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Biomedical subjects

Michael Lehmann

Publications and source records attributed to Michael Lehmann.

5 recordsLinked to original sources

Pipsqueak and GAGA factor act in concert as partners at homeotic and many other loci.

The Drosophila GAGA factor (GAF) controls transcription and other chromosome functions by altering chromatin structure. We found that a second GAGA-binding protein of Drosophila, Pipsqueak (Psq), can directly bind to GAF and is associated with GAF in vivo. Genetic interaction studies provide evidence that Psq and GAF act together in the transcriptional activation and silencing of homeotic genes. A complete colocalization of Psq and GAF on polytene interphase chromosomes and mitotic chromosomes suggests that the two proteins cooperate as general partners not only at homeotic loci, but also at hundreds of other chromosomal sites.

Alleles↗

The Drosophila Pipsqueak protein defines a new family of helix-turn-helix DNA-binding proteins.

Many prokaryotic and eukaryotic DNA-binding proteins use a helix-turn-helix (HTH) structure for DNA recognition. Here we describe a new family of eukaryotic HTH proteins, the Pipsqueak (Psq) family, which includes proteins from fungi, sea urchins, nematodes, insects, and vertebrates. Three subgroups of the Psq family can be distinguished. Like the HTH proteins of the prokaryotic resolvase family, members of the CENP-B/transposase subgroup catalyze site-specific recombination reactions. This functional conservation, together with a primary sequence similarity between the resolvase and Psq DNA-binding domains, suggests that the resolvase and Psq families are evolutionarily linked. More than half of the newly identified Drosophila Psq proteins contain a BTB protein-protein interaction domain. All proteins of this BTB subgroup belong to the conserved Tramtrack group of BTB-domain proteins. About half of the members of the Tramtrack group contain a Psq domain, while the other half is made up of proteins that contain a zinc finger domain. Thus, nearly all members of this group appear to be DNA-binding proteins. Among other developmental regulators, the Drosophila cell death protein E93 was found to contain a Psq motif and to define a third subgroup of Psq domain proteins. The high sequence conservation of the E93 Psq motif allowed the identification of E93 orthologs in humans and lower metazoans.

Amino Acid Sequence↗

Gender differences in arrhythmias.

Electrocardiographic and electrophysiologic differences between men and women have long been noted. Women have a higher intrinsic heart rate than men, along with a longer corrected QT interval and a shorter sinus nodal recovery time. The incidence of and risk factors for a variety of arrhythmias differ between men and women. Atrioventricular nodal reentry tachycardia has a 2:1 female-to-male predominance, while accessory pathways are twice as frequent in men. Although atrial fibrillation is more prevalent in men of all age groups, the absolute numbers of men and women with atrial fibrillation are equal, and the associated morbidity and mortality experienced by women with atrial fibrillation appear to be worse. Women have a lower incidence of sudden cardiac death, and female survivors of sudden cardiac death have a lower frequency of spontaneous or inducible ventricular tachycardia. On the other hand, drug-induced torsade de pointes and symptomatic long QT syndrome have a female predominance. Therefore, greater caution should be used when prescribing QT-prolonging drugs in women. The incidence of arrhythmias is increased during pregnancy, and management of pregnant patients poses a significant challenge. The mechanisms of these gender differences are unclear but may be related to hormonal effects and the shorter QT interval in adult males. Pharmacologic and nonpharmacologic therapies are usually equally efficacious, but the risks of pharmacologic therapy are different in men and women. Atrial fibrillation may be more difficult to treat in women.

Arrhythmias, Cardiac↗

Ferroelectric electron holography.

Ferroelectrics are increasingly important as materials in semiconductor technology, e.g. for building non-volatile memory chips. For optimisation of the properties of such devices, there is an urgent need for methods, which analyse the ferroelectric properties at nanometer scale. Furthermore, the basic understanding of the interaction of ferroelectrics with electrons in the transmission electron microscopy is still incomplete. It is shown that electron holography offers a promising way to understand and investigate ferroelectrics in the electron microscope.

Journal Article↗

Tutorial on off-axis electron holography.

Through recent years, off-axis electron holography has helped us to understand and to overcome some experimental restrictions in transmission electron microscopy. With development of powerful electron microscopes, slow-scan CCD cameras, and computers, holography is not an academic technique anymore used by specialized laboratories. Holography has proven its wide range of applications in solving real-world problems in materials science and biology. At medium resolution, that is, on nanometer scale, holography allows access to large area phase contrast produced by magnetic fields and electric potentials. In the high-resolution domain, holography unveils its power by unscrambling amplitude and phase of the electron wave, resulting in an improved lateral resolution up to the information limit. Holography is a thoroughly quantitative method, and, in combination with the perfect zero-loss filtering inherent to this method, the interpretation of the reconstructed data is strongly simplified. After outlining the basics of holography, in this tutorial we focus on development of a step-by-step procedure for recording and reconstruction of holograms. At the end, some recent applications are discussed.

Holography↗