Biomedical subjects
Gary Jones
Publications and source records attributed to Gary Jones.
Identifying the task variables that influence perceived object assembly complexity.
There is a general lack of understanding as to what issues affect assembly task performance when using diagrammatic instructions because few of the task variables contributing to assembly complexity have been identified. Using a task analysis of a range of self-assembly products, seven task variables hypothesized to predict assembly complexity were identified and studied in the instruction comprehension phase of assembly. Experiment 1 took nine real world assembly instructions and described each in terms of the seven task variables. Seventy-two participants gave a subjective rating of assembly difficulty for each assembly, showing a clear relationship between the task variables and perceived assembly difficulty. As real world assemblies provide little control a second experiment used an orthogonal design to systematically vary the values of each of the assembly task variables in 16 abstract assemblies. Forty-two participants compared the 16 assembly instructions to a final assembly. There was a clear relationship between the task variables and the time taken to view the instructions. Further, it was found that it is possible to predict the complexity of assembly tasks based upon the levels of the task variables identified. The task variables identified are a significant step towards identifying the factors that influence assembly complexity, together with providing progress towards a tool for predicting assembly complexity.
Propagation of Saccharomyces cerevisiae [PSI+] prion is impaired by factors that regulate Hsp70 substrate binding.
The Saccharomyces cerevisiae [PSI(+)] prion is believed to be a self-propagating cytoplasmic amyloid. Earlier characterization of HSP70 (SSA1) mutations suggested that [PSI(+)] propagation is impaired by alterations that enhance Ssa1p's substrate binding. This impairment is overcome by second-site mutations in Ssa1p's conserved C-terminal motif (GPTVEEVD), which mediates interactions with tetratricopeptide repeat (TPR) cochaperones. Sti1p, a TPR cochaperone homolog of mammalian Hop1 (Hsp70/90 organizing protein), activates Ssa1p ATPase, which promotes substrate binding by Ssa1p. Here we find that in SSA1-21 cells depletion of Sti1p improved [PSI(+)] propagation, while excess Sti1p weakened it. In contrast, depletion of Fes1p, a nucleotide exchange factor for Ssa1p that facilitates substrate release, weakened [PSI(+)] propagation, while overproducing Fes1p improved it. Therefore, alterations of Hsp70 cochaperones that promote or prolong Hsp70 substrate binding impair [PSI(+)] propagation. We also find that the GPTVEEVD motif is important for physical interaction with Hsp40 (Ydj1p), another Hsp70 cochaperone that promotes substrate binding but is dispensable for viability. We further find that depleting Cpr7p, an Hsp90 TPR cochaperone and CyP-40 cyclophilin homolog, improved [PSI(+)] propagation in SSA1 mutants. Although Cpr7p and Sti1p are Hsp90 cochaperones, we provide evidence that Hsp90 is not involved in [PSI(+)] propagation, suggesting that Sti1p and Cpr7p functionally interact with Hsp70 independently of Hsp90.
Testing two cognitive theories of insight.
Insight in problem solving occurs when the problem solver fails to see how to solve a problem and then--"aha!"--there is a sudden realization how to solve it. Two contemporary theories have been proposed to explain insight. The representational change theory (e.g., G. Knoblich, S. Ohlsson, & G. E. Rainey, 2001) proposes that insight occurs through relaxing self-imposed constraints on a problem and by decomposing chunked items in the problem. The progress monitoring theory (e.g., J. N. MacGregor, T. C. Ormerod, & E. P. Chronicle, 2001) proposes that insight is only sought once it becomes apparent that the distance to the goal is unachievable in the moves remaining. These 2 theories are tested in an unlimited move problem, to which neither theory has previously been applied. The results lend support to both, but experimental manipulations to the problem suggest that the representational change theory is the better indicator of performance. The findings suggest that testable opposing predictions can be made to examine theories of insight and that the use of eye movement data is a fruitful method of both examining insight and testing theories of insight.
The presence of morphologically intermediate papilla syndrome in United Kingdom populations of sand goby (Pomatoschistus spp): endocrine disruption?
The sand goby (Pomatoschistus spp.) is a small estuarine fish. Its abundance, life history, and sedentary nature lead to its adoption as a key species in the U.K. Endocrine Disruption in the Marine Environment (EDMAR) Program. This study investigated the presence of classic markers of estrogenic exposure by determining vitellogenin (VTG) and zona radiata protein (ZRP) mRNA levels and ovotestis in estuarine-caught male gobies and investigated morphological changes in the urogenital papilla (UGP). Laboratory exposures to estrogens were also conducted to ascertain the responses of these markers. Wild-caught male fish showed no evidence of ovotestis, VTG, or ZRP mRNA induction. Laboratory exposures suggested that sensitivity of the goby to VTG/ ZRP mRNA induction was similar to flounder. The UGP inspection of wild-caught specimens revealed evidence of feminization of male papillae, a condition denoted as morphologically intermediate papilla syndrome (MIPS). Morphologically intermediate papilla syndrome was more prevalent at estrogenically contaminated sites. Juvenile goby experimentally exposed to 17beta-estradiol for 11 to 32 weeks exhibited signs of the MIPS condition, showing that it was inducible by estrogenic exposure and could therefore be a form of estrogenic endocrine disruption. The estuaries where the MIPS condition was most prevalent (>50% at certain sites) were the Tees, Mersey, and Clyde. The potential of the MIPS condition to significantly interfere with reproductive performance is discussed as well as its use as a monitoring tool for endocrine disruption in the estuarine environment.
Amino acid residue 184 of yeast Hsp104 chaperone is critical for prion-curing by guanidine, prion propagation, and thermotolerance.
Inactivation of Hsp104 by guanidine is contended to be the mechanism by which guanidine cures yeast prions. We now find an Hsp104 mutation (D184N) that confers resistance to guanidine-curing of the yeast [PSI(+)] prion. In an independent screen we isolated an HSP104 allele altered in the same residue (D184Y) that dramatically impairs [PSI(+)] propagation in a temperature-dependent manner. Directed mutagenesis of HSP104 produced additional alleles that conferred varying degrees of resistance to guanidine-curing or impaired [PSI(+)] propagation. The mutations similarly affected propagation of the [URE3] prion. Basal and induced abundance of all mutant proteins was normal. Thermotolerance of cells expressing mutant proteins was variably resistant to guanidine, and the degree of thermotolerance did not correlate with [PSI(+)] stability. We thus show that guanidine cures yeast prions by inactivating Hsp104 and identify a highly conserved Hsp104 residue that is critical for yeast prion propagation. Our data suggest that Hsp104 activity can be reduced substantially without affecting [PSI(+)] stability, and that Hsp104 interacts differently with prion aggregates than with aggregates of thermally denatured protein.
nuvA, an Aspergillus nidulans gene involved in DNA repair and recombination, is a homologue of Saccharomyces cerevisiae RAD18 and Neurospora crassa uvs-2.
A 40 kb genomic clone and 2.3 kb EcoRI subclone that rescued the DNA repair and recombination defects of the Aspergillus nidulans nuvA11 mutant were isolated and the subclone sequenced. The subclone hybridized to a cosmid in a chromosome-specific library confirming the assignment of nuvA to linkage group IV and indicating its closeness to bimD. Amplification by PCR clarified the relative positions of nuvA and bimD. A region identified within the subclone, encoding a C3HC4 zinc finger motif, was used as a probe to retrieve a cDNA clone. Sequencing of this clone showed that the nuvA gene has an ORF of 1329 bp with two introns of 51 bp and 60 bp. Expression of nuvA appears to be extremely low. The putative NUVA polypeptide has two zinc finger motifs, a molecular mass of 48906 Da and has 39% identity with the Neurospora crassa uvs-2 and 25% identity with the Saccharomyces cerevisiae RAD18 translation products. Although mutations in nuvA, uvs-2 and RAD18 produce similar phenotypes, only the nuvA11 mutation affects meiotic recombination. A role for nuvA in both DNA repair and genetic recombination is proposed.
Medico-legal issues in radiological consultation.
Providers increasingly use radiological services for diagnosis and treatment. Both the referring physician and the radiological consultant can contribute to efficient and effective consultation, and direct interaction may facilitate the process further. Furthermore, inadequate communication can influence poor patient outcome. We examine the roles and responsibilities of referring physicians and consultant radiologists, and present a malpractice case, Townsend v. Turk 218 Cal. App. 3d 278 (1990), to identify medico-legal issues in radiological consultation. Important issues are implied by the Townsend case. First, it is the clinician's responsibility to include clinical information that is appropriate and adequate. Further, the radiologist is a valuable resource in the selection of the optimal procedure, provided that he or she is aware of the patient's history. The second issue discussed by the court represents a possibly more pervasive problem. The interaction between a consulting radiologist--indeed any specialist--and a treating physician is subject to difficulties caused by different conceptions of professional boundaries. The position taken by the court in the Townsend case is consistent with the traditional view that a consulting radiologist has an attenuated duty to the patient. It also would seem to receive at least some support from the language contained in the current revision of the ACR Standard for Communication: Diagnostic Radiology, effective Jan. 1, 2002: ...The referring physician or healthcare provider also shares in the responsibility of obtaining results of imaging studies they have ordered. Despite the result of the Townsend case and the current formulation of the ACR Standards, however, radiologists face risks of litigation. Indeed, the emerging trend in radiological consultation is the direct communication of results to the patient. It is clear that improved communication between radiologists and referring physicians is both desirable and imperative. Clinico-radiological encounters yield additional clinical information and guide the decision-making process. In the Townsend case, direct interaction would have resolved ambiguity.