The bioluminescent Listeria monocytogenes strain Xen32 is defective in flagella expression and highly attenuated in orally infected BALB/cJ mice

Abstract Background In vivo bioluminescence imaging (BLI) is a powerful method for the analysis of host-pathogen interactions in small animal models. The commercially available bioluminescent Listeria monocytogenes strain Xen32 is commonly used to analyse immune functions in knockout mice and pathomechanisms of listeriosis. Findings To analyse and image listerial dissemination after oral infection we have generated a murinised Xen32 strain (Xen32-mur) which expresses a previously described mouse-adapted internalin A. This strain was used alongside the Xen32 wild type strain and the bioluminescent L. monocytogenes strains EGDe-lux and murinised EGDe-mur-lux to characterise bacterial dissemination in orally inoculated BALB/cJ mice. After four days of infection, Xen32 and Xen32-mur infected mice displayed consistently higher rates of bioluminescence compared to EGDe-lux and EGDe-mur-lux infected animals. However, surprisingly both Xen32 strains showed attenuated virulence in orally infected BALB/c mice that correlated with lower bacterial burden in internal organs at day 5 post infection, smaller losses in body weights and increased survival compared to EGDe-lux or EGDe-mur-lux inoculated animals. The Xen32 strain was made bioluminescent by integration of a lux-kan transposon cassette into the listerial flaA locus. We show here that this integration results in Xen32 in a flaA frameshift mutation which makes this strain flagella deficient. Conclusions The bioluminescent L. monocytogenes strain Xen32 is deficient in flagella expression and highly attenuated in orally infected BALB/c mice. As this listerial strain has been used in many BLI studies of murine listeriosis, it is important that the scientific community is aware of its reduced virulence in vivo

Challenges of temperature measurement during the friction stir welding process

The exact determination of the process zone temperature can be considered as an increasingly important role in the control and monitoring of the friction stir welding process (FSW). At present, temperature measurement is carried out with the aid of a temperature sensor integrated into the tool (usually thermocouples). Since these cannot be attached directly to the joining area, heat dissipation within the tool and to the environment cause measurement deviations as well as a time delay in the temperature measurement. The article describes a process and the challenges that arise in this process, how a direct temperature measurement during the process can be achieved by exploiting the thermoelectric effect between tool and workpiece, without changing the tool by introducing additional temperature sensors

Influence of Internalin A murinisation on host resistance to orally acquired listeriosis in mice

Background: The bacterial surface protein internalin (InlA) is a major virulence factor of the food-born pathogen Listeria monocytogenes. It plays a critical role in the bacteria crossing the host intestinal barrier by a species-specific interaction with the cell adhesion molecule E-cadherin. In mice, the interaction of InlA with murine E-cadherin is impaired due to sequence-specific binding incompatibilities. We have previously used the approach of ‘murinisation’ to establish an oral listeriosis infection model in mice by exchanging two amino acid residues in InlA. This dramatically increases binding to mouse E-cadherin. In the present study, we have used bioluminescent murinised and non-murinised Listeria strains to examine the spatiotemporal dissemination of Listeria in four diverse mouse genetic backgrounds after oral inoculation. Results: The murinised Listeria monocytogenes strain showed enhanced invasiveness and induced more severe infections in all four investigated mouse inbred strains compared to the non-murinised Listeria strain. We identified C57BL/6J mice as being most resistant to orally acquired listeriosis whereas C3HeB/FeJ, A/J and BALB/cJ mice were found to be most susceptible to infection. This was reflected in faster kinetics of Listeria dissemination, higher bacterial loads in internal organs, and elevated serum levels of IL-6, IFN-γ, TNF-α and CCL2 in the susceptible strains as compared to the resistant C57BL/6J strain. Importantly, murinisation of InlA did not cause enhanced invasion of Listeria monocytogenes into the brain. Conclusion: Murinised Listeria are able to efficiently cross the intestinal barrier in mice from diverse genetic backgrounds. However, expression of murinized InlA does not enhance listerial brain invasion suggesting that crossing of the blood brain barrier and crossing of the intestinal epithelium are achieved by Listeria monocytogenes through different molecular mechanisms

Gesellschaftliche Leistungen des Ökolandbaus in den Pilotregionen Nordhessen und Rheinland. regiosöl-Profile.

Der Ökolandbau leistet einen wichtigen Beitrag zu vielen ökologischen und sozialen gesellschaftlichen Zielen. Um diese sozialen und ökologischen Leistungen (söL) durch verschiedene politische und markt-basierte Instrumente besser als bisher honorieren zu können, werden Möglichkeiten zu ihrer Erfassung und Kommunikation entwickelt. Diesem Ansatz liegt das Verständnis zugrunde, dass die Inwertsetzung von sozialen und ökologischen Leistungen in der Landwirtschaft nur über die Kaskade Bewusstsein – Wertschätzung – Wertschöpfung erfolgen kann. Ziel des regiosöl-Vorhabens ist es, die Leistungen des Ökolandbaus durch eine transparente Erfassung in einem regionalen Bezugsraum sichtbarer zu machen. Das Projekt verfolgt 3 spezifische Ziele: (1) eine verbesserte Erfassungsmethode für die söL des Ökolandbaus, (2) die Darstellung der Leistungen in regionalen Profilen, und (3) ein allgemeinverständlicher Kommunikationsansatz. Bestehende Erfassungs-, Kommunikations- und Honorierungsansätze für die gesellschaftlichen Leistungen des Ökolandbaus wurden gesichtet und bestehende Lücken identifiziert. Aufbauend auf der als besonders Praxis-geeigneten Regionalwert-Nachhaltigkeitsanalyse (RWNA) wurden Kriterien und Indikatoren für eine betriebliche und regionale Erfassung der gesellschaftlichen Leistungen des Ökolandbaus entwickelt. Diese regiosöl-Indikatoren wurden gemeinsam mit der RWNA mit Ökobetrieben in den Pilotregionen getestet und bzgl. ihrer Eignung, Aussagekraft und Bewertungsmöglichkeiten eingeschätzt. Für die beiden Pilotregionen wurden in transdisziplinärer Zusammenarbeit mit Praxisakteuren regiosöl-Profile erstellt. Während eine Erfassung von söL auf betrieblicher Ebene die Optimierung der söL-Bereitstellung des Betriebes bezweckt, sollen die Erkenntnisse der auf regionaler Ebene erfassten söL für eine Optimierung der Bereitstellung gesellschaftlicher Leistungen auf regionaler Ebene genutzt werden. Der regiosöl-Profil-Bericht für die Pilotregionen beinhaltet folglich nicht nur eine Status-Quo-Analyse gesellschaftlicher Leistungen des Ökolandbaus in der Region, sondern stellt basierend auf diesen Erkenntnissen auch regionale Handlungsstrategien für die Weiterentwicklung bzw. Verbesserung dieser gesellschaftlichen Leistungen dar und zeigt eine Entwicklungsperspektive auf

Effects of a video game intervention on symptoms, training motivation, and visuo-spatial memory in depression

BackgroundPeople with Major Depressive Disorder (MDD) often experience reduced affect, mood, and cognitive impairments such as memory problems. Although there are various treatments for MDD, many of them do not address the cognitive deficits associated with the disorder. Playing 3D video games has been found to improve cognitive functioning in healthy people, but it is not clear how they may affect depressed mood and motivation in people with MDD. The aim of this study was to investigate whether a six-week video game intervention leads to improvements in depressed mood, training motivation, and visuo-spatial (working) memory functions in patients with MDD.MethodsA total of 46 clinically depressed individuals were randomly assigned to one of three groups: an experimental “3D video gaming” group (n = 14) which played a video game, an active control group (n = 16) which trained with a computer program “CogPack,” and a treatment-as-usual group (n = 16) which received a standard clinical treatment including psychotherapy and/or pharmacotherapy. Participants performed a neuropsychological assessment, including self-report questionnaires asking for depressive symptoms, training motivation, and visuo-spatial (working) memory functions before and after the training intervention.ResultsRegarding depressive symptoms, a significant decrease in the proportion of participants who showed clinical levels of depressive symptoms as measured by the Beck Depression Inventory was only found in the 3D video gaming group. Additionally, mean motivational levels of performing the training were significantly higher in the 3D video gaming group when compared with the active control group. Moreover, whereas the 3D Video Gaming group only significantly improved on one visuo-spatial memory test, the active control group improved in all visuo-spatial memory functions. The 3D video gaming group did not perform significantly better than the CogPack group, and the TAU group.ConclusionBesides a standalone cognitive training, the current findings suggest that cognitive trainings using a video game have potential to increase subjective well-being, show higher levels of training motivation, and lead to improvements in visuo-spatial (working) memory functions in MDD. However, given the mixed and unblinded nature of this study, the results should be interpreted with caution. Further research with larger samples and follow-up measurements is needed

Groundswell : Preparing for Internal Climate Migration

This report, which focuses on three regions—Sub-Saharan Africa, South Asia, and Latin America that together represent 55 percent of the developing world’s population—finds that climate change will push tens of millions of people to migrate within their countries by 2050. It projects that without concrete climate and development action, just over 143 million people—or around 2.8 percent of the population of these three regions—could be forced to move within their own countries to escape the slow-onset impacts of climate change. They will migrate from less viable areas with lower water availability and crop productivity and from areas affected by rising sea level and storm surges. The poorest and most climate vulnerable areas will be hardest hit. These trends, alongside the emergence of “hotspots” of climate in- and out-migration, will have major implications for climate-sensitive sectors and for the adequacy of infrastructure and social support systems. The report finds that internal climate migration will likely rise through 2050 and then accelerate unless there are significant cuts in greenhouse gas emissions and robust development action

The proteolytic activation of (H3N2) influenza A virus hemagglutinin is facilitated by different type II transmembrane serine proteases

Cleavage of influenza virus hemagglutinin (HA) by host cell proteases is necessary for viral activation and infectivity. In humans and mice, members of the type II transmembrane protease family (TTSP), e.g., TMPRSS2, TMPRSS4, and TMPRSS11d (HAT), have been shown to cleave influenza virus HA for viral activation and infectivity in vitro. Recently, we reported that inactivation of a single HA-activating protease gene, Tmprss2, in knockout mice inhibits the spread of H1N1 influenza viruses. However, after infection of Tmprss2 knockout mice with an H3N2 influenza virus, only a slight increase in survival was observed, and mice still lost body weight. In this study, we investigated an additional trypsin-like protease, TMPRSS4. Both TMPRSS2 and TMPRSS4 are expressed in the same cell types of the mouse lung. Deletion of Tmprss4 alone in knockout mice does not protect them from body weight loss and death upon infection with H3N2 influenza virus. In contrast, Tmprss2-/- Tmprss4-/- double-knockout mice showed a remarkably reduced virus spread and lung pathology, in addition to reduced body weight loss and mortality. Thus, our results identified TMPRSS4 as a second host cell protease that, in addition to TMPRSS2, is able to activate the HA of H3N2 influenza virus in vivo

Metalloprotein entatic control of ligand-metal bonds quantified by ultrafast x-ray spectroscopy

The multifunctional protein cytochrome c (cyt c) plays key roles in electron transport and apoptosis, switching function by modulating bonding between a heme iron and the sulfur in a methionine residue. This Fe-S(Met) bond is too weak to persist in the absence of protein constraints. We ruptured the bond in ferrous cyt c using an optical laser pulse and monitored the bond reformation within the protein active site using ultrafast x-ray pulses from an x-ray free-electron laser, determining that the Fe-S(Met) bond enthalpy is ~4 kcal/mol stronger than in the absence of protein constraints. The 4 kcal/mol is comparable with calculations of stabilization effects in other systems, demonstrating how biological systems use an entatic state for modest yet accessible energetics to modulate chemical function

Techniknostalgie und Retrotechnologie

Die Faszination durch Technik der Vergangenheit, die Nostalgie für alte oder alt wirkende Artefakte, ist eine kulturelle Strömung, die erst vor kurzem von der Forschung entdeckt wurde. Dieser Sammelband entstand aus einem ersten interdisziplinären Workshop am Landesmuseum für Technik und Arbeit in Mannheim, der das Feld der Techniknostalgie und Retrotechnologie erkundete. Neben Beiträgen zur Relevanz des gesamten Bereichs enthält er Analysen zu drei technischen Feldern: Mobilität (Auto und Bahn), Architektur und Städtebau (reale und virtuelle Retro-Räume, Historismen in Konstruktion und Design sowie postapokalyptische nostalgiegeladene Utopien) und technische Medien (Photographie, Film und Videospiele). Sie präsentieren erste Ergebnisse von Untersuchungen zu ausgewählten Beispielen, die die Fruchtbarkeit dieses Forschungsfelds aufzeigen, und demonstrieren zugleich, dass die Forschung im Verhältnis zur rasanten Zunahme der betreffenden Phänomene bisher nicht Schritt gehalten hat. Nostalgie wurde jüngst verstärkt als allgemeine kulturelle Erscheinung, aber kaum in ihrer Relation zur technologischen Entwicklung betrachtet. Das vorliegende Buch stellt einen ersten Schritt dar, dieses Defizit zu beheben. Deutlich wird dabei vor allem, wie vielfältig Retro-Phänomene sind, wie stark sie in der gegenwärtigen Kultur verankert sind und welch komplexe Interaktionen mit aktueller Technik und modernen Medien bestehen

Altered interaction of physiological activity and behavior affects risky decision-making in ADHD

BackgroundAdult attention-deficit/hyperactivity disorder (ADHD) is often associated with risky decision-making behavior. However, current research studies are often limited by the ability to adequately reflect daily behavior in a laboratory setting. Over the lifespan impairments in cognitive functions appear to improve, whereas affective functions become more severe. We assume that risk behavior in ADHD arises predominantly from deficits in affective processes. This study will therefore aim to investigate whether a dysfunction in affective pathways causes an abnormal risky decision-making (DM) behavior in adult ADHD.MethodsTwenty-eight participants with ADHD and twenty-eight healthy controls completed a battery of questionnaires regarding clinical symptoms, self-assessment of behavior and emotional competence. Furthermore, skin conductance responses were measured during the performance in a modified version of the Balloon Analogue Risk Task. A linear mixed-effects model analysis was used to analyze emotional arousal prior to a decision and after feedback display.ResultsResults showed higher emotional arousal in ADHD participants before decision-making (β = −0.12, SE = 0.05, t = −2.63, p < 0.001) and after feedback display (β = −0.14, SE = 0.05, t = −2.66, p = 0.008). Although risky behavior was greater in HC than in ADHD, we found a significant interaction effect of group and anticipatory skin conductance responses regarding the response behavior (β = 107.17, SE = 41.91, t = 2.56, p = 0.011). Post hoc analyses revealed a positive correlation between anticipatory skin conductance responses and reaction time in HC, whereas this correlation was negative in ADHD. Self-assessment results were in line with the objective measurements.ConclusionWe found altered changes in physiological activity during a risky decision-making task. The results confirm the assumption of an aberrant relationship between bodily response and risky behavior in adult ADHD. However, further research is needed with respect to age and gender when considering physiological activities