The introduction of heavy atoms into the BODIPY-core structure has proven to be a straightforward strategy for optimizing the design of such dyes towards enhanced generation of singlet oxygen rendering them suitable as photosensitizers for photodynamic therapy (PDT). In this work, BODIPYs are presented by combining the concept of bromination with nucleophilic aromatic substitution (SNAr) of a pentafluorophenyl or a 4-fluoro-3-nitrophenyl moiety to introduce functional groups, thus improving the phototoxic effect of the BODIPYs as well as their solubility in the biological environment. The nucleophilic substitution enabled functionalization with various amines and alcohols as well as unprotected thiocarbohydrates. The phototoxic activity of these more than 50 BODIPYs has been assessed in cellular assays against four cancer cell lines in order to more broadly evaluate their PDT potential, thus accounting for the known variability between cell lines with respect to PDT activity. In these investigations, dibrominated polar-substituted BODIPYs, particularly dibrominated glyco-substituted compounds, showed promising potential as photomedicine candidates. Furthermore, the cellular uptake of the glycosylated BODIPYs has been confirmed via fluorescence microscopy.
Photochemotherapy , Photosensitizing Agents , Photosensitizing Agents/chemistry , Boron Compounds/chemistry , Cell Line
In this work, we propose to evaluate and validate an emerging spectroscopic space-resolved technique: atomic force microscopy coupled with infrared spectroscopy (AFM-IR) for inorganic materials in tapping mode at the nanoscale. For this aim, a preliminary investigation of sample preparation techniques was done and the stability of tapping AFM-IR spectra was evaluated on reference samples [poly(methyl methacrylate) and silica]. It was concluded that for a homogeneous polymer, it is possible to compare AFM-IR spectra with conventional Fourier-transform infrared (FTIR) spectra obtained in transmission. When an inorganic solid is considered, AFM-IR spectra are different from the global FTIR spectrum which indicates that the AFM-IR technique probes a volume which is not representative of global composition, that is, the external surface layer. Moreover, local infrared spectra recorded in the tapping mode of the external surface are significantly different depending on the analyzed regions of the same particle and between particles of the amorphous silica, implying surface heterogeneity. The AFM-IR technique allows surface description of amorphous inorganic materials at the nanoscale and opens new frontiers in the characterization of functional nanoscale and crystalline materials.
The generation of bio-targetable photosensitizers is of utmost importance to the emerging field of photodynamic therapy and antimicrobial (photo-)therapy. A synthetic strategy is presented in which chelating dipyrrin moieties are used to enhance the known photoactivity of iridium(III) metal complexes. Formed complexes can thus be functionalized in a facile manner with a range of targeting groups at their chemically active reaction sites. Dipyrrins with N- and O-substituents afforded (dipy)iridium(III) complexes via complexation with the respective Cp*-iridium(III) and ppy-iridium(III) precursors (dipy=dipyrrinato, Cp*=pentamethyl-η5 -cyclopentadienyl, ppy=2-phenylpyridyl). Similarly, electron-deficient [IrIII (dipy)(ppy)2 ] complexes could be used for post-functionalization, forming alkenyl, alkynyl and glyco-appended iridium(III) complexes. The phototoxic activity of these complexes has been assessed in cellular and bacterial assays with and without light; the [IrIII (Cl)(Cp*)(dipy)] complexes and the glyco-substituted iridium(III) complexes showing particular promise as photomedicine candidates. Representative crystal structures of the complexes are also presented.
Anti-Infective Agents , Coordination Complexes , Photochemotherapy , Coordination Complexes/pharmacology , Iridium , Photosensitizing Agents
Hydrophobic drug candidates require innovative formulation agents. We designed and synthesized lipid-DNA polymers containing varying numbers of hydrophobic alkyl chains. The hydrophobicity of these amphiphiles is easily tunable by introducing a defined number of alkyl chain-modified nucleotides during standard solid-phase synthesis of DNA using an automated DNA synthesizer. We observed that the resulting self-assembled micelles solubilize the poorly water-soluble drug, meta-tetra-hydroxyphenyl-chlorin (mTHPC) used in photodynamic therapy (PDT) with high loading concentrations and loading capacities. A cell viability study showed that mTHPC-loaded micelles exhibit good biocompatibility without irradiation, and high PDT efficacy upon irradiation. Lipid-DNAs provide a novel class of drug-delivery vehicle, and hybridization of DNA offers a potentially facile route for further functionalization of the drug-delivery system with, for instance, targeting or imaging moieties.
The role of the oxide support on the structure of the MoS2 active phase (size, morphology, orientation, sulfidation ratio, etc.) remains an open question in hydrotreating catalysis and biomass processing with important industrial implications for the design of improved catalytic formulations. The present work builds on an aqueous-phase surface-science approach using four well-defined α-alumina single crystal surfaces (C (0001), A (112Ì 0), M (101Ì 0), and R (11Ì 02) planes) as surrogates for γ-alumina (the industrial support) in order to discriminate the specific role of individual support facets. The reactivity of the various surface orientations toward molybdenum adsorption is controlled by the speciation of surface hydroxyls that determines the surface charge at the oxide/water interface. The C (0001) plane is inert, and the R (11Ì 02) plane has a limited Mo adsorption capacity while the A (112Ì 0) and M (101Ì 0) surfaces are highly reactive. Sulfidation of model catalysts reveals the highest sulfidation degree for the A (112Ì 0) and M (101Ì 0) planes suggesting weak metal/support interactions. Conversely, a low sulfidation rate and shorter MoS2 slabs are found for the R (11Ì 02) plane implying stronger Mo-O-Al bonds. These limiting cases are reminiscent of type I/type II MoS2 nanostructures. Structural analogies between α- and γ- alumina surfaces allow us to bridge the material gap with real Al2O3-supported catalysts. Hence, it can be proposed that Mo distribution and sulfidation rate are heterogeneous and surface-dependent on industrial γ-Al2O3-supported high-surface-area catalysts. These results demonstrate that a proper control of the γ-alumina morphology is a strategic lever for a molecular-scale design of hydrotreating catalysts.
BACKGROUND: The statistical analysis of nasal provocation tests is very complex. We compared the conventional analysis with the maximally selected test statistics and the hierarchical ordered logistic model. METHODS: We re-analyzed data from a trial with 112 patients suffering from grass pollen allergy. The patients had been randomized to receive either intralymphatic immunotherapy (ILIT) or subcutaneous immunotherapy (SCIT). RESULTS: The conventional analysis indicated that the logarithmized ratio between the pre- and the post-treatment threshold concentration was significantly lower for ILIT than for SCIT. The maximally selected test statistics was used to test different threshold symptom scores that would imply positive clinical symptoms at the given allergen concentration. A threshold score of 3 maximised the difference in improvement between the ILIT and the SCIT groups. The hierarchical ordered logistic model does not take threshold allergen concentrations as the basis for analysis, but the single scores measured at each concentration. This approach simultaneously considers the treatment effect (ILIT versus SCIT), the time effect (pre- versus post-treatment), and the dose effect (different allergen concentrations). The hierarchical ordered logistic model revealed that the clinical improvement was greater after ILIT than after SCIT. CONCLUSION: As the choice of method can affect the outcome, guidelines for analysis are highly needed.
Conjunctivitis, Allergic/therapy , Desensitization, Immunologic , Rhinitis, Allergic, Seasonal/therapy , Allergens , Cohort Studies , Humans , Logistic Models , Nasal Provocation Tests , Poaceae , Pollen , Reproducibility of Results , Treatment Outcome
We propose a method for analytically predicting single-component adsorption isotherms from molecular, microscopic and structural descriptors of the adsorbate-adsorbent system and concepts of statistical thermodynamics. Expressions for Henry's constant and the heat of adsorption at zero coverage are derived. These functions depend on the pore size, pore shape, chemical composition, and density of the adsorbent material. They quantify the strength of the solid-fluid interaction, which governs the low-pressure part of the adsorption isotherm. For intermediate and high pressures, the fluid-fluid interactions must also be taken into account. Both solid-fluid and fluid-fluid interactions are combined within the framework of the Ruthven statistical model (RSM). The RSM thus constructs theoretical adsorption isotherms that are entirely based on microscopic molecular and structural descriptors. The theoretical results that we obtained are compared with experimental data for the adsorption of pure CO2 and CH4 on all-silica zeolites. The developed methodology allows for the estimation of the optimum properties of a nonpolar adsorbent for the adsorption of CO2 in cyclic adsorption processes.
The confinement effect plays a key role in physisorption in microporous materials and many other systems. Confinement is related to the relationship between the pore geometry (pore size and topology) and the geometry of the adsorbed molecule. Geometric properties of the porous solid can be described using the concepts of Gaussian and mean curvatures. In this work we show that the Gaussian and mean curvatures are suited descriptors for mathematically quantifying the confinement of small molecules in porous solids. A method to determine these geometric parameters on microporous materials is presented. The new methodology is based on the reconstruction of the solid's accessible surface. Then, a numerical calculation of the Gaussian and mean curvatures is carried out over the reconstructed mesh. On the one hand, we show that the local curvature can be used to identify the most favourable adsorption sites. On the other hand, the global mean curvature of the solid is correlated to the heat of adsorption of CO2 and CH4 on several zeolites and MOFs. A theoretical justification for this empirical correlation is provided. In conclusion, our methodology allows for a semi-quantitative estimation of confinement, applicable to any pore geometry, independent of the chemical composition, and without the need for applying a force field.
Genome-wide association studies have reported an association between the A-allele of rs1006737 within CACNA1C and affective disorders and schizophrenia. The aim of the present study was to investigate the relationship between rs1006737 and established and potential endophenotypes for these disorders in a population-based cohort of 3793 subjects, using an analytical method designed to assess a previously reported sex-specific effect of CACNA1C. The investigated endophenotypes included personality traits and resilience factors. At 10-year follow-up, subjects were screened for depressive symptoms. All subjects were genotyped for rs1006737. The direction of the effect and mode of inheritance of rs1006737 differed between the sexes. In men, the A-allele was associated with higher emotional lability and lower resilience, that is, lower sense of coherence (P=0.021), lower perceived social support (P=0.018), lower dispositional optimism (P=0.032) and more depressive symptoms at follow-up (P=0.007). In women, the A-allele was associated with lower emotional lability and stronger resilience, that is, higher sense of coherence (P=0.00028), higher perceived social support (P=0.010), lower neuroticism (P=0.022) and fewer depressive symptoms at follow-up (P=0.035). After conservative Bonferroni correction for 32 tests, results only remained significant for sense of coherence in women (P=0.009). These results suggest that CACNA1C is involved in the genetic architecture of endophenotypes for affective disorders and schizophrenia, and that it shows a distinct sex-specific effect. Comprehensive phenotype characterization in case-control samples and the general population, as well as an adequate modeling of sex-specific genetic effects, may be warranted to elucidate the pathogenetic mechanisms conferred by robustly identified susceptibility genes.
Anxiety Disorders/complications , Calcium Channels, L-Type/genetics , Depression , Genetic Predisposition to Disease , Personality/genetics , Sex Characteristics , Adult , Aged , Anxiety Disorders/genetics , Cohort Studies , Community Health Planning , Depression/complications , Depression/genetics , Depression/psychology , Female , Genome-Wide Association Study , Genotype , Humans , Male , Middle Aged , Neuroticism , Personality Inventory , Retrospective Studies , Social Support , Statistics as Topic
The objective of this work was to study the adsorption and separation of the most important families of hydrocarbon compounds on metal-organic frameworks (MOFs), in comparison with zeolites. For this purpose, we have selected four probe molecules, each of them representing one of these families, i.e., o- and p-xylene as aromatics, 1-octene as an alkene, and n-octane as an alkane. The separation of these four molecules was studied by binary breakthrough experiments. To represent the large diversity of MOF structures, the experiments were carried out with (i) two MOFs with coordinatively unsaturated metal sites (CUS), i.e., Cu-btc (HKUST-1) and CPO-27-Ni, (ii) a MOF with an anionic framework and extraframework cations, i.e. RHO-ZMOF, and (iii) two rather apolar zeolitic imidazolate framework (ZIF) materials with different pore sizes, i.e. ZIF-8 and ZIF-76. Zeolite NaY and zeolite ß were used as polar and apolar reference adsorbents, respectively. The results can be briefly summarized as follows: ZIFs (not carrying any polar functional groups) behave like apolar adsorbents and exhibit very interesting and unexpected molecular sieving properties. CUS-MOFs behave like polar adsorbents but show the specificity of preferring alkenes over aromatics. This feature is rationalized thanks to DFT+D calculations. MOFs with extraframework cations behave like polar (cationic) zeolites.
This work reports the adsorption and coadsorption data of CO(2)/CH(4)/CO mixtures on several metal-organic frameworks [MOFs; MIL-100(Cr), MIL-47(V), MIL-140(Zr)-A, Cu-btc, and MIL-53(Cr)] and compares them with reference adsorbents, that is, zeolite NaX and an activated carbon material, AC35. We also evaluate the effect of H(2)O on CO(2) adsorption and on the stability of the structures. Based on the experimental adsorption data, the performance potential of MOFs in several pressure swing adsorption processes is estimated by making a ranking of working capacities and separation factors. We discuss the separation of biogas, the purification of H(2) produced by steam reforming of methane, and the removal of CO(2) from synthesis gas in IGCC (integrated gasification combined cycle) systems. Some MOFs are very well placed in the ranking of (isothermal) working capacity vs. selectivity. Yet, performance is not the only criterion for the selection of MOFs. Ease and cost of synthesis and long-term stability are other important aspects that have to be taken into account.
Carbon Dioxide/chemistry , Organometallic Compounds/chemistry , Pressure , Adsorption , Carbon Dioxide/isolation & purification , Carbon Monoxide/chemistry , Carbon Monoxide/isolation & purification , Hot Temperature , Methane/chemistry , Methane/isolation & purification , Water/chemistry , Zeolites/chemistry
Carbon dioxide is the main undesirable compound present in raw natural gas and biogas. Physisorption based adsorption processes such as pressure swing adsorption (PSA) are one of the solutions to selectively adsorb CO(2) from CH(4). Some hybrid crystalline porous materials that belong to the family of metal-organic frameworks (MOFs) show larger CO(2) adsorption capacity compared to the usual industrial adsorbents, such as zeolites and most activated carbons, which makes them potentially promising for such applications. However, their selectivity values have been most often determined using only single gas adsorption measurements combined with simple macroscopic thermodynamic models or by means of molecular simulations based on generic forcefields. The transfer of this systematic approach to all MOFs, whatever their complex physico-chemical features, needs to be considered with caution. In contrast, direct co-adsorption measurements collected on these new materials are still scarce. The aim of this study is to perform a complete analysis of the CO(2)-CH(4) co-adsorption in the mesoporous MIL-100(Cr) MOF (MIL stands for Materials from Institut Lavoisier) by means of a synergic combination of outstanding experimental and modelling tools. This solid has been chosen both for its fundamental interests, given its very large CO(2) adsorption capacities and its complexity with a combination of micropores and mesopores and the existence of unsaturated accessible metal sites. The predictions obtained by means of Grand Canonical Monte Carlo simulations based on generic forcefields as well as macroscopic thermodynamic (IAST, RAST) models will be compared to direct the co-adsorption experimental data (breakthrough curve and volumetric measurements).
Air Pollutants/chemistry , Carbon Dioxide/chemistry , Chromium/chemistry , Methane/chemistry , Adsorption , Air Pollution/prevention & control , Models, Chemical , Thermodynamics
Photodynamic inactivation (PDI) of bacteria is a promising approach for combating the increasing emergence of antibiotic resistance in pathogenic bacteria. To further improve the PDI efficiency on bacteria, a bacteria-targeting liposomal formulation was investigated. A generation II photosensitizer (temoporfin) was incorporated into liposomes, followed by conjugation with a specific lectin (wheat germ agglutinin, WGA) on the liposomal surface. WGA was successfully coupled to temoporfin-loaded liposomes using an activated phospholipid containing N-hydroxylsuccinimide residue. Methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa were selected to evaluate the WGA modified liposomes in terms of bacteria targeted delivery and in vitro PDI test. Fluorescence microscopy revealed that temoporfin was delivered to both kinds of bacteria, while flow cytometry demonstrated that WGA- modified liposomes delivered more temoporfin to bacteria compared to nonmodified liposomes. Consequently, the WGA- modified liposomes eradicated all MRSA and significantly enhanced the PDI of P. aeruginosa. In conclusion, the WGA- modified liposomes are a promising formulation for bacteria targeted delivery of temoporfin and for improving the PDI efficiency of temoporfin on both Gram-positive and Gram-negative bacterial cells.
Anti-Bacterial Agents/pharmacology , Bacteria/drug effects , Liposomes , Mesoporphyrins/pharmacology , Photochemotherapy , Photosensitizing Agents/pharmacology , Wheat Germ Agglutinins/chemistry , Flow Cytometry , Microbial Sensitivity Tests , Microscopy, Fluorescence , Pseudomonas aeruginosa/drug effects , Staphylococcus aureus/drug effects
Photodynamic antimicrobial chemotherapy (PACT) and antimicrobial peptides (AMPs) are two promising strategies to combat the increasing prevalence of antibiotic-resistant bacteria. To take advantage of these two strategies, we integrated a novel antimicrobial peptide (WLBU2) and a potent generation II photosensitizer (temoporfin) into liposomes by preparing WLBU2-modified liposomes, aiming at bacteria targeted delivery of temoporfin for PACT. WLBU2 was successfully coupled to temoporfin-loaded liposomes using a functional phospholipid. The delivery of temoporfin to bacteria was confirmed by fluorescence microscopy and flow cytometry, thus demonstrating that more temoporfin was delivered to bacteria by WLBU2-modified liposomes than by unmodified liposomes. Consequently, the WLBU2-modified liposomes eradicated all methicillin-resistant Staphylococcus aureus (MRSA) and induced a 3.3 log(10) reduction of Pseudomonas aeruginosa in the in vitro photodynamic inactivation test. These findings demonstrate that the use of AMP-modified liposomes is promising for bacteria-targeted delivery of photosensitizers and for improving the PACT efficiency against both gram-positive and gram-negative bacteria in the local infections.
Antimicrobial Cationic Peptides/chemistry , Bacteria/drug effects , Liposomes/chemistry , Mesoporphyrins/pharmacology , Photosensitizing Agents/pharmacology , Drug Resistance, Bacterial/drug effects , Flow Cytometry , Gram-Negative Bacteria/drug effects , Gram-Positive Bacteria/drug effects , Mesoporphyrins/chemistry , Methicillin-Resistant Staphylococcus aureus/drug effects , Microscopy, Fluorescence , Photochemotherapy , Photosensitizing Agents/chemistry , Pseudomonas aeruginosa/drug effects
A physico-chemical method has been developed as an alternative to the current bioassay in normocythaemic mice for estimating the biological activity of erythropoietin batches. Capillary zone electrophoresis was used for quantification of the isoforms and their substructures were further elucidated by N-glycan mapping techniques. The analytical study was carried out on a total of 40 batches of epoetin beta which were selected to cover an adequate range of precisely established potency values. The relationship between the biological and chemical parameters was evaluated statistically in order to identify suitable covariates for the prediction of the biological activity. Out of several alternatives, a prediction model which is based on the percentages of isoforms per batch and the degree of sialidation was selected and tested. This model is comparable in terms of accuracy to the established in vivo bioassay, but is far superior in terms of precision. Further advantages of the method are improved animal welfare and savings in time and effort. The question whether the prediction model already meets the requirements for replacing the bioassay according to the ICH guideline Q6B is discussed.
Animal Testing Alternatives , Electrophoresis, Capillary , Erythropoietin/analysis , Hematinics/analysis , Amino Acid Sequence , Animal Testing Alternatives/methods , Animal Testing Alternatives/standards , Animals , Anion Exchange Resins , Biological Assay , Chromatography, Ion Exchange , Erythropoietin/chemistry , Erythropoietin/pharmacology , Erythropoietin/standards , Glycosylation , Hematinics/chemistry , Hematinics/pharmacology , Hematinics/standards , Hematopoiesis/drug effects , Linear Models , Mice , Models, Biological , Molecular Sequence Data , Principal Component Analysis , Protein Conformation , Protein Isoforms , Quality Control , Recombinant Proteins , Reproducibility of Results , Sialic Acids/analysis , Surface Plasmon Resonance
The present study attempts to understand the use of the flexible porous chromium terephthalate Cr(OH)(O(2)C-C(6)H(4)-CO(2)) denoted MIL-53(Cr) (MIL = Material from Institut Lavoisier) for the separation of mixtures of CO(2) and CH(4) at ambient temperature. The coadsorption of CO(2) and CH(4) was studied by a variety of different techniques. In situ synchrotron X-ray Powder Diffraction allowed study of the breathing of the solid upon adsorption of the gas mixtures and simultaneously measured Raman spectra yielded an estimation of the adsorbed quantities of CO(2) and CH(4), as well as a quantification of the fraction of the narrow pore (NP) and the large pore (LP) form of MIL-53. Quantitative coadsorption data were then measured by gravimetry and by breakthrough curves. In addition, computer simulation was performed to calculate the composition of the adsorbed phase in comparison with experimental equilibrium isotherms and breakthrough results. The body of results shows that the coadsorption of CO(2) and CH(4) leads to a similar breathing of MIL-53(Cr) as with pure CO(2). The breathing is mainly controlled by the partial pressure of CO(2), but increasing the CH(4) content progressively decreases the transformation of LP to NP. CH(4) seems to be excluded from the NP form, which is filled exclusively by CO(2) molecules. The consequences in terms of CO(2)/CH(4) selectivity and the possible use of MIL-53(Cr) in a PSA process are discussed.
Carbon Dioxide/chemistry , Methane/chemistry , Adsorption , Carbon Dioxide/isolation & purification , Methane/isolation & purification , Spectrum Analysis, Raman , X-Ray Diffraction
Quality control for repeated bioassay runs can be performed by phase II control charts, well-known from industrial quality control. The value of interest is the potency, of which a single value per run is available. Parametric and non-parametric prediction intervals are described to estimate quality control intervals for future re-test runs. Violations against the normal distribution occur in real data frequently, particularly outliers. The non-parametric prediction intervals are limited to not too small sample sizes in both the historical and future sampling phases. Therefore, robust prediction intervals based on winsorization are proposed. R-functions for all prediction intervals are provided.
Biological Assay/statistics & numerical data , Biological Assay/standards , Data Interpretation, Statistical , Forecasting/methods , Biological Assay/methods , Computer Simulation , Dose-Response Relationship, Drug , Drug Evaluation, Preclinical/standards , Drug Evaluation, Preclinical/statistics & numerical data , Models, Theoretical , Probability , Quality Control , Reference Standards , Software Design , Validation Studies as Topic
The active core of the enzyme methane mono-oxygenase (MMO) contains an iron (or copper) dimer with histidine and glutamic acid ligands located on a His-x-x-Glu sequence of the peptide chain. We mimicked the active core of MMO by immobilising the His-Gly-Gly-Glu motif on a silica support, using the methods of solid phase peptide synthesis, and by allowing complexes with Cu and Fe cations to self-assemble. The dominating mode of coordination in the complexes was elucidated by a group fitting analysis of the extended X-ray absorption fine structure (EXAFS) spectra. The complexation of the metal cations by the short peptide significantly changed (improved) their catalytic properties in the oxidation of cyclohexane by H(2)O(2) or by 3-chloro-perbenzoic acid.
Metals/chemistry , Molecular Mimicry , Peptides/chemistry , Silicon Dioxide/chemistry , Catalysis , Spectrophotometry, Infrared
For the analysis of multiarmed clinical trials often a set consisting of a mixture of one- and two-sided tests can be preferred over a set of common two-sided hypotheses settings. Here we show the straightforward application of existing multiple comparison procedures for the difference and ratio of normally distributed means to complex trial designs, involving one and two test directions. The proposed contrast tests provide a more flexible framework than the existing methods at nearly similar power. An application is illustrated for an example with multiple treatment doses and two active controls; statistical software codes are included for R and SAS System.
Clinical Trials as Topic/statistics & numerical data , Confidence Intervals , Models, Statistical , Research Design , Aromatase Inhibitors/administration & dosage , Aromatase Inhibitors/pharmacology , Aromatase Inhibitors/therapeutic use , Clinical Trials as Topic/methods , Drug Therapy, Combination , Humans , Letrozole , Nitriles/administration & dosage , Nitriles/pharmacology , Nitriles/therapeutic use , Selective Estrogen Receptor Modulators/administration & dosage , Selective Estrogen Receptor Modulators/pharmacology , Selective Estrogen Receptor Modulators/therapeutic use , Tamoxifen/administration & dosage , Tamoxifen/pharmacology , Tamoxifen/therapeutic use , Triazoles/administration & dosage , Triazoles/pharmacology , Triazoles/therapeutic use
BACKGROUND: Damask roses (Rosa damascena Mill.) are mainly used for essential oil production. Previous studies have indicated that all production material in Bulgaria and Turkey consists of only one genotype. Nine polymorphic microsatellite markers were used to analyze the genetic diversity of 40 accessions of R. damascena collected across major and minor rose oil production areas in Iran. RESULTS: All microsatellite markers showed a high level of polymorphism (5-15 alleles per microsatellite marker, with an average of 9.11 alleles per locus). Cluster analysis of genetic similarities revealed that these microsatellites identified a total of nine different genotypes. The genotype from Isfahan province, which is the major production area, was by far the most common genotype (27/40 accessions). It was identical to the Bulgarian genotype. Other genotypes (each represented by 1-4 accessions) were collected from minor production areas in several provinces, notably in the mountainous Northwest of Iran. CONCLUSION: This is the first study that uncovered genetic diversity within Damask rose. Our results will guide new collection activities to establish larger collections and manage the Iranian Damask rose genetic resources. The genotypes identified here may be directly useful for breeding.
DNA, Plant/genetics , Microsatellite Repeats/genetics , Rosa/genetics , Bulgaria , Genotype , Geography , Iran , Rosa/classification , Turkey
