Synthesis of Metallic Nanowires Using Integrated DNA Molecules as Templates

The DNA double helix is inherently a nanoscale wire-like object, possessing a 2 nm diameter as well as a remarkable capability for molecular recognition and the interaction with other chemical compounds, thus making it an attractive material for biologically driven assembly of artificial nanostructures. In this work methods for the construction of functional electronic networks from single DNA molecules are presented. For this, (i) the generation of patterns of distinct interconnects between micro-fabricated contact pads are explored by stretching end-specifically thiol-functionalized, single-tethered DNA molecules using hydrodynamic flow as well as an electric field-induced thermal flow. (ii) These networks then serve as a template for a selective in-situ photoinduced nucleation and growth of platinum clusters of 4 nm diameter along the DNA molecules. In the synthesis exclusively platinum ions from an aqueous platinum nitrate solution bonded electrostatically to the backbone of the immobilized DNA can be reduced upon irradiation with UV light, while background metallization is inhibited. Furthermore, the metallization scheme is applied to DNA nanotubes and another photochemical deposition process is used to tune the interparticle gap space in a discontinuous platinum cluster chain to form conducting nanowires. The "process toolbox'' presented in this work offers a versatile alternative for the hierarchical patterning and incorporation of biotemplated nanomaterials into micro-/nanofabrication schemes.Ein doppelhelikaler DNA-Strang besitzt mit seinem hohen Aspektverhältnis von Natur aus Ähnlichkeit mit einem Kabel. Zusammen mit seinen einzigartigen Selbstassemblierungseigenschaften sowie der Fähigkeit, mit einer Vielzahl von chemischen Stoffen eine Verbindung einzugehen, macht dies ihn zu einem aussichtsreichen Baumaterial für den Aufbau von künstlichen Nanostrukturen. In dieser Arbeit werden deshalb verschiedene Methoden für den Bau von elektronischen Schaltkreisen aus einzelnen DNA-Strängen demonstriert. Dazu wird (i) die Herstellung von Verdrahtungsmustern zwischen lithographisch gefertigten Kontaktstrukturen untersucht. Endständig mit Thiolgruppen funktionalisierte DNA-Moleküle, die an nur einem Ende mit der Oberfläche verknüpft sind, werden mittels Strömung oder eines elektrothermisch induzierten Flusses zwischen Elektroden gespannt. (ii) Diese Netzwerke dienen im Weiteren als Vorlage für ein selektives, lichtinduziertes Wachstum von Platinpartikeln mit Durchmessern von 4 nm lokal entlang der DNA-Moleküle. Dabei werden unter UV-Bestrahlung nur solche Platinionen reduziert, die aus einer Platinnitrat-Lösung elektrostatisch an die immobilisierte DNA angebunden haben. Partikelwachstum in der umgebenden Lösung wird weitgehend verhindert. Darüber hinaus wird dieses Verfahren auch auf DNA-Nanoröhren angewendet und ein weiterer photochemischer Abscheideprozess eingesetzt, um unterbrochene Clusterkettern zusammenzuwachsen, mit dem Ziel, elektrisch leitfähige Nanodrähte zu erhalten. Die vorgestellten Verfahren stellen eine vielseitige Alternative zu herkömmlichen, hierarchischen Fabrikationsschemen der Mikro- und Nanotechnologie dar

Nanostructural organization of naturally occurring composites - part II: silica-chitin-based biocomposites

Investigations of the micro- and nanostructures and chemical composition of the sponge skeletons as examples for natural structural biocomposites are of fundamental scientific relevance. Recently, we show that some demosponges (Verongula gigantea, Aplysina sp.) and glass sponges (Farrea occa, Euplectella aspergillum) possess chitin as a component of their skeletons. The main practical approach we used for chitin isolation was based on alkali treatment of corresponding external layers of spicules sponge material with the aim of obtaining alkali-resistant compounds for detailed analysis. Here, we present a detailed study of the structural and physicochemical properties of spicules of the glass sponge Rossella fibulata. The structural similarity of chitin derived from this sponge to invertebrate alpha chitin has been confirmed by us unambiguously using physicochemical and biochemical methods. This is the first report of a silica-chitin composite biomaterial found in Rossella species. Finally, the present work includes a discussion related to strategies for the practical application of silica-chitin-based composites as biomaterials

A Dialogue between the Hypoxia-Inducible Factor and the Tumor Microenvironment

The hypoxia-inducible factor is the key protein responsible for the cellular adaptation to low oxygen tension. This transcription factor becomes activated as a result of a drop in the partial pressure of oxygen, to hypoxic levels below 5% oxygen, and targets a panel of genes involved in maintenance of oxygen homeostasis. Hypoxia is a common characteristic of the microenvironment of solid tumors and, through activation of the hypoxia-inducible factor, is at the center of the growth dynamics of tumor cells. Not only does the microenvironment impact on the hypoxia-inducible factor but this factor impacts on microenvironmental features, such as pH, nutrient availability, metabolism and the extracellular matrix. In this review we discuss the influence the tumor environment has on the hypoxia-inducible factor and outline the role of this factor as a modulator of the microenvironment and as a powerful actor in tumor remodeling. From a fundamental research point of view the hypoxia-inducible factor is at the center of a signaling pathway that must be deciphered to fully understand the dynamics of the tumor microenvironment. From a translational and pharmacological research point of view the hypoxia-inducible factor and its induced downstream gene products may provide information on patient prognosis and offer promising targets that open perspectives for novel “anti-microenvironment” directed therapies

Synthesis of Metallic Nanowires Using Integrated DNA Molecules as Templates

The DNA double helix is inherently a nanoscale wire-like object, possessing a 2 nm diameter as well as a remarkable capability for molecular recognition and the interaction with other chemical compounds, thus making it an attractive material for biologically driven assembly of artificial nanostructures. In this work methods for the construction of functional electronic networks from single DNA molecules are presented. For this, (i) the generation of patterns of distinct interconnects between micro-fabricated contact pads are explored by stretching end-specifically thiol-functionalized, single-tethered DNA molecules using hydrodynamic flow as well as an electric field-induced thermal flow. (ii) These networks then serve as a template for a selective in-situ photoinduced nucleation and growth of platinum clusters of 4 nm diameter along the DNA molecules. In the synthesis exclusively platinum ions from an aqueous platinum nitrate solution bonded electrostatically to the backbone of the immobilized DNA can be reduced upon irradiation with UV light, while background metallization is inhibited. Furthermore, the metallization scheme is applied to DNA nanotubes and another photochemical deposition process is used to tune the interparticle gap space in a discontinuous platinum cluster chain to form conducting nanowires. The "process toolbox'' presented in this work offers a versatile alternative for the hierarchical patterning and incorporation of biotemplated nanomaterials into micro-/nanofabrication schemes.Ein doppelhelikaler DNA-Strang besitzt mit seinem hohen Aspektverhältnis von Natur aus Ähnlichkeit mit einem Kabel. Zusammen mit seinen einzigartigen Selbstassemblierungseigenschaften sowie der Fähigkeit, mit einer Vielzahl von chemischen Stoffen eine Verbindung einzugehen, macht dies ihn zu einem aussichtsreichen Baumaterial für den Aufbau von künstlichen Nanostrukturen. In dieser Arbeit werden deshalb verschiedene Methoden für den Bau von elektronischen Schaltkreisen aus einzelnen DNA-Strängen demonstriert. Dazu wird (i) die Herstellung von Verdrahtungsmustern zwischen lithographisch gefertigten Kontaktstrukturen untersucht. Endständig mit Thiolgruppen funktionalisierte DNA-Moleküle, die an nur einem Ende mit der Oberfläche verknüpft sind, werden mittels Strömung oder eines elektrothermisch induzierten Flusses zwischen Elektroden gespannt. (ii) Diese Netzwerke dienen im Weiteren als Vorlage für ein selektives, lichtinduziertes Wachstum von Platinpartikeln mit Durchmessern von 4 nm lokal entlang der DNA-Moleküle. Dabei werden unter UV-Bestrahlung nur solche Platinionen reduziert, die aus einer Platinnitrat-Lösung elektrostatisch an die immobilisierte DNA angebunden haben. Partikelwachstum in der umgebenden Lösung wird weitgehend verhindert. Darüber hinaus wird dieses Verfahren auch auf DNA-Nanoröhren angewendet und ein weiterer photochemischer Abscheideprozess eingesetzt, um unterbrochene Clusterkettern zusammenzuwachsen, mit dem Ziel, elektrisch leitfähige Nanodrähte zu erhalten. Die vorgestellten Verfahren stellen eine vielseitige Alternative zu herkömmlichen, hierarchischen Fabrikationsschemen der Mikro- und Nanotechnologie dar

Synthesis of Metallic Nanowires Using Integrated DNA Molecules as Templates

The DNA double helix is inherently a nanoscale wire-like object, possessing a 2 nm diameter as well as a remarkable capability for molecular recognition and the interaction with other chemical compounds, thus making it an attractive material for biologically driven assembly of artificial nanostructures. In this work methods for the construction of functional electronic networks from single DNA molecules are presented. For this, (i) the generation of patterns of distinct interconnects between micro-fabricated contact pads are explored by stretching end-specifically thiol-functionalized, single-tethered DNA molecules using hydrodynamic flow as well as an electric field-induced thermal flow. (ii) These networks then serve as a template for a selective in-situ photoinduced nucleation and growth of platinum clusters of 4 nm diameter along the DNA molecules. In the synthesis exclusively platinum ions from an aqueous platinum nitrate solution bonded electrostatically to the backbone of the immobilized DNA can be reduced upon irradiation with UV light, while background metallization is inhibited. Furthermore, the metallization scheme is applied to DNA nanotubes and another photochemical deposition process is used to tune the interparticle gap space in a discontinuous platinum cluster chain to form conducting nanowires. The "process toolbox'' presented in this work offers a versatile alternative for the hierarchical patterning and incorporation of biotemplated nanomaterials into micro-/nanofabrication schemes.Ein doppelhelikaler DNA-Strang besitzt mit seinem hohen Aspektverhältnis von Natur aus Ähnlichkeit mit einem Kabel. Zusammen mit seinen einzigartigen Selbstassemblierungseigenschaften sowie der Fähigkeit, mit einer Vielzahl von chemischen Stoffen eine Verbindung einzugehen, macht dies ihn zu einem aussichtsreichen Baumaterial für den Aufbau von künstlichen Nanostrukturen. In dieser Arbeit werden deshalb verschiedene Methoden für den Bau von elektronischen Schaltkreisen aus einzelnen DNA-Strängen demonstriert. Dazu wird (i) die Herstellung von Verdrahtungsmustern zwischen lithographisch gefertigten Kontaktstrukturen untersucht. Endständig mit Thiolgruppen funktionalisierte DNA-Moleküle, die an nur einem Ende mit der Oberfläche verknüpft sind, werden mittels Strömung oder eines elektrothermisch induzierten Flusses zwischen Elektroden gespannt. (ii) Diese Netzwerke dienen im Weiteren als Vorlage für ein selektives, lichtinduziertes Wachstum von Platinpartikeln mit Durchmessern von 4 nm lokal entlang der DNA-Moleküle. Dabei werden unter UV-Bestrahlung nur solche Platinionen reduziert, die aus einer Platinnitrat-Lösung elektrostatisch an die immobilisierte DNA angebunden haben. Partikelwachstum in der umgebenden Lösung wird weitgehend verhindert. Darüber hinaus wird dieses Verfahren auch auf DNA-Nanoröhren angewendet und ein weiterer photochemischer Abscheideprozess eingesetzt, um unterbrochene Clusterkettern zusammenzuwachsen, mit dem Ziel, elektrisch leitfähige Nanodrähte zu erhalten. Die vorgestellten Verfahren stellen eine vielseitige Alternative zu herkömmlichen, hierarchischen Fabrikationsschemen der Mikro- und Nanotechnologie dar

Nanostructural Organization of Naturally Occurring Composites—Part I: Silica-Collagen-Based Biocomposites

Glass sponges, as examples of natural biocomposites, inspire investigations aiming at both a better understanding of biomineralization mechanisms and novel developments in the synthesis of nanostructured biomimetic materials. Different representatives of marine glass sponges of the class Hexactinellida (Porifera) are remarkable because of their highly flexible basal anchoring spicules. Therefore, investigations of the biochemical compositions and the micro- and nanostructure of the spicules as examples of naturally structured biomaterials are of fundamental scientific relevance. Here we present a detailed study of the structural and biochemical properties of the basal spicules of the marine glass sponge Monorhaphis chuni. The results show unambiguously that in this glass sponge a fibrillar protein of collagenous nature is the template for the silica mineralization in all silica-containing structural layers of the spicule. The structural similarity and homology of collagens derived from M. chuni spicules to other sponge and vertebrate collagens have been confirmed by us using FTIR, amino acid analysis and mass spectrometric sequencing techniques. We suggest that nanomorphology of silica formed on proteinous structures could be determined as an example of biodirected epitaxial nanodistribution of amorphous silica phase on oriented fibrillar collagen templates. Finally, the present work includes a discussion relating to silica-collagen-based hybrid materials for practical applications as biomaterials

Pilot study to test the feasibility of a trial design and complex intervention on PRIoritising MUltimedication in Multimorbidity in general practices (PRIMUMpilot)

OBJECTIVE: To improve medication appropriateness and adherence in elderly patients with multimorbidity, we developed a complex intervention involving general practitioners (GPs) and their healthcare assistants (HCA). In accordance with the Medical Research Council guidance on developing and evaluating complex interventions, we prepared for the main study by testing the feasibility of the intervention and study design in a cluster randomised pilot study. SETTING: 20 general practices in Hesse, Germany. PARTICIPANTS: 100 cognitively intact patients ≥65 years with ≥3 chronic conditions, ≥5 chronic prescriptions and capable of participating in telephone interviews; 94 patients completed the study. INTERVENTION: The HCA conducted a checklist-based interview with patients on medication-related problems and reconciled their medications. Assisted by a computerised decision-support system (CDSS), the GPs discussed medication intake with patients and adjusted their medication regimens. The control group continued with usual care. OUTCOME MEASURES: Feasibility of the intervention and required time were assessed for GPs, HCAs and patients using mixed methods (questionnaires, interviews and case vignettes after completion of the study). The feasibility of the study was assessed concerning success of achieving recruitment targets, balancing cluster sizes and minimising drop-out rates. Exploratory outcomes included the medication appropriateness index (MAI), quality of life, functional status and adherence-related measures. MAI was evaluated blinded to group assignment, and intra-rater/inter-rater reliability was assessed for a subsample of prescriptions. RESULTS: 10 practices were randomised and analysed per group. GPs/HCAs were satisfied with the interventions despite the time required (35/45 min/patient). In case vignettes, GPs/HCAs needed help using the CDSS. The study made no patients feel uneasy. Intra-rater/inter-rater reliability for MAI was excellent. Inclusion criteria were challenging and potentially inadequate, and should therefore be adjusted. Outcome measures on pain, functionality and self-reported adherence were unfeasible due to frequent missing values, an incorrect manual or potentially invalid results. CONCLUSIONS: Intervention and trial design were feasible. The pilot study revealed important limitations that influenced the design and conduct of the main study, thus highlighting the value of piloting complex interventions. TRIAL REGISTRATION NUMBER: ISRCTN99691973; Results

Götter und menschliche Willensfreiheit

Angefacht durch naturwissenschaftliche Erkenntnisse, wurde in den letzten Jahren die Diskussion um die Grenzen der menschlichen Selbstbestimmung in das Bewusstsein einer breiteren Öffentlichkeit zurückgerufen. Wesentliche Parameter der modernen Debatte liegen dabei in der antiken Auseinandersetzung mit dem Problemkreis der Willensfreiheit begründet. Ihm hat sich nicht nur die Philosophie, sondern auch die Epik des griechisch-römischen Altertums gewidmet. So sind Schicksal, göttlicher Wille und menschliches Tun die Koordinaten, in deren Spannungsfeld sich seit jeher die Handlung des antiken Erzählepos entwickelte. Jeder Autor hat ihr Verhältnis dem politischen, literarischen und philosophischen Horizont seiner Epoche entsprechend definiert und ausgestaltet. Im römischen Epos nach Vergil vollzieht sich dieser Prozess vor dem Hintergrund der Festigung des Prinzipats, einer Staatsform, welche die Frage nach den Handlungsmöglichkeiten des Einzelnen neu aufwarf. Der vorliegende Sammelband untersucht vor diesem Hintergrund die Wechselbeziehung von Schicksal, Gott und Mensch bei Lucan, Valerius Flaccus, Statius und Silius Italicus

Mesenchymal stromal cells mitigate liver damage after extended resection in the pig by modulating thrombospondin-1/TGF-β

Post-surgery liver failure is a serious complication for patients after extended partial hepatectomies (ePHx). Previously, we demonstrated in the pig model that transplantation of mesenchymal stromal cells (MSC) improved circulatory maintenance and supported multi-organ functions after 70% liver resection. Mechanisms behind the beneficial MSC effects remained unknown. Here we performed 70% liver resection in pigs with and without MSC treatment, and animals were monitored for 24 h post surgery. Gene expression profiles were determined in the lung and liver. Bioinformatics analysis predicted organ-independent MSC targets, importantly a role for thrombospondin-1 linked to transforming growth factor-β (TGF-β) and downstream signaling towards providing epithelial plasticity and epithelial-mesenchymal transition (EMT). This prediction was supported histologically and mechanistically, the latter with primary hepatocyte cell cultures. MSC attenuated the surgery-induced increase of tissue damage, of thrombospondin-1 and TGF-β, as well as of epithelial plasticity in both the liver and lung. This suggests that MSC ameliorated surgery-induced hepatocellular stress and EMT, thus supporting epithelial integrity and facilitating regeneration. MSC-derived soluble factor(s) did not directly interfere with intracellular TGF-β signaling, but inhibited thrombospondin-1 secretion from thrombocytes and non-parenchymal liver cells, therewith obviously reducing the availability of active TGF-β