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991.
Nadege Hamon Maurizio Quintiliani Jan Balzarini Christopher McGuigan 《Bioorganic & medicinal chemistry letters》2013,23(9):2555-2559
We report in this Letter the synthesis of prodrugs of 2-fluoro-2-deoxyarabinose-1-phosphate and 2,2-difluoro-2-deoxyribose-1-phosphate. We demonstrate the difficulty of realising a phosphorylation step on the anomeric position of 2-deoxyribose, and we discover that introduction of fluorine atoms on the 2 position of 2-deoxyribose enables the phosphorylation step: in fact, the stability of the prodrugs increases with the degree of 2-fluorination. Stability studies of produgs of 2-fluoro-2-deoxyribose-1-phosphate and 2,2-difluoro-2-deoxyribose-1-phosphate in acidic and neutral conditions were conducted to confirm our observation. Biological evaluation of prodrugs of 2,2-difluoro-2-deoxyribose-1-phosphate for antiviral and cytotoxic activity is reported. 相似文献
992.
993.
Anna Horváth Ignacio J. March Jan H. D. Wolf 《Studies on Neotropical Fauna and Environment》2013,48(3):169-176
We analyzed the abundance and diversity of Heteromyid and Murid rodents in the Lagos de Montebello National Park and adjacent areas, Chiapas, Mexico. We sampled three habitat types with different degrees of disturbance: pine-oak-liquidambar forest, ecotone and crop farming lands. Habitat types were defined considering characteristics such as heterogeneity, structural complexity and arboreal cover. We obtained ancillary habitat data considered important for small mammal requirements. Data on rodent communities were obtained by capture-mark-recapture between February and October 1996. We made 410 captures in 3820 trap-nights effort. Ten species were recorded, including one endemic with restricted distribution in Chiapas. Mouse diversity in the forest was significantly higher than within the farm lands. A Kendall correlation analysis showed positive relationship between rodent community species richness and habitat heterogeneity. Diversity of rodents was associated with the habitat complexity and structural elements, and negatively correlated with farming intensity. We found a high beta diversity and low similarity of the rodent communities in the three different habitats. Community composition strongly changed from the forest through the ecotone into the farm lands, with five species gained and seven species lost. The highest species richness was found in the ecotone; however, it showed a strong dominance of a single species that can convert into a plague of crops, and relatively low abundance of the other species. The pine-oak-liquidambar forest had the highest diversity indices, sheltering a particular rodent community within the study area, it therefore probably has the most important role in the conservation of the local biodiversity. 相似文献
994.
Jan Batelka 《法国昆虫学会纪事》2013,49(1):75-78
Macrosiagon deuvei n. sp., the second fossil representative of this extant genus of Ripiphoridae: Ripiphorinae: Macrosiagonini is described from the lowermost Eocene amber of Oise (France). The new species is compared with the extant species of the genus. Taxonomic position of other two fossil representatives of the family described from France by Perrichot et al. (2004) is discussed. The genus Paleoripiphorus Perrichot et al. 2004 is tentatively transferred from Ripiphorinae to Ripidiinae. 相似文献
995.
Monika H. E. Christensen Ellen M. Apalset Yngve Nordb? Jan Erik Varhaug Gunnar Mellgren Ernst A. Lien 《PloS one》2013,8(2)
Objective
Parathyroid hormone (PTH) and vitamin D are the most important hormones regulating calcium metabolism. In primary hyperparathyroidism (PHPT) excessive amounts of PTH are produced. Bone turnover is enhanced, leading to reduced bone mineral density and elevated levels of serum calcium. The aim of this study was to investigate relations between serum levels of 25-hydroxyvitamin D (25(OH)D), 1,25-dihydroxyvitamin D (1,25(OH)2D) and bone mineral density, as well as known genetic polymorphisms in the vitamin D receptor and enzymes metabolising vitamin D in patients with PHPT.Design/Subjects
We conducted a cross-sectional study of 52 patients with PHPT.Results
Mean level of 25(OH)D was 58.2 nmol/L and median 1,25(OH)2D level was 157 pmol/L. Among our patients with PHPT 36.5% had 25(OH)D levels below 50 nmol/L. Serum 1,25(OH)2D was inversely correlated to bone mineral density in distal radius (p = 0.002), but not to bone mineral density at lumbar spine or femoral neck. The vitamin D receptor polymorphism Apa1 (rs7975232) was associated with bone mineral density in the lumbar spine.Conclusions
The results suggest that PHPT patients with high blood concentrations of 1,25(OH)2D may have the most deleterious skeletal effects. Randomized, prospective studies are necessary to elucidate whether vitamin D supplementation additionally increases serum 1,25(OH)2D and possibly enhances the adverse effects on the skeleton in patients with PHPT. 相似文献996.
Keisuke Murakami Harish Bhandari Emma S. Lucas Satoru Takeda Caroline E. Gargett Siobhan Quenby Jan J. Brosens Bee K. Tan 《PloS one》2013,8(12)
Objectives
The mechanisms of obesity associated reproductive complications remain poorly understood. Endometrial mesenchymal stem-cells are critical for cyclic renewal and uterine function. Recently, W5C5+ cells, with high clonogenicity, capable of producing endometrial stroma in vivo, have been described. We sought to investigate the abundance and cloning efficiency of W5C5+ and W5C5− endometrial cells in relation to Body Mass Index, age and reproductive outcome.Design
W5C5+ and W5C5− cells were purified from mid-luteal endometrial biopsies (n = 54) by magnetic bead separation and subjected to in vitro colony-forming assays.Results
First trimester pregnancy losses were significantly higher in obese subjects (n = 12) compared to overweight (n = 20) and subjects with normal Body Mass Index (n = 22) (P<0.05, P<0.01, respectively). W5C5+ cells (%) were significantly lower in obese subjects compared to subjects with normal Body Mass Index (P<0.05). W5C5+ cloning efficiency was significantly lower in obese subjects compared to overweight and subjects with normal Body Mass Index (P<0.05, respectively). W5C5− cloning efficiency was significantly lower in obese subjects compared to subjects with normal Body Mass Index (P<0.05). Body Mass Index was significantly negatively correlated with W5C5+ cloning efficiency and W5C5− cloning efficiency (P<0.01, respectively), and positively correlated with first trimester loss (P<0.01). We found no significant results with age (P>0.05).Conclusions
Our observations suggest that the regenerative capacity and plasticity of the endometrium of obese women is suboptimal, which in turn may account for the increased risk of reproductive complications associated with obesity. 相似文献997.
Many previous studies have reported robust sex differences in olfactory perception. However, both men and women can be expected to vary in the degree to which they exhibit olfactory performance considered typical of their own or the opposite sex. Sex-atypicality is often described in terms of childhood gender nonconformity, which, however, is not a perfect correlate of non-heterosexual orientation. Here we explored intrasexual variability in psychophysical olfactory performance in a sample of 156 individuals (83 non-heterosexual) and found the lowest odor identification scores in heterosexual men. However, when childhood gender nonconformity was entered in the model along with sexual orientation, better odor identification scores were exhibited by gender-nonconforming men, and greater olfactory sensitivity by gender-conforming women, irrespective of their sexual orientation. Thus, sex-atypicality, but not sexual orientation predicts olfactory performance, and we propose that this might not be limited to olfaction, but represent a more general phenomenon. 相似文献
998.
Gabriel Fung Chen Seng Ng Jingchun Zhang Junyan Shi Jerry Wong Paulina Piesik Lillian Han Fanny Chu Julienne Jagdeo Eric Jan Takashi Fujita Honglin Luo 《PloS one》2013,8(11)
Stress granules (SGs) are dynamic cytosolic aggregates containing messenger ribonucleoproteins and target poly-adenylated (A)-mRNA. A key component of SGs is Ras-GAP SH3 domain binding protein-1 (G3BP1), which in part mediates protein-protein and protein-RNA interactions. SGs are modulated during infection by several viruses, however, the function and significance of this process remains poorly understood. In this study, we investigated the interplay between SGs and Coxsackievirus type B3 (CVB3), a member of the Picornaviridae family. Our studies demonstrated that SGs were formed early during CVB3 infection; however, G3BP1-positive SGs were actively disassembled at 5 hrs post-infection, while poly(A)-positive RNA granules persisted. Furthermore, we confirmed G3BP1 cleavage by 3Cpro at Q325. We also demonstrated that overexpression of G3BP1-SGs negatively impacted viral replication at the RNA, protein, and viral progeny levels. Using electron microscopy techniques, we showed that G3BP1-positive SGs localized near mitochondrial surfaces. Finally, we provided evidence that the C-terminal cleavage product of G3BP1 inhibited SG formation and promoted CVB3 replication. Taken together, we conclude that CVB3 infection selectively targets G3BP1-SGs by cleaving G3BP1 to produce a dominant-negative fragment that further inhibits G3BP1-SG formation and facilitates viral replication. 相似文献
999.
1000.
A 4-nucleotide (nt) deletion was made in the 36-nt-long intercistronic region separating the coat and replicase genes of the
single-stranded RNA phage MS2. This region is the focus of several RNA structures conferring high fitness. One such element
is the operator hairpin, which, in the course of infection, will bind a coat-protein dimer, thereby precluding further replicase
synthesis and initiating encapsidation. Another structure is a long-distance base pairing (MJ) controlling replicase expression.
The 4-nt deletion does not directly affect the operator hairpin but it disrupts the MJ pairing. Its main effect, however,
is a frame shift in the overlapping lysis gene. This gene starts in the upstream coat gene, runs through the 36-nt-long intercistronic
region, and ends in the downstream replicase cistron. Here we report and interpret the spectrum of solutions that emerges
when the crippled phage is evolved. Four different solutions were obtained by sequencing 40 plaques. Three had cured the frame
shift in the lysis gene by inserting one nt in the loop of the operator hairpin causing its inactivation. Yet these low-fitness
revertants could further improve themselves when evolved. The inactivated operator was replaced by a substitute and thereafter
these revertants found several ways to restore control over the replicase gene. To allow for the evolutionary enrichment of
low-probability but high-fitness revertants, we passaged lysate samples before plating. Revertants obtained in this way also
restored the frame shift, but not at the expense of the operator. By taking larger and larger lysates samples for such bulk
evolution, ever higher-fitness and lower-frequency revertants surfaced. Only one made it back to wild type. As a rule, however,
revertants moved further and further away from the wild-type sequence because restorative mutations are, in the majority of
cases, selected for their capacity to improve the phenotype by optimizing one of several potential alternative RNA foldings
that emerge as a result of the initial deletion. This illustrates the role of structural constraints which limit the path
of subsequent restorative mutations.
[Reviewing Editor: Dr. John Hulsenbeck] 相似文献