二甲基亚砜毒性研究

二甲基亚砜（Dimethyl sulfoxide DMSO）是一种含硫有机化合物,被誉为＂万能溶剂＂,广泛用作溶剂和反应试剂。在医药工业中,DMSO可直接用作某些药物的原料及载体。DMSO本身有消炎止痛,利尿,镇静等作用,亦誉为＂万灵药＂,常作为止痛药物的活性组分添加于药物之中。DMSO也是一种渗透性保护剂,能够降低细胞冰点,减少冰晶的形成,减轻自由基对细胞损害,改变生物膜对电解质、药物、毒物和代谢产物的通透性。DMSO作为组蛋白去乙酰化酶抑制剂（Histone Deacetylases-inhibitor HDACi）的一种,同样具有恢复组蛋白的乙酰化与去乙酰化平衡,抑制细胞程序性死亡,修复DNA双螺旋结构,抗放射性损伤,抗炎症反应及抗癌作用。鉴于其应用广泛,本文就其物理特性及毒性研究做一综述。     

Palatability and feeding preferences of Uresiphita maorialis (Lepidoptera: Crambidae) for three Sophora species

In a three-hour bioassay, we tested the palatability and feeding preferences of Uresiphita maorialis (kōwhai moth) for Sophora tetraptera, Sophora microphylla and Sophora prostrata. Palatability tests showed no differences among the Sophora species. Feeding preferences, on the other hand, showed that S. tetraptera and S. microphylla leaves are preferred over S. prostrata leaves. Our results support our field observations in Wellington city parks and gardens showing that S. tetraptera and S. microphylla plants frequently have higher densities of larvae than S. prostrata.     

Intramolecular versus intermolecular disulfide bonds in prion proteins

Prion protein (PrP) is the major component of the partially protease-resistant aggregate that accumulates in mammals with transmissible spongiform encephalopathies. The two cysteines of the scrapie form, PrP(Sc), were found to be in their oxidized (i.e. disulfide) form (Turk, E., Teplow, D. B., Hood, L. E., and Prusiner, S. B. (1988) Eur. J. Biochem. 176, 21-30); however, uncertainty remains as to whether the disulfide bonds are intra- or intermolecular. It is demonstrated here that the monomers of PrP(Sc) are not linked by intermolecular disulfide bonds. Furthermore, evidence is provided that PrP(Sc) can induce the conversion of the oxidized, disulfide-intact form of the monomeric cellular prion protein to its protease-resistant form without the temporary breakage and subsequent re-formation of the disulfide bonds in cell-free reactions.     

岱海流域土地利用动态模拟及生态系统服务价值测算

北方内陆湖泊面积萎缩严重,岱海作为典型的内陆湖之一,其面积变化尤为显著.为研究岱海湖面积变化及岱海流域生态系统服务价值(Esv)的动态趋势,本研究运用CA-Markov模型,基于1989-2018年6期的土地利用数据,预测2026年的土地利用状况,并采用当量因子法,对岱海流域ESV进行评估.结果 表明:岱海湖若不进行生...     

Common functionally important motions of the nucleotide‐binding domain of Hsp70

The 70 kDa heat shock proteins (Hsp70) are a family of molecular chaperones involved in protein folding, aggregate prevention, and protein disaggregation. They consist of the substrate‐binding domain (SBD) that binds client substrates, and the nucleotide‐binding domain (NBD), whose cycles of nucleotide hydrolysis and exchange underpin the activity of the chaperone. To characterize the structure–function relationships that link the binding state of the NBD to its conformational behavior, we analyzed the dynamics of the NBD of the Hsp70 chaperone from Bos taurus (PDB 3C7N:B) by all‐atom canonical molecular dynamics simulations. It was found that essential motions within the NBD fall into three major classes: the mutual class, reflecting tendencies common to all binding states, and the ADP‐ and ATP‐unique classes, which reflect conformational trends that are unique to either the ADP‐ or ATP‐bound states, respectively. “Mutual” class motions generally describe “in‐plane” and/or “out‐of‐plane” (scissor‐like) rotation of the subdomains within the NBD. This result is consistent with experimental nuclear magnetic resonance data on the NBD. The “unique” class motions target specific regions on the NBD, usually surface loops or sites involved in nucleotide binding and are, therefore, expected to be involved in allostery and signal transmission. For all classes, and especially for those of the “unique” type, regions of enhanced mobility can be identified; these are termed “hot spots,” and their locations generally parallel those found by NMR spectroscopy. The presence of magnesium and potassium cations in the nucleotide‐binding pocket was also found to influence the dynamics of the NBD significantly. Proteins 2015; 83:282–299. © 2014 Wiley Periodicals, Inc.     

Stability of polypeptide conformational states. II. Folding of a polypeptide chain by the scanning simulation method, and calculation of the free energy of the statistical coil

The scanning simulation method suggested by Meirovitch is extended to a study of the stability of decaglycine at 100 and 300 K. The model is based on the potential energy function ECEPP (Empirical Conformational Energy Program for Peptides) with rigid geometry and without solvent. The free energy of the statistical coil, which is defined over the whole phase space excluding the region of the right-handed α-helix, is calculated. At 100 K, the molecule is found to be unstable in the statistical coil region, and the method generates (i.e., “folds”) conformations that are left-handed or right-handed α-helices with very high preference. Their free energy is found to be comparable with that obtained by another method developed in our previous paper (paper I) [H. Meirovitch, M. Vásquez, and H. A. Scheraga, (1987) Biopolymers 26 , 651–671]. At 300 K the statistical coil becomes the most stable state; sample conformations of the coil are generated efficiently with the scanning method and the free energy is calculated. It appears that both the scanning method and the method of paper I can be used to carry out a complete analysis of the stability of a polypeptide based on free energy considerations.     

Relation between sequence similarity and structural similarity in proteins. Role of important properties of amino acids

In a previous paper we obtained ten (orthogonal) factors, linear combinations of which can express the properties of the 20 naturally occurring amino acids. In this paper, we assume that the most important properties (linear combinations of these ten factors) that determine the three-dimensional structure of a protein are conserved properties, i.e., are those that have been conserved during evolution. Two definitions of a conserved property are presented: (1) a conserved property for an average protein is defined as that linear combination of the ten factors that optimally expresses the similarity of one amino acid to another (hence, little change during evolution), as given by the relatedness odds matrix of Dayhoff et al.; (2) a conserved property for each position in the amino acid sequence (locus) of a specific family of homologous proteins (the cytochromec family or the globin family) is defined as that linear combination of the ten factors that is common among a set of amino acids at a given locus when the sequences are properly aligned. When the specificity at each locus is averaged over all loci, the same features are observed for three expressions of these two definitions, namely the conserved property for an average protein, the average conserved property for the cytochromec family, and the average conserved property for the globin family; we find that bulk and hydrophobicity (information about packing and long-range interactions) are more important than other properties, such as the preference for adopting a specific backbone structure (information about short-range interactions). We also demonstrate that the sequence profile of a conserved property, defined for each locus of a protein family (definition 2), corresponds uniquely to the three-dimensional structure, while the conserved property for an average protein (definition 1) is not useful for the prediction of protein structure. The amino acid sequences of numerous proteins are searched to find those that are similar, in terms of the conserved properties (definition 2), to sequences of the same size from one of the homologous families (cytochromec and globin, respectively) for whose loci the conserved properties were defined. Many similar sequences are found, the number of similarities decreasing with increasing size of the segment. However, the segments must be rather long (15 residues) before the comparisons become meaningful. As an example, one sufficiently large sequence (20 residues) from a protein of known structure (apo-liver alcohol dehydrogenase that is not a member of either family) is found to be similar in the conserved properties to a particular sequence of a member of the family of human hemoglobin chains, and the two sequences have similar structures. This means that, since conserved properties are expected to be structure determinants, we can use the conserved properties to predict an initial protein structure for subsequent energy minimization for a protein for which the conserved properties are similar to those of a family of proteins with a sufficiently large number of homologous amino acid sequences; such a large number of homologous sequences is required to define a conserved property for each locus of the homologous protein family.     

CYCLOHEXIMIDE AS A MEDIA AMENDMENT FOR ENUMERATING BACTERIAL POPULATIONS IN ANIMAL FEEDS

The present study was designed to evaluate cycloheximide as a potential media amendment for differential bacterial and fungal enumeration of animal feeds. The objectives of this study were to determine the effect of cycloheximide on bacterial growth rates and to evaluate its efficacy for the reduction of indigenous spreading fungi when enumerating bacterial populations in three types of feeds and after short or long-term storage. Escherichia coli, Bacillus cereus, Staphylococcus aureus, Listeria monocytogenes and Pseudomonas fluorescens were grown in tryptic soy broth containing cycloheximide to determine its effect on bacterial specific growth rates. Growth rates of B. cereus and S. aureus were significantly decreased by the addition of 600 and 1000 mg/L cycloheximide respectively, but other pure cultures were not significantly influenced by cycloheximide addition. Intrinsic bacterial populations from feed were not significantly affected by cycloheximide additions at concentrations from 10 to 300 mg/L, but the indigenous spreading molds from feeds were significantly decreased by these cycloheximide concentrations and were decreased below detection levels by 300 mg/L of cycloheximide. The addition of 300 mg/L of cycloheximide effectively eliminates fungal growth for accurate enumeration of bacterial populations in feeds.     

A computer modeling postulated mechanism for angiotensin II receptor activation

The angiotensin II receptor of the AT₁-type has been modeled starting from the experimentally determined three-dimensional structure of bacteriorhodopsin as the template. Intermediate 3D structures of rhodopsin and ₂-adrenergic receptors were built because no direct sequence alignment is possible between the AT₁ receptor and bacteriorhodopsin. Docking calculations were carried out on the complex of the modeled receptor with AII, and the results were used to analyze the binding possibilities of DuP753-type antagonistic non-peptide ligands. We confirm that the positively charged Lys¹⁹⁹ on helix 5 is crucial for ligand binding, as in our model; the charged side chain of this amino acid interacts strongly with the C-terminal carboxyl group of peptide agonists or with the acidic group at the 2-position of the biphenyl moiety of DuP753-type antagonists. Several other receptor residues which are implicated in the binding of ligands and the activation of receptor by agonists are identified, and their functional role is discussed. Therefore, a plausible mechanism of receptor activation is proposed. The three-dimensional docking model integrates most of the available experimental observations and helps to plan pertinent site-directed mutagenesis experiments which in turn may validate or modify the present model and the proposed mechanism of receptor activation.     

INDIGENOUS POULTRY FEED MICROFLORA RESPONSE TO ETHYL ALCOHOL AND BUFFERED PROPIONIC ACID ADDITION

The present study was designed to compare ethyl alcohol with buffered propionic acid feed treatment on the survival of indigenous poultry feed bacteria and fungi. The aerobic bacterial poultry feed populations were not substantially reduced by either ethyl alcohol or buffered propionic acid treatments. Likewise, indigenous poultry feed fungal populations also were not markedly reduced by buffered propionic acid treatment of the feed but fungal poultry feed populations exposed to ethyl alcohol treatments were significantly lower (P<0.05) than fungal populations recovered from either control and buffered propionic acid treated feeds. Ethyl alcohol treatment may have potential for reducing fungal contamination in poultry feed.