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The 2-imidazoline nitroxide derivatives of cymantrene—2-(η5-cyclopentadienyl)tricarbonylmanganese(I)-4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazole-3-oxide-1-oxyl (NNMn) and 2-(η5-cyclopentadienyl)tricarbonylmanganese(I)-4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazole-1-oxyl (INMn) were synthesized. It was shown that NNMn and INMn exhibit a sufficiently high kinetic stability both in solids and in solutions under normal conditions. Their structural characteristics, magnetic properties and electrochemical behavior are close to Re(I) analogs. This opens the prospect of using paramagnetic cymantrenes as prototypes in the design of Re(I) half-sandwiched derivatives for theranostics, where therapy is combined with diagnostics by magnetic resonance imaging due to the contrast properties of nitroxide radicals.

The paper consists of two parts. The first introductory part considers all the available testimonies about life and works of Hesychios of Miletos, the Byzantine historian and encyclopaedist of the 6th cent. A.D. The Introduction also contains a brief overview of the research literature on the issue. Some new assumptions are made about the dating and the purpose of the Roman and General History attributed to Hesychios. In particular, I suggest that the History was written in the early years of the reign of Justinian I and, perhaps, was intended for the upbringing and education of Hesychios’ son John. The second part of the paper contains a translation of the biography of Aristotle, which was attributed to Hesychios by V. Rose and which is believed to be a part of his Onomatologos or Table of Eminent Writers. The main value of this Biography is an extensive list of Aristotle’s writings. The translation is annotated and accompanied by an index of correspondences between the list of Hesychios and the two other extant lists of Aristotle’s works, belonging to Diogenes Laertius and Ptolemy-al-Garib.

Loss of function mutations in the FGD1 gene cause a rare X-linked disease, faciogenital dysplasia (FGDY, also known as Aarskog-Skott syndrome), which is associated with bone and urogenital abnormalities. The FGD1 gene encodes à CDC42-specific guanine nucleotide exchange factor. The mutations are frequently located in the DH module of FGD1 preventing its transformation to the active form. We previously reported that Golgi-associated FGD1 regulates post-Golgi transport of some conventional and bone-specific proteins in a CDC42-dependent manner. However, the downstream targets of FGD1/CDC42 signaling that operate to support transport from the Golgi remain elusive. Here, we demonstrate that Golgi-localized CDC42 effectors might be involved in FGD1-mediated post-Golgi transport, probably through coordination of Golgi membrane and cytoskeleton dynamics. Overexpression of effector-specific CDC42 mutants (exhibiting preferential affinities for PAK1, IQGAP1, N-WASP, or PAR6) only partially rescue membrane trafficking in FGD1-deficient cells, indicating that the orchestrated activities of several downstream targets of CDC42 are required to support FGD1-mediated export from the Golgi. Our findings provide new insights into understanding the molecular mechanisms behind FGD1/CDC42-dependent transport events and uncover new targets whose potential might be explored for correction of membrane trafficking in FGDY.

The work objective is searching new methods of strengthening processing of the cranked shaft. Modern constructive and processing methods of increasing the durability of the engine cranked shaft are considered. Some features of the key processing methods - nitriding, riveting on, steel shot blasting of fillets - are identified. The main task of the constructive methods to increase strength -crankshaft shaping that provides a more uniform stress distribution on shaft volume - both in the stress concentration zones, and outside them is considered. The required design shapes of the shaft are determined experimentally. New installation diagrams for the strengthening and stabilizing vibrowave and shock-vibrating machining of the engine crankshafts are proposed. It is experimentally established that the shock-vibrating machining allows the following: uniform hardening of the surface layer of all part features; sharp edge finishing and rounding; smooth transitions; avoidance of non-rigid shaft distortion that takes place at the local rolling of large part fillets.

In this study we report that, in response to proteasome inhibition, the E3-Ubiquitin ligase TRIM50 localizes to and promotes the recruitment and aggregation of polyubiquitinated proteins to the aggresome. Using Hdac6-deficient mouse embryo fibroblasts (MEF) we show that this localization is mediated by the histone deacetylase 6, HDAC6. Whereas Trim50-deficient MEFs allow pinpointing that the TRIM50 ubiquitin-ligase regulates the clearance of polyubiquitinated proteins localized to the aggresome. Finally we demonstrate that TRIM50 colocalizes, interacts with and increases the level of p62, a multifunctional adaptor protein implicated in various cellular processes including the autophagy clearance of polyubiquitinated protein aggregates. We speculate that when the proteasome activity is impaired, TRIM50 fails to drive its substrates to the proteasome-mediated degradation, and promotes their storage in the aggresome for successive clearance.

The efficacy of 3 doses (10, 15 and 20 mg/kg) of the new antischistosomal drug Ro 15-5458 (10-[2-(diethylamino)ethyl]-9-acridanone-(thiazolidin-2-ylidene)hy drazone, CAS 092928-47-7) against an Egyptian strain of S. mansoni was studied in mice. The effect of duration of infection on the response of mice to treatment with 20 mg/kg was evaluated at 7 and 12 weeks after infection. The criteria used for the assessment of drug efficacy were: worn count and distribution in the liver and portomesenteric system, oogram changes in the small intestine, estimation of the number of ova/g stood, liver and intestine and histopathological examination of mice liver. Data revealed a dose dependent decrease in number of adult worms and number of ova/g stool, liver and intestine. A reduction of 83.6, 89.4 and 94.9% in mean number of schistosomes compared to control was recorded following treatment with 10, 15 and 20 mg/ kg of the drug, respectively. Oogram changes were more remarkable following treatment with 20 mg/kg as evidenced by complete disappearance of all immature stages. Treatment with Ro 15-5458 in a dose of 20 mg/kg resulted in complete disappearance of couples and 100% shift or worms to the live. Examination of mice liver 2 weeks post treatment revealed on changes in pathology following treatment with 10 mg/kg compared to control. Treatment with 20 mg/kg gave better results comparable to 15 mg/kg, a decreased number and size of granulomas with minimal areas of necrosis was observed. Parasitological cure was effectively achieved when treatment was initiated 7 or 12 weeks post infection. However, histopathological data revealed that the earlier the treatment the better the results.

The in vivo effects of oxamniquine on the tegumental surface of adult Schistosoma mansoni were studied using scanning electron microscopy. Pronounced tegumental alterations were observed in all worms including marked oedema, wrinkling and distortion, atrophy, loss of tone and complete disorganization of suckers, blebbing, destruction of tubercles, collapse of sensory papillae and erosion or peeling of the surface layer. The amount of damage was more marked in males than females and varied considerably among worms recovered from the same host and even in different regions of the same worm. Damage was irreversible and all worms were eventually eliminated.

Levamisol which is highly effective against Ascaris infections, was shown to produce degenerative changes in the intestine and the reproductive system of the worm. Worms that were not expelled by treatment produced only nonviable eggs which could not develop in vitro. Levamisol is thus shown to be not only a highly curative drug, but a compound of significant epidemiological importance.

The response of mice infected with Schistosoma mansoni to a novel environment has been investigated in an attempt to study the effects of the disease on brain cognitive function by using opto-varimix instrument and autotrack computer program. Two to 18 weeks infected mice showed lower ambulatory activities than their matched controls with the largest reduction occurring between weeks 6 to 10. Maximum effects were observed in week 8. The first 5 minutes of ambulatory activities, designated as the "first session", were 22.3% lower in infected mice as compared with controls. The decline in the first session activities of infected mice was slower than the controls. Infected mice showed fewer stereotype movements with maximum reduction in week 16 of infection. There was no correlation between mice ambulatory activities or stereotype movements and infection duration. The importance of these findings in relation to the course of the disease and the underlying mechanism(s) are discussed.

By means of electrophoresis quantitative estimation of serum protein components were made at various intervals before and after treatment with oxamniquine. During infection of mice with S. mansoni serum protein fractions showed marked alterations. Significant increase of total protein, alpha-2 globulin and beta globulin started at week 4 and alpha-1 globulin and gamma globulin at week 6. The significant decrease of globulins at week 6 resulted in reduced albumin globulin ratios. Some of these changes developed during maturation of worms and became more evident with initiation of egg deposition. The possible cause of these variations and their significance were discussed. Oxamniquine treatment of infected mice inhibited such alterations. Administration of the drug to normal mice was followed by temporary increase of serum albumin.

The therapeutic efficiency of oxamniquine against the local strain of Schistosoma mansoni was investigated in experimentally infected mice. The drug was administered orally using a human-equivalent dose of 20 mg kg-1 day-1 for 3 consecutive days (total dose of 60 mg kg-1). Oxamniquine proved to be very effective as indicated by hepatic shift, oogram changes, complete elimination of adult worms and eradication of faecal eggs.