Development of a sulfidogenic bioreactor system for removal of co-existent selenium, iron and nitrate from drinking water sources.

The present study showed for the first time that selenium, iron, and nitrate could be simultaneously removed in a sulfidogenic bioreactor to meet drinking water standards. A bioreactor inoculated with mixed bacterial consortium was operated for around 330 days in anoxic environment at 30 °C under varying combination of influent selenate (200-1000 µg/L as selenium), and iron (3-10 mg/L) in presence of 50 mg/L of nitrate. Required amount of acetic acid (as carbon source) and sulfate were supplied and the reactor was operated at different empty bed contact time (EBCT) of 45-120 min. Along with complete removal of nitrate, the reactor removed both selenium and iron to meet the drinking water standards. Field emission transmission electron microscopy (FETEM) and X-ray diffraction (XRD) analyses confirmed the formation of selenium sulfide (SeS), achavalite (FeSe) and pyrite (FeS2), which were the possible removal mechanisms of selenium and iron. Thus, this study exhibited that selenium, iron, and nitrate can be simultaneously removed to meet the drinking water standards in a sulfidogenic bioreactor.

Bacterially-assisted recovery of cadmium and nickel as their metal sulfide nanoparticles from spent Ni-Cd battery via hydrometallurgical route.

Soaring demand for technology metals (e.g., Cd, Ni) and its ever-depleting primary resources ask for alternative recovery from secondary sources. Ni-Cd battery is one such source that can abridge the gap between demand and supply of such metals. Biogenic recovery, being environmentally benign, is explored for Cd and Ni recovery to manage the menace of spent Ni-Cd battery. Studies with 20, 40 and 60 mg/L Cd2+ initial concentrations in batch mode (in triplicates) at pH 7.0 ± 0.2, 30 ± 0.5 °C and 120 rpm were conducted using sulfate-reducing bacteria for 10 days. Analysis of extracellular polymeric substance revealed that protein secretion was enhanced, thereby forming Cd-EPS binding. Biosolids were collected and freeze-dried for morphological analysis viz. FESEM/EDX, PXRD and TEM, which revealed the formation of CdS nanoparticles (JCPDS card #00-042-1411) in range of 2-6 nm. Similarly, combined effect with 5, 10 and 20 mg/L Ni2+ at 20 mg/L Cd2+ were also investigated. Furthermore, to test the efficacy for real field application, spent Ni-Cd battery was dismantled and its powder was characterized, digested with concentrated HCl at 70 °C and was fed in batch mode after cooling, wherein nanoparticles of Ni and Cd sulfides were formed that has potential as semi-conducting material.

Dynamic regulatory network controlling TH17 cell differentiation.

Despite their importance, the molecular circuits that control the differentiation of naive T cells remain largely unknown. Recent studies that reconstructed regulatory networks in mammalian cells have focused on short-term responses and relied on perturbation-based approaches that cannot be readily applied to primary T cells. Here we combine transcriptional profiling at high temporal resolution, novel computational algorithms, and innovative nanowire-based perturbation tools to systematically derive and experimentally validate a model of the dynamic regulatory network that controls the differentiation of mouse TH17 cells, a proinflammatory T-cell subset that has been implicated in the pathogenesis of multiple autoimmune diseases. The TH17 transcriptional network consists of two self-reinforcing, but mutually antagonistic, modules, with 12 novel regulators, the coupled action of which may be essential for maintaining the balance between TH17 and other CD4(+) T-cell subsets. Our study identifies and validates 39 regulatory factors, embeds them within a comprehensive temporal network and reveals its organizational principles; it also highlights novel drug targets for controlling TH17 cell differentiation.

Concurrent removal of nitrate, arsenic and iron from simulated and real-life groundwater to meet drinking water standards: Effects of operational and environmental parameters.

The aim of this work was to study concurrent removal of nitrate, arsenic and iron in an attached growth reactor (AGR) based on bio-sulphidogenesis treating simulated and real-life ground water. A lab-scale bioreactor system was monitored for a period of 511 days under conditions identical to those prevailing at full-scale to assess the relative influence of empty bed contact time (EBCT) (20-90 min), backwash strategies (water-nitrogen and water-air), temperature (20-50 °C), pH (6.6-8.4) and shut down on reactor performance and recovery. Complete removal of nitrate (50 mg/L) and over 95% removal of iron (3 mg/L) occurred. Arsenic removal efficiency was around 99% (500 µg/L) and treated water arsenic concentration was in compliance with the World Health Organization and Indian Standard of 10 µg/L. Port sampling along the depth of bioreactor shows shifting of terminal electron accepting process zones at lower EBCT of 20 min and after air assisted backwashing. The temperature range of 20-50 °C and pH range of 6.6-8.4 were applicable for arsenic removal in natural conditions. Precipitated biosolids were analysed using electron microscopy. Biogenic sulphides resulted in the precipitation of arsenosulphides and iron sulphides, which concurrently removed arsenic and iron. This study suggests that a sulphidogenic bioreactor may help to set the basis for concurrent removal of nitrate, arsenic and iron from real-life groundwater using mixed biofilm bacterial community.

Transcription factor Oct1 is a somatic and cancer stem cell determinant.

Defining master transcription factors governing somatic and cancer stem cell identity is an important goal. Here we show that the Oct4 paralog Oct1, a transcription factor implicated in stress responses, metabolic control, and poised transcription states, regulates normal and pathologic stem cell function. Oct1(HI) cells in the colon and small intestine co-express known stem cell markers. In primary malignant tissue, high Oct1 protein but not mRNA levels strongly correlate with the frequency of CD24(LO)CD44(HI) cancer-initiating cells. Reducing Oct1 expression via RNAi reduces the proportion of ALDH(HI) and dye efflux(HI) cells, and increasing Oct1 increases the proportion of ALDH(HI) cells. Normal ALDH(HI) cells harbor elevated Oct1 protein but not mRNA levels. Functionally, we show that Oct1 promotes tumor engraftment frequency and promotes hematopoietic stem cell engraftment potential in competitive and serial transplants. In addition to previously described Oct1 transcriptional targets, we identify four Oct1 targets associated with the stem cell phenotype. Cumulatively, the data indicate that Oct1 regulates normal and cancer stem cell function.

Constitutive nuclear localization of NFAT in Foxp3+ regulatory T cells independent of calcineurin activity.

Foxp3 plays an essential role in conferring suppressive functionality to CD4(+)/Foxp3(+) regulatory T cells (Tregs). Although studies showed that Foxp3 has to form cooperative complexes with NFAT to bind to target genes, it remains unclear whether NFAT is available in the nucleus of primary Tregs for Foxp3 access. It is generally believed that NFAT in resting cells resides in the cytoplasm, and its nuclear translocation depends on calcineurin (CN) activation. We report that a fraction of NFAT protein constitutively localizes in the nucleus of primary Tregs, where it selectively binds to Foxp3 target genes. Treating Tregs with CN inhibitor does not induce export of NFAT from the nucleus, indicating that its nuclear translocation is independent of CN activity. Consistently, Tregs are resistant to CN inhibitors in the presence of IL-2 and continue to proliferate in response to anti-CD3 stimulation, whereas proliferation of non-Tregs is abrogated by CN inhibitors. In addition, PMA, which activates other transcription factors required for T cell activation but not NFAT, selectively induces Treg proliferation in the absence of ionomycin. TCR interaction with self-MHC class II is not required for PMA-induced Treg proliferation. Tregs expanded by PMA or in the presence of CN inhibitors maintain Treg phenotype and functionality. These findings shed light on Treg biology, paving the way for strategies to selectively activate Tregs.

Z-DNA-forming silencer in the first exon regulates human ADAM-12 gene expression.

Upregulation of ADAM-12, a novel member of the multifunctional ADAM family of proteins is linked to cancer, arthritis and cardiac hypertrophy. Basal expression of ADAM-12 is very low in adult tissues but rises markedly in response to certain physiological cues, such as during pregnancy in the placenta, during development in neonatal skeletal muscle and bone and in regenerating muscle. Studies on ADAM-12 regulation have identified a highly conserved negative regulatory element (NRE) at the 5'-UTR of human ADAM-12 gene, which acts as a transcriptional repressor. The NRE contains a stretch of dinucleotide-repeat sequence that is able to adopt a Z-DNA conformation both in vitro and in vivo and interacts with hZα(ADAR1), a bona fide Z-DNA-binding protein. Substitution of the dinucleotide-repeat-element with a non-Z-DNA-forming sequence inhibited NRE function. We have detected a NRE DNA-binding protein activity in several tissues where ADAM-12 expression is low while no such activity was seen in the placenta where ADAM-12 expression is high. These observations suggest that interaction of these proteins with ADAM-12 NRE is critical for transcriptional repression of ADAM-12. We also show that the Z-DNA forming transcriptional repressor element, by interacting with these putative Z-DNA-binding proteins, is involved in the maintenance of constitutive low-level expression of human ADAM-12. Together these results provide a foundation for therapeutic down-regulation of ADAM-12 in cancer, arthritis and cardiac hypertrophy.

Stem cells, stress, metabolism and cancer: a drama in two Octs.

It is a classic story of two related transcription factors. Oct4 is a potent regulator of pluripotency during early mammalian embryonic development, and is notable for its ability to convert adult somatic cells to pluripotency. The widely expressed Oct1 protein shares significant homology with Oct4, binds to the same sequences, regulates common target genes, and shares common modes of upstream regulation, including the ability to respond to cellular stress. Both proteins are also associated with malignancy, yet Oct1 cannot substitute for Oct4 in the generation of pluripotency. The molecular underpinnings of these phenomena are emerging, as are the consequences for adult stem cells and cancer, and thereby hangs a tale.

Phytochemical profiling and nephroprotective potential of ethanolic leaf extract of Polyalthia longifolia against cisplatin-induced oxidative stress in rat model.

ETHNOPHARMACOLOGICAL RELEVANCE: Kidney problems are becoming more common globally and are considered a major health issue in the modern world with high mortality rate. Polyalthia longifolia (Sonn.) Thwaites is a tropical ethnomedicinal plant used to treat various diseases like diabetes, hypertension and urinary disorders and possess antioxidant and anti-inflammatory properties. AIM OF THE STUDY: This study aimed to investigate the phytochemical composition of 70% ethanolic leaf extract of Polyalthia longifolia (Sonn.) Thwaites (PL) and evaluates its nephroprotective effects against cisplatin-induced nephrotoxicity in Wistar rats. MATERIALS AND METHODS: The leaves of PL were extracted with 70% ethanol and performed the phytochemical profiling using Liquid Chromatography-Mass Spectrometry (LC-MS). The nephroprotective effect of PL leaf extract was evaluated at three doses (150, 300 and 600 mg/kg, p.o.) for 14 days against cisplatin toxicity (16 mg/kg, i.p., once) in male Wistar rats. Body and kidney weight indices, kidney function markers and lipid profile markers in serum, and oxidative stress markers in kidney tissue were performed along with the histopathological analysis of kidney. RESULTS: The LC-MS chromatograph confirmed the presence of various phytocompounds include N-Methylhernagine (aporphine alkaloid), 4-Acetamidobutanoic acid (gamma amino acid) and choline, etc. in the PL leaf extract. Exposure of cisplatin (16 mg/kg, i.p., once only) to the animals significantly elevated the levels of kidney functional markers (i.e. serum urea, uric acid, creatinine) and the lipid markers (triglyceride and total cholesterol) in blood circulation with depletion of serum albumin which were reversed by the therapy of PL leaf extract (150, 300 and 600 mg/kg) in dose-dependent manner. The altered level of body and kidney weight in cisplatin treated group was also restored by the therapy. PL leaf extract effectively improved the antioxidant defense system of kidney at all doses by restoring the levels of tissue glutathione, superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase with the dose-dependent reduction of lipid peroxidation against cisplatin-induced renal oxidative stress. The histopathological observations also showed the significant recovery in cellular morphology after PL treatment when compared to the cisplatin toxicity group. The highest dose 600 mg/kg of PL leaf extract showed more pronounced renal recovery (p < 0.001) followed by other two doses, which was similar to the silymarin treatment group (a reference drug) against nephrotoxicity. CONCLUSION: The results of this study revealed the nephroprotective effects of PL leaves against cisplatin-induced nephrotoxicity by reversing the level of biochemical markers and mitigating oxidative stress as well as improving the architecture of renal tissues. This renal protection by PL might be due to the synergistic effect of its phytoconstituents and antioxidant efficacy.

Cereblon-based Bifunctional Degrader of SOS1, BTX-6654, Targets Multiple KRAS Mutations and Inhibits Tumor Growth.

Mutations within the oncogene KRAS drive an estimated 25% of all cancers. Only allele-specific KRAS G12C inhibitors are currently available and are associated with the emergence of acquired resistance, partly due to upstream pathway reactivation. Given its upstream role in the activation of KRAS, son of sevenless homolog 1 (SOS1), has emerged as an attractive therapeutic target. Agents that target SOS1 for degradation could represent a potential pan-KRAS modality that may be capable of circumventing certain acquired resistance mechanisms. Here, we report the development of two SOS1 cereblon-based bifunctional degraders, BTX-6654 and BTX-7312, cereblon-based bifunctional SOS1 degraders. Both compounds exhibited potent target-dependent and -specific SOS1 degradation. BTX-6654 and BTX-7312 reduced downstream signaling markers, pERK and pS6, and displayed antiproliferative activity in cells harboring various KRAS mutations. In two KRAS G12C xenograft models, BTX-6654 degraded SOS1 in a dose-dependent manner correlating with tumor growth inhibition, additionally exhibiting synergy with KRAS and MEK inhibitors. Altogether, BTX-6654 provided preclinical proof of concept for single-agent and combination use of bifunctional SOS1 degraders in KRAS-driven cancers.

Oct1 is a switchable, bipotential stabilizer of repressed and inducible transcriptional states.

Little is known regarding how the Oct1 transcription factor regulates target gene expression. Using murine fibroblasts and two target genes, Polr2a and Ahcy, we show that Oct1 recruits the Jmjd1a/KDM3A lysine demethylase to catalyze the removal of the inhibitory histone H3K9 dimethyl mark and block repression. Using purified murine T cells and the Il2 target locus, and a colon cancer cell line and the Cdx2 target locus, we show that Oct1 recruits the NuRD chromatin-remodeling complex to promote a repressed state, but in a regulated manner can switch to a different capacity and mediate Jmjd1a recruitment to block repression. These findings indicate that Oct1 maintains repression through a mechanism involving NuRD and maintains poised gene expression states through an antirepression mechanism involving Jmjd1a. We propose that, rather than acting as a primary trigger of gene activation or repression, Oct1 is a switchable stabilizer of repressed and inducible states.

Ameliorative impact of herbal formulation -Majoon-Dabeed-ul-ward and Sharbat-e-Deenar against CCl4 induced liver toxicity via regulation of antioxidant enzymes and oxidative stress.

Polyherbal Unani formulations have been used in the treatment of liver diseases for a long time. (Ibrahim M, Khaja MN, Aara A, Khan AA, Habeeb MA, Devi YP, Narasu ML, Habibullah CM. Hepatoprotective activity of Sapindus mukorossi and Rheum emodi extracts: in vitro and in vivo studies. World J Gastroenterol. 2008:14:2566-2571.) The aim of the present study was to investigate comparative hepatoprotective potential of Majoon-e-Dabeed-ul-ward (MD) and Sharbat-e-Deenar (SD) against CCl4 induced subchronic hepatic toxicity. In vivo study, albino rats were divided into 5 groups. Group I was control; Group II was experimental control treated with CCl4 (0.15 mL/kg, i.p. for 21 days); Groups III-IV treated with SD (2 mL/kg, p.o.) and MD (1,000 mg/kg, p.o.) for 5 days following CCl4 intoxication as in group 2 respectively; and Group V was positive control treated with silymarin (50 mg/kg, p.o.). In vitro hepatoprotective activity of SD and MD (25, 50, and 100 µg/mL) was assessed by SRB assay and flow cytometry analysis. CCl4 exposure significantly elevated the release of hepatic enzymes i.e. AST, ALT, LDH, and SALP in serum and lipid peroxidation in liver tissue which all these parameters were reversed after SD and MD administration. Therapy for 5 days also normalized the levels of antioxidant enzymes i.e. catalase, SOD, GPx, GR, tissue GSH, and aniline hydroxylase in CCl4 treated group. DNA damage and histological alterations caused by CCl4 were restored towards normal group. In vitro study showed protective effect of SD and MD against CCl4 treated HepG2 cell lines and rat hepatocytes. The results suggested that MD has a significant hepatoprotective potential and regulatory effect on oxidative stress than SD against CCl4 induced hepatotoxicity, and that this effect may be related to its antioxidant activity.

An allergy-associated polymorphism in a novel regulatory element enhances IL13 expression.

IL-13 is a central effector of Th2-mediated allergic inflammation and is critical for the induction of IgE synthesis. Common IL13 variants are associated with allergy phenotypes in populations of distinct ethnic background. We recently demonstrated that IL13 expression by human CD4+ T cells is paralleled by extensive IL13 locus remodeling, which results in the appearance of multiple DNase I hypersensitive sites. Among these, HS4 in the distal promoter is constitutive in both naïve and polarized Th1 and Th2 cells, and spans a common single nucleotide polymorphism, IL13-1512A>C (rs1881457), strongly associated with total serum IgE levels. We recently characterized HS4 as a novel cis-acting element that upregulates IL13 transcription in activated human and murine T cells. Here we show that IL13-1512A>C is a functional polymorphism that significantly enhances HS4-dependent IL13 expression by creating a binding site for the transcription factor Oct-1. Of note, endogenous Oct-1 was preferentially recruited to the IL13-1512C risk allele in primary CD4+ T cells from IL13-1512A>C heterozygous subjects. Moreover, the IL13-1512C allele was overexpressed in transfected Th2 cells from Oct1(+/+) mice, but not from Oct1(+/-) mice, demonstrating that increased activity was exquisitely dependent on physiologic levels of Oct-1. Our results illustrate how a functional variant in a regulatory element enhances transcription of an allergy-associated gene, thereby modulating disease susceptibility.

Biological attenuation of arsenic and nitrate in a suspended growth denitrifying-sulphidogenic bioreactor and stability check of arsenic-laden biosolids.

Co-occurrence of arsenic and nitrate in groundwater sources at a wide range of concentrations is reported. In this work, performance of suspended growth semi-batch reactor was assessed for co-removal of arsenic and nitrate from simulated groundwater to meet the drinking water standards in the absence of iron. The bioreactor was inoculated with mixed bacterial culture and operated in the absence of oxygen for more than 450 days under varying influent arsenate (200-800 µg/L), nitrate concentrations (50-250 mg/L), and hydraulic retention time of 3-6 days. Complete nitrate removal was observed at all tested concentrations. Arsenic removal was found to meet drinking water standards from initial concentrations and up to 600 µg/L. The extended toxicity characteristic leaching procedure leaching experiments indicated that arsenic-laden biosolids would not constitute a hazardous waste. The arsenic leaching was found to increase with an increase in dissolved oxygen and the final leachate concentrations of arsenic were below 150 µg/L. The leaching experiments suggested maintaining non-alkaline conditions for minimum arsenic release from arsenic biosolids formed under sulphidogenic conditions. This study is the first to report that nitrate and arsenic can be simultaneously removed to meet drinking standards in a suspended growth bioreactor.

Targeting transcriptional coregulator OCA-B/Pou2af1 blocks activated autoreactive T cells in the pancreas and type 1 diabetes.

The transcriptional coregulator OCA-B promotes expression of T cell target genes in cases of repeated antigen exposure, a necessary feature of autoimmunity. We hypothesized that T cell-specific OCA-B deletion and pharmacologic OCA-B inhibition would protect mice from autoimmune diabetes. We developed an Ocab conditional allele and backcrossed it onto a diabetes-prone NOD/ShiLtJ strain background. T cell-specific OCA-B loss protected mice from spontaneous disease. Protection was associated with large reductions in islet CD8+ T cell receptor specificities associated with diabetes pathogenesis. CD4+ clones associated with diabetes were present but associated with anergic phenotypes. The protective effect of OCA-B loss was recapitulated using autoantigen-specific NY8.3 mice but diminished in monoclonal models specific to artificial or neoantigens. Rationally designed membrane-penetrating OCA-B peptide inhibitors normalized glucose levels and reduced T cell infiltration and proinflammatory cytokine expression in newly diabetic NOD mice. Together, the results indicate that OCA-B is a potent autoimmune regulator and a promising target for pharmacologic inhibition.

Small molecule allosteric inhibitors of RORγt block Th17-dependent inflammation and associated gene expression in vivo.

Retinoic acid receptor-related orphan nuclear receptor (ROR) γt is a member of the RORC nuclear hormone receptor family of transcription factors. RORγt functions as a critical regulator of thymopoiesis and immune responses. RORγt is expressed in multiple immune cell populations including Th17 cells, where its primary function is regulation of immune responses to bacteria and fungi through IL-17A production. However, excessive IL-17A production has been linked to numerous autoimmune diseases. Moreover, Th17 cells have been shown to elicit both pro- and anti-tumor effects. Thus, modulation of the RORγt/IL-17A axis may represent an attractive therapeutic target for the treatment of autoimmune disorders and some cancers. Herein we report the design, synthesis and characterization of three selective allosteric RORγt inhibitors in preclinical models of inflammation and tumor growth. We demonstrate that these compounds can inhibit Th17 differentiation and maintenance in vitro and Th17-dependent inflammation and associated gene expression in vivo, in a dose-dependent manner. Finally, RORγt inhibitors were assessed for efficacy against tumor formation. While, RORγt inhibitors were shown to inhibit tumor formation in pancreatic ductal adenocarcinoma (PDAC) organoids in vitro and modulate RORγt target genes in vivo, this activity was not sufficient to delay tumor volume in a KP/C human tumor mouse model of pancreatic cancer.

A practical approach on reuse of drinking water treatment plant residuals for fluoride removal.

The sustainable management of the voluminous waste from drinking water treatment plants has motivated environmental researchers towards several reuse options. Water treatment residues (WTR) are proven adsorbent for remediation of many water- and soil-borne anions (perchlorate, selenium and arsenic), and may be able to remove fluoride from contaminated water. In this study, the sustainable reuse of the freely available waste of the drinking water treatment plants, namely WTR, was explored for their fluoride removal potential to meet drinking water standards. WTR was characterized by specific surface area, Fourier transform infrared (FT-IR), scanning electron microscopy and X-ray powder diffraction (XRD). Batch adsorption experiments were conducted as a function of WTR dose, contact time, agitation speed, initial fluoride concentration, initial temperature and water pH to get best adsorption capacity. About 90% fluoride removal (from initial 5.0 mg/L) was observed within 2 h contact time at WTR dose of 28 g/L. Also, WTR effectively removed fluoride in the pH range of 5-8, whereas removal efficiency decreased at pH 9 or higher. The adsorption equilibrium was established within 120-150 min. Adsorption isotherm data were best fit to Langmuir (R 2 = 0.984) and Freundlich models (R 2 = 0.983), while adsorption kinetic study exhibited that second-order kinetic model was followed with rate constant of 0.038 g/mg min. The FT-IR and XRD analyses affirmed that the metal hydroxyl and metal oxide groups contributed to the fluoride removal. The experimental results show the promising potential of WTR as an adsorbent in fluoride removal from real contaminated groundwater.

Effects of backwashing strategy and dissolved oxygen on arsenic removal to meet drinking water standards in a sulfidogenic attached growth reactor.

Efficiency and feasibility of two backwashing methods (water-nitrogen and water-air assisted) on arsenic and its co-pollutants removal were assessed through running a sulfidogenic attached growth reactor (AGR) treating arsenic spiked simulated groundwater for about 600 days. Replacing water with nitrogen assisted backwashing (WNAB) by water with air assisted backwashing (WAAB) introduced dissolved oxygen (DO) as an additional electron acceptor, which required an increased empty bed contact time (EBCT) to retain the entire terminal electron accepting zones (DO, nitrate, arsenate and sulfate) within the reactor. Removal of arsenic to below 10 µg/L required a longer EBCT at higher influent DO in backwash water. Notably, MiSeq sequencing analysis confirmed the presence of diverse bacterial community on biofilm which can utilize multiple terminal electron acceptors present in the bioreactor.

Bio-attenuation of arsenic and iron coupled with nitrate remediation in multi-oxyanionic system: Batch and column studies.

Co-occurrence of arsenic and iron along with nitrate in groundwater makes the trio an onerous combination both in terms of potability and treatment. To meet drinking water guidelines, batch and column laboratory trials were conducted on simulated and bore-well water for attenuation of arsenic (1000 µg/L), iron (5 mg/L) and nitrate (150 mg/L). Increment in sulphate showed a direct individual impact on iron removal, meeting WHO guidelines. The bio-kinetic parameters were in the range of: µmax = 0.079-0.551/d, Ks = 116.18-645.19 mg/L, Kd = 0.0009-0.0077/d and Y = 0.034-0.094 mg MLVSS/mg COD. Transmission electron microscopy (TEM) and X-ray diffraction (XRD) confirmed orpiment precipitation and/or co-precipitation with mackinawite are the key mechanisms for arsenic and iron attenuation. Column experiments were conducted by charging simulated groundwater containing arsenic (500 µg/L), nitrate (50 mg/L), sulphate (25 mg/L) and iron (3 mg/L) in an acetate (105 mg/L as COD) fed flow-through bioreactor at constant empty bed contact time of 60 min. Profile sampling illustrated segregation of different terminal electron accepting zones following thermodynamic yield for sequential removal of different oxyanions. This study showed the importance of considering microbially mediated terminal electron-accepting processes (TEAP) for multi-oxyanion removal in engineered systems.

Transcription factor Oct1 protects against hematopoietic stress and promotes acute myeloid leukemia.

A better understanding of the development and progression of acute myelogenous leukemia (AML) is necessary to improve patient outcome. Here we define roles for the transcription factor Oct1/Pou2f1 in AML and normal hematopoiesis. Inappropriate reactivation of the CDX2 gene is widely observed in leukemia patients and in leukemia mouse models. We show that Oct1 associates with the CDX2 promoter in both normal and AML primary patient samples, but recruits the histone demethylase Jmjd1a/Kdm3a to remove the repressive H3K9me2 mark only in malignant specimens. The CpG DNA immediately adjacent to the Oct1 binding site within the CDX2 promoter exhibits variable DNA methylation in healthy control blood and bone marrow samples, but complete demethylation in AML samples. In MLL-AF9-driven mouse models, partial loss of Oct1 protects from myeloid leukemia. Complete Oct1 loss completely suppresses leukemia but results in lethality from bone marrow failure. Loss of Oct1 in normal hematopoietic transplants results in superficially normal long-term reconstitution; however, animals become acutely sensitive to 5-fluorouracil, indicating that Oct1 is dispensable for normal hematopoiesis but protects blood progenitor cells against external chemotoxic stress. These findings elucidate a novel and important role for Oct1 in AML.