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Hemoglobin (Hb) performs its physiological function within the erythrocyte. Extracellular Hb has prooxidative and proinflammatory properties and is therefore sequestered by haptoglobin and bound by the CD163 receptor on macrophages. In the present study, we demonstrate a novel process of Hb uptake by macrophages independent of haptoglobin and CD163. Unexpectedly, macrophages do not degrade the entire Hb, but instead transfer it to neighboring cells. We have shown that the phenomenon of Hb transfer from macrophages to other cells is mainly mediated by extracellular vesicles. In contrast to the canonical Hb degradation pathway by macrophages, Hb transfer has not been reported before. In addition, we have used the process of Hb transfer in anticancer therapy, where macrophages are loaded with a Hb-anticancer drug conjugate and act as cellular drug carriers. Both mouse and human macrophages loaded with Hb-monomethyl auristatin E (MMAE) effectively killed cancer cells when co-cultured in vitro. [ABSTRACT FROM AUTHOR]

Simple Summary: Our research focuses on how parasitic worms, specifically Heligmosomoides polygyrus, can change the body's immune response. These parasites can lower the body's defense mechanisms, but exactly how they do this is not fully understood. We believe that a type of immune cell, called macrophages, might be involved. Changes in these cells could potentially help tumors grow. In our study, we looked at how substances produced by H. polygyrus affect these immune cells and, in turn, how they influence the growth of breast cancer cells in the lab. We discovered that these substances from H. polygyrus increase the activity of certain genes in the immune cells. These genes are responsible for both promoting and reducing inflammation. Additionally, these substances change the surface features of the immune cells. Our findings show that these changes in immune cells caused by H. polygyrus could lead to increased growth of breast cancer cells in a laboratory setting. This research helps us understand more about how changes in the immune system can affect tumor growth, which is important for developing new cancer treatments. In our study, we explored how parasitic nematodes, specifically Heligmosomoides polygyrus, influence the immune response, focusing on their potential role in tumor growth. The study aimed to understand the mechanisms by which these parasites modify immune cell activation, particularly in macrophages, and how this might create an environment conducive to tumor growth. Our methods involved analyzing the effects of H. polygyrus excretory-secretory antigens on macrophage activation and their subsequent impact on breast cancer cell lines EMT6 and 4T1. We observed that these antigens significantly increased the expression of genes associated with both pro-inflammatory and anti-inflammatory molecules, such as inducible nitric oxide synthase, TNF-α, (Tumor Necrosis Factor) Il-6 (Interleukin), and arginase. Additionally, we observed changes in the expression of macrophage surface receptors like CD11b, F4/80, and TLR4 (Toll-like receptor 4). Our findings indicate that the antigens from H. polygyrus markedly alter macrophage behavior and increase the proliferation of breast cancer cells in a laboratory setting. This study contributes to a deeper understanding of the complex interactions between parasitic infections and cancer development, highlighting the need for further research in this area to develop potential new strategies for cancer treatment. [ABSTRACT FROM AUTHOR]

This paper uses a novel experimental design to investigate the strategic value of making a public payoff sacrifice ("burning money") in a setting modelled after the battle-of-the-sexes game. Unlike prior studies, we find that subjects choose to burn money in a significant portion of decision trials and that burning makes the first movers more likely to achieve their preferred stage two equilibrium outcome. No such effect is observed in a control treatment where money burning is triggered unintentionally. This suggests that payoff sacrifices are important as deliberate signals of one's further intentions, and can be a source of strategic advantage different from that stemming from being the first party to move. These results are supported by an analysis of subjects' eye movements, which reveals patterns consistent with forward induction reasoning. [ABSTRACT FROM AUTHOR]

To celebrate the tenth anniversary of InterPore, we present an interdisciplinary review of colloid transport through porous media. This review aims to explore both classical colloid transport and topics that fall outside that purview and thus offer transformative insights into the physics governing transport behavior. First, we discuss the unique colloid characteristics relative to molecules and larger particles. Then, the classical advection–dispersion–filtration models (both conceptual and mathematical) of colloid transport are introduced as well as anomalous transport behaviors. Next, the forces of interaction between colloids and porous media surfaces are discussed. Fourth, applications that are interested in maximizing the transport of colloids through porous media are considered. Then the concept of motile, active biocolloids is introduced, and finally, colloid swarming as a newly recognized mode of transport is summarized. [ABSTRACT FROM AUTHOR]

Gas generation and flow in soil is relevant to applications such as the fate of leaking geologically sequestered carbon dioxide, natural releases of methane from peat and marine sediments, and numerous electro‐thermal remediation technologies for contaminated sites, such as electrical resistance heating. While traditional multiphase flow models generally perform poorly in describing unstable gas flow phenomena in soil, Macroscopic Invasion Percolation (MIP) models can reproduce key features of its behavior. When coupled with continuum heat and mass transport models, MIP has the potential to simulate complex subsurface scenarios. However, coupled MIP‐continuum models have not yet been validated against experimental data and lack key mechanisms required for electro‐thermal scenarios. Therefore, the purpose of this study was to (a) incorporate mechanisms required for steam generation and flow into an existing MIP‐continuum model (ET‐MIP), (b) validate ET‐MIP against an experimental lab‐scale electrical resistance heating study, and (c) investigate the sensitivity of water boiling and gas (steam) transport to key parameters. Water boiling plateaus (i.e., latent heat), heat recirculation within steam clusters, and steam collapse (i.e., condensation) mechanisms were added to ET‐MIP. ET‐MIP closely matched observed transient gas saturation distributions, measurements of electrical current, and temperature distributions. Heat recirculation and cluster collapse were identified as the key mechanisms required to describe gas flow dynamics using a MIP algorithm. Sensitivity analysis revealed that gas generation rates and transport distances, particularly through regions of cold water, are sensitive to the presence of dissolved gases. Key Points: Coupled Macroscopic Invasion Percolation (MIP) model with continuum heat and mass models accurately reproduced lab‐scale gas production and migrationSimulation of condensation mechanisms and heat recirculation within gas clusters were key to capturing gas flow dynamics with MIPHigher concentrations of dissolved oxygen and nitrogen increased gas mobilization and decreased steam condensation rates in cold water [ABSTRACT FROM AUTHOR]

We propose a novel method of using eye-tracking to study strategic decisions. The conventional approach is to hypothesize what eye-patterns should be observed if a given model of decision-making was accurate, and then proceed to verify if this occurs. When such hypothesis specification is difficult a priori, we propose instead to expose subjects to a variant of the original strategic task that should induce processing it in a way consistent with the postulated model. It is then possible to use machine learning pattern recognition techniques to check if the associated eye-patterns are similar to those recorded during the original task. We illustrate the method using simple examples of 2x2 matching-pennies and coordination games with or without feedback about the counterparts' past moves. We discuss the strengths and limitations of the method in this context. [ABSTRACT FROM AUTHOR]

The Canadian Nuclear Waste Management Organization (NWMO) has chosen a used fuel container (UFC) design that consists of an inner steel core and outer copper coating that resists corrosion in the anaerobic underground. However, in these anaerobic conditions, microbiologically influenced corrosion (MIC) can contribute to UFC corrosion if sulphides are present in the repository. Therefore, an engineered barrier system (EBS) consisting of bentonite blocks and pellets has been designed to inhibit production of sulphide by microorganisms and impede the movement of sulphides from the host rock to the UFC. Initially, the bentonite within the deep geological repository will contain no sulphides and it will take time for sulphide from the host rock to saturate the repository. To examine the transient effect of sulphide transport and the effectiveness of the EBS, a 3D numerical model was developed capable of simulating the diffusive transport of sulphide within the NWMO repository. The model was developed using COMSOL Multiphysics, a finite element software package. The developed model included the NWMO placement room, as well as a stand-alone UFC package. Conservative assumptions such as constant-concentration boundary condition and transport-limited corrosion were assumed. The time-dependent analysis predicted the inflow of sulphide into the EBS over time, and the results showed that a steady-state condition would be reached in over 2,000 years in the placement room. The model also showed that the highest sulphide flux occurred at the semi-spherical end caps of the UFC and consequently, that corrosion from sulphide diffusion would not be uniform over the container surface. This paper is part of a supplement on the 6th International Workshop on Long-Term Prediction of Corrosion Damage in Nuclear Waste Systems. [ABSTRACT FROM AUTHOR]

The Canadian Nuclear Waste Management Organization (NWMO) has chosen a used fuel container (UFC) design that consists of an inner steel core and outer copper coating that resists corrosion in the anaerobic underground. However, in these anaerobic conditions, microbiologically influenced corrosion (MIC) can contribute to UFC corrosion if sulphides are present in the repository. Therefore, an engineered barrier system (EBS) consisting of bentonite blocks and pellets has been designed to inhibit production of sulphide by microorganisms and impede the movement of sulphides from the host rock to the UFC. Initially, the bentonite within the deep geological repository will contain no sulphides and it will take time for sulphide from the host rock to saturate the repository. To examine the transient effect of sulphide transport and the effectiveness of the EBS, a 3D numerical model was developed capable of simulating the diffusive transport of sulphide within the NWMO repository. The model was developed using COMSOL Multiphysics, a finite element software package. The developed model included the NWMO placement room, as well as a stand-alone UFC package. Conservative assumptions such as constant-concentration boundary condition and transport-limited corrosion were assumed. The time-dependent analysis predicted the inflow of sulphide into the EBS over time, and the results showed that a steady-state condition would be reached in over 2,000 years in the placement room. The model also showed that the highest sulphide flux occurred at the semi-spherical end caps of the UFC and consequently, that corrosion from sulphide diffusion would not be uniform over the container surface. This paper is part of a supplement on the 6th International Workshop on Long-Term Prediction of Corrosion Damage in Nuclear Waste Systems. [ABSTRACT FROM PUBLISHER]

The aim of the study was to evaluate the effect of selenium supplementation on the expression of genes associated with glucose metabolism in humans, in order to explain the unclear relationship between selenium and the risk of diabetes. For gene expression analysis we used archival samples of cDNA from 76 non-diabetic subjects supplemented with selenium in the previous study. The supplementation period was six weeks and the daily dose of selenium was 200 µg (as selenium yeast). Blood for mRNA isolation was collected at four time points: before supplementation, after two and four weeks of supplementation, and after four weeks of washout. The analysis included 15 genes encoding selected proteins involved in insulin signaling and glucose metabolism. In addition, HbA1c and fasting plasma glucose were measured at three and four time points, respectively. Selenium supplementation was associated with a significantly decreased level of HbA1c but not fasting plasma glucose (FPG) and significant down-regulation of seven genes: INSR, ADIPOR1, LDHA, PDHA, PDHB, MYC, and HIF1AN. These results suggest that selenium may affect glycemic control at different levels of regulation, linked to insulin signaling, glycolysis, and pyruvate metabolism. Further research is needed to investigate mechanisms of such transcriptional regulation and its potential implication in direct metabolic effects. [ABSTRACT FROM AUTHOR]

Recent studies indicate the critical role of tumour associated macrophages, tumour associated neutrophils, dendritic cells, T lymphocytes, and natural killer cells in tumourigenesis. These cells can have a significant impact on the tumour microenvironment via their production of cytokines and chemokines. Additionally, products secreted from all these cells have defined specific roles in regulating tumour cell proliferation, angiogenesis, and metastasis. They act in a protumour capacity in vivo as evidenced by the recent studies indicating that macrophages, T cells, and neutrophils may be manipulated to exhibit cytotoxic activity against tumours. Therefore therapy targeting these cells may be promising, or they may constitute drug or anticancer particles delivery systems to the tumours. Herein, we discussed all these possibilities that may be used in cancer treatment. [ABSTRACT FROM AUTHOR]

Migrastatin and isomigrastatin analogues have been synthesised in order to contribute to structure-activity studies on tumour cell migration inhibitors. These include macrocycles varying in ring size, functionality and alkene stereochemistry, as well as glucuronides. The synthesis work included application of the Saegusa-Ito reaction for regio- and stereoselective unsaturated macroketone formation, diastereoselective Brown allylation to generate 9-methylmigrastatin analogues and chelation-induced anomerisation to vary glucuronide configuration. Compounds were tested in vitro against both breast and pancreatic cancer cell lines and inhibition of tumour cell migration was observed in both wound-healing (scratch) and Boyden chamber assays. One unsaturated macroketone showed low affinity for a range of secondary drug targets, indicating it is at low risk of displaying adverse side effects. [ABSTRACT FROM AUTHOR]

Background: Since targeting oxidative stress markers has been recently recognized as a novel therapeutic target in cancer, it is interesting to investigate whether genetic susceptibility may modify oxidative stress response in cancer. The aim of this study was to elucidate whether genetic polymorphism in the antioxidant enzymes is associated with lipid peroxidation in breast cancer.Methods: We conducted a study among Polish women, including 136 breast cancer cases and 183 healthy controls. The analysis included genetic polymorphisms in five redox related genes: GPX1 (rs1050450), GPX4 (rs713041), SOD2 (rs4880), SEPP1 (rs3877899) and SEP15 (rs5859), lipid peroxidation, the activities of antioxidant enzymes determined in blood compartments as well as plasma concentration of selenium - an antioxidant trace element involved in cancer. Genotyping was performed using the Real Time PCR. Lipid peroxidation was expressed as plasma concentration of thiobarbituric acid reactive substances (TBARS) and measured with the spectrofluorometric method. Glutathione peroxidase activity was spectrophotometrically determined in erythrocytes (GPx1) and plasma (GPx3) by the use of Paglia and Valentine method. Spectrophotometric methods were employed to measure activity of cytosolic superoxide dismutase (SOD1) in erythrocytes (Beauchamp and Fridovich method) and ceruloplasmin (Cp) in plasma (Sunderman and Nomoto method). Plasma selenium concentration was determined using graphite furnace atomic absorption spectrophotometry.Results: Breast cancer risk was significantly associated with GPX1 rs1050450 (Pro198Leu) polymorphism, showing a protective effect of variant (Leu) allele. As compared to the control subjects, lipid peroxidation and GPx1 activity were significantly higher in the breast cancer cases, whereas ceruloplasmin activity was decreased. After genotype stratification, both GPx1 activity and TBARS concentration were the highest in GPX1 Pro/Pro homozygotes affected by breast cancer. At the same time, there was a significant correlation between the level of lipid peroxidation and GPx1 activity among the cancer subjects possessing GPX1 Pro/Pro genotype (r = 0.3043; p = 0.0089), whereas such a correlation was completely absent in the cases carrying at least one GPX1 Leu allele as well as in the controls (regardless of GPX1 genotype).Conclusions: GPX1 polymorphism may be an important factor modifying oxidative stress response in breast cancer subjects. Further studies are needed to elucidate its potential clinical significance. [ABSTRACT FROM AUTHOR]

Purpose: NRF2 transcription factor is involved in modulation of various antioxidant and metabolic genes and, therefore, may modulate anti-carcinogenic potential. Association between polymorphisms of NRF2 and five NRF2-regulated genes and urinary bladder cancer (BC) risk was analyzed. Methods: The study group included 244 BC patients, while the control group comprised 365 individuals with no evidence of malignancy. Genotyping of GSTM1 (deletion), GSTT1 (deletion), GSTA1 −69C/T (rs3957357), GSTP1 Ile105Val (rs1695), SOD2 Ala16Val (rs4880) and NRF2 −617C/A (rs6721961) in blood genomic DNA was performed by means of real-time PCR assays. The associations between gene polymorphism and BC risk were computed by logistic regression. Results: The frequency of GSTA1, GSTP1, SOD2 and NRF2 genotypes did not differ in both groups. A significantly higher BC risk was associated with GSTM1 null genotype after adjusting to age, sex and smoking habit (OR 1.85, 95 % CI 1.30-2.62; P = 0.001). GSTT1 null (OR 0.50, 95 % CI 0.31-0.81; P = 0.005) and GSTP1 Val105Val (OR 0.52, 95 % CI 0.27-0.98; P = 0.04) genotypes were associated with reduced BC risk separately or in combination (OR 0.24, 95 % CI 0.11-0.51; P < 0.0001) ( P heterogeneity = 0.01). Combined GSTT1 null and SOD2 with at least one 16Val allele among never smokers encompass reduced BC risk (OR 0.14, 95 % CI 0.03-0.63; P = 0.01) ( P heterogeneity = 0.04). Conclusions: This study supports hypothesis that GSTM1 null genotype may be a moderate BC risk factor. The gene-gene and gene-environment interactions associated with combined GSTP1/ GSTT1 and combined GSTT1/ SOD2 genetic polymorphisms along with cigarette smoking habit may play a significant role in BC risk modulation. [ABSTRACT FROM AUTHOR]

Objectives To elucidate genetic polymorphisms of the matrix metalloproteinases ( MMPs) MMP1 (rs1799750) , MMP2 (rs243865) , MMP9 (rs3918242) , MMP12 (rs2276109) and tissue inhibitors of MMPs ( TIMPs) TIMP1 (rs2070584) and TIMP3 (rs9619311) genes that may be involved in susceptibility to bladder cancer ( BC)., Patients and Methods We enrolled 241 patients with BC and 199 controls., Genomic DNA samples were extracted from peripheral blood and polymorphisms were analysed by high-resolution melting analysis and by real-time polymerase chain reaction using Taq Man fluorescent probes., Results Of the six evaluated polymorphisms of MMPs and TIMPs, only one was found to be associated with BC risk., There was a significant difference for MMP1 (rs1799750) 2 G/1 G+1 G/1 G genotype (odds ratio [ OR] 0.62, 95% confidence interval [ CI] 0.39-0.98; P = 0.042). Additionally, there was a joint effect of this genotype on BC risk among 'ever smokers' ( OR 0.51, 95% CI 0.28-0.89; P = 0.019), but not in 'never smokers'., The combined genotype MMP2 -1306 C/ T (rs243865) allele T with MMP9 -1562 C/ T (rs3918242) allele T was found to increase BC risk ( OR 2.00, 95% CI 1.10-3.62; P = 0.022)., Conclusions Our results suggest that genetic variations in five polymorphisms of MMPs and TIMPs are not associated with a high risk of BC., Only MMP1 polymorphism may be related to the risk of BC, notably in 'ever smokers'., Our study suggests that the effects of polymorphisms of MMPs and TIMPs on BC risk deserve further investigation. [ABSTRACT FROM AUTHOR]

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In a perceptual decision-making task, we compared a neutral payoff and two asymmetric payoffs: a liberal one, favouring positive responses, and a conservative one, favouring negative responses. Participants were presented with ambiguous images composed of superimposed target and non-target photographs, and asked to decide whether the target dominated in the picture. Signal-detection analysis demonstrated that the liberal payoff yielded significantly higher sensitivity than other payoffs. We argue that the liberal payoff encourages confirming the target's domination, hence making it easier to ignore non-target elements of the picture. We conclude that payoff can influence perceptual decisions by changing the approach to the perceptual task, and how attention is allocated between different elements of the sensory input. [ABSTRACT FROM AUTHOR]

Background: MicroRNAs may act as oncogenes or tumour suppressor genes, which make these small molecules potential diagnostic/prognostic factors and targets for anticancer therapies. Several common oncogenic microRNAs have been found for canine mammary cancer and human breast cancer. On account of this, large-scale profiling of microRNA expression in canine mammary cancer seems to be important for both dogs and humans.Methods: Expression profiles of 317 microRNAs in 146 canine mammary tumours of different histological type, malignancy grade and clinical history (presence/absence of metastases) and in 25 control samples were evaluated. The profiling was performed using microarrays. Significance Analysis of Microarrays test was applied in the analysis of microarray data (both unsupervised and supervised data analyses were performed). Validation of the obtained results was performed using real-time qPCR. Subsequently, predicted targets for the microRNAs were searched for in miRBase.Results: Results of the unsupervised analysis indicate that the primary factor separating the samples is the metastasis status. Predicted targets for microRNAs differentially expressed in the metastatic vs. non-metastatic group are mostly engaged in cell cycle regulation, cell differentiation and DNA-damage repair. On the other hand, the supervised analysis reveals clusters of differentially expressed microRNAs unique for the tumour type, malignancy grade and metastasis factor.Conclusions: The most significant difference in microRNA expression was observed between the metastatic and non-metastatic group, which suggests a more important role of microRNAs in the metastasis process than in the malignant transformation. Moreover, the differentially expressed microRNAs constitute potential metastasis markers. However, validation of cfa-miR-144, cfa-miR-32 and cfa-miR-374a levels in blood samples did not follow changes observed in the non-metastatic and metastatic tumours. [ABSTRACT FROM AUTHOR]

The article reviews the article "Neural Mechanisms of Belief Inference During Cooperative Games," which appeared in the "Journal" in 2010.

Tumour cell migration can be stopped by small molecules such as migrastatin, a natural product that inhibits tumour cell migration (μM range) in vitro. In their Full Paper on page 18109 ff., P. Murphy et al. describe the synthesis and structure – activity studies of migrastatin and its analogues. Compounds were tested in vitro against both breast and pancreatic cancer cell lines and inhibition of tumour cell migration was observed in both wound ‐ healing (scratch) and Boyden chamber assays, with one analogue showing low affinity for a range of secondary drug targets, indicating it is at low risk of displaying adverse side effects. [ABSTRACT FROM AUTHOR]

Invited for the cover of this issue are Paul V. Murphy and co-workers at the National University of Ireland Galway (NUI Galway) and Warsaw University. The image depicts MGSTA-6 giving a stop signal to tumour cells that are on the move. Read the full text of the article at . [ABSTRACT FROM AUTHOR]