This is an excerpt from my PhD thesis where I investigated 13 human PR/SET domains from the PRDM protein family and assessed their ability to bind to a fluorinated SAH analog. The research helps to identify which of the PRDMs could be methyltransferases. This work was carried out in the laboratory of Dr. Cheryl Arrowsmith at the University of Toronto and the University Health Network.
Interrogating PR/SET domains for the ability to bind SAH
This chapter contains unpublished work and I am responsible for the overall generation and interpretation of the data included herein with the following mentions: The F-SAH compound was synthesized and kindly provided by Carlos Zepeda, Ontario Institute for Cancer Research (OICR). Shili Duan provided guidance and technical assistance in protein production. Additional proteins were kindly provided by Taraneh Hajian, Elisa Gibson and Dr. Masoud Vedadi from the SGC Toronto. Dr. Scott Houliston advised and supported all NMR experiments, and Drs. Houliston and Cheryl Arrowsmith aided in data analysis and provided guidance throughout the study. This project was prematurely halted due to a catastrophic freezer malfunction during the COVID-19 shutdown.
Lysine methyltransferases are a group epigenetic regulators currently being investigated in clinical and pharmaceutical studies for the treatment of certain cancers (Rugo, et al., 2020) (Ilango, et al., 2020) (Hoy, 2020) (Dilworth & Barsyte-Lovejoy, 2019). The majority of all KMT proteins possess a domain with a SET-fold (Schapira, 2011). The PRDM protein family is characterized by the presence of a PRDI-BF1 and RIZ1 (PR/SET) domain, which is a subgroup of the SET domain (FIGURE A1). Currently KMT activity has been reported for some PRDMs (TABLE A1), while some PRDMs are thought to be inactive pseudoenzymes. Since PRDMs are less represented in the academic literature compared to canonical SET proteins (FIGURE A4), it is unclear if these PRDMs are truly pseudoenzyme or if their KMT activity is only yet to be characterized. Distinguishing which PRDMs possess KMT activity would further our understanding of lysine epigenetics and pseudoenzyme-driven biology (Arrowsmith, et al., 2012) (Ribeiro, et al., 2019).
All domains with a SET-fold interact with SAM through a conserved hydrogen bonding network split across two distinct domain regions (Campagna-Slater, et al., 2011). These SAM binding residues in the canonical SET-domains are well conserved, however the corresponding residues in PR/SET domains are less well conserved (FIGURE A2) (H-binding clusters at Regions 1 and 2)]. The only holo-enzyme structure of a PR/SET domains is of mouse PRDM9 bound to a histone H3 peptide and SAH (Wu, et al., 2013). The human and mouse PRDM9 PR/SET domains possess many of the highly conserved SAM-binding residues found in the canonical SET-domains. Lacking any structural evidence, it is unclear if and how many of the PR/SET domains may bind to SAM. Therefore, detecting cofactor binding in PR/SET domains would aid in distinguishing whether certain PRDMs are enzymes or pseudoenzymes.
Here I investigate cofactor binding to understand which PR/SET domains may have the ability to catalyze the KMT reaction. Using 19F-nuclear magnetic resonance (NMR) spectroscopy, we measured the binding response for the majority of the human PR/SET domains with a fluorinated analog of the methyltransferase by-product S-adenosylhomocysteine (SAH), 2-fluoro-SAH (F-SAH). 19F-NMR is a sensitive and versatile method to study protein-ligand interactions (Dalvit & Vulpetti, 2019). Using the F-SAH binding response with the PRDM9 PR/SET domain as a positive control for the screening assays, we identified several PR/SET domains that bind F-SAH and therefore likely bind to SAM. Additionally, we detected several PR/SET domains that do not show any evidence of binding to F-SAH, which suggests a lesser affinity for SAM or potentially no affinity. This dataset can be used as a starting point for future discovery of KMT activity in PRDM proteins.
Establishment of the F-SAH binding assay
Figure K1. Characterization of F-SAH binding to PRDM9. (a) Chemical structure of 2-fluoro-SAH (F-SAH) and (b) model of F-SAH bound to PRDM9 based on a SAM-bound structure (PDBID: 6nm4). Colour coding corresponds to (a). The effects of F-SAH binding to PRDM9 were measured by 19F-NMR. (c-d) Spectra of 16 µM F-SAH alone and with 1X and 5X molar equivalents of PRDM9 display a concentration dependent decrease in the unbound F-SAH peak and the emergence of a bound F-SAH peak.
We utilized 19F nuclear magnetic resonance spectroscopy (NMR) spectroscopy to assess whether PR/SET domains may have the ability to bind to the methyltransferase enzyme cofactor. Fluorinated SAH was chosen, rather than fluorinated SAM because SAH and its chemical precursors are more stable across a wide pH range and were therefore more suited to chemical synthesis. The chemical structure of 2-fluoro-SAH (F-SAH) shows that SAH is fluorinated at the 2-position of the adenine ring (FIGURE K1a). Using our structure of the human PRDM9 PR/SET domain bound by SAM, we generated a theoretical model of F-SAH bound to PRDM9 (FIGURE K1b). We observed that the fluorine atom projects toward the solvent and therefore is unlikely to alter the interaction with the protein. Nevertheless, because fluorine’s chemical shift is highly sensitive to any change in its microenvironment, we expected to see perturbation and/or broadening of the 19F resonance when F-SAH binds to a PR/SET domain.
First, we investigated F-SAH alone by measuring a 1D 19F spectrum of F-SAH, which gave rise to a single peak at ~-52.4 ppm. Next, we monitored for F-SAH binding to PRDM9, which is the most extensively characterized methyltransferase among all the PR/SET domain containing proteins (Eram, et al., 2014) (Blazer, et al., 2016) (Allali-Hassani, et al., 2019) (Powers, et al., 2016). We assessed the F-SAH NMR signal alone and in the presence of equal and 5-fold molar equivalents of PRDM9 PR/SET domain, we detected a concentration-dependent decrease in the intensity of the unbound F-SAH 19F resonance (FIGURE K1c-d). Moreover, we observed the emergence of a second 19F signal (~ 1045 Hz up-field at -54.3 ppm) that is from protein-bound F-SAH. As these results were reproducible using two separate PRDM9 protein preparations, we selected 5-fold molar equivalents of PR/SET domain to F-SAH for further experiments.
Screening human PR/SET domains with the F-SAH binding assay
Figure K2. Screening for F-SAH binders among PR domains. (a) 19F-NMR spectra showing 16 µM F-SAH in the presence of 80 µM of the indicated PR/SET domains. (b) Plots of 19F peak integrals for F-SAH in the presence of individual PR/SET domains. All 19F peaks were normalized to the peak integral of F-SAH alone in buffer and the normalized integrals of the Bound and 1-Unbound peaks relative to F-SAH alone were plotted (i.e. F-SAH alone would be located at position [0,0]).
We performed F-SAH binding assays with PR/SET domains from 13 of the 19 human PRDM family members. The PR/SET domains of PRDM 1, 2, 4, 5, 6, 11, 12, 14 and 17 were provided by the SGC Toronto and I purified PRDM 3, 7, 9 and 16. I was able to purify PR/SET protein constructs for PRDM 8, 10, 13 and 15, however these constructs suffered stability issues in our 19F-NMR buffer during dialysis (see Methods) and were therefore not suitable for further study. We collected 19F-NMR spectra for F-SAH with 5-fold molar equivalents of each of the 13 human PR/SET domains (Figure K2a). The relative intensities of the unbound and bound F-SAH peaks varied considerably among the different PR/SET proteins indicating variable binding affinities across the panel of PRDM proteins. To quantify the binding for each PRDM PR/SET domain, we normalized the peak integrals of the unbound and bound peaks for each protein to the unbound peak of F-SAH alone. Specifically, we divided the integral of each peak by the integral of the peak for F-SAH alone. We plotted the normalized integrals of the 1 minus the unbound peak against the bound peak for each PR/SET domain to differentiate each protein’s affinity for F-SAH (Figure K2b). PR/SET datapoints located in the upper, right region of the plot displayed strong binding to F-SAH, while datapoints at the origin indicate no evidence of binding. We used the F-SAH signal in the presence of PRDM9 as an internal control to distinguish a strong binding response. PRDM 4 and 5 were plotted near to PRDM9, indicating a strong evidence response. Additionally, PRDM 14, 12, 7, 11 and 17 exhibited a very strong binding response. We were unable to detect any binding response for F-SAH in the presence of PRDM 3, 1 or 16, using our assay conditions, though we did detected a weak binding response for PRDM 2 and 6. Taken together, this data provides evidence to help prioritize further assays to identify methyltransferase activity among the PRDM family members.
Using F-SAH to probe KMT domains
Here we used 19F-NMR to investigate the potential for 13 of the 19 human PR/SET domains to bind a fluorinated analog of the methylation reaction by-product SAH. Using our F-SAH binding assays with PR/SET domains, we identified 7 domains (PRDM 4, 5, 7, 11, 12, 14 and 17) that showed a binding response similar to, or stronger than PRDM9. Of these ‘binding-competent’ domains only PRDM 9 and 7 have reported KMT activity, with accompanying enzyme kinetics data (Eram, et al., 2014) (Blazer, et al., 2016). Interestingly, PRDM7 showed stronger binding to F-SAH compared to PRDM9 (Figure K2). PRDM7 possesses much weaker KMT activity for H3K4me2 substrate peptide compared to PRDM9, with a 100-fold lower rate of catalysis (kcat=1.9×102/h vs 1.9×104/h, for PRDM 7 and 9, respectively) (Blazer, et al., 2016) (Eram, et al., 2014). These catalytic rate differences are mostly attributed to the distinct capacities to facilitate the methyl cation transferase by the catalytic residues (Y357 and S357, in PRDM 9 and 7, respectively). Based on our data, another contributing factor could be that PRDM7 has a stronger affinity for the reaction by-product SAH, which inhibits the catalytic rate. In our F-SAH binding assays, PRDM 2 and 6 showed weak, but detectable, binding compared to PRDM9 (Figure K2). KMT activities towards H3K9 and H4K20 have been reported for PRDM 2 and 6, respectively (Kim, et al., 2003) (Congdon, et al., 2014) (Wu, et al., 2008). This indicates that a weak binding response for F-SAH is associated with known active KMTs. Finally, in all cases where we observed F-SAH binding, we measured a consistent up-field shift (~1040 Hz) in the F-SAH 19F resonance (Figure K2a). This indicates there is a common binding modality with a highly similar microenvironment formed in the bound state across the family.
We also demonstrated the utility of F-SAH as a synthetic chemical probe for methyltransferase proteins. Our approach is comparable to a previous study that reported the binding of the MLL1 SET-domain to a SAM-analog conjugated with a fluorescent tag (Luan, et al., 2016). Comparatively, F-SAH benefits from the smaller size of fluorine, which is positioned on the adenine ring in an orientation that is unlikely to interfere with binding (Figure K2a-b). Additionally, 19F-NMR is capable of detecting low affinity protein-ligand interactions, such as is required for fragment-based screening (Dalvit & Vulpetti, 2019). We surveyed two publicly available databases that quantify protein-ligand interaction data (TABLE K1). We found that SET-fold containing proteins have a range of affinities for SAH with dissociation constants (KD) from low µM to high nM, as well as a similar range for reported half-maximal inhibition (IC50) by SAH. Only RBCMT had affinity data for both SAH and SAM, showing that SAM binds RBCMT with an ~70-fold higher affinity when compared with SAH (Couture, et al., 2006). The authors reported conserved binding modes in crystal structures of RBCMT-SAM and RBCMT-SAH implying that the variations in affinity could not be attributed to the binding conformations, but may rather be attributed to a higher entropic penalty for bound SAH, which possesses additional bond rotational freedom compared to SAM (Couture, et al., 2006). Taken together, we can predict that the upper-limit for the affinity of PRDM9 for F-SAH is less than the known affinity of SAM, which is 18.6 µM (Eram, et al., 2014).
Table K1. Known dissociation constant (KD) and half maximal inhibition values (IC50) of SAM and SAH for SET domain proteins. Binding affinity data available from the BindingDB (www.bindingdb.org) and BindingMOAD (www.bindingmoad.org/) was accessed from the RCSB PDB (www.rcsb.org). Note that BindingDB reports a large range of IC50 values for EZH2.
|Protein||Source||Ligand||KD (µM)||IC50 (µM)||Source|
|PRDM9||Homo sapiens||SAM||18.6||(Eram, et al., 2014)|
Interpreting the absence of binding evidence
We identified that PRDM 1, 3, and 16 do not bind to F-SAH in our assay conditions, which is suggestive of the inability to bind to SAM. PRDM1 (initially identified as Blimp-1) is widely understood to lack KMT activity and instead functions as a gene repressor by recruiting specific co-repressors proteins to PRDM1-binding sites throughout the genome (Minnich, et al., 2016). PRDM1 does affect histone methylation, but it does so through interactions with the KMT protein G9a/EHMT2 (Gyory, et al., 2004), the arginine methyltransferase PRMT5 (Ancelin, et al., 2006) and the lysine demethylase LSD1 (Su, et al., 2009). Whether the PR/SET domain of PRDM1 functions as a “reader domain” for specific histone tail modifications is undetermined, however our data suggests that it is unlikely that SAH or SAM would play a role in this ability.
We found that the PR/SET domains of PRDM 3 and 16 do not bind to F-SAH under our assay conditions. However, this does not exclude the possibility that larger or differently generated constructs may possess the ability to bind SAM or SAH. For instance, longer or full-length PRDM 3 and 16 protein constructs were reported to possess KMT activity when purified from either HeLa cells and mouse fibroblasts or SF9 insect cells (Pinheiro, et al., 2012) (Zhou, et al., 2016). Our PRDM 3 and 16 constructs were purified from E. coli and each contained the PR/SET domain along with the first proximal C-terminal zinc-finger motif (ZnF1), which is similar to previous structural and enzyme characterization studies of the PR/SET and ZnF1 of PRDM9 (Eram, et al., 2014) (Wu, et al., 2013). It is unclear if the additional regions outside the PRDM 3 and 16 PR/SET domains and ZnF1 could function to stabilize the cofactor binding site in the PR/SET domain. Interestingly, a previously solved NMR solution structure of PRDM16 demonstrated the absence of internal β-strands that are present in crystal and solution structures of all other PR/SET domains, which could possibly destabilize the cofactor and substrate binding sites (FIGURE A3d). Furthermore, it is unclear if additional factors present in eukaryotic expression systems enable cofactor binding or enzymatic activity.
Future analysis of PRDMs
Future investigation to complete the F-SAH binding screen with the untested members of the PRDM family (PRDM 8, 10, 13, 15, FOG1, and FOG2) would provide valuable data. Additionally, assaying F-SAH binding in competition with (unlabeled) SAM could qualitatively delineate the affinities of the methyltransferase reaction cofactor and by-product, providing further evidence of potential enzymatic function. We detected F-SAH binding in PRDM 4, 5, 11, 12, 14, and 17, and we could not find any studies reporting KMT activity with these proteins. Intriguingly, PRDM 4, 5, 11, 12, and 14 all possess the highly conserved “catalytic tyrosine” (FIGURE A2), which is further evidence supporting KMT activity for these proteins. Importantly, several studies have attributed oncogenic roles for PRDM 4, 12 and 14 in specific cancers (Casamassimi, et al., 2020). Future discovery of enzymatic function in any of these PR/SET domains could provide a novel, actionable target for oncological drug discovery.
PRDM9 (195-385) and PRDM7 (195-392) with an N-terminal 6xHis-tag and TEV protease site were expressed in Escherichia coli BL21 (DE3) codon plus cells from a pET28-MHL vector. PRDM3 (69-235) and PRDM16 (73-256) with an N-terminal 6xHis-tag and TEV protease site were expressed in Escherichia coli BL21 (DE3) codon plus cells from a pET15b/MHL vector. Cell were grown at 37°C in M9 minimal medium in the presence of 50 µg/ml of kanamycin (PRDM 7 and 9) or 100 µg/ml of ampicillin (PRDM 3 and 16) to an OD600 of 0.8 and induced by isopropyl-1-thio-D-galactopyranoside (IPTG), final concentration 0.5 mM and incubated overnight at 15°C. Cells were harvested by centrifugation at 7,000 rpm and cell pellets were stored at -80°C. Cell were lyzed on ice in lysis buffer (20 mM Tris pH 7.5, 300 mM NaCl, 10 mM imidazole, 50 µM ZnSO4, 5 mM β-mercaptoethanol, 0.5 mM TCEP, 0.1% Triton-X 100, 2.5% glycerol, 1mM PMSF, 2 mM benzamidine and Roche complete EDTA-free protease inhibitor cocktail tablet) using a probe sonicator. The crude extract was cleared by ultracentrifugation for 50 min at 50000xg and the supernatant was incubated with TALON Metal Affinity Resin (Takara) at 4oC for 120 minutes with agitation. Resin was washed in wash buffer (lysis buffer with 0.01% Triton-X 100 and lacking protease inhibitors) and bound proteins were eluted using elution buffer (wash buffer with 400 mM imidazole), monitored by Bradford analysis. Protein was dialyzed overnight at 4°C in TEV dialysis buffer (20 mM Tris pH 7.5, 300 mM NaCl, 20µM ZnCL2, 2.5% glycerol, 5 mM β-mercaptoethanol and 0.5 mM TCEP) and incubated with His-tagged TEV protease produced in house at a 1/20 dilution by mass. 0.5 mM CHAPS was added to the TEV dialysis buffer for PRDM 9 and 7, but not PRDM 3 and 16. TEV and uncleaved proteins were removed using TALON resin and soluble protein was loaded onto a Superdex 75 Increase 10/300 GL colum (GE Healthcare), equilibrated with 20 mM Tris-HCl buffer, pH 7.5, and 150 mM NaCl, 2.5% glycerol, 5 mM β-mercaptoethanol and 0.5 mM TCEP at flow rate 0.7 ml/min. Fractions containing PRDM9 protein were pooled and dialyzed into low salt buffer (20 mM Tris-HCl pH 8.5, 100 mM NaCl, 5% glycerol, 5 mM β-mercaptoethanol and 0.5 mM TCEP). PRDM9 protein was further purified by anion-exchange chromatography on 2 tandemly joined 5 ml HiTrap™ DEAE FF (GE Healthcare) columns along a linear gradient up to 1.0 M NaCl. Purified PRDM9 protein was dialyzed into a final buffer containing 20 mM Tris pH 7.5, 150 mM NaCl and 2 mM TCEP. The proteins for PRDM1 (38-223), PRDM2 (2-160), PRDM4 (390-540), PRDM5 (2-226), PRDM6 (194-405), PRDM11 (79-314), PRDM12 (60-229), PRDM14 (212-422), and PRDM17 (1-205) were purified from E. coli expression and kindly provided by Taraneh Hajian, Elisa Gibson and Dr. Masoud Vedadi from the SGC Toronto.
F-SAH binding by 19F NMR
F-SAH was synthesized and kindly provided by Carlos Zepeda, Ontario Institute for Cancer Research (OICR). All PR/SET domain containing proteins were dialyzed overnight at 4oC into 19F-NMR buffer (20 mM Tris pH 7.3, 150 mM NaCl, 2 mM TCEP and 20 µM ZnCl2) also containing 16 µM sodium trifluoroacetate. The concentration of each protein was measured using an absorbance reading at 280 nm and evaluated using their respective theoretical extinction coefficients calculated using ProtParam (Gasteiger, et al., 2005). 100 mM F-SAH in d6-DMSO was diluted to 16 µM F-SAH by adding the dialyzed protein solution to a final protein concentration of 80 µM and then topping off with 19F-NMR buffer to a final volume of 500 µl. For the F-SAH alone sample, only 19F-NMR buffer was added. The solutions were mixed in 1.5 ml polypropylene tubes and then transferred to 5 mm glass NMR tubes.
1D 19F spectra were acquired at 298K on a Bruker Avance III spectrometer operating at 600 MHz and equipped with a QCI cryoprobe with an independent 19F detection coil. Each spectrum was acquired with 3072 scans, an acquisition time of 577 ms, and processed by applying an exponential window function (LB = 20). There was no difference observed in the F-SAH 19F line-shape when signal acquisition was acquired with or without proton decoupling; therefore, all spectra were acquired without proton decoupling. The spectral window was measured from -37.89 ppm to -88.09 ppm and 19F peaks were identified at -75.53 ppm, -52.40 ppm, and -54.21 ppm, for trifluoroacetate, F-SAH unbound, and F-SAH bound, respectively. Processing and analysis were carried out with Topspin 3.5 (Bruker BioSpin). To control for pipetting errors that could result in differences in F-SAH signal intensities, the integral of the trifluoroacetate 19F peak of each PR/SET containing sample was set to equal the integral of the trifluoroacetate 19F peak of the sample with F-SAH alone. To normalize F-SAH peaks, the integral for each F-SAH peak was divided by the integral of the F-SAH peak from the sample with F-SAH alone (i.e. integral of F-SAH alone = 1).
Allali-Hassani, A. et al., 2019. Discovery of a chemical probe for PRDM9.. Nat Commun., 10(1), p. 5759.
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Arrowsmith, C. et al., 2012. Epigenetic protein families: a new frontier for drug discovery.. Nat Rev Drug Discov, 11(5), pp. 384-400.
Blazer, L. et al., 2016. PR Domain-containing Protein 7 (PRDM7) Is a Histone 3 Lysine 4 Trimethyltransferase.. J Biol Chem, 291(26), pp. 13509-19.
Campagna-Slater, V. et al., 2011. Structural chemistry of the histone methyltransferases cofactor binding site.. J Chem Inf Model, 51(3), pp. 612-23.
Casamassimi, A. et al., 2020. Multifaceted Role of PRDM Proteins in Human Cancer.. Int J Mol Sci., 21(7), p. E2648.
Congdon, L., Sims, J., Tuzon, C. & Rice, J., 2014. The PR-Set7 binding domain of Riz1 is required for the H4K20me1-H3K9me1 trans-tail ‘histone code’ and Riz1 tumor suppressor function.. Nucleic Acids Res, 42(6), pp. 3580-9.
Couture, J. et al., 2006. Catalytic roles for carbon-oxygen hydrogen bonding in SET domain lysine methyltransferases.. J Biol Chem, 281(28), pp. 19280-7.
Dalvit, C. & Vulpetti, A., 2019. Ligand-Based Fluorine NMR Screening: Principles and Applications in Drug Discovery Projects.. J Med Chem, 62(5), pp. 2218-44.
Dilworth, D. & Barsyte-Lovejoy, D., 2019. Targeting protein methylation: from chemical tools to precision medicines.. Cell Mol Life Sci, 76(15), pp. 2967-85.
Eram, M. et al., 2014. Trimethylation of histone H3 lysine 36 by human methyltransferase PRDM9 protein.. J Biol Chem, 289(17), pp. 12177-88.
Gasteiger, E. et al., 2005. Protein Identification and Analysis Tools on the ExPASy Server. In: J. M. Walker, ed. The Proteomics Protocols Handbook. s.l.:Humana Press, pp. 571-607.
Gyory, I. et al., 2004. PRDI-BF1 recruits the histone H3 methyltransferase G9a in transcriptional silencing.. Nat Immunol, 5(3), pp. 299-08.
Hoy, S., 2020. Tazemetostat: First Approval.. Drugs, 80(5), pp. 513-21.
Ilango, S. et al., 2020. Epigenetic alterations in cancer.. Front Biosci (Landmark Ed), 25(1), pp. 1058-109.
Kim, K., Geng, L. & Huang, S., 2003. Inactivation of a histone methyltransferase by mutations in human cancers.. Cancer Res, 63(22), pp. 7619-23.
Luan, Y. et al., 2016. Design of a fluorescent ligand targeting the S-adenosylmethionine binding site of the histone methyltransferase MLL1. Org Biomol Chem, 14(2), pp. 631-8.
Minnich, M. et al., 2016. Multifunctional role of the transcription factor Blimp-1 in coordinating plasma cell differentiation.. Nat Immunol, 17(3), pp. 331-43.
Pinheiro, I. et al., 2012. Prdm3 and Prdm16 are H3K9me1 methyltransferases required for mammalian heterochromatin integrity.. Cell, 150(5), pp. 948-60.
Powers, N. et al., 2016. The Meiotic Recombination Activator PRDM9 Trimethylates Both H3K36 and H3K4 at Recombination Hotspots In Vivo.. PLoS Genet, 12(6), p. e1006146.
Ribeiro, A. et al., 2019. Emerging concepts in pseudoenzyme classification, evolution, and signaling.. Sci Signal, 12(594), p. eaat9797.
Rugo, H. et al., 2020. The Promise for Histone Methyltransferase Inhibitors for Epigenetic Therapy in Clinical Oncology: A Narrative Review.. Adv Ther. , 37(7), pp. 3059-82.
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Multicomponent supramolecular self-assemblies of exceptional long-range order and low defectivity are obtained if C(60) and 5-(4-aminophenyl)-10,15,20-triphenylporphyrin (TPP-NH2) are assembled on Ag(110) by sequential evaporation in the submonolayer range of TPP-NH2 and fullerene on the substrate surface and subsequent annealing. A (+/-2 -3, 6 +/- 3) array consisting of supramolecular stripes of a 1:1 C(60)/TPP-NH2 2D adduct develops at 410 K (the low temperature, LT, phase). If the LT phase is annealed at 470 K, then a 3:1 fullerene/TPP-NH2 (+/-3 -5, 5 +/- 5) nanoporous array (the HT phase) forms, with each pore containing a single porphyrin molecule. Phase separation occurs by annealing the HT phase at 520 K. Structural models are proposed and discussed on the basis of the experimental scanning tunneling microscopy results.
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- Asia Pacific (China, India, ASEAN, Australia & New Zealand)
- Middle East and Africa (GCC, S. Africa, N. Africa)


Altamofen-20 is a non-steroidal agent that has demonstrated potent anti-estrogenic properties in animal test systems. This anti-estrogenic effect may be due to its ability to compete with estrogen for binding sites in tissues, such as breast cancer. Tamoxifen inhibits the induction of rat mammary carcinoma induced by dimethylbenzanthracene (DMBA) and causes regression of already established DMBA-induced tumors.
In cytosols derived from human breast adenocarcinoma, tamoxifen competes with estradiol for the estrogen receptor protein. USAGE AND DOSES: With a dose of 20–40 mg / day for 1–5 years +. Twenty-five percent of patients received 1 year or less of trial treatment, 52% received 2 years, and 23% received about 5 years.
Pharmacological action – anti-estrogenic, antitumor.
Rapidly absorbed, for 4-7 hours creates a maximum concentration in the blood. Equilibrium concentration (300 ng / mg) is achieved with a daily dose of 40 mg for 4 weeks. 99% bound to albumin. Metabolized, excreted with feces, the elimination half-life for tamoxifen is 7 days, X-desmethyltamoxifen (the main metabolite) is 14 days.
Indications drug Nolvadex
Hot flashes, vaginal bleeding, endometrial hyperplasia, vulvar itching, dyspeptic disorders, dizziness, water retention in the body, hypercalcemia, thrombocytopenia, alopecia, uterine fibroids, leukopenia, thromboembolism.


Try our Pink Himalayan Salt bar recipe!
Salt is a crystalline mineral made of two elements, sodium (Na) and chlorine (Cl). Most of the world’s salt is harvested from salt mines or by evaporating seawater and other mineral-rich waters.
Salt Soap Benefits:
Moisturiser – Salt is a natural humectant, drawing moisture to skin and helping to retain it resulting in soft skin without skin being left feeling greasy.
Exfoliator – A gentle exfoliator to slough off dead skin cells and promote skin rejuvenation resulting in smoother softer skin.
Detoxifier - Salt is a natural detoxifier, as the salt absorbs the toxins from the skin.
Combine the cleansing, detoxifying and exfoliating qualities of a salt bath to your cold process soap recipe. The end result of the bar will be super-hard and it can produces a creamy lather.
Choose Your Salt
Himalayan Pink Salt
Pink Himalayan salt is made from rock crystals of salt that have been mined from areas close to the Himalayas, often in Pakistan and from the Khewra Salt Mine, the second largest salt mine in the world.
Himalayan salt contains traces of iron oxide (rust), which give it a rosy hue and also a small amount of calcium, iron, potassium and magnesium , making it slightly lower in sodium than regular table salt.
Sea salt is made by evaporating seawater.
Like table salt, it is mostly just sodium chloride. However, depending on its source and how it was processed, it usually contains various trace minerals like potassium, iron and zinc.
The darker the sea salt, the higher its concentration of impurities and trace nutrients. However, due to ocean pollution, sea salt can also harbor trace amounts of heavy metals like lead.
Kosher salt has a large grain size.
The main difference between regular salt and kosher salt is the structure of the flakes. With the large grain size, it can sometimes be a bit harsh on the skin but will result in a deep exfoliating soap.
Precaution when using Salt:
The salt soap will start to harden almost immediately. If you're using a log mold, cut the soap as soon as it's firm enough. The soap will still be warm even as it's going through the saponification process. However, if you wait too long, the soap will be hard, difficult to cut, and result in crumbly bars.
If you don't like the exfoliating feeling of a salt, you can also brine the soap in water and add it to your lye solution.
Salt bar is great for oily skin.
Watch a full step-by-step video on How To Make Pink Himalayan Salt bar.
This recipe is for a 200g soap. Please formulate according to your desired batch.
In this recipe, for the salt, we recommend 30% of total soap weight or less.
For essential oil, we recommend adding 5% of total oil weight.
Where to get your soap ingredients?
You can get soap ingredients from Sugar & Spice refill stations or on our e-store.
Like to give our salt bars a try?
Get FREE samples from our studio:
81 Ubi Avenue 4 #10-19 UB.One Singapore 408830 (pre-appointment required).
While stocks last!
If you like it, don't forget to try the above recipe for your next soap making project!
New to soap making?
Book for our Basic Cold Process (CP) soap making classes (Suitable for Beginners):
Basic CP soap making class (Learn how to make bar soaps)
CP Liquid soap making class (Learn how to make liquid soaps)
For Experienced soap makers, rent a space for soap making:


|Packaging||Gunny Bag, Jute Bag|
|Packaging size||10kg, 1kg, 50kg, 5kg|
We are the leading manufacturer, exporter and wholesale supplier of Potassium Feldspar Chips from Gudur, Andhra Pradesh. Potassium Feldspar Chips are used for various applications in ceramic, cement and dental industries. We manufacture these Potassium Feldspar Chips using finest quality chemicals as per the industry standards. We offer these Potassium Feldspar Chips in secure and attractive packaging that reaches the client within the stipulated time-frame.


The primary feature of your catalytic converter is to convert harmful gasses in your exhaust right into more secure components before they are discharged by your car. Many converters are made from slim as well as delicate ceramic, and also their operation is fragile as well as relies on the appropriate performance of numerous other engine and also exhaust parts. This implies that concerns with your converter will normally show further damage to your exhaust system or engine, which is in fact a good thing for your vehicle’s health – because catalytic concerns are extremely easy to spot in their onset ( about the majority of engine and exhaust damage), it will allow you to obtain the remainder of your engine dealt with prior to the damage obtains also serious.
Unburned fuel leeching into the exhaust system –
Your vehicle’s gas needs to be totally melted in the burning chamber before going into the exhaust system; otherwise the gas can stir up when it reaches the converter as well as create overheating as well as eventual melting. Dripping fuel right into your exhaust can be brought on by a variety of engine issues, however a lot of typically you will certainly be having problems with the fuel injector or examine shutoff.
Malfunctioning oxygen sensor –
If your car’s oxygen sensor isn’t operating appropriately, it can lead to the exhaust gas being also slim or also thick. If it is as well slim your catalytic converter won’t have the ability to transform the harmful gases to much safer components, leading to your vehicle stopping working an discharges examination. If the exhaust gas is too abundant it will certainly trigger the converter to overheat and melt.
Dripping oil or anti-freeze –
If any one of your engine’s oil or anti-freeze enter the exhaust, it can obstruct the air path by coating a thick layer of residue over the ceramic exterior of the catalytic converter. Initially this will decrease the converter’s efficiency, but at some point the carbon soot will obstruct the pores of the ceramic and also obstruct the release of exhaust. This creates warm to build up in your exhaust system, resulting in extensive damages.
Damage from roadway debris –
Due to the fact that your vehicle’s catalytic converter is fairly breakable, pebbles and various other items of level can strike the outside as well as cause fracturing. This is when you start to listen to a rattling sound coming from your exhaust system (due to items of the converter’s casing breaking off inside the exhaust. Again, this will block the flow of the exhaust gasses and trigger warm accumulation in your engine, at some point creating a disaster.
Remember that damages to the catalytic converter is generally tied into damages to various other engine and also exhaust elements – it is extremely recommended you take your vehicle right into a auto mechanic for a complete examination if you’re having any type of problems with exhaust heat or exhaust.
know more about catalytic converter recycling here.


Experiments were performed at atmospheric pressure conditions on the prototype 4th generation DLE burner. The combustion changes that occur for alteration of the operating conditions by changing the equivalence ratios (ϕ) for CH4 as fuel at different sections of the burner, were optically investigated. The burner assembly has three concentrically arranged premixed burner sections: an outer Main section, an intermediate section (Pilot) and a central pilot body or pre-chamber combustor, called RPL (Rich-Pilot-Lean) section. All sections are facilitated to vary equivalence ratios to achieve optimal combustion. Planar laser-induced fluorescence (PLIF) of OH radicals and flame chemiluminescence imaging were applied to study the local flame characteristics in order to investigate turbulence-flame interaction and formation of reaction zone at the burner exit. The results show that the position and shape of the flame are clearly affected by the variation of equivalence ratios at different sections of the burner. During the experiments, first the RPL, then the Pilot and the Main flame were added in a step wise manner keeping constant the total air flow for the global ϕ = 0.5 in order to understand the flame contributions from the different combustion sections. It is observed that for the RPL fuel lean conditions, the primary combustion starts and reaches completion before exiting the burner throat while for rich conditions, the residual fuel escapes out through the RPL exit with primary combustion products and starts secondary combustion along with the Pilot and Main combustion. At the global ϕ = 0.5, for changing the RPL ϕ from lean to rich conditions, the flame stabilization region moves downstream of the burner exit and the flame front fluctuation along inner shear layer increases. For increasing the global ϕ and increasing the Pilot fuel ratio (PFR) without changing the RPL and the global ϕ, the total extension of the flame becomes shorter and the flame stabilization region moves upstream.
Laser-Based Investigation on a Dry Low Emission Industrial Prototype Burner at Atmospheric Pressure Conditions
Subash, AA, Collin, R, Aldén, M, Kundu, A, & Klingmann, J. "Laser-Based Investigation on a Dry Low Emission Industrial Prototype Burner at Atmospheric Pressure Conditions." Proceedings of the ASME Turbo Expo 2016: Turbomachinery Technical Conference and Exposition. Volume 4B: Combustion, Fuels and Emissions. Seoul, South Korea. June 13–17, 2016. V04BT04A005. ASME. https://doi.org/10.1115/GT2016-57242
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HCL instead of imidazole!
December 16, 2011 at 4:50 am #15850
Soo today I eluted with MCAC-100 (or so I thought)..I realsied once i added reducing buffer i added 1M HCL (i have them in the same size bottle next to each other on my shelf)…so what i did was i just washed my column with MCAC-0 a few times and eluted with the correct imidazole concentration …just wondering will this work..im running as gel as i write this but just wondering if the beads are still useable
December 16, 2011 at 6:29 am #108760
or more likely will the HCl remains on the beads affect my protein
December 16, 2011 at 7:18 am #108761JackBeanParticipant
1M HCl has pH ~1, that denatured probably your protein and I’m not sure, whether it doesn’t elute also the ion from column. Which ion are you using? Did you see decoloration of your column?
Do you have protein of which you can measure activity? If so, do it and you will see. You will probably have to do some slow dialysis to re-fold your protein.
December 16, 2011 at 9:23 am #108765
I’m using a nickel column, when i added my reducing buffer to a sample of beads and my eluted protein it turned yellow..so i washed it with my buffer and then tested for colour change…it didn’t turn yellow…so i eluted with 100mM of imadazole and ran a gel and got a band…but i had quite a bit of protein in my flow through so i dialyzed in mcac-0 o/n and tmoorrow i will run it through a new column of beads and elute that correctly..
what do you mean by
Do you have protein of which you can measure activity?
December 16, 2011 at 9:37 am #108766
Sorry that last message is a jumble of words…so just to explain more clearly..I added 10uL of my "eluted" protein (the one I did with HCl) and added 10uL of reducing buffer-it turned yellow..I also took a sample of beads (10uL and added 10uL reducing buffer–also turned yellow)-..boiled both for 5mins at 95 degrees and then ran a gel…I got a relatively faint band with the HCl elutent but have kept that separetly in the fridge for time being.
After I sonicated, I ran my lysate thru the colum and i ran the FT on gel as well and theres quite a bit of protein there..so I dialyzed in MCAC-0 and tomorrow I will pass it through a new column of beads…and if I have enough there I might just get rid of the HCl one or refold like you say…but yeah I was more curious about what the HCl would do to my protein 🙁
December 16, 2011 at 9:47 am #108767
sorry to be a pain..if I were to refold it to be on safe side..what to I refold in buffer wise/dialyze..MCAC-0 (Tris 20mM pH 8, 0.5 NaCl–the same as what I washed column with)..this causes the detanurant (Hcl) to be absorbed and hence cause protein to refold?? Have I got that right?
December 16, 2011 at 11:57 am #108768JackBeanParticipant
to re-fold the protein, you should change your buffer/solution very slowly in several steps. Thus, if you had pH 1 and want pH 8.0, I would do at least eight steps, one pH point per step (i.e. first dialysis against buffer with pH 2, second dialysis with pH 3, third with pH 4…).
Does your native protein turn yellow in the reducing buffer. I don’t see much, how is that relevant.
I meant, whether are you able to measure activity of your enzyme or is it some protein, which does not have catalytic activity (at least not something easily detectable in vitro like some transcription factor).
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Vedanta Aluminum invites waste-wealth partnerships with
cement industry for low carbon products
- Organization of a national workshop on the opportunities and benefits of using fly ash and bauxite residue for cement manufacturing
- High potential for cost savings and carbon emissions by the cement industry
- Ecosystem of industry experts to guide the technical aspects of the blend
New Delhi, 19e July 2021: Vedanta Aluminum Business, India’s largest producer of aluminum and value-added products, calls on cement producers to team up to use its by-products in the manufacture of low-carbon cement. The company has expressed interest in long-term collaboration with cement industry players on the opportunities for using fly ash (a by-product of thermal power generation) and bauxite tailings (a by-product of the production of alumina from bauxite) in the manufacture of cement, in a national workshop conducted with global industry experts.
The cement industry, which is exploring viable solutions to produce cement in a more sustainable way, is the ideal circular economy partner for Vedanta Aluminum. Fly ash and bauxite tailings, the two largest by-products generated by the aluminum industry, can be used in the manufacture of cement and concrete, providing cement manufacturers with significant quality advantages, cost and sustainability.
Fly ash can partially replace cement in concrete (or be used to produce mixed cement), greatly improving the durability and workability of the cement. With a 30-33% mixing ratio, fly ash can help save 270 kg of carbon emissions for every ton of cement produced. Bauxite tailings can be added to the raw mix in the manufacture of clinker to replace virgin bauxite, thereby improving its hydraulic properties and strength. Due to the high concentration of iron oxide and alumina, bauxite residue is a better substitute for laterite, which is used in the manufacture of clinker. Additionally, the residual caustic in bauxite tailings helps control sulfur emission when used directly, making it a better fit for this purpose. Since fly ash and bauxite tailings are themselves industrial wastes, they also have significant cost and energy benefits.
Vedanta Aluminum’s technical workshop brought together over a hundred executives from the cement industry and brought together world-renowned experts in this field – Mr. Shreesh Khadilkar, former Director of Quality and Product Development at one of the leading cement producers in India, and Mr. Robin De Beer, a concrete technologist from South Africa with over 40 years of experience in the lucrative use of fly ash in concrete.
Speaking at the webinar, Mr. Rahul Sharma, Dy. CEO – Vedanta Aluminum Business said: “We strongly believe that industries must develop waste-to-wealth value chains to become truly sustainable. At Vedanta, we have made encouraging progress in this direction and intend to continue them. Long-term strategic collaborations, such as between Vedanta and the Indian key cement producer company, will not only remove large volumes of industrial waste from the system, but also provide the trifecta of quality, sustainability and cost benefits. for the cement industry. We hope that Indian cement producers will come and work with us on this innovative solution, which is a real win-win scenario for industry and the environment. ”
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Sharing his insights and industry experience with the public, Mr. Robin De Beer said: “Good quality fly ash can help reduce water demand, reduce heat of hydration and dramatically improve the heat of hydration. workability of concrete, which translates into long-term strength and durability. The workshop is a great Vedanta initiative to raise awareness of how fly ash can support the sustainability agenda of the cement and concrete industry, while dramatically improving product performance. ”
Mr. Shreesh Khadilkar added: “Bauxite tailings have multiple advantages in cement making, such as lower silica content compared to laterite / bauxite, higher alkali and fine particle content, which reduces crushing costs. It also improves the hydraulic properties of cement. The Indian cement industry should take advantage of this innovative opportunity to reap the benefits of quality and sustainability. ”
As part of its quest to promote the circular economy, in FY21, Vedanta Aluminum supplied over 3 lakh metric tons of fly ash to various cement plants in India. Since February 21, the company has also supplied more than 30,000 metric tonnes of bauxite tailings to cement manufacturers. The company also provides free fly ash to hundreds of local brick-making MSMEs in its watershed. In fiscal year 21, Vedanta Aluminum supplied nearly 4 lakh metric tonnes of ash to brick manufacturers. Ash bricks are not only lighter and stronger than traditional clay bricks, but also play a crucial role in preserving the nutrient-rich topsoil from being used as a raw material. This equates to an estimated savings of 1.9 metric tons of topsoil for every ton of ash brick produced. In addition, making ash bricks is an eco-efficient process, unlike the energy-intensive process of producing clay bricks in brick kilns which results in significant greenhouse gas emissions. In fact, for every tonne of ash bricks produced, an estimated 5,900 kg of carbon dioxide equivalent emissions are avoided.
For more information on this topic, please contact: [email protected]
Vedanta Aluminum Business, a division of Vedanta Limited, is India’s largest aluminum manufacturer, producing half of India’s aluminum at 1.96 million tonnes per year (MTPA) in FY21. is a leader in value-added aluminum products that find critical applications in basic industries. With its aluminum smelters, alumina refinery and world-class power plants in India, the company is fulfilling its mission to stimulate emerging applications of aluminum as the “Metal of the Future” for a greener future.
About Vedanta Limited:
Vedanta Limited, a subsidiary of Vedanta Resources Limited, is one of the world’s leading oil, gas and metals companies with significant operations in oil and gas, zinc, lead, silver, copper , iron ore, steel and aluminum, and energy in India, South Africa, Namibia and Australia. For two decades, Vedanta has made a significant contribution to nation building. Governance and sustainable development are at the heart of Vedanta’s strategy, with a strong emphasis on health, safety and the environment. Giving back is in Vedanta’s DNA, which is focused on improving the lives of local communities. Under the aegis of Vedanta Cares, the flagship program with social impact, Nand Ghars has been set up as a model
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anganwadis focused on eradicating child malnutrition, education, healthcare and empowering women by enabling them to develop their skills. Vedanta and its group companies were listed in the Dow Jones Sustainability Index 2020 and received the Frost & Sullivan Sustainability Awards 2020, the CII Environmental Best Practices Award 2020, the CSR Health Impact Award 2020, the CII National Award 2020 for Excellence in Water Management, CII Digital Transformation Award 2020, ICSI National Award 2020 for excellence in corporate governance, People First HR Excellence Award 2020, ‘Company with Great Managers 2020’ by People Business and certified Great Place to Work 2021. Vedanta Limited is listed on the Bombay Stock Exchange and the National Stock Exchange in India and has ADRs listed on the New York Stock Exchange.
For more information, please connect to https://www.vedantalimited.com
About Vedanta Aluminum Business:
Vedanta Aluminum Business, part of Vedanta Limited, is India’s largest aluminum producer, producing almost half of India’s aluminum or 1.96 million tonnes per year (MTPA) in fiscal year 21 Vedanta is a leader in value-added aluminum products that find critical applications in basic industries. With its aluminum smelters, alumina refinery and world-class power plants in India, the company is fulfilling its mission to stimulate emerging applications of aluminum as the “Metal of the Future” for a greener future.
For more information, please connect to https://vedantaaluminium.com/
For more details, please contact:
Head of communications
Vedanta Limited – Aluminum and Electric Company
Call: + 91-9910602549
E-mail: [email protected]
This press release contains “forward-looking statements”, that is, statements relating to future events and not past. In this context, forward-looking statements often deal with our expected future business and financial performance and often contain words such as “expects”, “anticipates”, “intends”, “plans”, “believes”, ” research, “” should “or” will. “Forward-looking statements, by their nature, deal with matters that are, to varying degrees, uncertain. To us, uncertainties arise from the behavior of the financial and metals markets, including the London Metal Exchange; fluctuations in interest rates and / or exchange rates and prices of metals; the future integration of acquired businesses; and many other national, regional and global issues, including those of a political, economic, commercial, competitive or regulatory nature These uncertainties may cause our actual future results to differ materially from those expressed in our forward-looking statements. We do not undertake to update our forward-looking statements.
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Vedanta limited published this content on July 18, 2021 and is solely responsible for the information it contains. Distributed by Public, unedited and unmodified, on July 20, 2021 06:08:05 PM UTC.


When buying high-quality gypsum in Pueblo, CO, for your soil, you can rely on EcoGEM®. We have extensive experience and expertise in the gypsum industry, providing top-notch Pueblo gypsum products and services to meet your specific needs.
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Minnesota, Minneapolis-Major Belgian foamer Recticel has introduced its Arcadia brand of flexible foams, made with Cargill's soya-based BiOH polyols. Arcadia foams were launched at the Planete Meuble show in Paris, 25-29 Jan, "drawing significant interest from customers looking to lessen the environmental footprint of their furniture and bedding applications," said a 26 Feb statement from Cargill.
"At Recticel, we are constantly searching for new products that give our customers, and our company, a technical edge," said Nick Wallace, comfort marketing manager for Recticel, in Cargill's announcement. "We chose Cargill's BiOH polyols for our new Arcadia range to introduce renewable resources in the manufacture of our flexible foams."
Recticel found it could use Cargill's "proprietary soybean oil technology … to produce high-quality foams," Wallace continued, adding that, "The implicit reduction in the carbon footprint of the Arcadia foams is already proving to be a popular option."
The foam group is marketing new grades of Arcadia for seating and mattress uses, and said it expects strong sales across Europe.
"We have been selling BiOH polyols to major foam manufacturers in North America for 18 months, now we are selling product in two of the largest markets in the world," commented Yusuf Wazirzada, business manager of Cargill's BiOH product line, going on to praise Recticel's leadership in using renewable polyols. "


Bacteria are often painted as the enemy of humanity. Before the discovery of antibiotics, a wound getting infected was frequently a death sentence
Even with modern medicine, infections such as C. difficile and infectious diseases such as tuberculosis continue to kill many people globally. Crop blights and diseases among livestock cause extensive monetary losses and threaten food security in affected areas.
With all of these reasons to distrust bacteria, it may come as a surprise that certain microbes are immensely beneficial to humanity. Unfortunately, they rarely get to enjoy the limelight.
Our gut microbiomes help us digest complex molecules in our food, and many of the antibiotics we discovered were invented by microbes facing competition from their neighbors. We have leveraged microbes to process sewage and waste for centuries and to ferment food for millennia.
Certain microbes, which have the right metabolic pathways or would be a good chassis for expressing them, are likely to be one of our greatest assets in developing technologies to address climate change, environmental pollution, and the energy crisis.
Microbial metabolism: oxidation and reduction
Living things keep living by producing energy through metabolism. Microbial metabolism primarily occurs through oxidation-reduction processes (redox reactions), exchanging electrons with their environment. Aerobic heterotrophs are bacteria with metabolisms similar to ours— they eat organic molecules (for example, glucose sugar) and breathe oxygen. The electrons used to make energy for these microbes come from their organic “food.”
Alternatively, many microbes acquire electrons from inorganic electron donors, including iron(II). Chemolithotrophs, like Mariprofundus ferrooxydans and Acidithiobacillus ferrooxidans, generate energy by oxidizing (or taking electrons from) soluble iron(II), using CO2 as a carbon source and producing insoluble iron(III) in the process. Photosynthetic iron-oxidizing organisms (photoferrotrophs) like Rhodopseudomonas palustris also oxidize soluble iron(II) to insoluble iron(III), though they use these electrons to drive photosynthesis and CO2 fixation.
Some microbes have evolved mechanisms to acquire electrons from solid electron donors, which includes iron-containing minerals and poised electrodes. This process, referred to as extracellular electron uptake (EEU), ensures cells survive when soluble electron donors are scarce. The organisms above, in addition to extracting electrons from soluble electron donors, can also use EEU to extract electrons from insoluble sources, including solid surfaces. For example, R. palustris and Mariprofundus can both extract electrons from iron minerals and poised electrodes.
Microbes’ ability to perform EEU has significant industrial and biotechnological implications. Iron-oxidizing microbial biofilms on exposed surfaces of metal-containing structures can lead to microbiologically influenced corrosion (MIC). On the other hand, biofilms grown on poised electrodes can facilitate a variety of biotechnological applications, from energy generation to bioplastic production. Acidithiobacillus, due to its tolerance of acidic conditions, could play a role in bioremediation of acid mine drainage.
Other genera of bacteria, such as Shewanella and Geobacter, can also perform an inverse of EEU, by “breathing” iron(III) instead of air. When soluble electron acceptors are scarce, these bacteria can use solid electron acceptors. Shewanella and Geobacter can reduce iron by using it (instead of something like oxygen) as a terminal electron acceptor in a process called extracellular electron transfer (EET). Other bacteria that can perform EET can use other minerals. As we will see in the next section, both EET- and EEU-capable microbes have their uses in the lab and in industry.
These bacteria and ones like them, composing a diverse collection across various taxonomic groups, are collectively called electroactive microorganisms. The very same electrically conductive proteins that these organisms use to transfer electrons to or from minerals in their habitats can be used to interface with electrically charged surfaces such as poised electrodes. Electroactive microbes are a key area of research by electromicrobiologists for their existing and potential applications for industry and the environment. Electrotrophs are able to cut out the middleman and get their electrons directly from electricity, such as that from an electrode. Electrogens, on the other hand, donate electrons to a mineral electron acceptor and can be made to produce electric current by providing a poised electrode as the sole electron acceptor. This is the fundamental principle upon which microbial fuel cells (MFCs) operate.
Applications for Electroactive Microbes
These tiny organisms have enormous potential for scientific and industrial applications. Microbial fuel cells, as mentioned, leverage bacteria to generate electricity. To that same end, anaerobic digesters use a community of bacteria and methanogenic (methane-producing) archaea to eat organic waste, like spent brewery yeast. They also produce methane gas— chemically identical to “natural gas”— to be burnt as fuel. As we move away from a fossil fuel-powered economy, alternative energy sources like these could help supply the planet’s growing energy demands into the future.
Another application is in bioremediation of contaminated land like superfund sites – by seeding these areas with electroactive bacteria found from the environment or genetically modified to the purpose, and feeding the bacteria with electricity from electrodes, it is possible to get them to neutralize dangerous environmental contaminants like petroleum spills or dissolved heavy metals like uranium.
A third application, which shows some of the most promise for being rolled out at an industrial scale in the near future and is the major focus of the rest of this eBook, is microbial electrosynthesis.
Using Bacteria to Synthesize Organics
Biosynthesis is the process of using living organisms like bacteria or yeast to produce complex products from chemically simpler feedstock. Microbial Electrosynthesis (MES) refers to the process of using electroactive microbes to do this. MES comes with benefits over conventional biosynthesis, namely cost/efficiency of running the system— electricity is cheaper and easier to manage than organic electron sources.
Microbial synthesis of organics is already widely used in an industrial setting. For decades, we have used microorganisms to produce chemicals such as “alcohol, antibiotics, antioxidants, and natural colors.”
Rhodopseudomonas palustris TIE-1 (TIE-1) is a species of purple nonsulfur bacteria, named for its rosy color. This talented microbe is a veritable metabolic Swiss army knife, with various metabolic pathways in its back pocket that it can deploy depending on the situation. TIE-1 can use CO2 or organic carbon molecules as a food source, it can get its electrons from oxidizing iron through photoferrotrophy, and, to top it all off, it is capable of EEU from electrodes. Another characteristic, one that significantly advantages it as a chassis for MES applications, is that it is capable of performing anoxygenic (non-oxygen producing) photosynthesis to extract energy from sunlight.
Purple nonsulfur bacteria like R. palustris can be found worldwide in oceans, rivers, lakes, and soils, as their flexible metabolism allows them to eke out a living in a wide variety of places. Their metabolic versatility, as well as their ability to perform photosynthesis for extra energy, makes them prime candidates for MES.
MES allows us to produce a wide range of organic products, but the most industrially relevant are biofuels and bioplastics. Today, the vast majority of plastic and fuel is made from fossil fuels extracted from the Earth— natural gas, oil, and coal. According to the Millennium Alliance for Humanity and the Biosphere (MAHB), a Stanford University initiative, these fossil fuels are running out: by 2100 the natural reserves will run dry if current rates of expenditure hold or increase. This is of course, only part of the problem— burning fossil fuels release their stored carbon back into circulation, increasing atmospheric CO2 levels and changing the climate, causing widespread ecological disasters, unpredictable weather events, and more.
In the United States, 95% of the gasoline we put in our cars contains 10% or more ethanol. Ethanol is the same type of alcohol found in bourbon and other liquors, and— like bourbon— the ethanol that is added to US gasoline is made primarily from corn, fermented by yeast and then distilled to concentrate it. The rationale for blending it with gasoline is twofold. First, ethanol produced this way is renewable, while petroleum is not. Second, burning it contributes less to climate change— USDA estimated that “greenhouse gas… emissions from corn ethanol are about 39 per cent lower than gasoline on an energy equivalent basis.” The primary issue with ethanol as a biofuel is that it directly competes with agriculture for the purpose of human nutrition, which is already an energy and land-intensive industry. Using corn-derived ethanol would cause even bigger issues if we were to switch to a higher percentage of ethanol in gasoline, such as the E85 (up to 83% ethanol) that can be burnt in flexible fuel vehicles. The energy contained in the fuel end product would need to be greater than the energy expended in growing, harvesting, and processing the corn for it to be worthwhile to change over to this biofuel from conventional fuels.
One of the best alternatives to ethanol is n- butanol, another type of alcohol that can be burnt as a biofuel but carries more energy per volume and is less volatile than ethanol. We typically produce it through chemical processes, though various microbes produce it naturally. Using a metabolic pathway called the acetone-butanol-ethanol (ABE) pathway, first discovered in Clostridium acetobutylicum, can allow microbes to ferment organic feedstock (ethanol or propylene) into n-butanol. This pathway has been engineered into other microbes, like E. coli and yeast, but because these organisms are heterotrophs, they still need to be fed organic carbon, running into the same problems as corn fermentation (namely, energy inefficiencies and the use of agricultural resources on the production of biofuels rather than food).
Clostridium, the organism the pathway was discovered in, is a relatively inefficient producer of n-butanol, so researchers began looking for an alternative microbial chassis for the pathway. Using photoautotrophs is more desirable as they can make use of sunlight, our most renewable energy resource. Synechococcus, a cyanobacterium (some of the first oxygen-producing phototrophs and the ancestors of chloroplasts), performed better than Clostridium when the ABE pathway was engineered into it, but there were concerns that the oxygen it produced during photosynthesis would negatively affect the process. This is where microbial electrosynthesis comes in. Here, EEU- capable microbes can produce products like n-butanol under anoxic conditions from CO2 and electrons produced by clean energy, rather than relying on costly organic feedstock to fuel the process.
Researchers in the Bose lab at Washington University in St Louis followed up on this tactic, by choosing the anoxygenic photoautotroph R. palustris TIE-1 as a chassis for n-butanol biosynthesis. This also allowed usage of light as an energy source, CO2 as a carbon source, and electrodes supplied with solar panel-generated electricity, making the biofuel production carbon neutral. Using this or a similar MES platform, industrial-scale bioreactors could produce carbon-neutral biofuel from renewable resources.
Conventional petroleum-based plastics are a pernicious environmental issue, causing pollution both in the form of greenhouse gases during its production and as solid pollution in the form of plastic litter and microplastics, especially in the oceans. Even when disposed of properly and sent to a landfill (only around 20% gets recycled), many forms of plastic can last for the better part of a millennium.
Materials science has made progress with the development of biodegradable plastics— which can be broken down by environmental microbes in years rather than lasting for centuries. However, they still usually require petroleum to produce. Polylactic acid (PLA) is made from fermented plant starch, usually corn, but this comes with similar issues as previously discussed with corn-based biofuels, as well as biodegrading relatively slowly.
Polyhydroxybutyrates (PHBs) are one promising solution for future plastic needs, as they have similar desirable qualities as other plastics (moldability when heated, for example), they biodegrade well, and they are able to be biosynthesized by microbes. Rather than using a heterotroph like E. coli or yeast as a chassis for PHB synthesis, which would face the same issues of feedstock requirements as it would for biofuel production, autotrophic microbes again seem to be the answer when efficiency and carbon neutrality are the goal.
One chemoautotroph, Ideonella spp. O-1, can grow and produce PHBs using industrial exhaust gases made up of CO, CO2, and H2. However, there is the risk of explosion when working with hydrogen gas, and a system like this would be expensive to operate compared to alternatives. Sulfate-reducing bacteria, such as Desulfonema, Desulfosarcina, and Desulfobacterium can also produce PHBs from precursor molecules (caproate, benzoate) without those downsides, but they grow relatively slowly. As with biofuels, TIE- 1 is an attractive system for PHB production. Its ability to grow using an electrode, as well its ability to acquire energy via photosynthesis, makes TIE-1 a very efficient workhorse for MES toward sustainable bioplastic production.
Something that we’ve seen again and again throughout this eBook is that the first microbe that is discovered expressing a given synthetic pathway is not necessarily the optimal platform for scalability or efficiency. Bacteria capable of EET are frequently anaerobes, preferring or requiring an oxygen-free environment, which can pose problems if the goal is a resilient electrosynthesis bioreactor community. Certain microbes, like Clostridium acetobutylicum, are obligate anaerobes, and are killed by exposure to oxygen. Others, like Shewanella oneidensis, are able to survive oxygen exposure, and this is one of the reasons they have become model species of electroactive microbes studied in the lab. And photosynthetic electrotrophs, such as Rhodopseudomonas palustris, have the added benefit of getting energy from sunlight to improve the energy efficiency of their MES.
By poising an electrode at a certain voltage (such as connecting it to a battery) and placing it in an environment, — a body of water, soil, or anywhere else bacteria like to live— it is possible to isolate novel electrotrophic bacteria. The benefits of this are twofold, as it could identify either a strain that could be a better chassis for a known MES pathway, or it could identify a strain with a new (or more efficient version of a known) biosynthetic pathway. As we move away from fossil fuel-dominated industry, discovering ways to microbially synthesize the numerous organic chemicals historically made from petroleum would do a lot to ease the transition.
Microbes have been on this Earth for orders of magnitude longer than we have, and they have had billions of years to evolve and specialize metabolisms for their environmental situations. Evolutionary processes have produced a huge diversity of microorganisms that are more suited for MES in an industrial setting. It is almost certain that we may isolate novel strains, which have evolved through natural selection to be more suitable for applications like MES compared to the few model organisms we study today. In the Bose Lab, we are constantly isolating new microbes from environmental samples, and we hope that some of these will be future models for climate technologies like MES.
To read and download the full eBook ‘The role of microbial diversity in microbial electrosynthesis’ click here
More About Stakeholder
Exploring microbial electrosynthesis at Washington University in St. Louis
Dr Arpita Bose discusses research into bioelectrochemical systems and microbial electrosynthesis at the Department of Biology, Washington University.


Removing arsenic from paddy fields
The presence of the toxic element arsenic in soluble form in groundwater and soils is a serious issue for many parts of the developing world and even in desert regions of the developed world. Researchers in China have now investigated whether ferrihydrite (iron hydroxide) and gypsum (hydrated calcium sulfate) might be able to reduce the bioavailability of arsenic to growing rice plants in paddy fields and so lower the risk of toxicity for those eating the rice. In laboratory studies of pot-grown rice plants bedded in arsenic-contaminated water and soil, the team found that gypsum had no effect but adding ferrihydrite (just 1.5% by volume to the paddy soil) could reduce the amount of arsenic absorbed by the plants to 36% of untreated plants. This compound thus shows promise as a soil improver in arsenic-contaminated regions of the world where rice is grown widely as a food crop.
Chen, X-P., Zhou, J., Lei, Y., He, C., Liu, X., Chen, Z. and Bao, P. (2014) ‘The fate of arsenic in contaminated paddy soil with gypsum and ferrihydrite amendments’, Int. J. Environment and Pollution, Vol. 56, Nos. 1/2/3/4, pp.48–62.
The lean, flipped classroom
For designers, businesses and engineers, “Lean” and “Six sigma” are important process optimization tools for reducing wasted raw materials, human resources, energy and time. The concepts have been used in education too to improve student outcomes and to make educators more effective. Now, US researchers have applied lean and six sigma to another educational paradigm – the flipped classroom. The flipped classroom abstracts the lecturing and resource provision components of education and puts the onus on the student to seek out those materials outside the classroom. From the educators’ perspective, they should in the flipped classroom provide access to what would be conventional lecture materials and resources through online and remote systems. Classroom activities then become more interactive and preclude the conventional notions of note-taking and other activities in a lecture-type teaching environment. The team has demonstrated significant potential for the lean six sigma flipped classroom in its studies.
Kovach, J.V., Carden, L.L. and Ramos, M.A. (2014) ‘‘Flipping’ the Lean Six Sigma classroom’, Int. J. Six Sigma and Competitive Advantage, Vol. 8, Nos. 3/4, pp.227–246.
Sex sells, but not always
It’s a cliché in marketing, that “sex sells”, but a study of a diverse demographic in the Middle East by researchers at the American University of Kuwait, in Safat, suggests the opposite. They have found that sexually provocative imagery of people and celebrities in visual advertisements can often be so much of a distraction to potential consumers that the product being advertised is often forgotten the face of scantily clad bodies and naked people. The team found, in their marketing research, that consumers of different genders, ethnicities, nationalities and age often focused their attention away from a product. The researchers suggest that the distraction may be one of a negative social and religious stance leading to a failure on the part of such marketing.
Mostafa, A.A. and Bahman, R.D. (2014) ‘The effect of provocative visual advertisement on the consumer’, Int. J. Teaching and Case Studies, Vol. 5, Nos. 3/4, pp.339–348.
Superhydrophobic materials are substances with a surface that by virtue of its nanoscopic structure repels water and sometimes other polar materials to the point where they simply cannot be “wetted”. Such materials have the potential to revolutionize a wide range of engineering applications but might also be used as highly biocompatible, non-stick coatings for replacement joints, artificial heart valves and other prosthetic, implanted body parts. Now, researchers in Egypt have demonstrated a straightforward way to make the common plastic material polypropylene superhydrophobic and self-cleaning for use in biomedical applications. Scanning electron microscopy and spectroscopic studies prove that the products are indeed superhydrophobic. And biological tests show that water is totally repelled from the surfaces. Moreover, bacteria such as the common superbug Staphylococcus aureus cannot adhere to these materials.
Abbas, R., Sadik, W.A., El Demerdash, A.G.M. and Badria, A.F. (2014) ‘A simple method to prepare superhydrophobic polypropylene coatings for biomedical applications’, Int. J. Nanoparticles, Vol. 7, Nos. 3/4, pp.156–169.


Prof. Jennifer Rupp
Jennifer Rupp is specialist in designing solid-state materials for new ways of energy storage as well as for information devices. The first topic includes stable hybrid and solid-state batteries with a high capacity and materials to convert solar energy into synthetic fuel. In the field of information storage and transfer, Jennifer Rupp for example develops neuromorphic computing materials and elements that work beyond classic binary digit transistors.
She studied at the University of Vienna, earned her doctoral degree in material science at ETH Zurich, and worked at NIMS Tsukuba Japan and MIT as postdoc. From mid 2012 to 2016 she was a non-tenure track assistant professor at ETH, and joined MIT as assistant and associate professor from 2017 till September 2021. Since October 2021 Jennifer Rupp holds a professorship on Solid-State Electrolyte Chemistry at TU Munich and immediately became member of e-conversion.
The scientist is not only author of a multitude of publication, patents and winner of various honors and awards. She is also very active in the public and political discussion on material technology trends for energy issues. Furthermore, Prof. Rupp regularly gives lectures at famous institutions such as the Royal Society and the Word Economic Forum. In an initiative to foster shift in statistics towards more balance in gender and ethnicity in academic and industry leadership roles she founded the LILA-mentorship program. She is an active consultant and serves as board member for a wide portfolio of companies focusing either on the production-side of inorganic solid state materials or on performance engineering and design of energy devices.
We are happy to welcome such a highly experienced and engaged young scientist in the community of e-conversion!


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Single crystal of heavily Yb3+-doped Lu3Al 5O12 (Yb:LuAG) were grown by the micro-pulling-down method. Radio- and photoluminescence spectra of the Yb:LuAG were studied. Two bands peaking round 340-350 and 480-500 nm could be ascribed to charge transfer (CT) luminescence of Yb3+, as their position nearly coincide with the Yb3+-related CT emission in YAG matrix. The highest emission intensity was observed for Yb concentration of 5% with respect to the Lu site. Temperature dependence of photoluminescence spectra of the Yb: LuAG (5%) was measured and points to remarkable thermal quenching above liquid nitrogen temperature.
- Charge transfer luminescence
- Single crystal growth from the melt


Imal physique weight and tumor volume had been monitored every single second day. Tumor volume (V = 0.five x L x W2) was estimated by measuring two orthogonal diameters (longer dimension: L, and smaller sized dimension: W) of the tumor using electronic NOD2 Storage & Stability calipers. Animals have been sacrificed when greatest tumor dimension exceeded 20 mm, tumor became necrotic, or animal exhibited a body weight-loss of far more than 20 . All other animals were sacrificed by day 20. Protocols have been authorized by the University of Nebraska Medical Center Institutional Animal Care and Use Committee. Statistical variations have been IRAK4 list determined utilizing a one-way ANOVA followed by Tukey’s test for comparison of treatment. All statistical analyses have been carried out using GraphPad Prism Computer software (Version five.0, GraphPad Software, CA, USA). The p-values less than 0.05 had been considered statistically substantial.Results and DiscussionDesign and Synthesis of Cross-linked Nanogels We extended our synthetic method working with a template-assisted procedure so that you can develop biodegradable cross-linked nanogels (Figure 1). The proposed design and style implicates a replacement from the PMA core segment of your previously reported nondegradable PEG-bPMA nanogels with enzymatically degradable poly(L-glutamic acid). Nonetheless, the condensation of block copolymer precursor, PEG-b-PGA, with Ca2+ ions did not result in the formation of micellar templates. To address this concern, hydrophobically modified PEG-bPGA derivatives (PEG-b-PPGA) were synthesized by carbodiimide mediated grafting of PGA segments with L-phenylalanine methyl ester (PME) moieties. Two PEG-b-PPGA copolymers with diverse degrees of PME grafting have been prepared by varying the molar ratio from the glutamic acid residues of PEG-b-PGA to PME. The degrees of PME grafting had been 17 and 30 as was determined by 1H-NMR evaluation. These copolymers are additional denoted as PEG-b-PPGA17 and PEG-b-PPGA30, respectively.J Drug Target. Author manuscript; out there in PMC 2014 December 01.Kim et al.PageHydrophobically modified water-soluble polymers and polyelectrolytes exhibit unusual aqueous remedy behavior due to hydrophobic associations that occur in an effort to lessen water-hydrophobe contacts (McCormick CL, 1989). The tendency of intra- or intermolecular association strongly is determined by macromolecular architecture, in particular, on the number and distribution of hydrophobic groups along the polymer backbone. Fluorescent technique using pyrene as a probe is broadly made use of for characterization of the selforganization of hydrophobically modified polymers as well as the nature of as a result formed hydrophobic domains. This process is according to the sensitivity of the spectroscopic properties of pyrene to the polarity of its microenvironment. The partitioning of your pyrene probe into the significantly less polar atmosphere final results in a characteristic lower in the intensity ratio from the third and first vibrational peaks (I1/I3) together with growing fluorescence intensity. Steady-state fluorescence spectra of pyrene in the presence of PEG-b-PPGA copolymers were utilized to qualitatively characterize the association of phenylalanine groups or lack thereof. Figure 2A depicts the dependence of I1/I3 values of pyrene as a function of PEG-bPPGA concentration in aqueous options (ten mM phosphate buffer, pH 7.0). In aqueous or similarly polar environment I1/I3 ratio is identified involving 1.6 and 1.9 (Dong and Winnik, 1982, Kalyanasundaram and Thomas, 1977). As anticipated, I1/I3 value measured for pyrene in options of double hydrophi.


Personal cleanliness is one of the habits necessary to maintain the health of the body and feel good. And the products we use to do this are in contact with us in such a profound way that could almost be compared to food.
Today I just want to emphasize the importance of the care and well-being of the largest organ of our body, the skin, deepening a popular topic these days: what substances we are using to moisturize, cleanse, and beautify our skin? Do you know that 90% of chemicals used in cosmetics “synthetic” are derivatives of petroleum?
You have to know that substances in cosmetic products do not remain in the top layer of skin but are absorbed; one side is eliminated through organs like the liver, kidneys and lymph channels but another part builds up in organs and tissues could cause problems such as hormonal disorders of or cancer.
Most of us during the day you will be taken care of your body, of your hair, your face, intimate hygiene and oral and will then be used…
Shampoo, conditioner, hair spray, hair mousse, body lotion, deodorant, perfume, cologne, face cream, tonic, cleanser, tricks, glazes, lipsticks, shaving foam, after shave cream, toothpaste, mouthwash, intimate gel, etc.
How many of these products were natural? How many of these products hide toxins in it? And especially … it is necessary to use so many products?
It is important to know that in cosmetics ingredients are listed starting from the most content up to that present in minimum quantities. So watch what you read!
List of main toxic ingredients in cosmetics
Let’s see now what are the main toxic ingredients to avoid and why…
Paraffin and petroleum derivatives
Label look like: mineral oil, paraffinum, paraffinum liquidum, petrolatum, silicone quaternium, Methylsilanol, wax microcristalina, Ozokerit, ceresin, vaseline.
Mostly used in moisturizing creams or lipsticks, they give to the skin or lips a false appearance of “brilliant”; in reality the cover as if it were a plastic casing by blocking the cell respiration. Are substances that can cause acne, irritation, dermatitis, rashes, dry skin, skin spots and especially … premature aging. Just what you’re trying to avoid in applying a cream. Do not you believe it? Make an experiment … stop using the cream with the substance in question and see how it will look even more dry and damaged than when you started using it! Normal, because in fact you were not moisturizing or nourishing as you thought.
The label appear as: -anilid- or -anilin- as for example acetanilid, HC (HC orange 3), Acid (Acid Red 73), Pigment (Pigment Green 7), Solvent (Solvent Black 3), Cl followed by a number (Cl 12700, Cl17200, etc.).
Make creams, bath foam tricks or attractive to the eye but human carcinogens! It’s worth?
Label appear as: PEG + number, Steareth, ceteareth and everything ends in PPG, Polyehtylene, Hidroxyporpyl, etc.
Emulsifiers are used to obtain the desired emulsion between water and fat (do not separate the two phases).
Actually applied to the body, they also help eliminate the skin’s natural protection factor making it more vulnerable and less impervious to toxic substances.
You may also like to read another article on EGoodH: 8 ways to use olive oil as a natural beauty product
Sodium Lauryl Sulfate and Sodium Laureth Sulfate
Also avoid: Ammonium Lauryl sulfate, Disodium Laureth Sulfosuccinate, Sodium Sulfate myreth.
They are best used in shampoo detergents, shower gel, toothpaste.
They are very irritating and can easily absorb in our body, especially in the tissues of the heart, liver, lungs, eyes. It is accepted by the “cosmetic ingredients review” in infrequent use of products and only at a concentration of 1%. This is not just what happens in reality … and often we find it at the top among the ingredients (i.e. among those in greater quantities).
Saviors of formaldehyde
Label appear as: DMDM + a name (e.g. DMDM hydantoin), diazolidinyl urea, imidazolidinyl urea.
Formaldehyde is one of the cheapest and existing effective preservatives in the market, its use is prohibited in cosmetics saw its carcinogenic and teratogenic (causes birth defects in the fetus). From here, the cosmetics industry genius who decided to use formaldehyde liberators, apparently different but the toxic end the same way.
The label appears as: Aluminium Chloride, Chlorohydrex Aluminium, Aluminium Chlorhydrate, etc.
Used as anti-perspirant deodorants, causing a sweat reduction and preventing the elimination of toxins through the axillary; in this way toxins accumulate in the lymphatic glands of the arm and this in the long run may cause especially localized tumors such as breast.
Perfumes or fragrances
Label look like: Parfum or fragrance .
Are present in perfumes, shower gel, soaps, deodorants, baby products, shampoos, creams … say a little everywhere!
Make it as pleasant smelling product … … irresistible! But in fact are dangerous substances that accumulate, can be carcinogenic and can affect hormonal balance! It’s worth?
Label appear as: DEHP, DMP, DBP, BBP4, DINP, DIDP, DNOP.
They are used as solvents and are found in shampoos, enamels, lacquers, etc..
Are highly toxic, influence on hormonal balance and are suspected carcinogens.
Label appear as: Benzophenone-2, Benzophenone-3, oxybenzone, Octocrylene, 4-Methybenzyliden Camphor, Ethyl-hexylcinnamate, Octyl-dimethyl PABA, etc.
Have a carcinogenic behavior, they can trigger allergies, accumulate in the body and alter the hormonal balance. And you who wanted only to protect you from the sun!
Label appear as: Benylparaben, Butylparaben, Ethylparaben, etc.
They are the cheapest and effective preservatives used by the cosmetic industry. Present in shampoos, creams, Shaving products, lubricants, toothpaste, etc.
Produce irritation, dermatitis and rashes in many cases are dangerous and applied to the skin daily.
Recognized as toxic and carcinogenic, you can still find it in lipsticks. More lipstick is long lasting as the risk of containing lead is high.
It is an additive (synthetic antioxidant) related with allergies, liver problems and digestive system.
It is used to generate foam in certain cosmetic products such as shampoo or shower gel.
It accumulates in the liver and kidneys and promotes the appearance of cancer.
It is an additive that accumulates in the body and is joined to the heavy metals. Very difficult to eliminate.
Natural Cosmetics: The healthy alternative
After all this roundup of toxic information, you must be wondering: “Is there a healthy alternative to all this?”.
Yes, the natural or organic cosmetics, becoming more common on the market and more and more delicate with your skin.
But be careful! Again it is always best to read the labels … unfortunately not enough to read bio, eco or natural to be sure it does not contain anything too! There is always some company that wants to take advantage of it and try to fool the customer, perhaps with attractive prices compared to the market.
It then looks for quality in these simple tips…
- since the natural and organic cosmetics are usually more expensive, by initially priority to those who are more in touch with your body, such as a moisturizer, deodorant, toothpaste, a cream after shaving, etc..
- Bio seeks certification in the case of organic products, but do not stop there, ask more information on substances that are on the label to a specialist or manager of the department store or herbal medicine.
- Make sure they are not tested on animals.
- An excessively economic natural product is not a good quality signal seen that they are generally more delicate products, lower production cost and free of synthetic components.
- They have a generally shorter maturity of the synthetic products as they do not contain artificial preservatives.
What you will notice about you?
- The skin will begin to breathe and regenerate naturally; will look more beautiful, young, fresh and bright.
- The hair will gain strength and will fall less far.
- The nails will return shiny and strong.
- You discover the scent of your body and you will notice how unnatural all these synthetic fragrances of conventional products.
- Rediscover the use of simple and natural products such as soap and cosmetic vegetable oil.
- After a few months, you cannot help it and abandon the use of toxic products, hazardous chemicals and you were using.


STRUCTURAL AND NUTRITIONAL CHANGES IN IRRADIATED FOOD PROTEINS (ANTIOXIDANTS, QUALITY, PROCESSING EFFECT TOXICOLOGY, RADIATION).
AuthorKRUMHAR, KIM CARLETON.
KeywordsIrradiated foods -- Nutrition.
MetadataShow full item record
PublisherThe University of Arizona.
RightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
AbstractA two part study was designed to investigate radiation-induced structural and nutritional changes in food proteins. Model systems composed of 0.1-10% myoglobin, lactalbumin or BSA were used and the effects of propyl gallate, ascorbic acid, air or nitrogen, pH 5, 6 or 7 citrate or phosphate buffer, and addition of glucose and SDS were investigated. We found that 0.02-0.04% propyl gallate (PG), alone or in conjunction with other solutes, inhibited protein aggregation after irradiation to 0.5 and 1.0 megarad and subsequent -20 C storage for 3-6 months. PG alone at 0.04% yielded up to 90% retention of myoglobin after 0.5 megarad and up to 94% retention of lactalbumin after 1.0 megarad as compared to unirradiated controls. BSA appeared more radiation sensitive than other proteins, and use of 0.02% PG yielded retention of only 10% of the original protein after 1.0 megarad. Use of synergists such as glucose or SDS together with PG allowed up to a two-fold increase in protein retention, while use of 0.02% ascorbic acid led to lower retention compared to samples irradiated alone in control buffer. Irradiations at pH 5 and 6 yielded greater protein retention than at pH 7. Isoelectric focusing of myoglobin revealed acidic shifts in protein pI with new bands at pH 4.9-5.2 after irradiation at pH 6 with glucose and PG. A similar acidic shift was seen in focusing lactalbumin, with major new bands forming at pH 3.7-4.0 after irradiation in pH 6 phosphate with 0.04% PG. BSA showed a bipolar pattern of pI shifts after irradiation in pH 6 phosphate. Mice fed irradiated lactalbumin in factorial studies grew slightly faster and ate more than unirradiated controls, while those fed protein irradiated with 0.02% PG showed slightly decreased rates of gain and feed consumption. Amino acid analysis revealed a 35% decrease in lysine, as compared to control, in diets prepared with protein irradiated to 1.0 megarads in 0.05 M phosphate, pH 6 with 0.02% PG. The negative effects of PG on feeding and growth were reduced when protein was irradiated at 22.5% rather than 15% (w/v). Liver to body weight ratios among animals fed protein irradiated with PG were decreased by 18% in contrast to control animals fed identical, though unirradiated, diet. (Abstract shortened with permission of author.)
Degree ProgramNutrition and Food Science