compulsive symptoms in OCD but also for the disinhibited and impulsive symptoms characterizing ADHD. This article reviews the current literature of neuroimaging, neurochemical circuitry, neuropsychological and genetic findings considering similarities as well as differences between OCD and ADHD.}, language = {en} } @article{BittnerBingenerCaseyDietzetal.2014, author = {Bittner, R. and Bingener-Casey, J. and Dietz, U. and Fabian, M. and Ferzli, G. S. and Fortelny, R. H. and K{\"o}ckerling, F. and Kukleta, J. and LeBlanc, K. and Lomanto, D. and Misra, M. C. and Morales-Conde, S. and Ramshaw, B. and Reinpold, W. and Rim, S. and Rohr, M. and Schrittwieser, R. and Simon, T. and Smietanski, M. and Stechemesser, B. and Timoney, M. and Chowbey, P.}, title = {Guidelines for laparoscopic treatment of ventral and incisional abdominal wall hernias (International Endohernia Society [IEHS])—Part 2}, series = {Surgical Endoscopy}, volume = {28}, journal = {Surgical Endoscopy}, number = {2}, doi = {10.1007/s00464-013-3171-5}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-121510}, pages = {353 - 379}, year = {2014}, abstract = {Guidelines are increasingly determining the decision process in day-to-day clinical work. Guidelines describe the current best possible standard in diagnostics and therapy. They should be developed by an international panel of experts, whereby alongside individual experience, above all, the results of comparative studies are decisive. According to the results of high-ranking scientific studies published in peer-reviewed journals, statements and recommendations are formulated, and these are graded strictly according to the criteria of evidence-based medicine. Guidelines can therefore be valuable in helping particularly the young surgeon in his or her day-to-day work to find the best decision for the patient when confronted with a wide and confusing range of options. However, even experienced surgeons benefit because by virtue of a heavy workload and commitment, they often find it difficult to keep up with the ever-increasing published literature. All guidelines require regular updating, usually every 3 years, in line with progress in the field. The current Guidelines focus on technique and perioperative management of laparoscopic ventral hernia repair and constitute the first comprehensive guidelines on this topic. In this issue of Surgical Endoscopy, the first part of the Guidelines is published including sections on basics, indication for surgery, perioperative management, and key points of technique. The next part (Part 2) of the Guidelines will address complications and comparisons between open and laparoscopic techniques. Part 3 will cover mesh technology, hernia prophylaxis, technique-related issues, new technologic developments, lumbar and other unusual hernias, and training/education.}, language = {en} } @article{BittnerBingenerCaseyDietzetal.2014, author = {Bittner, R. and Bingener-Casey, J. and Dietz, U. and Fabian, M. and Ferzli, G. S. and Fortelny, R. H. and K{\"o}ckerling, F. and Kukleta, J. and LeBlanc, K. and Lomanto, D. and Misra, M. C. and Bansal, V. K. and Morales-Conde, S. and Ramshaw, B. and Reinpold, W. and Rim, S. and Rohr, M. and Schrittwieser, R. and Simon, T. and Smietanski, M. and Stechemesser, B. and Timoney, M. and Chowbey, P.}, title = {Guidelines for laparoscopic treatment of ventral and incisional abdominal wall hernias (International Endohernia Society (IEHS)—Part 1}, series = {Surgical Endoscopy}, volume = {28}, journal = {Surgical Endoscopy}, doi = {10.1007/s00464-013-3170-6}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-121294}, pages = {2-29}, year = {2014}, abstract = {Guidelines are increasingly determining the decision process in day-to-day clinical work. Guidelines describe the current best possible standard in diagnostics and therapy. They should be developed by an international panel of experts, whereby alongside individual experience, above all, the results of comparative studies are decisive. According to the results of high-ranking scientific studies published in peer-reviewed journals, statements and recommendations are formulated, and these are graded strictly according to the criteria of evidence-based medicine. Guidelines can therefore be valuable in helping particularly the young surgeon in his or her day-to-day work to find the best decision for the patient when confronted with a wide and confusing range of options. However, even experienced surgeons benefit because by virtue of a heavy workload and commitment, they often find it difficult to keep up with the ever-increasing published literature. All guidelines require regular updating, usually every 3 years, in line with progress in the field. The current Guidelines focus on technique and perioperative management of laparoscopic ventral hernia repair and constitute the first comprehensive guidelines on this topic. In this issue of Surgical Endoscopy, the first part of the Guidelines is published including sections on basics, indication for surgery, perioperative management, and key points of technique. The next part (Part 2) of the Guidelines will address complications and comparisons between open and laparoscopic techniques. Part 3 will cover mesh technology, hernia prophylaxis, technique-related issues, new technologic developments, lumbar and other unusual hernias, and training/education.}, language = {en} } @article{BittnerBingenerCaseyDietzetal.2014, author = {Bittner, R. and Bingener-Casey, J. and Dietz, U. and Fabian, M. and Ferzli, G. and Fortelny, R. and K{\"o}ckerling, F. and Kukleta, J. and LeBlanc, K. and Lomanto, D. and Misra, M. and Morales-Conde, S. and Ramshaw, B. and Reinpold, W. and Rim, S. and Rohr, M. and Schrittwieser, R. and Simon, T. and Smietanski, M. and Stechemesser, B. and Timoney, M. and Chowbey, P.}, title = {Guidelines for laparoscopic treatment of ventral and incisional abdominal wall hernias (International Endohernia Society [IEHS])—Part III}, series = {Surgical Endoscopy}, volume = {28}, journal = {Surgical Endoscopy}, number = {2}, doi = {10.1007/s00464-013-3172-4}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-121289}, pages = {380-404}, year = {2014}, abstract = {Guidelines are increasingly determining the decision process in day-to-day clinical work. Guidelines describe the current best possible standard in diagnostics and therapy. They should be developed by an international panel of experts, whereby alongside individual experience, above all, the results of comparative studies are decisive. According to the results of high-ranking scientific studies published in peer-reviewed journals, statements and recommendations are formulated, and these are graded strictly according to the criteria of evidence-based medicine. Guidelines can therefore be valuable in helping particularly the young surgeon in his or her day-to-day work to find the best decision for the patient when confronted with a wide and confusing range of options. However, even experienced surgeons benefit because by virtue of a heavy workload and commitment, they often find it difficult to keep up with the ever-increasing published literature. All guidelines require regular updating, usually every 3 years, in line with progress in the field. The current Guidelines focus on technique and perioperative management of laparoscopic ventral hernia repair and constitute the first comprehensive guidelines on this topic. In this issue of Surgical Endoscopy, the first part of the Guidelines is published including sections on basics, indication for surgery, perioperative management, and key points of technique. The next part (Part 2) of the Guidelines will address complications and comparisons between open and laparoscopic techniques. Part 3 will cover mesh technology, hernia prophylaxis, technique-related issues, new technologic developments, lumbar and other unusual hernias, and training/education.}, language = {en} } @article{LozovayaGataullinaTsintsadzeetal.2014, author = {Lozovaya, N. and Gataullina, S. and Tsintsadze, T. and Tsintsadze, V. and Pallesi-Pocachard, E. and Minlebaev, M. and Goriounova, N. A. and Buhler, E. and Watrin, F. and Shityakov, S. and Becker, A. J. and Bordey, A. and Milh, M. and Scavarda, D. and Bulteau, C. and Dorfmuller, G. and Delalande, O. and Represa, A. and Cardoso, C. and Dulac, O. and Ben-Ari, Y. and Burnashev, N.}, title = {Selective suppression of excessive GluN2C expression rescues early epilepsy in a tuberous sclerosis murine model}, series = {Nature Communications}, volume = {5}, journal = {Nature Communications}, number = {4563}, doi = {10.1038/ncomms5563}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-121276}, year = {2014}, abstract = {Tuberous sclerosis complex (TSC), caused by dominant mutations in either TSC1 or TSC2 tumour suppressor genes is characterized by the presence of brain malformations, the cortical tubers that are thought to contribute to the generation of pharmacoresistant epilepsy. Here we report that tuberless heterozygote \(Tsc1^{+/-}\) mice show functional upregulation of cortical GluN2C-containing N-methyl-D-aspartate receptors (NMDARs) in an mTOR-dependent manner and exhibit recurrent, unprovoked seizures during early postnatal life (