Serum high mobility group box-1 (HMGB1) is closely associated with the clinical and pathologic features of gastric cancer

<p>Abstract</p> <p>Background</p> <p>High mobility group box-1 (HMGB1) is a newly recognized factor regulating cancer cell tumorigenesis, expansion and invasion. We investigated the correlation between the serum HMGB1 levels and the clinical and pathologic features of gastric cancer and evaluated the validity of HMGB1 as a potential biomarker for the early diagnosis of gastric cancer.</p> <p>Methods</p> <p>A total of 227 subjects were classified into 5 disease groups according to the 'gastritis-dysplasia-carcinoma' sequence of gastric carcinogenesis and their serum levels of HMGB1 were analyzed by an enzyme-linked immunosorbent assay (ELISA) method. Clinical parameters, International Union Against Cancer (UICC) TNM stage, cancer size, differentiation or lymphatic invasion, vascular or perineural invasion and prognosis were used as analysis variables.</p> <p>Results</p> <p>The serum HMGB1 levels were significantly different among disease groups (ANOVA, <it>p < 0.05</it>) and HMGB1 levels tended to increase according to the progression of gastric carcinogenesis. Serum HMGB1 levels were significantly associated with depth of invasion, lymph node metastasis, tumor size, and poor prognosis (<it>p < 0.05</it>). However, HMGB1 levels were not associated with patient gender or age, differentiation of tumor cells, or lymphatic, vascular and perineural invasion, or the existence of distant metastasis in advanced cancer (<it>p > 0.05</it>). The sensitivity and specificity of serum HMGB1 was 71% and 67% (cut-off value of 5 ng/ml) for the diagnosis of early gastric cancer, and 70% and 64% (cut-off value of 4 ng/ml) for the diagnosis of high-risk lesions, respectively. These values were greater than those for carcinoembryonic antigen (CEA) (30–40% of sensitivity).</p> <p>Conclusion</p> <p>HMGB1 appears to be a useful serological biomarker for early diagnosis as well as evaluating the tumorigenesis, stage, and prognosis of gastric cancer.</p

Design and Test of a Forward Neutron Calorimeter for the ZEUS Experiment

A lead scintillator sandwich sampling calorimeter has been installed in the HERA tunnel 105.6 m from the central ZEUS detector in the proton beam direction. It is designed to measure the energy and scattering angle of neutrons produced in charge exchange ep collisions. Before installation the calorimeter was tested and calibrated in the H6 beam at CERN where 120 GeV electrons, muons, pions and protons were made incident on the calorimeter. In addition, the spectrum of fast neutrons from charge exchange proton-lucite collisions was measured. The design and construction of the calorimeter is described, and the results of the CERN test reported. Special attention is paid to the measurement of shower position, shower width, and the separation of electromagnetic showers from hadronic showers. The overall energy scale as determined from the energy spectrum of charge exchange neutrons is compared to that obtained from direct beam hadrons.Comment: 45 pages, 22 Encapsulated Postscript figures, submitted to Nuclear Instruments and Method

Toxoplasma gondii Syntaxin 6 is required for vesicular transport between endosomal-like compartments and the Golgi Complex

Apicomplexans are obligate intracellular parasites that invade the host cell in an active process that relies on unique secretory organelles (micronemes, rhoptries and dense granules) localized at the apical tip of these highly polarized eukaryotes. In order for the contents of these specialized organelles to reach their final destination, these proteins are sorted post-Golgi and it has been speculated that they pass through endosomal-like compartments (ELCs), where they undergo maturation. Here, we characterize a Toxoplasma gondii homologue of Syntaxin 6 (TgStx6), a well-established marker for the early endosomes and trans Golgi network (TGN) in diverse eukaryotes. Indeed, TgStx6 appears to have a role in the retrograde transport between ELCs, the TGN and the Golgi, because overexpression of TgStx6 results in the development of abnormally shaped parasites with expanded ELCs, a fragmented Golgi and a defect in inner membrane complex maturation. Interestingly, other organelles such as the micronemes, rhoptries and the apicoplast are not affected, establishing the TGN as a major sorting compartment where several transport pathways intersect. It therefore appears thatToxoplasma has retained a plant-like secretory pathway

Near-infrared autofluorescence induced by intraplaque hemorrhage and heme degradation as marker for high-risk atherosclerotic plaques

Atherosclerosis is a major cause of mortality and morbidity, which is mainly driven by complications such as myocardial infarction and stroke. These complications are caused by thrombotic arterial occlusion localized at the site of high-risk atherosclerotic plaques, of which early detection and therapeutic stabilization are urgently needed. Here we show that near-infrared autofluorescence is associated with the presence of intraplaque hemorrhage and heme degradation products, particularly bilirubin by using our recently created mouse model, which uniquely reflects plaque instability as seen in humans, and human carotid endarterectomy samples. Fluorescence emission computed tomography detecting near-infrared autofluorescence allows in vivo monitoring of intraplaque hemorrhage, establishing a preclinical technology to assess and monitor plaque instability and thereby test potential plaque-stabilizing drugs. We suggest that near-infrared autofluorescence imaging is a novel technology that allows identification of atherosclerotic plaques with intraplaque hemorrhage and ultimately holds promise for detection of high-risk plaques in patients

Every BCG with a strong radio AGN has an X-ray cool core: is the cool core - noncool core dichotomy too simple?

Radio AGN feedback in X-ray cool cores has been proposed as a crucial ingredient in the evolution of baryonic structures. However, it has long been known that strong radio AGN also exist in "noncool core" clusters, which brings up the question whether an X-ray cool core is always required for radio feedback. In this work, we present a systematic analysis of BCGs and strong radio AGN in 152 groups and clusters from the Chandra archive. All 69 BCGs with radio AGN more luminous than 2x10^23 W Hz^-1 at 1.4 GHz are found to have X-ray cool cores. The BCG cool cores can be divided into two classes, the large-cool-core (LCC) class and the corona class. Small coronae, easily overlooked at z>0.1, can trigger strong heating episodes in groups and clusters, long before large cool cores are formed. Strong radio outbursts triggered by coronae may destroy embryonic large cool cores and thus provide another mechanism to prevent formation of large cool cores. However, it is unclear whether coronae are decoupled from the radio feedback cycles as they have to be largely immune to strong radio outbursts. Our sample study also shows the absence of groups with a luminous cool core while hosting a strong radio AGN, which is not observed in clusters. This points to a greater impact of radio heating on low-mass systems than clusters. As examples of the corona class, we also present detailed analyses of a BCG corona associated with a strong radio AGN (ESO 137-006 in A3627) and one of the faintest coronae known (NGC 4709 in the Centaurus cluster). Our results suggest that the traditional cool core / noncool core dichotomy is too simple. A better alternative is the cool core distribution function, with the enclosed X-ray luminosity or gas mass.Comment: To appear in ApJ, Nov. 2009, emulateapj5.sty, 22 pages, 11 figures and 4 tables. The abstract has been abbreviated slightly. New changes include: adding seven systems (including AWM4), updating most figures and tables, expanding discussions. Conclusions are unchanged. A high-resolution PDF is available from http://www.astro.virginia.edu/~ms4ar/corona_RG.pd

Flux calibration of the Herschel-SPIRE photometer

We describe the procedure used to flux calibrate the three-band submillimetre photometer in the Spectral and Photometric Imaging Receiver instrument on the Herschel Space Observatory. This includes the equations describing the calibration scheme, a justification for using Neptune as the primary calibration source, a description of the observations and data processing procedures used to derive flux calibration parameters (for converting from voltage to flux density) for every bolometer in each array, an analysis of the error budget in the flux calibration for the individual bolometers and tests of the flux calibration on observations of primary and secondary calibrators. The procedure for deriving the flux calibration parameters is divided into two parts. In the first part, we use observations of astronomical sources in conjunction with the operation of the photometer internal calibration source to derive the unscaled derivatives of the flux calibration curves. To scale the calibration curves in Jy beam^(−1) V^(−1), we then use observations of Neptune in which the beam of each bolometer is mapped using a very fine scan pattern. The total instrumental uncertainties in the flux calibration for most individual bolometers is ∼0.5  per cent, although a few bolometers have uncertainties of ∼1–5  per cent because of issues with the Neptune observations. Based on application of the flux calibration parameters to Neptune observations performed using typical scan map observing modes, we determined that measurements from each array as a whole have instrumental uncertainties of 1.5  per cent. This is considerably less than the absolute calibration uncertainty associated with the model of Neptune, which is estimated at 4  per cent

LATS1 but not LATS2 represses autophagy by a kinase-independent scaffold function

Autophagy perturbation represents an emerging therapeutic strategy in cancer. Although LATS1 and LATS2 kinases, core components of the mammalian Hippo pathway, have been shown to exert tumor suppressive activities, here we report a pro-survival role of LATS1 but not LATS2 in hepatocellular carcinoma (HCC) cells. Specifically, LATS1 restricts lethal autophagy in HCC cells induced by sorafenib, the standard of care for advanced HCC patients. Notably, autophagy regulation by LATS1 is independent of its kinase activity. Instead, LATS1 stabilizes the autophagy core-machinery component Beclin-1 by promoting K27-linked ubiquitination at lysine residues K32 and K263 on Beclin-1. Consequently, ubiquitination of Beclin-1 negatively regulates autophagy by promoting inactive dimer formation of Beclin-1. Our study highlights a functional diversity between LATS1 and LATS2, and uncovers a scaffolding role of LATS1 in mediating a cross-talk between the Hippo signaling pathway and autophagy

Consensus-Based Technical Recommendations for Clinical Translation of Renal Phase Contrast MRI

BACKGROUND: Phase-contrast (PC) MRI is a feasible and valid noninvasive technique to measure renal artery blood flow, showing potential to support diagnosis and monitoring of renal diseases. However, the variability in measured renal blood flow values across studies is large, most likely due to differences in PC-MRI acquisition and processing. Standardized acquisition and processing protocols are therefore needed to minimize this variability and maximize the potential of renal PC-MRI as a clinically useful tool. PURPOSE: To build technical recommendations for the acquisition, processing, and analysis of renal 2D PC-MRI data in human subjects to promote standardization of renal blood flow measurements and facilitate the comparability of results across scanners and in multicenter clinical studies. STUDY TYPE: Systematic consensus process using a modified Delphi method. POPULATION: Not applicable. SEQUENCE FIELD/STRENGTH: Renal fast gradient echo-based 2D PC-MRI. ASSESSMENT: An international panel of 27 experts from Europe, the USA, Australia, and Japan with 6 (interquartile range 4–10) years of experience in 2D PC-MRI formulated consensus statements on renal 2D PC-MRI in two rounds of surveys. Starting from a recently published systematic review article, literature-based and data-driven statements regarding patient preparation, hardware, acquisition protocol, analysis steps, and data reporting were formulated. STATISTICAL TESTS: Consensus was defined as ≥75% unanimity in response, and a clear preference was defined as 60–74% agreement among the experts. RESULTS: Among 60 statements, 57 (95%) achieved consensus after the second-round survey, while the remaining three showed a clear preference. Consensus statements resulted in specific recommendations for subject preparation, 2D renal PC-MRI data acquisition, processing, and reporting. DATA CONCLUSION: These recommendations might promote a widespread adoption of renal PC-MRI, and may help foster the set-up of multicenter studies aimed at defining reference values and building larger and more definitive evidence, and will facilitate clinical translation of PC-MRI. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE:

Insights gained from the reverse engineering of gene networks in keloid fibroblasts

<p>Abstract</p> <p>Background</p> <p>Keloids are protrusive claw-like scars that have a propensity to recur even after surgery, and its molecular etiology remains elusive. The goal of reverse engineering is to infer gene networks from observational data, thus providing insight into the inner workings of a cell. However, most attempts at modeling biological networks have been done using simulated data. This study aims to highlight some of the issues involved in working with experimental data, and at the same time gain some insights into the transcriptional regulatory mechanism present in keloid fibroblasts.</p> <p>Methods</p> <p>Microarray data from our previous study was combined with microarray data obtained from the literature as well as new microarray data generated by our group. For the physical approach, we used the fREDUCE algorithm for correlating expression values to binding motifs. For the influence approach, we compared the Bayesian algorithm BANJO with the information theoretic method ARACNE in terms of performance in recovering known influence networks obtained from the KEGG database. In addition, we also compared the performance of different normalization methods as well as different types of gene networks.</p> <p>Results</p> <p>Using the physical approach, we found consensus sequences that were active in the keloid condition, as well as some sequences that were responsive to steroids, a commonly used treatment for keloids. From the influence approach, we found that BANJO was better at recovering the gene networks compared to ARACNE and that transcriptional networks were better suited for network recovery compared to cytokine-receptor interaction networks and intracellular signaling networks. We also found that the NFKB transcriptional network that was inferred from normal fibroblast data was more accurate compared to that inferred from keloid data, suggesting a more robust network in the keloid condition.</p> <p>Conclusions</p> <p>Consensus sequences that were found from this study are possible transcription factor binding sites and could be explored for developing future keloid treatments or for improving the efficacy of current steroid treatments. We also found that the combination of the Bayesian algorithm, RMA normalization and transcriptional networks gave the best reconstruction results and this could serve as a guide for future influence approaches dealing with experimental data.</p

Observing the Evolution of the Universe

How did the universe evolve? The fine angular scale (l>1000) temperature and polarization anisotropies in the CMB are a Rosetta stone for understanding the evolution of the universe. Through detailed measurements one may address everything from the physics of the birth of the universe to the history of star formation and the process by which galaxies formed. One may in addition track the evolution of the dark energy and discover the net neutrino mass. We are at the dawn of a new era in which hundreds of square degrees of sky can be mapped with arcminute resolution and sensitivities measured in microKelvin. Acquiring these data requires the use of special purpose telescopes such as the Atacama Cosmology Telescope (ACT), located in Chile, and the South Pole Telescope (SPT). These new telescopes are outfitted with a new generation of custom mm-wave kilo-pixel arrays. Additional instruments are in the planning stages.Comment: Science White Paper submitted to the US Astro2010 Decadal Survey. Full list of 177 author available at http://cmbpol.uchicago.ed