DTNBP1 is a susceptibility gene for schizophrenia. Specific risk and protective haplotypes were identified and replicated. Association with educational achievement may suggest protection mediated by IQ, although this needs to be confirmed in an independent data set.
At present, the cost of genotyping single nucleotide polymorphisms (SNPs) in large numbers of subjects poses a formidable problem for molecular genetic approaches to complex diseases. We have tested the possibility of using primer extension and denaturing high performance liquid chromatography to estimate allele frequencies of SNPs in pooled DNA samples. Our data show that this method should allow the accurate estimation of absolute allele frequencies in pooled samples of DNA and also of the difference in allele frequency between different pooled DNA samples. This technique therefore offers an efficient and cheap method for genotyping SNPs in large case-control and family-based association samples.
avelength-division multiplexing (WDM) is currently being deployed in telecommunications networks in order to satisfy the increased demand for capacity brought about by both narrowband services and new broadband services such as high-speed Internet. While it is thought that WDM will ultimately evolve to interconnected rings or perhaps a mesh network, the objective of the Wavelength Switched Packet Network (WASPNET) project is to gain a more long-term understanding of how optical networks will develop. WASPNET is a WDM transport network that uses optical packet switching, resulting in greater flexibility, functionality, and granularity than possible with the current generation of WDM networks. These optical packets may be used to carry asynchronous transfer mode (ATM) or IP, for example, and the network is also designed to support synchronous digital hierarchy/synchronous optical network (SDH/SONET) traffic, thus permitting a smooth upgrade path. Optical packet switches [1-3] have attracted considerable research interest internationally due to their potential for overcoming projected difficulties with very large electronic switching cores, such as connection, pinout, and electromagnetic interference (EMI) problems. A key problem when designing packet switches of any kind is contention resolution, since multiple packets may arrive asynchronously at the same time to go to the same output. Buffering is often employed to solve this problem, but since optical random access memory (RAM) does not exist, delay lines (usually made of optical fiber) must be used to store optical packets and implement buffering. Various solutions to optical packet switching have been proposed, dictated by the buffering strategy [1]. Implement Medium to Large Buffers-The switches implemented by this technique may be cascaded to implement very large buffers, suitable for bursty traffic. Use No Buffers in the Switch Nodes, but Employ Deflection Routing-When multiple packets arrive destined for a given output, all but one are "deflected" to other outputs, to find their way to the destination by another route through the network. This not only provides fast and flexible routing, but also allows nodes to have no buffering. However, each packet transmitted from a node may be routed across a different path to the same destination. Some packets may wander within the network and waste bandwidth. Consequently, each packet will experience different propagation delays, and the traffic may not arrive at the destination node in sequence. Compromise by Using a Small Amount of Buffering with Deflection Routing-There are various such 2 x 2 buffered switches consisting of a chain of 2 x 2 switch devices and delay lines.
Attention deficit hyperactivity disorder (ADHD) is a childhood onset disorder, for which there is good evidence that genetic factors contribute to the aetiology. Recently reported linkage findings suggested evidence of a susceptibility locus on chromosome 16p13 (maximum LOD score of 4.2, P ¼ 5 Â 10 À6). The GRIN2A (glutamate receptor, ionotropic, N-methyl D-aspartate 2A) gene that encodes the N-methyl D-aspartate receptor subunit 2A (NMDA2A) maps to this region of linkage. As this is also a good functional candidate gene for ADHD, we undertook family-based association analysis in a sample of 238 families. We found significant evidence of association with a GRIN2A exon 5 polymorphism (v 2 ¼ 5.7, P ¼ 0.01). Our data suggest that genetic variation in GRIN2A may confer increased risk for ADHD and that this, at least in part, might be responsible for the linkage result on 16p reported by Smalley et al. We conclude that replication is required and that further work examining for association of GRIN2A polymorphisms with ADHD is warranted.
Brown adipose tissue (BAT) is well recognised to have an important role in the maintenance of body temperature in animals and human neonates, its thermogenic action affected by a tissue-specific uncoupling protein; fatty acid oxidation within the numerous brown adipocyte mitochondria is rendered inefficient leading to heat, rather than adenosine triphosphate (ATP), production. BAT was believed to show rapid involution in early childhood, leaving only vestigial amounts in adults. However, recent evidence suggests that its expression in adults is far more common than previously appreciated, with a higher likelihood of detection in women and leaner individuals. It is conceivable that BAT activity might reduce the risk of developing obesity since fat stores are used for thermogenesis, and a directed enhancement of adipocyte metabolism might have value in weight reduction. However, it is as yet unclear how such manipulation of BAT might be achieved; even in animal models, the control of thermogenic activity is incompletely understood. Even so, there is still much to interest the endocrinologist in BAT, with a range of hormones affecting adipocyte activity. This may either contribute to normal physiological function, or the phenotypical presentation of states of pathological hormone excess or deficiency. Thus, the gender differences in BAT distribution may be attributable to the differential effects of male and female sex hormones, whilst BAT expansion may drive the weight loss associated with catecholamine-producing phaeochromocytomas. These observations support an important influence of the endocrine system on BAT activity and offer new potential targets in the treatment of obesity.
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