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Therapies: Progressive steps

Nature - Wed, 11/30/2016 - 01:00

Therapies: Progressive steps

Nature. doi:10.1038/540S7a

Author: Elie Dolgin

New drugs are beginning to show promise for people with one of the less common, and harder to treat, forms of multiple sclerosis.

Categories: Literature

Perspective: Who dares, wins

Nature - Wed, 11/30/2016 - 01:00

Perspective: Who dares, wins

Nature. doi:10.1038/540S10a

Author: Bibi Bielekova

It is time for a bolder approach to developing drugs for progressive multiple sclerosis, says Bibi Bielekova.

Categories: Literature

Stem cells: Stemming the tide

Nature - Wed, 11/30/2016 - 01:00

Stem cells: Stemming the tide

Nature. doi:10.1038/540S11a

Author: Asher Mullard

Could a high-risk treatment play a part in tackling multiple sclerosis?

Categories: Literature

Diet: Changing the recipe

Nature - Wed, 11/30/2016 - 01:00

Diet: Changing the recipe

Nature. doi:10.1038/540S13a

Author: Sujata Gupta

Dietary changes may be able to alleviate the symptoms of multiple sclerosis, but testing the effects of diet will need a different protocol to the one used for drugs.

Categories: Literature

Consistency in large pharmacogenomic studies

Nature - Wed, 11/30/2016 - 01:00

Consistency in large pharmacogenomic studies

Nature 540, 7631 (2016). doi:10.1038/nature19838

Authors: Paul Geeleher, Eric R. Gamazon, Cathal Seoighe, Nancy J. Cox & R. Stephanie Huang

arising fromB.Haibe-Kainset al. Nature504, 389–393 (2013); doi:10.1038/nature12831Haibe-Kains et al. reported inconsistency between two large-scale pharmacogenomic studies—the Cancer Cell Line Encyclopedia (CCLE) and the Cancer Genome Project (CGP). Upon careful analysis of the

Categories: Literature

Safikhani et al. reply

Nature - Wed, 11/30/2016 - 01:00

Safikhani et al. reply

Nature 540, 7631 (2016). doi:10.1038/nature19839

Authors: Zhaleh Safikhani, Nehme El-Hachem, Petr Smirnov, Mark Freeman, Anna Goldenberg, Nicolai J. Birkbak, Andrew H. Beck, Hugo J. W. L. Aerts, John Quackenbush & Benjamin Haibe-Kains

replying toP.Geeleher, E. R.Gamazon, C.Seoighe, N. J.Cox & R. S.HuangNature540, http://dx.doi.org/10.1038/nature19838 (2016).In the accompanying Comment, Geeleher et al. claim to have discovered overall consistency between the

Categories: Literature

Consistency in drug response profiling

Nature - Wed, 11/30/2016 - 01:00

Consistency in drug response profiling

Nature 540, 7631 (2016). doi:10.1038/nature20171

Authors: John Patrick Mpindi, Bhagwan Yadav, Päivi Östling, Prson Gautam, Disha Malani, Astrid Murumägi, Akira Hirasawa, Sara Kangaspeska, Krister Wennerberg, Olli Kallioniemi & Tero Aittokallio

arising fromB.Haibe-Kainset al. Nature504, 389–393 (2013); doi:10.1038/nature12831The comparative analysis by Haibe-Kains et al. concluded that data from two large-scale studies of cancer cell lines showed highly discordant results for drug sensitivity measurements, whereas

Categories: Literature

Safikhani et al. reply

Nature - Wed, 11/30/2016 - 01:00

Safikhani et al. reply

Nature 540, 7631 (2016). doi:10.1038/nature20172

Authors: Zhaleh Safikhani, Nehme El-Hachem, Petr Smirnov, Mark Freeman, Anna Goldenberg, Nicolai J. Birkbak, Andrew H. Beck, Hugo J. W. L. Aerts, John Quackenbush & Benjamin Haibe-Kains

replying toJ. P.Mpindiet al. Nature540, http://dx.doi.org/10.1038/nature20171 (2016).The accompanying Comment by Mpindi et al. is an important contribution to the discussion of pharmacogenomic consistency for several reasons. Mpindi et al. were able

Categories: Literature

Drug response consistency in CCLE and CGP

Nature - Wed, 11/30/2016 - 01:00

Drug response consistency in CCLE and CGP

Nature 540, 7631 (2016). doi:10.1038/nature20580

Authors: Mehdi Bouhaddou, Matthew S. DiStefano, Eric A. Riesel, Emilce Carrasco, Hadassa Y. Holzapfel, DeAnalisa C. Jones, Gregory R. Smith, Alan D. Stern, Sulaiman S. Somani, T. Victoria Thompson & Marc R. Birtwistle

arising fromB.Haibe-Kainset al. Nature504, 389–393 (2013); doi:10.1038/nature12831The Cancer Cell Line Encyclopedia (CCLE) and Cancer Genome Project (CGP) are two independent large-scale efforts to characterize genomes, mRNA expression, and anti-cancer drug dose–responses across cell lines,

Categories: Literature

Safikhani et al. reply

Nature - Wed, 11/30/2016 - 01:00

Safikhani et al. reply

Nature 540, 7631 (2016). doi:10.1038/nature20581

Authors: Zhaleh Safikhani, Nehme El-Hachem, Petr Smirnov, Mark Freeman, Anna Goldenberg, Nicolai J. Birkbak, Andrew H. Beck, Hugo J. W. L. Aerts, John Quackenbush & Benjamin Haibe-Kains

replying toM.Bouhaddouet al. Nature540, http://dx.doi.org/10.1038/nature20580 (2016).In the accompanying Comment, the authors make two main claims: (1) that viability metrics computed over the drug concentration range shared between datasets yield higher consistency than the same

Categories: Literature

Planetary science: Pluto's telltale heart

Nature - Wed, 11/30/2016 - 01:00

Planetary science: Pluto's telltale heart

Nature 540, 7631 (2016). doi:10.1038/540042a

Authors: Amy C. Barr

Studies of a large frost-filled basin on Pluto show that this feature altered the dwarf planet's spin axis, driving tectonic activity on its surface, and hint at the presence of a subsurface ocean. See Letters p.86, p.90, p.94 & p.97

Categories: Literature

Cell biology: Sort of unexpected

Nature - Wed, 11/30/2016 - 01:00

Cell biology: Sort of unexpected

Nature 540, 7631 (2016). doi:10.1038/540045a

Authors: Martin R. Pool

To reach the cell surface, membrane proteins are first targeted to an organelle called the endoplasmic reticulum. Several targeting pathways are known, but it now emerges that there is yet another pathway. See Letter p.134

Categories: Literature

Biogeochemistry: Projections of the soil-carbon deficit

Nature - Wed, 11/30/2016 - 01:00

Biogeochemistry: Projections of the soil-carbon deficit

Nature 540, 7631 (2016). doi:10.1038/540047a

Authors: Eric A. Davidson

Changes in the amount of carbon stored in soil might be a crucial feedback to climate change. Experimental field studies show that warming-induced soil carbon losses are greatest where carbon stocks are largest. See Letter p.104

Categories: Literature

The rapid formation of Sputnik Planitia early in Pluto’s history

Nature - Wed, 11/30/2016 - 01:00

The rapid formation of Sputnik Planitia early in Pluto’s history

Nature 540, 7631 (2016). doi:10.1038/nature20586

Authors: Douglas P. Hamilton, S. A. Stern, J. M. Moore & L. A. Young

Pluto’s Sputnik Planitia is a bright, roughly circular feature that resembles a polar ice cap. It is approximately 1,000 kilometres across and is centred on a latitude of 25 degrees north and a longitude of 175 degrees, almost directly opposite the side of Pluto that always faces Charon as a result of tidal locking. One explanation for its location includes the formation of a basin in a giant impact, with subsequent upwelling of a dense interior ocean. Once the basin was established, ice would naturally have accumulated there. Then, provided that the basin was a positive gravity anomaly (with or without the ocean), true polar wander could have moved the feature towards the Pluto–Charon tidal axis, on the far side of Pluto from Charon. Here we report modelling that shows that ice quickly accumulates on Pluto near latitudes of 30 degrees north and south, even in the absence of a basin, because, averaged over its orbital period, those are Pluto’s coldest regions. Within a million years of Charon’s formation, ice deposits on Pluto concentrate into a single cap centred near a latitude of 30 degrees, owing to the runaway albedo effect. This accumulation of ice causes a positive gravity signature that locks, as Pluto’s rotation slows, to a longitude directly opposite Charon. Once locked, Charon raises a permanent tidal bulge on Pluto, which greatly enhances the gravity signature of the ice cap. Meanwhile, the weight of the ice in Sputnik Planitia causes the crust under it to slump, creating its own basin (as has happened on Earth in Greenland). Even if the feature is now a modest negative gravity anomaly, it remains locked in place because of the permanent tidal bulge raised by Charon. Any movement of the feature away from 30 degrees latitude is countered by the preferential recondensation of ices near the coldest extremities of the cap. Therefore, our modelling suggests that Sputnik Planitia formed shortly after Charon did and has been stable, albeit gradually losing volume, over the age of the Solar System.

Categories: Literature

Ghost imaging with atoms

Nature - Wed, 11/30/2016 - 01:00

Ghost imaging with atoms

Nature 540, 7631 (2016). doi:10.1038/nature20154

Authors: R. I. Khakimov, B. M. Henson, D. K. Shin, S. S. Hodgman, R. G. Dall, K. G. H. Baldwin & A. G. Truscott

Ghost imaging is a counter-intuitive phenomenon—first realized in quantum optics—that enables the image of a two-dimensional object (mask) to be reconstructed using the spatio-temporal properties of a beam of particles with which it never interacts. Typically, two beams of correlated photons are used: one passes through the mask to a single-pixel (bucket) detector while the spatial profile of the other is measured by a high-resolution (multi-pixel) detector. The second beam never interacts with the mask. Neither detector can reconstruct the mask independently, but temporal cross-correlation between the two beams can be used to recover a ‘ghost’ image. Here we report the realization of ghost imaging using massive particles instead of photons. In our experiment, the two beams are formed by correlated pairs of ultracold, metastable helium atoms, which originate from s-wave scattering of two colliding Bose–Einstein condensates. We use higher-order Kapitza–Dirac scattering to generate a large number of correlated atom pairs, enabling the creation of a clear ghost image with submillimetre resolution. Future extensions of our technique could lead to the realization of ghost interference, and enable tests of Einstein–Podolsky–Rosen entanglement and Bell’s inequalities with atoms.

Categories: Literature

Quantifying global soil carbon losses in response to warming

Nature - Wed, 11/30/2016 - 01:00

Quantifying global soil carbon losses in response to warming

Nature 540, 7631 (2016). doi:10.1038/nature20150

Authors: T. W. Crowther, K. E. O. Todd-Brown, C. W. Rowe, W. R. Wieder, J. C. Carey, M. B. Machmuller, B. L. Snoek, S. Fang, G. Zhou, S. D. Allison, J. M. Blair, S. D. Bridgham, A. J. Burton, Y. Carrillo, P. B. Reich, J. S. Clark, A. T. Classen, F. A. Dijkstra, B. Elberling, B. A. Emmett, M. Estiarte, S. D. Frey, J. Guo, J. Harte, L. Jiang, B. R. Johnson, G. Kröel-Dulay, K. S. Larsen, H. Laudon, J. M. Lavallee, Y. Luo, M. Lupascu, L. N. Ma, S. Marhan, A. Michelsen, J. Mohan, S. Niu, E. Pendall, J. Peñuelas, L. Pfeifer-Meister, C. Poll, S. Reinsch, L. L. Reynolds, I. K. Schmidt, S. Sistla, N. W. Sokol, P. H. Templer, K. K. Treseder, J. M. Welker & M. A. Bradford

The majority of the Earth’s terrestrial carbon is stored in the soil. If anthropogenic warming stimulates the loss of this carbon to the atmosphere, it could drive further planetary warming. Despite evidence that warming enhances carbon fluxes to and from the soil, the net global balance between these responses remains uncertain. Here we present a comprehensive analysis of warming-induced changes in soil carbon stocks by assembling data from 49 field experiments located across North America, Europe and Asia. We find that the effects of warming are contingent on the size of the initial soil carbon stock, with considerable losses occurring in high-latitude areas. By extrapolating this empirical relationship to the global scale, we provide estimates of soil carbon sensitivity to warming that may help to constrain Earth system model projections. Our empirical relationship suggests that global soil carbon stocks in the upper soil horizons will fall by 30 ± 30 petagrams of carbon to 203 ± 161 petagrams of carbon under one degree of warming, depending on the rate at which the effects of warming are realized. Under the conservative assumption that the response of soil carbon to warming occurs within a year, a business-as-usual climate scenario would drive the loss of 55 ± 50 petagrams of carbon from the upper soil horizons by 2050. This value is around 12–17 per cent of the expected anthropogenic emissions over this period. Despite the considerable uncertainty in our estimates, the direction of the global soil carbon response is consistent across all scenarios. This provides strong empirical support for the idea that rising temperatures will stimulate the net loss of soil carbon to the atmosphere, driving a positive land carbon–climate feedback that could accelerate climate change.

Categories: Literature

Genomic evolution and chemoresistance in germ-cell tumours

Nature - Wed, 11/30/2016 - 01:00

Genomic evolution and chemoresistance in germ-cell tumours

Nature 540, 7631 (2016). doi:10.1038/nature20596

Authors: Amaro Taylor-Weiner, Travis Zack, Elizabeth O’Donnell, Jennifer L. Guerriero, Brandon Bernard, Anita Reddy, G. Celine Han, Saud AlDubayan, Ali Amin-Mansour, Steven E. Schumacher, Kevin Litchfield, Clare Turnbull, Stacey Gabriel, Rameen Beroukhim, Gad Getz, Scott L. Carter, Michelle S. Hirsch, Anthony Letai, Christopher Sweeney & Eliezer M Van Allen

Germ-cell tumours (GCTs) are derived from germ cells and occur most frequently in the testes. GCTs are histologically heterogeneous and distinctly curable with chemotherapy. Gains of chromosome arm 12p and aneuploidy are nearly universal in GCTs, but specific somatic genomic features driving tumour initiation, chemosensitivity and progression are incompletely characterized. Here, using clinical whole-exome and transcriptome sequencing of precursor, primary (testicular and mediastinal) and chemoresistant metastatic human GCTs, we show that the primary somatic feature of GCTs is highly recurrent chromosome arm level amplifications and reciprocal deletions (reciprocal loss of heterozygosity), variations that are significantly enriched in GCTs compared to 19 other cancer types. These tumours also acquire KRAS mutations during the development from precursor to primary disease, and primary testicular GCTs (TGCTs) are uniformly wild type for TP53. In addition, by functional measurement of apoptotic signalling (BH3 profiling) of fresh tumour and adjacent tissue, we find that primary TGCTs have high mitochondrial priming that facilitates chemotherapy-induced apoptosis. Finally, by phylogenetic analysis of serial TGCTs that emerge with chemotherapy resistance, we show how TGCTs gain additional reciprocal loss of heterozygosity and that this is associated with loss of pluripotency markers (NANOG and POU5F1) in chemoresistant teratomas or transformed carcinomas. Our results demonstrate the distinct genomic features underlying the origins of this disease and associated with the chemosensitivity phenotype, as well as the rare progression to chemoresistance. These results identify the convergence of cancer genomics, mitochondrial priming and GCT evolution, and may provide insights into chemosensitivity and resistance in other cancers.

Categories: Literature

The SND proteins constitute an alternative targeting route to the endoplasmic reticulum

Nature - Wed, 11/30/2016 - 01:00

The SND proteins constitute an alternative targeting route to the endoplasmic reticulum

Nature 540, 7631 (2016). doi:10.1038/nature20169

Authors: Naama Aviram, Tslil Ast, Elizabeth A. Costa, Eric C. Arakel, Silvia G. Chuartzman, Calvin H. Jan, Sarah Haßdenteufel, Johanna Dudek, Martin Jung, Stefan Schorr, Richard Zimmermann, Blanche Schwappach, Jonathan S. Weissman & Maya Schuldiner

In eukaryotes, up to one-third of cellular proteins are targeted to the endoplasmic reticulum, where they undergo folding, processing, sorting and trafficking to subsequent endomembrane compartments. Targeting to the endoplasmic reticulum has been shown to occur co-translationally by the signal recognition particle (SRP) pathway or post-translationally by the mammalian transmembrane recognition complex of 40 kDa (TRC40) and homologous yeast guided entry of tail-anchored proteins (GET) pathways. Despite the range of proteins that can be catered for by these two pathways, many proteins are still known to be independent of both SRP and GET, so there seems to be a critical need for an additional dedicated pathway for endoplasmic reticulum relay. We set out to uncover additional targeting proteins using unbiased high-content screening approaches. To this end, we performed a systematic visual screen using the yeast Saccharomyces cerevisiae, and uncovered three uncharacterized proteins whose loss affected targeting. We suggest that these proteins work together and demonstrate that they function in parallel with SRP and GET to target a broad range of substrates to the endoplasmic reticulum. The three proteins, which we name Snd1, Snd2 and Snd3 (for SRP-independent targeting), can synthetically compensate for the loss of both the SRP and GET pathways, and act as a backup targeting system. This explains why it has previously been difficult to demonstrate complete loss of targeting for some substrates. Our discovery thus puts in place an essential piece of the endoplasmic reticulum targeting puzzle, highlighting how the targeting apparatus of the eukaryotic cell is robust, interlinked and flexible.

Categories: Literature

Soils Could Release 55 Trillion Kilograms of Carbon By Mid-Century

Yale Environment 360 - Wed, 11/30/2016 - 00:24

The world’s soils act as critical storage for carbon, sequestering carbon from the atmosphere to fuel plant and microbial activity.

Permafrost in Greenland. But scientists warned this week that as soils warm in response to climate change, they could release 55 trillion kilograms of carbon by mid-century — roughly equivalent to the projected emissions of the United States, or 17 percent of all countries, during that same period. The largest losses will be from high-latitude ecosystems, the new study, led by scientists at the Yale School of Forestry & Environmental Studies and published in the journal Nature, said. This includes Arctic and sub-Arctic permafrost, where colder temperatures and slow microbial activity have led to the buildup of massive carbon reserves over thousands of years. The scientists found that for every 1 degree Celsius of global warming, soils will release approximately 30 trillion kilograms of carbon into the atmosphere, or twice the annual emissions from human activities.

Categories: Environmental News

Academia must resist political confirmation bias

Nature - Tue, 11/29/2016 - 01:00

Academia must resist political confirmation bias

Nature 540, 7631 (2016). doi:10.1038/540007a

It is crucial to fight discrimination in all its forms, but it is unhelpful to exclude conservative voices from debate.

Categories: Literature

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