A Technique for In-situ Measurement of Free Spectral Range and Transverse Mode Spacing of Optical Cavities

Length and g-factor are fundamental parameters that characterize optical cavities. We developed a technique to measure these parameters in-situ by determining the frequency spacing between the resonances of fundamental and spatial modes of an optical cavity. Two laser beams are injected into the cavity, and their relative frequency is scanned by a phase-lock loop, while the cavity is locked to either laser. The measurement of the amplitude of their beat note in transmission reveals the resonances of the longitudinal and the transverse modes of the cavity and their spacing. This method proves particularly useful to characterize complex optical systems, including very long and/or coupled optical cavities, as in gravitational wave interferometers. This technique and the results of its application to the coupled cavities of a 40-meter-long gravitational wave interferometer prototype are here presented

Pan-Bcl-2 inhibitor Obatoclax is a potent late stage autophagy inhibitor in colorectal cancer cells independent of canonical autophagy signaling

Background: Colorectal cancer is the third most common malignancy in humans and novel therapeutic approaches are urgently needed. Autophagy is an evolutionarily highly conserved cellular process by which cells collect unnecessary organelles or misfolded proteins and subsequently degrade them in vesicular structures in order to refuel cells with energy. Dysregulation of the complex autophagy signaling network has been shown to contribute to the onset and progression of cancer in various models. The Bcl-2 family of proteins comprises central regulators of apoptosis signaling and has been linked to processes involved in autophagy. The antiapoptotic members of the Bcl-2 family of proteins have been identified as promising anticancer drug targets and small molecules inhibiting those proteins are in clinical trials. Methods: Flow cytometry and colorimetric assays were used to assess cell growth and cell death. Long term 3D cell culture was used to assess autophagy in a tissue mimicking environment in vitro. RNA interference was applied to modulate autophagy signaling. Immunoblotting and q-RT PCR were used to investigate autophagy signaling. Immunohistochemistry and fluorescence microscopy were used to detect autophagosome formation and autophagy flux. Results: This study demonstrates that autophagy inhibition by obatoclax induces cell death in colorectal cancer (CRC) cells in an autophagy prone environment. Here, we demonstrate that pan-Bcl-2 inhibition by obatoclax causes a striking, late stage inhibition of autophagy in CRC cells. In contrast, ABT-737, a Mcl-1 sparing Bcl-2 inhibitor, failed to interfere with autophagy signaling. Accumulation of p62 as well as Light Chain 3 (LC3) was observed in cells treated with obatoclax. Autophagy inhibition caused by obatoclax is further augmented in stressful conditions such as starvation. Furthermore, our data demonstrate that inhibition of autophagy caused by obatoclax is independent of the essential pro-autophagy proteins Beclin-1, Atg7 and Atg12. Conclusions: The objective of this study was to dissect the contribution of Bcl-2 proteins to autophagy in CRC cells and to explore the potential of Bcl-2 inhibitors for autophagy modulation. Collectively, our data argue for a Beclin-1 independent autophagy inhibition by obatoclax. Based on this study, we recommend the concept of autophagy inhibition as therapeutic strategy for CRC

Mechanistic insight into acrylate metabolism and detoxification in marine dimethylsulfoniopropionate-catabolizing bacteria

Dimethylsulfoniopropionate (DMSP) cleavage, yielding dimethyl sulfide (DMS) and acrylate, provides vital carbon sources to marine bacteria, is a key component of the global sulfur cycle and effects atmospheric chemistry and potentially climate. Acrylate and its metabolite acryloyl-CoA are toxic if allowed to accumulate within cells. Thus, organisms cleaving DMSP require effective systems for both the utilization and detoxification of acrylate. Here, we examine the mechanism of acrylate utilization and detoxification in Roseobacters. We propose propionate-CoA ligase (PrpE) and acryloyl-CoA reductase (AcuI) as the key enzymes involved and through structural and mutagenesis analyses, provide explanations of their catalytic mechanisms. In most cases, DMSP lyases and DMSP demethylases (DmdAs) have low substrate affinities, but AcuIs have very high substrate affinities, suggesting that an effective detoxification system for acylate catabolism exists in DMSP-catabolizing Roseobacters. This study provides insight on acrylate metabolism and detoxification and a possible explanation for the high Km values that have been noted for some DMSP lyases. Since acrylate/acryloyl-CoA is probably produced by other metabolism, and AcuI and PrpE are conserved in many organisms across all domains of life, the detoxification system is likely relevant to many metabolic processes and environments beyond DMSP catabolism

APOE Inhibition of Remyelination and Regulation of OPC differentiation

Apolipoprotein E (APOE) interacts with the lipoprotein receptor to transport lipoproteins and facilitates ingestion of apoptotic cells, also known as efferocytosis. APOE-deficient macrophages ingest fewer apoptotic cells than wildtype cells. Because apoptotic cells are found in lesions of demyelination, we speculated that APOE and efferocytosis may be involved in remyelination. Our hypothesis is that APOE regulates OPC differentiation via the microglia secretome. To test this hypothesis, we assessed remyelination in vivo using APOE-/-, APOE2, APOE3, and APOE4 knock-in mice and in vitro using the OPC differentiation assay. In vivo, we found APOE3 mice showed delayed remyelination at the 5+2 week time point, but by 5+3 week the APOE3 variant was similar to WT. This indicates that APOE3 partly inhibits the remyelination process. Furthermore, it was found that APOE-/- had significantly more remyelination than other genotypes at the 5+1 time point, which suggests murine APOE inhibits remyelination temporarily. In vitro, the OPC differentiation assay showed that APOE3 and APOE-/- macrophage secretomes retained significantly more round and primary processes than the positive control indicating there were less factors driving initial cell differentiation. This suggests that murine APOE is required for efferocytosis and secretome content, but APOE3 may inhibit efferocytosis and alter the beneficial factors for OPC differentiation.Bachelor of Scienc

Mechanistic insight into acrylate metabolism and detoxification in marine dimethylsulfoniopropionate-catabolizing bacteria

Dimethylsulfoniopropionate (DMSP) cleavage, yielding dimethyl sulfide (DMS) and acrylate, provides vital carbon sources to marine bacteria, is a key component of the global sulfur cycle and effects atmospheric chemistry and potentially climate. Acrylate and its metabolite acryloyl-CoA are toxic if allowed to accumulate within cells. Thus, organisms cleaving DMSP require effective systems for both the utilization and detoxification of acrylate. Here, we examine the mechanism of acrylate utilization and detoxification in Roseobacters. We propose propionate-CoA ligase (PrpE) and acryloyl-CoA reductase (AcuI) as the key enzymes involved and through structural and mutagenesis analyses, provide explanations of their catalytic mechanisms. In most cases, DMSP lyases and DMSP demethylases (DmdAs) have low substrate affinities, but AcuIs have very high substrate affinities, suggesting that an effective detoxification system for acylate catabolism exists in DMSP-catabolizing Roseobacters. This study provides insight on acrylate metabolism and detoxification and a possible explanation for the high Km values that have been noted for some DMSP lyases. Since acrylate/acryloyl-CoA is probably produced by other metabolism, and AcuI and PrpE are conserved in many organisms across all domains of life, the detoxification system is likely relevant to many metabolic processes and environments beyond DMSP catabolism

Synergy Pattern of Short Cationic Antimicrobial Peptides Against Multidrug-Resistant Pseudomonas aeruginosa

With the rise of various multidrug-resistant (MDR) pathogenic bacteria, worldwide health care is under pressure to respond. Conventional antibiotics are failing and the development of novel classes and alternative strategies is a major priority. Antimicrobial peptides (AMPs) cannot only kill MDR bacteria, but also can be used synergistically with conventional antibiotics. We selected 30 short AMPs from different origins and measured their synergy in combination with polymyxin B, piperacillin, ceftazidime, cefepime, meropenem, imipenem, tetracycline, erythromycin, kanamycin, tobramycin, amikacin, gentamycin, and ciprofloxacin. In total, 403 unique combinations were tested against an MDR Pseudomonas aeruginosa isolate (PA910). As a measure of the synergistic effects, fractional inhibitory concentrations (FICs) were determined using microdilution assays with FICs ranges between 0.25 and 2. A high number of combinations between peptides and polymyxin B, erythromycin, and tetracycline were found to be synergistic. Novel variants of indolicidin also showed a high frequency in synergist interaction. Single amino acid substitutions within the peptides can have a very strong effect on the ability to synergize, making it possible to optimize future drugs toward synergistic interaction

Wandtafeln für den Unterricht in der Pflanzenkunde [Material gráfico]

Contenido parcial: [1]. Längsdurchschnitt eines der knolle entsprossenen jungen PflänschenFecha tomada de Botanisches CentralblattLám. con anilla

Thiertypen Säugethiere [Material gráfico]

Contenido parcial: II. Erste Reihe: Handthiere (Primates), Dritte Ordung: Die Halbaffen o der Aeffer (Hemipitheciod, Prosimii), Erste Familie: Kurzfüsser (Brachytarsi). Der Plumpe Lori, Der BartmakiContenido parcial: VII. VIII [Achte] Ordung: Die Klammerthiere (Tardigrada). Dus dreizehige faultierContenido parcial: VIII. Neunte Ordung: Die Schurrlhiere [Effodientia]. Narktschmänziges Gürtelthier (Dasypus Gymnurus). Zehnte Ordung: Die Kloaken oder Gubelthiere [Monotremata]. Ornithorhynchus paradoxus Schnabelthier / G. Mützel [grafiker]Contenido parcial: Fünfzehnte Ordung: Die Sierenen (Sirenia). Der schmalschanauzige Lamantin (Manatus australis) nach A. E. Brehm's illustrirtem ThierlebenContenido parcial: Die Wiederkäuer (Ruminantia). Entwickelungsstufen des Geweihes des Edelhirsches (Cervus elephus) nach Dr. W. SoemmeringFechas deducidas de la actividad del editorLám. con anilla

Fibrocytes are associated with vascular and parenchymal remodelling in patients with obliterative bronchiolitis

<p>Abstract</p> <p>Background</p> <p>The aim of the present study was to explore the occurrence of fibrocytes in tissue and to investigate whether the appearance of fibrocytes may be linked to structural changes of the parenchyme and vasculature in the lungs of patients with obliterative bronchiolitis (OB) following lung or bone marrow transplantation.</p> <p>Methods</p> <p>Identification of parenchyme, vasculature, and fibrocytes was done by histological methods in lung tissue from bone marrow or lung-transplanted patients with obliterative bronchiolitis, and from controls.</p> <p>Results</p> <p>The transplanted patients had significantly higher amounts of tissue in the alveolar parenchyme (46.5 ± 17.6%) than the controls (21.7 ± 7.6%) (p < 0.05). The patients also had significantly increased numbers of fibrocytes identified by CXCR4/prolyl4-hydroxylase, CD45R0/prolyl4-hydroxylase, and CD34/prolyl4-hydroxylase compared to the controls (p < 0.01). There was a correlation between the number of fibrocytes and the area of alveolar parenchyma; CXCR4/prolyl 4-hydroxylase (p < 0.01), CD45R0/prolyl 4-hydroxylase (p < 0.05) and CD34/prolyl 4-hydroxylase (p < 0.05). In the pulmonary vessels, there was an increase in the endothelial layer in patients (0.31 ± 0.13%) relative to the controls (0.037 ± 0.02%) (p < 0.01). There was a significant correlation between the number of fibrocytes and the total area of the endothelial layer CXCR4/prolyl 4-hydroxylase (p < 0.001), CD45R0/prolyl 4-hydroxylase (p < 0.001) and CD34/prolyl 4-hydroxylase (p < 0.01). The percent areas of the lumen of the vessels were significant (p < 0.001) enlarged in the patient with OB compared to the controls. There was also a correlation between total area of the lumen and number of fibrocytes, CXCR4/prolyl 4-hydroxylase (p < 0.01), CD45R0/prolyl 4-hydroxylase (p < 0.001) and CD34/prolyl 4-hydroxylase (p < 0.01).</p> <p>Conclusion</p> <p>Our results indicate that fibrocytes are associated with pathological remodelling processes in patients with OB and that tissue fibrocytes might be a useful biomarker in these processes.</p