Health-Based Criteria for Sediment Disposal Options: A Case Study of the Port of New York/New Jersey

Approximately 4 million cubic yards of sediment are dredged annually from the Port of New York and New Jersey in order to maintain navigable channels. In many cases, the sediments contain elevated levels of numerous contaminants. The New York District of the U.S. Army Corps of Engineers and U.S. Environmental Protection Agency Region II employ a framework of sediment quality evaluation to determine whether contaminated sediments are suitable for open ocean disposal (i.e., do not pose a health risk from bioaccumulation in human food chain) or whether more extensive and costly disposal methods are required. The degree to which chemicals can bioaccumulate from sediments into benthic invertebrates is a key determinant in the permitting decision. The maximally “acceptable” levels of bioaccumulation (bioaccumulation criteria) have been developed over a period of several years, using a variety of different methods. We reviewed the technical bases of these criteria and found that, while some values can be considered “risk-based,” others are based on historical background concentrations, Food and Drug Administration Action Levels, limits of detection, and other non-“risk-based” methodologies. Hence, the degree of uncertainty and health protection (or lack thereof) in the criteria varies considerably among the chemicals. We also reviewed the outcomes of several permit applications and found that the bioaccumulation criteria were not applied consistently. We propose the following refinements to the decision-making process: (1) bioaccumulation screening values based only upon risk-based criteria, using a single method that is applied for all chemicals; (2) increased consistency in decision-making and considerations of site-specific information where appropriate; and (3) assured availability of testing results for review and analysis by interested parties.     

Evaluating Landscape Options for Corridor Restoration between Giant Panda Reserves

The establishment of corridors can offset the negative effects of habitat fragmentation by connecting isolated habitat patches. However, the practical value of corridor planning is minimal if corridor identification is not based on reliable quantitative information about species-environment relationships. An example of this need for quantitative information is planning for giant panda conservation. Although the species has been the focus of intense conservation efforts for decades, most corridor projects remain hypothetical due to the lack of reliable quantitative researches at an appropriate spatial scale. In this paper, we evaluated a framework for giant panda forest corridor planning. We linked our field survey data with satellite imagery, and conducted species occupancy modelling to examine the habitat use of giant panda within the potential corridor area. We then conducted least-cost and circuit models to identify potential paths of dispersal across the landscape, and compared the predicted cost under current conditions and alternative conservation management options considered during corridor planning. We found that due to giant panda''s association with areas of low elevation and flat terrain, human infrastructures in the same area have resulted in corridor fragmentation. We then identified areas with high potential to function as movement corridors, and our analysis of alternative conservation scenarios showed that both forest/bamboo restoration and automobile tunnel construction would significantly improve the effectiveness of corridor, while residence relocation would not significantly improve corridor effectiveness in comparison with the current condition. The framework has general value in any conservation activities that anticipate improving habitat connectivity in human modified landscapes. Specifically, our study suggested that, in this landscape, automobile tunnels are the best means to remove current barriers to giant panda movements caused by anthropogenic interferences.     

Weighing on autophagy: A novel mechanism for the CNS regulation of energy balance

Comment on: Coupé B, et al. Cell Metab 2012; 15:247–55, Kaushik S, et al. EMBO Rep 2012; 13:258-65 and Quan W, et al. Endocrinology 2012; 153: In pressAutophagy has received considerable attention over the past decade owing to the fact that alteration of this cellular process, which degrades cytoplasmic materials, including organelles and misfolded proteins, contributes to a variety of diseases, such as cancer, muscular disorders and neurodegeneration.¹ Recent studies using conditional, cell-specific gene-targeting methods have also revealed the importance of autophagy in the regulation of energy balance. For example, the deletion of essential autophagy genes, such as the autophagy-related gene (Atg) 7, in the liver, pancreas or adipose tissue produces alterations in body weight, adiposity and glucose homeostasis.^2-6 Appetite, energy expenditure and metabolism are also carefully regulated by the central nervous system (CNS), particularly the pro-opiomelanocortin (POMC) neurons in the arcuate nucleus of the hypothalamus. These neurons act as major negative regulators of energy balance by reducing food intake and increasing energy expenditure. However, the role of CNS autophagy in the regulation of energy balance is largely unknown.Three recent studies, including one from our laboratory, have implicated CNS autophagy in the pathogenesis of obesity (Fig. 1).^7-9 These studies used a conditional cre-loxP approach to specifically delete Atg7 from POMC neurons. Pomc-Cre; Atg7^loxploxp mice display higher body weights, hyperphagia and impaired glucose tolerance.^7-9 These mice also exhibit an increased adiposity that is associated with leptin resistance.^7-9 Mice lacking autophagy in POMC neurons develop an increased sensitivity to weight gain when they are fed a high-fat/high-energy diet.^8,9Open in a separate windowFigure 1. Schematic diagram illustrating the metabolic and structural effects of autophagy deletion in hypothalamic POMC neurons. POMC, pro-opiomelanocortin; Atg, autophagy-related gene.Autophagy plays a particularly important role in biological processes that involve massive cellular elimination, such as neural development.¹⁰ Autophagy is constitutively present in the hypothalamus during important periods of development, and the loss of Atg7 in POMC neurons produces marked structural alterations during the first weeks of postnatal life and prior to the development of obesity(Fig. 1).⁷ Pomc-Cre; Atg7^loxPloxP mice exhibit a reduced density of POMC-containing projections to each of their target nuclei, including the paraventricular nucleus of the hypothalamus, as early as postnatal day 14. These abnormalities in POMC neural projections persist throughout adult life and appear to be the result of diminished capacity of POMC neurons to extend axons.⁷ However, all developmental processes are not affected by autophagy deficiency. No changes in POMC cell numbers between Pomc-Cre; Atg7^loxploxp and control mice are observed,^7-9 which suggests that autophagy does not influence neurogenesis or programmed cell death, but that it specifically affects axonal growth. However, autophagy may be involved in hypothalamic neurodegeneration, because aging is associated with a decline in hypothalamic autophagy and the accumulation of p62 (a polyubiquitin-binding protein that is normally degraded by autophagy) specifically in POMC neurons.⁸ In addition, axonal swelling, which is a hallmark of neurodegeneration, is observed in the hypothalamus of mice that lack autophagy in POMC neurons (Coupé and Bouret, unpublished data).Together, these recent studies suggest that autophagy is required for the proper development and function of POMC neurons, and that autophagy deficiency in POMC neurons causes marked metabolic and structural alterations. Autophagy is highly regulated by nutrient availability,¹¹ including during perinatal life, and further studies may provide novel mechanistic insights on the influence of perinatal dietary changes on the susceptibility to metabolic diseases.     

Criteria for Preparing, Evaluating, and Standardizing Iodinated Globulins for Radioimmunoassay Procedures

Procedures were examined for labeling immune globulins with radioactive iodine using chloramine-T as the oxidizing agent. The chloramine-T method was critically evaluated to establish the optimal conditions for preparing iodinated globulins with high specific radioactivities without impairing their immunospecificities for use in in vitro radioimmunoassays. The results showed that the use of 100 mug of chloramine-T per ml, 500 to 1,000 muCi of Na (125)I per mg of protein, and a 10-min oxidation reaction time produced globulins of both high specific radioactivities and immunospecificities. Criteria were established for evaluating and determining optimal concentrations of iodine-labeled globulin for use in radioimmunoassays. The results of this investigation indicated that the amount of labeled indicator globulin used in radioimmunoassays should be based upon protein concentration rather than radioactivity.     

Evaluating the Evidence for Hormesis: A Statistical Perspective

It is possible to account for hormesis under current regulatory guidelines by invoking criteria for departure from default risk assessment procedures. However, past experience suggests that it will be difficult to amass enough evidence for hormesis in an individual case to permit departure from default procedures. Accordingly, hormesis is likely to be important in agency risk assessments only if guidelines are modified to incorporate hormesis as a default assumption. This could be appropriate if hormesis is determined to be a universal or near-universal phenomenon. Although there is ample evidence that hormesis occurs in many specific situations, the overall prevalence of hormesis is very difficult to evaluate based on currently available data. The lack of a valid statistical test for hormesis is a major limitation when evaluating evidence for hormesis. The attempts at estimating the prevalence of hormesis reviewed herein did not adequately control for false positives and/or may have had inadequate power to detect hormesis. Some suggestions are made for constructing a database and analyzing the data therein that would provide more readily interpretable information on the prevalence of hormesis.     

A Commentary on Multiple Screening for Aminoacidopathies in the Newborn Infant

Multiple screening for aminoacidopathies has been attempted with a simple micromethod (Lancet, 2: 230, 1964) requiring only 10 μl. of plasma collected in a capillary tube and processed by a chromatographic technique. In a survey of 1250 infants, two newborn infants with phenylketonuria, two older infants with hypermethioninemia-tyrosinemia and hepatic cirrhosis were found, and approximately 10% of the premature infants had marked hypertyrosinemia. Multiple screening therefore has the advantage of multiple diagnosis over other techniques which screen specifically for a single disease. Pilot screening projects with this and other techniques could improve our knowledge of heritable metabolic disease so that mass screening for such problems may eventually be justifiable.     

Probabilistic Modeling Approach for Evaluating the Compliance of Ready-To-Eat Foods with New European Union Safety Criteria for Listeria monocytogenes

Among the new microbiological criteria that have been incorporated in EU Regulation 2073/2005, of particular interest are those concerning Listeria monocytogenes in ready-to eat (RTE) foods, because for certain food categories, they no longer require zero tolerance but rather specify a maximum allowable concentration of 100 CFU/g or ml. This study presents a probabilistic modeling approach for evaluating the compliance of RTE sliced meat products with the new safety criteria for L. monocytogenes. The approach was based on the combined use of (i) growth/no growth boundary models, (ii) kinetic growth models, (iii) product characteristics data (pH, a_w, shelf life) collected from 160 meat products from the Hellenic retail market, and (iv) storage temperature data recorded from 50 retail stores in Greece. This study shows that probabilistic analysis of the above components using Monte Carlo simulation, which takes into account the variability of factors affecting microbial growth, can lead to a realistic estimation of the behavior of L. monocytogenes throughout the food supply chain, and the quantitative output generated can be further used by food managers as a decision-making tool regarding the design or modification of a product's formulation or its “use-by” date in order to ensure its compliance with the new safety criteria. The study also argues that compliance of RTE foods with the new safety criteria should not be considered a parameter with a discrete and binary outcome because it depends on factors such as product characteristics, storage temperature, and initial contamination level, which display considerable variability even among different packages of the same RTE product. Rather, compliance should be expressed and therefore regulated in a more probabilistic fashion.     

A Role for the Superior Colliculus in Decision Criteria

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Commentary: statistics for biomarkers

This short commentary discusses Biomarkers' requirements for the reporting of statistical analyses in submitted papers. It is expected that submitters will follow the general instructions of the journal, the more detailed guidance given by the International Committee of Medical Journal Editors, the specific guidelines developed by the EQUATOR network, and those of various specialist groups. Biomarkers expects that the study design and subsequent statistical analyses are clearly reported and that the data reported can be made available for independent assessment. The journal recognizes that there is continuing debate about different approaches to statistical science. Biomarkers appreciates that the field continues to develop rapidly and encourages the use of new methodologies.     

Weighing in on ubiquitin: the expanding role of mass-spectrometry-based proteomics

Mass-spectrometry-based proteomics has become an essential tool for the qualitative and quantitative analysis of cellular systems. The biochemical complexity and functional diversity of the ubiquitin system are well suited to proteomic studies. This review summarizes advances involving the identification of ubiquitinated proteins, the elucidation of ubiquitin-modification sites and the determination of polyubiquitin chain linkages, as well as offering a perspective on the application of emerging technologies for mechanistic and functional studies of protein ubiquitination.