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Reprogramming of somatic cells to induced pluripotent stem cells, by overexpressing certain factors referred to as the reprogramming factors, can revolutionize regenerative medicine. To provide a coherent description of induced pluripotency from the gene regulation perspective, we use 35 microarray datasets to construct a reprogramming gene regulatory network. Comprising 276 nodes and 4471 links, the resulting network is, to the best of our knowledge, the largest gene regulatory network constructed for human fibroblast reprogramming and it is the only one built using a large number of experimental datasets. To build the network, a model that relates the expression profiles of the initial (fibroblast) and final (induced pluripotent stem cell) states is proposed and the model parameters (link strengths) are fitted using the experimental data. Twenty nine additional experimental datasets are collectively used to test the model/network, and good agreement between experimental and predicted gene expression profiles is found. We show that the model in conjunction with the constructed network can make useful predictions. For example, we demonstrate that our approach can incorporate the effect of reprogramming factor stoichiometry and that its predictions are consistent with the experimentally observed trends in reprogramming efficiency when the stoichiometric ratios vary. Using our model/network, we also suggest new (not used in training of the model) candidate sets of reprogramming factors, many of which have already been experimentally verified. These results suggest our model/network can potentially be used in devising new recipes for induced pluripotency with higher efficiencies. Additionally, we classify the links of the network into three classes of different importance, prioritizing them for experimental verification. We show that many of the links in the top ranked class are experimentally known to be important in reprogramming. Finally, comparing with other methods, we show that using our model is advantageous. [ABSTRACT FROM AUTHOR]

The dispatching of hydro-thermal system is a nonlinear programming problem with multiple constraints and high dimensions and the solution techniques of the model have been a hotspot in research. Based on the advantage of that the artificial bee colony algorithm (ABC) can efficiently solve the high-dimensional problem, an improved artificial bee colony algorithm has been proposed to solve DHTS problem in this paper. The improvements of the proposed algorithm include two aspects. On one hand, local search can be guided in efficiency by the information of the global optimal solution and its gradient in each generation. The global optimal solution improves the search efficiency of the algorithm but loses diversity, while the gradient can weaken the loss of diversity caused by the global optimal solution. On the other hand, inspired by genetic algorithm, the nectar resource which has not been updated in limit generation is transformed to a new one by using selection, crossover and mutation, which can ensure individual diversity and make full use of prior information for improving the global search ability of the algorithm. The two improvements of ABC algorithm are proved to be effective via a classical numeral example at last. Among which the genetic operator for the promotion of the ABC algorithm’s performance is significant. The results are also compared with those of other state-of-the-art algorithms, the enhanced ABC algorithm has general advantages in minimum cost, average cost and maximum cost which shows its usability and effectiveness. The achievements in this paper provide a new method for solving the DHTS problems, and also offer a novel reference for the improvement of mechanism and the application of algorithms. [ABSTRACT FROM AUTHOR]

Mitochondria play a critical role in the generation of metabolic energy and are crucial for eukaryotic cell survival and proliferation. In most sexual eukaryotes, mitochondrial DNA (mtDNA) is inherited from only one parent in non-Mendelian inheritance in contrast to the inheritance of nuclear DNA. The model organism Saccharomyces cerevisiae is commonly used to study mitochondrial biology. It has two mating types: MATa and MATα. Previous studies have suggested that the mtDNA inheritance patterns in hybrid diploid cells depend on the genetic background of parental strains. However, the underlying mechanisms remain unclear. To elucidate the mechanisms, we examined the effects of environmental factors on the mtDNA inheritance patterns in hybrids obtained by crossing S. cerevisiae with its close relative S. paradoxus. The results demonstrated that environmental factors can influence mtDNA transmission in hybrid diploids, and that the inheritance patterns are strain dependent. The fitness competition assay results showed that the fitness differences can explain the mtDNA inheritance patterns under specific conditions. However, in this study, we found that fitness differences cannot fully be explained by mitochondrial activity in hybrids under stress conditions. [ABSTRACT FROM AUTHOR]

Dysregulation of Fibroblast Growth Factor Receptor (FGFR) signaling through amplifications, mutations, and gene fusions has been implicated in a broad array of cancers (e.g. liver, gastric, ovarian, endometrial, and bladder). ARQ 087 is a novel, ATP competitive, small molecule, multi-kinase inhibitor with potent in vitro and in vivo activity against FGFR addicted cell lines and tumors. Biochemically, ARQ 087 exhibited IC50 values of 1.8 nM for FGFR2, and 4.5 nM for FGFR1 and 3. In cells, inhibition of FGFR2 auto-phosphorylation and other proteins downstream in the FGFR pathway (FRS2α, AKT, ERK) was evident by the response to ARQ 087 treatment. Cell proliferation studies demonstrated ARQ 087 has anti-proliferative activity in cell lines driven by FGFR dysregulation, including amplifications, fusions, and mutations. Cell cycle studies in cell lines with high levels of FGFR2 protein showed a positive relationship between ARQ 087 induced G1 cell cycle arrest and subsequent induction of apoptosis. In addition, ARQ 087 was effective at inhibiting tumor growth in vivo in FGFR2 altered, SNU-16 and NCI-H716, xenograft tumor models with gene amplifications and fusions. ARQ 087 is currently being studied in a phase 1/2 clinical trial that includes a sub cohort for intrahepatic cholangiocarcinoma patients with confirmed FGFR2 gene fusions (NCT01752920). [ABSTRACT FROM AUTHOR]

Bradysia odoriphaga (Diptera: Sciaridae) is the most important pest of Chinese chive (Allium tuberosum) in Asia; however, the molecular genetics are poorly understood. To explore the molecular biological mechanism of development, Illumina sequencing and de novo assembly were performed in the third-instar, fourth-instar, and pupal B. odoriphaga. The study resulted in 16.2 Gb of clean data and 47,578 unigenes (≥125bp) contained in 7,632,430contigs, 46.21% of which were annotated from non-redundant protein (NR), Gene Ontology (GO), Clusters of Orthologous Groups (COG), Eukaryotic Orthologous Groups (KOG), and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. It was found that 19.67% of unigenes matched the homologous species mainly, including Aedes aegypti, Culex quinquefasciatus, Ceratitis capitata, and Anopheles gambiae. According to differentially expressed gene (DEG) analysis, 143, 490, and 309 DEGs were annotated as involved in the developmental process in the GO database respectively, in the comparisons of third-instar and fourth-instar larvae, third-instar larvae and pupae, and fourth-instar larvae and pupae. Twenty-five genes were closely related to these processes, including developmental process, reproduction process, and reproductive organs development and programmed cell death (PCD). The information of unigenes assembled in B. odoriphaga through transcriptome and DEG analyses could provide a detailed genetic basis and regulated information for elaborating the developmental mechanism from the larval, pre-pupal to pupal stages of B. odoriphaga. [ABSTRACT FROM AUTHOR]

Nitrites commonly found in food, especially in fermented vegetables, are potential carcinogens. Therefore, limiting nitrites in food is critically important for food safety. A Lactobacillus strain (Lactobacillus sp. DMDL 9010) was previously isolated from fermented vegetables by our group, and is not yet fully characterized. A number of phenotypical and genotypical approaches were employed to characterize Lactobacillus sp. DMDL 9010. Its nitrite degradation capacity was compared with four other Lactobacillus strains, including Lactobacillus casei subsp. rhamnosus 719, Lactobacillus delbrueckii subsp. bulgaricu 1.83, Streptococcus thermophilus 1.204, and lactobacillus plantarum 8140, on MRS medium. Compared to these four Lactobacillus strains, Lactobacillus sp. DMDL 9010 had a significantly higher nitrite degradation capacity (P<0.001). Based on 16S rDNA sequencing and sequence comparison, Lactobacillus sp. DMDL 9010 was identified as either Lactobacillus plantarum or Lactobacillus pentosus. To further identify this strain, the flanking regions (922 bp and 806 bp upstream and downstream, respectively) of the L-lactate dehydrogenase 1 (L-ldh1) gene were amplified and sequenced. Lactobacillus sp. DMDL 9010 had 98.92 and 76.98% sequence identity in the upstream region with L. plantarum WCFS1 and L. pentosus IG1, respectively, suggesting that Lactobacillu sp. DMDL 9010 is an L. plantarum strain. It was therefore named L. plantarum DMDL 9010. Our study provides a platform for genetic engineering of L. plantarum DMDL 9010, in order to further improve its nitrite degradation capacity. [ABSTRACT FROM AUTHOR]

Disanthus cercidifolius subsp. longipes is an endangered species in China. Genetic diversity and structure analysis of this species was investigated using amplified fragments length polymorphism (AFLP) fingerprinting. Nei's gene diversity ranged from 0.1290 to 0.1394. The AMOVA indicated that 75.06% of variation was distributed within populations, while the between-group component 5.04% was smaller than the between populations-within-group component 19.90%. Significant genetic differentiation was detected between populations. Genetic and geographical distances were not correlated. PCA and genetic structure analysis showed that populations from East China were together with those of the Nanling Range. These patterns of genetic diversity and levels of genetic variation may be the result of D. c. subsp. longipes restricted to several isolated habitats and “excess flowers production, but little fruit set”. It is necessary to protect all existing populations of D. c. subsp. longipes in order to preserve as much genetic variation as possible. [ABSTRACT FROM AUTHOR]

Objectives: To assess the independent impact of new genetic variants on conversion to advanced stages of AMD, controlling for established risk factors, and to determine the contribution of genes in predictive models. Methods: In this prospective longitudinal study of 2765 individuals, 777 subjects progressed to neovascular disease (NV) or geographic atrophy (GA) in either eye over 12 years. Recently reported genetic loci were assessed for their independent effects on incident advanced AMD after controlling for 6 established loci in 5 genes, and demographic, behavioral, and macular characteristics. New variants which remained significantly related to progression were then added to a final multivariate model to assess their independent effects. The contribution of genes to risk models was assessed using reclassification tables by determining risk within cross-classified quintiles for alternative models. Results: Three new genetic variants were significantly related to progression: rare variant R1210C in CFH (hazard ratio (HR) 2.5, 95% confidence interval [CI] 1.2–5.3, P = 0.01), and common variants in genes COL8A1 (HR 2.0, 95% CI 1.1–3.5, P = 0.02) and RAD51B (HR 0.8, 95% CI 0.60–0.97, P = 0.03). The area under the curve statistic (AUC) was significantly higher for the 9 gene model (.884) vs the 0 gene model (.873), P = .01. AUC’s for the 9 vs 6 gene models were not significantly different, but reclassification analyses indicated significant added information for more genes, with adjusted odds ratios (OR) for progression within 5 years per one quintile increase in risk score of 2.7, P<0.001 for the 9 vs 6 loci model, and OR 3.5, P<0.001 for the 9 vs. 0 gene model. Similar results were seen for NV and GA. Conclusions: Rare variant CFH R1210C and common variants in COL8A1 and RAD51B plus six genes in previous models contribute additional predictive information for advanced AMD beyond macular and behavioral phenotypes. [ABSTRACT FROM AUTHOR]