Recent developments in the investigation of thyroid regulation and thyroid carcinogenesis

This review covers new mechanistic information spanning the past 10 years relevant to normal and abnormal thyroid growth and function that may assist in the risk assessment of chemicals inducing thyroid follicular cell neoplasia. Recent studies have shown that thyroid regulation occurs via a complex interactive network mediated through several different messenger systems. Increased thyroid-stimulating hormone (TSH) levels activate the signal transduction pathways to stimulate growth and differentiation of the follicular cell. The important role of TSH in growth as well as in function helps to explain how disruptions in the thyroid-pituitary axis may influence thyroid neoplasia in rodents. New investigations that couple mechanistic studies with information from animal cancer bioassays (e. g., sulfamethazine studies) confirm the linkage between prolonged disruption of the thyroid-pituitary axis and thyroid neoplasia. New initiation/promotion studies in rodents also support the concept that chronic stimulation of the thyroid induced by goitrogens can result in thyroid tumors. Some of these studies confirm previous suggestions regarding the importance of chemically induced thyroid peroxidase inhibition and the inhibition of 3,3',5, 5'-tetraiodothyronine (T4, thyroxine) deiodinases on disruption of the thyroid-pituitary axis leading to thyroid neoplasia. Some comparative physiologic and mechanistic data highlight certain differences between rodents and humans that could be expected to confer an increased vulnerability of rodents to chronic hypersecretion of TSH. New data from epidemiologic and molecular genetic studies in humans contribute further to an understanding of thyroid neoplasia. Acute exposure to ionizing radiation, especially in childhood, remains the only verified cause of thyroid carcinogenesis in humans. Iodine deficiency studies as a whole remain inconclusive, even though several new studies in humans examine the role of dietary iodine deficiency in thyroid cancer. Specific alterations in gene expression have been identified in human thyroid neoplasia, linked to tumor phenotype, and thus oncogene activation and tumor-suppressor gene inactivation may also be factors in the development and progression of thyroid cancer in humans. An analysis by the U.S. EPA Risk Assessment Forum, prepared as a draft report in 1988 and completed in 1997, focused on the use of a threshold for risk assessment of thyroid follicular tumors. New studies, involving several chemicals, provide further support that there will be no antithyroid activity until critical intracellular concentrations are reached. Thus, for chemically induced thyroid neoplasia linked to disruptions in the thyroid-pituitary axis, a practical threshold for thyroid cancer would be expected. More information on thyroid autoregulation, the role of oncogene mutations and growth factors, and studies directly linking persistently high TSH levels with the sequential cellular development of thyroid follicular cell neoplasia would provide further confirmation.     

Prenatal diagnosis of trisomy 13 on fetal cells obtained from maternal blood after minor enrichment

In a pilot study to establish fetal nucleated red blood cell (NRBC) detection in maternal blood, trisomy 13 was diagnosed by FISH analysis at 11 weeks' gestation. The NRBCs were detected after a single-step ficoll density gradient enrichment. In blood samples taken both before and after CVS, 52 and 80 NRBCs, respectively, were found to be positive for fetal haemoglobin. In 47 per cent of these cells, FISH analysis for X and Y chromosomes confirmed the fetal sex. Moreover, 48 per cent of these NRBCs showed three fluorescent signals for a chromosome 13 probe, which confirmed the diagnosis of trisomy 13, previously detected at CVS karyotyping. This is the first report of non-invasive prenatal diagnosis of trisomy 13, i.e., pre-CVS, in the first trimester. The high number of fetal NRBCs detected indicates a connection with aneuploidy, probably due to early impairment of the feto-maternal barrier.     

Roles of word frequency and age of acquisition in word naming and lexical decision.

Six experiments are reported that contrasted the effects of frequency and age of acquisition on written word recognition. Age of acquisition affected word-naming speed when frequency was controlled (Experiment 1), but there was no effect of frequency when age of acquisition was controlled (Experiment 2). Experiments 3 and 4 found an effect of age of acquisition upon immediate but not delayed naming speed, but no frequency effect on either immediate or delayed naming once age of acquisition was controlled. Independent effects of frequency and age of acquisition were observed in the lexical decision task (Experiments 5 and 6). Implications for theoretical accounts of word recognition and the possible roles of age of acquisition and frequency in word recognition are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Melanin Distribution in Human Skin: Influence of Cytoskeletal,Polarity, and Centrosome-Related Machinery of Stratum basale Keratinocytes

Melanin granules cluster within supra-nuclear caps in basal keratinocytes (KCs) of the human epidermis, where they protect KC genomic DNA against ultraviolet radiation (UVR) damage. While much is known about melanogenesis in melanocytes (MCs) and a moderate amount about melanin transfer from MC to KC, we know little about the fate of melanin once inside KCs. We recently reported that melanin fate in progenitor KCs is regulated by rare asymmetric organelle movement during mitosis. Here, we explore the role of actin, microtubules, and centrosome-associated machinery in distributing melanin within KCs. Short-term cultures of human skin explants were treated with cytochalasin-B and nocodazole to target actin filaments and microtubules, respectively. Treatment effects on melanin distribution were assessed by the Warthin–Starry stain, on centrosome-associated proteins by immunofluorescence microscopy, and on co-localisation with melanin granules by brightfield microscopy. Cytochalasin-B treatment disassembled supra-nuclear melanin caps, while nocodazole treatment moved melanin from the apical to basal KC domain. Centrosome and centriolar satellite-associated proteins showed a high degree of co-localisation with melanin. Thus, once melanin granules are transferred to KCs, their preferred apical distribution appears to be facilitated by coordinated movement of centrosomes and centriolar satellites. This mechanism may control melanin’s strategic position within UVR-exposed KCs.     

Microstructures and mechanical properties of welded Fe-12Cr-20Mn austenitic stainless steel

The effects of welding on the tensile and fatigue properties of fully annealed and cold-worked Fe-12Cr-20Mn austenitic stainless steel were evaluated. Room temperature and 500 °C tensile tests and room temperature cantilever beam fatigue tests were accomplished on specimens that contained autogenous bead-on-plate welds. The tensile and fatigue properties of the fully annealed material were not significantly influenced by welding. The tensile properties of the welded cold-worked material were also not significantly affected by the presence of a weldment. However, welding caused a large reduction of the fatigue life of the cold-worked material. Fatigue cracks preferentially initiated at large Mn-Si inclusions that formed in the fusion zones of the weldments.     

Length preferences and periodicity in {beta}-strands. Antiparallel edge {beta}-sheets are more likely to finish in non-hydrogen bonded rings

We analysed the length distributions of different types of ß-strandin a high resolution, non-homologous set of 500 protein structures,finding differences in their mean lengths. Antiparallel edgestrands in strand–turn–strand motifs show a preferencefor an even number of residues. This propensity is enhancedif the length is corrected for ß-bulges, which insertan extra residue into the strand. Residues in antiparallel edgeß-strands alternate between being in hydrogen bondedand non-hydrogen bonded rings. Antiparallel edges with an evennumber of residues are more likely to have their final ßresidue in a non-hydrogen bonded ring. This suggests that non-hydrogenbonded rings are intrinsically more stable than hydrogen bondedrings, perhaps because its side chain packing is closer. Therefore,we suggest that a simple way to increase ß-hairpinstability, or the stability of an antiparallel edge strand,is to have a non-hydrogen bonded ring at the end of the strand. Received June 19, 2003; revised October 25, 2003; accepted November 7, 2003     

The structural analysis of wheat flour glycerolipids

The compositions of the fatty acids in the 1, 2 and 3 positions of the principal glycerolipids and their various stereoisomers were determined. Fatty acids in the 1 and 3 positions of triglycerides were similar in composition and less unsaturated than those in the 2 position. Fatty acids in the 1,2-, 1,3- and 2,3-diglycerides were distributed in a pattern which indicated isomerization ofsn-1,2-diacylglycerol. Lysophosphatidyl choline (the principal monoacyl lipid) consisted of about 80% 1-acyl and 20% 2-acyl isomers. The fatty acid compositions indicated that most of the 2-lysophosphatidyl choline was formed by isomerization of 1-lysophosphatidyl choline. Most of the digly cerides and lysophosphatidyl choline were synthesized in the ripening wheat grain. However a small proportion of these partial glycerides and all of the other minor partial glycerides (monoglycerides, digalactosyl monoglycerides) appeared to be the result of limited lipolysis of the corresponding diacyl lipids in the wheat or in the freshly-milled flour. Fatty acids in the 2 position of all the fully acylated glycerides were very similar in composition, but there were considerable differences in the 1 position fatty acids.     

A prototype scanning stylus profilometer for rapid measurement of small surface areas

A novel stylus based profiling instrument has been developed for rapid measurement of small surface areas. Outlined in the following paper are some of the key features of the prototype system including the wideband stylus pick-up and the dedicated scanning traverse mechanism. In addition, some preliminary results obtained by scanning the instrument over several different surfaces are presented.     

User Preference for a Control-Based Reduced Processing Decision Support Interface

This study examined trainee crime-scene investigators' preference for, and accuracy in using, four different computer-based decision support interface designs, each of which incorporated a different reduced processing information acquisition strategy. The interfaces differed on the basis of the number of options that could be considered simultaneously and the level of control that could be exercised over the number and sequence in which feature values were accessed. Forty trainee investigators completed six decision scenarios in which they were asked to acquire information and formulate a decision by selecting one of three options. The study comprised two phases, the first of which involved familiarizing participants with each of the four interface designs and collecting performance and subjective data. The second phase involved trainees selecting one of the four interfaces to engage in a fifth and sixth decision scenario involving high or low levels of time-pressure. The results indicated that the “all options, full control” interface was the preferred option in the low time-pressure condition. Although the strategy remained the most frequently selected in the high time-pressure condition, this preference was not significant. It was concluded that the perceptions of difficulty and the degree of user control over information acquisition were more important than perceived efficiency in the selection of computer-based interface designs. The outcomes have implications for the design of decision support systems.     

Disquiet in the plasma

The metaphor of plasma is taken up to present and discuss movement and engagement by participants in mixed reality installation arts. Two works involving full body video portraits exhibited through large plasma screens in a variety of public settings are covered. Machinic mediations of video realism are considered in terms of embodied interaction in which viewer-participants contribute to the ‘disquiet’ of gendered figuring. Processural, proximal and personal aspects of responsive engagement are discussed. This is extended to performativity that may lead us to critical reflection of our own actions and responses in mixed reality arts.