N+ ion beam implantation of tannase-producing Aspergillus niger and optimization of its process parameters under submerged fermentation

Low-energy ion implantation as a novel mutagen has been increasingly applied in the microbial mutagenesis for its higher mutation frequency and wider mutation spectra. In this work, N⁺ ion beam implantation was used to enhance Aspergillus niger TA9701 in tannase yield. The optimization of process parameters under submerged fermentation was carried out to further improve the tannase yield of the mutant, Aspergillus niger J-T18. The results indicate that an excellent mutant J-T18 with a yield of 38.5 IU/mL, that is five times that of the original strain, was achieved by nine successive implantations under the conditions of 10 keV and 30–40 (×2.6?×?10¹³) ions/cm². This optimization further increased the yield of the mutant by 42 %, i.e. 53.6 U/mL which occurred in the mutant cultivated in the optimal fermentation culture medium composed of: rice flour 5 %; ammonium sulfate 1 %; tannic acid 2 %; calcium carbonate 0.5 %; manganese sulfate 0.1 %; and dipotassium phosphate 0.3 %; incubated at 30°C and 180 rpm for 72 h.     

Nanoporous Polytetrafluoroethylene/Silica Composite Separator as a High‐Performance All‐Vanadium Redox Flow Battery Membrane

A novel low‐cost nanoporous polytetrafluoroethylene (PTFE)/silica composite separator has been prepared and evaluated for its use in an all‐vanadium redox flow battery (VRB). The separator consists of silica particles enmeshed in a PTFE fibril matrix. It possesses unique nanoporous structures with an average pore size of 38 nm and a porosity of 48%. These pores function as the ion transport channels during redox flow battery operation. This separator provides excellent electrochemical performance in the mixed‐acid VRB system. The VRB using this separator delivers impressive energy efficiency, rate capability, and temperature tolerance. In additon, the flow cell using the novel separator also demonstrates an exceptional capacity retention capability over extended cycling, thus offering excellent stability for long‐term operation. The characteristics of low cost, excellent electrochemical performance and proven chemical stability afford the PTFE/silica nanoporous separator great potential as a substitute for the Nafion membrane used in VRB applications.     

The Leptin Gene Family and Colorectal Cancer: Interaction with Smoking Behavior and Family History of Cancer

Background

Pathologic condition associated with metabolic syndrome traits seems to increase the risk of colorectal cancer. One mechanism underlying this relationship may involve the growth-promoting effects of the circulation hormones associated with obesity and insulin resistance, such as leptin.

Methodology/Principal Findings

A two-stage case-control study was used to explore the role of polymorphisms of Leptin (LEP) and Leptin receptor (LEPR), either alone or in combination with environmental factors in colorectal carcinogenesis. In stage 1, 20 single nucleotide polymorphisms (SNPs) that tag common SNPs in these two genes were genotyped among 470 cases and 458 controls. In stage 2, another population with 314 cases and 355 controls were genotyped for the two most promising SNPs from stage 1. LEPR rs12037879 only presented modestly increased colorectal cancer risk, with odds ratios of 1.41 (95% confidence interval [CI] 1.13–1.76) and 1.74 (95%CI 1.08–2.81) for GA and AA genotype when compared with GG genotype in combined population. Smokers carrying LEPR rs12037879 A allele presented 1.67-fold (95%CI 1.39-fold to 2.01-fold) increased colorectal cancer risk when compared with non-smokers carrying GG genotype in combined analysis. Individuals with family history of cancer harboring LEPR rs12037879 A allele showed 1.52-fold (95%CI: 1.24-fold to 1.86-fold) increased colorectal cancer risk, compared with individuals without family history of cancer harboring GG genotype. Multifactor gene-environment interaction analysis revealed significant interactions among LEPR rs12037879, LEPR rs6690625, smoking status and family history of cancer, exhibiting a gradient of increased colorectal cancer risk along with the increasing number of risk factors (P = 9.82×10⁻¹⁰).

Conclusions/Significance

Our research supports that polymorphisms in LEPR may be associated with marginal increase in the risk for colorectal cancer. Moreover, this association could be strengthened by cigarette smoking and family history of cancer.     

Sucrose and starch metabolism during Fargesia yunnanensis shoot growth

Bamboo is one of the fastest growing plants in the world, but their shoot buds develop very slowly. Information about the sugar storage and metabolism during the shoot growth is lacking. In the present study, we determined the activity of sucrose and starch metabolizing enzymes during the developmental period of Fargesia yunnanensis from shoot buds to the young culms that have achieved their full height. The soluble sugars and starch contents were also determined and analyzed in shoot buds and shoots at different developmental stages. The results showed that there were higher sucrose contents in shoot buds than shoots, which coincides with the sweeter taste of shoot buds. As the shoot buds sprouted out of the ground, the starch and sucrose were depleted sharply. Coupled with this, the activity of soluble acid invertase (SAI), cell wall-bound invertase (CWI), sucrose synthase at cleavage direction (SUSYC) and starch phosphorylase (STP) increased significantly in the rapidly elongating internodes. These enzymes dominated the rapid elongation of internodes. The activities of SAI, CWI, SUSYC and STP and adenosine diphosphate-glucose pyrophosphorylase were higher as compared to other enzymes in the shoot buds, but were far lower than those in the developing shoots. The slow growth of shoot buds was correlated with the low activity of these enzymes. These results complement our understanding of the physiological differences between shoot buds and elongating shoots and ascertain the physiological mechanism for the rapid growth of bamboo shoots.     

Molecular chaperone HspB2 inhibited pancreatic cancer cell proliferation via activating p53 downstream gene RPRM,BAI1, and TSAP6

Heat shock proteins (HSPs) were known as the molecular chaperones, which play a pivotal role in the protein quality control system, ensuring correct folding of proteins, and facilitating the correct refolding of damaged proteins via the transient interaction with their substrate proteins. They also practice in the regulation of cell cycles and are involved in apoptosis. We found that HspB2 was almost completely silent in pancreatic cancer and few studies investigated the role of HspB2 in cancer cells, particularly in pancreatic cancer. Here, we reported that HspB2 effectively inhibited cell proliferation in Panc-1 cells. Specifically, we demonstrated that HspB2 could combine mut-p53 and change the DNA binding site of mutant p53, subsequently upregulated the expression of RPRM, BAI-1, and TSAP6 which were the downstream genes of wt-p53, participate in mediating downstream responses to p53, including inhibiting cell proliferation and angiogenesis. The main aim of this study is to investigate the relationship between HspB2 and p53, and provide a novel treatment strategy for pancreatic cancer.     

ProDCoNN: Protein design using a convolutional neural network

Designing protein sequences that fold to a given three-dimensional (3D) structure has long been a challenging problem in computational structural biology with significant theoretical and practical implications. In this study, we first formulated this problem as predicting the residue type given the 3D structural environment around the C _α atom of a residue, which is repeated for each residue of a protein. We designed a nine-layer 3D deep convolutional neural network (CNN) that takes as input a gridded box with the atomic coordinates and types around a residue. Several CNN layers were designed to capture structure information at different scales, such as bond lengths, bond angles, torsion angles, and secondary structures. Trained on a very large number of protein structures, the method, called ProDCoNN (protein design with CNN), achieved state-of-the-art performance when tested on large numbers of test proteins and benchmark datasets.     

Activation and competition of lipoylation of H protein and its hydrolysis in a reaction cascade catalyzed by the multifunctional enzyme lipoate–protein ligase A

Protein lipoylation is essential for the function of many key enzymes but barely studied kinetically. Here, the two-step reaction cascade of H protein lipoylation catalyzed by the multifunctional enzyme lipoate–protein ligase A (LplA) was quantitatively and differentially studied. We discovered new phenomena and unusual kinetics of the cascade: (a) the speed of the first reaction is faster than the second one by two orders of magnitude, leading to high accumulation of the intermediate lipoyl-AMP (Lip-AMP); (b) Lip-AMP is hydrolyzed, but only significantly at the presence of H protein and in competition with the lipoylation; (c) both the lipoylation of H protein and its hydrolysis is enhanced by the apo and lipoylated forms of H protein and a mutant without the lipoylation site. A conceptual mechanistic model is proposed to explain these experimental observations in which conformational change of LplA upon interaction with H protein and competitive nucleophilic attacks play key roles.     

Nicotine-Induced Neuroprotection Against Ischemic Injury Involves Activation of Endocannabinoid System in Rats

Nicotine has been reported to exert certain protective effect in the Parkinson’s and Alzheimer’s diseases. Whether it has a similar action in focal cerebral ischemia was unclear. In the present study, rats received either an injection of (?)-nicotine hydrogen tartrate salt (1.2 mg/kg, i.p.) or the vehicle 2 h before the 120 min middle cerebral artery occlusion. Neurological deficits and histological injury were assessed at 24 h after reperfusion. The content of endocannabinoids and the expression of cannabinoid receptor CB1 in brain tissues were determined at different time points after nicotine administration. Results showed that nicotine administration ameliorated neurological deficits and reduced infarct volume induced by cerebral ischemia in the rats. The neuroprotective effect was partially reversed by CB1 blockage. The content of the endocannabinoids N-arachidonylethanolamine and 2-arachidonoylglycerol, as well as the expression of cannabinoid receptor CB1 were up-regulated in brain tissues after nicotine delivery. These results suggest that endogenous cannabinoid system is involved in the nicotine-induced neuroprotection against transient focal cerebral ischemia.