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Science: Current Issue



The best in science news, commentary, and research



Published: 2017-01-19T14:00:04-05:00

 



[Review] Human tissues in a dish: The research and ethical implications of organoid technology

2017-01-20

The ability to generate human tissues in vitro from stem cells has raised enormous expectations among the biomedical research community, patients, and the general public. These organoids enable studies of normal development and disease and allow the testing of compounds directly on human tissue. Organoids hold the promise to influence the entire innovation cycle in biomedical research. They affect fields that have been subjects of intense ethical debate, ranging from animal experiments and the use of embryonic or fetal human tissues to precision medicine, organoid transplantation, and gene therapy. However, organoid research also raises additional ethical questions that require reexamination and potential recalibration of ethical and legal policies. In this Review, we describe the current state of research and discuss the ethical implications of organoid technology. Authors: Annelien L. Bredenoord, Hans Clevers, Juergen A. Knoblich






[Research Article] Distortion of histone octamer core promotes nucleosome mobilization by a chromatin remodeler

2017-01-20

Adenosine 5′-triphosphate (ATP)–dependent chromatin remodeling enzymes play essential biological roles by mobilizing nucleosomal DNA. Yet, how DNA is mobilized despite the steric constraints placed by the histone octamer remains unknown. Using methyl transverse relaxation–optimized nuclear magnetic resonance spectroscopy on a 450-kilodalton complex, we show that the chromatin remodeler, SNF2h, distorts the histone octamer. Binding of SNF2h in an activated ATP state changes the dynamics of buried histone residues. Preventing octamer distortion by site-specific disulfide linkages inhibits nucleosome sliding by SNF2h while promoting octamer eviction by the SWI-SNF complex, RSC. Our findings indicate that the histone core of a nucleosome is more plastic than previously imagined and that octamer deformation plays different roles based on the type of chromatin remodeler. Octamer plasticity may contribute to chromatin regulation beyond ATP-dependent remodeling. Authors: Kalyan K. Sinha, John D. Gross, Geeta J. Narlikar



[Research Article] Tumor aneuploidy correlates with markers of immune evasion and with reduced response to immunotherapy

2017-01-20

Immunotherapies based on immune checkpoint blockade are highly effective in a subset of patients. An ongoing challenge is the identification of biomarkers that predict which patients will benefit from these therapies. Aneuploidy, also known as somatic copy number alterations (SCNAs), is widespread in cancer and is posited to drive tumorigenesis. Analyzing 12 human cancer types, we find that, for most, highly aneuploid tumors show reduced expression of markers of cytotoxic infiltrating immune cells, especially CD8+ T cells, and increased expression of cell proliferation markers. Different types of SCNAs predict the proliferation and immune signatures, implying distinct underlying mechanisms. Using published data from two clinical trials of immune checkpoint blockade therapy for metastatic melanoma, we found that tumor aneuploidy inversely correlates with patient survival. Together with other tumor characteristics such as tumor mutational load, aneuploidy may thus help identify patients most likely to respond to immunotherapy. Authors: Teresa Davoli, Hajime Uno, Eric C. Wooten, Stephen J. Elledge



[Research Article] The role of dimer asymmetry and protomer dynamics in enzyme catalysis

2017-01-20

Freeze-trapping x-ray crystallography, nuclear magnetic resonance, and computational techniques reveal the distribution of states and their interconversion rates along the reaction pathway of a bacterial homodimeric enzyme, fluoroacetate dehalogenase (FAcD). The crystal structure of apo-FAcD exhibits asymmetry around the dimer interface and cap domain, priming one protomer for substrate binding. This asymmetry is dynamically averaged through conformational exchange on a millisecond time scale. During catalysis, the protomer conformational exchange rate becomes enhanced, the empty protomer exhibits increased local disorder, and water egresses. Computational studies identify allosteric pathways between protomers. Water release and enhanced dynamics associated with catalysis compensate for entropic losses from substrate binding while facilitating sampling of the transition state. The studies provide insights into how substrate-coupled allosteric modulation of structure and dynamics facilitates catalysis in a homodimeric enzyme. Authors: Tae Hun Kim, Pedram Mehrabi, Zhong Ren, Adnan Sljoka, Christopher Ing, Alexandr Bezginov, Libin Ye, Régis Pomès, R. Scott Prosser, Emil F. Pai



[Editorial] Everyone should try

2017-01-20

The new year brings opportunities to think creatively about finding solutions to difficult problems. It's a chance to affirm that although views may differ dramatically, we should try to work effectively with one another. My namesake believed in this. Jeremy Stone, the long-time president of the Federation of American Scientists, passed away on 1 January at the age of 81. As a graduate student, Stone attended mathematics classes taught by my father, and he and his wife Betty Jane (B.J.) Stone, also a distinguished mathematician and statistician, babysat my brother and me. Stone's career followed a remarkable and unusual path for a scientist—indeed, for anyone—and highlights how individuals with training in science, technology, engineering, and mathematics can contribute to society in diverse and profound ways. Author: Jeremy Berg



[In Brief] News at a glance

2017-01-20

In science news around the world, the United States confers protections to the Walrus Islands and a handful of other sites of archaeological significance by making them historic landmarks, a U.S. report finds that marijuana can treat chronic pain and notes that researchers who want to study the drug face significant obstacles, a new international particle accelerator located in Jordan takes a big step forward by achieving its first circulating beam of electrons, a U.K. study gives the go-ahead to build the world's first tidal lagoon power plant in the country, and more. Also, scientists express anger at the suggestion that U.S. President-elect Donald Trump might create a "vaccine safety" commission that could focus on scientifically discredited links between vaccines and autism. And a video game helps researchers understand how flocks of starlings keep predators at bay.



[In Depth] Science suffers in cold war over polar base

2017-01-20

It's summer in Antarctica, the season for science. But at the Princess Elisabeth Antarctica research station, Belgium's futuristic research outpost in East Antarctica, not a single Belgian researcher is at work. A protracted dispute between the Belgian government and the International Polar Foundation, which built and operates the station, has resulted in the cancellation of this year's Belgian expedition to Antarctica. The only scientists to pay a visit so far this year are two scientists from Switzerland and two private grantees. At the heart of the dispute is a straightforward question: Who controls the Princess Elisabeth? Author: Martin Enserink



[In Depth] Your self-driving car could kill radio astronomy

2017-01-20

Add energy-saving streetlights, self-driving cars, and balloon-borne internet services to the threats facing astronomers needing dark skies free of electromagnetic smog. The rise of all three technologies is posing new challenges to ground-based researchers who use the optical and radio spectrum to observe the universe, speakers warned earlier this month at the annual meeting of the American Astronomical Societ in Grapevine, Texas. The main problem with light-emitting diodes (LEDs) is not that they are brighter; it's that they are the wrong color. With a large element of blue light, which is preferentially scattered by the atmosphere, LEDs help create more of a light "haze" that obscures the view of telescopes. For radio astronomers, broadcasts at nearby frequencies can fill protected bands with an electromagnetic fog that mars observations. As the sources multiply, astronomers seeking ever-fainter signals from the cosmos are in the position of someone trying to listen to an insect's footsteps while there's a pneumatic drill operating nearby. Author: Daniel Clery



[In Depth] Mixed results from cancer replications unsettle field

2017-01-20

The first results of a high-profile effort to replicate dozens of influential papers in cancer biology are roiling the biomedical community. Of the five studies the project has tackled so far, some involving experimental treatments already in clinical trials, only two could be repeated; one could not, and technical problems stymied the remaining two replication efforts. Some scientists say these early findings from the Reproducibility Project: Cancer Biology, which appear this week in eLife, bolster concerns that too many basic biomedical studies don't hold up in other labs. But others say the results simply show that good studies can be hard to precisely reproduce, because biological systems are so variable. Author: Jocelyn Kaiser



[In Depth] Unique free electron laser laboratory opens in China

2017-01-20

China has become the latest country making a free electron laser available to its scientists. Researchers around the world want access to these lasers because they are an advance on the synchrotron light sources that have been the workhorses of protein crystallography, cell biology, and materials science. The completion of the $30 million Dalian Coherent Light Source, announced this week in Beijing, has a twist that makes it unique: It is the only large laser light source in the world dedicated to the particular wavelengths of light called vacuum ultraviolet, which researchers will use to probe and analyze molecules undergoing chemical reactions. China's scientists are also working on an x-ray free electron laser expected to come online in 2 years. Author: Dennis Normile



[In Depth] How do gut microbes help herbivores? Counting the ways

2017-01-20

No matter what a vegan may tell you, a solely plant-based diet is a tough way to get all the calories and nutrients you need. Unless you have the right microbial partners. At the recent annual meeting of the Society for Integrative and Comparative Biology, researchers made it clear that microbes lend a wide array of other talents to herbivores. One gut microbe helps a tropical ant recycle nitrogen, which is scarce in plant matter and is vital for making proteins. Another aids leaf beetles by breaking down the cell walls of the foliage they consume. And a third set of microbial allies explains how pack rats can munch on toxin-filled desert vegetation—a discovery that may suggest ways to thwart kidney stones in people. The work is showing just how broadly important microbes are in the animal kingdom. Author: Elizabeth Pennisi



[In Depth] A half-billion-dollar bid to head off emerging diseases

2017-01-20

In the wake of the Ebola crisis that erupted in West Africa in 2014, many public health leaders recognized that a more aggressive effort to develop vaccines could have moved a vaccine forward more quickly and prevented that outbreak from becoming an epidemic. A new organization was formed last year, the Coalition for Epidemic Preparedness Innovations (CEPI), to speed development of vaccines against emerging infectious diseases—but it had no serious financial backing. Now, CEPI has attracted nearly a half-billion dollars in funding, as it planned to announce at the World Economic Forum in Davos, Switzerland, this week. The Bill & Melinda Gates Foundation and the Wellcome Trust each donated $100 million, and the governments of Norway, Japan, and Germany make up the balance. CEPI also decided to focus initially on three diseases—Lassa, Nipah, and Middle East respiratory syndrome–coronavirus—and it will soon seek proposals from academia and industry to make these vaccines and conduct early phase trials so that they're at the ready for a real-word efficacy test when these pathogens emerge. Author: Jon Cohen



[Feature] Taming rabies

2017-01-20

An estimated 59,000 people die from rabies around the world every year. Their horrible suffering—including convulsions, terror, and aggression—and the fact that many victims are children led the World Health Organization and others to announce a goal to eliminate rabies deaths worldwide by 2030. The plan calls for cheaper and faster treatment for people. But its long-term bet is on vaccinating domestic dogs, which cause more than 99% of infections. The challenges are enormous in sub-Saharan Africa, where poor countries can hardly pay for millions of dogs to be vaccinated, and their governments often have trouble organizing vaccination campaigns across vast rural areas. In pilot projects underway in Tanzania, Kenya, and a few other African countries, scientists are testing strategies for reaching and vaccinating dogs more efficiently and quantifying the economic benefits of potentially expensive national campaigns. For Africa as a whole, rabies elimination might cost between $800 million to $1.55 billion. The price could come down, however, from dog vaccine banks, for example, and other ways to make vaccines cheaper and more easily distributed. Author: Erik Stokstad



[Perspective] Technology beats corruption

2017-01-20

More than 1.9 billion individuals in the developing world benefit from social safety net programs: noncontributory transfer programs that distribute cash or basic in-kind products to the poor. But despite their importance, high levels of corruption often stifle the effectiveness of these programs. If cash transfer programs are particularly prone to graft, then in-kind programs should be preferred in practice. In a recent paper, Muralidharan et al. report evidence to the contrary by showing that use of a modern banking technology—biometric smart cards—can help to drastically reduce corruption in cash transfer programs (1). Author: Rema Hanna



[Perspective] Unlocking the nucleosome

2017-01-20

Almost all eukaryotic genomes are packaged as nucleosomal building blocks that are assembled from an octameric core of histone proteins around which nearly two turns of DNA are wrapped. The apparent homogeneity and stability of nucleosomes has led to their depiction as beads, balls, and other simplifications that imply a largely static histone structural surface on which DNA wraps and unwraps. On page 263 of this issue, Sinha et al. (1) enrich our understanding of nucleosome behavior with direct evidence that the histone octamer must itself flex to undergo chromatin remodeling, a common step in many genome transactions. Authors: Andrew Flaus, Tom Owen-Hughes



[Perspective] Enzymes at work are enzymes in motion

2017-01-20

Enzymes provide the necessary impetus for chemical reactions to occur at a rate that can support biological life. They do so by forming a unique enzyme-substrate complex and thus lowering the energy required for a substrate to convert to a product. Numerous approaches have been used for more than 50 years to unravel the mechanisms of enzyme-mediated catalysis (1). Initial kinetic experiments helped to ascertain substrate specificity. Spectroscopic data have shown that enzymes are not static, and more recently, atomic-resolution nuclear magnetic resonance (NMR) data have revealed the extent and duration of the structural fluctuations (2–4). On page 262 of this issue, Kim et al. (5) use structural and computational methods to provide evidence for the crucial roles of protein dynamics and water in enzyme catalysis. Authors: Tamjeed Saleh, Charalampos G. Kalodimos



[Perspective] Big-data approaches to protein structure prediction

2017-01-20

A protein's structure determines its function. Experimental protein structure determination is cumbersome and costly, which has driven the search for methods that can predict protein structure from sequence information (1). About half of the known proteins are amenable to comparative modeling; that is, an evolutionarily related protein of known structure can be used as a template for modeling the unknown structure. For the remaining proteins, no satisfactory solution had been found. On page 294 of this issue, Ovchinnikov et al. (2) used recently developed methodology for predicting intraprotein amino acid contacts in combination with protein sequences from metagenomics of microbial DNA to compute reliable models for 622 protein families, and discovered more than 100 new folds along the way. The fast-paced growth of metagenomics data should enable reliable structure prediction of many more protein families. Author: Johannes Söding



[Perspective] Chromosomal chaos silences immune surveillance

2017-01-20

Not all cancers, and not all individuals with the same cancer type, respond equally to immunotherapy—the use of antibodies to block so-called immune checkpoints in T cells—thereby unleashing immune responses against tumor cells. This can be partially explained by nonsynonymous mutations, which can create neoantigen epitopes that induce T cell responses against cancer cells (1). However, such mutations scattered throughout the genome may or may not activate the immune system, and if they do, their effect wanes over time. Is there a role for other genomic abnormalities of cancer cells in immune surveillance beyond the generation of neoantigens? On page 261 of this issue, Davoli et al. (2) propose that structural abnormalities in chromosomes, including variation in the number of chromosome copies (aneuploidy), adversely affect immune cell action against the tumor. Author: Maurizio Zanetti



[Policy Forum] Closing global achievement gaps in MOOCs

2017-01-20

Advocates for free massive open online courses (MOOCs) have heralded them as vehicles for democratizing education and bridging divides within and across countries (1). More than 25 million people enrolled in MOOCs between 2012 and 2015, including 39% from less-developed countries (LDCs) (2). But the educated and affluent in all countries enroll in and complete MOOCs at relatively higher rates (3, 4). Judged by completion rates, MOOCs do not spread benefits equitably across global regions. Rather, they reflect prevailing educational disparities between nations (see the first chart) (5). Although the global achievement gap could be caused by barriers in LDCs, such as less broadband Internet access, formal education, and English proficiency, we explore another potential but underappreciated cause. Members of LDCs may suffer from the cognitive burden of wrestling with feeling unwelcome while trying to learn and, therefore, underperform. This can be exacerbated by social identity threat, which is the fear of being seen as less capable because of one's group (6). We discuss field experiments with interventions that targeted social identity threat and caused substantial improvements in MOOC persistence and completion rates among learners in LDCs, eliminating the global achievement gap. Authors: René F. Kizilcec, Andrew J. Saltarelli, Justin Reich, Geoffrey L. Cohen



[Book Review] Beyond Schrödinger's cat

2017-01-20

According to traditional flight physics, bees should not be able to fly. But fly they do, with mastery of non– steady state aerodynamics and little concern about our limited understanding of their capabilities. Building on recent insights in biophysics research, Furry Logic: The Physics of Animal Life uses a refreshing combination of scientific precision and colloquial wit to show how animals use heat, forces, fluids, sound, electricity, and light to their advantage. Author: Mirko Kovac



[Book Review] Born this way?

2017-01-20

How and why do the sexes differ? And why do we care? Few questions generate as much controversy and debatein both scientific and public arenas. In her book Testosterone Rex: Myths of Sex, Science, and Society, Cordelia Fine tackles the question from the perspective that has generated the most discussion: biological contributions to sex differences. Author: Sheri Berenbaum



[Letter] Building community for deaf scientists

2017-01-20

Authors: Gerry Buckley, Scott Smith, James DeCaro, Steve Barnett, Steve Dewhurst



[Letter] Wildlife-snaring crisis in Asian forests

2017-01-20

Authors: Thomas N. E. Gray, Antony J. Lynam, Teak Seng, William F. Laurance, Barney Long, Lorraine Scotson, William J. Ripple






[This Week in Science] Robots have a change of heart

2017-01-20

Author: Caitlin Czajka









[This Week in Science] Keeping roots water-tight

2017-01-20

Author: Pamela J. Hines









[This Week in Science] Deciding a protein's fate

2017-01-20

Author: Valda Vinson



[This Week in Science] Locking TNFR2 to kill ovarian cancer

2017-01-20

Author: Leslie K. Ferrarelli



[This Week in Science] Working as a pair

2017-01-20

Author: Valda Vinson



[This Week in Science] Ethics of organoid research

2017-01-20

Author: Beverly A. Purnell



[This Week in Science] Chromosomal chaos and tumor immunity

2017-01-20

Author: Paula A. Kiberstis






[This Week in Science] Moving transistors downscale

2017-01-20

Author: Phil Szuromi



[This Week in Science] Impending primate extinction

2017-01-20

Author: Michael Hochberg






[This Week in Science] Using technology to beat corruption

2017-01-20

Author: Julia Fahrenkamp-Uppenbrink



[Editors' Choice] Brain cancer therapy

2017-01-20

Author: Lisa D. Chong



[Editors' Choice] DNA methylation in hematopoietic cascade

2017-01-20

Author: Beverly A. Purnell



[Editors' Choice] An intelligent little sniffer

2017-01-20

Author: Marc S. Lavine






[Editors' Choice] Blind climber

2017-01-20

Author: Sacha Vignieri



[Editors' Choice] Know who you are asking for money

2017-01-20

Author: Gilbert Chin



[Editors' Choice] Making garnets the hard way

2017-01-20

Author: Brent Grocholski



[Report] Time-resolved x-ray absorption spectroscopy with a water window high-harmonic source

2017-01-20

Time-resolved x-ray absorption spectroscopy (TR-XAS) has so far practically been limited to large-scale facilities, to subpicosecond temporal resolution, and to the condensed phase. We report the realization of TR-XAS with a temporal resolution in the low femtosecond range by developing a tabletop high-harmonic source reaching up to 350 electron volts, thus partially covering the spectral region of 280 to 530 electron volts, where water is transmissive. We used this source to follow previously unexamined light-induced chemical reactions in the lowest electronic states of isolated CF4+ and SF6+ molecules in the gas phase. By probing element-specific core-to-valence transitions at the carbon K-edge or the sulfur L-edges, we characterized their reaction paths and observed the effect of symmetry breaking through the splitting of absorption bands and Rydberg-valence mixing induced by the geometry changes. Authors: Yoann Pertot, Cédric Schmidt, Mary Matthews, Adrien Chauvet, Martin Huppert, Vit Svoboda, Aaron von Conta, Andres Tehlar, Denitsa Baykusheva, Jean-Pierre Wolf, Hans Jakob Wörner



[Report] Transformation of bulk alloys to oxide nanowires

2017-01-20

One dimensional (1D) nanostructures offer prospects for enhancing the electrical, thermal, and mechanical properties of a broad range of functional materials and composites, but their synthesis methods are typically elaborate and expensive. We demonstrate a direct transformation of bulk materials into nanowires under ambient conditions without the use of catalysts or any external stimuli. The nanowires form via minimization of strain energy at the boundary of a chemical reaction front. We show the transformation of multimicrometer-sized particles of aluminum or magnesium alloys into alkoxide nanowires of tunable dimensions, which are converted into oxide nanowires upon heating in air. Fabricated separators based on aluminum oxide nanowires enhanced the safety and rate capabilities of lithium-ion batteries. The reported approach allows ultralow-cost scalable synthesis of 1D materials and membranes. Authors: Danni Lei, Jim Benson, Alexandre Magasinski, Gene Berdichevsky, Gleb Yushin



[Report] Scaling carbon nanotube complementary transistors to 5-nm gate lengths

2017-01-20

High-performance top-gated carbon nanotube field-effect transistors (CNT FETs) with a gate length of 5 nanometers can be fabricated that perform better than silicon complementary metal-oxide semiconductor (CMOS) FETs at the same scale. A scaling trend study revealed that the scaled CNT-based devices, which use graphene contacts, can operate much faster and at much lower supply voltage (0.4 versus 0.7 volts) and with much smaller subthreshold slope (typically 73 millivolts per decade). The 5-nanometer CNT FETs approached the quantum limit of FETs by using only one electron per switching operation. In addition, the contact length of the CNT CMOS devices was also scaled down to 25 nanometers, and a CMOS inverter with a total pitch size of 240 nanometers was also demonstrated. Authors: Chenguang Qiu, Zhiyong Zhang, Mengmeng Xiao, Yingjun Yang, Donglai Zhong, Lian-Mao Peng



[Report] Regional and global sea-surface temperatures during the last interglaciation

2017-01-20

The last interglaciation (LIG, 129 to 116 thousand years ago) was the most recent time in Earth’s history when global mean sea level was substantially higher than it is at present. However, reconstructions of LIG global temperature remain uncertain, with estimates ranging from no significant difference to nearly 2°C warmer than present-day temperatures. Here we use a network of sea-surface temperature (SST) records to reconstruct spatiotemporal variability in regional and global SSTs during the LIG. Our results indicate that peak LIG global mean annual SSTs were 0.5 ± 0.3°C warmer than the climatological mean from 1870 to 1889 and indistinguishable from the 1995 to 2014 mean. LIG warming in the extratropical latitudes occurred in response to boreal insolation and the bipolar seesaw, whereas tropical SSTs were slightly cooler than the 1870 to 1889 mean in response to reduced mean annual insolation. Authors: Jeremy S. Hoffman, Peter U. Clark, Andrew C. Parnell, Feng He



[Report] Root diffusion barrier control by a vasculature-derived peptide binding to the SGN3 receptor

2017-01-20

The root endodermis forms its extracellular diffusion barrier by developing ringlike impregnations called Casparian strips. A factor responsible for their establishment is the SCHENGEN3/GASSHO1 (SGN3/GSO1) receptor-like kinase. Its loss of function causes discontinuous Casparian strips. SGN3 also mediates endodermal overlignification of other Casparian strip mutants. Yet, without ligand, SGN3 function remained elusive. Here we report that schengen2 (sgn2) is defective in an enzyme sulfating peptide ligands. On the basis of this observation, we identified two stele-expressed peptides (CASPARIAN STRIP INTEGRITY FACTORS, CIF1/2) that complement sgn2 at nanomolar concentrations and induce Casparian strip mislocalization as well as overlignification—all of which depend on SGN3. Direct peptide binding to recombinant SGN3 identifies these peptides as SGN3 ligands. We speculate that CIF1/2-SGN3 is part of a barrier surveillance system, evolved to guarantee effective sealing of the supracellular Casparian strip network. Authors: Verónica G. Doblas, Elwira Smakowska-Luzan, Satoshi Fujita, Julien Alassimone, Marie Barberon, Mathias Madalinski, Youssef Belkhadir, Niko Geldner



[Report] A peptide hormone required for Casparian strip diffusion barrier formation in Arabidopsis roots

2017-01-20

Plants achieve mineral ion homeostasis by means of a hydrophobic barrier on endodermal cells called the Casparian strip, which restricts lateral diffusion of ions between the root vascular bundles and the soil. We identified a family of sulfated peptides required for contiguous Casparian strip formation in Arabidopsis roots. These peptide hormones, which we named Casparian strip integrity factor 1 (CIF1) and CIF2, are expressed in the root stele and specifically bind the endodermis-expressed leucine-rich repeat receptor kinase GASSHO1 (GSO1)/SCHENGEN3 and its homolog, GSO2. A mutant devoid of CIF peptides is defective in ion homeostasis in the xylem. CIF genes are environmentally responsive. Casparian strip regulation is not merely a passive process driven by root developmental cues; it also serves as an active strategy to cope with adverse soil conditions. Authors: Takuya Nakayama, Hidefumi Shinohara, Mina Tanaka, Koki Baba, Mari Ogawa-Ohnishi, Yoshikatsu Matsubayashi



[Report] The receptor kinase FER is a RALF-regulated scaffold controlling plant immune signaling

2017-01-20

In plants, perception of invading pathogens involves cell-surface immune receptor kinases. Here, we report that the Arabidopsis SITE-1 PROTEASE (S1P) cleaves endogenous RAPID ALKALINIZATION FACTOR (RALF) propeptides to inhibit plant immunity. This inhibition is mediated by the malectin-like receptor kinase FERONIA (FER), which otherwise facilitates the ligand-induced complex formation of the immune receptor kinases EF-TU RECEPTOR (EFR) and FLAGELLIN-SENSING 2 (FLS2) with their co-receptor BRASSINOSTEROID INSENSITIVE 1–ASSOCIATED KINASE 1 (BAK1) to initiate immune signaling. We show that FER acts as a RALF-regulated scaffold that modulates receptor kinase complex assembly. A similar scaffolding mechanism may underlie FER function in other signaling pathways. Authors: Martin Stegmann, Jacqueline Monaghan, Elwira Smakowska-Luzan, Hanna Rovenich, Anita Lehner, Nicholas Holton, Youssef Belkhadir, Cyril Zipfel



[Report] Evolutionary drivers of thermoadaptation in enzyme catalysis

2017-01-20

With early life likely to have existed in a hot environment, enzymes had to cope with an inherent drop in catalytic speed caused by lowered temperature. Here we characterize the molecular mechanisms underlying thermoadaptation of enzyme catalysis in adenylate kinase using ancestral sequence reconstruction spanning 3 billion years of evolution. We show that evolution solved the enzyme’s key kinetic obstacle—how to maintain catalytic speed on a cooler Earth—by exploiting transition-state heat capacity. Tracing the evolution of enzyme activity and stability from the hot-start toward modern hyperthermophilic, mesophilic, and psychrophilic organisms illustrates active pressure versus passive drift in evolution on a molecular level, refutes the debated activity/stability trade-off, and suggests that the catalytic speed of adenylate kinase is an evolutionary driver for organismal fitness. Authors: Vy Nguyen, Christopher Wilson, Marc Hoemberger, John B. Stiller, Roman V. Agafonov, Steffen Kutter, Justin English, Douglas L. Theobald, Dorothee Kern



[Report] Protein structure determination using metagenome sequence data

2017-01-20

Despite decades of work by structural biologists, there are still ~5200 protein families with unknown structure outside the range of comparative modeling. We show that Rosetta structure prediction guided by residue-residue contacts inferred from evolutionary information can accurately model proteins that belong to large families and that metagenome sequence data more than triple the number of protein families with sufficient sequences for accurate modeling. We then integrate metagenome data, contact-based structure matching, and Rosetta structure calculations to generate models for 614 protein families with currently unknown structures; 206 are membrane proteins and 137 have folds not represented in the Protein Data Bank. This approach provides the representative models for large protein families originally envisioned as the goal of the Protein Structure Initiative at a fraction of the cost. Authors: Sergey Ovchinnikov, Hahnbeom Park, Neha Varghese, Po-Ssu Huang, Georgios A. Pavlopoulos, David E. Kim, Hetunandan Kamisetty, Nikos C. Kyrpides, David Baker



[Report] Mechanistic basis for a molecular triage reaction

2017-01-20

Newly synthesized proteins are triaged between biosynthesis and degradation to maintain cellular homeostasis, but the decision-making mechanisms are unclear. We reconstituted the core reactions for membrane targeting and ubiquitination of nascent tail-anchored membrane proteins to understand how their fate is determined. The central six-component triage system is divided into an uncommitted client-SGTA complex, a self-sufficient targeting module, and an embedded but self-sufficient quality control module. Client-SGTA engagement of the targeting module induces rapid, private, and committed client transfer to TRC40 for successful biosynthesis. Commitment to ubiquitination is dictated primarily by comparatively slower client dissociation from SGTA and nonprivate capture by the BAG6 subunit of the quality control module. Our results provide a paradigm for how priority and time are encoded within a multichaperone triage system. Authors: Sichen Shao, Monica C. Rodrigo-Brenni, Maryann H. Kivlen, Ramanujan S. Hegde



[Association Affairs] AAAS 2017 Annual Meeting Program

2017-01-20

This issue of Science includes the program of the 2017 AAAS Annual Meeting. The theme of the AAAS Annual Meeting in Boston, 16 to 20 February 2017, is Serving Society Through Science Policy.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.aaas.org/meetings/.



[New Products] New Products

2017-01-20

A weekly roundup of information on newly offered instrumentation, apparatus, and laboratory materials of potential interest to researchers.



[Working Life] The transcontinental scientist

2017-01-20

Author: Wim Delva