[Research Article] Lipid transport by TMEM24 at ER–plasma membrane contacts regulates pulsatile insulin secretion ()
Insulin is released by β cells in pulses regulated by calcium and phosphoinositide signaling. Here, we describe how transmembrane protein 24 (TMEM24) helps coordinate these signaling events. We showed that TMEM24 is an endoplasmic reticulum (ER)–anchored membrane protein whose reversible localization to ER-plasma membrane (PM) contacts is governed by phosphorylation and dephosphorylation in response to oscillations in cytosolic calcium. A lipid-binding module in TMEM24 transports the phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] precursor phosphatidylinositol between bilayers, allowing replenishment of PI(4,5)P2 hydrolyzed during signaling. In the absence of TMEM24, calcium oscillations are abolished, leading to a defect in triggered insulin release. Our findings implicate direct lipid transport between the ER and the PM in the control of insulin secretion, a process impaired in patients with type II diabetes. Authors: Joshua A. Lees, Mirko Messa, Elizabeth Wen Sun, Heather Wheeler, Federico Torta, Markus R. Wenk, Pietro De Camilli, Karin M. Reinisch
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[Editorial] Data in public health ()
In 1854, physician John Snow helped curtail a cholera outbreak in a London neighborhood by mapping cases and identifying a central public water pump as the potential source. This event is considered by many to represent the founding of modern epidemiology. Data and analysis play an increasingly important role in public health today. This can be illustrated by examining the rise in the prevalence of autism spectrum disorders (ASDs), where data from varied sources highlight potential factors while ruling out others, such as childhood vaccines, facilitating wise policy choices. Author: Jeremy Berg
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[In Brief] News at a glance ()
In science news around the world, NASA selects three finalist landing sites for its next Mars rover, several animal welfare organizations sue the U.S. Department of Agriculture over the removal of thousands of documents from its website, a U.K. cancer charity announces up to £71 million in awards to four research teams tackling daunting problems in cancer research, Boston University neuroscientists push back against demands from the National Hockey League to release data from deceased players, and more. Also, monarch butterfly populations suffer another setback this winter from harsh storms. And Science rounds up the latest research-related news of the week related to the administration of U.S. President Donald Trump.
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[In Depth] European gravitational wave detector falters ()
On 20 February, dignitaries will descend on Virgo, Europe's premier gravitational wave detector near Pisa, Italy, for a dedication ceremony to celebrate a 5-year, €24 million upgrade. But the pomp will belie nagging problems that are likely to keep Virgo from joining its U.S. counterpart, the Laser Interferometer Gravitational-Wave Observatory (LIGO), in a hunt for gravitational wave sources that was meant to start next month. What has hobbled the 3-kilometer-long observatory: glass threads just 0.4 millimeters thick, which have proved unexpectedly fragile. Virgo should be ready to join LIGO when it resumes observations in spring 2018 after a break, but for now Virgo's sensitivity is compromised. Author: Daniel Clery
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[In Depth] Demise of stream rule won't revitalize coal industry ()
Environmentalists were outraged earlier this month after the Republican-led Congress used an obscure law to erase a new regulation aimed at reducing the environmental damage caused by coal mining. The votes to undo the so-called stream protection rule, released last month on President Barack Obama's last day in office, were "a disgraceful opening salvo from this Congress, as they begin to try and do the bidding of big polluters," Michael Brune, executive director of the San Francisco, California–based Sierra Club, said in a statement. But the demise of the rule, which took regulators years to craft, drew a less impassioned reaction from a scientist on the front lines of the fight over coal mining. The rule had been watered down in its final form, they say, and would not have barred one of the most destructive mining practices in Appalachia: blasting away mountaintops to uncover coal seams and piling the debris in adjacent stream valleys. And because the rule's demise won't do much to ease the economic headwinds buffeting the United States's coalfields, it is unlikely to unleash a mining boom. Still, environmentalists are bracing for more bad news. The stream rule was killed as part of an ongoing purge of science-based regulations approved late in the Obama administration. Using an obscure law, Republicans are expected to repeal about a half-dozen regulations. Potential targets include rules designed to reduce emissions of methane, a potent warming gas, improve the energy efficiency of vehicles and appliances, and new land use planning guidelines for public lands. Author: Warren Cornwall
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[In Depth] Congress sharpens its regulatory ax ()
Other rules that Congress could cancel using the Congressional Review Act include the following. Methane leaks: The House of Representatives has voted to undo a rule aimed at cutting leaks and burning of methane, a potent global warming gas, from drilling operations on public lands managed by the U.S. Bureau of Land Management (BLM). Land use planning: The House has also voted to repeal a BLM land use planning rule that critics say is too unfriendly to development and agriculture. Air pollution: Environmental Protection Agency rules aimed at reducing power plant pollutants could be targeted. Energy efficiency: Lawmakers are scrutinizing rules requiring more efficient vehicles and appliances. Author: Science News Staff
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[In Depth] A yellow light for embryo editing ()
Editing the DNA of a human embryo could be ethically allowable in limited circumstances, says a report released this week by a committee convened by the U.S. National Academy of Sciences and the National Academy of Medicine in Washington, D.C. Such experiments "might be permitted, but only following much more research" on risks and benefits, and "only for compelling reasons and under strict oversight," the group concludes. Those situations could be limited to couples who both have a serious genetic disease and for whom embryo editing is only option for having a healthy biological child. Some researchers are pleased, saying the report is consistent with previous conclusions that altering the DNA of human eggs, sperm, or early embryos—known as germline editing—could be permissible. But others see the report as lowering the bar for embryo editing. Author: Jocelyn Kaiser
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[In Depth] Drop in foreign applicants worries engineering schools ()
Amid the uncertainty over U.S. immigration policy, one fact is sending a chill through U.S. higher education: Some U.S. graduate programs in engineering, Science has learned, are seeing a sharp drop this year in the number of applications from international students. University administrators worry that the declines, as much as 30% from 2016 levels in some programs, reflect heightened fears among foreign-born students that the United States is tightening its borders. Given the timing, the officials suspect the cause is President Donald Trump's anti-immigrant rhetoric during the campaign and his election, rather than the White House's 27 January travel ban against seven Muslim-majority countries, which is now in legal limbo. A continued downturn, officials say, could threaten U.S. global leadership in science and engineering by shrinking the pool of talent available to carry out academic research. It could also hinder innovation in industry, given that most foreign-born engineering students take jobs with U.S. companies after graduation. Author: Jeffrey Mervis
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[In Depth] Easier cure for resistant TB ()
A new treatment strategy has had astonishing success against extensively drug-resistant tuberculosis (XDR TB), which kills more than 70% of patients. XDR and other drug-resistant forms of TB are burgeoning among people with HIV, and current treatments are so prolonged and toxic that many patients fail to adhere to them. But a small study now shows that a simpler, safer regimen can cure the disease. Called Nix-TB, the trial has had 34 people in South Africa with XDR on three antibiotics that have never been combined before to treat TB. After 6 months, the TB bacillus could not be cultured from anyone's sputum, a sign that they had cleared the infection. More impressive, 20 people stopped taking the drugs at that point and none relapsed. Author: Jon Cohen
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[In Depth] Parasitic worm may trigger mystery nodding syndrome ()
Between 1990 and 2013, thousands of children in war-torn South Sudan and northern Uganda suddenly developed a severe and puzzling form of epilepsy. When exposed to food or cold temperatures, affected children nodded their heads uncontrollably. Over time the seizures often worsened, leaving the children severely disabled. Many died of malnutrition, accidents, or secondary infections. The outbreak triggered an intense hunt for the cause, but searches for viruses, bacteria, environmental toxins, genetic factors, and nutritional deficits all came up empty. One key clue: Areas with nodding disease also had high rates of infection with the parasite Onchocerca volvulus, best known for causing so-called river blindness. Now, a study finds that the worm might trigger the body's own defenses to attack neurons. Author: Gretchen Vogel
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[In Depth] Failed spinal cord trial offers cautionary tale ()
Eight months after cell therapy company StemCells Inc. announced the failure of its closely watched clinical trial for spinal cord injury, some of the company's longtime academic collaborators have come forward with disheartening animal data—and an admonition for future trials. Researchers at the University of California, Irvine, found no benefit to the company's human neural stem cell product, derived from fetal tissue, in mice with damage to the upper spine. In a paper published this week in Stem Cell Reports, they caution that the large-scale clinical manufacturing of cell lines—a process often guarded as a trade secret—can change stem cells in unpredictable ways, and they argue for more thorough animal testing on the exact cell lines destined for patients. Author: Kelly Servick
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[Feature] The Birth of CRISPR Inc ()
Just 5 years ago, the community of researchers studying CRISPR, the powerful new genome editing tool, was small. When the first inklings that CRISPR could become a big business emerged, leading scientists expected to work together. But the attempt at unity collapsed—with a good deal of noise and dust. As the science grew even more compelling and venture capital (VC) beckoned, the jockeying to start CRISPR companies became intense. The research community was rent apart by concerns about intellectual property, academic credit, Nobel Prize dreams, geography, media coverage, egos, personal profit, and loyalty. A billion dollars poured into what might be called CRISPR Inc. from VC firms, pharmaceutical companies, and public stock offerings. And the companies and the academic license holders faced each other down in a battle royale over patents. Author: Jon Cohen
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[Perspective] Sweet relief for pollinators ()
During the first half of Earth's history, oxygen supplies were scant. Photosynthesis probably evolved soon after the appearance of life, but it was not until 2.4 to 2.1 billion years ago that photosynthetic organisms invented the ability to use water as an electron donor and began to produce molecular oxygen (O2) as a waste product. The production of O2 and its accumulation in the atmosphere facilitated the evolution of complex multicellular organisms; there are no exclusively anaerobic multicellular organisms. But although much of life depends on it, O2 is dangerous to handle: Using O2 in metabolism produces reactive oxygen species (ROS) that cause oxidative damage. On page 733 of this issue, Levin et al. (1) show how a group of relatively recently evolved animals—pollinators with high metabolic rates—use an ancient pathway to defeat oxidative stress. Authors: Carlos Martinez del Rio, Michael E. Dillon
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[Perspective] Relief for retinal neurons under pressure ()
Advancing age predisposes us to a number of neurodegenerative diseases, yet the underlying mechanisms are poorly understood. With some 70 million individuals affected, glaucoma is the world's leading cause of irreversible blindness. Glaucoma is characterized by the selective loss of retinal ganglion cells that convey visual messages from the photoreceptive retina to the brain. Age is a major risk factor for glaucoma, with disease incidence increasing near exponentially with increasing age. Treatments that specifically target retinal ganglion cells or the effects of aging on glaucoma susceptibility are currently lacking. On page 756 of this issue, Williams et al. (1) report substantial advances toward filling these gaps by identifying nicotinamide adenine dinucleotide (NAD+) decline as a key age-dependent risk factor and showing that restoration with long-term dietary supplementation or gene therapy robustly protects against neuronal degeneration. Authors: Jonathan Crowston, Ian Trounce
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[Perspective] Fighting the enemy within ()
The dynamic microbiota that populate all human body surfaces affect health and disease in complex and often subtle ways. At the same time, human gastrointestinal and respiratory tract microbiota are the reservoirs for most of the human pathogens that cause invasive bacterial infections. Antibiotic resistance in such pathogens has dramatically increased in recent years, resulting in infections that are much more difficult to treat (1, 2). To counter this rise, research and development efforts must target not only new broad-spectrum antibiotics, but also decolonization agents that disrupt the major endogenous reservoirs of antibiotic-resistant bacterial pathogens (ARBPs) and reduce the risk of infections that do not respond to treatment. Authors: Evelina Tacconelli, Ingo B. Autenrieth, Andreas Peschel
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[Perspective] Illuminating amination ()
Amines, molecules containing carbon-nitrogen (C–N) bonds, are among the most common and biologically important molecules in organic chemistry; 84% of small-molecule pharmaceuticals contain at least one C–N bond (1). Hydroamination, the direct addition of an N–H bond across a carbon-carbon double or triple bond, represents an ideal approach for the synthesis of amines (2). Despite extensive research over the past several decades, the efficient and direct intermolecular hydroamination of unactivated alkenes with anti-Markovnikov regio-selectivity (see the top panel of the figure) has remained a challenge. On page 727 of this issue, Musacchio et al. (3) report a photochemical strategy for creating reactive ammonium radical cations (ARCs) that can form these less stable isomers. Authors: Travis L. Buchanan, Kami L. Hull
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[Perspective] Dwarf planet Ceres and the ingredients of life ()
A fundamental question in the evolution of the early Earth is the origin of the oceans and of some of the organic molecules that were required for the formation of life. Earth formed in the protoplanetary disk, a mixture of gas and dust. At the location of Earth, temperatures were too high for water vapor and some more volatile organic components to condense. This led to the idea that those materials may have been delivered to Earth by asteroids and/or comets from the outer solar system. Recent spacecraft studies of Comet 67P/Churyumov-Gerasimenko with Rosetta (1, 2), and of Ceres on page 719 of this issue by De Sanctis et al. (3) and by Prettyman et al. (4) with the Dawn space probe, provide evidence that complex organic molecules and even amino acids are ubiquitous on small bodies in the solar system and that water ice is abundant in the asteroid belt. Author: Michael Küppers
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[Perspective] Fibroblasts become fat to reduce scarring ()
Following cutaneous injury in adult mammals, one of two outcomes can occur: successful healing with scar formation or nonsuccessful healing and a chronic wound. In humans, scar formation can be classified in terms of “normal scar” formation versus pathologically increased fibrosis, as seen in hypertrophic scarring and keloids (1). Although scarring does not look or function like surrounding unwounded skin, it allows one to survive injury (and hence, procreate). However, extensive scarring from burns and conditions such as scleroderma or epidermolysis bulosa are not only unsightly but also contribute to substantial morbidity owing to loss of functionality in affected tissues and limbs. In the United States alone, there are greater than 50 million incisions and lacerations each year, all of which heal with some degree of scarring (2). Thus, scarring represents an enormous and growing medical burden in our aging population. On page 748 of this issue, Plikus et al. (3) demonstrate that scarring could be mitigated by controlling fibroblast plasticity. This has very exciting translational implications for treating scar formation during wound repair. Authors: Charles K. F. Chan, Michael T. Longaker
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[Perspective] Oliver Smithies (1925–2017) ()
Oliver Smithies passed away on 10 January 2017, at the age of 91, in Chapel Hill, North Carolina. On that day, the world lost a legendary scientist, and I lost a colleague, collaborator, and friend. Smithies began his career as a physical biochemist and transitioned into genetics, earning a share of a Nobel Prize for his work in 2007. His interests and talents were wide ranging. In addition to his research, he rode motorcycles as a young man, sang in professional choirs throughout his life, and piloted small planes, setting a record for duo transatlantic flight that stood for nearly 20 years. Author: Aziz Sancar
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[Policy Forum] Ensuring scientific integrity in the Age of Trump ()
With the new Donald J. Trump Administration comes uncertainty in the role that science will play in the U.S. federal government. Early indications that the Administration plans to distort or disregard science and evidence, coupled with the chaos and confusion occurring within federal agencies, now imperil the effectiveness of our government. Evidence from the past 20 years demonstrates that, when faced with such threats, supporters of science can take steps to protect the integrity of science in the federal policy-making process. The scientific community will need to connect science-informed policy to positive outcomes and staunchly defend scientific freedom. It must also spotlight political interference in science-based policy development and be prepared to protect scientists—both within and outside the government—against executive or legislative overreach. A range of scientific integrity and transparency policies across federal agencies provides critical tools but must be enforced and protected. Authors: Gretchen T. Goldman, Emily Berman, Michael Halpern, Charise Johnson, Yogin Kothari, Genna Reed, Andrew A. Rosenberg
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[Policy Forum] CRISPR, surrogate licensing, and scientific discovery ()
Several institutions are embroiled in a legal dispute over the foundational patent rights to CRISPR-Cas9 gene-editing technology, and it may take years for their competing claims to be resolved (1–4). But even before ownership of the patents is finalized, the institutions behind CRISPR have wasted no time capitalizing on the huge market for this groundbreaking technology by entering into a series of license agreements with commercial enterprises (see the figure). With respect to the potentially lucrative market for human therapeutics and treatments, each of the key CRISPR patent holders has granted exclusive rights to a spinoff or “surrogate” company formed by the institution and one of its principal researchers (5, 6). Although this model, in which a university effectively outsources the licensing and commercialization of a valuable patent portfolio to a private company, is not uncommon in the world of university technology transfer, we suggest it could rapidly bottleneck the use of CRISPR technology to discover and develop useful human therapeutics. Authors: Jorge L. Contreras, Jacob S. Sherkow
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[Book Review] The tie that binds ()
We often need different scientific fields to work together to make sense of the world.  But for multidisciplinary approaches to work, a common ground first needs to exist between fields. Historian Peter Watson's new book, Convergence, sheds light on what can be gained when research areas come together, chronicling a series of major scientific milestones that span the past two centuries. Author: Joseph Swift
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[Book Review] Building the future ()
Engineering has an image problem. The phrase "engineering disaster" rolls off the tongue, while great technical achievements are more often heralded as "scientific miracles." Enter Dream Big. Sponsored by the American Society of Civil Engineers with support from Bechtel Corporation, the film sets out to reframe engineering as a force for good and a profession in service to people and the planet. Author: Donna Riley
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[Letter] U.S. immigration ban undermines scientists ()
Author: Mohamed Hassan
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[Letter] Maternal antibodies' role in immunity ()
Author: Hilmar Lemke
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[Letter] Maternal antibodies' role in immunity—Response ()
Authors: Katelyn M. Gostic, Monique Ambrose, Michael Worobey, James O. Lloyd-Smith
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[This Week in Science] Organic compounds detected on Ceres ()
Author: Keith T. Smith
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[This Week in Science] Hypoxic conditioning of immune cells ()
Author: Angela Colmone
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[This Week in Science] Coordinating cell wall synthesis and cell division ()
Author: Stella M. Hurtley
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[This Week in Science] Stamping hydrogen into metal ()
Author: Brent Grocholski
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[This Week in Science] Sugar rush ()
Author: Sacha Vignieri
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[This Week in Science] When is a mutation a true genetic variant? ()
Author: Laura M. Zahn
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[This Week in Science] Vitamin B3 protects mice from glaucoma ()
Author: Priscilla Kelly
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[This Week in Science] Touchdown for gut pathogen virulence ()
Author: Caroline Ash
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[This Week in Science] Peak HIV viremia pushes CD8+ T cells ()
Author: Lindsey Pujanandez
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[This Week in Science] Understanding insulin release ()
Author: Stella M. Hurtley
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[This Week in Science] Host-pathogen point-counterpoint ()
Author: Pamela J. Hines
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[This Week in Science] Hydroamination gets a light push uphill ()
Author: Jake Yeston
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[This Week in Science] Hair follicles: Secret to prevent scars? ()
Author: Beverly A. Purnell
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[This Week in Science] Passivating traps in perovskites ()
Author: Phil Szuromi
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[This Week in Science] Being selective in fighting infection ()
Author: Julia Fahrenkamp-Uppenbrink
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[This Week in Science] An encephalitis-boosting microRNA ()
Author: John F. Foley
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[This Week in Science] Missing meadows fail to mop up microbes ()
Author: Caroline Ash
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[Editors' Choice] Cracking the code underlying snowslides ()
Author: Brent Grocholski
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[Editors' Choice] Scientific curiosity versus polarization ()
Author: Barbara R. Jasny
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[Editors' Choice] Dissecting the effects of APOE ()
Author: Stella M. Hurtley
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[Editors' Choice] Vocalizations channeled by developmental affordances ()
Author: Pamela J. Hines
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[Editors' Choice] Electrical detection of diamond defects ()
Author: Ian S. Osborne
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[Editors' Choice] Strengthening the remaining synapses ()
Author: Peter Stern
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[Editors' Choice] A less structured way to better hydrogels ()
Author: Marc S. Lavine
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[Research Article] A paralogous decoy protects Phytophthora sojae apoplastic effector PsXEG1 from a host inhibitor ()
The extracellular space (apoplast) of plant tissue represents a critical battleground between plants and attacking microbes. Here we show that a pathogen-secreted apoplastic xyloglucan-specific endoglucanase, PsXEG1, is a focus of this struggle in the Phytophthora sojae–soybean interaction. We show that soybean produces an apoplastic glucanase inhibitor protein, GmGIP1, that binds to PsXEG1 to block its contribution to virulence. P. sojae, however, secretes a paralogous PsXEG1-like protein, PsXLP1, that has lost enzyme activity but binds to GmGIP1 more tightly than does PsXEG1, thus freeing PsXEG1 to support P. sojae infection. The gene pair encoding PsXEG1 and PsXLP1 is conserved in many Phytophthora species, and the P. parasitica orthologs PpXEG1 and PpXLP1 have similar functions. Thus, this apoplastic decoy strategy may be widely used in Phytophthora pathosystems. Authors: Zhenchuan Ma, Lin Zhu, Tianqiao Song, Yang Wang, Qi Zhang, Yeqiang Xia, Min Qiu, Yachun Lin, Haiyang Li, Liang Kong, Yufeng Fang, Wenwu Ye, Yan Wang, Suomeng Dong, Xiaobo Zheng, Brett M. Tyler, Yuanchao Wang
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[Research Article] Observation of the Wigner-Huntington transition to metallic hydrogen ()
Producing metallic hydrogen has been a great challenge in condensed matter physics. Metallic hydrogen may be a room-temperature superconductor and metastable when the pressure is released and could have an important impact on energy and rocketry. We have studied solid molecular hydrogen under pressure at low temperatures. At a pressure of 495 gigapascals, hydrogen becomes metallic, with reflectivity as high as 0.91. We fit the reflectance using a Drude free-electron model to determine the plasma frequency of 32.5 ± 2.1 electron volts at a temperature of 5.5 kelvin, with a corresponding electron carrier density of 7.7 ± 1.1 × 1023 particles per cubic centimeter, which is consistent with theoretical estimates of the atomic density. The properties are those of an atomic metal. We have produced the Wigner-Huntington dissociative transition to atomic metallic hydrogen in the laboratory. Authors: Ranga P. Dias, Isaac F. Silvera
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[Report] Localized aliphatic organic material on the surface of Ceres ()
Organic compounds occur in some chondritic meteorites, and their signatures on solar system bodies have been sought for decades. Spectral signatures of organics have not been unambiguously identified on the surfaces of asteroids, whereas they have been detected on cometary nuclei. Data returned by the Visible and InfraRed Mapping Spectrometer on board the Dawn spacecraft show a clear detection of an organic absorption feature at 3.4 micrometers on dwarf planet Ceres. This signature is characteristic of aliphatic organic matter and is mainly localized on a broad region of ~1000 square kilometers close to the ~50-kilometer Ernutet crater. The combined presence on Ceres of ammonia-bearing hydrated minerals, water ice, carbonates, salts, and organic material indicates a very complex chemical environment, suggesting favorable environments to prebiotic chemistry. Authors: M. C. De Sanctis, E. Ammannito, H. Y. McSween, A. Raponi, S. Marchi, F. Capaccioni, M. T. Capria, F. G. Carrozzo, M. Ciarniello, S. Fonte, M. Formisano, A. Frigeri, M. Giardino, A. Longobardo, G. Magni, L. A. McFadden, E. Palomba, C. M. Pieters, F. Tosi, F. Zambon, C. A. Raymond, C. T. Russell
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[Report] Efficient and stable solution-processed planar perovskite solar cells via contact passivation ()
Planar perovskite solar cells (PSCs) made entirely via solution processing at low temperatures (<150°C) offer promise for simple manufacturing, compatibility with flexible substrates, and perovskite-based tandem devices. However, these PSCs require an electron-selective layer that performs well with similar processing. We report a contact-passivation strategy using chlorine-capped TiO2 colloidal nanocrystal film that mitigates interfacial recombination and improves interface binding in low-temperature planar solar cells. We fabricated solar cells with certified efficiencies of 20.1 and 19.5% for active areas of 0.049 and 1.1 square centimeters, respectively, achieved via low-temperature solution processing. Solar cells with efficiency greater than 20% retained 90% (97% after dark recovery) of their initial performance after 500 hours of continuous room-temperature operation at their maximum power point under 1-sun illumination (where 1 sun is defined as the standard illumination at AM1.5, or 1 kilowatt/square meter). Authors: Hairen Tan, Ankit Jain, Oleksandr Voznyy, Xinzheng Lan, F. Pelayo García de Arquer, James Z. Fan, Rafael Quintero-Bermudez, Mingjian Yuan, Bo Zhang, Yicheng Zhao, Fengjia Fan, Peicheng Li, Li Na Quan, Yongbiao Zhao, Zheng-Hong Lu, Zhenyu Yang, Sjoerd Hoogland, Edward H. Sargent
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[Report] Catalytic intermolecular hydroaminations of unactivated olefins with secondary alkyl amines ()
The intermolecular hydroamination of unactivated alkenes with simple dialkyl amines remains an unsolved problem in organic synthesis. We report a catalytic protocol for efficient additions of cyclic and acyclic secondary alkyl amines to a wide range of alkyl olefins with complete anti-Markovnikov regioselectivity. In this process, carbon-nitrogen bond formation proceeds through a key aminium radical cation intermediate that is generated via electron transfer between an excited-state iridium photocatalyst and an amine substrate. These reactions are redox-neutral and completely atom-economical, exhibit broad functional group tolerance, and occur readily at room temperature under visible light irradiation. Certain tertiary amine products generated through this method are formally endergonic relative to their constituent olefin and amine starting materials and thus are not accessible via direct coupling with conventional ground-state catalysts. Authors: Andrew J. Musacchio, Brendan C. Lainhart, Xin Zhang, Saeed G. Naguib, Trevor C. Sherwood, Robert R. Knowles
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[Report] Seagrass ecosystems reduce exposure to bacterial pathogens of humans, fishes, and invertebrates ()
Plants are important in urban environments for removing pathogens and improving water quality. Seagrass meadows are the most widespread coastal ecosystem on the planet. Although these plants are known to be associated with natural biocide production, they have not been evaluated for their ability to remove microbiological contamination. Using amplicon sequencing of the 16S ribosomal RNA gene, we found that when seagrass meadows are present, there was a 50% reduction in the relative abundance of potential bacterial pathogens capable of causing disease in humans and marine organisms. Moreover, field surveys of more than 8000 reef-building corals located adjacent to seagrass meadows showed twofold reductions in disease levels compared to corals at paired sites without adjacent seagrass meadows. These results highlight the importance of seagrass ecosystems to the health of humans and other organisms. Authors: Joleah B. Lamb, Jeroen A. J. M. van de Water, David G. Bourne, Craig Altier, Margaux Y. Hein, Evan A. Fiorenza, Nur Abu, Jamaluddin Jompa, C. Drew Harvell
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[Report] Hawkmoths use nectar sugar to reduce oxidative damage from flight ()
Nectar-feeding animals have among the highest recorded metabolic rates. High aerobic performance is linked to oxidative damage in muscles. Antioxidants in nectar are scarce to nonexistent. We propose that nectarivores use nectar sugar to mitigate the oxidative damage caused by the muscular demands of flight. We found that sugar-fed moths had lower oxidative damage to their flight muscle membranes than unfed moths. Using respirometry coupled with δ13C analyses, we showed that moths generate antioxidant potential by shunting nectar glucose to the pentose phosphate pathway (PPP), resulting in a reduction in oxidative damage to the flight muscles. We suggest that nectar feeding, the use of PPP, and intense exercise are causally linked and have allowed the evolution of powerful fliers that feed on nectar. Authors: E. Levin, G. Lopez-Martinez, B. Fane, G. Davidowitz
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[Report] Host cell attachment elicits posttranscriptional regulation in infecting enteropathogenic bacteria ()
The mechanisms by which pathogens sense the host and respond by remodeling gene expression are poorly understood. Enteropathogenic Escherichia coli (EPEC), the cause of severe intestinal infection, employs a type III secretion system (T3SS) to inject effector proteins into intestinal epithelial cells. These effectors subvert host cell processes to promote bacterial colonization. We show that the T3SS also functions to sense the host cell and to trigger in response posttranscriptional remodeling of gene expression in the bacteria. We further show that upon effector injection, the effector-bound chaperone (CesT), which remains in the EPEC cytoplasm, antagonizes the posttranscriptional regulator CsrA. The CesT-CsrA interaction provokes reprogramming of expression of virulence and metabolic genes. This regulation is likely required for the pathogen’s adaptation to life on the epithelium surface. Authors: Naama Katsowich, Netanel Elbaz, Ritesh Ranjan Pal, Erez Mills, Simi Kobi, Tamar Kahan, Ilan Rosenshine
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[Report] Treadmilling by FtsZ filaments drives peptidoglycan synthesis and bacterial cell division ()
The mechanism by which bacteria divide is not well understood. Cell division is mediated by filaments of FtsZ and FtsA (FtsAZ) that recruit septal peptidoglycan-synthesizing enzymes to the division site. To understand how these components coordinate to divide cells, we visualized their movements relative to the dynamics of cell wall synthesis during cytokinesis. We found that the division septum was built at discrete sites that moved around the division plane. FtsAZ filaments treadmilled circumferentially around the division ring and drove the motions of the peptidoglycan-synthesizing enzymes. The FtsZ treadmilling rate controlled both the rate of peptidoglycan synthesis and cell division. Thus, FtsZ treadmilling guides the progressive insertion of new cell wall by building increasingly smaller concentric rings of peptidoglycan to divide the cell. Authors: Alexandre W. Bisson-Filho, Yen-Pang Hsu, Georgia R. Squyres, Erkin Kuru, Fabai Wu, Calum Jukes, Yingjie Sun, Cees Dekker, Seamus Holden, Michael S. VanNieuwenhze, Yves V. Brun, Ethan C. Garner
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[Report] GTPase activity–coupled treadmilling of the bacterial tubulin FtsZ organizes septal cell wall synthesis ()
The bacterial tubulin FtsZ is the central component of the cell division machinery, coordinating an ensemble of proteins involved in septal cell wall synthesis to ensure successful constriction. How cells achieve this coordination is unknown. We found that in Escherichia coli cells, FtsZ exhibits dynamic treadmilling predominantly determined by its guanosine triphosphatase activity. The treadmilling dynamics direct the processive movement of the septal cell wall synthesis machinery but do not limit the rate of septal synthesis. In FtsZ mutants with severely reduced treadmilling, the spatial distribution of septal synthesis and the molecular composition and ultrastructure of the septal cell wall were substantially altered. Thus, FtsZ treadmilling provides a mechanism for achieving uniform septal cell wall synthesis to enable correct polar morphology. Authors: Xinxing Yang, Zhixin Lyu, Amanda Miguel, Ryan McQuillen, Kerwyn Casey Huang, Jie Xiao
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[Report] Regeneration of fat cells from myofibroblasts during wound healing ()
Although regeneration through the reprogramming of one cell lineage to another occurs in fish and amphibians, it has not been observed in mammals. We discovered in the mouse that during wound healing, adipocytes regenerate from myofibroblasts, a cell type thought to be differentiated and nonadipogenic. Myofibroblast reprogramming required neogenic hair follicles, which triggered bone morphogenetic protein (BMP) signaling and then activation of adipocyte transcription factors expressed during development. Overexpression of the BMP antagonist Noggin in hair follicles or deletion of the BMP receptor in myofibroblasts prevented adipocyte formation. Adipocytes formed from human keloid fibroblasts either when treated with BMP or when placed with human hair follicles in vitro. Thus, we identify the myofibroblast as a plastic cell type that may be manipulated to treat scars in humans. Authors: Maksim V. Plikus, Christian F. Guerrero-Juarez, Mayumi Ito, Yun Rose Li, Priya H. Dedhia, Ying Zheng, Mengle Shao, Denise L. Gay, Raul Ramos, Tsai-Ching Hsi, Ji Won Oh, Xiaojie Wang, Amanda Ramirez, Sara E. Konopelski, Arijh Elzein, Anne Wang, Rarinthip June Supapannachart, Hye-Lim Lee, Chae Ho Lim, Arben Nace, Amy Guo, Elsa Treffeisen, Thomas Andl, Ricardo N. Ramirez, Rabi Murad, Stefan Offermanns, Daniel Metzger, Pierre Chambon, Alan D. Widgerow, Tai-Lan Tuan, Ali Mortazavi, Rana K. Gupta, Bruce A. Hamilton, Sarah E. Millar, Patrick Seale, Warren S. Pear, Mitchell A. Lazar, George Cotsarelis
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[Report] DNA damage is a pervasive cause of sequencing errors, directly confounding variant identification ()
Mutations in somatic cells generate a heterogeneous genomic population and may result in serious medical conditions. Although cancer is typically associated with somatic variations, advances in DNA sequencing indicate that cell-specific variants affect a number of phenotypes and pathologies. Here, we show that mutagenic damage accounts for the majority of the erroneous identification of variants with low to moderate (1 to 5%) frequency. More important, we found signatures of damage in most sequencing data sets in widely used resources, including the 1000 Genomes Project and The Cancer Genome Atlas, establishing damage as a pervasive cause of sequencing errors. The extent of this damage directly confounds the determination of somatic variants in these data sets. Authors: Lixin Chen, Pingfang Liu, Thomas C. Evans, Laurence M. Ettwiller
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[Report] Vitamin B3 modulates mitochondrial vulnerability and prevents glaucoma in aged mice ()
Glaucomas are neurodegenerative diseases that cause vision loss, especially in the elderly. The mechanisms initiating glaucoma and driving neuronal vulnerability during normal aging are unknown. Studying glaucoma-prone mice, we show that mitochondrial abnormalities are an early driver of neuronal dysfunction, occurring before detectable degeneration. Retinal levels of nicotinamide adenine dinucleotide (NAD+, a key molecule in energy and redox metabolism) decrease with age and render aging neurons vulnerable to disease-related insults. Oral administration of the NAD+ precursor nicotinamide (vitamin B3), and/or gene therapy (driving expression of Nmnat1, a key NAD+-producing enzyme), was protective both prophylactically and as an intervention. At the highest dose tested, 93% of eyes did not develop glaucoma. This supports therapeutic use of vitamin B3 in glaucoma and potentially other age-related neurodegenerations. Authors: Pete A. Williams, Jeffrey M. Harder, Nicole E. Foxworth, Kelly E. Cochran, Vivek M. Philip, Vittorio Porciatti, Oliver Smithies, Simon W. M. John
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[New Products] New Products ()
A weekly roundup of information on newly offered instrumentation, apparatus, and laboratory materials of potential interest to researchers.
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[Working Life] The America I believe in ()
Author: Hilal A. Lashuel
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