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[Report] Deformation-assisted fluid percolation in rock salt

Fri, 11/27/2015 - 00:00
Deep geological storage sites for nuclear waste are commonly located in rock salt to ensure hydrological isolation from groundwater. The low permeability of static rock salt is due to a percolation threshold. However, deformation may be able to overcome this threshold and allow fluid flow. We confirm the percolation threshold in static experiments on synthetic salt samples with x-ray microtomography. We then analyze wells penetrating salt deposits in the Gulf of Mexico. The observed hydrocarbon distributions in rock salt require that percolation occurred at porosities considerably below the static threshold due to deformation-assisted percolation. Therefore, the design of nuclear waste repositories in salt should guard against deformation-driven fluid percolation. In general, static percolation thresholds may not always limit fluid flow in deforming environments. Authors: Soheil Ghanbarzadeh, Marc A. Hesse, Maša Prodanović, James E. Gardner
Categories: Journal Articles

[Report] Predicting poverty and wealth from mobile phone metadata

Fri, 11/27/2015 - 00:00
Accurate and timely estimates of population characteristics are a critical input to social and economic research and policy. In industrialized economies, novel sources of data are enabling new approaches to demographic profiling, but in developing countries, fewer sources of big data exist. We show that an individual’s past history of mobile phone use can be used to infer his or her socioeconomic status. Furthermore, we demonstrate that the predicted attributes of millions of individuals can, in turn, accurately reconstruct the distribution of wealth of an entire nation or to infer the asset distribution of microregions composed of just a few households. In resource-constrained environments where censuses and household surveys are rare, this approach creates an option for gathering localized and timely information at a fraction of the cost of traditional methods. Authors: Joshua Blumenstock, Gabriel Cadamuro, Robert On
Categories: Journal Articles

[Report] A pharyngeal jaw evolutionary innovation facilitated extinction in Lake Victoria cichlids

Fri, 11/27/2015 - 00:00
Evolutionary innovations, traits that give species access to previously unoccupied niches, may promote speciation and adaptive radiation. Here, we show that such innovations can also result in competitive inferiority and extinction. We present evidence that the modified pharyngeal jaws of cichlid fishes and several marine fish lineages, a classic example of evolutionary innovation, are not universally beneficial. A large-scale analysis of dietary evolution across marine fish lineages reveals that the innovation compromises access to energy-rich predator niches. We show that this competitive inferiority shaped the adaptive radiation of cichlids in Lake Tanganyika and played a pivotal and previously unrecognized role in the mass extinction of cichlid fishes in Lake Victoria after Nile perch invasion. Authors: Matthew D. McGee, Samuel R. Borstein, Russell Y. Neches, Heinz H. Buescher, Ole Seehausen, Peter C. Wainwright
Categories: Journal Articles

[Report] Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota

Fri, 11/27/2015 - 00:00
Antibodies targeting CTLA-4 have been successfully used as cancer immunotherapy. We find that the antitumor effects of CTLA-4 blockade depend on distinct Bacteroides species. In mice and patients, T cell responses specific for B. thetaiotaomicron or B. fragilis were associated with the efficacy of CTLA-4 blockade. Tumors in antibiotic-treated or germ-free mice did not respond to CTLA blockade. This defect was overcome by gavage with B. fragilis, by immunization with B. fragilis polysaccharides, or by adoptive transfer of B. fragilis–specific T cells. Fecal microbial transplantation from humans to mice confirmed that treatment of melanoma patients with antibodies against CTLA-4 favored the outgrowth of B. fragilis with anticancer properties. This study reveals a key role for Bacteroidales in the immunostimulatory effects of CTLA-4 blockade. Authors: Marie Vétizou, Jonathan M. Pitt, Romain Daillère, Patricia Lepage, Nadine Waldschmitt, Caroline Flament, Sylvie Rusakiewicz, Bertrand Routy, Maria P. Roberti, Connie P. M. Duong, Vichnou Poirier-Colame, Antoine Roux, Sonia Becharef, Silvia Formenti, Encouse Golden, Sascha Cording, Gerard Eberl, Andreas Schlitzer, Florent Ginhoux, Sridhar Mani, Takahiro Yamazaki, Nicolas Jacquelot, David P. Enot, Marion Bérard, Jérôme Nigou, Paule Opolon, Alexander Eggermont, Paul-Louis Woerther, Elisabeth Chachaty, Nathalie Chaput, Caroline Robert, Christina Mateus, Guido Kroemer, Didier Raoult, Ivo Gomperts Boneca, Franck Carbonnel, Mathias Chamaillard, Laurence Zitvogel
Categories: Journal Articles

[Report] Commensal Bifidobacterium promotes antitumor immunity and facilitates anti–PD-L1 efficacy

Fri, 11/27/2015 - 00:00
T cell infiltration of solid tumors is associated with favorable patient outcomes, yet the mechanisms underlying variable immune responses between individuals are not well understood. One possible modulator could be the intestinal microbiota. We compared melanoma growth in mice harboring distinct commensal microbiota and observed differences in spontaneous antitumor immunity, which were eliminated upon cohousing or after fecal transfer. Sequencing of the 16S ribosomal RNA identified Bifidobacterium as associated with the antitumor effects. Oral administration of Bifidobacterium alone improved tumor control to the same degree as programmed cell death protein 1 ligand 1 (PD-L1)–specific antibody therapy (checkpoint blockade), and combination treatment nearly abolished tumor outgrowth. Augmented dendritic cell function leading to enhanced CD8+ T cell priming and accumulation in the tumor microenvironment mediated the effect. Our data suggest that manipulating the microbiota may modulate cancer immunotherapy. Authors: Ayelet Sivan, Leticia Corrales, Nathaniel Hubert, Jason B. Williams, Keston Aquino-Michaels, Zachary M. Earley, Franco W. Benyamin, Yuk Man Lei, Bana Jabri, Maria-Luisa Alegre, Eugene B. Chang, Thomas F. Gajewski
Categories: Journal Articles

[Report] Malaria parasites target the hepatocyte receptor EphA2 for successful host infection

Fri, 11/27/2015 - 00:00
The invasion of a suitable host hepatocyte by mosquito-transmitted Plasmodium sporozoites is an essential early step in successful malaria parasite infection. Yet precisely how sporozoites target their host cell and facilitate productive infection remains largely unknown. We found that the hepatocyte EphA2 receptor was critical for establishing a permissive intracellular replication compartment, the parasitophorous vacuole. Sporozoites productively infected hepatocytes with high EphA2 expression, and the deletion of EphA2 protected mice from liver infection. Lack of host EphA2 phenocopied the lack of the sporozoite proteins P52 and P36. Our data suggest that P36 engages EphA2, which is likely to be a key step in establishing the permissive replication compartment. Authors: Alexis Kaushansky, Alyse N. Douglass, Nadia Arang, Vladimir Vigdorovich, Nicholas Dambrauskas, Heather S. Kain, Laura S. Austin, D. Noah Sather, Stefan H.I. Kappe
Categories: Journal Articles

[Report] Gene essentiality and synthetic lethality in haploid human cells

Fri, 11/27/2015 - 00:00
Although the genes essential for life have been identified in less complex model organisms, their elucidation in human cells has been hindered by technical barriers. We used extensive mutagenesis in haploid human cells to identify approximately 2000 genes required for optimal fitness under culture conditions. To study the principles of genetic interactions in human cells, we created a synthetic lethality network focused on the secretory pathway based exclusively on mutations. This revealed a genetic cross-talk governing Golgi homeostasis, an additional subunit of the human oligosaccharyltransferase complex, and a phosphatidylinositol 4-kinase β adaptor hijacked by viruses. The synthetic lethality map parallels observations made in yeast and projects a route forward to reveal genetic networks in diverse aspects of human cell biology. Authors: Vincent A. Blomen, Peter Májek, Lucas T. Jae, Johannes W. Bigenzahn, Joppe Nieuwenhuis, Jacqueline Staring, Roberto Sacco, Ferdy R. van Diemen, Nadine Olk, Alexey Stukalov, Caleb Marceau, Hans Janssen, Jan E. Carette, Keiryn L. Bennett, Jacques Colinge, Giulio Superti-Furga, Thijn R. Brummelkamp
Categories: Journal Articles

[Report] Identification and characterization of essential genes in the human genome

Fri, 11/27/2015 - 00:00
Large-scale genetic analysis of lethal phenotypes has elucidated the molecular underpinnings of many biological processes. Using the bacterial clustered regularly interspaced short palindromic repeats (CRISPR) system, we constructed a genome-wide single-guide RNA library to screen for genes required for proliferation and survival in a human cancer cell line. Our screen revealed the set of cell-essential genes, which was validated with an orthogonal gene-trap–based screen and comparison with yeast gene knockouts. This set is enriched for genes that encode components of fundamental pathways, are expressed at high levels, and contain few inactivating polymorphisms in the human population. We also uncovered a large group of uncharacterized genes involved in RNA processing, a number of whose products localize to the nucleolus. Last, screens in additional cell lines showed a high degree of overlap in gene essentiality but also revealed differences specific to each cell line and cancer type that reflect the developmental origin, oncogenic drivers, paralogous gene expression pattern, and chromosomal structure of each line. These results demonstrate the power of CRISPR-based screens and suggest a general strategy for identifying liabilities in cancer cells. Authors: Tim Wang, Kıvanç Birsoy, Nicholas W. Hughes, Kevin M. Krupczak, Yorick Post, Jenny J. Wei, Eric S. Lander, David M. Sabatini
Categories: Journal Articles

[Report] Genome-wide inactivation of porcine endogenous retroviruses (PERVs)

Fri, 11/27/2015 - 00:00
The shortage of organs for transplantation is a major barrier to the treatment of organ failure. Although porcine organs are considered promising, their use has been checked by concerns about the transmission of porcine endogenous retroviruses (PERVs) to humans. Here we describe the eradication of all PERVs in a porcine kidney epithelial cell line (PK15). We first determined the PK15 PERV copy number to be 62. Using CRISPR-Cas9, we disrupted all copies of the PERV pol gene and demonstrated a >1000-fold reduction in PERV transmission to human cells, using our engineered cells. Our study shows that CRISPR-Cas9 multiplexability can be as high as 62 and demonstrates the possibility that PERVs can be inactivated for clinical application of porcine-to-human xenotransplantation. Authors: Luhan Yang, Marc Güell, Dong Niu, Haydy George, Emal Lesha, Dennis Grishin, John Aach, Ellen Shrock, Weihong Xu, Jürgen Poci, Rebeca Cortazio, Robert A. Wilkinson, Jay A. Fishman, George Church
Categories: Journal Articles

[Report] Cotranslational protein folding on the ribosome monitored in real time

Fri, 11/27/2015 - 00:00
Protein domains can fold into stable tertiary structures while they are synthesized on the ribosome. We used a high-performance, reconstituted in vitro translation system to investigate the folding of a small five-helix protein domain—the N-terminal domain of Escherichia coli N5-glutamine methyltransferase HemK—in real time. Our observations show that cotranslational folding of the protein, which folds autonomously and rapidly in solution, proceeds through a compact, non-native conformation that forms within the peptide tunnel of the ribosome. The compact state rearranges into a native-like structure immediately after the full domain sequence has emerged from the ribosome. Both folding transitions are rate-limited by translation, allowing for quasi-equilibrium sampling of the conformational space restricted by the ribosome. Cotranslational folding may be typical of small, intrinsically rapidly folding protein domains. Authors: Wolf Holtkamp, Goran Kokic, Marcus Jäger, Joerg Mittelstaet, Anton A. Komar, Marina V. Rodnina
Categories: Journal Articles

[New Products] New Products

Fri, 11/27/2015 - 00:00
A weekly roundup of information on newly offered instrumentation, apparatus, and laboratory materials of potential interest to researchers.
Categories: Journal Articles

[Podcast] Science Podcast: 27 November Show

Fri, 11/27/2015 - 00:00
On this week's show: Bioengineering vocal cords and a roundup of daily news stories.
Categories: Journal Articles

[Working Life] The best decision I ever made

Fri, 11/27/2015 - 00:00
Author: Kamal J. K. Gandhi
Categories: Journal Articles

[Editorial] Zero tolerance. Period

Thu, 10/29/2015 - 23:00
Earlier this month, famed astronomer Geoff Marcy's sexual harassment of female students was exposed. He has since resigned from the University of California, Berkeley, in the face of concerted pressure from peers and students. It is unconscionable for someone to use academic power to be a sexual predator, but the reality is that Marcy operated in an academic culture that turned a blind eye to such behavior. Author: Bernard Wood
Categories: Journal Articles

[In Brief] This week's section

Thu, 10/29/2015 - 23:00
In science news around the world, the U.S. Congress moves toward a budget agreement that would increase funding for domestic science agencies in 2016, Australian Prime Minister Malcolm Turnbull names neuroscientist Alan Finkel as the country's new science minister, researchers fly above Hurricane Patricia with a specially outfitted U.S. Navy bomber, a World Health Organization panel finds that the world's first malaria vaccine needs pilot tests to determine how to deliver it effectively, and improved data have produced a spike in global active tuberculosis cases. Also, astronomers unveil the largest image of the Milky Way ever assembled. And a report by Chinese and U.S. scientists warns that China's diminishing wetlands are nearing a critical threshold, below which losses could inflict severe and lasting harm on ecosystems.
Categories: Journal Articles

[In Depth] Europe's Mars rover to target ancient wetland

Thu, 10/29/2015 - 23:00
European planetary scientists are still building the roving laboratory they plan to send to Mars in 2018, but now they know where it will land: Oxia Planum. Clay deposits and landforms suggest this ancient region once hosted lakes, rivers, and a delta, making it just the sort of place to dig for signs of possible martian life. That is the mission of the ExoMars 2018 rover, one component of a multipart joint mission by the European Space Agency (ESA) and its Russian counterpart, Roscosmos. The landing site—chosen after intense discussions at the ESA's technology center in Noordwijk, the Netherlands—beat out three other candidates. One "must" for all four ExoMars sites was clay: fine-grained sediment that, on Earth, is deposited by water and is excellent at preserving the remains of ancient organisms. At Oxia Planum, the clays were covered by other material for billions of years and then recently uncovered by wind erosion. The long burial may have shielded them from ionizing radiation from space that could destroy organic molecules near the surface. Author: Daniel Clery
Categories: Journal Articles

[In Depth] Lifelong memories may reside in nets around brain cells

Thu, 10/29/2015 - 23:00
In 1898, Italian biologist Camillo Golgi saw something odd in the slices of brain tissue he examined under his microscope: weblike lattices surrounding many neurons. Golgi could not discern their purpose, and many dismissed the nets as an artifact of his staining technique. For the next century, the lattices remained largely obscure. But last week at the annual meeting of the Society for Neuroscience in Chicago, Illinois, researchers offered tantalizing new evidence that holes in these nets could be the storage sites for long-term memories. Perineuronal nets (PNNs), as they are known today, are scaffolds of linked proteins and sugars that resemble cartilage. A growing body of research suggests that PNNs may control the formation and function of synapses, the microscopic junctions between neurons that allow cells to communicate and that may play a role in learning and memory. Author: Emily Underwood
Categories: Journal Articles

[In Depth] How some of the world's biggest dinosaurs got that way

Thu, 10/29/2015 - 23:00
Paleontologists and the public alike have long been fascinated by the great titanosaurs, long necked sauropods which include the largest creatures ever to walk the earth. For example, Argentinosaurus, a South American species, stretched nearly 40 meters long from head to tail, and weighed more than 70 tons—as much as 15 adult elephants and more than twice as much as the classic sauropod, Apatosaurus. Yet the titanosaur fossil record has been pretty scrappy—just three complete skulls have been found—leaving major mysteries about these behemoths. In particular, researchers still need to learn more about how and why they grew so big, and how they managed to move their massive bodies. The picture is beginning to fill in, however. At a special session at the annual meeting of the Society of Vertebrate Paleontology in Dallas, Texas, researchers presented new fossils that chart titanosaur growth and development from embryo to adult, including a spectacular egg, a rare juvenile, and a modeling study of how titanosaur adults moved their massive necks. Author: Michael Balter
Categories: Journal Articles

[In Depth] Proposed study would closely track 10,000 New Yorkers

Thu, 10/29/2015 - 23:00
In a year and a half, 2500 households in New York City may receive a startling request: to allow a team of scientists to monitor in intimate detail how they lead their lives over the course of 20 years—where they go, what they eat, who they talk to, what they buy, and how their bodies grow, change, and deteriorate. That's the ambition of the Kavli Human Understanding through Measurement and Analysis (HUMAN) Project, a study now halfway through its 3-year planning phase, which released a preliminary study design this month. Many see the effort—which would amass information on health, behavior, and lifestyle as a resource for social scientists and biomedical researchers—as a symbol of the big data era, in which researchers collect data first and pose hypotheses later. Author: Kelly Servick
Categories: Journal Articles