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  • Articles  (15)
  • American Association for the Advancement of Science (AAAS)  (7)
  • American Heart Association (AHA)  (4)
  • The American Society for Biochemistry and Molecular Biology (ASBMB)  (4)
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  • Articles  (15)
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  • 1
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    Ice-nucleating bacteria control the order and dynamics of interfacial water (2016)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2016-04-28
    Description: Ice-nucleating organisms play important roles in the environment. With their ability to induce ice formation at temperatures just below the ice melting point, bacteria such as Pseudomonas syringae attack plants through frost damage using specialized ice-nucleating proteins. Besides the impact on agriculture and microbial ecology, airborne P. syringae can affect atmospheric glaciation processes, with consequences for cloud evolution, precipitation, and climate. Biogenic ice nucleation is also relevant for artificial snow production and for biomimetic materials for controlled interfacial freezing. We use interface-specific sum frequency generation (SFG) spectroscopy to show that hydrogen bonding at the water-bacteria contact imposes structural ordering on the adjacent water network. Experimental SFG data and molecular dynamics simulations demonstrate that ice-active sites within P. syringae feature unique hydrophilic-hydrophobic patterns to enhance ice nucleation. The freezing transition is further facilitated by the highly effective removal of latent heat from the nucleation site, as apparent from time-resolved SFG spectroscopy.
    Electronic ISSN: 2375-2548
    Topics: Natural Sciences in General
    Published by American Association for the Advancement of Science (AAAS)
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  • 2
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    Titin-Based Cardiac Myocyte Stiffening Contributes to Early Adaptive Ventricular Remodeling After Myocardial Infarction [Molecular Medicine] (2016)
    American Heart Association (AHA)
    Details
    Publication Date: 2016-10-14
    Description: Rationale: Myocardial infarction (MI) increases the wall stress in the viable myocardium and initiates early adaptive remodeling in the left ventricle to maintain cardiac output. Later remodeling processes include fibrotic reorganization that eventually leads to cardiac failure. Understanding the mechanisms that support cardiac function in the early phase post MI and identifying the processes that initiate transition to maladaptive remodeling are of major clinical interest. Objective: To characterize MI-induced changes in titin-based cardiac myocyte stiffness and to elucidate the role of titin in ventricular remodeling of remote myocardium in the early phase after MI. Methods and Results: Titin properties were analyzed in Langendorff-perfused mouse hearts after 20-minute ischemia/60-minute reperfusion (I/R), and mouse hearts that underwent ligature of the left anterior descending coronary artery for 3 or 10 days. Cardiac myocyte passive tension was significantly increased 1 hour after ischemia/reperfusion and 3 and 10 days after left anterior descending coronary artery ligature. The increased passive tension was caused by hypophosphorylation of the titin N2-B unique sequence and hyperphosphorylation of the PEVK (titin domain rich in proline, glutamate, valine, and lysine) region of titin. Blocking of interleukine-6 before left anterior descending coronary artery ligature restored titin-based myocyte tension after MI, suggesting that MI-induced titin stiffening is mediated by elevated levels of the cytokine interleukine-6. We further demonstrate that the early remodeling processes 3 days after MI involve accelerated titin turnover by the ubiquitin–proteasome system. Conclusions: We conclude that titin-based cardiac myocyte stiffening acutely after MI is partly mediated by interleukine-6 and is an important mechanism of remote myocardium to adapt to the increased mechanical demands after myocardial injury.
    Keywords: Ischemia, Myocardial Biology, Myocardial Infarction, Remodeling
    Print ISSN: 0009-7330
    Electronic ISSN: 1524-4571
    Topics: Medicine
    Published by American Heart Association (AHA)
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  • 3
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    Yap Localization during Mechanosensing Requires Filamentous Actin [Cell Biology] (2016)
    The American Society for Biochemistry and Molecular Biology (ASBMB)
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    Publication Date: 2016-03-19
    Description: Cell-cell contact inhibition and the mechanical environment of cells have both been shown to regulate YAP nuclear localization to modulate cell proliferation. Changes in cellular contractility by genetic, pharmacological, and matrix stiffness perturbations regulate YAP nuclear localization. However, because contractility and F-actin organization are interconnected cytoskeletal properties, it remains unclear which of these distinctly regulates YAP localization. Here we show that in the absence of cell-cell contact, actomyosin contractility suppresses YAP phosphorylation at Ser112, however, neither loss of contractility nor increase in YAP phosphorylation is sufficient for its nuclear exclusion. We find that actin cytoskeletal integrity is essential for YAP nuclear localization, and can override phosphoregulation or contractility-mediated regulation of YAP nuclear localization. This actin-mediated regulation is conserved during mechanotransduction, as substrate compliance increased YAP phosphorylation and reduced cytoskeletal integrity leading to nuclear exclusion of both YAP and Ser(P)112-YAP. These data provide evidence for two actin-mediated pathways for YAP regulation; one in which actomyosin contractility regulates YAP phosphorylation, and a second that involves cytoskeletal integrity-mediated regulation of YAP nuclear localization independent of contractility. We suggest that in non-contact inhibited cells, this latter mechanism may be important in low stiffness regimes, such as may be encountered in physiological environments.
    Print ISSN: 0021-9258
    Electronic ISSN: 1083-351X
    Topics: Biology , Chemistry and Pharmacology
    Published by The American Society for Biochemistry and Molecular Biology (ASBMB)
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  • 4
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    Species-specific Activation of Human TRPA1 by Protons [Neurobiology] (2013)
    The American Society for Biochemistry and Molecular Biology (ASBMB)
    Details
    Publication Date: 2013-07-13
    Description: The surveillance of acid-base homeostasis is concerted by diverse mechanisms, including an activation of sensory afferents. Proton-evoked activation of rodent sensory neurons is mainly mediated by the capsaicin receptor TRPV1 and acid-sensing ion channels. In this study, we demonstrate that extracellular acidosis activates and sensitizes the human irritant receptor TRPA1 (hTRPA1). Proton-evoked membrane currents and calcium influx through hTRPA1 occurred at physiological acidic pH values, were concentration-dependent, and were blocked by the selective TRPA1 antagonist HC030031. Both rodent and rhesus monkey TRPA1 failed to respond to extracellular acidosis, and protons even inhibited rodent TRPA1. Accordingly, mouse dorsal root ganglion neurons lacking TRPV1 only responded to protons when hTRPA1 was expressed heterologously. This species-specific activation of hTRPA1 by protons was reversed in both mouse and rhesus monkey TRPA1 by exchange of distinct residues within transmembrane domains 5 and 6. Furthermore, protons seem to interact with an extracellular interaction site to gate TRPA1 and not via a modification of intracellular N-terminal cysteines known as important interaction sites for electrophilic TRPA1 agonists. Our data suggest that hTRPA1 acts as a sensor for extracellular acidosis in human sensory neurons and should thus be taken into account as a yet unrecognized transduction molecule for proton-evoked pain and inflammation. The species specificity of this property is unique among known endogenous TRPA1 agonists, possibly indicating that evolutionary pressure enforced TRPA1 to inherit the role as an acid sensor in human sensory neurons.
    Print ISSN: 0021-9258
    Electronic ISSN: 1083-351X
    Topics: Biology , Chemistry and Pharmacology
    Published by The American Society for Biochemistry and Molecular Biology (ASBMB)
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  • 5
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    Characterization of the CagA-CagF Interaction [Molecular Biophysics] (2013)
    The American Society for Biochemistry and Molecular Biology (ASBMB)
    Details
    Publication Date: 2013-11-16
    Description: CagA is a virulence factor that Helicobacter pylori inject into gastric epithelial cells through a type IV secretion system where it can cause gastric adenocarcinoma. Translocation is dependent on the presence of secretion signals found in both the N- and C-terminal domains of CagA and an interaction with the accessory protein CagF. However, the molecular basis of this essential protein-protein interaction is not fully understood. Herein we report, using isothermal titration calorimetry, that CagA forms a 1:1 complex with a monomer of CagF with nm affinity. Peptide arrays and isothermal titration calorimetry both show that CagF binds to all five domains of CagA, each with μm affinity. More specifically, a coiled coil domain and a C-terminal helix within CagF contacts domains II-III and domain IV of CagA, respectively. In vivo complementation assays of H. pylori with a double mutant, L36A/I39A, in the coiled coil region of CagF showed a severe weakening of the CagA-CagF interaction to such an extent that it was nearly undetectable. However, it had no apparent effect on CagA translocation. Deletion of the C-terminal helix of CagF also weakened the interaction with CagA but likewise had no effect on translocation. These results indicate that the CagA-CagF interface is distributed broadly across the molecular surfaces of these two proteins to provide maximal protection of the highly labile effector protein CagA.
    Print ISSN: 0021-9258
    Electronic ISSN: 1083-351X
    Topics: Biology , Chemistry and Pharmacology
    Published by The American Society for Biochemistry and Molecular Biology (ASBMB)
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  • 6
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    Metaphosphate Stabilization in the Myosin ATPase [Enzymology] (2013)
    The American Society for Biochemistry and Molecular Biology (ASBMB)
    Details
    Publication Date: 2013-12-07
    Description: It has been proposed recently that ATP hydrolysis in ATPase enzymes proceeds via an initial intermediate in which the dissociated γ-phosphate of ATP is bound in the protein as a metaphosphate (PγO3−). A combined quantum/classical analysis of this dissociated nucleotide state inside myosin provides a quantitative understanding of how the enzyme stabilizes this unusual metaphosphate. Indeed, in vacuum, the energy of the ADP3−·PγO3−·Mg2+ complex is much higher than that of the undissociated ATP4−. The protein brings it to a surprisingly low value. Energy decomposition reveals how much each interaction in the protein stabilizes the metaphosphate state; backbone peptides of the P-loop contribute 50% of the stabilization energy, and the side chain of Lys-185+ contributes 25%. This can be explained by the fact that these groups make strong favorable interactions with the α- and β-phosphates, thus favoring the charge distribution of the metaphosphate state over that of the ATP state. Further stabilization (16%) is achieved by a hydrogen bond between the backbone C=O of Ser-237 (on loop Switch-1) and a water molecule perfectly positioned to attack the PγO3− in the subsequent hydrolysis step. The planar and singly negative PγO3− is a much better target for the subsequent nucleophilic attack by a negatively charged OH− than the tetrahedral and doubly negative PγO42− group of ATP. Therefore, we argue that the present mechanism of metaphosphate stabilization is common to the large family of nucleotide-hydrolyzing enzymes. Methodologically, this work presents a computational approach that allows us to obtain a truly quantitative conception of enzymatic strategy.
    Print ISSN: 0021-9258
    Electronic ISSN: 1083-351X
    Topics: Biology , Chemistry and Pharmacology
    Published by The American Society for Biochemistry and Molecular Biology (ASBMB)
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  • 7
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    Cell fusion potentiates tumor heterogeneity and reveals circulating hybrid cells that correlate with stage and survival (2018)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2018-09-13
    Description: High lethality rates associated with metastatic cancer highlight an urgent medical need for improved understanding of biologic mechanisms driving metastatic spread and identification of biomarkers predicting late-stage progression. Numerous neoplastic cell intrinsic and extrinsic mechanisms fuel tumor progression; however, mechanisms driving heterogeneity of neoplastic cells in solid tumors remain obscure. Increased mutational rates of neoplastic cells in stressed environments are implicated but cannot explain all aspects of tumor heterogeneity. We present evidence that fusion of neoplastic cells with leukocytes (for example, macrophages) contributes to tumor heterogeneity, resulting in cells exhibiting increased metastatic behavior. Fusion hybrids (cells harboring hematopoietic and epithelial properties) are readily detectible in cell culture and tumor-bearing mice. Further, hybrids enumerated in peripheral blood of human cancer patients correlate with disease stage and predict overall survival. This unique population of neoplastic cells provides a novel biomarker for tumor staging, as well as a potential therapeutic target for intervention.
    Electronic ISSN: 2375-2548
    Topics: Natural Sciences in General
    Published by American Association for the Advancement of Science (AAAS)
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  • 8
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    Coherent two-dimensional nanoscopy (2011)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2011-08-13
    Description: We introduce a spectroscopic method that determines nonlinear quantum mechanical response functions beyond the optical diffraction limit and allows direct imaging of nanoscale coherence. In established coherent two-dimensional (2D) spectroscopy, four-wave-mixing responses are measured using three ingoing waves and one outgoing wave; thus, the method is diffraction-limited in spatial resolution. In coherent 2D nanoscopy, we use four ingoing waves and detect the final state via photoemission electron microscopy, which has 50-nanometer spatial resolution. We recorded local nanospectra from a corrugated silver surface and observed subwavelength 2D line shape variations. Plasmonic phase coherence of localized excitations persisted for about 100 femtoseconds and exhibited coherent beats. The observations are best explained by a model in which coupled oscillators lead to Fano-like resonances in the hybridized dark- and bright-mode response.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Aeschlimann, Martin -- Brixner, Tobias -- Fischer, Alexander -- Kramer, Christian -- Melchior, Pascal -- Pfeiffer, Walter -- Schneider, Christian -- Struber, Christian -- Tuchscherer, Philip -- Voronine, Dmitri V -- New York, N.Y. -- Science. 2011 Sep 23;333(6050):1723-6. doi: 10.1126/science.1209206. Epub 2011 Aug 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Fachbereich Physik and Research Center OPTIMAS, Technische Universitat Kaiserslautern, Erwin-Schrodinger-Str. 46, 67663 Kaiserslautern, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21835982" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 9
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    Two-Dimensional Global Longitudinal Strain Rate Is a Preload Independent Index of Systemic Right Ventricular Contractility in Hypoplastic Left Heart Syndrome Patients After Fontan Operation [Congenital Heart Disease] (2014)
    American Heart Association (AHA)
    Details
    Publication Date: 2014-11-19
    Description: Background— Assessment of systemic right ventricular (RV) function in patients with hypoplastic left heart syndrome is important during long-term follow-up after Fontan repair. Traditional echocardiographic parameters to evaluate systolic ventricular function are affected by loading conditions. The only generally accepted load-independent parameter of systolic function, end systolic elastance ( E es ), requires invasive catheterization. Therefore, we sought to determine if parameters obtained by 2-dimensional speckle tracking (2DST) were affected by acute changes in preload and correlated with catheterization-derived indices of RV contractility in hypoplastic left heart syndrome patients after Fontan palliation. Methods and Results— Fifty-two patients with hypoplastic left heart syndrome (median age, 6.6; range 2.9–22.2 years) were prospectively enrolled to have echocardiography and conductance catheter studies performed simultaneously. We compared traditional echo, 2-dimensional speckle tracking and catheterization-derived parameters during different states of preload at baseline and during dobutamine infusion. Global longitudinal strain (S) showed a tendency to decrease with preload reduction, whereas global longitudinal strain rate (SR) did not change (S: –17.7±3.4% versus –16.9±3.8%, P =0.08; SR: –1.30±0.29 versus –1.34±0.34 s –1 , P =0.3). S did not change with dobutamine infusion (–17.7±3.4% versus –18.4±3.9%, P =0.24), whereas SR increased significantly (–1.30±0.29 versus –2.26±0.49 s –1 , P 〈0.001). RV E es correlated with SR ( r s = –0.47, P 〈0.001), but not with S ( r s =0.07, P =0.5) or other echocardiographic parameters. Conclusions— In contrast to S, SR was not affected by preload and correlated with E es of the systemic RV. SR may be a useful noninvasive surrogate of RV contractility and suitable for follow-up of patients with hypoplastic left heart syndrome after Fontan palliation.
    Keywords: Echocardiography, Other diagnostic testing, Pediatric and congenital heart disease, including cardiovascular surgery
    Print ISSN: 1941-9651
    Electronic ISSN: 1942-0080
    Topics: Medicine
    Published by American Heart Association (AHA)
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  • 10
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    Trends in Use and Adverse Outcomes Associated with Transvenous Lead Removal in the United States [Arrhythmia/Electrophysiology] (2015)
    American Heart Association (AHA)
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    Publication Date: 2015-12-24
    Description: Background— Transvenous lead removal (TLR) has made significant progress with respect to innovation, efficacy, and safety. However, limited data exist regarding trends in use and adverse outcomes outside the centers of considerable experience for TLR. The aim of our study was to examine use patterns, frequency of adverse events, and influence of hospital volume on complications. Methods and Results— Using the Nationwide Inpatient Sample, we identified 91 890 TLR procedures. We investigated common complications including pericardial complications (hemopericardium, cardiac tamponade, or pericardiocentesis), pneumothorax, stroke, vascular complications (consisting of hemorrhage/hematoma, incidents requiring surgical repair, and accidental arterial puncture), and in-hospital deaths described with TLR, defining them by the validated International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis code. We specifically assessed in-hospital death (2.2%), hemorrhage requiring transfusion (2.6%), vascular complications (2.0%), pericardial complications (1.4%), open heart surgery (0.2%), and postoperative respiratory failure (2.4%). Independent predictors of complications were female sex and device infections. Hospital volume was not independently associated with higher complications. There was a significant rise in overall complication rates over the study period. Conclusions— The overall complication rate in patients undergoing TLR was higher than previously reported. Female sex and device infections are associated with higher complications. Hospital volume was not associated with higher complication rates. The number of adverse events in the literature likely underestimates the actual number of complications associated with TLR.
    Keywords: Arrhythmias, Catheter Ablation and Implantable Cardioverter-Defibrillator, Electrophysiology, Quality and Outcomes
    Electronic ISSN: 1524-4539
    Topics: Medicine
    Published by American Heart Association (AHA)
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