Auditory evoked responses in awake rabbits after exposure to high intensity noise impulses

Impulse noise effects were tested in chronic experiments on 8 awake rabbits. Alterations of cochlear potentials and evoked responses from the inferior collinulus and the medial geniculate body were studied. The rabbits were subsequently exposed to 10 noise impulses of 144 dB SPL, then (after recovery) to 10 impulses of 153 and 164 dB SPL. After exposure the amplitudes of all potentials were reduced. Time of restitution depended on the intensity of the noise, the restitution failed after exposure to 164 dB SPL impulses. Time lapses of the amplitude-reduction and restitution process were comparable for both structures of the auditory pathway. The peak latencies were prolonged significantly in only two of the rabbits after this impulse intensity. Impulses of 164 dB SPL were followed by irreversible changes of all evoked responses.     

Abundance, distribution, and activity of Fe(II)-oxidizing and Fe(III)-reducing microorganisms in hypersaline sediments of Lake Kasin, southern Russia

The extreme osmotic conditions prevailing in hypersaline environments result in decreasing metabolic diversity with increasing salinity. Various microbial metabolisms have been shown to occur even at high salinity, including photosynthesis as well as sulfate and nitrate reduction. However, information about anaerobic microbial iron metabolism in hypersaline environments is scarce. We studied the phylogenetic diversity, distribution, and metabolic activity of iron(II)-oxidizing and iron(III)-reducing Bacteria and Archaea in pH-neutral, iron-rich salt lake sediments (Lake Kasin, southern Russia; salinity, 348.6 g liter(-1)) using a combination of culture-dependent and -independent techniques. 16S rRNA gene clone libraries for Bacteria and Archaea revealed a microbial community composition typical for hypersaline sediments. Most-probable-number counts confirmed the presence of 4.26 × 10(2) to 8.32 × 10(3) iron(II)-oxidizing Bacteria and 4.16 × 10(2) to 2.13 × 10(3) iron(III)-reducing microorganisms per gram dry sediment. Microbial iron(III) reduction was detected in the presence of 5 M NaCl, extending the natural habitat boundaries for this important microbial process. Quantitative real-time PCR showed that 16S rRNA gene copy numbers of total Bacteria, total Archaea, and species dominating the iron(III)-reducing enrichment cultures (relatives of Halobaculum gomorrense, Desulfosporosinus lacus, and members of the Bacilli) were highest in an iron oxide-rich sediment layer. Combined with the presented geochemical and mineralogical data, our findings suggest the presence of an active microbial iron cycle at salt concentrations close to the solubility limit of NaCl.     

Vitellogenin accumulation in the fat body and haemolymph of Locusta migratoria in relation to egg maturation

Vitellogenins first appear in the fat body of Locusta migratoria during subphase I of vitellogenesis and increase to a constant level during subphase II. A second increase occurs shortly before the oöcyte attains maximal size. Vitellogenin content of fat body subsequently returns to that of subphase I, appropriate to the size of the subterminal oöcyte. The absolute amount of vitellogenin in the fat body is low compared to that found in the haemolymph. Fat body and haemolymph vitellogenins have immunological properties similar to oöcyte yolk proteins—when challenged with oöcyte protein antiserum. They exhibit similar electrophoretic mobility in polyacrylamide gel electrophoresis and are complex glyco-lipoproteins.     

Caution in interpreting results from imputation analysis when linkage disequilibrium extends over a large distance: a case study on venous thrombosis

By applying an imputation strategy based on the 1000 Genomes project to two genome-wide association studies (GWAS), we detected a susceptibility locus for venous thrombosis on chromosome 11p11.2 that was missed by previous GWAS analyses that had been conducted on the same datasets. A comprehensive linkage disequilibrium and haplotype analysis of the whole locus where twelve SNPs exhibited association p-values lower than 2.23 10(-11) and the use of independent case-control samples demonstrated that the culprit variant was a rare variant located ~1 Mb away from the original hits, not tagged by current genome-wide genotyping arrays and even not well imputed in the original GWAS samples. This variant was in fact the rs1799963, also known as the FII G20210A prothrombin mutation. This work may be of major interest not only for its scientific impact but also for its methodological findings.     

Activation of adenosine monophosphate activated protein kinase inhibits growth of multiple myeloma cells

The role of adenosine monophosphate activated protein kinase (AMPK) in regulating multiple myeloma (MM) cell growth is not yet clear. In this study, we show that the AMPK activators 5-aminoimidazole-4-carboxamide riboside (AICAr) and D942 inhibit cell growth in MM cell lines. AICAr also induced an S-phase cell cycle arrest in all four tested cell lines and led to phosphorylation and thus activation of AMPK. Furthermore, the inhibition of a nucleoside transporter by nitrobenzyl-thio-9-beta-d-ribofuranosylpurine (NBTI), inhibition of the adenosine kinase by iodotubericidine and inhibition of AMPK by AMPKI Compound C reversed AICAr effects, indicating that the cellular effects of AICAr were mediated by AMPK. Activation of AMPK inhibited basal extracellular signal-regulated kinase (ERK), mammalian target of rapamycin (mTOR) and P70S6 kinase (P70S6K) as well as AKT phosphorylation, and blocked IL-6, IGF-1, and HS-5 stromal cell conditioned medium-induced increase of cell growth. Troglitazone, which has previously been shown to activate AMPK, similarly inhibited MM cell growth, activated AMPK, and decreased ERK and P70S6K phosphorylation. Our results suggest that activation of AMPK inhibits MM cell growth despite stimulation with IL-6, IGF-1, or HS-5 stromal cell conditioned medium and represents a potential new target in the therapy of MM.