|
sábado, 14 de maio de 2011
BOLETIM INFORMATIVO ABRASCO
O 
O presidente da 
A vice-presidente da ABRASCO, Lígia Bahia, participou da matéria "Setor suplementar ou privatização de direitos? O mercado dos planos privados no Brasil", no site da Escola Politécnica de Saúde Joaquim Venâncio (
"Qual o futuro papel dos Núcleos, passados 22 anos de implantação do Sistema Único (SUS)?" esta foi uma das questões problematizadoras feitas por Maria Fátima de Sousa, coordenadora do 
O Ministro da Saúde, Alexandre Padilha, deu posse ao novo diretor-presidente da Agência Nacional de Vigilância Sanitária (
Em sua nona edição, a 
Therapies Using Induced Pluripotent Stem Cells Could Encounter Immune Rejection Problems
ScienceDaily (May 13, 2011) — Biologists at UC San Diego have discovered that an important class of stem cells known as "induced pluripotent stem cells," or iPSCs, derived from an individual's own cells, could face immune rejection problems if they are used in future stem cell therapies.
 |
An infiltration of T cells, shown by dark brown color, can be seen in the tissues formed by iPSCs. |
In the journal Nature, the researchers report the first clear evidence of immune system rejection of cells derived from autologous iPSCs that can be differentiated into a wide variety of cell types.
Because iPSCs are not derived from embryonic tissue and are not subject to the federal restrictions that limit the use of embryonic stem cells, researchers regard them as a promising means to develop stem cell therapies. And because iPSCs are derived from an individual's own cells, many scientists had assumed that these stem cells would not be recognized by the immune system. As a consequence, the immune system would not try to mount an attack to purge them from the body.
In fact, scientists regarded iPSCs as particularly attractive candidates for clinical use because cells derived from embryonic stem cells will induce immune system rejection that requires physicians to administer immune suppressant medications that can compromise a person's overall health.
But the UCSD biologists, funded by NIH and an early translational grant from the California Institute for Regenerative Medicine, the state's stem-cell funding agency, found that iPSCs are subject to some of the same problems of immune system rejection as embryonic stem cells.
"The assumption that cells derived from iPSCs are totally immune tolerant has to be reevaluated before considering human trials," says Yang Xu, a professor of biology at UCSD who headed the team that published the study.
His team of biologists -- which included postdoctoral researchers Tongbiao Zhao, Zhen-Ning Zhang and Zhili Rong -- reached that conclusion after testing the immune response of an inbred strain of mice to embryonic stem cells and several types of iPSCs derived from the same strain of inbred mice.
The scientists found, not surprisingly, that the immune system of one mouse could not recognize the cells derived from embryonic stem cells of the same strain of mice. But the experiments also showed that the immune system rejected cells derived from iPSCs reprogrammed from fibroblasts of the same strain of mice, mimicking the situation whereby a patient would be treated with cells derived from iPSCs reprogrammed from the patient's own cells. The scientists also found that the abnormal gene expression during the differentiation of iPSCs causes the immune responses.
"This result doesn't suggest that iPSCs cannot be used clinically," says Xu. "It is important now to look at exactly what types of cells derived from iPSCs -- and there probably are not that many based on our findings -- are likely to generate immune system rejection."
"Our immune response assay is a robust method for checking the immune tolerance, and therefore, the safety of iPSC that may be developed," he added.
With grants from the California Institute for Regenerative Medicine, Xu's team is also developing strategies to minimize the formation of tumors that result from the use of human embryonic stem cells and to increase the immune tolerance of human embryonic stem cells.
Slow Road to a Synapse: Why Some Neuronal Proteins Take Their Time Getting to the Terminal
ScienceDaily (May 13, 2011) — Grappling with a question that has defied scientific explanation for decades, a small team of researchers from the University of California, San Diego School of Medicine offers the first evidence-based model to explain how certain proteins in neurons travel from the central body of the cell (where they are made) down its axon to the terminal synapse -- the junction where neurons communicate with each other.
 |
This is an image of a human neuron, stained. |
To function and survive, the central bodies of neurons operate like tiny factories, constantly manufacturing proteins that are shipped via the cell's long, thin axon to distant synapses.The research, led by Subhojit Roy, MD, PhD, a cell biologist and neuropathologist in the department of neurosciences at UC San Diego School of Medicine and the Shiley Marcos Alzheimer's Disease Research Center, appears in the May 12 issue of the journal Neuron.
"It can be quite a journey," said Roy. "Axons may be 10,000 times longer than the neuron's body is wide. Typically, they have thousands of times more volume. If you imagine my office as the cell-body, the axon would end in San Francisco. So the cell has to constantly ship things back and forth over comparatively enormous distances."
Some proteins make this journey via "fast axonal transport." They ride in motor-driven intracellular sacs called vesicles that speed to the synapses like an express train. But hundreds of other "cytosolic" proteins that do not anchor to vesicles take much longer to make the trip, and until now, no one has had a plausible explanation of how these soluble cargoes undertake "slow axonal transport."
In the 1970s, using pulse-chase radiolabeling, scientists discovered that cytosolic proteins (so-called because they reside in the cell's liquid medium, the cytosol) moved toward and through the axon in a directed, wave-like motion. Though this ruled out a passive diffusive process, scientists could not find a mechanistic explanation for the curious, slow, coordinated movement of proteins.
"The question just sort of lay there, dormant," Roy said. "The original discoverers took it as far as they possibly could, but there really was no way to address it until technology caught up."
Roy devised a strategy using photoactivatable green fluorescent proteins to monitor the bulk movement of these cytosolic proteins in living axons, simulating the slow movement. The motion was then dissected using contemporary imaging technologies, custom image-analyses tools and biochemistry and biophysical modeling. Collectively, the data indicate that soluble, cytosolic proteins assemble into larger supramolecular complexes that move out of the neuron's cell body and down the axon as a plume of proteins. The complexes themselves are transient and only move in short, vectorial spurts, making the overall motion slow.
Roy said the phenomenon was similar to the old, popular video arcade game "Frogger," which he once played as a student: "Imagine the cytosolic protein complex as the frog and think about how the frog hops on and off various fast-moving objects as it progresses forward and upward toward its goal. Remember that along the way the frogs get hit by buses or eaten by crocs, which is akin to the supramolecular complexes disassembling.
"Now imagine a thousand frogs hopping on and off fast-moving cargoes, appearing and disappearing all the time. That's sort of the picture you get with these protein plumes -- a slow, coordinated overall motion resulting from seemingly chaotic behavior. To my knowledge, it's a completely new type of intracellular motion that's never been described before. And it seems likely that cytosolic proteins in all cells likely use this strategy."
The proposed model does not answer all questions. In fact, said Roy, it raises many more. It's not known, for example, how the proteins assemble into the larger complexes, their composition or what precisely moves them along. One possibility for the last item is fast axonal transport. The cytosolic complexes may be driven indirectly by the energy of speeding vesicles. Roy and colleagues say they will now turn to investigating these mysteries.
Beyond teasing out further details of how neurons (and presumably other cell types) function, the research may prove to have practical implications as well. In neurological conditions, such as Parkinson's and Lou Gehrig's disease, transport abnormalities of cytosolic proteins α-synuclein and SOD-1 have been long implicated, but the link has never been directly tested. Roy said a system that visualizes slow axonal transport may help do just that. These experiments could lead to insights into the workings of these diseases and possibly new therapeutic targets.
Co-authors of the study are David A. Scott, Utpal Das and Yong Tang, all in the UCSD Department of Neurosciences. Roy also has an appointment in Pathology.
Funding for this research came, in part, from a grant from the March of Dimes.
Protein Might Be Key to Cutting Cancer Cells' Blood Supply
ScienceDaily (May 13, 2011) — UT Southwestern Medical Center researchers have discovered a protein that guides blood vessel development and eventually might lead to a treatment to keep cancer cells from spreading.
The researchers showed in mice that the Ras interacting protein 1 (Rasip1) is so specific and central to so many cellular processes that without it new blood vessels simply cannot form, said Dr. Ondine Cleaver, assistant professor of molecular biology at UT Southwestern and senior author of the study in the April issue ofDevelopmental Cell.
"What we've found is really the first factor that is important in all blood vessels for inner channel formation and tubulogenesis, i.e., the transformation of something that looks like a rope into something that looks like a garden hose," Dr. Cleaver said.
Cancer cells depend on the body's creation of new blood vessels to deliver the nutrients that fuel cancer's rapid growth. Cancerous tumors also use the circulatory system as a superhighway through which they send malignant cells to colonize other parts of the body. A Rasip1-blocking drug conceivably could fight cancer on two fronts: by starving the cancerous cells and by cutting off their transport routes, Dr. Cleaver said.
During fetal development the body creates many tube-shaped organs such as the intestines of the digestive system and the vessels of the cardiovascular system. The mechanisms by which blood vessel progenitor cells transform into tubes that can carry blood are only beginning to be understood, she said.
Scientists have found many regulatory molecules important in different tissues and even in other aspects of blood vessel formation or maintenance, but all of them are active in multiple body tissues. Rasip1 is the first blood vessel-specific regulator of molecular switches called GTPases, she said. The protein appears to be active only in the endothelium, the layer of cells that line the blood vessels, and is not found in the smooth muscle cells that make up the outside of the vessels.
The UT Southwestern scientists also discovered that Rasip1 and a protein binding partner are both required for blood vessels to form channels through which blood can flow, she said.
Most approaches to therapies aimed at blocking blood vessel formation have focused on growth factors that occur outside the cell rather than intrinsic cellular growth factors like Rasip1, Dr. Cleaver said.
"Although this is still a mouse study, we feel that future studies of Rasip1 and the molecular processes under its control hold great promise to provide tools and models for advancing clinical therapies aimed at blocking vessel formation in tumors," she said.
The researchers now plan to look for drugs that block Rasip1 in order to eventually develop strategies to stop the growth of functional blood vessels and starve cancerous tumors, she said.
Other UT Southwestern researchers involved in the study were lead author and doctoral candidate Ke Xu; Stephen Fu, research technician II; Diana Chong, former research associate; Brian Skaug, a student in the Medical Scientist Training Program; and Dr. Zhijian "James" Chen, professor of molecular biology and a Howard Hughes Medical Institute investigator. Researchers from the University of Missouri and the Dalton Cardiovascular Research Center also participated.
The study was funded by the National Institutes of Health, the American Heart Association and the March of Dimes.
Scientists Design New Anti-Flu Virus Proteins Using Computational Methods
ScienceDaily (May 13, 2011) — A research article May 12 in Science demonstrates the use of computational methods to design new antiviral proteins not found in nature, but capable of targeting specific surfaces of flu virus molecules.
One goal of such protein design would be to block molecular mechanisms involved in cell invasion and virus reproduction.
Computationally designed, surface targeting, antiviral proteins might also have diagnostic and therapeutic potential in identifying and fighting viral infections.
The lead authors of the study are Sarel J. Fleishman and Timothy Whitehead of the University of Washington (UW) Department of Biochemistry, and Damian C. Ekiert from the Department of Molecular Biology and the Skaggs Institute for Chemical Biology at The Scripps Research Institute. The senior authors are Ian Wilson from Scripps and David Baker from the UW and the Howard Hughes Medical Institute.
The researchers note that additional studies are required to see if such designed proteins can help in diagnosing, preventing or treating viral illness. What the study does suggest is the feasibility of using computer design to create new proteins with antiviral properties.
"Influenza presents a serious public health challenge," the researchers noted, "and new therapies are needed to combat viruses that are resistant to existing anti-viral medications or that escape the body's defense systems."
They focused their attention on the section of the flu virus known as the hemagglutinin stem region. They concentrated on trying to disable this part because of its function in invading the cells of the human respiratory tract.
Their approach was somewhat similar to engineering a small space shuttle with the right configuration and construction, as well as recognizance and interlocking mechanisms, to dock with a troublesome space station and upset its mission. Only these scientists attempted their engineering feat at an atomic and molecular level.
Central to their approach is the ability of biological molecules to recognize certain other molecules or their working parts, and to have an affinity for binding to them at pre-determined locations. This recognition has both physical and chemical bases. Protein-protein interactions underlie many biological activities, including those that disarm and deactivate viruses.
In their report, the researchers described their general computational methods for designing new, tiny protein molecules that could bind to a certain spot on large protein molecules. They took apart some protein structures and watched how these disembodied sections interacted with a target surface. They analyzed particular high-affinity interactions, and used this information to further refine computer-generated designs for interfaces.
"Protein surfaces are never flat, but have many crevices and bulges at the atomic scale," lead author Sarel Fleishman explained. "The challenge is to identify amino acid side chains that would fit perfectly into these surfaces. The fit must be precise both in shape and in other chemical properties such as electrostatic charge. This geometrical and biophysical problem can be computationally solved, but requires large computational resources."
The researchers made use of a peer-to-peer computing platform called Rosetta@Home for going through the hundreds of millions of possible interactions of designed proteins and the surface of hemagglutinin to solve this challenge.
Following optimization, the designed proteins bound hemagglutinin very tightly.
Through this method, the researchers created two designs for new proteins that could bind to a surface patch on the stem of the influenza hemagglutinin from the 1918 H1N1 pandemic flu virus.
The shortcomings of the approach, due to approximations, meant that the researchers started out with 73 possibilities of which just two were successful.
One of the disease-causing characteristics of the influenza hemagglutinin stem is that it changes shape by refolding when in an acidic environment. This reconfiguration appears to allow the virus reproduce itself inside of cells.
In this study, one of the newly designed proteins was shown to block a conformational change, not only in H1 influenza hemagglutinin, but also in a similar component in H5 avian influenza.
"This finding suggests that this new protein design may have virus-neutralizing effects against multiple influenza subtypes," the researchers reported.
What was unusual about the workable designs was that they had helical binding modes, roughly shaped like a spiral staircase, rather than the loop binding that naturally occurring antibodies employ.
X-ray crystallography of the proteins complex showed that the actual orientation of the bound proteins was almost identical to the way the binding mode was designed. The modified surface of the main recognition helix on the designed protein was packed into a groove on the desired region of the virus protein.
"Overall, the crystal structure is in excellent agreement with the designed interface," the researchers noted, "with no significant deviations at any of the contact points." The design and the actual formation were nearly identical.
The scientists were encouraged by this finding. Despite their limitations, the design methods, the scientists believe, capture the essential features of the desired protein-protein interaction.
In addition to Fleishman, Whitehead, Ekiert, Wilson and Baker, other scientists on the research team were Cyrille Dreyfus of The Scripps Research Institute, Jacob E. Corn, previously at the UW but now with Genentech in San Francisco, and Eva-Maria Strauch of the UW Department of Biochemistry.
Computational designs for this study were generated on resources provided by people around the world who donate their unused home computer time as part of Rosetta@Home and by the Argonne National Leadership Computing Facility.
The project was supported by a fellowship from the Human Frontier Science Program, the Jane Coffin Child's Memorial Fund, and a career development award from the National Institute of Allergy and Infectious Disease at the National Institutes of Health. Additional support came from the Defense Advanced Research Projects Agency, the NIH yeast resource center, the Defense Threat Reduction Agency, the Howard Hughes Medical Institute, the Achievement Rewards for College Scientists Foundation, the NIH Molecular Evolution Training Program and the Skaggs Institute for Chemical Biology.
Assinar:
Postagens (Atom)
