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51.
Abstract While it is well established that classical hydrogen bonds play an important role in enzyme structure, function and dynamics, the role of weaker, but ‘activated’ C-H donor hydrogen bonds is poorly understood. The most important such case involves histidine which often plays a direct role in enzyme catalysis and possesses the most acidic C-H donor group of the standard amino acids. In the present study, we obtained optimized geometries and hydrogen bond interaction energies for C-H…O hydrogen bonded complexes between methane, ethylene, benzene, acetylene, and imidazole with water at the MP2-FC/6-31++G(2d,2p) and MP2-FC/aug-cc-pVDZ//MP2-FC/6-31++G(2d,2p) levels of theory. A strong linear relationship is obtained between the stability of the various hydrogen bonded complexes and both separation distances for H…0 and C—O. In general, these calculations indicate that C-H…0 interactions can be classified as hydrogen bonding interactions, albeit significantly weaker than the classical hydrogen bonds, but significantly stronger than just van der Waals interactions. For instance, while the electronic energy of stabilization at the MP2-FC/aug-cc-pVDZ//MP2-FC/6-31++G(2d,2p) level of theory of a water C-H…O water hydrogen bond is 4.36 kcal/mol more stable than the methane C-H…O water interaction, the water-water hydrogen bond is only 2.06 kcal/mol more stable than the imidazole Ce?H…O water hydrogen bond. Neglecting this latter hydrogen bonding interaction is obviously unacceptable. We next compare the potential energy surfaces for the imidazole Ce?H…O water and imidazole Nd?H…O hydrogen bonded complexes computed at the MP2/6-31++G(2d,2p) level of theory with the potential energy surface computed using the AMBER molecular mechanics program and forcefields. While the Weiner et al and Cornell et al AMBER forcefields reasonably account for the imidazole N-H…O water interaction, these forcefields do not adequately account for the imidazole Ce?H…O water hydrogen bond. A forcefield modification is offered that results in excellent agreement between the ab initio and molecular mechanics geometry and energy for this C-H…O hydrogen bonded complex. 相似文献
52.
Janet E. Saunders Craig C. Beeson Rick G. Schnellmann 《Journal of bioenergetics and biomembranes》2013,45(1-2):87-99
Mitochondrial stress results in changes in mitochondrial function, morphology and homeostasis (biogenesis, fission/fusion, mitophagy) and may lead to changes in mitochondrial subpopulations. While flow cytometric techniques have been developed to quantify features of individual mitochondria related to volume, Ca2+ concentration, mtDNA content, respiratory capacity and oxidative damage, less information is available concerning the identification and characterization of mitochondrial subpopulations, particularly in epithelial cells. Mitochondria from rabbit kidneys were stained with molecular probes for cardiolipin content (nonyl acridine orange, NAO) and membrane potential (tetramethylrhodamine, TMRM) and analyzed using flow cytometry. We validated that side scatter was a better indicator of volume and that as side scatter (SSC) decreased mitochondrial volume increased. Furthermore, those mitochondria with the highest NAO content had greater side scattering and were most highly charged. Mitochondria with average NAO content were of average side scattering and maintained an intermediate charge. Those mitochondria with low NAO content had minimal side scattering and exhibited minimal charge. Upon titration with the uncoupler carbonylcyanide-4-(trifluoromethoxy)-phenylhydrazone (FCCP), it was found that the high NAO content subpopulations were more resistant to uncoupling than lower NAO content populations. Ca2+-induced swelling of mitochondria was evaluated using probability binning (PB) analyses of SSC. Interestingly, only 30 % of the mitochondria showed changes in response to Ca2+, which was blocked by cyclosporine A. In addition, the small, high NAO content mitochondria swelled differentially in response to Ca2+ over time. Our results demonstrate that flow cytometry can be used to identify mitochondrial subpopulations based on high, mid and low NAO content and/or volume/complexity. These subpopulations showed differences in membrane potential, volume, and responses to uncoupling and Ca2+-induced swelling. 相似文献
53.
Andrea Gómez Bravo María Gabriela Quintana Marcelo Abril Oscar Daniel Salomón 《Memórias do Instituto Oswaldo Cruz》2013,108(8):1071-1073
In 2004, the urban presence of Lutzomyia longipalpis was recorded
for the first time in Formosa province. In 2006, the first autochthonous case of
human urban visceral leishmaniasis (VL) was recorded in Misiones in the presence of
the vector, along with some canine VL cases. After this first case, the vector began
to spread primarily in northeast Argentina. Between 2008-2011, three human VL cases
were reported in Salta province, but the presence of Lu. longipalpis
was not recorded. Captures of Phlebotominae were made in Tartagal, Salta, in 2013,
and the presence of Lu. longipalpis was first recorded in northwest
Argentina at that time. Systematic sampling is recommended to observe the
distribution and dispersion patterns of Lu. longipalpis and consider
the risk of VL transmission in the region. 相似文献
54.
Zi-Feng Jiang Fangfang Xia Kipp W. Johnson Christopher D. Brown Elizabeth Bartom Jigyasa H. Tuteja Rick Stevens Robert L. Grossman Marina Brumin Kevin P. White Murad Ghanim 《Applied and environmental microbiology》2013,79(5):1757-1759
“Candidatus Portiera aleyrodidarum” is the primary endosymbiont of whiteflies. We report two complete genome sequences of this bacterium from the worldwide invasive B and Q biotypes of the whitefly Bemisia tabaci. Differences in the two genome sequences may add insights into the complex differences in the biology of both biotypes. 相似文献
55.
Marijke Haas Jimoh Akanbi Eduard Post Sander M. van Putten Louwe de Vries Jarmila Smisterova Anita H. Meter-Arkema Han A. B. Wösten Rick Rink Karin Scholtmeijer 《Applied microbiology and biotechnology》2013,97(10):4385-4392
The use of mushroom extracts has been common practice in traditional medicine for centuries, including the treatment of cancer. Proteins called hydrophobins are very abundant in mushrooms. Here, it was examined whether they have antitumor activity. Hydrophobin SC3 of Schizophyllum commune was injected daily intraperitoneally starting 1 day after tumor induction in two tumor mouse models (sarcoma and melanoma). SC3 reduced the size and weight of the melanoma significantly, but the sarcoma seemed not affected. However, microscopic analysis of the tumors 12 days after induction revealed a strong antitumor effect of SC3 on both tumors. The mitotic activity of the tumor decreased 1.6- (melanoma) to 2.3-fold (sarcoma), while the vital mass decreased 2.3- (melanoma) to 4.3-fold (sarcoma) compared to the control. Treatment did not cause any signs of toxicity. Behavior, animal growth, and weight of organs were similar to animals injected with vehicle, and no histological abnormalities were found in the organs. In vitro cell culture studies revealed no direct cytotoxic effect of SC3 towards sarcoma cells, while cytotoxic activity was observed towards melanoma cells at a high SC3 concentration. Daily treatment with SC3 did not result in detectable levels of anti-SC3 antibodies in the plasma. Instead, a cellular immune response was observed. Incubation of spleen cells with SC3 resulted in a 1.5- to 2.5-fold increase in interleukin-10 and TNF-α mRNA levels. In conclusion, the nontoxic fungal hydrophobin SC3 showed tumor-suppressive activity possibly via immunomodulation and may be of benefit as adjuvant in combination with chemotherapy and radiation. 相似文献
56.
Hung-Chun Yu Jennifer L. Sloan Gunter Scharer Alison Brebner Anita M. Quintana Nathan P. Achilly Irini Manoli Curtis R. Coughlin II Elizabeth A. Geiger Una Schneck David Watkins Terttu Suormala Johan L.K. Van Hove Brian Fowler Matthias R. Baumgartner David S. Rosenblatt Charles P. Venditti Tamim H. Shaikh 《American journal of human genetics》2013
57.
Xuanyao Liu Rick?Twee-Hee Ong Esakimuthu?Nisha Pillai Abier?M. Elzein Kerrin?S. Small Taane?G. Clark Dominic?P. Kwiatkowski Yik-Ying Teo 《American journal of human genetics》2013,92(6):866-881
Natural selection is a significant force that shapes the architecture of the human genome and introduces diversity across global populations. The question of whether advantageous mutations have arisen in the human genome as a result of single or multiple mutation events remains unanswered except for the fact that there exist a handful of genes such as those that confer lactase persistence, affect skin pigmentation, or cause sickle cell anemia. We have developed a long-range-haplotype method for identifying genomic signatures of positive selection to complement existing methods, such as the integrated haplotype score (iHS) or cross-population extended haplotype homozygosity (XP-EHH), for locating signals across the entire allele frequency spectrum. Our method also locates the founder haplotypes that carry the advantageous variants and infers their corresponding population frequencies. This presents an opportunity to systematically interrogate the whole human genome whether a selection signal shared across different populations is the consequence of a single mutation process followed subsequently by gene flow between populations or of convergent evolution due to the occurrence of multiple independent mutation events either at the same variant or within the same gene. The application of our method to data from 14 populations across the world revealed that positive-selection events tend to cluster in populations of the same ancestry. Comparing the founder haplotypes for events that are present across different populations revealed that convergent evolution is a rare occurrence and that the majority of shared signals stem from the same evolutionary event. 相似文献
58.
Lai-Ping Wong Rick?Twee-Hee Ong Wan-Ting Poh Xuanyao Liu Peng Chen Ruoying Li Kevin?Koi-Yau Lam Nisha?Esakimuthu Pillai Kar-Seng Sim Haiyan Xu Ngak-Leng Sim Shu-Mei Teo Jia-Nee Foo Linda?Wei-Lin Tan Yenly Lim Seok-Hwee Koo Linda?Seo-Hwee Gan Ching-Yu Cheng Sharon Wee Eric?Peng-Huat Yap Pauline?Crystal Ng Wei-Yen Lim Richie Soong Markus?Rene Wenk Tin Aung Tien-Yin Wong Chiea-Chuen Khor Peter Little Kee-Seng Chia Yik-Ying Teo 《American journal of human genetics》2013,92(1):52-66
Whole-genome sequencing across multiple samples in a population provides an unprecedented opportunity for comprehensively characterizing the polymorphic variants in the population. Although the 1000 Genomes Project (1KGP) has offered brief insights into the value of population-level sequencing, the low coverage has compromised the ability to confidently detect rare and low-frequency variants. In addition, the composition of populations in the 1KGP is not complete, despite the fact that the study design has been extended to more than 2,500 samples from more than 20 population groups. The Malays are one of the Austronesian groups predominantly present in Southeast Asia and Oceania, and the Singapore Sequencing Malay Project (SSMP) aims to perform deep whole-genome sequencing of 100 healthy Malays. By sequencing at a minimum of 30× coverage, we have illustrated the higher sensitivity at detecting low-frequency and rare variants and the ability to investigate the presence of hotspots of functional mutations. Compared to the low-pass sequencing in the 1KGP, the deeper coverage allows more functional variants to be identified for each person. A comparison of the fidelity of genotype imputation of Malays indicated that a population-specific reference panel, such as the SSMP, outperforms a cosmopolitan panel with larger number of individuals for common SNPs. For lower-frequency (<5%) markers, a larger number of individuals might have to be whole-genome sequenced so that the accuracy currently afforded by the 1KGP can be achieved. The SSMP data are expected to be the benchmark for evaluating the value of deep population-level sequencing versus low-pass sequencing, especially in populations that are poorly represented in population-genetics studies. 相似文献
59.
Daesoo Kim Greg Thoma Darin Nutter Franco Milani Rick Ulrich Greg Norris 《The International Journal of Life Cycle Assessment》2013,18(5):1019-1035