The c.469+46_56del mutation in the homeobox MSX1 gene—A novel risk factor in breast cancer?

Purpose: The aim of this study was to investigate the association of a 11 nucleotide deletion, the c.469+46_56del mutation, in the intron of the homeobox MSX1 gene and breast cancer occurrence and characteristics. Methods: The mutation was genotyped in peripheral blood lymphocytes of 200 breast cancer patients and 203 controls by single-strand conformational PCR and DNA sequencing. Results: The del/del variant of the c.469+46_56del mutation increased the risk of breast cancer occurrence (OR 2.20; 95% CI 1.41–3.44, p < 0.05). We did not observe any association between genotypes of this mutation and lymph node status, Bloom–Richardson grading, estrogen and progesterone receptors and HER2 expression. Conclusions: The del/del genotype of the c.469+46_56del mutation in the MSX1 gene may be associated with the increased risk of breast cancer in Polish population and may be considered as an early marker in this disease.     

Controlled microbiological in-situ stope leaching of a sulphidic ore

A mixed culture of Thiobacillus ferrooxidans, T. thiooxidans, and Leptospirillum ferrooxidans was used for inoculation of a sulphidic ore body for a bacterial in-situ stope-leaching experiment in the Ilba mine in Romania. The ore body was inoculated with 10⁷ cells/g ore. Measurements at six main sites of the ore body indicated that microbial leaching was started by the inoculation. After about 8 weeks, sufficient microbial activity was measurable only in the upper third of the ore body. Due to the angle of incidence of the ore (75°), the leach liquor percolated only through the upper part leaving two-thirds humidified unsatisfactorily. The leach results, metal mobilization, indicated that by inoculation with the indigenous microorganisms efficient leaching was achieved. Metal output after 18 months of operation amounted to 10% of Cu and 78% of Zn. In the winter months energy for aeration and circulation was not available and this was reflected by reduced values for microbial activity, temperature, and daily metal output. The biological metal mobilisation after 18 months of operation was as active as at the beginning. Cu was mobilised predominantly by microbial leaching whereas Zn was leached mainly by chemical reactions. Both mechanisms contributed equally to iron output.Correspondence to: W. Sand     

Microbial Diversity in Uranium Mine Waste Heaps

Two different uranium mine waste heaps near Ronneburg, Thuringia, Germany, which contain the remains of the activity of the former uranium-mining Soviet-East German company Wismut AG, were analyzed for the occurrence of lithotrophic and chemoorganotropic leach bacteria. A total of 162 ore samples were taken up to a depth of 5 m. Cell counts of ferrous iron-, sulfur-, sulfur compound-, ammonia-, and nitrite-oxidizing bacteria were determined quantitatively by the most-probable-number technique. Sulfate-, nitrate-, ferric iron-, and manganese-reducing bacteria were also detected. In addition, the metabolic activity of sulfur- and iron-oxidizing bacteria was measured by microcalorimetry. Generally, all microorganisms mentioned above were detectable in the heaps. Aerobic and anaerobic microorganisms thrived up to a depth of 1.5 to 2 m. Up to 99% of Thiobacillus ferrooxidans cells, the dominant leaching bacteria, occurred to this depth. Their numbers correlated with the microbial activity measurements. Samples below 1.5 to 2 m exhibited reduced oxygen concentrations and reduced cell counts for all microorganisms.     

Hemispheric specialization in domestic dogs (Canis familiaris) for processing different types of acoustic stimuli

Lateralization is considered to be a fundamental feature of vertebrate brains. The aim of the present study was to examine the impact of functional cerebral asymmetry on processing of auditory stimuli in the domestic dog (Canis familiaris) during the orientation reaction. The experiment was conducted on 46 dogs (25 females and 21 males). Four types of auditory stimuli were used in the experiment (three meaningful stimuli: cat meowing, dog barking, the "sit" command ("siad" in Polish), and a neutral word ("wir", meaning "whirl" in Polish). It was predicted that the orientation reaction (turning the head towards the stimuli) would take place only in the case of meaningful sounds. It was also expected that dogs would show consistent lateralization. As predicted, all three meaningful stimuli elicited the orientation reaction. The response of the examined dogs to cat meowing showed significant lateralization with dominant leftwards movement, which hints towards activation of the right cerebral hemisphere and may be related to strong emotions evoked by this stimulus. Contrary to results of previous studies, dogs reacting to dog barking turned their heads leftwards more often, which suggests activation of the right cerebral hemisphere, probably related to the emotional meaning of the stimulus. The "sit" command consistently evoked the orientation reaction but there was no significant lateralization of this movement.     

The stereoselective sulfate conjugation of 4'-methoxyfenoterol stereoisomers by sulfotransferase enzymes

The presystemic sulfate conjugation of the stereoisomers of 4′‐methoxyfenoterol, (R,R′)‐MF, (S,S′)‐MF, (R,S′)‐MF, and (S,R′)‐MF, was investigated using commercially available human intestinal S9 fractions, a mixture of sulfotransferase (SULT) enzymes. The results indicate that the sulfation was stereospecific and that an S‐configuration at the β‐OH carbon of the MF molecule enhanced the maximal formation rates with (S,R′)‐MF (S,S′)‐MF (R,S′)‐MF ≈ (R,R′)‐MF, and competition studies demonstrated that (S,R′)‐MF is an effective inhibitor of (R,R′)‐MF sulfation (IC₅₀ = 60 μM). In addition, the results from a cDNA‐expressed human SULT isoform screen indicated that SULT1A1, SULT1A3, and SULT1E1 can mediate the sulfation of all four MF stereoisomers. Previously published molecular models of SULT1A3 and SULT1A1 were used in docking simulations of the MF stereoisomers using Molegro Virtual Docker. The models of the MF‐SULT1A3 and MF‐SULT1A1 complexes indicate that each of the two chiral centers of MF molecule plays a role in the observed relative stabilities. The observed stereoselectivity is the result of multiple hydrogen bonding interactions and induced conformational changes within the substrate–enzyme complex. In conclusion, the results suggest that a formulation developed from a mixture of (R,R′)‐MF and (S,R′)‐MF may increase the oral bioavailability of (R,R′)‐MF. Chirality 24:796–803, 2012. © 2012 Wiley Periodicals, Inc. ¹      

Algal photoreceptors: in vivo functions and potential applications

Many algae, particularly microalgae, possess a sophisticated light-sensing system including photoreceptors and light-modulated signaling pathways to sense environmental information and secure the survival in a rapidly changing environment. Over the last couple of years, the multifaceted world of algal photobiology has enriched our understanding of the light absorption mechanisms and in vivo function of photoreceptors. Moreover, specific light-sensitive modules have already paved the way for the development of optogenetic tools to generate light switches for precise and spatial control of signaling pathways in individual cells and even in complex biological systems.     

Time-dependent effect of leptin on renal Na+,K+-ATPase activity

Leptin, secreted by adipose tissue, is involved in the pathogenesis of arterial hypertension, however, the mechanisms through which leptin increases blood pressure are incompletely elucidated. We investigated the effect of leptin, administered for different time periods, on renal Na(+),K(+)-ATPase activity in the rat. Leptin was infused under anesthesia into the abdominal aorta proximally to the renal arteries for 0.5-3 h. Leptin administered at doses of 1 and 10 microg/min per kg for 30 min decreased the Na(+),K(+)-ATPase activity in the renal medulla. This effect disappeared when the hormone was infused for > or =1 h. Leptin infused for 3 h increased the Na(+),K(+)-ATPase activity in the renal cortex and medulla. The stimulatory effect was abolished by a specific inhibitor of Janus kinases (JAKs), tyrphostin AG490, as well as by an NAD(P)H oxidase inhibitor, apocynin. Leptin increased urinary excretion of hydrogen peroxide (H(2)O(2)) between 2 and 3 h of infusion. The effect of leptin on renal Na(+),K(+)-ATPase and urinary H(2)O(2) was augmented by a superoxide dismutase mimetic, tempol, and was abolished by catalase. In addition, infusion of H(2)O(2) for 30 min increased the Na(+),K(+)-ATPase activity. Inhibitors of extracellular signal regulated kinases (ERKs), PD98059 or U0126, prevented Na(+),K(+)-ATPase stimulation by leptin and H(2)O(2). These data indicate that leptin, by acting directly within the kidney, has a delayed stimulatory effect on Na(+),K(+)-ATPase, mediated by JAKs, H(2)O(2) and ERKs. This mechanism may contribute to the abnormal renal Na(+) handling in diseases associated with chronic hyperleptinemia such as diabetes and obesity.     

Antimicrobial activity of chicken egg white cystatin

The cysteine protease inhibitor cystatin was purified from chicken egg white and its antimicrobial activity determined for a series of pathogenic bacteria. The results indicate that Acinetobacter lwoffii, Escherichia coli, Oligella sp. and Pseudomonas aeruginosa are highly sensitive to low concentrations of cystatin, which possesses bactericidal activity. No inhibition was observed with a Citrobacter freundii strain. Fifty percent growth inhibition (IC₅₀) was observed at cystatin concentrations in the range of 80 and 100g/ml, and the growth was completely inhibited at concentrations in the range of 100 and 200g/ml. Fifty percent growth inhibition (IC₅₀) for Staphylococcus aureus, Staphylococcus gallinarum, and Staphylococcus xylosus strains was observed at 150 and 200 g of cystatin/ml respectively, and growth was completely inhibited at cystatin concentrations in the range of 300 and 1000 g/ml. The activity of cysteine proteases was significantly decreased in the culture supernatant of microorganisms when chicken cystatin was added. In this study, we observed that chicken cystatin may be a candidate for antibacterial drug development aiming at controlling bacterial pathogens including Escherichia coli, Pseudomonas aeruginosa, and another possible application might be as a therapeutic agent for health improvement.