Friday, 31 July 2009

Blood Stem Cells Reprogrammed to Become Vision Cells

Blood Stem Cells Reprogrammed to Become Vision Cells Friday, 31 July 2009 University of Florida researchers were able to program bone marrow stem cells to repair damaged retinas in mice, suggesting a potential treatment for one of the most common causes of vision loss in older people. The success in repairing a damaged layer of retinal cells in mice implies that blood stem cells taken from bone marrow can be programmed to restore a variety of cells and tissues, including ones involved in cardiovascular disorders such as atherosclerosis and coronary artery disease. Maria B. Grant."To our knowledge, this is the first report using targeted gene manipulation to specifically program an adult stem cell to become a new cell type," said Maria B. Grant, M.D., a professor of pharmacology and therapeutics at UF’s College of Medicine. "Although we used genes, we also suggest you can do the same thing with drugs — but ultimately you would not give the drugs to the patient, you would give the drugs to their cells. Take the cells out, activate certain chemical pathways, and put the cells back into the patient." In a paper slated to appear in the September issue of the journal Molecular Therapy, scientists describe how they used a virus carrying a gene that gently pushed cultured adult stem cells from mice toward a fate as retinal cells. Only after the stem cells were reintroduced into the mice did they completely transform into the desired type of vision cells, apparently taking environmental cues from the damaged retinas. After studying the cell-transformation process, scientists were able to bypass the gene manipulation step entirely and instead use chemical compounds that mirrored environmental conditions in the body, thus pointing the stem cells toward their ultimate identities as vision cells. "First we were able to show you can over-express a protein unique to a retinal cell type and trick the stem cell into thinking it is that kind of cell," said Grant, who collaborated with Edward Scott, Ph.D., the director of the Program in Stem Cell Biology and Regenerative Medicine at UF’s McKnight Brain Institute. "As we proceeded, we found we could activate the stem cells by mimicking the body's natural signalling channels with chemicals. This implies a whole new field of stem cell research that uses drug manipulation rather than genetic manipulation to send these immature cells along new pathways." Scientists chose to build retinal pigment epithelial cells, which form the outer barrier of the retina. In addition to being very specialized and easy to identify, RPE cells are faulty in many retinal diseases, including age-related macular degeneration, which affects nearly 2 million people in the United States, and some forms of blindness related to diabetes. "This work applies to 85 percent of patients who have age-related macular degeneration," Grant said. "There are no therapies for this devastating disease." The work was supported by the National Eye Institute. Researchers removed blood stem cells from the bone marrow of mice, modified the cells in cultures, and injected them back into the animals' circulatory systems. From there, the stem cells were able to home in on the eye injury and become retinal cells. At 28 days after receiving the modified stem cells, mice that had previously demonstrated no retinal function were no different from normal mice in electrical measures of their response to light. Grant and UF have patented some technology involved in the research. ......... ZenMaster


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Thursday, 30 July 2009

Reprogramming Human Cells without Inserting Genes

Research team discovers a way to turn on stem cell genes in human skin cells without using viruses or inserting new genes Thursday, 30 July 2009 A research team comprised of faculty at Worcester Polytechnic Institute's (WPI) Life Sciences and Bioengineering Center (LSBC) and investigators at CellThera, a private company also located at the LSBC, has discovered a novel way to turn on stem cell genes in human fibroblasts (skin cells) without the risks associated with inserting extra genes or using viruses. This discovery opens a new avenue for reprogramming cells that could eventually lead to treatments for a range of human diseases and traumatic injuries by coaxing a patient's own cells to repair and regenerate the damaged tissues. The research team reported its findings in the paper "Induction of Stem Cell Gene Expression in Adult Human Fibroblasts without Transgenes," published online July 21, 2009 (in advance of September print publication) as a "fast track" paper from the journal Cloning and Stem Cells. Tanja Dominko."We show that by manipulating culture conditions alone, we can achieve changes in fibroblasts that would be beneficial in development of patient-specific cell therapy approaches," the authors wrote in the paper. Early on, the emerging field of regenerative medicine focused on embryonic stem cells, which are pluripotent, meaning they can grow into all the tissues of an adult organism. In the pluripotent state, several genes are known to be active, helping to control the stem cells. These genes, including OCT4, SOX2 and NANOG, are accepted as markers of pluripotency because they are active in stem cells, but become dormant once the stem cells begin to differentiate and head down the path to developing into a specific kind of cell type and tissue. While the study of embryonic stem cells continues to yield important knowledge, research teams around the world are also working to change, or reprogram, fully-differentiated cells like skin cells, back to a more pluripotent state. Called induced pluripotent stem cells (iPS), these reprogrammed cells could be used to regenerate tissue without some of the problems associated with embryonic stem cells, including ethical questions and the potential for embryonic stem cells to be rejected by a patient's immune system or to grow out of control and cause tumours. The first induced pluripotent stem cells were created in 2007 by Shinya Yamanaka's team at Kyoto University in Japan, which inserted extra copies of four known stem cell genes, including OCT4 and SOX2, into human skin cells. Those genes began expressing proteins that changed the skin cells back to a more pluripotent state. This technique, which has since been repeated by other labs and refined to the point were fewer additional genes are needed to achieve reprogramming, was a major scientific breakthrough. Its potential for use in human therapies is limited, however, because inserting new genes into adult cells, either directly or by using viruses to carry the genetic payload, can cause a host of problems. In the current study, the team at WPI and CellThera turned on the existing, yet dormant, stem cell genes OCT4, SOX2 and NANOG already in the skin cells by lowering the amount of atmospheric oxygen the cells were exposed to, and by adding a protein called fibroblast growth factor 2 (FGF2) to the culture medium. (FGF2 is a naturally occurring protein that is known to be vital for maintaining the pluripotency of embryonic stem cells.) Furthermore, once the stem cell genes were activated and began expressing proteins, the team found those proteins migrated back into the nucleus of the skin cells, precisely as would occur in induced pluripotent stem cells. "This was an exciting observation," said Raymond Page, PhD, research assistant professor of biology and biotechnology at WPI and lead author on the paper. "Having these proteins localize to the nucleus is the first step of reprogramming these cells." Even more surprising, the team found that the stem cell genes OCT4, SOX2 and NANOG were not completely dormant in untreated skins cells, as was presumed. Those genes were, in fact, sending out messages, but those messages were not being translated into the proteins that do the work of making cells pluripotent. "This was quite unexpected," said Tanja Dominko, DVM, PhD, associate professor of biology and biotechnology at WPI and president of CellThera. "Not only does this data force us to rethink what the true markers of pluripotency may be, it suggests there is a natural mechanism at work in these cells regulating the stem cell gene expression. That opens a whole new line of inquiry." About CellThera: CellThera is an early-stage biotechnology company focused on inducing somatic cells to revert to multi-potent states to facilitate wound-healing and tissue regeneration. The company was founded by Tanja Dominko, PhD, DVM, now an associate professor of biology and biotechnology at WPI. CellThera is located at WPI's Life Sciences & Bioengineering Center at Gateway Park in Worcester, Mass. About Worcester Polytechnic Institute: Founded in 1865 in Worcester, Mass., WPI was one of the nation's first engineering and technology universities. WPI's14 academic departments offer more than 50 undergraduate and graduate degree programs in science, engineering, technology, management, the social sciences, and the humanities and arts, leading to bachelor's, master's and PhD degrees. WPI's world-class faculty work with students in a number of cutting-edge research areas, leading to breakthroughs and innovations in such fields as biotechnology, fuel cells, information security, materials processing, and nanotechnology. Students also have the opportunity to make a difference to communities and organizations around the world through the university's innovative Global Perspective Program. There are more than 20 WPI project centers throughout North America and Central America, Africa, Australia, Asia, and Europe. Reference: Induction of Stem Cell Gene Expression in Adult Human Fibroblasts without Transgenes Raymond L. Page, Sakthikumar Ambady, William F. Holmes, Lucy Vilner, Denis Kole, Olga Kashpur, Victoria Huntress, Ina Vojtic, Holly Whitton, Tanja Dominko Cloning, Stem Cells. 2009 Jul 21, doi:10.1089/clo.2009.0015 ......... ZenMaster


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Wednesday, 29 July 2009

Stem Cell Research in China

From molecular physiology to therapeutic applications Wednesday, 29 July 2009 Stem cell research promises remedies to many devastating diseases that are currently incurable, ranging from diabetes and Parkinson's disease to paralysis. Totipotent embryonic stem cells have great potential for generating a wide range of different human cells that can be used to restore malfunctioning or damaged cells and tissues in patients. Recent studies have shown that pluripotent stem cells derived from adult bone marrow, the umbilical cord and the placenta could also be induced to differentiate into a variety of different tissues. In this issue, we have invited several scientists in China to summarize their pioneering works in the stem cell research field in the current issue of Science in China Series C - Life Sciences. Since 2001, Dr. Alex Yu Zhang has been a professor at Capital Medical University in Beijing and is Director of Cell Therapy Center at Xuanwu Hospital. His current research interest focuses on the understanding of basic biological properties of stem cells and developing nonhuman primate models for stem cell-based therapy of degenerative diseases. He has developed a stem cell mediated expression system for treating Parkinson's disease and his research using pancreatic progenitor cells for treating diabetes has demonstrated efficacy in monkey models. Professor Zhang has written an overview of cell replacement therapy of Parkinson's disease, which has been studied in both animal models and human patients for more than 20 years. Recent progress in stem cell biology has indicated that it is possible to avoid immunorejection of either nuclear transfer embryonic stem cells or induced pluripotent stem cells. On the other hand, recent post mortem analysis of patients who received foetal brain cell transplantation revealed that implanted cells are prone to degeneration just like endogenous neurons. Thus it appears that future cell replacement studies will have to focus on ameliorating disease symptoms as well as on slowing the progression of the disease [1]. Professor Robert Chunhua Zhao from the Chinese Academy of Medical Sciences is Executive Director of the National Center for Stem Cell Research. His group has taken stem cell therapy into phase II clinical trials in China, and is the leading runner in stem cell therapeutics. They have identified a mesenchymal stem cell (MSC) population from human foetal bone marrow and found that these cells could differentiate not only into osteogenic, adipogenic and endothelial lineages, but also hepatocyte-like cells, and neural and erythroid cells. They remained in some tissues and organs during gestation, could give rise to different kinds of pluripotent stem cells, and thus could potentially contribute to self-repair and self-renewal of tissues and organs. They generated cells not only for the damaged tissues in which they reside, but also for damaged tissues at other locations in the body via migration triggered by pro-inflammatory cytokines and growth factors. The potential use of MSCs in tissue regeneration has been shown in several models, including skin, muscle, lung, heart and the small intestine. MSCs have emerged as a promising therapeutic modality for tissue regeneration and autoimmune disease, although the mechanisms underlying the immune-modulatory effects of MSCs have not yet been clearly defined. In this review, Professor Robert Zhao summarizes the current literature on the complex mechanism of MSCs' immune modulation and clinical studies, and discusses future directions for utilizing MSCs for clinical treatments [2]. Professor Hongkui Deng from Peking University is working on the differentiation of human embryonic stem cells into pancreatic beta cells to treat diabetes. He is one of the two winners in China of the Bill and Melinda Gates Foundation's "Grand Challenges in Global Health". He obtained $1.9 million for his proposal to use stem cells to create mouse models for testing HIV and hepatitis C vaccines. Professor Deng has written a summary of recent progress in human embryonic and inducible pluripotent stem cell differentiation into functional pancreatic islet cells and discusses the challenges for future work [3]. Professor Qi Zhou is assistant Director of the Institute of Zoology at the Chinese Academy of Sciences. He has been studying the mechanism of differentiation and de-differentiation, cellular plasticity and totipotency of pluripotent cells, as well as that of somatic cells. He intends to build various cellular and animal models for human diseases, to uncover mechanisms underlying these different cellular processes and to discover new ways to improve cloning efficiency, which will provide a powerful tool for the study of mammalian reprogramming and ultimately offer important opportunities for regenerative medicine. Professor Zhou has helped to build the National Stem Cell Bank in Beijing, where clinical grade stem cell lines and patient specific cell lines have been created for future drug target candidate screening and therapeutic applications. Professor Qi Zhou has written a summary on human parthenogenetic embryonic stem cells as one potential resource for stem cell therapy[4]. Professor Lin Liu from Nankai University has been working on creating versatile patient-specific pluripotent stem cell lines that can be reliably used to fulfil the promise of stem cell therapy in regenerative medicine. Dr. Lin Liu's group found that pES cells generated from immature oocytes in mice exhibit pluripotency resembling fES cells, as evidenced by similarly high chimera production and germline transmission. Thus, immature eggs may provide an efficient source of autologous stem cells for regenerative medicine. This group also tested whether pESCs can be generated from older females. Dr. Lingyi Chen works on mechanisms of early embryonic differentiation. In their review of current special topics on stem cells, Drs. Lingyi Chen and Lin Liu analyze the current state of iPS research, particularly on limitations and advancements in this field, and propose possible future directions to meet the challenges of iPS cells for clinical applications [5]. Stem cell research has made significant progress in the past decade. Some therapeutic applications are coming closer to being on the market, but it is still hard to predict if and when stem cell therapy will replace largely traditional therapeutics. Given the early indications for success, we hope to see promising remedies for the many current incurable diseases being made available in the clinic over the coming years. References: 1 Ren Z, Zhang Y. Cell therapy for Parkinson's disease - So close and so far away. Sci China C-Life Sci, 2009, 52: 610—614 2 Wang L, Zhao R C. Mesenchymal stem cells targeting the GVHD. Sci China C-Life Sci, 2009, 52: 603—609 3 Zhang D, Jiang W, Shi Y, et al. Generation of Pancreatic islet cell from human embryonic stem cell. Sci China C-Life Sci, 2009, 52: 615—621 4 Hao J, Zhu W, Sheng C, et al. Human parthenogenetic embryonic stem cells: One potential resource for cell therapy. Sci China C-Life Sci, 2009, 52: 622—636 5 Chen L, Liu L. Current progress and prospect of induced pluripotent stem cell. Sci China C-Life Sci, 2009, 52: 622—636 ......... ZenMaster


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Male Germ Cells Directly Converted into Other Cell Types

Male Germ Cells Directly Converted into Other Cell Types Wednesday, 29 July 2009 Researchers have found a way to directly convert spermatogonial stem cells, the precursors of sperm cells, into tissues of the prostate, skin and uterus. Their approach, described this month in the journal Stem Cells, may prove to be an effective alternative to the medical use of embryonic stem cells. Veterinary biosciences professor Paul Cooke and doctoral student Liz Simon led a team that found that spermatogonial stem cells can be directly converted into other cell types. Credit: Photo by Diana Yates.The hunt for alternatives to embryonic stem cells has led to some promising yet problematic approaches, some of which involve spermatogonial stem cells (SSCs). Researchers recently observed, for example, that SSCs grown in the laboratory will eventually give rise to a few cells that look and act like embryonic stem cells. This process can take months, however, and only a small percentage of the SSCs are converted into "embryonic stem-like" cells. Other researchers have used viruses to insert genes into SSCs that will spur them to turn into ES-like cells. But this approach is problematic and the use of viruses to ferry in the needed genes has caused concern. The new method, recently developed at the University of Illinois, takes advantage of the unusual interaction of two tissue types: the epithelium and the mesenchyme. The epithelium lines the cavities and surfaces of glands and many organs and secretes enzymes and other factors that are essential to the function of these tissues. The mesenchyme is the connective tissue in embryos. (In adults, the connective tissue is called stroma.) In the 1950s, scientists discovered that the epithelium takes its developmental instructions from the mesenchyme. For example, when researchers put bladder epithelial cells on the mesenchyme of a prostate gland, the bladder cells were changed into prostatic epithelium. The prostatic mesenchyme had altered the fate of the bladder epithelium. "The mesenchyme – it's the director; it's controlling the show," said University of Illinois veterinary biosciences professor Paul Cooke, who led the new study with postdoctoral researcher Liz Simon. Cooke began the effort with what even he considered an unlikely proposition. "Could we take spermatogonial stem cells and cause them to directly change into other cell types by putting them with various mesenchymes and growing them in the body?" he said. "I thought it was possible, but I didn't think it would work." The experiment did work, however. When Simon placed SSCs from inbred mice on prostate mesenchyme and grafted the combination into living mice, the SSCs became prostatic epithelium. When combined with skin mesenchyme and grown in vivo, the SSCs became skin epithelium. The researchers were even able to convert SSCs into uterine epithelium by using uterine mesenchyme. The newly formed tissues had all the physical characteristics of prostate, skin or uterus, and produced the telltale markers of those tissue types, Cooke said. They also stopped looking and behaving like SSCs. To assure that their tests were not contaminated with epithelial cells from the source of the mesenchyme cells, the researchers repeated the experiments using a mouse whose cells contained a gene that fluoresces green under ultraviolet light. The SSCs were obtained from a green-fluorescing mouse, but the mesenchyme came from a non-fluorescing mouse. This enabled the researchers to trace the fate of the SSCs. If the newly formed prostatic epithelium glowed green even though the mesenchyme did not, for example, the researchers knew that the SSCs had been converted into prostatic epithelium. Cooke hopes that a more streamlined approach can be developed that makes use of a man's own SSCs and stroma (the adult equivalent of the mesenchyme) to produce new skin cells or other tissues when needed – for example, to replace skin damaged in a burn. And his team is investigating the use of ovarian stem cells instead of SSCs to see if the same results can be obtained with ovarian tissue. Reference: Direct Transdifferentiation of Stem/Progenitor Spermatogonia Into Reproductive and Nonreproductive Tissues of All Germ Layers Liz Simon, Gail C. Ekman, Natalia Kostereva, Zhen Zhang, Rex A. Hess, Marie-Claude Hofmann, Paul S. Cooke Stem Cells Vol. 27 No. 7 July 2009, pp. 1666 -1675, doi:10.1002/stem.93 ......... ZenMaster


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Tuesday, 28 July 2009

Placental Stem Cells and Lung Disease

Placenta-derived stem cells may help sufferers of lung diseases Tuesday, 28 July 2009 An Italian research team, publishing in the current issue of Cell Transplantation (18:4), has found that stem cells derived from human placenta may ultimately play a role in the treatment of lung diseases, such as pulmonary fibrosis and fibrotic diseases caused by tuberculosis, chemical exposure, radiation or pathogens. These diseases can ultimately lead to loss of normal lung tissue and organ failure. No known therapy effectively reverses or stops the fibrotic process. Placenta-derived stem cells are known to be able to engraft in solid organs, including the lungs. Human term placenta stem cells also demonstrate characteristics of high plasticity and low immunogenicity. "The potential application of foetal membrane-derived cells as a therapeutic tool for disorders characterized by inflammation and fibrosis is supported in previous studies," says Dr. Ornella Parolini, the study's lead author. "In line with the hypothesis that cells derived from the amniotic membrane have immunomodulatory properties and have been used as an anti-inflammatory agent, we set out to evaluate the effects of foetal membrane-derived cell transplantation in chemically-treated (bleomycin) mice." According to Dr. Parolini, cells delivered via intra-peritoneal transplant, regardless of the cells being allogeneic or xenogeneic (host's own cells or from another individual respectively), the procedure resulted in a significant anti-fibrotic effect on the lab animals. A "consistent" reduction in lung fibrosis, says Dr. Parolini, "provides convincing proof" that placenta-derived cells do confer benefits for bleomycin-induced lung injury. While the severity of inflammation did not show an overall reduction, there was a marked reduction in neutrophil (white blood cell) infiltration after both xeno-and-allo-transplantation. "It is worth noting," says Dr. Parolini, "that the presence of neutrophils is associated with poor prognosis for several lung diseases. However, the mechanism by which placenta-derived cells might affect infiltration by neutrophils is not known." The researchers speculated that these cells may produce soluble factors that induce anti-inflammatory effects. "Our findings suggest that foetal membrane-derived cells may prove useful for cell therapy of fibrotic diseases in the future," concludes Dr. Parolini. Dr. Cesar Borlongan, of the University of South Florida and associate editor for Cell Transplantation, notes that the present study adds an important application of placenta cells, indicating their therapeutic effects in lung diseases. The cells' ability to reduce neutrophils possibly via secreted anti-inflammatory factors implies their use either as autografts or allografts, thereby increasing the numbers of the target patient population. Reference: Transplantation of Allogeneic and Xenogeneic Placenta-Derived Cells Reduces Bleomycin-Induced Lung Fibrosis Authors: Cargnoni, Anna; Gibelli, Lucia; Tosini, Alessandra; Signoroni, Patrizia Bonassi; Nassuato, Claudia; Arienti, Davide; Lombardi, Guerino; Albertini, Alberto; Wengler, Georg S.; Parolini, Ornella Cell Transplantation, Volume 18, Number 4, 2009 , pp. 405-422(18) ......... ZenMaster


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The 15-Minute Genome

2009 Industrial Physics Forum features faster, cheaper genome sequencing Tuesday, 28 July 2009 In the race for faster, cheaper ways to read human genomes, Pacific Biosciences is hoping to set a new benchmark with technology that watches DNA being copied in real time. The device is being developed to sequence DNA at speeds 20,000 times faster than second-generation sequencers currently on the market and will ultimately have a price tag of $100 per genome. Chief Technology Officer Stephen Turner of Pacific Biosciences will discuss Single Molecule Real-Time (SMRT) sequencing, due to be released commercially in 2010, at the 2009 Industrial Physics Forum, a component of the 51st Annual Meeting of American Association of Physicists in Medicine, which takes place from July 26 - 30 in Anaheim, California. A decade ago, it took Celera Genomics and the Human Genome Project years to sequence complete human genomes. In 2008, James Watson's entire genetic code was read by a new generation of technology in months. SMRT sequencing aims to eventually accomplish the same feat in minutes. The method used in the Human Genome Project, Sanger sequencing, taps into the cell's natural machinery for replicating DNA. The enzyme DNA polymerase is used to copy strands of DNA, creating billions of fragments of varying length. Each fragment – a chain of building blocks called nucleotides – ends with a tiny fluorescent molecule that identifies only the last nucleotide in the chain. By lining these fragments up according to length, their glowing tips can be read off like letters on a page. Instead of inspecting DNA copies after polymerase has done its work, SMRT sequencing watches the enzyme in real time as it races along and copies an individual strand stuck to the bottom of a tiny well. Every nucleotide used to make the copy is attached to its own fluorescent molecule that lights up when the nucleotide is incorporated. This light is spotted by a detector that identifies the colour and the nucleotide – A, C, G, or T. By repeating this process simultaneously in many wells, the technology hopes to bring about a substantial boost in sequencing speed. "When we reach a million separate molecules that we're able to sequence at once … we'll be able to sequence the entire human genome in less than 15 minutes," said Turner. The speed of the reaction is currently limited by the ability of the detector to keep up with the polymerase. The first commercial instrument will operate at three to five bases per second, and Turner reports that lab tests have achieved 10 bases per second. The polymerase has the potential to go much faster, up to hundreds of bases per second. "To push past 50 bases per second, we will need brighter fluorescent reporters or more sensitive detection," says Turner. The device also has the potential to reduce the number of errors made in DNA sequencing. Current technologies achieve an accuracy of 99.9999 percent (three thousand errors in a genome of three billion base pairs). "For cancer, you need to be able to spot a single mutation in the genome," said Turner. Because the errors made by SMRT sequencing are random – not systematically occurring at the same spot – they are more likely to disappear as the procedure is repeated. The talk, "Single Molecule Real-Time DNA Sequencers," will be given at 4:00 p.m. PDT on Monday, July 27, at the 51st Annual Meeting of American Association of Physicists in Medicine in Anaheim, California. ......... ZenMaster


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Friday, 24 July 2009

Human Cells Secrete Cancer-Killing Protein

Human Cells Secrete Cancer-Killing Protein Friday, 24 July 2009 Human cells are able to secrete a cancer-killing protein, scientists at the University of Kentucky's Markey Cancer Center have found. Researchers led by Vivek Rangnekar, UK professor of radiation medicine, have determined that the tumour-suppressor protein Par-4, initially thought to be active only within cells expressing the Par-4 gene, is in fact secreted by most human and rodent cells and can target large numbers of cancer cells by binding to receptors on the cell surface. This discovery, published today in the leading journal Cell, makes Par-4 a very attractive molecule for future research aimed at developing new cancer treatments. "It was a pleasant surprise, when we noticed that Par-4 protein is secreted by cells," Rangnekar said. "This new finding means it is not necessary to make genetic modifications, or to employ recombinant viruses, to deliver the Par-4 gene to cancer cells, and it significantly expands the potential applications of Par-4 to selectively kill cancer cells." Funded by several grants from the National Institutes of Health, Rangnekar’s study found that when the Par-4 molecule binds to its receptor GRP78 on the surface of a tumour cell, it triggers a biological process called apoptosis or "cell suicide." Consistent with previous research by Rangnekar's laboratory with intracellular Par-4, the newly discovered secreted Par-4 acts selectively against cancer cells, leaving healthy cells unharmed. Few other molecules are known to exhibit such selectivity. One molecule, known as TRAIL, also exerts cancer-cell-specific effects. However, Rangnekar's most recent study discovered that apoptosis inducible by TRAIL is dependent upon extracellular Par-4 signalling via cell surface GRP78. Thus, the researchers conclude, Par-4 activates a novel pathway involving cell surface GRP78 receptor for induction of apoptosis. In other words, without Par-4, TRAIL lacks the ability to cause "cell suicide." Rangnekar first discovered the Par-4 gene in 1993. In 2007, Rangnekar's team introduced the gene into a mouse embryo, creating a cancer-resistant "supermouse" that did not develop tumours. In fact, the mice possessing Par-4 actually live a few months longer than lab mice without the gene, indicating that Par-4 mice have no toxic side effects. While Par-4 is not necessarily a "magic bullet" — it does not target every type of cancer cell — Rangnekar says it could play a major role in developing new combination treatment modalities for cancer patients. His hope is that the next generation of treatments will be even more effective than conventional treatments available today, with fewer and less severe side effects. “I look at this research from the standpoint of how it can be developed to benefit the cancer patient, and that’s what keeps us focused,” Rangnekar said, discussing the potential of Par-4 in 2007. “The pain that cancer patients go through — not just from the disease, but also from the treatment — is excruciating. If you can treat the cancer and not harm the patient, that’s a major breakthrough." Reference: The Tumor Suppressor Par-4 Activates an Extrinsic Pathway for Apoptosis Ravshan Burikhanov, Yanming Zhao, Anindya Goswami, Shirley Qiu, Steven R. Schwarze and Vivek M. Rangnekar Cell, Volume 138, Issue 2, 377-388, 23 July 2009, doi:10.1016/j.cell.2009.05.022 ......... ZenMaster


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Thursday, 23 July 2009

Second Chinese Group Produce Mice from iPS Cells

Second Chinese Group Produce Mice from iPS Cells Thursday, 23 July 2009 Two teams of Chinese researchers have created live mice from induced pluripotent stem (iPS) cells, answering a lingering question about the developmental potential of the cells. Animal cloners Qi Zhou of the Institute of Zoology in Beijing and Fanyi Zeng of Shanghai Jiao Tong University started by creating iPS cells the same way as Shinya Yamanaka of Kyoto University in Japan, by using viral vectors to introduce four genes into mouse fibroblast cells. The Chinese team tried hard, tweaking the culture medium and analysing 250 developing embryos before getting their first mouse. In the paper, the team reports 27 live births. With their best cell line and optimal recipe, they were able to get 22 live births from 624 injected embryos, a success rate of 3.5%. Some of their mice passed one of the most fundamental tests of health: all 12 mice that were mated produced offspring, and the offspring showed no abnormalities. The team says it now has hundreds of second-generation, and more than 100 third-generation, mice. The team found no tumours in the mice, although they have not systematically looked for them. The leader of the other team, Shaorong Gao of the National Institute of Biological Sciences in Beijing, also credits persistence for success. His group, which used the same basic technique as Zeng and Zhou, transferred iPS cells to 187 tetraploid complementation embryos to get just two live births (a 1.1% efficiency rate), although one died in infancy. "The chance for generating such a cell line is rare but we tried very hard," he says. Gao's team is now trying to mate its surviving mouse. Reference: iPS cells produce viable mice through tetraploid complementation Xiao-yang Zhao, Wei Li, Zhuo Lu, Lei Liu, Man Tong, Tang Hai, Jie Hao, Chang-long Guo, Qing-wen Ma, Liu Wang, Fanyi Zeng & Qi Zhou Nature advance online publication 23 July 2009, doi:10.1038/nature08267 See also: Mice made from induced stem cells David Cyranoski Nature News, Published online 23 July 2009, doi:10.1038/460560a Mice Grown from iPS Cells by Chinese Researchers Reprogrammed mouse fibroblasts can make a whole mouse CellNEWS - Thursday, 23 July 2009 ......... ZenMaster


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Mice Grown from iPS Cells by Chinese Researchers

Reprogrammed mouse fibroblasts can make a whole mouse Thursday, 23 July 2009 In a paper publishing online July 23 in Cell Stem Cell, a Cell Press journal, Dr. Shaorong Gao and colleagues from the National Institute of Biological Sciences in Beijing, China, report an important advance in the characterization of reprogrammed induced pluripotent stem cells, or iPSCs. Scientists working with iPSCs have been eager to find out if these cells are fully pluripotent, as this would tell us to what extent they have in fact been truly reprogrammed and resemble normal embryonic stem cells (ESCs). The generally accepted "gold standard" for determining whether a mouse iPSC line has been fully reprogrammed is to show that when injected into an early embryo (or blastocyst), the iPSCs can contribute to many different tissues in the resulting chimeric mouse, including the germline. However, unlike bona fide mouse ESCs, until now mouse iPSCs have not been able to pass a more stringent test of true pluripotency termed "tetraploid complementation," which uses a hybrid embryo method to generate full-term mice entirely comprised of ESC-derived cells. In their current report, Gao and his colleagues used established methods to reprogram mouse cells to isolate five new iPSC lines, and then found that, using one of these lines, they were able to make by tetraploid complementation embryos that survived until birth, and one embryo that also survived to adulthood. The authors decided to test this specific iPSC line in the tetraploid complementation experiment because it gave an unusually high level of chimerism when injected into blastocysts and thus might have unique characteristics not found in many other iPSC lines. As emphasized by Gao: "Although these findings are an important proof of principle, it would be premature to make claims about whether iPSCs in general are functionally equivalent to normal ESCs." As the authors remark in their paper, it will be interesting to determine if there are specific reasons why this particular line succeeded where others have failed. The demonstration that mouse iPSCs can, in fact, pass the most stringent test of pluripotency offers added hope that the process of reprogramming may indeed one day overcome the need for embryo destruction in order to derive pluripotent cells for research and potential therapies. However, it remains to be seen whether lessons obtained from these findings can be applied to human cells and thus whether human iPSCs will be a viable alternative to human ESCs in all circumstances. Reference: iPS Cells Can Support Full-Term Development of Tetraploid Blastocyst-Complemented Embryos Lan Kang, Jianle Wang, Yu Zhang, Zhaohui Kou and Shaorong Gao Cell Stem Cell, 23 July 2009, doi:10.1016/j.stem.2009.07.001 See also: Second Chinese Group Produce Mice from iPS Cells CellNEWS - Thursday, 23 July 2009 This press release is also available in Chinese. ......... ZenMaster


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Tuesday, 21 July 2009

Skin-like Tissue Developed from Human Embryonic Stem Cells

Skin-like Tissue Developed from Human Embryonic Stem Cells Tuesday, 21 July 2009 Dental and tissue engineering researchers at Tufts University School of Dental Medicine and the Sackler School of Graduate Biomedical Sciences at Tufts have harnessed the pluripotency of human embryonic stem cells (hESC) to generate complex, multilayer tissues that mimic human skin and the oral mucosa (the moist tissue that lines the inside of the mouth). The proof-of-concept study is published online in advance of print in Tissue Engineering Part A. "For the first time, we have established that a single source of hESC can provide the multiple cell types needed to interact within a three-dimensional tissue model to generate complex, multilayer tissues. We are a step closer to a practical therapy to help with diseases of the skin and mouth," said Jonathan Garlick, DDS, PhD, professor of oral and maxillofacial pathology at Tufts University School of Dental Medicine and a member of the cell, molecular & developmental biology program faculty at the Sackler School of Biomedical Sciences at Tufts. "Researchers have been seeking methods to grow skin-like tissues outside of the body using new sources of stem cells such as hESC, with the goal of advancing regenerative medicine as a new therapy to replace or repair damaged or diseased tissue. Little is known about how hESC can be developed into the multilayer tissues similar to those that line the gums, cheeks, lips, and other areas in the mouth. We used in vitro tissue engineering techniques to produce skin-like tissues that mimic the lining tissues found in the oral cavity," said Garlick. Using a combination of chemical nutrients and specialized surfaces for cell attachment, an hES cell line (H9) was directed to form two distinct specialized cell populations. The first population forms the surface layer (ectodermal, the precursor to epithelial tissue), while the second is found beneath the surface layer (mesenchymal). Following the isolation and characterization of these cell populations, the researchers incorporated them into an engineered, three-dimensional tissue system where they were grown at an air-liquid interface to mimic their growth environment in the oral cavity. Within two weeks, tissues developed that were similar in structure to those constructed using mature cells derived from newborn skin, which are the current gold standard for tissue fabrication. "These engineered tissues are remarkably similar to their human counterparts and can be used to address major concerns facing the field of stem cell biology that are related to their clinical use. We can now use these engineered tissues as 'tissue surrogates' to begin to predict how stable and safe hESC-derived cells will be after therapeutic transplantation. Our goal is to produce functional tissues to treat oral and skin conditions, like the early stages of cancer and inflammatory disease, as well as to accelerate the healing of recalcitrant wounds," said Garlick. Professor Jonathan Garlick is also director of the Center for Integrated Tissue Engineering (CITE) at Tufts University School of Dental Medicine, which is dedicated to furthering the understanding of regenerative medicine through the investigation of three-dimensional tissue models. Reference: Three-Dimensional Epithelial Tissues Generated from Human Embryonic Stem Cells Kyle J. Hewitt, Yulia Shamis, Mark W. Carlson, Edith Aberdam, Daniel Aberdam, Jonathan A. Garlick Tissue Engineering Part A, Published online July 6, 2009, doi: 10.1089/ten.tea.2009.0060 ......... ZenMaster


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Neural Stem Cells Offer Potential Treatment for Alzheimer's Disease

Transplanted cells 'nurse' brain back to health Tuesday, 21 July 2009 University of California at Irvine scientists have shown for the first time that neural stem cells can rescue memory in mice with advanced Alzheimer's disease, raising hopes of a potential treatment for the leading cause of elderly dementia that afflicts 5.3 million people in the U.S. Frank LaFerla, Mathew Blurton-Jones and colleagues found that neural stem cells could be a potential treatment for advanced Alzheimer's disease. Credit: Daniel A. Anderson / University Communications.Mice genetically engineered to have Alzheimer's performed markedly better on memory tests a month after mouse neural stem cells were injected into their brains. The stem cells secreted a protein that created more neural connections, improving cognitive function. "Essentially, the cells were producing fertilizer for the brain," said Frank LaFerla, director of UCI's Institute for Memory Impairments and Neurological Disorders, or UCI MIND, and co-author of the study, which appears online the week of July 20 in the Proceedings of the National Academy of Sciences. Lead author Mathew Blurton-Jones, LaFerla and colleagues worked with older mice predisposed to develop brains lesions called plaques and tangles that are the hallmarks of Alzheimer's. To learn how the stem cells worked, the scientists examined the mouse brains. To their surprise, they discovered that just 6 percent of the stem cells had turned into neurons. (The majority became the other two main types of brain cells, astrocytes and oligodendrocytes.) The stem cells did not improve cognition by becoming new neurons, nor did they act by reducing the number of plaques and tangles. BDNF.Rather, the stem cells were found to have secreted a protein called brain-derived neurotrophic factor, or BDNF. This caused existing tissue to sprout new neurites, strengthening and increasing the number of connections between neurons. When the team selectively reduced BDNF from the stem cells, the benefit was lost, providing strong evidence that BDNF is critical to the effect of stem cells on memory and neuronal function. "If you look at Alzheimer's, it's not the plaques and tangles that correlate best with dementia; it's the loss of synapses – connections between neurons," Blurton-Jones said. "The neural stem cells were helping the brain form new synapses and nursing the injured neurons back to health." Diseased mice injected directly with BDNF also improved cognitively but not as much as with the neural stem cells, which provided a more long-term and consistent supply of the protein. "This gives us a lot of hope that stem cells or a product from them, such as BDNF, will be a useful treatment for Alzheimer's," LaFerla said. ......... ZenMaster


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Sea Lamprey Discard One-fifth of Their Genome

Growing lamprey embryo’s discard millions of units of their DNA Tuesday, 21 July 2009 Mouth of a Sea lamprey, Petromyzon marinus.Researchers have discovered that the sea lamprey, which emerged from jawless fish first appearing 500 million years ago, dramatically remodels its genome. Shortly after a fertilized lamprey egg divides into several cells, the growing embryo discards millions of units of its DNA. The findings were published this month in the Proceedings of the National Academy of Sciences. The lead author is Jeramiah Smith, a postdoctoral fellow in genome sciences at the University of Washington (UW) working in the Benaroya Research Institute laboratory of Chris Amemiya, who is also a UW affiliate professor of biology. Theirs is believed to be the first recorded observation of a vertebrate – an animal with a spinal column – extensively reorganizing its genome as a normal part of development. A few invertebrate species, like some roundworms, have been shown to undergo extensive genome remodelling. However, stability was thought to be vital in vertebrates' genomes to assure their highly precise, normal functioning. Only slight modifications to allow for immune response were believed to occur in the vertebrate genome, not broad-scale rearrangements. Smith, Amemiya and their research team inadvertently discovered the dynamic transformations in the sea lamprey genome while studying the genetic origins of its immune system. The researchers were trying to deduce how the sea lamprey employs a copy-and-paste mechanism to generate diverse receptors for detecting a variety of pathogens. The researchers were surprised to notice a difference between the genome structure in the germline – the cells that become eggs and the sperm that fertilize them – and the genome structure in the resulting embryonic cells. The DNA in the early embryonic cells had myriad breaks that resembled those in dying cells, but the cells were not dying. The embryonic cells had considerably fewer repeat DNA sequences than did the sperm cells and their precursors. "The remodelling begins at the point when the embryo turns on its own genes and no longer relies on its mom's store of mRNA," said Smith. The restructuring does not occur all at once, but continues for a long while during embryonic development. It took at lot of work for the scientists to see what was lost and when. They learned, among other findings, that the remodelled genome had fewer repeats and specific gene-encoding sequences. Deletions along the strands of DNA are also thought to move certain regulatory switches in the genome closer to previously distant segments. The scientists do not know how this happens, or why. Smith said that his favourite hypothesis, yet unproven, is that the extra genetic material might play a role in the proliferation of precursor cells for sperm and eggs, and in early embryonic development. The genetic material might then be discarded either when it is no longer needed or to prevent abnormal growth. The alteration of the sea lamprey genome and of invertebrates that restructure their genome appears to be tightly regulated, according to Smith, yet the resulting structural changes seem almost like the DNA errors that give rise to cancers or other genomic disorders in higher animals. Learning how sea lamprey DNA rearrangements are regulated during development might provide information on what stabilizes or changes the genome, he said, as well the role of restructuring in helping form different types of body cells, like fin, muscle, or liver cells. If 20 percent of their genome disappears, how do sea lampreys pass along the full complement of their genes to their offspring? "The germline – those precursor cells for sperm and eggs – is a continuous lineage through time," Smith explained. "The precursor cells for sperm and egg are set apart early in lamprey development. The genome in that cell population should never change." Genetic material is assumed to be lost only in the early embryonic cells destined to become body parts and not in cells that give rise to the next generation. The researchers have been looking for the primordial stem cells for sperm and eggs hidden away in the lamprey, but they are difficult to find. Researchers do not yet know how the sea lamprey's genome guides the morphing it undergoes during its life. Sea lampreys have a long juvenile life as larvae in fresh water, where they eat on their own. Their short adult lives are normally spent in the sea as blood-sucking parasites. Their round, jawless mouths stick like suction cups to other fish. Several circular rows of teeth rasp through the skin of their unlucky hosts. Their appetite is voracious. Later, as they return to streams and rivers along the northern Atlantic seaboard, sea lampreys atrophy until they are little more than vehicles for reproduction. After mating, they perish. Populations of sea lamprey were landlocked in the Great Lakes and other nearby large lakes after canals and dams were built in the early 1900's. They thrive by parasitizing (and killing) commercially important fish species and are considered a nuisance in the Great Lakes region. Biologists are interested in the sea lamprey partly because of its alternating lifestyles, but largely because it represents a living fossil from around the time vertebrates originated. Close relatives of sea lampreys were on earth before the dinosaurs. It's possible that the sea lamprey's dynamic genome biology might someday be traced back in evolutionary history to a point near, and perhaps including, a common ancestor of all vertebrates living today, the authors of the study noted. "Sea lampreys have a half billion years of evolutionary history," Smith said. "Evolutionary biologists and geneticists can compare their genomes to other vertebrates and humans to see what parts of the lamprey genome might have been present in our primitive ancestors. We might begin to understand how changes in the sea lamprey genome led to their distinct body structure and how fishes evolved from jawless to jawed." Amemiya added: "We don't really know where this discovery about the sea lamprey's remodelling of its genome will take us. It is common in science for the implications of a finding not to be realized for several decades. It's less about connecting the dots to a specific application, and more about obtaining a broad understanding of how living things are put together." ......... ZenMaster


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Induced Pluripotent Stem Cells Repair Heart

New iPS therapy pioneered for heart attacks Tuesday, 21 July 2009 In a proof-of-concept study, Mayo Clinic investigators have demonstrated that induced pluripotent stem (iPS) cells can be used to treat heart disease. iPS cells are stem cells converted from adult cells. In this study, the researchers reprogrammed ordinary fibroblasts, cells that contribute to scars such as those resulting from a heart attack, converting them into stem cells that fix heart damage caused by infarction. The findings appear in the current online issue of the journal Circulation. "This study establishes the real potential for using iPS cells in cardiac treatment," says Timothy Nelson, M.D., Ph.D., first author on the Mayo Clinic study. "Bioengineered fibroblasts acquired the capacity to repair and regenerate infarcted hearts." This is the first application of iPS-based technology for heart disease therapy. Previously iPS cells have been used on only three other disease models: Parkinson's disease, sickle cell anaemia and haemophilia A. The ultimate goal is to use iPS cells derived from patients to repair injury. Using a person's own cells in the process eliminates the risk of rejection and the need for anti-rejection drugs. One day this regenerative medicine strategy may alleviate the demand for organ transplantation limited by donor shortage, the researchers say. "This iPS innovation lays the groundwork for translational applications," comments Andre Terzic, M.D., Ph.D., Mayo Clinic physician-scientist and senior author. "Through advances in nuclear reprogramming, we should be able to reverse the fate of adult cells and customize 'on demand' cardiovascular regenerative medicine." From Damage to Repair The Mayo Clinic team genetically reprogrammed fibroblasts via a "stemness-related" human gene set to dedifferentiate into an iPS cell capable of then re-differentiating into new heart muscle. When transplanted into damaged mouse hearts, iPS cells engrafted after two weeks, and after four weeks significantly contributed to improved structure and function of the damaged heart, in contrast to ineffective ordinary fibroblasts. Compared to non-engineered fibroblasts, the iPS cells:

  • Restored heart muscle performance lost after the heart attack
  • Stopped progression of structural damage in the damaged heart
  • Regenerated tissue at the site of heart damage

.........

ZenMaster
For more on stem cells and cloning, go to CellNEWS at http://cellnews-blog.blogspot.com/ and http://www.geocities.com/giantfideli/index.html

Monday, 20 July 2009

Discovery of Genetic Switch Advances Diabetes Research

Discovery of Genetic Switch Advances Diabetes Research Monday, 20 July 2009 Scientists have identified a master regulator gene for early embryonic development of the pancreas and other organs, putting researchers closer to coaxing stem cells into pancreatic cells as a possible cure for type1 diabetes. Researchers at Cincinnati Children's Hospital Medical Center report their findings in the July 21 Developmental Cell. Besides having important implications in diabetes research, the study offers new insights into congenital birth defects involving the pancreas and biliary system by concluding both organs share a common cellular ancestry in the early mouse embryo. This discovery reverses a long standing belief that the biliary system's origin is connected to early embryonic formation of the liver, the researchers said. The pancreas regulates digestion and blood sugar, and the biliary system is vital for digestion. If the organs do not form properly during foetal development, it can be fatal. James Wells, Ph.D., of Cincinnati Children's Hospital Medical Center, is shown with a microscopic image of fluoresced cells separating during normal embryonic development into a pancreas (green cells above) and the biliary system below. The image of part of a study appearing in the July 21 Developmental Cell that identifies a master regulator gene, Sox17, in early embryonic development of the pancreas and other organs, putting researchers closer to coaxing stem cells into pancreatic cells as a possible cure for type 1 diabetes. Credit: Cincinnati Children's Hospital Medical Center.The study reports that one gene, Sox17 (a transcription factor that controls which genes are turned on or off in a cell) is the key regulator for giving instruction to cells in early mouse embryos to become either a pancreatic cell or part of the biliary system. The first author on the paper is Jason Spence, Ph.D., a research fellow in the lab of the study's senior investigator, James Wells, Ph.D., a researcher in the Division of Developmental Biology at Cincinnati Children's and associate professor of paediatrics at the University of Cincinnati College of Medicine. "We show that Sox17 acts like a toggle or binary switch that sets off a cascade of genetic events," said Dr. Wells. "In normal embryonic development, when you have an undecided cell, if Sox17 goes one way the cell becomes part of the biliary system. If it goes the other way, the cell becomes part of the pancreas." The finding advances ongoing research by Dr. Wells and his team to guide embryonic stem cells to become pancreatic beta cells, which scientists believe could be used to treat or cure type1 diabetes. The disease occurs when the immune system attacks insulin producing beta cells in the pancreas, usually destroying them beyond repair before the illness is diagnosed. "With this study showing us that turning one gene on or off in a mouse embryo instructs a cell to become pancreatic or biliary, now we'll see if that same gene, Sox17, can be used to direct an embryonic stem cell to become a biliary cell instead of a pancreatic cell. This might be used one day to replace a diseased pancreas or bile duct in people," said Dr. Wells. The study explains that Sox17 initially works in conjunction with two other genes (the transcription factors Pdx1 and Hes1) to decide which organ fate ventral foregut progenitor cells will take. Researches demonstrated that Sox17's key role begins when the mouse embryo is 8 1/2 days old. If Sox17 toggles one way, with its expression repressed by its interaction with Hes1, then Pdx1 more or less takes over to prompt formation of the ventral pancreas. If Sox17 toggles the other way to increases its expression, the gene helps set off formation of the biliary system. Dr. Wells and his colleagues are also using data from the current study to conduct experiments that should reveal what other genes are turned on or off along molecular cascade set into motion by Sox17. "Although Sox17 is the master switch, it triggers a molecular cascade of switches, and a defect in any of those can cause the whole thing to go wrong, resulting in congenital defects of the pancreas and biliary system," Dr. Wells said. Jeffrey Whitsett, M.D., executive director of the Cincinnati Children's Perinatal Institute and one of the current study's authors, said the research provides important clues for clinicians managing congenital birth defects of the pancreas and biliary system, which includes the bile ducts and gall bladder. Malformations in this region of the gastrointestinal tract can cause blockage of bile ducts or the intestines. One of the common defects is a condition called biliary atresia, in which the bile ducts are blocked, causing bile to accumulate, back up and leading to potential damage of the pancreas or liver. "Babies in neonatal intensive care frequently are born with medically challenging birth defects. The present studies help unravel the complex genetic systems controlling the formation of the gastrointestinal tract and provide the framework for future therapies of disease affecting the formation and function of the pancreas, liver, and bile ducts," Dr. Whitsett said. Reference: Sox17 Regulates Organ Lineage Segregation of Ventral Foregut Progenitor Cells Jason R. Spence, Alex W. Lange, Suh-Chin J. Lin, Klaus H. Kaestner, Andrew M. Lowy, Injune Kim, Jeffrey A. Whitsett, James M. Wells Developmental Cell, Volume 17, Issue 1, 62-74, 21 July 2009, doi:10.1016/j.devcel.2009.05.012 ......... ZenMaster


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Sunday, 19 July 2009

Apollo 11 – The First Man on the Moon III.

Seen as it happened – Moonwalk – Dancing Shadows. 
Sunday, 19 July 2009


Moonwalk.“Dancing Shadows.” The first moonwalk as seen on Mother Earth. This picture was taken when it happened, from the TV screen, in 1969. Copyright: Lars Carlsson

Moonwalk.“Dancing Shadows.” The first moonwalk as seen on Mother Earth. This picture was taken when it happened, from the TV screen, in 1969. Copyright: Lars Carlsson
More pictures: 
Apollo 11 – The First Man on the Moon I. Seen as it happened – The Liftoff. Sunday, 19 July 2009
Apollo 11 – The First Man on the Moon II. Seen as it happened – The Eagle has landed. Sunday, 19 July 2009 
......... 


ZenMaster

For more on stem cells and cloning, go to CellNEWS at 
http://cellnews-blog.blogspot.com/ 

Apollo 11 – The First Man on the Moon II.

Seen as it happened – The Eagle has landed. 
Sunday, 19 July 2009

Ten meters left.“Ten meters left. Dust is thrown up.” This picture was taken when it happened, from the TV screen, in 1969. Copyright: Lars Carlsson


The Eagle has landed!“The Eagle has landed!” This picture was taken when it happened, from the TV screen, in 1969. Copyright: Lars Carlsson

More pictures: 
Apollo 11 – The First Man on the Moon I. Seen as it happened – The Liftoff. Sunday, 19 July 2009 
Apollo 11 – The First Man on the Moon III. Seen as it happened – Moonwalk: Dancing Shadows. Sunday, 19 July 2009
......... 

ZenMaster

For more on stem cells and cloning, go to
CellNEWS at 

Apollo 11 – The First Man on the Moon I.

Seen as it happened – The Liftoff. 
Sunday, 19 July 2009 
It is 40 years since the first human took his first step on the moon – Neil Armstrong and Buzz Aldrin. I was 18 and sat up all night watching my family’s black and white TV to follow this historic event. Finally, in the middle of the night where I lived, it was time for the Eagle to land on the Moon. With my camera, I took several pictures of the TV screen, to document for myself this truly historic moment in Homo sapiens history. I show some of these pictures here, as a contrast to the recently restored NASA pictures of this event. 
This is how it was truly seen around the world!

The Apollo rocket ten seconds to liftoff.The Apollo rocket ten seconds to liftoff at Cape Canaveral. This picture was taken when it happened, from the TV screen, in 1969. Copyright: Lars Carlsson

The Apollo rocket shortly after liftoff.The Apollo rocket shortly after liftoff from Cape Canaveral. This picture was taken when it happened, from the TV screen, in 1969. Copyright: Lars Carlsson


More pictures: 
Apollo 11 – The First Man on the Moon II. Seen as it happened – The Eagle has landed. Sunday, 19 July 2009 
Apollo 11 – The First Man on the Moon III. Seen as it happened – Moonwalk: Dancing Shadows. Sunday, 19 July 2009 
......... 

ZenMaster

For more on stem cells and cloning, go to CellNEWS at 

Friday, 17 July 2009

Why is Y Disappearing?

Male sex chromosome losing genes by rapid evolution 
Friday, 17 July 2009 

Scientists have long suspected that the sex chromosome that only males carry is deteriorating and could disappear entirely within a few million years, but until now, no one has understood the evolutionary processes that control this chromosome's demise. 

Now, a pair of Penn State scientists has discovered that this sex chromosome, the Y chromosome, has evolved at a much more rapid pace than its partner chromosome, the X chromosome, which both males and females carry. This rapid evolution of the Y chromosome has led to a dramatic loss of genes on the Y chromosome at a rate that, if maintained, eventually could lead to the Y chromosome's complete disappearance. The research team, which includes Associate Professor of Biology Kateryna Makova, the team's leader, and National Science Foundation Graduate Research Fellow Melissa Wilson, will publish its results in the 17 July 2009 issue of the journal PLoS Genetics. 
A wallaby is a marsupial. Credit: Kateryna Makova, Penn State.

"There are three classes of mammals," said Makova, "egg-laying mammals, like the platypus and the echidna; marsupials, like the opossum and the wallaby; and all other mammals – called eutherians – which include humans, dogs, mice, and giraffes. The X and Y chromosomes of marsupials and eutherians evolved from a pair of non-sex chromosomes to become sex chromosomes." 

Humans have 23 pairs of chromosomes, which are the structures that hold our DNA, but just one pair of these chromosomes are sex chromosomes, while the others are referred to as non-sex chromosomes. 

"In eutherian mammals, the sex chromosomes contain an additional region of DNA whereas, in the egg-laying mammals and marsupials, this additional region of DNA is located on the non-sex chromosomes," said Makova. 

"At first, bits of DNA within this additional region were readily swapped between the X and Y chromosomes, but some time between 80 and 130 million years ago, the region became two completely separate entities that no longer swapped DNA. One of the regions became specifically associated with the X chromosome and the other became specifically associated with the Y chromosome."

An echidna is a monotreme. Credit: Kateryna Makova, Penn State.

By comparing the DNA of the X and Y chromosomes in eutherian mammals to the DNA of the non-sex chromosomes in the opossum and platypus, the team was able to go back in time to the point when the X and Y chromosomes were still swapping DNA, just like the non-sex chromosomes in the opossum and platypus. The scientists then were able to observe how the DNA of the X and Y chromosomes changed over time relative to the DNA of the non-sex chromosomes. 

"Our research revealed that the Y-specific DNA began to evolve rapidly at the time that the DNA region split into two entities, while the X-specific DNA maintained the same evolutionary rate as the non-sex chromosomes," said Makova.

A giraffe is a eutherian mammal. Credit: Kateryna Makova, Penn State.

Once the biologists determined that the Y chromosome has been evolving more rapidly and has been losing more genes as a result, they wanted to find out why the Y chromosome has not already disappeared entirely.

"Today, the human Y chromosome contains less than 200 genes, while the human X chromosome contains around 1,100 genes," said Wilson. 

"We know that a few of the genes on the Y chromosome are important, such as the ones involved in the formation of sperm, but we also know that most of the genes were not important for survival because they were lost, which led to the very different numbers of genes we observe between the once-identical X and Y. Although there is evidence that the Y chromosome is still degrading, some of the surviving genes on the Y chromosome may be essential, which can be inferred because these genes have been maintained for so long." 

The team then decided to test the hypothesis that some of the genes on the Y chromosome are being maintained because they are essential. The team's approach was to compare the expression and function of genes on the Y chromosome with analogous genes on the X chromosome. 

"If the genes' expressions and/or functions were different, then it would make sense that the genes on the Y chromosome would be maintained because they are doing something that the genes on the X chromosome can't do," said Makova. 

"This hypothesis turned out to be correct." 

 Although some of the genes on the Y chromosome have been maintained, most of them have died, and the team found evidence that some others are on track to disappear, as well. 

"Even though some of the genes appear to be important, we still think there is a chance that the Y chromosome eventually could disappear," said Makova. 

"If this happens, it won't be the end of males. Instead, a new pair of non-sex chromosomes likely will start on the path to becoming sex chromosomes." 

 In the future, the team plans to use its newly generated data to create a computer model that tracks the degeneration of the Y chromosome. The scientists hope to determine how long it will take for the Y chromosome to disappear. They also hope to identify the processes that are most important for degeneration of the Y chromosome. 

Reference: 
Evolution and Survival on Eutherian Sex Chromosomes 
Melissa A. Wilson, Kateryna D. Makova 
PLoS Genet 2009, 5(7): e1000568. doi:10.1371/journal.pgen.1000568 
......... 


ZenMaster


For more on stem cells and cloning, go to CellNEWS at 
http://cellnews-blog.blogspot.com/