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Archive - Apr 2013

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April 4th

Stem Cells Used to Illuminate von Willebrand Disease; May Enable Personalized Treatment

Scientists have shed light on a common bleeding disorder by growing and analyzing stem cells from patients’ blood to discover the cause of the disease in individual patients. The technique may enable doctors to prescribe more effective treatments according to the defects identified in patients' cells. In the future, this approach could go much farther: these same cells could be grown, manipulated, and applied as treatments for diseases of the heart, blood, and circulation, including heart attacks and hemophilia. The new research is reported in an open-access article in the April 4, 2013 issue of the journal Blood. The study focused on von Willebrand disease (vWD), which is estimated to affect 1 in 100 people and can cause excessive, sometimes life-threatening, bleeding. vWD is caused by a deficiency of von Willebrand factor (vWF) (image), a blood component involved in making blood clot. vWF is produced by endothelial cells, which line the inside of every blood vessel in our body. Unfortunately, these cells are difficult to study because taking biopsies from patients is invasive and unpleasant. A group led by Dr. Anna Randi at the National Heart and Lung Institute, Imperial College London, used a new approach to investigate the disease. Dr. Richard Starke, a British Heart Foundation Intermediate Fellow and lead author of the study, took routine blood samples from eight patients with vWD, extracted stem cells called endothelial progenitor cells, and grew them in the lab to yield large numbers of endothelial cells. By testing these cells, the researchers were able to analyze each patient’s disease in unprecedented detail. In some patients, the scientists found new types of defect, which may enable them to recommend improved treatments.

New Discovery of Hearing Organ in South American Bush Cricket’s Ear Spurs Microphone Research

Research aimed at developing ultrasonic microphones with insect-like sensitivity is to continue in the rainforests of Colombia and Ecuador. Following the recent discovery of a previously unidentified hearing organ in the South American bush cricket’s ear, a scientist from the University of Lincoln (UK) will now study the role of this Auditory Vesicle in hearing sensitivity. Dr Fernando Montealegre-Zapata, from the University’s School of Life Sciences, aims to understand how bush crickets, also known as katydids, pick up on ultrasonic frequencies in their natural environment. The insects communicate using the highest-pitched calls in nature (130-150 kHz), which are not detected by humans. The males produce sound by rubbing their wings to attract distant females. Dr. Montealegre-Zapata said, “This animal can detect ultrasonic signals even at long distances. The problem is that at such high frequencies the sound travels in very short wavelengths which get diffracted, meaning the sound gets weaker as more obstacles are in the dispersive path. However, the bush cricket’s small ear is still able to detect this fading ultrasonic energy at long distances. I want to test how the bush crickets manage to do that in a field environment. The fluid in the katydid “cochlea,” which I named the Auditory Vesicle, is the key element in the hearing process. We want to investigate why this is the case and the first step is testing its sensitivity in their natural environment and revealing the chemical composition.” In mammals, hearing relies on three stages: an eardrum collecting sound, a middle ear impedance converter and a cochlear frequency analyzer. Dr Montealegre-Zapata recently demonstrated that the bush cricket’s ear performs these same steps in the hearing process, something previously unknown in insects.

Adult Stem Cells Isolated from Human Intestinal Tissue

For the first time, researchers at the University of North Carolina (UNC) at Chapel Hill, together with scientists from collaborating institutions, have isolated adult stem cells from human intestinal tissue. The accomplishment provides a much-needed resource for scientists eager to uncover the true mechanisms of human stem cell biology. It also enables them to explore new tactics to treat inflammatory bowel disease or to ameliorate the side effects of chemotherapy and radiation, which often damage the gut. "Not having these cells to study has been a significant roadblock to research," said senior study author Scott T. Magness, Ph.D., assistant professor in the departments of medicine, biomedical engineering, and cell and molecular physiology at UNC. "Until now, we have not had the technology to isolate and study these stem cells – now we have to tools to start solving many of these problems." The UNC study, published online on April 4, 2013, in the journal Stem Cells, represents a leap forward for a field that for many years has had to resort to conducting experiments in cells from mice. While significant progress has been made using mouse models, differences in stem cell biology between mice and humans have kept researchers from investigating new therapeutics for human afflictions. "While the information we get from mice is good foundational mechanistic data to explain how this tissue works, there are some opportunities that we might not be able to pursue until we do similar experiments with human tissue," lead study co-author Adam D. Gracz, a graduate student in Dr. Magness's lab. Megan K. Fuller, M.D., was also co-lead author of the study.

April 3rd

Eminent DNA Scientist Starts Blog on Major Nucleic Acid Developments

Dr. Gerald Zon (photo), a distinguished DNA scientist and Director of Business Development at TriLink BioTechnologies (trilinkbiotech.com) in San Diego, California, has just launched a biweekly blog that will post timely discussions of significant nucleic acid-related scientific content. This new blog promises to be of keen interest to many BioQuick readers and may be found at http://zon.trilinkbiotech.com. Dr. Zon’s inaugural article, posted on April 1, 2013, is entitled “60th Anniversary of the Discovery of DNA’s Double Helix Structure...Diamond Jubilee for the ‘Monarch of Molecules.’” The overall blog is called “Zone in with Zon--What’s Trending in Nucleic Acid Research.” A brief description of Dr. Zon’s broad experience is offered below. TriLink BioTechnologies is a company that offers cutting-edge services to researchers in the fields of gene therapy, nucleoside chemotherapy, and oligonucleotide therapy and diagnostics. TriLink specializes in the manufacture of modified nucleic acid products, including custom oligonucleotides, modified nucleoside triphosphates, CleanAmp™ PCR Products, RNA transcripts, phosphoramidites and other small molecules. Dr. Zon (Jerry) obtained his Ph.D. in chemistry from Princeton University in 1971. He subsequently developed automated synthesis of DNA analogs at the National Institutes of Health, and later at Applied Biosystems, Inc. (ABI). In 1992, he co-founded the ABI spin-off Lynx Therapeutics, an antisense company. He returned to ABI in 1999 to head up the DNA sequencing R&D group, and then he worked on novel methods for DNA sequencing as a Research Fellow at Life Technologies. In 2006, Dr. Zon was admitted as a Fellow of The Royal Society of Chemistry in the UK. At TriLink BioTechnologies since 2011, Dr. Zon has published over 260 papers and holds numerous patents.

April 2nd

Stem Cell Advance Should Speed Clinical Applications

A team of New York Stem Cell Foundation (NYSCF) Research Institute scientists led by David Kahler, Ph.D., NYSCF Director of Laboratory Automation, together with colleagues from Weill Cornell Medical College and Columbia University, has developed a new way to generate induced pluripotent stem (iPS) cell lines from human fibroblasts, acquired from both healthy and diseased donors. Reported online on March 29, 2013 in the open-acces journal PLOS ONE, this cell-sorting method consistently selects the highest quality, standardized iPS cells, representing a major step forward for drug discovery and the development of cell therapies. Employing a breakthrough method developed by 2012 Nobel laureate Shinya Yamanaka, M.D., Ph.D., adult cells are “reprogrammed” or caused to revert to an embryonic-like state, commonly through viral infection. Reprogramming is a dynamic process, resulting in a mixture of fully reprogrammed iPS cells, partially reprogrammed cells, and residual adult cells. Previous protocols to select promising fully reprogrammed cells rely primarily on judging stem cell colonies by eye through a microscope. Cell colonies selected by qualitative measures could include partially reprogrammed cells, a major concern for clinical applications of cell therapies because these cells could become any other cell type in a patient following transplantation. Additionally for drug efficacy assays and toxicity investigations on iPS cells, heterogeneous cell populations can mar the response of representative iPS cell lines. The NYSCF scientists developed a quantitative protocol, optimized over three and a half years, in order to consistently harvest early-reprogrammed cells. Using fluorescence activated cell sorting (FACS), fully reprogrammed cells were identified by two specific proteins, or pluripotency markers.

April 2nd

Vitamin P May Be Useful in Treating Damaged Motor Neurons

Biologists from the Ruhr-Universität Bochum (RUB) in Germany have explored how to protect neurons that control movements from dying off. In the journal Molecular and Cellular Neuroscience, the scientists report that the molecule 7,8-dihydroxyflavone, also known as vitamin P, ensures the survival of motor neurons in culture. It sends the survival signal on another path than the molecule brain-derived neurotrophic factor (BDNF), which was previously considered a candidate for the treatment of motor neuron diseases or after spinal cord damage. "The brain-derived neurotrophic factor only had a limited effect when tested on humans, and even had partially negative consequences," says Professor Stefan Wiese from the RUB Work Group for Molecular Cell Biology.. "Therefore we are looking for alternative ways to find new approaches for the treatment of neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS)." ALS is also known as Lou Gehrig’s disease. In previous studies, researchers hypothesized that vitamin P is an analogue of BDNF and thus works in the same way. This theory has been disproved in the current work by the team led by Dr. Teresa Tsai and Professor Stefan Wiese, from the RUB Group for Molecular Cell Biology and the Department of Cell Morphology and Molecular Neurobiology headed by Professor Andreas Faissner. Both substances ensure that isolated motor neurons of the mouse survive in cell culture and grow new processes, but what exactly the molecules trigger at the protein level varies. BDNF activates two signaling pathways, the so-called MAP kinase and PI3K/AKT signal paths. Vitamin P, on the other hand, activates only the PI3K/AKT signal path. However, vitamin P only exerted its positive effects on the motor neurons in a very small concentration range.

New Clues to Formulation of Mysterious Maya Blue Pigment

The recipe and process for preparing Maya Blue, a highly resistant pigment used for centuries in Mesoamerica, were lost. We know that the ingredients are a plant dye, indigo, and a type of clay known as palygorskite, but scientists do not know how they were “cooked” and combined together. Now, a team of chemists from the University of Valencia and the Polythecnic University of Valencia (Spain) have come up with a new hypothesis about how the mysterious pigment was prepared. Palace walls, sculptures, codices, and pieces of pottery produced by the ancient Maya incorporate the enigmatic Maya Blue. This pigment, which was also used by other Mesoamerican cultures, is characterised by its intense blue colour but, above all, by the fact that it is highly resistant to chemical and biological deterioration. Indeed, it was used centuries ago and when it is analyzed now it appears virtually unchangeable. There is no document that verifies how this paint was prepared and so it remains a mystery. Archaeologists and scientists have sought to uncover the mystery in recent years but it seems that researchers cannot come to an agreement. The dominant theory proposes that there is a single type of Maya Blue that was also prepared in a unique way and that a specific type of bond binds the two components: one organic component, indigo, the dye used for denim that is obtained from the Indigofera suffruticosa plant in Mesoamerica, and another inorganic component, palygorskite, a type of clay characterized by its crystal structure full of internal channels. But the work of a team from the University of Valencia (UV) and the Polytechnic University of Valencia (UPV) seems to contradict this “monoist” version.

Embryonic DNA Sampled after IVF for First Time Without Biopsy

Preimplantation genetic diagnosis (PGD) technologies allow identification of genetic disorders in human preimplantation embryos after in vitro fertilization (IVF) and before the embryo is transferred back to the patient. This technique allows couples with a high risk of passing on inherited diseases, to increase their chances of having a healthy baby. Despite the theoretical benefits of PGD, clinical outcomes using these technologies vary, possibly because of the need to remove one or more cells from the embryo using biopsy. In a study published on March 13, 2013 in Reproductive Biomedicine Online, a group of researchers from Italy and the United Kingdom sought to achieve diagnosis of genetic disease in embryonic DNA without the use of a biopsy. By extracting fluid from human embryos at the blastocyst stage they found that it contains DNA from the embryo. Blastocysts are 5- or 6-day-old embryos and are at the last free-living stage that can be studied in the laboratory prior to transfer into the uterus. Blastocysts contain between 50 and 300 cells that surround a fluid-filled cavity called the blastocoel.. The researchers carefully removed fluid from the blastocoel, leaving the cells intact. The sampled blastocysts were subsequently cryopreserved. This study employed real-time PCR to show that genomic DNA was present in about 90% of blastocoele fluid samples harvested. Moreover, the potential for determining embryo sex directly from blastocoele fluid was demonstrated by amplifying the multicopy genes TSPY1 (on the Y chromosome) and TBC1D3 (on chromosome 17). The authors said this opens up the possibility of screening embryos from couples carrying an X-linked disorder to identify male embryos at high risk of disease.

April 1st

Scientists Characterize Properties of Successfully Transmitted HIV-1

A new study by Los Alamos National Laboratory and University of Pennsylvania (U. Penn) scientists, together with colleagues from many other institutions, defines previously unknown properties of transmitted HIV-1, the virus that causes AIDS. The viruses that successfully pass from a chronically infected person to a new individual are both remarkably resistant to a powerful initial human immune-response mechanism, and blanketed in a greater amount of envelope protein that helps them access and enter host cells. These findings will help inform vaccine design and interpretation of vaccine trials, and provide new insights into the basic biology of viral/host dynamics of infection. During the course of each AIDS infection, the HIV-1 virus evolves within the infected person to escape the host’s natural immune response and adapt to the local environment within the infected individual. Because HIV evolves so rapidly and so extensively, each person acquires and harbors a complex, very diverse set of viruses that develops over the years of his or her infection. Yet when HIV is transmitted to a new person from his or her partner, typically only a single virus from the diverse set in the partner is transmitted to establish the new infection. The key discoveries here are the specific features that distinguish those specific viruses which successfully move to the new host, compared with the myriad forms in the viral population present in a chronically infected individual. “The viruses that make it through transmission barriers to infect a new person are particularly infectious and resilient,” said Los Alamos National Laboratory scientist Dr. Bette Korber.

Overexpressin of NUB1 Reduces Amounts of Mutant Huntingtin Protein

Researchers at Fudan University in China and the Novartis Institutes for Biomedical Research in Boston, together with colleagues from the Baylor College of Medicine, Texas Children’s Hospital, Harvard Medical School, and Massachusetts General Hospital have reported using high-throughput screening to identify genes that modify endogenous mutant huntingtin protein (mHTT) and demonstrated that the overexpression of a particular gene product (negative regulator of ubiquitin-like protein 1 or NUB1, rescues mHTT-induced death in a fruit fly model system. The authors said that NUB1 reduces mHTT amounts by enhancing polyubiquination and proteasomal degradation of mHTT protein. The process requires CUL3 and the ubiquitin-like rotein NEDD8 necessary for CUL3 activation. The authors noted that interferon- lowered mHTT and rescued neuronal toxicity through induction of NUB1. The article on this research was published online on March 24, 2013 in Nature Neurology. [Nature Neurology abstract]