High-energy particle acceleration in the shell of a supernova remnant

A significant fraction of the energy density of the interstellar medium is in the form of high-energy charged particles (cosmic rays). The origin of these particles remains uncertain. Although it is generally accepted that the only sources capable of supplying the energy required to accelerate the bulk of Galactic cosmic rays are supernova explosions, and even though the mechanism of particle acceleration in expanding supernova remnant (SNR) shocks is thought to be well understood theoretically, unequivocal evidence for the production of high-energy particles in supernova shells has proven remarkably hard to find. Here we report on observations of the SNR RX J1713.7 - 3946 (G347.3 - 0.5), which was discovered by ROSAT in the X-ray spectrum and later claimed as a source of high-energy gamma-rays of TeV energies (1 TeV = 10(12) eV). We present a TeV gamma-ray image of the SNR: the spatially resolved remnant has a shell morphology similar to that seen in X-rays, which demonstrates that very-high-energy particles are accelerated there. The energy spectrum indicates efficient acceleration of charged particles to energies beyond 100 TeV, consistent with current ideas of particle acceleration in young SNR shocks.     

Structural basis for inhibition of the replication licensing factor Cdt1 by geminin

To maintain chromosome stability in eukaryotic cells, replication origins must be licensed by loading mini-chromosome maintenance (MCM2-7) complexes once and only once per cell cycle. This licensing control is achieved through the activities of geminin and cyclin-dependent kinases. Geminin binds tightly to Cdt1, an essential component of the replication licensing system, and prevents the inappropriate reinitiation of replication on an already fired origin. The inhibitory effect of geminin is thought to prevent the interaction between Cdt1 and the MCM helicase. Here we describe the crystal structure of the mouse geminin-Cdt1 complex using tGeminin (residues 79-157, truncated geminin) and tCdt1 (residues 172-368, truncated Cdt1). The amino-terminal region of a coiled-coil dimer of tGeminin interacts with both N-terminal and carboxy-terminal parts of tCdt1. The primary interface relies on the steric complementarity between the tGeminin dimer and the hydrophobic face of the two short N-terminal helices of tCdt1 and, in particular, Pro 181, Ala 182, Tyr 183, Phe 186 and Leu 189. The crystal structure, in conjunction with our biochemical data, indicates that the N-terminal region of tGeminin might be required to anchor tCdt1, and the C-terminal region of tGeminin prevents access of the MCM complex to tCdt1 through steric hindrance.     

Intermediate-depth earthquake faulting by dehydration embrittlement with negative volume change

Earthquakes are observed to occur in subduction zones to depths of approximately 680 km, even though unassisted brittle failure is inhibited at depths greater than about 50 km, owing to the high pressures and temperatures. It is thought that such earthquakes (particularly those at intermediate depths of 50-300 km) may instead be triggered by embrittlement accompanying dehydration of hydrous minerals, principally serpentine. A problem with failure by serpentine dehydration is that the volume change accompanying dehydration becomes negative at pressures of 2-4 GPa (60-120 km depth), above which brittle fracture mechanics predicts that the instability should be quenched. Here we show that dehydration of antigorite serpentinite under stress results in faults delineated by ultrafine-grained solid reaction products formed during dehydration. This phenomenon was observed under all conditions tested (pressures of 1-6 GPa; temperatures of 650-820 degrees C), independent of the sign of the volume change of reaction. Although this result contradicts expectations from fracture mechanics, it can be explained by separation of fluid from solid residue before and during faulting, a hypothesis supported by our observations. These observations confirm that dehydration embrittlement is a viable mechanism for nucleating earthquakes independent of depth, as long as there are hydrous minerals breaking down under a differential stress.     

Phylogenetic origin of LI-cadherin revealed by protein and gene structure analysis

The intestine specific LI-cadherin differs in its overall structure from classical and desmosomal cadherins by the presence of seven instead of five cadherin repeats and a short cytoplasmic domain. Despite the low sequence similarity, a comparative protein structure analysis revealed that LI-cadherin may have originated from a five-repeat predecessor cadherin by a duplication of the first two aminoterminal repeats. To test this hypothesis, we cloned the murine LI-cadherin gene and compared its structure to that of other cadherins. The intron-exon organization, including the intron positions and phases, is perfectly conserved between repeats 3–7 of LI-cadherin and 1–5 of classical cadherins. Moreover, the genomic structure of the repeats 1–2 and 3–4 is identical for LI-cadherin and highly similar to that of the repeats 1–2 of classical cadherins. These findings strengthen our assumption that LI-cadherin originated from an ancestral cadherin with five domains by a partial gene duplication event.Received 22 December 2003; received after revision 9 February 2004; accepted 27 February 2004     

Transcriptional regulation of a metastasis suppressor gene by Tip60 and beta-catenin complexes

Defining the molecular strategies that integrate diverse signalling pathways in the expression of specific gene programmes that are critical in homeostasis and disease remains a central issue in biology. This is particularly pertinent in cancer biology because downregulation of tumour metastasis suppressor genes is a common occurrence, and the underlying molecular mechanisms are not well established. Here we report that the downregulation of a metastasis suppressor gene, KAI1, in prostate cancer cells involves the inhibitory actions of beta-catenin, along with a reptin chromatin remodelling complex. This inhibitory function of beta-catenin-reptin requires both increased beta-catenin expression and recruitment of histone deacetylase activity. The coordinated actions of beta-catenin-reptin components that mediate the repressive state serve to antagonize a Tip60 coactivator complex that is required for activation; the balance of these opposing complexes controls the expression of KAI1 and metastatic potential. The molecular mechanisms underlying the antagonistic regulation of beta-catenin-reptin and the Tip60 coactivator complexes for the metastasis suppressor gene, KAI1, are likely to be prototypic of a selective downregulation strategy for many genes, including a subset of NF-kappaB target genes.     

Somatic mutations in PTPN11 in juvenile myelomonocytic leukemia,myelodysplastic syndromes and acute myeloid leukemia

We report here that individuals with Noonan syndrome and juvenile myelomonocytic leukemia (JMML) have germline mutations in PTPN11 and that somatic mutations in PTPN11 account for 34% of non-syndromic JMML. Furthermore, we found mutations in PTPN11 in a small percentage of individuals with myelodysplastic syndrome (MDS) and de novo acute myeloid leukemia (AML). Functional analyses documented that the two most common mutations in PTPN11 associated with JMML caused a gain of function.     

Electron spin resonance studies of catalase and some of the catalase compounds

Zusammenfassung Rinderleberkatalase und einige Katalasekomplexe wurden bei einer Temperatur von 77°Kelvin mit der Methode der Elektronenspinresonanz untersucht. Aus den Elektronenspinresonanzspektren ist zu entnehmen, ob es sich bei der Katalaseverbindung um einen Gross-spin-Komplex, um einen Klein-spin-Komplex oder um eine Mischform beider Komplexarten handelt.     

Electron spin resonance investigations on ferricytochromec compounds

Zusammenfassung Ferricytochromc aus Pferdeherz wurde bei einer Temperatur von 77°K mit der Methode der Elektronenspinresonanz untersucht. Aus den Elektronenspinresonanzspektren ist zu entnehmen, dass Ferricytochromc bei neutralem und alkalischem pH ein Lowspin-Komplex ist, bei stark saurem pH ist es dagegen ein Mischkomplex der High- und Low-spin-Form. Ferricytochrom-c-Fluorid ist ein reiner High-spin-Komplex; dagegen sind die Azid- und Zyanidkomplexe Low-spin-Komplexe.