Synthesis of 8-Aza- and 8-Oxabicyclo[3.2.1]octanes via [3+2]-Cycloadditions of cyclopropanated Furan and Pyrrole Derivatives

The present thesis deals with the synthesis of 8-aza- and 8-oxabicyclo[3.2.1]octanes via a microwave-assisted, stereoselective 6π-electrocyclic ring-opening / [3+2]-cycloaddition cascade of monocyclopropanated pyrrole and furan derivatives with electron poor dipolarophiles. The key step of this transformation is a thermally induced selective cleavage of the non-activated, endocyclic C1-C3 cyclopropane bond in 2-aza- or 2-oxabicyclo[3.1.0]-hex-3-enes, resulting in 1,3-dipoles which can be trapped with suitable dipolarophiles. Starting from pyrroles or furans, 8-aza- and 8-oxabicyclo[3.2.1]octanes are accessible in two steps (cyclopropanation/cycloaddition) in diastereo- and enantioselective pure form, being versatile building blocks for the synthesis of pharmaceutically relevant targets. Various postfunctionalizations of the scaffolds obtained are possible, allowing their further diversifications

A Small RNA Controls Expression of the Chitinase ChiA in Listeria monocytogenes

In recent years, more than 60 small RNAs (sRNAs) have been identified in the gram-positive human pathogen Listeria monocytogenes, but their putative roles and mechanisms of action remain largely unknown. The sRNA LhrA was recently shown to be a post-transcriptional regulator of a single gene, lmo0850, which encodes a small protein of unknown function. LhrA controls the translation and degradation of the lmo0850 mRNA by an antisense mechanism, and it depends on the RNA chaperone Hfq for efficient binding to its target. In the present study, we sought to gain more insight into the functional role of LhrA in L. monocytogenes. To this end, we determined the effects of LhrA on global-wide gene expression. We observed that nearly 300 genes in L. monocytogenes are either positively or negatively affected by LhrA. Among these genes, we identified lmo0302 and chiA as direct targets of LhrA, thus establishing LhrA as a multiple target regulator. Lmo0302 encodes a hypothetical protein with no known function, whereas chiA encodes one of two chitinases present in L. monocytogenes. We show here that LhrA acts as a post-transcriptional regulator of lmo0302 and chiA by interfering with ribosome recruitment, and we provide evidence that both LhrA and Hfq act to down-regulate the expression of lmo0302 and chiA. Furthermore, in vitro binding experiments show that Hfq stimulates the base pairing of LhrA to chiA mRNA. Finally, we demonstrate that LhrA has a negative effect on the chitinolytic activity of L. monocytogenes. In marked contrast to this, we found that Hfq has a stimulating effect on the chitinolytic activity, suggesting that Hfq plays multiple roles in the complex regulatory pathways controlling the chitinases of L. monocytogenes

Plasma lipid profiles discriminate bacterial from viral infection in febrile children

Fever is the most common reason that children present to Emergency Departments. Clinical signs and symptoms suggestive of bacterial infection are often non-specific, and there is no definitive test for the accurate diagnosis of infection. The 'omics' approaches to identifying biomarkers from the host-response to bacterial infection are promising. In this study, lipidomic analysis was carried out with plasma samples obtained from febrile children with confirmed bacterial infection (n = 20) and confirmed viral infection (n = 20). We show for the first time that bacterial and viral infection produces distinct profile in the host lipidome. Some species of glycerophosphoinositol, sphingomyelin, lysophosphatidylcholine and cholesterol sulfate were higher in the confirmed virus infected group, while some species of fatty acids, glycerophosphocholine, glycerophosphoserine, lactosylceramide and bilirubin were lower in the confirmed virus infected group when compared with confirmed bacterial infected group. A combination of three lipids achieved an area under the receiver operating characteristic (ROC) curve of 0.911 (95% CI 0.81 to 0.98). This pilot study demonstrates the potential of metabolic biomarkers to assist clinicians in distinguishing bacterial from viral infection in febrile children, to facilitate effective clinical management and to the limit inappropriate use of antibiotics

Plasma lipid profiles discriminate bacterial from viral infection in febrile children

Fever is the most common reason that children present to Emergency Departments. Clinical signs and symptoms suggestive of bacterial infection are often non-specific, and there is no definitive test for the accurate diagnosis of infection. The 'omics' approaches to identifying biomarkers from the host-response to bacterial infection are promising. In this study, lipidomic analysis was carried out with plasma samples obtained from febrile children with confirmed bacterial infection (n = 20) and confirmed viral infection (n = 20). We show for the first time that bacterial and viral infection produces distinct profile in the host lipidome. Some species of glycerophosphoinositol, sphingomyelin, lysophosphatidylcholine and cholesterol sulfate were higher in the confirmed virus infected group, while some species of fatty acids, glycerophosphocholine, glycerophosphoserine, lactosylceramide and bilirubin were lower in the confirmed virus infected group when compared with confirmed bacterial infected group. A combination of three lipids achieved an area under the receiver operating characteristic (ROC) curve of 0.911 (95% CI 0.81 to 0.98). This pilot study demonstrates the potential of metabolic biomarkers to assist clinicians in distinguishing bacterial from viral infection in febrile children, to facilitate effective clinical management and to the limit inappropriate use of antibiotics

Plasma lipid profiles discriminate bacterial from viral infection in febrile children

Fever is the most common reason that children present to Emergency Departments. Clinical signs and symptoms suggestive of bacterial infection ar

Mögliche Maßnahmen zur Verringerung leerstehender Geschäftsflächen in Wiener Rand- und Nebenlagen

Literaturverz. S. 62 - 67Die Gründe für die Entstehung von Ladenleerständen sind sehr vielfältig. Die Entwicklung der Erdgeschoßflächen steht im Spannungsfeld unterschiedlichster Interessenslagen. Ein tiefgreifender Funktionswandel der Erdgeschoßlagen wurde durch Umstrukturierungsprozesse im gewerblichen Bereich wie im Einzelhandel, durch ein verändertes Konsumverhalten, durch soziale und kulturelle Werteverschiebungen, aber auch durch rechtliche Rahmenbedingungen bewirkt. Die theoretische Ausarbeitung setzt sich mit der aktuellen Geschäftsflächen- Situation in Wien auseinander. Einleitend wird der Begriff Geschäftsfläche definiert, Nutzungsmöglichkeiten vorgestellt und rechtliche sowie vermarktungsrelevante Rahmenbedingungen aufgezeigt. Anschließend wird auf die Problematik der Leerstandsflächen in weniger frequentierten Lagen näher eingegangen und die Ursachen für Leerstehungen in Rand- und Nebenlagen aufgezeigt. Abschließend werden bereits vorhandene kooperative Stadtentwicklungsinstrumente zur Revitalisierung innerstädtischer Geschäftslokale vorgestellt. In der empirischen Abhandlung wurden Experteninterviews mit den betroffenen Parteien geführt. Ziel der Expertengespräche war es Maßnahmen aufzuzeigen, die zur Verringerung der Leerstehungen von Geschäftsflächen in innerstädtischen Rand- und Nebenlagen der Stadt Wien beitragen können. Die erhobenen Maßnahmen wurden in fünf Kategorien zusammengefasst: Rechtliche Maßnahmen, Vermarktungsmaßnahmen, Sanierungsmaßnahmen, Fördermaßnahmen und Mögliche Initiativen. Die Thematik Leerstandsproblematik in Erdgeschoßflächen in Wien ist sehr Umfangreich, daher konnten die durchgeführten Experteninterviews mit den betroffenen Parteien nur einen Überblick über mögliche Maßnahmen zur Verringerung leerstehender Geschäftsflächen in innerstätischen Wiener Randlagen geben.Die Gründe für die Entstehung von Ladenleerständen sind sehr vielfältig. Die Entwicklung der Erdgeschoßflächen steht im Spannungsfeld unterschiedlichster Interessenslagen. Ein tiefgreifender Funktionswandel der Erdgeschoßlagen wurde durch Umstrukturierungsprozesse im gewerblichen Bereich wie im Einzelhandel, durch ein verändertes Konsumverhalten, durch soziale und kulturelle Werteverschiebungen, aber auch durch rechtliche Rahmenbedingungen bewirkt. Die theoretische Ausarbeitung setzt sich mit der aktuellen Geschäftsflächen- Situation in Wien auseinander. Einleitend wird der Begriff Geschäftsfläche definiert, Nutzungsmöglichkeiten vorgestellt und rechtliche sowie vermarktungsrelevante Rahmenbedingungen aufgezeigt. Anschließend wird auf die Problematik der Leerstandsflächen in weniger frequentierten Lagen näher eingegangen und die Ursachen für Leerstehungen in Rand- und Nebenlagen aufgezeigt. Abschließend werden bereits vorhandene kooperative Stadtentwicklungsinstrumente zur Revitalisierung innerstädtischer Geschäftslokale vorgestellt. In der empirischen Abhandlung wurden Experteninterviews mit den betroffenen Parteien geführt. Ziel der Expertengespräche war es Maßnahmen aufzuzeigen, die zur Verringerung der Leerstehungen von Geschäftsflächen in innerstädtischen Rand- und Nebenlagen der Stadt Wien beitragen können. Die erhobenen Maßnahmen wurden in fünf Kategorien zusammengefasst: Rechtliche Maßnahmen, Vermarktungsmaßnahmen, Sanierungsmaßnahmen, Fördermaßnahmen und Mögliche Initiativen. Die Thematik Leerstandsproblematik in Erdgeschoßflächen in Wien ist sehr Umfangreich, daher konnten die durchgeführten Experteninterviews mit den betroffenen Parteien nur einen Überblick über mögliche Maßnahmen zur Verringerung leerstehender Geschäftsflächen in innerstätischen Wiener7

How does early onset cannabis use affect working memory performance?

Background: Cannabis consumption is one of several factors affecting working memory performance. It remains unclear, however, whether this effect is due to cannabis consumption per se or the age of consumption onset. Methods: Young adult volunteers (18-30 years of age) were recruited on the basis of whether they consumed cannabis on a regular basis (≥ 1 joint per week for at least 12 months) or did not consume cannabis at all (≤ 5 times per lifetime). Cannabis consumption habits were assessed by a questionnaire based on the CoRolAR CORE survey. According to their age of consumption onset, participants were divided into three groups: Early-onset users (age of onset <16), late- onset users (age of onset ≥16), and controls (no cannabis consumption). Working memory and short-term memory performance were measured by the backward and forward conditions of the digit- and spatial span, respectively. Results: Early-onset users (N=5) did not differ significantly in their working memory as well as short-term memory performance from late-onset users (N=9) and controls (N=22). Conclusion: This study could not find any evidence for a potential influence of age of consumption onset on working memory performance. Future work should use a larger sample size and more sophisticated assessment tools for cannabis consumption when replicating this study

Early childcare and support in school during COVID-19: Investigating potential protective factors against educational inequality

peer reviewed4. Quality educatio

The Complex Function of Hsp70 in Metastatic Cancer

Elevated expression of the inducible heat shock protein 70 (Hsp70) is known to correlate with poor prognosis in many cancers. Hsp70 confers survival advantage as well as resistance to chemotherapeutic agents, and promotes tumor cell invasion. At the same time, tumor-derived extracellular Hsp70 has been recognized as a “chaperokine”, activating antitumor immunity. In this review we discuss localization dependent functions of Hsp70 in the context of invasive cancer. Understanding the molecular principles of metastasis formation steps, as well as interactions of the tumor cells with the microenvironment and the immune system is essential for fighting metastatic cancer. Although Hsp70 has been implicated in different steps of the metastatic process, the exact mechanisms of its action remain to be explored. Known and potential functions of Hsp70 in controlling or modulating of invasion and metastasis are discussed