Sunscreens containing titanium dioxide (TiO(2)) and zinc oxide (ZnO) nanoparticles (NP) are effective barriers against ultraviolet B (UVB) damage to skin, although little is known about their ...disposition in UVB-damaged skin. Pigs were exposed to UVB that resulted in moderate sunburn. For in vitro studies, skin in flow-through diffusion cells were treated 24 h with four sunscreen formulations as follows: 10% coated TiO(2) in oil/water (o/w), 10% coated TiO(2) in water/oil (w/o), 5% coated ZnO in o/w, and 5% uncoated ZnO in o/w. TiO(2) (rutile, crystallite) primary particle size was 10 × 50 nm with mean agglomerates of 200 nm (range ca. 90 nm--460 nm); mean for ZnO was 140 nm (range ca. 60--200 nm). Skin was processed for light microscopy, scanning (SEM) and transmission electron microscopy (TEM), and time-of-flight secondary ion mass spectrometry (TOF-SIMS). UVB-exposed skin had typical sunburn histology. TEM showed TiO(2) NP 17 layers into stratum corneum (SC), whereas ZnO remained on the surface. TOF-SIMS showed TiO(2) and ZnO epidermal penetration in both treatments. Perfusate analyzed by TEM/energy dispersive x-ray spectroscopy or inductively coupled plasma mass spectrometry detected no Ti or Zn, indicating minimal transdermal absorption. In vivo, skin was dosed at 24 h occluded with formulations and at 48 h. TiO(2) NP in o/w formulation penetrated 13 layers into UVB-damaged SC, whereas only 7 layers in normal skin; TiO(2) in w/o penetrated deeper in UVB-damaged SC. Coated and uncoated Zn NP in o/w were localized to the upper one to two SC layers in all skin. By SEM, NP were localized as agglomerates in formulation on the skin surface and base of hair. TOF-SIMS showed Ti within epidermis and superficial dermis, whereas Zn was limited to SC and upper epidermis in both treatments. In summary, UVB-damaged skin slightly enhanced TiO(2) NP or ZnO NP penetration in sunscreen formulations but no transdermal absorption was detected.
•Scheduling and capacity planning of an innovative, flexible ammonia process.•Physical and chemical characteristics require non-linear modeling.•We use convex non-linear programming to combine ...scheduling and capacity planning.•We demonstrate the working principle using hourly market electricity prices.
Economic assessment of energy-related processes needs to adapt to the development of large-scale integration of renewable energies into the energy system. Flexible electrochemical processes, such as the electrolysis of water to produce hydrogen, are foreseen as cornerstones to renewable energy systems. These types of technologies require the current methods of energy storage scheduling and capacity planning to incorporate their distinct non-linear characteristics in order to be able to fully assess their economic impact. A combined scheduling and capacity planning model for an innovative, flexible electricity-to-hydrogen-to-ammonia plant is derived in this paper. A heuristic is presented, which is able to translate the depicted, non-convex and mixed-integer problem into a set of convex and continuous non-linear problems. These can be solved with commercially available solvers. The global optimum of the original problem is encircled by the heuristic, and, as the numerical illustration with German electricity market data of 2013 shows, can be narrowed down and approximated very well. The results show, that it is not only meaningfulness, but also feasible to solve a combined scheduling and capacity problem on a convex non-linear basis for this and similar new process concepts. Application to other hydrogen based concepts is straightforward and to other, non-linear chemical processes generally possible.
Neuroblastoma is an embryonal tumor with a heterogeneous clinical course. The tumor is presumed to be derived from the neural crest, but the cells of origin remain to be determined. To date, few ...recurrent genetic changes contributing to neuroblastoma formation, such as amplification of the MYCN oncogene and activating mutations of the ALK oncogene, have been identified. The possibility to model neuroblastoma in mice allows investigation of the cell of origin hypothesis in further detail. Here we present the evidence that murine neural crest progenitor cells can give rise to neuroblastoma upon transformation with MYCN or ALK(F1174L). For this purpose we used JoMa1, a multipotent neural crest progenitor cell line, which is kept in a viable and undifferentiated state by a tamoxifen-activated c-Myc transgene (c-MycER(T)). Expression of MYCN or ALK(F1174L), one of the oncogenic ALK variants identified in primary neuroblastomas, enabled these cells to grow independently of c-MycER(T) activity in vitro and caused formation of neuroblastoma-like tumors in vivo in contrast to parental JoMa1 cells and JoMa1 cells-expressing TrkA or GFP. Tumorigenicity was enhanced upon serial transplantation of tumor-derived cells, and tumor cells remained susceptible to the MYC-inhibitor, NBT-272, indicating that cell growth depended on functional MYCN. Our findings support neural crest progenitor cells as the precursor cells of neuroblastoma, and indicate that neuroblastomas arise as their malignant progeny.
We report results of a search for light (≲10 GeV) particle dark matter with the XENON10 detector. The event trigger was sensitive to a single electron, with the analysis threshold of 5 electrons ...corresponding to 1.4 keV nuclear recoil energy. Considering spin-independent dark matter-nucleon scattering, we exclude cross sections σ(n)>7×10(-42) cm(2), for a dark matter particle mass m(χ)=7 GeV. We find that our data strongly constrain recent elastic dark matter interpretations of excess low-energy events observed by CoGeNT and CRESST-II, as well as the DAMA annual modulation signal.
Perivascular macrophages (pvMs) are associated with cerebral vasculature and mediate brain drainage and immune regulation. Here, using reporter mouse models, whole brain and section ...immunofluorescence, flow cytometry, and single cell RNA sequencing, besides the Lyve1
F4/80
CD206
CX3CR1
pvMs, we identify a CX3CR1
pvM population that shares phagocytic functions and location. Furthermore, the brain parenchyma vasculature mostly hosts Lyve1
MHCII
pvMs with low to intermediate CD45 expression. Using the double Cx3cr1
x Cx3cr1-Cre;Rosa
reporter mice for finer mapping of the lineages, we establish that CD45
CX3CR1
pvMs are derived from CX3CR1
precursors and require PU.1 during their ontogeny. In parallel, results from the Cxcr4-CreErt2;Rosa26
lineage tracing model support a bone marrow-independent replenishment of all Lyve1
pvMs in the adult mouse brain. Lastly, flow cytometry and 3D immunofluorescence analysis uncover increased percentage of pvMs following photothrombotic induced stroke. Our results thus show that the parenchymal pvM population is more heterogenous than previously described, and includes a CD45
and CX3CR1
pvM population.
Stable isotope analysis of carbon and nitrogen can deliver insights into trophic interactions between organisms. While many studies on free-living organisms are available, the number of those ...focusing on trophic interactions between hosts and their associated parasites still remains scarce. In some cases information about taxa (e.g. acanthocephalans) is completely missing. Additionally, available data revealed different and occasionally contrasting patterns, depending on the parasite's taxonomic position and its degree of development, which is most probably determined by its feeding strategy (absorption of nutrients through the tegument versus active feeding) and its localization in the host.
Using stable isotope analysis of carbon and nitrogen we provided first data on the trophic position of an acanthocephalan species with respect to its fish host. Barbels (Barbus barbus) infected only with adult acanthocephalans Pomphorhynchus laevis as well as fish co-infected with the larval (L4) nematodes Eustrongylides sp. from host body cavity were investigated in order to determine the factors shaping host-parasite trophic interactions. Fish were collected in different seasons, to study also potential isotopic shifts over time, whereas barbels with single infection were obtained in summer and co-infected ones in autumn.
Acanthocephalans as absorptive feeders showed lower isotope discrimination values of δ
N than the fish host. Results obtained for the acanthocephalans were in line with other parasitic taxa (e.g. cestodes), which exhibit a similar feeding strategy. We assumed that they feed mainly on metabolites, which were reprocessed by the host and are therefore isotopically lighter. In contrast, the nematodes were enriched in the heavier isotope δ
N with respect to their host and the acanthocephalans, respectively. As active feeders they feed on tissues and blood in the body cavity of the host and thus showed isotope discrimination patterns resembling those of predators. We also observed seasonal differences in the isotope signatures of fish tissues and acanthocephalans, which were attributed to changes in food composition of the host and to seasonality in the transmission and development of acanthocephalans.
This study provided first data on trophic interaction between an acanthocephalan species and its associated host, which support the tendency already described for other taxa with similar nutrition strategy (e.g. cestodes). Actively feeding taxa such as larval Eustrongylides sp., appear to act like predators as it can be seen from their isotope discrimination values. However, future research on additional host-parasite systems and especially on acanthocephalans is needed in order to corroborate these conclusions.
The psychosocial outcomes of adolescents and young adults (AYAs) diagnosed with cancer are poorer compared to their peers without cancer. However, AYAs with cancer from diverse racial and ethnic ...groups have been under-represented in research, which contributes to an incomplete understanding of the psychosocial outcomes of all AYAs with cancer. This paper evaluated the racial and ethnic representation in research on AYAs diagnosed with cancer using observational, cross-sectional data from the large Young Adults with Cancer in Their Prime (YACPRIME) study. The purpose was to better understand the psychosocial outcomes for those from diverse racial and ethnic groups. A total of 622 participants with a mean age of 34.15 years completed an online survey, including measures of post-traumatic growth, quality of life, psychological distress, and social support. Of this sample, 2% (
= 13) of the participants self-identified as Indigenous, 3% (
= 21) as Asian, 3% (
= 20) as "other," 4% (
= 25) as multi-racial, and 87% (
= 543) as White. A one-way ANOVA indicated a statistically significant difference between racial and ethnic groups in relation to
, a subscale of post-traumatic growth,
(4,548) = 6.02,
< 0.001. Post hoc analyses showed that those under the "other" category endorsed greater levels of spiritual change than those who identified as multi-racial (
< 0.001, 95% CI = 2.49,7.09) and those who identified as White (
< 0.001, 95% CI = 1.60,5.04). Similarly, participants that identified as Indigenous endorsed greater levels of spiritual change than those that identified as White (
= 0.03, 95% CI = 1.16,4.08) and those that identified as multi-racial (
= 0.005, 95% CI = 1.10,6.07). We provided an extensive discussion on the challenges and limitations of interpreting these findings, given the unequal and small sample sizes across groups. We concluded by outlining key recommendations for researchers to move towards greater equity, inclusivity, and culturally responsiveness in future work.
IntroductionPaediatric cancer affects children and families from diverse backgrounds. However, there is a limited understanding of how diversity/cultural factors play a role, especially in ...survivorship. This protocol outlines a systematic review on the cultural influences in survivors of childhood cancer.Methods and analysisThis protocol is reported based on the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA) guidelines checklist and is registered with PROSPERO. EMBASE, MEDLINE and PsycINFO are searched. Eligibility criteria include original research studies published in English, and an assessment of culture on survivors of childhood cancer. Search terms are developed with a medical librarian. Primary objective will be to describe culture (ethnic and population groups, migration status, acculturation, cultural characteristics) in survivors of paediatric cancer and study characteristics and methods. Secondary objective will be to identify the role of culture in outcomes of survivors of paediatric cancer. Data extraction will include participant characteristics such as the number of participants and/or controls, sex, age at diagnosis. Extraction will also include analytical approaches, type of cultural variables (predictor, moderator, mediator, outcome) and effect measures.Ethics and disseminationEthical approval was not required for this systematic review. Results from this systematic review will be disseminated in line with PRISMA guidelines through peer-reviewed publications and conference presentations. Findings will also be shared with our target communities, including survivors of childhood cancer and their families, through the creation of lay summaries and/or educational workshops in the community. Knowledge gathered from this review may help to identify gaps in knowledge and directions for future research. They may also inform the development of clinical recommendations for healthcare providers of survivors of childhood cancer.PROSPERO registration numberCRD42021234101.
Background Protein phosphatase 2A (PP2A) is a serine/threonine-selective holoenzyme that controls Ca 2+ homeostasis and contractility of the heart via dephosphorylation of regulatory proteins. In ...some genetically modified mouse models with increased arrhythmogenicity, a reduced expression of the regulatory subunit B56α of PP2A was found as a concomitant effect. Whether there is a general correlation between the abundance of B56α and the promotion of cardiac arrhythmogenesis remains unclear. Methods The aim of this study was therefore to investigate the role of PP2A-B56α in the propensity for arrhythmic activity in the heart. The experimental analysis of this question has been addressed by using a mouse model with deletion of the PP2A-B56α gene, PPP2R5A (KO), in comparison to wild-type animals (WT). Evidence for arrhythmogenicity was investigated in whole animal, isolated heart and cardiomyocytes by ECG, recording of monophasic action potential (MAP) induced by programmed electrical stimulation (PES), measurement of Ca 2+ transients under increased pacing frequencies and determination of total K + channel currents ( I K ). Results ECG measurements showed a prolongation of QT time in KO vs. WT. KO mice exhibited a higher rate of premature ventricular contractions in the ECG. MAP measurements in Langendorff-perfused KO hearts showed increased episodes of ventricular tachyarrhythmia induced by PES. However, the KO hearts showed values for MAP duration that were similar to those in WT hearts. In contrast, KO showed more myocardial cells with spontaneous arrhythmogenic Ca 2+ transient events compared to WT. The whole-cell patch-clamp technique applied to ventricular cardiomyocytes revealed comparable peak potassium channel current densities between KO and WT. Conclusion These findings support the assumption that a decrease or even the loss of PP2A-B56α leads to an increased propensity of triggered arrhythmias. This could be based on the increased spontaneous Ca 2+ tansients observed.
Understanding molecular mechanisms involved in atrial tissue remodeling and arrhythmogenesis in atrial fibrillation (AF) is essential for developing specific therapeutic approaches. Two-pore-domain ...potassium (K
2P
) channels modulate cellular excitability, and TASK-1 (K
2P
3.1) currents were recently shown to alter atrial action potential duration in AF and heart failure (HF). Finding animal models of AF that closely resemble pathophysiological alterations in human is a challenging task. This study aimed to analyze murine cardiac expression patterns of K
2P
channels and to assess modulation of K
2P
channel expression in murine models of AF and HF. Expression of cardiac K
2P
channels was quantified by real-time qPCR and immunoblot in mouse models of AF cAMP-response element modulator (CREM)-IbΔC-X transgenic animals or HF (cardiac dysfunction induced by transverse aortic constriction, TAC). Cloned murine, human, and porcine TASK-1 channels were heterologously expressed in
Xenopus laevis
oocytes. Two-electrode voltage clamp experiments were used for functional characterization. In murine models, among members of the K
2P
channel family, TASK-1 expression displayed highest levels in both atrial and ventricular tissue samples. Furthermore, K
2P
2.1, K
2P
5.1, and K
2P
6.1 showed significant expression levels. In CREM-transgenic mice, atrial expression of TASK-1 was significantly reduced in comparison with wild-type animals. In a murine model of TAC-induced pressure overload, ventricular TASK-1 expression remained unchanged, while atrial TASK-1 levels were significantly downregulated. When heterologously expressed in
Xenopus oocytes
, currents of murine, porcine, and human TASK-1 displayed similar characteristics. TASK-1 channels display robust cardiac expression in mice. Murine, porcine, and human TASK-1 channels share functional similarities. Dysregulation of atrial TASK-1 expression in murine AF and HF models suggests a mechanistic contribution to arrhythmogenesis.
PDF
