NIGMS Biomedical Beat
Sun Apr 24 04:14:31 EDT 2011
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Cool Image: Exploring HIV - If we can visualize a protein's shape, we can learn much more about how it functions and how we might block its activity. This was the guiding principle behind an NIH initiative launched 25 years ago to spur the discovery of HIV-related protein structures. Structures produced through the program have helped paint this detailed picture of the virus and have led to some important classes of drugs to treat the infection. Click on image to explore the structures of HIV.

Surprise! Light-Sensing Protein Also Senses Temperature - At one time, researchers believed that the protein rhodopsin functioned solely as a receptor for light in the eye. Now they know it also helps fruit fly larvae sense temperature. Without rhodopsin, fly larvae can avoid areas that are too hot or cold, but they cannot detect temperature variations within their comfort zone (64 to 75 degrees Fahrenheit). The research may shed light on how other animals--including people--sense temperature.

Cell Membranes Created By Assembly Line - A new computer-controlled process allows scientists to create complex cell membranes from simple starting materials. Cell membranes have been difficult to mass produce, but a new process driven by a microscopic circuit allows scientists to create synthetic membranes in an assembly line-like fashion. The synthetic membranes are lipid bilayers and researchers can even insert proteins, just like biological membranes. The work will help scientists better understand cellular membranes and compartmentalization, and could advance efforts to use membranes therapeutically.

How Men Pump Up Their X - Men have one X chromosome and women have two. To even things out, men must ramp up the activity of their X chromosome. Scientists recently figured out how it's done--at least in fruit flies. In the males, the molecular machinery that "reads" and transcribes DNA operates faster and travels further on X chromosome genes than on other chromosomes. A cluster of proteins called MSL is responsible for squeezing out this extra effort. MSL, which stands for "male-specific lethal," acts like a power tool custom-made for the X chromosome.

Structure of "Caffeine Receptor" Revealed - Our bodies sense and respond to caffeine the same way they do to fragrances, light and other stimuli--by tweaking a molecule called a G-protein coupled receptor (GPCR). Scientists recently determined the detailed, 3-D structure of an active caffeine receptor. The new structure is teaching many lessons about the large family of GPCRs, which are the targets of many drugs, including those that treat allergies, heart disease and Parkinson's. The research could inform the design of new drugs for a wide range of diseases.

Cool Image: New Technology Gleans Protein Structure from Nanocrystals - A protein’s three-dimensional structure can greatly aid research and drug development. But many proteins are too fragile or finicky to yield crystals big enough for X-ray crystallography. Now, researchers can avoid this problem by harnessing tiny nanocrystals. Blasted by ultra-brief pulses of an X-ray laser, the nanocrystals record a light-scatter pattern just before they vaporize. The technique even works for membrane proteins, which are attractive targets in the pharmaceutical industry and are difficult to crystallize. The work could impact fields ranging from medicine to clean energy.

Detecting Diseases by the Light of Fireflies - One persistent challenge in understanding how diseases develop and respond to treatment is monitoring, in real time, the chemical changes that accompany an illness. Recently, basic researchers created a chemical probe using luciferin, the pigment that makes fireflies glow. The new probe tracks production of hydrogen peroxide in living mice. Overproduction of hydrogen peroxide is linked to inflammation and many diseases, including cancer, diabetes, neurodegeneration and heart disease. The new probe offers a way to track chemical responses in an animal over time.

One Key to Human-Only Characteristics: “Jumping DNAs” - How can chimps and humans be 96% genetically identical, and yet differ in so many ways? One answer is a stretch of DNA called Alu, that can move around the genome. Alu elements, which are found in primates but no other mammals, can alter existing genes and can affect the speed of protein production. Because they tend to jump into genes that regulate thousands of other genes, they could have an enormous impact on the characteristics of an organism.

Piecing Together a Bacterial Pump - To the frustration of scientists, doctors and patients, bacteria sometimes evade the effects of antibiotics by pumping the drugs right back out. Structural biologists now have a molecular glimpse of part of one bacterial pump—a large, complicated protein called CusCBA. The structure, which includes two of the pump’s three components, is a significant step toward understanding how the pump assembles and functions. This knowledge could lead to new ways to block the pump’s activity and heighten bacterial sensitivity to antibiotics.

Animal with the Most Genes? A Water Flea - The animal with the most genes (so far) is the tiny crustacean Daphnia pulex (water flea). Nearly invisible to human eyes, Daphnia is intriguing in many ways—its genes turn on and off readily when its aquatic environment changes, one third of its genes are new to science and it can reproduce with or without males. It also has many genes in common with humans, suggesting it might make a good model organism to reveal how environmental pollutants affect people.

Cool Video: DNA’s Twisted Alter Ego Revealed - DNA’s well-known structure has an alter ego, at least for 1 percent of the time. Sure, DNA can flex, bend and occasionally even switch from a right-handed to a left-handed double helix. But now scientists have seen a new state of DNA in which certain pieces (bases) are flipped 180 degrees, breaking the normal rules. This “excited state” of DNA could contain a whole new level of genetic information, the scientists say.

Cancer-Fighters in Our Blood Vessels - To spread, tumors need a rich supply of blood vessels, thought to provide nutrients. Scientists recently discovered that blood vessels—specifically their endothelial cells—also deliver biochemical weapons that target cancer cells. So the researchers wondered whether implanting endothelial cells near a tumor could help treat cancer. The scientists developed a device made of endothelial cells embedded within a synthetic matrix that mimics the cells’ natural supportive environment. Already, implanting this device in mice significantly slowed the growth and spread of tumors.

New Way to Detect Cholera - If relief workers could detect cholera before it reaches epidemic proportions, they might be able to contain the potentially fatal diarrheal disease. Scientists recently devised a quick, inexpensive way to detect cholera toxin on the spot, without having to send samples to a lab. The technique uses nanoparticles coated with sugars. Cholera toxin sticks to the sugars and is detected by a sensor instrument. After further testing, the approach might lead to a valuable diagnostic tool and possibly even a new treatment for cholera.

Nerve Gaps Give Clues to Neurological Diseases - Nerve cells, which transmit electrical signals to and from the brain, are insulated by a membrane called the myelin sheath. The sheath is interrupted by small gaps called nodes of Ranvier, at which specialized proteins cluster. Researchers learned that one of these proteins, Neurofascin 186, is essential to nerve transmission (mice without it are paralyzed), and appears to be the central organizer that keeps together nodal protein clusters. The work could lead to future treatments for multiple sclerosis and related neurological disorders.

Understanding Anesthesia - Even though anesthetics have been used on patients for more than 150 years, we still don't know exactly how they work. Recent advances in cell biology, genetics and molecular biology have shed some light. For example, scientists now know that the brain’s processes of going under and waking up from anesthesia are different. This growing knowledge will help efforts to develop targeted, personalized anesthetics with fewer side effects. Ongoing research could reveal more about pain, memory and the nature of consciousness itself.

Cool Image: Ratcheting Ribosome - What looks like a jumble of rubber bands is the ribosome—the protein factory of living cells. Made of long chemical chains of RNA and proteins, the ribosome has two interlocked parts that behave as a single molecular machine. How exactly this machine operates to make proteins, though, has remained a mystery. New snapshots of the machine in motion show that ratchet and swivel movements enable protein synthesis. Since about half of all antibiotics target the ribosome, this understanding could lead to more effective drugs.

New Genes as Essential as Old Ones - Evolutionary biologists have long thought that ancient genes have been preserved because they confer a substantial survival advantage while newer ones serve less critical functions. Now, researchers have upended these assumptions by blocking individual genes in fruit flies and showing that survival depends equally on old and new genes. These findings have profound implications for studying evolutionary processes and suggest that important information may lie in the newer parts of the genome.

Intestinal Tissue from Stem Cells - Scientists have discovered a way to generate human intestinal tissue with stem cells. To do the job, they used human embryonic stem cells and pluripotent stem cells extracted from biopsied human skin cells. By adding chemicals and growth factor proteins to the two stem cell groups, the researchers were able to manipulate them to form three-dimensional intestinal tissue. This method could help researchers study normal intestinal development, explore new treatments for intestinal diseases and enhance the absorption of oral prescription drugs through intestinal cell membranes.

Nerve Highway Construction Crews - Nerve cells depend on a pair of microtubule "highways" to transport raw materials to their growing ends and rebuild themselves after injury. To function with maximum efficiency, the microtubules along each highway all point in the same direction. Using a fruit fly model, researchers have identified the proteins that keep the microtubules in line at key intersections along the highly branched half of the nerve, called the dendrite. The work improves understanding of how healthy neurons build microtubules and could inform research into treatments for nerve damage and disease.

Drugs from Deep Down • Mesmerized by Metals - n the latest issue of Findings, read about Brian Bachmann, a chemist in Tennessee who ventures into caves to find undiscovered organisms that produce substances with medicinal potential. Also meet Amy Palmer, a Colorado-based biochemist who created fluorescent sensors to study the role of zinc and other metals in brain signaling, bacterial infection and diseases like Alzheimer’s, diabetes and prostate cancer.

Cool Images: Our Gift to You! - Looking for a holiday treat? Feast your eyes on the colorful images and videos in the Biomedical Beat cool image gallery. From snapping neurons and blinking bacteria to brilliant probes and glowing salamanders, you’ll find something for every appetite. As always, the images are freely downloadable for educational purposes. You also can get them to go: Order the bookmark to enjoy and share the cool images wherever you are.

Genetically Engineering Plants to Produce New Drugs - The periwinkle plant is the source of the anticancer drug vinblastine. After a genetic makeover, it could also be the source of improved medicines that contain potentially performance-boosting chemical elements like chlorine or bromine. Although the plant doesn’t normally utilize these elements, some bacteria do. Scientists are upgrading the plant’s biochemical pathways by adding genes from these bacteria. The resulting periwinkle cells can produce vinblastine laced with chlorine or bromine—or potentially hundreds of other variations, any of which may turn out to be a new, improved medication.

How Fewer Calories Can Extend Life - For years, researchers have known that consuming fewer calories can slow the aging process and improve health in mammals. New research reveals how reduced caloric intake can also slow the deterioration of tissues and cells. Scientists found that mice on restricted diets had increased levels of Sirt3, an enzyme that influences cell fate and physiology. The amped up levels reduced damage caused by free radicals associated with age-related hearing loss. These findings give insight into the causes of aging and could lead to drugs that improve health in the elderly.

Transforming’ Fruit Fly Behavior - Like most animals, fruit flies behave differently toward males and females. When a male fly meets a female, he courts her. But when he encounters another male—a potential competitor—he puts up a fight. By manipulating a gene called transformer, researchers have uncovered the triggers for these sex-specific responses: In addition to the expected role played by pheromones, behavioral patterns associated with each sex are also important. Unraveling this decision-making process in flies could help reveal how other animals, including humans, make complex decisions governing behavior.

Debut of Series - Healthy diets involve watching how much fatty food we eat, but our bodies need a certain amount of fat to perform critical tasks such as storing energy, insulating us and helping to control basic metabolism. Learn more about the vital roles of fat in the first installment of "Inside Life Science," a new series on the NIGMS Web site that will also appear on LiveScience.com. And in the coming months, you’ll discover even more on what scientists have found--and are finding--about fundamental life processes happening inside our bodies.