Fully Dynamic High–Resolution Model for Dispersion of Icelandic Airborne Mineral Dust

Icelandic topsoil sediments, as confirmed by numerous scientific studies, represent the largest and the most important European source of mineral dust. Strong winds, connected with the intensive cyclonic circulation in the North Atlantic, induce intense emissions of mineral dust from local sources all year and carry away these fine aerosol particles for thousands of kilometers. Various impacts of airborne mineral dust particles on local air quality, human health, transportation, climate and marine ecosystems motivated us to design a fully dynamic coupled atmosphere–dust numerical modelling system in order to simulate, predict and quantify the Icelandic mineral dust process including: local measurements and source specification over Iceland. In this study, we used the Dust Regional Atmospheric Model (DREAM) with improved Icelandic high resolution dust source specification and implemented spatially variable particle size distribution, variable snow cover and soil wetness. Three case studies of intense short- and long-range transport were selected to evaluate the model performance. Results demonstrated the model’s capability to forecast major transport features, such as timing, and horizontal and vertical distribution of the processes. This modelling system can be used as an operational forecasting system, but also as a reliable tool for assessing climate and environmental Icelandic dust impacts. © 2022 by the authors

Gonadectomy in conditions affecting sex development: a registry-based cohort study

Objectives To determine trends in clinical practice for individuals with DSD requiring gonadectomy. Design Retrospective cohort study. Methods Information regarding age at gonadectomy according to diagnosis; reported sex; time of presentation to specialist centre; and location of centre from cases reported to the International DSD Registry and who were over 16 years old in January 2019. Results Data regarding gonadectomy were available in 668 (88%) individuals from 44 centres. Of these, 248 (37%) (median age (range) 24 (17, 75) years) were male and 420 (63%) (median age (range) 26 (16, 86) years) were female. Gonadectomy was reported from 36 centres in 351/668 cases (53%). Females were more likely to undergo gonadectomy (n = 311, P < 0.0001). The indication for gonadectomy was reported in 268 (76%). The most common indication was mitigation of tumour risk in 172 (64%). Variations in the practice of gonadectomy were observed; of the 351 cases from 36 centres, 17 (5%) at 9 centres had undergone gonadectomy before their first presentation to the specialist centre. Median age at gonadectomy of cases from high-income countries and low-/middle-income countries (LMIC) was 13.0 years (0.1, 68) years and 16.5 years (1, 28), respectively (P < 0.0001) with the likelihood of long-term retention of gonads being higher in LMIC countries. Conclusions The likelihood of gonadectomy depends on the underlying diagnosis, sex of rearing and the geographical setting. Clinical benchmarks, which can be studied across all forms of DSD will allow a better understanding of the variation in the practice of gonadectomy

A sex-related difference in the hypertrophic versus hyperplastic response of vascular smooth muscle cells to repeated passaging in culture

Activation of growth of vascular smooth muscle cells (VSMC) in adults participates in pathogenesis of dysplastic diseases of the vascular system. In this study, we examined the impact of gender of rat donors on the degree of hyperplastic and hypertrophic responses of VSMC in cultures subjected to repeated passaging. The cells were derived from the outgrowth zone of explants of the thoracic aorta and were studied up to passage 45. Under these conditions, the cells undergo repeated growth stimulation by the serum growth factors mimicking some pathological situations in vivo. At lower passages (5-7), the cells from both sex donors did not differ significantly in their doubling time, maximum population density, protein content and ploidy. At higher passages (40-45), we found that the hyperplastic response, monitored by doubling time and BrdU-revealed DNA synthesis, was more intense in VSMC of male origin. In contrast, female-derived cells reacted by more prominent hypertrophic changes. The latter included a relatively higher increase in the volume and protein content of cells. As indicated by the DNA content histograms and chromosome numbers, these cells also showed a higher degree of passage-dependent polyploidization. In addition, the female-derived VSMC were found to be more effective in adhesion to the growth support evidenced by wider spreading and higher resistance of these cells to trypsin-mediated detachment as well as higher expression of some integrin and cytoskeletal molecules. These features could partly account for the slower proliferation and polyploidization of these cells. The results suggest that rat VSMC populations of male and female origin contain cells which are intrinsically different with respect to their capability of reacting to growth stimuli. The lower responsiveness of femalederived cells to growth stimuli may contribute to less frequent formation of hyperplastic vascular lesions in female organisms

A sex-related difference in the hypertrophic versus hyperplastic response of vascular smooth muscle cells to repeated passaging in culture

Activation of growth of vascular smooth muscle cells (VSMC) in adults participates in pathogenesis of dysplastic diseases of the vascular system. In this study, we examined the impact of gender of rat donors on the degree of hyperplastic and hypertrophic responses of VSMC in cultures subjected to repeated passaging. The cells were derived from the outgrowth zone of explants of the thoracic aorta and were studied up to passage 45. Under these conditions, the cells undergo repeated growth stimulation by the serum growth factors mimicking some pathological situations in vivo. At lower passages (5-7), the cells from both sex donors did not differ significantly in their doubling time, maximum population density, protein content and ploidy. At higher passages (40-45), we found that the hyperplastic response, monitored by doubling time and BrdU-revealed DNA synthesis, was more intense in VSMC of male origin. In contrast, female-derived cells reacted by more prominent hypertrophic changes. The latter included a relatively higher increase in the volume and protein content of cells. As indicated by the DNA content histograms and chromosome numbers, these cells also showed a higher degree of passage-dependent polyploidization. In addition, the female-derived VSMC were found to be more effective in adhesion to the growth support evidenced by wider spreading and higher resistance of these cells to trypsin-mediated detachment as well as higher expression of some integrin and cytoskeletal molecules. These features could partly account for the slower proliferation and polyploidization of these cells. The results suggest that rat VSMC populations of male and female origin contain cells which are intrinsically different with respect to their capability of reacting to growth stimuli. The lower responsiveness of femalederived cells to growth stimuli may contribute to less frequent formation of hyperplastic vascular lesions in female organisms

Cisplatin induced gamma-glutamyltransferase up-regulation, hypertrophy and differentiation in astrocytic glioma cells in culture

Gamma-glutamyltransferase (GGT) hydrolyses gamma-glutamylated peptides, including glutathione and transports amino acids into the cells. The enzyme is up-regulated in some tumors, especially those with a higher degree of malignancy and resistance to cytostatics. In this study we examined the effects of Cisplatin (1.6 x 10-5M) on the activity of GGT in astrocytic C6 glioma cells in cultures monitored for growth, morphology and differentiation. Initially (24 h), the drug inhibited cell division and later (96 h), it caused apoptotic death of about half of the population. The more resistant and surviving cells became hypertrophic and more differentiated, as indicated by their larger size and higher protein content, including the maturationspecific GFAP. In addition, the activity of GGT was significantly elevated in these cells at 48 h and onwards. At 96 h, the biochemically determined enzyme activity was between 230% and 330% above the controls. Compared to the protein content, the GGT activity started to increase later (48 h) but it grew steeper towards 72-96 h. Similarly, histochemical analysis revealed a manifold increase in the number of GGT+ cells in the population and higher intensity of staining per cell from at 48 h and onwards. The study showed that the transformed astrocytic cells can up-regulate GGT activity as part of an adaptation and/or, survivalenhancing reaction triggered by Cisplatin

The Influence of Interleukin-1β on γ-Glutamyl Transpeptidase Activity in Rat Hippocampus

Summary Brain infections as well as peripheral challenges to the immune system lead to an increased production of interleukin1beta (IL-1β), a cytokine involved in leukocyte-mediated breakdown of the blood-brain barrier. The effects of IL-1β have been reported to depend on whether the route of administration is systemic or intracerebral. Using 50-day-old male rats, we compared the effects of IL-1β on brain γ-glutamyl transpeptidase (GGT; an enzymatic marker of brain capillary endothelium) at 2, 24 and 96 h after either an intravenous (i.v.) injection of 5 μg IL-1β or an intracerebroventricular (i.c.v. -lateral ventricle) infusion of 50 ng IL-1β. When the i.v. route was used, the GGT activity underwent small but significant changes; decreasing in the hippocampus 2 h after the i.v. injection, increasing 24 h later and returning to control levels at 96 h. No significant changes in the hippocampal GGT activity were observed at 2 and 24 h following the i.c.v. infusion. The GGT activity in the hypothalamus remained unchanged regardless of the route of IL-1β administrations. Similar changes in GGT activity were revealed histochemically. The labeling was found mainly in the capillary bed, the changes being most evident in the hippocampal stratum radiatum and stratum lacunosum-moleculare. A transient increase in GGT activity at 24 h, together with a less sharp delineation of GGT-stained vessels, may reflect IL-1β induced increased turnover of glutathione and/or oxidative stress, that may in turn, be related to altered permeability of the blood-brain barrier in some neurological and mental disorders, including schizophrenia