Partial deficiency of erythrocyte spectrin in hereditary spherocytosis

Hereditary spherocytosis (HS) is a common, clinically heterogeneous haemolytic anaemia in which the primary erythrocyte defect is believed to be some abnormality in the spectrin-actin membrane skeleton, leading to loss of surface membrane. Recessively inherited spectrin deficiency with extreme erythrocyte fragility and spherocytosis has been identified in certain mutant mice and two severely anaemic humans. Although suspected, deficiency of spectrin has not been demonstrated in less severe forms of human HS. We not report the quantitation of erythrocytes spectrin by radioimmunoassay. We found that normal erythrocytes contained 240,000 copies of spectrin heterodimer, whereas erythrocytes from 14 patients with a variety of types of HS were all partially deficient in spectrin (range 74,000-200,000 copies), the magnitude of the deficiency correlating with the severity of the disease. Spectrin deficiency of varying degrees is common in HS and probably represents the principal structural defect leading to loss of surface membrane.     

Putting endotoxin to work for us: Monophosphoryl lipid A as a safe and effective vaccine adjuvant

The development of non-infectious subunit vaccines greatly increases the safety of prophylactic immunization, but also reinforces the need for a new generation of immunostimulatory adjuvants. Because adverse effects are a paramount concern in prophylactic immunization, few new adjuvants have received approval for use anywhere in the developed world. The vaccine adjuvant monophosphoryl lipid A is a detoxified form of the endotoxin lipopolysaccharide, and is among the first of a new generation of Toll-like receptor agonists likely to be used as vaccine adjuvants on a mass scale in human populations. Much remains to be learned about this compound’s mechanism of action, but recent developments have made clear that it is unlikely to be simply a weak version of lipopolysaccharide. Instead, monophosphoryl lipid A’s structure seems to have fortuitously retained several functions needed for stimulation of adaptive immune responses, while shedding those associated with pro-inflammatory side effects. Received 25 April 2008; received after revision 05 June 2008; accepted 10 June 2008     

The far-ultraviolet signature of the 'missing' baryons in the Local Group of galaxies

The number of baryons detected in the low-redshift (z < 1) Universe is far smaller than the number detected in corresponding volumes at higher redshifts. Simulations of the formation of structure in the Universe show that up to two-thirds of the 'missing' baryons may have escaped detection because of their high temperature and low density. One of the few ways to detect this matter directly is to look for its signature in the form of ultraviolet absorption lines in the spectra of background sources such as quasars. Here we show that the amplitude of the average velocity vector of 'high velocity' O vi (O5+) absorption clouds detected in a survey of ultraviolet emission from active galactic nuclei decreases significantly when the vector is transformed to the frames of the Galactic Standard of Rest and the Local Group of galaxies. At least 82 per cent of these absorbers are not associated with any 'high velocity' atomic hydrogen complex in our Galaxy, and are therefore likely to result from a primordial warm-hot intergalactic medium pervading an extended corona around the Milky Way or the Local Group. The total mass of baryons in this medium is estimated to be up to approximately 10(12) solar masses, which is of the order of the mass required to dynamically stabilize the Local Group.