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News Article | April 25, 2017
Site: www.eurekalert.org

Neuroscientists have, for the first time, shown that gut bacteria "speak" to the brain to control food choices in animals. In a study publishing April 25 in the Open Access journal PLOS Biology, researchers identified two species of bacteria that have an impact on animal dietary decisions. The investigation was led by Carlos Ribeiro, and colleagues from the Champalimaud Centre for the Unknown in Lisbon, Portugal and Monash University, Australia. There's no question that nutrients and the microbiome, the community of bacteria that resides in the gut, impact health. For instance, diseases like obesity have been associated with the composition of the diet and the microbiome. However, the notion that microbes might also be able to control behavior seems a big conceptual leap. Yet that's what the new study shows. Experiments conducted using the fruit fly Drosophila melanogaster, a model organism allowed the scientists to dissect the complex interaction of diet and microbes and its effect on food preference. The scientists initially showed that flies deprived of amino acids showed decreased fertility and increased preference for protein-rich food. Indeed, the team found that the removal of any single essential amino acid was sufficient to increase the flies' appetite for protein-rich food. Furthermore, the scientists tested the impact on food choices of five different species of bacteria that are naturally present in the guts of fruit flies in the wild. The results exceeded the scientists' expectations: two specific bacterial species could abolish the increased appetite for protein in flies that were fed food lacking essential amino acids. "With the right microbiome, fruit flies are able to face these unfavorable nutritional situations," says Santos. "In the fruit fly, there are five main bacterial species; in humans there are hundreds," adds co-author Patrícia Francisco. This highlights the importance of using simple animal models to gain insights into factors that may be crucial for human health. How could the bacteria act on the brain to alter appetite? "Our first hypothesis was that these bacteria might be providing the flies with the missing essential amino acids," Santos explains. However, the experiments did not support this hypothesis. Instead, the gut bacteria "seem to induce some metabolic change that acts directly on the brain and the body, which mimics a state of protein satiety," Santos says. In sum, this study shows not only that gut bacteria act on the brain to alter what animals want to eat, but also that they might do so by using a new, unknown mechanism. In your coverage please use this URL to provide access to the freely available article in PLOS Biology: https:/ Citation: Leitão-Gonçalves R, Carvalho-Santos Z, Francisco AP, Fioreze GT, Anjos M, Baltazar C, et al. (2017) Commensal bacteria and essential amino acids control food choice behavior and reproduction. PLoS Biol 15(4): e2000862. doi:10.1371/journal.pbio.2000862 Funding: Portuguese Foundation for Science and Technology (FCT) (grant number postdoctoral fellowship SFRH/BPD/78947/2011). Received by RLG. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript; Portuguese Foundation for Science and Technology (FCT) (grant number PTDC/BIA-BCM/118684/2010). Received by CR. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript; Human Frontier Science Program (grant number RGP0022/2012). Received by CR. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript; EUROPEAN COMMISSION - MARIE CURIE ACTIONS (grant number FLiACT - Grant agreement no.: 289941). Received by CR. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript; Ciência sem Fronteiras program of the CNPq (grant number 200207/2012-1). Received by GTF. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript; Royal Society (grant number UF100158). Received by MDWP. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript; BIAL Foundation (grant number 283/14). Received by CR. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript; EMBO (grant number ALTF 1602-2011). Received by RLG. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript; Biotechnology and Biological Sciences Research Council (grant number BB/I011544/1). Received by MDWP. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript; Champalimaud Foundation. Received by CR. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript; Australian Research Council (grant number Australian Research Council Future Fellow - FT150100237). Received by MDWP. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript; Portuguese Foundation for Science and Technology (FCT) (grant number postdoctoral fellowship SFRH/BPD/76201/2011). Received by ZCS. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript; Portuguese Foundation for Science and Technology (FCT) (grant number postdoctoral fellowship SFRH/BPD/79325/2011 ). Received by PMI. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript; Kavli Foundation. Received by CR. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests. PMI has a commercial interest in the flyPAD open-source technology.


News Article | May 4, 2017
Site: www.eurekalert.org

Two independent studies have begun mapping the connections between and identities of the thousands of immune cells surrounding human tumors. One research group, looking at kidney cancer, found that tumors with different clinical outcomes have unique immune cell profiles. These profiles can also estimate a cancer patient's prognosis. The other group, looking at lung cancer, showed that even early tumors have disturbed immune cell activity. Both papers, appearing May 4 in the journal Cell, could inspire a new wave of precision immunotherapy clinical trials. "We've found that immune cells start to be dysfunctional very early during tumor formation, but immunotherapy is not typically given until patients relapse and the cancer is advanced," says senior author of the lung cancer study Miriam Merad (@MiriamMerad), of the Mount Sinai School of Medicine in New York. "We want to advocate for starting immunotherapy early, before it is too late." "Basic researchers are going to be very excited for this toolbox because they can study their immune cell or pathway of interest with higher resolution and compare it across individual tumors or tumor types," says senior author of the kidney cancer study Bernd Bodenmiller (@BodenmillerLab), of the University of Zürich in Switzerland. "For translational researchers, knowing that there are these immune cell differences among patients' tumors presents a tantalizing possibility for personalized immunotherapy." Immunotherapy is the use of drugs to stimulate immune cells to fight cancer the way they fight foreign invaders. A tumor's ability to grow unchecked is helped by its recruitment of immune cells to keep it hidden from the rest of the immune system. Tumors become so entrenched with our immune cells that they form mini ecosystems, with cell-to-cell relationships not seen in normal tissues. The atlases reveal these ecosystems and the connections between tumor immune cells in unmatched detail, such as which immune cells are present in a specific tumor and the frequency of a given cell type, but also their functional potential. Both studies generated the atlases by tagging single immune cells around the tumor with 30 to 40 antibodies that could bind to specific markers known to be present on various cells. Using this information, a detector could screen the cells and reveal their identities and whether the cells are functional or defective. "I think when most people see our data, they will first react with the thought that it's pure chaos," says Bodenmiller, whose group looked at tumor samples from 73 patients with renal cell carcinoma. "But if you look at the distributions of the cell phenotypes for a bit longer, you will see patterns. And then computational analysis reveals that there are relationships between the cell types in the tumor ecosystem that relate to a clinical outcome. We can even put this information into an equation and estimate survival." Merad's group looked at tumor samples and normal tissue from 28 patients at early or advanced stages of lung adenocarcinoma. Their analysis saw changes in cell type behavior much earlier than anticipated. Stage 1 tumors already showed a rich gathering of suppressive macrophages and T cells, as well as the depletion of NK cells that help activate the immune system. These tumors are typically removed surgically, and while they usually have a good prognosis, 25% of patients relapse. "In this study we identified many immune suppressive changes that could be targeted to induce an immune attack and an immune memory response against these small tumors, and we are currently testing these questions in animal models," Merad says. "We are very excited about these results because we believe that targeting tumor cells at this small stage has much higher chances to get rid of all tumor cells than if we unleashed an immune attack in larger tumors where risk of tumor cell dissemination is higher." Both groups described the creation of theirs atlases as significant undertakings and expensive, which means that it won't be something that can be used as a standard of care anytime soon. Bodenmiller predicts the technique will follow the same course as human genome sequencing, in which costs will fall over time. Merad says that generating and sharing these atlases with the cancer research community provides unprecedented knowledge about the cancer immune microenvironment and will help foster knowledge and the rational design of clinical trials. Cell, Chevrier and Levine et al: "An Immune Atlas of Clear Cell Renal Cell Carcinoma." http://www.cell.com/cell/fulltext/S0092-8674(17)30429-4 DOI: 10.1016/j.cell.2017.04.016 The research was funded by the Swiss National Science Foundation, SystemsX, the European Research Council, Roche, EMBO, RACP, CIHR/KCC, NHMRC, the National Institutes of Health, and the Memorial Sloan Kettering Cancer Center. Cell, Lavin et al.: "Innate Immune Landscape in Early Lung Adenocarcinoma by Paired Single-Cell Analyses." http://www.cell.com/cell/fulltext/S0092-8674(17)30427-0 The research was heavily funded by the National Institutes of Health. Basic research on immunotherapy is a major focus of the Cancer Moonshot Initiative. Additional support was provided by la Recherche Medicale. Cell (@CellCellPress), the flagship journal of Cell Press, is a bimonthly journal that publishes findings of unusual significance in any area of experimental biology, including but not limited to cell biology, molecular biology, neuroscience, immunology, virology and microbiology, cancer, human genetics, systems biology, signaling, and disease mechanisms and therapeutics. Visit http://www. . To receive Cell Press media alerts, contact press@cell.com.


Artist's depiction of a type IV secretion system nestled within a bacterial cell membrane. This structure shoots out thousands of toxic molecules (purple) into human cells during an infection. Credit: Caltech Experts predict that by 2050, antibiotic-resistant bacteria will cause as many deaths as cancer. Now, for the first time, Caltech scientists have created a 3-D image of a molecular structure that many different bacteria use to pump toxins into human cells and spread antibiotic-resistance genes to other bacteria. Understanding the architecture of this structure is a first step toward combating its effects. The study was conducted in the laboratory of Grant Jensen, professor of biophysics and biology and Howard Hughes Medical Institute Investigator. A paper describing the work first appeared online in the March 23 issue of EMBO Reports. The researchers looked specifically at Legionella, the bacteria that causes Legionnaires' disease, a severe and often lethal form of pneumonia. When Legionella invades a human cell, it wraps itself in a protective vesicle and opens the molecular structure, known as a type IV secretion system. The molecular "machine" sits in the cell membrane of the bacterium and proceeds to shoot tens of thousands of toxic molecules—hundreds of different types—into the human cell, hijacking cellular pathways and overwhelming the cell's defenses. Some type IV secretion systems are thought to be instrumental in spreading antibiotic-resistance genes throughout the bacterial population. "Understanding the structure of the type IV system is crucial to developing new antibiotics to disable it," says first author and postdoctoral scholar Debnath Ghosal. "While this study focuses only on the secretion system of Legionella, a very similar machine is used by many bacteria—such as the pathogens that cause stomach cancer, Q fever, and whooping cough." To image the structure—which, at 40 nanometers in diameter, is about 1,000 times too small to be seen by the human eye—the researchers employed a technique called electron cryotomography. In this method, bacteria are frozen alive and then rotated under a powerful electron microscope to create a series of 2-D images that can be digitally reconstructed into a 3-D picture. This was the first-ever image of a type IV machine within a bacterium. The imaging revealed that the structure is shaped into concentric arches, like the symbol for Wi-Fi. Understanding the structure should eventually aid efforts to design drugs that can block the machine. Developing a drug that would disable even one core protein component of the secretion system, Ghosal says, would enable human cells to fight back against the bacterial infection. "Most current antibiotics focus on destroying the cellular envelope that encompasses a bacterial cell, preventing it from replicating," says Jensen. "Developing new antibiotics that target different aspects of the bacterial cell, such as the type IV secretion system, would enable us to block infections in additional ways." The paper is titled "In situ structure of the Legionella Dot/Icm type IV secretion system by electron cryotomography." In addition to Ghosal and Jensen, coauthors are Caltech research scientist Yi Wei Chang, Kwang Cheol Jeong of the Washington University School of Medicine and the University of Florida, and Joseph Vogel of the Washington University School of Medicine. Funding was provided by the National Institutes of Health and the National Institute of Allergy and Infectious Diseases. Explore further: Spread of antibiotic resistance understood by unravelling bacterial secretion system


News Article | April 18, 2017
Site: www.futurity.org

Scientists have created a 3D image of a molecular structure that many different bacteria use to pump toxins into humans cells and spread antibiotic-resistance genes to other bacteria. Experts predict that by 2050, antibiotic-resistant bacteria will cause as many deaths as cancer. For the study, published in EMBO Reports, researchers looked specifically at Legionella, the bacteria that causes Legionnaires’ disease, a severe and often lethal form of pneumonia. When Legionella invades a human cell, it wraps itself in a protective vesicle and opens the molecular structure, known as a type IV secretion system. The molecular “machine” sits in the cell membrane of the bacterium and proceeds to shoot tens of thousands of toxic molecules—hundreds of different types—into the human cell, hijacking cellular pathways and overwhelming the cell’s defenses. Some type IV secretion systems are thought to be instrumental in spreading antibiotic-resistance genes throughout the bacterial population. “Understanding the structure of the type IV system is crucial to developing new antibiotics to disable it,” says first author Debnath Ghosal, a postdoctoral scholar at California Institute of Technology. “While this study focuses only on the secretion system of Legionella, a very similar machine is used by many bacteria—such as the pathogens that cause stomach cancer, Q fever, and whooping cough.” To image the structure—which, at 40 nanometers in diameter, is about 1,000 times too small to be seen by the human eye—the researchers employed a technique called electron cryotomography. In this method, bacteria are frozen alive and then rotated under a powerful electron microscope to create a series of 2D images that can be digitally reconstructed into a 3D picture. This was the first-ever image of a type IV machine within a bacterium. The imaging revealed that the structure is shaped into concentric arches, like the symbol for Wi-Fi. Understanding the structure should eventually aid efforts to design drugs that can block the machine. Developing a drug that would disable even one core protein component of the secretion system, Ghosal says, would enable human cells to fight back against the bacterial infection. “Most current antibiotics focus on destroying the cellular envelope that encompasses a bacterial cell, preventing it from replicating,” says Grant Jensen, professor of biophysics and biology. “Developing new antibiotics that target different aspects of the bacterial cell, such as the type IV secretion system, would enable us to block infections in additional ways.” Additional researchers from Caltech, Washington University School of Medicine, and the University of Florida are coauthors of the study. The National Institutes of Health and the National Institute of Allergy and Infectious Diseases funded the work.


News Article | February 22, 2017
Site: www.eurekalert.org

Heidelberg, 22 February 2017 - A common strategy to create high-yielding plants is hybrid breeding - crossing two different inbred lines to obtain characteristics superior to each parent. However, getting the inbred lines in the first place can be a hassle. Inbred lines consist of genetically uniform individuals and are created through numerous generations of self-crossing. In maize, the use of so-called "haploid inducers" provides a short cut to this cumbersome procedure, allowing to produce inbred lines in just one generation. A study by Laurine Gilles and colleagues, published today in The EMBO Journal, sheds light on the genetics behind haploid induction. "Knowing the molecular identity of haploid induction represents an important breakthrough to fully understand the fertilization process in plants, and hopefully will allow to translate this breeding tool to other species," said the study's senior author Dr. Thomas Widiez, an INRA (Institut National de la Recherche Agronomique) researcher at the École Normale Supérieure in Lyon, France. Haploid inducers were first discovered in the 1950s. Pollination of female flower with pollen of a haploid inducer strain will yield offspring that are haploid, meaning that they will only contain one single copy of each gene as opposed to the usual two copies. All their genetic material comes from the mother. Treating these haploid plants with a chemical that causes chromosome doubling will lead to plants with two identical copies of all genes in just one generation. With classical inbreeding, this condition takes seven to ten years to achieve. Haploid offspring in maize are not unusual; they emerge naturally, albeit at a very low rate. Haploid inducers can bring this rate up to about 10% of the progeny being haploid - enough to make it a useful tool for breeders. More than 50 years after the discovery of haploid inducers, Widiez and his team, in collaboration with Limagrain, have now identified the gene that mainly causes the phenomenon and termed it Not Like Dad to highlight the fact that its dysfunction induces embryos without genetic contribution from the father. The gene product is necessary for successful fertilization so that its failure promotes the formation of haploid embryos. Two other research groups have in parallel identified the same gene and come to similar conclusions. Haploid inducers are nowadays powerful breeding tools, but as yet the technology is restricted to maize, while in-vitro haploid induction in certain crops is labor-intense. Understanding the genes and molecular mechanism behind the process will help translate this technology to other crops. The identification of Not Like Dad is an important step to this end. While Not Like Dad is the most important contributor to haploid induction in inducer lines, there are at least seven more genes that play a role in increasing the rate of haploid offspring. Revealing their molecular identity, as well as understanding their mode of action, will be important to fully understand the process. Loss of pollen-specific phospholipase Not Like Dad (NLD) triggers gynogenesis in maize EMBO is an organization of more than 1700 leading researchers that promotes excellence in the life sciences. The major goals of the organization are to support talented researchers at all stages of their careers, stimulate the exchange of scientific information, and help build a European research environment where scientists can achieve their best work. EMBO helps young scientists to advance their research, promote their international reputations and ensure their mobility. Courses, workshops, conferences and scientific journals disseminate the latest research and offer training in techniques to maintain high standards of excellence in research practice. EMBO helps to shape science and research policy by seeking input and feedback from our community and by following closely the trends in science in Europe. ?For more information: http://www.


Pulverer B.,EMBO
EMBO Journal | Year: 2014

New guidelines for the reporting of research and source data enhance the interpretation and reproducibility of published research. New guidelines for the reporting of research and source data enhance the interpretation and reproducibility of published research. © 2014 The Author.


Pulverer B.,EMBO
EMBO Journal | Year: 2014

Systematic image screening at EMBO Press uncovers many problems, most of which can be resolved. Standardized pre-publication image screening would make for a more reliable literature. Flagging putative image manipulation post-publication remains an important control mechanism, but must not fall victim to an overzealous response. The STAP stem cell papers are a case in point. Systematic image screening at EMBO Press uncovers many irregularities, which are thereby prevented from entering the scientific literature. Such mechanisms may have helped thwart publication of manipulated images in recent high-profile papers. © 2014 The Author.


Pulverer B.,EMBO
EMBO Journal | Year: 2015

A reliable scientific literature is crucial for an efficient research process. Peer review remains a highly successful quality assurance mechanism, but it does not always prevent data and image aberrations and the publication of flawed data. Journals need to be in a position to detect such problems and take proportionate action. Publishers should apply consistent policies to correcting the published literature and adopt versioning. The scientific community ought to encourage corrections. Peer review is a successful quality assurance mechanism for a reliable scientific literature, but it does not always prevent the publication of flawed data. Journals need to be in a position to assess data and image aberrations and correct the literature. The scientific community should encourage author-initiated corrections. © 2015 The Author.


Pulverer B.,EMBO
EMBO Journal | Year: 2015

The San Francisco Declaration on Research Assessment (DORA) points out that using the Journal Impact Factor as a proxy measure for the value or quality of specific research and individual scientists leads to biased research assessment. How can we resist misusing metrics? © 2015 The Author.


An interview with Jeffery Taubenberger from NIAID about how understanding the evolution of influenza could inform vaccine development and public health measures to deal with flu pandemics. © 2014 The Author.

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