2,980 research outputs found
The Conformational Space of a Flexible Amino Acid at Metallic Surfaces
In interfaces between inorganic and biological materials relevant for
technological applications, the general challenge of structure determination is
exacerbated by the high flexibility of bioorganic components, chemical bonding,
and charge rearrangement at the interface. In this paper, we investigate a
chemically complex building block, namely, the arginine (Arg) amino-acid
interfaced with Cu, Ag and Au (111) surfaces. We investigate how the
environment changes the accessible conformational space of this amino acid, by
building and analyzing a database of thousands of structures optimized with the
PBE functional including screened pairwise van der Waals interactions. When in
contact with metallic surfaces, the accessible space for Arg is dramatically
reduced, while the one for Arg-H is instead increased if compared to the
gas-phase. This is explained by the formation of strong bonds between Arg and
the surfaces and by their absence and charge screening on Arg-H upon
adsorption. We also observe protonation-dependent stereoselective binding of
the amino acid to the metal surfaces: Arg adsorbs with its chiral CH
center pointing H away from the surfaces while Arg-H adsorbs with H
pointing toward the surface
3-D Ultrastructure of O. tauri: Electron Cryotomography of an Entire Eukaryotic Cell
The hallmark of eukaryotic cells is their segregation of key biological functions into discrete, membrane-bound organelles. Creating accurate models of their ultrastructural complexity has been difficult in part because of the limited resolution of light microscopy and the artifact-prone nature of conventional electron microscopy. Here we explored the potential of the emerging technology electron cryotomography to produce three-dimensional images of an entire eukaryotic cell in a near-native state. Ostreococcus tauri was chosen as the specimen because as a unicellular picoplankton with just one copy of each organelle, it is the smallest known eukaryote and was therefore likely to yield the highest resolution images. Whole cells were imaged at various stages of the cell cycle, yielding 3-D reconstructions of complete chloroplasts, mitochondria, endoplasmic reticula, Golgi bodies, peroxisomes, microtubules, and putative ribosome distributions in-situ. Surprisingly, the nucleus was seen to open long before mitosis, and while one microtubule (or two in some predivisional cells) was consistently present, no mitotic spindle was ever observed, prompting speculation that a single microtubule might be sufficient to segregate multiple chromosomes
Two-dimensional Polymer and Thin-Film Semiconductor-based Photonic Crystals for Biosensing Applications
Detecting biomolecules at very low concentrations is of a significant importance for a wide variety of applications ranging from human health to national security. A diverse class of sensing platforms utilizing the specificity of physical properties of materials and their change in the presence of target analytes has been developed. The main objective of such systems is to deliver cost-effective, ultrasensitive, and reliable sensors that can withstand noisy environments (i.e. dirty samples) with efficient operational characteristics (low power, high throughput, etc.). Optical, electrochemical, and mechanical sensors have demonstrated promising detection capabilities, which further encouraged research aimed at producing even much more sensitive systems that are capable of extending detection limits to single molecules.;The unique optical properties of photonic crystals (PhCs) as well as their nano-meter scale features, which can be comparable to that of single molecules, make them well suited as a basis for sensors capable of fulfilling the ultra-sensitive detection requirements. Semiconductor materials are commonly used to engineer PhCs that can either trap light at high efficiency in high-quality factor resonant cavities to enhance fluorescence emission from labeled molecules, or cause a very precise attenuation of the transmitted or reflected light after the adsorption of unlabeled molecules to the surface of these PhC structures. However, the high cost of sensing platforms utilizing semiconductor materials motivates the development of soft lithographic techniques to fabricate photonic crystals in biocompatible polymer materials and simplify their integration with microfluidic channels and optical waveguides.;The theory, design, fabrication, and optical characterization of PhC lattice structures as biosensing platforms in both semiconductor and polymer materials will be demonstrated throughout this thesis. Electron Beam Lithography as well as soft lithographic techniques are presented to achieve submicrometer scale PhC lattices in silicon, Polydimethylsiloxane (PDMS), and epoxy. The main focus will be on a passive detection modality in which the PhC structures are used to manipulate light emitted from fluorescing molecules to achieve an enhancement of this emission. A 27-fold enhancement factor has been recorded when IR-emitting quantum dots were utilized as the emitting molecules within the PhCs
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Ischemic axonal injury up-regulates MARK4 in cortical neurons and primes tau phosphorylation and aggregation.
Ischemic injury to white matter tracts is increasingly recognized to play a key role in age-related cognitive decline, vascular dementia, and Alzheimer's disease. Knowledge of the effects of ischemic axonal injury on cortical neurons is limited yet critical to identifying molecular pathways that link neurodegeneration and ischemia. Using a mouse model of subcortical white matter ischemic injury coupled with retrograde neuronal tracing, we employed magnetic affinity cell sorting with fluorescence-activated cell sorting to capture layer-specific cortical neurons and performed RNA-sequencing. With this approach, we identified a role for microtubule reorganization within stroke-injured neurons acting through the regulation of tau. We find that subcortical stroke-injured Layer 5 cortical neurons up-regulate the microtubule affinity-regulating kinase, Mark4, in response to axonal injury. Stroke-induced up-regulation of Mark4 is associated with selective remodeling of the apical dendrite after stroke and the phosphorylation of tau in vivo. In a cell-based tau biosensor assay, Mark4 promotes the aggregation of human tau in vitro. Increased expression of Mark4 after ischemic axonal injury in deep layer cortical neurons provides new evidence for synergism between axonal and neurodegenerative pathologies by priming of tau phosphorylation and aggregation
Probing ultra-subwavelength inhomogeneities embedded within dielectric targets using photonic nanojets
The use of optics to detect ultra-subwavelength features embedded within structures is a hot topic for a broad diversity of applications like spectroscopy, nanotechnology, microscopy, and optical data storage discs. Conventional objective lens based optical systems have a fundamental limit on the best possible resolution of about 200 \u03b7m due to the diffraction of light as it propagates into the far-field. There already exist several near-field techniques with the capability to overcome this limitation, but each of these systems has certain drawbacks related to the complexity of the system or to limitations imposed by the system. A photonic nanojet is a very particular beam of light that can provide a practical way to overcome the diffraction limit inherent to far-field techniques. A nanojet is an electromagnetic field envelope formed on the shadow-side surface of a plane-wave-illuminated dielectric microsphere of diameter larger than the wavelength and with refractive index contrast relative to the background medium of less than 2:1. It can maintain a subwavelength transversal beamwidth for distances greater than 2 wavelengths away from the surface of the generating microsphere. This Dissertation provides a computational test of the hypothesis that the backscattered spectrum resulting from photonic nanojet illumination of a three-dimensional (3-D) dielectric structure can reveal the presence and location of ultra-subwavelength, nanoscale-thin weakly contrasting dielectric inhomogeneities within dielectric targets. The effect of surface roughness on the illuminated side of the target is analyzed, and targets ranging from simple dielectric slabs to complex biological cells are studied. The present work is performed through computational electrodynamics modeling based upon the rigorous, large-scale solution of Maxwells equations. Specifically, the 3-D finite-difference time-domain (FDTD) method is employed to test the above hypothesis.\u2
Exploring the Interaction of G-quadruplex Binders with a (3 + 1) Hybrid G-quadruplex Forming Sequence within the PARP1 Gene Promoter Region
The enzyme PARP1 is an attractive target for cancer therapy, as it is involved in DNA repair processes. Several PARP1 inhibitors have been approved for clinical treatments. However, the rapid outbreak of resistance is seriously threatening the efficacy of these compounds, and alternative strategies are required to selectively regulate PARP1 activity. A noncanonical G-quadruplex-forming sequence within the PARP1 promoter was recently identified. In this study, we explore the interaction of known G-quadruplex binders with the G-quadruplex structure found in the PARP gene promoter region. The results obtained by NMR, CD, and fluorescence titration, also confirmed by molecular modeling studies, demonstrate a variety of different binding modes with small stabilization of the G-quadruplex sequence located at the PARP1 promoter. Surprisingly, only pyridostatin produces a strong stabilization of the G-quadruplex-forming sequence. This evidence makes the identification of a proper (3+1) stabilizing ligand a challenging goal for further investigation
Cooking with plants in ancient Europe and beyond
Plants have constituted the basis of human subsistence. This volume focuses on plant food ingredients that were consumed by the members of past societies and on the ways these ingredients were transformed into food. The thirty chapters of this book unfold the story of culinary transformation of cereals, pulses as well as of a wide range of wild and cultivated edible plants.
Regional syntheses provide insights on plant species choices and changes over time and fragments of recipes locked inside amorphous charred masses. Grinding equipment, cooking installations and cooking pots are used to reveal the ancient cooking steps in order to pull together the pieces of a culinary puzzle of the past. From the big picture of spatiotemporal patterns and changes to the micro-imaging of usewear on grinding tool surfaces, the book attempts for the first time a comprehensive and systematic approach to ancient plant food culinary transformation.
Focusing mainly on Europe and the Mediterranean world in prehistory, the book expands to other regions such as South Asia and Latin America and covers a time span from the Palaeolithic to the historic periods. Several of the contributions stem from original research conducted in the context of ERC project PlantCult: Investigating the Plant Food Cultures of Ancient Europe. The book’s exploration into ancient cuisines culminates with an investigation of the significance of ethnoarchaeology towards a better understanding of past foodways as well as of the impact of archaeology in shaping modern culinary and consumer trends.
The book will be of interest to archaeologists, food historians, agronomists, botanists as well as the wider public with an interest in ancient cooking
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Platform for High-Throughput Testing of the Effect of Soluble Compounds on 3D Cell Cultures
In vitro 3D culture could provide an important model of tissues in vivo, but assessing the effects of chemical compounds on cells in specific regions of 3D culture requires physical isolation of cells and thus currently relies mostly on delicate and low-throughput methods. This paper describes a technique (“cells-in-gels-in-paper”, CiGiP) that permits rapid assembly of arrays of 3D cell cultures and convenient isolation of cells from specific regions of these cultures. The 3D cultures were generated by stacking sheets of 200-μm-thick paper, each sheet supporting 96 individual “spots” (thin circular slabs) of hydrogels containing cells, separated by hydrophobic material (wax, PDMS) impermeable to aqueous solutions, and hydrophilic and most hydrophobic solutes. A custom-made 96-well holder isolated the cell-containing zones from each other. Each well contained media to which a different compound could be added. After culture and disassembly of the holder, peeling the layers apart “sectioned” the individual 3D cultures into 200-μm-thick sections which were easy to analyze using 2D imaging (e.g., with a commercial gel scanner). This 96-well holder brings new utilities to high-throughput, cell-based screening, by combining the simplicity of CiGiP with the convenience of a microtiter plate. This work demonstrated the potential of this type of assays by examining the cytotoxic effects of phenylarsine oxide (PAO) and cyclophosphamide (CPA) on human breast cancer cells positioned at different separations from culture media in 3D cultures.Chemistry and Chemical Biolog
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