Low-energy shock wave for enhancing recruitment of endothelial progenitor cells: a new modality to increase efficacy of cell therapy in chronic hind limb ischemia

Background— Stem and progenitor cell therapy is a novel approach to improve neovascularization and function of ischemic tissue. Enhanced tissue expression of chemoattractant factors such as stromal cell–derived factor 1 and vascular endothelial growth factor is crucial for the recruitment of circulating endothelial progenitor cells (EPCs) during acute ischemia. In chronic ischemia, however, expression of these chemoattractants is less pronounced, which results in insufficient EPC recruitment into the target tissue. Therefore, we investigated the effect of targeted extracorporeal shock wave (SW) application in order to facilitate EPC recruitment into nonischemic and chronic ischemic tissue

Quantifying in-situ gas hydrates at active seep sites in the eastern Black Sea using pressure coring technique

In the eastern Black Sea, we determined methane (CH4) concentrations, gas hydrate volumes, and their vertical distribution from combined gas and chloride (Cl−) measurements within pressurized sediment cores. The total gas volume collected from the cores corresponded to concentrations of 1.2–1.4 mol CH4 kg−1 porewater at in-situ pressure, which is equivalent to a gas hydrate saturation of 15–18% of pore volume and amongst the highest values detected in shallow seep sediments. At the central seep site, a high-resolution Cl− profile resolved the upper boundary of gas hydrate occurrence and a continuous layer of hydrates in a sediment column of 120 cm thickness. Including this information, a more precise gas hydrate saturation of 22–24% pore volume could be calculated. This volume was higher in comparison to a saturation calculated from the Cl− profile alone, resulting in only 14.4%. The likely explanation is an active gas hydrate formation from CH4 gas ebullition. The hydrocarbons at Batumi Seep are of shallow biogenic origin (CH4 > 99.6%), at Pechori Mound they originate from deeper thermocatalytic processes as indicated by the lower ratios of C1 to C2–C3 and the presence of C5

The Shroud Around the Twin Radio Jets in NGC 1052

(Abridged) We discuss multiple VLBI continuum and spectral line observations and WSRT spectroscopy of NGC 1052. Sub-parsec scale features move outward at approximately 0.26c in bi-symmetric jets, most likely oriented near the plane of the sky. Absorption and emission signatures reveal ionised, atomic, and molecular components of the surrounding medium. Seven-frequency (1.4 to 43 GHz) VLBA observations show free-free absorption in the inner parsec, probably together with synchrotron self-absorption. There is apparently a geometrically thick but patchy structure oriented roughly orthogonal to the jets. The western jet is receding: it is covered more deeply and extensively. HI spectral line VLBI reveals atomic gas in front of both jets. There appear to be three velocity systems. The deepest, at "high velocities" (receding by 125 to 200 km/s), seems restricted to a shell 1 to 2 pc away from the core, within which this gas might be largely ionised. WSRT spectroscopy has revealed 1667 and 1665 MHz OH absorption with their line ratio varying roughly from 1:1 to 2:1 between -35 and 200 km/s. In the high velocity system the OH profiles are similar to HI, suggesting co-location of that atomic and molecular gas, and leaving unclear the connection to the H2O masing gas seen elsewhere. We have also detected both 18cm OH satellite lines in the high velocity system. They have conjugate profiles: 1612 MHz is in absorption, and 1720 MHz in emission.Comment: 16 pages, 14 figures, LaTeX, includes aa.cls, accepted for publication in Astronomy and Astrophysic

Quantifying in-situ gas hydrates at active seep sites in the eastern

www.biogeosciences.net/8/3555/2011

A seasonal cycle and an abrupt change in the variability characteristics of the intraday variable source S4 0954+65

The BLLac object S4 0954+65 is one of the main targets of the Urumqi monitoring program targeting IntraDay Variable (IDV) sources. Between August 2005 and December 2009, the source was included in 41 observing sessions, carried out at a frequency of 4.8 GHz. The time analysis of the collected light curves, performed by applying both a structure function analysis and a specifically developed wavelet-based algorithm, discovered an annual cycle in the variability timescales, suggesting that there is a fundamental contribution by interstellar scintillation to the IDV pattern of the source. The combined use of the two analysis methods also revealed that there was a dramatic change in the variability characteristics of the source between February and March 2008, at the starting time of a strong outburst phase. The analysis' results suggest that the flaring state of the source coincides with the appearance of multiple timescales in its light curves, indicating that changes in the structure of the relativistically moving emitting region may strongly influence the variability observed on IDV timescales.Comment: 9 pages, 8 figures and 3 tables. Accepted for publication in Astronomy and Astrophysic

Multimodal Treatment Eliminates Cancer Stem Cells and Leads to Long-Term Survival in Primary Human Pancreatic Cancer Tissue Xenografts.

Copyright: 2013 Hermann et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.PURPOSE: In spite of intense research efforts, pancreatic ductal adenocarcinoma remains one of the most deadly malignancies in the world. We and others have previously identified a subpopulation of pancreatic cancer stem cells within the tumor as a critical therapeutic target and additionally shown that the tumor stroma represents not only a restrictive barrier for successful drug delivery, but also serves as a paracrine niche for cancer stem cells. Therefore, we embarked on a large-scale investigation on the effects of combining chemotherapy, hedgehog pathway inhibition, and mTOR inhibition in a preclinical mouse model of pancreatic cancer. EXPERIMENTAL DESIGN: Prospective and randomized testing in a set of almost 200 subcutaneous and orthotopic implanted whole-tissue primary human tumor xenografts. RESULTS: The combined targeting of highly chemoresistant cancer stem cells as well as their more differentiated progenies, together with abrogation of the tumor microenvironment by targeting the stroma and enhancing tissue penetration of the chemotherapeutic agent translated into significantly prolonged survival in preclinical models of human pancreatic cancer. Most pronounced therapeutic effects were observed in gemcitabine-resistant patient-derived tumors. Intriguingly, the proposed triple therapy approach could be further enhanced by using a PEGylated formulation of gemcitabine, which significantly increased its bioavailability and tissue penetration, resulting in a further improved overall outcome. CONCLUSIONS: This multimodal therapeutic strategy should be further explored in the clinical setting as its success may eventually improve the poor prognosis of patients with pancreatic ductal adenocarcinoma

A rational approach for generating cardiac troponin I selective Spiegelmers

We report the first protein selective Spiegelmers of diagnostic relevance by rational identification of a target epitope and reverse screening of Spiegelmer candidates following the selection procedure. Application of the presented approach resulted in isolation of cardiac troponin I selective Spiegelmers with low nanomolar dissociation constant and functionality in serum

cGMP-Dependent Protein Kinase I Is Crucial for Angiogenesis and Postnatal Vasculogenesis

Background Endothelium-derived nitric oxide plays an important role for the bone marrow microenvironment. Since several important effects of nitric oxide are mediated by cGMP-dependent pathways, we investigated the role of the cGMP downstream effector cGMP-dependent protein kinase I (cGKI) on postnatal neovascularization. Methodology/Principal Findings In a disc neovascularization model, cGKI -/- mice showed an impaired neovascularization as compared to their wild-type (WT) littermates. Infusion of WT, but not cGKI -/- bone marrow progenitors rescued the impaired ingrowth of new vessels in cGKI-deficient mice. Bone marrow progenitors from cGKI -/- mice showed reduced proliferation and survival rates. In addition, we used cGKI alpha leucine zipper mutant (LZM) mice as model for cGKI deficiency. LZM mice harbor a mutation in the cGKI alpha leucine zipper that prevents interaction with downstream signaling molecules. Consistently, LZM mice exhibited reduced numbers of vasculogenic progenitors and impaired neovascularization following hindlimb ischemia compared to WT mice. Conclusions/Significance Our findings demonstrate that the cGMP-cGKI pathway is critical for postnatal neovascularization and establish a new role for cGKI in vasculogenesis, which is mediated by bone marrow-derived progenitors