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Structural Biology Planet

October 21, 2016

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[Review] Metal-catalyzed reductive coupling of olefin-derived nucleophiles: Reinventing carbonyl addition

α-Olefins are the most abundant petrochemical feedstock beyond alkanes, yet their use in commodity chemical manufacture is largely focused on polymerization and hydroformylation. The development of byproduct-free catalytic C–C bond–forming reactions that convert olefins to value-added products remains an important objective. Here, we review catalytic intermolecular reductive couplings of unactivated and activated olefin-derived nucleophiles with carbonyl partners. These processes represent an alternative to the longstanding use of stoichiometric organometallic reagents in carbonyl addition. Authors: Khoa D. Nguyen, Boyoung Y. Park, Tom Luong, Hiroki Sato, Victoria J. Garza, Michael J. Krische

by Khoa D. Nguyen at October 21, 2016 12:00 AM

[Research Article] Structural basis for the gating mechanism of the type 2 ryanodine receptor RyR2

RyR2 is a high-conductance intracellular calcium (Ca2+) channel that controls the release of Ca2+ from the sarco(endo)plasmic reticulum of a variety of cells. Here, we report the structures of RyR2 from porcine heart in both the open and closed states at near-atomic resolutions determined using single-particle electron cryomicroscopy. Structural comparison reveals a breathing motion of the overall cytoplasmic region resulted from the interdomain movements of amino-terminal domains (NTDs), Helical domains, and Handle domains, whereas almost no intradomain shifts are observed in these armadillo repeats–containing domains. Outward rotations of the Central domains, which integrate the conformational changes of the cytoplasmic region, lead to the dilation of the cytoplasmic gate through coupled motions. Our structural and mutational characterizations provide important insights into the gating and disease mechanism of RyRs. Authors: Wei Peng, Huaizong Shen, Jianping Wu, Wenting Guo, Xiaojing Pan, Ruiwu Wang, S. R. Wayne Chen, Nieng Yan

by Wei Peng at October 21, 2016 12:00 AM

[Editorial] A short presidential reading list

A new U.S. president will be sworn into office in less than 3 months. Because scientific issues cut across many aspects of modern life, in both the public and private sectors, the president has several challenges. He or she must ensure that the government has access to robust advice about scientific issues to guide policy development. The president must select, and the U.S. Senate must confirm, the leaders for agencies with a substantial science focus. Finally, the new president must set the tone regarding the importance of science in the nation's progress. Two short, 70-year-old documents outline many central issues that are still relevant today. Author: Jeremy Berg

by Jeremy Berg at October 21, 2016 12:00 AM

[In Brief] News at a glance

In science news around the world, a new study finds that hundreds of mammals around the world are now being hunted to extinction, the U.S. Department of the Treasury authorizes U.S. biomedical and public health scientists to freely collaborate with their Cuban counterparts, U.K. scientists debate a controversial bill that would set up an organization to oversee the country's research funding, Brazilian scientists worry over how a pending constitutional amendment capping public spending will affect science research, and world leaders meet in Rwanda and agree to curb the use of hydrofluorocarbons. Also, a silica-rich ocean may have helped fossilize the enigmatic Ediacara biota. And an experiment in the Bolivian Andes suggests that blood cells change shape at high altitude to cope with low-oxygen conditions.

October 21, 2016 12:00 AM

[In Depth] ‘Green hell’ has long been home for humans

For centuries, tropical rainforests were seen as the very definition of wilderness, largely untouched by humans. As late as the 1970s, anthropologists described rainforests as a "counterfeit paradise," arguing that their soil lacked the nutrients to sustain agriculture or complex human societies. It's now becoming clear, however, that human ancestors not only lived in the rainforest but transformed it over tens of thousands of years. Archaeologists have found clever ways to uncover ancient humans' impact on today's jungles, from ancient collagen in bones to laser scanning by aircraft. At a recent conference on the topic, organized by the Max Planck Institute for the Science of Human History in Jena, Germany, presentation after presentation highlighted how prehistoric people burned the forest, cleared it, farmed it, nurtured certain of its tree species, and even built cities in it, leaving lasting, if subtle, marks. Author: Andrew Curry

by Andrew Curry at October 21, 2016 12:00 AM

[In Depth] Odd computer zips through knotty tasks

A century-old theoretical model of magnetism is giving rise to a hybrid computer, part classical and part quantum, that may capable of solving problems that overwhelm conventional computers. The so-called Ising machine, described in 100-bit and 2000-bit versions in two reports this week in Science, could tackle optimization problems that require finding the best solution among myriad possibilities, such as predicting how a protein will fold or allotting bandwidth in cellular communications networks. The machines take their name from the Ising model, which was developed in 1920 in an attempt to explain magnetism. Curiously, many optimization problems can be mapped onto the Ising model. Now, two overlapping groups at Stanford University in Palo Alto, California, and at NTT Basic Research Laboratories in Atsugi, Japan, have developed optical machines specifically designed to solve the model, at least approximately. Developers hope Ising machines may soon replace or aid conventional computers for some applications, although some researchers note it is not yet clear that the new machines can best ordinary computers. Author: Adrian Cho

by Adrian Cho at October 21, 2016 12:00 AM

[In Depth] Colombia peace deal blow dismays ecologists

For decades, Colombia's most interesting and diverse ecosystems have been occupied by guerrilla fighters and other armed groups, forcing scientists to stay away. But for a hopeful week, the threat finally seemed to have lifted. On 26 September, Colombia's government and the Revolutionary Armed Forces of Colombia signed an agreement ending 52 years of conflict. As the fighters pledged to lay down their weapons, scientists made plans to return to the field—sometimes to research stations they had been forced to abandon years earlier. But on 2 October, Colombians in a referendum narrowly rejected the peace accord, leaving researchers wondering when it will truly be safe for fieldwork, and whether Colombia will ever be able to direct its resources away from war and toward research. Author: Lizzie Wade

by Lizzie Wade at October 21, 2016 12:00 AM

[In Depth] Are labmade human eggs coming soon?

There's no need to start rereading Brave New World just yet. But this week's announcement that biologists in Japan have grown mouse egg cells entirely in a lab dish gave new meaning to the term "test tube babies." The eggs, generated in a dish from two kinds of stem cells, gave rise to pups after being fertilized and implanted into rodent foster mothers. Beyond offering researchers a new way to study egg development, the feat suggests that scientists could someday make human eggs in the lab from almost any type of cell, including genetically altered ones. That may spark hope of new infertility treatments, but will also likely revive fears among those opposed to designer babies. But for now the method, which sometimes produced defective eggs and rarely generated healthy pups, is far from making an impact in the clinic. Author: Gretchen Vogel

by Gretchen Vogel at October 21, 2016 12:00 AM

[In Depth] Alien fungus blights Hawaii's native trees

An ecological disaster is unfolding on Hawaii's largest island. Rapid 'Ōhi'a Death, caused by an imported fungus, is causing Hawaii's iconic native 'ōhi'a tree to perish in droves. Some 20,000 hectares are now affected, according to a recent survey. Abundant across the archipelago, 'ōhi'a are the only native tree in Hawaii that colonizes lava flows, and they provide habitat for several rare species of native birds and insects. The outbreak exploded in 2014, in dense 'ōhi'a groves in Hilo Forest Reserve on Big Island, and has worsened ever since. Characterizing the fungus, Ceratocystis fimbriata, might help researchers mount a defense for 'ōhi'a, as well as determine whether other native plants or crops are vulnerable. Scientists are also trying to unravel precisely how the fungus spreads. Author: Inga Vesper

by Inga Vesper at October 21, 2016 12:00 AM

[Feature] Science lessons for the next president

New presidents typically move into the White House neither expecting to spend much time on scientific issues, nor prepared to. But history shows that, ready or not, every president ends up grappling with a host of science-related policy issues or crises. What technical issues will the next president face? Climate change is sure to loom large, as will the annual debates over how much the government should spend on basic research and help industry commercialize new discoveries. Technological advances, from self-driving cars to new genetic-engineering techniques, will pose new regulatory challenges. And there are likely to be unplanned events, such as disease outbreaks, oil spills, and natural disasters. In each case, a little science savvy might help a president better understand how best to respond. With that in mind, we offer crash courses in six areas of science that are likely to demand attention in the Oval Office over the next 4 or 8 years. On our list: sea level rise, brain health, pathogen evolution, risk perception, artificial intelligence, and new genome-editing tools. And we provide a timeline that highlights major science-related policy decisions and events faced by presidents since Franklin Roosevelt.

October 21, 2016 12:00 AM