Spatial patterns of mercury in macroinvertebrates and fishes from streams of two contrasting forested landscapes in the eastern United States

Controls on mercury bioaccumulation in lotic ecosystems are not well understood. During 2007–2009, we studied mercury and stable isotope spatial patterns of macroinvertebrates and fishes from two medium-sized (<80 km²) forested basins in contrasting settings. Samples were collected seasonally from multiple sites across the Fishing Brook basin (FB_NY), in New York’s Adirondack Mountains, and the McTier Creek basin (MC_SC), in South Carolina’s Coastal Plain. Mean methylmercury (MeHg) concentrations within macroinvertebrate feeding groups, and mean total mercury (THg) concentrations within most fish feeding groups were similar between the two regions. However, mean THg concentrations in game fish and forage fish, overall, were much lower in FB_NY (1300 and 590 ng/g dw, respectively) than in MC_SC (2300 and 780 ng/g dw, respectively), due to lower trophic positions of these groups from FB_NY (means 3.3 and 2.7, respectively) than MC_SC (means 3.7 and 3.3, respectively). Much larger spatial variation in topography and water chemistry across FB_NY contributed to greater spatial variation in biotic Hg and positive correlations with dissolved MeHg and organic carbon in streamwater. Hydrologic transport distance (HTD) was negatively correlated with biotic Hg across FB_NY, and was a better predictor than wetland density. The small range of landscape conditions across MC_SC resulted in no consistent spatial patterns, and no discernable correspondence with local-scale environmental factors. This study demonstrates the importance of local-scale environmental factors to mercury bioaccumulation in topographically heterogeneous landscapes, and provides evidence that food-chain length can be an important predictor of broad-scale differences in Hg bioaccumulation among streams.     

Diterpenoids from the freshwater green algae Rhizoclonium hieroglyphicum with antibacterial activity

Three new isopimarane diterpenes 7β-hydroxy-19α-methylmalonyloxy-isopimara-8(14),15-diene (1), 7β-hydroxy-14-oxo-isopimara-8(9),15-dien-19oic acid (2), and 7β-hydroxy-14-oxo-19α-methylmalonyloxy-isopimara-9(11),15-diene (3) in addition to the known compounds isopimaric acid (4), 7oxo-13-epi-pimara-14,15-dien-18oic acid (5), 7oxo-13-epi-pimara-8,15-dien-18oic acid (6), and 6β-hydroxyisopimaric acid (7) were isolated from the hexane extract of Rhizoclonium hieroglyphicum. The structures of compounds 1-7 were established by 1D and 2D NMR techniques. The isolated diterpenoids were screened for antimicrobial activity against gram-positive and gram-negative bacteria and yeast strains.     

Rosiglitazone delayed weight loss and anorexia while attenuating adipose depletion in mice with cancer cachexia

Cachexia is characterized by severe weight loss, including adipose and muscle wasting, and occurs in a large percentage of cancer patients. Insulin resistance contributes to dysregulated metabolism in cachexia and occurs prior to weight loss in mice with colon-26 tumor-induced cachexia. Therefore, we hypothesized that the insulin sensitizer, rosiglitazone, would attenuate the loss of adipose and muscle to result in improved outcomes for mice with late-stage cachexia. Male CD2F1 mice were inoculated with colon-26 adenocarcinoma cells or vehicle. Treatments included vehicle, rosiglitazone (10 mg/kg body weight/day) or rosiglitazone plus pair-feeding to food intake of vehicle-treated mice with tumors. Rosiglitazone delayed weight loss onset by 2 d over the 16 d duration of this aggressive tumor model. This finding was associated, in part, with increased food intake. In addition, adipose mass, adipocyte cross-sectional area and inflammation were improved with rosiglitazone. However, at the time of necropsy 16 d after tumor inoculation rosiglitazone had no effect on retention of muscle mass, strength or proteolysis in late-stage cachexia. We did not measure stamina or endurance in this study. In early-stage cachexia, rosiglitazone normalized PDK4 and PPAR-delta mRNA in quadriceps muscle and rescued the decrease in insulin-stimulated glucose disappearance in mice with tumors. Rosiglitazone may delay weight loss onset by decreasing tumor-induced markers of metabolic change in early-stage cachexia. These changes predict for modest improvement in adipose, but no improvement in muscle strength in late-stage cachexia.     

New Immunomodulatory Drugs in Myeloma

Multiple myeloma (MM) is an incurable malignancy of plasma cells. The introduction of thalidomide was a milestone in the treatment of MM. Thalidomide analogues termed immunomodulatory drugs (IMiDs) have been developed that are more effective and have less toxicity than thalidomide. The role of lenalidomide in relapsed MM has been well defined. This review discusses the data regarding the upfront use of lenalidomide with dexamethasone or in multidrug combinations, as well as its potential role as maintenance therapy. It also reviews our experience with pomalidomide, a new IMid with remarkable activity in relapsed, refractory MM.     

Impact of dexamethasone responsiveness on long term outcome in patients with newly diagnosed multiple myeloma

Dexamethasone (Dex), alone or in combination, is commonly used for treating multiple myeloma. Dex as single agent for initial therapy of myeloma results in overall response rates of 50–60%. It is unclear whether steroid responsiveness reflects any biological characteristic that impacts long‐term outcome. We studied a cohort of 182 patients with newly diagnosed myeloma seen between March 1998 and June 2007, initially treated with single‐agent Dex for at least 4 weeks. The median age at diagnosis was 63 years (range, 39–81) and the median estimated survival was 55 months. At a median duration of therapy of 15 weeks, 91 (50%) patients had a partial response or better, 80 (44%) had less than partial response and the remaining (6%) patients were not evaluable. The median overall survival from diagnosis for the responders was 75 months compared to 71 months for remaining patients, P = 0·6.There was no correlation between baseline disease characteristics and Dex responsiveness. While overall survival was longer for the 130 (70%) patients who proceeded to an autologous stem cell transplant, no correlation was found between survival and Dex responsiveness among either group. Among this cohort of patients with myeloma, failure to respond to single agent steroid did not have an adverse impact on eventual outcome.     

Longitudinal association between toenail selenium levels and measures of subclinical atherosclerosis: The CARDIA trace element study

Objectives

To examine the longitudinal association between toenail selenium levels and subclinical atherosclerosis over an 18-year period.

Methods

Toenail selenium concentrations were examined among 3112 Americans age 20–32 years in 1987 and measured by instrumental neutron-activation analysis. Subclinical atherosclerosis, including common, bulb and internal carotid intima–media thickness (CIMT), was measured in 2005 and coronary artery calcium (CAC) score in 2000 and 2005. General linear regression was developed examining the relation between toenail selenium levels and CIMTs, and logistic regression for repeated outcomes was employed estimating the risk of having CAC > 0.

Results

After adjustment for potential confounders, no associations were observed between toenail selenium levels and CIMTs as well as CAC score. Comparing participants in the highest with the lowest quintile of selenium, the CIMT was 0.005 mm (SE = 0.008 mm, P_trend = 0.39), 0.018 mm (SE = 0.019 mm, P_trend = 0.49), and 0.017 mm (SE = 0.014 mm, P_trend = 0.21) thicker measured in common, bulb and internal carotid, respectively. The adjusted odds ratio of having CAC > 0 was 0.95 (95% CI: 0.67–1.35; P_trend = 0.999).

Conclusions

No associations were observed between toenail selenium and measures of subclinical atherosclerosis among American young adults. This study does not support an atherosclerotic mechanism of selenium for risk reduction of cardiovascular disease.     

Escherichia coli condensin MukB stimulates topoisomerase IV activity by a direct physical interaction

In contrast to the current state of knowledge in the field of eukaryotic chromosome segregation, relatively little is known about the mechanisms coordinating the appropriate segregation of bacterial chromosomes. In Escherichia coli, the MukB/E/F complex and topoisomerase IV (Topo IV) are both crucial players in this process. Topo IV removes DNA entanglements following the replication of the chromosome, whereas MukB, a member of the structural maintenance of chromosomes protein family, serves as a bacterial condensin. We demonstrate here a direct physical interaction between the dimerization domain of MukB and the C-terminal domain of the ParC subunit of Topo IV. In addition, we find that MukB alters the activity of Topo IV in vitro. Finally, we isolate a MukB mutant, D692A, that is deficient in its interaction with ParC and show that this mutant fails to rescue the temperature-sensitive growth phenotype of a mukB(-) strain. These results show that MukB and Topo IV are linked physically and functionally and indicate that the activities of these proteins are not limited to chromosome segregation but likely also play a key role in the control of higher-order bacterial chromosome structure.     

Urinary Phthalate Metabolites in Relation to Preterm Birth in Mexico City

Background

Rates of preterm birth have been rising over the past several decades. Factors contributing to this trend remain largely unclear, and exposure to environmental contaminants may play a role.

Objective

We investigated the relationship between phthalate exposure and preterm birth.

Methods

Within a large Mexican birth cohort study, we compared third-trimester urinary phthalate metabolite concentrations in 30 women who delivered preterm (< 37 weeks of gestation) with those of 30 controls (≥ 37 weeks of gestation).

Results

Concentrations of most of the metabolites were similar to those reported among U.S. females, although in the present study mono-n-butyl phthalate (MBP) concentrations were higher and monobenzyl phthalate (MBzP) concentrations lower. In a crude comparison before correcting for urinary dilution, geometric mean urinary concentrations were higher for the phthalate metabolites MBP, MBzP, mono(3-carboxylpropyl) phthalate, and four metabolites of di(2-ethyl-hexyl) phthalate among women who subsequently delivered preterm. These differences remained, but were somewhat lessened, after correction by specific gravity or creatinine. In multivariate logistic regression analysis adjusted for potential confounders, elevated odds of having phthalate metabolite concentrations above the median level were found.

Conclusions

We found that phthalate exposure is prevalent among this group of pregnant women in Mexico and that some phthalates may be associated with preterm birth.     

Influence of Prenatal Lead Exposure on Genomic Methylation of Cord Blood DNA

Background

Fetal lead exposure is associated with adverse pregnancy outcomes and developmental and cognitive deficits; however, the mechanism(s) by which lead-induced toxicity occurs remains unknown. Epigenetic fetal programming via DNA methylation may provide a pathway by which environmental lead exposure can influence disease susceptibility.

Objective

This study was designed to determine whether prenatal lead exposure is associated with alterations in genomic methylation of leukocyte DNA levels from umbilical cord samples.

Methods

We measured genomic DNA methylation, as assessed by Alu and LINE-1 (long interspersed nuclear element-1) methylation via pyrosequencing, on 103 umbilical cord blood samples from the biorepository of the Early Life Exposures in Mexico to Environmental Toxicants (ELEMENT) study group. Prenatal lead exposure had been assessed by measuring maternal bone lead levels at the mid-tibial shaft and the patella using a spot-source ¹⁰⁹Cd K-shell X-ray fluorescence instrument.

Results

We found an inverse dose–response relationship in which quartiles of patella lead correlated with cord LINE-1 methylation (p for trend = 0.01) and and tibia lead correlated with Alu methylation (p for trend = 0.05). In mixed effects regression models, maternal tibia lead was negatively associated with umbilical cord genomic DNA methylation of Alu (β= −0.027; p = 0.01). We found no associations between cord blood lead and cord genomic DNA methylation.

Conclusions

Prenatal lead exposure is inversely associated with genomic DNA methylation in cord blood. These data suggest that the epigenome of the developing fetus can be influenced by maternal cumulative lead burden, which may influence long-term epigenetic programming and disease susceptibility throughout the life course.