CBS domains form energy-sensing modules whose binding of adenosine ligands is disrupted by disease mutations

CBS domains are defined as sequence motifs that occur in several different proteins in all kingdoms of life. Although thought to be regulatory, their exact functions have been unknown. However, their importance was underlined by findings that mutations in conserved residues within them cause a variety of human hereditary diseases, including (with the gene mutated in parentheses): Wolff-Parkinson-White syndrome (γ2 subunit of AMP-activated protein kinase); retinitis pigmentosa (IMP dehydrogenase-1); congenital myotonia, idiopathic generalized epilepsy, hypercalciuric nephrolithiasis, and classic Bartter syndrome (CLC chloride channel family members); and homocystinuria (cystathionine β-synthase). AMP-activated protein kinase is a sensor of cellular energy status that is activated by AMP and inhibited by ATP, but the location of the regulatory nucleotide-binding sites (which are prime targets for drugs to treat obesity and diabetes) was not characterized. We now show that tandem pairs of CBS domains from AMP-activated protein kinase, IMP dehydrogenase-2, the chloride channel CLC2, and cystathionine β-synthase bind AMP, ATP, or S-adenosyl methionine,while mutations that cause hereditary diseases impair this binding. This shows that tandem pairs of CBS domains act, in most cases, as sensors of cellular energy status and, as such, represent a newly identified class of binding domain for adenosine derivatives

A quasi classical approach to fully differential ionization cross sections

A classical approximation to time dependent quantum mechanical scattering in the M\o{}ller formalism is presented. Numerically, our approach is similar to a standard Classical-Trajectory-Monte-Carlo calculation. Conceptually, however, our formulation allows one to release the restriction to stationary initial distributions. This is achieved by a classical forward-backward propagation technique. As a first application and for comparison with experiment we present fully differential cross sections for electron impact ionization of atomic hydrogen in the Erhardt geometry.Comment: 6 pages, 2 figure

A semi-classical over-barrier model for charge exchange between highly charged ions and one-optical electron atoms

Absolute total cross sections for electron capture between slow, highly charged ions and alkali targets have been recently measured. It is found that these cross sections follow a scaling law with the projectile charge which is different from the one previously proposed basing on a classical over-barrier model (OBM) and verified using rare gases and molecules as targets. In this paper we develop a "semi-classical" (i.e. including some quantal features) OBM attempting to recover experimental results. The method is then applied to ion-hydrogen collisions and compared with the result of a sophisticated quantum-mechanical calculation. In the former case the accordance is very good, while in the latter one no so satisfactory results are found. A qualitative explanation for the discrepancies is attempted.Comment: RevTeX, uses epsf; 6 pages text + 3 EPS figures Journal of Physics B (scehduled March 2000). This revision corrects fig.

Books

Progress in Medical Virology. Vol. 39. Ed. by J. L. Melnick. Pp. x + 270. Illustrated. £115,70. Basel: S Karger. 1992.Assisted reproduction Micromanipulation of Human Gametes and Embryos. By J. Cohen, H. E. Malter, Beth E. Talansky and J. Grifo. pp. ix + 325. Illustrated. $111,50. New York: Raven Press. 1992.Congenital rubella syndrome EpideIDio1ogy and Infection. Vo!. 107 No. 1. Ed. by J. R. Partison, D. Baxby, J. G. Cruickshank, C. R. Madeley and W. C. Noble. Pp. viii + 239. Illustrated. £25. Cambridge: Cambridge University Press. 1991.Rural and urban hospitals The Hospital in Rural and Urban Districts: Report of a WHO Study Group on the Function of Hospitals at the First Referral Level. pp. vii + 74. SFr.120. Geneva: World Health Organisation. 1992.Perinatology Perinato1ogy: Nestle Nutrition Workshop Series. Vol. 26. Ed. by Erich Saling. pp. xiii + 194. illustrated.$69. New York: Raven Press. 1992.Anaesthetists Five Decades: The South African Society· of Anaesthetists 1943 - 1993. By Nagin Parbhoo. 330 pages and 70 phoros and illustrations. Published by the South African Society of Anaesthetists. Printed by National Book Printers.

Rapamycin Regulates Bleomycin-Induced Lung Damage in SP-C-Deficient Mice

Injury to the distal respiratory epithelium has been implicated as an underlying cause of idiopathic lung diseases. Mutations that result in SP-C deficiencies are linked to a small subset of spontaneous and familial cases of interstitial lung disease (ILD) and interstitial pulmonary fibrosis (IPF). Gene-targeted mice that lack SP-C (Sftpc−/−) develop an irregular ILD-like disease with age and are a model of the human SP-C related disease. In the current study, we investigated whether rapamycin could ameliorate bleomycin-induced fibrosis in the lungs of Sftpc−/− mice. Sftpc+/+ and −/− mice were exposed to bleomycin with either preventative administration of rapamycin or therapeutic administration beginning eight days after the bleomycin injury. Rapamycin-treatment increased weight loss and decreased survival of bleomycin-treated Sftpc+/+ and Sftpc−/− mice. Rapamycin did not reduce the fibrotic disease in the prophylactic or rescue experiments of either genotype of mice. Further, rapamycin treatment augmented airway resistance and reduced lung compliance of bleomycin-treated Sftpc−/− mice. Rapamycin treatment was associated with an increased expression of profibrotic Th2 cytokines and reduced expression of INF-γ. These findings indicate that novel therapeutics will be required to treat individuals with SP-C deficient ILD/IPF

Cross section and analyzing power of pol{p}p -> pn pi+ near threshold

The cross section and analyzing power of the pol{p}p -> pn pi+ reaction near threshold are estimated in terms of data obtained from the pol{p}p -> d pi+ and pp -> pp pi0 reactions. A simple final state interaction theory is developed which depends weakly upon the form of the pion-production operator and includes some Coulomb corrections. Within the uncertainties of the model and the input data, the approach reproduces well the measured energy dependence of the total cross section and the proton analyzing power at a fixed pion c.m. angle of 90deg, from threshold to T_p = 330 MeV. The variation of the differential cross section with pion angle is also very encouraging.Comment: 20 pages, Latex including 4 eps figure

Quasiclassical double photoionization from the 2^{1,3}S excited states of helium including shakeoff

We account for the different symmetries of the 2^{1,3}S helium excited states in a quasiclassical description of the knockout mechanism augmented by a quantum shakeoff contribution. We are thus able to formulate the separate contribution of the knockout and shakeoff mechanisms for double photoionization for any excess energy from the 2^{1,3}S states. Photoionization ratios and singly differential cross sections calculated for the 2^{1,3}S excited states of helium are found to be in very good agreement with recent theoretical results.Comment: 9 pages, 5 figure

Surprising variations in the rotation of the chemically peculiar stars CU Virginis and V901 Orionis

CU Vir and V901 Ori belong among these few magnetic chemically peculiar stars whose rotation periods vary on timescales of decades. We aim to study the stability of the periods in CU Vir and V901 Ori using all accessible observational data containing phase information. We collected all available relevant archived observations supplemented with our new measurements of these stars and analysed the period variations of the stars using a novel method that allows for the combination of data of diverse sorts. We found that the shapes of their phase curves were constant, while the periods were changing. Both stars exhibit alternating intervals of rotational braking and acceleration. The rotation period of CU Vir was gradually shortening until the year 1968, when it reached its local minimum of 0.52067198 d. The period then started increasing, reaching its local maximum of 0.5207163 d in the year 2005. Since that time the rotation has begun to accelerate again. We also found much smaller period changes in CU Vir on a timescale of several years. The rotation period of V901 Ori was increasing for the past quarter-century, reaching a maximum of 1.538771 d in the year 2003, when the rotation period began to decrease. A theoretically unexpected alternating variability of rotation periods in these stars would remove the spin-down time paradox and brings a new insight into structure and evolution of magnetic upper-main-sequence stars.Comment: 5 pages, 3 figure