bluuebunny/crossref_metadata_2025_split huggingface dataset:
Big Data Analytics for Scanning Transmission Electron Microscopy Ptychography
Authors: Jesse S. , Chi M. , Belianinov A. , Beekman C. , Kalinin S. V. , Borisevich A. Y. , Lupini A. R. 
Published: May 2016

AbstractElectron microscopy is undergoing a transition; from the model of producing only a few micrographs, through the current state where many images and spectra can be digitally recorded, to a new mode where very large volumes of data (movies, ptychographic and multi-dimensional series) can be rapidly obtained. Here, we discuss the application of so-called “big-data” methods to high dimensional microscopy data, using unsupervised multivariate statistical techniques, in order to explore salient image features in a specific example of BiFeO3 domains. Remarkably, k-means clustering reveals domain differentiation despite the fact that the algorithm is purely statistical in nature and does not require any prior information regarding the material, any coexisting phases, or any differentiating structures. While this is a somewhat trivial case, this example signifies the extraction of useful physical and structural information without any prior bias regarding the sample or the instrumental modality. Further interpretation of these types of results may still require human intervention. However, the open nature of this algorithm and its wide availability, enable broad collaborations and exploratory work necessary to enable efficient data analysis in electron microscopy.
Assembling Composite Dermal Papilla Spheres with Adipose-derived Stem Cells to Enhance Hair Follicle Induction
Authors: Huang Chin-Fu , Chang Ya-Ju , Hsueh Yuan-Yu , Huang Chia-Wei , Wang Duo-Hsiang , Huang Tzu-Chieh , Wu Yi-Ting , Su Fong-Chin , Hughes Michael , Chuong Cheng-Ming , Wu Chia-Ching 
Published: May 2016

AbstractIntradermal adipose tissue plays an essential role for hair follicles (HFs) regeneration by regulating hair cycles. However, the effect of reconstruction of HFs and the involvement of adipose-related cells are poorly understood. We investigated assembly strategies for the interactions of dermal papilla (DP) cells with adipose-derived stem cells (ASCs) in promoting hair formation. DP cells lose DP traits during adherent culture, but preserved DP markers with a unified sphere diameter by seeding on chitosan-coated microenvironments. Next, ASCs isolated from rats were co-cultured with DP spheres by different assembling approaches to determine their interactions; a mixed sphere of ASCs with DP cells (MA-DPS), or a core-shell structure, outer ASCs shell and an inner DP core (CSA-DPS). CSA-DPS exhibited superior DP characteristics compared to MA-DPS. Conditional medium from ASCs, but not differentiated adipocytes, promoted DP markers and functional alkaline phosphatase activity from the DP cells. In vivo patch assay showed the core-shell assembling of CSA-DPS can reconstruct cellular arrangements and microenvironmental niches as dominated by PPARα signal in ASCs to induce the greater hair induction than MA-DPS or DP spheres alone. Therefore, the assembling of a core-shell sphere for DP with ASCs could reconstruct the HF cellular arrangement for hair formation. This paper set the groundwork for further evaluation of the input of other cell types.
Mechanism of p27 Unfolding for CDK2 Reactivation
Authors: Rath Soumya Lipsa , Senapati Sanjib 
Published: May 2016

AbstractCell-cycle regulatory protein, CDK2 is active when bound to its complementary partner protein, CyclinA or E. Recent discovery of the Kip/Cip family of proteins has indicated that the activity of CDK2 is also regulated by a member protein, p27. Although, the mechanism of CDK2 inhibition by p27 binding is known from crystal structure, little is known about the mechanism of CDK2 reactivation. Here, we execute classical and accelerated molecular dynamics simulations of unphosphorylated- and phosphorylated-p27 bound CDK2/CyclinA to unravel the CDK2 reactivation mechanism at molecular-to-atomic detail. Results suggest that the phosphorylation of p27 Y88 residue (pY88-p27) first disrupts the p27/CDK2 hybrid β-sheet and subsequently ejects the p27 310 helix from CDK2 catalytic cleft. The unbinding of p27 from CDK2/CyclinA complex, thus, follows a two-step unfolding mechanism, where the 310 helix ejection constitutes the rate-limiting step. Interestingly, the unfolding of p27 leaves CDK2/CyclinA in an active state, where the prerequisite CDK2-CyclinA interfacial contacts were regained and ATP achieved its native position for smooth transfer of phosphate. Our findings match very well with NMR chemical shift data that indicated the flip-out of p27 310 helix from CDK2 pocket and kinetic experiments that exhibited significant kinase activity of CDK2 when saturated with pY88-p27.
GBIQ: a non-arbitrary, non-biased method for quantification of fluorescent images
Authors: Ninomiya Youichirou , Zhao Wei , Saga Yumiko 
Published: May 2016

AbstractNon-arbitrary and non-biased quantification of fluorescent images is an essential tool for the data-centric approach to biological systems. Typical application is high-content analysis, where various phenotypic changes in cellular components and/or morphology are measured from fluorescent image data. A standard protocol to detect cellular phenotypes is cell-segmentation, in which boundaries of cellular components, such as cell nucleus and plasma membrane, are first identified to define cell segments, then acquiring various phenotypic data of each segment. To achieve reliable outcome, cell-segmentation requires manual adjustments of many parameters; this requirement could hamper automated image processing in high-throughput workflow, whose quantification must be non-arbitrary and non-biased. As a practical alternative to the segmentation-based method, we developed GBIQ (Grid Based Image Quantification), which allows comparison of cellular information without identification of single cells. GBIQ divides an image with tiles of fixed size grids and records statistics of the grids with their location coordinates, minimizing arbitrary intervenes. GBIQ requires only one parameter (size of grid) to be set; nonetheless it robustly produces results suitable for further statistical evaluation. The simplicity of GBIQ allows it to be readily implemented in an automated high-throughput image analysis workflow.
An essential role for the baseplate protein Gp45 in phage adsorption to Staphylococcus aureus
Authors: Li Xuehua , Koç Cengiz , Kühner Petra , Stierhof York-Dieter , Krismer Bernhard , Enright Mark C. , Penadés José R. , Wolz Christiane , Stehle Thilo , Cambillau Christian , Peschel Andreas , Xia Guoqing 
Published: May 2016

AbstractDespite the importance of phages in driving horizontal gene transfer (HGT) among pathogenic bacteria, the underlying molecular mechanisms mediating phage adsorption to S. aureus are still unclear. Phage ϕ11 is a siphovirus with a high transducing efficiency. Here, we show that the tail protein Gp45 localized within the ϕ11 baseplate. Phage ϕ11 was efficiently neutralized by anti-Gp45 serum and its adsorption to host cells was inhibited by recombinant Gp45 in a dose-dependent manner. Flow cytometry analysis demonstrated that biotin-labelled Gp45 efficiently stained the wild-type S. aureus cell but not the double knockout mutant ΔtarM/S, which lacks both α- and β-O-GlcNAc residues on its wall teichoic acids (WTAs). Additionally, adsorption assays indicate that GlcNAc residues on WTAs and O-acetyl groups at the 6-position of muramic acid residues in peptidoglycan are essential components of the ϕ11 receptor. The elucidation of Gp45-involved molecular interactions not only broadens our understanding of siphovirus-mediated HGT, but also lays the groundwork for the development of sensitive affinity-based diagnostics and therapeutics for S. aureus infection.
Unique 1D Co3O4 crystallized nanofibers with (220) oriented facets as high-performance lithium ion battery anode material
Authors: Tan Yanli , Gao Qiuming , Li Zeyu , Tian Weiqian , Qian Weiwei , Yang Chunxiao , Zhang Hang 
Published: May 2016

AbstractA novel one-step hydrothermal and calcination strategy was developed to synthesize the unique 1D oriented Co3O4 crystal nanofibers with (220) facets on the carbon matrix derived from the natural, abundant and low cost wool fibers acting as both carbon precursor and template reagent. The resultant W2@Co3O4 nanocomposite exhibited very high specific capacity and favorable high-rate capability when used as anode material of lithium ion battery. The high reversible Li+ ion storage capacity of 986 mAh g−1 was obtained at 100 mA g−1 after 150 cycles, higher than the theoretical capacity of Co3O4 (890 mAh g−1). Even at the higher current density of 1 A g−1, the electrode could still deliver a remarkable discharge capacity of 720 mAh g−1 over 150 cycles.
Interaction of single and multi wall carbon nanotubes with the biological systems: tau protein and PC12 cells as targets
Authors: Zeinabad Hojjat Alizadeh , Zarrabian Alireza , Saboury Ali Akbar , Alizadeh Ali Mohammad , Falahati Mojtaba 
Published: May 2016

AbstractSubtle changes in the structure of nanoparticles influence their surface tension and corresponding interaction with cells and proteins. Here, the interaction of the single wall carbon nanotube (SWCNT) and multiwall carbon nanotube (MWCNT) with different surface tension with tau protein was evaluated using a variety of techniques including far and near circular dichroism, fluorescence spectroscopy, dynamic light scattering, Zeta potential, and TEM evaluation. Also the cytotoxicity of SWCNT and MWCNT on the PC12 cell line as a model of nervous system cell line was investigated by the MTT, LDH, acridine orange/ethidium bromide staining, flow cytometry, caspase 3 activity, cell and membrane potential assays. It was observed that SWCNT induced more structural changes of tau protein relative to MWCNT/tau protein interaction. It was also revealed that SWCNT and MWCNT impaired the viability and complexity of PC12 cells in different modes of cytotoxicity. Analysis of cellular outcomes indicated that MWCNT in comparison with SWCNT resulted in induction of necrotic modes of cell death, whereas apoptotic modes of cell death were activated in SWCNT-incubated cells. Together these findings suggest that surface tension may be used to determine how nanoparticle structure affects neurotoxicity and protein conformational changes.
Small molecule activation of NOTCH signaling inhibits acute myeloid leukemia
Authors: Ye Qi , Jiang Jue , Zhan Guanqun , Yan Wanyao , Huang Liang , Hu Yufeng , Su Hexiu , Tong Qingyi , Yue Ming , Li Hua , Yao Guangmin , Zhang Yonghui , Liu Hudan 
Published: May 2016

AbstractAberrant activation of the NOTCH signaling pathway is crucial for the onset and progression of T cell leukemia. Yet recent studies also suggest a tumor suppressive role of NOTCH signaling in acute myeloid leukemia (AML) and reactivation of this pathway offers an attractive opportunity for anti-AML therapies. N-methylhemeanthidine chloride (NMHC) is a novel Amaryllidaceae alkaloid that we previously isolated from Zephyranthes candida, exhibiting inhibitory activities in a variety of cancer cells, particularly those from AML. Here, we report NMHC not only selectively inhibits AML cell proliferation in vitro but also hampers tumor development in a human AML xenograft model. Genome-wide gene expression profiling reveals that NMHC activates the NOTCH signaling. Combination of NMHC and recombinant human NOTCH ligand DLL4 achieves a remarkable synergistic effect on NOTCH activation. Moreover, pre-inhibition of NOTCH by overexpression of dominant negative MAML alleviates NMHC-mediated cytotoxicity in AML. Further mechanistic analysis using structure-based molecular modeling as well as biochemical assays demonstrates that NMHC docks in the hydrophobic cavity within the NOTCH1 negative regulatory region (NRR), thus promoting NOTCH1 proteolytic cleavage. Our findings thus establish NMHC as a potential NOTCH agonist that holds great promises for future development as a novel agent beneficial to patients with AML.
Participants’ above-chance recognition of own-heart sound combined with poor metacognitive awareness suggests implicit knowledge of own heart cardiodynamics
Authors: Azevedo Ruben T. , Aglioti Salvatore Maria , Lenggenhager Bigna 
Published: May 2016

AbstractMounting evidence suggests that interoceptive signals are fundamentally important for the experience of the self. Thus far, studies on interoception have mainly focused on the ability to monitor the timing of ongoing heartbeats and on how these influence emotional and self-related processes. However, cardiac afferent signalling is not confined to heartbeat timing and several other cardiac parameters characterize cardiodynamic functioning. Building on the fact that each heart has its own self-specific cardio-dynamics, which cannot be expressed uniquely by heart rate, we devised a novel task to test whether people could recognize the sound of their own heart even when perceived offline and thus not in synchrony with ongoing heartbeats. In a forced-choice paradigm, participants discriminated between sounds of their own heartbeat (previously recorded with a Doppler device) versus another person’s heart. Participants identified the sound of their own heart above chance, whereas their metacognition of performance – as calculated by contrasting performance against ratings of confidence - was considerably poorer. These results suggest an implicit access to fine-grained neural representations of elementary cardio-dynamic parameters beyond heartbeat timing.
Inappropriate cadherin switching in the mouse epiblast compromises proper signaling between the epiblast and the extraembryonic ectoderm during gastrulation
Authors: Basilicata M. Felicia , Frank Marcus , Solter Davor , Brabletz Thomas , Stemmler Marc P. 
Published: May 2016

AbstractCadherin switching from E-cadherin (E-cad) to N-cadherin (N-cad) is a key step of the epithelial-mesenchymal transition (EMT) processes that occurs during gastrulation and cancer progression. We investigate whether cadherins actively participate in progression of EMT by crosstalk to signaling pathways. We apply ectopic cadherin switching before the onset of mouse gastrulation. Mutants with an induced E-cad to N-cad switch (Ncadki) die around E8.5. Severe morphological changes including a small epiblast, a rounded shape, an enlarged extra-embryonic compartment and lack of the amnion, combined with a massive cell detachment from the ectodermal layer are detected. In contrast to epiblast-specific E-cad depletion, gastrulation is initiated in Ncadki embryos, but patterning of the germ-layers is abnormal. An overall reduction in BMP signaling, expansion ofNodalandEomesdomains, combined with reducedWnt3aexpression at the primitive streak is observed. Our results show that in addition to cadherin-dependent adhesion, proper embryonic development requires E-cad mediated signaling function to facilitate a feedback loop that stabilizesBmp4andBmp2expression in the extraembryonic ectoderm and sustained downstream activity in the epiblast. Moreover, for proper morphogenesis a fine-tuned spatio-temporal control of cadherin switching is required during EMT at gastrulation to avoid premature cell detachment and migration.
Engineering a 3D microfluidic culture platform for tumor-treating field application
Authors: Pavesi Andrea , Adriani Giulia , Tay Andy , Warkiani Majid Ebrahimi , Yeap Wei Hseun , Wong Siew Cheng , Kamm Roger D. 
Published: May 2016

AbstractThe limitations of current cancer therapies highlight the urgent need for a more effective therapeutic strategy. One promising approach uses an alternating electric field; however, the mechanisms involved in the disruption of the cancer cell cycle as well as the potential adverse effects on non-cancerous cells must be clarified. In this study, we present a novel microfluidic device with embedded electrodes that enables the application of an alternating electric field therapy to cancer cells in a 3D extracellular matrix. To demonstrate the potential of our system to aid in designing and testing new therapeutic approaches, cancer cells and cancer cell aggregates were cultured individually or co-cultured with endothelial cells. The metastatic potential of the cancer cells was reduced after electric field treatment. Moreover, the proliferation rate of the treated cancer cells was lower compared with that of the untreated cells, whereas the morphologies and proliferative capacities of the endothelial cells were not significantly affected. These results demonstrate that our novel system can be used to rapidly screen the effect of an alternating electric field on cancer and normal cells within an in vivo-like microenvironment with the potential to optimize treatment protocols and evaluate synergies between tumor-treating field treatment and chemotherapy.
Cultured pericytes from human brain show phenotypic and functional differences associated with differential CD90 expression
Authors: Park Thomas I-H. , Feisst Vaughan , Brooks Anna E. S. , Rustenhoven Justin , Monzo Hector J. , Feng Sheryl X. , Mee Edward W. , Bergin Peter S. , Oldfield Robyn , Graham E. Scott , Curtis Maurice A. , Faull Richard L. M. , Dunbar P. Rod , Dragunow Mike 
Published: May 2016

AbstractThe human brain is a highly vascular organ in which the blood-brain barrier (BBB) tightly regulates molecules entering the brain. Pericytes are an integral cell type of the BBB, regulating vascular integrity, neuroinflammation, angiogenesis and wound repair. Despite their importance, identifying pericytes amongst other perivascular cell types and deciphering their specific role in the neurovasculature remains a challenge. Using primary adult human brain cultures and fluorescent-activated cell sorting, we identified two CD73+CD45− mesenchymal populations that showed either high or low CD90 expression. CD90 is known to be present on neurons in the brain and peripheral blood vessels. We found in the human brain, that CD90 immunostaining localised to the neurovasculature and often associated with pericytes. In vitro, CD90+ cells exhibited higher basal proliferation, lower expression of markers αSMA and CD140b, produced less extracellular matrix (ECM) proteins, and exhibited lesser pro-inflammatory responses when compared to the CD90− population. Thus, CD90 distinguishes two interrelated, yet functionally distinct pericyte populations in the adult human brain that may have discrete roles in neurovascular function, immune response and scar formation.
Structure-based site-directed photo-crosslinking analyses of multimeric cell-adhesive interactions of voltage-gated sodium channel β subunits
Authors: Shimizu Hideaki , Miyazaki Haruko , Ohsawa Noboru , Shoji Shisako , Ishizuka-Katsura Yoshiko , Tosaki Asako , Oyama Fumitaka , Terada Takaho , Sakamoto Kensaku , Shirouzu Mikako , Sekine Shun-ichi , Nukina Nobuyuki , Yokoyama Shigeyuki 
Published: May 2016

AbstractThe β1, β2 and β4 subunits of voltage-gated sodium channels reportedly function as cell adhesion molecules. The present crystallographic analysis of the β4 extracellular domain revealed an antiparallel arrangement of the β4 molecules in the crystal lattice. The interface between the two antiparallel β4 molecules is asymmetric and results in a multimeric assembly. Structure-based mutagenesis and site-directed photo-crosslinking analyses of the β4-mediated cell-cell adhesion revealed that the interface between the antiparallel β4 molecules corresponds to that in the trans homophilic interaction for the multimeric assembly of β4 in cell-cell adhesion. This trans interaction mode is also employed in the β1-mediated cell-cell adhesion. Moreover, the β1 gene mutations associated with generalized epilepsy with febrile seizures plus (GEFS+) impaired the β1-mediated cell-cell adhesion, which should underlie the GEFS+ pathogenesis. Thus, the structural basis for the β-subunit-mediated cell-cell adhesion has been established.
Selective serotonin 5-HT1A receptor biased agonists elicitdistinct brain activation patterns: a pharmacoMRI study
Authors: Becker G. , Bolbos R. , Costes N. , Redouté J. , Newman-Tancredi A. , Zimmer L. 
Published: May 2016

AbstractSerotonin 1A (5-HT1A) receptors are involved in several physiological and pathological processes and constitute therefore an important therapeutic target. The recent pharmacological concept of biased agonism asserts that highly selective agonists can preferentially direct receptor signaling to specific intracellular responses, opening the possibility of drugs targeting a receptor subtype in specific brain regions. The present study brings additional support to this concept thanks to functional magnetic resonance imaging (7 Tesla-fMRI) in anaesthetized rats. Three 5-HT1A receptor agonists (8-OH-DPAT, F13714 and F15599) and one 5-HT1A receptor antagonist (MPPF) were compared in terms of influence on the brain blood oxygen level-dependent (BOLD) signal. Our study revealed for the first time contrasting BOLD signal patterns of biased agonists in comparison to a classical agonist and a silent antagonist. By providing functional information on the influence of pharmacological activation of 5-HT1A receptors in specific brain regions, this neuroimaging approach, translatable to the clinic, promises to be useful in exploring the new concept of biased agonism in neuropsychopharmacology.
Experimental evidence of incomplete fluorescence quenching of pyrene bound to humic substances: implications for Koc measurements
Authors: Shirshin E. A. , Budylin G. S. , Grechischeva N. Yu , Fadeev V. V. , Perminova I. V. 
Published: May 2016

Abstract
Fluorescence quenching (FQ) is extensively used for quantitative assessment of partition coefficients (K
oc) of polycyclic aromatic hydrocarbons (PAHs) to natural organic materials–humic substances (HS). The presence of bound PAHs with incompletely quenched fluorescence would lead to underestimation of the K
oc values measured by this technique. The goal of this work was to prove the validity of this assumption using an original experimental setup, which implied FQ measurements upon excitation into two distinct vibronically coupled electronic states. Pyrene was used as a fluorescent probe, and aquatic fulvic acid (SRFA) and leonardite humic acid (CHP) were used as the humic materials with low and high binding affinity for pyrene, respectively. Excitation of pyrene into the forbidden (S0–S1) and allowed (S0–S2) electronic states yielded two pairs of nonidentical FQ curves. This was indicative of incomplete quenching of the bound pyrene, and the divergence of the two FQ curves was much more pronounced for CHP as compared to SRFA. The two component model of fluorescence response formation was proposed to estimate the K
oc values from the data obtained. The resulting pyrene K
oc value for CHP (220 ± 20) g L-1 was a factor 3 higher compared to the K
oc value determined with the use of the Stern–Volmer formalism (68 ± 2) g L-1. At the same time for aquatic FA the difference in FQ curves was almost negligible, which enables the use of the Stern–Volmer formalism for weakly interacting HS and PAHs.
Correction: Cucurbit[7]uril inclusion complexation as a supramolecular strategy for color stabilization of anthocyanin model compounds
Authors: Held Barbara , Tang Hao , Natarajan Palani , Silva Cassio Pacheco Da , Silva Volnir De Oliveira , Bohne Cornelia , Quina Frank H. 
Published: May 2016

Abstract
Correction for ‘Cucurbit[7]uril inclusion complexation as a supramolecular strategy for color stabilization of anthocyanin model compounds’ by Barbara Held, et al., Photochem. Photobiol. Sci., 2016, DOI: 10.1039/c6pp00060f.