Synthesis of acyloxymethyl ester prodrugs of the transferable protein farnesyl transferase substrate farnesyl methylenediphosphonate

Three isoprenoid diphosphate analogues of farnesyl diphosphate (FPP) where the diphosphate has been replaced by methylene diphosphonate and the negative charges masked by frangible pivaloyloxymethyl (POM) esters were prepared. Farnesyl methylenediphosphonate is a sub-micromolar substrate for protein farnesyl transferase. The tripivaloyloxymethyl esters of isoprenoid methylenediphosphonate have significantly increased lipophilicity and may act as important farnesyl diphosphate prodrugs.     

Using biosorption to enrich the biomass of <Emphasis Type="Italic">Chlorella vulgaris </Emphasis>with microelements to be used as mineral feed supplement

The paper discusses biosorption of Cr(III), Cu(II), Mn(II), Zn(II) and Co(II) to the biomass of Chlorella vulgaris, to produce a biologically bound, concentrated form of microelements. The kinetics of biosorption was described with a pseudo-second order equation and equilibrium with the Langmuir isotherm. The mechanism of biosorption was identified as cation-exchange with alkaline metals. Cation-exchange capacity was evaluated as 4.07 meq g⁻¹. The effect of operation conditions, pH and temperature, on biosorption performance was investigated and the best operation conditions for biosorption were selected (pH 5, temperature 25 °C). The maximum sorption capacity of microelements was determined in single-metal system at pH 5 and 25 °C: Zn(II) 3.30 meq g⁻¹, Cu(II) 1.77 meq g⁻¹, Co(II) 1.75 meq g⁻¹, Cr(III) 1.74 meq g⁻¹, Mn(II) 0.764 meq g⁻¹. Biosorption experiments were also carried out in multi-metal system. The biomass of C. vulgaris enriched with microelements via the process of biosorption in both single- and multi-metal system was discussed in terms of preparation of feed supplement for laying hens and piglets. The experiments showed that 1 kg of conventional feed for laying hens can be supplemented with 0.20 g of the biomass enriched with microelements and for piglets with 0.15 g of the preparation.     

The potential role of arbuscular mycorrhizal fungi in protecting endangered plants and habitats

Ecosystems worldwide are threatened with the extinction of plants and, at the same time, invasion by new species. Plant invasiveness and loss of species can be caused by similar but opposing pressures on the community structures. Arbuscular mycorrhizal fungi (AMF) can have multiple positive effects on plant growth, productivity, health, and stress relief. Many endangered species live in symbiosis with AMF. However, the list of the International Union for Conservation of Nature and Natural Resources (IUCN Red List of Threatened Species) indicates that the mycorrhizal status of most of the threatened species has not been assessed. Rare plants often occur in specialized and also endangered habitats and might utilize specialized or unique AMF. The specificity of any endangered plant to its AMF population has not been investigated. Because most of the current AMF isolates that are available colonize a broad range of plant species, selected inocula could be used to promote growth of endangered plants before the proper and more effective indigenous AMF are characterized. Application of AMF in field sites to protect endangered plants is hardly feasible due to the complexity of plant community structures and the large amount of fungal inocula needed. Endangered plants could, however, be grown as greenhouse cultures together with appropriate fungi, and, at the relevant developmental stage, they could be re-planted into native sites to prevent extinction and to preserve plant community ecology.     

Microbiological external quality assurance program (MEQAP)--evaluation of results obtained in sanitary epidemiological laboratories in 2002

The aim of this study was to evaluate reliability of identification and determination of sensitivity to antibiotics and chemotherapeutics of some Gram positive cocci strains in 34 sanitary-epidemiological stations. All laboratories engaged in this study received 3 strains: S. aureus (S. aureus SC+ CF+, resistant to methicillin., or S. aureus SC - CF+, sensitive to methicillin), coagulase-negative staphylococci (S. epidermidis or S. haemolyticus or S. saprophyticus) and Enterococcus sp. (E. faecalis HLAR-positive or E. faecalis HLAR-negative or E. faecium or E. gallinarum). All these strains previously were identified in Department of Bacteriology of National Institute of Hygiene. Of the 68 staphylococci strains tested, 66 isolates were correctly identified. Among the 34 enterococcal strains studied the greatest difficulty in identification was caused by E. gallinarum strain--(8 out of 13 strains were incorrectly recognised). The determination of the sensitivity of the control strains to antibiotics and chemotherapeutic agents, generally was performed correctly in accordance with to the NCCLS and national recommendations. Some incorrect results of the antibiograms were caused by an erroneous interpretation of the zones of inhibition.     

Maximizing microbial degradation of perchlorate using a genetic algorithm: Media optimization

Microbial communities are under constant influence of physical and chemical components in ecosystems. Shifts in conditions such as pH, temperature or carbon source concentration can translate into shifts in overall ecosystem functioning. These conditions can be manipulated in a laboratory setup using evolutionary computation methods such as genetic algorithms (GAs). In work described here, a GA methodology was successfully applied to define sets of environmental conditions for microbial enrichments and pure cultures to achieve maximum rates of perchlorate degradation. Over the course of 11 generations of optimization using a GA, we saw a statistically significant 16.45 and 16.76-fold increases in average perchlorate degradation rates by Dechlorosoma sp. strain KJ and Dechloromonas sp. strain Miss R, respectively. For two bacterial consortia, Pl6 and Cw3, 5.79 and 5.75-fold increases in average perchlorate degradation were noted. Comparison of zero-order kinetic rate constants for environmental conditions in GA-determined first and last generations of all bacterial cultures additionally showed marked increases.     

The race concept in six regions: variation without consensus

Race, once the central concept in physical anthropology worldwide, now varies in the degree of support it receives in different regions. We present the currently available information on the status of the concept in the United States, the Spanish language areas, Poland, Europe, Russia, and China. Rejection of race ranges from high to low with the highest rejection occurring among anthropologists in the United States (and Canada). Rejection of race is moderate in Europe, sizeable in Poland and Cuba, and lowest in Russia and China. A discussion on the scientific and contextual reasons influencing these variations is presented. The tension between scientific evidence and social influences varies from region to region. The methods used in the studies reported here included questionnaires and content analysis. Response rates to questionnaires were often around 50 percent (with exception of the Polish studies). We discuss reasons for the low rates. Although a uniform method of data gathering is desirable, it may not suit scientists working in different traditions of theory and research. We conclude that it is once again timely to discuss the race concept in international meetings where all scientific and political changes occurring throughout the world in recent past decades are taken into account.     

Effects of melatonin on luteinizing hormone secretion in anestrous ewes following dopamine and opiate receptor blockade

In the present investigation we have examined the ability of melatonin to modify the pulsatile LH secretion induced by treatment with a DA antagonist (sulpiride, SULP) or opioid antagonist (naloxone, NAL) in intact mid-anestrous ewes. The experimental design comprised the following treatments-in experiment 1: (1) intracerebroventricular (i.c.v.) infusion of vehicle (control I); (2) pretreatment with SULP (0.6 mg/kg subcutaneously) and then i.c.v. infusion of vehicle (SULP + veh); (3) pretreatment with SULP and then i.c.v. infusion of melatonin (SULP + MLT, 100 microg per 100 microl/h, total 400 microg). In experiment 2: (4) i.c.v. infusion of vehicle (control II); (5) i.c.v. infusion of NAL (NAL-alone, 100 microg per 100 microl/h, total 300 microg); (6) i.c.v. infusion of NAL in combination with MLT (NAL + MLT, 100 microg + 100 microg per 100 microl/h). All infusions were performed during the afternoon hours. Pretreatment with SULP induced a significant (P < 0.01) increase in LH pulse frequency, but not in mean LH concentration, compared with control I. In SULP + MLT-treated animals, the LH concentration was significantly (P < 0.01) higher during MLT infusion, but due to highly increased LH secretion in only one ewe. The significant changes in the SULP + MLT group occurred in LH pulse frequency. A few LH pulses were noted after melatonin administration compared with the number during the infusion (P < 0.05) and after vehicle infusion in the SULP + MLT group (P < 0.05). The i.c.v. infusion of NAL evoked a significant increase in the mean LH concentration (P < 0.001) and amplitude of LH pulses (P < 0.01) compared with these before the infusion. The enhanced secretion of LH was also maintained after i.c.v. infusion of NAL (P < 0.01) with a concomitant decrease in LH pulse frequency (P < 0.05). In NAL + MLT-treated ewes, mean plasma LH concentrations increased significantly during and after the infusion compared with that noted before ( P < 0.001). No difference in the amplitude of LH pulses was found in the NAL + MLT group, but this parameter was significantly higher in ewes during infusion of both drugs than during infusion of the vehicle (P < 0.01). The LH pulse frequency differed significantly (p < 0.05), increasing slightly during NAL + MLT administration and decreasing after the infusion. In conclusion, these results demonstrate that: (1) in mid-anestrous ewes EOPs, besides DA, are involved in the inhibition of the GnRH/LH axis; (2) brief administration of melatonin in long-photoperiod-inhibited ewes suppresses LH pulse frequency after the elimination of the inhibitory DA input, but seems to not affect LH release following opiate receptor blockade.     

Carnitine: transport and physiological functions in the brain

Carnitine (4-N-trimethylammonium-3-hydroxybutyric acid), a compound necessary for a transfer of fatty acids for their oxidation within the cell, accumulates in brain although β-oxidation of fatty acids is very low in neurons. Carnitine accumulates to lower extent in the brain than in peripheral tissues and the mechanism of its transport through the blood–brain barrier is discussed, with the involvement of two transporters, OCTN2 and B^0,+ being presented. A limitation by the blood–brain barrier of carnitine supply for the brain and the mechanism of its transport to neural cells by a protein belonging to neurotransmitters' transporters superfamily is further discussed.

Due to the beneficial effects of administration of acetylcarnitine in case of patients with dementia, the role of this acylcarnitine is presented in the context of neuronal cell metabolism and the role of acetylcarnitine in the synthesis of acetylcholine. The roles of long-chain acyl derivatives of carnitine, in particular palmitoylcarnitine, responsible for interaction with the membranes, lipids acylation and specific interactions with proteins have been summarized. Stimulation of protein palmitoylation and a possibility of changing the acylation status of G proteins is described, as well as interaction of palmitoylcarnitine with protein kinase C. Diminished interaction of the isoform δ of this kinase with GAP-43 (B-50, neuromodulin), whose expression increases upon accumulation of either carnitine or palmitoylcarnitine points to a possible regulation of differentiation by these compounds and their role in neuroregeneration.     

A high frequency of apoptosis was found in cultures of lymphocytes isolated from the venous blood of children born with a low birth weight

Children born with a low birth weight (below 2500 g) exhibit a slower rate of development, and a greater tendency towards morbidity and mortality, together with a deficit of weight and height. One reason could be an increase in the level of cell elimination by apoptosis. The aim of this study was to evaluate and compare the incidence of apoptotic and necrotic (dead) cells in cultures of peripheral blood lymphocytes obtained from children born with a low birth weight and from children with a normal birth weight. Peripheral blood lymphocytes were obtained by venipuncture (10 ml) and isolated using the density gradient centrifugation method. The lymphocytes were cultured for 48 h in a culture medium containing low concentrations of fetal calf serum. A comparison study was performed between low birth weight children and normal birth weight children and the susceptibility of their lymphocytes to apoptosis and to necrosis in serum-deficient feeding culture conditions. The amount of apoptotic cells and the percentage of dead cells were significantly higher in cultures of lymphocytes obtained from low birth weight children than in cultures from normal birth weight children. The two estimated parameters inversely correlated with the concentration of fetal calf serum in the culture medium. Pulsed field gel electrophoresis showed increased DNA degradation patterns in the cultures of lymphocytes obtained from low birth weight children. Our results should be perceived as an indication that, under worse feeding conditions, the elimination of cells by apoptosis and by necrosis is significantly higher for lymphocytes of low birth weight children than for those of normal birth weight children. The enhanced elimination of lymphocytes is related to a greater susceptibility to infections, especially of the respiratory tract, as established in the retrospective analysis of the anamneses of the examined group of low birth weight children.