An experimental and theoretical approach to the molecular structure of 2-{4-[3-(2,5-dimethylphenyl)-3-methylcyclobutyl]thiazol-2-yl}isoindoline-1,3-dione

The title compound, 2-{4-[3-(2,5-dimethylphenyl)-3-methylcyclobutyl]thiazol-2-yl}isoindoline-1,3-dione (C₂₄H₂₂N₂O₂S), was synthesized and characterized by IR-NMR spectroscopy and single-crystal X-ray diffraction. The compound crystallizes in the monoclinic space group P2₁/c with a?=?19.7799(13) Å, b?=?6.7473(4) Å, c?=?15.7259(9) Å and β?=?103.416(5)°. In addition, the molecular geometry, vibrational frequencies and gauge including atomic orbital (GIAO) ¹H and ¹³C chemical shift values of the title compound in the ground state have been calculated by using the Hartree-Fock (HF) and density functional method (DFT/B3LYP) with 6–31G(d), 6–31 + G(d,p) and LANL2DZ basis sets, and compared with the experimental data. To determine conformational flexibility, molecular energy profile of the title compound was obtained by semi-empirical (AM1) calculations with respect to two selected degrees of torsional freedom, which were varied from ?180° to +180° in steps of 5°. Besides, molecular electrostatic potential, frontier molecular orbitals (FMO) analysis and thermodynamic properties of the title compound were investigated by theoretical calculations.     

Effects of Plantago lanceolata L. extract on full-thickness excisional wound healing in a mouse model

Wound healing requires cells that increase both collagen production as a result of inflammatory events and regeneration of epithelial tissue. The Plantago species of herbs have been used in traditional treatment of skin disorders and infectious diseases, and digestive, respiratory, reproductive and circulatory conditions. We investigated the efficacy of different concentrations of Plantago lanceolata L. extract (PLE) for wound healing owing to its anti-inflammatory, anti-bacterial, anti-fungal, anti-oxidant, anti-ulcerative, analgesic and immunomodulatory properties. We used 72 mice in four groups of 18. An excisional 1 cm wound was created in the skin on the back of the mice in all groups. An ointment containing 10% PLE was applied to the wound in group 1, an ointment containing 20% PLE was applied in group 2 and vaseline was applied in group 3. In group 4, no treatment was applied to the wound. On days 7, 14, and 21 of the experiment, six animals in each group were sacrificed after the wounds were photographed and specimens from the wound sites were examined. On day 14, epithelialization was more prominent in group 2, while vascularization and collagen deposition was more advanced in groups 1 and 2 compared to the other groups. Immunohistochemical examination revealed that TGF-β1 expression was elevated on day 14 in all groups; however, this elevation was more limited in groups 1 and 2 than in groups 3 and 4. Although ANGPT-2 expression increased in groups 1 and 4 on day 14, it decreased significantly in groups 2 and 3. We found that different concentrations of PLE exhibited positive effects on wound healing. Application of 10% PLE ointment may be a useful strategy for wound healing.     

Systems pathology analysis identifies neurodegenerative nature of age‐related vitreoretinal interface diseases

Aging is a phenomenon that is associated with profound medical implications. Idiopathic epiretinal membrane (iEMR) and macular hole (MH) are the major vision‐threatening vitreoretinal diseases affecting millions of aging people globally, making these conditions an important public health issue. iERM is characterized by fibrous tissue developing on the surface of the macula, which leads to biomechanical and biochemical macular damage. MH is a small breakage in the macula and is associated with many ocular conditions. Although several individual factors and pathways are suggested, a systems pathology level understanding of the molecular mechanisms underlying these disorders is lacking. Therefore, we performed mass spectrometry‐based label‐free quantitative proteomics analysis of the vitreous proteomes from patients with iERM and MH to identify the key proteins, as well as the multiple interconnected biochemical pathways, contributing to the development of these diseases. We identified a total of 1,014 unique proteins, many of which are linked to inflammation and the complement cascade, revealing the inflammation processes in retinal diseases. Additionally, we detected a profound difference in the proteomes of iEMR and MH compared to those of diabetic retinopathy with macular edema and rhegmatogenous retinal detachment. A large number of neuronal proteins were present at higher levels in the iERM and MH vitreous, including neuronal adhesion molecules, nervous system development proteins, and signaling molecules, pointing toward the important role of neurodegenerative component in the pathogenesis of age‐related vitreoretinal diseases. Despite them having marked similarities, several unique vitreous proteins were identified in both iERM and MH, from which candidate targets for new diagnostic and therapeutic approaches can be provided.     

Cheating on Cheaters Stabilizes Cooperation in Pseudomonas aeruginosa

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A high-powered replication study finds no effect of starting or stopping hormonal contraceptive use on relationship quality

A number of recent studies have implicated that incongruent use of hormonal contraceptives (HCs) negatively affects various aspects of women's romantic relationships. It has been suggested that women with incongruent HC use (a discrepancy in HC use status between when they first met their current partner and the time of study participation) report less sexual satisfaction and higher jealousy scores compared to women with congruent HC use. A similar effect has also been hypothesized for general relationship satisfaction, and recent findings suggest that the association between HC incongruency and women's general relationship satisfaction is moderated by third-party ratings of facial attractiveness of the women's male partners. Using a large convenience sample (N = 948) of Finnish women, we attempted to replicate previously reported findings but found no support for the HC congruency hypothesis, despite excellent statistical power (≥98.7%) to detect previously reported effect sizes. Instead, after dividing our sample into four groups based on HC congruency/incongruency, we found that the largest differences in jealousy, sexual satisfaction, and relationship satisfaction scores tended to be found between women who were consistent HC users and consistent non-users (i.e., between women with different kinds of congruent HC use). We also detected a significant main effect of current HC use on jealousy. We conclude that HC congruency effects reported in previous studies may have spuriously arisen from unequal distributions of current HC users within congruent and incongruent HC user groups.     

Evaluation of chalcones as inhibitors of glutathione S‐transferase

Glutathione S‐transferases (GSTs) are the superfamily of multifunctional detoxification isoenzymes and play an important role in cellular signaling. In the present study, potential inhibition effects of chalcones were tested against human GST. For this purpose, GST was purified from human erythrocytes with 5.381 EU?mg^?1 specific activity and 51.95% yield using a GSH–agarose affinity chromatographic method. The effects of chalcones on in vitro GST activity were tested at various concentrations. K_i constants of chalcones were found in the range of 7.76–41.93 μM. According to the results, 4‐fluorochalcone showed a better inhibitory effect compared with the other compounds. The inhibition mechanisms of 2'‐hydroxy‐4‐methoxychalcone and 4‐methoxychalcone were noncompetitive, whereas the inhibition mechanisms of 4'‐ hydroxychalcone, 4‐ fluorochalcone, and 4,4'‐ diflurochalcone were competitive.     

Lipid vesicles affect the aggregation of 4-hydroxy-2-nonenal-modified α-synuclein oligomers

Parkinson's disease (PD) and other synucleinopathies are characterized by accumulation of misfolded aggregates of α-synuclein (α-syn). The normal function of α-syn is still under investigation, but it has been generally linked to synaptic plasticity, neurotransmitter release and the maintenance of the synaptic pool. α-Syn localizes at synaptic terminals where it can bind to synaptic vesicles as well as to other cellular membranes. It has become clear that these interactions have an impact on both α-syn functional role and its propensity to aggregate. In this study, we investigated the aggregation process of α-syn covalently modified with 4-hydroxy-2-nonenal (HNE). HNE is a product of lipid peroxidation and has been implicated in the pathogenesis of different neurodegenerative diseases by modifying the kinetics of soluble toxic oligomers. Although HNE-modified α-syn has been reported to assemble into stable oligomers, we found that slightly acidic conditions promoted further protein aggregation. Lipid vesicles delayed the aggregation process in a concentration-dependent manner, an effect that was observed only when they were added at the beginning of the aggregation process. Co-aggregation of lipid vesicles with HNE-modified α-syn also induced cytotoxic effects on differentiated SHSY-5Y cells. Under conditions in which the aggregation process was delayed cell viability was reduced. By exploring the behavior and potential cytotoxic effects of HNE-α-syn under acidic conditions in relation to protein-lipid interactions our study gives a framework to examine a possible pathway leading from a physiological setting to the pathological outcome of PD.     

Effects of frost hardening on the composition of galactolipids and phospholipids occurring during isolation of chloroplast thylakoids from needles of scots pine

Frost hardening of seedlings of Scots pine (Pinus sylvestris) at a non-freezing temperature of 4°C resulted in a 2-fold increase of the acyl lipids of the needles. This was because of increases in phospholipids and triglycerides. The galactolipid content of the needles was almost the same in unhardened and frost-hardened seedlings. In unhardened seedlings the mol ratio of monogalactosyl diacylglycerol (MGDG) to digalactosyl diacylglycerol (DGDG) was 1.7 ± 0.3 and 0.9 ± 0.2 in needles and isolated thylakoids, respectively. Corresponding ratios for frost-hardened seedlings were 1.5 ± 0.2 and 0.3 ± 0.03. The lower ratios found in isolated thylakoids, particularly in thylakoids from frost-hardened seedlings, are suggested to depend on the enzyme galactolipid: galactolipid galactosyltransferase being active during the isolation procedure. This is deduced from the result that the content of MGDG decreased and that of DGDG and 1.2 diglycerides increased. Needles of Scots pine also contain phospholipidase D. This enzyme was active during thylakoid preparation, particularly after frost hardening, as judged from the large amount of phosphatidic acid found the in thylakoid fraction isolated from frost-hardening needles. The fatty acid composition of the acyl lipids showed no major changes due to hardening at non-freezing temperature.     

Defective Gene Product in <Emphasis Type="Italic">dna</Emphasis>F Mutant of <Emphasis Type="Italic">Escherichia coli</Emphasis>

The dnaF mutant of Escherichia coli has been shown to contain very low ribonucleoside diphosphate reductase activity. The B1 sub unit of the reductase is heat-sensitive in the mutant.     

Digitonin reaction in electron microscopy

Summary The ultrastructural localization of cholesterol (3-hydroxysterols) has been studied by the digitonin reaction adapted to the electron microscope. The reaction was undertaken in the adrenal gland, liver, and seminiferous tubules of adult albino rats. The digitonincholesterol crystals formed in the reaction proved to be an osmiophilous cylindrical structure made up of coaxial lamellae.