TY  - JOUR
A1  - Aad, G.
A1  - Abbott, B.
A1  - Abdallah, J.
A1  - Abdel Khalek, S.
A1  - Abdelalim, A. A.
T1  - Search for the Standard Model Higgs boson in the H→WW(⋆)→ℓνℓνH→WW(⋆)→ℓνℓν decay mode with 4.7 fb\(^{−1}\) of ATLAS data at \(\sqrt{s}\)=7 TeV
JF  - Physics Letters B
N2  - A search for the Standard Model Higgs boson in the H→WW(⋆)→ℓνℓνH→WW(⋆)→ℓνℓν (ℓ=e,μℓ=e,μ) decay mode is presented. The search is performed using proton–proton collision data corresponding to an integrated luminosity of 4.7 fb\(^{−1}\) at a centre-of-mass energy of 7 TeV collected during 2011 with the ATLAS detector at the Large Hadron Collider. No significant excess of events over the expected background is observed. An upper bound is placed on the Higgs boson production cross section as a function of its mass. A Standard Model Higgs boson with mass in the range between 133 GeV and 261 GeV is excluded at 95% confidence level, while the expected exclusion range is from 127 GeV to 233 GeV.
KW  - ATLAS
KW  - LHC
KW  - Higgs
KW  - WW
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-127307
VL  - 761
IS  - 1
ER  - 
TY  - JOUR
A1  - Aad, G.
A1  - Abbott, B.
A1  - Abdallah, J.
A1  - Abdelalim, A. A.
A1  - Abdesselam, A.
T1  - Electron performance measurements with the ATLAS detector using the 2010 LHC proton-proton collision data
JF  - The European Physical Journal C
N2  - Detailed measurements of the electron performance of the ATLAS detector at the LHC are reported, using decays of the Z, W and J/ψ particles. Data collected in 2010 at s√=7 TeV are used, corresponding to an integrated luminosity of almost 40 pb\(^{−1}\). The inter-alignment of the inner detector and the electromagnetic calorimeter, the determination of the electron energy scale and resolution, and the performance in terms of response uniformity and linearity are discussed. The electron identification, reconstruction and trigger efficiencies, as well as the charge misidentification probability, are also presented.
KW  - electromagnetic calorimeter
KW  - Atlas detector
KW  - calorimeter
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-127313
VL  - 72
IS  - 1909
ER  - 
TY  - JOUR
A1  - Aad, G.
A1  - Abbott, B.
A1  - Abdallah, J.
A1  - Abdelalim, A. A.
A1  - Abdesselam, A.
T1  - Performance of the ATLAS Trigger System in 2010
JF  - The European Physical Journal C
N2  - Proton–proton collisions at √s=7 TeV and heavy ion collisions at \(\sqrt{sNN}\)=2.76 TeV were produced by the LHC and recorded using the ATLAS experiment’s trigger system in 2010. The LHC is designed with a maximum bunch crossing rate of 40 MHz and the ATLAS trigger system is designed to record approximately 200 of these per second. The trigger system selects events by rapidly identifying signatures of muon, electron, photon, tau lepton, jet, and B meson candidates, as well as using global event signatures, such as missing transverse energy. An overview of the ATLAS trigger system, the evolution of the system during 2010 and the performance of the trigger system components and selections based on the 2010 collision data are shown. A brief outline of plans for the trigger system in 2011 is presented.
KW  - ATLAS
KW  - Trigger System
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-127321
VL  - 72
IS  - 1849
ER  - 
TY  - JOUR
A1  - Aad, G.
A1  - Abbott, B.
A1  - Abdallah, J.
A1  - Abdelalim, A. A.
A1  - Abdesselam, A.
T1  - Forward-backward correlations and charged-particle azimuthal distributions in pp interactions using the ATLAS detector
JF  - Journal of High Energy Physics
N2  - Using inelastic proton-proton interactions at s√=900 GeV and 7 TeV, recorded by the ATLAS detector at the LHC, measurements have been made of the correlations between forward and backward charged-particle multiplicities and, for the first time, between forward and backward charged-particle summed transverse momentum. In addition, jet-like structure in the events is studied by means of azimuthal distributions of charged particles relative to the charged particle with highest transverse momentum in a selected kinematic region of the event. The results are compared with predictions from tunes of the pythia and herwig++ Monte Carlo generators, which in most cases are found to provide a reasonable description of the data.
KW  - Hadron-Hadron Scattering
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-127336
VL  - 7
IS  - 19
ER  - 
TY  - THES
A1  - Aaken, Claas van
T1  - Adjuvante Radiochemotherapie des Rektumkarzinoms - multizentrische retrospektive Analyse von 534 Patienten in Franken - Behandlungsergebnisse der Strahlentherapie und Evaluation (A) - eine retrospektive Analyse des Krankengutes 6 fränkischer Strahlenkliniken im Zeitraum 4/93 bis 3/98
T1  - Adjuvant radiochemotherapy of rectal cancer - a multi-institutional retrospective quality control analysis of 534 patients - results of radiotherapy and evaluation (A) -
N2  - Die adjuvante Radiochemotherapie des Rektumkarzinoms im UICC-Stadium II/III wird seit 1991 vom National Cancer Institute (NCI) und in Deutschland seit 1994 als Standard empfohlen. Die Qualität und Ergebnisse der postoperativen Therapie in der täglichen klinischen Praxis wurden flächendeckend retrospektiv untersucht. Insgesamt wurden 534 Patienten aus sechs Institutionen ausgewertet, die zwischen 1993 und 1998 behandelt wurden. Die beteiligten Kliniken versorgten strahlentherapeutisch flächendeckend große Teile des nordbayerischen Raumes. Die Stadienverteilung der Patienten war: UICC I 1%, II 28%, III 69% und IV 2%. 92% erhielten eine RChT, 8% eine alleinige RT. Die mediane Nachbeobachtungszeit der Patienten betrug 40 Monate. Ergebnisse (Teil A): Nur etwa 37% der epidemiologisch erwarteten Patienten wurden entsprechend der Konsensusvereinbarung einer postoperativen Therapie zugewiesen. Nach 5 Jahren betrug die aktuarische lokale Kontrolle 75%, die Freiheit von Fernmetastasen 56%, das krankheitsfreie Überleben 53% und das Gesamtüberleben 57%. Weitere Ergebnisse siehe Teil B. Schlussfolgerung: Der niedrige Anteil von der adjuvanten Therapie zugewiesenen Patienten sowie die im Vergleich zu randomisierten Studien ungünstigeren Ergebnisse weisen auf die Auswahl eines Risikokollektivs hin. Anstelle einer stadienbezogenen Zuweisung scheint eine Auswahl mit individueller Risikoabschätzung bevorzugt zu werden. Neben Therapieverbesserungen durch randomisierte Studien sollten ebenso Anstrengungen zur Übertragung dieser Ergebnisse in die flächendeckende Praxis übernommen werden.
N2  - Radiochemotherapy as adjuvant treatment for rectal cancer UICC stage II/III has been recommended by the National Cancer Institute (NCI) since 1991 and in Germany since 1994. Quality and results of postoperative treatment in day-to-day clinical practice in a complete region are evaluated retrospectively in a multi-institutional approach. 534 patients from six institutions treated between 1993 and 1998 were evaluated. The institutions covered a complete region with radiotherapeutic care. Patients were staged as follows: UICC I 1%, II 28%, III 69%, and IV 2%. 92% received RChT, 8% RT alone. Median follow-up of patients was 40 months. Results (Part A): Only about 37% of expected patients were referred for postoperative treatment. The 5-year actuarial rate was as follows: local control 75%, freedom from distant metastases 56%, disease-free survival 53%, and overall survival 57%. For further results see part B. Conclusion: While the quality of adjuvant treatment followed consensus guidelines, the number of referred patients which was lower as expected and the inferior treatment results as compared to randomized studies indicated that the consensus recommendations for adjuvant treatment have not been fully accepted. Instead of patient referral according to UICC stage, patient selection by the surgeons has been performed according to individual risk factors. Efforts have to be made not only to improve treatment results in randomized studies but also to transfer and control these standards in daily practice.
KW  - Rektumkarzinom
KW  - Adjuvante Behandlung
KW  - Radiochemotherapie
KW  - Qualitätskontrolle
KW  - rectal cancer
KW  - adjuvant treatment
KW  - radiochemotherapy
KW  - patterns of care
Y1  - 2003
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-7681
ER  - 
TY  - THES
A1  - Abbas, Eid Nagy Eid
T1  - Demotic Texts from Medinet Habu (Philological, Paleographical, and Cultural Study)
T1  - Demotische Texte aus Medinet Habu (Philologische, paläographische und kulturelle Studie)
N2  - The current study presents a new a group of Demotic ostraca in the belongings of the Cairo Museum. A large part of this group stem from Medinet Habu in the western bank of modern Luxor in Upper Egypt and was discovered in the beginning of the thirties of the last century by the Chicago Oriental Institute (recently renamed as Institute for the Study of Ancient Cultures ‘ISAC’). A small portion of the collection under consideration come from other Upper Egyptian provenances including Gebelein, Edfu, Kom Ombo, and possibly elsewhere in Thebes. The main goal of the present dissertation is to decipher, translate, and provide a philological, paleographical, and cultural analysis of the group of texts in question. The results of this study are spread over two main parts, the first of which is dedicated to the main and largest part of the collection, i.e. ostraca from Medinet Habu, while the second is concerned with ostraca from other places. The first part comprises of five sections beginning with receipts of money and in-kind payments including some receipts for the payments of the different capitation charges in the Ptolemaic and Roman Periods, a few for land-related payments, as well as others related to different Ptolemaic monopolies or trades such as a receipt for the price of oil, one for the linen tax, in addition to a unique receipt for the rarely attested fish tax. The second section includes accounts and lists of different kinds be it monetary, in-kind, agriculture, or any other type of lists or accounts that record different everyday transactions. The following section presents a relatively different type of lists, namely lists of personal names. The fourth section incorporates a variety of texts of different concerns, e.g. texts of religious nature, letters, temples oaths, or other private documents. Unidentified texts occupy the fifth and final section of the first part. The second part of the study, which comprises texts that originate from different Upper Egyptian localities, includes three sections, i.e. receipts, accounts, and lists of names.
N2  - Die aktuelle Studie stellt eine neue Gruppe demotischer Ostraka im Bestand des Kairoer Museums vor. Ein großer Teil dieser Gruppe stammt aus Medinet Habu am Westufer des heutigen Luxor in Oberägypten und wurde Anfang der dreißiger Jahre des letzten Jahrhunderts vom Chicago Oriental Institute (kürzlich in Institute for the Study of Ancient Cultures „ISAC“ umbenannt) entdeckt. Ein kleiner Teil der untersuchten Sammlung stammt aus anderen oberägyptischen Provenienzen, darunter Gebelein, Edfu, Kom Ombo und möglicherweise anderswo in Theben. Das Hauptziel der vorliegenden Dissertation ist die Entzifferung, Übersetzung und Bereitstellung einer philologischen, paläographischen und kulturellen Analyse der betreffenden Textgruppe. Die Ergebnisse dieser Studie verteilen sich auf zwei Hauptteile, von denen der erste dem Haupt und größten Teil der Sammlung, d.h. Ostraka aus Medinet Habu, gewidmet ist, während sich der zweite mit Ostraka aus anderen oberägyptischen Orten befasst. Der erste Teil besteht aus fünf Abschnitten, beginnend mit Quittungen in Geld oder Naturalien, darunter einige Zahlungsquittungen für die verschiedenen Kopfsteuern in der ptolemäischen und römischen Zeit, einige für landbezogene Zahlungen sowie Zahlungusquittungen über verschiedene ptolemäische Monopole oder Gewerben wie z.B. ein Quittung für den Preis des Öls, eine über Leinensteuer sowie eine einzigartige Quittung über die selten belegete Fischsteuer. Der zweite Abschnitt umfasst Listen und Abrechnungen unterschiedlicher Art, sei es über Geld, Natur, Landwirtschaft, oder jede andere Art, die verschiedene alltägliche Transaktionen aufzeichnen. Im folgenden Abschnitt wird eine andere Art von Listen vorgestellt, nämlich Namenlisten. Der vierte Abschnitt enthält eine Vielzahl von Texten zu unterschiedlichen Themen, wie z.B. Texte religiöser Natur, Briefe, Tempeleide oder andere private Dokumente. Nicht identifizierte Texte belegen den fünften und letzten Abschnitt des ersten Teils der Studie. Der zweite Teil dieser Studie, der Texte umfasst, die aus verschiedenen oberägyptischen Fundorten stammen, enthält drei Abschnitte: Quittungen, Abrechnungen  sowie Namenlisten.
KW  - Demotic
KW  - Ostraca
KW  - Medinet Habu
KW  - Tax Receipts
KW  - Accounts
KW  - Lists
Y1  - 2024
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-352653
ER  - 
TY  - JOUR
A1  - Abboud, Tammam
A1  - Asendorf, Thomas
A1  - Heinrich, Jutta
A1  - Faust, Katharina
A1  - Krieg, Sandro M.
A1  - Seidel, Kathleen
A1  - Mielke, Dorothee
A1  - Matthies, Cordola
A1  - Ringel, Florian
A1  - Rohde, Veit
A1  - Szelényi, Andrea
T1  - Transcranial versus direct cortical stimulation for motor-evoked potentials during resection of supratentorial tumors under general anesthesia (the TRANSEKT-trial): study protocol for a randomized controlled trial
JF  - Biomedicines
N2  - Background: Monitoring of motor function during surgery for supratentorial tumors under general anesthesia applies either transcranial electrical stimulation (TES) or direct cortical stimulation (DCS) to elicit motor-evoked potentials. To date, there is no guideline that favor one method over the other. Therefore, we designed this randomized study to compare between both methods regarding the prediction of postoperative motor deficits and extent of tumor resection. Methods: This is a multicenter (six centers in Germany and one in Switzerland), double blind, parallel group, exploratory, randomized controlled clinical trial. Patients without or with mild paresis, who are scheduled for surgical resection of motor-eloquent brain tumors under general anesthesia will be randomized to surgical resection under TES or surgical resection under DCS. The primary endpoint is sensitivity and specificity in prognosis of motor function 7 days after surgery. The main secondary endpoint is the extent of tumor resection. The study is planned to include 120 patients within 2 years. Discussion: The present exploratory study should compare TES and DCS regarding sensitivity and specificity in predicting postoperative motor deficit and extent of tumor resection to calculate the required number of patients in a confirmatory trial to test the superiority of one method over the other.
KW  - threshold criterion
KW  - amplitude criterion
KW  - intraoperative monitoring
KW  - transcranial motor-evoked potentials
KW  - direct cortical stimulation
KW  - threshold level
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-248513
SN  - 2227-9059
VL  - 9
IS  - 10
ER  - 
TY  - JOUR
A1  - Abd El-Aziz, Asmaa M.
A1  - El-Maghraby, Azza
A1  - Ewald, Andrea
A1  - Kandil, Sherif H.
T1  - In-vitro cytotoxicity study: cell viability and cell morphology of carbon nanofibrous scaffold/hydroxyapatite nanocomposites
JF  - Molecules
N2  - Electrospun carbon nanofibers (CNFs), which were modified with hydroxyapatite, were fabricated to be used as a substrate for bone cell proliferation. The CNFs were derived from electrospun polyacrylonitrile (PAN) nanofibers after two steps of heat treatment: stabilization and carbonization. Carbon nanofibrous (CNF)/hydroxyapatite (HA) nanocomposites were prepared by two different methods; one of them being modification during electrospinning (CNF-8HA) and the second method being hydrothermal modification after carbonization (CNF-8HA; hydrothermally) to be used as a platform for bone tissue engineering. The biological investigations were performed using in-vitro cell counting, WST cell viability and cell morphology after three and seven days. L929 mouse fibroblasts were found to be more viable on the hydrothermally-modified CNF scaffolds than on the unmodified CNF scaffolds. The biological characterizations of the synthesized CNF/HA nanofibrous composites indicated higher capability of bone regeneration.
KW  - HA modifiedCNF membranes
KW  - cytotoxicity
KW  - WST test
KW  - cell counting
KW  - cell viability
KW  - cell morphology
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-234037
SN  - 1420-3049
VL  - 26
IS  - 6
ER  - 
TY  - JOUR
A1  - Abda, Ebrahim M.
A1  - Krysciak, Dagmar
A1  - Krohn-Molt, Ines
A1  - Mamat, Uwe
A1  - Schmeisser, Christel
A1  - Förstner, Konrad U.
A1  - Schaible, Ulrich E.
A1  - Kohi, Thomas A.
A1  - Nieman, Stefan
A1  - Streit, Wolfgang R.
T1  - Phenotypic Heterogeneity Affects Stenotrophomonas maltophilia K279a Colony Morphotypes and \(\beta\)-Lactamase Expression
JF  - Frontiers in Microbiology
N2  - Phenotypic heterogeneity at the cellular level in response to various stresses, e.g., antibiotic treatment has been reported for a number of bacteria. In a clonal population, cell-to-cell variation may result in phenotypic heterogeneity that is a mechanism to survive changing environments including antibiotic therapy. Stenotrophomonas rnaltophilia has been frequently isolated from cystic fibrosis patients, can cause numerous infections in other organs and tissues, and is difficult to treat due to antibiotic resistances. S. maltophilia K279a produces the Li and L2 beta-lactamases in response to beta-lactam treatment. Here we report that the patient isolate S. rnaltophilia K279a diverges into cellular subpopulations with distinct but reversible morphotypes of small and big colonies when challenged with ampicillin. This observation is consistent with the formation of elongated chains of bacteria during exponential growth phase and the occurrence of mainly rod-shaped cells in liquid media. RNA-seq analysis of small versus big colonies revealed differential regulation of at least seven genes among the colony morphotypes. Among those, bleu and bla(L2) were transcriptionally the most strongly upregulated genes. Promoter fusions of b/a(L1) and b/a(L2) genes indicated that expression of both genes is also subject to high levels of phenotypic heterogeneous expression on a single cell level. Additionally, the comE homolog was found to be differentially expressed in homogenously versus heterogeneously bla(L2) expressing cells as identified by RNA(seq) analysis. Overexpression of cornE in S. maltophilia K279a reduced the level of cells that were in a bla(L2)-ON mode to 1% or lower. Taken together, our data provide strong evidence that S. maltophilia K279a populations develop phenotypic heterogeneity in an ampicillin challenged model. This cellular variability is triggered by regulation networks including b/a(L1), b/a(L2), and comE.
KW  - xanthomonas maltophilia
KW  - gram-negative bacteria
KW  - RNA-seq
KW  - pseudomas aeruginosa
KW  - antibiotic resistance
KW  - colony morphotypes
KW  - beta-lactamases
KW  - K279a
KW  - Stenotrophomonas maltophilia
KW  - phenotypic heterogeneity
KW  - persister cells
KW  - streptococcus pneumoniae
KW  - nosocomial pathogen
KW  - membrane vesicles
KW  - sinorhizobium fredii NGR234
KW  - red fluorescent protein
KW  - escherichia coli
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-136446
VL  - 6
IS  - 1373
ER  - 
TY  - JOUR
A1  - Abdali, Narges
A1  - Barth, Enrico
A1  - Norouzy, Amir
A1  - Schulz, Robert
A1  - Nau, Werner M.
A1  - Kleinekathofer, Ulrich
A1  - Tauch, Andreas
A1  - Benz, Roland
T1  - Corynebacterium jeikeium jk0268 Constitutes for the 40 Amino Acid Long PorACj, Which Forms a Homooligomeric and Anion- Selective Cell Wall Channel
JF  - PLoS ONE
N2  - Corynebacterium jeikeium, a resident of human skin, is often associated with multidrug resistant nosocomial infections in immunodepressed patients. C. jeikeium K411 belongs to mycolic acid-containing actinomycetes, the mycolata and contains a channel-forming protein as judged from reconstitution experiments with artificial lipid bilayer experiments. The channel-forming protein was present in detergent treated cell walls and in extracts of whole cells using organic solvents. A gene coding for a 40 amino acid long polypeptide possibly responsible for the pore-forming activity was identified in the known genome of C. jeikeium by its similar chromosomal localization to known porH and porA genes of other Corynebacterium strains. The gene jk0268 was expressed in a porin deficient Corynebacterium glutamicum strain. For purification temporarily histidine-tailed or with a GST-tag at the N-terminus, the homogeneous protein caused channel-forming activity with an average conductance of 1.25 nS in 1M KCl identical to the channels formed by the detergent extracts. Zero-current membrane potential measurements of the voltage dependent channel implied selectivity for anions. This preference is according to single-channel analysis caused by some excess of cationic charges located in the channel lumen formed by oligomeric alpha-helical wheels. The channel has a suggested diameter of 1.4 nm as judged from the permeability of different sized hydrated anions using the Renkin correction factor. Surprisingly, the genome of C. jeikeium contained only one gene coding for a cell wall channel of the PorA/PorH type found in other Corynebacterium species. The possible evolutionary relationship between the heterooligomeric channels formed by certain Corynebacterium strains and the homooligomeric pore of C. jeikeium is discussed.
KW  - antibiotics
KW  - detergents
KW  - anions
KW  - corynebacterium diphtheriae
KW  - membrane potential
KW  - corynebacteria
KW  - cell walls
KW  - permeability
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-129989
VL  - 8
IS  - 10
ER  - 
TY  - JOUR
A1  - Abdali, Narges
A1  - Younas, Farhan
A1  - Mafakheri, Samaneh
A1  - Pothula, Karunakar R.
A1  - Kleinekathöfer, Ulrich
A1  - Tauch, Andreas
A1  - Benz, Roland
T1  - Identification and characterization of smallest pore-forming protein in the cell wall of pathogenic Corynebacterium urealyticum DSM 7109
JF  - BMC Biochemistry
N2  - Background: Corynebacterium urealyticum, a pathogenic, multidrug resistant member of the mycolata, is known as causative agent of urinary tract infections although it is a bacterium of the skin flora. This pathogenic bacterium shares with the mycolata the property of having an unusual cell envelope composition and architecture, typical for the genus Corynebacterium. The cell wall of members of the mycolata contains channel-forming proteins for the uptake of solutes. Results: In this study, we provide novel information on the identification and characterization of a pore-forming protein in the cell wall of C. urealyticum DSM 7109. Detergent extracts of whole C. urealyticum cultures formed in lipid bilayer membranes slightly cation-selective pores with a single-channel conductance of 1.75 nS in 1 M KCl. Experiments with different salts and non-electrolytes suggested that the cell wall pore of C. urealyticum is wide and water-filled and has a diameter of about 1.8 nm. Molecular modelling and dynamics has been performed to obtain a model of the pore. For the search of the gene coding for the cell wall pore of C. urealyticum we looked in the known genome of C. urealyticum for a similar chromosomal localization of the porin gene to known porH and porA genes of other Corynebacterium strains. Three genes are located between the genes coding for GroEL2 and polyphosphate kinase (PKK2). Two of the genes (cur_1714 and cur_1715) were expressed in different constructs in C. glutamicum Delta porA Delta porH and in porin-deficient BL21 DE3 Omp8 E. coli strains. The results suggested that the gene cur_1714 codes alone for the cell wall channel. The cell wall porin of C. urealyticum termed PorACur was purified to homogeneity using different biochemical methods and had an apparent molecular mass of about 4 kDa on tricine-containing sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Conclusions: Biophysical characterization of the purified protein (PorACur) suggested indeed that cur_1714 is the gene coding for the pore-forming protein in C. urealyticum because the protein formed in lipid bilayer experiments the same pores as the detergent extract of whole cells. The study is the first report of a cell wall channel in the pathogenic C. urealyticum.
KW  - cell wall channel
KW  - mycolic acid
KW  - porin
KW  - Corynebacterium urealyticum
KW  - lipid bilayer membrane
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-226959
VL  - 19
ER  - 
TY  - THES
A1  - Abdel Rahman, Faisal Mirghani
T1  - Systematic analysis of genes expressed in the retinal pigment epithelium (RPE) and identification of candidates for genetic susceptibility to age-related macular degeneration (AMD)
N2  - Age related macular degeneration (AMD) is the leading cause of visual impairment in the elderly and the major cause of blindness in the developed world. To date, the molecular mechanisms underlying the disease are not well understood although in recent years a primary involvement of the retinal pigment epithelium (RPE) has become evident. The aim of the present study is to systematically analyse genes which are differentially expressed in the RPE, and to assess their possible association with mechanisms and pathways likely to be related to retinal disease, in particular AMD. Towards this goal, 2379 expressed sequence tags (ESTs) were established from an inhouse generated RPE cDNA library. This library was constructed by using the suppression subtraction hybridization (SSH) technique which normalises redundant sequences and ensures enrichment of rare transcripts. In a first phase, 1002 ESTs were sequenced and subjected to comprehensive alignment with public nucleotide and protein databases. A search of the 1002 ESTs against the human genome draft sequence yielded 168 known genes, 51 predicted genes, 15 unknown transcripts and 41 clones with no significant similarity. Reverse Northern blot hybridization was performed for 318 EST clusters to identify abundantly expressed genes in the RPE and to prioritize subsequent analyses. Representative clones were spotted onto a nylon membrane and hybridized with cDNA probes of driver (heart and liver) and tester (RPE) used in the cDNA library construction. Subsequently, 107 EST clusters were subjected to Northern blot hybridizations. These analyses identified 7 RPE-specific, 3 retina-specific, 7 RPE/retina-specific, and 7 tissue restricted transcripts, while 29 EST clusters were ubiquitously expressed, and evaluation was not possible for another 54 EST clusters. Of the 24 transcripts with specific or restricted expression, 16 clones were selected for further characterization. The predicted gene MGC2477 and 2 novel isoforms of the human transient receptor potential cation channel, subfamily M, member 3 (TRPM3) were cloned and further described in detail. In addition, polymorphic variations for these 2 genes as well as for the human MT-Protocadherin gene were determined. For MGC2477, 15 single nucleotide polymorphisms (SNPs) were identified, with 13 having a frequency of the minor allele greater than 20%. 10 of the 15 SNPs have not been reported in so far in public SNP repertoires. Partial assessment of the TRPM3 gene yielded 35 SNPs. Of these, 30 (85.7%) were highly frequent (0.17-0.5%), and 14 (40%) were novel. The MT-Protocadherin gene revealed 35 SNPs, including 28 (80%) with high frequency of the minor allele. 23 (65.7%) were novel SNPs. These SNPs will be used to construct the most common haplotypes. These will be used in case/control association studies in 400 AMD patients and 200 ethnically and aged matched controls to assess a possible contribution of these genes in the etiology of AMD.
N2  - Die altersabhängige Makuladegeneration (AMD) ist die häufigste Ursache von gravierenden Einschränkungen des Sehvermögens im fortgeschrittenen Lebensalter. In den Industriestaaten ist die AMD zudem die Hauptursache für Altersblindheit. Die molekularen Mechanismen, die zur Entstehung der AMD führen, sind bisher nur unzureichend bekannt. In den letzten Jahren hat es sich jedoch herausgestellt, dass das retinale Pigmentepithel (RPE) eine primäre Rolle in der Pathogenese der AMD spielt. Ziel dieser Arbeit war die systematische Analyse von Genen, welche im RPE differentiell exprimiert werden. Entsprechende Kandidatengene sollten auf deren mögliche Beteiligung an der Entstehung von Erkrankungen der Retina, insbesondere der AMD, untersucht werden. Zunächst wurden 2379 ESTs aus einer innerhalb der Arbeitsgruppe generierten RPE cDNA Bibliothek definiert. Die dazu verwendete cDNA Bibliothek wurde durch die Suppressions- Subtraktions Hybridisierungs-Technik (SSH) konstruiert. Diese Technik gestattet eine Normalisierung gegenüber redundanten Sequenzen und begünstigt gleichzeitig die Anreicherung von seltenen Transkripten. In einer ersten Phase wurden 1002 ESTs sequenziert und einer umfassenden bioinformatischen Analyse mit Hilfe der verfügbaren DNA- und Protein Datenbanken unterzogen. Der Vergleich der 1002 ESTs mit der Draft Sequenz des menschlichen Genoms ergab den Hinweis auf 168 bereits bekannte Gene, 51 mögliche Gene, 15 völlig unbekannte Transkripte und 41 nicht weiter zuordenbare cDNA Klone. 318 EST Cluster wurden einer reversen Northen-Blot Analyse unterzogen um hochexprimierte Gene zu identifizieren und damit Prioritäten für die weiteren Analysen zu setzen. Im Rahmen der Northern-Analyse wurden repräsentative Klone von 107 EST-Klustern mit cDNA Sonden der ursprünglichen cDNA-Bibliothek hybridisiert. Als Ergebnis dieser Analyse fanden sich 7 RPE-spezifische, 3 Retina-spezifische, 7 sowohl RPE- als auch Retinaspezifische sowie 7 auf einzelne Gewebe limitierte Transkripte. 29 EST Cluster erwiesen sich als ubiquitär exprimiert, und 54 Kluster konnten nicht näher zugeordnet werden. Von den 24 Transkripten mit spezifischer oder zumindest begrenzter Expression wurden 16 Klone zur weiteren Charakterisierung ausgewählt. Aus diesen Material wurden im Rahmen dieser Arbeit das Kandidatengen MGC2477 sowie 2 neue Isoformen des menschlichen TRPM3-Gens kloniert und näher charakterisiert. Weiterhin wurden polymorphe Varianten dieser beiden Isoformen und des menschlichen MTProtocadherin- Gens definiert. Im Gen MGC2477 wurden 15 SNPs identifiziert, wovon die Allelhäufigkeit des selteneren Allels bei 13 der SNPs über 20% lag. Für 10 der insgesamt 15 vii SNPs dieses Gens fanden sich bisher keine Einträge in den entprechenden Datenbanken. Die SNP-Suche wurde auch für das TRPM3-Gen durchgeführt und ergab 35 SNPs, wovon 30 (85,7%) als hochfrequent eingestuft werden konnten. 14 dieser 35 SNPs waren bisher nicht in den Datenbanken verzeichnet. Beim MT-Protocadherin-Gen fanden sich ebenfalls 35 SNPs, wobei 80% eine hohe Frequenz des selteneren Allels aufwiesen. In diesem Fall handelte es sich bei 23 der insgesamt 35 SNPs um bisher unbekannte Allele. Diese SNPs bilden den Ausgangspunkt zur Konstruktion der häufigsten Haplotypen der genannten Gene. Mit der Charakterisierung der Einzel-Nukleotid Polymorphismen der Kandidatengene wurde die Grundlage zur Durchführung von Fall/Kontrollstudien gelegt, in deren Rahmen die Bedeutung der jeweiligen Kandidatengene in der Pathogense der AMD untersucht werden kann.
KW  - Senile Makuladegeneration / Pigmentepithel / Genexpression
KW  - RPE
KW  - AMD
KW  - RPE specific genes
Y1  - 2003
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-7053
ER  - 
TY  - JOUR
A1  - Abdel-Latif, Rania
A1  - Fathy, Moustafa
A1  - Anwar, Hend Ali
A1  - Naseem, Muhammad
A1  - Dandekar, Thomas
A1  - Othman, Eman M.
T1  - Cisplatin-induced reproductive toxicity and oxidative stress: ameliorative effect of kinetin
JF  - Antioxidants
N2  - Cisplatin is a commonly used chemotherapeutic agent; however, its potential side effects, including gonadotoxicity and infertility, are a critical problem. Oxidative stress has been implicated in the pathogenesis of cisplatin-induced testicular dysfunction. We investigated whether kinetin use at different concentrations could alleviate gonadal injury associated with cisplatin treatment, with an exploration of the involvement of its antioxidant capacity. Kinetin was administered in different doses of 0.25, 0.5, and 1 mg/kg, alone or along with cisplatin for 10 days. Cisplatin toxicity was induced via a single IP dose of 7 mg/kg on day four. In a dose-dependent manner, concomitant administration of kinetin with cisplatin significantly restored testicular oxidative stress parameters, corrected the distorted sperm quality parameters and histopathological changes, enhanced levels of serum testosterone and testicular StAR protein expression, as well as reduced the up-regulation of testicular TNF-α, IL-1β, Il-6, and caspase-3, caused by cisplatin. It is worth noting that the testicular protective effect of the highest kinetin dose was comparable/more potent and significantly higher than the effects of vitamin C and the lowest kinetin dose, respectively. Overall, these data indicate that kinetin may offer a promising approach for alleviating cisplatin-induced reproductive toxicity and organ damage, via ameliorating oxidative stress and reducing inflammation and apoptosis.
KW  - cytokinins
KW  - kinetin
KW  - cisplatin
KW  - reproductive toxicity
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-271223
SN  - 2076-3921
VL  - 11
IS  - 5
ER  - 
TY  - JOUR
A1  - Abdelhafez, Omnia Hesham
A1  - Fawzy, Michael Atef
A1  - Fahim, John Refaat
A1  - Desoukey, Samar Yehia
A1  - Krischke, Markus
A1  - Mueller, Martin J.
A1  - Abdelmohsen, Usama Ramadan
T1  - Hepatoprotective potential of Malvaviscus arboreus against carbon tetrachloride-induced liver injury in rats
JF  - PLoS ONE
N2  - Malvaviscus arboreus Cav. is a medicinal plant belonging to family Malvaceae with both ethnomedical and culinary value; however, its phytochemical and biological profiles have been scarcely studied. Accordingly, this work was designed to explore the chemical composition and the hepatoprotective potential of M. arboreus against carbon tetrachloride (CCl\(_4\))-induced hepatotoxicity. The total extract of the aerial parts and its derived fractions (petroleum ether, dichloromethane, ethyl acetate, and aqueous) were orally administered to rats for six consecutive days, followed by injection of CCl\(_4\) (1:1 v/v, in olive oil, 1.5 ml/kg, i.p.) on the next day. Results showed that the ethyl acetate and dichloromethane fractions significantly alleviated liver injury in rats as indicated by the reduced levels of alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), total bilirubin (TB), and malondialdehyde (MDA), along with enhancement of the total antioxidant capacities of their livers, with the maximum effects were recorded by the ethyl acetate fraction. Moreover, the protective actions of both fractions were comparable to those of silymarin (100 mg/kg), and have been also substantiated by histopathological evaluations. On the other hand, liquid chromatography-high resolution electrospray ionization mass spectrometry (LC‒HR‒ESI‒MS) metabolomic profiling of the crude extract of M. arboreus aerial parts showed the presence of a variety of phytochemicals, mostly phenolics, whereas the detailed chemical analysis of the most active fraction (i.e. ethyl acetate) resulted in the isolation and identification of six compounds for the first time in the genus, comprising four phenolic acids; β-resorcylic, caffeic, protocatechuic, and 4-hydroxyphenylacetic acids, in addition to two flavonoids; trifolin and astragalin. Such phenolic principles, together with their probable synergistic antioxidant and liver-protecting properties, seem to contribute to the observed hepatoprotective potential of M. arboreus.
KW  - high performance liquid chromatography
KW  - phenols
KW  - phytochemicals
KW  - antioxidants
KW  - metabolomics
KW  - medicinal plants
KW  - Egypt
KW  - xenobiotic metabolism
KW  - Malvaviscus arboreus
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-177243
VL  - 13
IS  - 8
ER  - 
TY  - JOUR
A1  - Abdelhameed, Reda F. A.
A1  - Eltamany, Enas E.
A1  - Hal, Dina M.
A1  - Ibrahim, Amany K.
A1  - AboulMagd, Asmaa M.
A1  - Al-Warhi, Tarfah
A1  - Youssif, Khayrya A.
A1  - Abd El-kader, Adel M.
A1  - Hassanean, Hashim A.
A1  - Fayez, Shaimaa
A1  - Bringmann, Gerhard
A1  - Ahmed, Safwat A.
A1  - Abdelmohsen, Usama Ramadan
T1  - New cytotoxic cerebrosides from the Red Sea cucumber Holothuria spinifera supported by in-silico studies
JF  - Marine Drugs
N2  - Bioactivity-guided fractionation of a methanolic extract of the Red Sea cucumber Holothuria spinifera and LC-HRESIMS-assisted dereplication resulted in the isolation of four compounds, three new cerebrosides, spiniferosides A (1), B (2), and C (3), and cholesterol sulfate (4). The chemical structures of the isolated compounds were established on the basis of their 1D NMR and HRMS spectral data. Metabolic profiling of the H. spinifera extract indicated the presence of diverse secondary metabolites, mostly hydroxy fatty acids, diterpenes, triterpenes, and cerebrosides. The isolated compounds were tested for their in vitro cytotoxicities against the breast adenocarcinoma MCF-7 cell line. Compounds 1, 2, 3, and 4 displayed promising cytotoxic activities against MCF-7 cells, with IC\(_{50}\) values of 13.83, 8.13, 8.27, and 35.56 µM, respectively, compared to that of the standard drug doxorubicin (IC\(_{50}\) 8.64 µM). Additionally, docking studies were performed for compounds 1, 2, 3, and 4 to elucidate their binding interactions with the active site of the SET protein, an inhibitor of protein phosphatase 2A (PP2A), which could explain their cytotoxic activity. This study highlights the important role of these metabolites in the defense mechanism of the sea cucumber against fouling organisms and the potential uses of these active molecules in the design of new anticancer agents.
KW  - LC-HRESIMS
KW  - Holothuria spinifera
KW  - cerebrosides
KW  - molecular docking
KW  - cytotoxicity
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-211089
SN  - 1660-3397
VL  - 18
IS  - 8
ER  - 
TY  - JOUR
A1  - Abdelhameed, Reda F. A.
A1  - Habib, Eman S.
A1  - Eltahawy, Nermeen A.
A1  - Hassanean, Hashim A.
A1  - Ibrahim, Amany K.
A1  - Mohammed, Anber F.
A1  - Fayez, Shaimaa
A1  - Hayallah, Alaa M.
A1  - Yamada, Koji
A1  - Behery, Fathy A.
A1  - Al-Sanea, Mohammad M.
A1  - Alzarea, Sami I.
A1  - Bringmann, Gerhard
A1  - Ahmed, Safwat A.
A1  - Abdelmohsen, Usama Ramadan
T1  - New cytotoxic natural products from the Red Sea sponge Stylissa carteri
JF  - Marine Drugs
N2  - Bioactivity-guided isolation supported by LC-HRESIMS metabolic profiling led to the isolation of two new compounds, a ceramide, stylissamide A (1), and a cerebroside, stylissoside A (2), from the methanol extract of the Red Sea sponge Stylissa carteri. Structure elucidation was achieved using spectroscopic techniques, including 1D and 2D NMR and HRMS. The bioactive extract’s metabolomic profiling showed the existence of various secondary metabolites, mainly oleanane-type saponins, phenolic diterpenes, and lupane triterpenes. The in vitro cytotoxic activity of the isolated compounds was tested against two human cancer cell lines, MCF-7 and HepG2. Both compounds, 1 and 2, displayed strong cytotoxicity against the MCF-7 cell line, with IC\(_{50}\) values at 21.1 ± 0.17 µM and 27.5 ± 0.18 µM, respectively. They likewise showed a promising activity against HepG2 with IC\(_{50}\) at 36.8 ± 0.16 µM for 1 and IC\(_{50}\) 30.5 ± 0.23 µM for 2 compared to the standard drug cisplatin. Molecular docking experiments showed that 1 and 2 displayed high affinity to the SET protein and to inhibitor 2 of protein phosphatase 2A (I2PP2A), which could be a possible mechanism for their cytotoxic activity. This paper spreads light on the role of these metabolites in holding fouling organisms away from the outer surface of the sponge, and the potential use of these defensive molecules in the production of novel anticancer agents.
KW  - LC-HRESIMS
KW  - Stylissa carteri
KW  - ceramide
KW  - cerebroside
KW  - docking
KW  - cytotoxic activity
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-205795
SN  - 1660-3397
VL  - 18
IS  - 5
ER  - 
TY  - JOUR
A1  - Abdelhameed, Reda F. A.
A1  - Habib, Eman S.
A1  - Goda, Marwa S.
A1  - Fahim, John Refaat
A1  - Hassanean, Hashem A.
A1  - Eltamany, Enas E.
A1  - Ibrahim, Amany K.
A1  - AboulMagd, Asmaa M.
A1  - Fayez, Shaimaa
A1  - Abd El-kader, Adel M.
A1  - Al-Warhi, Tarfah
A1  - Bringmann, Gerhard
A1  - Ahmed, Safwat A.
A1  - Abdelmohsen, Usama Ramadan
T1  - Thalassosterol, a New Cytotoxic Aromatase Inhibitor Ergosterol Derivative from the Red Sea Seagrass Thalassodendron ciliatum
JF  - Marine Drugs
N2  - Thalassodendron ciliatum (Forssk.) Den Hartog is a seagrass belonging to the plant family Cymodoceaceae with ubiquitous phytoconstituents and important pharmacological potential, including antioxidant, antiviral, and cytotoxic activities. In this work, a new ergosterol derivative named thalassosterol (1) was isolated from the methanolic extract of T. ciliatum growing in the Red Sea, along with two known first-reported sterols, namely ergosterol (2) and stigmasterol (3), using different chromatographic techniques. The structure of the new compound was established based on 1D and 2D NMR spectroscopy and high-resolution mass spectrometry (HR-MS) and by comparison with the literature data. The new ergosterol derivative showed significant in vitro antiproliferative potential against the human cervical cancer cell line (HeLa) and human breast cancer (MCF-7) cell lines, with IC\(_{50}\) values of 8.12 and 14.24 µM, respectively. In addition, docking studies on the new sterol 1 explained the possible binding interactions with an aromatase enzyme; this inhibition is beneficial in both cervical and breast cancer therapy. A metabolic analysis of the crude extract of T. ciliatum using liquid chromatography combined with high-resolution electrospray ionization mass spectrometry (LC-ESI-HR-MS) revealed the presence of an array of phenolic compounds, sterols and ceramides, as well as di- and triglycerides.
KW  - cytotoxic activity
KW  - ergosterol derivative
KW  - metabolic analysis
KW  - docking studies
KW  - seagrass
KW  - Thalassodendron ciliatum
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-236085
VL  - 18
IS  - 7
ER  - 
TY  - THES
A1  - Abdelmohsen, Usama Ramadan
T1  - Antimicrobial Activities from Plant Cell Cultures and Marine Sponge-Associated Actinomycetes
T1  - Antimikrobielle Aktivitäten aus Pflanzenzellkulturen und marinen Schwamm-assoziierten Actinomyceten
N2  - This thesis is divided into three parts with the main goal allocating novel antimicrobial compounds that could be used as future antibiotics. The first part aimed to evaluate the potential of plant suspension cultures for the production of antimicrobial proteins. The extracellular, intracellular and cell wall bound fractions of seven heterotrophic and photomixotrophic plant cell suspension cultures treated with nine different elicitors were tested for the elicitor dependent production of antimicrobial proteins. Bioactivities were tested against a selected panel of human isolates including Gram-positive and Gram-negative bacteria as well as fungi using the disc diffusion assay. The intracellular fractions of elicited cell cultures were more active than extracellular fractions while the cell wall bound fractions showed lowest activities. Among the 21 fractions tested, the intracellular fraction of Lavendula angustifolia elicited with DC3000 was most active against Candida maltosa. The second most active fraction was the intracellular fraction of Arabidopsis thaliana elicited with salicylic acid which was moreover active against all test strains. The antimicrobial activity of elicited Arabidopsis thaliana cell cultures was tested by bioautography to locate the antimicrobial proteins in the crude extract. The intracellular fraction of photomixotrophic Arabidopsis thaliana cells elicited with salicylic acid was selected for further gel filtration chromatography on S-200 column leading to the purification of one 19 kDa antimicrobially active protein, designated, AtAMP. Our findings suggest that elicited plant cell cultures may present a new promising alternative source of antimicrobial proteins. The second part comprises the isolation of actinomycetes associated with marine sponges and testing the bioactivities of new species for further investigations. Actinobacterial communities of eleven taxonomically different sponges that had been collected from offshore Ras Mohamed (Egypt) and from Rovinj (Croatia) were investigated by a culture-based approach using different standard media for isolation of actinomycetes and media enriched with aqueous sponge extract to target rare and new actinomycete species. Phylogenetic characterization of 52 representative isolates out of 90 based on almost complete sequences of genes encoding 16S rRNA supported their assignment to 18 different actinomycete genera. Altogether 14 putatively new species were identified based on sequence similarity values below 98.2% to other strains in the NCBI database. The use of M1 agar amended with aqueous sponge extract yielded a putative new genus related to Rubrobacter which highlighting the need for innovative cultivation protocols. Biological activity testing showed that five isolates were active against Gram-positives only, one isolate was active against Candida albicans only and one isolate showed activity against both groups of pathogens. Moreover, the antiparasistic activity was documented for four isolates. These results showed a high diversity of actinomycetes associated with marine sponges as well as highlighted their potential to produce anti-infective agents. The third part of the thesis focused on the isolation and structure elucidation of new bioactive compounds. Streptomyces strain RV15 recovered from sponge Dysidea tupha, was selected for further chemical analysis by virtue of the fact that it exhibited the greatest antimicrobial potential against Staphylococcus aureus as well as Candida albicans among the all tested strains. Moreover, members of the genus Streptomyces are well known as prolific producers of interesting pharmacologically active metabolites. Chemical analysis of the methanolic crude extract using different chromatographic tools yielded four new compounds. The structures of the new compounds were spectroscopically elucidated to be four new cyclic peptides, namely, cyclodysidins A-D. Their bioactivity was tested against different proteases, bacteria and Candida as well as tumor cell lines. The compounds did not show any significant activities at this point.
N2  - Die hier vorliegende Dissertation ist in drei Kapitel gegliedert und hatte die Bereitstellung neuer antimikrobieller Substanzen, die zukünftig als Antibiotika genutzt werden könnten, zum Hauptziel. Das erste Kapitel befasst sich mit dem Potenzial von Pflanzen zur Produktion von Proteinen mit antimikrobieller Wirkung. Pflanzenzellkulturen wurden mit neun verschiedenen Induktoren stimuliert und anschließend auf die Produktion von Proteinen mit antimikrobieller Wirkung hin untersucht. Dafür wurden die extra-, intrazellulären sowie die membrangebundenen Proteinfraktionen von sieben heterotrophen und photomixotrophen Pflanzenzellkulturen extrahiert. Mittels Diffusionstests wurden die Wirkung der Proteine gegen eine Sammlung menschlicher Pathogene inklusive Gram-positiver und Gram-negativer Bakterien, sowie Pilze getestet. Die intrazellulären Fraktionen zeigten dabei höhere Aktivitäten als die extrazellulären, wohingegen die membrangebundenen Proteine die geringsten Aktivitäten aufwiesen. Von den insgesamt 21 getesteten Proteinfraktionen wies die mit DC3000 induzierte intrazelluläre Fraktion von Lavendula angustifolia die größte Wirkung gegen Candida maltosa auf. Die mit Salicylsäure induzierte intrazelluläre Proteinfraktion von Arabidopsis thaliana zeigte eine Hemmung aller getesteten pathogenen Stämme. Die antimikrobielle Aktivität der induzierten Arabidopsis thaliana-Zellkultur wurde mittels Bioautography weiter untersucht, um das wirksame Protein im Gesamt-(Roh-) extrakt einzugrenzen. Die intrazelluläre Fraktion der photomixotrophen Arabidopsis thaliana-Zellkultur wurde ausgewählt, um ein 19 kDa Protein mit antimikrobieller Wirkung, genannt AtAMP, mittels Gelfitrationschromatography über eine S-200 Säule aufzureinigen. Unsere Ergebnisse weisen darauf hin, dass induzierte Pflanzenzellkulturen zukünftig als aussichtsreiche alternative Quelle für antimikrobiell wirksame Proteine herangezogen werden können. Der zweite Teil dieser Dissertation beinhaltet die Isolation von mit marinen Schwämmen assoziierten Actinomyceten und deren Testung auf Bioaktivität. Aus 11 taxonomisch verschiedenen, an den Küsten von Ras Mohamed (Ägypten) und Rovinj (Kroatien) gesammelten Schwammspezies, wurden Actinobakterien auf verschiedenen Standardmedien kultiviert. Um seltene, neue Stämme zu isolieren, wurden diese Medien mit wässrigen Schwammextrakten angereichert. Die auf der 16S rRNA-Gensequenz basierenden phylogenetischen Charakterisierung von 52 der insgesamt 90 Isolate, zeigte die Zugehörigkeit zu 18 verschiedenen Actinomyceten-Gattungen. Die 16S rRNA-Gene von 14 Isolaten zeigten Homologien von weniger als 98,2% zu denen anderer in Datenbanken abgelegten Bakterien und stellen somit vermutlich neue Arten dar. Die Verwendung von mit Schwammextrakt angereichertem M1-Agar resultierte in der Kultivierung einer mutmaßlich neuen, mit Rubrobacter verwandten Gattung und bestätigt die Notwendigkeit der Entwicklung neuer innovativer Kultivierungsprotokolle. Aktivitätstests von fünf Isolaten zeigten deren hemmende Wirkung nur gegen Gram-positive Bakterien, ein Isolat zeigte Aktivität nur gegen Candida albicans und ein Isolat war wirksam gegen beide genannten Pathogengruppen. Desweiteren konnten antiparasitäre Wirkungen von vier Isolaten dokumentiert werden. Die hier beschriebenen Ergebnisse zeigen die große Diversität von mit Schwämmen assoziierten Actinomyceten und deren Potential Antiinfektiva zu produzieren. Der dritte Teil dieser Arbeit fokussierte sich auf die Isolation und Strukturaufklärung neuer bioaktiver Substanzen. Streptomyceten sind bekannt für die Produktion von interessanten, pharmakologisch aktiven Metaboliten. Der aus dem Schwamm Dysidea tupha isolierte Stamm Streptomyces RV 15 zeigte eine hohe Aktivität gegen Staphylococcus aureus und C. albicans und wurde deshalb für nähere Untersuchungen ausgewählt. Die chemische Analyse des Methanol-Rohextrakts unter der Verwendung verschiedener Chromatographie-Verfahren resultierte in der Isolation von vier Substanzen. Die spektroskopische Analyse zeigte, dass diese neuen Substanzen zyklische Peptidstrukturen aufweisen und wurden daraufhin als Cyclodysidin A-D benannt. Die Bioaktivitäten dieser Substanzen wurden gegen verschiedene Proteasen, Bakterien und Candida sowie gegen verschiedene Tumorzelllinien getestet. Bis zum jetzigen Zeitpunkt zeigte keine der getesteten Peptide eine aussagekräftige Wirkung.
KW  - Antimikrobieller Wirkstoff
KW  - Pflanzenzelle
KW  - Zellkultur
KW  - Antimikrobielle Aktivitäten
KW  - Pflanzenzellkulturen
KW  - Proteinen mit antimikrobieller Wirkung
KW  - Actinomyceten
KW  - zyklische Peptide
KW  - Antimicrobial activities
KW  - Plant cell cultures
KW  - Antimicrobial proteins
KW  - Actinomycetes
KW  - Cyclic peptides
Y1  - 2010
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-51483
ER  - 
TY  - JOUR
A1  - Abdelmohsen, Usama Ramadan
A1  - Cheng, Cheng
A1  - Viegelmann, Christina
A1  - Zhang, Tong
A1  - Grkovic, Tanja
A1  - Ahmed, Safwat
A1  - Quinn, Ronald J.
A1  - Hentschel, Ute
A1  - Edrada-Ebel, RuAngelie
T1  - Dereplication Strategies for Targeted Isolation of New Antitrypanosomal Actinosporins A and B from a Marine Sponge Associated-Actinokineospora sp EG49
JF  - Marine Drugs
N2  - High resolution Fourier transform mass spectrometry (HRFTMS) and nuclear magnetic resonance (NMR) spectroscopy were employed as complementary metabolomic tools to dereplicate the chemical profile of the new and antitrypanosomally active sponge-associated bacterium Actinokineospora sp. EG49 extract. Principal Component (PCA), hierarchical clustering (HCA), and orthogonal partial least square-discriminant analysis (OPLS-DA) were used to evaluate the HRFTMS and NMR data of crude extracts from four different fermentation approaches. Statistical analysis identified the best culture one-strain-many-compounds (OSMAC) condition and extraction procedure, which was used for the isolation of novel bioactive metabolites. As a result, two new O-glycosylated angucyclines, named actinosporins A (1) and B (2), were isolated from the broth culture of Actinokineospora sp. strain EG49, which was cultivated from the Red Sea sponge Spheciospongia vagabunda. The structures of actinosporins A and B were determined by 1D- and 2D-NMR techniques, as well as high resolution tandem mass spectrometry. Testing for antiparasitic properties showed that actinosporin A exhibited activity against Trypanosoma brucei brucei with an IC₅₀ value of 15 µM; however no activity was detected against Leishmania major and Plasmodium falciparum, therefore suggesting its selectivity against the parasite Trypanosoma brucei brucei; the causative agent of sleeping sickness.
KW  - dereplication
KW  - secondary metabolomics
KW  - anti-trypanosoma
KW  - Actinokineospora
KW  - Spheciospongia vagabunda
KW  - actinosporins
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-119876
SN  - 1660-3397
VL  - 12
IS  - 3
ER  - 
TY  - JOUR
A1  - Abdelmohsen, Usama Ramadan
A1  - Pimentel-Elardo, Sheila M.
A1  - Hanora, Amro
A1  - Radwan, Mona
A1  - Abou-El-Ela, Soad H.
A1  - Ahmed, Safwat
A1  - Hentschel, Ute
T1  - Isolation, Phylogenetic Analysis and Anti-infective Activity Screening of Marine Sponge-Associated Actinomycetes
N2  - Terrestrial actinomycetes are noteworthy producers of a multitude of antibiotics, however the marine representatives are much less studied in this regard. In this study, 90 actinomycetes were isolated from 11 different species of marine sponges that had been collected from offshore Ras Mohamed (Egypt) and from Rovinj (Croatia). Phylogenetic characterization of the isolates based on 16S rRNA gene sequencing supported their assignment to 18 different actinomycete genera representing seven different suborders. Fourteen putatively novel species were identified based on sequence similarity values below 98.2% to other strains in the NCBI database. A putative new genus related to Rubrobacter was isolated on M1 agar that had been amended with sponge extract, thus highlighting the need for innovative cultivation protocols. Testing for anti-infective activities was performed against clinically relevant, Gram-positive (Enterococcus faecalis, Staphylococcus aureus) and Gram-negative (Escherichia coli, Pseudomonas aeruginosa) bacteria, fungi (Candida albicans) and human parasites (Leishmania major, Trypanosoma brucei). Bioactivities against these pathogens were documented for 10 actinomycete isolates. These results show a high diversity of actinomycetes associated with marine sponges as well as highlight their potential to produce anti-infective agents.
KW  - Biologie
KW  - actinomycetes
KW  - marine sponges
KW  - anti-infective
KW  - anti-parasitic
KW  - phylogenetic
Y1  - 2010
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-68307
ER  -