Effects of interleukin-1 on glucose uptake and energy homeostasis in lymphocytes

Die Arbeitsgruppe, in der diese Dissertation entstand, hat bereits gezeigt, dass Interleukin- 1 (IL-1) eine ausgeprägte, langanhaltende und insulin-unabhängige Hypoglykämie verursacht. Diese IL-1-induzierte Hypoglykämie wird durch Mechanismen erzeugt, welche sowohl auf peripherer, als auch zentraler Ebene wirken. Erst kürzlich haben wir berichtet, dass IL-1 trotz der gleichzeitigen Hypoglykämie in vivo die energetische Aktivität im Gehirn steigert und in vitro die Glukose-Aufnahme von Neuronen und Astrozyten erhöht. Das Ziel dieser Arbeit ist es zu erforschen, ob IL-1 die Glukose-Aufnahme durch Immunzellen ebenfalls beeinflussen kann. Für diesen Zweck wurden murine Splenozyten mit Lipopolysaccharid (LPS) stimuliert und das während 4 oder 24 Stunden produzierte IL-1 mit IL-1 Rezeptor-Antagonist (IL-1Ra) neutralisiert. Die Glukoseaufnahme wurde mit dem fluoreszierenden Glukose-Analog 2-(N-(7-Nitrobenz-2-oxa-1,3-diazol-4-yl)- Amino)-2-Deoxyglukose (2-NBDG) und Durchflusszytometrie bestimmt. Die Resultate zeigen, dass IL-1Ra die 2-NBDG-Aufnahme in LPS-stimulierten Zellen zu einem Grad verringert, der vergleichbar mit der Blockade von Glukose-Transportern durch Phloretin ist. Prozentual war die Verringerung der 2-NBDG-Aufnahme infolge der IL-1 Blockade in LPS-stimulierten B-Zellen nach 24 h in vitro höher als in nicht stimulierten B-Zellen, was auf eine aktivationsabhängige Zunahme der Glukoseaufnahme durch IL-1 schließen lässt. Der Agonist IL-1b erhöhte die 2-NBDG-Aufnahme in B-Zellen innerhalb einer Stunde. Allerdings war die prozentuale Erhöhung der 2-NBDG-Aufnahme vergleichsweise gering, da die IL-1 Rezeptoren unter den in vitro Bedingungen dieser Arbeit vermutlich fast alle bereits durch IL-1 gebunden waren. Weder Myeloid Differentiation Primary Response 88 (MyD88), ein Signal-Adapter Protein des angeborenen Immunsystems, noch der einwärts gleichrichtende Kaliumkanal 6.2 (Kir6.2) scheinen eine relevante Rolle im Signalweg zu haben, der die Glukoseaufnahme durch IL-1 beeinflusst. Eine pharmakologische Inhibition von AKT/PKB konnte die Effekte von IL-1 auf die Glukoseaufnahme von B-Zellen nicht verhindern, während die Ergebnisse in T-Zellen nicht eindeutig waren. Die Effekte von endogen produziertem IL-1 auf den energetischen Metabolismus von Splenozyten wurden ebenfalls untersucht. Durch die Verwendung von live cell real-time metabolic flux Analysen wurde beobachtet, dass die Blockade von endogenem IL-1 in einer verringerten oxygen consumption rate (OCR) resultierte, die sich sukzessiv innerhalb einer Stunde wieder auf den Ausgangswert normalisierte. Die Verringerung der OCR war von vergleichbarem Ausmaß wie die Inhibition der mitochondriellen ATP-Erzeugung durch Oligomycin. In der initialen Phase der IL-1Ra-Inhibition in nicht stimulierten Splenozyten wurde die Verringerung der oxidativen Phosphorylierung von einem Anstieg der extracellular acidification rate (ECAR) begleitet, welche ein Marker für die Laktatproduktion durch Glykolyse ist. In LPS-stimulierten Splenozyten wurde die ECAR nach IL-1Ra-Injektion nicht weiter erhöht, da die Glykolyse wahrscheinlich nicht weiter beschleunigt werden kann. Die metabolischen Effekte der IL-1-Blockade sind nicht MyD88-abhängig. Die Resultate deuten darauf hin, dass endogen produziertes IL-1 die Glukoseaufnahme und den energetischen Metabolismus von Immunzellen erhöhen kann und möglicherweise damit zur Relokation von Energie zum Immunsystem beiträgt

Much more than just a Roman camp: diachronic interpretation of magnetic data from Danube Limes in Croatia

First large-scale magnetic gradiometer surveys with flexible sensor arrays started at the Danube Limes in 2020 and continue. The investigation of Danube Limes sites with extensions of several dozens of hectares revealed unknown Roman military structures as well as archaeological and historical features from Prehistory to modern era. The diachronic approach to magnetic data interpretation is most appropriate for the palimpsest-like historical landscape of the southern Pannonian Basin

Integrating path dependency and path creation in a general understanding of path constitution

Path dependency as it is described by Arthur and David portrays technological developments as historically embedded, emergent processes. In contrast, Garud and Karnøe's notion of path creation emphasises the role of strategic change and deliberate action for the development of new technologies. In this article, we integrate both concepts into a general understanding of path processes which accounts for emergent as well as deliberate modes of path constitution. In addition, we distinguish between three consecutive phases of technological path developments. Both conceptualisations are used to create an analytical grid against which empirical cases of path processes can be matched. Based on this general understanding, we further outline how concepts from science and technology studies and institutional theory can help to elaborate the role of deliberate action and emergence in the stabilisation of technological paths over time

Córdoba – Qurtuba – Corduba: More than two millennia of construction activity. Geophysical prospection examples from 2004 to 2008

The Andalusian city of Cordoba (Spain) has experienced several peaks during its history of more than 2000 years. In the 3rd century AD it became the capital, called Corduba, of the Roman province of Hispania Ulterior Baetica. It played a role of importance again in the Byzantine and Visigoth Empires. In the 8th century it reached its apogee as Qurtuba, the capital of the Umayyad Caliphate. Declining from the beginning of 11th century when the Caliphate collapsed, it did not recover until afte..

Feasibility of thin seam coal mining at Dorstfontein Coal Mine

Please read the abstract in the section 00front of this documentDissertation (MSc)--University of Pretoria, 2003.GeologyUnrestricte

Magnetic prospection in the Eastern lower city of Artashat-Artaxata in the Ararat Plain of Armenia

In March of 2021, the Berlin-based company cmp continued geophysical prospection works at the ancient city of Artashat-Artaxata (Ararat Province, Armenia). The city was founded by Artashes-Artaxias I in the early 2nd century BC and served as his capital. First magnetic measurements were conducted by the Eastern Atlas company in September 2018. In 2021, during the 5-day survey a total surface of approximately 19.5 ha was investigated by use of the LEA MAX magnetic gradiometer array. This system was configured with seven fluxgate gradiometer probes, similar to the system used in the first survey of 2018. The investigated areas of the Eastern Lower City of Artaxata, located to the south of the investigated field of 2018, had good surface conditions with a moderate amount of sources causing disturbance. However, the general level of the magnetic gradient values measured was significantly lower compared to the 2018 data. Despite the lower magnetic field intensity, a continuation of linear structures towards the south was observed. These lines, most likely reflecting streets and pathways, criss-cross the central part of the Eastern Lower City in a NW–SE and NE–SW direction and exhibit partly positive, partly negative magnetic anomalies. Attached to them, some isolated spots with building remains were identified. The negative linear anomalies point to remains of limestone foundations, as detected in the northern part of the Lower City. The low magnetic intensity and fragmentation of the observed structures are most likely due to severe destruction of the ancient layers by 20th-century earthworks for agricultural purposes. Moreover, the southern part of the surveyed area was affected by major changes caused by modern quarries at Hills XI and XII. In general, the results of the two magnetic prospection campaigns greatly aid our understanding of the archaeological situation in the area of the Eastern Lower City of Artaxata, justifying further investigations that will surely contribute to greater contextualization of the identified archaeological structures. The full data sets are also published in open access on Zenodo

Die Konstitution technologischer Pfade: Überlegungen jenseits der Dichotomie von Pfadabhängigkeit und Pfadkreation

Die Entstehung, Stabilisierung und Fortsetzung von Technologien erhält in der Forschung in den letzten Jahrzehnten weltweit hohe Aufmerksamkeit, schließlich prägen Technologien doch nahezu alle Bereiche des Zusammenlebens und Zusammenarbeitens moderner Gesellschaften, und sind sie tief ins Innere ihrer Infrastrukturen eingeschrieben. Besondere Beachtung erhält dabei in der Soziologie und der Ökonomie die Frage, aus welchen Gründen sich bestimmte Technologien gegen andere durchsetzen können. Vor diesem Hintergrund wirft der Beitrag einen Blick auf die konzeptionellen Erklärungsansätze der Pfadabhängigkeit und Pfadkreation und zu ersten Überlegungen für eine soziologische Erweiterung der Betrachtung von Technologieentwicklung. Hierzu werden in einem ersten Schritt zunächst die den Konzepten der Pfadabhängigkeit und Pfadkreation unterliegenden Vorstellungen von Technikkonstitution diskutiert. Im zweiten Schritt wird anschließend ein Vorschlag für eine begriffliche Reformulierung der mit den beiden Konzepten von Technologieentwicklung angesprochenen Prozesse entworfen, die ein vertieftes Verständnis dieser Prozesse ermöglicht. Überlegungen zur theoretischen Weiterarbeit im dritten Schritt beschließen die Ausführungen. (ICG2

Geophysical survey of two rural sites in Mallorca (Balearic Islands, Spain): unveiling Roman villae

Two rural sites on the island of Mallorca (Balearic Islands, Spain) have been investigated with geophysical methods. A previous archaeological field survey provided surface ceramics that allowed for a first classification of the sites as possible Roman rural settlements, possibly villae. The objective of the investigation was to work towards the identification of architectural remains to better understand the nature of the sites. Using the 7-probe fluxgate gradiometer array LEA MAX, magnetic measurements were executed on a large area on each site. GPR measurements were subsequently carried out to examine selected areas of interest in detail by means of the IDS GPR system based on the Fast-Wave module. The investigated areas demonstrated excellent surface conditions with a negligible number of sources of disturbance, permitting a detailed interpretation of the geophysical data. The results helped to reveal the presence of architectural remains beneath the soil at both sites

Imaging glutathione depletion in the rat brain using ascorbate-derived hyperpolarized MR and PET probes.

Oxidative stress is a critical feature of several common neurologic disorders. The brain is well adapted to neutralize oxidative injury by maintaining a high steady-state concentration of small-molecule intracellular antioxidants including glutathione in astrocytes and ascorbic acid in neurons. Ascorbate-derived imaging probes for hyperpolarized 13C magnetic resonance spectroscopy and positron emission tomography have been used to study redox changes (antioxidant depletion and reactive oxygen species accumulation) in vivo. In this study, we applied these imaging probes to the normal rat brain and a rat model of glutathione depletion. We first studied hyperpolarized [1-13C]dehydroascorbate in the normal rat brain, demonstrating its robust conversion to [1-13C]vitamin C, consistent with rapid transport of the oxidized form across the blood-brain barrier. We next showed that the kinetic rate of this conversion decreased by nearly 50% after glutathione depletion by diethyl maleate treatment. Finally, we showed that dehydroascorbate labeled for positron emission tomography, namely [1-11C]dehydroascorbate, showed no change in brain signal accumulation after diethyl maleate treatment. These results suggest that hyperpolarized [1-13C]dehydroascorbate may be used to non-invasively detect oxidative stress in common disorders of the brain

Origin and emergence of entrepreneurship as a research field

This paper seeks to map out the emergence and evolution of entrepreneurship as an independent field in the social science literature from the early 1990s to 2009. Our analysis indicates that entrepreneurship has grown steadily during the 1990s but has truly emerged as a legitimate academic discipline in the latter part of the 2000s. The field has been dominated by researchers from Anglo-Saxon countries over the past 20 years, with particularly strong representations from the US, UK, and Canada. The results from our structural analysis, which is based on a core document approach, point to five large knowledge clusters and further 16 sub-clusters. We characterize the clusters from their cognitive structure and assess the strength of the relationships between these clusters. In addition, a list of most cited articles is presented and discussed