Composition,Characteristic and Activity of Rare Earth Element-Bound Polysaccharide from Tea

The compositions and structural characteristics of rare earth elements-bound polysaccharides from tea (REE-TPS) were studied with the methods of Inductively Coupled Plasma Mass Spectrometry (ICP-MS), Gas Chromatography (GC) and Extended X-ray Absorption Fine Structure (EXAFS) spectroscopy. The results show that polysaccharide from tea (TPS) was a sort of glycoprotein and coordinated with Rare Earth Elements (REE) closely. The sugar fraction was composed of Rha, Ara, Xyl, Fuc, Glc, and Gal. There existed almost all natural amino acids with Glx, Asx, and Hyp as the major parts in the protein fraction. The REEs in REE-TPS were mainly composed of La, Ce, and Nd, especially, more than 75% of them was La. The coordination atom of the first coordination shell of La in REE-TPS was oxygen, the coordination number of which was 6, and the average distance between the atoms was 2.52 Å. The second shell was formed from sulfur atoms, the coordination number and the average distance were 3 and 2.91 Å, respectively. The bio-experiments show that REE-TPS could decrease the content of blood glucose in mice significantly.     

MAVS-Mediated Apoptosis and Its Inhibition by Viral Proteins

Background

Host responses to viral infection include both immune activation and programmed cell death. The mitochondrial antiviral signaling adaptor, MAVS (IPS-1, VISA or Cardif) is critical for host defenses to viral infection by inducing type-1 interferons (IFN-I), however its role in virus-induced apoptotic responses has not been elucidated.

Principal Findings

We show that MAVS causes apoptosis independent of its function in initiating IFN-I production. MAVS-induced cell death requires mitochondrial localization, is caspase dependent, and displays hallmarks of apoptosis. Furthermore, MAVS^−/− fibroblasts are resistant to Sendai virus-induced apoptosis. A functional screen identifies the hepatitis C virus NS3/4A and the Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) nonstructural protein (NSP15) as inhibitors of MAVS-induced apoptosis, possibly as a method of immune evasion.

Significance

This study describes a novel role for MAVS in controlling viral infections through the induction of apoptosis, and identifies viral proteins which inhibit this host response.     

稀土多元复合肥和三种稀土元素的遗传毒性研究

采用蚕豆根尖细胞微核技术,研究市售稀土多元复合肥和稀土元素镧、铈、铒的化合物对蚕豆根尖细胞的遗传毒性和细胞毒性。结果表明,稀土复合肥和三种稀土元素均可诱发微核效应,在一定浓度下可损伤细胞,影响根尖的正常生长,其中稀土复合肥的微核效应表现出明显的剂量-效应关系。稀土复合肥和稀土元素镧、铈、铒的化合物对蚕豆根尖细胞具有一定的遗传毒性作用和细胞毒性作用,在施用稀土微肥和使用稀土制品时应引起重视。 Abstract：This paper presents the study of genetic toxicity and cell toxicity that is give n by rare earth multi-element compound fertilizer and a chemical compound of rar e earth elements-La3＋、Ce4＋、Er3＋ in root tip cells of Vicia faba.The technique used is micronucleus in root tip cells of Vicia faba.The experiment statistical result shows that both the rare earth compound fertilizer and the three kinds of rare earth elements can cause micronucleus ef fect and under certain concentration,they can hurt cells, affect root tip gro wth .The micronucleus effect of the rare earth compound fertilizer shows a clear relation of dosage-effect. The conclusion is that rare earth compound fertilize r and the chemical compound of rare earth elements La3＋、Ce4＋、E r3＋cause certain genetic toxicity and cell toxicity effect to root tip cells of Vicia faba.Therefore a close attention should be paid when the rar e earth multi-fertilizer and other things made by rare earth are used.     

Criticality of the Rare Earth Elements

Recent constraints on supplies of the rare earth elements (REEs) have led to concerns about their long‐term availability as well as the consequences that shortages would pose for modern technology. To assess this situation, we apply a comprehensive “criticality” methodology to the REE: lanthanum (La); cerium (Ce); praseodymium (Pr); neodymium (Nd); samarium (Sm); europium (Eu); gadolinium (Gd); terbium (Tb); dysprosium (Dy); holmium (Ho); erbium (Er); thulium (Tm); ytterbium (Yb); lutetium (Lu); and yttrium (Y). Assessments are made on national (U.S. and China) and global levels for the year 2008. Evaluations of each indicator are presented and the results plotted in “criticality space” on a 0 to 100 scale. Over the medium term (5 to 10 years), supply risk (SR) for all REEs is moderate with minimal variation (62.8 to 65.1). Over the long term (10 to 100 years), SR is low (42.1 to 49.2). Environmental implications scores, reflecting the economic allocation of environmental burdens, range from 4.2 for La to 34.4 for Lu. Eu, Er, and Dy have the highest vulnerability to supply restriction (VSR) at the global level (50.6, 49.2, and 47.4, respectively), whereas Sm has the lowest (15.1). This is mainly a reflection of their substitution potential. Similarly, at the national level for the United States and China, Eu and Sm have the highest and lowest VSR scores, respectively, although there are notable differences in scores among the REEs and between countries. Although China's export restrictions render REE supplies inadequate to meet demand at present, our analysis indicates a lower criticality for REEs over the longer term than for a number of other industrially used metals.     

Mechanism of mda-5 Inhibition by Paramyxovirus V Proteins

The RNA helicases encoded by melanoma differentiation-associated gene 5 (mda-5) and retinoic acid-inducible gene I (RIG-I) detect foreign cytoplasmic RNA molecules generated during the course of a virus infection, and their activation leads to induction of type I interferon synthesis. Paramyxoviruses limit the amount of interferon produced by infected cells through the action of their V protein, which binds to and inhibits mda-5. Here we show that activation of both mda-5 and RIG-I by double-stranded RNA (dsRNA) leads to the formation of homo-oligomers through self-association of the helicase domains. We identify a region within the helicase domain of mda-5 that is targeted by all paramyxovirus V proteins and demonstrate that they inhibit activation of mda-5 by blocking dsRNA binding and consequent self-association. In addition to this commonly targeted domain, some paramyxovirus V proteins target additional regions of mda-5. In contrast, V proteins cannot bind to RIG-I and consequently have no effect on the ability of RIG-I to bind dsRNA or to form oligomers.     

Oxidative Inhibition of Protein Phosphatase 2A Activity: Role of Catalytic Subunit Disulfides

A molecular basis for the inhibition of brain protein phosphatase 2A (PP2A) activity by oxidative stress was examined in a high-speed supernatant (HSS) fraction from rat cerebral cortex. PP2A activity was subject to substantial disulfide reducing agent-reversible inhibition in the HSS fraction. Results of gel electrophoresis support the conclusions that inhibition of PP2A activity was associated with the both the disulfide cross-linking of the catalytic subunit (PP2A_C) of the enzyme to other brain proteins and with the formation of an apparent novel intramolecular disulfide bond in PP2A_C. Additional findings that the vicinal dithiol cross-linking reagent phenylarsine oxide (PAO) produced a potent dithiothreitol-reversible inhibition of PP2A activity suggest that the cross-linking of PP2A_C vicinal thiols to form an intramolecular disulfide bond may be sufficient to inhibit PP2A activity under oxidative stress. We propose that the dithiol–disulfide equilibrium of a vicinal thiol pair of PP2A_C may confer redox sensitivity on cellular PP2A.     

Inhibition of EZH2 Catalytic Activity Selectively Targets a Metastatic Subpopulation in Triple-Negative Breast Cancer

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Inhibition of Wheat Nitrate Reductase Activity by Zinc

The effect of Zn^2- on nitrate reductase (NR, EC 1.6.6.1) activity was studied in botá wheat (Triticum aestivum cv. Oasis) leaves and in the NR enzyme partially purified from wheat leaves. Leaf segments were floated on 0 to 5 mM ZnSO₄ solutions (pH 6.0) for 24 h under continuous light. Zn^2- at 250 M decreased NR activity and increased membrane permeability. However, parameters of cellular oxidative damage were scarcely affected by Zn^2- treatments. Accordingly, the decrease of NR activity induced by Zn^2- was not prevented by benzoate (a scavenger of oxygen radicals). The effect of Zn^2- was dependent on leaf age: it decreased NR activity in mature but not in young leaves. Zn² inhibited the partially purified NR. This inhibition was not reversed by either co- or post-incubation with cysteine, and the amount of -SH groups of the purified NR was not affected by Zn²⁺ indicating that Zn^2- inhibition does not involve key -SH groups of the enzyme. However, o-phenantroline both prevented and reversed Zn²⁺-induced NR inhibition. We concluded that the effect of Zn²⁺ on NR activity in vivo is not associated with an increase in active oxygen generation and involves a direct and reversible inhibition of the enzyme.     

Inhibition of Porphobilinogen Synthase Activity by 4,5-Dioxovalerate

The effect of 4,5-dioxovaleric acid on the activity of porphobilinogen(PBG) synthase (formerly 5-aminolevulinic acid dehydratase,EC 4.2.1.24 [EC] ) of the porphyrin synthetic pathway was studiedwith the enzyme purified from Chlorella regularis. 4,5-Dioxovalericacid, a metabolite of 5-aminolevulinic acid, competitively inhibitedPBG synthase with a K_i value of 1.4 mM. The concentration forthe half inhibition of 4,5-dioxovaleric acid (7 mM) was slightlylower than that for the known competitive inhibitor, levulinicacid (12 mM). (Received October 8, 1984; Accepted December 13, 1984)     

Mechanism for Inhibition of Deoxyribonuclease Activity by Antisera

The activity of bovine DNase, but not that of porcine DNase, is inhibited by antisera against bovine DNase, and vice versa. Inhibition of DNase is found in the immunoglobulin G-containing fractions, as shown by ion exchange chromatography. Inactive DNase, carboxymethylated specifically at the active site His¹³⁴, competes with active DNase and reverses the antisera inhibition of DNase, suggesting that the epitode responsible for inhibition does not contain the active site His¹³⁴. Alignment of the sequences of DNase of these two species shows that the greatest variation occurs between residues 153 and 163, within which are three consecutive peptide bonds, Lys-Trp-His-Leu, that are readily cleaved by trypsin, chymotrypsin, or thermolysin. The 8-hr digest of DNase by each of these three proteases has lost the ability to reverse antisera inhibition. The degree of antisera inhibition varies with the metal ion used as the activator for DNase-catalyzed reactions. When Mn²⁺, Co²⁺, or Mg²⁺ plus Ca²⁺ are used as activators, inhibition is approximately 50%. When pBR322 plasmid is used as substrate, gel electrophoresis shows that the DNase-catalyzed DNA hydrolysis produces a significant amount of double-strand cuts with Mn²⁺, Co²⁺, or Mg²⁺ plus Ca²⁺ as activators and antisera inhibit DNase action only on double-strand cuts. With only Mg²⁺ as the activator no double-strand cuts are observed, either in the presence or absence of antisera, and the DNase activity is not significantly inhibited. We conclude that antisera inhibition is due to antibody binding of the DNase polypeptide chain within residues 153 and 163. These residues are not crucial for catalysis, but are required for DNA binding, which results in double-strand cuts.     

Inhibition of the Host Proteasome Facilitates Papaya Ringspot Virus Accumulation and Proteosomal Catalytic Activity Is Modulated by Viral Factor HcPro

The ubiquitin/26S proteasome system plays an essential role not only in maintaining protein turnover, but also in regulating many other plant responses, including plant–pathogen interactions. Previous studies highlighted different roles of the 20S proteasome in plant defense during virus infection, either indirectly through viral suppressor-mediated degradation of Argonaute proteins, affecting the RNA interference pathway, or directly through modulation of the proteolytic and RNase activity of the 20S proteasome, a component of the 20S proteasome, by viral proteins, affecting the levels of viral proteins and RNAs. Here we show that MG132, a cell permeable proteasomal inhibitor, caused an increase in papaya ringspot virus (PRSV) accumulation in its natural host papaya (Carica papaya). We also show that the PRSV HcPro interacts with the papaya homologue of the Arabidopsis PAA (α1 subunit of the 20S proteasome), but not with the papaya homologue of Arabidopsis PAE (α5 subunit of the 20S proteasome), associated with the RNase activity, although the two 20S proteasome subunits interacted with each other. Mutated forms of PRSV HcPro showed that the conserved KITC54 motif in the N-terminal domain of HcPro was necessary for its binding to PAA. Co-agroinfiltration assays demonstrated that HcPro expression mimicked the action of MG132, and facilitated the accumulation of bothtotal ubiquitinated proteins and viral/non-viral exogenous RNA in Nicotiana benthamiana leaves. These effects were not observed by using an HcPro mutant (KITS54), which impaired the HcPro – PAA interaction. Thus, the PRSV HcPro interacts with a proteasomal subunit, inhibiting the action of the 20S proteasome, suggesting that HcPro might be crucial for modulating its catalytic activities in support of virus accumulation.     

桂皮酸-8-羟基喹啉稀土配合物的合成、抑菌活性及其对DNA的作用

以稀土离子为模板,用桂皮酸、8-羟基喹啉为原料,在乙醇溶液中首次合成了两种稀土三元配合物,采用元素分析、摩尔电导、红外光谱、紫外光谱和荧光光谱进行表征,并研究了配合物对常见细菌大肠杆菌和金黄色葡萄球菌的抑菌活性以及与DNA的相互作用.结果表明:配合物的抑菌活性较配体和稀土离子均有提高,能使细胞正常的DNA复制生理功能受到影响.     

Diverse Mechanisms of CRISPR-Cas9 Inhibition by Type II Anti-CRISPR Proteins

Clustered regularly interspaced short palindromic repeats (CRISPR)-Cas (CRISPR-associated proteins) systems provide bacteria and archaea with an adaptive immune response against invasion by mobile genetic elements like phages, plasmids, and transposons. These systems have been repurposed as very powerful biotechnological tools for gene editing applications in both bacterial and eukaryotic systems. The discovery of natural off-switches for CRISPR-Cas systems, known as anti-CRISPR proteins, provided a mechanism for controlling CRISPR-Cas activity and opened avenues for the development of more precise editing tools. In this review, we focus on the inhibitory mechanisms of anti-CRISPRs that are active against type II CRISPR-Cas systems and briefly discuss their biotechnological applications.     

稀土元素生物效应中的Hormesis现象

综述了稀土元素在动物、植物和微生物生理、生化过程中的Hormesis现象,并就其机理进行了讨论,以期为进一步弄清稀土元素的生物效应机制提供参考。     

稀土积累对水体中藻类生长的影响

为了解稀土积累对水体中藻类生长的生态效应,本文研究了单一稀土氧化镧（Ｌａ２Ｏ３）积累对水体中混合藻生长量的影响。结果表明,稀土浓度为５０、１００、２００、３００、４００、６００、８００ｐｐｍ时,对混合藻的生长多表现为抑制作用。整个试验期间藻的叶绿素（ａ）含量及藻细胞数量均随着稀土浓度的升高而降低。只是稀土浓度为１００ｐｐｍ,培养１５天时对藻产生轻微刺激作用。当稀土浓度＞４００ｐｐｍ时,混合藻的生长几乎完全被抑制。     

Inhibition of CRISPR-Cas9 with Bacteriophage Proteins

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