The Sequential Application of Macroalgal Biosorbents for the Bioremediation of a Complex Industrial Effluent

Fe-treated biochar and raw biochar produced from macroalgae are effective biosorbents of metalloids and metals, respectively. However, the treatment of complex effluents that contain both metalloid and metal contaminants presents a challenging scenario. We test a multiple-biosorbent approach to bioremediation using Fe-biochar and biochar to remediate both metalloids and metals from the effluent from a coal-fired power station. First, a model was derived from published data for this effluent to predict the biosorption of 21 elements by Fe-biochar and biochar. The modelled outputs were then used to design biosorption experiments using Fe-biochar and biochar, both simultaneously and in sequence, to treat effluent containing multiple contaminants in excess of water quality criteria. The waste water was produced during ash disposal at an Australian coal-fired power station. The application of Fe-biochar and biochar, either simultaneously or sequentially, resulted in a more comprehensive remediation of metalloids and metals compared to either biosorbent used individually. The most effective treatment was the sequential use of Fe-biochar to remove metalloids from the waste water, followed by biochar to remove metals. Al, Cd, Cr, Cu, Mn, Ni, Pb, Zn were reduced to the lowest concentration following the sequential application of the two biosorbents, and their final concentrations were predicted by the model. Overall, 17 of the 21 elements measured were remediated to, or below, the concentrations that were predicted by the model. Both metalloids and metals can be remediated from complex effluent using biosorbents with different characteristics but derived from a single feedstock. Furthermore, the extent of remediation can be predicted for similar effluents using additive models.     

Pharmacogenetic-Based Efavirenz Dose Modification: Suggestions for an African Population and the Different CYP2B6 Genotypes

Background

Pharmacogenetics contributes to inter-individual variability in pharmacokinetics (PK) of efavirenz (EFV), leading to variations in both efficacy and toxicity. The purpose of this study was to assess the effect of genetic factors on EFV pharmacokinetics, treatment outcomes and genotype based EFV dose recommendations for adult HIV-1 infected Ugandans.

Methods

In total, 556 steady-state plasma EFV concentrations from 99 HIV infected patients (64 female) treated with EFV/lamivudine/zidovidine were analyzed. Patient genotypes for CYP2B6 (*6 & *11), CYP3A5 (*3,*6 & *7) and ABCB1 c.4046A>G, baseline biochemistries and CD4 and viral load change from baseline were determined. A one-compartment population PK model with first-order absorption (NONMEM) was used to estimate genotype effects on EFV pharmacokinetics. PK simulations were performed based upon population genotype frequencies. Predicted AUCs were compared between the product label and simulations for doses of 300 mg, 450 mg, and 600 mg.

Results

EFV apparent clearance (CL/F) was 2.2 and 1.74 fold higher in CYP2B6*6 (*1/*1) and CYP2B6*6 (*1/*6) compared CYP2B6*6 (*6/*6) carriers, while a 22% increase in F1 was observed for carriers of ABCB1 c.4046A>G variant allele. Higher mean AUC was attained in CYP2B6 *6/*6 genotypes compared to CYP2B6 *1/*1 (p<0.0001). Simulation based AUCs for 600 mg doses were 1.25 and 2.10 times the product label mean AUC for the Ugandan population in general and CYP2B6*6/*6 genotypes respectively. Simulated exposures for EFV daily doses of 300 mg and 450 mg are comparable to the product label. Viral load fell precipitously on treatment, with only six patients having HIV RNA >40 copies/mL after 84 days of treatment. No trend with exposure was noted for these six patients.

Conclusion

Results of this study suggest that daily doses of 450 mg and 300 mg might meet the EFV treatment needs of HIV-1 infected Ugandans in general and individuals homozygous for CYP2B6*6 mutation, respectively.     

Wintering Habitat Model for the North Atlantic Right Whale (Eubalaena glacialis) in the Southeastern United States

The coastal waters off the southeastern United States (SEUS) are a primary wintering ground for the endangered North Atlantic right whale (Eubalaena glacialis), used by calving females along with other adult and juvenile whales. Management actions implemented in this area for the recovery of the right whale population rely on accurate habitat characterization and the ability to predict whale distribution over time. We developed a temporally dynamic habitat model to predict wintering right whale distribution in the SEUS using a generalized additive model framework and aerial survey data from 2003/2004 through 2012/2013. We built upon previous habitat models for right whales in the SEUS and include data from new aerial surveys that extend the spatial coverage of the analysis, particularly in the northern portion of this wintering ground. We summarized whale sightings, survey effort corrected for probability of whale detection, and environmental data at a semimonthly resolution. Consistent with previous studies, sea surface temperature (SST), water depth, and survey year were significant predictors of right whale relative abundance. Additionally, distance to shore, distance to the 22°C SST isotherm, and an interaction between time of year and latitude (to account for the latitudinal migration of whales) were also selected in the analysis presented here. Predictions from the model revealed that the location of preferred habitat differs within and between years in correspondence with variation in environmental conditions. Although cow-calf pairs were rarely sighted in the company of other whales, there was minimal evidence that the preferred habitat of cow-calf pairs was different than that of whale groups without calves at the scale of this study. The results of this updated habitat model can be used to inform management decisions for a migratory species in a dynamic oceanic environment.     

Macular Pigment Optical Density Measured by Heterochromatic Modulation Photometry

Purpose

To psychophysically determine macular pigment optical density (MPOD) employing the heterochromatic modulation photometry (HMP) paradigm by estimating 460 nm absorption at central and peripheral retinal locations.

Methods

For the HMP measurements, two lights (B: 460 nm and R: 660 nm) were presented in a test field and were modulated in counterphase at medium or high frequencies. The contrasts of the two lights were varied in tandem to determine flicker detection thresholds. Detection thresholds were measured for different R:B modulation ratios. The modulation ratio with minimal sensitivity (maximal threshold) is the point of equiluminance. Measurements were performed in 25 normal subjects (11 male, 14 female; age: 30±11 years, mean ± sd) using an eight channel LED stimulator with Maxwellian view optics. The results were compared with those from two published techniques – one based on heterochromatic flicker photometry (Macular Densitometer) and the other on fundus reflectometry (MPR).

Results

We were able to estimate MPOD with HMP using a modified theoretical model that was fitted to the HMP data. The resultant MPOD_HMP values correlated significantly with the MPOD_MPR values and with the MPOD_HFP values obtained at 0.25° and 0.5° retinal eccentricity.

Conclusions

HMP is a flicker-based method with measurements taken at a constant mean chromaticity and luminance. The data can be well fit by a model that allows all data points to contribute to the photometric equality estimate. Therefore, we think that HMP may be a useful method for MPOD measurements, in basic and clinical vision experiments.     

A Translatable Predictor of Human Radiation Exposure

Terrorism using radiological dirty bombs or improvised nuclear devices is recognized as a major threat to both public health and national security. In the event of a radiological or nuclear disaster, rapid and accurate biodosimetry of thousands of potentially affected individuals will be essential for effective medical management to occur. Currently, health care providers lack an accurate, high-throughput biodosimetric assay which is suitable for the triage of large numbers of radiation injury victims. Here, we describe the development of a biodosimetric assay based on the analysis of irradiated mice, ex vivo-irradiated human peripheral blood (PB) and humans treated with total body irradiation (TBI). Interestingly, a gene expression profile developed via analysis of murine PB radiation response alone was inaccurate in predicting human radiation injury. In contrast, generation of a gene expression profile which incorporated data from ex vivo irradiated human PB and human TBI patients yielded an 18-gene radiation classifier which was highly accurate at predicting human radiation status and discriminating medically relevant radiation dose levels in human samples. Although the patient population was relatively small, the accuracy of this classifier in discriminating radiation dose levels in human TBI patients was not substantially confounded by gender, diagnosis or prior exposure to chemotherapy. We have further incorporated genes from this human radiation signature into a rapid and high-throughput chemical ligation-dependent probe amplification assay (CLPA) which was able to discriminate radiation dose levels in a pilot study of ex vivo irradiated human blood and samples from human TBI patients. Our results illustrate the potential for translation of a human genetic signature for the diagnosis of human radiation exposure and suggest the basis for further testing of CLPA as a candidate biodosimetric assay.     

Morbidity and Mortality of Invertebrates,Amphibians, Reptiles,and Mammals at a Major Exotic Companion Animal Wholesaler

The authors formally investigated a major international wildlife wholesaler and subsequently confiscated more than 26,400 nonhuman animals of 171 species and types. Approximately 80% of the nonhuman animals were identified as grossly sick, injured, or dead, with the remaining in suspected suboptimal condition. Almost 3,500 deceased or moribund animals (12% of stock), mostly reptiles, were being discarded on a weekly basis. Mortality during the 6-week “stock turnover” period was determined to be 72%. During a 10-day period after confiscation, mortality rates (including euthanasia for humane reasons) for the various taxa were 18% for invertebrates, 44.5% for amphibians, 41.6% for reptiles, and 5.5% for mammals. Causes of morbidity and mortality included cannibalism, crushing, dehydration, emaciation, hypothermic stress, infection, parasite infestation, starvation, overcrowding, stress/injuries, euthanasia on compassionate grounds, and undetermined causes. Contributing factors for disease and injury included poor hygiene; inadequate, unreliable, or inappropriate provision of food, water, heat, and humidity; presumed high levels of stress due to inappropriate housing leading to intraspecific aggression; absent or minimal environmental enrichment; and crowding. Risks for introduction of invasive species through escapes and/or spread of pathogens to naive populations also were identified.     

CYP105—diverse structures,functions and roles in an intriguing family of enzymes in Streptomyces

The cytochromes P450 (CYP or P450) are a large superfamily of haem‐containing enzymes found in all domains of life. They catalyse a variety of complex reactions, predominantly mixed‐function oxidations, often displaying highly regio‐ and/or stereospecific chemistry. In streptomycetes, they are predominantly associated with secondary metabolite biosynthetic pathways or with xenobiotic catabolism. Homologues of one family, CYP105, have been found in all Streptomyces species thus far sequenced. This review looks at the diverse biological functions of CYP105s and the biosynthetic/catabolic pathways they are associated with. Examples are presented showing a range of biotransformative abilities and different contexts. As biocatalysts capable of some remarkable chemistry, CYP105s have great biotechnological potential and merit detailed study. Recent developments in biotechnological applications which utilize CYP105s are described, alongside a brief overview of the benefits and drawbacks of using P450s in commercial applications. The role of CYP105s in vivo is in many cases undefined and provides a rich source for further investigation into the functions these enzymes fulfil and the metabolic pathways they participate in, in the natural environment.     

Critical Role for NAD Glycohydrolase in Regulation of Erythropoiesis by Hematopoietic Stem Cells through Control of Intracellular NAD Content

NAD glycohydrolases (NADases) catalyze the hydrolysis of NAD to ADP-ribose and nicotinamide. Although many members of the NADase family, including ADP-ribosyltransferases, have been cloned and characterized, the structure and function of NADases with pure hydrolytic activity remain to be elucidated. Here, we report the structural and functional characterization of a novel NADase from rabbit reticulocytes. The novel NADase is a glycosylated, glycosylphosphatidylinositol-anchored cell surface protein exclusively expressed in reticulocytes. shRNA-mediated knockdown of the NADase in bone marrow cells resulted in a reduction of erythroid colony formation and an increase in NAD level. Furthermore, treatment of bone marrow cells with NAD, nicotinamide, or nicotinamide riboside, which induce an increase in NAD content, resulted in a significant decrease in erythroid progenitors. These results indicate that the novel NADase may play a critical role in regulating erythropoiesis of hematopoietic stem cells by modulating intracellular NAD.