Journal Articles

Regulation of DNA replication at the end of the mitochondrial D-loop involves the helicase TWINKLE and a conserved sequence element

Nucleic Acids Research - Fri, 10/30/2015 - 04:05

The majority of mitochondrial DNA replication events are terminated prematurely. The nascent DNA remains stably associated with the template, forming a triple-stranded displacement loop (D-loop) structure. However, the function of the D-loop region of the mitochondrial genome remains poorly understood. Using a comparative genomics approach we here identify two closely related 15 nt sequence motifs of the D-loop, strongly conserved among vertebrates. One motif is at the D-loop 5'-end and is part of the conserved sequence block 1 (CSB1). The other motif, here denoted coreTAS, is at the D-loop 3'-end. Both these sequences may prevent transcription across the D-loop region, since light and heavy strand transcription is terminated at CSB1 and coreTAS, respectively. Interestingly, the replication of the nascent D-loop strand, occurring in a direction opposite to that of heavy strand transcription, is also terminated at coreTAS, suggesting that coreTAS is involved in termination of both transcription and replication. Finally, we demonstrate that the loading of the helicase TWINKLE at coreTAS is reversible, implying that this site is a crucial component of a switch between D-loop formation and full-length mitochondrial DNA replication.

Categories: Journal Articles

Mapping the interactions of the single-stranded DNA binding protein of bacteriophage T4 (gp32) with DNA lattices at single nucleotide resolution: gp32 monomer binding

Nucleic Acids Research - Fri, 10/30/2015 - 04:05

Combining biophysical measurements on T4 bacteriophage replication complexes with detailed structural information can illuminate the molecular mechanisms of these ‘macromolecular machines’. Here we use the low energy circular dichroism (CD) and fluorescent properties of site-specifically introduced base analogues to map and quantify the equilibrium binding interactions of short (8 nts) ssDNA oligomers with gp32 monomers at single nucleotide resolution. We show that single gp32 molecules interact most directly and specifically near the 3'-end of these ssDNA oligomers, thus defining the polarity of gp32 binding with respect to the ssDNA lattice, and that only 2–3 nts are directly involved in this tight binding interaction. The loss of exciton coupling in the CD spectra of dimer 2-AP (2-aminopurine) probes at various positions in the ssDNA constructs, together with increases in fluorescence intensity, suggest that gp32 binding directly extends the sugar-phosphate backbone of this ssDNA oligomer, particularly at the 3'-end and facilitates base unstacking along the entire 8-mer lattice. These results provide a model (and ‘DNA map’) for the isolated gp32 binding to ssDNA targets, which serves as the nucleation step for the cooperative binding that occurs at transiently exposed ssDNA sequences within the functioning T4 DNA replication complex.

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Retraction of “Efficient Reactivation of p53 in Cancer Cells by a Dual MdmX/Mdm2 Inhibitor”

Journal of American Chemical Society - Fri, 10/30/2015 - 01:00
Journal of the American Chemical SocietyDOI: 10.1021/jacs.5b11033
Categories: Journal Articles

[Editorial] Zero tolerance. Period

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

[In Brief] This week's section

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

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

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

Science - Thu, 10/29/2015 - 23:00
Paleontologists and the public alike have long been fascinated by the great titanosaurs, long necked sauropods which include the largest creatures ever to walk the earth. For example, Argentinosaurus, a South American species, stretched nearly 40 meters long from head to tail, and weighed more than 70 tons—as much as 15 adult elephants and more than twice as much as the classic sauropod, Apatosaurus. Yet the titanosaur fossil record has been pretty scrappy—just three complete skulls have been found—leaving major mysteries about these behemoths. In particular, researchers still need to learn more about how and why they grew so big, and how they managed to move their massive bodies. The picture is beginning to fill in, however. At a special session at the annual meeting of the Society of Vertebrate Paleontology in Dallas, Texas, researchers presented new fossils that chart titanosaur growth and development from embryo to adult, including a spectacular egg, a rare juvenile, and a modeling study of how titanosaur adults moved their massive necks. Author: Michael Balter
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[In Depth] Proposed study would closely track 10,000 New Yorkers

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

Science - Thu, 10/29/2015 - 23:00
Budget cuts and a weak ruble have forced Russia to put on ice one of its highest profile science projects: a 20-year odyssey to drill into a lake under the Antarctic Ice Sheet in search of long-buried life. In 2012, the Russian Antarctic Expedition completed drilling through nearly 4 kilometers of ice to reach the surface of subglacial Lake Vostok. Subsequent expeditions have attempted to retrieve pristine samples of water from the lake in hopes of discovering life. Postponing the pricey effort for the current scientific season is a sign of hard times in Russia's broader Antarctic program. But some outside scientists, concerned about contamination, think it is time to rethink the complex project. Author: Carolyn Gramling
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[In Depth] Crisis manager with 194 bosses

Science - Thu, 10/29/2015 - 23:00
As director-general of the World Health Organization (WHO), Margaret Chan is often ranked among the most powerful women in the world. But her agency appeared to be powerless to stop a devastating epidemic of Ebola last year. Critics have slammed WHO's performance, and reviews have called for drastic reforms (Science, 17 July, p. 223). Chan is used to crises; as director of health in Hong Kong, China, she fought devastating outbreaks of bird flu and SARS before taking WHO's top job in 2006. Science talked to Chan on 10 October in Berlin, Germany, where she spoke about the lessons from Ebola and the dangers of antimicrobial resistance at a meeting of the G7 health ministers. Chan complained that many countries were not serious about managing the WHO and she said she was determined to push through reform of the organization: "I only have 21 months," she said. Author: Kai Kupferschmidt
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[Feature] Cradle of life

Science - Thu, 10/29/2015 - 23:00
The Amazon rainforest contains 10% of the world's known species, making it one of the most biodiverse places in the world. But when, and why, did it come to be that way? Scientists agree that the Amazon's rich biodiversity was shaped by convulsive geological changes—mountains rising, coasts shifting, rivers changing course. By fragmenting and transforming habitats, these landscape changes would have driven bursts of speciation. But the experts differ, often vehemently, about just what form those upheavals took and which of them supercharged Amazonian speciation. Was it a flood of seawater invading the continent from the Caribbean? Or was it an extremely old mountain range rising along South America's west coast? As competing scientific teams descend on the Amazon in search of data, a solution to the longstanding mystery of its staggering species richness may finally be at hand. Author: Lizzie Wade
Categories: Journal Articles

[Book Review] Adventures in time and space

Science - Thu, 10/29/2015 - 23:00
From the robots of Isaac Asimov to the vision of cyberspace conjured by William Gibson, science fiction can both inspire scientific advancement and offer readers a glimpse into how today's technologies might fit into the world of tomorrow. Not to mention the fact that the fantastical story lines for which the genre is well known make for awfully fun reading. The prestigious Nebula and Hugo awards recognize outstanding new works in science fiction and fantasy, as nominated and chosen by members of the Science Fiction and Fantasy Writers of America and World Science Fiction Society, respectively. Here, we review the most recent winners and finalists for best novel for each of these awards.
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[Book Review] Culture shock

Science - Thu, 10/29/2015 - 23:00
Categories: Journal Articles

[Books et al.] Books Received

Science - Thu, 10/29/2015 - 23:00
A listing of books received at Science during the week ending 23 October 2015.
Categories: Journal Articles

[Perspective] Pinched topography initiates the critical zone

Science - Thu, 10/29/2015 - 23:00
In Earth sciences, the critical zone represents the intersection of the biosphere with the atmosphere, hydrosphere, and lithosphere (1, 2). The myriad interactions and feedbacks among these systems assure us of a world with considerable complexity, in which the critical zone varies in thickness, mineralogy, permeability (3), and structure of ecosystems (4). It is no wonder, then, that we lack a general theory of how the critical zone works. On page 534 of this issue, St. Clair et al. (5) argue that we must take the broadest possible view of, and acknowledge a role for, largescale tectonic stresses in guiding the pattern of cracking of rock in the subsurface. Author: Robert S. Anderson
Categories: Journal Articles

[Policy Forum] A unified initiative to harness Earth's microbiomes

Science - Thu, 10/29/2015 - 23:00
Despite their centrality to life on Earth, we know little about how microbes (1) interact with each other, their hosts, or their environment. Although DNA sequencing technologies have enabled a new view of the ubiquity and diversity of microorganisms, this has mainly yielded snapshots that shed limited light on microbial functions or community dynamics. Given that nearly every habitat and organism hosts a diverse constellation of microorganisms—its “microbiome”—such knowledge could transform our understanding of the world and launch innovations in agriculture, energy, health, the environment, and more (see the photo). We propose an interdisciplinary Unified Microbiome Initiative (UMI) to discover and advance tools to understand and harness the capabilities of Earth's microbial ecosystems. The impacts of oceans and soil microbes on atmospheric CO2 are critical for understanding climate change (2). By manipulating interactions at the root-soil-microbe interface, we may reduce agricultural pesticide, fertilizer, and water use enrich marginal land and rehabilitate degraded soils. Microbes can degrade plant cell walls (for biofuels), and synthesize myriad small molecules for new bioproducts, including antibiotics (3). Restoring normal human microbial ecosystems can save lives [e.g., fecal microbiome transplantation for Clostridium difficile infections (4)]. Rational management of microbial communities in and around us has implications for asthma, diabetes, obesity, infectious diseases, psychiatric illnesses, and other afflictions (5, 6). The human microbiome is a target and a source for new drugs (7) and an essential tool for precision medicine (8). Authors: A. P. Alivisatos, M. J. Blaser, E. L. Brodie, M. Chun, J. L. Dangl, T. J. Donohue, P. C. Dorrestein, J. A. Gilbert, J. L. Green, J. K. Jansson, R. Knight, M. E. Maxon, M. J. McFall-Ngai, J. F. Miller, K. S. Pollard, E. G. Ruby, S. A. Taha,
Categories: Journal Articles

[Perspective] Randomness rules

Science - Thu, 10/29/2015 - 23:00
Phase transitions are perfect examples of physical phenomena for which statistical physics offers powerful predictions. Different types of phase transitions, ranging from liquid-vapor to ferromagnetic transitions, can be treated within the same theoretical framework. This yields useful expressions for characteristic physical properties of the system, such as resistivity, heat capacity, or free energy near the phase transition. The theoretical predictions can be strongly affected by random disorder, such as impurities or vacancies that are inevitably present in all real physical systems. In some systems, rare but large spatial regions are present in which there are no impurities. Such rare regions may be in a phase different from that of the bulk of the system and can dramatically alter the nature of the transition, causing certain physical properties of the system to diverge to infinity in the vicinity of the transition. These infinities are called Griffiths singularities (1) and can be expected to occur in a variety of systems, but they are not easily observed experimentally (2). On page 542 of this issue, Xing et al. (3) report the first experimental evidence of a Griffiths singularity near a quantum phase transition in a two-dimensional (2D) superconducting system. Author: Nina Markovic
Categories: Journal Articles

[Perspective] Neuroscience Neurotransmitter-tailored dendritic trees

Science - Thu, 10/29/2015 - 23:00
GABA (γ-aminobutyric acid) is the major inhibitory neurotransmitter in the mature brain but functions as an excitatory transmitter in the developing nervous system (1, 2). GABA has also been identified as a trophic factor stimulating growth of the embryonic nervous system (3, 4). On page 554 of this issue, Chen and Kriegstein (5) forge a link between neuronal excitation by GABA, calcium signaling, and the morphogenesis of specific neocortical neurons in the growing brain, setting a new standard for analysis of activity-dependent neuronal circuit assembly. The changes in dendritic trees that they report are consistent with those observed in schizophrenia and autism (6, 7). Author: Nicholas C. Spitzer
Categories: Journal Articles
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