UNASSIGNED: The recurrence and drug resistance of temporal lobe epilepsy (TLE) has been ceaselessly challenging scientists and epilepsy experts. There has been an accumulation of evidence linking the dysregulation of postsynaptic proteins etiology and the pathology of epilepsy. For example, NMDA receptors, AMPA receptors, and metabotropic glutamate receptors (mGluRs). Furthermore, our earlier proteomic analysis proved there to be differential expressions of cytoskeletons like microtubules among rat groups. These differential expressions were shown in TLE-spontaneous recurrent seizures (TLE-SRS), TLE without SRS (TLE-NSRS) and control groups. Therefore, we aimed to understand how the microtubule system of the hippocampal postsynaptic density (PSD) regulates the development of TLE.
UNASSIGNED: In this study, a pilocarpine-induced Sprague-Dawley rat TLE model were used, and Western blot, Nissl staining, and the immunoelectron microscopic method were utilized to determine the dynamic change of microtubules (α- and β-tubulin) in PSD and the extent of hippocampal neuron loss respectively in acute SE, and latent and chronic (spontaneous seizures) periods. Animal models were then stereotactically treated using colchicine, a microtubule depolymerizer, and paclitaxel, a microtubule polymerization agent, after each animal\'s acute SE period so as to further explore the function of PSD microtubules.
UNASSIGNED: Our study revealed 3 principal findings. One, both α- and β-tubulin were decreased from the 3rd to the 30th day (lowest at the 7th day) in the seizure group compared with the controls. Two, both α- and β-tubulin were found to be more downregulated in the TLE-SRS and the TLE-NSRS group than in the control group (especially in the TLE-SRS group). The same trend was also noticed for hippocampal neuron loss. Three, the paclitaxel lowered the chronic SRS rate and increased the expression of PSD β-tubulin in the hippocampus.
UNASSIGNED: Altogether, these results indicate that the microtubule system of PSD may play an essential role in the development and recurrence of epilepsy, and it may be used as a new target for the prevention and treatment of this refractory disease.

BACKGROUND: Resistance to benzimidazole (BZ) compounds is common in Teladorsagia circumcincta populations in sheep and goats worldwide. Given the importance of anthelmintic resistance and shortage of information on single nucleotide polymorphisms (SNPs) in this prevalent nematode in Iran, this study was conducted.
METHODS: From June to September 2016, abomasa of 139 sheep of different sexes and ages in Amol City slaughterhouse, northern Iran were examined for isolation of nematodes. Totally 45 male T. circumcincta confirmed by both microscopical and nested-PCR-RFLP methods were included in this study. Susceptibility or resistance of each single T. circumcincta worm to benzimidazoles was assessed using allele-specific PCR.
RESULTS: Frequency of genotypes in the present study were 33.33% heterozygote BZ and 66.67% BZ homozygote sensitive. No homozygote resistant worm was found.
CONCLUSIONS: Resistance against BZs in T. circumcincta of sheep has occurred at a low prevalence in the north of Iran. However, mutated genes might get dominant under drug selection in future. Hence, periodic investigations for early detection of mutated alleles in nematode populations using accurate and sensitive molecular methods such as PCR-RFLP is recommended.

In this work, through a docking analysis of compounds from the ZINC chemical library on human β-tubulin using high performance computer cluster, we report new polycyclic aromatic compounds that bind with high energy on the colchicine binding site of β-tubulin, suggesting three new key amino acids. However, molecular dynamic analysis showed low stability in the interaction between ligand and receptor. Results were confirmed experimentally in in vitro and in vivo models that suggest that molecular dynamics simulation is the best option to find new potential β-tubulin inhibitors. Graphical abstract Bennett\'s acceptance ratio (BAR) method.

Taxol is one of the most important anti-cancer drugs. The interaction between different variants of Taxol, by altering one of its chiral centers at a time, with β-tubulin protein has been investigated. To achieve such goal, docking and molecular dynamics (MD) simulation studies have been performed. In docking studies, the preferred conformers have been selected to further study by MD method based on the binding energies reported by the AutoDock program. The best result of docking study which shows the highest affinity between ligand and protein has been used as the starting point of the MD simulations. All of the complexes have shown acceptable stability during the simulation process, based on the RMSDs of the backbone of the protein structure. Finally, MM-GBSA calculations have been carried out to select the best ligand, considering the binding energy criteria. The results predict that two of the structures have better affinity toward the mentioned protein, in comparison with Taxol. Three of the structures have affinity similar to that of the Taxol toward the β-tubulin.