DURHAM, N.C. – Duke University Medical Center scientists have found a mechanism that allows cells starved of iron to shut down energy-making processes that depend on iron and use a less efficient pathway involving glucose. This metabolic reshuffling mechanism, found in yeast cells, helps explain how humans respond to iron deficiency, and may help with diabetes research as well.
"If we can understand what metabolic changes happen along a gradient of iron deficiency, then we might be able to identify signatures of a modest iron deficiency in humans," said lead researcher Dennis J. Thiele, Ph.D., who is the George Barth Geller Professor of the Duke Department of Pharmacology and Cancer Biology, "We could head it off at the pass."
"This basic science discovery in yeast sheds important new light on how humans may respond to iron deficiency, which is the most common nutritional disorder," said Duke School of Medicine Dean Nancy C. Andrews, an expert in human diseases of iron metabolism.
The findings, published in the June issue of Cell Metabolism, are also potentially important for those studying diabetes. "Evidence is growing that if there is an iron imbalance in the beta cells of the pancreas, these cells won't produce insulin properly," Thiele said. "Now we know what happens in yeast in terms of glucose (sugar) utilization. We need to learn whether the same cause and effect holds true in mammals."
Iron deficiency anemia affects nearly 2 billion people worldwide, most often pregnant women, premature babies, and young children, Thiele said. Anemia profoundly affects cognitive development, and motor and neuronal development, he said.
The scientists wanted to know how organisms establish a balance of iron in their cells. "We now know when yeast cells encounter iron deficiency, they reorganize their metabolism by degrading specific messenger RNAs (mRNAs) and leaving other messenger RNAs alone, which begins a sequence of events," said Thiele. Messenger RNAs are molecules that carry coding information from the DNA to the structures that make proteins, which in turn regulate the body's structures and functions.
The first response to iron deficiency is to shut down the energy hub of the cell, the mitochondria, which takes glucose and turns it efficiently into cell energy fuel, or ATP. The mitochondria depend greatly on iron. As a cell becomes more starved for iron, it "dials down" the mitochondrial processes by degrading the mRNAs encoding the proteins involved in such processes, and thus, some iron is freed up, Thiele said.
The second response is to shut down iron storage pathways and other, more dispensable biochemical reactions that depend on iron. "When you are low on iron, you don't want to save it and take it out of use," Thiele explained.
The third response is to increase glucose utilization pathways outside of the mitochondria, which is a much less efficient way to produce energy. Glucose molecules processed for energy outside of the mitochondria create about 18 times less energy, said co-author Sandra Vergara, a doctoral student in Thiele's lab.
"Cellular iron balance follows the rules of economics," Vergara said. "During scarcity, the cell prioritizes the utilization of iron, saving it for more essential processes. This prioritization comes at a cellular cost, which is reflected in the higher demand for glucose, so the cell can keep the correct amount of energy flowing."
If we run low on ATP, we become tired and lethargic, which are symptoms of iron deficiency, Thiele said. "Iron is hard for humans to get from plant sources, which form the basis for most of the world's diet." Iron is very abundant in nature, but cells have a hard time taking it up, because it can change its form inside the body.
Thiele stressed that the findings show what happens during iron deficiency in baker's yeast cells, but probably in some way do extend to people. "Nearly 35 percent of all known human disease genes have a counterpart in the yeast genome. A scientist is always conservative about extrapolating. I think we can make predictions that the metabolic reshuffling that we observe in yeast, the same types of key proteins and enzymes that are involved during iron deficiency, are likely to follow similar patterns in human cells."
Most of the primary metabolism pathways are conserved at the molecular level from yeast to humans, Vergara said.
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The third co-author on this work was Sergi Puig, who was a postdoctoral fellow in the Thiele lab and now is an assistant professor at the University of Valencia in Spain. This research was funded by a grant from the Spanish Ministerio de Educacion y Ciencia and FEDER funds from the European Community, an NIH grant from the National Institute of General Medical Sciences and an NIH predoctoral fellowship.
Monday, June 9, 2008
Duke University Medical Center : Duke scientists show why cells starved of iron burn more glucose
Wiley-Blackwell : Specialist nurses can play a key role in supporting patients having radiotherapy
Cancer patients who attended a specialist nurse clinic rather than a consultant-led clinic for regular radiotherapy reviews benefited from longer, more frequent consultations and good symptom management, according to a paper in the June issue of the Journal of Clinical Nursing.
And because the clinical nurse specialist was able to carry out 83 per cent of the consultations without referring issues to the consultant, patients also avoided the need to see their doctor on a routine basis.
Researchers from the University of Dundee and the City's Ninewells Hospital also found that the patients – who were undergoing treatment for head and neck cancer – were more likely to be referred to members of the multi-disciplinary team. This resulted in better management of common radiotherapy side effects, like oral and nutritional problems.
When researchers compared the 23 patients attending the nurse specialist-led clinics with the 20 who had attended consultant-led clinics in the previous six months, they found that the patients reported few significant differences in quality of life. Their comments also showed that they particularly valued the relationship they had built up with the clinical nurse specialist.
Feedback from the family doctors who took part in the study was also good. They were positive about the timing and content of the information they received from the clinical nurse specialist about their patients' ongoing treatment.
"Our study showed that clinical nurse specialists can play a key role in the management of head and neck cancer patients having radiotherapy and this may take the pressure off busy consultants, with no reduction in the quality of care provided" says lead author Dr Mary Wells, a Lecturer and Clinical Research Fellow in Cancer Nursing from the University.
"As a result of our research, the majority of radiotherapy review clinics at Ninewells Hospital are now conducted by a clinical nurse specialist. But greater investment is needed to develop specialist nursing roles if initiatives like this are to be replicated elsewhere in the UK."
Key findings of the study included:
Nurses were able to spend 16 minutes on each consultation - four times as long as the consultants - and patients had shorter waits to see them (two minutes versus nine).
Overall quality of life scores were similar in both groups, but patients in the consultant-led clinic group reported slightly higher emotional functioning.
Baseline pain scores were higher in the nurse-led group but rose less sharply than in the medical group.
Patients in the nurse-led group had better scores for social eating, social contact, dry mouth, sticky saliva, teeth problems and weight loss.
Patients in the medical group were more likely to have lost weight and less likely to have gained weight, despite receiving more nutritional supplements.
"Our study demonstrates that clinical nurse specialists in radiotherapy can effectively lead on-treatment reviews for patients using a protocol-based approach and that patients and family doctors appreciate the support, information and communication provided by nurse-led clinics" says Dr Wells.
"The findings suggest that when nurses work as part of a supportive multi-disciplinary team they can manage the majority of these routine consultations without direct input from the consultant, even in this highly symptomatic and complex group."
The study has led to direct changes in the way neck and head cancer patients are managed at Ninewells Hospital and the majority of the radiotherapy review clinics are now conducted by a clinical nurse specialist with specific training and expertise in radiotherapy care.
"The clinical nurse specialist is now able to prescribe a wider range of medication and is responsible for coordinating complex treatment regimes and supporting patients with complex symptoms" says Dr Wells.
"We also believe there is considerable potential to develop the assessment and care of patients with head and neck cancer before and after treatment as well as during radiotherapy.
"Clinical nurse specialists are ideally placed to provide information and advice on issues like health education, smoking cessation and alcohol consumption, to help reduce the impact of the patient's symptoms and improve their quality of life.
"They could also provide support, community liaison and symptom management immediately after treatment when patients are no longer in day-to-day contact with the hospital but the side effects continue to affect their daily life."
However the researchers point out that the potential to develop nurse-led radiotherapy clinics across the UK is hampered by a lack of investment in radiotherapy nursing.
"Nurses working in radiotherapy are relatively few and far between, postholders often work in isolation and their contribution has not been sufficiently acknowledged" says Dr Wells.
"We hope that our study, and the service developments it has inspired, will stimulate a debate about the valuable role that nurses can play in supporting cancer patients undergoing radiotherapy.
"We also hope that it will highlight the need for greater investment in this valuable speciality."
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Notes to editors
A study to evaluate nurse-led on-treatment review for patients undergoing radiotherapy for head and neck cancer. Wells et al. Journal of Clinical Nursing. 17, 1428-1439. (June 2008)
Founded in 1992, Journal of Clinical Nursing is a highly regarded peer reviewed Journal that has a truly international readership. The Journal embraces experienced clinical nurses, student nurses and health professionals, who support, inform and investigate nursing practice. It enlightens, educates, explores, debates and challenges the foundations of clinical health care knowledge and practice worldwide. Edited by Professor Roger Watson, it is published 10 times a year by Blackwell Publishing Ltd, part of the international Blackwell Publishing group. www.blackwellpublishing.com/jcn
About Wiley-Blackwell. Wiley-Blackwell was formed in February 2007 as a result of the acquisition of Blackwell Publishing Ltd. by John Wiley & Sons, Inc., and its merger with Wiley's Scientific, Technical, and Medical business. Together, the companies have created a global publishing business with deep strength in every major academic and professional field. Wiley-Blackwell publishes approximately 1,400 scholarly peer-reviewed journals and an extensive collection of books with global appeal. For more information on Wiley-Blackwell, please visit www.blackwellpublishing.com or http://interscience.wiley.com
Weber Shandwick Worldwide Prevent a bone break, drink milk to boost calcium
New study finds adding calcium could help prevent adult fractures
Boosting calcium intake by drinking milk could reduce healthy adults' chances of a debilitating bone break. In a new study published in the American Journal of Clinical Nutrition, healthy men and women supplemented with 1,200 mg of calcium per day – the amount in four glasses of milk – reduced their risk of bone fractures by 72%.
An international team of researchers from University Hospital Zurich and Dartmouth Medical School divided 930 healthy men and women ages 27 to 80 into two groups for a four year intervention study. One group was given a placebo, while the other took a daily calcium supplement containing 1,200mg of calcium daily – the calcium recommendation for adults over the age of 51.
The researchers found that those receiving an additional 1,200 mg of calcium were significantly less likely to have a bone fracture of any sort during the four-year period, including everyday activity fractures (bone breaks that occurred while walking or standing) and seemingly unavoidable accident-related fractures (bone breaks sustained during falls, running, sports injuries or car accidents). In fact, during the four-year intervention, not a single adult receiving calcium experienced a fracture tied to everyday activities – fractures that researchers call "potentially preventable" and more likely linked to bone health.
To sustain the benefits, researchers found that the adults needed to maintain their calcium intakes. After the four-year supplementation period ended, the bone benefits dissipated, underscoring the need to adopt lifelong habits, like drinking milk, to prevent bone loss.
Adult bones continue to grow in density and strength until about age 35. After that, preventing further bone loss is essential. Poor bone health and bone fractures can have negative consequences for adults of all ages, interfering with recreational activities, ability to work or physical capacity to exercise and stay healthy. These adult bone fractures may also be an early sign of risk for osteoporosis – a serious condition of brittle bones afflicting more than 10 million Americans.
The Dietary Guidelines for Americans recommend three servings of fat-free or lowfat milk each day, providing 90% of the recommended daily value of calcium for most adults. Milk is also an excellent source of vitamin D, helping the body absorb this much-needed calcium to help maintain strong bones and reduce the risk of osteoporosis.
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Sources:
Bischoff-Ferrari HA, Rees JR, Grau MV, Barry E, Gui J, Baron JA. Effect of calcium supplementation on fracture risk: a double-blind randomized controlled trial. American Journal of Clinical Nutrition. 2008;87:1945-1951.
American Chemical Society : American Chemical Society
ARTICLE #1 FOR IMMEDIATE RELEASE
"Super paper:" New nanopaper more break-resistant than cast iron Biomacromolecules
Researchers in Sweden and Japan report development of a new type of paper that resists breaking when pulled almost as well as cast iron. The new material, called "cellulose nanopaper," is made of sub-microscopic particles of cellulose and may open the way for expanded use of paper as a construction material and in other applications, they suggest. Their study is scheduled for the June 9 issue of ACS' Biomacromolecules, a monthly journal.
In the new study, Lars A. Berglund and colleagues note that cellulose — a tough, widely available substance obtained from plants — has potential as a strong, lightweight ingredient in composites and other materials in a wide range of products. Although cellulose-based composites have high strength, existing materials are brittle and snap easily when pulled.
The study described a solution to this problem. It involves exposing wood pulp to certain chemicals to produce cellulose nanopaper. Their study found that its tensile strength — a material's ability to resist pull before snapping — exceeded that of cast iron. They also were able to adjust the paper's strength by changing its internal structure. — MTS
ARTICLE #1 FOR IMMEDIATE RELEASE "Cellulose Nanopaper Structures of High Toughness"
DOWNLOAD FULL TEXT ARTICLE http://dx.doi.org/10.1021/bm800038n
CONTACT: Lars A. Berglund, Ph.D. Royal Institute of Technology Stockholm, Sweden Phone: 46-8-7908118 Fax: 46-8-7908101 Email: blund@kth.se
Compared to bottled garlic, fresh garlic contains higher levels of an ingredient called allicin, which can help prevent blood clots and bacterial infections.
Click here for more information.
ARTICLE #2 FOR IMMEDIATE RELEASE
Love that garlic? Fresh may be healthier than bottled Journal of Agricultural and Food Chemistry
The next time you use garlic for its renowned antibacterial effects, consider fresh garlic instead of those bottles of chopped garlic. Researchers in Japan report that fresh garlic maintains higher levels of a key healthy ingredient than preserved versions and may be better for you. Their study is scheduled for the June 25 issue of ACS' Journal of Agricultural and Food Chemistry, a bi-weekly publication.
In the new study, Toyohiko Ariga and colleagues point out that allicin is one of the main active ingredients in garlic. Other studies have shown that allicin has beneficial effects in preventing blood clots, cancer, and bacterial infection. Although commercially bottled garlic is often stored in oil or water, researchers did not know how various storage and preservation methods affect levels of allicin, which is fragile and disappears quickly.
To find out, Ariga's group compared allicin levels in extracts of fresh garlic after 1-2 weeks of storage in water, alcohol, and vegetable oil. Garlic stored in water at room temperature lost about half its allicin in 6 days and garlic in vegetable oil lost half its allicin in less than an hour. The garlic lost its antibacterial action as allicin broke down. However, allicin broke down into materials that still are believed to have some anticancer and anti-blood clot effects. — MTS
ARTICLE #2 FOR IMMEDIATE RELEASE "Biological and Chemical Stability of Garlic-Derived Allicin"
DOWNLOAD FULL TEXT ARTICLE http://dx.doi.org/10.1021/jf8000907
CONTACT: Toyohiko Ariga, Ph.D. Nihon University Fujisawa, Japan Phone: 81-466-84-3948 Fax: 81-466-84-3949 Email: ariga@brs.nihon-u.ac.jp
ARTICLE #3 FOR IMMEDIATE RELEASE
Sniffing out a broad-spectrum of airborne threats in seconds Analytical Chemistry
Scientists in California are reporting successful laboratory and field tests of a new device that can sniff out the faintest traces of a wide range of chemical, biological, nuclear, and explosive threats - and illicit drugs - from the air in minutes with great accuracy. The ultra-sensitive detector, known as the single-particle aerosol mass spectrometry (SPAMS) system, could tighten security at airports, sports stadiums and other large-scale facilities, according to their report, scheduled for the July 1 issue of ACS' Analytical Chemistry, a semi-monthly journal.
Matthias Frank and colleagues explain that chemical, biological, nuclear, and explosive materials, as well as illicit drugs, all release minute amounts of aerosol particles into the air. Detecting these particles requires a device with a high sensitivity, low probability of false alarms, and a fast response time. "SPAMS uniquely meets these requirements in realistic field environments," the report states. While other aerosol detectors exist, SPAMS is specifically designed for the rapid detection of low-concentration aerosols, it adds.
The study describes laboratory tests of SPAMS and extended field tests at San Francisco International Airport. It showed that within seconds, SPAMS detected a diverse set of materials including simulants for potentially hazardous biological, chemical and radiological materials, as well as actual explosives and drugs. The study terms SPAMS a "significant and important advance in rapid aerosol threat detection." — AD
ARTICLE #3 FOR IMMEDIATE RELEASE "Autonomous, Broad-Spectrum Detection of Hazardous Aerosols in Seconds"
DOWNLOAD FULL TEXT ARTICLE http://dx.doi.org/10.1021/ac8004428
CONTACT: Matthias Frank, Ph.D. Lawrence Livermore National Laboratory Livermore, California 94550 Phone: (925) 423-5068 Fax: (925) 424-2778 Email: frank1@llnl.gov
ARTICLE #4 FOR IMMEDIATE RELEASE
Inhalable form of gene-therapy takes aim at lung cancer and inflammatory lung disease Molecular Pharmaceutics
A new inhalable form of gene therapy — based on technology recognized in the 2006 Nobel medicine prize, shows increasing promise for treating lung cancer, infectious diseases and inflammatory lung disease, scientists have concluded after an exhaustive review of worldwide research on the topic. Their report is scheduled for the June 2 issue of ACS' Molecular Pharmaceutics, a bi-monthly journal.
In the article, Sally-Ann Cryan, Niamh Durcan, and Charlotte Murphy focus on research efforts to develop an inhalable form of RNA interference (RNAi), a gene-therapy technique that interferes with or "silences" genes that make disease-causing proteins. The authors explain that RNAi has advantages over other gene therapies. It is potent, very specific, and appears to have a low risk of side effects.
They cite encouraging results with RNAi in laboratory studies in cells and animals with a range of lung diseases, including lung cancer, certain respiratory infections and inflammatory lung disease. Keys to successful therapy in humans include careful design of the gene-silencing agents, determining the most effective doses, and developing better ways of delivering RNAi agents to the lungs, the scientists say. — MTS
ARTICLE #4 FOR IMMEDIATE RELEASE "Inhalable siRNA: Potential as a Therapeutic Agent in the Lungs"
DOWNLOAD FULL TEXT ARTICLE http://dx.doi.org/10.1021/mp070048k
CONTACT: Sally-Ann Cryan, Ph.D. Royal College of Surgeons in Ireland Dublin, Ireland Phone: 353-1-4022741 Fax: 353-1-4022765 Email: scryan@rcsi.ie
ARTICLE #5 EMBARGOED FOR 9 A.M., EASTERN TIME, June 9, 2008
Researchers band together in global battle on bacterial biofilms Chemical & Engineering News
The discovery that bacteria are not loners, but social creatures that congregate and chemically communicate in communities — termed biofilms — has sparked a global scientific effort to control spread of these slimy coatings that grow on hospital surfaces, inside tubing, and a multitude of other places. That's the topic of an article scheduled for the June 9 issue of Chemical & Engineering News, ACS' weekly newsmagazine.
In the C&EN cover story, Senior Editor Lisa M. Jarvis points that biofilms are the major culprit behind hospital-acquired infections that are now the fourth leading cause of death in the United States, claiming thousands of lives each year. Biofilms also cause other problems ranging from dental plaque to the biofouling of ship hulls. The films are large, complex communities of bacteria that are difficult to kill.
But researchers from academia and industry are now collaborating in a global effort to develop promising new strategies to combat this problem. New approaches include the development of non-stick surfaces and the identification of chemicals that silence bacterial communication or starve them of key nutrients. The first commercial compound to specifically target biofilms is still a few years away, according to the article.
ARTICLE #5 EMBARGOED FOR 9 A.M., EASTERN TIME, June 9, 2008 "Communal Living"
This story will be available on June 9 at http://pubs.acs.org/cen/coverstory/86/8623cover.html
FOR ADVANCE INFORMATION, CONTACT: Michael Bernstein ACS News Service Phone: 202-872-6042 Fax: 202-872-4370 Email: m_bernstein@acs.org
Journalists' Resources
Save the Date: ACS's 236th National Meeting, August 17-21, Philadelphia One of 2008's largest and most important scientific conferences — the 236th National Meeting and Exposition of the American Chemical Society will be held Aug. 17-21, 2008, in Philadelphia, Pa. At least 12,000 scientists and others are expected for the event, which will include more than 8,000 reports on new discoveries in chemistry. The multi-disciplinary theme is Chemistry for Health: Catalyzing Transitional Research. Stay tuned for information on registration, housing, press releases, and onsite press briefings that will be available via the Internet.
ChemMatters Matters for Journalists This quarterly ACS magazine for high school chemistry students, teachers, and others explains the chemistry that underpins everyday life in a lively, understandable fashion. ChemMatters is available at www.acs.org/chemmatters. You can also receive the most recent issues by contacting the editor, Pat Pages, at: 202-872-6164 or chemmatters@acs.org.
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Saturday, June 7, 2008
Offspring PR : Galiximab in combination with rituximab in patients with previously untreated follicular lymphoma
Data from phase II clinical trial presented at International Conference on Malignant Lymphoma
Lugano, Switzerland – June 7, 2008 – The Cancer and Leukemia Group B (CALGB) today announced data from a phase II clinical trial showing that 70 percent of patients with previously untreated follicular lymphoma responded to treatment with galiximab, an investigational anti-CD80 monoclonal antibody, when given in combination with rituximab. Of the 61 patients in the study, 44 percent achieved a complete response and 26 percent had a partial response. The data were presented at the 10th International Conference on Malignant Lymphoma (ICML).
The results of this open label study suggest that adding galiximab to rituximab may be a promising regimen for patients with follicular lymphoma (FL), a common type of non-Hodgkin lymphoma (NHL), and that further study is warranted. The objective of the CALGB-coordinated study is to determine the overall response rate (ORR) and time-to-progression of the disease after treatment with a combined regimen of galiximab and rituximab. At this point, however, it is too early to assess the time-to-progression endpoint.
"Most non-Hodgkin lymphoma patients receive rituximab, either as a single agent or in combination with chemotherapy," said Myron Czuczman, M.D., Roswell Park Cancer Institute, principal investigator of this study. "Now, 'biologic' agents are being studied in combination to assess the efficacy of dual antibody therapies as potential alternatives to chemotherapy-based regimens."
Patients enrolled in the study had been diagnosed with CD20-positive FL but had not received treatment for the disease. Study patients were given galiximab plus rituximab together once a week for four weeks and then every two months for the next eight months. This "extended induction" schedule was chosen based on results from an earlier Swiss (SAKK) trial using the same schedule with single-agent rituximab. Thirteen percent of patients reported a grade 3 adverse event; no grade 4 toxicities were associated with this combination immunotherapy regimen.
Galiximab is an anti-CD80 monoclonal antibody that has been studied as a single-agent in previously treated FL and in combination with rituximab against relapsed FL. The CD80 molecule is found on the surface of activated macrophages, dendritic cells and cells from various subtypes of NHL. Galiximab's potential mechanisms of action include Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC) and possible immunomodulatory effects on host effector cells affecting the tumor microenvironment.
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The trial was sponsored by the National Cancer Institute (NCI), part of the National Institutes of Health and was led by CALGB, which is one of NCI's Cooperative Clinical Trials Groups. In addition to this trial, CALGB is planning to study galiximab as a single agent in a proof-of-concept trial in relapsed Hodgkin lymphoma. More information about clinical trials involving galiximab is available at www.clinicaltrials.gov.
About Non-Hodgkin Lymphoma
An estimated 360,000 Americans have NHL and more than 58,000 new cases are diagnosed annually. Approximately 85 percent of all cases of NHL involve abnormal immune cells called B-cells. Of those diagnosed with NHL, about 30 percent of patients have a slow-growing, but incurable (low-grade) form of the disease -- the most common type is called follicular lymphoma (FL). Although FL progresses slowly, the median survival time is seven to 10 years. In addition, relapse is common and less than half of FL patients who experience a relapse will survive for five years. Approximately 31 percent of those diagnosed with NHL have DLBCL, a faster-growing subtype of NHL that multiplies and spreads rapidly in the body, and if left untreated, can be fatal.
About CALGB
The Cancer and Leukemia Group B (CALGB) is a national clinical research group sponsored by the National Cancer Institute, with its Central Office headquartered at the University of Chicago and its Statistical Center located at Duke University. The CALGB was founded in 1956 with a goal of bringing together clinical oncologists and laboratory investigators to develop better treatments for cancer. Since 1956, CALGB has grown into a national network of 26 university medical centers, over 225 community hospitals and more than 3,000 oncology specialists who collaborate in clinical research studies aimed at reducing the morbidity and mortality from cancer, relating the biological characteristics of cancer to clinical outcomes and developing new strategies for the early detection and prevention of cancer.
The American Ceramics Society : Microspheres to carry hydrogen, deliver drugs, filter gases and detect nuclear development
The answer is contained in the June issue of The Bulletin, the monthly magazine of The American Ceramic Society, which carries the first news of a never-before-seen class of materials and technology developed by scientists at the Savannah River National Laboratory. (The full article can be downloaded at
SRNL Researchers G.G. Wicks, L.K. Heung, and R.F. Schumacher have been able to use these open channels to fill the microballons with gas absorbents and other materials. Hydrogen or other reactive gases can then enter the microspheres through the pores, creating a relatively safe, contained, solid-state storage system.
Photographs of these glass-absorbent composites also reveal that the wall porosity generates entirely new nano-structures.
Wicks, Heung and Schumacher have shown that the PW-HGM's permeable walls can be used for non-composite purposes, too. For example, the porosity can be altered and controlled in various ways that allow the spheres to filter mixed gas streams within a system.
Another feature of the microballoons is that their mechanical properties can be altered so they can be made to flow like a liquid. This suggests that an existing infrastructure that currently transports, stores and distributes liquids such as the existing gasoline distribution and retail network can be used. This property and their relative strength also make the PW-HGMs suitable for reuse and recycling.
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Founded in 1898, The American Ceramics Society is the professional membership organization for international ceramics and materials scientists, engineers, researchers, manufacturers, plant personnel, educators, students. Drawing members from 60 countries, ACerS serves the informational, educational, and professional needs of its 6,000 members and provides them with access to periodicals and books, meetings and expositions, and online technical information. Besides The Bulletin, ACerS publishes the peer-reviewed Journal of the American Ceramic Society and the International Journal of Applied Ceramic Technology, two of the most cited ceramic publications in the world.
Schepens Eye Research Institute : Brain stem cells can be awakened, say Schepens scientists
Study findings promise to help in treatment of brain diseases
Boston, MA-Scientists at Schepens Eye Research Institute have identified specific molecules in the brain that are responsible for awakening and putting to sleep brain stem cells, which, when activated, can transform into neurons (nerve cells) and repair damaged brain tissue. Their findings are published online this week in the Proceedings of the National Academy of Science (PNAS).
An earlier paper (published in the May issue of Stem Cells) by the same scientists laid the foundation for the PNAS study findings by demonstrating that neural stem cells exist in every part of the brain, but are mostly kept silent by chemical signals from support cells known as astrocytes.
³The findings from both papers should have a far-reaching impact,² says principal investigator, Dr. Dong Feng Chen, who is an associate scientist at Schepens Eye Research Institute and an assistant professor of ophthalmology at Harvard Medical School. Chen believes that tapping the brain¹s dormant, but intrinsic, ability to regenerate itself is the best hope for people suffering from brain-ravaging diseases such as Parkinson¹s or Alzheimer¹s disease or traumatic brain or spinal cord injuries.
Until these studies, which were conducted in the adult brains of mice, scientists assumed that only two parts of the brain contained neural stem cells and could turn them on to regenerate brain tissue-- the subgranular zone (SGZ) of the hippocampus and the subventricular zone (SVZ). The hippocampus is responsible for learning and memory, while the SVZ is a brain structure situated throughout the walls of lateral ventricles (part of the ventricular system in the brain) and is responsible for generating neurons reponsible for smell. So scientists believed that when neurons died in other areas of the brain, they were lost forever along with their functions.
In the first study, Chen¹s team learned that stem cells existed everywhere in the brain by testing tissue from different parts of adult mice brains in cultures containing support cells (known as astrocytes) from the hippocampus, where stem cells do regenerate.
In the cultures the stem cells from other brain regions came to life and turned into neurons.
When they compared the chemical makeup of the areas known to generate new neurons in the hippocampus with other parts of the brain, the team discovered that astrocytes in the hippocampus were sending one signal to the stem cells and that those from the rest of the brain were sending a different signal to stem cells.
In the second (PNAS) study, the team went on to discover the exact nature of those different chemical signals. They learned that in the areas where stem cells were sleeping, astrocytes were producing high levels of two related molecules--ephrin-A2 and ephrin-A3. They also found that removing these molecules (with a genetic tool) activated the sleeping stem cells.
The team also found that astrocytes in the hippocampus produce not only much lower levels of ephrin-A2 and ephrin-A3, but also release a protein named sonic hedghoc that, when added in culture or injected into the brain, stimulates neural stem cells to divide and become new neurons.
³These findings identify a key pathway that controls neural stem cell growth in the adult brain and suggest that it may be possible to reactivate the dormant regenerative potential by adding sonic hedgehoc, or blocking ephrin-A2 or ephrin-A3,² says Dr. Jianwei Jiao, the first author of the two papers.
The next step for the team will be to stimulate the sleeping stem cells in animals who are models of neurodegenerative disorders, such as Parkinson's disease, to see if the brains can repair themselves and restore their damaged functions.
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Schepens Eye Research Institute is an affiliate of Harvard Medical School and the largest independent eye research institute in the country.
University of Wisconsin-Madison : Scientific information largely ignored when forming opinions about stem cell research
MADISON - When forming attitudes about embryonic stem cell research, people are influenced by a number of things. But understanding science plays a negligible role for many people.
That's the surprising finding from a team of University of Wisconsin-Madison communications researchers who have spent the past two years studying public attitudes toward embryonic stem cell research. Reporting in the most recent issue of the International Journal of Public Opinion, the researchers say that scientific knowledge - for many citizens - has an almost negligible effect on how favorably people regard the field.
"More knowledge is good - everybody is on the same page about that. But will that knowledge necessarily help build support for the science?" says Dietram Scheufele, a UW-Madison professor of life sciences communication and one of the paper's three authors. "The data show that no, it doesn't. It does for some groups, but definitely not for others."
Along with Dominique Brossard, a UW-Madison professor of journalism and mass communication, and graduate student Shirley Ho, Scheufele used national public opinion research to analyze how public attitudes are formed about controversial scientific issues such as nanotechnology and stem cells. What they have found again and again is that knowledge is much less important than other factors, such as religious values or deference to scientific authority.
In the case of stem cells, values turn out to be key, says Scheufele. For respondents who reported that religion played a strong role in their lives, scientific knowledge had no effect on their attitudes toward stem cell research. But for those who claimed to be less religious, understanding the science was linked to more positive views of the research.
"Highly religious audiences are different from less religious audiences. They are looking for different things, bringing different things to the table," explains Scheufele. "It is not about providing religious audiences with more scientific information. In fact, many of them are already highly informed about stem cell research, so more information makes little difference in terms of influencing public support. And that's not good or bad. That's just what the data show."
On the other hand, a value system held by a much smaller portion of the American public works in just the opposite direction. The attitudes of individuals who are deferential to science - who tend to trust scientists and their work - are influenced by their level of scientific understanding.
Overall, says Brossard, "more understanding doesn't always change attitudes. A lot depends on people's values. And those values need to be considered carefully when we communicate with the public about these issues."
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- Nicole Miller, (608) 262-3636, nemiller2@wisc.edu
National Science Foundation : A New Way to Think About Earth's First Cells
Study provides insight into how Earth's earliest cells may have interacted with their environment
A team of researchers at Harvard University have modeled in the laboratory a primitive cell, or protocell, that is capable of building, copying and containing DNA.
Since there are no physical records of what the first primitive cells on Earth looked like, or how they grew and divided, the research team's protocell project offers a useful way to learn about how Earth's earliest cells may have interacted with their environment approximately 3.5 billion years ago.
The protocell's fatty acid membrane allows chemical compounds, including the building blocks of DNA, to enter into the cell without the assistance of the protein channels and pumps required by today's highly developed cell membranes. Also unlike modern cells, the protocell does not use enzymes for copying its DNA.
Supported with funding from the National Science Foundation and led by Jack W. Szostak of the Harvard Medical School, the research team published its findings in the June 4, 2008, edition of the journal Nature's advance online publication.
"Szostak's group took a creative approach to this research challenge and made a significant contribution to our understanding of small molecule transport through membranes," said Luis Echegoyen, director of the NSF Division of Chemistry. "This is a great outcome of NSF's support of basic research."
Some scientists have proposed that ancient hydrothermal vents may have been sites where prebiotic molecules--molecules made before the origin of life, such as fatty acids and amino acids--were formed. An animation (accessible at upper right) created by Janet Iwasa of the Szostak Laboratory shows a theoretical scenario in which fatty acids are formed on the surface of minerals deep underground, and then brought to the surface by the eruption of a geyser.
When fatty acids are in an aqueous environment, they spontaneously arrange so that their hydrophilic, or water-loving, "heads" interact with the surrounding water molecules and their hydrophobic, or water-fearing, "tails" are shielded from the water, resulting in the formation of tiny spheres of fatty acids called micelles.
Depending upon chemical concentrations and the pH of their environment, micelles can convert into layered membrane sheets or enclosed vesicles. Researchers commonly use vesicles to model the cellular membranes of protocells. A second animation created by Iwasa (accessible at lower right) shows how vesicles may have been formed.
When the team started its work, the researchers were not sure that the building blocks required for copying the protocell's genetic material would be able to enter the cell.
"By showing that this can happen, and indeed happen quite efficiently, we have come a little closer to our goal of making a functional protocell that, in the right environment, is able to grow and divide on its own," said Szostak.
Co-authors of the Nature paper include Sheref S. Mansy, Jason P. Schrum, Mathangi Krishnamurthy, Sylvia Tobe and Douglas A. Treco of the Szostak Laboratory.
The research was supported by NSF Division of Chemistry award number 0434507. Jack W. Szostak was also supported by National Aeronautics and Space Administration Exobiology Program award number EXB02-0031-0018. Sheref S. Mansy was supported by National Institutes of Health award number F32 GM07450601.
Funding for Exploring Life's Origins Web site project was provided by NSF award number 0610117.
-NSF-
Media ContactsJennifer A. Grasswick, NSF (703) 292-4972 jgrasswi@nsf.govJoshua A. Chamot, NSF (703) 292-7730 jchamot@nsf.gov
Program ContactsKatharine J. Covert, NSF (703) 292-4950 kcovert@nsf.gov
Principal InvestigatorsJack W. Szostak, Harvard Medical School (617) 726-5981 szostak@molbio.mgh.harvard.edu
Related WebsitesSzostak Laboratory: http://genetics.mgh.harvard.edu/szostakweb/Exploring Life's Origins: http://exploringorigins.org/
The National Science Foundation (NSF) is an independent federal agency that supports fundamental research and education across all fields of science and engineering, with an annual budget of $5.92 billion. NSF funds reach all 50 states through grants to over 1,700 universities and institutions. Each year, NSF receives about 42,000 competitive requests for funding, and makes over 10,000 new funding awards. The NSF also awards over $400 million in professional and service contracts yearly.
Receive official NSF news electronically through the e-mail delivery and notification system, MyNSF (formerly the Custom News Service). To subscribe, visit www.nsf.gov/mynsf/ and fill in the information under "new users".
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California Institute of Technology Research : Caltech scientists decipher the neurological basis of timely movement
PASADENA, Calif--Contrary to what one might imagine, the way in which each of us interacts with the world is not a simple matter of seeing (or touching, or smelling) and then reacting. Even the best baseball hitter eyeing a fastball does not swing at what he sees. The neurons and neural connections that make up our sensory systems are far too slow for this to work. "Everything we sense is a little bit in the past," says Richard A. Andersen of the California Institute of Technology, who has now uncovered the trick the brain uses to get around this puzzling problem.
Work by Andersen, the James G. Boswell Professor of Neuroscience at Caltech, and his colleagues Grant Mulliken of MIT and Sam Musallam of McGill University, offers the first neural evidence that voluntary limb movements are guided by our brain's prediction of what will happen an instant into the future. "The brain is generating its own version of the world, a 'forward model,' which allows you to know where you actually are in real time. It takes the delays out of the system," Andersen says.
The research in Andersen's laboratory is focused on understanding the neurobiological underpinnings of brain processes, including the senses of sight, hearing, balance, and touch, and the neural mechanisms of action. The lab is working toward the development of implanted neural prosthetic devices that would serve as an interface between severely paralyzed individuals' brain signals and their artificial limbs--allowing thoughts to control movement.
Research along these lines conducted at the University of Pittsburgh and Carnegie Mellon University recently allowed monkeys to feed themselves using a robotic limb that they controlled only with their thoughts. Their thoughts were picked up via an array of electrodes sitting on top of the primary motor cortex, a lower level brain region responsible for carrying out motor functions.
Andersen's group focuses on a more high-level area of cortex called the posterior parietal cortex (PPC), which is where sensory stimuli are actually transformed into movement plans.
In their experiments, Andersen and his colleagues trained two monkeys to use a joystick to move a cursor on a computer screen from a small red circle into a green circle, while keeping their gaze fixed on the red circle. The monkeys typically generated curved trajectories, but to increase the curvature one monkey was trained to move the cursor around an obstacle. The obstacle (a large blue circle) was placed between the initial location of the cursor and the target circle, and the monkey had to guide the cursor around the obstacle, without touching it, and over to the green circle. As the monkeys conducted the tasks, electrodes measured the activity of neurons in the PPC. This allowed Andersen and his colleagues to monitor signals--commands for movement--in real time.
The studies showed that neurons in the PPC produce signals that represent the brain's estimation of the current and upcoming movement of the cursor. "An internal estimate of the current state of the cursor can be used immediately by the brain to rapidly correct a movement, avoiding having to rely entirely on late-arriving sensory information, which can result in slow and unstable control," Mulliken says.
"The idea is that you feed back the command you make for movement into those areas of the brain that plan the movement (i.e., the PPC)," Andersen says. "The signal about the movement taking place is adjusted to be perfectly aligned in time with the actual movement--what you're moving in your head matches with what you're moving in the real world." The effect is akin to an athlete visualizing his performance in his mind. Studies have previously shown that these simulations of movement trajectories run through the posterior parietal cortex, and run at actual speed, taking the same amount of time as the activity would in real life.
In the Pittsburgh robotic arm study, the neural signal driving the robotic limb was what is known as a "trajectory signal," which represents the path that must be taken to move from one point to another, like using a computer mouse to drag an object across a screen. Previously Andersen's lab had shown that a different signal in the posterior parietal cortex, called the "goal signal," can also be used to directly jump an object from one point to another.
"This goal signal is much faster for reaching a goal than a trajectory signal," Andersen says. "Fast goal decoding is very advantageous for rapid sequences such as typing. Our new study shows that the posterior parietal cortex codes the trajectory as well as the goal, which makes this brain area an attractive target for neural prosthesis. Not only does this increase the versatility and the number of prosthetic applications, but it also makes the decoding easier since the trajectories can be better estimated if the goal is known."
The paper, "Forward Estimation of Movement State in Posterior Parietal Cortex," will be published in a future print issue the Proceedings of the National Academy of Sciences but is now available online. First author, Grant Mulliken, was a graduate student at Caltech and is now a postdoctoral fellow at the Massachusetts Institute of Technology; coauthor Sam Musallam was a postdoctoral fellow at Caltech and is currently an assistant professor at McGill University in Montreal, Canada.
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Contact: Kathy Svitil(626) 395-8022ksvitil@caltech.edu
Visit the Caltech Media Relations website at: http://pr.caltech.edu/media.
McLaughlin-Rotman Centre for Global Health : Brazil's biotech firms: From imitators to innovators in health-related products
New Brazilian products emerge for local health needs; same trend seen also in emerging markets of India, China
Brazil is in the midst of a transition from imitator to innovator in health-related products, according to the most comprehensive analysis to date of barriers and opportunities facing that country's health biotech industry.
In the third study of its kind, the McLaughlin-Rotman Centre for Global Health (MRC), says South America's largest and most populous country has the scientific and market capacity to emerge as a major global player. It is held back, however, by a number of important challenges including regulatory barriers, limited access to private equity and a general lack of coordination and collaboration among stakeholders. MRC's previous studies focused on India and China.
Says study co-author Peter A. Singer, MD, Interim Director of the MRC, based at the University Health Network and the University of Toronto: "One thing is clear: when you think of biotechnology, its no longer just San Francisco, Boston, London and Tokyo. It's also Hyderabad, Shanghai, and Sao Paulo. While in the emerging economies it is still in it's adolescence, biotechnology is no longer the sole hegemony of the rich world. Biotechnology innovation is becoming globalized."
"Unlike most developing nations, what is holding back Brazil has little to do with the level of scientific expertise," adds Dr. Singer. "In fact, its science is world class. It is unfortunate that a set of relatively smaller challenges continues to slow down the country's transition to becoming a significant global innovator in health biotechnology."
The study says the fact that several of Brazil's small and medium-sized enterprises (SMEs) have succeeded in making innovative products is a testament to the country's strength in health sciences and to its entrepreneurs' creativity and astute management.
Published June 6 by Nature Biotechnology, the paper is based on case studies of 19 diverse Brazilian-owned private health biotech companies and four public institutes.
Having now analyzed biotech industry trends in Brazil, India and China, MRC says some common patterns and differences are evident. (A fourth study in the series, for release later this year, focuses on South Africa).
"Although each country faces a different set of challenges we are seeing a clear trend," says study co-author and MRC researcher Sarah E. Frew. "Countries such as China and India are emerging as major global players in health biotechnology, with the expertise and resources to produce new drugs and vaccines at a fraction of the costs of the big pharmaceutical companies. There is little reason to think that Brazil cannot do the same provided it deals with a few key remaining challenges."
While biotech entrepreneurs in China, India and Brazil employ some of the same core business models and strategies, there are also significant differences stimulated by firms' attempts to adapt to local conditions.
One common feature among health biotech enterprises in all three countries is a heavy reliance on a hybrid business model, where revenues from early activities – typically generics and modification of existing technologies as well as services – are reinvested in innovative products.
One difference is that, while Indian firms are among the world's leading vaccine manufacturers and supply the country's national immunization program, in Brazil this activity is primarily the domain of public institutes.
Also, in addition to their large domestic markets, Indian and Chinese companies also have a greater focus on exports than their Brazilian counterparts.
Rahim Rezaie, a co-author of the Brazilian study, states that: "Brazil faces a dilemma – how to reap the economic benefits of a robust private sector while finding affordable and sustainable solutions to local health needs. If the country can strike an effective balance between its public and private sectors, it could not only maximize health and economic benefits to Brazilians but also provide a compelling model for health biotech in other developing countries."
Neglected diseases and other business opportunities
Most companies interviewed report growing focus on innovative diagnostics or drug products. A number have a particular focus on developing and marketing affordable, easy to use products which address neglected diseases and other local health needs.
"What you call a neglected disease, I call a business opportunity," says Fernando Kreutz, president of Porto Alegre based FK Biotecnologia. The company produces monoclonal antibodies for various diagnostic tests while other firms such as Katal Biotecnológica, based in Belo Horizonte, and Labtest Diagnóstica, of Lagoa Santa, produce diagnostic kits suitable for small laboratories and rural settings in Brazil, a market usually neglected by large companies.
Katal is responding to Brazil's approximately 140.000 annual cases of tuberculosis by developing a $25 TB test to replace the current $150 version. It also supplies the public health system with an innovative test for screening the 25 million Brazilian men over 45 at risk of prostate cancer and has developed a test for Chagas disease that can be read by widely available equipment, removing the requirement for expensive laboratory machinery.
MRC investigators also found many private companies developing innovative therapeutics. Aché Laboratories is marketing the topical anti-inflammatory Acheflan, a natural product extracted from the Cordia curassavica plant, while Pele Nova Biotecnologia's BIOCURE is a natural latex membrane derived from the plant Havea brasiliensis for the treatment of skin lesions.
Silvestre Laboratories, of Rio de Janeiro, is marketing several drugs that have resulted from significant in-house R&D, including a treatment for burns and other skin lesions.
Notable products in the pipeline of various companies include:
several monoclonal antibodies for cancer treatment (Recepta Biopharma, of São Paulo);
a recombinant protein for treating melanoma as well as anti-hypertensive and an analgesic peptide – both isolated from snake venom (COINFAR, of São Paulo); and
fetal, neonatal and adult stem cell therapies for cardiac disease, type I diabetes and neonatal hypoxia (Cryopraxis, Rio de Janeiro).
Barriers to development
Major challenges include:
A patent regime in desperate need of reform
The Brazilian patent office can take over seven years to process patent applications for drug candidates. Brazilian law prohibits patenting some important biotechnologies, such as recombinant versions of proteins found in nature. Some companies are also concerned that once a pharmaceutical product has been approved by the patent office, ANVISA (the national regulatory agency that approves health products, among other activities) can withhold approval on grounds such as eventual public access issues.
Regulatory issues
The main regulatory roadblock highlighted by both public and private sector interviewees is the lack of practical experience in product development and manufacturing on the part of ANVISA regulators. Other commonly cited stumbling blocks include long delays in the ethics approval process for clinical trials as well as biosafety and biodiversity regulations.
Human resources
Although Brazil has been successful in raising the overall level of biotech expertise, there is evidence of a disconnect between the output of existing training programs and the actual needs of the health biotech sector. Lack of sufficiently specialized and targeted training programs and the "academic model" of university preparation are limiting the supply of appropriately-trained personnel. An additional challenge for private industry, especially SMEs, is their inability to match or exceed the incentive system in place for careers in the public sector.
Recommendations for Brazil
The government of Brazil has been proactive by making legislative changes and increasing public financing for innovative activities. However, these recent moves are unlikely to be sufficient on their own.
The MRC study says basic building blocks for an innovative health biotech sector are largely in place in Brazil. Recommendations to accelerate development and commercialization of innovative health products in the country include:
Improve the performance and transparency of government institutions involved in health product development, regulation, ethics review and intellectual property (IP) assessment and approval;
Promote and support the filing of patents outside Brazil and develop policies that encourage partnerships between Brazilian and off-shore collaborators based on the formation of international IP assets;
Administer biosafety and biodiversity laws in ways that encourage use of Brazilian resources for product discovery and creation while still preserving the knowledge rights of the indigenous population;
Identify crucial gaps in health product development infrastructure and stimulate the creation of facilities to provide required services;
Modify or remove policies that levy taxes or otherwise penalize companies that must out-source portions of their development programs to off-shore vendors;
Help build a culture of innovation by stimulating dialogue among regulators, policy makers, academics and the private sector to raise awareness and seek resolution of issues that hamper health product development;
Clarify the domain within which the public-sector will operate so as to allow the private sector to better target their investments;
Substantially increase R&D commitment to private firms to ensure they are viable employment destinations for academic researchers;
Build stronger linkages between firms to strengthen industry associations, identify challenges and pursue solutions;
Identify human resource requirements in specific disciplines and technical specialties and create and/or adapt training programs to meet the identified needs;
Stimulate the creation and expansion of academic and executive programs in entrepreneurial training specifically for the biotech sector;
Use public procurement mechanisms to support innovative startup firms.
Next steps in the MRC program
The MRC will continue to study health biotechnology companies in the developing world, and expand its focus to include Africa.
The next phase of MRC's Emerging Economies Program will involve continued research into commercialization of innovative health biotechnology products and services and its application in emerging markets.
Programme activities will follow two distinct tracks, each with its own research and commercialization phase:
1. Accelerate development of health products and services for improved global health by identifying better, cheaper and faster ways to produce health products including vaccines, drugs and diagnostics to improve global health. The research focus will examine how the innovative and productive capacity of emerging economy firms can be harnessed to strengthen health biotechnology development. Commercialization will involve linking innovative firms in emerging economies with the global health community, including other firms in developed and developing countries, investors, donors and product development partnerships.
2. Encouraging North-South entreprenurial collaboration in the health biotechnology sector to the benefit of all.
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The study on Brazil was funded primarily by Genome Canada through the Ontario Genomics Institute and Bioventures for Global Health. Additional contributors are listed at www.mrcglobal.org
The McLaughlin-Rotman Centre for Global Health is based at the University Health Network and the University of Toronto. It conducts global health research and helps researchers and companies get life sciences technologies to those who need them in the developing world. The vision of the MRC is a world where everyone benefits from new diagnostics, vaccines, drugs and other life science solutions.
For more information: www.mrcglobal.org and www.facebook.com, under "Global Health Engage"