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In flies (Diptera), the ovary displays several distinct patterns of the follicular epithelium formation and diversification. Two main patterns have been identified in the true flies or Brachycera, namely the Rhagio type and the Drosophila type. These patterns align with the traditional division of Brachycera into Orthorrhapha and Cyclorrhapha. However, studies of the follicular epithelium morphogenesis in cyclorrhaphans other than Drosophila are scarce. We characterise the developmental changes associated with the emergence of follicle cell (FC) diversity in two cyclorrhaphans belonging to the family Tephritidae (Brachycera, Cyclorrhapha). Our analysis revealed that the diversification of FCs in these species shows characteristics of both the Rhagio and Drosophila types. First, a distinct cluster of FCs, consisting of polar cells and border‐like cells, differentiates at the posterior pole of the ovarian follicle. This feature is unique to the Rhagio type and has only been reported in species representing the Orthorrhapha group. Second, morphological criteria have identified a significantly smaller number of subpopulations of FCs than in Drosophila. Furthermore, while the general pattern of FC migration is similar to that of Drosophila, the distinctive migration of the anterior‐dorsal FCs is absent. In the studied tephritids, the migration of the anterior polar cell/border cell cluster towards the anterior pole of the oocyte is followed by the posterior migration of the main body cuboidal FCs to cover the expanding oocyte. Finally, during the onset of vitellogenesis, a distinct subset of FCs migrates towards the centre of the ovarian follicle to cover the oocyte's anterior pole. Our study also highlights specific actions of some FCs that accompany the migration process, which has not been previously documented in cyclorrhaphans. These results support the hypothesis that the posterior and centripetal migrations of morphologically unique FC subsets arose in the common ancestor of Cyclorrhapha. These events appear to have occurred fairly recently in the evolutionary timeline of Diptera. [ABSTRACT FROM AUTHOR]

The alarming increase in the resistance of bacteria to the currently available antibiotics necessitates the development of new effective antimicrobial agents that are active against bacterial pathogens causing major public health problems. For this purpose, our in-house libraries were screened against a wide panel of clinically relevant Gram-positive and Gram-negative bacteria, based on which compound I was selected for further optimization. Synthetic efforts in a group of arylurea derivatives of aryloxy(1-phenylpropyl) alicyclic diamines, followed with an in vitro evaluation of the activity against multidrug-resistant strains identified compound 44 (1-(3-chlorophenyl)-3-(1-{3-phenyl-3-[3-(trifluoromethyl)phenoxy] propyl}piperidin- 4-yl)urea). Compound 44 showed antibacterial activity against Gram-positive bacteria including fatal drug-resistant strains i.e., Staphylococcus aureus (methicillin-resistant, MRSA; vancomycin-intermediate, VISA) and Enterococcus faecium (vancomycin-resistant, VR Efm) at low concentrations (0.78–3.125 μg/mL) comparable to last resort antibiotics (i.e., vancomycin and linezolid). It is also potent against biofilm-forming S. aureus and Staphylococcus epidermidis (including linezolid-resistant, LRSE) strains, but with no activity against Gram-negative bacteria (Escherichia coli , Klebsiella pneumoniae and Pseudomonas aeruginosa). Compound 44 showed strong bactericidal properties against susceptible and drug-resistant Gram-positive bacteria. Depolarization of the bacterial cytoplasmic membrane induced by compound 44 suggests a dissipation of the bacterial membrane potential as its mechanism of antibacterial action. The high antimicrobial activity of compound 44 , along with its selectivity over mammalian cells (lung MCR-5 and skin BJ fibroblast cell lines) and no hemolytic properties toward horse erythrocytes, proposes arylurea derivatives of aryloxy(1-phenylpropyl) alicyclic diamines for development of novel antibacterial agents. [Display omitted] • Arylurea derivatives with bactericidal activity against Gram-positive bacteria. • Compound 44 overcomes the antibiotic resistance of MRSA, VISA, LRSE and VR E strains. • Compound 44 inhibits the growth of biofilm-forming S. aureus and S. epidermidis strains. • Compound 44 displays selectivity over MCR-5 and BJ fibroblast cell line and horse erythrocytes. • Depolarization of bacterial membrane as proposed mechanism of action for compound 44. [ABSTRACT FROM AUTHOR]

R-(-)-ketamine has emerged as a potentially improved medication over that of the (S)-isomer (marketed as Spravato for depression). Recent data have suggested (R)-ketamine could have value in the treatment of substance use disorder. The present set of experiments was undertaken to examine whether (R)-ketamine might prevent tolerance development. Rapid ethanol (ETOH) tolerance was studied since racemic ketamine had previously been shown to block this tolerance development in rats. In the present study, male Sprague-Dawley rats were given two large doses of ETOH on Day 1 (2.3 + 1.7 g/kg) and 2.3 g/kg ETOH on Day 2. Animals were tested for effects of 2.3 g/kg ETOH on grip strength, inclined screen performance and rotarod performance on Day 1 with or without (R)-ketamine as a pretreatment. (R)-ketamine alone was tested at the highest dose studied (10 mg/kg) and did not significantly influence any dependent measure. (R)-ketamine (1-10 mg/kg) did not alter the acute effects of ETOH except for enhancing the effects of ETOH on the inclined screen test at 3 mg/kg. Between-subjects analysis documented that tolerance developed to the effects of ETOH only on the measure of grip strength. (R)-ketamine (3 mg/kg) given prior to ETOH on Day 1 exhibited a strong trend toward preventing tolerance development (p = 0.062). The present results extend prior findings on the potential value of (R)-ketamine in substance abuse disorder therapeutics and add to the literature on NMDA receptor blockade as a tolerance-regulating mechanism., (Copyright © 2021 Elsevier Inc. All rights reserved.)