Sox18 is transiently expressed during angiogenesis in granulation tissue of skin wounds with an identical expression pattern to Flk-1 mRNA

Sox18 encodes a member of the Sry-related high mobility group box (SOX) family of developmental transcription factors. Examination of Sox18 expression during embryogenesis has shown that Sox18 is expressed transiently in endothelial cells of developing blood vessels, and mutations in Sox18 have been found to underlie the mouse vascular and hair follicle mutant ragged. In this study we have examined the expression of Sox18 in angiogenesis during wound healing. Full-thickness skin wounds were created in mice, and subsequent expression of vascular endothelial growth factor (VEGF), the VEGF receptor Flk-1, alpha1 (iv) collagen (Col4a1), and Sox18 were studied using in situ hybridization. As has been previously reported, VEGF was expressed predominantly in the keratinocytes at the wound margins. Sox18 expression was found Rye days after wounding during capillary sprouting in granulation tissue and persisted through the proliferative phase of healing, but was not detected in fully epithelialized wounds 21 days after wounding. Sox18 mRNA expression was detected in capillaries within the granulation tissue and showed an identical pattern of distribution to Flk-1 and Col4a1 mRNA expression in endothelial cells. Immunostaining with a polyclonal anti-Sox18 antibody showed SOX18 protein localized in capillary endothelial cells within the granulation tissue. capillaries in the subcutaneous tissue of unwounded skin showed no Sox18 expression. Sox18 may therefore represent a transcription factor involved in the induction of angiogenesis during wound healing and tissue repair, but not in the maintenance of endothelial cells in undamaged tissue.

Hyaline tissue of thermally unaltered conodont elements and the enamel of vertebrates

Comparison of the ultrastructure of the hyaline tissue of conodont elements and the enamel of vertebrates provides little support for a close phylogenetic relationship between conodonts and vertebrates. Transmission and scanning electron microscopy shows that the mineralised component of the hyaline tissue of Panderodus and of Cordylodus elements consists of large, flat, oblong crystals, arranged in layers that run parallel to the long axis of the conodont. Enamel in the dentition of a living vertebrate, the lungfish Neoceratodus forsteri, has crystals of calcium hydroxyapatite, arranged in layers, and extending in groups from the dentine-enamel junction; the crystals are slender, elongate spicules perpendicular to the surface of the tooth plate, Similar crystal arrangements to those of lungfish are found in other vertebrates, but none resembles the organisation of the hyaline tissue of conodont elements, The crystals of hydroxyapatite in conodont hyaline tissue are exceptionally large, perpendicular or parallel to the surface of the element, with no trace of prisms, unlike the protoprismatic radial crystallite enamel of fish teeth and scales, or the highly organised prismatic enamel of mammals.

Growth and hard tissue remodelling in the dentition of the Australian lungfish, Neoceratodus forsteri (Osteichthyes: Dipnoi)

The extant lungfish, including three genera, the Australian, South American and African lungfishes, retain a dentition that appeared first in the Devonian, in some of the oldest members of this group. The dentition consists of permanent tooth plates with persistent cusps that appear early in development of the fish. The cusps, separate early in development, form ridges that are arranged in a radiating pattern, and fusion of the cusps to each other and to the underlying jaw bone produces a tooth plate. The lungfish dentition is based on a template of mantle dentine that surrounds bone trabeculae enclosed in the tooth plate. The mantle layer is covered by enamel. In most derived dipnoans, this framework encloses two further forms of dentine, known as interdenteonal and circumdenteonal dentines. The tooth plates grow in area and in depth without evidence of macroscopic resorption of dentines or of enamel. Increase in size and changes in shape of lungfish tooth plates is actually achieved by a process involving microscopic remodelling of the bone contained within the margin of each tooth plate, and the later addition of new dentines and enamel within and around the bone. This is accomplished without creating weakness in the structural integrity of the tooth plate and bone complex, and proceeds in line with growth and remodelling of the jaw bones attached to the tooth plates.

Nuclear RelB(+) cells are found in normal lymphoid organs and in peripheral tissue in the context of inflammation, but not under normal resting conditions

Differentiated dendritic cells (DC) have been identified by the presence of nuclear RelB (nRelB) and HLA-DR, and the absence of CD20 or high levels of CD68, in lymph nodes and active rheumatoid arthritis synovial tissue. The current studies aimed to identify conditions in which nRelB is expressed in human tissues, by single and double immunohistochemistry of formalin-fixed peripheral and lymphoid tissue. Normal peripheral tissue did not contain nRelB(+) cells. nRelB(+) DC were located only in T- or B-cell areas of lymphoid tissue associated with normal organs or peripheral tissues, including tonsil, colon, spleen and thymus, or in association with T cells in inflamed peripheral tissue. Inflamed sites included skin delayed-type hypersensitivity reaction, and a wide range of tissues affected by autoimmune disease. Nuclear RelB(+) -HLA-DR- follicular DC were located in B-cell follicles in lymphoid organs and in lymphoid-like follicles of some tissues affected by autoimmune disease. Lymphoid tissue T-cell areas also contained nRelB(-) -HLA-DR+ cells, some of which expressed CD123 and/or CD68. Nuclear RelB(+) cells are found in normal lymphoid organs and in peripheral tissue in the context of inflammation, but not under normal resting conditions.

Interaction between natural and sexual selection during the evolution of mate recognition

The interaction between natural and sexual selection is central to many theories of how mate choice and reproductive isolation evolve, but their joint effect on the evolution of mate recognition has not, to my knowledge, been investigated in an evolutionary experiment. Natural and sexual selection were manipulated in interspecific hybrid populations of Drosophila to determine their effects on the evolution of a mate recognition system comprised of cuticular hydrocarbons (CHCs). The effect of natural selection in isolation indicated that CHCs were costly for males and females to produce. The effect of sexual selection in isolation indicated that females preferred males with a particular CHC composition. However, the interaction between natural and sexual selection had a greater effect on the evolution of the mate recognition system than either process in isolation. When natural and sexual selection were permitted to operate in combination, male CHCs became exaggerated to a greater extent than in the presence of sexual selection alone, and female CHCs evolved against the direction of natural selection. This experiment demonstrated that the interaction between natural and sexual selection is critical in determining the direction and magnitude of the evolutionary response of the mate recognition system.

Gene-Environment Interaction Effects on Behavioral Variation and Risk of Complex Disorders: The Example of Alcoholism and Other Psychiatric Disorders

There have been few replicated examples of genotype x environment interaction effects on behavioral variation or risk of psychiatric disorder. We review some of the factors that have made detection of genotype x environment interaction effects difficult, and show how genotype x shared environment interaction (GxSE) effects are commonly confounded with genetic parameters in data from twin pairs reared together. Historic data on twin pairs reared apart can in principle be used to estimate such GxSE effects, but have rarely been used for this purpose. We illustrate this using previously published data from the Swedish Adoption Twin Study of Aging (SATSA), which suggest that GxSE effects could account for as much as 25% of the total variance in risk of becoming a regular smoker. Since few separated twin pairs will be available for study in the future, we also consider methods for modifying variance components linkage analysis to allow for environmental interactions with linked loci.

Sun exposure and interaction with family history in risk of melanoma, Queensland, Australia

Sun exposure is the main environmental risk factor for melanoma, but the timing of exposure during life that confers increased risk is controversial. Here we provide the first report of the association between lifetime and age-specific cumulative ultraviolet exposure and cutaneous melanoma in Queensland, Australia, an area of high solar radiation, and examine the association separately for families at high, intermediate and low familial melanoma risk. Subjects were a population-based sample of melanoma cases diagnosed and registered in Queensland between 1982 and 1990 and their relatives. The analysis included 1,263 cases and relatives with confirmed cutaneous melanoma and 3,111 first-degree relatives without melanoma as controls. Data an lifetime residence and sun exposure, family history and other melanoma risk factors were collected by a mailed questionnaire. Using conditional multiple logistic regression with stratification by family, cumulative sun exposure in childhood and in adulthood after age 20 was significantly associated with melanoma, with estimated relative risks of 1.15 per 5,000 minimal erythemal doses (MEDs) from age 5 to 12 years, and 1.52 per 5 MEDs/day from age 20. There was no association with sun exposure in families at high familial melanoma risk. History of nonmelanoma skin cancer (relative risk [RR] = 1.26) and multiple sunburns (RR = 1.31) were significant risk factors. These findings indicate that sun exposure in childhood and in adulthood are important determinants of melanoma but not in those rare families with high melanoma susceptibility, in which genetic factors are likely to be more important. (C) 2002 Wiley-Liss, Inc.

Atom lasers, coherent states, and coherence II. Maximally robust ensembles of pure states

As discussed in the preceding paper [Wiseman and Vaccaro, preceding paper, Phys. Rev. A 65, 043605 (2002)], the stationary state of an optical or atom laser far above threshold is a mixture of coherent field states with random phase, or, equivalently, a Poissonian mixture of number states. We are interested in which, if either, of these descriptions of rho(ss) as a stationary ensemble of pure states, is more natural. In the preceding paper we concentrated upon the question of whether descriptions such as these are physically realizable (PR). In this paper we investigate another relevant aspect of these ensembles, their robustness. A robust ensemble is one for which the pure states that comprise it survive relatively unchanged for a long time under the system evolution. We determine numerically the most robust ensembles as a function of the parameters in the laser model: the self-energy chi of the bosons in the laser mode, and the excess phase noise nu. We find that these most robust ensembles are PR ensembles, or similar to PR ensembles, for all values of these parameters. In the ideal laser limit (nu=chi=0), the most robust states are coherent states. As the phase noise or phase dispersion is increased through nu or the self-interaction of the bosons chi, respectively, the most robust states become more and more amplitude squeezed. We find scaling laws for these states, and give analytical derivations for them. As the phase diffusion or dispersion becomes so large that the laser output is no longer quantum coherent, the most robust states become so squeezed that they cease to have a well-defined coherent amplitude. That is, the quantum coherence of the laser output is manifest in the most robust PR ensemble being an ensemble of states with a well-defined coherent amplitude. This lends support to our approach of regarding robust PR ensembles as the most natural description of the state of the laser mode. It also has interesting implications for atom lasers in particular, for which phase dispersion due to self-interactions is expected to be large.

Selective loss of expression of glutamate GluR2/R3 receptor subunits in cerebellar tissue from a patient with olivopontocerebellar atrophy

Expression of the mRNAs encoding the astrocytic (EAAT1, EAAT2) and neuronal (EAAT3, EAAT4) excitatory amino acid transporters and the AMPA-type glutamate receptor subunits GluR2 and GluR3 was investigated in postmortem cerebellar extracts from a patient with olivopontocerebellar atrophy (OPCA) and in material from three age-matched controls. Decreased expression in the steady state level of EAAT4 mRNA in the OPCA sample was correlated with the selective loss of Purkinje cells. Neuropathological evaluation revealed reactive gliosis and concomitantly increased expression of the mRNA encoding astrocytic glial fibrillary acidic protein (GFAP). Expression of the mRNAs encoding the AMPA receptor subunits GluR2 and GluR3 subunits was found to be decreased in OPCA suggesting that excitotoxic mechanism could play a role in the pathogenesis of the selective neuronal cell death in this disorder.