Molecular biology of 11β-hydroxylase and 11β-hydroxysteroid dehydrogenase enzymes

There are two steroid 11β-hydroxylase isozymes encoded by the CYP11B1 and CYP11B2 genes on human chromosome 8q. The first is expressed at high levels in the normal adrenal gland, has 11β-hydroxylase activity and is regulated by ACTH. Mutations in the corresponding gene cause congenital adrenal hyperplasia due to 11β-hydroxylase deficiency; thus, this isozyme is required for cortisol biosynthesis. The second isozyme is expressed at low levels in the normal adrenal gland but at higher levels in aldosterone-secreting tumors, and has 11β-hydroxylase, 18-hydroxylase and 18-oxidase activities. The corresponding gene is regulated by angiotensin II, and mutations in this gene are found in persons who are unable to synthesize aldosterone due to corticosterone methyloxidase II deficiency. Thus, this isozyme is required for aldosterone biosynthesis.

Cortisol and aldosterone are both effective ligands of the “mineralocorticoid” receptor in vitro, but only aldosterone is a potent mineralocorticoid in vivo. This apparent specificity occurs because 11β-hydroxysteroid dehydrogenase in the kidney converts cortisol to cortisone, which is not a ligand for the receptor. This enzyme is a “short-chain” dehydrogenase which is encoded by a single gene on human chromosome 1. It is possible that mutations in this gene cause a form of childhood hypertension called apparent mineralocorticoid excess, in which the mineralocorticoid receptor is not protected from high concentrations of cortisol.     

杧果剪叶象的寄主适合度研究

寄主适合度是指寄主植物对昆虫下一代的繁殖贡献,其大小反映了食物对昆虫的综合影响。杧果(Mangifera indica)和扁桃(M.sylvatica)是杧果剪叶象(Deporaus marginatus Pascoe)的两个主要寄主。本文测定了三种杧果品种和扁桃的适合度,现报道如下。     

The relative lengths of individual telomeres are defined in the zygote and strictly maintained during life

Previous studies have indicated that average telomere length is partly inherited ( Slagboom et al., 1994 ; Rufer et al., 1999 ) and that there is an inherited telomere pattern in each cell ( Graakjaer et al., 2003 ); ( Londoño‐Vallejo et al., 2001 ). In this study, we quantify the importance of the initially inherited telomere lengths within cells, in relation to other factors that influence telomere length during life. We have estimated the inheritance by measuring telomere length in monozygotic (MZ) twins using Q‐FISH with a telomere specific peptide nucleic acid (PNA)‐probe. Homologous chromosomes were identified using subtelomeric polymorphic markers. We found that identical homologous telomeres from two aged MZ twins show significantly less differences in relative telomere length than when comparing the two homologues within one individual. This result means that towards the end of life, individual telomeres retain the characteristic relative length they had at the outset of life and that any length alteration during the lifespan impacts equally on genetically identical homologues. As the result applies across independent individuals, we conclude that, at least in lymphocytes, epigenetic/environmental effects on relative telomere length are relatively minor during life.     

Human Bcl-2 protects against AMPA receptor-mediated apoptosis

Dysfunctions of the (S)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) subtype of ionotropic receptor for the brain's major excitatory neurotransmitter, L-glutamate, occur in various neurological conditions. We have previously demonstrated that AMPA receptor-mediated excitotoxicity occurs by apoptosis and here examined the influence of the expression of cell death repressor gene Bcl-2 on this excitotoxic insult. Using neuronal cortical cultures prepared from transgenic mice expressing the human Bcl-2 gene, the influence of Bcl-2 on AMPA receptor-mediated neuronal death was compared with that seen with staurosporine and H2O2. At day 6 cultures were exposed to AMPA (0.1-100 microM), and cellular injury was analyzed 48 h after insult using phase-contrast microscopy, a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide viability assay, and DNA staining with 4,6-diamidino-2-phenylindole and Sytox Green. AMPA produced a concentration-dependent increase in cell death that was significantly attenuated by human Bcl-2. AMPA (3 microM) increased the number of apoptotic nuclei to 60% of control in wild-type cultures, and human Bcl-2 significantly decreased the number of apoptotic nuclei to 30% of AMPA-treated cultures. Human Bcl-2 only provided significant neuroprotection against neuronal injury induced by low concentrations of staurosporine (1-10 nM) and H2O2 (0.1-30 microM) and where neuronal death was by apoptosis, but not against H2O2-induced necrosis. Our findings indicate that overexpression of Bcl-2 in primary cultured neurons protects in an insult-dependent manner against AMPA receptor-mediated apoptosis, whereas protection was not seen against more traumatic insults. This study provides new insights into the molecular therapeutics of neurodegenerative conditions.     

Estimating maximum economic yield in multispecies fisheries: a review

Fisheries can generate substantial economic returns to society if managed with economic targets as the main objective, that is with biomass, catch, and effort levels that correspond to maximum economic yield (MEY), although the move to such targets presents a number of challenges. These are compounded in multispecies fisheries, as it is not possible to achieve all individual targets simultaneously if targets are set on a species-by-species basis. Identifying appropriate targets both conceptually and empirically has also proven challenging, and consequently the implementation of economic targets to real world fisheries have been limited to a small number of data-rich and high-valued fisheries, with reliance on proxy target reference points in other fisheries. Moreover, these application has been limited due to unknowns as to what proxies should be used under different circumstances. Here, we review the alternative ways in which MEY has been estimated and applied in multispecies fisheries. We also review the roles and potential use of proxy target reference points for multispecies MEY in data-limited fisheries, building on Australian’s experience in implementing such a policy.     

Lineage‐specific plasmid acquisition and the evolution of specialized pathogens in Bacillus thuringiensis and the Bacillus cereus group

Bacterial plasmids can vary from small selfish genetic elements to large autonomous replicons that constitute a significant proportion of total cellular DNA. By conferring novel function to the cell, plasmids may facilitate evolution but their mobility may be opposed by co‐evolutionary relationships with chromosomes or encouraged via the infectious sharing of genes encoding public goods. Here, we explore these hypotheses through large‐scale examination of the association between plasmids and chromosomal DNA in the phenotypically diverse Bacillus cereus group. This complex group is rich in plasmids, many of which encode essential virulence factors (Cry toxins) that are known public goods. We characterized population genomic structure, gene content and plasmid distribution to investigate the role of mobile elements in diversification. We analysed coding sequence within the core and accessory genome of 190 B. cereus group isolates, including 23 novel sequences and genes from 410 reference plasmid genomes. While cry genes were widely distributed, those with invertebrate toxicity were predominantly associated with one sequence cluster (clade 2) and phenotypically defined Bacillus thuringiensis. Cry toxin plasmids in clade 2 showed evidence of recent horizontal transfer and variable gene content, a pattern of plasmid segregation consistent with transfer during infectious cooperation. Nevertheless, comparison between clades suggests that co‐evolutionary interactions may drive association between plasmids and chromosomes and limit wider transfer of key virulence traits. Proliferation of successful plasmid and chromosome combinations is a feature of specialized pathogens with characteristic niches (Bacillus anthracis, B. thuringiensis) and has occurred multiple times in the B. cereus group.     

Identification of S-(2,5-dihydroxyphenyl)-cysteine and S-(2,5-dihydroxyphenyl)-N-acetyl-cysteine as urinary metabolites of acetaminophen in the mouse. Evidence for p-benzoquinone as a reactive intermediate in acetaminophen metabolism

S-(2,5-Dihydroxyphenyl)-cysteine and S-(2,5-dihydroxyphenyl)-N-acetyl-cysteine [the cysteine- and N-acetyl-cysteine adducts, respectively, of hydroquinone (HQ)] were identified and quantified in the urine of mice administered [ring-U-14C]acetaminophen [14C]APAP, 200 mg kg-1, i.p.). Urine was collected for 24 h and fractionated by HPLC to isolate the above adducts. These conjugates were then converted to a common derivative, viz. O,O',S-tris-acetyl-3-thio-hydroquinone, which was characterized by GC/MS. Neither of the HQ adducts was detected in the urine of control mice which had not received APAP. Quantification of urinary HQ-cysteine and HQ-N-acetyl-cysteine was performed by HPLC techniques, which indicated that these conjugates accounted for approx. 1.5% of the administered dose of APAP after 24 h, a figure which is equivalent to 6.3% of the corresponding APAP-thiol conjugates in the urine. These findings provide strong indirect evidence that p-benzoquinone is formed as a reactive, but apparently non-hepatotoxic, metabolite of APAP in vivo.     

Observations on the length and angle of declination of the vulva and its relation to fertility in the mare.

An instrument has been designed to measure the effective length (l) and angle of declination (a) of the vulva in the mare. The product, la, provides an index (Caslick Index) suitable for determining the necessity for Caslick's operation in mares not exhibiting the classical symptoms associated with pneumovagina. The value l showed a significant increase (P less than 0.05) with increased age in breeding mares. Studies on 9020 mares revealed that all caslicked mares, and mares with a Caslick Index of less than 150, had a significantly higher pregnancy rate than non-caslicked mares of similar age and a Caslick Index greater than 150. Values of 100 and over should be an indication for more careful clinical appraisal of the genital tract in those mares not as yet clinically affected. Nulliparous mares caslicked for racing had a significantly higher pregnancy rate than non-casliked maiden mares in their first year at stud.