Embed Size (px)
Citation preview
Ups and downs
By combining DNA microarray andproteomics approaches, Swiss researchershave analysed how bacteria combat antibioticdrugs. To address this question, HansGmuender and his colleagues usedHaemophilus influenzae and two antibiotics –novobiocin and ciprofloxacin – that havedifferent mechanisms of action. Thecombined results of gene transcription andtranslation, provided by the gene chips and 2Dgel electrophoresis, respectively, provide areal-time picture of which genes areupregulated, and which are downregulated inthe presence of the two antibiotics. Analysis ofsuch gene expression profiles, which willdepend on which antibiotic is used, willfacilitate the development of new antibioticdrugs and aid our understanding of drugresistance. The results were presented in theJanuary issue of Genome Research. AH
I can’t get no...The neurotransmitter dopamine regulates thebrain processes that control movement,emotional response and the ability toexperience pleasure and pain. It plays a majorrole in addiction: cocaine, alcohol and otherdrugs alter dopamine function, promotingfeelings of satisfaction and pleasure. ABrookhaven National Laboratory study[Lancet (2001) 357, 354–357] now indicatesthat obese individuals have fewer dopaminereceptors, which might explain the need to eatmore to stimulate these pleasure pathways,analogous to the increasing cravings of drugaddicts. ‘Since eating, like the use of addictivedrugs, is a highly reinforcing behavior,inducing feelings of gratification and pleasure,we suspected that obese people might haveabnormalities in brain dopamine activity aswell,’ says psychiatrist Nora Volkow, who wasalso involved in the study. Dopamine-receptorlevels were tested in ten severely obeseindividuals and ten normal-weight controlindividuals by injection of a radiotracer thatwas tagged to bind to dopamine receptors.Positron emission tomography (PET)scanning then indicated receptor intensity bythe strength of the signal. Obese individualshad fewer dopamine receptors than normal-
weight individuals. Furthermore, the numberof dopamine receptors decreased as theobesity of the individual increased. It is notconclusive whether dopamine receptor levelsare endogenously low in obese individuals,thereby triggering over-eating, or whether thedecrease in the number of receptors is a resultof the brain’s effort to compensate forchronically high dopamine levels broughtabout by over-eating. ‘The results from thisstudy suggest that strategies aimed atimproving dopamine function might bebeneficial in the treatment of obeseindividuals,’ says physician Gene-Jack Wang,the lead scientist on the study. Drugs alteringdopamine function are often themselvesaddictive and are therefore of limited use.Exercise, however, is known to increasedopamine release and raise the number ofdopamine receptors – a most beneficial effect,in view of these recent results. S. de B.(http://www.bnl.gov/bnlweb/pubaf/pr/bnlpr020101.htm)
‘A’ forming experience
The stringent guidelines for vitamin A intakeduring pregnancy have been justified by theidentification of a single enzyme that activatesthe expression of specific target genesthroughout the embryo. The enzyme CPY26metabolizes retinoic acid (RA), an essentialderivative of vitamin A. The unevendistribution of this vitamin along the central-body axis of the developing embryo isessential for normal development. Over- orunder-dosage of vitamin A during pregnancyresults in morphological defects ranging fromcranio-facial, cardiac, lung and genito-urinaryabnormalities to neurological abnormalities.The level of RA in the embryo is maintained bya delicate balance between RA synthesis andRA degradation. Hiroshi Hamada et al. [GenesDev. (2001) 15, 213–225] and Martin Petkovichet al. [Genes Dev. (2001) 15, 226–240],
performed genetic ablation of murine CYP26,which resulted in elevated RA levels in specificembryonic areas. The mutant mouseembryos were not viable – major defectsincluding spina bifida, truncation of theposterior body and abnormalities of thekidney, brain and vertebrae were seen. CPY26seems, therefore, to protect the developingembryo from the deleterious effects ofexcessive RA activity. S. de B.(http://meds.queensu.ca/medicine/crl/petkovich)
Genome newsAt long last the wait is over and last month,after a huge build up, results of the initialsequencing and analysis of the humangenome appeared both in Nature (whopublished the sequence analysis and maps ofthe publicly funded consortium) and inScience (who presented the privately fundedCelera data). Here is just a taster of theinformation that was revealed by the 2.9billion bases that make up our genome. Alltold, we have about 35 000 genes(approximately twice as many asCaenorhabditis elegans). Although this wasno great surprise to insiders (who had beenfrantically revising down initial estimates of150 000 genes), it was to those more removedfrom the action. About 223 of our genes (allencoding enzymes) appear to have beenobtained via horizontal gene transfer frombacteria. Moreover, approximately half ourgenome is made up of repeat elements, ahigher percentage than that found in theArabidopsis and C. elegans genomes, andvastly more than the 3% of repeat sequencespresent in the Drosophila melanogastergenome. This could explain why the shotgunapproach to sequencing and compilinggenomes was more successful for the fly thanfor the human genome. Another surprisingfact was that the variation across humangenomes is low (~1 nucleotide per thousand),indicating that we probably evolved from avery small population of individuals.However, to really find out what makes us tick,the complete story can be obtained fromNature (2001) 409, 745–964 and Science(2001) 291, 1145–1434. EW
TRENDS in Biochemical Sciences Vol.26 No.3 March 2001
http://tibs.trends.com 0968-0004/01/$ – see front matter © 2001 Elsevier Science Ltd. All rights reserved.
154 News&Comment
Stephanie de [email protected] [email protected] [email protected]
