Connecting complex disorders through biology

Mutations in CTC1, which encodes a key telomere component, have been identified as the cause of Coats plus syndrome. This discovery provides an important pathophysiological link between Coats plus and the clinically related telomere disorders dyskeratosis congenita, Revesz syndrome and Hoyeraal-Hreidarsson syndrome.     

Substrate twinning activates the signal recognition particle and its receptor

Signal sequences target proteins for secretion from cells or for integration into cell membranes. As nascent proteins emerge from the ribosome, signal sequences are recognized by the signal recognition particle (SRP), which subsequently associates with its receptor (SR). In this complex, the SRP and SR stimulate each other's GTPase activity, and GTP hydrolysis ensures unidirectional targeting of cargo through a translocation pore in the membrane. To define the mechanism of reciprocal activation, we determined the 1.9 A structure of the complex formed between these two GTPases. The two partners form a quasi-two-fold symmetrical heterodimer. Biochemical analysis supports the importance of the extensive interaction surface. Complex formation aligns the two GTP molecules in a symmetrical, composite active site, and the 3'OH groups are essential for association, reciprocal activation and catalysis. This unique circle of twinned interactions is severed twice on hydrolysis, leading to complex dissociation after cargo delivery.     

The production of chromosome structural changes by radiation

This paper attempts an update and comment upon some of the topics of chromosome aberration formation which Lea raised in Chapter VI of his classic work 'Actions of Radiations on living Cells'. Only the first nine sections of this chapter are covered, which deal primarily with the qualitative aspects of aberrations, their formation, classification and interrelationships. In commenting upon these topics, pertinent references are made to work with mammalian and human cells. Increased knowledge of the importance of DNA as a fundamental target and the integral part it plays in the complex structure of the chromosome, coupled with cellular techniques not available to these earlier workers necessitate some revision and modification of early ideas. However, inspite of the enormous accumulation of data and ideas since the original work was published in 1946, the foundation that these early workers laid is still very solid. Surprisingly, we are still puzzled by many of the problems that perplexed them.     

A genome-wide association study of nonsynonymous SNPs identifies a type 1 diabetes locus in the interferon-induced helicase (IFIH1) region

In this study we report convincing statistical support for a sixth type 1 diabetes (T1D) locus in the innate immunity viral RNA receptor gene region IFIH1 (also known as mda-5 or Helicard) on chromosome 2q24.3. We found the association in an interim analysis of a genome-wide nonsynonymous SNP (nsSNP) scan, and we validated it in a case-control collection and replicated it in an independent family collection. In 4,253 cases, 5,842 controls and 2,134 parent-child trio genotypes, the risk ratio for the minor allele of the nsSNP rs1990760 A --> G (A946T) was 0.86 (95% confidence interval = 0.82-0.90) at P = 1.42 x 10(-10).     

Late Eocene of Burma yields earliest anthropoid primate, Pondaungia cotteri.

In April 1978, a fragment of a primate lower jaw containing the second and third molar teeth was found in late Eocene exposures of the Pondaung Hills about 1 mile north-west of Mogaung village in northwestern Central Burma. This approximately 40-Myr-old specimen is the first fossil primate found in Burma since the fragmentary remains of the controversial earliest anthropoids Pondaungia cotteri Pilgrim and Amphipithecus mogaungensis Colbert were recovered more than 50 yr ago. The jaw described here is believed to represent further evidence of P. cotteri. Its recovery from undoubled late Eocene exposures coupled with its salient higher primate characters and excellent state of preservation provides the opportunity to substantiate further that the Pondaung primates of Burma are the earliest known record of the Anthropoidea.     

Nanomechanics: response of a strained semiconductor structure

The nanomechanical properties of thin silicon films will become increasingly critical in semiconductor devices, particularly in the context of substrates that consist of a silicon film on an insulating layer (known as silicon-on-insulator, or SOI, substrates). Here we use very small germanium crystals as a new type of nanomechanical stressor to demonstrate a surprising mechanical behaviour of the thin layer of silicon in SOI substrates, and to show that there is a large local reduction in the viscosity of the oxide on which the silicon layer rests. These findings have implications for the use of SOI substrates in nanoelectronic devices.