Solar lentigines are strongly related to sun exposure in contrast to ephelides

Solar lentigines and ephelides are different types of pigmented skin lesions predominantly present on sun-exposed skin. Both lesions are risk indicators for melanoma and non-melanoma skin cancer. Solar lentigines are considered as a sign of photodamage although well-conducted epidemiological studies are lacking on this subject. Ephelides are associated with fair skin type and red hair. The aim of the present study was to investigate the relation of sun-exposure estimates with solar lentigines and ephelides. In the Leiden Skin cancer Study 577 patients with malignant melanoma and/or non-melanoma skin cancer and 385 individuals without a history of skin cancer were studied. The presence of solar lentigines and ephelides in the face and on the back was assessed. Data on skin type, hair color, sun-exposure variables and cutaneous signs of photodamage were collected, by questionnaire and physical examination. Data were analyzed by chi-square or Student t-tests and with multivariable regression. Exposure odds ratios with 95% confidence intervals (95% CI) were calculated to estimate the relative risk for the presence of solar lentigines and ephelides dependent on signs of photodamage. The association with age was strongly positive for solar lentigines whereas it was strongly negative for ephelides (P-values for trend <0.0001). After adjustment for age, sex and skin type, solar lentigines on the back were positively associated with cumulative (P = 0.01) and intermittent (P = 0.0002) sun exposure. After adjustment, solar lentigines on the back were also associated with a history of sunburns before the age of 20 yr (P = 0.0003) and the number of sunburns in childhood (P = 0.002). Solar lentigines in the face were significantly associated with cutaneous signs of photodamage, i.e. elastosis (odds ratio 2.4, 95% CI 1.7-3.3) and actinic keratosis (odds ratio 1.8, 95% CI 1.3-2.4) whereas ephelides were not. Ephelides in the face and on the back showed an inverse association with chronic sun exposure but after adjustment theses associations disappeared. Sunburns before the age of 20 appeared to be positively associated with ephelides on the back (P = 0.04). In contrast to lentigines, ephelides were much more associated with constitutional host factors such as fair skin and/or red hair (both P < 0.0001). This study indicates that both chronic and acute sun exposure are important in the pathogenesis of solar lentigines.     

The effect of digitonin-containing fixatives on the retention of free cholesterol and cholesterol esters

Synopsis The influence of several fixation and dehydration procedures on the retention of free cholesterol and cholesterol esters was studied in filter paper preparations. The retention of free cholesterol by the filter paper proved to be decreased by the addition of digitonin to the aldehyde fixative (aqueous phase) and was only slightly enhanced by partial dehydration (alcoholic phase, up to 70% ethanol). Furthermore, digitonin or the presumably formed cholesterol-digitonide complex bound hardly any osmium oxides in glass-fibre paper.Up to 26% of the cholesterol esters was mobilized during the aqueous phase when digitonin was added to the aldehyde fixative. When the glass-fibre papers containing the digitonin cholesterol-ester-osmate complexes were stored in distilled water after fixation, the fluid became turbid. Particulate material isolated from this turbid solution showed ultrastructurally a close resemblance to the whorls observed by several authors in tissue fixed by a digitonin-containing aldehyde fixative.Digitonin also changed the ultrastructural appearance of liposomes, containing lecithin: cholesterol: phosphatidic acid, in a molar ratio 721. Our observations lead to the conclusion that the use of digitonin-containing fixatives should be abandoned, because they give results which cannot be interpreted. By the use of K₄[Fe(CN)₆] containing OsO₄ in the post-fixation step we were able to demonstrate an increase in the visualization of membranous structures (liposomes).     

The relationship between plankton-feeding Bonaparte's and Mew Gulls and tidal upwelling at Active Pass, British Columbia

The food habits of Bonaparte's (Larus Philadelphia) and MewGulls (L. canus) were studied at Active Pass, British Columbia,in relation to upwelling of zooplankton. Bonaparte's Gulls fedmostly on planktonic crustaceans during September-November andagain during April-May, while Mew Gulls foraged there chieflyin February and March. Both species ate predominantly the euphausiid,Thysanoessa raschii, in spring, while Bonaparte's Gulls fedmainly on the amphipods, Parathemisto pacifica and Calliopiuslaeviusculus, in fall. Year-round sampling of zooplankton andcollection of temperature and salinity data showed gull numbersto correlate with times of maximum upwelling and abundance ofzooplankton prey in surface waters. Outside the upwelling zonein Active Pass, Bonaparte's and Mew Gulls fed mostly on fishesand intertidal organisms, but also on zooplankton along tidelines.     

erbB1 functions as a sensor of airway epithelial integrity by regulation of protein phosphatase 2A activity

Two enzymes, protein phosphatase 2A and atypical protein kinase C, are associated with the tight junction and regulate its function. For example, phosphorylation of the tight junction protein occludin is required for its incorporation into the junction. The association of a kinase and phosphatase with the tight junction suggests that a balance between their activities exists and is required for normal tight junction function. This hypothesis predicts that loss of epithelial integrity may disrupt this balance in such a way as to facilitate restoration of epithelial integrity. Our previous data have shown that apically localized growth factors segregate from their basolaterally localized erbB receptors. Loss of epithelial integrity allows ligand access to the basolateral membrane where it immediately binds to and activates erbB receptors. We found that activation of erbB1 leads to phosphorylation of protein phosphatase 2A, inhibiting its activity. Importantly, this phosphorylation event was dependent on factors in the overlying airway surface liquid; washing away this liquid prevented phosphorylation. erbB1-mediated inhibition of phosphatase activity would shift the balance in favor of the kinase such that tight junction proteins would regain their phosphorylation, allowing for their incorporation into the junction complex. This mechanism provides a rapid means of sensing the loss of epithelial integrity and subsequently restoring barrier function.     

Warming up the system: higher predator feeding rates but lower energetic efficiencies

Predictions on the consequences of the rapidly increasing atmospheric CO₂ levels and associated climate warming for population dynamics, ecological community structure and ecosystem functioning depend on mechanistic energetic models of temperature effects on populations and their interactions. However, such mechanistic approaches combining warming effects on metabolic (energy loss of organisms) and feeding rates (energy gain by organisms) remain a key, yet elusive, goal. Aiming to fill this void, we studied the metabolic rates and functional responses of three differently sized, predatory ground beetles on one mobile and one more resident prey species across a temperature gradient (5, 10, 15, 20, 25 and 30 °C). Synthesizing metabolic and functional‐response theory, we develop novel mechanistic predictions how predator–prey interaction strengths (i.e., functional responses) should respond to warming. Corroborating prior theory, warming caused strong increases in metabolism and decreases in handling time. Consistent with our novel model, we found increases in predator attack rates on a mobile prey, whereas attack rates on a mostly resident prey remained constant across the temperature gradient. Together, these results provide critically important information that environmental warming generally increases the direct short‐term per capita interaction strengths between predators and their prey as described by functional‐response models. Nevertheless, the several fold stronger increase in metabolism with warming caused decreases in energetic efficiencies (ratio of per capita feeding rate to metabolic rate) for all predator–prey interactions. This implies that warming of natural ecosystems may dampen predator–prey oscillations thus stabilizing their dynamics. The severe long‐term implications; however, include predator starvation due to energetic inefficiency despite abundant resources.     

Cucurbitacin E and I target the JAK/STAT pathway and induce apoptosis in Sézary cells

Cutaneous T-cell lymphomas and leukemias (CTCLs) are a heterogeneous group of extranodal non-Hodgkin's lymphomas. These are characterized by an accumulation of malignant CD4⁺ T-lymphocytes in the skin, lymph nodes, and peripheral blood. Novel treatment options are needed for patients who progress to advanced stage disease. Cucurbitacin I has previously shown promising results in Sézary syndrome (Sz). A plethora of cucurbitacins, however, have not yet been tested in CTCL. Herein, we investigated the effect of cucurbitacin E and I in two CTCL cell lines. We show that both cucurbitacins decrease viability and cause apoptosis in these cell lines, although HuT-78 was more affected than SeAx (IC₅₀ of 17.38 versus 22.01 μM for cucurbitacin E and 13.36 versus 24.47 μM for cucurbitacin I). Moreover, both cucurbitacins decrease viability of primary cells of a Sz patient (56.46% for cucurbitacin E and 59.07% for cucurbitacin I). Furthermore, while JAK2 inhibition leads to decreased viability in SeAx cells (IC₅₀ of 9.98 and 29.15 μM for AZD1480 and ruxolitinib respectively), both JAK1 and JAK3 do not. This suggests that JAK2 has a preferential role in promoting survival. Western blotting in SeAx cells revealed that both cucurbitacins inhibit STAT3 activation (P < 0.0001), while only cucurbitacin I inhibits STAT5 activation (P = 0.05). This suggests that STAT3 plays a preferential role in the mechanism of action of these cucurbitacins. Nevertheless, a role of STAT5 and JAK2 cannot be excluded and should be explored further. This knowledge could contribute to the development of effective therapies for CTCL and other malignancies involving dysfunction of the JAK/STAT pathway.