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Archive - 2016

December 23rd

Scientists Crack Genetic Code Determining Leaf Shape in Cotton; Discovery Opens Door to Producing Cotton Varieties Ideally Suited for Agriculture

Researchers know that the variation in leaf shapes can mean big differences in a farmer's bottom line. Now, a new discovery gives plant breeders key genetic information they need to develop crop varieties that make the most of these leaf-shape differences. In a paper published online on Dec. 20, 2016 in PNAS, NC State researchers and colleagues from the Danforth Plant Science Center, the U.S. Department of Agriculture, and Cotton Incorporated describe how they used genomic and molecular tools to find the location of the DNA sequence that determines major leaf shapes in upland cotton. The article is titled “Modifications to a LATE MERISTEM IDENTITY-1 Gene Are Responsible for the Major Leaf Shapes of Upland Cotton.” The researchers also describe how they manipulated the genetic code to alter the shape of a cotton plant's leaves in potentially beneficial ways. This discovery represents a significant step toward developing cotton varieties that produce higher yields at less cost to the farmers, said Dr. Vasu Kuraparthy, an Associate Professor with NC State's Department of Crop and Soil Sciences and the project's principal investigator. Scientists have recognized that cotton plants with leaves that have five deep lobes, like the leaves of the okra plant, offer advantages to farmers over what researchers refer to as "normal" leaves. Dr. Ryan Andres, a postdoctoral researcher who worked in Dr. Kuraparthy's lab while he was a graduate student, said the so-called "okra" leaf cottons are less susceptible to boll rot than the stably yielding "normal" leaf cotton varieties. The okra leaves also allow a spray to be more evenly dispersed across a plant and are associated with higher rates of flowering and earlier rates of maturity in cotton, Dr. Andres added.

December 22nd

piRNA Pathway Plays Key Role in Health & Lifespan, Fly Study Shows

Humans and other animals carry rogue sequences of DNA in their genomes called transposable elements (TEs). To prevent passing TEs to their offspring, they employ the piRNA pathway in their reproductive organs to block the elements from being active in their sperm and eggs. With a new study in flies, Brown University biologists are the first to show that the anti-TE activity of the piRNA pathway also operates in a normal non-reproductive body tissue, the fly fat body, and that it helps to sustain the life of the animal. "It's required for normal health and longevity," said Dr. Stephen Helfand, senior author of the study in Nature Communications and a Professor of Biology at Brown University. The open-access article is titled “A Somatic piRNA Pathway in the Drosophila Fat Body Ensures Metabolic Homeostasis and Normal Lifespan. Most previous reports of piRNA at work outside of reproductive organs were in cancer or stem cells, with one study suggesting it may also be present in a subset of adult fly neurons, but no one had ever measured its consequences in normal health and aging. In experiments led by Brown graduate student Brian Jones, the research team tracked several components of the pathway, such as the presence of piRNAs and the expression of associated "piwi" and "flamenco" genes, in the fat body tissue of flies. The fat body is akin to adipose and liver tissues in mammals and also contributes to flies' immune systems. Once the researchers confirmed that the piRNA pathway was active in a normal, mature body tissue, they conducted several experiments to see what happened in the flies when they knocked out components of the pathway. For example, with the piwi gene gone, flies had significantly fewer piRNAs than flies who had a copy.

Firefly Nuptial Gifts Are Complex, Elegant Structures Manufactured by a Number of Male Glands

Female fireflies have long known that the best romances are with a male firefly that offers the most nourishing and largest "nuptial gift" - a protein-packed capsule of sperm that is rich with egg-producing and life-extending nutrients for the female. However, the molecular composition of nuptial gifts has remained unknown even though the gifts offer benefits that keep a female firefly coming back for more. Now, new research at Tufts University, in collaboration with MIT scientists, reveals the mystery of this special package, offers the first peek into the content of firefly gifts, and sheds new light on post-mating sexual selection. The findings were published online on December 22,2016 in Scientific Reports. The open-access article is titled “Molecular Characterization of Firefly Nuptial Gifts: A Multi-Omics Approach Sheds Light on Postcopulatory Sexual Selection.” Focusing on the common Eastern firefly, Photinus pyralis, also known as the Big Dipper, researchers found more than 200 identifiable proteins within the nuptial gifts. The proteins' diverse functions can be inferred based on their resemblance to proteins known from other insects. Some are structural proteins that make up the fabric of the nuptial gift, while others are enzymes that may help unpackage the gift, allowing its contents to be released. Still other enzymes appear to be a biochemical way of nudging the female to lay more eggs. The researchers also identified enzymes that might enhance a male's paternity success by expediting sperm storage or by increasing the ability of male sperm to fertilize the female's eggs. Corresponding author Sara Lewis, Ph.D., Professor of Biology in the School of Arts and Sciences at Tufts University, said new technologies enabled the research group to decipher exactly what's inside these amorous bundles.

December 21st

Mechanism of Successful Horizontal Gene Transfer Between Divergent Organisms May Be Explained

The transfer of genes from one organism to another is potentially a rapid way for evolution to occur and for complicated novel functions to emerge. However, even when the two organisms in question are in close proximity to each other, such as in a symbiotic or parasitic relationship, the transfer of genetic material and its introduction into a new genome only marks the initial step for successful horizontal gene transfer. It is also necessary for the gene to be expressed in a way that benefits the new host and ensures that it is passed down through the generations. In a new discovery that increases our understanding of gene transfer, a research team centered at the University of Tsukuba in Japan has studied a gene in marine invertebrates (ascidians) that originally came from a common bacterium. The team has revealed the likely mechanism by which this gene ended up being expressed in a functionally important and tissue-specific way in ascidians. The work is described in an article "Transcriptional Regulation of a Horizontally Transferred Gene from Bacterium to Chordate" that was published in Proceedings of the Royal Society of London B on December 21, 2016. The team focused on marine filter feeders called ascidians and their cellulose synthase gene. This gene encodes a protein that helps form an external protective coating, the loss of which leads to a lack of cellulose production and has adverse effects on these organisms. This gene is specifically expressed in the protective outer layer of cells called the epidermis, which was suggested to be key to its coating-related function. "We showed that a region adjacent to the cellulose synthase gene is responsible for its specific epidermal expression," study co-author Dr. Yosuke Ogura says.

Researchers Identify New Suppressor Effects of the NOX4 Protein in Liver Cancer

Researchers of the TGF-beta and Cancer group of Bellvitge Biomedical Research Institute (IDIBELL), in collaboration with King's College London, have unveiled the role of NADPH oxidase NOX4 as an inhibitor of the epithelial-amoeboid transition, a process that contributes to the migration and invasion of tumor cells. The study was published online on December 12, 2016 in Oncogene. The open-access article is titled “The NADPH Oxidase NOX4 Represses Epithelial to Amoeboid Transition and Efficient Tumour Dissemination.” In previous studies, the researchers suggested that NOX4 acts as a tumor suppressor in the liver, through inhibiting cell proliferation. "In this work, we proved that NOX4 also is an important inhibitor of the invasion and metastasis of liver tumor cells," explains Dr. Isabel Fabregat, leader of the IDIBELL research group. In vitro studies indicate that NOX4 silencing in liver tumor cells induces a migratory movement known as “amoeboid.” The amoeboid movement, related to cell contractility, is regulated by the Rho family of proteins; increased expression of these proteins results in this type of movement, associated with aggressive metastases. In the study in hepatocellular carcinoma patients, it was observed that a significant number of cases present NOX4 deletions; in addition, those patients with a low expression of NOX4 and a high expression of Rho proteins had a much worse prognosis. "This gives to our in vitro study a translational relevance, since it brings forward new prognostic biomarkers for this type of cancer", the IDIBELL researcher comments. NOX4 is regulated at the transcriptional level by the TGF-beta cytokine, which has been studied by the research group for more than 15 years.

Variant Genome Region Associated with Cold Adaptation in Arctic Inuits May Be Traced Back to Ancient Denisovan Populations

In the Arctic, the Inuits have adapted to severe cold and a predominantly seafood diet. After the first population genomic analysis of the Greenland Inuits (Fumagalli, Moltke et al. 2015, Science doi:10.1126/science.aab2319), a region in the genome containing two genes (TBX15 and WARS2) has now been scrutinized by scientists. This region is thought to be central to cold adaptation by coding for the generation of heat from a specific type of body fat, and was earlier found to be a candidate for adaptation in the Inuits. Now, a team of scientists led by Fernando Racimo, Rasmus Nielsen, et al. has followed up on the first natural selection study in Inuits to trace back the origins of these adaptations. To perform the study, the scientists used the genomic data from nearly 200 Greenlandic Inuits and compared this to data from the 1000 Genomes Project and ancient hominid DNA from Neanderthals and Denisovans. The results, published in the advanced online edition of Molecular Biology and Evolution, provide convincing evidence that the Inuit variant of the TBX15/WARS2 region first came into modern humans from an archaic hominid population, likely related to the Denisovans. "The Inuit DNA sequence in this region matches very well with the Denisovan genome, and it is highly differentiated from other present-day human sequences, though we can't discard the possibility that the variant was introduced from another archaic group whose genomes we haven't sampled yet,” said Dr. Racimo, lead author of the study. The authors found that the variant is present at low-to-intermediate frequencies throughout Eurasia, and at especially high frequencies in the Inuits and Native American populations, but almost absent in Africa.

December 20th

Malaria Drug Artemesin May Also Be Effective Against Tuberculosis

A centuries-old herbal medicine, discovered by Chinese scientists and used to effectively treat malaria, has been found to potentially aid in the treatment of tuberculosis and may slow the evolution of drug resistance. In a promising study led by Robert Abramovitch, Ph.D., a Michigan State University microbiologist and TB expert, the ancient remedy artemisinin stopped the ability of TB-causing bacteria, known as Mycobacterium tuberculosis, to become dormant. This stage of the disease often makes the use of antibiotics ineffective. The study was published online on December 19, 2016 in Nature Chemical Biology. The article is titled “Inhibitors of Mycobacterium tuberculosis DosRST Signaling and Persistence.” “When TB bacteria are dormant, they become highly tolerant [resistant] to antibiotics," Dr. Abramovitch said, an Assistant Professor in the College of Veterinary Medicine. "Blocking dormancy makes the TB bacteria more sensitive to these drugs and could shorten treatment times." One-third of the world's population is infected with TB and the disease killed 1.8 million people in 2015, according to the Centers for Disease Control and Prevention. Mycobacterium tuberculosis (Mtb) needs oxygen to thrive in the body. The immune system starves this bacterium of oxygen to control the infection. Dr. Abramovitch and his team found that artemisinin attacks a molecule called heme, which is found in the Mtb oxygen sensor. By disrupting this sensor and essentially turning it off, the artemisinin stopped the disease's ability to sense how much oxygen it was getting. "When the Mtb is starved of oxygen, it goes into a dormant state, which protects it from the stress of low-oxygen environments," Dr. Abramovitch said. "If Mtb can't sense low oxygen, then it can't become dormant and will die." Dr.

Mapping the Molecules Made by a Lichen's Resident Microbes

An international team of researchers has spatially mapped molecules produced by an intact, complex microbial community for the first time. Using a tiny slice of lichen, the team used imaging mass spectrometry to track and plot metabolites made by both bacterial and fungal lichen members. Their approach, published online on December 20, 2016 in mSystems®, an open-access journal of the American Society for Microbiology, shows how researchers can tease apart the chemistry that shapes and maintains a complex, three-dimensional microbial community. The article is titled “Spatial Molecular Architecture of the Microbial Community of a Peltigera Lichen.” "Until now, there had not been a single microbial community studied from the chemical standpoint--particularly how they are organized with respect to the molecules being produced," says Pieter Dorrestein, Ph.D., Chemistry Professor in the University of California, San Diego School of Pharmacy and senior author on the study. The team, which included researchers from the US, Canada, Germany, and Russia, chose the Peltigera hymenina lichen, which lives in humid environments on soils in forests and roadsides, as a test-bed community. Using a postage-stamp-sized sample of the lichen collected in British Columbia, Canada, the team first analyzed the relative abundance of all known genes present and found that the lichen was made up of about 81% bacteria (including cyanobacteria) 0.001% archaea, and about 19% eukaryotes (including fungi). More than 75,000 of those genes, or 13% overall, were found to be for enzymes involved in producing secondary metabolites. These metabolites "are really responsible for driving and shaping the microbial community," Dr. Dorrestein says.

Genome-Wide Changes in Chromatin Accessibility Associated with Differences in T-Cell Activity

In a bid to better understand the gene expression patterns that control T cell activity, researchers at the La Jolla Institute for Allergy and Immunology have mapped genome-wide changes in chromatin accessibility as T cells respond to acute and chronic virus infections. Their findings, published online on December 20, 2016 in Immunity, shed light on the molecular mechanisms that determine the fate of T lymphocytes and open new approaches to clinical intervention strategies to modulate T cell activity and improve immune function. The article is titled “Genome-Wide Changes in Chromatin Accessibility in CD8 T Cells During Viral Infection." "Identifying the different factors that determine different T cell states and therefore their function helps us understand if T cells will be able or not to fight viral infections or tumor growth, and if they will be able or not to provide long-term protection," says the study's first author Dr. James Scott-Browne, a postdoctoral fellow in the laboratory of Anjana Rao, Ph.D., a Professor in the Division of Signaling and Gene Expression. "We may be able to revert the exhaustion phenotype of T cells and render them better able to fight tumors or chronic viral infections such as HIV, or generate better memory cells in response to vaccines." When viruses invade or cells turn malignant, the immune system mobilizes a small cohort of naïve or immature CD8 T cells, a crucial subdivision of the immune system charged with killing virus-infected and cancerous cells. Upon activation, they mature and proliferate exponentially into highly specific effector T cells that eliminate virus-infected or otherwise compromised cells. After their job is done, most effector T cells die, leaving behind only a small contingent of memory T cell that confer long-term protection.

New Chip Captures Circulating Cancer Cells and Exosomes from Small Blood Samples, Enabling Liquid Biopsy

A chip developed by mechanical engineers at Worcester Polytechnic Institute (WPI) in Massachusetts can trap and identify metastatic cancer cells in a small amount of blood drawn from a cancer patient. The breakthrough technology uses a simple mechanical method that has been shown to be more effective in trapping cancer cells than the microfluidic approach employed in many existing devices. The WPI device uses antibodies attached to an array of carbon nanotubes at the bottom of a tiny well. Cancer cells settle to the bottom of the well, where they selectively bind to the antibodies based on their surface markers (unlike other devices, the chip can also trap tiny structures called exosomes produced by cancers cells). This “liquid biopsy,” described in a recent issue of the journal Nanotechnology, could become the basis of a simple lab test that could quickly detect early signs of metastasis and help physicians select treatments targeted at the specific cancer cells identified. Metastasis is the process by which a cancer can spread from one organ to other parts of the body, typically by entering the bloodstream. Different types of tumors show a preference for specific organs and tissues; circulating breast cancer cells, for example, are likely to take root in bones, lungs, and the brain. The prognosis for metastatic cancer (also called stage IV cancer) is generally poor, so a technique that could detect these circulating tumor cells before they have a chance to form new colonies of tumors at distant sites could greatly increase a patient’s survival odds. “The focus on capturing circulating tumor cells is quite new,” said Balaji Panchapakesan, Ph.D., Associate Professor of Mechanical Engineering at WPI and Director of the Small Systems Laboratory.