5-LO inhibitors eliminate cells in culture and mouse models
FRANKFURT. Despite improved therapy, only one out of every two adult patients survive acute myeloid leukaemia (AML). The mean survival time for this disease, which predominantly occurs in the elderly, is less than a year for patients over 65 years. It is assumed that leukaemic stem cells, which cannot be completely eliminated during treatment, are the origin of relapse. However, as has been discovered by a team of Frankfurt-based researchers, these cells do have a weakness: In the current edition of the high impact journal "Cancer Research", they report that the enzyme 5-lipoxygenase (5-LO) plays a significant role in the survival of leukaemic AML stem cells.
5-LO is known for its role in inflammatory diseases like asthma. A team led by Dr. Marin Ruthardt from the Haematology Department of the Medical Clinic II and Dr. Jessica Roos, Prof. Diester Steinhilber and Prof. Thorsten Jürgen Maier from the Institute for Pharmaceutical Chemistry showed that the leukaemic stem cells in a subgroup of AML could be selectively and efficiently attacked by 5-LO inhibitors. This was demonstrable in cell culture models as well as in leukaemia mouse models.
"These results provide the basis for the potential implementation of 5-LO-inhibitors as stem cell therapeutic agents for a sustained AML cure, although this must be investigated further in preclinical and clinical studies in humans," explains Dr. Ruthardt. "In addition, there are plans for further molecular biological studies with the objective of understanding exactly how the 5-LO inhibitors act on the leukaemic cells." Prof. Maier continued.
Roos et al.: 5-lipoxygenase is a candidate target for therapeutic management of stem cell-like cells in acute myeloid leukemia, in Cancer Research Volume (2014), Published OnlineFirst July 31, 2014;
Information PD Dr. Martin Ruthardt, Haematology/Medical Clinic II, Tel. +49/ 69/6301–5338, email: firstname.lastname@example.org or Prof. Dr. Thorsten Jürgen Maier, Institute for Pharmaceutical Chemistry, Riedberg Campus, Tel.: +49/69/7982-934, email: email@example.com.
Frankfurt hydrologist publishes more accurate data
FRANKFURT. In what parts of the world and to what degree have groundwater reservoirs been depleted over the past 50 years? The Frankfurt hydrologist Prof. Petra Döll has been researching this using the global water model WaterGAP. Her conclusion: The rate at which groundwater reservoirs are being depleted is increasing, but that the rate is not as high as previously estimated.
In what parts of the world and to what degree have groundwater reservoirs been depleted over the past 50 years? The Frankfurt hydrologist Prof. Petra Döll has been researching this using the global water model WaterGAP. She has arrived at the most reliable estimate to date by taking into consideration processes which are important in dry regions of the world. The values calculated were compared with monitoring data from many different wells and data from the GRACE satellites. These satellites measure changes in the Earth's gravity field. Döll has come to the conclusion that the rate at which groundwater reservoirs are being depleted is increasing, but that the rate is not as high as previously estimated.
90 percent of water consumption is due to irrigation for farming purposes. Only the comparatively small remainder is used for potable water and industrial production. As an example, 40 percent of the cereals produced around the world is irrigated. However, in many cases this results in increased scarcity of water resources and puts a burden on ecosystems. In dry regions, the amount taken from groundwater reservoirs can easily exceed the amount being replenished, so that the groundwater reservoir is overused and depleted.
"By comparing the modelled and measured values of groundwater depletion, we were able for the first time to show on a global scale that farmers irrigate more sparingly in regions where groundwater reservoirs are being depleted. They only use about 70 percent of the optimal irrigation amounts", explains Petra Döll from the Institute of Physical Geography at the Goethe University.
The rate at which the Earth's groundwater reservoirs are being depleted is constantly increasing. Annual groundwater depletion during the first decade of this century was twice as high as it was between 1960 and 2000. India, the USA, Iran, Saudi Arabia and China are the countries with the highest rates of groundwater depletion. About 15 percent of global groundwater consumption is not sustainable, meaning that it comes from non-renewable groundwater resources. On the Arabian Peninsula, in Libya, Egypt, Mali, Mozambique and Mongolia, over 30 percent of groundwater consumption is from non-renewable groundwater.
The new estimate of global groundwater depletion is 113,000 million cubic meters per year for the period from 2000 to 2009, which is lower than previous, widely varying estimates. This can be considered to be the most reliable value to date, since it is based on improved groundwater consumption data which takes the likely deficit irrigation into account, and since the model results correlate well with independent comparative data.
The increased use of groundwater for irrigation also results in a rise in sea levels: According to Döll's calculations, sea level rise due to groundwater depletion was 0.31 millimetres per year during the period from 2000 to 2009. This corresponds to roughly one tenth of the total sea level rise.
The work was funded by the Deutsche Forschungsgemeinschaft through the priority program "Mass transport and Mass distribution in the System Earth".
Publication Döll, P., Müller Schmied, H., Schuh, C., Portmann, F.T., Eicker, A., (2014): Global-scale assessment of groundwater depletion and related groundwater abstractions: Combining hydrological modelling with information from well observations and GRACE satellites. Water Resour. Res. 50, doi: 10.1002/2014WR015595.
Online publication: http://dx.doi.org/10.1002/2014WR015595
Information Prof. Petra Döll, Institute of Physical Geography, Riedberg Campus, Phone: (069)798-40219: firstname.lastname@example.org.
A research unit approved by the German Research Foundation, under the leadership of researchers based in Frankfurt, has made it their goal to throw light on the infection process and the adaptation mechanisms of the bacterium.
The antibiotic-resistant bacterium Acinetobacter baumanii often causes fatal nosocomial infections. A research unit approved by the German Research Foundation, under the leadership of researchers based in Frankfurt, has made it their goal to throw light on the infection process and the adaptation mechanisms of the bacterium. The fundamental insights gained by the research unit will pave the way for the clinical management of this bacterium.
FRANKFURT. Multi-drug resistant bacteria have increased dramatically in hospitals in recent years and present immense challenges to staff and patients, often with fatal results. New pathogens have come to light in the past few years in addition to the bacteria that are already well-known, such as Staphylococcus aureus. One of these is the Gram negative bacterium Acinetobacter baumannii. Today, the German Research Foundation has now approved a new research unit, under the leadership of researchers based in Frankfurt, which will uncover the molecular basis for the dramatic increase in multi-drug resistant A. baumannii strains.
A. baumannii has become a common and excellently adapted nosocomial pathogen in developed countries. It causes 5% to 10% of nosocomial pneumonias and 2% to 10% of all infections in intensive care wards in European clinics. The increase in antibiotic resistance is alarming. The bacterium belongs to the group of six "ESKAPE" organisms that evade antibiotic treatment. Therefore, infections with A. baumannii are frequently fatal.
Several institutes from the Goethe University are involved in the research unit 2251 "Adaptation and persistence of Acinetobacter baumannii": the Department of Molecular Microbiology & Bioenergetics, the Institute of Medical Microbiology and Hygiene, the Institute for Cell Biology and Neuroscience, and the Institute for Biochemistry. The Universities of Cologne and Regenburg, as well as the Robert Koch Institute, are additional collaborators. The researchers will study the biology, infection process and the basis for multi-drug resistance of A. baumannii using a highly interdisciplinary approach. The objective is to determine how it has adapted so well to the hospital environment and what its multi-drug resistance is based on. The answers to these questions will facilitate treatment related to this dramatically increasing nosocomial pathogen.
Information: Prof. Volker Müller, Coordinator of the Research Unit 2251, Molecular Microbiology and Bioenergetics, Riedberg Campus, Tel: (069)798-29507; email@example.com., http://www.bio.uni-frankfurt.de/51172482
The Goethe University is an institution with particularly strong research capabilities based in the European financial metropolis of Frankfurt. It celebrates its 100th year of existence in 2014. The university was founded in 1914 through private means from liberally-orientated citizens of Frankfurt and has devoted itself to fulfilling its motto "Science for the Society" in its research and teaching activity right up to the present day. Many of the founding donors were of Jewish origin. During the last 100 years, the pioneering services offered by the Goethe University have impacted the fields of social, societal and economic sciences, chemistry, quantum physics, neurological research and labour law. On January 1st, 2008, it achieved an exceptional degree of independence as it returned to its historical roots as a privately funded university. Today it is one of the ten universities that are most successful in obtaining external research funding and one of the three largest universities in Germany with centres of excellence in medicine, life sciences and humanities.
Researchers of the German Biodiversity and Climate Centre and the Goethe University now found out, that the prime example of an invasive species is originally from Central Europe and thus no “immigrant” after all.
Frankfurt am Main, Germany, June 18th 2014. Spanish slugs (Arion lusitanicus) are one of the most common slug species in Central Europe. The animals sometimes nicknamed “killer slugs” are known to do their fair share of damage in fields and gardens. The slug was thought to have originated in Southern Europe. However researchers of the German Biodiversity and Climate Centre and the Goethe University now found out, that the prime example of an invasive species is originally from Central Europe and thus no “immigrant” after all. Control measures, such as the EU regulation on prevention, early warning, rapid response, and management of invasive species which is being discussed currently, would therefore not apply to this species.
For some time conservationists have made aware of the fact that the rapidly growing number of brown Spanish slugs is replacing the native black slug in Central Europe as well as inflicting significant damage on natural vegetation and agricultural products. The numbers speak for themselves: today Arion lusitanicus is the most common species of snail in Germany. It is also ranked among the "100 of the worst" invasive animal and plant species in Central Europe that are thought to have a significant negative impact on biodiversity, economy and health. Allegedly the Spanish Slug made its way to Central Europe with imports of fruit and vegetables in the 1950s.
No Spanish slugs to be found in Spain
When taking stock German researchers however could not find a single individual of the slug in its presumed home country. In the spring of 2010 researchers of the Biodiversity and Climate Research Centre and the Goethe University collected 300 specimens of the snail in 60 locations in France, Spain, the UK and the Benelux countries and identified the species they came from. "Instead of the Spanish slug we found numerous, so-called cryptic species, which are indistinguishable using traditional methods of taxonomy which is based on morphology. Therefore, the animals were identified using DNA sequence data" lead author Prof. Markus Pfenninger, who conducts research on BiK-F and the Goethe University and teaches, explains.
Many cryptic species
Many of the specimens examined did not fit to a previously described, genetically characterized species. "We found a lot of unnamed, sometimes highly divergent haplotypes. This indicates the presence of several undescribed Arion species which we only discover using DNA taxonomy. It follows that Arion is very unresolved genus from a taxonomic point of view." But looking into the genes of the slugs yielded even more insights. Shared mutations in the genetic information of different individuals indicate relationships between them. "On the basis of this we created a phylogenetic tree and related it to the geographic distribution. It showed why we could not find Arion lusitanicus in its alleged homeland. The species is definitely not native to Spain but originated in Central Europe" concludes Pfenninger.
EU-regulations on alien species would not necessarily apply
According to experts there are more than 12,000 non-native species in Europe, and the number is increasing. Alien species are one of the main threats to biodiversity and native species as well as causing immense economic damage, e.g. via yield losses in agriculture. In April 2014 the EU parliament therefore approved a proposal for EU-wide measures to ban further import of non-native species and combatting non-native species which are already at home in EU more effectively. “Whether a species is classified as native or not will influence its management policy. Our research goes to show that we should be more prudent in labeling a species ‘invasive’ or non-native when the evidence for anthropogenic introduction is poor”, says Pfenninger and adds: “Perhaps the rapid increase in Spanish slugs we have seen in the last decades is caused by changes of land use practice. It may seem like an invasion when in truth there isn’t one going on “.
For further information please contact
Prof. Dr. Markus Pfenninger
LOEWE Biodiversity and Climate Research Centre (BiK-F)
Tel. +49 (0)69 7542 1841
LOEWE Biodiversity and Climate Research Centre (BiK-F),
Tel. +49 (0)69 7542 1838
In a new study researchers from LOEWE Biodiversity and Climate Research Centre (BiK-F) and the Goethe University Frankfurt am Main present evidence of genetic changes minimizing the harmful effects of H2S which enable the fish to survive in this deleterious environment.
Frankfurt am Main, Germany, May 12, 2014. Hydrogen sulphide (H2S) is a potent inhibitor of aerobic respiration. However populations of shortfin molly fish managed to colonise springs with high concentrations of dissolved hydrogen sulphide. In a new study researchers from LOEWE Biodiversity and Climate Research Centre (BiK-F) and the Goethe University Frankfurt am Main present evidence of genetic changes minimizing the harmful effects of H2S which enable the fish to survive in this deleterious environment. The study provides insight into the molecular mechanisms of this key adaptation for the first time. It is published online today in "Nature Communications".
Shortfin molly fishes (Poecilia mexicana) may only measure a few inches, but they are still exceptional. Populations of Poecilia mexicana, whose relatives are the well-known guppy, colonised sulphide-rich volcanic springs in Southern Mexico. In making this particular habitat their home, they have made the impossible possible, because hydrogen sulphide (H2S), as for many other animal, is lethal. Even at low concentrations the gas blocks the cytochrome c oxidase-complex (COX). The higher the level of hydrogen sulphide, the more the activity of COX is inhibited. As it is essential for respiration, this turns out to be lethal in the end.
Changes in genetic make-up make less susceptible to poison
A team led by Prof. Dr. Markus Pfenninger, LOEWE Biodiversity and Climate Research Centre (BiK-F) and PD Dr. Martin Plath, Goethe University, has taken a closer look at the survivors. Their analysis showed that the COX activity of individuals of shortfin molly fish which colonise H2S-rich waters remains virtually unchanged under high H2S concentrations. This is due to a number of changes in the cox1 and cox3 genes, which have only occurred in populations living in the poisonous springs. Thus, transplanting individuals from non-sulphidic habitat to springs with high H2S levels kills them for sure.
Molecular mechanisms of adaptation to extreme habitat
"In this paper we analyse the key adaptation to an extreme habitat up to its molecular basis at the level of amino acids. This way, for the first time, we are able to point out, where exactly the adaption has taken place." Pfenninger concludes. The team also modelled three dimensional protein structures in order to shed light on necessary significant structural changes of amino acids in the cox1 gene. Without these structural changes, the colonisation of the H2S-containing water for the fish would have been impossible. By colonising the poisonous springs, where there are hardly any other competitors, the fish may feed on resistant midge larvae that also occur there.
Closely related fish follow different paths to adaptation
The study also shows that closely related populations of a species follow parallel as well as disparate paths in response to similar environmental conditions. Three shortfin molly fish populations were sampled for study. Two of the populations show the same changes in their genetic material in adapting to the hostile conditions. However this proved to be not the case for the third population of shortfin molly fish. Whereas these fish also tolerate high levels hydrogen sulphide, the mechanism enabling their adaptation is still subject to ongoing research.
Pfenninger, M. et al.: Parallel evolution of cox-genes in H2S- tolerant fish as key adaptation to a toxic environment – Nature Communications, DOI: 10.1038/ncomms4873
For more information please contact:
Prof. Dr. Markus Pfenninger
Goethe University &
LOEWE Biodiversity and Climate Research Centre (BiK-F)
Tel. +49 (0)69 7542 1841
LOEWE Biodiversity and Climate Research Centre (BiK-F)
Tel. +49 (0)69 7542 1838
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