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Single Molecule
Imaging mRNA and protein interactions within neurons
Feb 22, 2017   Proceedings Of The National Academy Of Sciences Of The United States Of America
Eliscovich C, Shenoy SM, Singer RH
Imaging mRNA and protein interactions within neurons
Feb 22, 2017
Proceedings Of The National Academy Of Sciences Of The United States Of America
UNASSIGNED: RNA-protein interactions are essential for proper gene expression regulation, particularly in neurons with unique spatial constraints. Currently, these interactions are defined biochemically, but a method is needed to evaluate them quantitatively within morphological context. Colocalization of two-color labels using wide-field microscopy is a method to infer these interactions. However, because of chromatic aberrations in the objective lens, this approach lacks the resolution to determine whether two molecules are physically in contact or simply nearby by chance. Here, we developed a robust super registration methodology that corrected the chromatic aberration across the entire image field to within 10 nm, which is capable of determining whether two molecules are physically interacting or simply in proximity by random chance. We applied this approach to image single-molecule FISH in combination with immunofluorescence (smFISH-IF) and determined whether the association between an mRNA and binding protein(s) within a neuron was significant or accidental. We evaluated several mRNA-binding proteins identified from RNA pulldown assays to determine which of these exhibit bona fide interactions. Surprisingly, many known mRNA-binding proteins did not bind the mRNA in situ, indicating that adventitious interactions are significant using existing technology. This method provides an ability to evaluate two-color registration compatible with the scale of molecular interactions.
Integrated view of internal friction in unfolded proteins from single-molecule FRET, contact quenching, theory, and simulations
Feb 22, 2017   Proceedings Of The National Academy Of Sciences Of The United States Of America
Soranno A, Holla A, Dingfelder F, Nettels D, Makarov DE, Schuler B
Integrated view of internal friction in unfolded proteins from single-molecule FRET, contact quenching, theory, and simulations
Feb 22, 2017
Proceedings Of The National Academy Of Sciences Of The United States Of America
UNASSIGNED: Internal friction is an important contribution to protein dynamics at all stages along the folding reaction. Even in unfolded and intrinsically disordered proteins, internal friction has a large influence, as demonstrated with several experimental techniques and in simulations. However, these methods probe different facets of internal friction and have been applied to disparate molecular systems, raising questions regarding the compatibility of the results. To obtain an integrated view, we apply here the combination of two complementary experimental techniques, simulations, and theory to the same system: unfolded protein L. We use single-molecule Förster resonance energy transfer (FRET) to measure the global reconfiguration dynamics of the chain, and photoinduced electron transfer (PET), a contact-based method, to quantify the rate of loop formation between two residues. This combination enables us to probe unfolded-state dynamics on different length scales, corresponding to different parts of the intramolecular distance distribution. Both FRET and PET measurements show that internal friction dominates unfolded-state dynamics at low denaturant concentration, and the results are in remarkable agreement with recent large-scale molecular dynamics simulations using a new water model. The simulations indicate that intrachain interactions and dihedral angle rotation correlate with the presence of internal friction, and theoretical models of polymer dynamics provide a framework for interrelating the contribution of internal friction observed in the two types of experiments and in the simulations. The combined results thus provide a coherent and quantitative picture of internal friction in unfolded proteins that could not be attained from the individual techniques.
Identification of a
Feb 22, 2017   MBio
Doberenz S, Eckweiler D, Reichert O, Jensen V, Bunk B, Spröer C, Kordes A, Frangipani E, Luong K, Korlach J, Heeb S, Overmann J, Kaever V, Häussler S
Identification of a
Feb 22, 2017
MBio
UNASSIGNED: DNA methylation is widespread among prokaryotes, and most DNA methylation reactions are catalyzed by adenine DNA methyltransferases, which are part of restriction-modification (R-M) systems. R-M systems are known for their role in the defense against foreign DNA; however, DNA methyltransferases also play functional roles in gene regulation. In this study, we used single-molecule real-time (SMRT) sequencing to uncover the genome-wide DNA methylation pattern in the opportunistic pathogen Copyright © 2017 Doberenz et al.
The focal adhesion targeting (FAT) domain of p130 Crk associated substrate (p130Cas) confers mechanosensing function
Feb 22, 2017   Journal Of Cell Science
Bradbury PM, Turner K, Mitchell C, Griffin KR, Middlemiss S, Lau L, Dagg R, Taran E, Cooper-White J, Fabry B, O'Neill GM
The focal adhesion targeting (FAT) domain of p130 Crk associated substrate (p130Cas) confers mechanosensing function
Feb 22, 2017
Journal Of Cell Science
UNASSIGNED: The Cas family of focal adhesion proteins contain a highly conserved C-terminal focal adhesion targeting (FAT) domain. To determine the role of the FAT domain we compared wildtype exogenous NEDD9 with a hybrid construct in which the NEDD9 FAT domain is exchanged for the p130Cas FAT domain. Fluorescence recovery after photobleaching (FRAP) revealed significantly slowed exchange of the fusion protein at focal adhesions and significantly slower 2D migration. No differences were detected in cell stiffness measured with Atomic Force Microscopy (AFM) and cell adhesion forces measured with a magnetic tweezer device. Thus the slowed migration was not due to changes in cell stiffness or adhesion strength. Analysis of cell migration on surfaces of increasing rigidity revealed a striking reduction of cell motility in cells expressing the p130Cas FAT domain. The p130Cas FAT domain induced rigidity-dependent tyrosine phosphorylation of the NEDD9 substrate domain. This in turn reduced post-translational cleavage of NEDD9 which we show inhibits NEDD9-induced migration. Collectively, our data therefore suggest that the p130Cas FAT domain uniquely confers mechanosensing function. © 2017. Published by The Company of Biologists Ltd.
Nanomechanics of pH-Responsive, Drug-loaded, Bi-layered Polymer Grafts
Feb 21, 2017   ACS Applied Materials & Interfaces
Nalam PC, Lee HS, Bhatt N, Carpick RW, Eckmann DM, Composto RJ
Nanomechanics of pH-Responsive, Drug-loaded, Bi-layered Polymer Grafts
Feb 21, 2017
ACS Applied Materials & Interfaces
UNASSIGNED: Stimuli-responsive polymer films play an important role in the development of smart antibacterial coatings. In this study, we consider complementary architectures of polyelectrolyte films including a thin chitosan layer (CH), poly (acrylic acid) (PAA) brushes and a bilayer structure of CH grafted to PAA brushes (CH/PAA) as possible candidates for targeted drug delivery platforms. Atomic force microscopy (AFM) was employed to study the structure-mechanical property relationship for these mono- and bi- layered polymer grafts at pH 7.4 and pH 4.0, corresponding to physiological and biofilm formation conditions, respectively. Herein, the surface interactions between polymer grafts and the negatively-charged silica colloid attached to an AFM lever are considered as representative interactions between the antibacterial coating and a bacteria/biofilm. The bi-layered structure of CH/PAA showed significantly reduced adhesive interactions in comparison to pure CH but slightly higher interactions in comparison to PAA films. Among PAA and CH/PAA films, upon grafting CH over the PAA brushes the normal stiffness increased by 10 fold at pH 7.4 and 20 fold at pH 4.0. Notably, the study also showed that the addition of an antibiotic drug such as multi-cationic Tobramycin (TOB) impacts the mechanical properties of the antibacterial coatings. Competition between TOB and water molecules for the PAA chains is shown to determine the structural properties of PAA and CH/PAA films loaded with TOB. At high pH (7.4), the TOB molecules, which remain multi-cationic, strongly interact with polyanionic PAA thereby reducing the film's compressibility. On contrary at low pH (4.0), the water molecules preferentially interact with TOB in comparison to uncharged PAA chains and upon TOB release, results in a stronger film collapse together with an increase in adhesive interactions between the probe and the surface and the elastic modulus of the film. The bacterial proliferation on these platforms when compared to the measured mechanical properties shows a direct correlation and hence understanding nano-mechanical properties can provide insights into designing new antibacterial polymer coatings.
Molecular Seesaw: Intricate Dynamics and Versatile Chemistry of Heteroaromatics on Metal Surfaces
Feb 23, 2017   The Journal Of Physical Chemistry Letters
Filimonov SN, Liu W, Tkatchenko A
Molecular Seesaw: Intricate Dynamics and Versatile Chemistry of Heteroaromatics on Metal Surfaces
Feb 23, 2017
The Journal Of Physical Chemistry Letters
The design of novel elementary surface processes is important for applications in catalysis, single-molecule junctions, molecular sensors, switches and surface mounted molecular machines. Here we demonstrate by van der Waals inclusive density functional theory calculations that a small and relatively simple heteroaromatic compound s-triazine (C$_3$H$_3$N$_3$) unexpectedly possesses five metastable states when adsorbed on the Pt(111) surface. This diversity of the adsorption states stems from an interplay between versatile molecule/surface chemical bonding and van der Waals interactions and from ``softening'' of the aromatic ring by nitrogen substitution, which makes folding of the aromatic ring energetically much less demanding as compared to benzene. The intricate seesaw-like surface dynamics and tunable electronic structure of s-triazine show promise for applications in molecular sensors and switches. The broad implications of our findings are demonstrated for triazine- and pyrimidine-based heteroaromatic compounds and other metal surfaces.
Epitopes and Mechanism of Action of the Clostridium Difficile Toxin A-Neutralizing Antibody Actoxumab
Feb 24, 2017   Journal Of Molecular Biology
Hernandez LD, Kroh HK, Hsieh E, Yang X, Beaumont M,   . . . . . .   , Fischer P, Sher X, Gupta P, Lacy DB, Therien AG
Epitopes and Mechanism of Action of the Clostridium Difficile Toxin A-Neutralizing Antibody Actoxumab
Feb 24, 2017
Journal Of Molecular Biology
The exotoxins TcdA and TcdB are produced by the bacterial pathogen Clostridium difficile and are responsible for the pathology associated with C. difficile infection (CDI). The antitoxin antibodies actoxumab and bezlotoxumab bind to and neutralize TcdA and TcdB, respectively. Bezlotoxumab was recently approved by the FDA for reducing the recurrence of CDI. We have previously shown that a single molecule of bezlotoxumab binds to two distinct epitopes within the TcdB CROP domain preventing toxin binding to host cells. In this study we characterize the binding of actoxumab to TcdA and examine its mechanism of toxin neutralization. Using a combination of approaches including a number of biophysical techniques, we show there are 2 distinct actoxumab binding sites within the CROP domain of TcdA centered around identical amino acid sequences at residues 2162-2189 and 2410-2437. Actoxumab binding caused aggregation of TcdA especially at higher antibody:toxin concentration ratios. Actoxumab prevented association of TcdA with target cells demonstrating that actoxumab neutralizes toxin activity by inhibiting the first step of the intoxication cascade. This mechanism of neutralization is similar to that observed with bezlotoxumab and TcdB. Comparisons of the putative TcdA epitope sequences across several C. difficile ribotypes and homologous repeat sequences within TcdA suggest a structural basis for observed differences in actoxumab binding and/or neutralization potency. These data provide a mechanistic basis for the protective effects of the antibody in vitro and in vivo, including in various preclinical models of CDI.Copyright © 2017. Published by Elsevier Ltd.
Confining Cation Injection to Enhance CBRAM Performance by Nanopore Graphene Layer
Feb 24, 2017   Small (Weinheim An Der Bergstrasse, Germany)
Zhao X, Liu S, Niu J, Liao L, Liu Q, Xiao X, Lv H, Long S, Banerjee W, Li W, Si S, Liu M
Confining Cation Injection to Enhance CBRAM Performance by Nanopore Graphene Layer
Feb 24, 2017
Small (Weinheim An Der Bergstrasse, Germany)
Conductive-bridge random access memory (CBRAM) is considered a strong contender of the next-generation nonvolatile memory technology. Resistive switching (RS) behavior in CBRAM is decided by the formation/dissolution of nanoscale conductive filament (CF) inside RS layer based on the cation injection from active electrode and their electrochemical reactions. Remarkably, RS is actually a localized behavior, however, cation injects from the whole area of active electrode into RS layer supplying excessive cation beyond the requirement of CF formation, leading to deterioration of device uniformity and reliability. Here, an effective method is proposed to localize cation injection into RS layer through the nanohole of inserted ion barrier between active electrode and RS layer. Taking an impermeable monolayer graphene as ion barrier, conductive atomic force microscopy results directly confirm that CF formation is confined through the nanohole of graphene due to the localized cation injection. Compared with the typical Cu/HfO© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Hydrophilicities of amylose and natural cellulose are regulated by the linkage between sugar rings
Feb 24, 2017   Nanoscale
Bao Y, Xu D, Qian L, Zhao L, Lu ZY, Cui S
Hydrophilicities of amylose and natural cellulose are regulated by the linkage between sugar rings
Feb 24, 2017
Nanoscale
Comparative studies of single molecule force spectroscopy and molecular dynamics simulations indicate that natural cellulose is more hydrophobic than amylose at the single-chain level, implying that the hydrophobicities of these polymeric isomers are regulated by only one parameter in the chains, the linkage between the sugar rings.
Phthalocyanine supported dinuclear Ln
Feb 24, 2017   Dalton Transactions (Cambridge, England : 2003)
Ge JY, Wang HY, Li J, Xie JZ, Song Y, Zuo JL
Phthalocyanine supported dinuclear Ln
Feb 24, 2017
Dalton Transactions (Cambridge, England : 2003)
Three dinuclear lanthanide complexes, [Ln
High-bandwidth nanopore data analysis by using a modified hidden Markov model
Feb 24, 2017   Nanoscale
Zhang J, Liu X, Ying YL, Gu Z, Meng FN, Long YT
High-bandwidth nanopore data analysis by using a modified hidden Markov model
Feb 24, 2017
Nanoscale
Nanopore-based sensing is an emerging analytical technique with a number of important applications, including single-molecule detection and DNA sequencing. In this paper, we developed a Modified Hidden Markov Model (MHMM) to analyze directly the raw (unfiltered) nanopore current blockade data, which significantly reduced the filtering-induced distortion of the nanopore events. Traditionally, prior to further analysis, the measured nanopore data need to be pre-filtered to supress the strong noises. Nonetheless, this would result in the distortion of the shape of the blockade current especially for rapid translocations and bumping blockades. The HMM has been proved to be robust with respect to highly noisy data and thus ideally suitable for processing raw nanopore data directly. Unfortunately, its performance is somehow sensitive to the initial parameters usually preset arbitrarily. To overcome this problem, we use the Fuzzy c-Means (FCM) algorithm to initialize the HMM parameters automatically. Then we use the Viterbi training algorithm to optimize the HMM. Finally, the application results on both the simulated and experimental data are presented to demonstrate the practicability of the developed method for accurate detection of the nanopore current blockade events. The proposed method enables detection of the nanopore events at the highest bandwidth of the commercial instruments to extract the true useful information about the single molecules under analysis.
Comprehensive profiling and quantitation of oncogenic mutations in non-small cell lung carcinoma using single-molecule amplification and re-sequencing technology
Feb 20, 2017   Tumour Biology : The Journal Of The International Society For Oncodevelopmental Biology And Medicine
Shi J, Yuan M, Wang ZD, Xu XL, Hong L, Sun S
Comprehensive profiling and quantitation of oncogenic mutations in non-small cell lung carcinoma using single-molecule amplification and re-sequencing technology
Feb 20, 2017
Tumour Biology : The Journal Of The International Society For Oncodevelopmental Biology And Medicine
UNASSIGNED: The carcinogenesis of non-small cell lung carcinoma has been found to associate with activating and resistant mutations in the tyrosine kinase domain of specific oncogenes. Here, we assessed the type, frequency, and abundance of epithelial growth factor receptor, KRAS, BRAF, and ALK mutations in 154 non-small cell lung carcinoma specimens using single-molecule amplification and re-sequencing technology. We found that epithelial growth factor receptor mutations were the most prevalent (44.2%), followed by KRAS (18.8%), ALK (7.8%), and BRAF (5.8%) mutations. The type and abundance of the mutations in tumor specimens appeared to be heterogeneous. Thus, we conclude that identification of clinically significant oncogenic mutations may improve the classification of patients and provide valuable information for determination of the therapeutic strategies.
Telomerase Activity Detection with Amplification-Free Single Molecule Stochastic Binding Assay
Feb 20, 2017   Analytical Chemistry
Su X, Li Z, Yan X, Wang L, Zhou X, Wei L, Xiao L, Yu C
Telomerase Activity Detection with Amplification-Free Single Molecule Stochastic Binding Assay
Feb 20, 2017
Analytical Chemistry
UNASSIGNED: Since the elongation of telomeres is associated with tumorigenesis, it is of great interest to develop rapid and high-confidence telomerase activity detection methods for disease diagnosis. Currently, amplification based strategies have been extensively explored for telomerase detection in vitro and in vivo. However, amplification typically associated with poor reproducibility and high background which hamper their further applications particularly for real sample assay. Here, we demonstrated a new amplification-free single molecule imaging method for telomerase activity detection in vitro based on nucleic acid stochastic binding with total internal reflection fluorescence microscopy (TIRFM). The dynamic stochastic binding of short fluorescent DNA probe with genuine target yields a distinct kinetic signature from the background noise, allowing us to identify telomerase reaction products (TRPs) at single molecule level. A limit-of-detection (LOD) as low as 0.5 fM and a dynamic range of 0.5-500 fM for TRPs detection were readily achieved. With this method, telomerase extracted from cancer cells was determined with sensitivity down to 10 cells. Moreover, the length distribution of TRPs was also determined by multiple stochastic probing which would provide deep insight into the mechanism study of telomerase catalysis.
Atomic structure of granulin determined from native nanocrystalline granulovirus using an X-ray free-electron laser
Feb 16, 2017   Proceedings Of The National Academy Of Sciences Of The United States Of America
Gati C, Oberthuer D, Yefanov O, Bunker RD, Stellato F,   . . . . . .   , Goldie KN, Jehle JA, Metcalf P, Barty A, Chapman HN
Atomic structure of granulin determined from native nanocrystalline granulovirus using an X-ray free-electron laser
Feb 16, 2017
Proceedings Of The National Academy Of Sciences Of The United States Of America
UNASSIGNED: To understand how molecules function in biological systems, new methods are required to obtain atomic resolution structures from biological material under physiological conditions. Intense femtosecond-duration pulses from X-ray free-electron lasers (XFELs) can outrun most damage processes, vastly increasing the tolerable dose before the specimen is destroyed. This in turn allows structure determination from crystals much smaller and more radiation sensitive than previously considered possible, allowing data collection from room temperature structures and avoiding structural changes due to cooling. Regardless, high-resolution structures obtained from XFEL data mostly use crystals far larger than 1 μm
Ligand-modulated folding of the full-length adenine riboswitch probed by NMR and single-molecule FRET spectroscopy
Feb 16, 2017   Nucleic Acids Research
Warhaut S, Mertinkus KR, Höllthaler P, Fürtig B, Heilemann M, Hengesbach M, Schwalbe H
Surface microtopography modulates sealing zone development in osteoclasts cultured on bone
Feb 16, 2017   Journal Of The Royal Society, Interface
Shemesh M, Addadi L, Geiger B
Surface microtopography modulates sealing zone development in osteoclasts cultured on bone
Feb 16, 2017
Journal Of The Royal Society, Interface
UNASSIGNED: Bone homeostasis is continuously regulated by the coordinated action of bone-resorbing osteoclasts and bone-forming osteoblasts. Imbalance between these two cell populations leads to pathological bone diseases such as osteoporosis and osteopetrosis. Osteoclast functionality relies on the formation of sealing zone (SZ) rings that define the resorption lacuna. It is commonly assumed that the structure and dynamic properties of the SZ depend on the physical and chemical properties of the substrate. Considering the unique complex structure of native bone, elucidation of the relevant parameters affecting SZ formation and stability is challenging. In this study, we examined in detail the dynamic response of the SZ to the microtopography of devitalized bone surfaces, taken from the same area in cattle femur. We show that there is a significant enrichment in large and stable SZs (diameter larger than 14 µm; lifespan of hours) in cells cultured on rough bone surfaces, compared with small and fast turning over SZ rings (diameter below 7 µm; lifespan approx. 7 min) formed on smooth bone surfaces. Based on these results, we propose that the surface roughness of the physiologically relevant substrate of osteoclasts, namely bone, affects primarily the local stability of growing SZs. © 2017 The Author(s).
Nucleosome-like, ssDNA-histone octamer complexes and the implication for DNA double-strand break repair
Feb 16, 2017   The Journal Of Biological Chemistry
Adkins NL, Swygert SG, Kaur P, Niu H, Grigoryev SA, Sung P, Wang H, Peterson CL
Nucleosome-like, ssDNA-histone octamer complexes and the implication for DNA double-strand break repair
Feb 16, 2017
The Journal Of Biological Chemistry
UNASSIGNED: Repair of DNA double strand breaks (DSBs) is key for maintenance of genome integrity. When DSBs are repaired by homologous recombination, DNA ends can undergo extensive processing, producing long stretches of single-stranded DNA (ssDNA). In vivo, DSB processing occurs in the context of chromatin, and studies indicate that histones may remain associated with processed DSBs. Here we demonstrate that histones are not evicted from ssDNA after in vitro chromatin resection. In addition, we reconstitute histone-ssDNA complexes (termed ssNucs) with ssDNA and recombinant histones and analyze these particles by a combination of native gel electrophoresis, sedimentation velocity, electron microscopy, and a recently developed electrostatic force microscopy technique, DREEM (Dual-Resonance-frequency-Enhanced Electrostatic force Microscopy). The reconstituted ssNucs are homogenous and relatively stable, and DREEM reveals ssDNA wrapping around histones. We also find that histone octamers are easily transferred in trans from ssNucs to either double-stranded DNA or ssDNA. Furthermore, the Fun30 remodeling enzyme, which has been implicated in DNA repair, binds ssNucs preferentially over nucleosomes, and ssNucs are effective at activating Fun30 ATPase activity. Our results indicate that ssNucs may be a hallmark of processes that generate ssDNA, and that posttranslational modification of ssNucs may generate novel signaling platforms involved in genome stability. Copyright © 2017, The American Society for Biochemistry and Molecular Biology.
Free-Standing Single-Molecule Thick Crystals Consisting of Linear Long-Chain Polymers
Feb 15, 2017   Nano Letters
Liu R, Fan S, Xiao D, Zhang J, Liao M, Yu S, Meng F, Liu B, Gu L, Meng S, Zhang G, Zheng W, Hu S, Li M
Free-Standing Single-Molecule Thick Crystals Consisting of Linear Long-Chain Polymers
Feb 15, 2017
Nano Letters
UNASSIGNED: Organic two-dimensional (2D) crystals are fundamentally important for development of future devices. Despite that more than a half of man-made products contain polymers, 2D crystals consisting of long linear chains have yet to be explored. Here we report on the fabrication of 2D polyaniline (PANI) crystals via rational electrochemical polymerization followed by liquid-phase exfoliation. The 2D PANI is molecularly thin (∼0.8 nm) and composed of PANI chains with a number-average molecular weight of ∼31 000. The chains are parallel to each other with the benzene rings standing almost vertically to the surface, implying a face-to-face arrangement of the neighboring chains held together by abundant π-π interactions augmented with hydrogen bonds. The 2D PANI can be readily transferred to various solid surfaces and exhibit interesting electrical and optical properties, suggesting that they would be potentially useful in photoelectronic devices and other applications.
Extracellular protonation modulates cell-cell interaction mechanics and tissue invasion in human melanoma cells
Feb 16, 2017   Scientific Reports
Hofschröer V, Koch KA, Ludwig FT, Friedl P, Oberleithner H, Stock C, Schwab A
Extracellular protonation modulates cell-cell interaction mechanics and tissue invasion in human melanoma cells
Feb 16, 2017
Scientific Reports
UNASSIGNED: Detachment of cells from the primary tumour precedes metastatic progression by facilitating cell release into the tissue. Solid tumours exhibit altered pH homeostasis with extracellular acidification. In human melanoma, the Na
Ultrasensitive Surface-Enhanced Raman Scattering Sensor of Gaseous Aldehydes as Biomarkers of Lung Cancer on Dendritic Ag Nanocrystals
Feb 17, 2017   Analytical Chemistry
Zhang Z, Yu W, Wang J, Luo D, Qiao X, Qin X, Wang T
Ultrasensitive Surface-Enhanced Raman Scattering Sensor of Gaseous Aldehydes as Biomarkers of Lung Cancer on Dendritic Ag Nanocrystals
Feb 17, 2017
Analytical Chemistry
UNASSIGNED: Surface-enhanced Raman scattering (SERS) is expected as a technique that even theoretically detected chemicals at the single molecule level by surface plasmon phenomena of noble metal nanostructures. Insensitivity of detecting Raman weak-intensity molecules and low adsorptivity of gaseous molecules on solid substrates are two main factors hindering the application of SERS in gas detectors. In this manuscript, we demonstrated an operational SERS strategy to detect gaseous Raman weak-intensity aldehydes that have been considered as a biomarker of lung cancer for abnormal content was measured in volatile organic compounds (VOCs) of lung cancer patients. To enhance the adsorption of gaseous molecules, dendritic Ag nanocrystals mimicking the structural feature (dendritic) of moth's antennae were formed, wherein the existence of numerous cavity traps in Ag dendritic nanocrystals prolonged reaction time of the gaseous molecules on the surface of solid surface through the "cavity-vortex" effect. By the nucleophilic addition reaction with the Raman-active probe molecule p-aminothiophenol (4-ATP) pregrafted on dendritic Ag nanocrystals, the gaseous aldehyde molecules were sensitively captured to detect at the ppb (parts per billion) level. Additionally, the sensitivity of this operational SERS strategy to detection of lung cancer biomarkers was not affected by the humidity, which represented a great potential in fast, easy, cost-effective, and noninvasive recognition of lung malignancies.
Role of Myocardial Collagen in Severe Aortic Stenosis With Preserved Ejection Fraction and Symptoms of Heart Failure
Feb 20, 2017   Revista Espanola De Cardiologia (English Ed.)
Echegaray K, Andreu I, Lazkano A, Villanueva I, Sáenz A,   . . . . . .   , Elósegui-Artola A, Roca-Cusachs P, Díez J, Ravassa S, Querejeta R
Role of Myocardial Collagen in Severe Aortic Stenosis With Preserved Ejection Fraction and Symptoms of Heart Failure
Feb 20, 2017
Revista Espanola De Cardiologia (English Ed.)
INTRODUCTION AND OBJECTIVES: We investigated the anatomical localization, biomechanical properties, and molecular phenotype of myocardial collagen tissue in 40 patients with severe aortic stenosis with preserved ejection fraction and symptoms of heart failure. METHODS: Two transmural biopsies were taken from the left ventricular free wall. Mysial and nonmysial regions of the collagen network were analyzed. Myocardial collagen volume fraction (CVF) was measured by picrosirius red staining. Young's elastic modulus (YEM) was measured by atomic force microscopy in decellularized slices to assess stiffness. Collagen types I and III were measured as C RESULTS: Compared with controls, patients exhibited increased mysial and nonmysial CVF and nonmysial:mysial CVF ratio (P < .05). In patients, nonmysial CVF (r = 0.330; P = .046) and the nonmysial:mysial CVF ratio (r = 0.419; P = .012) were directly correlated with the ratio of maximal early transmitral flow velocity in diastole to early mitral annulus velocity in diastole. Both the C CONCLUSIONS: These findings suggest that, in patients with severe aortic stenosis with preserved ejection fraction and symptoms of heart failure, diastolic dysfunction is associated with increased nonmysial deposition of collagen, predominantly type I, resulting in increased extracellular matrix stiffness. Therefore, the characteristics of collagen tissue may contribute to diastolic dysfunction in these patients. Copyright © 2016 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.
Rheology and microstructure of aqueous suspensions of nanocrystalline cellulose rods
Feb 19, 2017   Journal Of Colloid And Interface Science
Xu Y, Atrens AD, Stokes JR
Rheology and microstructure of aqueous suspensions of nanocrystalline cellulose rods
Feb 19, 2017
Journal Of Colloid And Interface Science
HYPOTHESIS: Nanocrystalline cellulose (NCC) is a negatively charged rod-like colloid obtained from the hydrolysis of plant material. It is thus expected that NCC suspensions display a rich set of phase behaviour with salt and pH because of its anisotropic shape and electrical double layer that gives rise to liquid crystallinity and self-assembly respectively. It should thus be possible to tune the rheological properties of NCC suspensions for a wide variety of end-use applications. EXPERIMENTS: Rheology and structural analysis techniques are used to characterise surface-sulphated NCC suspensions as a function of pH, salinity (NaCl) and NCC concentration. Structural techniques include atomic force microscopy, Zeta potential, dynamic light scattering, and scanning electron microscopy. FINDINGS: A phase diagram is developed based on the structure-rheology measurements showing various states of NCC that form as a function of salt and NCC concentration, which go well beyond those previously reported. This extended range of conditions reveals regions where the suspension is a viscous fluid and viscoelastic soft solid, as well as regions of instability that is suggested to arise when there is sufficient salt to reduce the electrical double layer (as explained qualitatively using DLVO theory) but insufficient NCC to form a load bearing network. Copyright © 2017 Elsevier Inc. All rights reserved.
Resequencing and annotation of the Nostoc punctiforme ATTC 29133 genome: facilitating biofuel and high-value chemical production
Feb 17, 2017   AMB Express
Moraes LE, Blow MJ, Hawley ER, Piao H, Kuo R, Chiniquy J, Shapiro N, Woyke T, Fadel JG, Hess M
Resequencing and annotation of the Nostoc punctiforme ATTC 29133 genome: facilitating biofuel and high-value chemical production
Feb 17, 2017
AMB Express
UNASSIGNED: Cyanobacteria have the potential to produce bulk and fine chemicals and members belonging to Nostoc sp. have received particular attention due to their relatively fast growth rate and the relative ease with which they can be harvested. Nostoc punctiforme is an aerobic, motile, Gram-negative, filamentous cyanobacterium that has been studied intensively to enhance our understanding of microbial carbon and nitrogen fixation. The genome of the type strain N. punctiforme ATCC 29133 was sequenced in 2001 and the scientific community has used these genome data extensively since then. Advances in bioinformatics tools for sequence annotation and the importance of this organism prompted us to resequence and reanalyze its genome and to make both, the initial and improved annotation, available to the scientific community. The new draft genome has a total size of 9.1 Mbp and consists of 65 contiguous pieces of DNA with a GC content of 41.38% and 7664 protein-coding genes. Furthermore, the resequenced genome is slightly (5152 bp) larger and contains 987 more genes with functional prediction when compared to the previously published version. We deposited the annotation of both genomes in the Department of Energy's IMG database to facilitate easy genome exploration by the scientific community without the need of in-depth bioinformatics skills. We expect that an facilitated access and ability to search the N. punctiforme ATCC 29133 for genes of interest will significantly facilitate metabolic engineering and genome prospecting efforts and ultimately the synthesis of biofuels and natural products from this keystone organism and closely related cyanobacteria.
Chitosan-Recombinamer Layer-by-Layer Coatings for Multifunctional Implants
Feb 17, 2017   International Journal Of Molecular Sciences
Govindharajulu JP, Chen X, Li Y, Rodriguez-Cabello JC, Battacharya M, Aparicio C
Chitosan-Recombinamer Layer-by-Layer Coatings for Multifunctional Implants
Feb 17, 2017
International Journal Of Molecular Sciences
UNASSIGNED: The main clinical problems for dental implants are (1) formation of biofilm around the implant-a condition known as peri-implantitis and (2) inadequate bone formation around the implant-lack of osseointegration. Therefore, developing an implant to overcome these problems is of significant interest to the dental community. Chitosan has been reported to have good biocompatibility and anti-bacterial activity. An osseo-inductive recombinant elastin-like biopolymer (P-HAP), that contains a peptide derived from the protein statherin, has been reported to induce biomineralization and osteoblast differentiation. In this study, chitosan/P-HAP bi-layers were built on a titanium surface using a layer-by-layer (LbL) assembly technique. The difference in the water contact angle between consecutive layers, the representative peaks in diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS), X-ray photoelectron spectroscopy (XPS), and the changes in the topography between surfaces with a different number of bi-layers observed using atomic force microscopy (AFM), all indicated the successful establishment of chitosan/P-HAP LbL assembly on the titanium surface. The LbL-modified surfaces showed increased biomineralization, an appropriate mouse pre-osteoblastic cell response, and significant anti-bacterial activity against Streptococcus gordonii, a primary colonizer of tissues in the oral environment.
DYNC1H1 mutations associated with neurological diseases compromise processivity of dynein-dynactin-cargo adaptor complexes
Feb 15, 2017   Proceedings Of The National Academy Of Sciences Of The United States Of America
Hoang HT, Schlager MA, Carter AP, Bullock SL
DYNC1H1 mutations associated with neurological diseases compromise processivity of dynein-dynactin-cargo adaptor complexes
Feb 15, 2017
Proceedings Of The National Academy Of Sciences Of The United States Of America
UNASSIGNED: Mutations in the human

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