Summary
Background
Pollen‐associated food allergy is common. However, systemic reactions or even life‐threatening anaphylaxis are rare.
Objective
The aim of this study was to investigate the clinical ...impact of native, heat‐processed and encapsulated hazelnuts (HN) in patients with proven HN allergy.
Methods
One hundred and thirty‐two patients with a positive history of HN allergy were recruited. Sensitization was confirmed by a skin prick test (SPT) and sIgE against HN. After an HN‐free diet, double‐blind placebo‐controlled challenges were performed with increasing amounts of native and roasted HN. A subset of patients were given HN capsules to circumvent the oral mucosa. Basophil activation was measured by flow cytometry before and after provocation but also ex vivo using native and roasted HN extracts.
Results
Three groups of HN‐allergic patients were identified depending on their clinical reaction pattern. The dosages by which allergic reactions were elicitated varied for native HN from 0.01 to 2.0 g, with a median of 0.1 g, for roasted HN from 0.01 to 10.0 g, with a median of 0.23 g, and for encapsulated HN from 0.1 to 3.0 g, with a median of 0.3 g. Accordingly, the SPT was more frequently positive and resulted in greater weal reactions if native HN was used. This finding was confirmed by ex vivo basophil activation showing that significantly higher allergen extract concentrations (roasted>native) were necessary to induce 50% basophil activation.
Conclusion
Our data show that heat processing of HN reduces its allergenicity. SPT but also the basophil activation test can be used to determine the reactivity of an allergen extract.
Controlled maturation of ovarian follicles is necessary for fertility. Follicles are restrained at an immature stage until stimulated by FSH secreted by pituitary gonadotropes. FSH acts on granulosa ...cells within the immature follicle to inhibit apoptosis, promote proliferation, stimulate production of steroid and protein hormones, and induce ligand receptors and signaling intermediates. The phosphoinositide 3-kinase (PI3K)/AKT (protein kinase B) pathway is a pivotal signaling corridor necessary for transducing the FSH signal. We report that protein kinase A (PKA) mediates the actions of FSH by signaling through multiple targets to activate PI3K/AKT. PKA uses a route that promotes phosphorylation of insulin receptor substrate-1 (IRS-1) on Tyr ⁹⁸⁹, a canonical binding site for the 85-kDa regulatory subunit of PI3K that allosterically activates the catalytic subunit. PI3K activation leads to activation of AKT through phosphorylation of AKT on Thr ³⁰⁸ and Ser ⁴⁷³. The adaptor growth factor receptor bound protein 2-associated binding protein 2 (GAB2) is present in a preformed complex with PI3K heterodimer and IRS-1, it is an A-kinase anchoring protein that binds the type I regulatory subunit of PKA, and it is phosphorylated by PKA on Ser ¹⁵⁹. Overexpression of GAB2 enhances FSH-stimulated AKT phosphorylation. GAB2, thus, seems to coordinate signals from the FSH-stimulated rise in cAMP that leads to activation of PI3K/AKT. The ability of PKA to commandeer IRS-1 and GAB2, adaptors that normally integrate receptor/nonreceptor tyrosine kinase signaling into PI3K/AKT, reveals a previously unrecognized route for PKA to activate a pathway that promotes proliferation, inhibits apoptosis, enhances translation, and initiates differentiation of granulosa cells.
The data assimilation scheme used in the Met Office's Operational Sea Surface Temperature and Ice Analysis (OSTIA) system has been updated from an Optimal Interpolation (OI)‐type scheme to a ...variational assimilation scheme. The updated system includes a dual length‐scale background error correlation operator, and a flow‐dependent component to adjust the length‐scale combination in favour of the short scale in regions of high sea surface temperature (SST) variability. The variational assimilation scheme improves both the analysis performance and the representation of SST features in the OSTIA analysis compared to the OI scheme of the original system. The results of spectral analysis, assessment of horizontal SST gradients and the response of an atmospheric model to the OSTIA SST analysis as a boundary condition indicate that the flow‐dependent formulation successfully contributes to improvements in the feature resolution capability of the analysis. Overall, using a short length‐scale of 15 km and including a flow‐dependent adjustment component produces the best results compared to using either 40 km or the first Rossby radius of deformation as the short length‐scale. The new system successfully captures realistic ocean variability without introducing noise into the analysis, allowing the feature resolution capability of the new system to out‐perform that of other comparable SST analysis products.
The data assimilation scheme used in the Met Office's OSTIA (Operational Sea Surface Temperature and Ice Analysis) system has been updated from an OI‐type scheme to a variational assimilation scheme, NEMOVAR. Updates include a flow‐dependent component to the background error correlation operator, which shortens the length‐scale in regions of high sea surface temperature (SST) variability. The analysis performance and representation of SST features (as demonstrated in the figure) are improved using the updated system.
Summary
Background
Acral lentiginous melanoma (ALM) is one of the four major subtypes in cutaneous melanoma (CM). Although ALM has a poorer prognosis than other CM subtypes, the prognostic factors ...associated with ALM have only been verified in small‐sized cohorts because of the low incidence of ALM worldwide.
Objectives
To investigate the clinical characteristics of ALM and to evaluate their prognostic values based on a large dataset from the Central Malignant Melanoma Registry (CMMR) of the German Dermatologic Society.
Methods
The Kaplan–Meier method was used to estimate the potential influence of clinical and histological parameters on ALM disease‐specific survival (DSS) curves, which were compared using the log‐rank test. A Cox proportional hazards model was used to identify independent prognostic factors for DSS.
Results
In total, 2050 patients with ALM were identified from 58 949 patients with CM recorded by the CMMR with follow‐up data. In multivariate analyses, age (P = 0·006), ulceration (P = 0·013), tumour thickness (P < 0·001) and tumour spread (P < 0·001) turned out to be significant prognostic factors for DSS in ALM whereas sex, nevus association and level of invasion were not independent factors.
Conclusions
ALM has the same prognostic factors as other subtypes of melanoma. Unfavourable prognosis probably derives from the delay in diagnosis in comparison with other melanoma subtypes.
What's already known about this topic?
Acral lentiginous melanoma (ALM) has a poorer prognosis than other cutaneous melanoma subtypes.
Several published articles have reported various factors that influence the prognosis in ALM but the results of these studies were based on small‐sized cohorts because of the rarity of ALM.
What does this study add?
This study investigated prognostic factors in the largest‐ever cohort of patients with ALM documented by the Central Malignant Melanoma Registry of the German Dermatologic Society.
Four parameters including age, ulceration, tumour thickness and tumour spread were identified as independent significant prognostic factors for disease‐specific survival in ALM.
The present American Joint Committee on Cancer classification is valid for ALM.
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A new highly sensitive method for incoherent broad-band cavity-enhanced absorption measurements of gaseous samples, using a white-light source is demonstrated. The light of a short-arc Xe-lamp ...transmitted by an optically stable cavity is dispersed with a grating monochromator and detected by a sensitive photodiode-array. The technique is a development of the previously published principle of cavity-enhanced absorption spectroscopy. The method is characterized by great experimental simplicity, high sensitivity, and high temporal resolution. These features are demonstrated on basis of the
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Forest structure and species composition in many western U.S. coniferous forests have been altered through fire exclusion, past and ongoing harvesting practices, and livestock grazing over the 20th ...century. The effects of these activities have been most pronounced in seasonally dry, low and mid-elevation coniferous forests that once experienced frequent low to moderate intensity, fire regimes. In this paper, we report the effects of Fire and Fire Surrogate (FFS) forest stand treatments on fuel load profiles, potential fire behavior, and fire severity under three weather scenarios from six western U.S. FFS sites. This replicated, multisite experiment provides a framework for drawing broad generalizations about the effectiveness of prescribed fire and mechanical treatments on surface fuel loads, forest structure, and potential fire severity. Mechanical treatments without fire resulted in combined 1-, 10-, and 100-hour surface fuel loads that were significantly greater than controls at three of five FFS sites. Canopy cover was significantly lower than controls at three of five FFS sites with mechanical-only treatments and at all five FFS sites with the mechanical plus burning treatment; fire-only treatments reduced canopy cover at only one site. For the combined treatment of mechanical plus fire, all five FFS sites with this treatment had a substantially lower likelihood of passive crwon fire as indicated by the very high torching indices. FFS sites that experienced significant increases in 1-, 10-, and 100-hour combined surface fuel loads utilized harvest systems that left all activity fuels within experimental units. When mechanical treatments were followed by prescribed burning or pile burning, they were the most effective treatment for reducing crown fire potential and predicted tree mortality because of low surface fuel loads and increased vertical and horizontal canopy separation. Results indicate that mechanical plus fire, fire-only, and mechanical-only treatments using whole-tree harvest systems were all effective at reducing potential fire severity under severe fire weather conditions. Retaining the largest trees within stands also increased fire resistance.
Say–Barber–Biesecker–Young–Simpson syndrome (SBBYSS) and genitopatellar syndrome (GTPTS) are clinically similar disorders with some overlapping features. Although they are currently considered to be ...distinct clinical entities, both were found to be caused by de novo truncating sequence variants in the KAT6B (lysine acetyltransferase 6B) gene, strongly suggesting that they are allelic disorders. Herein, we report the clinical and genetic findings in a girl presenting with a serious multiple congenital anomaly syndrome with phenotypic features overlapping both SBBYSS and GTPTS; pointing out that the clinical distinction between these disorders is not exact and there do exist patients, in whom conventional clinical classification is problematic. Genetic analyses revealed a truncating c.4592delA (p.Asn1531Thrfs*18) variant in the last KAT6B exon. Our findings support that phenotypes associated with typical KAT6B disease‐causing variants should be referred to as ‘KAT6B spectrum disorders’ or ‘KAT6B related disorders’, rather than their current SBBYSS and GTPTS classification.
Changes in vegetation and fuels were evaluated from measurements taken before and after fuel reduction treatments (prescribed fire, mechanical treatments, and the combination of the two) at 12 Fire ...and Fire Surrogate (FFS) sites located in forests with a surface fire regime across the conterminous United States. To test the relative effectiveness of fuel reduction treatments and their effect on ecological parameters we used an information-theoretic approach on a suite of 12 variables representing the overstory (basal area and live tree, sapling, and snag density), the understory (seedling density, shrub cover, and native and alien herbaceous species richness), and the most relevant fuel parameters for wildfire damage (height to live crown, total fuel bed mass, forest floor mass, and woody fuel mass). In the short term (one year after treatment), mechanical treatments were more effective at reducing overstory tree density and basal area and at increasing quadratic mean tree diameter. Prescribed fire treatments were more effective at creating snags, killing seedlings, elevating height to live crown, and reducing surface woody fuels. Overall, the response to fuel reduction treatments of the ecological variables presented in this paper was generally maximized by the combined mechanical plus burning treatment. If the management goal is to quickly produce stands with fewer and larger diameter trees, less surface fuel mass, and greater herbaceous species richness, the combined treatment gave the most desirable results. However, because mechanical plus burning treatments also favored alien species invasion at some sites, monitoring and control need to be part of the prescription when using this treatment.
Polynyas play an important role in the regional meteorology and oceanography of the high latitudes and in the global ocean circulation. Unique low‐level observations of an Antarctic coastal polynya, ...the Ronne Polynya, were conducted using an instrumented aircraft. At the time of the observations, the polynya was mostly covered with thin ice perforated with holes and was composed of two distinct regimes: an inner region of newly formed and thin ice and an outer region of thicker more consolidated ice. The sensible heat flux over the polynya was ∼100 W m−2 and decreased with fetch, primarily as a result of the thickening ice cover. The mean sensible heat transfer and drag coefficients over the polynya were CHN10 = (0.7 ± 0.1) × 10−3 and CDN10 = (1.1 ± 0.2) × 10−3, respectively. The heat transfer coefficient is similar to that found over heterogeneous sea ice and is significantly lower than has been used in previous studies of heat fluxes over polynyas, which are often assumed to be open water. The transfer coefficients were not found to be a function of fetch or ice conditions as represented by the surface temperature and albedo. The data were used in an investigation of the output of sensible heat flux, potential temperature, and boundary layer depth from a simple fetch‐dependent model. For this case study, surface temperatures and transfer coefficients appropriate to an ice‐covered surface were required for an accurate simulation.
In somatic cells, RHOA mediates actin dynamics through a GNA13-mediated signaling cascade involving RHO kinase (ROCK), LIM kinase (LIMK), and cofilin. RHOA can be negatively regulated by protein ...kinase A (PRKA), and it interacts with members of the A-kinase anchoring (AKAP) family via intermediary proteins. In spermatozoa, actin polymerization precedes the acrosome reaction, which is necessary for normal fertility. The present study was undertaken to determine whether the GNA13-mediated RHOA signaling pathway may be involved in acrosome reaction in bovine caudal sperm, and whether AKAPs may be involved in its targeting and regulation. GNA13, RHOA, ROCK2, LIMK2, and cofilin were all detected by Western blot in bovine caudal sperm. Overlay, immunoprecipitation, and subsequent mass spectrometry analysis identified several RHOA-interacting proteins, including proacrosin, angiotensin-converting enzyme, tubulin, aldolase C, and AKAP4. Using overlay and pulldown techniques, we demonstrate that phosphorylation of AKAP3 increases its interaction with the RHOA-interacting proteins PRKAR2 (the type II regulatory subunit of PRKA, formerly RII) and ropporin (ROPN1, a PRKAR2-like protein, or R2D2). Varying calcium concentrations in pulldown assays did not significantly alter binding to R2D2 proteins. These data suggest that the actin-regulating GNA13-mediated RHOA-ROCK-LIMK-cofilin pathway is present in bovine spermatozoa, that RHOA interacts with proteins involved in capacitation and the acrosome reaction, and that RHOA signaling in sperm may be targeted by AKAPs. Finally, AKAP3 binding to PRKAR2 and ROPN1 is regulated by phosphorylation in vitro.
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