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101.
Susanne Gauggel-Lewandowski Alexandra H. Heussner Pablo Steinberg Bart Pieterse Bart van der Burg Daniel R. Dietrich 《Chemico-biological interactions》2013
Due to increasing energy demand and limited fossil fuels, renewable energy sources have gained in importance. Particulate matter (PM) in general, but also PM from the combustion of wood is known to exert adverse health effects in human. These are often related to specific toxic compounds adsorbed to the PM surface, such as polycyclic aromatic hydrocarbons (PAH), of which some are known human carcinogens. This study focused on the bioavailability of PAHs and on the tumor initiation potential of wood combustion PM, using the PAH CALUX® reporter gene assay and the BALB/c 3T3 cell transformation assay, respectively. For this, both cell assays were exposed to PM and their respective organic extracts from varying degrees of combustion. The PAH CALUX® experiments demonstrated a concentration–response relationship matching the PAHs detected in the samples. Contrary to expectations, PM samples from complete (CC) and incomplete combustion (IC) provided for a stronger and weaker response, respectively, suggesting that PAH were more readily bioavailable in PM from CC. These findings were corroborated via PAH spiking experiments indicating that IC PM contains organic components that strongly adsorb PAH thereby reducing their bioavailability. The results obtained with organic extracts in the cell transformation assay presented the highest potential for carcinogenicity in samples with high PAH contents, albeit PM from CC also demonstrated a carcinogenic potential. In conclusion, the in vitro assays employed emphasize that CC produces PM with low PAH content however with a general higher bioavailability and thus with a nearly similar carcinogenic potential than IC PM. 相似文献
102.
Daniel R. Matute Alexandra Harris 《Evolution; international journal of organic evolution》2013,67(8):2451-2460
Drosophila yakuba and D. santomea are sister species that differ in their levels of abdominal pigmentation; D. yakuba shows heavily pigmented posterior abdominal segments in both sexes, whereas D. santomea lacks dark pigment anywhere on its body. Using naturally collected lines, we demonstrate the existence of altitudinal variation in abdominal pigmentation in D. yakuba but not in D. santomea. We use the variation in pigmentation within D. yakuba and two body‐color mutants in D. yakuba to elucidate selective advantage of differences in pigmentation. Our results indicate that although differences in abdominal pigmentation have no effect on desiccation resistance, lighter pigmentation confers ultraviolet radiation resistance in this pair of species. 相似文献
103.
Jan P. Madej Lucie Mikulov Alexandra Goroov tpn Mikula Zdenk ehk Frantiek Tichý Marcela Buchtov 《Acta zoologica》2013,94(4):478-489
The bat skin shows an unusual morphology that corresponds to flying adaptations but also performs multiple functions including a protective barrier against microbes and parasites. Here, we compare the microscopic structure of the skin and hairs collected from the membranes with other body parts in the Common Pipistrelle (Pipistrellus pipistrellus) in relation to parasite availability. Statistical analysis of whole‐skin thickness revealed two main groups according to body regions; the first with thin skin (wing and tail membrane) and the second with thick skin (head and dorsum, abdomen, footpad). The density of hair was evaluated by a novel method, and it revealed that the density was significantly higher in the head region than in dorsal and ventral body parts. These differences possibly play a role for bat ectoparasites when choosing the preferred region of their host. Along the axis of each hair, the scale morphology was found to be variable. Hair morphology, however, did not vary among body regions. Mast cells were numerous in the hairy areas around vessels and hair follicles of the dorsum and abdomen, which are easily accessible to ectoparasites. Increased numbers of mast cells in hair‐bearing skin are part of the host adaptation system in parasite‐preferred locations. 相似文献
104.
Michael?R. Knowles Margaret?W. Leigh Lawrence?E. Ostrowski Lu Huang Johnny?L. Carson Milan?J. Hazucha Weining Yin Jonathan?S. Berg Stephanie?D. Davis Sharon?D. Dell Thomas?W. Ferkol Margaret Rosenfeld Scott?D. Sagel Carlos?E. Milla Kenneth?N. Olivier Emily?H. Turner Alexandra?P. Lewis Michael?J. Bamshad Deborah?A. Nickerson Jay Shendure Maimoona?A. Zariwala the Genetic Disorders of Mucociliary Clearance?Consortium 《American journal of human genetics》2013,92(1):99-106
Primary ciliary dyskinesia (PCD) is a genetically heterogeneous, autosomal-recessive disorder, characterized by oto-sino-pulmonary disease and situs abnormalities. PCD-causing mutations have been identified in 14 genes, but they collectively account for only ∼60% of all PCD. To identify mutations that cause PCD, we performed exome sequencing on six unrelated probands with ciliary outer dynein arm (ODA) defects. Mutations in CCDC114, an ortholog of the Chlamydomonas reinhardtii motility gene DCC2, were identified in a family with two affected siblings. Sanger sequencing of 67 additional individuals with PCD with ODA defects from 58 families revealed CCDC114 mutations in 4 individuals in 3 families. All 6 individuals with CCDC114 mutations had characteristic oto-sino-pulmonary disease, but none had situs abnormalities. In the remaining 5 individuals with PCD who underwent exome sequencing, we identified mutations in two genes (DNAI2, DNAH5) known to cause PCD, including an Ashkenazi Jewish founder mutation in DNAI2. These results revealed that mutations in CCDC114 are a cause of ciliary dysmotility and PCD and further demonstrate the utility of exome sequencing to identify genetic causes in heterogeneous recessive disorders. 相似文献
105.
Peter W. Glunz Xiaojun Zhang Yan Zou Indawati Delucca Alexandra H. Nirschl Xuhong Cheng Carolyn A. Weigelt Daniel L. Cheney Anzhi Wei Rushith Anumula Joseph M. Luettgen Alan R. Rendina Mark Harpel Gang Luo Robert Knabb Pancras C. Wong Ruth R. Wexler E. Scott Priestley 《Bioorganic & medicinal chemistry letters》2013,23(18):5244-5248
Aminoisoquinoline and isoquinoline groups have successfully replaced the more basic P1 benzamidine group of an acylsulfonamide factor VIIa inhibitor. Inhibitory activity was optimized by the identification of additional hydrophobic and hydrophilic P′ binding interactions. The molecular details of these interactions were elucidated by X-ray crystallography and molecular modeling. We also show that decreasing the basicity of the P1 group results in improved oral bioavailability in this chemotype. 相似文献
106.
Joseph B. Ahrens Elizabeth Borda Rômulo Barroso Paulo C. Paiva Alexandra M. Campbell Alexander Wolf Maggy M. Nugues Greg W. Rouse Anja Schulze 《Molecular ecology》2013,22(8):2280-2291
Over the last few decades, advances in molecular techniques have led to the detection of strong geographic population structure and cryptic speciation in many benthic marine taxa, even those with long‐lived pelagic larval stages. Polychaete annelids, in particular, generally show a high degree of population divergence, especially in mitochondrial genes. Rarely have molecular studies confirmed the presence of ‘cosmopolitan’ species. The amphinomid polychaete Hermodice carunculata was long considered the sole species within its genus, with a reported distribution throughout the Atlantic and adjacent basins. However, recent studies have indicated morphological differences, primarily in the number of branchial filaments, between the East and West Atlantic populations; these differences were invoked to re‐instate Hermodice nigrolineata, formerly considered a junior synonym of H. carunculata. We utilized sequence data from two mitochondrial (cytochrome c oxidase subunit I, 16S rDNA) markers and one nuclear (internal transcribed spacer) marker to examine the genetic diversity of Hermodice throughout its distribution range in the Atlantic Ocean, including the Mediterranean Sea, the Caribbean Sea, the Gulf of Mexico and the Gulf of Guinea. Our analyses revealed generally low genetic divergences among collecting localities and between the East and West Atlantic, although phylogenetic trees based on mitochondrial data indicate the presence of a private lineage in the Mediterranean Sea. A re‐evaluation of the number of branchial filaments confirmed differences between East and West Atlantic populations; however, the differences were not diagnostic and did not reflect the observed genetic population structure. Rather, we suspect that the number of branchial filaments is a function of oxygen saturation in the environment. Our results do not support the distinction between H. carunculata in the West Atlantic and H. nigrolineata in the East Atlantic. Instead, they re‐affirm the older notion that H. carunculata is a cohesive species with a broad distribution across the Atlantic Ocean. 相似文献
107.
Markus Geisen Chantal Billard Alexandra Broerse Lluisa Cros Ian Probert Jeremy Young 《欧洲藻类学杂志》2013,48(4):531-550
New holococcolith-heterococcolith life-cycle associations are documented based on observations of combination coccospheres. Daktylethra pirus is shown to be a life-cycle phase of Syracosphaera pulchra and Syracolithus quadriperforatus a life-cycle phase of Calcidiscus leptoporus. In addition, new observations from cultures confirm the life-cycle associations of Crystallolithus braarudii with Coccolithus pelagicus and of Zygosphaera hellenica with Coronosphaera mediterranea. In all four cases previous work has shown that the heterococcolithophorid species is associated with another holococcolithophorid. Two other examples of a heterococcolithophorid being associated with two holococcolithophorids have previously been identified, so this seems to be a common phenomenon. The six examples are reviewed to determine whether a single underlying mechanism is likely to be responsible for all cases. It is concluded that there is no single mechanism but rather that the six examples fall into three categories: (a) in two cases the holococcolith types are probably simply ecophenotypic morphotypes; (b) in two other cases the holococcolith types are discrete and are paralleled by morphometric differences in the heterococcolith types; (c) in the final two cases the holococcolith types are discrete but are not paralleled by any obvious morphological variation in the heterococcolith morphology. We infer that cryptic speciation may be widespread in heterococcolithophorid phases and that study of holococcolithophorid phases can provide key data to elucidate this phenomenon. 相似文献
108.
Catherine Gomez Prishila Ponien Nawal Serradji Aazdine Lamouri Alix Pantel Estelle Capton Vincent Jarlier Guillaume Anquetin Alexandra Aubry 《Bioorganic & medicinal chemistry》2013,21(4):948-956
Novel 3′-piperazinyl derivatives of the 8-hydrogeno and 8-methoxy-6-fluoro-1-cyclopropyl-4-quinolone-3-carboxylic acid scaffolds were designed, synthesized and characterized by 1H, 13C and 19F NMR, and HRMS. The activity of these derivatives against pathogenic mycobacteria (M. leprae and M. tuberculosis), wild-type (WT) strains or strains harboring mutations implicated in quinolone resistance, were determined by measuring drug concentrations inhibiting cell growth (MIC) and/or DNA supercoiling by DNA gyrase (IC50), or inducing 25% DNA cleavage by DNA gyrase (CC25). Compound 4 (with a methoxy in R8 and a secondary carbamate in R3′) and compound 5 (with a hydrogen in R8 and an ethyl ester in R3′) displayed biological activities close to those of ofloxacin but inferior to those of gatifloxacin and moxifloxacin against M. tuberculosis and M. leprae WT DNA gyrases, whereas all of the compounds were less active in inhibiting M. tuberculosis growth and M. leprae mutant DNA gyrases. Since R3′ substitutions have been poorly investigated previously, our results may help to design new quinolone derivatives in the future. 相似文献
109.
Penelope Bouziotis Eleni Gourni George Patsis Dimitrios Psimadas Christos Zikos Melpomeni Fani Stavros Xanthopoulos George Loudos Maria Paravatou-Petsotas Evangelia Livaniou Alexandra D. Varvarigou Ioannis Pirmettis Minas Papadopoulos 《Bioorganic & medicinal chemistry》2013,21(21):6699-6707
Bombesin is a neuropeptide widely studied due to its ability to target various types of cancers. Technetium-99m on the other hand is ideal for diagnostic tumor targeting. The aim of the present study is the investigation of the coupling of the ligand (S)-(2-(2′-pyridyl)ethyl)-d,l-cysteine with the BN-peptide Gln-Arg-Leu-Gly-Asn-Gln-Trp-Ala-Val-Gly-His-Leu-Met(CONH2) through the spacer aminohexanoic acidand the labeling of the resulting derivative MBN with the synthon [M(CO)3(H2O)3]+ (M = 99mTc, Re). The peptide was synthesized according to the SPPS method, purified and characterized by ESI-MS. The new 99mTc-labeled biomolecule was stable in vitro, showed high affinity for the human GRP receptor expressed in PC3 cells and the rate of internalization was found to be time-dependent tissue distribution of the radiopeptide was evaluated in normal mice and in prostate cancer experimental models and significant radioactivity uptake was observed in the pancreas of normal mice as well as in PC3 tumors. Dynamic studies of the radiopeptide showed satisfactory tumor images. 相似文献
110.
Alexandra Wasmuth Christina Ludwig Henning D. Mootz 《Bioorganic & medicinal chemistry》2013,21(12):3495-3503
Protein trans-splicing by split inteins holds great potential for the chemical modification and semisynthesis of proteins. However, the structural requirements of the extein sequences immediately flanking the intein are only poorly understood. This knowledge is of particular importance for protein labeling, when synthetic moieties are to be attached to the protein of interest as seamlessly as possible. Using the semisynthetic Ssp DnaB intein both in form of its wild-type sequence and its evolved M86 mutant, we systematically varied the sequence upstream of the short synthetic IntN fragment using both proteinogenic amino acids and unnatural building blocks. We could show for the wild-type variant that the native N-extein sequence could be reduced to the glycine residue at the (?1) position directly flanking the intein without significant loss of activity. The glycine at this position is strongly preferred over building blocks containing a phenyl group or extended alkyl chain adjacent to the scissile amide bond of the N-terminal splice junction. Despite their negative effects on the splicing yields, these unnatural substrates were well processed in the N–S acyl shift to form the respective thioesters and did not result in an increased decoupling of the asparagine cyclization step at the C-terminal splicing junction. Therefore, the transesterification step appeared to be the bottleneck of the protein splicing pathway. The fluorophore 7-hydroxycoumarinyl-4-acetic acid as a minimal N-extein was efficiently ligated to the model protein, in particular with the M86 mutant, probably because of its higher resemblance to glycine with an aliphatic c-α carbon atom at the (?1) position. This finding indicates a way for the virtually traceless labeling of proteins without inserting extra flanking residues. Due to its overall higher activity, the M86 mutant appears most promising for many protein labeling and chemical modification schemes using the split intein approach. 相似文献