Svaneholmes4810

The GPER mediated rapid non-genomic actions play an important role in the process leading to the adverse effects observed in experimental animals and even in human beings.The impact of oil exploration and production activities on the environment of sub-saharan African countries is not well studied. This study aimed at determining concentrations, sources, and bioaccumulation of 13 polycyclic aromatic hydrocarbons (PAHs) in sediments and fish from the White Nile near Melut oil fields, South Sudan. The study also assessed the ecological and human health risk associated with PAHs in this aquatic system. Total (∑13) PAH concentrations ranged from 566 to 674 ng g-1dry weight (dw) in sediments, while those in fish were 191-1143 ng g-1 wet weight (ww). ∑13PAH concentrations were significantly higher in C. gariepinus than in other fish species. Low molecular weight PAHs (LPAHs) dominated the profile of PAHs in sediments (constituted 95% of ∑13PAHs) and fish (97% of ∑13PAHs). Compared to Sediment Quality Guidelines of the United States Oceanic and Atmospheric Administration, the levels of LPAHs in this study were all above the threshold effect limits, but below the probable effect level, while those of high molecular weight PAHs (HPAHs) were all below the lowest effect levels. The carcinogenic potency equivalent concentrations of PAHs in L. niloticus and C. gariepinus were above the US EPA screening level; suggesting consumption of these species could adversely affect human health. Biota-sediment accumulation factor values (range 0.006-3.816 g OC g-1 lipid) for PAHs showed high bioaccumulation of LPAHs in fish muscle, and that bioaccumulation decreased with increase in hydrophobicity of the compounds. This is possibly because LPAHs have higher aqueous solubilities which increases their bioavailability through water-gill transfers compared to HPAHs. Profiles of PAHs in the White Nile environment indicate predominant contribution from petrogenic sources, which could be attributed to presence of crude oil reservoirs and oil production operations. More research into the levels of other environmental pollutants in the oil-rich area is recommended.Sedum alfredii is a Cd/Zn hyperaccumulator native to China, which was collected from a mined area where Mn content in soil was extremely high, together with Zn and Cd content. We investigated the tolerance and accumulation ability of Mn and its possible association with Cd hyperaccumulation in this plant species by using MP-AES, SR-μ-XRF, and RT-PCR. The results showed that the hyperaccumulating ecotype (HE) S. alfredii exhibited high tolerance to Mn and accumulating around 10,000 and 12,000 mg kg-1 Mn in roots and shoots, respectively, without exhibiting toxicity under 5000 mg kg-1 Mn treatment for 4 weeks. Exposure to Cd significantly reduced plant uptake of Mn. In contrast, exogenous Mn application significantly improved root uptake and root-to-shoot translocation of Cd, resulting in the increased Cd accumulation in the shoots of HE S. alfredii. SR-μ-XRF analysis demonstrated that high Mn (20 μM) exposure resulted in higher intensities of Cd localized in both stem vascular bundles and cortex, as well as leaf mesophyll cells, than in those treated with low Mn levels (0.2 μM or 2.0 μM). TED347 RT-PCR analysis of several genes possibly involved in Mn/Cd transportation showed that expression of SaNramp3 in roots was significantly reduced under high Mn exposure. These results suggested a significant interaction between Cd and Mn in the HE S. alfredii plants, possibly through their competition for transporters and theoretically provided a strategy to improve the efficiency of Cd extraction from polluted soils by this plant species, after using appropriate nutrient management of Mn.Pendimethalin (PDM) is a dinitroaniline crop pesticide that is extensively utilized worldwide. However, the reproductive toxicity and cellular mechanisms of PDM have not been identified. Therefore, we elucidated the adverse effects of PDM on the reproductive system using mouse testicular Leydig and Sertoli cells (TM3 and TM4 cells, respectively). Our results demonstrated that PDM suppressed the viability and proliferation of TM3 and TM4 cells. Additionally, PDM induced cytosolic calcium upregulation and permeabilization of mitochondrial membrane potential in both TM3 and TM4 cells. We also verified that PDM activates the endoplasmic reticulum (ER) stress pathway and autophagy. Furthermore, we confirmed that activation of ER stress and autophagy were blocked by 2-aminoethoxydiphenyl borate (2-APB) treatment. Finally, we confirmed PDM-induced cell cycle arrest and apoptosis in TM3 and TM4 cells. Thus, we first demonstrated that PDM impedes the survival of testis cells, and further, their function.In addition to endocrine disruption, bisphenol A (BPA) is known to induce inflammation through the activation of nuclear factor-κB (NF-κB). However, detailed studies on the mechanism of NF-κB activation by BPA have not been sufficiently conducted. In the present study, we observed that low concentrations of BPA (≤1 μM) upregulated the release of proinflammatory mediators, including nitric oxide (NO) and prostaglandin E2 (PGE2), as well as proinflammatory cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-12, and IL-6. Molecular modeling predicted that BPA docked with the Toll-like receptor 4 (TLR4)/myeloid differentiation factor 2 (MD2) complex activates downstream molecules including myeloid differentiation primary response 88 (MyD88) and IL-1 receptor-associated kinase 4 (IRAK-4) and results in the upregulation of the NF-κB signaling pathway. Additionally, BPA increased morphological abnormalities and mortality in zebrafish larvae and enhanced the dispersal of macrophages and neutrophils in the whole body, thereby causing an endotoxemia-like disorder. However, a specific TLR4 inhibitor, TLR4-IN-C34, mitigated BPA-induced mortality and morphological abnormalities, which indicates that the TLR4/MD2 complex is a molecular target of BPA-induced immunotoxicity. Collectively, our results indicate that low concentrations of BPA, which is a potential agonist of the TLR4/MD2 complex, can intensify the immune response and eventually cause an endotoxemia-like disorder.The microbiome has been described as an additional host "organ" with well-established beneficial roles. However, the effects of exposures to chemicals on both structure and function of the gut microbiome of fishes are understudied. To determine effects of benzo[a]pyrene (BaP), a model persistent organic pollutant, on structural shifts of gut microbiome in juvenile fathead minnows (Pimephales promelas), fish were exposed ad libitum in the diet to concentrations of 1, 10, 100, or 1000 μg BaP g-1 food, in addition to a vehicle control, for two weeks. To determine the link between exposure to BaP and changes in the microbial community, concentrations of metabolites of BaP were measured in fish bile and 16S rRNA amplicon sequencing was used to evaluate the microbiome. Exposure to BaP only reduced alpha-diversity at the greatest exposure concentrations. However, it did alter community composition assessed as differential abundance of taxa and reduced network complexity of the microbial community in all exposure groups. Results presented here illustrate that environmentally-relevant concentrations of BaP can alter the diversity of the gut microbiome and community network connectivity.Nucleosome remodeling provides access to genomic DNA for recruitment of the transcriptional machinery to mediate gene expression. The aberrant function of nucleosome remodeling complexes has been correlated to human cancer, making them emerging therapeutic targets. The bromodomain PHD finger transcription factor, BPTF, is the largest member of the human nucleosome remodeling factor NURF. Over the last five years, BPTF has become increasingly identified as a protumorigenic factor, prompting investigations into the molecular mechanisms associated with BPTF function. Despite a druggable bromodomain, small molecule discovery is at an early stage. Here we highlight recent investigations into the biology being discovered for BPTF, chemical biology approaches used to study its function, and small molecule inhibitors being designed as future chemical probes and therapeutics.Human leukocyte antigens of class-I (HLA-I) molecules are hyper-expressed in insulin-containing islets (ICI) of type 1 diabetic (T1D) donors. This study investigated the HLA-I expression in autoantibody positive (AAB+) donors and defined its intra-islet and intracellular localization as well as proximity to infiltrating CD8 T cells with high-resolution confocal microscopy. We found HLA-I hyper-expression had already occurred prior to clinical diagnosis of T1D in islets of AAB+ donors. Interestingly, throughout all stages of disease, HLA-I was mostly expressed by alpha cells. Hyper-expression in AAB+ and T1D donors was associated with intra-cellular accumulation in the Golgi. Proximity analysis showed a moderate but significant correlation between HLA-I and infiltrating CD8 T cells only in ICI of T1D donors, but not in AAB+ donors. These observations not only demonstrate a very early, islet-intrinsic immune-independent increase of HLA-I during diabetes pathogenesis, but also point towards a role for alpha cells in T1D.Endocytic traffic is a complex and elegant operation involving cargo sorting, membrane budding and tubulation, generation of force, and the formation of organellar contacts. The role of specific proteins and lipids in these processes has been studied extensively. By comparison, precious little is understood about the contribution of the endocytic fluid to these events, despite much evidence that alteration of the contents can severely affect membrane traffic along the endocytic pathway. In particular, it has long been appreciated that dissipation of ionic gradients arrests endosome-to-lysosome maturation. How cells sense inorganic ions and transmit this information have remained largely enigmatic. Herein, we review the experimental findings that reveal an intimate association between luminal ions, their transport, and endocytic traffic. We then discuss the ionic sensors and the mechanisms proposed to convert ion concentrations into protein-based trafficking events, highlighting the current paucity of convincing explanations.The dynamics and interactions of cellular organelles underlie many aspects of cellular functioning. Until recently, assessment of organelle dynamics has been primarily observational or required whole-cell perturbations to assess the implications of altered organelle motility and positioning. However, thanks to recently developed and optimized intervention strategies, we now have the ability to control organelles in their unperturbed state, altering organelle positioning, membrane trafficking pathways, as well as organelle interactions. This can be performed both globally and locally, giving fine control over the range, reversibility, and extent of organelle dynamics. Here, we describe how these tools are currently used for controlling organelles and give insight into the exciting future of this emerging field.