Molecular Structure of Gaseous Oxopivalate Co(II): Electronic States of Various Multiplicities.

Synchronous electron diffraction/mass spectrometry was used to study the composition and structure of molecular forms existing in a saturated vapor of cobalt(II) oxopivalate at T = 410 K. It was found that monomeric complexes Co4O(piv)6 dominate in the vapor. The complex geometry possesses the C3 symmetry with bond lengths Co-Oc = 1.975(5) Å and Co-O = 1.963(5) Å, as well as bond angles Oc-Co-O = 111.8(3)°, Co-Oc-Co = 110.4(6)°, O-Co-O = 107.1(3)° in the central OcCo4 fragment and four OcCoO3 fragments. The presence of an open 3d shell for each Co atom leads to the possibility of the existence of electronic states of the Co4O(piv)6 complex with Multiplicities 1, 3, 5, 7, 9, 11, and 13. For them, the CASSCF and XMCQDPT2 calculations predict similar energies, identical shapes of active orbitals, and geometric parameters, the difference between which is comparable with the error of determination by the electron diffraction experiment. QTAIM and NBO analysis show that the Co-Oc and Co-O bonds can be attributed to ionic (or coordination) bonds with a significant contribution of the covalent component. The high volatility and simple vapor composition make it possible to recommend cobalt (II) oxopivalate as precursors in the preparation of oxide films or coatings in the CVD technologies. The features of the electronic and geometric structure of the Co4O(piv)6 complex allows for the conclude that only a very small change in energy is required for the transition from antiferromagnetically to ferromagnetically coupled Co atoms.

A prospective randomised comparison of earlier function after total hip arthroplasty with a mini posterior approach or supercapsular percutaneously-assisted total hip approach: a gait analysis study.

BACKGROUND: The supercapsular percutaneously-assisted total hip (SuperPATH) approach is a muscle sparing surgical technique for total hip arthroplasty (THA). The literature reports good clinical and functional results of the SuperPATH technique in the short term. We aimed to compare early outcomes and gait analysis of THA using the mini posterior approach (MPA) and supercapsular percutaneously-assisted total hip (SuperPATH) approach. METHODS: 44 patients who underwent THA, were randomly allocated to either MPA or SuperPATH. The data were then collected prospectively (preoperatively and postoperatively at 6 weeks). Plain anteroposterior radiographs of the pelvis and instrumental gait analysis were obtained. The visual analogue scale (VAS), Harris Hip Score (HHS) and Hip disability and Osteoarthritis Outcome Scores (HOOS) were used to assess functional and clinical outcomes. RESULTS: No significant difference was found in patients' surgical outcomes. Patients in the SuperPATH group had less pain according to the VAS score at follow-up than the MPA group (p < 0.01). There was also a significant improvement in HHS and HOOS scores for all patients (p < 0.001) with the SuperPATH group showing superior changes. The comparison of mean differences in gait velocity between preoperative and 6 weeks postoperative result, revealed improvement in the SuperPATH group over the MPA group (p = 0.06). Limping was more persistent in the MPA group. Kinematic parameters demonstrated improved hip joint excursion slightly higher in the MPA group. There was no significant improvement in kinetic and kinematic parameters at different walking moments for all patients at 6 weeks compared to preoperative gait patterns. CONCLUSIONS: SuperPATH and MPA both show excellent results. This study reveals that the SuperPATH technique was associated with lower postoperative pain levels, and higher physical function and quality of life. Improved functional outcomes allowed earlier postoperative rehabilitation and faster recovery. Specific improvement in gait patterns were identified with nonsignificant differences between the 2 approaches at 6 weeks follow-up.

Role of Mono- and Divalent Ions in Peptide Glu-Asp-Arg-DNA Interaction.

The interaction of the regulatory biologically active peptide Glu-Asp-Arg (EDR) with DNA is considered by spectral, NMR, viscosimetry, and molecular dynamics methods. It was shown that EDR can partly penetrate into the major groove of DNA and affect the base atoms, mainly the N7 and O6 of guanine. It was observed that Mg2+ ions can promote DNA-EDR interaction due to their effective screening of the negatively charged phosphate groups of DNA. This action of Mg2+ remains in salted solution as well.

Clathrin-Mediated Endocytosis Delivers Proteolytically Active Phytaspases Into Plant Cells.

Phytaspases belong to the family of plant subtilisin-like proteases and are distinct from other family members, as they have strict and rarely occurring aspartate cleavage specificity and unusual localization dynamics. After being secreted into the apoplast of healthy plant tissues, phytaspases are able to return back into cells that have been committed to cell death due to a variety of biotic and abiotic stresses. It was recently discovered that retrograde transport of phytaspases involves clathrin-mediated endocytosis. Here, consequences of phytaspase internalization were studied. Proteolytic activity of phytaspases in the apoplast and intracellular protein fractions obtained from Nicotiana benthamiana leaves containing either endogenous phytaspase only or transiently producing Nicotiana tabacum phytaspase-EGFP protein (NtPhyt-EGFP) was determined. We demonstrated that triggering phytaspase internalization by antimycin A-induced oxidative stress is accompanied by re-distribution of phytaspase activity from the apoplast to the cell interior. Inhibition of clathrin-mediated endocytosis by co-production of the Hub protein prevented phytaspase internalization and phytaspase activity re-localization. Specificity of endocytic uptake of phytaspases was demonstrated by the co-production of an apoplast-targeted mRFP protein marker, which retained its apoplastic localization when phytaspase internalization was essentially complete. Overproduction of NtPhyt-EGFP, but not of the proteolytically inactive phytaspase mutant, per se caused moderate damage in young Nicotiana benthamiana seedlings, whereas antimycin A treatment induced a pronounced loss of cell viability independent of the NtPhyt-EGFP overproduction. Interestingly, inhibition of clathrin-mediated endocytosis abrogated cell death symptoms in both cases. In contrast to stress-induced internalization of tobacco phytaspase, Arabidopsis thaliana phytaspase-EGFP protein (AtPhyt-EGFP) was spontaneously internalized when transiently produced in N. benthamiana leaves. The AtPhyt-EGFP uptake was dependent on clathrin-mediated endocytosis as well, the internalized protein being initially visualized within the membranous vesicles. At later time points, the EGFP tag was cleaved off from AtPhyt, though the elevated level of intracellular AtPhyt proteolytic activity persisted. Our data, therefore, point to clathrin-mediated endocytosis as a means to deliver proteolytically active phytaspases into plant cells. It would be interesting to learn whether or not phytaspases are unique among the large family of plant subtilisin-like proteases in their ability to utilize retrograde trafficking.

A Novel Small Molecule Supports the Survival of Cultured Dopamine Neurons and May Restore the Dopaminergic Innervation of the Brain in the MPTP Mouse Model of Parkinson's Disease.

We previously showed that monoterpenoid (1R,2R,6S)-3-methyl-6-(prop-1-en-2-yl)cyclohex-3-ene-1,2-diol 1 alleviates motor manifestations of Parkinson's disease in animal models. In the present study, we designed and synthesized monoepoxides of (1R,2R,6S)-3-methyl-6-(prop-1-en-2-yl)cyclohex-3-ene-1,2-diol 1 and evaluated their biological activity in the MPTP mouse model of Parkinson's disease. We also assessed the ability of these compounds to penetrate the blood-brain barrier (BBB). According to these data, we chose epoxide 4, which potently restored the locomotor activity in MPTP-treated mice and efficiently penetrated the BBB, to further explore its potential mechanism of action. Epoxide 4 was found to robustly promote the survival of cultured dopamine neurons, protect dopamine neurons against toxin-induced degeneration, and trigger the mitogen-activated protein kinase (MAPK) signaling cascade in cells of neuronal origin. Meanwhile, neither the survival-promoting effect nor MAPK activation was observed in non-neuronal cells treated with epoxide 4. In the MPTP mouse model of Parkinson's disease, compound 4 increased the density of dopamine neuron fibers in the striatum, which can highlight its potential to stimulate striatal reinnervation and thus halt disease progression. Taken together, these data indicate that epoxide 4 can be a promising compound for further development, not only as a symptomatic but also as a neuroprotective and neurorestorative drug for Parkinson's disease.

Synthesis and evaluation of antitumor, anti-inflammatory and analgesic activity of novel deoxycholic acid derivatives bearing aryl- or hetarylsulfanyl moieties at the C-3 position.

Novel deoxycholic acid (DCA) derivatives were stereoselectively synthesised with -OH and -CH2SR moieties at the C-3 position, where R was a substituted aryl [2-aminophenyl (8) or 4-chlorophenyl (9)] or hetaryl [1-methylimidazolyl (5), 1,2,4-triazolyl (6), 5-amino-1,3,4-thiadiazolyl (7), pyridinyl (10) or pyrimidinyl (11)]. These compounds were prepared in good yields from the C-3ß-epoxy derivative 2 in the epoxide ring-opening reaction by S-nucleophiles. These derivatives were evaluated for their in vitro anti-proliferation activity in a panel of tumor cell lines. Data showed that: (i) heterocycle-containing derivatives displayed higher cytotoxicity profiles than the parent molecule; (ii) heterocyclic substituents were more preferable than aryl moieties for enhancing anti-proliferation activity; (iii) the sensitivity of tumor cell lines to analysed compounds decreased in the following order: HuTu-80 (duodenal carcinoma)>KB-3-1 (cervical carcinoma)>HepG2 (hepatocellular carcinoma)>MH-22a (hepatoma); (iv) compounds 5, 6 and 11 exhibited a high cytotoxic selectivity index (HuTu-80: SI>7.7, 38.5 and 12.0, respectively). Compounds 2 and 6-8 markedly inhibited NO synthesis by interferon γ-induced macrophages. Screening for anti-inflammatory activity of these derivatives in vivo showed their high potency on histamine- (5, 10) and formalin- (2, 10, 11) induced paw edema models.

Highly potent activity of (1R,2R,6S)-3-methyl-6-(prop-1-en-2-yl)cyclohex-3-ene-1,2-diol in animal models of Parkinson's disease.

(1R,2R,6S)-3-Methyl-6-(prop-1-en-2-yl)cyclohex-3-ene-1,2-diol 1 possesses potent antiparkinsonian activity in both MPTP and haloperidol animal models. The use of compound 1 resulted in nearly full recovery of the locomotor and exploratory activities and was as effective as the comparator agent (levodopa). All eight stereoisomers of compound 1 have been synthesized and the influence of the absolute configuration on the antiparkinsonian activity of compound 1 was shown.