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41.
Xiang Zhou Jennifer J. Michal Lifan Zhang Bo Ding Joan K. Lunney Bang Liu Zhihua Jiang 《International journal of biological sciences》2013,9(2):200-208
Secretion of interferons (IFNs) from virus-infected cells is a hallmark of host antiviral immunity and in fact, IFNs exert their antiviral activities through the induction of antiviral proteins. The IFN-induced protein with tetratricopeptide repeats (IFITs) family is among hundreds of IFN-stimulated genes. This family contains a cluster of duplicated loci. Most mammals have IFIT1, IFIT2, IFIT3 and IFIT5; however, bird, marsupial, frog and fish have only IFIT5. Regardless of species, IFIT5 is always adjacent to SLC16A12. IFIT family genes are predominantly induced by type I and type III interferons and are regulated by the pattern recognition and the JAK-STAT signaling pathway. IFIT family proteins are involved in many processes in response to viral infection. However, some viruses can escape the antiviral functions of the IFIT family by suppressing IFIT family genes expression or methylation of 5'' cap of viral molecules. In addition, the variants of IFIT family genes could significantly influence the outcome of hepatitis C virus (HCV) therapy. We believe that our current review provides a comprehensive picture for the community to understand the structure and function of IFIT family genes in response to pathogens in human, as well as in animals. 相似文献
42.
Michal Kicinski 《PloS one》2013,8(11)
Introduction
Positive results have a greater chance of being published and outcomes that are statistically significant have a greater chance of being fully reported. One consequence of research underreporting is that it may influence the sample of studies that is available for a meta-analysis. Smaller studies are often characterized by larger effects in published meta-analyses, which can be possibly explained by publication bias. We investigated the association between the statistical significance of the results and the probability of being included in recent meta-analyses.Methods
For meta-analyses of clinical trials, we defined the relative risk as the ratio of the probability of including statistically significant results favoring the treatment to the probability of including other results. For meta-analyses of other studies, we defined the relative risk as the ratio of the probability of including biologically plausible statistically significant results to the probability of including other results. We applied a Bayesian selection model for meta-analyses that included at least 30 studies and were published in four major general medical journals (BMJ, JAMA, Lancet, and PLOS Medicine) between 2008 and 2012.Results
We identified 49 meta-analyses. The estimate of the relative risk was greater than one in 42 meta-analyses, greater than two in 16 meta-analyses, greater than three in eight meta-analyses, and greater than five in four meta-analyses. In 10 out of 28 meta-analyses of clinical trials, there was strong evidence that statistically significant results favoring the treatment were more likely to be included. In 4 out of 19 meta-analyses of observational studies, there was strong evidence that plausible statistically significant outcomes had a higher probability of being included.Conclusions
Publication bias was present in a substantial proportion of large meta-analyses that were recently published in four major medical journals. 相似文献43.
Christina R?hr Martin Kerick Axel Fischer Alexander Kühn Karl Kashofer Bernd Timmermann Andriani Daskalaki Thomas Meinel Dmitriy Drichel Stefan T. B?rno Anja Nowka Sylvia Krobitsch Alice C. McHardy Christina Kratsch Tim Becker Andrea Wunderlich Christian Barmeyer Christian Viertler Kurt Zatloukal Christoph Wierling Hans Lehrach Michal R. Schweiger 《PloS one》2013,8(7)
MiRNAs are discussed as diagnostic and therapeutic molecules. However, effective miRNA drug treatments with miRNAs are, so far, hampered by the complexity of the miRNA networks. To identify potential miRNA drugs in colorectal cancer, we profiled miRNA and mRNA expression in matching normal, tumor and metastasis tissues of eight patients by Illumina sequencing. We validated six miRNAs in a large tissue screen containing 16 additional tumor entities and identified miRNA-1, miRNA-129, miRNA-497 and miRNA-215 as constantly de-regulated within the majority of cancers. Of these, we investigated miRNA-1 as representative in a systems-biology simulation of cellular cancer models implemented in PyBioS and assessed the effects of depletion as well as overexpression in terms of miRNA-1 as a potential treatment option. In this system, miRNA-1 treatment reverted the disease phenotype with different effectiveness among the patients. Scoring the gene expression changes obtained through mRNA-Seq from the same patients we show that the combination of deep sequencing and systems biological modeling can help to identify patient-specific responses to miRNA treatments. We present this data as guideline for future pre-clinical assessments of new and personalized therapeutic options. 相似文献
44.
Lesia Dmytrenko Michal Cicanic Miroslava Anderova Ivan Vorisek Ole Petter Ottersen Eva Sykova Lydia Vargova 《PloS one》2013,8(7)
Aquaporin-4 (AQP4) is the primary cellular water channel in the brain and is abundantly expressed by astrocytes along the blood-brain barrier and brain-cerebrospinal fluid interfaces. Water transport via AQP4 contributes to the activity-dependent volume changes of the extracellular space (ECS), which affect extracellular solute concentrations and neuronal excitability. AQP4 is anchored by α-syntrophin (α-syn), the deletion of which leads to reduced AQP4 levels in perivascular and subpial membranes. We used the real-time iontophoretic method and/or diffusion-weighted magnetic resonance imaging to clarify the impact of α-syn deletion on astrocyte morphology and changes in extracellular diffusion associated with cell swelling in vitro and in vivo. In mice lacking α-syn, we found higher resting values of the apparent diffusion coefficient of water (ADCW) and the extracellular volume fraction (α). No significant differences in tortuosity (λ) or non-specific uptake (k′), were found between α-syn-negative (α-syn −/−) and α-syn-positive (α-syn +/+) mice. The deletion of α-syn resulted in a significantly smaller relative decrease in α observed during elevated K+ (10 mM) and severe hypotonic stress (−100 mOsmol/l), but not during mild hypotonic stress (−50 mOsmol/l). After the induction of terminal ischemia/anoxia, the final values of ADCW as well as of the ECS volume fraction α indicate milder cell swelling in α-syn −/− in comparison with α-syn +/+ mice. Shortly after terminal ischemia/anoxia induction, the onset of a steep rise in the extracellular potassium concentration and an increase in λ was faster in α-syn −/− mice, but the final values did not differ between α-syn −/− and α-syn +/+ mice. This study reveals that water transport through AQP4 channels enhances and accelerates astrocyte swelling. The substantially altered ECS diffusion parameters will likely affect the movement of neuroactive substances and/or trophic factors, which in turn may modulate the extent of tissue damage and/or drug distribution. 相似文献
45.
Michal S. Shoshan Edit Y. Tshuva Deborah E. Shalev 《Journal of visualized experiments : JoVE》2013,(82)
Copper (I) binding by metallochaperone transport proteins prevents copper oxidation and release of the toxic ions that may participate in harmful redox reactions. The Cu (I) complex of the peptide model of a Cu (I) binding metallochaperone protein, which includes the sequence MTCSGCSRPG (underlined is conserved), was determined in solution under inert conditions by NMR spectroscopy.NMR is a widely accepted technique for the determination of solution structures of proteins and peptides. Due to difficulty in crystallization to provide single crystals suitable for X-ray crystallography, the NMR technique is extremely valuable, especially as it provides information on the solution state rather than the solid state. Herein we describe all steps that are required for full three-dimensional structure determinations by NMR. The protocol includes sample preparation in an NMR tube, 1D and 2D data collection and processing, peak assignment and integration, molecular mechanics calculations, and structure analysis. Importantly, the analysis was first conducted without any preset metal-ligand bonds, to assure a reliable structure determination in an unbiased manner. 相似文献
46.
Allison Jones Andrew E. Teschendorff Quanxi Li Jane D. Hayward Athilakshmi Kannan Tim Mould James West Michal Zikan David Cibula Heidi Fiegl Shih-Han Lee Elisabeth Wik Richard Hadwin Rupali Arora Charlotte Lemech Henna Turunen P?ivi Pakarinen Ian J. Jacobs Helga B. Salvesen Milan K. Bagchi Indrani C. Bagchi Martin Widschwendter 《PLoS medicine》2013,10(11)
47.
Petr Martinek Josef Hedbávný Tomáš Kudláček Michal Šťasta Emanuel Kula 《Entomologia Experimentalis et Applicata》2020,168(8):635-643
The adaptation of insects to environmental changes can constitute a crucial factor in their development and activity. The response of Cabera pusaria L. (Lepidoptera: Geometridae) caterpillars to high manganese (Mn) concentrations in the diet was studied. Birch leaves were treated by dipping in MnCl2·4H2O solutions, thereby achieving Mn contents of 370 (T0), 695 (T1), 3 198 (T2), and 6 302 mg kg−1 (T3). The reactions were determined by observing caterpillar mortality, development time, food consumption, and pupal weight. Manganese concentrations in larval excrement, pupae, and food were determined. Manganese in the diet at unnaturally increased concentrations caused great stress for caterpillars. All individuals in the treatment with the highest Mn concentration (T3) died during rearing and successful pupation occurred in only four individuals in T2. Even in the case of caterpillars from T1 (twofold higher than T0) a negative reaction (increased food consumption and prolonged development) was recorded. We also determined significantly increased Mn concentration in pupae from T1 (T2 and T3 were not included in this evaluation due to mortality) and excrement (T1‒T3) compared with T0 having a natural Mn concentration. Caterpillars were seen to eliminate negatively acting dietary Mn by its translocation to excrement. However, the highest mortality rate in T2 and T3 and negative reactions of individuals in T1 very likely demonstrate energy insufficiency and the high energy requirements of Mn elimination mechanisms. 相似文献
48.
Michal Otyepka Zdeněk Kříž Jaroslav Koča 《Journal of biomolecular structure & dynamics》2013,31(2):141-154
Abstract This article presents a molecular dynamics (MD) study of the cdk2 enzyme and its two complexes with the inhibitors isopentenyladenine and roscovitine using the Cornell et al. force field from the AMBER software package. The results show that inserting an inhibitor into the enzyme active site does not considerably change enzyme structure but it seemingly changes the distribution of internal motions. The inhibitor causes differences in the domain motions in free cdk2 and in its complexes. It was found out that repulsion of roscovitine N9 substituent causes conformational change on Lys 33 side chain. Isopentenyladenine forms with Lys 33 side chain terminal amino group a hydrogen bond. It implies that the cavity, where N9 substituent of roscovitine is buried, can adopt larger substituent due to Lys 33 side chain flexibility. The composition of electrostatic and van der Waals interactions between the inhibitor and the enzyme were also calculated along both cdk2/inhibitor MD trajectories together with MM-PB/GBSA analysis. These results show that isopentenyladenine-like inhibitors could be more effective after modifications leading to an increase in their van der Waals contact with the enzyme. We suggest that a way leading to better inhibitors occupying isopentenyladenine binding mode could be: to keep N9 and N7 purine positions free, to keep 3,3-dimethylallylamino group at C6 position, and to add, e.g., benzylamino group at C2 position. The results support the idea that the isopentenyladenine binding mode can be used for cdk2 inhibitors design and that all possibilities to improve this binding mode were not uncovered yet. 相似文献
49.
Kristina Hasakova Marian Vician Richard Reis Michal Zeman 《Chronobiology international》2013,30(10):1423-1434
ABSTRACTRecent evidence supports the important role of the circadian system in cancer progression in humans. The aim of the present study is to evaluate clock (cry1, cry2 and per2) and clock-controlled (vascular endothelial growth factor-a, early growth response protein 1 and estrogen receptor β) gene expression in colorectal cancer and adjacent tissue and identify a possible link between survival of patients and expression of above mentioned genes. The study includes 64 patients of both sexes with previously diagnosed colorectal cancer. RNA was extracted from the tumor tissue and adjacent parts of the resected colon, and real-time PCR was used for detection of clock gene expression. Expression of cry2 and per2 was significantly downregulated in tumor tissue compared to adjacent tissues. After splitting of the cohort according to sex, we detected downregulated levels of cry2 and per2 in male patients, but not in females. Splitting of male and female sub-cohorts according to presence of metastases revealed significant donwregulation of cry2 expression in female patients without distant metastasis. Better survival rate was associated with low expression of cry2 in female patients. Moreover, we observed an increase in cry1 expression in female patients with distant metastases in tumor compared to adjacent tissue. Accordingly, women with high expression of cry1 in tumor tissue displayed worse survival, which was not observed in men. Taken together, expression of clock and clock-controlled genes in tumors of males and females clustered according to presence of distant metastases correlated with survival analysis. Studied clock-controlled genes also showed sex-dependent changes. Low expression of vegf-a in tumor correlated with better survival in men but not in women. High expression of estrogen receptor β mRNA was related to better survival in women but not in men. Low expression of vegf-a, egr1 and estrogen receptor β was associated with worse survival in women compared to men. Our data indicate sex-dependent associations between clock and clock-controlled gene expression in cancer tissue and patient’s survival prognosis. 相似文献
50.
Root structure parameters, root biomass and allometric relationships between above- and belowground biomass were investigated in young Norway spruce (Picea abies [L.] Karst.) trees cultivated inside the glass domes with ambient (AC, 375 μmol(CO2) mol?1) and elevated (EC, A + 375 μmol(CO2) mol?1) atmospheric CO2 concentrations ([CO2]). After 8 years of fumigation, a mean EC tree in comparison with AC one exhibited about 37 % higher belowground biomass. The growth of primary root structure was unaffected by elevated [CO2]; however, the biomass of secondary roots growing on the primary root structure and the biomass of secondary roots growing in the zone between the soil surface and the first primary root ramification were significantly higher in EC comparing with AC treatment about 58 and 70 %, respectively. The finest root’s (diameter up to 1 mm) biomass as well as length and surface area of both primary and secondary root structures showed the highest difference between the treatments; advancing EC to AC by 43 % on average. Therefore, Norway spruce trees cultivated under well-watered and rather nitrogen-poor soil conditions responded to the air elevated [CO2] environment by the enhancement of the secondary root structure increment, by enlargement of root length and root absorbing area, and also by alternation of root to aboveground organ biomass proportion. Higher root to leaf and root to stem basal area ratios could be beneficial for Norway spruce trees to survive periods with limited soil water availability. 相似文献