Plasminogen activator levels are influenced by location and varicosity in greater saphenous vein

AbstractPurpose: The plasminogen system, which includes tissue type plasminogen activator (tPA), urokinase type plasminogen activator (uPA), and their main inhibitor, plasminogen activator inhibitor type 1 (PAI-1), plays a major role in both fibrinolysis and tissue remodeling. This study compares the levels of tPA, uPA, and PAI-1 at the groin and ankle in normal and varicose greater saphenous vein (GSV).Methods: GSV was collected from patients undergoing varicose vein (VV) removal and from normal vein (NV) from arterial bypass procedures. Portions of the GSV at the groin and the ankle were minced and placed in serum-free media for 48 hours. Assays of the supernatants were obtained for tPA, uPA, and PAI-1 protein by enzyme-linked immunosorbent assay. Cyclohexamide and actinomycin D were also added to the media of the VV tissue explant supernatants to inhibit protein and RNA synthesis, respectively.Results: Levels of tPA were significantly higher at the groin (11 ± 2) than the ankle (5 ± 1) in the VV ( p < 0.005), and this trend was also seen in the NV (groin 10 ± 2 and ankle 7 ± 3). Levels of uPA were significantly higher in the groin VV (14 ± 4.3) than in NV (3.0 ± 0.8, p < 0.05). This difference, although not statistically significant, applied to the ankle as well (VV 14.5 ± 6.3 and NV 5.3 ± 2.7). No significant difference was seen between NV and VV for PAI-1 (NV, groin 155 ± 73 and ankle 113 ± 53, VV, groin 161 ± 20 and ankle 142 ± 38) or tPA. Inhibitor studies revealed no significant difference among control, cyclohexamide, and actinomycin D supernatants for tPA, suggesting release of protein rather than active synthesis. In contrast, inhibitor supernatants were significantly lower for uPA and PAI-1 than control supernatants ( p < 0.05), suggesting that uPA and PAI-1 were actively synthesized.Conclusions: In the tissue explant supernatant model uPA and PAI-1 are actively synthesized, but tPA is not. Levels of PAI-1 were comparable in all four groups. Levels of uPA in the varicose GSV were higher than in NV, suggesting a role for uPA in the pathologic makeup of VV. Levels of tPA were higher at the groin versus the ankle position, potentially explaining the previously described increased fibrinolytic activity seen at the groin. (J Vasc Surg 1996;24:719-24.

Very High Gas Fractions and Extended Gas Reservoirs in z=1.5 Disk Galaxies

We present evidence for very high gas fractions and extended molecular gas reservoirs in normal, near-infrared selected (BzK) galaxies at z~1.5, based on multi-configuration CO[2-1] observations obtained at the IRAM PdBI. Six of the six galaxies observed were securely detected. High resolution observations resolve the CO emission in four of them, implying sizes of order of 6-11 kpc and suggesting the presence of rotation. The UV morphologies are consistent with clumpy, unstable disks, and the UV sizes are consistent with the CO sizes. The star formation efficiencies are homogeneously low and similar to local spirals - the resulting gas depletion times are ~0.5 Gyr, much higher than what is seen in high-z submm galaxies and quasars. The CO luminosities can be predicted to within 0.15 dex from the star formation rates and stellar masses, implying a tight correlation of the gas mass with these quantities. We use dynamical models of clumpy disk galaxies to derive dynamical masses. These models are able to reproduce the peculiar spectral line shapes of the CO emission. After accounting for the stellar and dark matter masses we derive gas masses of 0.4-1.2x10^11 Msun. The conversion factor is very high: alpha_CO=3.6+-0.8, consistent with the Galaxy but four times higher than that of local ultra-luminous IR galaxies. The gas accounts for an impressive 50-65% of the baryons within the galaxies' half light radii. We are witnessing truly gas-dominated galaxies at z~1.5, a finding that explains the high specific SFRs observed for z>1 galaxies. The BzK galaxies can be viewed as scaled-up versions of local disk galaxies, with low efficiency star formation taking place inside extended, low excitation gas disks. They are markedly different than local ULIRGs and high-z submm galaxies, which have more excited and compact gas.Comment: Accepted for publication in Astrophysical Journal, 22 pages, 18 figures, minor revision

An ATP-binding cassette-type cysteine transporter in Campylobacter jejuni inferred from the structure of an extracytoplasmic solute receptor protein

Campylobacter jejuni is a Gram-negative food-borne pathogen associated with gastroenteritis in humans as well as cases of the autoimmune disease Guillain Barre syndrome. C. jejuni is asaccharolytic because it lacks an active glycolytic pathway for the use of sugars as a carbon source. This suggests an increased reliance on amino acids as nutrients and indeed the genome sequence of this organism indicates the presence of a number of amino acid uptake systems. Cj0982, also known as CjaA, is a putative extracytoplasmic solute receptor for one such uptake system as well as a major surface antigen and vaccine candidate. The crystal structure of Cj0982 reveals a two-domain protein with density in the enclosed cavity between the domains that clearly defines the presence of a bound cysteine ligand. Fluorescence titration experiments were used to demonstrate that Cj0982 binds cysteine tightly and specifically with a K-d of similar to 10(-7) M consistent with a role as a receptor for a high- affinity transporter. These data imply that Cj0982 is the binding protein component of an ABC-type cysteine transporter system and that cysteine uptake is important in the physiology of C. jejuni

Cold molecular gas in massive disk galaxies at z=1.5

We report the detection of the CO J=1-0 emission line in three near-infrared selected star-forming galaxies at z~1.5 with the Very Large Array (VLA) and the Green Bank telescope (GBT). These observations directly trace the bulk of molecular gas in these galaxies. We find H_2 gas masses of 8.3 \pm 1.9 x 10^{10} M_sun, 5.6 \pm 1.4 x 10^{10} M_sun and 1.23 \pm 0.34 x 10^{11} M_sun for BzK-4171, BzK-21000 and BzK-16000, respectively, assuming a conversion alpha_CO=3.6 M_sun (K km s^{-1} pc^{2})^{-1}. We combined our observations with previous CO 2-1 detections of these galaxies to study the properties of their molecular gas. We find brightness temperature ratios between the CO 2-1 and CO 1-0 emission lines of 0.80_{-0.22}^{+0.35}, 1.22_{-0.36}^{+0.61} and 0.41_{-0.13}^{+0.23} for BzK-4171, BzK-21000 and BzK-16000, respectively. At the depth of our observations it is not possible to discern between thermodynamic equilibrium or sub-thermal excitation of the molecular gas at J=2. However, the low temperature ratio found for BzK-16000 suggests sub-thermal excitation of CO already at J=2. For BzK-21000, a Large Velocity Gradient model of its CO emission confirms previous results of the low-excitation of the molecular gas at J=3. From a stacked map of the CO 1-0 images, we measure a CO 2-1 to CO 1-0 brightness temperature ratio of 0.92_{-0.19}^{+0.28}. This suggests that, on average, the gas in these galaxies is thermalized up to J=2, has star-formation efficiencies of ~100 L_sun (K km s^{-1} pc^2)^{-1} and gas consumption timescales of ~0.4 Gyr, unlike SMGs and QSOs at high redshifts.Comment: Accepted for publication in Ap

The identification and functional annotation of RNA structures conserved in vertebrates

Structured elements of RNA molecules are essential in, e.g., RNA stabilization, localization, and protein interaction, and their conservation across species suggests a common functional role. We computationally screened vertebrate genomes for conserved RNA structures (CRSs), leveraging structure-based, rather than sequence-based, alignments. After careful correction for sequence identity and GC content, we predict ∼516,000 human genomic regions containing CRSs. We find that a substantial fraction of human–mouse CRS regions (1) colocalize consistently with binding sites of the same RNA binding proteins (RBPs) or (2) are transcribed in corresponding tissues. Additionally, a CaptureSeq experiment revealed expression of many of our CRS regions in human fetal brain, including 662 novel ones. For selected human and mouse candidate pairs, qRT-PCR and in vitro RNA structure probing supported both shared expression and shared structure despite low abundance and low sequence identity. About 30,000 CRS regions are located near coding or long noncoding RNA genes or within enhancers. Structured (CRS overlapping) enhancer RNAs and extended 3′ ends have significantly increased expression levels over their nonstructured counterparts. Our findings of transcribed uncharacterized regulatory regions that contain CRSs support their RNA-mediated functionality.</jats:p

Electron-based crystalline undulator

We discuss the features of a crystalline undulator of the novel type based on the effect of a planar channeling of ultra-relativistic electrons in a periodically bent crystals. It is demonstrated that an electron-based undulator is feasible in the tens of GeV range of the beam energies, which is noticeably higher than the energy interval allowed in a positron-based undulator. Numerical analysis of the main parameters of the undulator as well as the characteristics of the emitted undulator radiation is carried out for 20 and 50 GeV electrons channeling in diamond and silicon crystals along the (111) crystallographic planes.Comment: 16 pages, 8 figures, Latex, IOP styl

Up-regulation of bone marrow stromal protein 2 (BST2) in breast cancer with bone metastasis

<p>Abstract</p> <p>Background</p> <p>Bone metastases are frequent complications of breast cancer. Recent literature implicates multiple chemokines in the formation of bone metastases in breast cancer. However, the molecular mechanism of metastatic bone disease in breast cancer remains unknown. We have recently made the novel observation of the BST2 protein expression in human breast cancer cell lines. The purpose of our present study is to investigate the expression and the role of BST2 in bone metastatic breast cancer.</p> <p>Methods</p> <p>cDNA microarray analysis was used to compare the BST2 gene expression between a metastatic to bone human breast cancer cell line (MDA-231BO) and a primary human breast cancer cell line (MDA-231). The BST2 expression in one bone metastatic breast cancer and seven non-bone metastatic breast cancer cell lines were also determined using real-time RT-PCR and Western blot assays. We then employed tissue array to further study the BST2 expression in human breast cancer using array slides containing 20 independent breast cancer tumors that formed metastatic bone lesions, 30 non-metastasis-forming breast cancer tumors, and 8 normal breast tissues. In order to test the feasibility of utilizing BST2 as a serum marker for the presence of bone metastasis in breast cancer, we had measured the BST2 expression levels in human serums by using ELISA on 43 breast cancer patients with bone metastasis, 43 breast cancer patients without bone metastasis, and 14 normal healthy controls. The relationship between cell migration and proliferation and BST2 expression was also studied in a human breast recombinant model system using migration and FACS analysis.</p> <p>Results</p> <p>The microarray demonstrated over expression of the BST2 gene in the bone metastatic breast cancer cell line (MDA-231BO) compared to the primary human breast cancer cell line (MDA-231). The expression of the BST2 gene was significantly increased in the bone metastatic breast cancer cell lines and tumor tissues compared to non-bone metastatic breast cancer cell lines and tumor tissues by real time RT-PCR, Western blot and TMA. Furthermore, serum levels of BST2 measured by ELISA were also significantly higher among patients with breast cancer metastatic to bone compared to breast cancer patients without metastatic to bone (P < .0001). Most importantly, the breast cancer cell line that transfected with BST2 demonstrated increased BST2 expressions, which was associated with increased cancer cell migration and cell proliferation.</p> <p>Conclusion</p> <p>These results provide novel data indicating the BST2 protein expression is associated with the formation of bone metastases in human breast cancer. We believe that BST2 may be a potential biomarker in breast cancer with bone metastasis.</p

First enantioseparation and circular dichroism spectra of Au38 clusters protected by achiral ligands

Bestowing chirality to metals is central in fields such as heterogeneous catalysis and modern optics. Although the bulk phase of metals is symmetric, their surfaces can become chiral through adsorption of molecules. Interestingly, even achiral molecules can lead to locally chiral, though globally racemic, surfaces. A similar situation can be obtained for metal particles or clusters. Here we report the first separation of the enantiomers of a gold cluster protected by achiral thiolates, Au38(SCH2CH2Ph)24, achieved by chiral high-performance liquid chromatography. The chirality of the nanocluster arises from the chiral arrangement of the thiolates on its surface, forming 'staple motifs'. The enantiomers show mirror-image circular dichroism responses and large anisotropy factors of up to 4×10−3. Comparison with reported circular dichroism spectra of other Au38 clusters reveals that the influence of the ligand on the chiroptical properties is minor

Report on unexpected emissions of CFC-11

peer reviewedEXECUTIVE SUMMARY Global CFC-11 emissions were expected to decrease steadily after 2010 because of the full phaseout of production and consumption. Surprisingly, however, CFC-11 emissions began to increase in 2013 and were high from 2014 to 2018. After the publication of this emission increase in 2018, emissions were substantially lower in 2019. A large fraction of the emission increase was attributed to Eastern China based on regional emission estimates. These regional emissions also declined substantially from 2017 to 2019. The increase in global CFC-11 emissions was not a result of increased bank releases. The amounts of CFC-11 in banks and the release rates from the banks remain highly uncertain. The increases in emissions observed to date are small enough not to have a major impact on CFC-11 atmospheric abundances, so they will not have a major impact on the expected stratospheric ozone recovery. However, the increases in banks and how they might augment future emissions have large uncertainties

A Regression-based K nearest neighbor algorithm for gene function prediction from heterogeneous data

BACKGROUND: As a variety of functional genomic and proteomic techniques become available, there is an increasing need for functional analysis methodologies that integrate heterogeneous data sources. METHODS: In this paper, we address this issue by proposing a general framework for gene function prediction based on the k-nearest-neighbor (KNN) algorithm. The choice of KNN is motivated by its simplicity, flexibility to incorporate different data types and adaptability to irregular feature spaces. A weakness of traditional KNN methods, especially when handling heterogeneous data, is that performance is subject to the often ad hoc choice of similarity metric. To address this weakness, we apply regression methods to infer a similarity metric as a weighted combination of a set of base similarity measures, which helps to locate the neighbors that are most likely to be in the same class as the target gene. We also suggest a novel voting scheme to generate confidence scores that estimate the accuracy of predictions. The method gracefully extends to multi-way classification problems. RESULTS: We apply this technique to gene function prediction according to three well-known Escherichia coli classification schemes suggested by biologists, using information derived from microarray and genome sequencing data. We demonstrate that our algorithm dramatically outperforms the naive KNN methods and is competitive with support vector machine (SVM) algorithms for integrating heterogenous data. We also show that by combining different data sources, prediction accuracy can improve significantly. CONCLUSION: Our extension of KNN with automatic feature weighting, multi-class prediction, and probabilistic inference, enhance prediction accuracy significantly while remaining efficient, intuitive and flexible. This general framework can also be applied to similar classification problems involving heterogeneous datasets