Monozygotic twins discordant for phacomatosis pigmentovascularis: evidence for the concept of twin spotting.

The term phacomatosis pigmentovascularis (PPV) refers to the occurrence of vascular nevi with melanocytic or epidermal nevi. We report on monozygotic twins (MZTs) discordant for phacomatosis cesioflammea (PPV type II) providing evidence for the mechanism of twin spotting in the development of PPV. The affected twin had a nevus flammeus on the right arm and the right maxilla, and a pigmented area on the trunk in keeping with a persistent, aberrant Mongolian spot. The affected twin had bilateral ocular melanocytosis with abnormal scleral pigmentation, iris mamillations, increased pigmentation of the trabecular meshwork, and increased fundal pigmentation and secondary glaucoma. DNA testing confirmed monozygosity. This case of MZTs discordant for PPV supports the hypothesis that PPV results from mosaicism due to a post-zygotic mutational event and the concept of twin spotting.

Cancer incidence and mortality in patients with insulin-treated diabetes: a UK cohort study

Raised risks of several cancers have been found in patients with type II diabetes, but there are few data on cancer risk in type I diabetes. We conducted a cohort study of 28 900 UK patients with insulin-treated diabetes followed for 520 517 person-years, and compared their cancer incidence and mortality with national expectations. To analyse by diabetes type, we examined risks separately in 23 834 patients diagnosed with diabetes under the age of 30 years, who will almost all have had type I diabetes, and 5066 patients diagnosed at ages 30 - 49 years, who probably mainly had type II. Relative risks of cancer overall were close to unity, but ovarian cancer risk was highly significantly raised in patients with diabetes diagnosed under age 30 years ( standardised incidence ratio ( SIR) = 2.14; 95% confidence interval (CI) 1.22 - 3.48; standardised mortality ratio (SMR) = 2.90; 95% CI 1.45 - 5.19), with greatest risks for those with diabetes diagnosed at ages 10 - 19 years. Risks of cancer at other major sites were not substantially raised for type I patients. The excesses of obesity- and alcohol-related cancers in type II diabetes may be due to confounding rather than diabetes per se.

GALEX AND PAN-STARRS1 DISCOVERY OF SN IIP 2010aq: THE FIRST FEW DAYS AFTER SHOCK BREAKOUT IN A RED SUPERGIANT STAR

We present the early UV and optical light curve of Type IIP supernova (SN) 2010aq at z = 0.0862, and compare it to analytical models for thermal emission following SN shock breakout in a red supergiant star. SN 2010aq was discovered in joint monitoring between the Galaxy Evolution Explorer (GALEX) Time Domain Survey (TDS) in the NUV and the Pan-STARRS1 Medium Deep Survey (PS1 MDS) in the g, r, i, and z bands. The GALEX and Pan-STARRS1 observations detect the SN less than 1 day after the shock breakout, measure a diluted blackbody temperature of 31,000 +/- 6000 K 1 day later, and follow the rise in the UV/optical light curve over the next 2 days caused by the expansion and cooling of the SN ejecta. The high signal-to-noise ratio of the simultaneous UV and optical photometry allows us to fit for a progenitor star radius of 700 +/- 200R(circle dot), the size of a red supergiant star. An excess in UV emission two weeks after shock breakout compared with SNe well fitted by model atmosphere-code synthetic spectra with solar metallicity is best explained by suppressed line blanketing due to a lower metallicity progenitor star in SN 2010aq. Continued monitoring of PS1 MDS fields by the GALEX TDS will increase the sample of early UV detections of Type II SNe by an order of magnitude and probe the diversity of SN progenitor star properties.

The Disappearance of the Progenitors of Supernovae 1993J and 2003gd

Using images from the Hubble Space Telescope and the Gemini Telescope, we confirmed the disappearance of the progenitors of two type II supernovae (SNe) and evaluated the presence of other stars associated with them. We found that the progenitor of SN 2003gd, an M-supergiant star, is no longer observed at the SN location and determined its intrinsic brightness using image subtraction techniques. The progenitor of SN 1993J, a K-supergiant star, is also no longer present, but its B-supergiant binary companion is still observed. The disappearance of the progenitors confirms that these two supernovae were produced by red supergiants.

Histological and ultrastructural investigation of retinal microaneurysm development in diabetic patients

BACKGROUND: Although microaneurysms are a clinicopathological hallmark of diabetic retinopathy, there have been few ultrastructural studies of these important lesions. As a result, knowledge of the mechanisms involved in the pathogenesis of microaneurysms remains fragmentary. This study provides histological and ultrastructural evidence of various stages in microaneurysm formation within the retinal vasculature. METHODS: The eyes of three type II diabetic patients, obtained within 24 hours of death, were studied by the trypsin digest technique. Eyes from two further type II diabetics were fixed in 2.5% glutaraldehyde within 12 hours of death and processed for electron microscopy. RESULTS: In the trypsin digest preparations, small saccular and fusiform microaneurysms were observed in the peripheral retinal. In the central retina, the microaneurysms ranged in morphology from thin walled, cellular forms to dense, acellular, hyalinised forms. Ultrastructurally, four distinct groups of microaneurysm were observed. Type I showed an extensive accumulation of polymorphonuclear cells into the lumen. The endothelium remained intact, although pericytes were invariably absent. Type II microaneurysms were typified by large numbers of red blood cells (RBCs) in the lumen. Endothelial cells and pericytes were completely absent. The type III microaneurysm was also non-perfused and contained aggregates of irregularly shaped RBC profiles and RBC breakdown products. Recanalisation by new vessels into the occluded lumen was observed in one microaneurysm. Type IV microaneurysms were almost or completely sclerosed, with extensive fibrosis and lipid infiltration into the lumen and basement membrane wall. CONCLUSION: This investigation describes several distinctive stages in the formation of microaneurysms during diabetic retinopathy. With reference to the pathogenesis of retinal microaneurysms, the interaction of various cell types is discussed and the significance of vascular cell death and localised hypertensive events highlighted.

Association Analysis of the PIP4K2A Gene on Chromosome 10p12 and Schizophrenia in the Irish Study of High Density Schizophrenia Families (ISHDSF) and the Irish Case-Control Study of Schizophrenia (ICCSS)

Molecular studies support pharmacological evidence that phosphoinositide signaling is perturbed in schizophrenia and bipolar disorder. The phosphatidylinositol-4-phosphate-5-kinase type-II alpha (PIP4K2A) gene is located on chromosome 10p12. This region has been implicated in both diseases by linkage, and PIP4K2A directly by association. Given linkage evidence in the Irish Study of High Density Schizophrenia Families (ISHDSF) to a region including 10p12, we performed an association study between genetic variants at PIP4K2A and disease. No association was detected through single-marker or haplotype analysis of the whole sample. However, stratification into families positive and negative for the ISHDSF schizophrenia high-risk haplotype (HRH) in the DTNBP1 gene and re-analysis for linkage showed reduced amplitude of the 10p12 linkage peak in the DTNBP1 HRH positive families. Association analysis of the stratified sample showed a trend toward association of PIP4K2A SNPs rs1417374 and rs1409395 with schizophrenia in the DTNBP1 HRH positive families. Despite this apparent paradox, our data may therefore suggest involvement of PIP4K2A in schizophrenia in those families for whom genetic variation in DTNBP1 appears also to be a risk factor. This trend appears to arise from under-transmission of common alleles to female cases. Follow-up association analysis in a large Irish schizophrenia case-control control sample (ICCSS) showed significant association with disease of a haplotype comprising these same SNPs rs1417374-rs1409395, again more so in affected females, and in cases with negative family history of the disease. This study supports a minor role for PIP4K2A in schizophrenia etiology in the Irish population. (C) 2009 Wiley-Liss, Inc.

Repression of NHE1 Expression by PPAR gamma Activation Is a Potential New Approach for Specific Inhibition of the Growth of Tumor Cells In vitro and In vivo

Ligand-induced activation of peroxisome proliferator-activated receptor gamma (PPAIR gamma) inhibits proliferation in cancer cells in vitro and in vivo; however, the downstream targets remain undefined. We report the identification of a peroxisome proliferator response element in the promoter region of the Na+/ H transporter gene NHE1, the overexpression of which has been associated with carcinogenesis. Exposure of breast cancer cells expressing high levels of PPAR gamma to its natural and synthetic agonists resulted in downregulation of NHE1 transcription as well as protein expression. Furthermore, the inhibitory effect of activated PPAR gamma on tumor colony-forming ability was abrogated on overexpression of NHE1, whereas small interfering RNA-mediated gene silencing of NHE1 significantly increased the sensitivity of cancer cells to growth-inhibitory stimuli. Finally, histopathologic analysis of breast cancer biopsies obtained from patients with type II diabetes treated with the synthetic agonist rosiglitazone showed significant repression of NHE1 in the tumor tissue. These data provide evidence for tumor-selective downregulation of NHE1 by activated PPAR gamma in vitro and in pathologic specimens from breast cancer patients and could have potential implications for the judicious use of low doses of PPAR gamma ligands in combination chemotherapy regimens for an effective therapeutic response. [Cancer Res 2009;69(22):8636-44]

Preconception care for women with diabetes: the midwife's role

Diabetes mellitus is a chronic illness which affects a significant number of childbearing women. Despite the potential for adverse consequences for both maternal and fetal wellbeing, few women with diabetes plan their pregnancies to ensure that they enter pregnancy in optimal health. Furthermore, whilst adverse pregnancy outcomes are well documented for women with type I diabetes, it is now apparent that an increasing number of women with type II diabetes are becoming pregnant with similar adverse associated risk. There is an increasing recognition that significant adverse pregnancy outcomes are determined prior to a woman initiating pregnancy care, many of which could be minimised with the introduction of preconception care. As formalised preconception care clinics remain scant across the United Kingdom, there is an urgent need to increase the opportunities for the provision of preconception care and advice to women with diabetes. Midwives are ideally placed to provide preconception advice to women and could provide the missing link in terms of preconception advice for women with diabetes.

A Spitzer Space Telescope study of SN 2003gd: Still no direct evidence that core-collapse supernovae are major dust factories

We present a new, detailed analysis of late-time mid-infrared observations of the Type II-P supernova (SN) 2003gd. At about 16 months after the explosion, the mid-IR flux is consistent with emission from 4 x 10(-5) M. of newly condensed dust in the ejecta. At 22 months emission from pointlike sources close to the SN position was detected at 8 and 24 mu m. By 42 months the 24 mu m flux had faded. Considerations of luminosity and source size rule out the ejecta of SN 2003gd as the main origin of the emission at 22 months. A possible alternative explanation for the emission at this later epoch is an IR echo from preexisting circumstellar or interstellar dust. We conclude that, contrary to the claim of Sugerman and coworkers, the mid-IR emission from SN 2003gd does not support the presence of 0.02 M. of newly formed dust in the ejecta. There is, as yet, no direct evidence that core-collapse supernovae are major dust factories.

UV dosimeter based on dichloroindophenol and tin(IV) oxide

A UVB specific dosimeter is described comprising: a redox dye (2,6-dichloroindophenol, DCIP), a semiconductor ( tin(IV) oxide, SnO2) and a sacrificial electron donor ( glycerol) dispersed in a polymer ( hydroxy ethyl cellulose, HEC) film. The dosimeter is blue in the absence of UVB light but rapidly loses colour on exposure to UVB light. The spectral characteristics of a typical UVB dosimeter film and the mechanism by which the colour change occurs are detailed. DCIP UVB dosimeter films exhibit a response that is related to the irradiance level and duration of UVB exposure, the level of SnO2 present and to a lesser extent the level of glycerol present. The response of the dosimeter appears to be independent of dye concentration and film thickness. Furthermore, DCIP UVB dosimeter films respond to solar simulated light, exhibiting a colour loss that can be simply related to the Minimal Erythemal Dose (MED) exposure for skin type II. As a consequence, such indicators have potential for measuring solar radiation exposure and providing an early warning of erythema for most Caucasian skin (i.e. skin type II).

A viologen-based UV indicator and dosimeter

A UV indicator/dosimeter based on benzyl viologen (BV2+) encapsulated in polyvinyl alcohol (PVA) is described. Upon exposure to UV light, the BV2+/PVA film turns a striking purple colour due to the formation of the cation radical, BV center dot+. The usual oxygen sensitivity of BV center dot+ is significantly reduced due to the very low oxygen permeability of the encapsulating polymer, PVA. Exposure of a typical BV2+/PVA film, for a set amount of time, to UVB light with different UV indices produces different levels of BV center dot+, as measured by the absorbance of the film at 550 nm. A plot of the change in absorbance at this wavelength, Delta Abs(550), as a function of UV index, UVI, produces a linear calibration curve which allows the film to be used as a UVB indicator, and a similar procedure could be employed to allow it to be used as a solar UVI indicator. A typical BV2+/PVA film generates a significant, semi-permanent (stable for > 24 h) saturated purple colour (absorbance similar to 0.8-0.9) upon exposure to sunlight equivalent to a minimal erythemal dose associated with Caucasian skin, i.e. skin type II. The current drawbacks of the film and the possible future use of the BV2+/PVA film as a personal solar UV dosimeter for all skin types are briefly discussed.

Hubble Space Telescope imaging of the progenitor sites of six nearby core-collapse supernovae

The search for the progenitors of six core-collapse supernovae (CCSNe) in archival Hubble Space Telescope (HST) WFPC2 pre-explosion imaging is presented. These SNe are 1999an, 1999br, 1999ev, 2000ds, 2000ew and 2001B. Post-explosion imaging of the SNe, with the HST ACS/WFC, has been utilized with the technique of differential astrometry to identify the progenitor locations on the pre-explosion imaging. SNe 1999br, 1999ev, 2000ew and 2001B are recovered in late-time imaging, and estimates of the progenitor locations on the pre-explosion imaging, with subpixel accuracy, have been made. Only the progenitor of the Type II-P SN 1999ev has been recovered, on pre-explosion F555W imaging, at a 4.8 sigma significance level. Assuming a red supergiant progenitor, the pre-explosion observation is consistent with M-ZAMS = 15-18 M-circle dot. The progenitors of the other five SNe were below the 3 sigma detection threshold of the pre-explosion observations. The detection thresholds were translated to mass limits for the progenitors by comparison with stellar evolution models. Pre-explosion observations of the peculiarly faint SN 1999br limit the mass of a red supergiant progenitor to M-ZAMS

Cloning of new Rhodococcus extradiol dioxygenase genes and study of their distribution in different Rhodococcus strains

Four extradiol dioxygenase genes which encode enzymes active against catechol and substituted catechols were cloned from two different Rhodococcus strains, and their nucleotide sequences were determined. A catechol 2,3-dioxygenase gene (edoC) was shown to be identical to the previously described ipbC gene from the isopropylbenzene operon of Rhodococcus erythropolis. Amino acid sequences deduced from the three other genes (edoA, edoB and edoD) were shown to have various degrees of homology to different extradiol dioxygenases, The EdoA and EdoB dioxygenases were classified as belonging to the third family of type I oxygenases and represented two new subfamilies, whereas the EdoD dioxygenase was a type II enzyme. Analysis of six Rhodococcus strains revealed a wide distribution of the above dioxygenase genes. Rhodococcus sp. I1 was shown to harbour all four of the analysed dioxygenase genes. Nucleotide sequences homologous to the edoB gene were present in all of the strains, including R. erythropolis NCIMB 13065, which did not utilize any of the aromatic compounds analysed. The latter finding points to the existence of a silent pathway(s) for degradation of aromatic compounds in this Rhodococcus strain.

Functional responses of the intertidal amphipod Echinogammarus marinus: effects of prey supply, model selection and habitat complexity.

The influence of predation in structuring ecological communities can be informed by examining the shape and magnitude of the functional response of predators towards prey. We derived functional responses of the ubiquitous intertidal amphipod Echinogammarus marinus towards one of its preferred prey species, the isopod Jaera nordmanni. First, we examined the form of the functional response where prey were replaced following consumption, as compared to the usual experimental design where prey density in each replicate is allowed to deplete. E. marinus exhibited Type II functional responses, i.e. inversely density-dependent predation of J. nordmanni that increased linearly with prey availability at low densities, but decreased with further prey supply. In both prey replacement and non-replacement experiments, handling times and maximum feeding rates were similar. The non-replacement design underestimated attack rates compared to when prey were replaced. We then compared the use of Holling’s disc equation (assuming constant prey density) with the more appropriate Rogers’ random predator equation (accounting for prey depletion) using the prey non-replacement data. Rogers’ equation returned significantly greater attack rates but lower maximum feeding rates, indicating that model choice has significant implications for parameter estimates. We then manipulated habitat complexity and found significantly reduced predation by the amphipod in complex as opposed to simple habitat structure. Further, the functional response changed from a Type II in simple habitats to a sigmoidal, density-dependent Type III response in complex habitats, which may impart stability on the predator−prey interaction. Enhanced habitat complexity returned significantly lower attack rates, higher handling times and lower maximum feeding rates. These findings illustrate the sensitivity of the functional response to variations in prey supply, model selection and habitat complexity and, further, that E. marinus could potentially determine the local exclusion and persistence of prey through habitat-mediated changes in its predatory functional responses.

Trait-mediated indirect interactions in a marine intertidal system as quantified by functional responses

Studies of trait-mediated indirect interactions (TMIIs) typically focus on effects higher predators have on per capita consumption by intermediate consumers of a third, basal prey resource. TMIIs are usually evidenced by changes in feeding rates of intermediate consumers and/or differences in densities of this third species. However, understanding and predicting effects of TMIIs on population stability of such basal species requires examination of the type and magnitude of the functional responses exhibited towards them. Here, in a marine intertidal system consisting of a higher-order fish predator, the shanny Lipophrys pholis, an intermediate predator, the amphipod Echinogammarus marinus, and a basal prey resource, the isopod Jaera nordmanni, we detected TMIIs, demonstrating the importance of habitat complexity in such interactions, by deriving functional responses and exploring consequences for prey population stability. Echinogammarus marinus reacted to fish predator diet cues by reducing activity, a typical anti-predator response, but did not alter habitat use. Basal prey, Jaera nordmanni, did not respond to fish diet cues with respect to activity, distribution or aggregation behaviour. Echinogammarus marinus exhibited type II functional responses towards J. nordmanni in simple habitat, but type III functional responses in complex habitat. However, while predator cue decreased the magnitude of the type II functional response in simple habitat, it increased the magnitude of the type III functional response in complex habitat. These findings indicate that, in simple habitats, TMIIs may drive down consumption rates within type II responses, however, this interaction may remain de-stabilising for prey populations. Conversely, in complex habitats, TMIIs may strengthen regulatory influences of intermediate consumers on prey populations, whilst potentially maintaining prey population stability. We thus highlight that TMIIs can have unexpected and complex ramifications throughout communities, but can be unravelled by considering effects on intermediate predator functional response types and magnitudes.