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181.
182.
Lagos CF Araya-Secchi R Thomas P Pérez-Acle T Tapia RA Salas CO 《Journal of molecular modeling》2012,18(5):2055-2064
Trypanosoma cruzi glutamate cysteine ligase (TcGCL) is considered a potential drug target to develop novel antichagasic drugs. We have used
a variety of computational methods to investigate the interactions between TcGCL with Glutathione (GSH). The three-dimensional
structure of TcGCL was constructed by comparative modeling methods using the Saccharomyces cerevisiae glutamate cysteine ligase as template. Molecular dynamics simulations were used to validate the TcGCL model and to analyze
the molecular interactions with GSH. Using RMSD clustering, the most prevalent GSH binding modes were identified paying attention
to the residues involved in the molecular interactions. The GSH binding modes were used to propose pharmacophore models that
can be exploited in further studies to identify novel antichagasic compounds. 相似文献
183.
G?tz Palfner Valentina Valenzuela-Mu?oz Cristian Gallardo-Escarate Luís E. Parra José Becerra Mario Silva 《Mycological Progress》2012,11(3):733-739
Cordyceps cuncunae Palfner sp. nov. is reported from Valdivian rainforest in southern Chile, parasiting larvae of an unidentified ghost moth species (Lepidoptera, Hepialidae) which probably feed on roots of Laureliopsis philippiana. Morphology and anatomy of stromata as well as morphological and molecular characteristics of mycelium in pure culture which produces two anamorphs, one of them Lecanicillium-like, are described. The systematic position of the new taxon within the most recent generic concept is discussed. This is the first record of an endemic Cordyceps species from Chile. 相似文献
184.
Milani L Ghiselli F Passamonti M 《Journal of experimental zoology. Part B, Molecular and developmental evolution》2012,318(3):182-189
In most metazoans mitochondria are inherited maternally. However, in some bivalve molluscs, two mitochondrial lineages are present: one transmitted through females (F-type), the other through males (M-type). This unique system is called Doubly Uniparental Inheritance (DUI) of mitochondria. In DUI species, M-type mitochondria have to invade the germ line of male embryos during development, otherwise sperm would transmit F-type mtDNA and DUI would fail. The mechanisms by which sperm mitochondria enter the germ line are still unknown. To address this question, we traced the movement of spermatozoon mitochondria (M-type) in embryos of the DUI species Ruditapes philippinarum by fertilizing eggs with sperm stained with the mitochondrial-specific vital dye MitoTracker Green. As in Mytilus DUI species, in R. philippinarum the distribution of sperm mitochondria follows two different patterns: an aggregated one in which these organelles locate near the first cleavage furrow, and a dispersed one in which sperm mitochondria are scattered. The presence of the two mitochondrial patterns in these taxa, together with their absence in species with Strictly Maternal Inheritance (SMI), confirms that their occurrence is related to DUI. Moreover, a Real-Time qPCR analysis showed that neither M-type nor F-type mitochondria undergo replication boosts in the earliest embryo development. This is the first study on sex-linked mtDNA copy number carried out by qPCR analysis on embryos of a DUI species and the first time the segregation patterns of sperm mitochondria are described in a DUI system other than Mytilus. 相似文献
185.
Li J Harris RA Cheung SW Coarfa C Jeong M Goodell MA White LD Patel A Kang SH Shaw C Chinault AC Gambin T Gambin A Lupski JR Milosavljevic A 《PLoS genetics》2012,8(5):e1002692
The hotspots of structural polymorphisms and structural mutability in the human genome remain to be explained mechanistically. We examine associations of structural mutability with germline DNA methylation and with non-allelic homologous recombination (NAHR) mediated by low-copy repeats (LCRs). Combined evidence from four human sperm methylome maps, human genome evolution, structural polymorphisms in the human population, and previous genomic and disease studies consistently points to a strong association of germline hypomethylation and genomic instability. Specifically, methylation deserts, the ~1% fraction of the human genome with the lowest methylation in the germline, show a tenfold enrichment for structural rearrangements that occurred in the human genome since the branching of chimpanzee and are highly enriched for fast-evolving loci that regulate tissue-specific gene expression. Analysis of copy number variants (CNVs) from 400 human samples identified using a custom-designed array comparative genomic hybridization (aCGH) chip, combined with publicly available structural variation data, indicates that association of structural mutability with germline hypomethylation is comparable in magnitude to the association of structural mutability with LCR-mediated NAHR. Moreover, rare CNVs occurring in the genomes of individuals diagnosed with schizophrenia, bipolar disorder, and developmental delay and de novo CNVs occurring in those diagnosed with autism are significantly more concentrated within hypomethylated regions. These findings suggest a new connection between the epigenome, selective mutability, evolution, and human disease. 相似文献
186.
Demirkan A van Duijn CM Ugocsai P Isaacs A Pramstaller PP Liebisch G Wilson JF Johansson Å Rudan I Aulchenko YS Kirichenko AV Janssens AC Jansen RC Gnewuch C Domingues FS Pattaro C Wild SH Jonasson I Polasek O Zorkoltseva IV Hofman A Karssen LC Struchalin M Floyd J Igl W Biloglav Z Broer L Pfeufer A Pichler I Campbell S Zaboli G Kolcic I Rivadeneira F Huffman J Hastie ND Uitterlinden A Franke L Franklin CS Vitart V;DIAGRAM Consortium Nelson CP Preuss M;CARDIoGRAM Consortium Bis JC O'Donnell CJ 《PLoS genetics》2012,8(2):e1002490
Phospho- and sphingolipids are crucial cellular and intracellular compounds. These lipids are required for active transport, a number of enzymatic processes, membrane formation, and cell signalling. Disruption of their metabolism leads to several diseases, with diverse neurological, psychiatric, and metabolic consequences. A large number of phospholipid and sphingolipid species can be detected and measured in human plasma. We conducted a meta-analysis of five European family-based genome-wide association studies (N = 4034) on plasma levels of 24 sphingomyelins (SPM), 9 ceramides (CER), 57 phosphatidylcholines (PC), 20 lysophosphatidylcholines (LPC), 27 phosphatidylethanolamines (PE), and 16 PE-based plasmalogens (PLPE), as well as their proportions in each major class. This effort yielded 25 genome-wide significant loci for phospholipids (smallest P-value = 9.88×10−204) and 10 loci for sphingolipids (smallest P-value = 3.10×10−57). After a correction for multiple comparisons (P-value<2.2×10−9), we observed four novel loci significantly associated with phospholipids (PAQR9, AGPAT1, PKD2L1, PDXDC1) and two with sphingolipids (PLD2 and APOE) explaining up to 3.1% of the variance. Further analysis of the top findings with respect to within class molar proportions uncovered three additional loci for phospholipids (PNLIPRP2, PCDH20, and ABDH3) suggesting their involvement in either fatty acid elongation/saturation processes or fatty acid specific turnover mechanisms. Among those, 14 loci (KCNH7, AGPAT1, PNLIPRP2, SYT9, FADS1-2-3, DLG2, APOA1, ELOVL2, CDK17, LIPC, PDXDC1, PLD2, LASS4, and APOE) mapped into the glycerophospholipid and 12 loci (ILKAP, ITGA9, AGPAT1, FADS1-2-3, APOA1, PCDH20, LIPC, PDXDC1, SGPP1, APOE, LASS4, and PLD2) to the sphingolipid pathways. In large meta-analyses, associations between FADS1-2-3 and carotid intima media thickness, AGPAT1 and type 2 diabetes, and APOA1 and coronary artery disease were observed. In conclusion, our study identified nine novel phospho- and sphingolipid loci, substantially increasing our knowledge of the genetic basis for these traits. 相似文献
187.
188.
van der Star WR van de Graaf MJ Kartal B Picioreanu C Jetten MS van Loosdrecht MC 《Applied and environmental microbiology》2008,74(14):4417-4426
Anaerobic ammonium oxidation is a recent addition to the microbial nitrogen cycle, and its metabolic pathway, including the production and conversion of its intermediate hydrazine, is not well understood. Therefore, the effect of hydroxylamine addition on the hydrazine metabolism of anaerobic ammonium-oxidizing (anammox) bacteria was studied both experimentally and by mathematical modeling. It was observed that hydroxylamine was disproportionated biologically in the absence of nitrite into dinitrogen gas and ammonium. Little hydrazine accumulated during this process; however, rapid hydrazine production was observed when nearly all hydroxylamine was consumed. A mechanistic model is proposed in which hydrazine is suggested to be continuously produced from ammonium and hydroxylamine (possibly via nitric oxide) and subsequently oxidized to N(2). The electron acceptor for hydrazine oxidation is hydroxylamine, which is reduced to ammonium. A decrease in the hydroxylamine reduction rate, therefore, leads to a decrease in the hydrazine oxidation rate, resulting in the observed hydrazine accumulation. The proposed mechanism was verified by a mathematical model which could explain and predict most of the experimental data. 相似文献
189.
Constantina Heltianu Simona-Adriana Manea Cristian Guja Carina Mihai Constantin Ionescu-Tirgoviste 《Central European Journal of Biology》2008,3(3):243-249
Advanced glycation end products (AGEs) are involved in the occurrence of vascular complications in diabetes. The present study
was undertaken to investigate the level of low-molecular weight products of AGEs (LMW-AGEs) in relation to microvascular complications
in type 1 diabetes, and the possible relationship with nitric oxide (NO) as a marker of endothelial function. Patients with
normal renal function (NRF) were classified into two groups: (1) without, and (2) with diabetic neuropathy; and patients with
renal impairment also into two groups: (3) diabetic renal disease, and (4) end-stage renal disease. The fluorescence of LMW-AGEs
and measurement of NO metabolites was assessed in 277 serum samples. In addition, multiple regression analysis was performed.
In group 1, LMW-AGEs level (9.3±1.1 AF%) was higher than in the control group (2.4±0.3 AF%). A trend in the increase of LMW-AGEs
with neuropathy (29.7±5.5 AF%, group 2), and further with renal impairment (47.0±8.0, group 3 and 137.8±25.5 AF%, group 4),
was observed. In multivariate regression analysis LMW-AGEs were associated with NO metabolites in group 2. In NRF patients,
diabetic neuropathy was significantly correlated with LMW-AGEs and NO metabolites, independently of serum creatinine and duration
of diabetes. This relationship suggests that the NO and LMW-AGEs’ actions (possibly synergistic) in endothelial activation
possess a role in the initiation and development of diabetic microvascular complications. 相似文献
190.
Caramelli D Milani L Vai S Modi A Pecchioli E Girardi M Pilli E Lari M Lippi B Ronchitelli A Mallegni F Casoli A Bertorelle G Barbujani G 《PloS one》2008,3(7):e2700