Liquorice in moderate doses does not affect sex steroid hormones of biological importance although the effect differs between the genders

BACKGROUND/AIM: Liquorice is commonly consumed, at least in the western world, and we have earlier shown that even moderate doses of liquorice have significant effects on the cortisol metabolism by inhibiting 11beta-hydroxysteroid dehydrogenase type 2. The suggestion that liquorice decreases the testosterone levels in men makes it vital to study the effect of moderate doses of liquorice on sex steroid hormones. METHODS: Fifteen women and 21 men (healthy volunteers and subjects with essential hypertension) consumed 100 g of liquorice (150 mg glycyrrhetinic acid) daily in a 9-week, open-treatment trial. Blood and 24-hour urine samples were collected for hormone analysis before and after 4 weeks of liquorice consumption and 4 weeks after cessation of liquorice intake. RESULTS: The liquorice induced a moderate decrease in the serum concentrations of dehydroepiandrostenedione sulphate in men (p = 0.002). The relative change in serum levels of dehydroepiandrosterone sulphate differed between the genders (p = 0.03). No significant changes were observed in the serum testosterone levels after 4 weeks of liquorice consumption, and the urine excretion of androgens (etiocholanolone and androstenedione) did not change. CONCLUSIONS: Liquorice in moderate doses primarily affects the cortisol metabolism and only marginally the androgen hormones. Gender may influence the action of liquorice.     

Tumor-specific expression of the novel cytochrome P450 enzyme, CYP2W1

A novel human cytochrome P450, CYP2W1, was cloned and expressed heterologously. No or very low CYP2W1 mRNA levels were detected in fetal and adult human tissues, expression was however seen in 54% of human tumor samples investigated (n=37), in particular colon and adrenal tumors. Western blotting also revealed high expression of CYP2W1 in some human colon tumors. In rat tissues, CYP2W1 mRNA was expressed preferentially in fetal but also in adult colon. The CYP2W1 gene was shown to encompass one functional CpG island in the exon 1-intron 1 region which was methylated in cell lines lacking CYP2W1 expression, but unmethylated in cells expressing CYP2W1. Re-expression of CYP2W1 was seen following demethylation by 5-Aza-2'-deoxycytidine. Transfection of HEK293 cells with CYP2W1 caused the formation of a properly folded enzyme, which was catalytically active with arachidonic acid as a substrate. It is concluded that CYP2W1 represents a tumor-specific P450 isoform with potential importance as a drug target in cancer therapy.     

Endothelial nitric oxide synthase reduces nitrite anions to NO under anoxia

In this work, we demonstrate that endothelial nitric oxide synthase is capable of anoxic reduction of nitrite anions to nitric oxide at physiological pH by absorption and EPR spectroscopy and electrochemical measurements. The nitrite reduction is achieved at the oxygenase domain of the protein and proceeds even in the absence of the tetrahydrobiopterin cofactor. The nitrite pathway increases by sixfold the NO production with respect to the regular arginine pathway under hypoxia, which is largely blocked. Therefore, basal levels of NO release could be sustained by anoxic nitrite reduction. The reaction suggests a new pathway for fast NO delivery under hypoxia, precisely when the vasodilating properties of nitric oxide are most needed.     

Characterization of late acyltransferase genes of Yersinia pestis and their role in temperature-dependent lipid A variation

Yersinia pestis is an important human pathogen that is maintained in flea-rodent enzootic cycles in many parts of the world. During its life cycle, Y. pestis senses host-specific environmental cues such as temperature and regulates gene expression appropriately to adapt to the insect or mammalian host. For example, Y. pestis synthesizes different forms of lipid A when grown at temperatures corresponding to the in vivo environments of the mammalian host and the flea vector. At 37 degrees C, tetra-acylated lipid A is the major form; but at 26 degrees C or below, hexa-acylated lipid A predominates. In this study, we show that the Y. pestis msbB (lpxM) and lpxP homologs encode the acyltransferases that add C12 and C(16:1) groups, respectively, to lipid IV(A) to generate the hexa-acylated form, and that their expression is upregulated at 21 degrees C in vitro and in the flea midgut. A Y. pestis deltamsbB deltalpxP double mutant that did not produce hexa-acylated lipid A was more sensitive to cecropin A, but not to polymyxin B. This mutant was able to infect and block fleas as well as the parental wild-type strain, indicating that the low-temperature-dependent change to hexa-acylated lipid A synthesis is not required for survival in the flea gut.     

Cultivation and transplantation of boar type A spermatogonia

A cell population enriched with type A spermatogonia has been isolated from the boar testes. Cell types occurring during isolation were morphologically characterized, factors maintaining the cultured spermatogonia in the undifferentiated state were studied, and these cells were transferred to sterile recipients preliminarily treated with busulfan. The cells of spermatogenic epithelium cultivated in vitro for 24 h were used for transfer experiments. The transfer efficiency was estimated within 27 and 29 days according to the histological picture of the testes and the isolated cultures. Spermatogenic cells at various developmental stages and a few Sertoli ells and spermatozoa were found on sections and in cell suspensions. Sperm samples could be taken from recipient boars within nine months after the transfer. Microsatellite analysis of DNA showed the endogenous pattern of spermatogenesis. Thus, it was shown that spermatogenic donor cells can restore and maintain spermatogenesis of a recipient for at least 30 days. However, the donor cells were fully forced by the recipient reserve cells, type A0 spermatogonia, within eight to nine months.     

Laser nanosurgery in cell biology

Since their first use in the early 60's, pulsed lasers have become increasingly popular for their ability to ablate biological tissue. Short laser pulses allow high precision surgery for biological and medical applications with minimal invasiveness. Performing highly targeted manipulation and ablation allows experiments impossible so far in development biology, cellular biology or even assisted reproductive technologies and laser surgery has been increasingly used over the last five years to answer key questions in Biology. Recently, picosecond UV and femtosecond IR laser pulses have been used to cleave microtubules and to severe actin stress fibers in vivo with a spatial precision in the submicrometer range to study their dynamics without affecting cell viability. We review recent findings on the underlying principles of pulsed laser nanosurgery mechanisms showing how the use of ultra short laser pulses increases precision and non-invasiveness of laser surgery. We show how the understanding of the surgical process allows one to distinguish between single cell ablation in living organisms or intracellular nanosurgery in living cells and we review recent applications to the study of forces and the quantification of cytoskeleton dynamics.     

An anthropoid-specific segmental duplication on human chromosome 1q22

Segmental duplications (SDs) play a key role in genome evolution by providing material for gene diversification and creation of variant or novel functions. They also mediate recombinations, resulting in microdeletions, which have occasionally been associated with human genetic diseases. Here, we present a detailed analysis of a large genomic region (about 240 kb), located on human chromosome 1q22, that contains a tandem SD, SD1q22. This duplication occurred about 37 million years ago in a lineage leading to anthropoid primates, after their separation from prosimians but before the Old and New World monkey split. We reconstructed the hypothetical unduplicated ancestral locus and compared it with the extant SD1q22 region. Our data demonstrate that, as a consequence of the duplication, new anthropoid-specific genetic material has evolved in the resulting paralogous segments. We describe the emergence of two new genes, whose new functions could contribute to the speciation of anthropoid primates. Moreover, we provide detailed information regarding structure and evolution of the SD1q22 region that is a prerequisite for future studies of its anthropoid-specific functions and possible linkage to human genetic disorders.     

13C, 15N Resonance Assignment of Parts of the HET-s Prion Protein in its Amyloid Form

The partial ¹⁵N and ¹³C solid-state NMR resonance assignment of the HET-s prion protein fragment 218–289 in its amyloid form is presented. It is based on experiments measured at MAS frequencies in the range of 20–40 kHz using exclusively adiabatic polarization-transfer schemes. The resonance assignment within each residue is based on two-dimensional ¹³C––¹³C correlation spectra utilizing the DREAM mixing scheme. The sequential linking of the assigned residues used a set of two- and three-dimensional ¹⁵N––¹³C correlation experiments. Almost all cross peaks visible in the spectra are assigned, but only resonances from 43 of the 78 amino-acid residues could be detected. The missing residues are thought to be highly disordered and/or highly dynamic giving rise to broad resonance lines that escaped detection in the experiments applied. The line widths of the observed resonances are narrow and comparable to line widths observed in micro-crystalline samples. The 43 assigned residues are located in two fragments of about 20 residues. Electronic Supplementary Material Supplementary material is available for this article at and is accessible for authorized users.     

A systematic review of randomised clinical trials of Tripterygium wilfordii for rheumatoid arthritis.

Tripterygium wilfordii is a Chinese herb with immunosuppressive effects and an established history of use in the treatment of rheumatoid arthritis (RA). We have carried out a systematic review of randomised clinical trials (RCTs) which assess the effectiveness of T. wilfordii in this indication. We included only randomised and controlled studies which tested the effectiveness of T. wilfordii monopreparations in the treatment of RA. Studies in any language were included. A search of five electronic databases from inception to February 2005 identified 18 articles which could potentially meet our inclusion criteria. Only 16 of these could be retrieved from the scientific literature and after reading these in full, only two unique RCTs meeting our inclusion criteria were identified. Both indicated that T. wilfordii has beneficial effects on the symptoms of RA. However, the literature indicates that T. wilfordii is associated with serious adverse events which make the risk-benefit analysis for this herb unfavourable. Therefore, we cannot recommend its use.     

Expression of otd orthologs in the amphipod crustacean, Parhyale hawaiensis

The arthropod head is a complex metameric structure. In insects, orthodenticle (otd) functions as a ‘head gap gene’ and plays a significant role in patterning and development of the anterior head ectoderm, the protocerebrum, and the ventral midline. In this study, we characterize the structure and developmental deployment of two otd paralogs in the amphipod crustacean, Parhyale hawaiensis. Photd1 is initially expressed at gastrulation through germband stages in a bilaterally symmetric, restricted region of the anterior head ectoderm and also in a single column of cells along the ventral midline. Late in embryogenesis, Photd1 is expressed within the developing anterior brain and the expression along the embryonic midline has become restricted to a stereotypic group of segmentally reiterated cells. The second ortholog Photd2, however, has a unique temporal–spatial expression pattern and is not detected until after the head lobes have been organized in the developing ectoderm of the germband during late germband stages. Anteriorly, Photd2 is coincident with the Photd1 head expression domain; however, Photd2 is not detected along the ventral midline during formation of the germband and only appears in the ventral midline late in embryonic development in a restricted group of cells distinct from those expressing Photd1. The early expression of Photd1 in the anterior head ectoderm is consistent with a role as a head gap gene. The more posterior expression of Photd1 is suggestive of a role in patterning the embryonic ventral midline. Photd2 expression appears too late to play a role in early head patterning but may contribute to latter patterning in restricted regions of both the head and the ventral midline. The comparative analysis of otd reveals the divergence of gene expression and gene function associated with duplication of this important developmental gene.Electronic Supplementary Material Supplementary material is available in the online version of this article at