Abstract  A cell line, designated as PHF, has been established from caudal fin of Pangasianodon hypophthalmus. The cell line was developed using explant method and PHF cells have been subcultured for more than 72 passages over a period of 14 months. The cells were able to grow at temperatures between 24 and 32° C, with an optimum temperature of 28° C. The growth rate of PHF cells was directly proportional to FBS concentration, with optimum growth observed at 20% FBS concentration. On the basis of immunophenotyping assay, PHF cells were confirmed to be of epithelial type. Karyotyping of PHF cells revealed diploid number of chromosomes (2n = 60) at 39th and 65th passage, which indicated that the developed cell line is chromosomally stable. The origin of the cell line was confirmed by amplification and sequencing of cytochrome oxidase c subunit I and 16S rRNA genes. The cell line was tested for Mycoplasma contamination and found to be negative. The cells were successfully transfected with GFP reporter gene suggesting that the developed cell line could be utilized for gene expression studies in future. The cell line could be successfully employed for evaluating the cytotoxicity of heavy metals, namely mercuric chloride and sodium arsenite suggesting that PHF cell line can be potential surrogate for whole fish for studying the cytotoxicity of water soluble compounds. The result of virus susceptibility to tilapia lake virus (TiLV) revealed that PHF cells were refractory to TiLV virus. The newly established cell line would be a useful tool for investigating disease outbreaks particularly of viral etiology, transgenic as well as cytotoxicity studies.

Abstract  In the Bengal deltaic region, the shallow groundwater laced with arsenic is used for irrigation frequently and has elevated the soil arsenic in agricultural soil. However, the areas with seasonal flooding reduce arsenic in top layers of the soils. Study shows arsenic accumulation in the deeper soil layers with time in the contaminated agricultural soil (19.40±0.38mg/kg in 0-5cm, 27.17±0.44mg/kg in 5-10cm and 41.24±0.48mg/kg in 10-15cm) in 2013 whereas depletion in 2014 and its buildup in different parts of monsoon rice plant in Nadia, India. Principal Component Analysis and Cluster Analysis were performed, and Enrichment Factor was calculated to identify the sources of arsenic in the soil. Potential Ecological Risk was also calculated to estimate the extent of risk posed by arsenic in soil, along with the potential risk of dietary arsenic exposure. Remarkably, the concentration of arsenic detected in the rice grain showed average value of 1.4mg/kg in 2013 which has increased to 1.6 in 2014, both being above the permissible limit (1mg/kg). These results indicate that monsoon flooding enhances the infiltration of arsenic in the deeper soil layer, which lead to further contamination of shallow groundwater.

Abstract  Information on trace element pollution in the terrestrial environment and its biota is limited compared to the marine environment. In the present study, we collected body feathers and blood of 37 Northern goshawk (Accipiter gentilis) nestlings from Tromsø (northern Norway), Trondheim (central Norway), and Murcia (southeastern Spain) to study regional exposure, hypothesizing the potential health risks of metals and other trace elements. Blood and body feathers were analyzed by a high resolution inductively coupled plasma mass spectrometer (HR-ICP-MS) for aluminum (Al), nickel (Ni), copper (Cu), zinc (Zn), arsenic (As), selenium (Se), cadmium (Cd), mercury (Hg) and lead (Pb). The influence of regional differences, urbanization and agricultural land usage in proximity to the nesting Northern goshawks was investigated using particular spatial analysis techniques. Most trace elements were detected below literature blood toxicity thresholds, except for elevated concentrations (mean ± SD µgml(-1) ww) found for Zn (5.4 ± 1.5), Cd (0.00023 ± 0.0002), and Hg (0.021 ± 0.01). Corresponding mean concentrations in feathers (mean ± SD µgg(-1) dw) were 82.0 ± 12.4, 0.0018 ± 0.002, and 0.26 ± 0.2 for Zn, Cd and Hg respectively. Multiple linear regressions indicated region was a significant factor influencing Al, Zn, Se and Hg feather concentrations. Blood Cd and Hg concentrations were significantly influenced by agricultural land cover. Urbanization did not have a significant impact on trace element concentrations in either blood or feathers. Overall metal and trace element levels do not indicate a high risk for toxic effects in the nestlings. Levels of Cd in Tromsø and Hg in Trondheim were however above sub-lethal toxic threshold levels. For holistic risk assessment purposes it is important that the concentrations found in the nestlings of this study indicate that terrestrial raptors are exposed to various trace elements.

Abstract  This study analyzed the concentrations and distributions of Al, As, Cd, Cr, Cu, Hg, Mn, Ni, Pb and Zn in three different cattail species growing spontaneously in a natural wetland subject to municipal wastewater and metal contamination. The cattail species included Typha domingensis, T. latifolia and T. angustifolia. Results showed that all Typha species have similar element concentrations in roots, rhizomes and leaves, and similar element mobility from sediments to roots and from roots to leaves. This study corroborated three patterns of Typha species growing in metal contaminated environments: high tolerance to toxic conditions, bulk element concentrations in roots, and restricted element translocation from roots to leaves. This study showed that three different Typha species respond similarly to metal inputs under the same polluting field conditions. Given their similar metal content and similar biomass size, our results suggest that T. domingensis, T. latifolia and T. angustifolia may have comparable capacity of phytoremediation. High element uptake and large biomass make Typha species some of the best species for phytoremediation of metal contaminated environments.

Abstract  The aim of the study was to compare the phytoextraction abilities of six tree species (Acer platanoides L., Acer pseudoplatanus L., Betula pendula Roth, Quercus robur L., Tilia cordata Miller, Ulmus laevis Pall.), cultivated on mining sludge contaminated with arsenic (As), cadmium (Cd), copper (Cu), lead (Pb), thallium (Tl), and zinc (Zn). All six tree species were able to survive on such an unpromising substrate. However, A. platanoides and T. cordata seedlings grown on the polluted substrate showed significantly lower biomass than control plants (55.5 and 45.6%, respectively). As, Cd, Cu, Pb, and Tl predominantly accumulated in the roots of all the analyzed tree species with the following highest contents: 1616, 268, 2432, 547, and 856 mg kg(-1), respectively. Zn was predominantly localized in shoots with the highest content of 5801 and 5732 mg kg(-1) for U. laevis and A. platanoides, respectively. A. platanoides was the most effective in Zn phytoextaction, with a bioconcentration factor (BCF) of 8.99 and a translocation factor (TF) of 1.5. Furthermore, with the exception of A. pseudoplatanus, the analyzed tree species showed a BCF > 1 for Tl, with the highest value for A. platanoides (1.41). However, the TF for this metal was lower than 1 in all the analyzed tree species. A. platanoides showed the highest BCF and a low TF and could, therefore, be a promising species for Tl phytostabilization. In the case of the other analyzed tree species, their potential for effective phytoextraction was markedly lower. Further studies on the use of A. platanoides in phytoremediation would be worth conducting.

Abstract  Arsenic (As) contamination in groundwater has become a geo-environmental as well as a toxicological problem across the globe affecting more than 100-million people in nearly 21 countries with its associated disease "arsenicosis." Arsenic poisoning may lead to fatal skin and internal cancers. In present review, an attempt has been made to generate awareness among the readers about various sources of occurrence of arsenic, its geochemistry and speciation, mobilization, metabolism, genotoxicity, and toxicological exposure on humans. The article also emphasizes the possible remedies for combating the problem. The knowledge of these facts may help to work on some workable remedial measure.

Abstract  The quality of groundwater used for human consumption and irrigation in the Hetao Basin of Inner Mongolia, China is affected by elevated salinity as well as high arsenic (As) concentrations. However, the origin of high salinity and its potential impact on As mobility in the Basin remain unclear. This study explores both issues using stable isotopic compositions and Cl/Br ratios of groundwater as well as the major ions of both groundwater and leachable salts in aquifer sediments. Limited variations in δ18O and δ2H (-11.13 to -8.10, -82.23 to -65.67) with the wide range of Total Dissolved Solid (TDS, 351-6734mg/L) suggest less contribution of direct evaporation to major salinity in groundwater. Deuterium excess shows that non-direct evaporation (capillary evaporation, transpiration) and mineral/evaporite dissolution contribute to >60% salinity in groundwater with TDS>1000mg/L. Non-direct evaporation, like capillary evaporation and transpiration, is proposed as important processes contributing to groundwater salinity based on Cl/Br ratio and halite dissolution line. The chemical weathering of Ca, Mg minerals and evaporites (Na2SO4and CaSO4) input salts into groundwater as well. This is evidenced by the fact that lacustrine environment and the arid climate prevails in Pleistocene period. Dissolution of sulfate salts not only promotes groundwater salinity but affects As mobilization. Due to the dissolution of sulfate salts and non-direct evaporation, groundwater SO42-prevails and its reduction may enhance As enrichment. The higher As concentrations (300-553μg/L) are found at the stronger SO42-reduction stage, indicating that reduction of Fe oxide minerals possibly results from HS-produced by SO42-reduction. This would have a profound impact on As mobilization since sulfate is abundant in groundwater and sediments. The evolution of groundwater As and salinity in the future should be further studied in order to ensure sustainable utilization of water resource in this water scarce area.

Abstract  Soil pollution by metal(loid)s resulting from rapid economic development is a major concern. Accurately estimating the spatial distribution of soil metal(loid) pollution has great significance in preventing and controlling soil pollution. In this study, 126 topsoil samples were collected in Kunshan City and the geo-accumulation index was selected as a pollution index. We used Kriging interpolation and BP neural network methods to estimate the spatial distribution of arsenic (As) and cadmium (Cd) pollution in the study area. Additionally, we introduced a cross-validation method to measure the errors of the estimation results by the two interpolation methods and discussed the accuracy of the information contained in the estimation results. The conclusions are as follows: data distribution characteristics, spatial variability, and mean square errors (MSE) of the different methods showed large differences. Estimation results from BP neural network models have a higher accuracy, the MSE of As and Cd are 0.0661 and 0.1743, respectively. However, the interpolation results show significant skewed distribution, and spatial autocorrelation is strong. Using Kriging interpolation, the MSE of As and Cd are 0.0804 and 0.2983, respectively. The estimation results have poorer accuracy. Combining the two methods can improve the accuracy of the Kriging interpolation and more comprehensively represent the spatial distribution characteristics of metal(loid)s in regional soil. The study may provide a scientific basis and technical support for the regulation of soil metal(loid) pollution.

Abstract  To assess the importance of variation among arugula (Eruca vesicaria subsp. sativa) cultivars in the ability to accumulate arsenic (As) in above-ground tissues, uptake of As by 16 cultivars was measured in the field and in hydroponic culture. In the field trial on soil contaminated by past pesticide use, As soil-plant uptake coefficients varied by a factor of 2.7 among different cultivars, approaching a value of one for the strongest accumulators. Compared to the field assay, hydroponically grown arugula accumulated much lower concentrations of As when nutrient solutions contained standard (high) concentrations of phosphate along with 1.0 mg L-1As in the form of soluble arsenate. However, As accumulation was much greater in hydroponic culture using low-P nutrient solutions, an indication that phosphate strongly competed with arsenate for root uptake. Analysis of arugula roots after exposure to arsenate at 1.0 mg As L-1and low phosphate revealed from 24 to 400 times greater As concentration in roots than tops, with S concentrations significantly greater in As-exposed than control roots. This indicated greater sulfate uptake by roots exposed to arsenate, and suggested that thiol-mediated As immobilization occurred in the roots which strongly restricted translocation to the tops.

Abstract  Despite the antitumor effects of asrsenic trioxide (As2O3), tetraarsenic hexoxide (As4O6 or PR) and tetraarsenic tetrasulfide (As4S4) in several cancers, their adverse poisoning, toxicity and resistance are still hot issues for effective cancer therapy. Here, antitumor mechanism of arsenic herbal mixture PROS including PR and OS (Oldenlandia diffusa and Salvia miltiorrhiza extract) was elucidated in non-small cell lung cancer cells (NSCLCs), since PR alone showed resistant cytotoxicity in NSCLCs compared to other cancers. PROS exerted significant cytotoxicity, induced sub-G1 phase and S phase arrest, increased apoptotic bodies, and attenuated the expression of pro-PARP, Bcl-2, Cyclin E, Cyclin A, CDK2, E2F1, p-Src, p-STAT3, p-ERK, p-AKT, COX-2 and SOCS-1 in A549 and H460 cells along with disrupted binding of STAT3 with CDK2 or VEGF. Notably, PROS inhibited VEGF induced proliferation, migration and tube formation in HUVECs and suppressed angiogenesis in chorioallantoic membrane (CAM) assay via reduced phosphorylation of VEGFR2, Src and STAT3. Consistently, PROS reduced the growth of H460 cells implanted in BALB/c athymic nude mice via inhibition of STAT3, and VEGF and activation of caspase 3. Overall, these findings suggest that PROS exerts antiangiogenic and apoptotic effects via inhibition of STAT3/ VEGF/ CDK2 axis signaling as a potent anticancer agent for lung cancer treatment.

Abstract  A new porous indium metal organic framework namely (AUBM-1) was successfully synthesized via a solvothermal reaction of pyromellitic acid and indium chloride. Single crystal X-ray analysis revealed the formation of a 3D framework with a pts topology. The resulting MOF structure showed high chemical stability at different pH values. Thus, the activated indium MOF was applied for As removal from water for the first time and showed a high arsenate uptake capacity of 103.1 mg g-1at neutral pH, which is higher than the commercial adsorbents (usually less than 100 mg g-1at neutral pH). Finally, the kinetics and thermodynamic studies revealed that the As adsorption was an endothermic process and followed a pseudo-second-order kinetic model.

Abstract  Arsenic (As) is ubiquitous in the earth's crust, with typical dietary intake in developed countries <1 μg/kg bw/d, and atypical groundwater exposures in developing countries approaching 50 μg/kg bw/d. Arsenic exposures are linked with human diseases and doses of toxicological concern are similar to typical dietary intake estimates. The methylation of arsenite by arsenite-3-methyltransferase (As3MT) promotes the clearance of arsenic as pentavalent species, but also generates reactive trivalent intermediates. This study measured inorganic arsenic and its metabolites in pentavalent and trivalent states in blood, tissues, and excreta after oral administration of arsenite (50-200 μg/kg bw). While liver was a major site for clearance of arsenite and formation of methylated species, it also had extensive binding of trivalent intermediates; however, thiol exchange and oxidation reactions of trivalent arsenic were facile since dimethylarsinic acid (DMAV) was the predominant species in blood and urine. Consistent evidence was observed for a non-linear relationship between doses above 50 μg/kg bw and levels of bound trivalent As metabolites. The abundance of protein-bound trivalent arsenic within target tissues should correlate with disruption of critical cellular processes, which rely on defined interactions of thiol functional groups, and could provide dose-response relationships from animal models for human risk assessment.

Abstract  Arsenic (As) is a naturally toxin which exists ubiquitously in foods and various environment media, incurring diverse toxicities and health problems. Previous studies have shown that oxidative stress, genotoxic damage and pro-apoptotic pathways are ascribed to As-associated detrimental effects. Meanwhile, epigenetic regulations (such as miRNAs and histone modifications) were also reported to contribute to As-induced adverse effects. Nonetheless, whether long non-coding RNAs (LncRNAs) are indispensable for the regulation of As-induced biological outcomes are nearly unknown. In this study, we identified that a lncRNA UCA1 was markedly induced by As treatment in human hepatocytes. Functional assessments revealed that UCA1 played a critical role in protecting hepatocytes from As-induced autophagy inhibition. Furthermore, through RNA-seq assay, oxidative stress induced growth inhibitor 1 (OSGIN1) was uncovered to be the most responsive target downstream of UCA1, and miR-184 acted as an intermediate for the regulation of UCA1 on the level of OSGIN1 through a competing endogenous RNAs (ceRNAs) mechanism. Further mechanistic investigations demonstrated that UCA1/OSGIN1 signaling contributed to As-induced autophagic flux blockage through activating mTOR/p70S6 K cascade, resulting in compromised cell death. Collectively, our study deciphered a lncRNA-dictated molecular mechanism responsible for As toxicity: UCA1 leads a protective role against As-induced cell death through blocking autophagic flux.

Abstract  Intercropping of arsenic (As) hyperaccumulator and cash crops during remediation of contaminated soil has been applied in farmland remediation project. However, little is known about the fate of As fractions in the soil profile and As uptake within the intercropping plants under field condition. In this study, As removal, uptake, and translocation were investigated within an intercropping system of Pteris vittata L. (P. vittata) and maize (Zea mays). Results indicated that the concentration of As associated with amorphous Fe (hydr)oxides in the 10-20 cm soil layer was significantly lower under malposed intercropping of P. vittata and maize, and As accumulation in P. vittata and biomass of P. vittata were simultaneously higher under malposed intercropping than under coordinate intercropping, leading to a 2.4 times higher rate of As removal. Although maize roots absorbed over 13.4 mg kg-1As and maize leaves and flowers accumulated over 21.5 mg kg-1As (translocation factor higher than 1), grains produced in all intercropping modes accumulated lower levels of As, satisfying the standard for human consumption. Our results suggested that malposed intercropping of a hyperaccumulator and a low-accumulation cash crop was an ideal planting pattern for As remediation in soil. Furthermore, timely harvest of P. vittata, agronomic strategies during remediation, and appropriate management of the above ground parts of P. vittata and high-As tissues of cash crops may further improve remediation efficiency.

Abstract  Nanocrystalline iowaite, a Mg/Fe-based layered double hydroxide (LDH) intercalated with chloride, was synthesized to evaluate its performance for arsenic removal from water and to investigate the contributing dearsenication mechanisms. It is characterized by fast arsenic sorption rates and has a much higher arsenic uptake capacity than other LDHs that are commonly used for water dearsenication. The surface adsorption of the solution arsenic onto the iowaite samples and the anion exchange of the arsenic in solution with chloride, which is originally in the iowaite interlayers, are the primary mechanisms for the uptake of arsenic by iowaite. In addition to the Coulombic attraction between arsenate/arsenite and positively charged layers of iowaite, the inner-sphere complexation of arsenic with Fe (instead of Mg) in the iowaite layers is responsible for the formation of more stable and stronger arsenic bonds, as indicated by both XPS and EXAFS analyses. Specifically, bidentate-binuclear and monodentate-mononuclear As-Fe complexes were detected in the arsenate removal experiments, whereas bidentate-mononuclear, bidentate-binuclear, and monodentate-mononuclear As-Fe complexes were present for the arsenite-treated iowaite samples. This study shows that nanocrystalline iowaite is a promising, low-cost material for arsenic removal from natural arsenic-rich waters or contaminated high-arsenic waters.

Abstract  Abandoned mine sites continue to present serious environmental hazards because the heavy metals associated with extractive waste are continuously released into the environment, where they threaten human life and the environment. Remediating and securing extractive waste are complex, lengthy and costly processes. Thus, in most European countries, a site is considered for intervention when it poses a risk to human health and the surrounding environment. As a consequence, risk analysis presents a viable decisional approach towards the management of extractive waste. To evaluate the effects posed by extractive waste to human health and groundwater, a risk analysis approach was used for an abandoned nickel extraction site in Campello Monti in North Italy. This site is located in the Southern Italian Alps. The area consists of large and voluminous mafic rocks intruded by mantle peridotite. The mining activities in this area have generated extractive waste. A risk analysis of the site was performed using Risk Based Corrective Action (RBCA) guidelines, considering the properties of extractive waste and water for the properties of environmental matrices. The results showed the presence of carcinogenic risk due to arsenic and risks to groundwater due to nickel. The results of the risk analysis form a basic understanding of the current situation at the site, which is affected by extractive waste.

Abstract  The constant interplay between environment (including both exogenous and endogenous factors) and epigenome (defined as the combination of chromatin, its covalent modifications and noncoding RNAs) triggers epigenetic events that, by modulating gene expression, capture information about changes in the environment. In this mini review, we will focus on the neurodevelopmental implications of exposure to adverse prenatal milieu with emphasis on mechanistic and functional aspects. Several neurotoxic insults have been shown to affect epigenetics with negative consequences on the development of the nervous system; among them are methylmercury, lead, arsenic and cadmium, as well as excess of glucocorticoids. Further investigations on the individual susceptibility to epigenetic changes are needed to propose and validate such modifications as possible biomarkers for early identification of neurological/neurodevelopmental disorders and for predicting/monitoring response to treatment.

Abstract  The occurrence of a large number of diverse arsenic species in the environment and in biological systems makes it important to compare their relative toxicity. The toxicity of arsenic species has been examined in various cell lines using different assays, making comparison difficult. We report real-time cell sensing of two human cell lines to examine the cytotoxicity of fourteen arsenic species: arsenite (AsIII), monomethylarsonous acid (MMAIII) originating from the oxide and iodide forms, dimethylarsinous acid (DMAIII), dimethylarsinic glutathione (DMAGIII), phenylarsine oxide (PAOIII), arsenate (AsV), monomethylarsonic acid (MMAV), dimethylarsinic acid (DMAV), monomethyltrithioarsonate (MMTTAV), dimethylmonothioarsinate (DMMTAV), dimethyldithioarsinate (DMDTAV), 3-nitro-4-hydroxyphenylarsonic acid (Roxarsone, Rox), and 4-aminobenzenearsenic acid (p-arsanilic acid, p-ASA). Cellular responses were measured in real time for 72hr in human lung (A549) and bladder (T24) cells. IC50values for the arsenicals were determined continuously over the exposure time, giving rise to IC50histograms and unique cell response profiles. Arsenic accumulation and speciation were analyzed using inductively coupled plasma-mass spectrometry (ICP-MS). On the basis of the 24-hr IC50values, the relative cytotoxicity of the tested arsenicals was in the following decreasing order: PAOIII≫MMAIII≥DMAIII≥DMAGIII≈DMMTAV≥AsIII≫MMTTAV>AsV>DMDTAV>DMAV>MMAV≥Rox≥p-ASA. Stepwise shapes of cell response profiles for DMAIII, DMAGIII, and DMMTAVcoincided with the conversion of these arsenicals to the less toxic pentavalent DMAV. Dynamic monitoring of real-time cellular responses to fourteen arsenicals provided useful information for comparison of their relative cytotoxicity.

Abstract  Mineral content of complete pet food is regulated to ensure health of the companion animal population. Analysis of adherence to these regulatory guidelines has not been conducted. Here, mineral composition of complete wet (n = 97) and dry (n = 80) canine and feline pet food sold in the UK was measured to assess compliance with EU guidelines. A majority of foods complied with ≥8 of 11 guidelines (99% and 83% for dry and wet food, respectively), but many failed to provide nutritional minimum (e.g. Cu, 20% of wet food) or exceeded nutritional maximum (e.g. Se, 76% of wet food). Only 6% (6/97) of wet and 38% (30/80) of dry food were fully compliant. Some foods (20-30% of all analysed) had mineral imbalance, such as not having the recommended ratio of Ca:P (between 1:1 to 2:1). Foods with high fish content had high levels of undesirable metal elements such as arsenic. This study highlights broad non-compliance of a range of popular pet foods sold in the UK with EU guidelines (94% and 61% of wet and dry foods, respectively). If fed exclusively and over an extended period, a number of these pet foods could impact the general health of companion animals.

Abstract  BACKGROUND AND PURPOSE: The purpose of this case-cohort study was to examine urinary arsenic levels in relation to incident ischemic stroke in the United States.

METHODS: We performed a case-cohort study nested within the REGARDS (REasons for Geographic and Racial Differences in Stroke) cohort. A subcohort (n=2486) of controls was randomly sampled within region-race-sex strata while all incident ischemic stroke cases from the full REGARDS cohort (n=671) were included. Baseline urinary arsenic was measured by inductively coupled plasma-mass spectrometry. Arsenic species, including urinary inorganic arsenic and its metabolites monomethylarsonic acid and dimethylarsinic acid, were measured in a random subset (n=199). Weighted Cox's proportional hazards models were used to calculate hazard ratios and 95% confidence intervals of ischemic stroke by arsenic and its species.

RESULTS: The average follow-up was 6.7 years. Although incident ischemic stroke showed no association with total arsenic or total inorganic arsenic, for each unit higher level of urinary monomethylarsonic acid on a log-scale, after adjustment for potential confounders, ischemic stroke risk increased ≈2-fold (hazard ratio=1.98; 95% confidence interval: 1.12-3.50). Effect modification by age, race, sex, or geographic region was not evident.

CONCLUSIONS: A metabolite of arsenic was positively associated with incident ischemic stroke in this case-cohort study of the US general population, a low-to-moderate exposure area. Overall, these findings suggest a potential role for arsenic methylation in the pathogenesis of stroke, having important implications for future cerebrovascular research.

Abstract  InEscherichia coli, the transcription of genes related to metal homeostasis is activated by the presence of target metals. The promoter regions of those genes can be fused with reporter genes to generate whole-cell bioreporters (WCBs); these organisms sense the presence of target metals through reporter gene expression. However, the limited number of available promoters for sensing domains restricts the number of WCB targets. In this study, we have demonstrated an alternative method to generate novel WCBs, based on the notion that since the sensing mechanisms of WCBs are related to metal transportation systems, their properties can be modulated by disrupting metal homeostasis. MutantE. colistrains were generated by deleting theznt-operon geneszntA, which encodes a zinc-export protein, andzntR, which encodes aznt-operon regulatory protein, to investigate the effects on the metal-sensing properties of WCBs. Deletion ofzntAincreased the sensitivity but abolished the selectivity of cadmium-sensing WCBs, whereas arsenic-sensing WCBs gained sensitivity toward cadmium. WhenzntRwas deleted, cadmium-sensing WCBs lost the ability to detect cadmium, and this was recovered by introducing exogenouszntR. In addition, the metal-binding site of ZntR was genetically engineered to modulate metal selectivity. This study provides a valuable platform for the development of novelE. coli-based WCBs.

Abstract  BACKGROUND: Although bariatric procedures are commonly performed in clinical practice, long-term data on the comparative effectiveness and safety of different procedures on sustained weight loss, comorbidities, and adverse effects are limited, especially in important patient subgroups (eg, individuals with diabetes, older patients, adolescents, and minority patients).

OBJECTIVE: The objective of this study was to create a population-based cohort of patients who underwent 3 commonly performed bariatric procedures-adjustable gastric band (AGB), Roux-en-Y gastric bypass (RYGB), and sleeve gastrectomy (SG)-to examine the long-term comparative effectiveness and safety of these procedures in both adults and adolescents.

METHODS: We identified adults (20 to 79 years old) and adolescents (12 to 19 years old) who underwent a primary (first observed) AGB, RYGB, or SG procedure between January 1, 2005 and September 30, 2015 from 42 health systems participating in the Clinical Data Research Networks within the National Patient-Centered Clinical Research Network (PCORnet). We extracted information on patient demographics, encounters with healthcare providers, diagnoses recorded and procedures performed during these encounters, vital signs, and laboratory test results from patients' electronic health records (EHRs). The outcomes of interest included weight change, incidence of major surgery-related adverse events, and diabetes remission and relapse, collected for up to 10 years after the initial bariatric procedure.

RESULTS: A total of 65,093 adults and 777 adolescents met the eligibility criteria of the study. The adult subcohort had a mean age of 45 years and was predominantly female (79.30%, 51,619/65,093). Among adult patients with non-missing race or ethnicity information, 72.08% (41,248/57,227) were White, 21.13% (12,094/57,227) were Black, and 20.58% (13,094/63,637) were Hispanic. The average highest body mass index (BMI) recorded in the year prior to surgery was 49 kg/m2. RYGB was the most common bariatric procedure among adults (49.48%, 32,208/65,093), followed by SG (45.62%, 29,693/65,093) and AGB (4.90%, 3192/65,093). The mean age of the adolescent subcohort was 17 years and 77.5% (602/777) were female. Among adolescent patients with known race or ethnicity information, 67.3% (473/703) were White, 22.6% (159/703) were Black, and 18.0% (124/689) were Hispanic. The average highest recorded BMI in the year preceding surgery was 53 kg/m2. The majority of the adolescent patients received SG (60.4%, 469/777), followed by RYGB (30.8%, 239/777) and AGB (8.9%, 69/777). A BMI measurement (proxy for follow-up) was available in 84.31% (44,978/53,351), 68.09% (20,783/30,521), and 68.56% (7159/10,442) of the eligible adult patients at 1, 3, and 5 years of follow-up, respectively. The corresponding proportion was 82.0% (524/639), 49.9% (174/349), and 38.8% (47/121) in the adolescent subcohort.

CONCLUSIONS: Our study cohort is one of the largest cohorts of patients with bariatric procedures in the United States. Patients are geographically and demographically diverse, which improves the generalizability of the research findings and allows examination of treatment effect heterogeneity. Ongoing and planned investigations will provide real-world evidence on the long-term benefits and risks of these most commonly used bariatric procedures in current clinical practice.

Abstract  The presence of arsenic in groundwater has become a global concern due to the health risks from drinking water with elevated concentrations. The Water Framework Directive (WFD) of the European Union calls for drinking water risk assessment for member states. The present study amalgamates readily available national and sub-national scale datasets on arsenic in groundwater in the Republic of Ireland. However, due to the presence of high levels of left censoring (i.e. arsenic values below an analytical detection limit) and changes in detection limits over time, the application of conventional statistical methods would inhibit the generation of meaningful results. In order to handle these issues several arsenic databases were integrated and the data modelled using statistical methods appropriate for non-detect data. In addition, geostatistical methods were used to assess principal risk components of elevated arsenic related to lithology, aquifer type and groundwater vulnerability. Geographic statistical methods were used to overcome some of the geographical limitations of the Irish Environmental Protection Agency (EPA) sample database. Nearest-neighbour inverse distance weighting (IDW) and local indicator of spatial association (LISA) methods were used to estimate risk in non-sampled areas. Significant differences were also noted between different aquifer lithologies, indicating that Rhyolite, Sandstone and Shale (Greywackes), and Impure Limestone potentially presented a greater risk of elevated arsenic in groundwaters. Significant differences also occurred among aquifer types with poorly productive aquifers, locally important fractured bedrock aquifers and regionally important fissured bedrock aquifers presenting the highest potential risk of elevated arsenic. No significant differences were detected among different groundwater vulnerability groups as defined by the Geological Survey of Ireland. This research will assist management and future policy directions of groundwater resources at EU level and guide future research focused on understanding arsenic mobilisation processes to facilitate in guiding future development, testing and treatment requirements of groundwater resources.

Abstract  Arsenic promotes hippocampal neuronal damage inducing cognitive impairments. However, mechanism arbitrating arsenic-mediated cognitive deficits remains less-known. Here, we identified that chronic exposure to environmentally relevant doses of arsenic increased apoptosis, characterized by caspase-3 activation, poly(ADP-ribose) polymerase cleavage and Terminal deoxynucleotidyl transferase dUTP nick-end labeling of rat hippocampal neurons, marked by NeuN. Investigating apoptotic mechanism through invivo and invitro studies revealed that arsenic promoted bone morphogenetic protein-2 (BMP2) expression, supported by increased BMP-receptor2 (BMPR2) and p-Smad1/5 in hippocampal neurons. BMP2-silencing and treatment with BMP antagonist, noggin, attenuated the arsenic-induced apoptosis and loss in hippocampal neurons. We then investigated whether BMP2/Smad signaling stimulated neuronal apoptosis independently or required other intermediate pathways. We hypothesized participation of brain-derived neurotrophic factor (BDNF) that promotes neuronal survival. We identified an arsenic-mediated attenuation of BDNF-dependent TrkB signaling, and observed that co-treatment with recombinant-BDNF reinstated BDNF/TrkB and reduced neuronal apoptosis. To probe whether BMP2/Smad and BDNF/TrkB pathways could be linked, we co-treated arsenic with noggin or recombinant BDNF. We detected a noggin-mediated restored BDNF/TrkB, while recombinant-BDNF failed to affect BMP2/Smad signaling. In addition, we found that TrkB-inhibitor, K252a, nullified noggin-induced protection, proving the necessity of a downstream reduced BDNF/TrKB signaling for BMP2/Smad-mediated apoptosis in arsenic-treated neurons. We further related our observations with cognitive performances, and detected noggin-mediated restoration of transfer latency time and learning-memory ability for passive avoidance and Y-Maze tests respectively in arsenic-treated rats. Overall, our study proves that arsenic promotes hippocampal neuronal apoptosis through an up-regulated BMP2/Smad-dependent attenuation of BDNF/TrkB pathway, inducing cognitive deficits.