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PubMed2004

Paul Ehrlich--in search of the magic bullet.

In 2004, we celebrate the 150th anniversary of the birth of Paul Ehrlich, considered the founder of immunology. His life and work can be divided into three creative periods: first, he developed histological staining, then he accomplished his ground-breaking work on immunology, and eventually invented chemotherapy. Paul Ehrlich can be perceived as a man whose success was not the consequence of a will to power, but of his substantial interest in science.

Allergy and Immunology↗
PubMed2003

Caffeine and human DNA metabolism: the magic and the mystery.

The ability of caffeine to reverse cell cycle checkpoint function and enhance genotoxicity after DNA damage was examined in telomerase-expressing human fibroblasts. Caffeine reversed the ATM-dependent S and G2 checkpoint responses to DNA damage induced by ionizing radiation (IR), as well as the ATR- and Chk1-dependent S checkpoint response to ultraviolet radiation (UVC). Remarkably, under conditions in which IR-induced G2 delay was reversed by caffeine, IR-induced G1 arrest was not. Incubation in caffeine did not increase the percentage of cells entering the S phase 6-8h after irradiation; ATM-dependent phosphorylation of p53 and transactivation of p21(Cip1/Waf1) post-IR were resistant to caffeine. Caffeine alone induced a concentration- and time-dependent inhibition of DNA synthesis. It inhibited the entry of human fibroblasts into S phase by 70-80% regardless of the presence or absence of wildtype ATM or p53. Caffeine also enhanced the inhibition of cell proliferation induced by UVC in XP variant fibroblasts. This effect was reversed by expression of DNA polymerase eta, indicating that translesion synthesis of UVC-induced pyrimidine dimers by DNA pol eta protects human fibroblasts against UVC genotoxic effects even when other DNA repair functions are compromised by caffeine.

Ataxia Telangiectasia Mutated Proteins↗
PubMed2004

The potion's magic.

During remembering, a perception of the past is constructed that includes sensory details of the original episode. In this issue of Neuron, Gottfried and colleagues provide evidence for selective piriform activation during recognition of visual cues previously paired with scents. These data provide evidence of sensory-specific reactivation of olfactory cortex during remembering.

Auditory Cortex↗
PubMed2005

Phyllotaxis--a new chapter in an old tale about beauty and magic numbers.

Phyllotaxis, the regular arrangement of leaves and flowers around the stem, is one of the most fascinating patterning phenomena in biology. Numerous theoretical models, that are based on biochemical, biophysical and other principles, have been proposed to explain the development of the patterns. Recently, auxin has been identified as the inducer of organ formation. An emerging model for phyllotaxis states that polar auxin transport in the plant apex generates local peaks in auxin concentration that determine the site of organ formation and thereby the different phyllotactic patterns found in nature. The PIN proteins play a primary role in auxin transport. These proteins are localized in a polar fashion, reflecting the directionality of polar auxin transport. Recent evidence shows that most aspects of phyllotaxis can be explained by the expression pattern and the dynamic subcellular localization of PIN1.

Body Patterning↗
PubMed2006

The diagnostic accuracies of chronic obstructive pulmonary disease (COPD) in general practice: The results of the MAGIC (Manchester Airways Group Identifying COPD) study.

BACKGROUND: Although it is generally accepted that chronic obstructive pulmonary disease (COPD) is underdiagnosed, there is little objective information concerning the size of the problem in the UK. METHOD: Patients from two general practices were offered spirometry if they were aged 30 or older, had reported ever smoking in one of four postal respiratory surveys (1993-2001), and/or reported four or more symptoms or risk factors in 2001 indicating likely obstructive airways disease. RESULTS: Of 2646 subjects invited, 871 attended and 825 had adequate spirometry results for analysis. In all, 163 patients had spirometrically-confirmed COPD; 103 of these (63.2%) had no recorded COPD in their practice records, including 14 out of 31 (45.2%) whose spirometry results classified them as having severe or very severe COPD. CONCLUSION: This study found a considerable under-recording of COPD in two general practices. This may be due to a combination of administrative and diagnostic problems (including the under-use of spirometers), and a reluctance of patients to present with their symptoms. These results have important implications in terms of unmet need and resource utilisation.

Adult↗
PubMed2005

Spectral editing based on selective excitation and Lee-Goldburg cross-polarization under magic angle spinning.

We show that a Gaussian-shaped pulse can be used to excite selected 1H signals in hydroxyapatite, monetite and H-Y zeolite loaded with trimethylphosphine oxide (TMPO). This selective excitation method can be incorporated into Lee-Goldburg (LG) cross-polarization to obtain useful spectral editing opportunity. This new strategy has been applied to identify the Brønsted and the Lewis acid sites in H-Y zeolite using TMPO as the probe molecule.

Algorithms↗
PubMed2004

Magic touch: how does cell-cell adhesion trigger actin assembly?

The formation of cadherin-mediated cell-cell junctions is accompanied by a profound remodeling of the actin cytoskeleton. The Arp2/3 complex and its activator cortactin drive the assembly of branching actin-filament arrays, and formin-1 promotes the nucleation of non-branching actin filaments. Recruitment of these actin nucleators to nascent adhesions, formation of the links between them and the cytoplasmic cadherin domain, and triggering of their actin-polymerizing functions are vital steps in the development of cell-cell junctions. In this article, I discuss recent results showing that proteins involved in the regulation of actin polymerization have crucial roles in the development and maintenance of the cadherin junctions.

Actins↗
PubMed2005

Small non-coding RNAs as magic bullets.

RNA interference (RNAi) - inhibition of gene expression by small, non-coding RNAs [small interfering RNAs (siRNAs) or microRNAs (miRNAs)] - has changed our view of regulation of expression dramatically. The application of siRNAs for both functional analysis of genes and medication raises several questions. These include the design of the double-stranded oligonucleotides, their preparation and introduction into cells or animals either as chemically synthesized entities or as transcripts from a suitable vector. Delivery of the oligonucleotides, choice of vector, chemical modification to stabilize against nucleases and avoidance of side effects (e.g. stimulation of interferons) are major challenges. Work to identify the multiple targets of miRNAs is still in its infancy, and a clear distinction between siRNAs and miRNAs is difficult in some instances. Moreover, transcriptional silencing by RNAi is poorly understood; it is evident that the siRNA machinery is involved but the details await clarification. Given the multitude of interactions of the small non-coding RNAs revealed so far, we should be prepared to encounter, as yet, undiscovered interactions and mechanisms.

Animals↗
PubMed2006

Heterosis: revisiting the magic.

Heterosis results in the phenotypic superiority of a hybrid over its parents with respect to traits such as growth rate, reproductive success and yield. This hybrid vigor is determined by non-mutually exclusive mechanisms, including dominance complementation, overdominance and epistasis. Heterotic genes responsible for elevating crop yields are now being sought using genomics, particularly transcriptomics, but with contradictory results. Because heterosis is an environmentally modified quantitative phenotype, genomic analyses alone will not suffice. Future research should focus on integrating genomic tools in a framework of comprehensive quantitative trait locus (QTL)-based phenotyping, followed by map-based cloning. This 'phenomics' approach should identify loci controlling heterotic phenotypes, and improve understanding of the role of heterosis in evolution and the domestication of crop plants.

Animals↗
PubMed2005

The 'magic' of L-dopa: why is it the gold standard Parkinson's disease therapy?

The chronic treatment of Parkinson's disease with L-dopa is often associated with fluctuations of motor response and dyskinesias. Therefore, to overcome the adverse effects of the long-term use of L-dopa, directly acting dopamine receptor agonists have been introduced. However, L-dopa remains the most effective treatment of the slowness of movement, increased muscle tone, and tremor that are typical of Parkinson's disease. Why is this so? In this article, we discuss evidence that suggests that dopamine produced from L-dopa has a larger number of actions compared with dopamine receptor agonists. In addition to stimulating D1- and D2-like dopamine receptors, dopamine might also activate adrenoceptors, novel dopamine sites, the dopamine transporter and trace amine receptors, all of which might contribute to the superior effect of L-dopa in Parkinson's disease.

Antiparkinson Agents↗
PubMed2003

Cardioplegia in pediatric cardiac surgery: do we believe in magic?

Cardioplegia has become the gold standard of myocardial protection for practically every type of heart surgery during which the ascending aorta must be clamped. Although there is little doubt about the efficacy of cardioplegia in the adult heart, there are few studies on the pediatric heart and their results are contradictory. The physiology of pediatric heart muscle differs considerably from that of the adult myocardium. The pediatric heart distinguishes itself from that of the adult most impressively in its greater tolerance for ischemia. This ischemia tolerance is enhanced by the use of hypothermia. Considering that hypothermia is a powerful tool to prolong ischemia tolerance and that most pediatric cardiac surgeons report similar results using different types of cardioplegia, some surgeons are tempted to suspect that the contribution of the cardioplegia composition to protecting the pediatric heart may be overestimated. This provocative statement is critically discussed in this article. We examine the protective potential of cardioplegia (in various compositions), or of hypothermia, or of both in pediatric cardiac surgery. We pay special attention to several key differences between the physiologies of the pediatric myocardium and the adult myocardium and attempt to relate them to the available surgical methods of myocardial protection. We conclude that the composition of cardioplegia indeed is an important component of successful operative management in pediatric heart surgery. We provide evidence that the benefit of cardioplegia over hypothermia alone is minor at low temperatures (below 15 degrees C), but becomes substantial when the temperature increases.

Cardiac Surgical Procedures↗