Structure and characterisation of hydroxyethylcellulose–silica nanoparticles

Functionalising nanoparticles with polymers has gained much interest in recent years, as it aids colloidal stability and manipulation of surface properties. Here, polymer-coated thiolated silica nanoparticles were synthesised by self-condensation of 3-mercaptopropyltrimethoxysilane in the presence of hydroxyethylcellulose. These nanoparticles were characterised by dynamic light scattering, small angle neutron scattering, Nanoparticle Tracking Analysis, Raman spectroscopy, FT-IR spectroscopy, thermogravimetric analysis, Ellman's assay, transmission electron microscopy and cryo-transmission electron microscopy. It was found that increasing the amount of hydroxyethylcellulose in the reaction mixture increased the nanoparticle size and reduced the number of thiol groups on their surface. Additionally, by utilising small angle neutron scattering and dynamic light scattering, it was demonstrated that higher concentrations of polymer in the reaction mixture (0.5–2% w/v) resulted in the formation of aggregates, whereby several silica nanoparticles are bridged together with macromolecules of hydroxyethylcellulose. A correlation was identified between the aggregate size and number of particles per aggregate based on size discrepancies observed between DLS and SANS measurements. This information makes it possible to control the size of aggregates during a simple one-pot synthesis; a prospect highly desirable in the design of potential drug delivery systems

Uncertainty Principle for Control of Ensembles of Oscillators Driven by Common Noise

We discuss control techniques for noisy self-sustained oscillators with a focus on reliability, stability of the response to noisy driving, and oscillation coherence understood in the sense of constancy of oscillation frequency. For any kind of linear feedback control--single and multiple delay feedback, linear frequency filter, etc.--the phase diffusion constant, quantifying coherence, and the Lyapunov exponent, quantifying reliability, can be efficiently controlled but their ratio remains constant. Thus, an "uncertainty principle" can be formulated: the loss of reliability occurs when coherence is enhanced and, vice versa, coherence is weakened when reliability is enhanced. Treatment of this principle for ensembles of oscillators synchronized by common noise or global coupling reveals a substantial difference between the cases of slightly non-identical oscillators and identical ones with intrinsic noise.Comment: 10 pages, 5 figure

Ferritin is secreted via 2 distinct nonclassical vesicular pathways

Ferritin turnover plays a major role in tissue iron homeostasis, and ferritin malfunction is associated with impaired iron homeostasis and neurodegenerative diseases. In most eukaryotes, ferritin is considered an intracellular protein that stores iron in a nontoxic and bioavailable form. In insects, ferritin is a classically secreted protein and plays a major role in systemic iron distribution. Mammalian ferritin lacks the signal peptide for classical endoplasmic reticulum–Golgi secretion but is found in serum and is secreted via a nonclassical lysosomal secretion pathway. This study applied bioinformatics and biochemical tools, alongside a protein trafficking mouse models, to characterize the mechanisms of ferritin secretion. Ferritin trafficking via the classical secretion pathway was ruled out, and a 2:1 distribution of intracellular ferritin between membrane-bound compartments and the cytosol was observed, suggesting a role for ferritin in the vesicular compartments of the cell. Focusing on nonclassical secretion, we analyzed mouse models of impaired endolysosomal trafficking and found that ferritin secretion was decreased by a BLOC-1 mutation but increased by BLOC-2, BLOC-3, and Rab27A mutations of the cellular trafficking machinery, suggesting multiple export routes. A 13-amino-acid motif unique to ferritins that lack the secretion signal peptide was identified on the BC-loop of both subunits and plays a role in the regulation of ferritin secretion. Finally, we provide evidence that secretion of iron-rich ferritin was mediated via the multivesicular body–exosome pathway. These results enhance our understanding of the mechanism of ferritin secretion, which is an important piece in the puzzle of tissue iron homeostasis

Complex and unexpected dynamics in simple genetic regulatory networks

Peer reviewedPublisher PD

The study of expanded tri-lobed flap in a rabbit model: possible flap model in ear reconstruction?

BACKGROUND: Local flaps are widely used in reconstructive surgery. Tri-lobed skin flap is a relatively new flap and there has been no experimental model of this flap. This flap can be used for repair of full thickness defects in the face, ears and alar region. Based on the size of ears in a rabbit, we designed a model of ear reconstruction using expanded tri-lobed flap. Local flaps are more advantageous in that they provide excellent color and texture matching up with those of the face, adequately restore ear contour, place scars in a favorable location and ideally accomplish these goals in a single stage with minimal donor site morbidity. METHODS: Eight adult New Zealand rabbits were divided into two groups. 50 ml round tissue expander were implanted to four rabbits. After completion of the expansion, a superiorly based tri-lobed flap was elevated and a new ear was created from the superior dorsal skin of each rabbit. Scintigraphy with Technetium-99m pertecnetate was performed to evaluate flap viability. RESULTS: Subtotal flap necrosis was seen in all animals in non-expanded group. New ear in dimensions of the original ear was created in expanded group without complication. Perfusion and viability of the flaps were proved by Technetium-99m pertecnetate scintigraphy. CONCLUSION: According to our knowledge this study is the first to demonstrate animal model in tri-lobed flap. Also, our technique is the first application of the trilobed flap to the possible ear reconstruction. We speculated that this flap may be used mastoid based without hair, in human. Also, tri-lobed flap may be an alternative in reconstruction of cylindrical organs such as penis or finger

An Electronic Analog of Synthetic Genetic Networks

An electronic analog of a synthetic genetic network known as the repressilator is proposed. The repressilator is a synthetic biological clock consisting of a cyclic inhibitory network of three negative regulatory genes which produces oscillations in the expressed protein concentrations. Compared to previous circuit analogs of the repressilator, the circuit here takes into account more accurately the kinetics of gene expression, inhibition, and protein degradation. A good agreement between circuit measurements and numerical prediction is observed. The circuit allows for easy control of the kinetic parameters thereby aiding investigations of large varieties of potential dynamics

A Feedback Quenched Oscillator Produces Turing Patterning with One Diffuser

Efforts to engineer synthetic gene networks that spontaneously produce patterning in multicellular ensembles have focused on Turing's original model and the “activator-inhibitor” models of Meinhardt and Gierer. Systems based on this model are notoriously difficult to engineer. We present the first demonstration that Turing pattern formation can arise in a new family of oscillator-driven gene network topologies, specifically when a second feedback loop is introduced which quenches oscillations and incorporates a diffusible molecule. We provide an analysis of the system that predicts the range of kinetic parameters over which patterning should emerge and demonstrate the system's viability using stochastic simulations of a field of cells using realistic parameters. The primary goal of this paper is to provide a circuit architecture which can be implemented with relative ease by practitioners and which could serve as a model system for pattern generation in synthetic multicellular systems. Given the wide range of oscillatory circuits in natural systems, our system supports the tantalizing possibility that Turing pattern formation in natural multicellular systems can arise from oscillator-driven mechanisms

Anatomy of Heinrich Layer 1 and its role in the last deglaciation

X-ray fluorescence (XRF) core scanning and X-ray computed tomography data were measured every 1 mm to study the structure of Heinrich Event 1 during the last deglaciation at International Ocean Discovery Program Site U1308. Heinrich Layer 1 comprises two distinct layers of ice-rafted detritus (IRD), which are rich in detrital carbonate (DC) and poor in foraminifera. Each DC layer consists of poorly sorted, coarse-grained clasts of IRD embedded in a dense, fine-grained matrix of glacial rock flour that is partially cemented. The radiocarbon ages of foraminifera at the base of the two layers indicate a difference of 1400 $^{14}$C years, suggesting that they are two distinct events, but the calendar ages depend upon assumptions made for surface reservoir ages. The double peak indicates at least two distinct stages of discharge of the ice streams that drained the Laurentide Ice Sheet through Hudson Strait during HE1 or, alternatively, the discharge of two independent ice streams containing detrital carbonate. Heinrich Event 1.1 was the larger of the two events and began at ~16.2 ka (15.5–17.1 ka) when the polar North Atlantic was already cold and Atlantic Meridional Overturning Circulation (AMOC) weakened. The younger peak (H1.2) at ~15.1 ka (14.3 to 15.9 ka) was a weaker event than H1.1 that was accompanied by minor cooling. Our results support a complex history for Heinrich Stadial 1 (HS1) with reduction in AMOC during the early part (~20–16.2 ka) possibly driven by melting of European ice sheets, whereas the Laurentide Ice Sheet assumed a greater role during the latter half (~16.2–14.7 ka).This research used data acquired at the XRF Core Scanner Lab at the MARUM–Center for Marine Environmental Sciences, University of Bremen, Germany. This research used samples provided by the International Ocean Discovery Program (IODP). Funding for this research was provided by the UK Natural Environmental Research Council (NERC) to Hodell. The NERC Radiocarbon Facility supported two radiocarbon dates, and Wally Broecker generously supported the remainder with funding from the Comer Family Foundation. Research by Rodríguez-Tovar and Dorador was financed by Project CGL2015-66835-P. B.M. acknowledges support from the CSIC-Ramón y Cajal postdoctoral programme RYC-2013-14073. J.F.E. would like to acknowledge funding under ERC Advanced grant 320750- Nanopaleomagnetism

Dynasore, a Dynamin Inhibitor, Inhibits Trypanosoma cruzi Entry into Peritoneal Macrophages

BACKGROUND: Trypanosoma cruzi is an intracellular parasite that, like some other intracellular pathogens, targets specific proteins of the host cell vesicular transport machinery, leading to a modulation of host cell processes that results in the generation of unique phagosomes. In mammalian cells, several molecules have been identified that selectively regulate the formation of endocytic transport vesicles and the fusion of such vesicles with appropriate acceptor membranes. Among these, the GTPase dynamin plays an important role in clathrin-mediated endocytosis, and it was recently found that dynamin can participate in a phagocytic process. METHODOLOGY/PRINCIPAL FINDINGS: We used a compound called dynasore that has the ability to block the GTPase activity of dynamin. Dynasore acts as a potent inhibitor of endocytic pathways by blocking coated vesicle formation within seconds of its addition. Here, we investigated whether dynamin is involved in the entry process of T. cruzi in phagocytic and non-phagocytic cells by using dynasore. In this aim, peritoneal macrophages and LLC-MK2 cells were treated with increasing concentrations of dynasore before interaction with trypomastigotes, amastigotes or epimastigotes. We observed that, in both cell lines, the parasite internalization was drastically diminished (by greater than 90% in LLC-MK2 cells and 70% in peritoneal macrophages) when we used 100 microM dynasore. The T. cruzi adhesion index, however, was unaffected in either cell line. Analyzing these interactions by scanning electron microscopy and comparing peritoneal macrophages to LLC-MK2 cells revealed differences in the stage at which cell entry was blocked. In LLC-MK2 cells, this blockade is observed earlier than it is in peritoneal macrophages. In LLC-MK2 cells, the parasites were only associated with cellular microvilli, whereas in peritoneal macrophages, trypomastigotes were not completely engulfed by a host cell plasma membrane. CONCLUSIONS/SIGNIFICANCE: Taken together our results demonstrate that dynamin is an essential molecule necessary for cell invasion and specifically parasitophorous vacuole formation by host cells during interaction with Trypanosoma cruzi