A strategy for generation and balancing of autosome: Y chromosome translocations

We describe a method for generation and maintenance of translocations that move large autosomal segments onto the Y chromosome. Using this strategy we produced (2;Y) translocations that relocate between 1.5 and 4.8 Mb of the 2^nd chromosome.. All translocations were easily balanced over a male-specific lethal 1 (msl-1) mutant chromosome. Both halves of the translocation carry visible markers, as well as P-element ends that enable molecular confirmation. Halves of these translocations can be separated to produce offspring with duplications and with lethal second chromosome deficiencies . Such large deficiencies are otherwise tedious to generate and maintain.     

Oscillatory signaling processes: the how, the why and the where

Oscillatory processes in biological signal transduction have come under progressively increasing scrutiny in terms of their functional significance and mechanisms of emergence and regulation. Since oscillatory processes can be a by-product of rapid adaptation and can also easily emerge if the feedback underlying adaptive processes is inadvertently artificially enhanced, one needs to exercise caution in both claiming the existence of in vivo oscillations and seeking to assign to them a specific functional significance. Nevertheless, oscillations can be a powerful means of encoding and transferring information both in time and in space, thus possessing important potential advantages for evolutionary selection and stabilization. Thus periodicity in the cell responses to diverse persistent external stimuli might become a more recognized and even expected feature of signaling processes.     

Primary angioplasty: preprocedural pharmacological therapy

Primary coronary angioplasty has been shown to be an effective reperfusion therapy for patients with acute myocardial infarction, not only for those who present to PTCA centres but also for patients who present to hospitals without angioplasty facilities. With the increasing use of primary angioplasty more patients will be transferred to a (tertiary) PTCA centre. An increase in treatment delay is associated with a worse clinical outcome. The importance of an open infarct-related vessel at acute angiography is becoming clear. Pharmacological pretreatment of patients during transportation to a PTCA centre with the aim to open the infarct-related vessel in advance might be beneficial. Glycoprotein IIb/IIIa receptor blockers seem to be the agents of choice for facilitated PTCA. The safety and (cost) effectiveness of this pretreatment of patients transported to undergo primary angioplasty remain to be evaluated.     

Chiral phosphites derived from carboranes: electronic effect in catalytic asymmetric hydrogenation

A series of new fine-tunable monodentate phosphite and phosphoramidite ligands based on carboranes have been synthesized and used for asymmetric Rh-catalyzed hydrogenation of prochiral olefins with the result of up to 99.8% ee. Dependence of the enantioselectivity on the electron-withdrawing or electron-donating properties of the carboranyl substituent has been studied.     

RING domains functioning as E3 ligases reveal distinct structural features: a molecular dynamics simulation study

RING domain, a cysteine-rich motif that chelates two zinc ions, has been shown to regulate many biological processes such as mediating a crucial step in the ubiquitinylation pathway. In order to investigate the distinct structural features for the RING domains functioning as E3 ligases, several molecular dynamics simulations involving the c-Cbl, CNOT4 (with E3 ligase function), and p44 (no E3 ligase function) RING domains were conducted in this study. Our results reveal that the structural stability of the recognition site is a basic requirement for the RING domains functioning as E3 ligases. The structural stability of the recognition site is maintained by the hydrophobic core and hydrogen bonding network. Another important structural feature of the RING domains functioning as E3 ligases is the stable distances between the recognition site and the zinc ion binding sites S1 and S2. Moreover, the RING domains functioning as E3 ligases seem to exhibit lower beta stability due to the higher proportion of proline residues in their sequences. However, no significant difference of the other secondary (alpha and turn) and the tertiary structural stabilities can be observed among these three RING domains.