Implantation of undifferentiated and pre-differentiated human neural stem cells in the R6/2 transgenic mouse model of Huntington’s disease

Background

The expression pattern and function of miRNAs in the rat model of temporal lobe epilepsy have not been well defined. Profiling miRNA expression in the rat model of temporal lobe epilepsy and investigating the function of specific miRNAs in epilepsy offers the prospect of a deeper understanding of the mechanisms of epilepsy.

Methods

The lithium-pilocarpine-induced status epilepticus model and the temporal lobe epilepsy model were established in Sprague?CDawley rats. Samples were analysed to detect deregulated miRNAs in the hippocampal temporal lobe, and several of these deregulated miRNAs were confirmed by qPCR. The expression of the pro-apoptotic miR-34a was detected at 1?day, 7?days and 2?weeks post-status epilepticus and at 2?months after temporal lobe epilepsy. The antagomir of miR-34a was then utilised. The expression of miR-34a after targeting and the expression change of activated caspase-3 protein were examined. The effects of altering the expression of miR-34a and activated caspase-3 protein on neuronal survival and neuronal death or apoptosis post-status epilepticus were assessed.

Results

The miRNA microarray detected 9 up-regulated miRNAs (miR-146a, -211, -203, -210, -152, -31, -23a, -34a, -27a) and 15 down-regulated miRNAs (miR-138*, -301a, -136, -153, -19a, -135b, -325-5p, -380, -190, -542-3p, -33, -144, -542-5p, -543, -296*). Some of the deregulated miRNAs (miR-146a, miR-210, miR-27a, miR-135b and miR-33) were confirmed using qPCR. Furthermore, an increase in expression of the pro-apoptotic miR-34a was demonstrated in the post-status epilepticus rat hippocampus. miR-34a was significantly up-regulated at 1?day, 7?days and 2?weeks post-status epilepticus and at 2?months after temporal lobe epilepsy. Experiments with the miR-34a antagomir revealed that targeting miR-34a led to an inhibition of activated caspase-3 protein expression, which may contribute to increased neuronal survival and reduced neuronal death or apoptosis.

Conclusions

Our study showed the expression profile of miRNAs in the hippocampus in a rat model of temporal lobe epilepsy and an increase in the expression of the pro-apoptotic miR-34a in post-status epilepticus rats. The results show that miR-34a is up-regulated during seizure-induced neuronal death or apoptosis, and targeting miR-34a is neuroprotective and is associated with an inhibition of an increase in activated caspase-3 protein.     

Phase behaviour,structural properties and intermolecular interactions of systems based on substituted thiacalix[4]arene and nonionic surfactants

Supramolecular organised materials were prepared from nonionic surfactants and the following macrocyclic ionic liquids: n-tert-butylthiacalix[4]arenes containing quaternary ammonium fragments with amino acid substituents. Tetraethylene glycol monododecyl ether and decadiethylene glycol monododecyl ether were used as nonionic surfactants. They form lamellar and hexagonal mesophases in aqueous media, respectively. Liquid crystal and structural properties of these systems were studied. Intermolecular interactions of system components leading to formation of lyomesophases were estimated. Molecular structure of thiacalixarene contributes to the formation of a hydrogen bonding with surfactants. This process, in turn, initiates formation of a denser packed hexagonal structure.     

Radical–anion coupling through reagent design: hydroxylation of aryl halides

The design and development of an oxime-based hydroxylation reagent, which can chemoselectively convert aryl halides (X = F, Cl, Br, I) into phenols under operationally simple, transition-metal-free conditions is described. Key to the success of this approach was the identification of a reducing oxime anion which can interact and couple with open-shell aryl radicals. Experimental and computational studies support the proposed radical-nucleophilic substitution chain mechanism.

The design and development of an oxime-based hydroxylation reagent, which can chemoselectively convert aryl halides (X = F, Cl, Br, I) into phenols under operationally simple, transition-metal-free conditions is described.     

Why density augmentation occurs in dilute supercritical solutions

The conventional explanation of the density augmentation in a supercritical solvent, observed spectroscopically when a small amount of a solute was added, involved the clustering of the solvent about individual solute molecules. Here it is suggested that the augmentation is not caused by the solute, but rather it is due to the preexisting near critical fluctuations in the pure solvent and the preference of the solute for the high density regions of the supercritical solvent. It is also shown that the local composition of the solute molecules about a solute molecules is enhanced compared to its bulk composition.     

Multiplex metal-detection based assay (MMDA) for COVID-19 diagnosis and identification of disease severity biomarkers

The ongoing COVID-19 pandemic caused by SARS-CoV-2 highlights the urgent need to develop sensitive methods for diagnosis and prognosis. To achieve this, multidimensional detection of SARS-CoV-2 related parameters including virus loads, immune response, and inflammation factors is crucial. Herein, by using metal-tagged antibodies as reporting probes, we developed a multiplex metal-detection based assay (MMDA) method as a general multiplex assay strategy for biofluids. This strategy provides extremely high multiplexing capability (theoretically over 100) compared with other reported biofluid assay methods. As a proof-of-concept, MMDA was used for serologic profiling of anti-SARS-CoV-2 antibodies. The MMDA exhibits significantly higher sensitivity and specificity than ELISA for the detection of anti-SARS-CoV-2 antibodies. By integrating the high dimensional data exploration/visualization tool (tSNE) and machine learning algorithms with in-depth analysis of multiplex data, we classified COVID-19 patients into different subgroups based on their distinct antibody landscape. We unbiasedly identified anti-SARS-CoV-2-nucleocapsid IgG and IgA as the most potently induced types of antibodies for COVID-19 diagnosis, and anti-SARS-CoV-2-spike IgA as a biomarker for disease severity stratification. MMDA represents a more accurate method for the diagnosis and disease severity stratification of the ongoing COVID-19 pandemic, as well as for biomarker discovery of other diseases.

A MMDA platform is developed by using metal-tagged antibodies as reporting probes combined with machine learning algorithms, as a general strategy for highly multiplexed biofluid assay.     

Synthesis,Structure and Molecular Docking of New 4,5-Dihydrothiazole Derivatives Based on 3,5-Dimethylpyrazole and Cytisine and Salsoline Alkaloids

The interaction results of 1,2-dibromo-3-isothiocyanatopropane with some pyrazoles as well as cytisine and salsoline alkaloids were presented in this paper. It was shown that the reaction resulted in one one-step and rather mild method for the preparation of the corresponding 1,3-thiazoline bromomethyl derivatives. The yield of this reaction was affected by the presence of a base and an order in which reagents were added. Molecular docking of the synthesized 1,3-thiazoline derivatives for putative antibacterial activity was carried out using the penicillin-binding target protein (PBP4) of the bacteria E. coli “Homo sapiens” and S. aureus “Homo sapiens” as an example. Molecular docking demonstrated that the compounds had insignificant binding energies at the level of selected reference drugs (Cephalotin and Chloramphenicol). The presence of natural alkaloids in the structure of thiazoline derivatives somewhat increased the affinity of these substrates for target proteins selected.     

Counterion, temperature, and time modulation of nanometric chiral ribbons from gemini-tartrate amphiphiles

Amphiphile supramolecular assemblies result from the cooperative effects of multiple weak interactions between a large number of subcomponents. As a result, prediction of and control over the morphologies of such assemblies remains difficult to achieve. Here, we described the fine-tuning of the shape, size, and morphology transitions of twisted and helical membranes formed by non-chiral dicationic n-2-n gemini amphiphiles complexed with chiral tartrate anions. We have reported that such systems express the chirality of the tartrate components at a supramolecular level and that the mechanism of the chiral induction by counterions involves specific anion cation recognition and the induction of conformationally labile chirality in the cations. Here, we demonstrate that the morphologies and dimensions of twisted and helical ribbons, as well as tubules, can be controlled and that interconversion between these structures can be induced upon modifying temperature, upon introducing small amounts of additives, or slightly modifying molecular structure. Specifically, electron microscopy, IR spectroscopy, and small-angle X-ray scattering show that (i) varying the hydrophobic chain length or adding gemini having bromide counterions (1%) or the opposite enantiomer (10%) leads to an increase of the diameter of membrane tubules from 33 to 48.5 nm; (ii) further addition (1.5%) of gemini bromide or a slight increase in temperature induces a transition from tubules to twisted ribbons; (iii) the twist pitch of the ribbons can be continuously tuned by varying enantiomeric excess; and (iv) it was also observed that the morphologies of these ribbons much evolve with time. Such unprecedented observations over easy tuning of the chiral supramolecular structures are clearly related to the original feature that the induction of chirality is solely due the counterions, which are much more mobile than the amphiphiles.