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Radial glia require PDGFD–PDGFRβ signalling in human but not mouse neocortex

Nature - Wed, 11/12/2014 - 01:00

Radial glia require PDGFD–PDGFRβ signalling in human but not mouse neocortex

Nature 515, 7526 (2014). doi:10.1038/nature13973

Authors: Jan H. Lui, Tomasz J. Nowakowski, Alex A. Pollen, Ashkan Javaherian, Arnold R. Kriegstein & Michael C. Oldham

Evolutionary expansion of the human neocortex underlies many of our unique mental abilities. This expansion has been attributed to the increased proliferative potential of radial glia (RG; neural stem cells) and their subventricular dispersion from the periventricular niche during neocortical development. Such adaptations may have evolved through gene expression changes in RG. However, whether or how RG gene expression varies between humans and other species is unknown. Here we show that the transcriptional profiles of human and mouse neocortical RG are broadly conserved during neurogenesis, yet diverge for specific signalling pathways. By analysing differential gene co-expression relationships between the species, we demonstrate that the growth factor PDGFD is specifically expressed by RG in human, but not mouse, corticogenesis. We also show that the expression domain of PDGFRβ, the cognate receptor for PDGFD, is evolutionarily divergent, with high expression in the germinal region of dorsal human neocortex but not in the mouse. Pharmacological inhibition of PDGFD–PDGFRβ signalling in slice culture prevents normal cell cycle progression of neocortical RG in human, but not mouse. Conversely, injection of recombinant PDGFD or ectopic expression of constitutively active PDGFRβ in developing mouse neocortex increases the proportion of RG and their subventricular dispersion. These findings highlight the requirement of PDGFD–PDGFRβ signalling for human neocortical development and suggest that local production of growth factors by RG supports the expanded germinal region and progenitor heterogeneity of species with large brains.

Categories: Literature

New Mapping Tool Highlights Carbon-Trapping Forests in Peru

Yale Environment 360 - Tue, 11/11/2014 - 11:45

A new, high-resolution mapping technique can be used to help identify and prioritize tracts of forest land with the highest

Enlarge

Greg Asner Map of carbon storage potential of land in Peru carbon-sequestering potential, according to research published in the Proceedings of the National Academy of Sciences. In the study, researchers with the Carnegie Institution for Science applied the technique, which integrated satellite imaging data and advanced, three-dimensional forest mapping information, to the 128 million hectares that comprise the nation of Peru. The analysis considered each landscape's unique climate, topography, geology, and hydrology to produce a map showing a range of landscapes with varying carbon densities — a potentially crucial tool as nations prepare to negotiate global forest protections as part of United Nations climate talks next month Lima, Peru.

Categories: Environmental News

A Scourge for Coal Miners Stages a Brutal Comeback

Yale Environment 360 - Tue, 11/11/2014 - 07:32

Black lung — a debilitating disease caused by inhaling coal dust — was supposed to be wiped out by a landmark 1969 U.S. mine safety law. But a recent study shows that the worst form of the disease now affects a larger share of Appalachian coal miners than at any time since the early 1970s. BY KEN WARD JR.

Categories: Environmental News

High ambition

Nature - Tue, 11/11/2014 - 01:00

High ambition

Nature 515, 7526 (2014). doi:10.1038/515163b

The European Space Agency can be proud of its comet mission— whatever happens.

Categories: Literature

Edits to ethics code rankle

Nature - Tue, 11/11/2014 - 01:00

Edits to ethics code rankle

Nature 515, 7526 (2014). http://www.nature.com/doifinder/10.1038/515174a

Author: Heidi Ledford

Clinical-trial obligations introduced into the Helsinki declaration called too onerous by some.

Categories: Literature

Ethical dilemma for Ebola drug trials

Nature - Tue, 11/11/2014 - 01:00

Ethical dilemma for Ebola drug trials

Nature 515, 7526 (2014). http://www.nature.com/doifinder/10.1038/515177a

Author: Erika Check Hayden

Public-health officials split on use of control groups in tests of experimental treatments.

Categories: Literature

Public Views of Climate Science Hinge on Solutions, Study Finds

Yale Environment 360 - Mon, 11/10/2014 - 10:03

People often evaluate scientific evidence not on the basis of its perceived merits, but on whether they agree with the policy implications of the research, according to a study published in the Journal of Personality and Social Psychology. Using issues like climate change and air pollution as test cases, Duke University researchers sought to determine if what they call a "solution aversion" bias could be detected among self-identified Republican or Democratic survey participants. In one example, participants were provided a scientific assertion that global average temperatures could rise as much as 3.2 degrees by the end of the century, after which they were presented with potential policy solutions. If that solution involved government regulation or increased taxes, just 22 percent of Republican participants expressed confidence in the initial scientific finding. But if the solution emphasized using market forces to curb temperatures, the percentage of Republicans accepting the initial temperature predictions rose to 55 percent. Self-identified Democrats displayed no difference in the same experiment, but liberal biases were clearly elicited on other issues, the researchers found.

Categories: Environmental News

Overcoming the limitations of directed C–H functionalizations of heterocycles

Nature - Mon, 11/10/2014 - 01:00

Overcoming the limitations of directed C–H functionalizations of heterocycles

Nature 515, 7527 (2014). doi:10.1038/nature13885

Authors: Yue-Jin Liu, Hui Xu, Wei-Jun Kong, Ming Shang, Hui-Xiong Dai & Jin-Quan Yu

In directed C–H activation reactions, any nitrogen or sulphur atoms present in heterocyclic substrates will coordinate strongly with metal catalysts. This coordination, which can lead to catalyst poisoning or C–H functionalization at an undesired position, limits the application of C–H activation reactions in heterocycle-based drug discovery, in which regard they have attracted much interest from pharmaceutical companies. Here we report a robust and synthetically useful method that overcomes the complications associated with performing C–H functionalization reactions on heterocycles. Our approach employs a simple N-methoxy amide group, which serves as both a directing group and an anionic ligand that promotes the in situ generation of the reactive PdX2 (X = ArCONOMe) species from a Pd(0) source using air as the sole oxidant. In this way, the PdX2 species is localized near the target C–H bond, avoiding interference from any nitrogen or sulphur atoms present in the heterocyclic substrates. This reaction overrides the conventional positional selectivity patterns observed with substrates containing strongly coordinating heteroatoms, including nitrogen, sulphur and phosphorus. Thus, this operationally simple aerobic reaction demonstrates that it is possible to bypass a fundamental limitation that has long plagued applications of directed C–H activation in medicinal chemistry.

Categories: Literature

Italian seismologists cleared of manslaughter

Nature - Mon, 11/10/2014 - 01:00

Italian seismologists cleared of manslaughter

Nature 515, 7526 (2014). http://www.nature.com/doifinder/10.1038/515171a

Authors: Alison Abbott & Nicola Nosengo

Appeals court says six scientists did not cause deaths in 2009 L'Aquila earthquake and cuts sentence of a government official.

Categories: Literature

Landing on a comet: A guide to Rosetta’s perilous mission

Nature - Mon, 11/10/2014 - 01:00

Landing on a comet: A guide to Rosetta’s perilous mission

Nature 515, 7526 (2014). http://www.nature.com/doifinder/10.1038/515172a

Author: Elizabeth Gibney

A graphical guide identifies the dangers ahead for the Philae probe.

Categories: Literature

Organized Chinese Crime Behind Tanzania's Elephant Slaughter, Report Says

Yale Environment 360 - Fri, 11/07/2014 - 10:28

Chinese-led criminal organizations have been conspiring with corrupt Tanzanian officials to traffic huge amounts

Poached elephant skull in Selous Reserve of ivory — a trade that has caused half of Tanzania’s elephants to be poached in the past five years — according to a report by the London-based Environmental Investigation Agency. In some cases, Chinese military officials appeared to be complicit in the illegal activities, the report says, and in other instances, prominent Tanzanian businessmen and politicians helped protect ivory traffickers. Tanzania is the largest source of poached ivory in the world, and China is the largest importer of smuggled tusks, according to EIA. Tanzania’s famed Selous Reserve saw its elephant population plunge by 67 percent in four years, from 50,000 animals to 13,000. Tanzania appears to have lost more elephants to poaching during this period than any other country, EIA said.

Categories: Environmental News

What Is the Carbon Limit? That Depends Who You Ask

Yale Environment 360 - Thu, 11/06/2014 - 07:30

Scientists are offering widely varying estimates of how much carbon we can emit into the atmosphere without causing dangerous climate change. But establishing a so-called carbon budget is critical if we are to keep the planet a safe place to live in the coming century. BY FRED PEARCE

Categories: Environmental News

Infectious disease: Tough choices to reduce Ebola transmission

Nature - Thu, 11/06/2014 - 01:00

Infectious disease: Tough choices to reduce Ebola transmission

Nature 515, 7526 (2014). doi:10.1038/515192a

Authors: Christopher J. M. Whitty, Jeremy Farrar, Neil Ferguson, W. John Edmunds, Peter Piot, Melissa Leach & Sally C. Davies

Christopher J. M. Whitty and colleagues explain why the United Kingdom is funding many small community centres to isolate suspected cases in Sierra Leone.

Categories: Literature

Scientists Call For Greater Diversity of Viewpoints on Conservation

Yale Environment 360 - Thu, 11/06/2014 - 00:45

In a call to arms published this week in the journal Nature, a group of more than 200 environmental scientists, academics and others involved in the fields of conservation research, policy and advocacy, condemned what they called a lack of diversity within their ranks and the philosophical polarization they say it has engendered. Spearheaded by Heather Tallis, lead scientist at the Nature Conservancy, and Jane Lubchenco, a professor of marine biology at Oregon State University and former head of the National Oceanic and Atmospheric Administration, the commentary argues that a once-spirited but constructive debate between two conservation philosophies — one viewing nature as intrinsically valuable, the other connecting its value with its utility — was now mired in vitriol and acrimony. "We believe that this situation is stifling productive discourse, inhibiting funding and halting progress," the authors wrote, adding that the situation was being made worse because the "dispute has become dominated by only a few voices, nearly all of them men’s."

Categories: Environmental News

Lobbying sways NIH grants

Nature - Wed, 11/05/2014 - 18:00

Lobbying sways NIH grants

Nature 515, 7525 (2014). http://www.nature.com/doifinder/10.1038/515019a

Author: Sara Reardon

Pressure on lawmakers from patient-advocacy groups has shaped agency spending on rare-disease research.

Categories: Literature

Norway Best Prepared Nation For Climate Change, Global Index Shows

Yale Environment 360 - Wed, 11/05/2014 - 10:25

Norway is the best prepared country for climate change, and has been so for almost 20 years, according to

Lofoten, Norway rankings compiled by the University of Notre Dame. New Zealand, Sweden, Finland, and Denmark rounded out the top five, while Chad, Burundi, Eritrea, Central African Republic, and Congo make up the bottom of the Global Adaptation Index. The rankings highlight the disparities between the world’s relatively wealthy, developed nations and its developing economies when it comes to dealing with climate change. Many of the highest ranking countries do face moderate exposure to climate change, the researchers said, but access to amenities such as electricity, sanitation, clean drinking water, and functional governance have left them better prepared. The economies of many developing countries, however, depend on natural resources, which makes their political and economic stability more susceptible to climate change. The index ranked 178 countries on their vulnerability and readiness to adapt to natural disasters associated with global warming.

Categories: Environmental News

Biochemistry: Succinate strikes

Nature - Wed, 11/05/2014 - 01:00

Biochemistry: Succinate strikes

Nature 515, 7527 (2014). doi:10.1038/nature13941

Authors: Luke A. J. O'Neill

The high levels of tissue-damaging reactive oxygen species that arise during a stroke or heart attack have been shown to be generated through the accumulation of the metabolic intermediate succinate. See Letter p.431

Categories: Literature

Approaching disorder-free transport in high-mobility conjugated polymers

Nature - Wed, 11/05/2014 - 01:00

Approaching disorder-free transport in high-mobility conjugated polymers

Nature 515, 7527 (2014). doi:10.1038/nature13854

Authors: Deepak Venkateshvaran, Mark Nikolka, Aditya Sadhanala, Vincent Lemaur, Mateusz Zelazny, Michal Kepa, Michael Hurhangee, Auke Jisk Kronemeijer, Vincenzo Pecunia, Iyad Nasrallah, Igor Romanov, Katharina Broch, Iain McCulloch, David Emin, Yoann Olivier, Jerome Cornil, David Beljonne & Henning Sirringhaus

Conjugated polymers enable the production of flexible semiconductor devices that can be processed from solution at low temperatures. Over the past 25 years, device performance has improved greatly as a wide variety of molecular structures have been studied. However, one major limitation has not been overcome; transport properties in polymer films are still limited by pervasive conformational and energetic disorder. This not only limits the rational design of materials with higher performance, but also prevents the study of physical phenomena associated with an extended π-electron delocalization along the polymer backbone. Here we report a comparative transport study of several high-mobility conjugated polymers by field-effect-modulated Seebeck, transistor and sub-bandgap optical absorption measurements. We show that in several of these polymers, most notably in a recently reported, indacenodithiophene-based donor–acceptor copolymer with a near-amorphous microstructure, the charge transport properties approach intrinsic disorder-free limits at which all molecular sites are thermally accessible. Molecular dynamics simulations identify the origin of this long sought-after regime as a planar, torsion-free backbone conformation that is surprisingly resilient to side-chain disorder. Our results provide molecular-design guidelines for ‘disorder-free’ conjugated polymers.

Categories: Literature

Ischaemic accumulation of succinate controls reperfusion injury through mitochondrial ROS

Nature - Wed, 11/05/2014 - 01:00

Ischaemic accumulation of succinate controls reperfusion injury through mitochondrial ROS

Nature 515, 7527 (2014). doi:10.1038/nature13909

Authors: Edward T. Chouchani, Victoria R. Pell, Edoardo Gaude, Dunja Aksentijević, Stephanie Y. Sundier, Ellen L. Robb, Angela Logan, Sergiy M. Nadtochiy, Emily N. J. Ord, Anthony C. Smith, Filmon Eyassu, Rachel Shirley, Chou-Hui Hu, Anna J. Dare, Andrew M. James, Sebastian Rogatti, Richard C. Hartley, Simon Eaton, Ana S. H. Costa, Paul S. Brookes, Sean M. Davidson, Michael R. Duchen, Kourosh Saeb-Parsy, Michael J. Shattock, Alan J. Robinson, Lorraine M. Work, Christian Frezza, Thomas Krieg & Michael P. Murphy

Ischaemia-reperfusion injury occurs when the blood supply to an organ is disrupted and then restored, and underlies many disorders, notably heart attack and stroke. While reperfusion of ischaemic tissue is essential for survival, it also initiates oxidative damage, cell death and aberrant immune responses through the generation of mitochondrial reactive oxygen species (ROS). Although mitochondrial ROS production in ischaemia reperfusion is established, it has generally been considered a nonspecific response to reperfusion. Here we develop a comparative in vivo metabolomic analysis, and unexpectedly identify widely conserved metabolic pathways responsible for mitochondrial ROS production during ischaemia reperfusion. We show that selective accumulation of the citric acid cycle intermediate succinate is a universal metabolic signature of ischaemia in a range of tissues and is responsible for mitochondrial ROS production during reperfusion. Ischaemic succinate accumulation arises from reversal of succinate dehydrogenase, which in turn is driven by fumarate overflow from purine nucleotide breakdown and partial reversal of the malate/aspartate shuttle. After reperfusion, the accumulated succinate is rapidly re-oxidized by succinate dehydrogenase, driving extensive ROS generation by reverse electron transport at mitochondrial complex I. Decreasing ischaemic succinate accumulation by pharmacological inhibition is sufficient to ameliorate in vivo ischaemia-reperfusion injury in murine models of heart attack and stroke. Thus, we have identified a conserved metabolic response of tissues to ischaemia and reperfusion that unifies many hitherto unconnected aspects of ischaemia-reperfusion injury. Furthermore, these findings reveal a new pathway for metabolic control of ROS production in vivo, while demonstrating that inhibition of ischaemic succinate accumulation and its oxidation after subsequent reperfusion is a potential therapeutic target to decrease ischaemia-reperfusion injury in a range of pathologies.

Categories: Literature

The participation of cortical amygdala in innate, odour-driven behaviour

Nature - Wed, 11/05/2014 - 01:00

The participation of cortical amygdala in innate, odour-driven behaviour

Nature 515, 7526 (2014). doi:10.1038/nature13897

Authors: Cory M. Root, Christine A. Denny, René Hen & Richard Axel

Innate behaviours are observed in naive animals without prior learning or experience, suggesting that the neural circuits that mediate these behaviours are genetically determined and stereotyped. The neural circuits that convey olfactory information from the sense organ to the cortical and subcortical olfactory centres have been anatomically defined, but the specific pathways responsible for innate responses to volatile odours have not been identified. Here we devise genetic strategies that demonstrate that a stereotyped neural circuit that transmits information from the olfactory bulb to cortical amygdala is necessary for innate aversive and appetitive behaviours. Moreover, we use the promoter of the activity-dependent gene arc to express the photosensitive ion channel, channelrhodopsin, in neurons of the cortical amygdala activated by odours that elicit innate behaviours. Optical activation of these neurons leads to appropriate behaviours that recapitulate the responses to innate odours. These data indicate that the cortical amygdala plays a critical role in generating innate odour-driven behaviours but do not preclude its participation in learned olfactory behaviours.

Categories: Literature

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