Team IGEM Bielefeld built a Synthetic Biofilter to Remove Estrogens from Drinking Water

This project has the potential to solve problems of micro contaminations in sewage water

Removing Estrogen from Drinking Water

image of a sewage plant
Sewage Plant in Bielefeld – Hundreds of samples were needed to reach success: The synthetic biofilter developed by Bielefeld University’s iGEM team can filter out estrogens from contaminated water.

The birth control pill is a widespread contraception method. However, large amounts of these modified estrogens leave the body again in urine. The conventional methods in sewage treatment plants are unable to treat this waste water sufficiently because the most frequently used estrogen ethinylestradiol is very difficult to break down. As a result, the hormone finds its way into rivers and lakes and also accumulates in drinking water with serious consequences for fish and other aquatic life. These range from reproductive and severe developmental disorders to the formation of female sexual characteristics in males. The long-term consequences of increasing estrogen pollution for human beings are still largely unknown. Nonetheless, declining sperm counts and thereby increasing infertility in men living in industrial nations may well relate to this hormonal pollution. In addition, testicular and prostate cancers as well as osteoporosis (a reduction in bone density) could be a consequence of overly high concentrations of estrogen in the human body. The goal of the Bielefeld iGEM team is to develop a biological filter in which certain enzymes (so-called laccases) break down the estrogen.

Bielefeld students on a par with teams from international elite universities

Months of painstaking work in the laboratory at Bielefeld University‘s Center for Biotechnology (CeBiTec) have paid off: the 15 students participating in this year’s ‘international Genetically Engineered Machine competition’ (iGEM) at the Massachusetts Institute of Technology (MIT) have good reason to celebrate. The goal of their project was to develop a biological filter that removes estrogen from drinking water. It was a success: they managed to produce enzymes that break down the hormone. On Monday 5 November, the competition finals came to a close in Boston. From 190 teams throughout the world, Bielefeld’s students made it through to the ‘Sweet Sixteen’, the selection of the 16 best teams in the company of teams from such prestigious universities as Stanford University (USA), the Canadian University of Calgary, and Jiaotong University in Shanghai, China.

More than 70 teams from throughout the world got through to the finals of the top student competition in synthetic biology. The Bielefeld team was one of five German teams at the start. Bielefeld University has now participated in the iGEM competition for the third year running and already succeeded in qualifying for Boston in 2010 and 2011. This year’s team, like its predecessors, made it into the ‘Sweet Sixteen’. ‘We stand in direct comparison with universities like Stanford and Cornell. At first, that seemed very intimidating, but we soon noticed they were having to fight exactly the same problems as we were. And with our know-how, we can match the pace here’, says Moritz Müller, a master student of molecular biotechnology.

Enzymes from fungi growing on trees filter out medicine residues from sewage and drinking water

Conventional methods of filtering waste water in sewage treatment plants are unable to completely remove medicine residues such as the estrogens in birth control pills. These residues then find their way into rivers and lakes and also accumulate in our drinking water. For fish and other aquatic life, estrogens can lead to reproductive and developmental disorders and even to the formation of female characteristics in males. The potential long-term consequences for human beings – declining sperm counts, infertility, various cancers, and osteoporosis – are still largely unknown.

The Bielefeld iGEM team has developed a biological filter in which specific enzymes (so-called laccases) break down these medicine residues. One known source of particularly efficient laccases is the turkey tail, a type of fungus that grows on trees. Using methods from synthetic biology, the students succeeded in synthesizing this enzyme and applying it to filter material. ‘We didn’t want to invent something totally crazy with our project – just because it’s technically feasible. We wanted to do something that could actually be put to use in the near future, perhaps in 20 years, and be a real benefit’, explains Robert Braun, a master student of molecular biotechnology. ‘The biofilter is such a project. And we have shown that our idea works. In principle, a company could now come along and develop our filter further. We ourselves have got to get back to our studies – most of us have rather neglected them for the last 6 months. However, the experiences we have gathered more than compensate for that’.

International competition

The iGEM competition has been held every year since 2003 by the Massachusetts Institute of Technology (MIT) in Boston. Starting as an MIT study course, the number of competitors has grown rapidly from five teams in 2004 to 190 in the present year. All teams face the same task: taking their project from the idea across the laboratory work to gaining funding and communicating the findings. On the student level, the iGEM can be seen as the world championship in synthetic biology that shows the future potential of this still young field of research. The Bielefeld iGEM team is being funded by Bielefeld University‘s Center for Biotechnology (CeBiTec) and the BIO.NRW Cluster Biotechnology North Rhine-Westphalia.

Sources:
  • TOXIC COMPOUNDS IN NATURAL WATER – A CASE FOR LACCASE, Team:Bielefeld-Germany, 2012.
  • Synthetic biofilter wins through to the top ‘Sweet Sixteen’ in Boston, ekvv.uni news, Nov 2012.
  • Removing estrogen from drinking water, Phys.org News, June 2012.

PVC Flooring related to Human Uptake of Phthalates in Infants

#Phthalates – used as softeners in PVC flooring material and suspected as #EDCs – are absorbed by the body of the infants and the amount absorbed depends up on the body area of the infants.

Image of an infant on pvc flooring
Phthalates are absorbed by the body of  infants. The amount absorbed depends up on the infants body area

Phthalates are chemical compounds present in commonly used materials like cleaning solvents, toys, etc. They are also used as softeners in poly vinyl chloride (PVC) flooring material. Earlier studies have found that phthalates can result in several chronic diseases in children like asthma and allergies. They are suspected to be endocrine disrupting chemicals (EDCs). A 2012 study conducted by scientists from Karlstad University in Sweden and published in the journal Indoor Air has found that phthalates can be absorbed by the bodies of infants and produce asthma in them.

For their research, the scientists led by Carl-Gustaf Bornehag, professor of public health at Karlstad University, randomly selected 83 children from Varmland, Western Sweden. All the children were between the ages of two and six months. Urine samples, collected from the children, were analyzed for the presence of metabolites of di-ethyl phthalate (DEP), di-butyl phthalate (DBP), butyl benzyl phthalate (BBzP) and di-ethylhexyl phthalate (DEHP). The family members of the children were also asked to fill up a questionnaire elated to their lifestyles and to their indoor environmental factors including the flooring material used in their homes.

The researchers found that the levels of metabolites of BBzP were significantly higher in those infants whose bedroom had PVC flooring. It was also seen that the levels of this metabolite in the urine corresponded to the surface area of the infants. It was noted that the levels of the metabolites of DHEP were higher in two months old infants who were not solely on breast milk compared to those who were completely breast fed.

The study clearly shows that phthalates are absorbed by the body of the infants and the amount absorbed depends up on the body area of the infants. These chemicals also reach the infant formula through indoor dust and can be absorbed through the food.

Sources and More Information:

Mammography Screening Behaviors of Women exposed prenatally to DiEthylStilbestrol

Because of the potential elevated risk for breast cancer in women exposed prenatally to DES, continued monitoring is recommended for this group, which is predominantly over the age of 45

Abstract

image of PubMed NCBI The Endocrine Society logo
Because of the potential elevated risk for breast cancer in women exposed prenatally to DES, continued monitoring of standard mammography recommendations is recommended for this group, which is predominantly over the age of 45.

BACKGROUND:
In utero diethylstilboestrol (DES) exposure is a risk factor for rare development of vaginal and cervical cancer and may potentially be a risk factor for breast cancer.
Mammography use in this population is relatively unknown; therefore, this study aims to determine if in utero DES exposure is associated with the frequency of mammography screening examinations while considering demographic and clinical factors.

METHODS:
Using combined DES cohort questionnaire data, self-reported mammography screening over the past 5 years (2001-2006) was analyzed in women aged ≥45 years. Binary logistic regression assessed if DES exposure was associated with mammography use after adjustment for benign breast disease (BBD), previous cancer diagnosis, and whether insurance access influenced screening use.

RESULTS:
Overall, the frequency of mammography examinations was similar for both DES-exposed and unexposed women. DES-exposed (n=2986) and unexposed women (n=1397) over the age of 44 reported receiving ≥3 mammography examinations in the past 5 years (73.8% and 74.0%, respectively). After adjustment, DES exposure was not associated with ≥3 mammograms in the past 5 years compared to ≤2 examinations (odds ratio [OR] 1.00, 95% confidence interval [CI] 0.86-1.17), p=0.99).

CONCLUSIONS:
In utero DES exposure was not associated with mammography use, nor was health insurance status or a BBD or cancer diagnosis. Because of the potential elevated risk for breast cancer in women exposed prenatally to DES, continued monitoring of standard mammography recommendations is recommended for this group, which is predominantly over the age of 45.

Sources

  • Mammography screening behaviors of women exposed prenatally to diethylstilbestrol, NCBI, PMID: pubmed 22150213, 2012 Feb;21.
  • Full text: Mary Ann Liebert, Inc. publishers, doi:10.1089/jwh.2011.2741.
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Six Times as Many People Died of Methadone Overdoses in 2009 than a Decade Before…

Use prescription painkillers only as directed by a health care provider
Get help for substance abuse problems if needed (1-800-662-HELP)

Prescription Painkiller Overdoses in the US 2012
Use prescription painkillers only as directed by a health care provider – Get help for substance abuse problems if needed (1-800-662-HELP) – @CDC_eHealth

Prescription painkiller overdoses – opioid or narcotic pain relievers, including drugs such as Vicodin (hydrocodone), OxyContin (oxycodone), Opana (oxymorphone), and methadone – were responsible for more than 15,500 deaths in 2009. While all prescription painkillers have contributed to an increase in overdose deaths over the last decade, methadone has played a central role in the epidemic. More than 30% of prescription painkiller deaths involve methadone, even though only 2% of painkiller prescriptions are for this drug. Six times as many people died of methadone overdoses in 2009 than a decade before.

Methadone has been used safely and effectively to treat drug addiction for decades. It has been prescribed increasingly as a painkiller because it is a generic drug that can provide long-lasting pain relief. But as methadone’s use for pain has increased, so has nonmedical use of the drug and the number of overdoses.

Sources
  • Prescription Painkiller Overdoses in the USCDC,methadoneoverdoses, July 2012 – PDF.
  • Vital Signs: Overdoses of Prescription Opioid Pain Relievers — United States, 1999–2008CDCmm6043a4.htm, November 4, 2011

Prenatal DES Exposure – Altered Immune Functions and Increased Susceptibility to AutoImmune Disease

Prenatal exposure of mice to diethylstilbestrol disrupts T-cell differentiation by regulating Fas/Fas ligand expression through estrogen receptor element and nuclear factor-κB motifs

Abstract

image of PubMed NCBI The Endocrine Society logo
Prenatal exposure to Diethylstilbestrol DES may affect T-cell differentiation and cause long-term effects on the immune functions .

Prenatal exposure to Diethylstilboestrol (DES) is known to cause altered immune functions and increased susceptibility to autoimmune disease in humans. In the current study, we investigated the effect of prenatal exposure to DES on thymocyte differentiation involving apoptotic pathways. Prenatal DES exposure caused thymic atrophy, apoptosis, and up-regulation of Fas and Fas ligand (FasL) expression in thymocytes. To examine the mechanism underlying DES-mediated regulation of Fas and FasL, we performed luciferase assays using T cells transfected with luciferase reporter constructs containing full-length Fas or FasL promoters. There was significant luciferase induction in the presence of Fas or FasL promoters after DES exposure. Further analysis demonstrated the presence of several cis-regulatory motifs on both Fas and FasL promoters. When DES-induced transcription factors were analyzed, estrogen receptor element (ERE), nuclear factor κB (NF-κB), nuclear factor of activated T cells (NF-AT), and activator protein-1 motifs on the Fas promoter, as well as ERE, NF-κB, and NF-AT motifs on the FasL promoter, showed binding affinity with the transcription factors. Electrophoretic mobility-shift assays were performed to verify the binding affinity of cis-regulatory motifs of Fas or FasL promoters with transcription factors. There was shift in mobility of probes (ERE or NF-κB2) of both Fas and FasL in the presence of nuclear proteins from DES-treated cells, and the shift was specific to DES because these probes failed to shift their mobility in the presence of nuclear proteins from vehicle-treated cells. Together, the current study demonstrates that prenatal exposure to DES triggers significant alterations in apoptotic molecules expressed on thymocytes, which may affect T-cell differentiation and cause long-term effects on the immune functions.

Sources:
  • Prenatal exposure of mice to diethylstilbestrol disrupts T-cell differentiation by regulating Fas/Fas ligand expression through estrogen receptor element and nuclear factor-κB motifs, NCBI, PMD: 22888145, doi: 10.1124/jpet.112.196121. Epub 2012 Aug 10. Full text PMC3477208 J Pharmacol Exp Ther. Nov 2012; 343(2): 351–361.
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About One-Third of People with Autism also have Epilepsy

The connection between Autism and Epilepsy

Epilepsy in young adults with autism: a prospective population-based follow-up study of 120 individuals diagnosed in childhood

Abstract

Jasper's Basic Mechanisms of the Epilepsies
The Connection between Autism And Epilepsy

PURPOSE:
Little is known about the long-term outcome of epilepsy in autism and the epilepsy characteristics of adults with autism. This prospective population-based study was conducted in an attempt to point out differences on a group basis between adults with autism with or without epilepsy, and to describe the occurrence, the seizure characteristics, and the outcome of epilepsy in autism.

METHODS:
One hundred eight of 120 individuals with autism diagnosed in childhood and followed up prospectively for a period of 13-22 years were reevaluated at ages 17-40 years. As adults, the majority had mental retardation and autistic disorder or autistic-like condition. Interviews were performed with the caretakers of 42 of 43 individuals with a history of epilepsy, and their medical records were reviewed.

RESULTS:
Adults with autism and mental retardation constituted a severely disabled group. On a group basis, both the cognitive level and the adaptive behavior level were lower in the epilepsy group than in the nonepilepsy group (p<0.05). In all, 38% had epilepsy. One third had epilepsy onset before age 2 years. Remission of epilepsy was seen in 16%. Partial seizures with or without secondarily generalized seizures were the dominating seizure type.

CONCLUSIONS:
In a community sample of individuals with autism followed up from childhood through to adult age, one of three had epilepsy since childhood/adolescence. Severe mental retardation and autism are significantly associated with epilepsy, especially in female patients. Seizure frequency has a great impact on the individuals’ lives. Specialist medical care is needed in this severely communication-disabled population.

Pathophysiology of Epilepsy in Autism Spectrum Disorders

Excerpt

Epilepsy occurs frequently in individuals with autism spectrum disorders (ASD). However, the mechanisms responsible for increased seizure susceptibility in ASD are largely unknown. Clues to neural hyperexcitability in the autistic brain might be derived from disorders in which single gene mutations cause both epilepsy and an autistic phenotype, such as fragile X syndrome and tuberous sclerosis complex. This chapter summarizes current understanding of epilepsy in individuals with ASD and explores potential links between the genetic disruption of neural circuits and cellular signaling pathways that contribute to both epilepsy and ASD.

Sources and Press Release
  • The Connection Between Autism And Epilepsy, LiveScience, 45951-autism-epilepsy-connection by Dr. Megdad Zaatreh,
    May 29, 2014.
  • Pathophysiology of Epilepsy in Autism Spectrum Disorders, NCBI, PMID: 22787637, National Center for Biotechnology Information (US); 2012. Full text NBK98169.
  • Epilepsy in young adults with autism: a prospective population-based follow-up study of 120 individuals diagnosed in childhood, NCBI, PMID: 15946331, Epilepsia. 2005 Jun;46(6):918-23.
    Full text PDF.

Estrogen Receptor-α mediates DES-induced Feminization of the Seminal Vesicle in Male Mice

These data suggest that DES-induced SV toxicity and feminization are primarily mediated by Estrogen Receptor-α; however, some aspects of androgen response may require the action of ERβ

Abstract

image of PubMed NCBI The Endocrine Society logo
Feminization of the male mouse reproductive tract after prenatal exposure to Diethylstilbestrol.

BACKGROUND:
Studies have shown that perinatal exposure to the synthetic estrogen diethylstilbestrol (DES) leads to feminization of the seminal vesicle (SV) in male mice, as illustrated by tissue hyperplasia, ectopic expression of the major estrogen-inducible uterine secretory protein lactoferrin (LF), and reduced expression of SV secretory protein IV (SVS IV).

OBJECTIVES:
The present study was designed to evaluate the role of the estrogen receptor (ER) in this action by using ER-knockout (ERKO) mice.

METHODS:
Wild-type (WT), ERα-null (αERKO), and ERβ-null (βERKO) male mice were treated with either vehicle or DES (2 μg/day) on neonatal days 1-5. These mice were divided into two groups: In the first group, intact mice were sacrificed at 10 weeks of age; in the second group, mice were castrated at 10 weeks of age, allowed to recover for 10 days, treated with dihydrotestosterone (DHT) or placebo, and sacrificed 2 weeks later. Body weights and SV weights were recorded, and mRNA expression levels of Ltf (lactoferrin), Svs4, and androgen receptor (Ar) were assessed.

RESULTS:
In DES-treated intact mice, SV weights were reduced in WT and βERKO mice but not in αERKO mice. DES-treated WT and βERKO males, but not αERKO males, exhibited ectopic expression of LF in the SV. DES treatment resulted in decreased SVS IV protein and mRNA expression in WT males, but no effect was seen in αERKO mice. In addition, DES-treated βERKO mice exhibited reduced Svs4 mRNA expression but maintained control levels of SVS IV protein. In DES-treated castrated mice, DHT implants restored SV weights to normal levels in αERKO mice but not in WT mice, suggesting full androgen responsiveness in αERKO mice.

CONCLUSIONS:
These data suggest that DES-induced SV toxicity and feminization are primarily mediated by ERα; however, some aspects of androgen response may require the action of ERβ.

Sources:
  • Estrogen receptor-α mediates diethylstilbestrol-induced feminization of the seminal vesicle in male mice, NCBI, PMID: 22275727, 2012 Apr;120(4):560-5. doi: 10.1289/ehp.1103678. Epub 2012 Jan 24.
  • Additional article information, full text PMC, /articles/PMC3339448/, Apr 2012; 120(4): 560–565. PDF
More DES DiEthylStilbestrol Resources

How the Plastic Particles in Your Food and Water are killing You

BPA and EDCs are associated with many health issues

Aaron Dykes hosts a segment on Bisphenol A, the dangerous estrogenic in plastic drinking bottles and food containers. BPA is a known toxic substance outlawed in Canada and Europe, but still used in the United States, even though the FDA raised concerns regarding exposure of fetuses, infants and young children to the substance.

  • Video by InfoPlanetWars published on 3 Jan 2013.
More information

How to avoid Bisphenol-A

Exposure to BPA – which binds to our steroid receptors, meaning it can affect estrogen, thyroid and testosterone function – has been underestimated

infographics on how to avoid bpa
Exposure to BPA has been underestimated

We know that the active form of Bisphenol-A (BPA) binds to our steroid receptors, meaning it can affect estrogen, thyroid and testosterone function. A new University of Missouri study shows that the exposure to the controversial chemical BPA through diet has been underestimated by previous lab tests.

Read Exposure to BPA has been underestimated, new MU research says / Bye Bye estrogen, thyroid and testosterone, by Health Research Report, Medical Science not Medical Industry

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Guide des 4000 médicaments utiles, inutiles ou dangereux

Les professeurs Bernard Debré et Philippe Even ont rué dans les brancards

image du livre Guide-des-4000-medicaments
Après de violentes critiques de la part d’éminents médecins partout en France, les professeurs Bernard Debré et Philippe Even ont été sanctionnés pour leur guide sur les médicaments.

Après les affaires de l’hormone de croissance, du Vioxx, de l’Isoméride du Mediator, et de plusieurs médicaments retirés du marché en quelques mois, une véritable, mais salutaire inquiétude s’est manifestée dans la population concernant l’utilité et les risques des traitements. La publication soudaine de listes de médicaments “sous surveillance renforcée”, dont beaucoup, inutiles ou dangereux, devraient avoir disparu depuis longtemps, souligne la timidité ou l’incompétence des pouvoirs publics et a fait monter d’un cran l’anxiété des patients. Les professeurs Even et Debré ont donc décidé de passer en revue les 4.000 médicaments sur le marché et d’identifier ceux qui sont efficaces, ceux qui le sont moins, ceux qui ne le sont pas du tout et, parallèlement, d’analyser leur degré de toxicité éventuelle intrinsèque et celle qui pourrait résulter des interactions entre eux, de l’âge des malades et des pathologies associées et préciser quel pays les a découverts, leur prix et leur coût pour la Sécurité Sociale. Ce guide, écrit pour les malades et parfois les médecins généralistes, ne peut évidemment répondre dans le détail à toutes les questions, mais il peut alerter, aider et, en cas de doute, conduire à consulter son médecin. Il devrait aussi aider les politiques à revoir et contrôler réellement le monde délirant des médicaments, ses milliers de médicaments inutiles, ses centaines dangereux.

Lire les commentaires en ligne et ces quelques articles de presse:

  • Pétition: Soutien aux Prs. Debré et Even qui dénoncent la corruption des laboratoires pharmaceutiques! MesOpinions, 20/03/2014
  • Big Pharma : Les Pr Even et Debré sanctionnés pour leur guide sur les médicaments, Chaos-Controle, 19 mars 2014
  • Les professeurs Philippe Even et Bernard Debré interdits d’exercer la médecine pendant un an, Le Monde, 18 mars 2014
  • Les 56 médicaments dangereux ou inutiles, Le Figaro, 13 sept 2012
  • Un livre choc dénonce l’excès de médicaments inutiles, Le Figaro, 13 sept 2012

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