Abundant hydrocarbons in the disk around a very-low-mass star.

Very-low-mass stars (those less than 0.3 solar masses) host orbiting terrestrial planets more frequently than other types of stars. The compositions of those planets are largely unknown but are expected to relate to the protoplanetary disk in which they form. We used James Webb Space Telescope mid-infrared spectroscopy to investigate the chemical composition of the planet-forming disk around ISO-ChaI 147, a 0.11-solar-mass star. The inner disk has a carbon-rich chemistry; we identified emission from 13 carbon-bearing molecules, including ethane and benzene. The high column densities of hydrocarbons indicate that the observations probe deep into the disk. The high carbon-to-oxygen ratio indicates radial transport of material within the disk, which we predict would affect the bulk composition of any planets forming in the disk.

Water in the terrestrial planet-forming zone of the PDS 70 disk.

Terrestrial and sub-Neptune planets are expected to form in the inner (less than 10 AU) regions of protoplanetary disks1. Water plays a key role in their formation2-4, although it is yet unclear whether water molecules are formed in situ or transported from the outer disk5,6. So far Spitzer Space Telescope observations have only provided water luminosity upper limits for dust-depleted inner disks7, similar to PDS 70, the first system with direct confirmation of protoplanet presence8,9. Here we report JWST observations of PDS 70, a benchmark target to search for water in a disk hosting a large (approximately 54 AU) planet-carved gap separating an inner and outer disk10,11. Our findings show water in the inner disk of PDS 70. This implies that potential terrestrial planets forming therein have access to a water reservoir. The column densities of water vapour suggest in-situ formation via a reaction sequence involving O, H2 and/or OH, and survival through water self-shielding5. This is also supported by the presence of CO2 emission, another molecule sensitive to ultraviolet photodissociation. Dust shielding, and replenishment of both gas and small dust from the outer disk, may also play a role in sustaining the water reservoir12. Our observations also reveal a strong variability of the mid-infrared spectral energy distribution, pointing to a change of inner disk geometry.

The diverse chemistry of protoplanetary disks as revealed by JWST.

Early results from the James Webb Space Telescope-Mid-InfraRed Instrument (JWST-MIRI) guaranteed time programs on protostars (JOYS) and disks (MINDS) are presented. Thanks to the increased sensitivity, spectral and spatial resolution of the MIRI spectrometer, the chemical inventory of the planet-forming zones in disks can be investigated with unprecedented detail across stellar mass range and age. Here, data are presented for five disks, four around low-mass stars and one around a very young high-mass star. The mid-infrared spectra show some similarities but also significant diversity: some sources are rich in CO2, others in H2O or C2H2. In one disk around a very low-mass star, booming C2H2 emission provides evidence for a "soot" line at which carbon grains are eroded and sublimated, leading to a rich hydrocarbon chemistry in which even di-acetylene (C4H2) and benzene (C6H6) are detected. Together the data point to an active inner disk gas-phase chemistry that is closely linked to the physical structure (temperature, snowlines, presence of cavities and dust traps) of the entire disk and which may result in varying CO2/H2O abundances and high C/O ratios >1 in some cases. Ultimately, this diversity in disk chemistry will also be reflected in the diversity of the chemical composition of exoplanets.

Rationale for a reverse tapered body shift implant for immediate placement.

Immediate implant placement holds considerable value, yet primary implant stability is often a critical factor. The aim of this study was to evaluate the stability, volumetric viability, and buccal gap size of reverse tapered body shift (RTBS) implants after immediate placement. Peak insertion torque measurements of two RTBS designs (apical 40% vs. apical 50%), relative to conventionally tapered implants, were assessed in simulated extraction sockets prepared in synthetic bone blocks. Additionally, the proximity of the RTBS implants to neighbouring teeth and anatomical structures, and the buccal gap distance were evaluated in human cadavers. The mean (± standard deviation) insertion torque was 12.00±1.40N•cm for the conventionally tapered implants (n=50), 35.36±2.74N•cm (n=50) for RTBS-1, and 48.20±2.90N•cm (n=50) for RTBS-2; the difference between designs was statistically significant (P<0.01). In total, 40 RTBS implants (20 per design) were placed in six cadaveric premaxillae. Only one locus was inappropriate for both RTBS implant designs, due to the proximity of neighbouring teeth. The average buccal gap for both implant designs was 2.8mm (P=0.104). The improved primary stability and increased buccal gap size with RTBS implants may enhance the feasibility of immediate placement. The study findings should be further validated in clinical trials.

Analgesia (mis)usage on a dental emergency service: a patient survey.

OBJECTIVES: Analgesics are one of the most frequently used medicines. Self-medication and misuse have been described in the literature. The purpose of this study was to document analgesic (mis)use in a population seeking emergency dental treatment. MATERIAL AND METHODS: Patients consulting a dental emergency service were randomly asked to complete a questionnaire on analgesic use, knowledge and information on the analgesics and on their pain history. A photobook was used as an aid to identify products used. Descriptive statistics were combined with chi-square and Mann-Whitney U testing. RESULTS: Ninety-eight patients were included. Acetaminophen (69.4%) and ibuprofen (65.3%) were the most frequently used products. Nearly half of the subjects (43.9%) combined at least two analgesics. Although 42.9% of subjects were aware of the maximum daily dose, 62.2% of the subjects exceeded this limit, specifically 76.6% of subjects using ibuprofen and 32.4% of subjects using acetaminophen overdosing. Females overdosed significantly more than males. Ingestion on medical advice did not affect the overdose rates significantly. No significant relation was found between the absence of knowledge on the maximum daily dose and actual overdosing. No higher pain reduction was found in patients overdosing analgesics. The average number of days patients experienced pain before consulting the emergency unit was 12. A significant relation was found between the lag time and overdosing. CONCLUSIONS: A large portion of the patients overdosed analgesics. Even prior medical advice did not reduce significantly overdose rates. CLINICAL RELEVANCE: Dentists treating emergency cases clearly need to be aware of the high risk and high rates of overdosing analgesics in their patients.

Effect of fumagillin on adipocyte differentiation and adipogenesis.

BACKGROUND: Inhibition of angiogenesis may impair adipose tissue development. METHODS: The effect of fumagillin (a methionine aminopeptidase-2 inhibitor) on adipocyte differentiation and de novo adipogenesis was investigated in murine model systems. RESULTS: During in vitro differentiation of murine 3T3-F442A preadipocytes, administration of fumagillin (>/=1 muM) resulted in reduced expression of methionine aminopeptidase-2, and in enhanced differentiation rate. In vivo, de novo development of adipose tissue following injection of preadipocytes in nude mice kept on high fat diet was somewhat, but not significantly (p=0.06), reduced by administration of fumagillin (1 mg/kg/day during 4 weeks by oral gavage). This was not associated with effects on blood vessel size or density, whereas blood vessel density normalized to adipocyte density was enhanced upon fumagillin treatment. In vivo BrdU incorporation experiments did not reveal effects of fumagillin on cell proliferation in adipose tissues, and cellular apoptosis was also not affected. Treatment with fumagillin enhances in vitro differentiation of preadipocytes, but has only a minor effect on in vivo adipogenesis. GENERAL SIGNIFICANCE: These studies on in vitro and in vivo preadipcoyte differentiation thus do not support an anti-obesity effect of fumagillin as a result of effects on adipocyte differentiation.

Angiogenesis and development of adipose tissue.

Obesity is a common disorder and related diseases, such as diabetes, atherosclerosis, hypertension, cardiovascular disease and cancer, are a major cause of mortality and morbidity in Western-type societies. Development of obesity is associated with substantial modulation of adipose tissue structure. The plasticity of the adipose tissue is reflected by its remarkable ability to expand or to reduce in size throughout adult lifespan. The expansion of adipose tissue is linked to the development of its vasculature. Indeed, adipogenesis is tightly associated with angiogenesis, as shown by the findings that adipose tissue explants trigger blood vessel formation, whereas in turn adipose tissue endothelial cells promote preadipocyte differentiation. Different components have been identified that play a role in adipose tissue associated angiogenesis. Modulation of angiogenesis may have the potential to impair adipose tissue development and thus may provide a novel therapeutic approach for prevention and treatment of obesity.

No functional role of plasminogen activator inhibitor-1 in murine adipogenesis or adipocyte differentiation.

OBJECTIVE: To substantiate a potential role of plasminogen activator inhibitor-1 (PAI-1) in adipogenesis, we have studied its effects on in vitro adipocyte differentiation and on in vivo adipose tissue formation. RESULTS: Our in vitro data do not support a functional role of PAI-1, as substantiated by our findings that: (i) inhibition of PAI-1 with a neutralizing antibody did not affect differentiation of 3T3-F442A preadipocytes; (ii) overexpression of murine PAI-1 in 3T3-F442A cells had no effect on differentiation; and (iii) differentiation of PAI-1-deficient murine embryonic fibroblasts into mature adipocytes was comparable to wild-type (WT) cells. Furthermore, our in vivo studies did not reveal an important role for PAI-1, as suggested by our findings that: (i) de novo fat pad formation in NUDE mice following injection of 3T3-F442A cells was not affected by a PAI-1 neutralizing antibody; and (ii) adipose tissue formation following combined injection of Matrigel and basic fibroblast growth factor was comparable in WT and in PAI-1 deficient mice. CONCLUSION: Taken together, these in vitro and in vivo studies in murine model systems do not support an important functional role of PAI-1 in adipogenesis.

Mechanisms of androgen receptor signalling via steroid receptor coactivator-1 in prostate.

The androgen receptor (AR) is a member of the nuclear receptor superfamily. These ligand-activated transcription factors usually contain two activation functions, a ligand-independent activation function 1(AF1) in the divergent N-terminal domain and a ligand-dependent AF2 in the more conserved C-terminal ligand-binding domain. To promote transcription from target promoters, DNA-bound nuclear receptors recruit coactivator proteins that promote transcription by modifying histones within nucleosomes, resulting in altered topology of chromatin to allow access of the basal transcriptional machinery, or stabilising the pre-initiation complex. It is well known that most coactivators interact with AF2 of many nuclear receptors via conserved, helical LxxLL motifs (where L is leucine and x is any amino acid). The AF2 of the AR is very weak, but we were able to demonstrate that its intrinsic ligand-dependent activity is potentiated by steroid receptor coactivator-1 (SRC1) and that this region interacts with coactivators via LxxLL motifs. However, a mutant SRC1 coactivator with no functional LxxLL motifs was still able to potentiate AR activity. We found that SRC1 can also be recruited to (and increase activity of) AF1 of the AR via a conserved, glutamine-rich region. Point mutations within this region abolish SRC1 interaction with AF1 and also abolish or severely impair its ability to potentiate AR activity on all promoters tested. Thus the AR interacts with SRC1 via two different regions and the AF1 interaction is functionally the more important, although the contribution of the two interactions varies in a promoter-dependent fashion. SRC1 then potentiates receptor activity via recruitment of CBP/p300, a histone acetyltranferase. This is important in the context of prostate cancer as SRC1 and other coactivators including CBP are coexpressed with AR in the luminal epithelial cells of the prostate, where over 90% of prostate tumours arise. There is a need for effective second-line prostate cancer therapy aimed at blocking the AR pathway when anti-androgen therapy has failed. Since there is growing evidence that nuclear receptor cofactors may be implicated in the progression of hormone-dependent tumours to hormone-independent states, novel targets could include the interaction of AR with coactivator proteins. We suggest that the N-terminal interaction would be a more specific and effective target in the case of prostate cancer than the LxxLL/AF2 interaction.