Structure of oxidized alpha-haemoglobin bound to AHSP reveals a protective mechanism for haem

The synthesis of haemoglobin A (HbA) is exquisitely coordinated during erythrocyte development to prevent damaging effects from individual alpha- and beta-subunits. The alpha-haemoglobin-stabilizing protein (AHSP) binds alpha-haemoglobin (alphaHb), inhibits the ability of alphaHb to generate reactive oxygen species and prevents its precipitation on exposure to oxidant stress. The structure of AHSP bound to ferrous alphaHb is thought to represent a transitional complex through which alphaHb is converted to a non-reactive, hexacoordinate ferric form. Here we report the crystal structure of this ferric alphaHb-AHSP complex at 2.4 A resolution. Our findings reveal a striking bis-histidyl configuration in which both the proximal and the distal histidines coordinate the haem iron atom. To attain this unusual conformation, segments of alphaHb undergo drastic structural rearrangements, including the repositioning of several alpha-helices. Moreover, conversion to the ferric bis-histidine configuration strongly and specifically inhibits redox chemistry catalysis and haem loss from alphaHb. The observed structural changes, which impair the chemical reactivity of haem iron, explain how AHSP stabilizes alphaHb and prevents its damaging effects in cells.     

Rapid,quantitative adipose conversion of chicken fibroblasts by high concentrations of chicken serum or plasma

Summary Rapid, quantitative adipose conversion of chicken fibroblasts occurs when these cells are cultured in undiluted commercial chicken serum or plasma. Fresh serum and plasma acquire this property after ageing.These studies were carried out with grants from the Richardson Foundation, the National Cancer Institute of Canada, and the Canadian Heart Foundations.To whom requests for reprints should be sent.     

Age dependent variation of serum creatine phosphokinase levels in pigs

Zusammenfassung Infolge Muskeltätigkeit steigt bekanntlich der Creatin-Phosphokinase-Spiegel (CPK) im Serum. Es wird nun eine Abhängigkeit des Serum-CPK-Wertes vom Alter festgestellt. Es ist daher wichtig, nichtspezifische Ursachen eines gesteigerten CPK-Spiegels auszuschalten, ehe eine Diagnose der Muskelerkrankung gestellt wird.

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We thankR. T. Naude for advice. This work was supported by the Atomic Energy Board of South Africa and the Senate of the University of the Witwatersrand.     

Functional analysis of secreted and transmembrane proteins critical to mouse development.

We describe the successful application of a modified gene-trap approach, the secretory trap, to systematically analyze the functions in vivo of large numbers of genes encoding secreted and membrane proteins. Secretory-trap insertions in embryonic stem cells can be transmitted to the germ line of mice with high efficiency and effectively mutate the target gene. Of 60 insertions analyzed in mice, one-third cause recessive lethal phenotypes affecting various stages of embryonic and postnatal development. Thus, secretory-trap mutagenesis can be used for a genome-wide functional analysis of cell signaling pathways that are critical for normal mammalian development and physiology.     

Anti-planetward auroral electron beams at Saturn

Strong discrete aurorae on Earth are excited by electrons, which are accelerated along magnetic field lines towards the planet. Surprisingly, electrons accelerated in the opposite direction have been recently observed. The mechanisms and significance of this anti-earthward acceleration are highly uncertain because only earthward acceleration was traditionally considered, and observations remain limited. It is also unclear whether upward acceleration of the electrons is a necessary part of the auroral process or simply a special feature of Earth's complex space environment. Here we report anti-planetward acceleration of electron beams in Saturn's magnetosphere along field lines that statistically map into regions of aurora. The energy spectrum of these beams is qualitatively similar to the ones observed at Earth, and the energy fluxes in the observed beams are comparable with the energies required to excite Saturn's aurora. These beams, along with the observations at Earth and the barely understood electron beams in Jupiter's magnetosphere, demonstrate that anti-planetward acceleration is a universal feature of aurorae. The energy contained in the beams shows that upward acceleration is an essential part of the overall auroral process.