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Redox-triggered buoyancy and size modulation of a dynamic covalent gel
The development of stimuli-responsive materials capable of transducing external stimuli into mechanical and physical changes has always been an intriguing challenge and an inspiration for scientists. Several stimuli-responsive gels have been developed and applied to biomimetic actuators or artificial muscles. Redox active actuators in which the mechanical motion is driven chemically or electrochemically have attracted much interest and their actuation mechanism is based on the change in electrostatic repulsion and the loss or gain of counterions to balance newly formed charges. Actuation can also be promoted by changing the hydration state of the material leading to the release/adsorption of water molecules from the network, inducing a direct shrinking/swelling of the material respectively. A cationic crystalline dynamic covalent gel was obtained via the formation of imine bonds between 2,6-diformyl pyridine and triamino guanidinium chloride. The gel exhibits a reversible contraction/expansion behavior in response to base (oxidation, βH+, βeβ) and acid (reduction +H+, +eβ) respectively. The oxidation induces a color change and contraction of the gel with a concomitant increase in its strength. As synthesized, the cationic gel is denser than water and sinks when placed in water. Upon oxidation, the radical cationic gel expels water molecules rendering it less dense than water and the gel is propelled to the surface without any loss of its structural integrity. These results demonstrate that a careful choice of amine and aldehyde linkers can give rise to imine-linked materials capable of tolerating and resisting extreme acidic and basic conditions while performing work
Immune Function in Alcoholism: A Controlled Study
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66331/1/j.1530-0277.1993.tb00763.x.pd
Image informatics strategies for deciphering neuronal network connectivity
Brain function relies on an intricate network of highly dynamic neuronal connections that rewires dramatically under the impulse of various external cues and pathological conditions. Among the neuronal structures that show morphologi- cal plasticity are neurites, synapses, dendritic spines and even nuclei. This structural remodelling is directly connected with functional changes such as intercellular com- munication and the associated calcium-bursting behaviour. In vitro cultured neu- ronal networks are valuable models for studying these morpho-functional changes. Owing to the automation and standardisation of both image acquisition and image analysis, it has become possible to extract statistically relevant readout from such networks. Here, we focus on the current state-of-the-art in image informatics that enables quantitative microscopic interrogation of neuronal networks. We describe the major correlates of neuronal connectivity and present workflows for analysing them. Finally, we provide an outlook on the challenges that remain to be addressed, and discuss how imaging algorithms can be extended beyond in vitro imaging studies
Multidimensional Recording (MDR) and Data Sharing: An Ecological Open Research and Educational Platform for Neuroscience
Primate neurophysiology has revealed various neural mechanisms at the single-cell level and population level. However, because recording techniques have not been updated for several decades, the types of experimental design that can be applied in the emerging field of social neuroscience are limited, in particular those involving interactions within a realistic social environment. To address these limitations and allow more freedom in experimental design to understand dynamic adaptive neural functions, multidimensional recording (MDR) was developed. MDR obtains behavioral, neural, eye position, and other biological data simultaneously by using integrated multiple recording systems. MDR gives a wide degree of freedom in experimental design because the level of behavioral restraint is adjustable depending on the experimental requirements while still maintaining the signal quality. The biggest advantage of MDR is that it can provide a stable neural signal at higher temporal resolution at the network level from multiple subjects for months, which no other method can provide. Conventional event-related analysis of MDR data shows results consistent with previous findings, whereas new methods of analysis can reveal network mechanisms that could not have been investigated previously. MDR data are now shared in the public server Neurotycho.org. These recording and sharing methods support an ecological system that is open to everyone and will be a valuable and powerful research/educational platform for understanding the dynamic mechanisms of neural networks
Gibberellin Biosynthetic Inhibitors Make Human Malaria Parasite Plasmodium falciparum Cells Swell and Rupture to Death
Malaria remains as one of the most devastating infectious disease, and continues to exact an enormous toll in medical cost and days of labor lost especially in the tropics. Effective malaria control and eventual eradication remain a huge challenge, with efficacious antimalarials as important intervention/management tool. Clearly new alternative drugs that are more affordable and with fewer side effects are desirable. After preliminary in vitro assays with plant growth regulators and inhibitors, here, we focus on biosynthetic inhibitors of gibberellin, a plant hormone with many important roles in plant growth, and show their inhibitory effect on the growth of both apicomplexa, Plasmodium falciparum and Toxoplasma gondii. Treatment of P. falciparum cultures with the gibberellin biosynthetic inhibitors resulted in marked morphological changes that can be reversed to a certain degree under hyperosmotic environment. These unique observations suggest that changes in the parasite membrane permeability may explain the pleiotropic effects observed within the intracellular parasites
Hybrid materials for molecular sieves
Hybrid microporous organosilica membranes for molecular separations made by acid-catalyzed solgel synthesis from bridged silsesquioxane precursors have demonstrated good performance in terms of flux and selectivity and remarkable hydrothermal stability in various pervaporation and gas separation processes. The availability of wide range of Ξ±,Ο-bis(trialkoxysilyl)alkane and 1,4-bis (triethoxysilyl)benzene precursors allows tuning of membrane properties such as pore size and chemistry. This chapter presents an overview of the synthesis and application of hybrid organosilica microporous membranes in liquid and gas separation processes. After a concise discussion of the history of solgel-derived microporous ceramic membranes for molecular separations, the solgel chemistry of bridged silsesquioxanes and all relevant processing steps needed to obtain a supported microporous films suitable for molecular separations are discussed. The performance of these membranes is correlated with the membrane compositional properties, such as nature, stiffness and length of the bridging group, and details of the solgel process
A Systematic Screen to Discover and Analyze Apicoplast Proteins Identifies a Conserved and Essential Protein Import Factor
Parasites of the phylum Apicomplexa cause diseases that impact global health and economy. These unicellular eukaryotes possess a relict plastid, the apicoplast, which is an essential organelle and a validated drug target. However, much of its biology remains poorly understood, in particular its elaborate compartmentalization: four membranes defining four different spaces. Only a small number of organellar proteins have been identified in particular few proteins are known for non-luminal apicoplast compartments. We hypothesized that enlarging the catalogue of apicoplast proteins will contribute toward identifying new organellar functions and expand the realm of targets beyond a limited set of characterized pathways. We developed a bioinformatic screen based on mRNA abundance over the cell cycle and on phyletic distribution. We experimentally assessed 57 genes, and of 30 successful epitope tagged candidates eleven novel apicoplast proteins were identified. Of those, seven appear to target to the lumen of the organelle, and four localize to peripheral compartments. To address their function we then developed a robust system for the construction of conditional mutants via a promoter replacement strategy. We confirm the feasibility of this system by establishing conditional mutants for two selected genes β a luminal and a peripheral apicoplast protein. The latter is particularly intriguing as it encodes a hypothetical protein that is conserved in and unique to Apicomplexan parasites and other related organisms that maintain a red algal endosymbiont. Our studies suggest that this peripheral plastid protein, PPP1, is likely localized to the periplastid compartment. Conditional disruption of PPP1 demonstrated that it is essential for parasite survival. Phenotypic analysis of this mutant is consistent with a role of the PPP1 protein in apicoplast biogenesis, specifically in import of nuclear-encoded proteins into the organelle
Validation of tissue microarray technology in squamous cell carcinoma of the esophagus
Tissue microarray (TMA) technology has been developed to facilitate high-throughput immunohistochemical and in situ hybridization analysis of tissues by inserting small tissue biopsy cores into a single paraffin block. Several studies have revealed novel prognostic biomarkers in esophageal squamous cell carcinoma (ESCC) by means of TMA technology, although this technique has not yet been validated for these tumors. Because representativeness of the donor tissue cores may be a disadvantage compared to full sections, the aim of this study was to assess if TMA technology provides representative immunohistochemical results in ESCC. A TMA was constructed containing triplicate cores of 108 formalin-fixed, paraffin-embedded squamous cell carcinomas of the esophagus. The agreement in the differentiation grade and immunohistochemical staining scores of CK5/6, CK14, E-cadherin, Ki-67, and p53 between TMA cores and a subset of 64 randomly selected donor paraffin blocks was determined using kappa statistics. The concurrence between TMA cores and donor blocks was moderate for Ki-67 (ΞΊβ=β0.42) and E-cadherin (ΞΊβ=β0.47), substantial for differentiation grade (ΞΊβ=β0.65) and CK14 (ΞΊβ=β0.71), and almost perfect for p53 (ΞΊβ=β0.86) and CK5/6 (ΞΊβ=β0.93). TMA technology appears to be a valid method for immunohistochemical analysis of molecular markers in ESCC provided that the staining pattern in the tumor is homogeneous
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