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  • 1
    Publication Date: 2017-06-02
    Description: Myocardial blood flow (MBF) is the critical determinant of cardiac function. However, its response to increases in partial pressure of arterial CO 2 (PaCO 2 ), particularly with respect to adenosine, is not well characterized because of challenges in blood gas control and limited availability of validated approaches to ascertain MBF in vivo. Methods: By prospectively and independently controlling PaCO 2 and combining it with 13 N-ammonia PET measurements, we investigated whether a physiologically tolerable hypercapnic stimulus (~25 mm Hg increase in PaCO 2 ) can increase MBF to that observed with adenosine in 3 groups of canines: without coronary stenosis, subjected to non–flow-limiting coronary stenosis, and after preadministration of caffeine. The extent of effect on MBF due to hypercapnia was compared with adenosine. Results: In the absence of stenosis, mean MBF under hypercapnia was 2.1 ± 0.9 mL/min/g and adenosine was 2.2 ± 1.1 mL/min/g; these were significantly higher than at rest (0.9 ± 0.5 mL/min/g, P 〈 0.05) and were not different from each other ( P = 0.30). Under left-anterior descending coronary stenosis, MBF increased in response to hypercapnia and adenosine ( P 〈 0.05, all territories), but the effect was significantly lower than in the left-anterior descending coronary territory (with hypercapnia and adenosine; both P 〈 0.05). Mean perfusion defect volumes measured with adenosine and hypercapnia were significantly correlated ( R = 0.85) and were not different ( P = 0.12). After preadministration of caffeine, a known inhibitor of adenosine, resting MBF decreased; and hypercapnia increased MBF but not adenosine ( P 〈 0.05). Conclusion: Arterial blood CO 2 tension when increased by 25 mm Hg can induce MBF to the same level as a standard dose of adenosine. Prospectively targeted arterial CO 2 has the capability to evolve as an alternative to current pharmacologic vasodilators used for cardiac stress testing.
    Print ISSN: 0022-3123
    Topics: Medicine
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  • 2
    Publication Date: 2017-05-12
    Description: The integration of endocytic routes is critical to regulate receptor signaling. A nonclathrin endocytic (NCE) pathway of the epidermal growth factor receptor (EGFR) is activated at high ligand concentrations and targets receptors to degradation, attenuating signaling. Here we performed an unbiased molecular characterization of EGFR-NCE. We identified NCE-specific regulators, including the endoplasmic reticulum (ER)–resident protein reticulon 3 (RTN3) and a specific cargo, CD147. RTN3 was critical for EGFR/CD147-NCE, promoting the creation of plasma membrane (PM)–ER contact sites that were required for the formation and/or maturation of NCE invaginations. Ca 2+ release at these sites, triggered by inositol 1,4,5-trisphosphate (IP 3 )–dependent activation of ER Ca 2+ channels, was needed for the completion of EGFR internalization. Thus, we identified a mechanism of EGFR endocytosis that relies on ER-PM contact sites and local Ca 2+ signaling.
    Keywords: Cell Biology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Geosciences , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2017-10-18
    Description: This study was aimed at improving the functional attributes and shelf life of burrata cheese by using protective lactobacilli ( Lactobacillus plantarum LPAL and Lactobacillus rhamnosus LRB), fructooligosaccharides, and inulin. Six burrata cheeses were made using (i) the traditional protocol (control), (ii) the addition of 0.5% fructooligosaccharides and inulin (DF cheese), (iii) protective lactobacilli in milk alone (PL cheese), (iv) protective lactobacilli in milk and governing liquid (2PL cheese), (v) protective lactobacilli in milk and dietary fibers (DF_PL cheese), and (vi) protective lactobacilli in milk and governing liquid and dietary fibers (DF_2PL cheese). As expected, DF, DF_PL, and DF_2PL cheeses showed 1.5% of total fibers. Burrata cheeses produced by adding protective lactobacilli only in milk (PL and DF_PL cheeses) showed the lowest acidification during cheese making and storage. Lactic and acetic acids and ethanol were found at the lowest concentrations in these samples. Analyses of cultivable microbiota and the microbiome showed that protective lactobacilli reduced the house microbiota components (e.g., Streptococcus thermophilus , Lactococcus lactis , and Leuconostoc lactis ) during cheese making and storage. Protective lactobacilli slowed the growth of staphylococci, coliforms, and Pseudomonas spp., especially in early storage. According to the different microbiome assemblies, burrata samples differed in peptide profiles and the levels of free amino acids. As shown by a sensory analysis, the addition of protective lactobacilli in milk improved the flavor and increased the shelf life of burrata cheese. In comparison to cheeses made using protective cultures only in milk, the shelf lives of those containing cultures also in the governing liquid were not further prolonged and they received lower acceptability scores by the panelists. IMPORTANCE This study provides more in-depth knowledge of the microbiome of burrata cheese and the set-up for a novel biotechnology using prebiotic dietary fibers and protective probiotic Lactobacillus plantarum LPAL and Lactobacillus rhamnosus LRB in milk. The biotechnology proposed in this study should be considered a useful tool to improve the functional value of burrata cheese. The use of protective lactobacilli in milk enhanced the flavor formation and shelf life of burrata cheese.
    Print ISSN: 0099-2240
    Electronic ISSN: 1098-5336
    Topics: Biology
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  • 4
    Publication Date: 2017-07-04
    Description: Purpose: LKB1 is a key sensor of metabolic stress, including hypoxia and glucose deprivation, two features of the tumor microenvironment exacerbated by antiangiogenic therapy. We investigated the role of LKB1 as a potential predictive marker of sensitivity to bevacizumab in advanced non–small cell lung cancer (aNSCLC). Experimental design: We retrospectively analyzed LKB1 expression by IHC in 98 samples from 125 patients with aNSCLC, including 59 patients treated with chemotherapy and 39 treated with chemotherapy plus bevacizumab. IHC intensity was recoded in two classes (negative/weak vs. moderate/intense) and correlated with outcome according to treatment arm. Patient-derived tumor xenografts (PDXs) were used to investigate mechanisms involved in preclinical models. Results: In the whole study population (125), median OS and PFS were 11.7 [95% confidence interval (CI), 9.1–15.3] and 6.7 (95% CI, 5.7–7.2) months, respectively. Differential impact of the marker on outcome of the 98 patients was highlighted according to the treatment. Patients with negative/weak LKB1 status did not have a statistically significant benefit from bevacizumab added to chemotherapy (HR for patients treated with bevacizumab: 0.89; 95% CI, 0.51–1.56; P = 0.6803), whereas patients expressing moderate/intense LKB1 and receiving bevacizumab had significant lower risk of death compared with those not receiving bevacizumab (HR, 0.26; 95% CI, 0.10–0.64; P = 0.0035). Loss of LKB1 was associated with reduced AMPK activation in PDXs and increased tumor necrosis following bevacizumab administration, highlighting impaired control of the metabolic stress caused by this antiangiogenic drug. Conclusions: Our data hint at a possible predictive impact of LKB1 expression in patients with aNSCLC treated with chemotherapy plus bevacizumab. Clin Cancer Res; 23(13); 3316–24. ©2017 AACR .
    Print ISSN: 1078-0432
    Electronic ISSN: 1557-3265
    Topics: Medicine
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  • 5
    Publication Date: 2016-10-18
    Description: Adherent/invasive Escherichia coli (AIEC) strains have recently been receiving increased attention because they are more prevalent and persistent in the intestine of Crohn's disease (CD) patients than in healthy subjects. Since AIEC strains show a high percentage of similarity to extraintestinal pathogenic E. coli (ExPEC), neonatal meningitis-associated E. coli (NMEC), and uropathogenic E. coli (UPEC) strains, here we compared AIEC strain LF82 with a UPEC isolate (strain EC73) to assess whether LF82 would be able to infect prostate cells as an extraintestinal target. The virulence phenotypes of both strains were determined by using the RWPE-1 prostate cell line. The results obtained indicated that LF82 and EC73 are able to adhere to, invade, and survive within prostate epithelial cells. Invasion was confirmed by immunofluorescence and electron microscopy. Moreover, cytochalasin D and colchicine strongly inhibited bacterial uptake of both strains, indicating the involvement of actin microfilaments and microtubules in host cell invasion. Moreover, both strains belong to phylogenetic group B2 and are strong biofilm producers. In silico analysis reveals that LF82 shares with UPEC strains several virulence factors: namely, type 1 pili, the group II capsule, the vacuolating autotransporter toxin, four iron uptake systems, and the pathogenic island (PAI). Furthermore, compared to EC73, LF82 induces in RWPE-1 cells a marked increase of phosphorylation of mitogen-activated protein kinases (MAPKs) and of NF-B already by 5 min postinfection, thus inducing a strong inflammatory response. Our in vitro data support the hypothesis that AIEC strains might play a role in prostatitis, and, by exploiting host-cell signaling pathways controlling the innate immune response, likely facilitate bacterial multiplication and dissemination within the male genitourinary tract.
    Print ISSN: 0019-9567
    Electronic ISSN: 1098-5522
    Topics: Medicine
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  • 6
    Publication Date: 2016-11-23
    Description: Discoveries from multibeam bathymetry and geochemical surveys performed off Zannone Island (western Pontine Archipelago, Tyrrhenian Sea) provide evidence of an undocumented hydrothermal field characterized by ongoing fluid emissions and morphologically complex giant depressions located in shallow water (〈150 m water depth). Based on a detailed morpho-bathymetric study we identify the seabed morphologies produced by hydrothermal fluid emission activity. We recognize five giant depressions (length 〉250 m) that host pockmarks, mounds, small cones and active fluid vents, and which are interpreted as complex fluid escape features developed both through vigorous-explosive events and steady seepage. Their spatial distribution suggests that the NE-SW trending faults bounding the Ponza-Zannone structural high and the shallow fractured basement are favorable conditions for the upward migration of hydrothermal fluids. Moreover, we performed a detailed geochemical study to investigate the source of the hydrothermal fluids. The geochemical signature of the collected fluids provides information of active CO 2 -dominated degassing with a significant contribution of mantle volatiles, with measured 3 He/ 4 He values 〉 3.0 Ra that are similar to those recorded at Stromboli and Panarea volcanoes. The hydrothermal system produces volatiles that may originate from residual magma batches, similar to the Pleistocene trachytes cropping out in the SE sector of Ponza Island, that were probably intruded in the shallow crustal levels and never erupted. The discovery of the Zannone hydrothermal field updates the record of active hydrothermal areas of the Mediterranean Sea. Moreover, the recognition of several giant hydrothermal depressions characterized by a complex morphology is peculiar for the Mediterranean Sea.
    Print ISSN: 0148-0227
    Topics: Geosciences , Physics
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  • 7
    Publication Date: 2018-03-27
    Description: Author(s): G. V. Karnad, C. Gorini, K. Lee, T. Schulz, R. Lo Conte, A. W. J. Wells, D.-S. Han, K. Shahbazi, J.-S. Kim, T. A. Moore, H. J. M. Swagten, U. Eckern, R. Raimondi, and M. Kläui We measure and analyze the effective spin Hall angle of platinum in the low-residual resistivity regime by second-harmonic measurements of the spin-orbit torques for a multilayer of Pt | Co | AlO x . An angular-dependent study of the torques allows us to extract the effective spin Hall angle responsible f... [Phys. Rev. B 97, 100405(R)] Published Mon Mar 26, 2018
    Keywords: Magnetism
    Print ISSN: 1098-0121
    Electronic ISSN: 1095-3795
    Topics: Physics
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  • 8
    Publication Date: 2021-11-08
    Description: Discoveries from multibeam bathymetry and geochemical surveys performed off Zannone Island (western Pontine Archipelago, Tyrrhenian Sea) provide evidence of an undocumented hydrothermal field characterized by ongoing fluid emissions and morphologically complex giant depressions located in shallow water (〈150m water depth). Based on a detailed morpho-bathymetric study we identify the seabed morphologies produced by hydrothermal fluid emission activity. We recognize five giant depressions (length 〉250 m) that host pockmarks, mounds, small cones, and active fluid vents, which are interpreted as complex fluid-escape features developed both through vigorous-explosive events and steady seepage. Their spatial distribution suggests that the NE-SW trending faults bounding the Ponza-Zannone structural high and the shallow fractured basement are favorable conditions for the upward migration of hydrothermal fluids. Moreover, we performed a detailed geochemical study to investigate the source of the hydrothermal fluids. The geochemical signature of the collected fluids provides information of active CO2-dominated degassing with a significant contribution of mantle volatiles, with measured 3He/4He values〉3.0 Ra that are similar to those recorded at Stromboli and Panarea volcanoes. The hydrothermal system produces volatiles that may originate from residual magma batches, similar to the Pleistocene trachytes cropping out in the SE sector of Ponza Island that were probably intruded in the shallow crustal levels and never erupted. The discovery of the Zannone hydrothermal field updates the record of active hydrothermal areas of the Mediterranean Sea. Moreover, the recognition of several giant hydrothermal depressions characterized by a complex morphology is peculiar for the Mediterranean Sea.
    Description: Published
    Description: 8396-8414
    Description: 5V. Dinamica dei processi eruttivi e post-eruttivi
    Description: JCR Journal
    Keywords: gas geochemistry ; submarine hydrothermalism ; Quaternary volcanism ; Pontine islands ; geochemical characterization submarine vents
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
    Type: article
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