History of Wildlife Toxicology and the Interpretation of Contaminant Concentrations in Tissues

The detection and interpretation of contaminants in tissues of wildlife belongs to the field of toxicology, a scientific discipline with a long, intriguing, and illustrious history (reviewed by Hayes 1991, Gallo 2001, Gilbert and Hayes 2006, Wax 2006). We review its history briefly, to provide a context for understanding the use of tissue residues in toxicology, and to explain how their use has developed over time. Because so much work has been conducted on mercury, and dioxins and polychlorinated biphenyls (PCBs), separate case histories are included that describe the evolution of the use of tissue concentrations to assess exposure and effects of these two groups of contaminants in wildlife. The roots of toxicology date back to early man, who used plant and animal extracts as poisons for hunting and warfare. The Ebers papyrus (Egypt -1550 BC) contains formulations for hemlock, aconite (arrow poison), opium, and various metals used as poisons. Hippocrates (-400 BC) is sometimes credited with proposing the treatment of poisoning by decreasing absorption and using antidotes (Lane and Borzelleca 2007). Chanakya (350-283 BC), Indian advisor of the Maurya Emperor Chandragupta (340-293 BC), urged the use of food tasters as a precaution against poisoning, and the Roman emperor Claudius may have even been poisoned by his taster Halotus in 54 AD. Moses ben Maimon (1135-1204), author of a treatise on poisoning, noted that dairy products could delay absorption of some poisons. Paracelsus (1493-1541) shaped the field of toxicology with his corollaries that experimentation is essential to examining the response, that therapeutic properties should be distinguished from toxic properties, that chemicals have specific modes of action, and that the dose makes the poison. The art of concocting and using poisons reached its zenith during the Italian Renaissance, eventually culminating in its commercialization by Catherine Deshayes (a.k.a., La Voisine, 1640-1680) in France. One of the first to suggest a chemical method for the detection of a poison in modern times was Herman Boerhaave (1668-1738), a physician and botanist, who, according to Jurgen Thorwald (The Century of the Detective), placed the suspected poison on red-hot coals, and tested for odors. The Spanish physician Orfila (1787-1853) served in the French court, and was the first toxicologist to systematically use autopsy and chemical analysis to prove poisoning. He has been credited with developing and refining techniques to detect arsenic poisoning. Other historic accounts include extraction of alkaloids from postmortem specimens (Jean Servais Stas ~1851) as evidence in a nicotine poisoning case (Levine 2003). The chemical analysis of organs and tissues became the basis for establishing poisoning. Much of the early history of toxicology addressed whether someone had been poisoned and how to treat poisoning

Saúde Brasil 2011 : uma análise da situação de saúde e a vigilância da saúde da mulher

Introdução: No Brasil, ocorrem cerca de 3 milhões de nascimentos ao ano, sendo grande parte deles por meio de cesarianas. Entender como se distribui esse procedimento no País é relevante para a reflexão sobre o papel das políticas públicas nesse contexto. Objetivos: a) Descrever: magnitude e tendência da taxa de cesáreas*1 no País; morbimortalidade materna e neonatal associada a tipo de parto; e características dos hospitais; b) analisar o preenchimento das variáveis da nova versão da Declaração de Nascido Vivo (DNV) que permitirão monitoramento das indicações de cesárea; c) descrever as respostas institucionais para o enfrentamento do problema. Métodos: Estudo descritivo de série histórica da taxa de cesarianas, no País e macrorregiões, segundo características sociodemográficas, morbimortalidade e tipo de provedor, com fonte em bancos de dados oficiais. Analisou-se a completitude de variáveis da versão da DNV de 2010 para monitoramento das indicações de cirurgia. Foram pesquisados documentos oficiais, visando identificar iniciativas para qualificar a atenção a partos e nascimentos e reduzir cesarianas desnecessárias. Resultados: A taxa de cesarianas foi de 32%, em 1994, e de 52%, em 2010, sendo menor no Norte e Nordeste. Mulheres submetidas a cesáreas tiveram 3,5 vezes mais probabilidade de morrer (entre 1992–2010) e 5 vezes mais de ter infecção puerperal (entre 2000–2011) que as de parto normal. No período, a proporção de prematuros se elevou, mais nas cesáreas (7,8%, sendo 6,4% nos partos normais em 2010). Em 2010, hospitais não públicos apresentaram taxas maiores (63,6%) e maior aumento no período de 2006 a 2010 (14,0%); para os públicos, as taxas foram de 47,8% (federais), de 39,6% (estaduais) e de 34,0% (municipais). Conclusão: A cesariana é frequente e sua proporção ascende no País, sendo muito elevada no setor de Saúde Suplementar. Para reverter essa tendência, serão necessárias várias medidas, incluindo a qualificação da informação para monitorar a efetividade das medidas propostas

Mechanochemically synthesized Pb-free halide perovskite-based Cs2AgBiBr6–Cu–RGO nanocomposite for photocatalytic CO2 reduction

Pb-based halide perovskites have recently showed great potential in various applications such as solar cells, optoelectronics and photocatalysis. Despite their high performance, the Pb2+ toxicity along with poor stability hinders long term applications in photocatalysis. Herein, we report mechanochemically prepared Pb-free Cs2AgBiBr6 double perovskite nanoplates and their heterostructure with Cu-loaded reduced graphene oxide (Cu–RGO) for gas-phase photocatalytic CO2 reduction using water vapor as the proton source in the absence of a hole scavenger. The resulting Cs2AgBiBr6–Cu–RGO nanocomposite shows significant photocatalytic activity of 10.7 (±0.6) μmol CH4 g−1 h−1, 1.9 (±0.3) μmol CO g−1 h−1 and 1.0 (±0.2) μmol H2 g−1 h−1, with a CH4 selectivity of 93.0 (±0.5)% on an electron basis with 1 sun and a remarkable apparent quantum efficiency of 0.89 (±0.21)% at 590 nm. A further 32% enhancement in photocatalytic activity on an electron basis is achieved when the light intensity is doubled (2 suns). The high performance was attributed to their improved charge separation and suppressed electron–hole recombination, along with extended visible light absorption, better stability in a humid environment and improved CO2 adsorption. These findings support Cs2AgBiBr6 as a potential Pb-free alternative to conventional halide perovskites for photocatalytic solar-to-fuel conversion and CO2 utilization

Coupling of the nucleus and cytoplasm: role of the LINC complex

The nuclear envelope defines the barrier between the nucleus and cytoplasm and features inner and outer membranes separated by a perinuclear space (PNS). The inner nuclear membrane contains specific integral proteins that include Sun1 and Sun2. Although the outer nuclear membrane (ONM) is continuous with the endoplasmic reticulum, it is nevertheless enriched in several integral membrane proteins, including nesprin 2 Giant (nesp2G), an 800-kD protein featuring an NH2-terminal actin-binding domain. A recent study (Padmakumar, V.C., T. Libotte, W. Lu, H. Zaim, S. Abraham, A.A. Noegel, J. Gotzmann, R. Foisner, and I. Karakesisoglou. 2005. J. Cell Sci. 118:3419–3430) has shown that localization of nesp2G to the ONM is dependent upon an interaction with Sun1. In this study, we confirm and extend these results by demonstrating that both Sun1 and Sun2 contribute to nesp2G localization. Codepletion of both of these proteins in HeLa cells leads to the loss of ONM-associated nesp2G, as does overexpression of the Sun1 lumenal domain. Both treatments result in the expansion of the PNS. These data, together with those of Padmakumar et al. (2005), support a model in which Sun proteins tether nesprins in the ONM via interactions spanning the PNS. In this way, Sun proteins and nesprins form a complex that links the nucleoskeleton and cytoskeleton (the LINC complex)

High-Flux Thermal Management With Supercritical Fluids

A novel thermal management approach is explored, which uses supercritical carbon dioxide (sCO2) as a working fluid to manage extreme heat fluxes in electronics cooling applications. In the pseudocritical region, sCO2 has extremely high volumetric thermal capacity, which can enable operation with low pumping requirements, and without the potential for two-phase critical heat flux (CHF) and flow instabilities. A model of a representative microchannel heat sink is evaluated with single-phase liquid water and FC-72, two-phase boiling R-134a, and sCO2. For a fixed pumping power, sCO2 is found to yield lower heat-sink wall temperatures than liquid coolants. Practical engineering challenges for supercritical thermal management systems are discussed, including the limits of predictive heat transfer models, narrow operating temperature ranges, high working pressures, and pump design criteria. Based on these findings, sCO2 is a promising candidate working fluid for cooling high heat flux electronics, but additional thermal transport research and engineering are needed before practical systems can be realized

Cellular Resolution Maps of X Chromosome Inactivation: Implications for Neural Development, Function, and Disease

SummaryFemale eutherian mammals use X chromosome inactivation (XCI) to epigenetically regulate gene expression from ∼4% of the genome. To quantitatively map the topography of XCI for defined cell types at single cell resolution, we have generated female mice that carry X-linked, Cre-activated, and nuclear-localized fluorescent reporters—GFP on one X chromosome and tdTomato on the other. Using these reporters in combination with different Cre drivers, we have defined the topographies of XCI mosaicism for multiple CNS cell types and of retinal vascular dysfunction in a model of Norrie disease. Depending on cell type, fluctuations in the XCI mosaic are observed over a wide range of spatial scales, from neighboring cells to left versus right sides of the body. These data imply a major role for XCI in generating female-specific, genetically directed, stochastic diversity in eutherian mammals on spatial scales that would be predicted to affect CNS function within and between individuals

Dose Dependent Effects on Cell Cycle Checkpoints and DNA Repair by Bendamustine

Bendamustine (BDM) is an active chemotherapeutic agent approved in the U. S. for treating chronic lymphocytic leukemia and non-Hodgkin lymphoma. Its chemical structure suggests it may have alkylator and anti-metabolite activities; however the precise mechanism of action is not well understood. Here we report the concentration-dependent effects of BDM on cell cycle, DNA damage, checkpoint response and cell death in HeLa cells. Low concentrations of BDM transiently arrested cells in G2, while a 4-fold higher concentration arrested cells in S phase. DNA damage at 50, but not 200 µM, was efficiently repaired after 48 h treatment, suggesting a difference in DNA repair efficiency at the two concentrations. Indeed, perturbing base-excision repair sensitized cells to lower concentrations of BDM. Timelapse studies of the checkpoint response to BDM showed that inhibiting Chk1 caused both the S- and G2-arrested cells to prematurely enter mitosis. However, whereas the cells arrested in G2 (low dose BDM) entered mitosis, segregated their chromosomes and divided normally, the S-phase arrested cells (high dose BDM) exhibited a highly aberrant mitosis, whereby EM images showed highly fragmented chromosomes. The vast majority of these cells died without ever exiting mitosis. Inhibiting the Chk1-dependent DNA damage checkpoint accelerated the time of killing by BDM. Our studies suggest that BDM may affect different biological processes depending on drug concentration. Sensitizing cells to killing by BDM can be achieved by inhibiting base-excision repair or disrupting the DNA damage checkpoint pathway

Spectrum of centrosome autoantibodies in childhood varicella and post-varicella acute cerebellar ataxia

BACKGROUND: Sera from children with post-varicella infections have autoantibodies that react with centrosomes in brain and tissue culture cells. We investigated the sera of children with infections and post-varicella ataxia and related conditions for reactivity to five recombinant centrosome proteins: γγ-enolase, pericentrin, ninein, PCM-1, and Mob1. METHODS: Sera from 12 patients with acute post-varicella ataxia, 1 with post-Epstein Barr virus (EBV) ataxia, 5 with uncomplicated varicella infections, and other conditions were tested for reactivity to cryopreserved cerebellum tissue and recombinant centrosome proteins. The distribution of pericentrin in the cerebellum was studied by indirect immunofluorescence (IIF) using rabbit antibodies to the recombinant protein. Antibodies to phospholipids (APL) were detected by ELISA. RESULTS: Eleven of 12 children with post-varicella ataxia, 4/5 children with uncomplicated varicella infections, 1/1 with post-EBV ataxia, 2/2 with ADEM, 1/2 with neuroblastoma and ataxia, and 2/2 with cerebellitis had antibodies directed against 1 or more recombinant centrosome antigens. Antibodies to pericentrin were seen in 5/12 children with post-varicella ataxia but not in any of the other sera tested. IIF demonstrated that pericentrin is located in axons and centrosomes of cerebellar cells. APL were detected in 75% of the sera from children with post-varicella ataxia and 50% of children with varicella without ataxia and in none of the controls. CONCLUSION: This is the first study to show the antigen specificity of anti-centrosome antibodies in children with varicella. Our data suggest that children with post-varicella ataxia have unique autoantibody reactivity to pericentrin

An electrochemical system for efficiently harvesting low-grade heat energy

Efficient and low-cost thermal energy-harvesting systems are needed to utilize the tremendous low-grade heat sources. Although thermoelectric devices are attractive, its efficiency is limited by the relatively low figure-of-merit and low-temperature differential. An alternative approach is to explore thermodynamic cycles. Thermogalvanic effect, the dependence of electrode potential on temperature, can construct such cycles. In one cycle, an electrochemical cell is charged at a temperature and then discharged at a different temperature with higher cell voltage, thereby converting heat to electricity. Here we report an electrochemical system using a copper hexacyanoferrate cathode and a Cu/Cu2+ anode to convert heat into electricity. The electrode materials have low polarization, high charge capacity, moderate temperature coefficients and low specific heat. These features lead to a high heat-to-electricity energy conversion efficiency of 5.7% when cycled between 10 and 60 degrees C, opening a promising way to utilize low-grade heat.open121

Use of terrestrial field studies in the derivation of bioaccumulation potential of chemicals

Field-based studies are an essential component of research addressing the behavior of organic chemicals, and a unique line of evidence that can be used to assess bioaccumulation potential in chemical registration programs and aid in development of associated laboratory and modeling efforts. To aid scientific and regulatory discourse on the application of terrestrial field data in this manner, this article provides practical recommendations regarding the generation and interpretation of terrestrial field data. Currently, biota-to-soil-accumulation factors (BSAFs), biomagnification factors (BMFs), and bioaccumulation factors (BAFs) are the most suitable bioaccumulation metrics that are applicable to bioaccumulation assessment evaluations and able to be generated from terrestrial field studies with relatively low uncertainty. Biomagnification factors calculated from field-collected samples of terrestrial carnivores and their prey appear to be particularly robust indicators of bioaccumulation potential. The use of stable isotope ratios for quantification of trophic relationships in terrestrial ecosystems needs to be further developed to resolve uncertainties associated with the calculation of terrestrial trophic magnification factors (TMFs). Sampling efforts for terrestrial field studies should strive for efficiency, and advice on optimization of study sample sizes, practical considerations for obtaining samples, selection of tissues for analysis, and data interpretation is provided. Although there is still much to be learned regarding terrestrial bioaccumulation, these recommendations provide some initial guidance to the present application of terrestrial field data as a line of evidence in the assessment of chemical bioaccumulation potential and a resource to inform laboratory and modeling efforts