A Noise-Filtering Method for Link Prediction in Complex Networks

Link prediction plays an important role in both finding missing links in networked systems and complementing our understanding of the evolution of networks. Much attention from the network science community are paid to figure out how to efficiently predict the missing/future links based on the observed topology. Real-world information always contain noise, which is also the case in an observed network. This problem is rarely considered in existing methods. In this paper, we treat the existence of observed links as known information. By filtering out noises in this information, the underlying regularity of the connection information is retrieved and then used to predict missing or future links. Experiments on various empirical networks show that our method performs noticeably better than baseline algorithms.     

Lactic Acid Production from Pretreated Hydrolysates of Corn Stover by a Newly Developed Bacillus coagulans Strain

An inhibitor-tolerance strain, Bacillus coagulans GKN316, was developed through atmospheric and room temperature plasma (ARTP) mutation and evolution experiment in condensed dilute-acid hydrolysate (CDH) of corn stover. The fermentabilities of other hydrolysates with B. coagulans GKN316 and the parental strain B. coagulans NL01 were assessed. When using condensed acid-catalyzed steam-exploded hydrolysate (CASEH), condensed acid-catalyzed liquid hot water hydrolysate (CALH) and condensed acid-catalyzed sulfite hydrolysate (CASH) as substrates, the concentration of lactic acid reached 45.39, 16.83, and 18.71 g/L by B. coagulans GKN316, respectively. But for B. coagulans NL01, only CASEH could be directly fermented to produce 15.47 g/L lactic acid. The individual inhibitory effect of furfural, 5-hydroxymethylfurfural (HMF), vanillin, syringaldehyde and p-hydroxybenzaldehyde (pHBal) on xylose utilization by B. coagulans GKN316 was also studied. The strain B. coagulans GKN316 could effectively convert these toxic inhibitors to the less toxic corresponding alcohols in situ. These results suggested that B. coagulans GKN316 was well suited to production of lactic acid from undetoxified lignocellulosic hydrolysates.     

Chemically defined media modifications to lower tryptophan oxidation of biopharmaceuticals

Oxidation of biopharmaceuticals is a major product quality issue with potential impacts on activity and immunogenicity. At Eli Lilly and Company, high tryptophan oxidation was observed for two biopharmaceuticals in development produced in Chinese hamster ovary cells. A switch from historical hydrolysate‐containing media to chemically defined media with a reformulated basal powder was thought to be responsible, so mitigation efforts focused on media modification. Shake flask studies identified that increasing tryptophan, copper, and manganese and decreasing cysteine concentrations were individual approaches to lower tryptophan oxidation. When amino acid and metal changes were combined, the modified formulation had a synergistic impact that led to substantially less tryptophan oxidation for both biopharmaceuticals. Similar results were achieved in shake flasks and benchtop bioreactors, demonstrating the potential to implement these modifications at manufacturing scale. The modified formulation did not negatively impact cell growth and viability, product titer, purity, charge variants, or glycan profile. A potential mechanism of action is presented for each amino acid or metal factor based on its role in oxidation chemistry. This work served not only to mitigate the tryptophan oxidation issue in two Lilly biopharmaceuticals in development, but also to increase our knowledge and appreciation for the impact of media components on product quality. © 2015 American Institute of Chemical Engineers Biotechnol. Prog., 32:178–188, 2016     

Sequential and compartmentalized action of Rabs,SNAREs, and MAL in the apical delivery of fusiform vesicles in urothelial umbrella cells

Uroplakins (UPs) are major differentiation products of urothelial umbrella cells and play important roles in forming the permeability barrier and in the expansion/stabilization of the apical membrane. Further, UPIa serves as a uropathogenic Escherichia coli receptor. Although it is understood that UPs are delivered to the apical membrane via fusiform vesicles (FVs), the mechanisms that regulate this exocytic pathway remain poorly understood. Immunomicroscopy of normal and mutant mouse urothelia show that the UP-delivering FVs contained Rab8/11 and Rab27b/Slac2-a, which mediate apical transport along actin filaments. Subsequently a Rab27b/Slp2-a complex mediated FV–membrane anchorage before SNARE-mediated and MAL-facilitated apical fusion. We also show that keratin 20 (K20), which forms a chicken-wire network ∼200 nm below the apical membrane and has hole sizes allowing FV passage, defines a subapical compartment containing FVs primed and strategically located for fusion. Finally, we show that Rab8/11 and Rab27b function in the same pathway, Rab27b knockout leads to uroplakin and Slp2-a destabilization, and Rab27b works upstream from MAL. These data support a unifying model in which UP cargoes are targeted for apical insertion via sequential interactions with Rabs and their effectors, SNAREs and MAL, and in which K20 plays a key role in regulating vesicular trafficking.     

Genome-wide dissection of segregation distortion using multiple inter-subspecific crosses in rice

Mendelian inheritance can ensure equal segregation of alleles from parents to offspring, which provides fundamental basis for genetics and molecular biology. Segregation distortion(SD) leads to preferential transmission of certain alleles from generation to generation. Such violation of Mendelian genetic principle is often accompanied by reproductive isolation and eventually speciation. Although SD is observed in a wide range of species from plants to animals, genome-wide dissection of such biased transmission of gametes is rare. Using nine inter-subspecific rice crosses, a genome-wide screen for SD loci is performed, which reveals 61 single-locus quantitative trait loci and 194 digenic interactions showing distorted transmission ratio, among which 24 new SD loci are identified. Biased transmission of alleles is observed in all nine crosses, suggesting that SD exists extensively in rice populations. 72.13% distorted regions are repeatedly detected in multiple populations, and the most prevalent SD hotspot that observed in eight populations is mapped to chromosome 3. Xian alleles are transmitted at higher frequencies than geng alleles in inter-subspecific crosses, which change the genetic composition of the rice populations. Epistatic interaction contributes significantly to the deviation of Mendelian segregation at the whole-genome level in rice, which is distinct from that in animals. These results provide an extensive archive for investigating the genetic basis of SD in rice, which have significant implications in understanding the reproductive isolation and formation of inter-subspecific barriers during the evolution.