Gold(I)-Triphenylphosphine Complexes with Hypoxanthine-Derived Ligands: In Vitro Evaluations of Anticancer and Anti-Inflammatory Activities

A series of gold(I) complexes involving triphenylphosphine (PPh₃) and one N-donor ligand derived from deprotonated mono- or disubstituted hypoxanthine (HL_n) of the general composition [Au(L_n)(PPh₃)] (1–9) is reported. The complexes were thoroughly characterized, including multinuclear high resolution NMR spectroscopy as well as single crystal X-ray analysis (for complexes 1 and 3). The complexes were screened for their in vitro cytotoxicity against human cancer cell lines MCF7 (breast carcinoma), HOS (osteosarcoma) and THP-1 (monocytic leukaemia), which identified the complexes 4–6 as the most promising representatives, who antiproliferative activity was further tested against A549 (lung adenocarcinoma), G-361 (melanoma), HeLa (cervical cancer), A2780 (ovarian carcinoma), A2780R (ovarian carcinoma resistant to cisplatin), 22Rv1 (prostate cancer) cell lines. Complexes 4–6 showed a significantly higher in vitro anticancer effect against the employed cancer cells, except for G-361, as compared with the commercially used anticancer drug cisplatin, with IC₅₀ ≈ 1–30 µM. Anti-inflammatory activity was evaluated in vitro by the assessment of the ability of the complexes to modulate secretion of the pro-inflammatory cytokines, i.e. tumour necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), in the lipopolysaccharide-activated macrophage-like THP-1 cell model. The results of this study identified the complexes as auspicious anti-inflammatory agents with similar or better activity as compared with the clinically applied gold-based antiarthritic drug Auranofin. In an effort to explore the possible mechanisms responsible for the biological effect, the products of interactions of selected complexes with sulfur-containing biomolecules (L-cysteine and reduced glutathione) were studied by means of the mass-spectrometry study.     

Characterization of the cellulase complex from Cellulomonas grown on bagasse pith

Summary The effect of physico-chemical parameters on the cellulolytic activity of Cellulomonas sp. IIbc grown on sugarcane bagasse pith was investigated, and the optimum ranges for enzyme activity were established. The cellulases were more stable when incubated at the optimum growth temperature (32°C) than under optimum activity conditions (45°C for -glucosidases and 50°C for CMC- and FP-cellulases). The -glucosidases were the thermostability-limiting enzymes of the complex. Two types of endoglucanases could be recognized according to their adsorption properties on bagasse: one weakly-bound and one tightly-bound type, the latter constituting approximately 73% of the extracellular endoglucanases at exponential growth phase. Four forms active on filter paper and three active on CMC were obtained by HPLC separation of the extracellular fraction of the culture at stationary phase.Abbreviations CMC carboxymethylcellulose - FP filter paper     

Cultivation ofCandida lipolytica 4-1 on hydrocarbons

The length of the carbon chain of the hydrocarbon substrate affects markedly the fatty acid composition in the cell lipids of the yeastCandida lipolytica 4-1. During cell growth onn-hexadecane dissolved in deparaffinated gas oil, direct incorporation of palmitic acid into lipids takes place. During growth onn-dodecane, on the other hand, an immediate synthesis and incorporation into oleic acid is observed. The cells contain only little lauric acid (maximum 11%). During fermentation of then-alkanes dissolved in deparaffinated gas oil which contains a mixture of isoalkanes, alkylated aromatic and cyclic hydrocarbons, free fatty acids accumulate in the oil phase. The fatty acid composition in the oil differs markedly according to the growth stage of cells. At the beginning of the logarithmic phase of growth, the fatty acid composition in the oil phase reflects the acid composition in the cell lipids, toward the end of cell growth, the cooxidation products of the isoalkanes accumulate. The aqueous phase contains lower fatty acids and cooxidation products of isoalkanes and of alkylated aromatic and alicyclic hydrocarbons. Part III. Oxidation and Utilization of Individual Pure Hydrocarbons—seeFolia Microbiol. 14,334 (1969).     

Studies on methanol-oxidizing yeasts

A series of yeast strains utilizing methanol as the only source of carbon and energy were isolated both from soil and waste waters. Growth of the yeasts was studied in a mineral medium with yeast extract at 30°C. Growth parameters, Q_{o 2} and composition of biomass were studied in the strain 11Bh producing in shaken flasks highest yields of biomass. The biomass was found to contain 44% of crude proteins, 2% esterified fatty acids, 3% non-esterified fatty acids, 6% RNA and 0.25% DNA. Amino acid analysis revealed a high content of essential amino acids, lysine, leucine, valine and threonine in particular.     

Cultivation of the yeastCandida lipolytica on hydrocarbon

The ability of the yeastCandida lipolytica 4-1 to oxidize and utilize various pure aliphatic hydrocarbons occurring in gas oil was studied. It was found that the given strain ofCandida lipolytica oxidized n-alkanes without adaptation, starting with heptane, and utilized them for growth, starting with nonane. Isoalkanes with a single methyl group in the side chain were also oxidized and utilized for growth, but less than the corresponding n-alkanes. The site of the methyl group in the isoalkane chain influences its conversion to biomass. Branched chains at both ends of the isoalkane molecule prevent its utilization for growth ofCandida lipolytica. 1-olefines are also oxidized and utilized for growth, though less than the corresponding n-paraffins. Alkylaromatic hydrocarbons are oxidized from amylbenzene up to decylbenzene, which is utilized only slightly for growth of the yeast.     

Chlorophyll a is the crucial redox sensor and transmembrane signal transmitter in the cytochrome b6f complex. Components and mechanisms of state transitions from the hydrophobic mismatch viewpoint

The cytochrome (cyt) b₆f complex is involved in the transmembrane redox signaling that triggers state transitions in cyanobacteria and chloroplasts. However, the components and molecular mechanisms are still unclear. In an attempt to solve this long-standing problem, we first focused on the unknown role of a single chlorophyll a (Chla) in cyt b₆f with a new approach based on Chla structural properties. Various b₆f X-ray crystal structures were analyzed to identify their differences, which correlate with differences in Chla molecular volume. We found that the distance of the Rieske [2Fe-2S] cluster to Chla correlates with the distance between a pair of residues at the Q_o-site and the distance between a pair of residues at the opposite membrane side. These correlations were accompanied by the rotation of a key peripheral residue and by changes in the hydrophobic thickness of cyt b₆f. Parallel analysis of cyt bc₁ crystal structures allowed us to conclude that Chla acts as the crucial redox sensor and transmembrane signal transmitter in b₆f for changes in the plastoquinone pool redox state. The hydrophobic mismatch induced by the changed hydrophobic thickness of cyt b₆f is the driving force for the structural reorganizations of the photosynthetic apparatus during induction and the progression of state transitions in cyanobacteria and chloroplasts. A mechanism for LHCII kinase activation in chloroplasts is also proposed. Our understanding of the dynamic structural changes in bc-complexes during turnover at the Q_o-site and state transitions is augmented by the time-sequence ordering of 56 bc crystal structures.     

Investigating the Role of Assessment Method on Reports of Déjà Vu and Tip-of-the-Tongue States during Standard Recognition Tests

Déjà vu and tip-of-the-tongue (TOT) are retrieval-related subjective experiences whose study relies on participant self-report. In four experiments (ns = 224, 273, 123 and 154), we explored the effect of questioning method on reported occurrence of déjà vu and TOT in experimental settings. All participants carried out a continuous recognition task, which was not expected to induce déjà vu or TOT, but were asked about their experiences of these subjective states. When presented with contemporary definitions, between 32% and 58% of participants nonetheless reported experiencing déjà vu or TOT. Changing the definition of déjà vu or asking participants to bring to mind a real-life instance of déjà vu or TOT before completing the recognition task had no impact on reporting rates. However, there was an indication that changing the method of requesting subjective reports impacted reporting of both experiences. More specifically, moving from the commonly used retrospective questioning (e.g. “Have you experienced déjà vu?”) to free report instructions (e.g. “Indicate whenever you experience déjà vu.”) reduced the total number of reported déjà vu and TOT occurrences. We suggest that research on subjective experiences should move toward free report assessments. Such a shift would potentially reduce the presence of false alarms in experimental work, thereby reducing the overestimation of subjective experiences prevalent in this area of research.     

The first genomewide interaction and locus-heterogeneity linkage scan in bipolar affective disorder: strong evidence of epistatic effects between loci on chromosomes 2q and 6q

We present the first genomewide interaction and locus-heterogeneity linkage scan in bipolar affective disorder (BPAD), using a large linkage data set (52 families of European descent; 448 participants and 259 affected individuals). Our results provide the strongest interaction evidence between BPAD genes on chromosomes 2q22-q24 and 6q23-q24, which was observed symmetrically in both directions (nonparametric LOD [NPL] scores of 7.55 on 2q and 7.63 on 6q; P<.0001 and P=.0001, respectively, after a genomewide permutation procedure). The second-best BPAD interaction evidence was observed between chromosomes 2q22-q24 and 15q26. Here, we also observed a symmetrical interaction (NPL scores of 6.26 on 2q and 4.59 on 15q; P=.0057 and .0022, respectively). We covered the implicated regions by genotyping additional marker sets and performed a detailed interaction linkage analysis, which narrowed the susceptibility intervals. Although the heterogeneity analysis produced less impressive results (highest NPL score of 3.32) and a less consistent picture, we achieved evidence of locus heterogeneity at chromosomes 2q, 6p, 11p, 13q, and 22q, which was supported by adjacent markers within each region and by previously reported BPAD linkage findings. Our results provide systematic insights in the framework of BPAD epistasis and locus heterogeneity, which should facilitate gene identification by the use of more-comprehensive cloning strategies.