@article{NazzalHowariYaslametal.2022, author = {Nazzal, Yousef and Howari, Fares M. and Yaslam, Aya and Iqbal, Jibran and Maloukh, Lina and Ambika, Lakshmi Kesari and Al-Taani, Ahmed A. and Ali, Ijaz and Othman, Eman M. and Jamal, Arshad and Naseem, Muhammad}, title = {A methodological review of tools that assess dust microbiomes, metatranscriptomes and the particulate chemistry of indoor dust}, series = {Atmosphere}, volume = {13}, journal = {Atmosphere}, number = {8}, issn = {2073-4433}, doi = {10.3390/atmos13081276}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-285957}, year = {2022}, abstract = {Indoor house dust is a blend of organic and inorganic materials, upon which diverse microbial communities such as viruses, bacteria and fungi reside. Adequate moisture in the indoor environment helps microbial communities multiply fast. The outdoor air and materials that are brought into the buildings by airflow, sandstorms, animals pets and house occupants endow the indoor dust particles with extra features that impact human health. Assessment of the health effects of indoor dust particles, the type of indoor microbial inoculants and the secreted enzymes by indoor insects as allergens merit detailed investigation. Here, we discuss the applications of next generation sequencing (NGS) technology which is used to assess microbial diversity and abundance of the indoor dust environments. Likewise, the applications of NGS are discussed to monitor the gene expression profiles of indoor human occupants or their surrogate cellular models when exposed to aqueous solution of collected indoor dust samples. We also highlight the detection methods of dust allergens and analytical procedures that quantify the chemical nature of indoor particulate matter with a potential impact on human health. Our review is thus unique in advocating the applications of interdisciplinary approaches that comprehensively assess the health effects due to bad air quality in built environments.}, language = {en} } @article{AbdelLatifFathyAnwaretal.2022, author = {Abdel-Latif, Rania and Fathy, Moustafa and Anwar, Hend Ali and Naseem, Muhammad and Dandekar, Thomas and Othman, Eman M.}, title = {Cisplatin-induced reproductive toxicity and oxidative stress: ameliorative effect of kinetin}, series = {Antioxidants}, volume = {11}, journal = {Antioxidants}, number = {5}, issn = {2076-3921}, doi = {10.3390/antiox11050863}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-271223}, year = {2022}, abstract = {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.}, language = {en} } @article{FathySaadEldinNaseemetal.2022, author = {Fathy, Moustafa and Saad Eldin, Sahar M. and Naseem, Muhammad and Dandekar, Thomas and Othman, Eman M.}, title = {Cytokinins: wide-spread signaling hormones from plants to humans with high medical potential}, series = {Nutrients}, volume = {14}, journal = {Nutrients}, number = {7}, issn = {2072-6643}, doi = {10.3390/nu14071495}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-271017}, year = {2022}, abstract = {Nature is a rich source of biologically active novel compounds. Sixty years ago, the plant hormones cytokinins were first discovered. These play a major role in cell division and cell differentiation. They affect organogenesis in plant tissue cultures and contribute to many other physiological and developmental processes in plants. Consequently, the effect of cytokinins on mammalian cells has caught the attention of researchers. Many reports on the contribution and potential of cytokinins in the therapy of different human diseases and pathophysiological conditions have been published and are reviewed here. We compare cytokinin effects and pathways in plants and mammalian systems and highlight the most important biological activities. We present the strong profile of the biological actions of cytokinins and their possible therapeutic applications.}, language = {en} } @article{NaseemOsmanoğluKaltdorfetal.2020, author = {Naseem, Muhammad and Osmanoğlu, {\"O}zge and Kaltdorf, Martin and Alblooshi, Afnan Ali M. A. and Iqbal, Jibran and Howari, Fares M. and Srivastava, Mugdha and Dandekar, Thomas}, title = {Integrated framework of the immune-defense transcriptional signatures in the Arabidopsis shoot apical meristem}, series = {International Journal of Molecular Sciences}, volume = {21}, journal = {International Journal of Molecular Sciences}, number = {16}, issn = {1422-0067}, doi = {10.3390/ijms21165745}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-285730}, year = {2020}, abstract = {The growing tips of plants grow sterile; therefore, disease-free plants can be generated from them. How plants safeguard growing apices from pathogen infection is still a mystery. The shoot apical meristem (SAM) is one of the three stem cells niches that give rise to the above ground plant organs. This is very well explored; however, how signaling networks orchestrate immune responses against pathogen infections in the SAM remains unclear. To reconstruct a transcriptional framework of the differentially expressed genes (DEGs) pertaining to various SAM cellular populations, we acquired large-scale transcriptome datasets from the public repository Gene Expression Omnibus (GEO). We identify here distinct sets of genes for various SAM cellular populations that are enriched in immune functions, such as immune defense, pathogen infection, biotic stress, and response to salicylic acid and jasmonic acid and their biosynthetic pathways in the SAM. We further linked those immune genes to their respective proteins and identify interactions among them by mapping a transcriptome-guided SAM-interactome. Furthermore, we compared stem-cells regulated transcriptome with innate immune responses in plants showing transcriptional separation among their DEGs in Arabidopsis. Besides unleashing a repertoire of immune-related genes in the SAM, our analysis provides a SAM-interactome that will help the community in designing functional experiments to study the specific defense dynamics of the SAM-cellular populations. Moreover, our study promotes the essence of large-scale omics data re-analysis, allowing a fresh look at the SAM-cellular transcriptome repurposing data-sets for new questions.}, language = {en} } @article{NaseemOthmanFathyetal.2020, author = {Naseem, Muhammad and Othman, Eman M. and Fathy, Moustafa and Iqbal, Jibran and Howari, Fares M. and AlRemeithi, Fatima A. and Kodandaraman, Geema and Stopper, Helga and Bencurova, Elena and Vlachakis, Dimitrios and Dandekar, Thomas}, title = {Integrated structural and functional analysis of the protective effects of kinetin against oxidative stress in mammalian cellular systems}, series = {Scientific Reports}, volume = {10}, journal = {Scientific Reports}, doi = {10.1038/s41598-020-70253-1}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-231317}, year = {2020}, abstract = {Metabolism and signaling of cytokinins was first established in plants, followed by cytokinin discoveries in all kingdoms of life. However, understanding of their role in mammalian cells is still scarce. Kinetin is a cytokinin that mitigates the effects of oxidative stress in mammalian cells. The effective concentrations of exogenously applied kinetin in invoking various cellular responses are not well standardized. Likewise, the metabolism of kinetin and its cellular targets within the mammalian cells are still not well studied. Applying vitality tests as well as comet assays under normal and hyper-oxidative states, our analysis suggests that kinetin concentrations of 500 nM and above cause cytotoxicity as well as genotoxicity in various cell types. However, concentrations below 100 nM do not cause any toxicity, rather in this range kinetin counteracts oxidative burst and cytotoxicity. We focus here on these effects. To get insights into the cellular targets of kinetin mediating these pro-survival functions and protective effects we applied structural and computational approaches on two previously testified targets for these effects. Our analysis deciphers vital residues in adenine phosphoribosyltransferase (APRT) and adenosine receptor (A2A-R) that facilitate the binding of kinetin to these two important human cellular proteins. We finally discuss how the therapeutic potential of kinetin against oxidative stress helps in various pathophysiological conditions.}, language = {en} } @article{MehmoodAlsalehWantetal.2023, author = {Mehmood, Rashid and Alsaleh, Alanoud and Want, Muzamil Y. and Ahmad, Ijaz and Siraj, Sami and Ishtiaq, Muhammad and Alshehri, Faizah A. and Naseem, Muhammad and Yasuhara, Noriko}, title = {Integrative molecular analysis of DNA methylation dynamics unveils molecules with prognostic potential in breast cancer}, series = {BioMedInformatics}, volume = {3}, journal = {BioMedInformatics}, number = {2}, issn = {2673-7426}, doi = {10.3390/biomedinformatics3020029}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-321171}, pages = {434 -- 445}, year = {2023}, abstract = {DNA methylation acts as a major epigenetic modification in mammals, characterized by the transfer of a methyl group to a cytosine. DNA methylation plays a pivotal role in regulating normal development, and misregulation in cells leads to an abnormal phenotype as is seen in several cancers. Any mutations or expression anomalies of genes encoding regulators of DNA methylation may lead to abnormal expression of critical molecules. A comprehensive genomic study encompassing all the genes related to DNA methylation regulation in relation to breast cancer is lacking. We used genomic and transcriptomic datasets from the Cancer Genome Atlas (TGCA) Pan-Cancer Atlas, Genotype-Tissue Expression (GTEx) and microarray platforms and conducted in silico analysis of all the genes related to DNA methylation with respect to writing, reading and erasing this epigenetic mark. Analysis of mutations was conducted using cBioportal, while Xena and KMPlot were utilized for expression changes and patient survival, respectively. Our study identified multiple mutations in the genes encoding regulators of DNA methylation. The expression profiling of these showed significant differences between normal and disease tissues. Moreover, deregulated expression of some of the genes, namely DNMT3B, MBD1, MBD6, BAZ2B, ZBTB38, KLF4, TET2 and TDG, was correlated with patient prognosis. The current study, to our best knowledge, is the first to provide a comprehensive molecular and genetic profile of DNA methylation machinery genes in breast cancer and identifies DNA methylation machinery as an important determinant of the disease progression. The findings of this study will advance our understanding of the etiology of the disease and may serve to identify alternative targets for novel therapeutic strategies in cancer.}, language = {en} } @article{FathyDarwishAbdelhamidetal.2022, author = {Fathy, Moustafa and Darwish, Mostafa A. and Abdelhamid, Al-Shaimaa M. and Alrashedy, Gehad M. and Othman, Othman Ali and Naseem, Muhammad and Dandekar, Thomas and Othman, Eman M.}, title = {Kinetin ameliorates cisplatin-induced hepatotoxicity and lymphotoxicity via attenuating oxidative damage, cell apoptosis and inflammation in rats}, series = {Biomedicines}, volume = {10}, journal = {Biomedicines}, number = {7}, issn = {2227-9059}, doi = {10.3390/biomedicines10071620}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-281686}, year = {2022}, abstract = {Though several previous studies reported the in vitro and in vivo antioxidant effect of kinetin (Kn), details on its action in cisplatin-induced toxicity are still scarce. In this study we evaluated, for the first time, the effects of kinetin in cisplatin (cp)- induced liver and lymphocyte toxicity in rats. Wistar male albino rats were divided into nine groups: (i) the control (C), (ii) groups 2,3 and 4, which received 0.25, 0.5 and 1 mg/kg kinetin for 10 days; (iii) the cisplatin (cp) group, which received a single intraperitoneal injection of CP (7.0 mg/kg); and (iv) groups 6, 7, 8 and 9, which received, for 10 days, 0.25, 0.5 and 1 mg/kg kinetin or 200 mg/kg vitamin C, respectively, and Cp on the fourth day. CP-injected rats showed a significant impairment in biochemical, oxidative stress and inflammatory parameters in hepatic tissue and lymphocytes. PCR showed a profound increase in caspase-3, and a significant decline in AKT gene expression. Intriguingly, Kn treatment restored the biochemical, redox status and inflammatory parameters. Hepatic AKT and caspase-3 expression as well as CD95 levels in lymphocytes were also restored. In conclusion, Kn mitigated oxidative imbalance, inflammation and apoptosis in CP-induced liver and lymphocyte toxicity; therefore, it can be considered as a promising therapy.}, language = {en} } @article{DandekarBencurovaOsmanogluetal.2021, author = {Dandekar, Thomas and Bencurova, Elena and Osmanoglu, {\"O}zge and Naseem, Muhammad}, title = {Klimapflanzen und biologische Wege zu negativen Kohlendioxidemissionen}, series = {BIOspektrum}, volume = {27}, journal = {BIOspektrum}, number = {7}, issn = {1868-6249}, doi = {10.1007/s12268-021-1677-2}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-270067}, pages = {769-772}, year = {2021}, abstract = {Climate plants are critical to prevent global warming as all efforts to save carbon dioxide are too slow and climate disasters on the rise. For best carbon dioxide harvesting we compare algae, trees and crop plants and use metagenomic analysis of environmental samples. We compare different pathways, carbon harvesting potentials of different plants as well as synthetic modifications including carbon dioxide flux balance analysis. For implementation, agriculture and modern forestry are important.}, language = {de} } @article{OthmanFathyBekhitetal.2021, author = {Othman, Eman M. and Fathy, Moustafa and Bekhit, Amany Abdlrehim and Abdel-Razik, Abdel-Razik H. and Jamal, Arshad and Nazzal, Yousef and Shams, Shabana and Dandekar, Thomas and Naseem, Muhammad}, title = {Modulatory and toxicological perspectives on the effects of the small molecule kinetin}, series = {Molecules}, volume = {26}, journal = {Molecules}, number = {3}, issn = {1420-3049}, doi = {10.3390/molecules26030670}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-223064}, year = {2021}, abstract = {Plant hormones are small regulatory molecules that exert pharmacological actions in mammalian cells such as anti-oxidative and pro-metabolic effects. Kinetin belongs to the group of plant hormones cytokinin and has been associated with modulatory functions in mammalian cells. The mammalian adenosine receptor (A2a-R) is known to modulate multiple physiological responses in animal cells. Here, we describe that kinetin binds to the adenosine receptor (A2a-R) through the Asn253 residue in an adenosine dependent manner. To harness the beneficial effects of kinetin for future human use, we assess its acute toxicity by analyzing different biochemical and histological markers in rats. Kinetin at a dose below 1 mg/kg had no adverse effects on the serum level of glucose or on the activity of serum alanine transaminase (ALT) or aspartate aminotransferase (AST) enzymes in the kinetin treated rats. Whereas, creatinine levels increased after a kinetin treatment at a dose of 0.5 mg/kg. Furthermore, 5 mg/kg treated kinetin rats showed normal renal corpuscles, but a mild degeneration was observed in the renal glomeruli and renal tubules, as well as few degenerated hepatocytes were also observed in the liver. Kinetin doses below 5 mg/kg did not show any localized toxicity in the liver and kidney tissues. In addition to unraveling the binding interaction between kinetin and A2a-R, our findings suggest safe dose limits for the future use of kinetin as a therapeutic and modulatory agent against various pathophysiological conditions.}, language = {en} } @article{NaseemKunzDandekar2014, author = {Naseem, Muhammad and Kunz, Meik and Dandekar, Thomas}, title = {Probing the unknowns in cytokinin-mediated immune defense in Arabidopsis with systems biology approaches}, series = {Bioinformatics and Biology Insights}, volume = {8}, journal = {Bioinformatics and Biology Insights}, issn = {1177-9322}, doi = {10.4137/bbi.s13462}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-120199}, pages = {35-44}, year = {2014}, abstract = {Plant hormones involving salicylic acid (SA), jasmonic acid (JA), ethylene (Et), and auxin, gibberellins, and abscisic acid (ABA) are known to regulate host immune responses. However, plant hormone cytokinin has the potential to modulate defense signaling including SA and JA. It promotes plant pathogen and herbivore resistance; underlying mechanisms are still unknown. Using systems biology approaches, we unravel hub points of immune interaction mediated by cytokinin signaling in Arabidopsis. High-confidence Arabidopsis protein-protein interactions (PPI) are coupled to changes in cytokinin-mediated gene expression. Nodes of the cellular interactome that are enriched in immune functions also reconstitute sub-networks. Topological analyses and their specific immunological relevance lead to the identification of functional hubs in cellular interactome. We discuss our identified immune hubs in light of an emerging model of cytokinin-mediated immune defense against pathogen infection in plants.}, language = {en} } @phdthesis{Naseem2009, author = {Naseem, Muhammad}, title = {Role of cytokinins in plant immunity}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-37555}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2009}, abstract = {Phytohormone spielen eine zentrale Rolle in der Regelung normalen Wachstums, der Entwicklung und der Mitwirkung an Abwehrmechanismen in Pflanzen. Allgemein betrachtet k{\"o}nnen Phytohormone in zwei Klassen unterteilt werden - in solche, die in Beziehung zu Stressreaktionen stehen und in jene, die das Wachstum beg{\"u}nstigen. Salizyls{\"a}ure, und Jasmons{\"a}ure sind in erster Linie an der Stressresonanz, Ethylen, Auxine, Cytokinine (CKs) und Gibberilline an Entwicklungsprozessen beteiligt. In den letzten Jahrzehnten wurde den Phytohormonen aus diesem Betrachtungswinkel starke Aufmerksamkeit gewidmet und heute stehen ihre wechselseitigen Beeinflussungen im Fokus. Die Tatsache, dass Pflanzenpathogene ein hormonelles Ungleichgewicht an der Wirtspflanzen-Pathogen Schnittstelle bedingen und es begleitend zu physiologischen Ver{\"a}nderungen kommt, wird dabei als Werkzeug f{\"u}r Erforschungen in Pflanzengeweben genutzt. Abgesehen von der bekannten Bedeutung, die Cytokinine f{\"u}r Wachstum und Entwicklung haben, sind sie bisher am meisten vernachl{\"a}ssigt worden und eher als Konsequenz denn als Grund von Pathogeninfektionen angesehen worden. Die Ergebnisse dieser Arbeit basieren auf der Hyphothese, dass erh{\"o}hte Gehalte an CKs die Pflanzen mit einer Resistenz gegen hemibiotrophe Pathogene ausstatten. In diesem Zusammenhang wurden transgenetische Pflanzen untersucht, in welchen das bakterielle Gen IPT {\"u}berexpremiert wurde. Kontrolliert wurde die Expression durch einen pathogen-induzierbaren, einen tetracyclin-induzierbaren oder durch einen wachstumsabh{\"a}ngigen Promotor. F{\"u}r die weitere Validierung der an den transgenetischen Pflanzen gewonnenen Ergebnisse wurden unterschiedliche Cytokinin von abgeschnittenen Tabakbl{\"a}tter aufgenommen. Alle transgenetischen Ans{\"a}tze und exogen applizierten Cytokiningaben zeigten {\"a}hnliche verringerte Krankheitsanzeichen. Diese Art der Resistenz wurde im Weiteren mit verschiedenen zellul{\"a}ren, biochemischen, mikrobiellen Techniken sowie durch Signalwirkungstests fundiert. Die Gehalte von SA und JA blieben unver{\"a}ndert, w{\"a}hrend die Expression des Gens PR1 in Proben mit erh{\"o}htem Cytokiningehalt stark hoch reguliert wurde. Dar{\"u}ber hinaus konnte eine verringerte Akkumulation von ROS in IPT exprimierenden Bl{\"a}ttern gegen{\"u}ber der entsprechende Kontrolle beobachtet wurden. Zus{\"a}tzlich konnte weder ein direkter Effekt im Wachstum von P. syringae pv. tabaci noch die Pr{\"a}senz von antimikrobiellen Peptiden in Cytokinin-angereicherten Extrakten festgestellt werden. Interessanterweise ist die verst{\"a}rkte Akkumulation von Phytoalexinen bei erh{\"o}htem CKs-Status der Pflanze als ein m{\"o}gliches Anzeichen f{\"u}r die Gef{\"a}hrdung durch die Ausbreitung von Pathogenen belegt. Im Gegensatz dazu konnten wir keine Wachstumsverlangsamung f{\"u}r Sclerotinia sclerotiorum in Bl{\"a}ttern mit erh{\"o}hten CKs-Gehalten feststellen. Neben der Wirt-Pathogen Interaktion im Hinblick auf erh{\"o}hte CK-Gehalte wurden die Auswirkungen eines modulierten Kohlenstoffhaushalts auf das Wachstum von Pathogenen untersucht. Daf{\"u}r wurden zuvor generierte transgenetische Tabakpflanzen, basierend auf ein regulierbarem Invertase Enzym verwendet. Es konnte gezeigt werden, dass induzierte und nicht-induzierte Expression von CIN1 unter der Kontrolle des Tet-Promotors das Wachstum von P. syringae pv. tabaci nicht beeinflusst. Dar{\"u}ber hinaus zeigten Linien, welche den Invertaseinhibitor NtCIF unter Kontrolle desselben Tet-Promotors exprimieren, keine differenzielle Ver{\"a}nderung des Wachstums von P. syringae pv. tabaci bei induziertem und nicht-induziertem Status der Pflanze. {\"A}hnlich waren die Resultate in der transgenetischen Tomaten-Linie Lin6::NtCIF f{\"u}r P.syringae pv. tomato DC 3000. Interessanterweise zeigten die Bl{\"a}tter von Lin6::NtCIF Tomatenpflanzen starke Symptome nach Behandlung mit Botrytis cinerea verglichen zum Wildtyp. Eine m{\"o}gliche Verbindung zwischen Cytokininen und Zuckermetabolismus im Bezug auf die Wirt-Pathogen Beziehung wurde ebenfalls untersucht. Die Expression des IPT-Gens unter der Kontrolle des pathogeninduzierbaren Promotors (4xJERE::IPT) im transgenetischen Hintergrund von Tet::CIN1 ergab lokale Unterschiede in der Entwicklung der Symptom von P. syringae pv. tabaci. Bei exogen appliziertem Kinetin an abgeschnittenen Tabakbl{\"a}ttern von Tet::CIN1 verz{\"o}gerte sich ebenfalls das Wachstum von P. syringae pv. Tabaci im Vergleich zu Tet-induzierten Bl{\"a}ttern. Diese Ergebnisse f{\"u}hren zu der Schlussfolgerung, dass die extrazellul{\"a}re Invertase keine essentielle Rolle in der Cytokinin-vermittelten Resistenz gegen hemibiotrophe Pathogene spielt.}, subject = {Pflanzenhormon}, language = {en} } @article{KaltdorfBreitenbachKarletal.2023, author = {Kaltdorf, Martin and Breitenbach, Tim and Karl, Stefan and Fuchs, Maximilian and Kessie, David Komla and Psota, Eric and Prelog, Martina and Sarukhanyan, Edita and Ebert, Regina and Jakob, Franz and Dandekar, Gudrun and Naseem, Muhammad and Liang, Chunguang and Dandekar, Thomas}, title = {Software JimenaE allows efficient dynamic simulations of Boolean networks, centrality and system state analysis}, series = {Scientific Reports}, volume = {13}, journal = {Scientific Reports}, doi = {10.1038/s41598-022-27098-7}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-313303}, year = {2023}, abstract = {The signal modelling framework JimenaE simulates dynamically Boolean networks. In contrast to SQUAD, there is systematic and not just heuristic calculation of all system states. These specific features are not present in CellNetAnalyzer and BoolNet. JimenaE is an expert extension of Jimena, with new optimized code, network conversion into different formats, rapid convergence both for system state calculation as well as for all three network centralities. It allows higher accuracy in determining network states and allows to dissect networks and identification of network control type and amount for each protein with high accuracy. Biological examples demonstrate this: (i) High plasticity of mesenchymal stromal cells for differentiation into chondrocytes, osteoblasts and adipocytes and differentiation-specific network control focusses on wnt-, TGF-beta and PPAR-gamma signaling. JimenaE allows to study individual proteins, removal or adding interactions (or autocrine loops) and accurately quantifies effects as well as number of system states. (ii) Dynamical modelling of cell-cell interactions of plant Arapidopsis thaliana against Pseudomonas syringae DC3000: We analyze for the first time the pathogen perspective and its interaction with the host. We next provide a detailed analysis on how plant hormonal regulation stimulates specific proteins and who and which protein has which type and amount of network control including a detailed heatmap of the A.thaliana response distinguishing between two states of the immune response. (iii) In an immune response network of dendritic cells confronted with Aspergillus fumigatus, JimenaE calculates now accurately the specific values for centralities and protein-specific network control including chemokine and pattern recognition receptors.}, language = {en} } @article{NaseemSrivastavaDandekar2014, author = {Naseem, Muhammad and Srivastava, Mugdha and Dandekar, Thomas}, title = {Stem-cell-triggered immunity safeguards cytokinin enriched plant shoot apexes from pathogen infection}, series = {Frontiers in Plant Science}, volume = {5}, journal = {Frontiers in Plant Science}, issn = {1664-462X}, doi = {10.3389/fpls.2014.00588}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-118247}, pages = {588}, year = {2014}, abstract = {Intricate mechanisms discriminate between friends and foes in plants. Plant organs deploy overlapping and distinct protection strategies. Despite vulnerability to a plethora of pathogens, the growing tips of plants grow bacteria free. The shoot apical meristem (SAM) is among three stem cells niches, a self-renewable reservoir for the future organogenesis of leaf, stem, and flowers. How plants safeguard this high value growth target from infections was not known until now. Recent reports find the stem cell secreted 12-amino acid peptide CLV3p (CLAVATA3 peptide) is perceived by FLS2 (FLAGELLIN SENSING 2) receptor and activates the transcription of immunity and defense marker genes. No infection in the SAM of wild type plants and bacterial infection in clv3 and fls2 mutants illustrate this natural protection against infections. Cytokinins (CKs) are enriched in the SAM and regulate meristem activities by their involvement in stem cell signaling networks. Auxin mediates plant susceptibility to pathogen infections while CKs boost plant immunity. Here, in addition to the stem-cell-triggered immunity we also highlight a potential link between CK signaling and CLV3p mediated immune response in the SAM.}, language = {en} } @article{NaseemDandekar2012, author = {Naseem, Muhammad and Dandekar, Thomas}, title = {The Role of Auxin-Cytokinin Antagonism in Plant-Pathogen Interactions}, series = {PLOS Pathogens}, volume = {8}, journal = {PLOS Pathogens}, number = {11}, doi = {10.1371/journal.ppat.1003026}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-131901}, pages = {e1003026}, year = {2012}, abstract = {No abstract available.}, language = {en} } @article{OsmanogluKhaledAlSeiariAlKhoorietal.2021, author = {Osmanoglu, {\"O}zge and Khaled AlSeiari, Mariam and AlKhoori, Hasa Abduljaleel and Shams, Shabana and Bencurova, Elena and Dandekar, Thomas and Naseem, Muhammad}, title = {Topological Analysis of the Carbon-Concentrating CETCH Cycle and a Photorespiratory Bypass Reveals Boosted CO\(_2\)-Sequestration by Plants}, series = {Frontiers in Bioengineering and Biotechnology}, volume = {9}, journal = {Frontiers in Bioengineering and Biotechnology}, issn = {2296-4185}, doi = {10.3389/fbioe.2021.708417}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-249260}, year = {2021}, abstract = {Synthetically designed alternative photorespiratory pathways increase the biomass of tobacco and rice plants. Likewise, some in planta-tested synthetic carbon-concentrating cycles (CCCs) hold promise to increase plant biomass while diminishing atmospheric carbon dioxide burden. Taking these individual contributions into account, we hypothesize that the integration of bypasses and CCCs will further increase plant productivity. To test this in silico, we reconstructed a metabolic model by integrating photorespiration and photosynthesis with the synthetically designed alternative pathway 3 (AP3) enzymes and transporters. We calculated fluxes of the native plant system and those of AP3 combined with the inhibition of the glycolate/glycerate transporter by using the YANAsquare package. The activity values corresponding to each enzyme in photosynthesis, photorespiration, and for synthetically designed alternative pathways were estimated. Next, we modeled the effect of the crotonyl-CoA/ethylmalonyl-CoA/hydroxybutyryl-CoA cycle (CETCH), which is a set of natural and synthetically designed enzymes that fix CO₂ manifold more than the native Calvin-Benson-Bassham (CBB) cycle. We compared estimated fluxes across various pathways in the native model and under an introduced CETCH cycle. Moreover, we combined CETCH and AP3-w/plgg1RNAi, and calculated the fluxes. We anticipate higher carbon dioxide-harvesting potential in plants with an AP3 bypass and CETCH-AP3 combination. We discuss the in vivo implementation of these strategies for the improvement of C3 plants and in natural high carbon harvesters.}, language = {en} }