Mutant chromatin remodeling protein SMARCAL1 causes Schimke immuno-osseous dysplasia.

Schimke immuno-osseous dysplasia (SIOD, MIM 242900) is an autosomal-recessive pleiotropic disorder with the diagnostic features of spondyloepiphyseal dysplasia, renal dysfunction and T-cell immunodeficiency. Using genome-wide linkage mapping and a positional candidate approach, we determined that mutations in SMARCAL1 (SWI/SNF2-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a-like 1), are responsible for SIOD. Through analysis of data from persons with SIOD in 26 unrelated families, we observed that affected individuals from 13 of 23 families with severe disease had two alleles with nonsense, frameshift or splicing mutations, whereas affected individuals from 3 of 3 families with milder disease had a missense mutation on each allele. These observations indicate that some missense mutations allow retention of partial SMARCAL1 function and thus cause milder disease.     

THE DEVELOPMENT OF A MANIKIN TO SIMULATE THE THERMAL PHYSIOLOGY OF PREMATURE INFANTS

This paper describes a manikin (also known as mannequin) to simulate the thermal physiology of premature infants and experiments performed on it.The performance of the manikin is shown to compare well with that a selection of premature infants in terms of their rate of heat loss.     

Proteolytic inactivation of human leukocyte elastase

Human leukocyte elastase can be proteolytically inactivated by bovine pancreatic trypsin. Neither porcine pancreatic elastase nor bovine pancreatic chymotrypsin causes inactivation of leukocyte elastase, nor are trypsin, pancreatic elastase, or chymotrypsin themselves susceptible to proteolysis. The trypsin-catalyzed inactivation of leukocyte elastase can be slowed by inhibition of trypsin with benzamidine or by occupation of elastase's active site with elastatinal.     

5-methyl-3-butyl-octahydroindolizine,a novel type of pheromone attractive to Pharaoh's ants (Monomorium pharaonis (L.)

Zusammenfassung Aus Arbeiterinnen der AmeiseMonomorium pharaonis (L.) wurde 5-Methyl-3-butyl-octahydroindolizin isoliert. Dieses Pheromon übt eine starke Lockstoffwirkung auf die Arbeiterinnen dieser Ameisenart aus. Die Struktur wurde durch Spektral-analyse und Synthese aufgeklärt. Unseres Wissens ist dies das erste Pheromon aus Insekten mit dem Indolizingerüst.

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Acknowledgment. This work was supported by the Ministry of Health and Environmental Hygiene of the Netherlands. Pharaoh's ants were supplied by Dr.A. Buschinger, Bonn, and Mr.W. R. C. M. van der Loo, Rotterdam. The spectroscopical work was done by a team includingR. Deen, P. J. F. Nooijen andS. J. Spijk andJ. M. Timmner assisted in the synthesis.     

How guanylate-binding proteins achieve assembly-stimulated processive cleavage of GTP to GMP

Interferons are immunomodulatory cytokines that mediate anti-pathogenic and anti-proliferative effects in cells. Interferon-gamma-inducible human guanylate binding protein 1 (hGBP1) belongs to the family of dynamin-related large GTP-binding proteins, which share biochemical properties not found in other families of GTP-binding proteins such as nucleotide-dependent oligomerization and fast cooperative GTPase activity. hGBP1 has an additional property by which it hydrolyses GTP to GMP in two consecutive cleavage reactions. Here we show that the isolated amino-terminal G domain of hGBP1 retains the main enzymatic properties of the full-length protein and can cleave GDP directly. Crystal structures of the N-terminal G domain trapped at successive steps along the reaction pathway and biochemical data reveal the molecular basis for nucleotide-dependent homodimerization and cleavage of GTP. Similar to effector binding in other GTP-binding proteins, homodimerization is regulated by structural changes in the switch regions. Homodimerization generates a conformation in which an arginine finger and a serine are oriented for efficient catalysis. Positioning of the substrate for the second hydrolysis step is achieved by a change in nucleotide conformation at the ribose that keeps the guanine base interactions intact and positions the beta-phosphates in the gamma-phosphate-binding site.     

Geochemistry: does U-Pb date Earth's core formation?

Constraining the timing of the formation of Earth's core, which defines the birth of our planet, is essential for understanding the early evolution of Earth-like planets. Wood and Halliday and Halliday discuss the apparent discrepancy between the U-Pb (60-80 Myr) and Hf-W clocks (30 Myr) in determining the timescale of Earth's accretion and core formation. We find that the information the authors present is at times contradictory (for example, compare Fig. 1 in ref. 1 with Fig. 1 in ref. 2) and confusing and could suggest that the U-Pb clock constrains core formation better than the Hf-W system. Here we point out the limitations of the U-Pb system and show that the U-Pb age cannot be used to argue for protracted accretion and/or core formation (>50 Myr) because this clock only records the processes that occurred during the last 1% of Earth's accretion and core formation in the Wood and Halliday mechanism.