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Doping and compositional tuning of Cs(2)AInCl(6) (A = Ag, Na) double perovskite nanocrystals (PNCs) is considered a promising strategy toward the development of light-emitting sources for applications in solution-processed optoelectronic devices. Oleic acid and oleylamine are by far the most often used surface capping ligands for PNCs. However, the undesirable desorption of these ligands due to proton-exchange reaction during isolation and purification processing results in colloidal and structural instabilities. Thus, the improvement of colloidal and optical stability of PNCs represents one of the greatest challenges in the field. Here, we report a trioctylphosphine-mediated synthesis and purification method toward Sb-alloyed Cs2NaInCl6 PNCs with excellent stability and optical features. Nuclear magnetic resonance spectroscopy enabled one to explain the role of trioctylphosphine and to reveal the reaction mechanism during crystal nucleation and growth. Under the optimized reaction conditions, in situ-generated trioctylphosphonium chloride and benzoyl trioctylphosphonium chloride serve as highly reactive halide sources, while benzoyl trioctylphosphonium and oleylammonium cations together with the oleate anion serve as surface capping ligands, which are bound strongly to the PNC surface. The tightly bound ionic pair of oleylammonium oleate and benzoyl trioctylphosphonium chloride/oleate ligands allows one to obtain monodispersed bright-blue-emitting PNCs with high photoluminescence quantum yields exceeding 50% at an optimum Sb content (0.5%), which also exhibit long-term colloidal stability. The approach based on dual cationic ligand passivation of double PNCs opens the doors for applications in other systems with a potential to achieve higher stability along with superior optical properties. Web of Science 13 40 47859 47845

The ammonium transporter (AMT) family gene is an important transporter involved in ammonium uptake and transfer in plants and is mainly engaged in the uptake and transport of ammonium from the environment by roots and the reabsorption of ammonium in the aboveground parts. In this study, the expression pattern, functional identification, and genetic transformation of the PtrAMT1;6 gene, a member of the ammonium transporter protein family in P. trichocarpa, were investigated as follows: (1) Fluorescence quantitative PCR demonstrated that the PtrAMT1;6 gene was preferentially expressed in the leaves, with both dark-induced and light-inhibited expression patterns. (2) A functional restoration assay using the yeast ammonium transporter protein mutant strain indicated that the PtrAMT1;6 gene restored the ability of the mutant to transport ammonium with high affinity. (3) Arabidopsis was transformed with pCAMBIA-PtrAMT1;6P, and the transformed lines were stained with GUS, which showed that the rootstock junction, cotyledon petioles, and the leaf veins and pulp near the petioles of the transformed plants could be stained blue, indicating that the promoter of the PtrAMT1;6 gene had promoter activity. (4) The overexpression of the PtrAMT1;6 gene caused an imbalance in carbon and nitrogen metabolism and reduced nitrogen assimilation ability in ‘84K’ poplar and ultimately reduced biomass. The above results suggest that PtrAMT1;6 may be involved in ammonia recycling during nitrogen metabolism in aboveground parts, and overexpression of PtrAMT1;6 may affect the process of carbon and nitrogen metabolism, as well as nitrogen assimilation in plants, resulting in stunted growth of overexpression plants.

Crohn’s disease and ulcerative colitis are chronic inflammatory bowel diseases, which are often accompanied by inflammation of other organs. This article presents modern data on etiology, pathogenesis and clinical course of inflammatory bowel diseases, as well as information on extraintestinal eye manifestations of nonspecific ulcerative colitis and Crohn’s disease. The role of microbiota, genetic factors, immune system defects in pathogenesis of intestinal inflammation and extraintestinal eye manifestations is considered. The possibility the development of ophthalmopathology not only against the background of intestinal inflammation, but also as a consequence of therapeutic and surgical methods of treatment of ulcerative colitis and Crohn’s disease is noted. The peculiarities of the course of episcleritis/scleritis, keratitis, uveitis, chorioretinitis, optical neuritis for patients with inflammatory bowel diseases are considered. The presence of these complications may reflect the activity of the underlying disease, which in some cases requires correction of therapy. Anterior uveitis and episcleritis/scleritis are the most common extraintestinal manifestations of inflammatory bowel disease. Inflammation of tissues of the posterior segment of the eye and optic nerve against the background of ulcerative colitis and Crohn’s disease are less common, but are of clinical importance, as they can catastrophically damage the structures of the eye and, as a consequence, lead to complete blindness. Considering the possibility of mild clinical symptoms and asymptomatic course of inflammation in the eye envelopes, the importance of ophthalmological examination of all patients with ulcerative colitis and Crohn’s disease is emphasized. Aspects of modern therapy of ophthalmopathology and background intestinal inflammation are highlighted. Biological preparations — antagonists of pro-inflammatory cytokines — have been identified as the most promising in the treatment of inflammatory intestinal diseases and extraintestinal manifestations. The important role of proper nutrition and biologically active supplements containing omega-3 fatty acids, vitamin D, microelements, was noted as auxiliary therapy of both intestinal and extraintestinal inflammation.

Background Thymic epithelial tumors (TETs) are rare neoplasms, originating from epithelial thymic cells. The oncogenic potential of these rare neoplasms is still largely undefined, and a deeper molecular characterization could result in a relevant advance in their management, greatly improving diagnosis, prognosis and treatment choice. Deregulation of N6-methyladenosine (m6A) RNA modification, catalyzed by the METTL3/METTL14 methyltransferase complex, is emerging as a relevant event in cell differentiation and carcinogenesis. Various studies have reported that altered expression of METTL3 is associated with an aggressive malignant phenotype and favors migration and invasiveness, but its role in Thymic Tumors remains unknown. Results In this study, we characterized that METTL3 contributes to Thymic Epithelial Tumor phenotype. We evidenced that METTL3 is overexpressed in tumor tissue compared to normal counterpart. Silencing of METTL3 expression in thymic carcinoma cells results in reduced cell proliferation and overall translation rate. Of note, METTL3 is responsible for the induction of c-MYC expression in TET cells. Specifically, high expression of c-MYC protein is enabled by lncRNA MALAT1, which is methylated and delocalized by METTL3. Interestingly, blocking of c-MYC by using JQ1 inhibitor cooperates with METTL3 depletion in the inhibition of proliferation and induction of cell death. Conclusion This study highlighted METTL3 as a tumor promoter in Thymic tumors and c-MYC as a promising target to be exploited for the treatment of TET.

Breast cancer is the most common cancer type with a high annual death rate. Finding meaningful tissue-related or body-fluid-accessible biomarkers is necessary to characterize cancer subtype, predict tumor behavior, choose the most effective therapy, predict severe treatment-related toxicities, and also the opportunity to personalize treatments for each patient. There is increasing evidence that various kallikrein-related peptidases (Klk) gene family members can modulate the immune response and are differentially regulated in breast cancer, and therefore are proposed to be potential prognostic biomarkers. This work established and validated an experimental setup to study the roles of selected kallikrein-related peptidases (KLK5, KLK7, KLK14) in breast cancer in vivo using gene-deficient mouse models previously generated in our laboratory. We used the CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats) editing system to generate several E0771 cell line-based reporter and gene-deficient cell lines. These allowed enhanced monitoring of cancer progression in vivo and studying KLKs roles in tumor immune microenvironment of C57Bl/6N mice. Finally, we present the analysis of the initial in vivo experiments using these tools combined with established Klk-deficient mouse models. Our...

Rein tension signals are, in essence, pressures applied on the horse's mouth or nose, via the bit/noseband, by a rider or trainer. These pressures may feel uncomfortable or even painful to the horse and therefore it is important to reduce rein tension magnitude to a minimum. The aim of this study was to investigate the magnitude of a rein tension signal for backing up, using negative reinforcement. We wanted to assess how much the magnitude of rein tension could be reduced over eight trials and if the learning process would differ depending on headstall (bridle/halter). Twenty Warmblood horses were trained to step back from a rein tension signal with the handler standing next to the horse, holding the hands above the horse's withers. As soon as the horses stepped back, rein tension was released. The horses were either trained with a bridle first (first treatment, eight trials) and then with a halter (second treatment, eight trials), or vice versa in a cross-over design. All horses wore a rein tension meter and behavior was recorded from video. The sum of left and right maximum rein tension from onset of the rein tension signal to onset of backing (signaling rein tension) was determined for each trial. Mixed linear and logistic regression models were used for the data analysis. In both treatments, signaling rein tension was significantly lower in trial 7-8 than the first trial (p < 0.02). Likewise, signaling rein tension was significantly lower (p < 0.01), and the horses responded significantly faster, (p < 0.001) in the second treatment compared to the first, regardless of headstall. The maximum rein tension was reduced from 35 N to 17 N for bridle (sum of left and right rein) and from 25 N to 15 N for halter in the first eight trials. Rein tension was then further reduced to 10 N for both bridle and halter over the eight additional trials in the second treatment, i.e. to approximately 5 N in each rein. There was no significant difference in learning performance depending on headstall, but the bitted bridle was associated with significantly more head/neck/mouth behaviors. These results suggest that it is possible to reduce maximum rein tension by half in just eight trials. The findings demonstrate how quickly the horse can be taught to respond to progressively lower magnitudes of rein tension through the correct application of negative reinforcement, suggesting possibilities for substantial improvement of equine welfare during training.

N6-methyladenosine (m6A) is an RNA modification well-known for its contribution to different processes controlling RNA metabolism, including splicing, stability, and translation of mRNA. Conversely, the role of m6A on the biogenesis and function of circular RNAs (circRNAs) has yet to be addressed. circRNAs belong to a class of covalently closed transcripts produced via a back-splicing reaction whereby a downstream 5' splice donor site fuses to an upstream 3' splice acceptor site. Starting from circ-ZNF609 as a study case, we discover that specific m6As control its accumulation and that METTL3 and YTHDC1 are required to direct the back-splicing reaction. This feature is shared with other circRNAs because we find a significant direct correlation among METTL3 requirement, YTHDC1 binding, and the ability of m6A exons to undergo back-splicing. Finally, because circ-ZNF609 displays the ability to be translated, we show that m6A modifications, through recognition by YTHDF3 and eIF4G2, modulate its translation.

Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Veronika Šulová Supervisor: doc. PharmDr. Lukáš Červený, Ph.D. External supervisor: pplk. doc. MUDr. Jaroslav Pejchal, Ph.D. et Ph.D. Title of diploma thesis: Changes of internal organs after percutaneous exposure to sulfur mustard Sulfur mustard is a chemical warfare agent belonging to the group of blistering agents. The theoretical section of the thesis is mainly focused on the description of acute toxic effects, the mechanism of action, and deals with the current possibilities of poisoning therapy. The experimental section is focused on monitoring the effect of sulfur mustard poisoning in the liver, lung, and kidney of female C57BL/6J mice after the percutaneous administration. This work aimed to evaluate markers of oxidative stress and histopathological changes of the selected organs at 3, 5, and 7 days after the poisoning. Ferric reducing antioxidant power (FRAP) and thiobarbituric acid reactive substances (TBARS) methods were used to determine markers of oxidative stress. Histopathological changes were evaluated microscopically using the hematoxylin-eosin staining method. The airness of the lung parenchyma was also assessed by computer image analysis. First, the LD50 of sulfur mustard was...

Norovirus is commonly associated with food and waterborne outbreaks. Genetic susceptibility to norovirus is largely dependent on presence of histo-blood group antigens (HBGA), specifically ABO, secretor, and Lewis phenotypes. The aim of the study was to determine the association between HBGAs to norovirus susceptibility during a large norovirus foodborne outbreak linked to genotype GII.6 in an office-based company in Stockholm, Sweden, 2015. A two-episode outbreak with symptoms of diarrhea and vomiting occurred in 2015. An online questionnaire was sent to all 1109 employees that had worked during the first outbreak episode. Food and water samples were collected from in-house restaurant and tested for bacterial and viral pathogens. In addition, fecal samples were collected from 8 employees that had diarrhea. To investigate genetic susceptibility during the outbreak, 98 saliva samples were analyzed for ABO, secretor, and Lewis phenotypes using ELISA. A total of 542 of 1109 (49%) employees reported gastrointestinal symptoms. All 8 fecal samples tested positive for GII norovirus, which was also detected in coleslaw collected from the in-house restaurant. Eating at the in-house restaurant was significantly associated with risk of symptom development. Nucleotide sequencing was successful for 5/8 fecal samples and all belonged to the GII.6 genotype. HBGA characterization showed a strong secretor association to norovirus-related symptoms (P = 0.014). No association between norovirus disease and ABO phenotypes was observed. The result of this study shows that non-secretors were significantly less likely to report symptoms in a large foodborne outbreak linked to the emerging GII.6 norovirus strain. Funding Agencies|Linkoping University; Swedish Research CouncilSwedish Research Council [320301]; Swedish Foundation for Strategic ResearchSwedish Foundation for Strategic Research

The aim of this work was to gain new knowledge about mechanisms of autoimmune uveitis and to test new therapeutic possibilities that have not yet been studied in uveitis or whose effect is questionable. The main emphasis was placed on the role of microorganisms in the process of uveitis. A mouse model of experimental autoimmune uveitis including a germ-free model was used to achieve the aims and samples of patients' intraocular fluids were analyzed. In the experimental model, the intensity of inflammation was evaluated in vivo clinically and post mortem histologically. The effect of immunomodulatory treatment was evaluated. The intensity of inflammation was compared between groups of germ-free and conventional mice. The therapeutic effect of antibiotics administered to affect microbiome was investigated in conventional mice. In intraocular fluid samples of patients with autoimmune uveitis signs of infection were monitored and levels of cytokines and other factors were evaluated. Evaluation of the effect of immunomodulatory therapy has demonstrated the efficacy of mycophenolate mofetil, which supports its wider use in the treatment of autoimmune posterior uveitis in human medicine. The decrease in bacterial load has led to a decrease in the intensity of inflammation, thereby confirming the importance of...

Maletoyvayamite, Au3Se4Te6, is a new mineral discovered in a heavy-mineral concentrate from the Gaching occurrence of the Maletoyvayam deposit, Kamchatka, Russia (60°19′51.87″N, 164°46′25.65″E). It forms anhedral grains (10 to 50 μm in size) and is found in intergrowths with native gold (Au–Ag), Au tellurides (calaverite), unnamed phases (AuSe, Au2TeSe and Au oxide), native tellurium, sulfosalts (tennantite, tetrahedrite, goldfieldite and watanabeite) and supergene tripuhyite. Maletoyvayamite has a good cleavage on {010} and {001}. In plane-polarised light, maletoyvayamite is grey, has strong bireflectance (grey to bluish grey), and strong anisotropy; it exhibits no internal reflections. Reflectance values for maletoyvayamite in air (Rmin,Rmaxin %) are: 38.9, 39.1 at 470 nm; 39.3, 39.5 at 546 nm; 39.3, 39.6 at 589 nm; and 39.4, 39.7 at 650 nm. Sixteen electron-microprobe analyses of maletoyvayamite gave an average composition: Au 34.46, Se 16.76, Te 47.23 and S 0.84, total 99.29 wt.%, corresponding to the formula Au2.90(Se3.52S0.44)Σ3.96Te6.14based on 13 atoms; the average of eleven analyses on synthetic analogue is: Au 34.20, Se 19.68 and Te 45.42, total 99.30 wt.%, corresponding to Au2.90Se4.16Te5.94. The calculated density is 7.98 g/cm3. The mineral is triclinic, space groupP1, witha= 8.901(2),b= 9.0451(14),c= 9.265(4) Å, α = 97.66(3), β = 106.70(2), γ = 101.399(14)°,V= 685.9(4) Å3andZ= 2. The crystal structure of maletoyvayamite represents a unique structure type resembling a molecular structure. There are cube-like [Au6Se8Te12] clusters linkedviavan der Waals interactions. The structural identity of maletoyvayamite with the synthetic Au3Se4Te6was confirmed by powder X-ray diffraction and Raman spectroscopy.

Background: Homocysteine is a sulfur amino acid whose metabolism is activated in two pathways: remethylation to methionine, which requires folate and vitamin B12, and transsulfuration to cystathionine, which needs pyridoxal-5’-phosphate. High homocysteine level increases the risk of developing heart disease, stroke, peripheral vascular diseases, and cognitive impairment. Some evidence showed that exposure to these metals increased plasma homocysteine levels. Methods: A systematic review was carried out to clarify the relationship between homocysteine blood levels and exposure to toxic heavy metals (Lead, Cadmium, Mercury, and Chromium). Results: The results of this systematic review indicate that exposure to Pb, Cr, Cd, and Hg is connected with nonphysiological homocysteine levels or vitamin B12 and folate serum concentrations. Conclusions: These findings reinforce the importance of involvement in exposure to heavy metals in homocysteine metabolism. This supports the role of blood metals as potential upstream modifiable risk factors to prevent the development of other established risk factors as hyperhomocysteinemia.

Arbuscular mycorrhizal (AM) fungi can ameliorate not only plant phosphorus (P) nutrition but also soil P mobilization, while P mobilization occurs secondarily and may in turn limit P acquisition at certain crop growth stages. It can be termed as the &ldquo, mycorrhiza-inducible P limitation&rdquo, which has so far largely escaped study. A pot experiment was conducted to test the dynamic P acquisition of maize (Zea mays L.) at the vegetative growth stage and P mobilization in the soil in response to AM fungal inoculation in an unsterilized arable alkaline soil. The experiment included two fertilization levels and two AM inoculation levels, i.e., nitrogen (N), P, and potassium (K) fertilization (NPK) and non-fertilization (control), as well as Funneliformis mosseae inoculation (+M) and non-inoculation (&ndash, M). Regardless of fertilization, +M increased mycorrhizal colonization and plant biomass at weeks 4 and 8 but increased tissue P concentration only at week 4 compared with those of &ndash, M. In addition, the plant P acquisition and shoot biomass in the control+M treatment at weeks 4 and 8 were close to and much lower than those of NPK&ndash, M, respectively. Furthermore, the increase in soil P mobilization potential, which was achieved by the accelerated soil alkaline phosphatase activity and the decreased soil pH, was lower than the increase in root P-acquiring efficiency, which was achieved by the enhanced mycorrhization and ZEAma, Pht1, 6 (a mycorrhiza- inducible Pi transporter in maize root) expression. Regardless of fertilization, +M thus significantly decreased soil available P concentrations compared with those in the &ndash, M treatments. Therefore, there was a large, real gap between soil P mobilization and root P acquisition in response to enhanced root mycorrhizal colonization, substantially limiting plant P acquisition and growth.

Bu araştırmadaokuma tutumunun, Türkçe dersine ilişkin tutum üzerindeki etkisi ve bu etkidecinsiyetin rolünün yapısal eşitlik modellemesi yoluyla incelenmesiamaçlanmıştır. Araştırma ilişkiseltarama yoluyla gerçekleştirilmiştir. Çalışma grubu basit seçkisiz örneklemeyoluyla belirlenmiş olup 6, 7 ve 8. sınıfta öğrenim göre317 öğrenciden oluşmaktadır. Verilerin toplanmasında Özbay ve Uyar(2009)’ın geliştirdiği “OkumayaYönelik Tutum Ölçeği” ile Ünal ve Köse (2014)’ningeliştirdiği “Türkçe Dersine Yönelik Tutum Ölçeği” kullanılmıştır. Verilerin analizinde yapısal eşitlikmodellemesi kullanılmıştır. Araştırmadaki modellere dair parametrelerintahmininde maksimum olabilirlik (Maximum Likehood) yöntemi, uyum iyiliğideğerlerinin incelenmesinde ise χ2/df, CFI, GFI, TLI, NFI, IFI,RMSEA ve SRMR uyum indeksleri kullanılmıştır. Araştırma sonucunda tüm hipotezmodellerin geçerli olduğu; okuma tutumunun, Türkçe dersine ilişkin tutumun%40’ını açıkladığı görülmüştür. Bunun yanı sıra erkek öğrencilere ilişkinoluşturulan modelde okuma tutumunun, Türkçe dersine ilişkin tutumun %30’unu,kız öğrencilere ilişkin oluşturulan modelde ise %40’ını açıkladığıbelirlenmiştir., In this study, the aim was to investigatethe effect of the attitude towards reading on the attitude toward the Turkishcourse and the role of gender on this effect through structural equationmodeling. The research was conducted, using relational survey model. The studygroup was formed through simple random sampling and consisted of 317 studentswho were 6th, 7th and 8th graders. For datacollection, the “Attitude Scale towards Reading” developed by Özbay and Uyar(2009) and the “Attitude Scale towards the Turkish Course” developed by Ünaland Köse (2014) were used. Structural equation modeling was used for dataanalysis. The Maximum Likelihood method was used for the prediction of theparameters for the models, and the χ2/df, CFI, GFI, TLI, NFI, IFI,RMSEA and SRMR fit indices were used for the analysis of the goodness of fitvalues. In the end, it was found that all hypothesis models were valid and thatthe reading attitude accounted for 40% of the attitude towards the Turkishcourse. In addition, it was determined that in the model for the male students thereading attitude accounted for 30% of the attitude toward the Turkish courseand in the model for the female students, it accounted for 40%.

Atomically-thin magnetic crystals have been recently isolated experimentally, greatly expanding the family of two-dimensional materials. In this Article we present an extensive comparative analysis of the electronic and magnetic properties of ${\rm Cr}_2{\rm Ge}_2{\rm Te}_6$, based on density functional theory (DFT). We first show that the often-used ${\rm DFT}+U$ approaches fail in predicting the ground-state properties of this material in both its monolayer and bilayer forms, and even more spectacularly in its bulk form. In the latter case, the fundamental gap {\it decreases} by increasing the Hubbard-$U$ parameter, eventually leading to a metallic ground state for physically relevant values of $U$, in stark contrast with experimental data. On the contrary, the use of hybrid functionals, which naturally take into account nonlocal exchange interactions between all orbitals, yields good account of the available ARPES experimental data. We then calculate all the relevant exchange couplings (and the magneto-crystalline anisotropy energy) for monolayer, bilayer, and bulk ${\rm Cr}_2{\rm Ge}_2{\rm Te}_6$ with a hybrid functional, with super-cells containing up to $270$ atoms, commenting on existing calculations with much smaller super-cell sizes. In the case of bilayer ${\rm Cr}_2{\rm Ge}_2{\rm Te}_6$, we show that two distinct intra-layer second-neighbor exchange couplings emerge, a result which, to the best of our knowledge, has not been noticed in the literature., 13 pages, 6 figures, 3 tables

Aquaporins (AQPs) are one diverse family of membrane channel proteins that play crucial regulatory roles in plant stress physiology. However, the heat stress responsiveness of AQP genes in soybean remains poorly understood. In this study, 75 non-redundant AQP encoding genes were identified in soybean. Multiple sequence alignments showed that all GmAQP proteins possessed the conserved regions, which contained 6 trans-membrane domains (TM1 to TM6). Different GmAQP members consisted of distinct Asn-Pro-Ala (NPA) motifs, aromatic/arginine (ar/R) selectivity filters and Froger&rsquo, s positions (FPs). Phylogenetic analyses distinguished five sub-families within these GmAQPs: 24 GmPIPs, 24 GmTIPs, 17 GmNIPs, 8 GmSIPs, and 2 GmXIPs. Promoter cis-acting elements analyses revealed that distinct number and composition of heat stress and hormone responsive elements existed in different promoter regions of GmAQPs. QRT-PCR assays demonstrated that 12 candidate GmAQPs with relatively extensive expression in various tissues or high expression levels in root or leaf exhibited different expression changes under heat stress and hormone cues (abscisic acid (ABA), l-aminocyclopropane-l-carboxylic acid (ACC), salicylic acid (SA) and methyl jasmonate (MeJA)). Furthermore, the promoter activity of one previously functionally unknown AQP gene-GmTIP2, 6 was investigated in transgenic Arabidopsis plants. The beta-glucuronidase (GUS) activity driven by the promoter of GmTIP2, 6 was strongly induced in the heat- and ACC-treated transgenic plants and tended to be accumulated in the hypocotyls, vascular bundles, and leaf trichomes. These results will contribute to uncovering the potential functions and molecular mechanisms of soybean GmAQPs in mediating heat stress and hormone signal responses.

Due to DNA heterozygosity and repeat content, assembly of non-model plant genomes is challenging. Herein, we report a high-quality genome reference of one of the oldest known domesticated species, fig (Ficus carica L.), using Pacific Biosciences single-molecule, real-time sequencing. The fig genome is ~333 Mbp in size, of which 80% has been anchored to 13 chromosomes. Genome-wide analysis of N6 -methyladenine and N4 -methylcytosine revealed high methylation levels in both genes and transposable elements, and a prevalence of methylated over non-methylated genes. Furthermore, the characterization of N6 -methyladenine sites led to the identification of ANHGA, a species-specific motif, which is prevalent for both genes and transposable elements. Finally, exploiting the contiguity of the 13 pseudomolecules, we identified 13 putative centromeric regions. The high-quality reference genome and the characterization of methylation profiles, provides an important resource for both fig breeding and for fundamental research into the relationship between epigenetic changes and phenotype, using fig as a model species.

Chiral (R)-(-) and (S)-(+)-8-amino-5,6,7,8-tetrahydroquinoline, hereafter defined (R)-CAMPY and (S)-CAMPY, have proved to be valuable chiral ligands in Ru(II) precatalysts for the reduction of prochiral ketones by asymmetric hydrogen transfer AHT. These ligands bear chiral information on an alkyl ring fused to a pyridine and therefore have a flat nature, characterized by a high conformational rigidity. It represent the first application in AHT of a member of a family of ancillary ligands already known as starting material for medicinal compouds. The reaction with [RuCl2PPh3] furnished the (OC-6-14)-[RuCl2(PPh3)2(CAMPY)] which evolved to (OC-6-42-C)- [RuCl2(PPh3)2(CAMPY)] in refluxing toluene. The absence of a suitable crystal for X-ray structure was easily overcame by a combination of routines 2D-NMR experiments based on an unprecedent 4-bond P-H coupling. The formation of (OC-6-42-C)- [RuCl2(PPh3)2(CAMPY)] is totally stereoselective at the chiral metal center; the same behavior is followed when triphenyl phosphines are displaced by chelating diphosphines like Ph2P(CH2)4PPh2 (DPPB) and Ph2P(CH2)3PPh2 (DPPP). The flat and rigid nature of CAMPY alone gave catalyst able to reduce acetophenone with moderate e.e.; substitution of triphenylphosphines in the complex with an achiral chelating diphosphines produce Ru-catalysts witch gave enantioselectivities up to 96%. © 2012 Bentham Science Publishers.

Background/Aims: Preterm birth (PTB) and low birth weight (LBW) significantly influence mortality and morbidity of the offspring in early life and also have long-term consequences in later life. A better understanding of the molecular mechanisms of preterm birth could provide new insights regarding putative preventive strategies. Metabolomics provides a powerful analytic tool to readout complex interactions between genetics, environment and health and may serve to identify relevant biomarkers. In this study, the association between 163 targeted maternal blood metabolites and gestational age was investigated in order to find candidate biomarkers for PTB. Methods: Five hundred twenty-three women were included into this observational study. Maternal blood was obtained before delivery. The concentration of 163 maternal serum metabolites was measured by flow injection tandem mass spectrometry. To find putative biomarkers for preterm birth, a three-step analysis was designed: bivariate correlation analysis followed by multivariable regression analysis and a comparison of mean values among gestational age groups. Results: Bivariate correlation analysis showed that 2 acylcarnitines (C16:2, C2), 1 amino acids (xLeu), 8 diacyl-PCs (PCaaC36:4, PCaaC38:4, PCaaC38:5, PCaaC38:6, PCaaC40:4, PCaaC40:5, PCaaC40:6, PCaaC42:4), and 1 Acylalkyl-PCs (PCaeC40:5) were inversely correlated with gestational age. Multivariable regression analysis confounded for PTB history, maternal body mass index (BMI) before pregnancy, systolic blood pressure at the third trimester, and maternal body weight at the third trimester, showed that the diacyl-PC PCaaC38:6 was the only metabolite inversely correlated with gestational age. Conclusions: Maternal blood concentrations of PCaaC38:6 are independently associated with gestational age.

Introduction:Uveitis in an ocular inflammation affecting mostly people of working age. Uveitis is responsible for severe visual impairment despite of expanding new therapeutics. The animal models of uveitis were established, because the wide clinical variability of uveitis limits the studies in human medicine. The goal our project was to establish a reproducible model of experimental autoimmune uveitis in Czech Republic, and further on this model to observe the frequency of CD3+ and F4/80+ cells in retina, to assess the influence of microbial environment on intensity of intraocular inflammation and to test the therapeutical possibilities. Material and methods: The C57BL/6J mice were immunized by retinal antigen (IRBP 1-20, interphotoreceptor retinoid binding protein), enhanced by complete Freund's adjuvant and pertussis toxin and mild posterior autoimmune uveitis was induced. The mice were bred in conventional and germ-free (gnotobiotic) conditions. The uveitis intensity was evaluated in vivo biomicroscopically and post mortem histologically on hematoxylin eosin stained sections according to the standard protocol. The histological eye specimen were analyzed also by imunohistochemisty and by flow cytometry. Each experiment was performed for 35 days. The conventional mice with uveitis were treated...

The rodent faunas of the palaeoestuaries at Tourville and Tancarville have the same age (MIS 7) even if they are not exactly synchronous. The correlation between Tourville and Tancarville is confirmed. Saalian (fluvial or fluvio-marine aeolian) and Eemian (fluvial, aeolian) formations cover these palaeoestuaries., Les faunes de rongeurs des paleoestuaires de Tourville et de Tancarville sont du même âge (stade isotopique 7) même si elles ne sont pas exactement synchrones. La corrélation entre ces deux paléoestuaires est confirmée. Des formations saaliennes (fluviatiles ou fluviomarines, éoliennes) puis eemiennes (sables fluviatiles, dune) les recouvrent., Cordy Jean Marie, Carpentier Gérard, Lautridou Jean Pierre. Les paléo-estuaires du stade isotopique 7 à Tourville-La-rivière et à Tancarville (Seine) : faune de rongeurs et cadre stratigraphique. In: Quaternaire, vol. 14, n°1, 2003. Le Quaternaire de Normandie: nouvelles données biochronologiques et géochronologiques. pp. 15-23.

We report a preliminary study evaluating the encapsulation modalities in microparticles of the antiischemic drug N(6)-cyclopentyladenosine (CPA). The effects of release systems have been evaluated on the stability in human whole blood of CPA and its affinity toward human adenosine A(1) receptors. The microspheres were prepared by an emulsion-solvent evaporation method (different CPA amounts and two stirring rates were employed) using poly(lactic acid). Free and encapsulated CPA was incubated in human blood and the drug stability was analyzed. The affinity of CPA to human A(1) receptor was also obtained in the presence and in the absence of unloaded microspheres. The microspheres obtained using 1200 rpm showed a broad size distribution and a mean diameter value of 21+/-9 microm. Using 1700 rpm the mean diameter decreased to 5+/-2 microm and a more homogeneous size distribution was obtained. The CPA release changed with the particle size and the different amounts of drug employed during the preparation of the microspheres. The degradation in human whole blood of CPA encapsulated in the microspheres was negligible, with respect to that of free CPA. Affinity values of CPA obtained in the absence and in the presence of unloaded microspheres were the same.

Application of haptic devices expanded to fields like virtual manufacturing, virtual assembly or medical simulations. Advances in development of haptic devices have resulted in a wide distribution of assymetric 6/3-DOF haptic devices. However, current haptic rendering algorithms work correctly only for symmetric devices. This thesis analyzes 3-DOF and 6-DOF haptic rendering algorithms and proposes an algorithm for 6/3-DOF haptic rendering involving pseudo-haptics. The 6/3-DOF haptic rendering algorithm is implemented based on the previous analysis and tested in a user study.

We measured elastic scattering angular distributions and cross sections for heavy residue production for the systems 6,7 Li+ 64 Zn at different energies around the Coulomb barrier. The elastic scattering angular distributions have been reproduced by optical model fits using a renormalized double folding potential for the real and imaginary parts. Absence of usual threshold anomaly in the optical potential was found. The excitation functions for heavy residue production were measured using an activation technique. Comparison with different calculations suggest that complete fusion is the dominant reaction mechanism above the barrier whereas, below the Coulomb barrier, incomplete fusion and transfer dominate.

Cis -RuCl 2 (diphosphine)(CAMPY) complexes, chiral at the metal centre with matching or mismatching chiralities between diphosphine and CAMPY were prepared and the configuration at the metal was determined in solution by a complete set of NMR investigations; CAMPY is ( R )-(−) or ( S )-(+)-8-amino-5,6,7,8-tetrahydroquinoline. The complexes were used in ATH reactions of different aryl ketones with 2-propanol as hydrogen source. The effects of the chirality at the metal were studied and enantiomeric excesses up to 99% were obtained.

Bis (2,2,6,6-tetramethyl-4-piperidinyl) maleate is a key intermediate for the synthesis of new types of hindered amine light stabilizers (HALS), so new synthetic routes to this compound are desirable. Through an orthogonal design and follow-up single factor experiments optimal reaction conditions were determined for synthesizing bis (2,2,6,6-tetramethyl-4-piperidiny) maleate using dimethyl maleate, 2,2,6,6-tetramethyl-4-piperidinol and zeolite supported tetraisopropyl titanate as catalyst. Under the selected conditions, the reaction rate and the yield are high, the selectivity is good, the catalyst can be recycled, and there are fewer wastes. The product was characterized and quantitatively analyzed by elemental analysis, mass spectrometry, infrared spectroscopy, nuclear magnetic resonance spectroscopy and ion suppression chromatography.

2-Chloro-1,3-dithiane was obtained by the chlorination of 1,3-dithiane with N-chlorosuccinimide. Reactions of 2-chloro-1,3-dithiane with various substituted phenols lead to 2-(1,3-dithianyl)phenols (3). Hexakis-[p-(1,3-dithian-2-yl)phenoxy]cyclotriphosphazene (6) was obtained by reaction with hexachlorotriazacyclotriphosphazene (5).

Epidemiological or in vitro evidence suggests a potential role for flavonoids as anti-inflammatory agents; we investigated the effect of flavonoids-rich foods or supplements on tumor necrosis factor- alpha (TNF-α) and interleukin-6 (IL-6) in long-term placebo-controlled human intervention trials. From 110 human intervention studies selected (MEDLINE, EMBASE, CHORANE, and FSTA databases), 32 long-term placebo-controlled trials were suitable for meta-analysis. After sensitivity analysis, seven studies imputed of bias were excluded and 25 studies were analyzed (TNF-α, n = 2404; IL-6, n = 2174). Levels of TNF-α decreased after flavonoid consumption in the fixed model only (mean difference (MD) (95% CI): -0.098 (-0.188, -0.009), p = 0.032), but metaregression results showed that neither higher dose, nor a longer duration of intervention were associated with a greater effect size. Subgroup analysis did not reveal any significant effect for quercetin and soy, but other sources (red wine, pomegranate, and tea extracts) showed a significant effect size both in fixed (MD (95% CI): TNF-α -0.449 (-0.619, -0.280), p < 0.001; IL-6 -0.346 (-0.612, -0.079), p = 0.011) and random (MD (95% CI): TNF-α -0.783 (-1.476, -0.090), p = 0.027; IL-6, -0.556 (-1.062, -0.050), p = 0.031) effect models. High-quality placebo-controlled trials are needed in order to identify flavonoids as the active ingredients.

The influence of new types of additives, such as halogen- and antimony-free flame-retardant master batches based on phosphorus, α-zirconium dihydrogen phosphate, and β-cyclodextrin nanosponges, on the flame retardancy of polyamide 6,6 (PA6,6) by means of cone calorimetry and limiting oxygen index (LOI) tests was investigated. A significant decrease of the heat release rate, depending by the type of additive used, was observed. Furthermore, with the consideration that the life safety during the fire could be improved by a decrease in the fire hazard, a decrease in the quantity of the smoke and its toxicity, depending also on the type of additive, was revealed. With regard to the LOI test, neat PA6,6 showed a slight increase in the LOI value in comparison with the PA6,6 composites. However, all of the PA6,6/composites showed a slower burning velocity and antidripping effects at oxygen concentrations corresponding to the LOI value. To understand the flame-retardancy mechanism of these novel PA6,6 composites, we thoroughly investigated their thermal decomposition behavior and microstructure/elemental analysis by scanning electron microscopy/energy-dispersive X-ray spectroscopy. Furthermore, the combustion behavior of these novel PA6,6 composites was compared with that of conventional nanofillers (e.g., modified montmorillonite clay and carbon nanotubes). © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012

4,6,4′-Trimethylangelicin, a well-known effective photosensitizer described as a pure monofunctional reactant with DNA, can induce interstrand cross-links in mammalian cell DNA in vivo (about 15% relative to 8-methoxypsoralen), as observed using alkaline elution and Chinese hamster ovary cells. Experiments performed using the two-step irradiation method and HeLa cells support these data. In contrast with 4,6,4′-trimethylangelicin, 4′-methylangelicin and 4,4′-dimethylangelicin do not form interstrand cross-links. These results are consistent with those recently reported by Chen et al. (X. Chen, J. Kagan, F. Dall'Acqua, D. Averbeck and E. Bisagni, J. Photochem. Photobiol. B: Biol., 22 (1994) 51–57) using pBR322 and M13 DNA. The cross-linking ability of 4,6,4′-trimethylangelicin does not seem to be related to a particular feature of these DNAs but to the compound itself.

n- and p-doped c-Si (100) are textured by a SF 6 /O 2 plasma chemical etching, under conditions avoiding ion bombardment. The study of the effects of plasma parameters on morphology and on surface reflectance of textured c-Si reveals a strong impact of silicon doping on texturing characteristics. SF 6 /O 2 plasma etches anisotropically n-type c-Si creating a square-based hillock-like morphology with a surface reflectivity of 6%. Conversely, for p-type Si, a H 2 plasma pretreatment is necessary to activate silicon etching and obtain a nano-textured surface with a reflectivity of 16%.

The bis (1-hydroxy-2,2,6,6-tetramethyl-4-piperidinyl)-decandioate called IAC, is a new non-peptidyl low molecular weight radical scavenger able to give a fast reaction with the majority of radical species involved in the oxidative stress. This intrinsic property might be of particular interest in all the processes where it presents an over production of reactive oxygen/nitrogen species (ROS/RNS) such as inflammation. Indeed, it is well known that systemic inflammatory response is associated with the production of ROS, nitric oxide (NO), which in turn deplete the endogenous GSH, mediating cytotoxicity. It has been shown that IAC through its antioxidant activity, exerted a protective effect in vitro in islets isolated from type-2 diabetic patients, and in vivo in a non-obese diabetic mouse model and in DNBS-induced colitis in rats. The ability of IAC to protect brain from ischemia, suggests a possible use of the compound in broad range of inflammatory-related diseases. It is well known that the use of non steroidal anti-inflammatory drugs (NSAIDs) is associated with a broad spectrum of untoward side-effects such as gastrointestinal ulceration. The major pathogenetic element in the development of these effects is the depletion of prostaglandins (PGs) through inhibition of cyclooxygenase. The evidence that IAC protects gastric mucosa in an animal model of indomethacin-induced ulcer, through local increase of PGE 2 levels and antioxidant activity, candidates this compound as a novel, promising, anti-inflammatory compound avoiding the major common untoward side-effects elicited by NSAID's.

The degradation of the six anthocyanidins (pelargonidin, cyanidin, delphinidin, peonidin, petunidin and malvidin) mediated by the nitroxides: 2, 2, 6, 6-tetramethylpiperidine-1-oxyl (Tempo), 4-hydroxy-2, 2, 6, 6-tetramethylpiperidine-1-oxyl (Tempol) and 4-methoxy-2, 2, 6, 6-tetramethylpiperidine1-oxyl (4-CH3O-Tempo) at 25 ºC in aqueous acid solution was investigated spectrophotometrically and by EPR and HPLC measurements. The reaction kinetics were followed under pseudo-first order conditions using a large excess of nitroxide reactants. The spontaneous degradation of anthocyanidins under these conditions is several orders of magnitude slower, and it did not influence the measurements. However, it was found that the reaction rate increases with the age of acidified nitroxide solutions, reaching a maximum after 24 hours. This result indicates that in every case the oxoammonium cation, generated by disproportionation of nitroxyl radicals, is somewhat more reactive toward anthocyanidins than the nitroxyl itself. The products were identified by HPLC as ring substituted benzoic acids. The relative reactivities of the six anthocyanidins and the accelerating influence of the p-substituent of nitroxides on the reaction is discussed.

Thermodynamic properties of the aqueous solutions of a newly synthesized homologous series of N -[2-(2,3,4,6-tetra- O -acetyl-β- d -glucopyranosyl)ethyl]- N , N -dimethyl- N -alkylammonium bromides with hydrophobic tails of 8, 12 and 16 carbon atoms, determined as a function of concentration by means of direct methods, are here reported for the first time. Dilution enthalpies, densities and sound velocities were measured at 298 K, allowing for the determination of apparent and partial molar enthalpies, volumes and compressibilities. Changes in thermodynamic quantities upon micellization were derived using a pseudo-phase transition approach. The trends of apparent and partial molar enthalpies versus m confirm the increase in global hydrophobicity of the molecule, already suggested by the value of the cmc of C 12 AGCB, lower than that of DTAB, and show that, also in the case of surfactants with a bulky substitution on the polar head, the group contribution of the –CH 2 – is additive both in the plateau (−1.3 kJ mol −1 group −1 ) and in the micellization enthalpy changes (−1.5 kJ mol −1 group −1 ). The determination of apparent molar volumes and compressibilities presents some experimental problems, due to the strong tendency of this class of surfactants to adsorb on the glass surfaces. Even so, the group contribution of the methylene group results as being additive and comparable to that of other cationic and anionic surfactants. From the comparison with DTAB, the volume of (2,3,4,6-tetra- O -acetyl-β- d -glucopyranosyl)ethyl group results as 291 cm 3 mol −1 .

Pyrrolizidine alkaloids are naturally occurring genotoxic chemicals produced by a large number of plants. The high toxicity of many pyrrolizidine alkaloids has caused considerable loss of free-ranging livestock due to liver and pulmonary lesions. Chronic exposure of toxic pyrrolizidine alkaloids to laboratory animals induces cancer. This investigation studies the metabolic activation of retrorsine, a representative naturally occurring tumorigenic pyrrolizidine alkaloid, and shows that a genotoxic mechanism is correlated to the tumorigenicity of retrorsine. Metabolism of retrorsine by liver microsomes of F344 female rats produced two metabolites, 6, 7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP), at a rate of 4.8 ± 0.1 nmol/mg/min, and retrorsine-N-oxide, at a rate of 17.6±0.5 nmol/mg/min. Metabolism was enhanced 1.7-fold by using liver microsomes prepared from dexamethasone-treated rats. DHP formation was inhibited 77% and retrorsine N-oxide formation was inhibited 29% by troleandomycin, a P450 3A enzyme inhibitor. Metabolism of retrorsine with lung, kidney, and spleen microsomes from dexamethasone-treated rats also generated DHP and the N-oxide derivative. When rat liver microsomal metabolism of retrorsine occurred in the presence of calf thymus DNA, a set of DHP-derived DNA adducts was formed; these adducts were detected and quantified by using a previously developed 32P-postlabeling/HPLC method. These same DNA adducts were also found in liver DNA of rats gavaged with retrorsine. Since DHP-derived DNA adducts are suggested to be potential biomarkers of riddelliine-induced tumorigenicity, our results indicate that (i) similar to the metabolic activation of riddelliine, the mechanism of retrorsine-induced carcinogenicity in rats is also through a genotoxic mechanism involving DHP; and (ii) the set of DHP-derived DNA adducts found in liver DNA of rats gavaged with retrorsine or riddelliine can serve as biomarkers for the tumorigenicity induced by retronecine-type pyrrolizidine alkaloids.

Chemo-selective synthesis and characterization of of N-[(4-nitrophenyl)sulphanyl]- 2 and N-[(4-nitrophenyl)sulphinyl]- 3 N-[(4-aminophenyl)sulphonyl]- 5 and N-(4-aminobenzoyl)- 7 derivatives of 1a, 2, 6, 6a-tetrahydro-1H, 4H-[1, 3]dioxepino[5, 6-b]azirines, starting from 1a, 2, 6, 6a-tetrahydro-1H, 4H-[1, 3]dioxepino[5, 6-b]azirine (1), are described. Their solid state conformational behaviour based on crystallographic analysis shows that: • dioxepinoazirine moiety of 3, 5 and 7 adopts a boat-chair (BC) conformation, while dioxepinoaziridine moiety of 3 adopts a twist-boat (TB) conformation • the substituent on aziridine nitrogen is always in trans and never in cis position in relation to the dioxepane ring, • the orientation of sulphanyl-, sulphinyl- sulphonyl- and carbonyl- moiety in 2, 3, 5 and 7 are defined by torsion angles C1-S1-N1-C7 of 110.7(2)°, 82.6(2)°, 88.80(11)°and C1-C-N1-C7 of 64.9(5)°, respectively, • Phenyl moiety of sulphinyl and sulphonyl derivatives, 3 and 5 is perpendicular to S-N bond with the torsion angles N1-S1-C1-C2 of 67.9(3)° and -92.54(13)°, respectively, while that one of sulphanyl- 2 and carbonyl- 7 derivatives is coplanar to S-N or C-N bonds with the torsion angles N1-S1-C1-C2 and N1-C-C1-C2 of 168.5(2)° and 170.9(4)°, respectively. Obtained data will serve for further investigation of steric and electronic properties of studied compounds directed toward design of antihyperglycaemicaly more potent analogues.

Za uspješno provođenje mjera zaštite šuma protiv šumskih štetnika veliku ulogu igraju točne prognoze njihovih gustoća populacija. U ovom je radu testirana metoda prognoza gustoće populacije malog mrazovca Operophtera brumata L. (Lepidoptera, Geometridae) pomoću seksualnih feromonskih pripravaka. Testirani je feromon Operowit&reg ; ; te klopke Monotrap&reg ; ; , Traptest &reg ; ; i Mastrap L &reg ; ; . Trenutno se u šumarstvu koristi metoda ljepljivih prstenova koja ima svoje nedostatke. Prvi rezultati ukazuju na prednosti Mastrap L &reg ; ; klopki u odnosu na druge tipove jer postiže veće ulove i ima veliki kapacitet prihvaćanja leptira. Tijekom cijele sezone lovljenja testirani feromonski pripravak bio je vrlo selektivan

Novel pyrimido[1,2-a]pyrimidinones 14, 15 and 16 and imidazo[1,2-a] pyrimidinones 19 and 20, designed as conformationally constrained analogues of 1-(3-amino-2-hydroxypropyl)thymine and 1-(2-amino-3-hydroxypropyl)thymine, respectively, were synthesized by the ring-opening/ ring-closure rearrangement of the corresponding byciclic oxygen-containing amino compounds 12 and 17.

We measured sodium atomic lines belonging to the n2S1/2-32P1/2;3/2 (n = 5,6,7) series, originating from a high-pressure sodium-cadmium plasma. The observed line shapes are compared with the calculations of the line shapes made within the Bartels' method. The electron density is estimated by Vidal approach (a refined Inglis-Teller method), and the density of sodium and cadmium has been determined using the relationships between the interaction constants of the sodium-sodium (sodium-cadmium) quasimolecule and the shift of the self-absorbed peaks of the sodium resonance line. We assume that the main line-broadening mechanisms of n2S1/2-32P1/2;3/2 spectral lines are Stark broadening (by electrons), self-broadening (by neutral sodium atoms) and van der Waals broadening (by cadmium atoms). The electron temperatures are determined by Bartels' method, fitting the calculated to the experimentally measured n2S1/2-32P1/2;3/2 line profiles. All three measured lines possess a red asymmetry that can not be attributed to the electron broadening, self-broadening or foreign gas broadening. We suggest that this red asymmetry could be caused by interaction of the radiating sodium atom with sodium and cadmium ions., Mjerili smo natrijeve linije niza n2S1/2–32P1/2;3/2 (n = 5, 6, 7) koje nastaju u visokotlačnom izboju u natrij-kadmijevoj plazmi. Određeni oblici linija se uspored –uju s računatima na osnovi Bartelsove metode. Elektronske se gustoće ocjenjuju Vidalovim postupkom (poboljšanom Inglis-Tellerovom metodom), a gustoća natrija i kadmija se određuje odnosom interakcijskih konstanti kvazimolekula natrij-natrij (natrij-kadmij) i pomaka vrhova zbog samoapsorpcije natrijeve rezonantne linije. Pretpostavljamo da su glavni mehanizmi širenja spektralnih linija n2S1/2–32P1/2;3/2 Starkovo širenje (elektronima), vlastito-širenje (neutralnim natrijevim atomima) i van der Waalsovo širenje (kadmijevim atomima). Elektronske su temperature određene Bartelsovom metodom kojom smo načinili prilagodbe eksperimentalno određenim profilima n2S1/2–32P1/2;3/2 linija. Sve linije pokazuju “crvenu” asimetriju koja se ne može objasniti elektronskim širenjem, vlastitim-širenjem ili širenjem stranim atomima. Smatramo da je “crvena” asimetrija uzrokovana interakcijom natrijevih atoma koji zrače s natrijevim i kadmijevim ionima.

The oxygen heterocyclic compounds (coumarins, psoralens and polymethoxylated flavones) present in the nonvolatile residue of the essential oils of Mandarin, Sweet Orange, Bitter Orange, Bergamot and Grapefruit were analysed with an HPLC/API/MS system equipped with an APcI probe in positive mode. The use of hyphenated techniques, such as LC/MS provides a great information about the content and nature of constituents of natural complex matrices, such as essential oils. In this work, MS spectra were recorded at different voltages, to obtain structural information in addition to molecular weight information. The different response of the compounds identified has been also evaluated. The method allowed the confirmation of the identification of the main components of the fraction, previously reported for the different oils. MS characteristics of coumarins, psoralens and polymethoxylated flavones with different substitution patterns were determined on the basis of the response obtained with the APcI interface. Interface parameters were optimised to obtain a contemporaneous response for all the three classes of components.

The asymmetric unit contains two independent molecules. The title compound is the first example of a derivative of the bicyclol tautomer in the allantoin series and the key intermediate in the asymmetric synthesis of the X-ray structure determination confirm its diastereomeric identity and establish the absolute (1R, 5R) configuration.

Some photobiological properties of l'-thieno-4,6,4′-tri-methylangelicin (TTMA), a new isoster of 4,6,4′-trimeth-ylangelicin (TMA) were studied in comparison with the parent compound. The TTMA absorbs UVA light and photobinds in vitro to DNA more efficiently than TMA; however, in Ehrlich cells in vivo TTMA linked to DNA to a lesser extent than the parent compound. In general, the formation of damage into DNA is in line with this last result: In fact, TTMA and TMA form equivalent amounts of interstrand cross-links (ISC) both in vitro in linearized PM2 DNA and in vivo in HeLa cells. In this system TTMA induces DNA-protein cross-links (DPC) more efficiently than TMA; on the contrary, no significant amounts of single-strand breaks were detected with both compounds. The antiproliferative activity of TTMA is consistent with these results, being only slightly more pronounced than that of TMA. Experiments carried out using double irradiation demonstrated that these drugs are capable of inducing antiproliferative effects by bi-photonic reactions, including the formation of both ISC and DPC. Thus, replacement of the oxygen atom by a sulfur increases the UV absorption of the drug and its capacity to photobind to DNA in vitro but does not yield a comparable enhancement of its photosensitizing properties in vivo; this might be due to various reasons, for instance to an increase in the lipophilic character that could modify the behavior in vivo.