The increased incidence of diseases, including metabolic syndrome and infertility, may be related to exposure to the mixture of chemicals, which are ubiquitous in the modern environment ...(environmental chemicals, ECs). Xeno-detoxification occurs within the liver which is also the source of many plasma proteins and growth factors and plays an important role in the regulation of homeostasis.
The objective of this study was to investigate the effects of ECs on aspects of liver function, in a well characterized ovine model of exposure to a real-life EC mixture.
Four groups of sheep (n = 10–12/sex/treatment) were maintained long-term on control or sewage sludge-fertilized pastures: from conception to culling at 19 months of age in females and from conception to 7 months of age and thereafter in control plots until culling at 19 months of age in males. Environmental chemicals were measured in sheep livers and RNA and protein extracts were assessed for exposure markers. Liver proteins were resolved using 2D differential in-gel electrophoresis and differentially expressed protein spots were identified by liquid chromatography/tandem mass spectroscopy.
Higher levels of polycyclic aromatic hydrocarbons (PAHs) and lower levels of polychlorinated biphenyls (PCBs) in the livers of control males compared to control females indicated sexually dimorphic EC body burdens. Increased levels of the PAHs Benzoaanthracene and chrysene and reduced levels of PCB 153 and PCB 180 were observed in the livers of continuously exposed females. EC exposure affected xenobiotic and detoxification responses and the liver proteome in both sexes and included major plasma-secreted and blood proteins, and metabolic enzymes whose pathway analysis predicted dysregulation of cancer-related pathways and altered lipid dynamics. The latter were confirmed by a reduction in total lipids in female livers and up-regulation of cancer-related transcript markers in male livers respectively by sewage sludge exposure.
Our results demonstrate that chronic exposure to ECs causes major physiological changes in the liver, likely to affect multiple systems in the body and which may predispose individuals to increased disease risks.
•Chronic exposure to environmental chemicals affects liver physiology.•Proteomic measurements showed widespread dysregulation in the exposed livers.•Exposure dysregulated important plasma proteins such as albumin and transferrin•Reduction in total lipids in the exposed female livers•Increase in cancer markers in the exposed male livers
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The results for nuclei above curium, produced in multi-nucleon transfer reactions of
48
Ca +
248
Cm at the velocity filter SHIP of GSI Darmstadt, are presented. Spontaneous fission and
α
...-activities have been used to study the population of nuclei with lifetimes ranging from few milliseconds to several days. We observed several, relatively neutron-rich isotopes with atomic numbers
Z
≥
98
; among them a weak 224 millisecond activity which we tentatively attributed to
260
No. The measured cross-sections of the observed nuclei give hope that multi-nucleon transfer reactions are a way to reach new neutron-rich heavy and superheavy nuclei, which are not accessible in other reactions. We compare our results with data from earlier experiments and discuss limitations and future perspectives of the method.
Bone disease in myeloma occurs as a result of complex interactions between myeloma cells and the bone marrow microenvironment. A custom-built DNA single nucleotide polymorphism (SNP) chip containing ...3404 SNPs was used to test genomic DNA from myeloma patients classified by the extent of bone disease. Correlations identified with a Total Therapy 2 (TT2) (Arkansas) data set were validated with Eastern Cooperative Oncology Group (ECOG) and Southwest Oncology Group (SWOG) data sets. Univariate correlates with bone disease included: EPHX1, IGF1R, IL-4 and Gsk3β. SNP signatures were linked to the number of bone lesions, log2DKK-1 myeloma cell expression levels and patient survival. Using stepwise multivariate regression analysis, the following SNPs: EPHX1 (P=0.0026); log2DKK-1 expression (P=0.0046); serum lactic dehydrogenase (LDH) (P=0.0074); Gsk3β (P=0.02) and TNFSF8 (P=0.04) were linked to bone disease. This assessment of genetic polymorphisms identifies SNPs with both potential biological relevance and utility in prognostic models of myeloma bone disease.
In experiments that measure the lifetime of trapped particles, in addition to loss mechanisms with exponential survival probability functions, particles can be lost by mechanisms with non-exponential ...survival probability functions. Failure to account for such loss mechanisms produces systematic measurement error and associated systematic uncertainties in these measurements. In this work, we develop a general competing risks survival analysis method to account for the joint effect of loss mechanisms with either exponential or non-exponential survival probability functions, and a method to quantify the size of systematic effects and associated uncertainties for lifetime estimates. As a case study, we apply our survival analysis formalism and method to the Ultra Cold Neutron lifetime experiment at NIST. In this experiment, neutrons can escape a magnetic trap before they decay due to a wall loss mechanism with an associated non-exponential survival probability function.
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