Studies on copper toxicity in nickel-resistant strains ofNeurospora crassa

Copper toxicity has been studied in three nickel-resistant strains ofNeurospora crassa (Ni^R1, Ni^R2, and Ni^R3). Ni^R1 and Ni^R2, but not Ni^R3, were two-to threefold more sensitive than the parent wild strain (N. crassa EM 5297a) to Cu²⁺ on a normal N medium. On a nitrate N medium, Cu²⁺ was 16-fold more toxic to Ni^R3 because of reduced synthesis of nitrite reductase; Ni^R1 and Ni^R2 were only fivefold more sensitive to Cu²⁺, and nitrite reductase synthesis was unaffected. Mn²⁺ reversed Cu²⁺ toxicity on normal N medium only, in all strains. Fe³⁺ counteracted Cu²⁺ toxicity on nitrate N medium also. It was shown that Cu²⁺ affected Fe³⁺ utilization for nitrite reductase synthesis in Ni^R3 only and that in these Ni²⁺-resistant strains, Fe³⁺ antagonized effects of Cu²⁺, but not of other toxic metal ions.     

Mycobacterial and nonbacterial pulmonary complications in hospitalized patients with human immunodeficiency virus infection: A prospective, cohort study

Background  

A prospective observational study was done to describe nonbacterial pulmonary complications in hospitalized patients with human immunodeficiency virus (HIV) infection.     

Morphological studies of polycystic mouse ovaries induced by dehydroepiandrosterone

Summary Morphological alterations induced by dehydroepiandrosterone (DHA) were studied in polycystic mouse ovaries (PCO). Treated mice showed ovulatory failure and cystic changes; cysts and follicles in various stages of growth and atresia were present although corpora lutea were absent. The levels of testosterone, dihydrotestosterone, 3- and 3-androstanediol, estrone and androstenedione increased, whereas estradiol was not detectable.The ultrastructure of granulosa cells in healthy and atretic follicles was similar to that of control animals, although the membrana granulosa in cysts was reduced to a monolayer of flattened cells. The theca interna of healthy and atretic follicles and ovarian cysts showed ultrastructural signs of abnormal steroidogenic stimulation.No significant differences (0.7<P<0.8) were found between the extensive surface area of gap junctions of healthy follicles of control and DHA-treated animals. On the P-face of granulosa cells of large healthy follicles, meandering strands of tight junctional particles were observed; their average length was significantly longer than those in healthy follicles of control animals (P<0.001). This increase was probably related to the large amounts of androgens present in the treated animals.Theca interna cells possessed small gap junctions; no significant differences (P>0.9) in gap-junction surface area were observed between DHA-treated and control animals. These results suggest that the size of gap junctions is probably unrelated to the steroidogenic activities of theca cells.The following trivial names have been used: Dihydrotestosterone: 5-androstan 17 ol-13 one; 3-androstanediol: 5-androstan 3,17 diol; 3-androstanediol: 5-androstan 3,17 diol     

Cation-aromatic database

Cation-aromatic database (CAD) is a publicly available web-based database that aims to provide further understanding of interaction between a cation and the pi interactions. A tool to identify the interactions in a user-given protein is also added to the database. CAD is freely accessible via the Internet at http://203.199.182.73/gnsmmg/databases/cad/.     

Effect of time delay in specific growth rate on the periodic operation of bioreactors with input multiplicities

The effect of time delay in specific growth rate () on the periodic operation of bioreactors with input multiplicities is theoretically analyzed for productivity improvement. A periodic rectangular pulse is applied either in feed substrate concentration (S_f) or in dilution rate (D). Periodic operation under feed substrate concentration cycling gives improvement in productivity at lower value of ¯S_f of the two steady-state multiplicities of S_f only when the time delay in is larger. Whereas the larger value of ¯S_f gives improvement in average productivity for all values of time delay. Dilution rate (D) cycling gives an improvement in average productivity particularly for larger time delay in . This improvement in average productivity is obtained only at smaller value of dilution rate out of the two steady-state input multiplicities of D.List of Symbols D 1/h dilution rate - F memory function - g dummy variable - K_i g/l substrate inhibition constant - K_m g/l substrate saturation constant - P g/l product concentration - P_m g/l product saturation constant - Q g/(hl) product cell produced per unit time - S g/l substrate concentration - S_f g/l feed substrate concentration - S_f,p g/l feed substrate concentration during fraction of a period - X g/l biomass concentration - Y_X/S g/g cell mass yield - w variable either S or Z - Z g/l weighted average of substrate concentration Greek Letters 1/h time delay parameter - ₁ , ₂ product yield parameters, g/g and 1/h - pulse width expressed as a fraction of a period - 1/h specific growth rate - _m 1/h maximum specific growth rate - h period of oscillation - – average value     

Beneficial role of aminoguanidine on acute cardiomyopathy related to doxorubicin-treatment

Doxorubicin (DOX) is a broad-spectrum anthracycline antibiotic that has cardiotoxicity as a major side effect. One mechanism of this toxicity is believed to involve the reactive oxygen radical species (ROS); these agents likely account for the pathophysiology of DOX-induced cardiomyopathy. Aminoguanidine (AG) is an effective antioxidant and free radical scavenger which has long been known to protect against ROS formation. We investigated the effects of AG on DOX-induced changes in thiobarbituric acid reactive substances (TBARS) and reduced glutathione (GSH) content. The rats were divided into four groups:1) Control; 2) DOX group; injected intraperitoneally (i.p.) with DOX 20 mg/kg in a single dose 3) AG-treated group; injected i.p. in single dose of 20 mg/kg DOX plus 100 mg/kg AG 1 h before the DOX for 3 days, 4) AG group; injected i.p. with AG 100 mg/kg for 3 days. DOX administration to control rats increased TBARS and decreased GSH levels. AG administration before DOX injection caused significant decrease in TBARS and increase in GSH levels in the heart tissue when compared with DOX only. Morphological changes, including severe myocardial fibrosis and inflammatory cell infiltration were clearly observed in the DOX-treated heart. AG reversed the DOX-induced heart damage. Therefore AG could protect the heart tissue against free radical injury. The application of AG during cancer chemotherapy may attenuate tissue damage and improve the therapeutic index of DOX.     

Triacylglycerol synthesis in developing seeds of groundnut (Arachis hypogaea): pathway and properties of enzymes of sn-glycerol 3-phosphate formation

The enzymatic pathway for the synthesis of sn-glycerol 3-phosphate was investigated in developing groundnut seeds (Arachis hypogaea). Glycerol-3-phosphate dehydrogenase was not detected in this tissue but an active glycerokinase was demonstrated in the cytosolic fraction. It showed an optimum pH at 8.6 and positive cooperative interactions with both glycerol and ATP. Triosephosphate isomerase and glyceraldehyde-3-phosphate phosphatase were observed mainly in the cytosolic fraction while an active glyceraldehyde reductase was found mainly in the mitochondrial and microsomal fractions. The glyceraldehyde 3-phosphate phosphatase showed specificity and positive cooperativity with respect to glyceraldehyde 3-phosphate. The glyceraldehyde reductase was active toward glucose and fructose but not toward formaldehyde and showed absolute specificity toward NADPH. It is concluded that in the developing groundnut seed, sn-glycerol 3-phosphate is synthesized essentially by the pathway dihydroxyacetone phosphate----glyceraldehyde 3-phosphate Pi----glyceraldehyde NADPH----glycerol ATP----glycerol 3-phosphate. All the enzymes of this pathway showed activity profiles commensurate with their participation in triacylglycerol synthesis which is maximal during the period 15-35 days after fertilization. Glycerokinase appears to be the rate-limiting enzyme in this pathway.     

Experimental vaccine strategies for cancer immunotherapy

Recently, cancer immunotherapy has emerged as a therapeutic option for the management of cancer patients. This is based on the fact that our immune system, once activated, is capable of developing specific immunity against neoplastic but not normal cells. Increasing evidence suggests that cell-mediated immunity, particularly T-cell-mediated immunity, is important for the control of tumor cells. Several experimental vaccine strategies have been developed to enhance cell-mediated immunity against tumors. Some of these tumor vaccines have generated promising results in murine tumor systems. In addition, several phase I/II clinical trials using these vaccine strategies have shown extremely encouraging results in patients. In this review, we will discuss many of these promising cancer vaccine strategies. We will pay particular attention to the strategies employing dendritic cells, the central player for tumor vaccine development.     

Crystal structure of Pseudomonas aeruginosa PAK pilin suggests a main-chain-dominated mode of receptor binding

Fibers of pilin monomers (pili) form the dominant adhesin of Pseudomonas aeruginosa, and they play an important role in infections by this opportunistic bacterial pathogen. Blocking adhesion is therefore a target for vaccine development. The receptor-binding site is located in a C-terminal disulphide-bonded loop of each pilin monomer, but functional binding sites are displayed only at the tip of the pilus. A factor complicating vaccination is that different bacterial strains produce distinct, and sometimes highly divergent, pilin variants. It is surprising that all strains still appear to bind a common receptor, asialo-GM1. Here, we present the 1.63 A crystal structure of pilin from P. aeruginosa strain PAK. The structure shows that the proposed receptor-binding site is formed by two beta-turns that create a surface dominated by main-chain atoms. Receptor specificity could therefore be maintained, whilst allowing side-chain variation, if the main-chain conformation is conserved. The location of the binding site relative to the proposed packing of the pilus fiber raises new issues and suggests that the current fiber model may have to be reconsidered. Finally, the structure of the C-terminal disulphide-bonded loop will provide the template for the structure-based design of a consensus sequence vaccine.