Feedback Cooling of a Single Neutral Atom

We demonstrate feedback cooling of the motion of a single rubidium atom trapped in a high-finesse optical resonator to a temperature of about 160 \mu K. Time-dependent transmission and intensity-correlation measurements prove the reduction of the atomic position uncertainty. The feedback increases the 1/e storage time into the one second regime, 30 times longer than without feedback. Feedback cooling therefore rivals state-of-the-art laser cooling, but with the advantages that it requires less optical access and exhibits less optical pumping.Comment: 5 pages, 4 figure

A Combined Score of Circulating miRNAs Allows Outcome Prediction in Critically Ill Patients

Background and aims: Identification of patients with increased risk of mortality represents an important prerequisite for an adapted adequate and individualized treatment of critically ill patients. Circulating micro-RNA (miRNA) levels have been suggested as potential biomarkers at the intensive care unit (ICU), but none of the investigated miRNAs displayed a sufficient sensitivity or specificity to be routinely employed as a single marker in clinical practice. Methods and results: We recently described alterations in serum levels of 7 miRNAs (miR-122, miR-133a, miR-143, miR-150, miR-155, miR-192, and miR-223) in critically ill patients at a medical ICU. In this study, we re-analyzed these previously published data and performed a combined analysis of these markers to unravel their potential as a prognostic scoring system in the context of critical illness. Based on the Youden’s index method, cut-off values were systematically defined for dysregulated miRNAs, and a “miRNA survival score” was calculated. Patients with high scores displayed a dramatically impaired prognosis compared to patients with low values. Additionally, the predictive power of our score could be further increased when the patient’s age was additionally incorporated into this score. Conclusions: We describe the first miRNA-based biomarker score for prediction of medical patients’ outcome during and after ICU treatment. Adding the patients’ age into this score was associated with a further increase in its predictive power. Further studies are needed to validate the clinical utility of this score in risk-stratifying critically ill patients

Relevance of Serum Leptin and Leptin-Receptor Concentrations in Critically Ill Patients

The adipocyte-derived cytokine leptin was implicated to link inflammation and metabolic alterations. We investigated the potential role of leptin components in critically ill patients, because systemic inflammation, insulin resistance, and hyperglycemia are common features of critical illness. Upon admission to Medical Intensive Care Unit (ICU), free leptin and soluble leptin-receptor serum concentrations were determined in 137 critically ill patients (95 with sepsis, 42 without sepsis) and 26 healthy controls. Serum leptin or leptin-receptor did not differ between patients or controls and were independent of sepsis. However, serum leptin was closely associated with obesity and diabetes and clearly correlated with markers of metabolism and liver function. Leptin-receptor was an unfavourable prognostic indicator, associated with mortality during three years follow-up. Our study indicates a functional role of leptin in the pathogenesis of severe illness and emphasizes the impact of complex metabolic alterations on the clinical outcome of critically ill patients

Phosphocholine-Modified Lipooligosaccharides of Haemophilus influenzae Inhibit ATP-Induced IL-1beta Release by Pulmonary Epithelial Cells

Phosphocholine-modified bacterial cell wall components are virulence factors enabling immune evasion and permanent colonization of the mammalian host, by mechanisms that are poorly understood. Recently, we demonstrated that free phosphocholine (PC) and PC-modified lipooligosaccharides (PC-LOS) from Haemophilus influenzae, an opportunistic pathogen of the upper and lower airways, function as unconventional nicotinic agonists and efficiently inhibit the ATP-induced release of monocytic IL-1beta. We hypothesize that H. influenzae PC-LOS exert similar effects on pulmonary epithelial cells and on the complex lung tissue. The human lung carcinoma-derived epithelial cell lines A549 and Calu-3 were primed with lipopolysaccharide from Escherichia coli followed by stimulation with ATP in the presence or absence of PC or PC-LOS or LOS devoid of PC. The involvement of nicotinic acetylcholine receptors was tested using specific antagonists. We demonstrate that PC and PC-LOS efficiently inhibit ATP-mediated IL-1beta release by A549 and Calu-3 cells via nicotinic acetylcholine receptors containing subunits alpha7, alpha9, and/or alpha10. Primed precision-cut lung slices behaved similarly. We conclude that H. influenzae hijacked an endogenous anti-inflammatory cholinergic control mechanism of the lung to evade innate immune responses of the host. These findings may pave the way towards a host-centered antibiotic treatment of chronic airway infections with H. influenzae

FTY720 treatment in the convalescence period improves functional recovery and reduces reactive astrogliosis in photothrombotic stroke

Background: The Sphingosine-1-phosphate (S1P) signaling pathway is known to influence pathophysiological processes within the brain and the synthetic S1P analog FTY720 has been shown to provide neuroprotection in experimental models of acute stroke. However, the effects of a manipulation of S1P signaling at later time points after experimental stroke have not yet been investigated. We examined whether a relatively late initiation of a FTY720 treatment has a positive effect on long-term neurological outcome with a focus on reactive astrogliosis, synapses and neurotrophic factors. Methods: We induced photothrombotic stroke (PT) in adult C57BL/6J mice and allowed them to recover for three days. Starting on post-stroke day 3, mice were treated with FTY720 (1 mg/kg b.i.d.) for 5 days. Behavioral outcome was observed until day 31 after photothrombosis and periinfarct cortical tissue was analyzed using tandem mass-spectrometry, TaqMan®analysis and immunofluorescence. Results: FTY720 treatment results in a significantly better functional outcome persisting up to day 31 after PT. This is accompanied by a significant decrease in reactive astrogliosis and larger post-synaptic densities as well as changes in the expression of vascular endothelial growth factor α (VEGF α). Within the periinfarct cortex, S1P is significantly increased compared to healthy brain tissue. Conclusion: Besides its known neuroprotective effects in the acute phase of experimental stroke, the initiation of FTY720 treatment in the convalescence period has a positive impact on long-term functional outcome, probably mediated through reduced astrogliosis, a modulation in synaptic morphology and an increased expression of neurotrophic factors