A meta-analysis of tumor necrosis factor-alpha, interleukin-6, and interleukin-10 in preeclampsia

Inflammation may play a major role in the pathogenesis of preeclampsia (PE). In this meta-analysis, we determined whether maternal polymorphisms and serum concentrations of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-10 (IL-10) were associated with PE. All studies investigating the associations between PE and maternal polymorphisms of TNF-α-308G/A, IL-6-174G/C, and IL-10-1082A/G or serum concentrations of TNF-α, IL-6, and IL-10 were reviewed. We found that neither maternal TNF-α-308G/A (p=0.86, odds ratio [OR]=0.98, 95% confidence interval [CI], 0.76-1.25), IL-6 174G/C (p=0.14, OR=1.23, 95% CI, 0.93-1.61), nor IL-10-1082A/G (p=0.72, OR=1.07, 95% CI, 0.75-1.52) were associated with PE. On the other hand, maternal TNF-α (p<0.00001, weighted mean difference [WMD]=19.63 pg/ml, 95% CI, 18.54-20.72 pg/ml), IL-6 (p<0.00001, WMD=6.58 pg/ml, 95% CI, 5.49-7.67 pg/ml), and IL-10 (p=0.0005, WMD=19.30 pg/ml, 95% CI, 8.42-30.17 pg/ml) concentrations were significantly higher in PE patients versus controls. Our findings strengthen the clinical evidence that PE is accompanied by exaggerated inflammatory responses, but do not support TNF-α-308G/A, IL-6-174G/C, and IL-10-1082A/G as candidate susceptibility loci in PE.     

FTO regulates adipogenesis by controlling cell cycle progression via m6A-YTHDF2 dependent mechanism

N⁶-methyladenosine (m⁶A) is the most prevalent internal mRNA modification in eukaryotes. Loss of m⁶A demethylase FTO increases m⁶A levels and inhibits adipogenesis of preadipocytes. However, its underlying mechanism remains elusive. Here, we demonstrated that silencing FTO inhibited adipogenesis of preadipocytes through impairing cell cycle progression at the early stage of adipogenesis. FTO knockdown markedly decreased the expression of CCNA2 and CDK2, crucial cell cycle regulators, leading to delayed entry of MDI-induced cells into G2 phase. Furthermore, the m⁶A levels of CCNA2 and CDK2 mRNA were significantly upregulated following FTO knockdown. m⁶A-binding protein YTHDF2 recognized and decayed methylated mRNAs of CCNA2 and CDK2, leading to decreased protein expression, thereby prolonging cell cycle progression and suppressing adipogenesis. Our work unravels that FTO regulates adipogenesis by controlling cell cycle progression in an m⁶A-YTHDF2 dependent manner, which provides insights into critical roles of m⁶A methylation in adipogenesis.     

FamPipe: An Automatic Analysis Pipeline for Analyzing Sequencing Data in Families for Disease Studies

In disease studies, family-based designs have become an attractive approach to analyzing next-generation sequencing (NGS) data for the identification of rare mutations enriched in families. Substantial research effort has been devoted to developing pipelines for automating sequence alignment, variant calling, and annotation. However, fewer pipelines have been designed specifically for disease studies. Most of the current analysis pipelines for family-based disease studies using NGS data focus on a specific function, such as identifying variants with Mendelian inheritance or identifying shared chromosomal regions among affected family members. Consequently, some other useful family-based analysis tools, such as imputation, linkage, and association tools, have yet to be integrated and automated. We developed FamPipe, a comprehensive analysis pipeline, which includes several family-specific analysis modules, including the identification of shared chromosomal regions among affected family members, prioritizing variants assuming a disease model, imputation of untyped variants, and linkage and association tests. We used simulation studies to compare properties of some modules implemented in FamPipe, and based on the results, we provided suggestions for the selection of modules to achieve an optimal analysis strategy. The pipeline is under the GNU GPL License and can be downloaded for free at http://fampipe.sourceforge.net.

This is a PLOS Computational Biology Software article.

     

Titanium Elastic Nail (TEN) versus Reconstruction Plate Repair of Midshaft Clavicular Fractures: A Finite Element Study

BackgroundThe biomechanical characteristics of midshaft clavicular fractures treated with titanium elastic nail (TEN) is unclear. This study aimed to present a biomechanical finite element analysis of biomechanical characteristics involved in TEN fixation and reconstruction plate fixation for midshaft clavicular fractures.MethodsFinite element models of the intact clavicle and of midshaft clavicular fractures fixed with TEN and with a reconstruction plate were built. The distal clavicle displacement, peak stress, and stress distribution on the 3 finite element models were calculated under the axial compression and cantilever bending.ResultsIn both loading configurations, TEN generated the highest displacement of the distal clavicle, followed by the intact clavicle and the reconstruction plate. TEN showed higher peak bone and implant stresses, and is more likely to fail in both loading configurations compared with the reconstruction plate. TEN led to a stress distribution similar to that of the intact clavicle in both loading configurations, whereas the stress distribution with the reconstruction plate was nonphysiological in cantilever bending.ConclusionsTEN is generally preferable for treating simple displaced fractures of the midshaft clavicle, because it showed a stress distribution similar to the intact clavicle. However, TEN provides less stability, and excessive exercise of and weight bearing on the ipsilateral shoulder should be avoided in the early postoperative period. Fixation with a reconstruction plate was more stable but showed obvious stress shielding. Therefore, for patients with a demand for early return to activity, reconstruction plate fixation may be preferred.     

Nicotine degradation by two novel bacterial isolates of <Emphasis Type="Italic">Acinetobacter</Emphasis> sp. TW and <Emphasis Type="Italic">Sphingomonas</Emphasis> sp. TY and their responses in the presence of neonicotinoid insecticides

Two novel nicotine-degrading bacterial strains were isolated from tobacco waste and identified as Acinetobacter sp. TW and Sphingomonas sp. TY based on morphology, physiological and biochemical tests, Biolog analysis and 16S rDNA sequencing. The 16S rDNA sequences have been deposited in GenBank under the accession numbers FJ753401 for TW and FJ754274 for TY. The best culture conditions for nicotine degradation were 25–37°C and pH 7.0–8.0 for strain TW and 25–30°C and pH 6.0–7.0 for strain TY. Under the best conditions, the cell growth and nicotine-degradation kinetics of the two isolates were assessed, and 1.0 g/l nicotine was completely degraded within 12 and 18 h for TW and TY, respectively. Moreover, the presence of four widely-used commercial neonicotinoid insecticides in the medium had no effects on nicotine degradation by TW; among the four tested neonicotinoids, only thiamethoxam significantly delayed nicotine degradation by TY. TW and TY were also able to degrade selected neonicotinoids. This is the first report of nicotine degradation by Acinetobacter sp. and Sphingomonas sp. This study showed that these two newly isolated bacteria may be suitable for the disposal of tobacco waste and the reduction of nicotine in tobacco leaves.     

Cyclic strain induces expression of specific smooth muscle cell markers in human endothelial cells

The objective of this study was to determine whether cyclic strain could promote human umbilical vein endothelial cells (HUVECs) to express markers in common with the mature smooth muscle cell (SMC) phenotype, suggesting endothelial cell to SMC transdifferentiation. HUVECs were cultured on stretched membranes at 10% stretch and 60 cycles/min for 24-96 hr, and demonstrated elongation with enhanced and organized F-actin distribution. By using real-time polymerase chain reaction analysis, the mRNA levels of five specific SMC markers, SM22-alpha, alpha-smooth muscle actin (alpha-SMA), caldesmon-1, smooth muscle myosin heavy chain (SMMHC), and calponin-1 were significantly increased in cyclic strain-treated HUVECs as compared with those in static control cells. Protein levels of SM22-alpha and alpha-SMA were also substantially increased by Western blot and immunofluorescence staining. In addition, two specific endothelial markers, von Willebrand factor (vWF) and vascular endothelial growth factor receptor-2 (VEGFR-2), showed a reduction in mRNA expression. In addition, cyclic strain-induced increase of SM22-alpha and alpha-SMA expression were reversible when cells were cultured back to the static condition. These results demonstrate a possible endothelial cell to SMC transdifferentiation in response to cyclic strain. Hemodynamic forces in modulating endothelial phenotype may play an important role in the vascular system.     

Anthraquinones in the biosynthesis of sterigmatocystin by Aspergillus versicolor.

14C-labeled averufin, versiconal hemiacetal acetate, and versicolorin A were efficiently converted to sterigmatocystin by Aspergillus versicolor, thus providing experimental evidence that these anthraquinones are biosynthetic precursors of sterigmatocystin, a xanthone.     

Update of ichthyofauna diversity and ecological status of a coastal River Nero (Côte d’Ivoire – West Africa)

The general aim of this study is to update the inventory of the fish species and to specify distribution patterns in the Nero River ichthyofauna in order to establish some basis for the conservation of these fish communities and their habitat. From February 2009 to January 2010, thirty-three sites were sampled monthly with gill nets and a backpack electrofisher, and environmental variables were recorded. Overall, 46 species included in 33 genuses, 24 families and 9 orders were collected. Eleven families and 30 species were the first records for the Nero River. Including all species previously listed in the literature, the number of species presently known in the Nero River and its tributaries is revised to 59. Four families, Alestidae (21%), Schilbeidae (19%), Cyprinidae (17%) and Cichlidae (16%) that made up 73% of the total number of the catches, were the most dominant. The most dominant numerical species were Schilbe mandibularis and Brycinus longipinnis. Fish species and sampling sites along with eight environmental variables were ordinated with canonical correspondence analysis (CCA) coupled to the Monte Carlo test. Ecological status based on fish assemblage according to environmental variables and anthropogenic pressures showed that miss dead wood leaves and roots, electrical conductivity, total dissolved solids, mud, nitrite, basin width, dissolved oxygen and pH, were the primary factors influencing fish distribution. The environmental tolerance index (ETI), ecological tolerance (t_k) and optima (u_k) values of 10 species to 8 different environmental variables were analyzed. Six species (Hemichromis fasciatus, Epiplatys chaperi, Barbus ablabes, B. longipinnis, Hemichromis bimaculatus and Chromidotilapia guntheri) have high ETI and a cosmopolitan distribution in the Nero River. In the tributaries of the middle course, high concentrations of nitrite in the water, added to the presence of a lot of tolerant species in the ichthyofauna are indications of disturbance of these areas. Subsequent recommendations were formulated for efficient restoration and conservation management of this River.     

MicroRNA-21 promotes cell proliferation and down-regulates the expression of programmed cell death 4 (PDCD4) in HeLa cervical carcinoma cells

MicroRNAs are involved in cancer-related processes. The microRNA-21(miR-21) has been identified as the only miRNA over-expressed in a wide variety of cancers, including cervical cancer. However, the function of miR-21 is unknown in cervical carcinomas. In this study, we found that the inhibition of miR-21 in HeLa cervical cancer cells caused profound suppression of cell proliferation, and up-regulated the expression of the tumor suppressor gene PDCD4. We also provide direct evidence that PDCD4-3′UTR is a functional target of miR-21 and that the 18 bp putative target site can function as the sole regulatory element in HeLa cells. These results suggest that miR-21 may play an oncogenic role in the cellular processes of cervical cancer and may serve as a target for effective therapies.