Landslides are one of several natural hazards. As other natural hazards, landslides are difficult to predict, and their forecasts are uncertain. The uncertainty depends on the poor understanding of the phenomena that control the slope failures, and on the inherent complexity and chaotic nature of the landslides. This is similar to other natural hazards, including hurricanes, earthquakes, volcanic eruptions, floods, and droughts. Due to the severe impact of landslides on the population, the environment, and the economy, forecasting landslides is of scientific interest and of societal relevance, and scientists attempting to forecast landslides face known and new problems intrinsic to the multifaceted interactions between science, decision-making, and the society. The problems include deciding on the authority and reliability of individual scientists and groups of scientists, and evaluating the performances of individual scientists, research teams, and their institutions. Related problems lay in the increasing subordination of research scientists to politics and decision-makers, and in the conceptual and operational models currently used to organize and pay for research, based on apparently objective criteria and metrics, considering science as any other human endeavor, and favoring science that produces results of direct and immediate application. The paper argues that the consequences of these problems have not been considered fully.

Some physico-chemical properties and the concentrations of the metals Fe, Mn, Ni, Cd, Cr, Co, Cu, Pb, and Zn in water and sediments were examined from September 2011 to January 2012 in Bodo Creek, where oil spills have been recurrent. Temperature, pH, total dissolved solid, conductivity, salinity, dissolved oxygen, biological oxygen demand (BOD), chemical oxygen demand (COD), total hardness, sulfate, nitrate, and phosphate were determined in surface water. Particle size, total organic matter (TOM), and pH were also determined in the sediments. The parameters were within permissible limits except the mean values of BOD, COD, total hardness, and sulfate that exceeded levels permissible for domestic use. The sediments consisted mainly of sand, with TOM ranging from 0.2% to 5.5%. With the exception of cadmium that was below detection limit, metal levels (mg kg) in the sediments were 12 (Mn), 1070 (Fe), 10 (Cu), 10 (Zn), 5.3 (Cr), 1.1 (Pb), 1.0 (Ni), and 0.5 (Co) while in water they were 24, 98, 21, 6.9, 4.0, 0.6, 0.18, and 0.16, respectively. The latter were higher than World Health Organization recommended permissible levels for both surface and drinking water.

Dichloroacetate (DCA) and trichloroacetate (TCA) are water chlorination byproducts, and their mixtures were previously found to induce additive to greater than additive effects on hepatic oxidative stress (OS) induction in mice after subchronic exposure. To investigate the roles of antioxidant enzymes and glutathione (GSH) in those effects, livers of B6C3F1 mice treated by gavage with 7.5, 15, or 30 mg DCA/kg/day, 12.5, 25, or 50 mg TCA/kg/day, and mixtures (Mix I, Mix II and Mix III) at DCA:TCA ratios corresponding to 7.5:12.5, 15:25 and 25:50 mg/kg/day, respectively, for 13 weeks. Livers were assayed for superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), as well as for GSH levels. In general, DCA suppressed SOD and GSH-Px activities and GSH levels but caused no changes in CAT activity; TCA increased SOD and CAT activities, suppressed GSH-Px activity, but did not change GSH levels; mixtures of DCA and TCA increased SOD and CAT activities and suppressed GSH-Px activity and GSH levels. In conclusion, antioxidant enzymes contribute to DCA-, TCA- and mixtures-induced OS, but not to changes from additive to greater than additive effects produced by different mixture compositions of the compounds. GSH on the hand may contribute to these changes.

Indoor and outdoor air pollution is known to contribute to increased lung cancer incidence. This study is the first to address the contribution of home heating fuel and geographical course particulate matter (PM) concentrations to lung cancer rates in New Hampshire, U.S. First, Pearson correlation analysis and Geographically weighted regression were used to investigate spatial relationships between outdoor PM and lung cancer rates. While the aforementioned analyses did not indicate a significant contribution of PM to lung cancer in the state, there was a trend towards a significant association in the northern and southwestern regions of the state. Second, case-control data were used to estimate the contributions of indoor pollution and second hand smoke to risk of lung cancer with adjustment for confounders. Increased risk was found among those who used wood or coal to heat their homes for more than 10 winters before the age of 18, with a significant increase in risk per winter. Resulting data suggest that further investigation of the relationship between heating-related air pollution levels and lung cancer risk is needed.

Autism is defined by a behavioral set of stereotypic and repetitious behavioral patterns in combination with social and communication deficits. There is emerging evidence supporting the hypothesis that autism may result from a combination of genetic susceptibility and exposure to environmental toxins at critical moments in development. Mercury (Hg) is recognized as a ubiquitous environmental neurotoxin and there is mounting evidence linking it to neurodevelopmental disorders, including autism. Of course, the evidence is not derived from experimental trials with humans but rather from methods focusing on biomarkers of Hg damage, measurements of Hg exposure, epidemiological data, and animal studies. For ethical reasons, controlled Hg exposure in humans will never be conducted. Therefore, to properly evaluate the Hg-autism etiological hypothesis, it is essential to first establish the biological plausibility of the hypothesis. This review examines the plausibility of Hg as the primary etiological agent driving the cellular mechanisms by which Hg-induced neurotoxicity may result in the physiological attributes of autism. Key areas of focus include: (1) route and cellular mechanisms of Hg exposure in autism; (2) current research and examples of possible genetic variables that are linked to both Hg sensitivity and autism; (3) the role Hg may play as an environmental toxin fueling the oxidative stress found in autism; (4) role of mitochondrial dysfunction; and (5) possible role of Hg in abnormal neuroexcitory and excitotoxity that may play a role in the immune dysregulation found in autism. Future research directions that would assist in addressing the gaps in our knowledge are proposed.

The purpose of this blinded study was to evaluate potential environmental toxicity in a cohort of neurotypical children ( = 28) living in a suburban area of north-central Texas in the United States (US) with a comparable age- and gender-matched cohort of neurotypical children ( = 28) living in a suburban area of southeastern France using urinary porphyrin testing: uroporphyrin (uP), heptacarboxyporphyrin (7cxP), hexacarboxyporphyrin (6cxP), pentacarboxyporphyrin (5cxP), precoproporphyrin (prcP), and coproporphyrin (cP). Results showed significantly elevated 6cxP, prcP (an atypical, mercury-specific porphyrin), and cP levels, and increasing trends in 5cxP levels, among neurotypical children in the USA compared to children in France. Data suggest that in US neurotypical children, there is a significantly increased body-burden of mercury (Hg) compared to the body-burden of Hg in the matched neurotypical children in France. The presence of lead contributing to the higher levels of cP also needs to be considered. Further, other factors including genetics can not be completely ruled out.

An immunology-based in vivo screening regime was used to assess the potential pathogenicity of biotechnology-related microbes. Strains of Bacillus cereus (Bc), Bacillus subtilis (Bs), Bacillus thuringiensis (Bt), and Bt commercial products (CPs) were tested. Balb/c mice were endotracheally instilled with purified spores, diluted CP, or vegetative cells (VC) (live or dead). Exposed mice were evaluated for changes in behavioral and physical symptoms, bacterial clearance, pulmonary granulocytes, and pulmonary and circulatory pyrogenic cytokines (interleukins (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α), as well as acute phase biomarkers (fibrinogen and serum amyloid A). Except for some differences in clearance rates, no marked effects were observed in mice exposed to any spore at 10(6) or 10(7) colony forming units (cfu). In contrast, live Bc or Bt VCs (10(5) or 10(6) cfu) produced shock-like symptoms (lethargy, hunched appearance, ruffled fur, and respiratory distress), and 11-200-fold elevations in pyrogenic cytokines at 2-h post-exposure. In the study, 4-h effects included increased lethargy, ocular discharge, and 1.5-4-fold rise in circulatory acute phase markers, but no indications of recovery. Bs VC did not produce any changes in symptoms or biomarkers. After 2 or 4 h of exposure to dead VC, increases of only plasma IL-1? and TNF-α (4.6- and 12.4-fold, respectively) were observed. These findings demonstrate that purified spores produced no marked effects in mice compared to that of metabolically active bacteria. This early screening regime was successful in distinguishing the pathogenicity of the different Bacillus species, and might be useful for assessing the relative hazard potential of other biotechnology-related candidate strains.

Dichloroacetate (DCA) and trichloroacetate (TCA) were previously found to induce various levels of oxidative stress in the hepatic tissues of mice after subacute and subchronic exposure. The cells are known to have several protective mechansims against production of oxidative stress by different xenobiotics. To assess the roles of the antioxidant enzymes and glutathione (GSH) in DCA- and TCA-induced oxidative stress, groups of B6C3F1 mice were administered either DCA or TCA at doses of 7.7, 77, 154 and 410 mg/kg/day, by gavage for 4 weeks (4-W) and 13 weeks (13-W), and superoxide dismutase (SOD) catalase (CAT) and glutathione peroxidase (GSH-Px) activities, as well as GSH were determined in the hepatic tissues. DCA at doses ranging between 7.7-410, and 7.7-77 mg/kg/day, given for 4-W and 13-W, respectively, resulted in either suppression or no change in SOD, CAT and GSH-Px activities, but doses of 154-410 mg DCA/kg/day administered for 13-W were found to result in significant induction of the three enzyme activities. TCA administration on the other hand, resulted in increases in SOD and CAT activities, and suppression of GSH-Px activity in both periods. Except for the DCA doses of 77-154 mg/kg/day administered for 13-W that resulted in significant reduction in GSH levels, all other DCA, as well as TCA treatments produced no changes in GSH. Since these enzymes are involved in the detoxification of the reactive oxygen species (ROS), superoxide anion (SA) and H(2)O(2), it is concluded that SA is the main contributor to DCA-induced oxidative stress while both ROS contribute to that of TCA. The increases in the enzyme activities associated with 154-410 mg DCA/kg/day in the 13-W period suggest their role as protective mechanisms contributing to the survival of cells modified in response to those treatments.

Sensory neurons originating in nodose and jugular ganglia that innervate airway epithelium (airway neurons) play a role in inflammation observed following exposure to inhaled environmental irritants such as ozone (O(3)). Airway neurons can mediate airway inflammation through release of the neuropeptide substance P (SP). While susceptibility to airway irritants is increased in early life, the developmental dynamics of afferent airway neurons are not well characterized. The hypothesis of this study was that airway neuron number might increase with increasing age, and that an acute, early postnatal O(3) exposure might increase both the number of sensory airway neurons as well as the number SP-containing airway neurons. Studies using Fischer 344 rat pups were conducted to determine if age or acute O(3) exposure might alter airway neuron number. Airway neurons in nodose and jugular ganglia were retrogradely labeled, removed, dissociated, and counted by means of a novel technique employing flow cytometry. In Study 1, neuron counts were conducted on postnatal days (PD) 6, 10, 15, 21, and 28. Numbers of total and airway neurons increased significantly between PD6 and PD10, then generally stabilized. In Study 2, animals were exposed to O(3) (2 ppm) or filtered air (FA) on PD5 and neurons were counted on PD10, 15, 21, and 28. O(3) exposed animals displayed significantly less total neurons on PD21 than FA controls. This study shows that age-related changes in neuron number occur, and that an acute, early postnatal O(3) exposure significantly alters sensory neuron development.

Cadmium (Cd(+2)), a known carcinogen mimics the effects of estrogen in the uterus and mammary gland suggesting its possible involvement in the development and progression of breast cancer. This lab showed through analysis of a small set of archival human diagnostic specimens that the third isoform of the classic Cd(+2) binding protein metallothionein (MT-3), is not expressed in normal breast tissue, but is expressed in some breast cancers and that expression tends to correlate with a poor disease outcome. The goals of the present study were to verify that overexpression of MT-3 in a large set of archival human diagnostic specimens tends to correlate with poor disease outcome and define the mechanism of MT-3 gene regulation in the normal breast epithelial cell. The results showed that MT-3 was expressed in approximately 90% of all breast cancers and was absent in normal breast epithelium. The lack of MT-3 staining in some cancers correlated with a favorable patient outcome. High frequency of MT-3 staining was also found for in situ breast cancer suggesting that MT-3 might be an early biomarker for breast cancer. The study also demonstrated that the MCF-10A cell line, an immortalized, non-tumorigenic model of human breast epithelial cells, displayed no basal expression of MT-3, nor was it induced by Cd(+2). Treatment of the MCF-10A cells with the demethylation agent, 5-Aza-2'-deoxycytidine, or the histone deacetylase inhibitor, MS-275, restored MT-3 mRNA expression. It was also shown that the MT-3 metal regulatory elements are potentially active binders of protein factors following treatment with these inhibitors suggesting that MT-3 expression may be subject to epigenetic regulation.

The abilities of various doses of 3,3',4,4',5-pentachlorobiphenyl (PCB126) to induce changes in antioxidant enzyme activities and glutathione levels in the brain tissues of rats were examined in rats after subchronic exposure. Groups of rats were administered 10,30, 100, 300, 550 or 1000 ng PCB 126/kg/day, p.o., for 13 weeks and the activities of supeoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px), as well as (GSH) levels were determined in the brain tissue homogenates. Treatment resulted in significant and dose-dependent increases in the activities of the three tested enzymes. While maximal increase GSH-Px activity was achieved with a dose of 100-175 mg/kg/day, CAT and SOD activities continued to increase in response to maximal dose used for this study. GSH levels on the other hand, were suppressed significantly in a dose-dependent fashion. Data suggest that previously observed increase in oxidative stress production by PCB-126 in the brain tissues of rats is associated with dose-dependent rise in antioxidant enzyme activities and GSH depletion. However, the increases in the antioxidant enzyme activities can not provide full protection against oxidative damage induced by the same doses. In addition, GSH depletion plays a critical role in the previously observed oxidative stress in response to this compound.

The aryl hydrocarbon receptor (AHR) is a cytosolic transcription factor with numerous endogenous and xenobiotic ligands, most notably 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Recent data suggests that TCDD may induce regulatory T cells, while a second AHR ligand, FICZ, promotes Th17 differentiation. The aim was to examine whether injection of recipient mice with either TCDD or FICZ altered skin allograft rejection in a fully mismatched model. TCDD or FICZ was given to recipient C57BL/6 mice intraperitoneally (IP). Twenty-four hr later, donor skin was grafted from BALB/c mice. An additional dose of FICZ was given on day 3. Treatment with TCDD delayed graft rejection for more than 4 weeks while FICZ treatment accelerated rejection by 1 - 2 days. In vivo exposure with TCDD led to a rise in the frequency of FoxP3(+) CD4(+) T cells in the spleen, while FICZ increased IL-17 secretion by splenocytes from treated animals. Activation of the AHR receptor by different AHR ligands in vivo resulted in opposing effects on skin graft survival. AHR serves as a sensor to environmental signals, with effects on the acquired immune system that may alter outcomes after organ transplantation. This model will be useful to further delineate direct effects of the environment on the immune system and outcomes of organ transplantation.

High urban atmospheric pollution is caused by economic and industrial growth, especially in developing countries. The objective of this study was to assess possible relationships between effects on human alveolar epithelial cells of source-related dust types collected at Sulaimani City (Iraq), and to determine their mineralogical and chemical composition. A passive sampler was used to collect dust particles at a rural, an industrial and an urban sampling site during July and August 2014. The samples were size-fractionated by a low-pressure impactor to obtain respirable dust with aerodynamic diameters of less than 10 μm. The dust was mainly composed of quartz and calcite. Chrysotile fibres (white asbestos) were also found at the urban site. Dust from the industrial and urban sites triggered cytotoxic and genotoxic effects in the cells, whereas only minor effects were observed for the sample from the rural site.

Components of the innate immune system such as macrophages and dendritic cells are instrumental in determining the fate of immune responses and are, also, among the most sensitive targets of early life environmental alterations including developmental immunotoxicity (DIT). DIT can impede innate immune cell maturation, disrupt tissue microenvironment, alter immune responses to infectious challenges, and disrupt regulatory responses. Dysregulation of inflammation, such as that observed with DIT, has been linked with an increased risk of chronic inflammatory diseases in both children and adults. In this review, we discuss the relationship between early-life risk factors for innate immune modulation and promotion of dysregulated inflammation associated with chronic inflammatory disease. The health risks from DIT-associated inflammation may extend beyond primary immune dysfunction to include an elevated risk of several later-life, inflammatory-mediated diseases that target a wide range of physiological systems and organs. For this reason, determination of innate immune status should be an integral part of drug and chemical safety evaluation.

Sucralose is partially absorbed after oral ingestion, with the majority excreted in the feces. We aimed to measure plasma sucralose concentrations following ingestion of doses reflecting a range of consumption (from one can of diet soda up to multiple sodas over the course of a day) and to compare concentrations in children and adults. Eleven adults (7 females, 4 males) consumed 355 mL water containing 0 mg sucralose (control) or 68, 170, or 250 mg sucralose (equivalent to 1-4 diet sodas). A second group of adults (n=11, 6 females and 5 males) consumed 355 mL Diet Rite Cola™ (68 mg sucralose and 41 mg acesulfame-potassium (ace-K)) or 68 mg sucralose and 41 mg ace-K in seltzer. Beverages were provided at separate visits in randomized order, prior to an oral glucose tolerance test. Eleven children (7 females and 4 males) consumed 0 or 68 mg sucralose in 240 mL water, in an identical study design. Blood was collected before beverage ingestion and serially for 120 min. Sucralose doses (corrected for weight) resulted in similar plasma concentrations in children and adults. Children reached peak concentrations of 145-400 ng/mL after 68 mg (mean 262.3 ± 24.6 ng/mL). Most adults reached similar peak concentrations (200-400 ng/mL after 250 mg (365.6 ± 69.9 ng/mL)) with the exception of two adults (1520 ng/mL and 1557 ng/mL, respectively). Concentrations were comparable whether sucralose was administered in water, combined with ace-K, or in diet soda. Due to their lower body weight and blood volume, children have markedly higher plasma sucralose concentrations after consumption of a typical diet soda, emphasizing the need to determine the clinical implications of sucralose use in children.

The marine toxin, okadaic acid (OA) is produced by dinoflagellates of the genera Prorocentrum and Dinophysis and is the causative agent of the syndrome known as diarrheic shellfish poisoning (DSP). In addition, OA acts as both a tumor promoter, attributed to OA-induced inhibition of protein phosphatases as well as an inducer of apoptosis. To better understand the potentially divergent toxicological profile of OA, the concentration dependent cytotoxicity and alterations in gene expression on the human liver tumor cell line HepG2 upon OA exposure were determined using RNA microarrays, DNA fragmentation, and cell proliferation assays as well as determinations of cell detachment and cell death in different concentrations of OA. mRNA expression was quantified for approximately 15,000 genes. Cell attachment and proliferation were both negatively correlated with OA concentration. Detached cells displayed necrotic DNA signatures but apoptosis also was broadly observed. Data suggest that OA has a concentration dependent effect on cell cycle, which might explain the divergent effects that at low concentration OA stimulates genes involved in the cell cycle and at high concentrations it stimulates apoptosis.

Per- and poly-fluoroalkyl substances, especially perfluorooctanesulfonic acid, have been extensively used for over 50 years. A growing body of evidence has emerged demonstrating the potential adverse effects of these substances, including its effect on the development of non-alcoholic fatty liver disease, as one of the most prevalent chronic liver diseases. Nonetheless, there is no report of effects of perfluorobutanesulfonic acid, the major replacement for perfluorooctanesulfonic acid, on non-alcoholic fatty liver disease. Therefore, the effects of perfluorobutanesulfonic acid exposure on fat accumulation in a human hepatoma cell line were examined. Cells were exposed to perfluorobutanesulfonic acid with or without 300 μmol/L fatty acid mixture (oleic acid:palmitic acid = 2:1) conjugated by bovine serum albumin as an inducer of steatosis for 48 hours. Perfluorobutanesulfonic acid at 200 μmol/L significantly increased the triglyceride level in the presence of fatty acid compared to the control, but not without fatty acid, which was abolished by a specific peroxisome proliferator-activated receptor gamma antagonist. Perfluorobutanesulfonic acid upregulated key genes controlling lipogenesis and fatty acid uptake. Perfluorobutanesulfonic acid treatment also promoted the production of reactive oxygen species, an endoplasmic reticulum stress marker and cytosolic calcium. In conclusion, perfluorobutanesulfonic acid increased fat accumulation, in part, via peroxisome proliferator-activated receptor gamma-mediated pathway in hepatoma cells.

It is well known that lead (Pb) produces reduced haemoglobin (Hb) levels and risk of anemia when blood lead levels (BPb) are greater than 20 µg dL. Two recent studies reported an increased risk of anemia in children with BPb between 10-20 µg dL, but few studies examined the association between Hb levels or risk of anemia and BPb under 10 µg dL. In the present study this association was examined using data of 140 preschool children from a larger prospective cohort study in China. Data showed that compared to children with BPb <5 µg dL, children with BPb between 7.5-10 µg dL had significantly lower Hb levels, but there were no marked differences for other groups. A linear regression model showed a negative relationship between BPb and Hb levels after controlling for age, gender, height, weight, and iron (Fe) deficiency. This finding, although limited by a small sample size, suggests it may be important to examine Pb-induced hemosynthesis effect at concentrations less than 10 µg dL.

The toxic effects of mercury are known to be complex with specific enzyme inhibitions and subsequent oxidative stress adding to the damaging effects. There are likely other factors involved, such as the development of impaired metal ion homeostasis and depletion of thiol and selenium based metabolites such as cysteine and selenium. Much of the toxicity of mercury occurs at the intracellular level via binding of Hg(2+) to thiol groups in specific proteins. Therefore, amelioration of mercury toxicity by the use of chelation would likely be enhanced by the use of a chelator that could cross the cell membrane and the blood brain barrier. It would be most favorable if this compound was of low toxicity, had appropriate pharmacokinetics, bound and rendered mercury cation non-toxic and had antioxidant properties. Herein we report on such a chelator, N,N'-bis(2-mercaptoethyl)isophthalamide (NBMI), and, using an animal model, show that it prevented the toxic effects associated with acute exposure induced by injected mercury chloride.

Per- and polyfluoroalkyl substances, a group of fluoro-surfactants widely detected in the environment, wildlife and humans, have been linked to adverse health effects. A growing body of literature has addressed their effects on obesity, diabetes and non-alcoholic fatty liver disease/ non-alcoholic steatohepatitis. This review summarizes the brief historical use and chemistry of per- and polyfluoroalkyl substances, routes of human exposure, as well as the epidemiologic evidence for associations between exposure to per- and polyfluoroalkyl substances and the development of obesity, diabetes and non-alcoholic fatty liver disease/ non-alcoholic steatohepatitis. We identified 22 studies on obesity and 32 studies on diabetes, while only 1 study was found for non-alcoholic fatty liver disease/ non-alcoholic steatohepatitis by searching PubMed for human studies. Approximately 2/3 of studies reported positive associations between per- and polyfluoroalkyl substances exposure and the prevalence of obesity and/or type 2 diabetes. Causal links between per- and polyfluoroalkyl substances and obesity, diabetes and non-alcoholic fatty liver disease/ non-alcoholic steatohepatitis, however, require further large-scale prospective cohort studies combined with mechanistic laboratory studies to better assess these associations.