A "little-noticed" bill signed by President Bush this month, which grants NIH Director Elias Zerhouni greater budget authority over the institute's research, has prompted concern among patient advocacy groups who fear their research will be compromised, the Wall Street Journal reports. Under the law, Zerhouni and future NIH directors will be able to organize a "common fund" that eventually would pool about 5% of NIH's money to fund research projects that span traditional biomedical fields. The institute's budget previously was managed by the 27 separate institutes and centers within NIH, all of which have ties to patient advocacy groups representing a variety of diseases. Such groups are concerned that the common fund will increase "at the expense of their own research, carving money out of their funds," the Journal reports. Zerhouni says new funding will promote trans-disciplinary research, and obesity and nanotechnology research will be high priorities. According to the Journal, a successful pilot project for the common fund, called the NIH Roadmap, "helped bolster the case for more centralized pooling of funds." The NIH Roadmap and other trans-NIH programs currently account for 1% of NIH's budget. Zerhouni acknowledged that it would take "multiple years" for the fund to increase to 5% of the overall budget. Once it does, Zerhouni must report to Congress, which has earmarked $483 million for the common fund in its proposed fiscal year 2007 budget resolution. Under the law, the common fund eventually could grow larger than 5% of the budget. According to Zerhouni, funding will be awarded by a peer-review process and an NIH special council will advise on spending. Rep. Joe Barton (R-Texas), at times a critic of NIH, said the new legislation would "strengthen the research efforts of the NIH and will provide the foundation for future scientific and medical advancement" (Wysocki, Wall Street Journal, 1/31).
"Reprinted with permission from kaisernetwork. You can view the entire Kaiser Daily Health Policy Report, search the archives, or sign up for email delivery at kaisernetwork/dailyreports/healthpolicy. The Kaiser Daily Health Policy Report is published for kaisernetwork, a free service of The Henry J. Kaiser Family Foundation . © 2005 Advisory Board Company and Kaiser Family Foundation. All rights reserved.
вторник, 14 июня 2011 г.
понедельник, 13 июня 2011 г.
Unraveling The Natural History Of The Lion Using Host And Virus Population Genomics
The lion (Panthera leo) is one of the world's most charismatic carnivores. In an article published November 7 in the open-access journal PLoS
Genetics, an international team of researchers provides insights into the genetic structure and history of lion populations. Their work refutes the
hypothesis that African lions consist of a single, randomly breeding (panmictic) population. It also indicates the importance of preserving
populations in decline as opposed to prioritizing larger-scale conservation efforts.
Understanding the broader aspects of the evolutionary history of the lion has been hindered by a lack of comprehensive sampling and appropriately
informative genetic markers. Nevertheless, the unique social ecology of lions and the well-documented infectious diseases they have experienced,
including lion-specific feline immunodeficiency virus (FIVPle), provides the opportunity to study lion evolutionary history using both host and virus
genetic information.
In total, a comprehensive sample of 357 individuals from most of the major lion populations in Africa and Asia were studied. The authors compared the
large multigenic dataset from lions with patterns of genetic variation of FIVPle to characterize the genomic legacy of lion populations. The research
reveals evidence of unsuspected genetic diversity even in the well-studied lion population of the Serengeti ecosystem, which consists of recently
admixed animals derived from three distinct genetic groups.
"The Evolutionary Dynamics of the Lion Panthera leo Revealed by Host and Viral Population Genomics."
Antunes A, Troyer JL, Roelke ME, Pecon-Slattery J, Packer C, et al. (2008)
PLoS Genet 4(11): e1000251. doi:10.1371/journal.pgen.1000251
Click here to view article online
About PLoS Genetics
PLoS Genetics reflects the full breadth and interdisciplinary nature of genetics and genomics research by publishing
outstanding original contributions in all areas of biology. All works published in PLoS Genetics are open access. Everything is immediately and freely
available online throughout the world subject only to the condition that the original authorship and source are properly attributed. Copyright is
retained by the authors. The Public Library of Science uses the Creative Commons Attribution License.
PLoS Genetics
About the Public Library of Science
The Public Library of Science (PLoS) is a non-profit organization of scientists and physicians committed to making the world's scientific and medical
literature a freely available public resource. For more information, visit plos.
Public Library of Science
Genetics, an international team of researchers provides insights into the genetic structure and history of lion populations. Their work refutes the
hypothesis that African lions consist of a single, randomly breeding (panmictic) population. It also indicates the importance of preserving
populations in decline as opposed to prioritizing larger-scale conservation efforts.
Understanding the broader aspects of the evolutionary history of the lion has been hindered by a lack of comprehensive sampling and appropriately
informative genetic markers. Nevertheless, the unique social ecology of lions and the well-documented infectious diseases they have experienced,
including lion-specific feline immunodeficiency virus (FIVPle), provides the opportunity to study lion evolutionary history using both host and virus
genetic information.
In total, a comprehensive sample of 357 individuals from most of the major lion populations in Africa and Asia were studied. The authors compared the
large multigenic dataset from lions with patterns of genetic variation of FIVPle to characterize the genomic legacy of lion populations. The research
reveals evidence of unsuspected genetic diversity even in the well-studied lion population of the Serengeti ecosystem, which consists of recently
admixed animals derived from three distinct genetic groups.
"The Evolutionary Dynamics of the Lion Panthera leo Revealed by Host and Viral Population Genomics."
Antunes A, Troyer JL, Roelke ME, Pecon-Slattery J, Packer C, et al. (2008)
PLoS Genet 4(11): e1000251. doi:10.1371/journal.pgen.1000251
Click here to view article online
About PLoS Genetics
PLoS Genetics reflects the full breadth and interdisciplinary nature of genetics and genomics research by publishing
outstanding original contributions in all areas of biology. All works published in PLoS Genetics are open access. Everything is immediately and freely
available online throughout the world subject only to the condition that the original authorship and source are properly attributed. Copyright is
retained by the authors. The Public Library of Science uses the Creative Commons Attribution License.
PLoS Genetics
About the Public Library of Science
The Public Library of Science (PLoS) is a non-profit organization of scientists and physicians committed to making the world's scientific and medical
literature a freely available public resource. For more information, visit plos.
Public Library of Science
воскресенье, 12 июня 2011 г.
Breakthrough In The Design Of New Drugs - New Way Of Recognising DNA
Scientists led by Mike Hannon at the University of Birmingham and Miquel Coll at the Spanish Research Council in Barcelona have discovered a new way that drugs can attach themselves to DNA, which is a crucial step forward for researchers who are developing drugs to combat cancer and other diseases.
DNA contains the information which encodes life itself; its double-helical structure was recognised 50 years ago. Scientists soon started designing drugs to target DNA and used them to treat diseases such as cancer, viral infections and sleeping sickness. In the 1960s, scientists discovered three different classes of clinical drug, each of which recognised DNA in a different way. Subsequent drugs have used only these three ways to recognise the DNA. Now the Birmingham and Barcelona teams have found a fourth which is completely different and opens up entirely new possibilities for drug design.
The scientists have developed a synthetic drug agent that targets and binds to the centre of a 3-way junction in the DNA. These 3-way junction structures are formed where three double-helical regions join together. They are particularly exciting as they have been found to be present in diseases, such as some Huntington's disease and myotonic dystrophy, in viruses and whenever DNA replicates itself, for example, during cancer growth.
First of all, the Birmingham team created a nanosize synthetic drug in the shape of a twisted cylinder. Together with researchers in the UK, Spain and Norway they showed that is had unprecedented effects on DNA. Now molecular level pictures taken by the Barcelona team have shown that it binds itself in a new way to the DNA, by fixing itself to the centre of a DNA junction, which had three strands. It is all held together because the cylinder is positively charged and the DNA is negatively charged. In addition the drug is a perfect fit in the heart of the junction: a round peg in a round hole.
DNA is the genetic code in humans which carries all the information needed by our bodies in order to function properly. It is divided into units of genes. When a disease is present, genes are either working too hard or not enough, so to combat this, scientists are looking for ways to target those genes to turn them off or on or to make them work slower or faster. A number of current anti-cancer drugs target disease at DNA level, but they are not specific in their approach and this means that they can cause unpleasant side effects. Moreover some of these drugs suffer from developed resistance as the body learns how to deal with drugs that act in a particular way. By creating drugs which act in completely different ways this acquired resistance could be overcome.
Professor Mike Hannon, from the University of Birmingham's School of Chemistry, says, 'This is a significant step in drug design for DNA recognition and it is an absolutely crucial step forward for medical science researchers worldwide who are working on new drug targets for cancer and other diseases. This discovery will revolutionise the way that we think about how to design molecules to interact with DNA. It will send chemical drug research off on a new tangent. By targeting specific structures in the DNA scientists may finally start to achieve control over the way our genetic information is processed and apply that to fight disease'
Professor Miquel Coll's team from the Spanish Research Council in Barcelona was able to obtain the molecular level picture of how the drug interacts with the DNA using a technique called X-ray crystallography at the European Synchrotron facility at Grenoble in France. Professor Miquel Coll says, 'In 1999 we solved the structure of the four-way DNA junction -also called Holliday junction- which is how two DNA helices can 'recombine' (swop genetic information) and which is important in producing genetic diversity in humans and other organisms. But that junction was rather compact, without cavities or holes that could be used for drug binding. Now we have discovered that three-way DNA junctions are much more suitable for drug design: they leave a central cavity where a drug can fit perfectly and this opens a door for the design of new and quite unprecedented anti-DNA agents.'
1. DNA holds the human genetic code. To express this information, DNA copies itself into RNA, which holds exactly the same information. The RNA molecules create proteins which have a specific job to carry out, for example, they can be enzymes. To combat disease drug targets can be developed to work with DNA, RNA or proteins. For scientists, it is easier to target DNA, as only one molecule of the drug target is needed.
2. This work is part of a trans-European collaborative effort led by Prof. Mike Hannon, leader of the Birmingham research team and based around the agents developed by that team. The consortium which is funded by the European Commission Framework research programme involves research teams at: CSIC Barcelona, Spain; Chalmers University, Gothenburg, Sweden; Bergen University, Norway, University of Barcelona, Spain; Institute of Biophysics, Brno, Czech Republic. The work is focused on designing and studying the DNA binding of synthetic agents that are similar in size to the agents biology uses to recognise DNA. The team leader at CSIC Barcelona is structural biologist Prof. Miquel Coll.
3. The three previous modes of DNA recognition used by drugs are:
a. Slotting in between the DNA base pairs at the heart of the DNA (usually described by scientists as "intercalation"). This is like a sandwich with the DNA bases being the bread and the drug being the filling. An early example of such a drug used to treat cancer was doxorubicin (trade name 'Adriamycin' or 'Rubex'). This drug, launched in the 1960s, gave much impetus to the field and has been followed by a number of varients. This 'intercalation' binding mode was recognized in the early 1960s. Doxorubicin is classified by clinicians as an "anthracycline antiobiotic."
b. Binding in the grooves which are formed as the DNA strands wrap about each other to form the spiral (double-helical) structure. Examples of such drugs include berenil and stilbamidine, pentamidine. This mode of binding had been recognized in the late 1960s; some of the drugs were in the clinic by this time.
c. Forming direct bonds to the DNA bases that hold the genetic information and causing distortions to DNA structure. This mode of action is used by the platinum drugs that are among the most widely used anti-cancer agents in clinic today. The original platinum drug cis-platin (marketed as 'platinol') was discovered in the mid 1960s when its mode of DNA-binding was first established. It was introduced into the clinic in the 1970s. Three further platinum drugs (carboplatin - trade name 'Paraplatin', nedaplatin and most recently oxaliplatin - trade name Eloxatin) are also in clinical use. Clinicians refer to this general group of chemotherapy drugs as alkylating agents.
4. The journal Angewandte Chemie is the highest impact, primary-research Chemistry journal in the world. It has judged this work so important that it has not only assigned the paper VIP status (Very Important Paper), but also elected to feature the work on its front cover and has commissioned a 'Highlight article' (from a leading player in the field of DNA recognition and metal-based drugs: Professor B. Lippert of the University of Dortmund) to be positioned at the start of the journal issue to place the work in context and underline its importance.
Peer reviewed publication and references
Angewandte Chemie
UNIVERSITY OF BIRMINGHAM
Edgbaston
Birmingham
B15 2TT
UK
The University was founded in 1900 by the citizens of Birmingham who wanted their own university to train and educate the people who would create and manage the burgeoning businesses and industries of the midlands.
bham.ac.uk
View drug information on Eloxatin.
DNA contains the information which encodes life itself; its double-helical structure was recognised 50 years ago. Scientists soon started designing drugs to target DNA and used them to treat diseases such as cancer, viral infections and sleeping sickness. In the 1960s, scientists discovered three different classes of clinical drug, each of which recognised DNA in a different way. Subsequent drugs have used only these three ways to recognise the DNA. Now the Birmingham and Barcelona teams have found a fourth which is completely different and opens up entirely new possibilities for drug design.
The scientists have developed a synthetic drug agent that targets and binds to the centre of a 3-way junction in the DNA. These 3-way junction structures are formed where three double-helical regions join together. They are particularly exciting as they have been found to be present in diseases, such as some Huntington's disease and myotonic dystrophy, in viruses and whenever DNA replicates itself, for example, during cancer growth.
First of all, the Birmingham team created a nanosize synthetic drug in the shape of a twisted cylinder. Together with researchers in the UK, Spain and Norway they showed that is had unprecedented effects on DNA. Now molecular level pictures taken by the Barcelona team have shown that it binds itself in a new way to the DNA, by fixing itself to the centre of a DNA junction, which had three strands. It is all held together because the cylinder is positively charged and the DNA is negatively charged. In addition the drug is a perfect fit in the heart of the junction: a round peg in a round hole.
DNA is the genetic code in humans which carries all the information needed by our bodies in order to function properly. It is divided into units of genes. When a disease is present, genes are either working too hard or not enough, so to combat this, scientists are looking for ways to target those genes to turn them off or on or to make them work slower or faster. A number of current anti-cancer drugs target disease at DNA level, but they are not specific in their approach and this means that they can cause unpleasant side effects. Moreover some of these drugs suffer from developed resistance as the body learns how to deal with drugs that act in a particular way. By creating drugs which act in completely different ways this acquired resistance could be overcome.
Professor Mike Hannon, from the University of Birmingham's School of Chemistry, says, 'This is a significant step in drug design for DNA recognition and it is an absolutely crucial step forward for medical science researchers worldwide who are working on new drug targets for cancer and other diseases. This discovery will revolutionise the way that we think about how to design molecules to interact with DNA. It will send chemical drug research off on a new tangent. By targeting specific structures in the DNA scientists may finally start to achieve control over the way our genetic information is processed and apply that to fight disease'
Professor Miquel Coll's team from the Spanish Research Council in Barcelona was able to obtain the molecular level picture of how the drug interacts with the DNA using a technique called X-ray crystallography at the European Synchrotron facility at Grenoble in France. Professor Miquel Coll says, 'In 1999 we solved the structure of the four-way DNA junction -also called Holliday junction- which is how two DNA helices can 'recombine' (swop genetic information) and which is important in producing genetic diversity in humans and other organisms. But that junction was rather compact, without cavities or holes that could be used for drug binding. Now we have discovered that three-way DNA junctions are much more suitable for drug design: they leave a central cavity where a drug can fit perfectly and this opens a door for the design of new and quite unprecedented anti-DNA agents.'
1. DNA holds the human genetic code. To express this information, DNA copies itself into RNA, which holds exactly the same information. The RNA molecules create proteins which have a specific job to carry out, for example, they can be enzymes. To combat disease drug targets can be developed to work with DNA, RNA or proteins. For scientists, it is easier to target DNA, as only one molecule of the drug target is needed.
2. This work is part of a trans-European collaborative effort led by Prof. Mike Hannon, leader of the Birmingham research team and based around the agents developed by that team. The consortium which is funded by the European Commission Framework research programme involves research teams at: CSIC Barcelona, Spain; Chalmers University, Gothenburg, Sweden; Bergen University, Norway, University of Barcelona, Spain; Institute of Biophysics, Brno, Czech Republic. The work is focused on designing and studying the DNA binding of synthetic agents that are similar in size to the agents biology uses to recognise DNA. The team leader at CSIC Barcelona is structural biologist Prof. Miquel Coll.
3. The three previous modes of DNA recognition used by drugs are:
a. Slotting in between the DNA base pairs at the heart of the DNA (usually described by scientists as "intercalation"). This is like a sandwich with the DNA bases being the bread and the drug being the filling. An early example of such a drug used to treat cancer was doxorubicin (trade name 'Adriamycin' or 'Rubex'). This drug, launched in the 1960s, gave much impetus to the field and has been followed by a number of varients. This 'intercalation' binding mode was recognized in the early 1960s. Doxorubicin is classified by clinicians as an "anthracycline antiobiotic."
b. Binding in the grooves which are formed as the DNA strands wrap about each other to form the spiral (double-helical) structure. Examples of such drugs include berenil and stilbamidine, pentamidine. This mode of binding had been recognized in the late 1960s; some of the drugs were in the clinic by this time.
c. Forming direct bonds to the DNA bases that hold the genetic information and causing distortions to DNA structure. This mode of action is used by the platinum drugs that are among the most widely used anti-cancer agents in clinic today. The original platinum drug cis-platin (marketed as 'platinol') was discovered in the mid 1960s when its mode of DNA-binding was first established. It was introduced into the clinic in the 1970s. Three further platinum drugs (carboplatin - trade name 'Paraplatin', nedaplatin and most recently oxaliplatin - trade name Eloxatin) are also in clinical use. Clinicians refer to this general group of chemotherapy drugs as alkylating agents.
4. The journal Angewandte Chemie is the highest impact, primary-research Chemistry journal in the world. It has judged this work so important that it has not only assigned the paper VIP status (Very Important Paper), but also elected to feature the work on its front cover and has commissioned a 'Highlight article' (from a leading player in the field of DNA recognition and metal-based drugs: Professor B. Lippert of the University of Dortmund) to be positioned at the start of the journal issue to place the work in context and underline its importance.
Peer reviewed publication and references
Angewandte Chemie
UNIVERSITY OF BIRMINGHAM
Edgbaston
Birmingham
B15 2TT
UK
The University was founded in 1900 by the citizens of Birmingham who wanted their own university to train and educate the people who would create and manage the burgeoning businesses and industries of the midlands.
bham.ac.uk
View drug information on Eloxatin.
суббота, 11 июня 2011 г.
Network-based Diffusion Analysis: A New Method For Detecting Social Learning
Social learning is a key mechanism by which many animals acquire adaptive behaviours from other group members, which eventually can lead to the emergence of traditions, with human culture being the most complex example.
However, our ability to investigate social learning dynamics in animals is limited by the methods that are currently available. We address this challenge with an innovative, new approach that analyzes the spread of traits through animal groups.
We tested our method with artificially generated learning data. Our results demonstrate the superior power of our method in comparison to another widely-used method.
Proceedings of the Royal Society B: Biological Sciences
Proceedings B is the Royal Society's flagship biological research journal, dedicated to the rapid publication and broad dissemination of high-quality research papers, reviews and comment and reply papers. The scope of the journal is diverse and is especially strong in organismal biology.
Proceedings of the Royal Society B: Biological Sciences
However, our ability to investigate social learning dynamics in animals is limited by the methods that are currently available. We address this challenge with an innovative, new approach that analyzes the spread of traits through animal groups.
We tested our method with artificially generated learning data. Our results demonstrate the superior power of our method in comparison to another widely-used method.
Proceedings of the Royal Society B: Biological Sciences
Proceedings B is the Royal Society's flagship biological research journal, dedicated to the rapid publication and broad dissemination of high-quality research papers, reviews and comment and reply papers. The scope of the journal is diverse and is especially strong in organismal biology.
Proceedings of the Royal Society B: Biological Sciences
пятница, 10 июня 2011 г.
Differentiation Blocked In Tumor Stem Cells
A new comparison of normal stem cells and cancer stem cells reveals that the cancer stem cells are abnormally trapped at an early stage of development. The research, published by Cell Press in the January issue of Cancer Cell, significantly advances the understanding of glioma pathophysiology and provides new directions for design of therapeutic strategies that are targeted to specific types of tumors.
Tumor-initiating cells with stem like properties (TICs) are thought to be a small population of tumor cells that have many characteristics in common with normal stem cells (NSCs) in that they are self-replicating and capable of giving rise to populations of differentiated cells. Previous research has demonstrated that TICs are present in different types of brain tumors, including glioblastomas. Although the TICs share many properties with NSCs, they are known to possess genetic aberrations that support a tumorigenic phenotype.
"Thus far, there have been few, if any, reports demonstrating exactly where along the developmental pathway of tissue-specific stem cell maturation and differentiation tumor stem cells arise, and which, if any, of the intrinsic stem cell signaling pathways are perturbed in tumor stem cells remains largely unknown," explains Dr. Howard A. Fine from the National Cancer Institute in Bethesda, Maryland. To better understand the development and differentiation pathways that play a significant role in cancer stem cells, Dr. Fine and colleagues isolated TICs from primary human glioblastomas and compared them to human and mouse NSCs at various developmental stages.
The researchers found that the TICs isolated from an adult patient are more similar to early embryonic stem cells than to later embryonic or adult-derived stem cells. Specifically, the TICs appear to be stuck at this early developmental stage, at least in part, due to epigenetic repression of bone morphogenic protein receptor 1B (BMPR1B) expression mediated through a polycomb repressive complex. BMPs are known to mediate proliferation, differentiation and apoptosis in NSCs, depending on the stage of cell development and the local environment. Importantly, forced expression of the silenced BMPR1B restored normal differentiation capacity to the isolated TICs, halting further cell division and inducing terminal differentiation.
"Our research provides an example of a temporally deregulated and aberrantly fixed normal stem cell developmental block to differentiation contributing to the pathogenesis of a human tumor. Not only will such insights pave the way for a more thorough understanding of tumor stem cell biology, but they also identify BMPR1B as a promising molecular target and open the potential for targeted therapeutic approaches for agents that can induce terminal differentiation of tumor stem cells," offers Dr. Fine.
The researchers include Jeongwu Lee, Myung Jin Son, Kevin Woolard, Nicholas M. Donin, Aiguo Li, Chui H. Cheng, Svetlana Kotliarova, Yuri Kotliarov, Jennifer Walling, Susie Ahn, Misuk Kim, Mariam Totonchy, Thomas Cusack, Chibawanye Ene, Hilary Ma, Qin Su, Jean Claude Zenklusen, Wei Zhang, Dragan Maric, and Howard A. Fine of the Neuro-Oncology Branch, National Cancer Institute, National Institute of Neurological Diseases and Stroke, National Institutes of Health in Bethesda.
This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research.
Lee et al.: "Epigenetic-Mediated Dysfunction of the Bone Morphogenetic Protein Pathway Inhibits Differentiation of Glioblastoma-Initiating Cells." Publishing in Cancer Cell 13, 69-80, January 2008. DOI 10.1016/j.ccr.2007.12.005. cancercell/
Source: Cathleen Genova
Cell Press
Tumor-initiating cells with stem like properties (TICs) are thought to be a small population of tumor cells that have many characteristics in common with normal stem cells (NSCs) in that they are self-replicating and capable of giving rise to populations of differentiated cells. Previous research has demonstrated that TICs are present in different types of brain tumors, including glioblastomas. Although the TICs share many properties with NSCs, they are known to possess genetic aberrations that support a tumorigenic phenotype.
"Thus far, there have been few, if any, reports demonstrating exactly where along the developmental pathway of tissue-specific stem cell maturation and differentiation tumor stem cells arise, and which, if any, of the intrinsic stem cell signaling pathways are perturbed in tumor stem cells remains largely unknown," explains Dr. Howard A. Fine from the National Cancer Institute in Bethesda, Maryland. To better understand the development and differentiation pathways that play a significant role in cancer stem cells, Dr. Fine and colleagues isolated TICs from primary human glioblastomas and compared them to human and mouse NSCs at various developmental stages.
The researchers found that the TICs isolated from an adult patient are more similar to early embryonic stem cells than to later embryonic or adult-derived stem cells. Specifically, the TICs appear to be stuck at this early developmental stage, at least in part, due to epigenetic repression of bone morphogenic protein receptor 1B (BMPR1B) expression mediated through a polycomb repressive complex. BMPs are known to mediate proliferation, differentiation and apoptosis in NSCs, depending on the stage of cell development and the local environment. Importantly, forced expression of the silenced BMPR1B restored normal differentiation capacity to the isolated TICs, halting further cell division and inducing terminal differentiation.
"Our research provides an example of a temporally deregulated and aberrantly fixed normal stem cell developmental block to differentiation contributing to the pathogenesis of a human tumor. Not only will such insights pave the way for a more thorough understanding of tumor stem cell biology, but they also identify BMPR1B as a promising molecular target and open the potential for targeted therapeutic approaches for agents that can induce terminal differentiation of tumor stem cells," offers Dr. Fine.
The researchers include Jeongwu Lee, Myung Jin Son, Kevin Woolard, Nicholas M. Donin, Aiguo Li, Chui H. Cheng, Svetlana Kotliarova, Yuri Kotliarov, Jennifer Walling, Susie Ahn, Misuk Kim, Mariam Totonchy, Thomas Cusack, Chibawanye Ene, Hilary Ma, Qin Su, Jean Claude Zenklusen, Wei Zhang, Dragan Maric, and Howard A. Fine of the Neuro-Oncology Branch, National Cancer Institute, National Institute of Neurological Diseases and Stroke, National Institutes of Health in Bethesda.
This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research.
Lee et al.: "Epigenetic-Mediated Dysfunction of the Bone Morphogenetic Protein Pathway Inhibits Differentiation of Glioblastoma-Initiating Cells." Publishing in Cancer Cell 13, 69-80, January 2008. DOI 10.1016/j.ccr.2007.12.005. cancercell/
Source: Cathleen Genova
Cell Press
четверг, 9 июня 2011 г.
How Does CO2 Insufflation Pressure Affect Proliferation And Improve Apoptosis?
Under 10 mmHg CO2 pressure, there were no obvious effects on MKN-45 cells' proliferation and apoptosis. At 15 mmHg CO2 insufflation pressure, cells proliferation was inhibited and apoptosis improved. It may be that CO2 gas affected the growth of gastric cancer cells.
This study was performed by a team led by Professor Pei-Wu Yu. The research article is published in the World Journal of Gastroenterology.
There is an ongoing debate on the deleterious effects of CO2 on tumor cell behavior. Some authors showed an increase in cell proliferation and tumor growth and others found beneficial effects of CO2 exposition in vitro and in animal studies.
In the view of the authors, the extracellular pH differed significantly during CO2 versus helium exposure and it decreased very sharply with the insufflated pressure. The extracellular and intracellular pH was an important regulator of cell functions, such as ATP production, cell cycle, intracellular signaling and apoptosis. It is likely that all these changes influence the favorability of tumor-cell implantation at the time of laparoscopic surgery.
The role of peritoneal microenvironment in tumor-cell growth awaits further studies and looks for the safest approach to laparoscopic oncologic surgery.
Reference: Hao YX, Zhong H, Zhang C, Zeng DZ, Shi Y, Tang B, Yu PW. Effects of simulated carbon dioxide and helium pneumoperitoneum on gastric cancer cells' proliferation and apoptosis. World J Gastroenterol 2008; 14(14): 2241-2245 wjgnet/1007-9327/14/2241.asp
Correspondence to: Pei-Wu Yu, Professor, Department of General Surgery and Center of Minimal Invasive Gastrointestinal Surgery, Southwest Hospital, Third Military Medical University, Gaotanyan Street, Shapingba district, Chongqing 400038, China.
About World Journal of Gastroenterology
World Journal of Gastroenterology (WJG), a leading international journal in gastroenterology and hepatology, has established a reputation for publishing first class research on esophageal cancer, gastric cancer, liver cancer, viral hepatitis, colorectal cancer, and H pylori infection for providing a forum for both clinicians and scientists. WJG has been indexed and abstracted in Current Contents/Clinical Medicine, Science Citation Index Expanded (also known as SciSearch) and Journal Citation Reports/Science Edition, Index Medicus, MEDLINE and PubMed, Chemical Abstracts, EMBASE/Excerpta Medica, Abstracts Journals, Nature Clinical Practice Gastroenterology and Hepatology, CAB Abstracts and Global Health. ISI JCR 2003-2000 IF: 3.318, 2.532, 1.445 and 0.993. WJG is a weekly journal published by WJG Press. The publication dates are the 7th, 14th, 21st, and 28th day of every month. The WJG is supported by The National Natural Science Foundation of China, No. 30224801 and No. 30424812, and was founded with the name of China National Journal of New Gastroenterology on October 1, 1995, and renamed WJG on January 25, 1998.
About The WJG Press
The WJG Press mainly publishes World Journal of Gastroenterology.
Source: Jing Zhu
World Journal of Gastroenterology
This study was performed by a team led by Professor Pei-Wu Yu. The research article is published in the World Journal of Gastroenterology.
There is an ongoing debate on the deleterious effects of CO2 on tumor cell behavior. Some authors showed an increase in cell proliferation and tumor growth and others found beneficial effects of CO2 exposition in vitro and in animal studies.
In the view of the authors, the extracellular pH differed significantly during CO2 versus helium exposure and it decreased very sharply with the insufflated pressure. The extracellular and intracellular pH was an important regulator of cell functions, such as ATP production, cell cycle, intracellular signaling and apoptosis. It is likely that all these changes influence the favorability of tumor-cell implantation at the time of laparoscopic surgery.
The role of peritoneal microenvironment in tumor-cell growth awaits further studies and looks for the safest approach to laparoscopic oncologic surgery.
Reference: Hao YX, Zhong H, Zhang C, Zeng DZ, Shi Y, Tang B, Yu PW. Effects of simulated carbon dioxide and helium pneumoperitoneum on gastric cancer cells' proliferation and apoptosis. World J Gastroenterol 2008; 14(14): 2241-2245 wjgnet/1007-9327/14/2241.asp
Correspondence to: Pei-Wu Yu, Professor, Department of General Surgery and Center of Minimal Invasive Gastrointestinal Surgery, Southwest Hospital, Third Military Medical University, Gaotanyan Street, Shapingba district, Chongqing 400038, China.
About World Journal of Gastroenterology
World Journal of Gastroenterology (WJG), a leading international journal in gastroenterology and hepatology, has established a reputation for publishing first class research on esophageal cancer, gastric cancer, liver cancer, viral hepatitis, colorectal cancer, and H pylori infection for providing a forum for both clinicians and scientists. WJG has been indexed and abstracted in Current Contents/Clinical Medicine, Science Citation Index Expanded (also known as SciSearch) and Journal Citation Reports/Science Edition, Index Medicus, MEDLINE and PubMed, Chemical Abstracts, EMBASE/Excerpta Medica, Abstracts Journals, Nature Clinical Practice Gastroenterology and Hepatology, CAB Abstracts and Global Health. ISI JCR 2003-2000 IF: 3.318, 2.532, 1.445 and 0.993. WJG is a weekly journal published by WJG Press. The publication dates are the 7th, 14th, 21st, and 28th day of every month. The WJG is supported by The National Natural Science Foundation of China, No. 30224801 and No. 30424812, and was founded with the name of China National Journal of New Gastroenterology on October 1, 1995, and renamed WJG on January 25, 1998.
About The WJG Press
The WJG Press mainly publishes World Journal of Gastroenterology.
Source: Jing Zhu
World Journal of Gastroenterology
среда, 8 июня 2011 г.
Battle Of The Sexes, Fruit-Fly Style
Pity the female fruit fly. Being a looker is simply not enough. To get a date, much less a proposal, you have to act like a girl, even smell like one. Otherwise, you might just have a fight on your hands.
Like most animals, fruit flies must distinguish between a potential mate and a potential competitor. When a male fruit fly suspects he's encountered a female, he'll court; when he senses the other is a male, he'll fight. What triggers these sex-specific responses?
According to new research by scientists at Harvard Medical School, the answer lies with both pheromonal profiles and behavioral patterns. The researchers investigated the effects of taste and action by manipulating a gene that governs both the sex specificity of a fruit fly's body-surface hydrocarbons, or pheromones, and the sex-linked behavioral cues that issue through the dense nerve-cell network that constitutes the fly's brain.
"These findings underscore the importance of behavioral feedback in the manifestation of aggression," says Edward Kravitz, the George Packer Berry Professor of Neurobiology at Harvard Medical School.
The research is published in the November 23 issue of PLoS Biology.
MarГa de la Paz FernГЎndez and Yick-Bun Chan, post-doctoral researchers in the Kravitz lab, discovered these links to aggression when investigating whether a male fruit fly would ever attack a female. They focused on a particular gene called transformer, which is active in females but not in males. Through blocking transformer expression in a variety of different tissues in females, the researchers could specifically alter the "femaleness" or "maleness" of the pheromones, which in turn altered the patterns of aggressive behavior encoded in the fly's brain.
When they changed pheromone profiles so that females "tasted" like males, the researchers found that males would attack them. This indicated that pheromonal cues alone could label another fly as a competitor. But the researchers were surprised to discover that males also attacked "aggressive females" - flies that still looked, smelled and tasted female but had been genetically altered to display male-like patterns of behavior.
When the researchers turned the tables by triggering the expression of transformer in males so as to feminize both the pheromonal and behavioral profiles, control males showed no aggression toward the transformed males. Instead, they began to court them. These results show that it is possible to completely reverse normal behavioral responses by presenting males with unanticipated and conflicting sensory cues.
"Future studies will aim at unraveling the neuronal circuitry that governs this type of decision-making behavior, as such decisions are essential for survival," says Kravitz. "With the powerful genetic methods available in fly neurobiology, it should be possible to dissect the decision-making circuitry at far greater levels of detail than have heretofore been possible in other species."
"This study addresses a classic question in animal behavior: What motivates an individual to do X rather than Y, or vice versa," said Laurie Tompkins, Ph.D., who manages Kravitz's and other behavioral genetics grants at the National Institutes of Health. "Because the general principles of how behaviors are controlled are conserved among species, Kravitz's conclusions about how flies make simple choices may illuminate how humans and other animals make more complex decisions."
Notes:
The study was supported by grants from the National Institute of General Medical Science and by a Pew Latin American Fellowship awarded to FernГЎndez.
Written by Ann Marie Menting.
CITATION: PLoS Biology, 8(11): e1000541; doi:10.1371/journal.pbio.1000541, Nov 23, 2010
"Pheromonal and Behavioral Cues Trigger Male-to-Female Aggression in Drosophila"
MarГa de la Paz FernГЎndez (1), Yick-Bun Chan (1), Joanne Y. Yew (2,3,4), Jean-Christophe Billeter (5), Klaus Dreisewerd (3), Joel D. Levine (5), Edward A. Kravitz (1)
(1) Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA
(2) Temasek Life Sciences Laboratories, 1 Research Linkn National University of Singapore, Singapore
(3) Institute of Medical Physics and Biophysics, Westfälische Wilhelms-Universität Münster, Münster, Germany
(4) Department of Biological Sciences, National University of Singapore, Singapore
(5) Department of Biology, University of Toronto at Mississauga, Mississauga, Ontario, Canada
Source:
David Cameron
Harvard Medical School
Like most animals, fruit flies must distinguish between a potential mate and a potential competitor. When a male fruit fly suspects he's encountered a female, he'll court; when he senses the other is a male, he'll fight. What triggers these sex-specific responses?
According to new research by scientists at Harvard Medical School, the answer lies with both pheromonal profiles and behavioral patterns. The researchers investigated the effects of taste and action by manipulating a gene that governs both the sex specificity of a fruit fly's body-surface hydrocarbons, or pheromones, and the sex-linked behavioral cues that issue through the dense nerve-cell network that constitutes the fly's brain.
"These findings underscore the importance of behavioral feedback in the manifestation of aggression," says Edward Kravitz, the George Packer Berry Professor of Neurobiology at Harvard Medical School.
The research is published in the November 23 issue of PLoS Biology.
MarГa de la Paz FernГЎndez and Yick-Bun Chan, post-doctoral researchers in the Kravitz lab, discovered these links to aggression when investigating whether a male fruit fly would ever attack a female. They focused on a particular gene called transformer, which is active in females but not in males. Through blocking transformer expression in a variety of different tissues in females, the researchers could specifically alter the "femaleness" or "maleness" of the pheromones, which in turn altered the patterns of aggressive behavior encoded in the fly's brain.
When they changed pheromone profiles so that females "tasted" like males, the researchers found that males would attack them. This indicated that pheromonal cues alone could label another fly as a competitor. But the researchers were surprised to discover that males also attacked "aggressive females" - flies that still looked, smelled and tasted female but had been genetically altered to display male-like patterns of behavior.
When the researchers turned the tables by triggering the expression of transformer in males so as to feminize both the pheromonal and behavioral profiles, control males showed no aggression toward the transformed males. Instead, they began to court them. These results show that it is possible to completely reverse normal behavioral responses by presenting males with unanticipated and conflicting sensory cues.
"Future studies will aim at unraveling the neuronal circuitry that governs this type of decision-making behavior, as such decisions are essential for survival," says Kravitz. "With the powerful genetic methods available in fly neurobiology, it should be possible to dissect the decision-making circuitry at far greater levels of detail than have heretofore been possible in other species."
"This study addresses a classic question in animal behavior: What motivates an individual to do X rather than Y, or vice versa," said Laurie Tompkins, Ph.D., who manages Kravitz's and other behavioral genetics grants at the National Institutes of Health. "Because the general principles of how behaviors are controlled are conserved among species, Kravitz's conclusions about how flies make simple choices may illuminate how humans and other animals make more complex decisions."
Notes:
The study was supported by grants from the National Institute of General Medical Science and by a Pew Latin American Fellowship awarded to FernГЎndez.
Written by Ann Marie Menting.
CITATION: PLoS Biology, 8(11): e1000541; doi:10.1371/journal.pbio.1000541, Nov 23, 2010
"Pheromonal and Behavioral Cues Trigger Male-to-Female Aggression in Drosophila"
MarГa de la Paz FernГЎndez (1), Yick-Bun Chan (1), Joanne Y. Yew (2,3,4), Jean-Christophe Billeter (5), Klaus Dreisewerd (3), Joel D. Levine (5), Edward A. Kravitz (1)
(1) Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA
(2) Temasek Life Sciences Laboratories, 1 Research Linkn National University of Singapore, Singapore
(3) Institute of Medical Physics and Biophysics, Westfälische Wilhelms-Universität Münster, Münster, Germany
(4) Department of Biological Sciences, National University of Singapore, Singapore
(5) Department of Biology, University of Toronto at Mississauga, Mississauga, Ontario, Canada
Source:
David Cameron
Harvard Medical School
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