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[Report] Molecular architecture of the active mitochondrial protein gate

Thu, 09/24/2015 - 23:00
Mitochondria fulfill central functions in cellular energetics, metabolism, and signaling. The outer membrane translocator complex (the TOM complex) imports most mitochondrial proteins, but its architecture is unknown. Using a cross-linking approach, we mapped the active translocator down to single amino acid residues, revealing different transport paths for preproteins through the Tom40 channel. An N-terminal segment of Tom40 passes from the cytosol through the channel to recruit chaperones from the intermembrane space that guide the transfer of hydrophobic preproteins. The translocator contains three Tom40 β-barrel channels sandwiched between a central α-helical Tom22 receptor cluster and external regulatory Tom proteins. The preprotein-translocating trimeric complex exchanges with a dimeric isoform to assemble new TOM complexes. Dynamic coupling of α-helical receptors, β-barrel channels, and chaperones generates a versatile machinery that transports about 1000 different proteins. Authors: Takuya Shiota, Kenichiro Imai, Jian Qiu, Victoria L. Hewitt, Khershing Tan, Hsin-Hui Shen, Noriyuki Sakiyama, Yoshinori Fukasawa, Sikander Hayat, Megumi Kamiya, Arne Elofsson, Kentaro Tomii, Paul Horton, Nils Wiedemann, Nikolaus Pfanner, Trevor Lithgow, Toshiya Endo
Categories: Journal Articles

[Report] Arrested replication forks guide retrotransposon integration

Thu, 09/24/2015 - 23:00
Long terminal repeat (LTR) retrotransposons are an abundant class of genomic parasites that replicate by insertion of new copies into the host genome. Fungal LTR retrotransposons prevent mutagenic insertions through diverse targeting mechanisms that avoid coding sequences, but conserved principles guiding their target site selection have not been established. Here, we show that insertion of the fission yeast LTR retrotransposon Tf1 is guided by the DNA binding protein Sap1 and that the efficiency and location of the targeting depend on the activity of Sap1 as a replication fork barrier. We propose that Sap1 and the fork arrest it causes guide insertion of Tf1 by tethering the integration complex to target sites. Authors: Jake Z. Jacobs, Jesus D. Rosado-Lugo, Susanne Cranz-Mileva, Keith M. Ciccaglione, Vincent Tournier, Mikel Zaratiegui
Categories: Journal Articles

[Association Affairs] Gordon Research Conferences

Thu, 09/24/2015 - 23:00
This issue of Science includes the program of the 2016 AAAS Annual Meeting. 2016 “Session I” Meetings will be held between January 9 and March 25 in Ventura, CA and Galveston, TX in the United States, and internationally in the Tuscany region of Italy. A PDF of the program as it appears in this issue is available here; for more information on the meeting (including registration forms and information on accommodations), please visit www.grc.org.
Categories: Journal Articles

[Business Office Feature] Synthetic biology's clinical applications

Thu, 09/24/2015 - 23:00
Engineered systems of genes and other molecular components created through synthetic biology make medical treatments more effective and promise cures for a range of health problems. Perhaps equally important, recent technologies make it easier for a broader range of scientists to apply synthetic-biology approaches that drive expanding clinical applications, from designing new diagnostics and building molecularly engineered tissues to developing new drugs and vaccines.Read the Feature (Full-Text HTML)Read the Feature (PDF)Read New Products (PDF) Author: Mike May
Categories: Journal Articles

[New Products] New Products

Thu, 09/24/2015 - 23:00
A weekly roundup of information on newly offered instrumentation, apparatus, and laboratory materials of potential interest to researchers.
Categories: Journal Articles

[Podcast] Science Podcast: 25 September Show

Thu, 09/24/2015 - 23:00
On this week's show: 3-parent gene therapy to treat mitochondrial diseases and a roundup of daily news stories.
Categories: Journal Articles

[Working Life] How science fairs shaped my career

Thu, 09/24/2015 - 23:00
Author: Rachel Yoho
Categories: Journal Articles

[Editorial] Preparing for the next Katrina

Thu, 08/27/2015 - 23:00
Ten years ago, Katrina, a category 5 hurricane at peak strength, slammed into New Orleans. Its associated storm surge breached the extensive levee system that had protected the city. Nearly 2000 residents died, and damages exceeded $100 billion. The storm remains the costliest natural disaster in U.S. history, and the resulting economic, social, and environmental turmoil led to the largest mass migration since the U.S. Civil War. A distinguished panel* of scientists and engineers who had been on the scene of Katrina was convened on the eve of the 10th anniversary of this event to address the question: Are American cities better prepared for the next major hurricane? Author: Marcia McNutt
Categories: Journal Articles

[In Brief] This week's section

Thu, 08/27/2015 - 23:00
In science news around the world, the IS group destroys an ancient temple in Palmyra, Syria, the U.S. Food and Drug Administration approves a "female Viagra" drug, eight protestors are arrested in Hawaii attempting to block construction of the Daniel K. Inouye Solar Telescope, a new quantum processor breaks the "1000-qubit barrier," and more. Also, the National Oceanic and Atmospheric Administration declares the deaths of 30 large whales in the Gulf of Alaska since May an "unusual mortality event," triggering a focused investigation into the cause of the deaths. And Science chats with Jorge Cham, creator of the comic Piled Higher and Deeper (PHD), about his new, upcoming movie.
Categories: Journal Articles

[In Depth] Fiscal crisis has Brazilian scientists scrambling

Thu, 08/27/2015 - 23:00
Brazilian scientists are facing one of the nation's worst funding climates in decades. Battling a slumping economy and debt, Brazil's federal government has taken an ax to spending, and it isn't sparing science. President Dilma Rousseff's administration has cut by 25% the Ministry of Science's projected 2015 budget, and sliced 9% from the budget of the Ministry of Education, which plays an important role in funding graduate students. Research agencies are withholding money for grants that have already been awarded, and have canceled or postponed new calls for proposals. And Rousseff is redirecting funds once earmarked largely for research to send Brazilian students abroad to study. The funding climate is "the worst in 20 years," says Helena Nader, president of the Brazilian Society for the Advancement of Science. At the root of the problem are changes in how Brazil's government spends the royalties generated by Brazil's lucrative offshore oil fields, which have been a major source of funding for science and technology development. In recent years, Brazil's government has redirected much of the oil revenue to other priorities, including health care and education. Author: Herton Escobar
Categories: Journal Articles

[In Depth] Many psychology papers fail replication test

Thu, 08/27/2015 - 23:00
The largest effort yet to replicate psychology studies has yielded both good and bad news. On the down side, of the 100 prominent papers analyzed, only 39% could be replicated unambiguously, as a group of 270 researchers describes on page 943. On the up side, despite the sobering results, the effort seems to have drawn little of the animosity that greeted a similar replication effort last year. This time around, even some of the original authors see the replications as a useful addition to their own research. "This is how science works," says Joshua Correll, a psychologist at the University of Colorado, Boulder, and one of the authors whose results could not be replicated. "How else will we converge on the truth? Really, the surprising thing is that this kind of systematic attempt at replication is not more common." That's encouraging news to Brian Nosek, a psychologist at the University of Virginia in Charlottesville who led the mass replication effort, which began in 2011 with the goal of putting psychological science on more rigorous experimental footing. Author: John Bohannon
Categories: Journal Articles

[In Depth] Plugged pores may underlie some ALS, dementia cases

Thu, 08/27/2015 - 23:00
It is famous for robbing Lou Gehrig of his life and Stephen Hawking of his mobility and voice, but just how amyotrophic lateral sclerosis (ALS) destroys motor neurons in the brain and spinal cord remains a mystery. Now, scientists are converging on an explanation, at least for a fraction of the ALS cases caused by a mutation also associated with a kind of dementia. In cells with the mutation, the new work shows, pores in the membrane separating the nucleus and cytoplasm become clogged, preventing vital molecules from passing through and creating a fatal cellular traffic jam. For now, the work applies only to the mutation dubbed C9orf72—a DNA stutter in which a short nucleotide sequence, GGGGCC, is repeated hundreds to thousands of times in a gene on chromosome 9. Nor do the multiple labs reporting results this week agree on exactly what plugs those nuclear pores and how the cells die. Still, many in the field are calling the work a major breakthrough, and say the findings could point to new therapies, as well as a novel mechanism for neurodegeneration. Author: Emily Underwood
Categories: Journal Articles

[In Depth] Dark horse scores a fusion coup

Thu, 08/27/2015 - 23:00
Nuclear fusion has always required titanic machines and vast amounts of public money—and success is always decades away. Now, a privately funded company has taken what some physicists say is a significant step toward mastering fusion energy with a smaller, cheaper, faster approach. Tri Alpha Energy announced this week that it has built a machine that forms a ball of gas—superheated to about 10 million degrees Celsius—and holds it steady for 5 milliseconds without decaying. Those conditions are well short of what is needed for fusion, but the feat shows for the first time that Tri Alpha's unorthodox approach can trap hot fusion gas in a steady state. Now, the scientists hope to scale up the technique toward times and temperatures that cause atomic nuclei in the gas to fuse together, releasing energy. Author: Daniel Clery
Categories: Journal Articles

[In Depth] Orchids' dazzling diversity explained

Thu, 08/27/2015 - 23:00
With more than 25,000 species, orchids are the largest group of plants. A new family tree shows how they owe their diversity to a series of innovations that individually or jointly touched off explosions of new species. The pace of diversification rose after orchids developed a way to lump their pollen into balls called pollinia, which allowed them to exclusively rely on certain insect species for pollination. Many lineages benefited from the evolution of a kind of water-saving photosynthesis. A shift to living in trees opened up many niches, as did a move into tropical mountains such as the Andes. Author: Erik Stokstad
Categories: Journal Articles

[Feature] The missing mudbug

Thu, 08/27/2015 - 23:00
In North America, crayfish have diversified into roughly 400 species—two-thirds of the world's total—and live mainly in the southeast. Biologists estimate nearly half of U.S. species are imperiled, whereas about a third of the world's crayfish are. Spurred by growing concerns that pollution, habitat destruction, and other threats are placing many crayfish species in harm's way, federal officials are taking a hard look at whether to give legal protection to two: the Guyandotte River crayfish found in southern West Virginia and the Big Sandy crayfish found in Kentucky, West Virginia, and Virginia. If the listings go through, a broad range of economically important activities that affect the crayfish, including mining, logging, and recreation, could feel an impact. So government officials are proceeding with care, seeking to learn as much as possible about the enigmatic invertebrates before making decisions—and they are asking researchers like West Liberty University's Zachary Loughman for help. Author: Emily DeMarco
Categories: Journal Articles

[Feature] Birth of the moralizing gods

Thu, 08/27/2015 - 23:00
Today's most successful religions have one thing in common: moralizing gods that care about how people treat one another and will punish those who are selfish and cruel. But for most of human history, these "big gods" were the exception. If today's hunter-gatherers are any guide, for thousands of years our ancestors conceived of deities as utterly indifferent to the human realm, and to whether we behaved well or badly. Now, to crack the mystery of why and how people around the world came to believe in moralizing gods, researchers are using a novel tool in religious studies: the scientific method. By combining laboratory experiments, cross-cultural fieldwork, and analysis of the historical record, an interdisciplinary team has proposed that belief in judgmental deities was key to the cooperation needed to build and sustain large, complex societies. And once big gods and big societies existed, their moralizing deities helped religions as dissimilar as Islam and Mormonism to spread by making groups of the faithful more cooperative and therefore more successful. Critics say the big gods team is projecting modern values onto ancient cultures, and that belief in moralizing deities is a byproduct of other social changes. To settle the debate, researchers are looking for quantitative data in novel places, including the historical record. Author: Lizzie Wade
Categories: Journal Articles

[Feature] Turning history into a binary code

Thu, 08/27/2015 - 23:00
To test his hypothesis about how moralizing, prosocial religions evolved, University of British Columbia psychologist Ara Norenzayan needs help from the humanities. Did moralizing gods, community-wide rituals, and supernatural punishment emerge before or after societies became politically complex? Has any large-scale society succeeded without prosocial religion? And what does "moralizing" really mean at different times and in difficult cultures? To answer these questions in a rigorous, scientific way, he and his colleagues are trying to convince historians to turn the nuanced knowledge in their heads into the kind of data scientists need: a database's binary code of yes/no answers. By creating the Database of Religious History, the big gods team is attempting to bridge the gulf between humanistic and scientific scholarship—but success hinges on enticing leading historians and religious studies scholars to join them. Author: Lizzie Wade
Categories: Journal Articles

[Perspective] Synthetic communities, the sum of parts

Thu, 08/27/2015 - 23:00
Cooperation between cells is one of evolution's fundamental innovations. It allows cells to specialize: Different members of a consortium assume different responsibilities, increasing overall productivity and allowing for more complex behavior than is possible with a single cell or a monoculture (1). These features of natural systems have attracted the attention of synthetic biologists, who have made engineering of cooperation between cells a long-standing goal. On page 986 of this issue, Chen et al. (2) report the creation of a synthetic consortium of cooperating Escherichia coli bacteria. The design principles they demonstrate have important implications for the construction of multicellular synthetic systems. Authors: Brian P. Teague, Ron Weiss
Categories: Journal Articles

[Perspective] As simple as [2+2]

Thu, 08/27/2015 - 23:00
Olefin cycloadditions, pericyclic reactions in which the relatively weak π bonds of these unsaturated species are swapped out for stronger σ bonds, are among the most widely exploited transformations in organic synthesis (1). Indeed, the Diels-Alder reaction—a [4π+2π] cycloaddition (a [4+2] cycloaddition for short) that forms six-membered rings from a diene (the 4π component) and an olefin (the 2π component)—has a storied history in the many branches of synthetic chemistry and proceeds readily under thermal conditions (see the figure, panel A) (2). However, a similarly fundamental pericyclic reaction—the corresponding [2+2] cycloaddition of two olefins, leading to cyclobutane rings—usually requires photochemical conditions to proceed efficiently, a fact enforced by the constraints of orbital symmetry (3). On page 960 of this issue, Hoyt et al. (4) report the development of catalysts based on iron that transform simple feedstock olefins into cyclobutanes through [2+2] cycloadditions under mild, thermal conditions. Authors: Myles W. Smith, Phil S. Baran
Categories: Journal Articles