Recebi há poucos minutos a notícia do falecimento de minha tia do lado paterno, Maria Luiza, a “Tia Tudica”. Nasceu em 1917 e tinha portanto 98 anos. Foi uma mulher que passou orando a vida toda, sua casa sempre foi muito organizada e limpa. Tinha muitos amigos e amigas porque gostava muito de conversar. Com certeza ela não passou a vida em brancas nuvens. Nessas ocasiões, dizemos sempre : Que Deus a tenha”. Certamente a terá. Deixa uma filha, Eunice, muitos netos e bisnetos.
Sidenei Melo
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SLU pharmacology researchers Thomas Burris, Ph.D., and Colin Flaveny, Ph.D., discuss their cancer research. Credit: Courtesy of Saint Louis University In research published in Cancer Cell, Thomas Burris, Ph.D., chair of pharmacology and physiology at Saint Louis University, has, for the first time, found a way to stop cancer cell growth by targeting the Warburg Effect, a trait of cancer cell metabolism that scientists have been eager to exploit. Unlike recent advances in personalized medicine that focus on specific genetic mutations associated with different types of cancer, this research targets a broad principle that applies to almost every kind of cancer: its energy source. The Saint Louis University study, which was conducted in animal models and in human tumor cells in the lab, showed that a drug developed by Burris and colleagues at Scripps Research Institute can stop cancer cells without causing damage to healthy cells or leading to other severe side effects. The Warburg Effect Metabolism -- the ability to use energy -- is a feature of all living things. Cancer cells aggressively ramp up this process, allowing mutated cells to grow unchecked at the expense of surrounding tissue. "Targeting cancer metabolism has become a hot area over the past few years, though the idea is not new," Burris said. Since the early 1900s, scientists have known that cancer cells prefer to use glucose as fuel even if they have plenty of other resources available. In fact, this is how doctors use PET (positron emission tomography) scan images to spot tumors. PET scans highlight the glucose that cancer cells have accumulated. This preference for using glucose as fuel is called the Warburg effect, or glycolysis. In his paper, Burris reports that the Warburg effect is the metabolic foundation of oncogenic (cancer gene) growth, tumor progression and metastasis as well as tumor resistance to treatment. Cancer's goal: to grow and divide Cancer cells have one goal: to grow and divide as quickly as possible. And, while there are a number of possible molecular pathways a cell could use to find food, cancer cells have a set of preferred pathways. "In fact, they are addicted to certain pathways," Burris said. "They need tools to grow fast and that means they need to have all of the parts for new cells and they need new energy." "Cancer cells look for metabolic pathways to find the parts to grow and divide. If they don't have the parts, they just die," said Burris. "The Warburg effect ramps up energy use in the form of glucose to make chemicals required for rapid growth and cancer cells also ramp up another process, lipogenesis, that lets them make their own fats that they need to rapidly grow." If the Warburg effect and lipogenesis are key metabolic pathways that drive cancer progression, growth, survival, immune evasion, resistance to treatment and disease recurrence, then, Burris hypothesizes, targeting glycolysis and lipogenesis could offer a way to stop a broad range of cancers. Cutting off the energy supply Burris and his colleagues created a class of compounds that affect a receptor that regulates fat synthesis. The new compound, SR9243, which started as an anti-cholesterol drug candidate, turns down fat synthesis so that cells can't produce their own fat. This also impacts the Warburg pathway, turning cancer cells into more normal cells. SR9243 suppresses abnormal glucose consumption and cuts off cancer cells' energy supply. When cancer cells don't get the parts they need to reproduce through glucose or fat, they simply die. Because the Warburg effect is not a feature of normal cells and because most normal cells can acquire fat from outside, SR9243 only kills cancer cells and remains non-toxic to healthy cells. The drug also has a good safety profile; it is effective without causing weight loss, liver toxicity, or inflammation. Promising Results So far, SR9243 has been tested in cultured cancer cells and in human tumor cells grown in animal models. Because the Warburg pathway is a feature of almost every kind of cancer, researchers are testing it on a number of different cancer models. "It works in a wide range of cancers both in culture and in human tumors developing in animal models," Burris said. "Some are more sensitive to it than others. In several of these pathways, cells had been reprogramed by cancer to support cancer cell growth. This returns the metabolism to that of more normal cells." In human tumors grown in animal models, Burris said, "It worked very well on lung, prostate, and colorectal cancers, and it worked to a lesser degree in ovarian and pancreatic cancers." It also seems to work on glioblastoma, an extremely difficult to treat form of brain cancer, though it isn't able to cross the brain/blood barrier very effectively. The challenge for researchers in this scenario will be to find a way to allow the drug to cross this barrier, the body's natural protection for the brain, which can make it difficult for drug treatments to reach their target. And, in even more promising news, it appears that when SR9243 is used in combination with existing chemotherapy drugs, it increases their effectiveness, in a mechanism apart from SR9243's own cancer fighting ability. Story Source: The above post is reprinted from materials provided by Saint Louis University. Note: Materials may be edited for content and length. Journal Reference:
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Low flu vaccination rates, medication compliance and limited access to primary care providers have contributed to the high pediatric asthma rates in California, say UC Davis pediatricians Ulfat Shaikh and Robert Byrd, who have published an extensive study describing the challenges faced by children with asthma in California. Analyzing data from the 2011-12 California Health Interview Survey, the study details several issues affecting asthma care and offers a number of public policy strategies that could help remedy these shortcomings. The research was published in the journal Population Health Management. "Asthma is one of the most common chronic pediatric conditions in the U.S. and a major reason for emergency department visits and hospitalizations in children," said Shaikh, clinical quality officer at the California Department of Health Care Services and director of Healthcare Quality at the UC Davis School of Medicine. "Emergency department visits for chronic conditions such as asthma are frequently the bellwether of sub-optimal primary care and community-based support. However, by creating better support structures around these children, we can have a significant impact on their health and quality of life." To understand the status of asthma in California, the researchers mined data from the most recent California Health Interview Survey, which includes 44,000 households from every county in California. Nearly 10 percent of the state's children, close to 500,000, suffer from asthma. The care these children receive can vary widely, even though more than 96 percent have a primary care provider. Most concerning is that their flu vaccination rates are not much different from the general pediatric population. Flu can pose a significant health risk, sending many children with asthma to the hospital. "We were surprised to see that about half of all children with asthma had not received a flu shot in the past year," said Shaikh. "Children with asthma are at high risk of becoming really sick from the flu and of developing pneumonia, even if their asthma is mild or their symptoms are well-controlled." The study also highlighted problems with asthma control. A third of children with asthma had to go to the emergency department for asthma symptoms in the past year, and for 20 percent of children, this was due to an inability to see their own health care provider. Even more striking is that only 38 percent of children with asthma receive a written-care plan from their clinicians. While Shaikh finds these primary care shortcomings deeply troubling, she and study authors also point to solutions. They believe a safety net of existing providers and resources could support primary care providers' efforts to combat pediatric asthma. Involving interdisciplinary teams for population-health management of pediatric asthma is key, they say. Pharmacists, school nurses, social workers, community health workers and emergency department patient navigators could be enlisted to encourage vaccination, improve medication compliance, follow up higher-risk children more closely, point families toward resources and educate families to improve self-care. "These findings are important because they will better guide our efforts to improve both clinical quality and population health for our children with asthma," noted Neal Kohatsu, medical director at the California Department of Health Care Services, which partially funded the study. Story Source: The above post is reprinted from materials provided by University of California - Davis Health System. Note: Materials may be edited for content and length. Journal Reference:
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 (l-r) Faran Zhou, physics and astronomy doctoral student; Terry Han, who just earned his Ph.D. in physics and astronomy; and Chong-Yu Ruan, associate professor of physics and astronomy. They are part of a team that developed an ultrafast microscope that allows researchers to view changes in materials caused by laser pulses. Credit: Harley Seeley Research led by Michigan State University could someday lead to the development of new and improved semiconductors. In a paper published in the journal Science Advances, the scientists detailed how they developed a method to change the electronic properties of materials in a way that will more easily allow an electrical current to pass through. The electrical properties of semiconductors depend on the nature of trace impurities, known as dopants, which when added appropriately to the material will allow for the designing of more efficient solid-state electronics. The MSU researchers found that by shooting an ultrafast laser pulse into the material, its properties would change as if it had been chemically "doped." This process is known as "photo-doping." "The material we studied is an unconventional semiconductor made of alternating atomically thin layers of metals and insulators," said Chong-Yu Ruan, an associate professor of physics and astronomy who led the research effort at MSU. "This combination allows many unusual properties, including highly resistive and also superconducting behaviors to emerge, especially when 'doped.'" An ultrafast electron-based imaging technique developed by Ruan and his team at MSU allowed the group to observe the changes in the materials. By varying the wavelengths and intensities of the laser pulses, the researchers were able to observe phases with different properties that are captured on the femtosecond timescale. A femtosecond is 1 quadrillionth, or 1 millionth of 1 billionth, of a second. "The laser pulses act like dopants that temporarily weaken the glue that binds charges and ions together in the materials at a speed that is ultrafast and allow new electronic phases to spontaneously form to engineer new properties," Ruan said. "Capturing these processes in the act allows us to understand the physical nature of transformations at the most fundamental level." Philip Duxbury, a team member and chairperson of the department of physics and astronomy, said ultrafast photo-doping "has potential applications that could lead to the development of next-generation electronic materials and possibly optically controlled switching devices employing undoped semiconductor materials." A semiconductor is a substance that conducts electricity under some conditions but not others, making it a good medium for the control of electrical current. They are used in any number of electronics, including computers. Story Source: The above post is reprinted from materials provided by Michigan State University. Note: Materials may be edited for content and length. Journal Reference:
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A new route to ultrahigh density, ultracompact integrated photonic circuitry has been discovered by researchers with the Lawrence Berkeley National Laboratory (Berkeley Lab) and the University of California (UC) Berkeley. The team has developed a technique for effectively controlling pulses of light in closely packed nanoscale waveguides, an essential requirement for high-performance optical communications and chip-scale quantum computing. Xiang Zhang, director of Berkeley Lab's Materials Sciences Division, led a study in which a mathematical concept called "adiabatic elimination" is applied to optical nanowaveguides, the photonic versions of electronic circuits. Through the combination of coupled systems -- a standard technique for controlling the movement of light through a pair of waveguides -- and adiabatic elimination, Zhang and his research team are able to eliminate an inherent and vexing "crosstalk" problem for nanowaveguides that are too densely packed. Integrated electronic circuitry is approaching its limits because of heat dissipation and power consumption issues. Photonics, in which electrical signals moving through copper wires and cables are replaced by pulses of light carrying data over optical fibers, is a highly touted alternative, able to carry greater volumes of data at faster speeds, while giving off much less heat and using far less power. However, the crosstalk problem in coupled optical nanowaveguides has been a major technological roadblock. "When nanowaveguides in close proximity are coupled, the light in one waveguide impacts the other. This coupling becomes particularly severe when the separation is below the diffraction limit, placing a restriction on how close together the waveguides can be placed," Zhang says. "We have experimentally demonstrated an adiabatic elimination scheme that effectively cuts off the cross-talk between them, enabling on-demand dynamical control of the coupling between two closely packed waveguides. Our approach offers an attractive route for the control of optical information in integrated nanophotonics, and provides a new way to design densely packed, power-efficient nanoscale photonic components, such as compact modulators, ultrafast optical signal routers and interconnects." Zhang, who also holds an appointment with the Kavli Energy NanoSciences Institute (ENSI) at Berkeley, is the corresponding author of a paper describing this research in Nature Communications. The paper is titled "Adiabatic elimination based coupling control in densely packed subwavelength waveguides." Michael Mrejen, Haim Suchowski and Taiki Hatakeyama are the lead authors. Other authors are Chih-hui Wu, Liang Feng, Kevin O'Brien and Yuan Wang. "A general approach to achieving active control in coupled waveguide systems is to exploit optical nonlinearities enabled by a strong control pulse," Zhang says. "However this approach suffers from the nonlinear absorption induced by the intense control pulse as the signal and its control propagate in the same waveguide." Zhang and his group turned to the adiabatic elimination concept, which has a proven track record in atomic physics and other research fields. The idea behind adiabatic elimination is to decompose large dynamical systems into smaller ones by using slow versus fast dynamics. "Picture three buckets side-by-side with the first being filled with water from a tap, the middle being fed from the first bucket though a hole while feeding the third bucket through another hole," says co-lead author Mrejen. "If the flow rate into the middle bucket is equal to the flow rate out of it, the second bucket will not accumulate water. This, in a basic manner, is adiabatic elimination. The middle bucket allows for some indirect control on the dynamics compared to the case in which water goes directly from the first bucket to the third bucket." Zhang and his research group apply this concept to a coupled system of optical nanowaveguides by inserting a third waveguide in the middle of the coupled pair. Only about 200 nanometers separate each of the three waveguides, a proximity that would normally generate too much cross-talk to allow for any control over the coupled system. However, the middle waveguide operates in a "dark" mode, in the sense that it doesn't seem to participate in the exchange of light between the two outer waveguides since it does not accumulate any light. "Even though the dark waveguide in the middle doesn't seem to be involved, it nonetheless influences the dynamics of the coupled system," says co-lead author Suchowski, who is now with the Tel Aviv University. "By judiciously selecting the relative geometries of the outer and intermediate waveguides, we achieve adiabatic elimination, which in turn enables us to control the movement of light through densely packed nanowaveguides. Until now, this has been almost impossible to do." Story Source: The above post is reprinted from materials provided by DOE/Lawrence Berkeley National Laboratory. The original item was written by Lynn Yarris. Note: Materials may be edited for content and length. Journal Reference:
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 Corie Ralston and Cheryl Kerfeld at ALS Beamline 5.0.2 where crystal structures of the Orange Carotenoid Protein in cyanobacteria were recorded as the protein transitioned from light-absorber to photoprotector. Credit: Roy Kaltschmidt Overexposure to sunlight, which is damaging to natural photosynthetic systems of green plants and cyanobacteria, is also expected to be damaging to artificial photosynthetic systems. Nature has solved the problem through a photoprotection mechanism called "nonphotochemical-quenching," in which excess solar energy is safely dissipated as heat from one molecular system to another. With an eye on learning from nature's success, a team of Berkeley Lab researchers has discovered a surprising key event in this energy-quenching process. In a study led by Cheryl Kerfeld, a structural biologist with Berkeley Lab's Physical Biosciences Division, the research team found that in cyanobacteria the energy-quenching mechanism is triggered by an unprecedented, large-scale movement (relatively speaking) from one location to another of the carotenoid pigment within a critical light-sensitive protein called the Orange Carotenoid Protein (OCP). As a result of this translocation, the carotenoid changes its shape slightly and interacts with a different set of amino acid neighbors causing the protein to shift from an "orange" light-absorbing state to a "red" photoprotective state. This turns out to be an unanticipated molecular priming event in photoprotection. "Prior to our work, the assumption was that carotenoids are static, held in place by the protein scaffold," Kerfeld says. "Having shown that the translocation of carotenoid within the protein is a functional trigger for photoprotection, scientists will need to revisit other carotenoid-binding protein complexes to see if translocation could play a role in those as well. Understanding the dynamic function of carotenoids should be useful for the design of future artificial photosynthetic systems." Kerfeld is the corresponding author of a paper in Science describing this research titled "A 12 Å carotenoid translocation in a photoswitch associated with cyanobacterial photoprotection." Co-authors are Ryan Leverenz, Markus Sutter, Adjélé Wilson, Sayan Gupta, Adrien Thurotte, Céline Bourcier de Carbon, Christopher Petzold, Corie Ralston, François Perreau and Diana Kirilovsky. Through photosynthesis, green plants and algae are able to harvest solar energy and convert it to chemical energy. Creating an efficient artificial version of photosynthesis would realize the dream of solar power as the ultimate green and renewable source of electrical energy. However, if a sunlight-harvesting system becomes overloaded with absorbed solar energy, it most likely will suffer some form of damage. "We know that the interactions of pigment molecules with one another and with proteins are of fundamental importance to the light harvesting and photoprotective functions essential to oxygenic photosynthesis," Kerfeld says. "We also know that the distance between two pigment molecules is important for the transfer of energy, which means that knowing precisely a pigment molecule's structural arrangement and its location at any given time in the process is critical." Kerfeld and her co-authors focused on the OCP, a pigment-binding protein in cyanobacteria that absorbs blue-green light and binds to the the cyanobacterial antenna to cause the dissipation of excess captured energy. Cyanobacteria are aquatic microbes that have been called the "architects of Earth's atmosphere" because they generated most of the atmosphere's oxygen during the Archaean and Proterozoic Eras. The chloroplasts that enable green plants to carry out photosynthesis today are descendants of ancient cyanobacteria. As orange-state OCP absorbs blue-green light, it undergoes structural changes that result in red-state OCP. Once the excess solar energy has been quenched, OCP interacts with a second protein, the Fluorescence Recovery Protein (FRP), causing it to revert back to the light-harvesting orange state. Working at Berkeley Lab's Advanced Light Source, a U.S. Department of Energy (DOE) Office of Science national user facility, Kerfeld and her co-authors used the protein crystallography capabilities of ALS Beamlines 5.0.1 and 5.0.2 to obtain crystal structures of these key photoprotective proteins. "These crystal structures revealed that OCP photoactivation is accompanied by a 12 Å translocation of the pigment within the protein and a dramatic reconfiguration of carotenoid-protein interactions," Kerfeld says. "Our results also identified the origin of the photochromic changes in the OCP triggered by light and revealed the structural determinants required for interaction with the light-harvesting antenna during photoprotection." To confirm that this translocation actually occurs when OCP is in its natural solution environment and was not due to structural changes that the protein undergoes during crystal formation, Kerfeld and her colleagues turned to ALS Beamline 5.0.3 and X-ray Footprinting (XFP), a powerful technique in structural biology for the study of macromolecular structures and dynamics of proteins and nucleic acids in solution. "In any protein crystallography study, there is always the question about whether the crystallized protein represents the protein in real life," says biophysicist Corie Ralston, director of the Berkeley Center for Structural Biology (BCSB), which operates the ALS Beamlines used in this study, and a co-author of the Science paper. "One of the most powerful things about XFP is that you can look at proteins and/or nucleic acids in the solution state, and often under conditions that are close to physiological." With the XFP study having confirmed the protein crystallography results as real, Kerfeld says the next step will be to understand the detailed mechanism behind OCP's interaction with the antenna to dissipate energy. "Some cyanobacteria have multiple homologs to the OCP," she says. "What are these homologs doing? Do they allow for fine-tuning of photoprotection? If we can learn the answers we might be able to engineer smart photoprotection in cyanos or even improve photosynthesis in green plants." Story Source: The above post is reprinted from materials provided by DOE/Lawrence Berkeley National Laboratory. The original item was written by Lynn Yarris. Note: Materials may be edited for content and length. Journal Reference:
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Estas imagens são uma janela para o passado, presente e futuro de um povo extraordinário.
Cativado pela riqueza das culturas da África, as fotógrafas Carol Beckwith e Angela Fisher foram apaixonadamente a rituais e cerimônias de suas tradições culturais. Imagens inspiradoras que refletem o legado das grandes culturas africanas antigas e evidência a vitalidade da criatividade humanidade. Beckwith e Fisher publicaram 11 livros sobre a vida Africana.
source :www.mariapreta.org
