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African American (AA) women confront distinct disparities in breast cancer rates, and the impact of their living environment is unclear. This study aimed to examine the association between breast cancer incidence and environmental factors among a high-risk female population. The study recruited 355 AA women ages 20–88 in Memphis from 2016–2018. Their addresses were geocoded and linked to environmental and socioeconomic data. The final dataset contained 50 cases and 157 controls. Associations between breast cancer incidence and social and environmental factors were examined using logistic regression. Spatial analysis in ArcGIS showed that cases clustered in Southwest Memphis. Proximity to traffic and Superfund sites had odds ratios of 1.636 (95% CI: 25 1.046, 2.560) and 12.262 (95% CI: 1.814, 82.864), respectively. Mediating analyses further revealed that environmental inequities contributed significantly to breast cancer inequalities. In conclusion, the built environment plays a role in breast cancer onset among AA females. [ABSTRACT FROM AUTHOR]

Simple Summary: Breast cancer (BC) is the leading cause of cancer deaths among adult women in Ethiopia. The death toll associated with breast cancer is high among women of African ancestry. The cause of the disparity in mortality is unclear. Recently, studies conducted in the United States and other high-income countries highlighted the role of microbial dysbiosis in breast cancer initiation, growth and treatment outcome. However, whether differences in abundance and composition of microbiota are associated with clinical and histopathological parameters in Ethiopian women has not been studied. The aim of our study was to conduct microbial profiling on breast tumor and normal adjacent tissues of the same donor. Further, the study aimed to identify the association of the differences in microbial composition and abundance with clinicopathological factors in Ethiopian women with breast cancer. This is the first study to report an association between breast microbial dysbiosis and clinicopathological factors in Ethiopian women. Breast cancer (BC) is the leading cause of cancer mortality among women in Ethiopia. Overall, women of African ancestry have the highest death toll due to BC compared to other racial/ethnic groups. The cause of the disparity in mortality is unclear. Recently, studies conducted in the United States and other high-income countries highlighted the role of microbial dysbiosis in BC initiation, tumor growth, and treatment outcome. However, the extent to which inter-individual differences in the makeup of microbiota are associated with clinical and histopathological outcomes in Ethiopian women has not been studied. The goal of our study was to profile the microbiome in breast tumor and normal adjacent to tumor (NAT) tissues of the same donor and to identify associations between microbial composition and abundance and clinicopathological factors in Ethiopian women with BC. We identified 14 microbiota genera in breast tumor tissues that were distinct from NAT tissues, of which Sphingobium, Anaerococcus, Corynebacterium, Delftia, and Enhydrobacter were most significantly decreased in breast tumors compared to NAT tissues. Several microbial genera significantly differed by clinicopathological factors in Ethiopian women with BC. Specifically, the genus Burkholderia more strongly correlated with aggressive triple negative (TNBC) and basal-like breast tumors. The genera Alkanindiges, Anoxybacillus, Leifsonia, and Exiguobacterium most strongly correlated with HER2-E tumors. Luminal A and luminal B tumors also correlated with Anoxybacillus but not as strongly as HER2−E tumors. A relatively higher abundance of the genus Citrobacter most significantly correlated with advanced-stage breast tumors compared to early-stage tumors. This is the first study to report an association between breast microbial dysbiosis and clinicopathological factors in Ethiopian women. [ABSTRACT FROM AUTHOR]

Simple Summary: We previously showed that breast tumor tissues from women display an imbalance in abundance and composition of microbiota compared to normal healthy breast tissues. It is unknown whether these differences in breast tumor microbiota may be driven by alterations in microbial metabolites, leading to potentially protective or pathogenic consequences. The aim of our study was to conduct global metabolic profiling on normal and breast tumor tissues to identify differences in metabolite profiles and to determine whether breast microbial dysbiosis may be associated with enrichment of microbial metabolites in triple-negative breast cancer (TNBC) which disproportionately affects women of African ancestry. We observed significant correlations between elevated lipid metabolism pathways and microbial dysbiosis in TNBC tissues from both non-Hispanic black and white women. This is the first study to report an association between breast microbial dysbiosis and alterations in host metabolic pathways in breast tumors, including TNBC, of non-Hispanic black and non-Hispanic white women. Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer that is non-responsive to hormonal therapies and disproportionately impact women of African ancestry. We previously showed that TN breast tumors have a distinct microbial signature that differs from less aggressive breast tumor subtypes and normal breast tissues. However, it is unknown whether these differences in breast tumor microbiota may be driven by alterations in microbial metabolites, leading to potentially protective or pathogenic consequences. The goal of this global metabolomic profiling study was to investigate alterations in microbial metabolism pathways in normal and breast tumor tissues, including TNBC, of non-Hispanic black (NHB) and non-Hispanic white (NHW) women. In this study, we profiled the microbiome (16S rRNA) from breast tumor tissues and analyzed 984 metabolites from a total of 51 NHB and NHW women. Breast tumor tissues were collected from 15 patients with TNBC, 12 patients with less aggressive luminal A-type (Luminal) breast cancer, and 24 healthy controls for comparison using UHPLC-tandem mass spectrometry. Principal component analysis and hierarchical clustering of the global metabolomic profiling data revealed separation between metabolic signatures of normal and breast tumor tissues. Random forest analysis revealed a unique biochemical signature associated with elevated lipid metabolites and lower levels of microbial-derived metabolites important in controlling inflammation and immune responses in breast tumor tissues. Significant relationships between the breast microbiome and the metabolome, particularly lipid metabolism, were observed in TNBC tissues. Further investigations to determine whether alterations in sphingolipid, phospholipid, ceramide, amino acid, and energy metabolism pathways modulate Fusobacterium and Tenericutes abundance and composition to alter host metabolism in TNBC are necessary to help us understand the risk and underlying mechanisms and to identify potential microbial-based targets. [ABSTRACT FROM AUTHOR]

Summary: Sickle cell disease (SCD) affects over 2 million people worldwide with high morbidity and mortality in underdeveloped countries. Therapeutic interventions aimed at reactivating fetal haemoglobin (HbF) is an effective approach for improving survival and ameliorating the clinical severity of SCD. A class of agents that inhibit DNA methyltransferase (DNMT) activity show promise as HbF inducers because off‐target effects are not observed at low concentrations. However, these compounds are rapidly degraded by cytidine deaminase when taken by oral administration, creating a critical barrier to clinical development for SCD. We previously demonstrated that microRNA29B (MIR29B) inhibits de novo DNMT synthesis, therefore, the goal of our study was to determine if MIR29 mediates HbF induction. Overexpression of MIR29B in human KU812 cells and primary erythroid progenitors significantly increased the percentage of HbF positive cells, while decreasing the expression of DNMT3A and the HBG repressor MYB. Furthermore, HBG promoter methylation levels decreased significantly following MIR29B overexpression in human erythroid progenitors. We subsequently, observed higher MIR29B expression in SCD patients with higher HbF levels compared to those with low HbF. Our findings provide evidence for the ability of MIR29B to induce HbF and supports further investigation to expand treatment options for SCD. [ABSTRACT FROM AUTHOR]

Desilylation of the 2-phosphinophosphinine 2-PPh2-3-Me-6-SiMe3-PC5h2 with HCl gave 2-PPh2-3-Me-PC5H3, demonstrating the late-stage modification of this bidentate heterocyclic ligand. Group 6 metal carbonyl complexes of these ligands showed κ2 binding and very small bite angles of 65.1-68.3°, and also demonstrated that the donor properties of 2-phosphinophosphinines can be tuned readily by the presence of the SiMe3 group, which gives a more π accepting phosphinine ligand. The properties of 2-phosphinophosphinines were compared to those of bidentate diphosphorus ligands computationally, contextualizing them in the ligand knowledge base for bidentate P,P donor ligands (LKB-PP), and were found to occupy an area of ligand space adjacent to Ar2PN(R)NAr2 ligands that have been successfully used in ethylene oligomerization reactions, but with well-separated properties in the second principal component. Testing 2-phosphinophosphinines in Cr-catalyzed ethylene oligomerization reactions showed key differences from standard PNP ligands in that a high proportion of alkyl- and alkenylcyclopentanes were formed. This demonstrates that the different donor properties of 2-phosphinophosphinines influence the reactivity of the key seven-membered metallacycle postulated in the metallacyclic reaction mechanism, generating products from isomerization and subsequent ethylene insertion. Alkyl- and alkenylcyclopentanes represent new products for the key industrial feedstock ethylene, with the alkenes having potential as new monomers, comonomers, or additives for plastics. Computational evaluation of ligand properties and the resulting property maps can play a role in suggesting future ligand developments to change the selectivity of this industrially relevant system, in the pursuit of new products generated from ethylene. [ABSTRACT FROM AUTHOR]

The Multiple Streams Framework offers a theoretical account of how policy proposals move from latent possibilities to becoming favored for implementation. We apply this framework in the context of the policy response to the 2013–2014 flooding of the Somerset Levels and Moors. Stakeholder interviews and analysis of news media coverage evidence the way in which a specific policy option that had fallen out of favor with the national Environment Agency – dredging – came to the fore and was eventually adopted during the period in which the conjunction of problem, policy, and political pressures came to a head. Local political activists mobilized a wider campaign with the help of social media and capitalized on national political sensitivities to successfully promote dredging. What is less clear is the longevity of the policy reversal, given funding constraints. [ABSTRACT FROM AUTHOR]

The aim of this article is to present a selection of primary findings culled from empirical data collected in Dublin with post-European Union enlargement Polish migrants as the cohort in study. One aspect of the project was to investigate how that group interpreted home since they have left Poland. Based on the outcomes of interviews with thirty-one informants, the narratives reveal a group of individuals who continuously contest social constraints and push the boundaries of previously held notions of migration, identity, and home. This article situates their aspirations, preferences, and practices within discourses of transnationalism, thereby connecting their migration experiences with a consciousness of feeling at home in the world. This article breaks up "home" as interpreted by the informants into three categories-centered home, sentimental home, and transportable home. The wide range of perspectives held by informants and the inability to clearly define their position with regard to the notion of "home" reinforces the hypothesis of this article that, for a transnational cohort, the meaning of home is contested. In relation to the wider international literature regarding concepts of home, this article makes a contribution to the deepening scope of migration research in Ireland. [ABSTRACT FROM AUTHOR]

There is a dearth of qualitative research concerning the migrant experience to Ireland and this limits our ability to understand the opportunities and constraints migrants encounter as they negotiate access through a new place. Due to a lack of knowledge and familiarity with a city and its systems, migrants may experience a housing system differently than previously settled households. Therefore, the role of housing takes on different meaning in their lives and can impact on their quality of life in different ways. The aim of this article is to reveal primary findings culled from empirical data collected in Dublin with thirty-one Polish origin migrants as the cohort in the study. By illuminating the housing experiences of migrant households, otherwise referred to as 'newcomers' here, this article seeks to be added to the growing field of Irish literature produced on the migrant experience. Through the use of participant narratives, findings reveal a highly reflexive group of people who describe how they identify with housing and their personal aspirations in relation to it. Conclusions are drawn about their conceptualisations of home by connecting a collection of their responses back into two main themes: their identification with home ownership and their relationship with a transnational lifestyle. [ABSTRACT FROM AUTHOR]

Growing evidence highlights an association between an imbalance in the composition and abundance of bacteria in the breast tissue (referred as microbial dysbiosis) and breast cancer in women. However, studies on the breast tissue microbiome have not been conducted in non-Hispanic Black (NHB) women. We investigated normal and breast cancer tissue microbiota from NHB and non-Hispanic White (NHW) women to identify distinct microbial signatures by race, stage, or tumor subtype. Using 16S rRNA gene sequencing, we observed that phylum Proteobacteria was most abundant in normal (n = 8), normal adjacent to tumor (normal pairs, n = 11), and breast tumors from NHB and NHW women (n = 64), with fewer Firmicutes, Bacteroidetes, and Actinobacteria. Breast tissues from NHB women had a higher abundance of genus Ralstonia compared to NHW tumors, which could explain a portion of the breast cancer racial disparities. Analysis of tumor subtype revealed enrichment of family Streptococcaceae in TNBC. A higher abundance of genus Bosea (phylum Proteobacteria) increased with stage. This is the first study to identify racial differences in the breast tissue microbiota between NHB and NHW women. Further studies on the breast cancer microbiome are necessary to help us understand risk, underlying mechanisms, and identify potential microbial targets. [ABSTRACT FROM AUTHOR]

Volatile organic solvents are used in almost every industry currently in operation. Their key advantage, being easily removed from products, is overshadowed by the issues associated with their vapour emissions, inhalation risks, smog formation, and flammability. There is, therefore, a dire need for replacement solvents that are much less volatile and yet are as easily removed from products. Switchable-hydrophilicity solvents (SHS) meet this need. SHS are solvents that alternate between water-miscible and water-immiscible states upon the application of a trigger. Carbon dioxide functions as the trigger, as it acidifies the solution and causes protonation of the switchable solvent, which in the past has almost always been a liquid amine. Anionic SHS (ASHS) systems, a recently discovered variation on the idea of an SHS, consist of a hydrophobic carboxylic acid paired with a water-soluble base. In these systems, the low miscibility carboxylic acid (in its neutral state) is combined with a base dissolved in water. Avery small number of ASHS have been reported, but they can only function in the presence of an amine and an unacceptably large excess of water. We sought an SHS that has as little toxicity as possible, and for that reason, we preferred one that contains no amine at all. We now report that the combination of branched carboxylic acids and a substoichiometric quantity of either NaHCO3 or NaOH forms an SHS with very little toxicity and does not require a large excess of water. Two applications of these new switchable solvents are described. [ABSTRACT FROM AUTHOR]

Obesity is a chronic condition resulting from a long-term pattern of poor diet and lifestyle. Long-term consumption of high-fat diet (HFD) leads to persistent activation and leptin resistance in AgRP neurons in the arcuate nucleus of the hypothalamus (ARH). Here, for the first time, we demonstrate acute effects of HFD on AgRP neuronal excitability and highlight a critical role for diet composition. In parallel with our earlier finding in obese, long-term HFD mice, we found that even brief HFD feeding results in persistent activation of ARH AgRP neurons. However, unlike long-term HFD-fed mice, AgRP neurons from short-term HFD-fed mice were still leptin-sensitive, indicating that the development of leptin-insensitivity is not a prerequisite for the increased firing rate of AgRP neurons. To distinguish between diet composition, caloric intake, and body weight, we compared acute and long-term effects of HFD and CD in pair-fed mice on AgRP neuronal spiking. HFD consumption in pair-fed mice resulted in a significant increase in AgRP neuronal spiking despite controls for weight gain and caloric intake. Taken together, our results suggest that diet composition may be more important than either calorie intake or body weight for electrically remodeling arcuate AgRP/NPY neurons. [ABSTRACT FROM AUTHOR]