Anion binding and controlled aggregation of human interleukin-1 receptor antagonist

Highly concentrated human recombinant interleukin-1 receptor antagonist (IL-1ra) aggregates at elevated temperature without perturbation in its secondary structure. The protein aggregation can be suppressed depending on the buffer ionic strength and the type of anion present in the sample solution. Phosphate is an approximately 4-fold weaker suppressant than either citrate or pyrophosphate on the basis of the measured protein aggregation rates. This is in agreement with the strength of protein-anion interactions at the IL-1ra single anion-binding site as judged by the estimated dissociation constant values of 2.9 mM, 3.8 mM, and 13.7 mM for pyrophosphate, citrate, and phosphate, respectively. The strength of binding also correlates with the anion size and with the number of ionized groups available per molecule at a given pH. Affinity probing of IL-1ra with methyl acetyl phosphate (MAP) in combination with proteolytic digestion and mass spectral analysis show that an anion-binding site location on the IL-1ra surface is contributed by lysine-93 and lysine-96 of the loop 84-98 as well as by lysine-6 of the unstructured N-terminal region 1-7. The replacement of lysine-93 with alanine by site-directed mutagenesis results in dramatically suppressed IL-1ra aggregation. Furthermore, when the unstructured N-terminal region of IL-1ra is removed by limited proteolysis, a 2-fold increase in the time course of the aggregation lag phase is observed for the truncated protein. An anion-controlled mechanism of IL-1ra aggregation is proposed by which the anion competition for the protein cationic site prevents formation of intermolecular cation-pi interactions and, thus, interferes with the protein asymmetric self-association pathway.     

The composition and structure of a protected coral reef in Cam Ranh Bay in the South China Sea

A nonstructural reef at Hon Nai Island in Cam Ranh Bay (southern Vietnam) was investigated. In comparison with most of the coastal continental and island coral reefs of this region, it is characterized by high species richness of reef-building corals, among them scleractinians. A total of 34 species of Acropora were found, which represent 80% of the total species composition of this scleractinian genus on the reefs of Vietnam and 25% on the reefs of the Indo-Pacific. Among 169 species of scleractinians found on the reef of Hon Nai, Favia sp. nov. was previously unknown to science. The vertical bionomic zonality of the reef corresponds to a zonal distribution of environmental factors and is similar to that on reefs of the Gulf of Siam and various areas of the Pacific and the Caribbean Basin. The thriving of the Hon Nai island reef may be connected with protective measures undertaken by the Government of Vietnam and the minimization of anthropogenic impacts due to the activities of the Sanest Co.     

Proapoptotic activity of cytochrome c in living cells: effect of K72 substitutions and species differences

Cytochrome c is one of the key proteins involved in the programmed cell death, and lysine 72 is known to be required for its apoptogenic activity. We have engineered a number of horse and murine cytochrome c single-point mutants with various substitutions at position 72 and compared quantitatively their proapoptotic activity in living cells. Apoptosis was activated by transferring exogenous cytochrome c into the cytoplasm of cells via a nontraumatic electroporation procedure. All mutant proteins studied exhibited significantly reduced proapoptotic activities in comparison with those for the wild type cytochromes. Relative activity of the horse (h(K72X)) and murine (m(K72W)) mutant proteins diminished in the order: h(K72R) > h(K72G) > h(K72A) > h(K72E) > h(K72L) > h(K72W) > m(K72W). As estimated, the horse and murine K72W mutants were at least 200- and 500-fold less active than corresponding wild type proteins. Thus, the K72W-substituted cytochrome c can serve as an adequate candidate for knock-in studies of cytochrome c-mediated apoptosis. The proapoptotic activity of wild-type cytochrome c from different species in murine monocytic WEHI-3 cells reduced in the order: murine cytochrome c > human cytochrome c approximately horse cytochrome c, thus indicating that apoptotic effect of cytochrome c depends on the species compatibility.     

Population Dynamics of the Japanese Scallop <Emphasis Type="Italic">Mizuhopecten yessoensis</Emphasis> (Bivalvia) Under Conditions of Enhanced Hydrodynamics

A population of the Japanese scallop, Mizuhopecten yessoensis, found in the open area of Peter the Great Bay (Sea of Japan), which was not protected against southeastern summer monsoons, has been studied. Specimens of different ages, from 1 year old to 11 years old, were found in the population. According to a provisional estimation, the total reserve of the Japanese scallop in the population reached 30 000 specimens. After strong typhoons, up to 6 000 specimens were stranded along the shoreline. Even after repeatedly occurring typhoons observed during one particular summer season, the population of M. yessoensis remained rather stable, although its age structure demonstrated both uneven annual recruitment in the population and different survival rates in different generations. Specimens of the highly productive generation of 1999 constituted the bulk of the bottom population and coastal wreckage. At older ages, the probability for the Japanese scallop to be stranded during a storm decreases significantly.Original Russian Text Copyright ¢ 2005 by Biologiya Morya, Silina, Latypov.     

Reef-Building Corals and Reefs of Vietnam: 1. The Gulf of Thailand

This paper deals with the history and investigations of the reefs and coral communities of the Gulf of Thailand based on published and unpublished materials, including the author's. The state of the art in the study of reef-building scleractinian corals and reefs of this region is presented. Characterized by remarkable distinctive features, the coral fauna and reefs of the Gulf of Thailand exhibit high similarity in coral species composition to other regions of Vietnam and form a single complex of species of the equatorial Indo-Pacific.     

Capitalizing on multi-element interactions through bal-anced nutrition——A pathway to improve nitrogen use efficiency in China,India and North America

A viable option for increasing nitrogen (N) use efficiency and mitigation of negative impacts of N on the environment is to capitalize on multi-element interactions through implementation of nutrient management programs that provide balanced nutrition. Numerous studies have demonstrated the immediate efficacy of this approach in the developing regions like China and India as well as developed countries in North America. Based on 241 site-years of experiments in these countries, the first-year N recovery efficiency (RE) for the conventional or check treatments averaged 21% while the balanced treatments averaged 54% RE, for an average increase of 33% in RE due to balanced nutrition. Effective policies to promote adoption are most likely those that enable site-specific approaches to nutrient management decisions rather than sweeping, nation-wide incentives supporting one nutrient over another. Local farmers, advisers and officials need to be empowered with tools and information to help them define necessary changes in practices to create more balanced nutrient management.     

Peripartum Cardiomyopathy Presenting With Ventricular Tachycardia: A Rare Presentation

A 25-year-old previously asymptomatic pregnant woman at 36 weeks'' gestation was noticed to have repetitive monomorphic ventricular tachycardia. A dilated left ventricle with moderately reduced systolic function was found on echocardiographic examination. This is a very rare presentation of peripartum cardiomyopathy (PPCMP) presenting with repetitive monomorphic ventricular tachycardia.     

Synthesis and primary evaluation of the hepatoprotective properties of novel pyrimidine derivatives

Based on the active ingredient of the drug Ximedon (1,2-dihydro-4,6-dimethyl-1-N-(2-hydroxyethyl)pyrimidone-2, referred below to as pyrimidine (I), novel derivatives containing biogenic acids: succinic, L-ascorbic, para-aminobenzoic, nicotinic, and L-2-amino-4-(methylthio)butanoic (L-methionine) acids have been synthesized. The parameters of acute toxicity (LD₅₀) have been studied. The antitoxic effect of the compounds upon the injury by the hepatotropic poison carbon tetrachloride has been examined as the primary evaluation of their hepatoprotective properties. It has been found that, according to toxicological safety, the compounds synthesized belong to classes III and IV (moderately and little toxic compounds). The conjugates of pyrimidine (I) with ascorbic acid and methionine (LD₅₀ more than 5400 mg/kg) are least toxic. Pyrimidine (I) and its derivatives possess the antitoxic activity upon acute poisoning with carbon tetrachloride; the combined injection of carbon tetrachloride with pyrimidine (I) or its derivatives leads to an increase in the survival of animals and the normalization of the integral functional parameters, weight and body temperature, which decrease upon toxic injury. In addition, pyrimidine (I) and some of its derivatives (conjugates with L-ascorbic, succinic, para-aminobenzoic, and nicotinic acids) decrease the weight coefficients of the liver and kidneys (the organ-to-body-weight ratio) and the activity of transaminases, the markers of hepatic cytolysis, which increase upon toxic injury with carbon tetrachloride. The area of the pathological injury of the liver by steatosis and necrosis decreases by the action of pyrimidine (I) and its novel derivatives (conjugates with L-ascorbic, succinic, and nicotinic acids) two to three times. Advantages of pyrimidine (I) and its novel derivatives over the hepatoprotective drug Thiotriazolin have been revealed.