Phosphatidylinositol 4-kinasebeta is critical for functional association of rab11 with the Golgi complex

Phosphatidylinositol 4-kinasebeta (PI4Kbeta) plays an essential role in maintaining the structural integrity of the Golgi complex. In a search for PI4Kbeta-interacting proteins, we found that PI4Kbeta specifically interacts with the GTP-bound form of the small GTPase rab11. The PI4Kbeta-rab11 interaction is of functional significance because inhibition of rab11 binding to PI4Kbeta abolished the localization of rab11 to the Golgi complex and significantly inhibited transport of vesicular stomatitis virus G protein from the Golgi complex to the plasma membrane. We propose that a novel function of PI4Kbeta is to act as a docking protein for rab11 in the Golgi complex, which is important for biosynthetic membrane transport from the Golgi complex to the plasma membrane.     

Age at onset in two common neurodegenerative diseases is genetically controlled

To identify genes influencing age at onset (AAO) in two common neurodegenerative diseases, a genomic screen was performed for AAO in families with Alzheimer disease (AD; n=449) and Parkinson disease (PD; n=174). Heritabilities between 40%–60% were found in both the AD and PD data sets. For PD, significant evidence for linkage to AAO was found on chromosome 1p (LOD = 3.41). For AD, the AAO effect of APOE (LOD = 3.28) was confirmed. In addition, evidence for AAO linkage on chromosomes 6 and 10 was identified independently in both the AD and PD data sets. Subsequent unified analyses of these regions identified a single peak on chromosome 10q between D10S1239 and D10S1237, with a maximum LOD score of 2.62. These data suggest that a common gene affects AAO in these two common complex neurodegenerative diseases.     

The influence of cavity shape on the stresses in composite dental restorations: a finite element study

Dental restoration adhering to the cavity exhibits fundamentally different load transfer mechanisms from non-adhering restorations. It is therefore questionable that traditional cavity designs are optimal from a purely mechanical point of view when working with composite materials. Drawing from general engineering experience, it can be hypothesised that smooth, well rounded designs with bevelled margins are superior. A finite element model is used in the present investigation to determine the stress field in four different cavity designs as it develops during the curing of the restoration. The results show that a significant reduction of the stress along the adhesive interface between the tooth and the restoration can be achieved through the use of a rounded cavity shape. They also show that the adoption of bevelled margins leads to a reduction of the stress concentration at this location. These results are confirmed by a set of experimental results published in the literature. It is concluded that adhering restorations will perform better from a mechanical point of view if an appropriate cavity shape is selected.     

Improving the comparative map of porcine chromosome 9 with respect to human chromosomes 1, 7 and 11

Conserved segments have been identified by ZOO-FISH between pig chromosome 9 (SSC9) and human chromosomes 1, 7 and 11. To assist in the identification of positional candidate genes for QTL on SSC9, the comparative map was further developed. Primers were designed from porcine EST sequence homologous to genes in regions of human chromosomes 1, 7 and 11. Porcine ESTs were then physically assigned using the INRA somatic cell hybrid panel (INRASCHP) and the high-resolution radiation hybrid panel (IMpRH). Seventeen genes (PEPP3, RAB7L1, FNBP2, MAPKAPK2, GNAI1, ABCB1, STEAP, AKAP9, CYP51A1, SGCE, ROBO4, SIAT4C, GLUL, CACNA1E, PTGS2, C1orf16 and ETS1) were mapped to SSC9, while GUSB, CPSF4 and THG-1 were assigned to SSC3.     

The morphological basis of hallucal orientation in extant birds

The perching foot of living birds is commonly characterized by a reversed or opposable digit I (hallux). Primitively, the hallux of nonavian theropod dinosaurs was unreversed and lay parallel to digits II-IV. Among basal birds, a unique digital innovation evolved in which the hallux opposes digits II-IV. This digital configuration is critical for grasping and perching. I studied skeletons of modern birds with a range of hallucal designs, from unreversed (anteromedially directed) to fully reversed (posteriorly directed). Two primary correlates of hallucal orientation were revealed. First, the fossa into which metatarsal I articulates is oriented slightly more posteriorly on the tarsometatarsus, rotating the digit as a unit. Second, metatarsal I exhibits a distinctive torsion of its distal shaft relative to its proximal articulation with the tarsometatarsus, reorienting the distal condyles and phalanges of digit I. Herein, I present a method that facilitates the re-evaluation of hallucal orientation in fossil avians based on morphology alone. This method also avoids potential misinterpretations of hallucal orientation in fossil birds that could result from preserved appearance alone.     

Attitudes of deaf adults toward genetic testing for hereditary deafness.

Recent advances within molecular genetics to identify the genes for deafness mean that it is now possible for genetic-counseling services to offer genetic testing for deafness to certain families. The purpose of this study is to document the attitudes of deaf adults toward genetic testing for deafness. A structured, self-completion questionnaire was given to delegates at an international conference on the "Deaf Nation," held at the University of Central Lancashire in 1997. The conference was aimed at well-educated people, with an emphasis on Deaf culture issues. Eighty-seven deaf delegates from the United Kingdom returned completed questionnaires. The questionnaire had been designed to quantitatively assess attitudes toward genetics, interest in prenatal diagnosis (PND) for deafness, and preference for having deaf or hearing children. The results from this study provide evidence of a predominantly negative attitude toward genetics and its impact on deaf people, in a population for whom genetic-counseling services are relevant. Fifty-five percent of the sample thought that genetic testing would do more harm than good, 46% thought that its potential use devalued deaf people, and 49% were concerned about new discoveries in genetics. When asked about testing in pregnancy, 16% of participants said that they would consider having PND, and, of these, 29% said that they would prefer to have deaf children. Geneticists need to appreciate that some deaf persons may prefer to have deaf children and may consider the use of genetic technology to achieve this. Any genetic-counseling service set up for families with deafness can only be effective and appropriate if clinicians and counselors take into consideration the beliefs and values of the deaf community at large.     

Secretion of Elastinolytic Enzymes and Their Propeptides by Pseudomonas aeruginosa

Elastase of Pseudomonas aeruginosa is synthesized as a preproenzyme. The signal sequence is cleaved off during transport across the inner membrane and, in the periplasm, proelastase is further processed. We demonstrate that the propeptide and the mature elastase are both secreted but that the propeptide is degraded extracellularly. In addition, reduction of the extracellular proteolytic activity led to the accumulation of unprocessed forms of LasA and LasD in the extracellular medium, which shows that these enzymes are secreted in association with their propeptides. Furthermore, a hitherto undefined protein with homology to a Streptomyces griseus aminopeptidase accumulated under these conditions.