Cortical Inactivation by Cooling in Small Animals

Reversible inactivation of the cortex by surface cooling is a powerful method for studying the function of a particular area. Implanted cooling cryoloops have been used to study the role of individual cortical areas in auditory processing of awake-behaving cats. Cryoloops have also been used in rodents for reversible inactivation of the cortex, but recently there has been a concern that the cryoloop may also cool non-cortical structures either directly or via the perfusion of blood, cooled as it passed close to the cooling loop. In this study we have confirmed that the loop can inactivate most of the auditory cortex without causing a significant reduction in temperature of the auditory thalamus or other subcortical structures. We placed a cryoloop on the surface of the guinea pig cortex, cooled it to 2°C and measured thermal gradients across the neocortical surface. We found that the temperature dropped to 20–24°C among cells within a radius of about 2.5 mm away from the loop. This temperature drop was sufficient to reduce activity of most cortical cells and led to the inactivation of almost the entire auditory region. When the temperature of thalamus, midbrain, and middle ear were measured directly during cortical cooling, there was a small drop in temperature (about 4°C) but this was not sufficient to directly reduce neural activity. In an effort to visualize the extent of neural inactivation we measured the uptake of thallium ions following an intravenous injection. This confirmed that there was a large reduction of activity across much of the ipsilateral cortex and only a small reduction in subcortical structures

Ratlas-LH: An MRI template of the Lister hooded rat brain with stereotaxic coordinates for neurosurgical implantations

There is currently no brain atlas available to specifically determine stereotaxic coordinates for neurosurgery in Lister hooded rats despite the popularity of this strain for behavioural neuroscience studies in the UK and elsewhere. We have created a dataset, which we refer to as 'Ratlas-LH' (for Lister hooded). Ratlas-LH combines in vivo magnetic resonance images of the brain of young adult male Lister hooded rats with micro-computed tomography images of the ex vivo skull, as well as a set of delineations of brain regions, adapted from the Waxholm Space Atlas of the Sprague Dawley Rat Brain. Ratlas-LH was produced with an isotropic resolution of 0.15 mm. It has been labelled in such a way as to provide a stereotaxic coordinate system for the determination of distances relative to the skull landmark of bregma. We have demonstrated that the atlas can be used to determine stereotaxic coordinates to accurately target brain regions in the Lister hooded rat brain. Ratlas-LH is freely available to facilitate neurosurgical procedures in the Lister hooded rat. https://mc.manuscriptcentral.com/bna Brain and Neuroscience Advance

Toxoplasma gondii Actively Inhibits Neuronal Function in Chronically Infected Mice

Upon infection with the obligate intracellular parasite Toxoplasma gondii, fast replicating tachyzoites infect a broad spectrum of host cells including neurons. Under the pressure of the immune response, tachyzoites convert into slow-replicating bradyzoites, which persist as cysts in neurons. Currently, it is unclear whether T. gondii alters the functional activity of neurons, which may contribute to altered behaviour of T. gondii–infected mice and men. In the present study we demonstrate that upon oral infection with T. gondii cysts, chronically infected BALB/c mice lost over time their natural fear against cat urine which was paralleled by the persistence of the parasite in brain regions affecting behaviour and odor perception. Detailed immunohistochemistry showed that in infected neurons not only parasitic cysts but also the host cell cytoplasm and some axons stained positive for Toxoplasma antigen suggesting that parasitic proteins might directly interfere with neuronal function. In fact, in vitro live cell calcium (Ca2+) imaging studies revealed that tachyzoites actively manipulated Ca2+ signalling upon glutamate stimulation leading either to hyper- or hypo-responsive neurons. Experiments with the endoplasmatic reticulum Ca2+ uptake inhibitor thapsigargin indicate that tachyzoites deplete Ca2+ stores in the endoplasmatic reticulum. Furthermore in vivo studies revealed that the activity-dependent uptake of the potassium analogue thallium was reduced in cyst harbouring neurons indicating their functional impairment. The percentage of non-functional neurons increased over time In conclusion, both bradyzoites and tachyzoites functionally silence infected neurons, which may significantly contribute to the altered behaviour of the host

Activated Platelets in Carotid Artery Thrombosis in Mice Can Be Selectively Targeted with a Radiolabeled Single-Chain Antibody

BACKGROUND: Activated platelets can be found on the surface of inflamed, rupture-prone and ruptured plaques as well as in intravascular thrombosis. They are key players in thrombosis and atherosclerosis. In this study we describe the construction of a radiolabeled single-chain antibody targeting the LIBS-epitope of activated platelets to selectively depict platelet activation and wall-adherent non-occlusive thrombosis in a mouse model with nuclear imaging using in vitro and ex vivo autoradiography as well as small animal SPECT-CT for in vivo analysis. METHODOLOGY/PRINCIPAL FINDINGS: LIBS as well as an unspecific control single-chain antibody were labeled with (111)Indium ((111)In) via bifunctional DTPA ( = (111)In-LIBS/(111)In-control). Autoradiography after incubation with (111)In-LIBS on activated platelets in vitro (mean 3866 ± 28 DLU/mm(2), 4010 ± 630 DLU/mm(2) and 4520 ± 293 DLU/mm(2)) produced a significantly higher ligand uptake compared to (111)In-control (2101 ± 76 DLU/mm(2), 1181 ± 96 DLU/mm(2) and 1866 ± 246 DLU/mm(2)) indicating a specific binding to activated platelets; P<0.05. Applying these findings to an ex vivo mouse model of carotid artery thrombosis revealed a significant increase in ligand uptake after injection of (111)In-LIBS in the presence of small thrombi compared to the non-injured side, as confirmed by histology (49630 ± 10650 DLU/mm(2) vs. 17390 ± 7470 DLU/mm(2); P<0.05). These findings could also be reproduced in vivo. SPECT-CT analysis of the injured carotid artery with (111)In-LIBS resulted in a significant increase of the target-to-background ratio compared to (111)In-control (1.99 ± 0.36 vs. 1.1 ± 0.24; P < 0.01). CONCLUSIONS/SIGNIFICANCE: Nuclear imaging with (111)In-LIBS allows the detection of platelet activation in vitro and ex vivo with high sensitivity. Using SPECT-CT, wall-adherent activated platelets in carotid arteries could be depicted in vivo. These results encourage further studies elucidating the role of activated platelets in plaque pathology and atherosclerosis and might be of interest for further developments towards clinical application

Management of urban restructuring under consideration of special urban planning legislation

Am 07.05.2015 hat der Autor den Doktorgrad an die vergebende Einrichtung zurückgegeben. Der Zugang zum Dokument ist daher gesperrt.Die Stadtentwicklungsplanung hatte in den letzten Jahrzehnten in der Bundesrepublik und großen Teilen Europas die Aufgabe, das kontinuierliche Wachstum zu steuern. Die Problematik der Schrumpfung von Städten hingegen ist zumindest in der Bundesrepublik ein relativ neues Phänomen. Der deshalb notwendige Stadtumbau als städtebauliche Gesamtmaßnahme ist als eine Bündelung hochkomplexer, vielschichtiger und dynamischer Prozesse im baulichen Bestand mit einer Vielzahl von Akteuren mit divergierenden Interessenslagen zu verstehen. Grund für diesen Paradigmenwechsel in der Stadtentwicklungsplanung sind die stattfindenden tiefgreifenden demografischen und gesellschaftlichen Veränderungsprozesse, die zu einer signifikant rückläufigen Wohnungsnachfrage, verbunden mit Leerständen, einem Werteverfall von Immobilien und einer geringen Infrastrukturauslastung führen. Ein wesentliches Ergebnis dieser Entwicklungen sind städtebauliche Funktionsverluste. Es ergeben sich infolge der Funktionsverluste völlig neue Aufgaben für die Gemeinden, die vorrangig als Anpassungsleistungen städtischer Bau-, Raum- und Infrastrukturen, verbunden mit der Gestaltung der demografischen Umbrüche und des gesellschaftlichen Wandels unter besonderer Berücksichtigung von immobilienökonomischen Problemlagen zu beschreiben sind. Stadtumbau ist deshalb ein permanenter Prozess, bei dem hohe Anforderungen an die Akteure gestellt werden. Deshalb ist es notwendig, ein effizientes Prozessmanagement zu installieren um einen flexiblen Umgang mit Zielen, Instrumenten und Methoden zu ermöglichen. Die Untersuchungen haben ergeben, dass es notwendig ist, Erkenntnisse aus der allgemeinen Managementlehre, insbesondere der des allgemeinen Prozessmanagements in das Stadtumbaumanagement zu implementieren. Dies wurde deutlich herausgearbeitet und entsprechende Vorschläge unterbreitet. Zu Beginn der Stadtumbaumaßnahme sind auch Elemente des Change Managements zu verwenden. Im Prozessmanagement im Rahmen des Stadtumbaus müssen die unterschiedlichen Handlungsmuster der Akteure gemanagt werden. Diese Handlungsmuster wurden charakterisiert. Spezifische prozessgestaltende Instrumente (Tools) und die prozessgestaltenden Fähigkeiten und Fertigkeiten (Skills) sind für ein erfolgreiches Stadtumbaumanagement notwendig. Die durch die Gemeinde zu realisierende zentrale Prozessteuerung erfolgt konsensual, hoheitlich, als „Angebot zum Zwang“ oder als Mischung von Vorgenanntem. Im konsensualen Bereich kommt dem Vertragsmanagement eine besondere Rolle zu. Dass Aktivierungs- und Befähigungsstrategien im Gegensatz zu der Stadtentwicklung unter Wachstumsbedingungen eine große Rolle spielen, wurde hierbei aufgezeigt. Dem städtebaulichen Entwicklungskonzept mit regelmäßig gesamtstädtischen Aussagen als strategischer Planungstyp unter Schrumpfungsbedingungenkommt eine besondere Bedeutung zu. Immobilienwirtschaftliche Rektionen, wie Dereliktion, Erbausschlagung oder Zwangsversteigerungen, sind im Stadtumbauprozess neben dem Leerstandsphänomen besonders zu würdigen. Die bisher eher unbeachtete Thematik der verbindlichen Bauleitplanung wurde vertieft untersucht. Das Planungserfordernis nach dem Baugesetzbuch besteht auch hier. Allerdings ist das Planen im Bestand von rechtlichen Besonderheiten geprägt. Probleme bezüglich der Erhaltung von Baurechten, des Verlustes von Baurechten, der Herabzonung oder des Planungsschadens sind genauso zu beachten wie die Problematik des Bestandsschutzes von baulichen Anlagen.Over the past decades urban development planning in Germany and in a big part of Europe has been targeting to manage continuous growth. The problem of shrinking cities is at least in Germany a relatively new phenomenon. Thus, the necessary urban consolidation as an overall urban development program must be seen as a package of highly complex and multilayer dynamic processes in the existing building stock with a big number of stakeholders with diverging interests. The reason for this paradigm shift in urban development planning is the persistent radical demographic and social change, which leads to a significant fall in demand for housing. This is connected with vacancy, value loss of real estate and a low capacity utilization of infrastructure. An essential result of this development is a loss of functionality of the cities concerned. Consequently, the municipalities are facing new challenges that can primarily be described as structural adaptation of urban patterns and infrastructures, combined with the need to deal with demographic and social change under particular consideration of issues related to the real estate market. Urban restructuring is therefore a permanent process making great demands on the stakeholders. Hence it is necessary to establish an efficient process management to allow a flexible handling of objectives, tools and methods. Research showed the need to implement methods from general management studies, in particular general process management, into the management of urban restructuring. These findings were further developed and adequate proposals made. In the beginning of urban restructuring measures also elements of change management have to be applied. Process management in the context of urban restructuring has to manage the different operation schemes of the stakeholders. These operation schemes were characterized. Successful management of urban restructuring requires specific tools and skills that are shaping this process. Task management to be realized by the municipality may happen by consensus, sovereign, as “offer for compulsion” or as a mix of the above-mentioned. Contract management plays a crucial role in the consensual approach. The study showed the important role of an activation and empowering strategy in contrast to urban development under conditions of growth. The urban development plan with normative statements for the entire city is a type of plan of particular relevance under conditions of shrinkage. The reaction of the real estate market, such as dereliction, waiving of inheritance, forced sale, or the phenomenon of vacancy deserves closer attention. The study researched also into the up-to-now rather unnoticed topic of a mandatory general development planning. The requirement of a development plan pursuant to the building law persists even there. However, planning within in the existing building stock is characterized by specific legal features, as problems regarding the preservation or loss of the right to build, the reduction in value of properties through downgraded zoning regulations as well as the problem of protection of continuance of buildings have to be observed

Cavity-enhanced raman spectroscopy for food chain management

Comprehensive food chain management requires the monitoring of many parameters including temperature, humidity, and multiple gases. The latter is highly challenging because no low-cost technology for the simultaneous chemical analysis of multiple gaseous components currently exists. This contribution proposes the use of cavity enhanced Raman spectroscopy to enable online monitoring of all relevant components using a single laser source. A laboratory scale setup is presented and characterized in detail. Power enhancement of the pump light is achieved in an optical resonator with a Finesse exceeding 2500. A simulation for the light scattering behavior shows the influence of polarization on the spatial distribution of the Raman scattered light. The setup is also used to measure three relevant showcase gases to demonstrate the feasibility of the approach, including carbon dioxide, oxygen and ethene

Habenula and interpeduncular nucleus differentially modulate predator odor-induced innate fear behavior in rats

Fear is an important behavioral system helping humans and animals to survive potentially dangerous situations. Fear can be innate or learned. Whereas the neural circuits underlying learned fear are already well investigated, the knowledge about the circuits mediating innate fear is still limited. We here used a novel, unbiased approach to image in vivo the spatial patterns of neural activity in odor-induced innate fear behavior in rats. We intravenously injected awake unrestrained rats with a 99m-technetium labeled blood flow tracer (99mTc-HMPAO) during ongoing exposure to fox urine or water as control, and mapped the brain distribution of the trapped tracer using single-photon emission computed tomography (SPECT). Upon fox urine exposure blood flow increased in a number of brain regions previously associated with odor-induced innate fear such as the amygdala, ventromedial hypothalamus and dorsolateral periaqueductal grey, but, unexpectedly, decreased at higher significance levels in the interpeduncular nucleus (IPN). Significant flow changes were found in regions monosynaptically connected to the IPN. Flow decreased in the dorsal tegmentum and entorhinal cortex. Flow increased in the habenula (Hb) and correlated with odor effects on behavioral defensive strategy. Hb lesions reduced avoidance of but increased approach to the fox urine while IPN lesions only reduced avoidance behavior without approach behavior. Our study identifies a new component, the IPN, of the neural circuit mediating odor-induced innate fear behavior in mammals and suggests that the evolutionarily conserved Hb-IPN system, which has recently been implicated in cued fear, also forms an integral part of the innate fear circuitry

Enhancement techniques to improve Raman spectroscopy of gases

The reliable chemical analysis of gas mixtures is a challenging task that is often approached by employing optical technologies because of their high reliability, sensitivity, and selectivity as well as the possibility of contactless measurement. When monitoring single or a few components of industrial or natural processes, absorption spectroscopy methods are frequently used. However, this approach becomes tedious when many gas species have to be identified and quantified. In this scenario Raman spectroscopy may offer a viable alternative for multi-gas analysis. In particular, spontaneous Raman scattering offers the possibility to qualitatively and quantitatively detect most molecules with a single laser source. Large-scale use of the technique currently fails due to the little amount of Raman-scattered light, which is a result of the small Raman-scattering cross-section. To mitigate this disadvantage, a number of approaches are currently being researched with the goal to obtain larger scattering intensities. To this effect currently popular methods aim to increase the effective amount of light via the use of optical resonators or photonic hollow fibres. In this article, both approaches are presented and the results achieved in natural gas analysis and food chain management are presented