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This study, conducted in Debrecen, Hungary, aimed to analyse atmospheric particulate matter (APM or PM) through radiocarbon and PIXE analyses during the winter smog (23-25 January) and spring (15-18 May) seasons. The information presented in this pilot study aims to provide insight into the importance of utilising detailed characteristics of the mass size distributions of fossil carbon (f f ) and contemporary carbon (f C ) content. Additionally, it seeks to compare these characteristics with the size distributions of various elements to enable even more accurate PM source identification. In winter, APM concentrations were 86.27 μg/m 3 (total), 17.07 μg/m 3 (f C ) and 10.4 μg/m 3 (f f ). In spring, these values changed to 29.5 μg/m 3 , 2.64 μg/m 3 and 7.01 μg/m 3 , respectively. Notably, differences in mass size distribution patterns were observed between the two seasons, suggesting varied sources for contemporary carbon. Biomass burning emerged as a crucial source during the smog period, supported by similar MMAD (Mass Median Aerodynamic Diameter) values and a strong correlation (r = 0.95, p < 0.01) between potassium and f C. In spring, a significant change in the concentration and distribution of f C occurred, with a broad, coarse mode and a less prominent accumulation mode. F f was found to have similar distributions as PM, with nearly the same MMADs, during both periods. Finally, a comprehensive comparison of modal characteristics identified specific sources for the various components, including biomass burning, vehicle exhaust, coal and oil combustion, vehicle non-exhaust, road dust, tyre abrasion, mineral dust and biogenic emission. This study showcases how using radiocarbon and PIXE analysis in size distribution data can enhance our understanding of the sources of PM and their effects on different size fractions of PM., (© 2024. The Author(s).)

The focused electron beam-induced deposition (FEBID) process was used by employing a GeminiSEM with a beam characteristic of 1 keV and 24 pA to deposit pillars and line-shaped nanostructures with heights between 9 nm and 1 μm and widths from 5 nm to 0.5 μm. All structures have been analyzed to their composition looking at a desired Si/O/C content measuring a 1:2:0 ratio. The C content of the structure was found to be ∼over 60% for older deposits kept in air (∼at room temperature) and less than 50% for later deposits, only 12 h old. Upon depositing Si(OEt) 4 at high rates and at a deposition temperature of under 0 °C, the obtained Si content of our structures was between 10 and 15 atom % (compositional percentage). The FEBID structures have been deposited on Au(111)/SiO 2 . The Au(111) was chosen as a substrate for the deposition of Si(OEt) 4 due to its structural and morphological properties. With its surface granulation following a Chevron pattern and surface defects having an increased contribution to the changes in the composition of the final structure content, the Au(111) surface characteristic behavior at the deposition of Si(OEt) 4 is an increase in the O ratio and a reduction in the nanodeposit heights., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Ion beam analysis plays an important role in cultural heritage (CH) studies as it offers a combination of simultaneous and complementary analytical techniques (PIXE/PIGE/RBS) and spatially resolved mapping functions. Despite being considered non-destructive, the potential risk of beam-induced modifications during analysis is increasingly discussed. This work focuses on the impact of proton beams on parchment, present in our CH in form of unique historical manuscripts. Parchment is one of the organic, protein-based CH materials believed to be the most susceptible to radiation-induced changes. Various modification patterns, observed on parchment cross-sections by optical and electron microscopy are reported: discoloration (yellowing), formation of cavities and denaturation of collagen fibers. Considerable modifications were detected up to 100 µm deep into the sample for beam fluences of 4 µC/cm 2 and higher. The presence of ultramarine paint on the parchment surface appears to increase the harmful effects of proton radiation. Based on our results, a maximum radiation dose of 0.5 µC/cm 2 can be considered as 'safe boundary' for 2.3 MeV PIXE analysis of parchment under the applied conditions., (© 2022. The Author(s).)

The P-type ATPase CrpA is an important Cu 2+ /Cd 2+ pump in the Aspergilli, significantly contributing to the heavy metal stress tolerance of these ascomycetous fungi. As expected, the deletion of crpA resulted in Cu 2+ /Cd 2+ -sensitive phenotypes in Aspergillus nidulans on stress agar plates inoculated with conidia. Nevertheless, paradoxical growth stimulations were observed with the ΔcrpA strain in both standard Cu 2+ stress agar plate experiments and cellophane colony harvest (CCH) cultures, when exposed to Cd 2+ . These observations reflect efficient compensatory mechanisms for the loss of CrpA operating under these experimental conditions. It is remarkable that the ΔcrpA strain showed a 2.7 times higher Cd biosorption capacity in CCH cultures, which may facilitate the development of new, fungal biomass-based bioremediation technologies to extract harmful Cd 2+ ions from the environment. The nullification of crpA also significantly changed the spatial distribution of Cu and Cd in CCH cultures, as demonstrated by the combined particle-induced X-ray emission and scanning transmission ion microscopy technique. Most important, the centers of gravity for Cu and Cd accumulations of the ΔcrpA colonies shifted toward the older regions as compared with wild-type surface cultures., (© 2020 The Authors. Journal of Basic Microbiology published by Wiley-VCH Verlag GmbH & Co. KGaA.)

Around a quarter of the global adult population have metabolic syndrome (MetS) and therefore increased risk of cardiovascular mortality and diabetes. Docosahexaenoic acid, oat beta-glucan and grape anthocyanins have been shown to be effective in reducing MetS risk factors when administered as isolated compounds, but their effect when administered as bioactive-enriched foods has not been evaluated., Objective: The overall aim of the PATHWAY-27 project was to evaluate the effectiveness of bioactive-enriched food consumption on improving risk factors of MetS. A pilot study was conducted to assess which of five bioactive combinations provided within three different food matrices (bakery, dairy or egg) were the most effective in adult volunteers. The trial also evaluated the feasibility of production, consumer acceptability and gastrointestinal tolerance of the bioactive-enriched food., Method: The study included three monocentric, parallel-arm, double-blind, randomised, dietary intervention trials without a placebo. Each recruiting centre tested the five bioactive combinations within a single food matrix., Results: The study was completed by 167 participants (74 male, 93 female). The results indicated that specific bioactive/matrix combinations have effects on serum triglyceride or HDL-cholesterol level without adverse effects., Conclusion: The study evidenced that bioactive-enriched food offers a promising food-based strategy for MetS prevention, and highlighted the importance of conducting pilot studies.

Infantile malignant osteopetrosis (IMO) is a rare, lethal, autosomal recessive disorder characterized by nonfunctional osteoclasts. More than 50% of the patients have mutations in the TCIRG1 gene, encoding for a subunit of the osteoclast proton pump. The aim of this study was to develop a clinically applicable lentiviral vector expressing TCIRG1 to correct osteoclast function in IMO. Two mammalian promoters were compared: elongation factor 1α short (EFS) promoter and chimeric myeloid promoter (ChimP). EFS promoter was chosen for continued experiments, as it performed better. IMO osteoclasts corrected in vitro by a TCIRG1-expressing lentiviral vector driven by EFS (EFS-T) restored Ca 2+ release to 92% and the levels of the bone degradation product CTX-I to 95% in the media compared to control osteoclasts. IMO CD34 + cells from five patients transduced with EFS-T were transplanted into NSG mice. Bone marrow was harvested 9-19 weeks after transplantation, and human CD34 + cells were selected, expanded, and seeded on bone slices. Vector-corrected IMO osteoclasts had completely restored Ca 2+ release. CTX-I levels in the media were 33% compared to normal osteoclasts. Thus, in summary, evidence is provided that transduction of IMO CD34+ cells with the clinically applicable EFS-T vector leads to full rescue of osteoclasts in vitro and partial rescue of osteoclasts generated from NSG mice engrafting hematopoietic cells. This supports the continued clinical development of gene therapy for IMO.

Infantile malignant osteopetrosis (IMO) is a rare, recessive disorder characterized by increased bone mass caused by dysfunctional osteoclasts. The disease is most often caused by mutations in the TCIRG1 gene encoding a subunit of the V-ATPase involved in the osteoclasts capacity to resorb bone. We previously showed that osteoclast function can be restored by lentiviral vector-mediated expression of TCIRG1, but the exact threshold for restoration of resorption as well as the cellular response to vector-mediated TCIRG1 expression is unknown. Here we show that expression of TCIRG1 protein from a bicistronic TCIRG1/GFP lentiviral vector was only observed in mature osteoclasts, and not in their precursors or macrophages, in contrast to GFP expression, which was observed under all conditions. Thus, vector-mediated TCIRG1 expression appears to be post-transcriptionally regulated, preventing overexpression and/or ectopic expression and ensuring protein expression similar to that of wild-type osteoclasts. Codon optimization of TCIRG1 led to increased expression of mRNA but lower levels of protein and functional rescue. When assessing the functional rescue threshold in vitro, addition of 30 % CB CD34 + cells to IMO CD34 + patient cells was sufficient to completely normalize resorptive function after osteoclast differentiation. From both an efficacy and a safety perspective, these findings will clearly be of benefit during further development of gene therapy for osteopetrosis.

Anthocyanins, water soluble polyphenols, have been associated with several beneficial health effects. The aim of this study was to determine how the baking process and food matrix affect anthocyanin stability and bioaccessibility in bakery products in order to develop functional foods. Three well known regularly consumed bakery products (buns, breadsticks and biscuits) were enriched with anthocyanin (AC) isolated from grape skin alone or in combination with docosahexaenoic acid (AC + DHA) to reveal knowledge on AC as active ingredients in real food systems rather than pure compounds. Anthocyanin amounts added to the formulations of buns, breadsticks and biscuits were 34 mg per 100 g, 40 mg per 100 g and 37 mg per 100 g, respectively. The effect of processing, storage and the food matrix on AC stability and bioaccessibility was investigated. In addition, the sensory properties of bakery products were evaluated. Breadsticks enriched with AC and AC + DHA received the lowest scores in the pre-screening sensory test. Therefore breadsticks were excluded from further analysis. AC retentions, which were monitored by determination of malvidin 3-O-glucoside, in the bun and biscuit after baking were 95.9% (13.6 mg per 100 g) and 98.6% (15.2 mg per 100 g), respectively. Biscuits and buns enriched only with AC showed significantly higher anthocyanin bioaccessibilities (57.26% and 57.30%, respectively) than the same ones enriched with AC + DHA. AC stability in enriched products stored for 21 days was significantly lower than in products stored for 7 days (p < 0.05). However, this loss can be accepted as negligible since more than 70% of AC was retained in all the products.

Hypoxia is an important factor in the hematopoietic stem cell (HSC) niche in the bone marrow, but whether it also plays a role in the regulation of fetal liver (FL) HSCs is unclear. Vascular endothelial growth factor A (VEGFA) is essential for adult HSC survival, and hypoxic induction of VEGFA in adult HSCs is required for proper function. Loss of hypoxia-regulated VEGFA expression increases the number of phenotypically defined hematopoietic stem and progenitor cells in the FL, but whether stem cell function is affected in FL HSCs has not, to our knowledge, been assessed. We show that fetal erythropoiesis is severely impaired when hypoxic induction of VEGFA is lacking. FL HSCs deficient for hypoxia-induced VEGFA expression have normal HSC function, arguing against a hypoxic FL HSC niche. However, after adaptation of FL HSCs to the bone marrow microenvironment, FL HSCs lose their function, as measured by serial transplantation., (Copyright © 2014 ISEH - International Society for Experimental Hematology. Published by Elsevier Inc. All rights reserved.)

In this case study, the elemental composition and mass size distribution of indoor aerosol particles were determined in a working environment where soldering of printed circuit boards (PCB) took place. Single particle analysis using ion and electron microscopy was carried out to obtain more detailed and reliable data about the origin of these particles. As a result, outdoor and indoor aerosol sources such as wave soldering, fluxing processes, workers' activity, mineral dust, biomass burning, fertilizing and other anthropogenic sources could be separated. With the help of scanning electron microscopy, characteristic particle types were identified. On the basis of the mass size distribution data, a stochastic lung deposition model was used to calculate the total and regional deposition efficiencies of the different types of particles within the human respiratory system. The information presented in this study aims to give insights into the detailed characteristics and the health impact of aerosol particles in a working environment where different kinds of soldering activity take place., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Background: Osteoclasts play a critical role in bone resorption under basal conditions, but they also contribute to pathological bone loss during diseases including postmenopausal osteoporosis. Phospholipase Cγ2 (PLCγ2) is an important signalling molecule in diverse haematopoietic lineages. Here, we tested the role of PLCγ2 in basal and ovariectomy-induced bone resorption, as well as in in vitro osteoclast cultures using PLCγ2-deficient (PLCγ2(-/-) ) mice., Materials and Methods: The trabecular architecture of long bone metaphyses was tested by micro-CT and histomorphometric analyses. Postmenopausal osteoporosis was modelled by surgical ovariectomy. Osteoclast development and function, gene expression and PLCγ2 phosphorylation were tested on in vitro osteoclast and macrophage cultures., Results:   PLCγ2(-/-) mice had significantly higher trabecular bone mass under basal conditions than wild-type mice. PLCγ2 was required for in vitro development and resorptive function of osteoclasts, but not for upregulation of osteoclast-specific gene expression. PLCγ2 was phosphorylated in a Src-family-dependent manner upon macrophage adhesion but not upon stimulation by M-CSF or RANKL. Surprisingly, ovariectomy-induced bone resorption in PLCγ2(-/-) mice was similar to, or even more robust than, that in wild-type animals., Conclusions: Our results indicate that PLCγ2 participates in bone resorption under basal conditions, likely because of its role in adhesion receptor signalling during osteoclast development. In contrast, PLCγ2 does not appear to play a major role in ovariectomy-induced bone loss. These results suggest that basal and oestrogen deficiency-induced bone resorption utilizes different signalling pathways and that PLCγ2 may not be a suitable therapeutic target in postmenopausal osteoporosis., (© 2011 The Authors. European Journal of Clinical Investigation © 2011 Stichting European Society for Clinical Investigation Journal Foundation.)

Lymphangiomas are uncommun congenital malformations of the lymphatic system, that involve the skin and subcutaneous tissues. Of the several types of treatment, surgical excision has been the preferred. There is a high recurrence rate because lymphangiomas tend to infiltrate the surrounding tissues. The bleomycin is a cytotoxic antitumoral antibiotic, that causes modifications of DNA. It has been also successfully used in intralesional injection treatment of cystic hygromas and haemangiomas, based specifically on a high sclerosing effect on vascular endothelium. We report the cases of five patients, with congenital lymphangioma, localized on the leg, in cervical and latero-thoracal region, treated with repeated intralesional bleomycin injections. The treatment indication was given by the location of this lesions and the infiltration of the surrounding vital tissues, that made the complete surgical excision impossible. Intralesional injection of bleomycin into the lymphangiomas was given at a dose, not exceeding 0,5 mg/kg of body weight, at intervals of 4 weeks. Complete resolution (n = 4) or significant improvement (n = 1) occurred in all patients treated. No other treatment was needed. We didn't notice local or general adverse effects. With this method we set the purpose to treat effectively this congenital malformations, obviating the need for invasive primary surgery or systemic treatment regimens. Toward other methods, intralesional bleomycin injections have a minimal risk of side effects (ulceration, pulmonary fibrosis).

Beta(2) integrins of neutrophils play a critical role in innate immune defense, but they also participate in tissue destruction during autoimmune inflammation. p190RhoGAP (ArhGAP35), a regulator of Rho family small GTPases, is required for integrin signal transduction in fibroblasts. Prior studies have also suggested a role for p190RhoGAP in beta(2) integrin signaling in neutrophils. To directly test that possibility, we have generated a novel targeted mutation completely disrupting the p190RhoGAP-encoding gene in mice. p190RhoGAP deficiency led to perinatal lethality and defective neural development, precluding the analysis of neutrophil functions in adult p190RhoGAP(-/-) animals. This was overcome by transplantation of fetal liver cells from p190RhoGAP(-/-) fetuses into lethally irradiated wild-type recipients. Neutrophils from such p190RhoGAP(-/-) bone marrow chimeras developed normally and expressed normal levels of various cell surface receptors. Although p190RhoGAP(-/-) neutrophils showed moderate reduction of beta(2) integrin-mediated adherent activation, they showed mostly normal migration in beta(2) integrin-dependent in vitro and in vivo assays and normal beta(2) integrin-mediated killing of serum-opsonized Staphylococcus aureus and Escherichia coli. A neutrophil- and beta(2) integrin-dependent transgenic model of the effector phase of autoimmune arthritis also proceeded normally in p190RhoGAP(-/-) bone marrow chimeras. In contrast, all the above responses were completely blocked in CD18(-/-) neutrophils or CD18(-/-) bone marrow chimeras. These results suggest that p190RhoGAP likely does not play a major indispensable role in beta(2) integrin-mediated in vitro and in vivo neutrophil functions or the effector phase of experimental autoimmune arthritis.

Primary non-Hodgkin's lymphoma (NHL) of the genital tract is a rare entity. Etiology and pathogenesis of these NHLs are unknown, although there might be a possible association between chronic inflammation and lymphomas. The most common histological subtype is the diffuse large B-cell lymphoma. We report two cases of uterine lymphoma and one case of prostate lymphoma in this paper. The symptoms and the differential diagnosis are also discussed. Because of the low incidence, there is no widely accepted consensus on its treatment. We demonstrate that the rituximab and CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone; R-CHOP) chemoimmunotherapy is a good and tolerable treatment option in all cases. The two young patients are disease-free nowadays; the older patient with poor prognostic histological-type lymphoma relapsed in a short time and died after second relapse. A multicenter analysis is necessary to evaluate the long-term results of chemoimmunotherapy in these rare extranodal lymphoma entities.

Titanium dioxide (TiO2) nanoparticles are ubiquitously used materials in everyday life (e.g. paints,household products and plastic goods). However, despite the wide array of common applications, their pathogenetic role was also suggested under certain conditions (e.g. pulmonary neoplasias and lung fibrosis). From a dermatological point of view, it is also of great importance that TiO2 also serves as a physical photoprotective agent in sunscreens and is widely used in various cosmetic products. However, the effect of TiO2 on human cutaneous functions is still unknown. Therefore, in the current study, we investigated the in vivo penetration of TiO2 via human skin transplanted to immunodeficient mice and,furthermore, we measured the in vitro effects of nanoparticles on various functional properties of numerous epidermal and dermal cells in culture. Hereby, using various nuclear microscopy methods, we provide the first evidence that TiO2nanoparticles in vivo do not penetrate through the intact epidermal barrier. However, we also report that TiO2, when exposed directly to cell cultures in vitro, exerts significant and cell-type dependent effects on such cellular functions as viability, proliferation, apoptosis and differentiation. Therefore, our novel findings will hopefully inspire one to systemically explore in future, clinically oriented trials whether there is indeed a risk from micronized TiO2-containing products on skin with an impaired stratum corneum barrier function.

Increased common carotid artery (CCA) intima-media thickness (IMT) measured by B-mode ultrasound is an early marker of the atherosclerotic process. Arterial calcification is not clearly understood. Using the particle-induced X-ray emission (PIXE) method, we have looked for the location in the artery wall where calcium accumulated in the early phase of atherosclerosis. Twelve segments of CCAs of deceased stroke patients were investigated. In-vivo, carotid duplex ultrasound was performed with bilateral CCA IMT measurement at plaque-free sections. During autopsy, segments of carotid arteries were collected and filled under pressure with a stained histologic embedding material. The frozen arteries were cut into 60-microm-thick slices. Calcium distribution maps from the segments of arteries were determined by PIXE method. IMT measured by ultrasound and calcium distribution maps measured by PIXE were compared. In our cross-sectional study, using the PIXE analysis and ultrasound images, we could demonstrate early calcium accumulation in the media layer. Our results have also shown a significant relationship between calcium content of distributional maps measured by PIXE analysis and corresponding IMT on B-mode ultrasound images of human CCAs.

There is an increasing body of evidence that suggests that genes involved in cell fate decisions and pattern formation during development also play a key role in the continuous cell fate decisions made by adult tissue stem cells. Here we show that prolonged in vitro culture (14 days) of murine bone marrow lineage negative cells in medium supplemented with three early acting cytokines (stem cell factor, Flk-2/Flt-3 ligand, thrombopoietin) and with immobilized Notch ligand, Jagged-1, resulted in robust expansion of serially transplantable hematopoietic stem cells with long-term repopulating ability. We found that the absolute number of marrow cells was increased approximately 8 to 14-fold in all cultures containing recombinant growth factors. However, the frequency of high quality stem cells was markedly reduced at the same time, except in cultures containing growth factors and Jagged-1-coated Sepharose-4B beads. The absolute number of hematopoietic cells with long-term repopulating ability was increased approximately 10 to 20-fold in the presence of multivalent Notch ligand. These results support a role for combinatorial effects by Notch and cytokine-induced signaling pathways in regulating hematopoietic stem cell fate and to a potential role for Notch ligand in increasing cell numbers in clinical stem cell transplantation.

Notch signaling defines an evolutionarily ancient cell interaction mechanism. The signals transmitted through the Notch receptor, in combination with other cellular factors influence differentiation, proliferation and apoptotic events at all stages of development. Recent advances have elucidated both the biochemical mechanism regulating receptor activation and the molecular participants forming the intracellular signaling cascade. Authors present description of the main signaling components involved in the Notch pathway and how it can affect the growth and function of lymphocytes. Notch signaling is critical during lymphocyte development, and dysregulation of the pathway can give rise to leukemia. It is conceivable that appropriate manipulation of Notch signaling may become a useful tool in addressing a variety of human dysplastic condition and tissue regeneration.

Lysis of group A and B erythrocytes by human complement was studied by an anti-A (BRIC.131) and an anti-B (BRIC.30) IgM monoclonal antibody in a 51Cr-release assay. The relative concentration of membrane-bound immunoglobulins was detected by flow cytometric analysis, and the amount of C1q and C3 bound to the sensitized red cells was measured by using purified, 125I-labelled molecules. The direct haemolysis was identical with both reagents in the presence of excess and suboptimal complement over a wide range of antibody concentration (between 50 and 7000 ng/ml). The indirect effect of membrane-bound antibody, i.e. its influence on complement binding by sensitized bystander cells, was examined in a cold target competition assay in which sensitized, non-labelled cells are present when complement is incubated with sensitized labelled cells. We have found that the competitive capacity of sensitized erythrocytes correlated with the amount of membrane-bound immunoglobulins. In accordance with our earlier findings, an equal level of target and competitor cell lysis was obtained only if the fluid phase anti-B antibody concentration was 2 to 4 times higher than that of the anti-A antibodies. We demonstrate in this paper that the different competitive activity of IgM anti-A and anti-B monoclonal antibodies might be accounted for by differences in their C1q and C3 binding capacities.

The lysis of group AB erythrocytes by human complement was studied by different anti-A and anti-B IgM monoclonal antibodies (mabs) in a 51Cr-release assay. The concentration of membrane-bound immunoglobulin was detected by ELISA, and the amount of C1q and C3 bound to sensitized red cells was measured by using purified, 125I-labelled molecules. We have demonstrated that there is an exponential relationship between the concentration of the sensitizing IgM mabs and C1q binding to the sensitized AB cell. The efficiency of binding was related to the number of antibodies bound; thus, anti-A sensitized cells bound 3-6 times more C1q than anti-B sensitized cells did. AB cells, on the other hand, bound similar amounts of C3 whether anti-A or anti-B was present. The lytic efficiencies of the various IgM mabs during short incubation times were different, suggesting that the complement activation rates vary widely with different antibodies on the AB cell membrane. The binding of C1q to an antibody-sensitized target activates a cascade, whose components may migrate away from the sensitizing antibody; interactions between the activation processes generated by the anti-A and anti-B antibodies may thus occur. Choosing appropriate pairs of anti-A and anti-B mabs for the simultaneous sensitization of AB cells has indeed resulted in stimulation in some and inhibition in other combinations of mabs. It is suggested that stimulation is observed when the activated intermediates are produced in excess, whereas inhibition occurs when a shortage of activated intermediates prevents mutual utilization.