Holographic imaging of an array of submicron light scatterers at low photon numbers

We experimentally test a recently proposed holographic method for imaging coherent light scatterers which are distributed over a 2-dimensional grid. In our setup the scatterers consist of a back-illuminated, opaque mask with submicron-sized holes. We study how the imaging fidelity depends on various parameters of the set-up. We observe that a few hundred scattered photons per hole already suffice to obtain a fidelity of 96% to correctly determine whether a hole is located at a given grid point. The holographic method demonstrated here has a high potential for applications with ultracold atoms in optical lattices.Comment: 8 pages, 9 figure

A small series of pole sport injuries

Pole sport is a relatively new athletic sport that is gaining increasing popularity and for which national and international championships are held. It evolved from pole dance and harbours the risk of falls from heights of up to three metres. Currently, no studies on pole sport injuries are available. This is the first description of a small series of five pole sport injuries. A retrospective review of the case histories and radiological findings was performed, and in addition, a follow-up interview was carried out. All the patients were female and had a mean age of 27.2 years. Most injuries were located in the head, neck or spine. The use of proper training equipment like landing mats and grip aids could probably reduce accidents

Combining callers improves the detection of copy number variants from whole-genome sequencing

Copy Number Variants (CNVs) are deletions, duplications or insertions larger than 50 base pairs. They account for a large percentage of the normal genome variation and play major roles in human pathology. While array-based approaches have long been used to detect them in clinical practice, whole-genome sequencing (WGS) bears the promise to allow concomitant exploration of CNVs and smaller variants. However, accurately calling CNVs from WGS remains a difficult computational task, for which a consensus is still lacking. In this paper, we explore practical calling options to reach the best compromise between sensitivity and sensibility. We show that callers based on different signal (paired-end reads, split reads, coverage depth) yield complementary results. We suggest approaches combining four selected callers (Manta, Delly, ERDS, CNVnator) and a regenotyping tool (SV2), and show that this is applicable in everyday practice in terms of computation time and further interpretation. We demonstrate the superiority of these approaches over array-based Comparative Genomic Hybridization (aCGH), specifically regarding the lack of resolution in breakpoint definition and the detection of potentially relevant CNVs. Finally, we confirm our results on the NA12878 benchmark genome, as well as one clinically validated sample. In conclusion, we suggest that WGS constitutes a timely and economically valid alternative to the combination of aCGH and whole-exome sequencing

Late-Stage Modification of Aminoglycoside Antibiotics Overcomes Bacterial Resistance Mediated by APH(3') Kinases

The continuous emergence of antimicrobial resistance is causing a threat to patients infected by multidrug‐resistant pathogens. In particular, the clinical use of aminoglycoside antibiotics, broad‐spectrum antibacterials of last resort, is limited due to rising bacterial resistance. One of the major resistance mechanisms in Gram‐positive and Gram‐negative bacteria is phosphorylation of these amino sugars at the 3’‐position by O‐phosphotransferases [APH(3’)s]. Structural alteration of these antibiotics at the 3’‐position would be an obvious strategy to tackle this resistance mechanism. However, the access to such derivatives requires cumbersome multi‐step synthesis, which is not appealing for pharma industry in this low‐return‐on‐investment market. To overcome this obstacle and combat bacterial resistance mediated by APH(3’)s, we introduce a novel regioselective modification of aminoglycosides in the 3’‐position via palladium‐catalyzed oxidation. To underline the effectiveness of our method for structural modification of aminoglycosides, we have developed two novel antibiotic candidates overcoming APH(3’)s‐mediated resistance employing only four synthetic steps

Downregulation of sphingosine 1-phosphate (S1P) receptor 1 by dexamethasone inhibits S1P-induced mesangial cell migration

Sphingosine 1-phosphate (S1P) is generated by sphingosine kinase (SK)-1 and -2 and acts mainly as an extracellular ligand at five specific receptors, denoted S1P1-5. After activation, S1P receptors regulate important processes in the progression of renal diseases, such as mesangial cell migration and survival. Previously, we showed that dexamethasone enhances SK-1 activity and S1P formation, which protected mesangial cells from stress-induced apoptosis. Here we demonstrate that dexamethasone treatment lowered S1P1 mRNA and protein expression levels in rat mesangial cells. This effect was abolished in the presence of the glucocorticoid receptor antagonist RU-486. In addition, in vivo studies showed that dexamethasone downregulated S1P1 expression in glomeruli isolated from mice treated with dexamethasone (10 mg/kg body weight). Functionally, we identified S1P1 as a key player mediating S1P-induced mesangial cell migration. We show that dexamethasone treatment significantly lowered S1P-induced migration of mesangial cells, which was again reversed in the presence of RU-486. In summary, we suggest that dexamethasone inhibits S1P-induced mesangial cell migration via downregulation of S1P1. Overall, these results demonstrate that dexamethasone has functional important effects on sphingolipid metabolism and action in renal mesangial cells

Downregulation of sphingosine 1-phosphate (S1P) receptor 1 by dexamethasone inhibits S1P-induced mesangial cell migration

Sphingosine 1-phosphate (S1P) is generated by sphingosine kinase (SK)-1 and -2 and acts mainly as an extracellular ligand at five specific receptors, denoted S1P1-5. After activation, S1P receptors regulate important processes in the progression of renal diseases, such as mesangial cell migration and survival. Previously, we showed that dexamethasone enhances SK-1 activity and S1P formation, which protected mesangial cells from stress-induced apoptosis. Here we demonstrate that dexamethasone treatment lowered S1P1 mRNA and protein expression levels in rat mesangial cells. This effect was abolished in the presence of the glucocorticoid receptor antagonist RU-486. In addition, in vivo studies showed that dexamethasone downregulated S1P1 expression in glomeruli isolated from mice treated with dexamethasone (10 mg/kg body weight). Functionally, we identified S1P1 as a key player mediating S1P-induced mesangial cell migration. We show that dexamethasone treatment significantly lowered S1P-induced migration of mesangial cells, which was again reversed in the presence of RU-486. In summary, we suggest that dexamethasone inhibits S1P-induced mesangial cell migration via downregulation of S1P1. Overall, these results demonstrate that dexamethasone has functional important effects on sphingolipid metabolism and action in renal mesangial cells

Identification of inhibitors targeting the energy-coupling factor (ECF) transporters

The energy-coupling factor (ECF) transporters are a family of transmembrane proteins involved in the uptake of vitamins in a wide range of bacteria. Inhibition of the activity of these proteins could reduce the viability of pathogens that depend on vitamin uptake. The central role of vitamin transport in the metabolism of bacteria and absence from humans make the ECF transporters an attractive target for inhibition with selective chemical probes. Here, we report on the identification of a promising class of inhibitors of the ECF transporters. We used coarse-grained molecular dynamics simulations on Lactobacillus delbrueckii ECF-FolT2 and ECF-PanT to profile the binding mode and mechanism of inhibition of this novel chemotype. The results corroborate the postulated mechanism of transport and pave the way for further drug-discovery efforts.</p

Treatment characteristics and outcomes of pure Acinar cell carcinoma of the pancreas - A multicentric European study on radically resected patients

Background: Acinar cell carcinomas (ACC) belong to the exocrine pancreatic malignancies. Due to their rarity, there is no consensus regarding treatment strategies for resectable ACC. Methods: This is a retrospective multicentric study of radically resected pure pancreatic ACC. Primary endpoints were overall survival (OS) and disease-free survival (DFS). Further endpoints were oncologic outcomes related to tumor stage and therapeutic protocols. Results: 59 patients (44 men) with a median age of 64 years were included. The median tumor size was 45.0&nbsp;mm. 61.0% were pT3 (n&nbsp;=&nbsp;36), nodal positivity rate was 37.3% (n&nbsp;=&nbsp;22), and synchronous distant metastases were present in 10.1% of the patients (n&nbsp;=&nbsp;6). 5-Years OS was 60.9% and median DFS 30 months. 24 out of 31 recurred systemically (n&nbsp;=&nbsp;18 only systemic, n&nbsp;=&nbsp;6 local and systemic). Regarding TNM-staging, only the N2-stage negatively influenced OS and DFS (p&nbsp;=&nbsp;0.004, p&nbsp;=&nbsp;0.001). Adjuvant treatment protocols (performed in 62.7%) did neither improve OS (p&nbsp;=&nbsp;0.542) nor DFS (p&nbsp;=&nbsp;0.159). In 9 cases, radical resection was achieved following neoadjuvant therapy. Discussion: Radical surgery is currently the mainstay for resectable ACC, even for limited metastatic disease. Novel (neo)adjuvant treatment strategies are needed, since current systemic therapies do not result in a clear survival benefit in the perioperative setting