Metal contamination at a wood preservation site : characterisation and experimental studies on remediation

http://www.elsevier.com/locate/issn/00489697The aim of this investigation was to determine the occurrence of As, Cu, Cr and Zn in the soil at an abandoned wood preservation unit and to examine some possible extractants for the contaminants in the soil.The mean As content of the contaminated surface soils (0–10 cm) was 186 mg kgy1, where as the mean concentrations of Cu, Cr and Zn in soils from the contaminated area were 26, 29 and 91 mg kgy1, respectively.The elevated As content in the mineral soils is related to adsorption of inorganic As phases in the fine grained fractions, which are characterised by large surface area and high positive surface charge under the current acidic conditions.Cu and Cr were found to be rather mobile, which is reflected in their lower abundance in soils and significant accumulation in sediments in the drainage leaving the area.The fine fraction of the soil (-0.125 mm) has an average metal content increased by nearly 34% as compared to the -2-mm fraction conventionally used for the analysis and assessment of soil contamination.The -2-mm fraction constitutes approximately 65% of the total weight while the fine fraction (- 0.125 mm) constitutes approximately 10%.These facts, taken together, are essential for the choice of remediation measures.Oxalate solutions have been tested as extractants for soil remediation. Dark acid oxalate extraction dissolves the amorphous Al- and Fe-oxides and hydroxides and mobilises the adsorbed inorganic As species.Oxalate also acts as a ligand for the cationic heavy metals, releasing them from exchangeable sites.With a three-step sequential leaching, up to 98–99% of the metals could be removed.At lower concentrations and higher pH, the leaching decreased to approximately 70%

Safeguarding groundwater from arseniferous aquifers

Safeguarding groundwater from arseniferous aquifer

Commodity Price Volatility and World Market Integration since 1700

Poor countries are more volatile than rich countries, and we know this volatility impedes their growth. We also know that commodity price volatility is a key source of those shocks. This paper explores commodity and manufactures price over the past three centuries to answer three questions: Has commodity price volatility increased over time? The answer is no: there is little evidence of trend since 1700. Have commodities always shown greater price volatility than manufactures? The answer is yes. Higher commodity price volatility is not the modern product of asymmetric industrial organizations - oligopolistic manufacturing versus competitive commodity markets - that only appeared with the industrial revolution. It was a fact of life deep into the 18th century. Does world market integration breed more or less commodity price volatility? The answer is less. Three centuries of history shows unambiguously that economic isolation caused by war or autarkic policy has been associated with much greater commodity price volatility, while world market integration associated with peace and pro-global policy has been associated with less commodity price volatility. Given specialization and comparative advantage, globalization has been good for growth in poor countries at least by diminishing price volatility. But comparative advantage has never been constant. Globalization increased poor country specialization in commodities when the world went open after the early 19th century; but it did not do so after the 1970s as the Third World shifted to labor-intensive manufactures. Whether price volatility or specialization dominates terms of trade and thus aggregate volatility in poor countries is thus conditional on the century.

Oct-2, although not required for early B-cell development, is critical for later B-cell maturation and for postnatal survival

Oct-2, a POU homeo domain transcription factor, is believed to stimulate B-cell-restricted expression of immunoglobulin genes through binding sites in immunoglobulin gene promoters and enhancers. To determine whether Oct-2 is required for B-cell development or function, or has other developmental roles, the gene was disrupted by homologous recombination. Oct-2^(-/-) mice develop normally but die within hours of birth for undetermined reasons. Mutants contain normal numbers of B-cell precursors but are somewhat deficient in IgM+ B cells. These B cells have a marked defect in their capacity to secrete immunoglobulin upon mitogenic stimulation in vitro. Thus, Oct-2 is not required for the generation of immunoglobulin-bearing B cells but is crucial for their maturation to immunoglobulin-secreting cells and for another undetermined organismal function

PERP, an apoptosis-associated target of p53, is a novel member of the PMP-22/gas3 family

The p53 tumor suppressor activates either cell cycle arrest or apoptosis in response to cellular stress. Mouse embryo fibroblasts (MEFs) provide a powerful primary cell system to study both p53-dependent pathways. Specifically, in response to DNA damage, MEFs undergo p53-dependent G(1) arrest, whereas MEFs expressing the adenovirus E1A oncoprotein undergo p53-dependent apoptosis. As the p53-dependent apoptosis pathway is not well understood, we sought to identify apoptosis-specific p53 target genes using a subtractive cloning strategy. Here, we describe the characterization of a gene identified in this screen, PERP, which is expressed in a p53-dependent manner and at high levels in apoptotic cells compared with G(1)-arrested cells. PERP induction is linked to p53-dependent apoptosis, including in response to E2F-1-driven hyperproliferation. Furthermore, analysis of the PERP promoter suggests that PERP is directly activated by p53. PERP shows sequence similarity to the PMP-22/gas3 tetraspan membrane protein implicated in hereditary human neuropathies such as Charcot-Marie-Tooth, Like PMP-22/gas3, PERP is a plasma membrane protein, and importantly, its expression causes cell death in fibroblasts. Taken together, these data suggest that PERP is a novel effector of p59-dependent apoptosis

The Next Generation of Orthotopic Thyroid Cancer Models: Immunocompetent Orthotopic Mouse Models of BRAF

Background: While the development of new treatments for aggressive thyroid cancer has advanced in the last 10 years, progress has trailed headways made with other malignancies. A lack of reliable authenticated human cell lines and reproducible animal models is one major roadblock to preclinical testing of novel therapeutics. Existing xenograft and orthotopic mouse models of aggressive thyroid cancer rely on the implantation of highly passaged human thyroid carcinoma lines in immunodeficient mice. Genetically engineered models of papillary and undifferentiated (anaplastic) thyroid carcinoma (PTC and ATC) are immunocompetent; however, slow and stochastic tumor development hinders high-throughput testing. Novel models of PTC and ATC in which tumors arise rapidly and synchronously in immunocompetent mice would facilitate the investigation of novel therapeutics and approaches. Methods: We characterized and utilized mouse cell lines derived from PTC and ATC tumors arising in genetically engineered mice with thyroid-specific expression of endogenous BrafV600E/WTand deletion of either Trp53 (p53) or Pten. These murine thyroid cancer cells were transduced with luciferase- and GFP-expressing lentivirus and implanted into the thyroid glands of immunocompetent syngeneic B6129SF1/J mice in which the growth characteristics were assessed. Results: Large locally aggressive thyroid tumors form within one week of implantation. Tumors recapitulate their histologic subtype, including well-differentiated PTC and ATC, and exhibit CD3+, CD8+, B220+, and CD163+ immune cell infiltration. Tumor progression can be followed in vivo using luciferase and ex vivo using GFP. Metastatic spread is not detected at early time points. Conclusions: We describe the development of the next generation of murine orthotopic thyroid cancer models. The implantation of genetically defined murine BRAF-mutated PTC and ATC cell lines into syngeneic mice results in rapid and synchronous tumor formation. This model allows for preclinical investigation of novel therapeutics and/or therapeutic combinations in the context of a functional immune system

Context-Dependent Transformation of Adult Pancreatic Cells by Oncogenic K-Ras

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal human malignancies. To investigate the cellular origin(s) of this cancer, we determined the effect of PDAC-relevant gene mutations in distinct cell types of the adult pancreas. We show that a subpopulation of Pdx1-expressing cells is susceptible to oncogenic K-Ras-induced transformation without tissue injury, whereas insulin-expressing endocrine cells are completely refractory to transformation under these conditions. However, chronic pancreatic injury can alter their endocrine fate and allow them to serve as the cell of origin for exocrine neoplasia. These results suggest that one mechanism by which inflammation and/or tissue damage can promote neoplasia is by altering the fate of differentiated cells that are normally refractory to oncogenic stimulation.National Cancer Institute (U.S.) (Cancer Center Support (Core) Grant, P30 CA14051)National Institutes of Health (U.S.) (grant 1 PO1 CA117969 01)American Cancer Society (ACS Research Professor)Anna Fuller FundMassachusetts Institute of Technology (Daniel K. Ludwig Foundation Cancer Research Professor)Howard Hughes Medical Institute (Investigator

Circadian Rhythm Disruption Promotes Lung Tumorigenesis

Circadian rhythms are 24-hr oscillations that control a variety of biological processes in living systems, including two hallmarks of cancer, cell division and metabolism. Circadian rhythm disruption by shift work is associated with greater risk for cancer development and poor prognosis, suggesting a putative tumor-suppressive role for circadian rhythm homeostasis. Using a genetically engineered mouse model of lung adenocarcinoma, we have characterized the effects of circadian rhythm disruption on lung tumorigenesis. We demonstrate that both physiologic perturbation (jet lag) and genetic mutation of the central circadian clock components decreased survival and promoted lung tumor growth and progression. The core circadian genes Per2 and Bmal1 were shown to have cell-autonomous tumor-suppressive roles in transformation and lung tumor progression. Loss of the central clock components led to increased c-Myc expression, enhanced proliferation, and metabolic dysregulation. Our findings demonstrate that both systemic and somatic disruption of circadian rhythms contribute to cancer progression

Serum Creatinine and Tacrolimus Assessment With VAMS Finger-Prick Microsampling: A Diagnostic Test Study

Rationale & Objective: Kidney transplant recipients require frequent venipunctures. Microsampling methods that use a finger-prick draw of capillary blood, like volumetric absorptive microsamplers (VAMS), have the potential to reduce the pain, inconvenience, and volume of blood loss associated with venipuncture. This study aimed to provide diagnostic accuracy using VAMS for measurement of tacrolimus and creatinine compared to gold standard venous blood in adult kidney transplant recipients. Study Design: Diagnostic test study. Prospective blood samples for measurement of tacrolimus and creatinine were collected using Mitra VAMS and venipuncture immediately before and 2 hours after tacrolimus dosing. Setting & Participants: A convenience sample of 40 adult kidney transplant participants in the outpatient setting. Tests Compared: Method comparison was assessed by Passing-Bablok regression and Bland-Altman analysis. The predictive performance of VAMS measurement compared to venipuncture was also assessed through estimation of the median prediction error and median absolute percentage prediction error. Results: A total of 74 tacrolimus samples and 70 creatinine samples were analyzed from 40 participants. Passing-Bablok regression showed a systematic difference between VAMS and venipuncture when measuring tacrolimus and creatinine with a slope of 1.08 (95% CI, 1.03-1.13) and a slope of 0.65 (95% CI, 0.6-0.7), respectively. These values were then corrected for the systematic difference. When used for Bland-Altman analysis, corrected values of tacrolimus and creatinine showed a bias of -0.1 μg/L and 0.04 mg/dL, respectively. Tacrolimus (corrected) and creatinine (corrected) microsampling values when compared to corresponding venipuncture values met median prediction error and median absolute percentage prediction error predefined acceptability limits of <15%. Limitations: This study was conducted in a controlled environment using a trained nurse to collect VAMS samples. Conclusions: In this study, VAMS was used to reliably measured tacrolimus and creatinine. This represents a clear opportunity for more frequent and less invasive sampling for patients