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Archive - Oct 22, 2012

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Sequencing Used in Study of Gut Bacteria/Diet in Kittens

For animals as well as people, diet affects what grows in the gut. The gut microbial colonies, also known as the gut microbiome, begin to form at birth. Their composition affects how the immune system develops and is linked to the later onset of metabolic diseases such as obesity. Common wisdom is that cats, by nature carnivorous, are healthiest when fed high-protein diets. Researchers at the University of Illinois, and collborators, wanted to find out if this is true. "There are a lot of diets now, all natural, that have high protein and fat and not much dietary fiber or carbohydrates," said animal sciences researcher Dr. Kelly Swanson. He and his team examined the effect of dietary protein:carbohydrate ratio on the gut microbiomes of growing kittens and reported their results online on August 31, 2012 in the British Journal of Nutrition. One month before mating, eight domestic shorthair female cats were randomly assigned to one of two dry diets: high-protein, low-carbohydrate (HPLC) or moderate-protein, moderate-carbohydrate (MPMC). When the kittens were born, they were housed with their mothers until they were 8 weeks old, weaned, and then fed the same diets as their mothers. After weaning, the 30+ kittens were twin- and triple-housed within the dietary-group cages. They were allowed to go into a common area furnished with toys and scratching posts to play with people and each other. "It became quite a party right away," said Dr. Swanson. "It was a bit chaotic but fun as well." Twelve of the kittens became part of the study. The researchers took fecal samples at weaning and 4 and 8 weeks after weaning. They extracted bacterial DNA and used bioinformatics techniques to estimate total bacterial diversity.

3D Structure of an Unmodified GPCR in Its Natural Enviroment

Scientists have determined the three-dimensional structure of a complete, unmodified G-protein-coupled receptor in its native environment: embedded in a membrane in physiological conditions. Using NMR spectroscopy, the team mapped the arrangement of atoms in a protein called CXCR1, which detects the inflammatory signal interleukin 8 and, through a G protein located inside the cell, triggers a cascade of events that can mobilize immune cells, for example. Because G-protein-coupled receptors are critical for many cellular responses to external signals, they have been a major target for drugs. More precise knowledge of the shapes of these receptors will allow drugmakers to tailor small molecules to better fit specific targets, avoiding collateral hits that can cause detrimental side effects. "This finding will have a major impact on structure-based drug development since for the first time the principal class of drug receptors can be studied in their biologically active forms where they interact with other proteins and potential drugs," said Dr. Stanley Opella, professor of chemistry and biochemistry at the University of California, San Diego, who led the work, which Nature published online on October 21, 2012, in advance of the print edition. Protein structures are most often determined by reading the diffraction patterns of X-rays beamed at their crystalline form, but crystallizing such large, unwieldy molecules is a challenge often met with strategies such as snipping off floppy ends. Those changes can alter the shape of critical regions of the protein. "Our approach was to not touch the protein," Dr. Opella said. "We are working with molecules in their active form." Their strategy has revealed a new view of these receptors. Previous reports have all noted seven helices weaving through the membrane.

How Bacteria Recognize and Exclude Arsenate

Not long ago, some unassuming bacteria found themselves at the center of a scientific controversy: a group claimed that these microorganisms, which live in an environment that is rich in the arsenic-based compound arsenate, could take up that arsenate and use it – instead of the phosphate on which all known life on Earth depends. The claim, since disproved, raised another question: How do organisms living with arsenate pick and choose the right substance? Chemically, arsenate is nearly indistinguishable from phosphate. Professor Dan Tawfik of the Biological Chemistry Department at the Weizmann Institute of Science in Israel says: “Phosphate forms highly stable bonds in DNA and other key biological compounds, while bonds to arsenate are quickly broken. But how does a microorganism surrounded by arsenate distinguish between two molecules that are almost the same size and have identical shapes and ionic properties?” To investigate, Dr. Tawfik, postdoctoral fellow Dr. Mikael Elias, Ph.D. student Alon Wellner, and lab assistant Korina Goldin, in collaboration with Drs. Tobias Erb and Julia Vorholt of ETH Zurich, looked at a protein in bacteria that takes up phosphate. This protein, called PBP (short for phosphate binding protein), sits near the bacteria’s outer membrane, where it latches onto phosphates and passes them on to pumps that transport them into the cell. In research published online on October 3, 2012 in Nature, the team, which also included Dr. Eric Chabriere from the CNRS-Université de la Méditerranée, compared the activity of several different PBPs – some from bacteria like E. coli that are sensitive to arsenate and others, like those from the arsenic-rich environment, which are tolerant of the chemical.

New X-Ray Approach May Permit Early Detection of Severe Lung Diseases

Severe lung diseases are among the leading causes of death worldwide. To date, they have been difficult to diagnose at an early stage. Within an international collaboration, scientists from Munich have now developed an X-ray technology to do just that. Their results were published online on October 16, 2012 in PNAS. Now they are working on bringing the procedure into medical practice. Chronic obstructive pulmonary disease (COPD) is considered the fourth most common cause of death in the United States. Usually the precursor to this life-threatening lung disease is a chronic bronchitis. Partially destroyed alveoli and an over-inflation of the lungs, known as emphysema, are serious side effects. However, the subtle differences in the tissue are barely discernable in standard X-ray images. In addition to the conventional X-ray images, the Munich scientists analyzed the radiation scattered by the tissue. From these data they calculated detailed images of the lungs of the investigated mice. Using such images, physicians can see not only if a patient is diseased, but also how strongly which parts of the lung are affected. “Especially in early stages of the disease, identification, precise quantification, and localization of emphysema through the new technology would be very helpful”, says Professor Maximilian Reiser, head of the Institute for Clinical Radiology at Ludwig-Maximilians-University Munich.

Protein Signal from Microenvironment May Trigger Metastasis in Breast Cancer

A new study from Johns Hopkins researchers and colleagues suggests that the lethal spread of breast cancer is as dependent on a tumor’s protein-rich environment as on genetic changes inside tumor cells. In a report in the September 25, 2005 issue of PNAS, the scientists conclude that a molecular signal in the protein meshwork surrounding the breast cancer cells may provide the critical trigger to initiate the life-threatening process of metastasis to distant sites in the body. Moreover, their experiments suggest that the environment surrounding a tumor can even coax healthy breast cells to invade surrounding tissue just as cancer cells do, and that a healthy environment can cause cancer cells to stay put and not spread as they usually do. “The most dangerous aspect of breast cancer is its ability to spread to distant sites, and most tumors are initially unable to do that,” says Andrew Ewald, Ph.D., assistant professor of cell biology at the Johns Hopkins School of Medicine and member of the Institute for Basic Biomedical Sciences’ Center for Cell Dynamics. Learning more specifically what triggers metastases may provide additional targets for preventing and treating the malignant process that causes cancer deaths, Dr. Ewald adds. It’s widely accepted that cancers acquire the ability to spread through the gradual accumulation of genetic changes, and experiments have also shown that these changes occur in parallel with changes in the protein content and 3-dimensional patterning of the protein meshwork that creates the cancer’s immediate surroundings. What has been unclear is whether those immediate surroundings play a role in initiating and encouraging cancer’s spread, or whether they are more “effect” then “cause.” To sort out the contributions of both the genetic changes and the environment, Dr.