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Showing papers by "Uppsala University published in 2014"



Journal ArticleDOI
TL;DR: AliView is an alignment viewer and editor designed to meet the requirements of next-generation sequencing era phylogenetic datasets and works as an easy-to-use alignment editor for small as well as large datasets.
Abstract: Summary: AliView is an alignment viewer and editor designed to meet the requirements of next-generation sequencing era phylogenetic datasets. AliView handles alignments of unlimited size in the formats most commonly used, i.e. FASTA, Phylip, Nexus, Clustal and MSF. The intuitive graphical interface makes it easy to inspect, sort, delete, merge and realign sequences as part of the manual filtering process of large datasets. AliView also works as an easy-to-use alignment editor for small as well as large datasets. Availability and implementation: AliView is released as open-source software under the GNU General Public License, version 3.0 (GPLv3), and is available at GitHub (www.github.com/AliView). The program is cross-platform and extensively tested on Linux, Mac OS X and Windows systems. Downloads and help are available at http://ormbunkar.se/aliview Contact: es.uu.cbe@nossral.sredna Supplementary information: Supplementary data are available at Bioinformatics online.

2,071 citations


Journal ArticleDOI
TL;DR: This work focuses on nature as represented by aspects of the physical environment relevant to planning, design, and policy measures that serve broad segments of urbanized societies and considers research on pathways between nature and health involving air quality, physical activity, social cohesion, and stress reduction.
Abstract: Urbanization, resource exploitation, and lifestyle changes have diminished possibilities for human contact with nature in many societies. Concern about the loss has helped motivate research on the health benefits of contact with nature. Reviewing that research here, we focus on nature as represented by aspects of the physical environment relevant to planning, design, and policy measures that serve broad segments of urbanized societies. We discuss difficulties in defining “nature” and reasons for the current expansion of the research field, and we assess available reviews. We then consider research on pathways between nature and health involving air quality, physical activity, social cohesion, and stress reduction. Finally, we discuss methodological issues and priorities for future research. The extant research does describe an array of benefits of contact with nature, and evidence regarding some benefits is strong; however, some findings indicate caution is needed in applying beliefs about those benefits,...

2,046 citations


Journal ArticleDOI
Andrew R. Wood1, Tõnu Esko2, Jian Yang3, Sailaja Vedantam4  +441 moreInstitutions (132)
TL;DR: This article identified 697 variants at genome-wide significance that together explained one-fifth of the heritability for adult height, and all common variants together captured 60% of heritability.
Abstract: Using genome-wide data from 253,288 individuals, we identified 697 variants at genome-wide significance that together explained one-fifth of the heritability for adult height. By testing different numbers of variants in independent studies, we show that the most strongly associated ∼2,000, ∼3,700 and ∼9,500 SNPs explained ∼21%, ∼24% and ∼29% of phenotypic variance. Furthermore, all common variants together captured 60% of heritability. The 697 variants clustered in 423 loci were enriched for genes, pathways and tissue types known to be involved in growth and together implicated genes and pathways not highlighted in earlier efforts, such as signaling by fibroblast growth factors, WNT/β-catenin and chondroitin sulfate-related genes. We identified several genes and pathways not previously connected with human skeletal growth, including mTOR, osteoglycin and binding of hyaluronic acid. Our results indicate a genetic architecture for human height that is characterized by a very large but finite number (thousands) of causal variants.

1,872 citations


Journal ArticleDOI
Erich D. Jarvis1, Siavash Mirarab2, Andre J. Aberer3, Bo Li4, Bo Li5, Bo Li6, Peter Houde7, Cai Li4, Cai Li5, Simon Y. W. Ho8, Brant C. Faircloth9, Benoit Nabholz, Jason T. Howard1, Alexander Suh10, Claudia C. Weber10, Rute R. da Fonseca11, Jianwen Li, Fang Zhang Zhang, Hui Li, Long Zhou, Nitish Narula12, Nitish Narula7, Liang Liu13, Ganesh Ganapathy1, Bastien Boussau, Shamsuzzoha Bayzid2, Volodymyr Zavidovych1, Sankar Subramanian14, Toni Gabaldón15, Salvador Capella-Gutierrez, Jaime Huerta-Cepas, Bhanu Rekepalli16, Bhanu Rekepalli17, Kasper Munch18, Mikkel H. Schierup18, Bent E. K. Lindow11, Wesley C. Warren19, David A. Ray, Richard E. Green20, Michael William Bruford21, Xiangjiang Zhan22, Xiangjiang Zhan21, Andrew Dixon, Shengbin Li6, Ning Li23, Yinhua Huang23, Elizabeth P. Derryberry24, Elizabeth P. Derryberry25, Mads F. Bertelsen26, Frederick H. Sheldon24, Robb T. Brumfield24, Claudio V. Mello27, Claudio V. Mello28, Peter V. Lovell28, Morgan Wirthlin28, Maria Paula Cruz Schneider27, Francisco Prosdocimi27, José Alfredo Samaniego11, Amhed Missael Vargas Velazquez11, Alonzo Alfaro-Núñez11, Paula F. Campos11, Bent O. Petersen29, Thomas Sicheritz-Pontén29, An Pas, Thomas L. Bailey, R. Paul Scofield30, Michael Bunce31, David M. Lambert14, Qi Zhou, Polina L. Perelman32, Amy C. Driskell33, Beth Shapiro20, Zijun Xiong, Yongli Zeng, Shiping Liu, Zhenyu Li, Binghang Liu, Kui Wu, Jin Xiao, Xiong Yinqi, Quiemei Zheng, Yong Zhang, Huanming Yang, Jian Wang, Linnéa Smeds10, Frank E. Rheindt34, Michael J. Braun35, Jon Fjeldså11, Ludovic Orlando11, F. Keith Barker5, Knud A. Jønsson5, Warren E. Johnson33, Klaus-Peter Koepfli33, Stephen J. O'Brien36, David Haussler, Oliver A. Ryder, Carsten Rahbek5, Eske Willerslev11, Gary R. Graves33, Gary R. Graves5, Travis C. Glenn13, John E. McCormack37, Dave Burt38, Hans Ellegren10, Per Alström, Scott V. Edwards39, Alexandros Stamatakis3, David P. Mindell40, Joel Cracraft5, Edward L. Braun41, Tandy Warnow42, Tandy Warnow2, Wang Jun, M. Thomas P. Gilbert5, M. Thomas P. Gilbert31, Guojie Zhang11, Guojie Zhang4 
12 Dec 2014-Science
TL;DR: A genome-scale phylogenetic analysis of 48 species representing all orders of Neoaves recovered a highly resolved tree that confirms previously controversial sister or close relationships and identifies the first divergence in Neoaves, two groups the authors named Passerea and Columbea.
Abstract: To better determine the history of modern birds, we performed a genome-scale phylogenetic analysis of 48 species representing all orders of Neoaves using phylogenomic methods created to handle genome-scale data. We recovered a highly resolved tree that confirms previously controversial sister or close relationships. We identified the first divergence in Neoaves, two groups we named Passerea and Columbea, representing independent lineages of diverse and convergently evolved land and water bird species. Among Passerea, we infer the common ancestor of core landbirds to have been an apex predator and confirm independent gains of vocal learning. Among Columbea, we identify pigeons and flamingoes as belonging to sister clades. Even with whole genomes, some of the earliest branches in Neoaves proved challenging to resolve, which was best explained by massive protein-coding sequence convergence and high levels of incomplete lineage sorting that occurred during a rapid radiation after the Cretaceous-Paleogene mass extinction event about 66 million years ago.

1,624 citations


Journal ArticleDOI
12 Jun 2014-PLOS ONE
TL;DR: The additional genes identified in this study, have an array of functions previously implicated in Alzheimer's disease, including aspects of energy metabolism, protein degradation and the immune system and add further weight to these pathways as potential therapeutic targets in Alzheimers disease.
Abstract: Background: Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This s ...

1,518 citations


Journal ArticleDOI
TL;DR: Prevalence of sarcopenia is substantial in most geriatric settings, and well-designed, standardised studies evaluating exercise or nutrition interventions are needed before treatment guidelines can be developed.
Abstract: OBJECTIVE: to examine the clinical evidence reporting the prevalence of sarcopenia and the effect of nutrition and exercise interventions from studies using the consensus definition of sarcopenia proposed by the European Working Group on Sarcopenia in Older People (EWGSOP).METHODS: PubMed and Dialog databases were searched (January 2000-October 2013) using pre-defined search terms. Prevalence studies and intervention studies investigating muscle mass plus strength or function outcome measures using the EWGSOP definition of sarcopenia, in well-defined populations of adults aged ≥50 years were selected.RESULTS: prevalence of sarcopenia was, with regional and age-related variations, 1-29% in community-dwelling populations, 14-33% in long-term care populations and 10% in the only acute hospital-care population examined. Moderate quality evidence suggests that exercise interventions improve muscle strength and physical performance. The results of nutrition interventions are equivocal due to the low number of studies and heterogeneous study design. Essential amino acid (EAA) supplements, including ∼2.5 g of leucine, and β-hydroxy β-methylbutyric acid (HMB) supplements, show some effects in improving muscle mass and function parameters. Protein supplements have not shown consistent benefits on muscle mass and function.CONCLUSION: prevalence of sarcopenia is substantial in most geriatric settings. Well-designed, standardised studies evaluating exercise or nutrition interventions are needed before treatment guidelines can be developed. Physicians should screen for sarcopenia in both community and geriatric settings, with diagnosis based on muscle mass and function. Supervised resistance exercise is recommended for individuals with sarcopenia. EAA (with leucine) and HMB may improve muscle outcomes.

1,415 citations


Journal ArticleDOI
TL;DR: Global rates of change suggest that only 16 countries will achieve the MDG 5 target by 2015, with evidence of continued acceleration in the MMR, and MMR was highest in the oldest age groups in both 1990 and 2013.

1,383 citations


Journal ArticleDOI
TL;DR: The ecology of antibiotics and the ability of subinhibitory concentrations to select for bacterial resistance are discussed and the effects of low-level drug exposure on bacterial physiology are considered, including the generation of genetic and phenotypic variability, as well as the able of antibiotics to function as signalling molecules.
Abstract: The widespread use of antibiotics results in the generation of antibiotic concentration gradients in humans, livestock and the environment. Thus, bacteria are frequently exposed to non-lethal (that is, subinhibitory) concentrations of drugs, and recent evidence suggests that this is likely to have an important role in the evolution of antibiotic resistance. In this Review, we discuss the ecology of antibiotics and the ability of subinhibitory concentrations to select for bacterial resistance. We also consider the effects of low-level drug exposure on bacterial physiology, including the generation of genetic and phenotypic variability, as well as the ability of antibiotics to function as signalling molecules. Together, these effects accelerate the emergence and spread of antibiotic-resistant bacteria among humans and animals.

1,226 citations


Journal ArticleDOI
M. G. Aartsen1, Markus Ackermann, Jenni Adams2, Juanan Aguilar3  +299 moreInstitutions (41)
TL;DR: Results from an analysis with a third year of data from the complete IceCube detector are consistent with the previously reported astrophysical flux in the 100 TeV-PeV range at the level of 10(-8) GeV cm-2 s-1 sr-1 per flavor and reject a purely atmospheric explanation for the combined three-year data at 5.7σ.
Abstract: A search for high-energy neutrinos interacting within the IceCube detector between 2010 and 2012 provided the first evidence for a high-energy neutrino flux of extraterrestrial origin. Results from an analysis using the same methods with a third year (2012-2013) of data from the complete IceCube detector are consistent with the previously reported astrophysical flux in the 100 TeV-PeV range at the level of 10(-8) GeV cm(-2) s(-1) sr(-1) per flavor and reject a purely atmospheric explanation for the combined three-year data at 5.7 sigma. The data are consistent with expectations for equal fluxes of all three neutrino flavors and with isotropic arrival directions, suggesting either numerous or spatially extended sources. The three-year data set, with a live time of 988 days, contains a total of 37 neutrino candidate events with deposited energies ranging from 30 to 2000 TeV. The 2000-TeV event is the highest-energy neutrino interaction ever observed.

1,183 citations



Journal ArticleDOI
TL;DR: A new term is recommended, “primary age-related tauopathy” (PART), to describe a pathology that is commonly observed in the brains of aged individuals, yet this pathological process cannot be specifically identified pre-mortem at the present time.
Abstract: We recommend a new term, "primary age-related tauopathy" (PART), to describe a pathology that is commonly observed in the brains of aged individuals. Many autopsy studies have reported brains with neurofibrillary tangles (NFTs) that are indistinguishable from those of Alzheimer's disease (AD), in the absence of amyloid (Aβ) plaques. For these "NFT+/Aβ-" brains, for which formal criteria for AD neuropathologic changes are not met, the NFTs are mostly restricted to structures in the medial temporal lobe, basal forebrain, brainstem, and olfactory areas (bulb and cortex). Symptoms in persons with PART usually range from normal to amnestic cognitive changes, with only a minority exhibiting profound impairment. Because cognitive impairment is often mild, existing clinicopathologic designations, such as "tangle-only dementia" and "tangle-predominant senile dementia", are imprecise and not appropriate for most subjects. PART is almost universally detectable at autopsy among elderly individuals, yet this pathological process cannot be specifically identified pre-mortem at the present time. Improved biomarkers and tau imaging may enable diagnosis of PART in clinical settings in the future. Indeed, recent studies have identified a common biomarker profile consisting of temporal lobe atrophy and tauopathy without evidence of Aβ accumulation. For both researchers and clinicians, a revised nomenclature will raise awareness of this extremely common pathologic change while providing a conceptual foundation for future studies. Prior reports that have elucidated features of the pathologic entity we refer to as PART are discussed, and working neuropathological diagnostic criteria are proposed.

Journal ArticleDOI
TL;DR: The abundance and size distribution of lakes is critical to quantifying limnetic contributions to the global carbon cycle as discussed by the authors, however, estimates of global lake abundance are not accurate and are unreliable.
Abstract: An accurate description of the abundance and size distribution of lakes is critical to quantifying limnetic contributions to the global carbon cycle. However, estimates of global lake abundance are ...

Journal ArticleDOI
Anubha Mahajan1, Min Jin Go, Weihua Zhang2, Jennifer E. Below3  +392 moreInstitutions (104)
TL;DR: In this paper, the authors aggregated published meta-analyses of genome-wide association studies (GWAS), including 26,488 cases and 83,964 controls of European, east Asian, south Asian and Mexican and Mexican American ancestry.
Abstract: To further understanding of the genetic basis of type 2 diabetes (T2D) susceptibility, we aggregated published meta-analyses of genome-wide association studies (GWAS), including 26,488 cases and 83,964 controls of European, east Asian, south Asian and Mexican and Mexican American ancestry. We observed a significant excess in the directional consistency of T2D risk alleles across ancestry groups, even at SNPs demonstrating only weak evidence of association. By following up the strongest signals of association from the trans-ethnic meta-analysis in an additional 21,491 cases and 55,647 controls of European ancestry, we identified seven new T2D susceptibility loci. Furthermore, we observed considerable improvements in the fine-mapping resolution of common variant association signals at several T2D susceptibility loci. These observations highlight the benefits of trans-ethnic GWAS for the discovery and characterization of complex trait loci and emphasize an exciting opportunity to extend insight into the genetic architecture and pathogenesis of human diseases across populations of diverse ancestry.

Journal ArticleDOI
TL;DR: The Randolph Glacier Inventory (RGI) as discussed by the authors is a collection of digital outlines of glaciers, excluding the ice sheets, developed to meet the needs of the Fifth Assessment of the Intergovernmental Panel on Climate Change for estimates of past and future mass balance.
Abstract: The Randolph Glacier Inventory (RGI) is a globally complete collection of digital outlines of glaciers, excluding the ice sheets, developed to meet the needs of the Fifth Assessment of the Intergovernmental Panel on Climate Change for estimates of past and future mass balance. The RGI was created with limited resources in a short period. Priority was given to completeness of coverage, but a limited, uniform set of attributes is attached to each of the � 198 000 glaciers in its latest version, 3.2. Satellite imagery from 1999-2010 provided most of the outlines. Their total extent is estimated as 726 800 � 34 000 km 2 . The uncertainty, about � 5%, is derived from careful single-glacier and basin-scale uncertainty estimates and comparisons with inventories that were not sources for the RGI. The main contributors to uncertainty are probably misinterpretation of seasonal snow cover and debris cover. These errors appear not to be normally distributed, and quantifying them reliably is an unsolved problem. Combined with digital elevation models, the RGI glacier outlines yield hypsometries that can be com- bined with atmospheric data or model outputs for analysis of the impacts of climatic change on glaciers. The RGI has already proved its value in the generation of significantly improved aggregate estimates of glacier mass changes and total volume, and thus actual and potential contributions to sea-level rise.

Journal ArticleDOI
TL;DR: The Global Burden of Disease 2013 study provides a consistent and comprehensive approach to disease estimation for between 1990 and 2013, and an opportunity to assess whether accelerated progress has occured since the Millennium Declaration.

Journal ArticleDOI
Guojie Zhang1, Guojie Zhang2, Cai Li1, Qiye Li1, Bo Li1, Denis M. Larkin3, Chul Hee Lee4, Jay F. Storz5, Agostinho Antunes6, Matthew J. Greenwold7, Robert W. Meredith8, Anders Ödeen9, Jie Cui10, Qi Zhou11, Luohao Xu1, Hailin Pan1, Zongji Wang12, Lijun Jin1, Pei Zhang1, Haofu Hu1, Wei Yang1, Jiang Hu1, Jin Xiao1, Zhikai Yang1, Yang Liu1, Qiaolin Xie1, Hao Yu1, Jinmin Lian1, Ping Wen1, Fang Zhang1, Hui Li1, Yongli Zeng1, Zijun Xiong1, Shiping Liu12, Long Zhou1, Zhiyong Huang1, Na An1, Jie Wang13, Qiumei Zheng1, Yingqi Xiong1, Guangbiao Wang1, Bo Wang1, Jingjing Wang1, Yu Fan14, Rute R. da Fonseca2, Alonzo Alfaro-Núñez2, Mikkel Schubert2, Ludovic Orlando2, Tobias Mourier2, Jason T. Howard15, Ganeshkumar Ganapathy15, Andreas R. Pfenning15, Osceola Whitney15, Miriam V. Rivas15, Erina Hara15, Julia Smith15, Marta Farré3, Jitendra Narayan16, Gancho T. Slavov16, Michael N Romanov17, Rui Borges6, João Paulo Machado6, Imran Khan6, Mark S. Springer18, John Gatesy18, Federico G. Hoffmann19, Juan C. Opazo20, Olle Håstad21, Roger H. Sawyer7, Heebal Kim4, Kyu-Won Kim4, Hyeon Jeong Kim4, Seoae Cho4, Ning Li22, Yinhua Huang22, Michael William Bruford23, Xiangjiang Zhan13, Andrew Dixon, Mads F. Bertelsen24, Elizabeth P. Derryberry25, Wesley C. Warren26, Richard K. Wilson26, Shengbin Li27, David A. Ray19, Richard E. Green28, Stephen J. O'Brien29, Darren K. Griffin17, Warren E. Johnson30, David Haussler28, Oliver A. Ryder, Eske Willerslev2, Gary R. Graves31, Per Alström21, Jon Fjeldså32, David P. Mindell33, Scott V. Edwards34, Edward L. Braun35, Carsten Rahbek32, David W. Burt36, Peter Houde37, Yong Zhang1, Huanming Yang38, Jian Wang1, Erich D. Jarvis15, M. Thomas P. Gilbert39, M. Thomas P. Gilbert2, Jun Wang 
12 Dec 2014-Science
TL;DR: This work explored bird macroevolution using full genomes from 48 avian species representing all major extant clades to reveal that pan-avian genomic diversity covaries with adaptations to different lifestyles and convergent evolution of traits.
Abstract: Birds are the most species-rich class of tetrapod vertebrates and have wide relevance across many research fields. We explored bird macroevolution using full genomes from 48 avian species representing all major extant clades. The avian genome is principally characterized by its constrained size, which predominantly arose because of lineage-specific erosion of repetitive elements, large segmental deletions, and gene loss. Avian genomes furthermore show a remarkably high degree of evolutionary stasis at the levels of nucleotide sequence, gene synteny, and chromosomal structure. Despite this pattern of conservation, we detected many non-neutral evolutionary changes in protein-coding genes and noncoding regions. These analyses reveal that pan-avian genomic diversity covaries with adaptations to different lifestyles and convergent evolution of traits.

Journal ArticleDOI
27 Feb 2014-Cell
TL;DR: It is shown that in adult humans new neurons integrate in the striatum, which is adjacent to this neurogenic niche, and this findings demonstrate a unique pattern of neurogenesis in the adult human brain.

Journal ArticleDOI
TL;DR: In this article, the authors present a detailed review of the state-of-the-art for electrochromics and its applications in smart windows and provide ample references to current literature of particular relevance.

Journal ArticleDOI
02 Jan 2014-Nature
TL;DR: The findings reveal that western Eurasian genetic signatures in modern-day Native Americans derive not only from post-Columbian admixture, as commonly thought, but also from a mixed ancestry of the First Americans.
Abstract: The origins of the First Americans remain contentious. Although Native Americans seem to be genetically most closely related to east Asians, there is no consensus with regard to which specific Old World populations they are closest to. Here we sequence the draft genome of an approximately 24,000-year-old individual (MA-1), from Mal'ta in south-central Siberia, to an average depth of 1×. To our knowledge this is the oldest anatomically modern human genome reported to date. The MA-1 mitochondrial genome belongs to haplogroup U, which has also been found at high frequency among Upper Palaeolithic and Mesolithic European hunter-gatherers, and the Y chromosome of MA-1 is basal to modern-day western Eurasians and near the root of most Native American lineages. Similarly, we find autosomal evidence that MA-1 is basal to modern-day western Eurasians and genetically closely related to modern-day Native Americans, with no close affinity to east Asians. This suggests that populations related to contemporary western Eurasians had a more north-easterly distribution 24,000 years ago than commonly thought. Furthermore, we estimate that 14 to 38% of Native American ancestry may originate through gene flow from this ancient population. This is likely to have occurred after the divergence of Native American ancestors from east Asian ancestors, but before the diversification of Native American populations in the New World. Gene flow from the MA-1 lineage into Native American ancestors could explain why several crania from the First Americans have been reported as bearing morphological characteristics that do not resemble those of east Asians. Sequencing of another south-central Siberian, Afontova Gora-2 dating to approximately 17,000 years ago, revealed similar autosomal genetic signatures as MA-1, suggesting that the region was continuously occupied by humans throughout the Last Glacial Maximum. Our findings reveal that western Eurasian genetic signatures in modern-day Native Americans derive not only from post-Columbian admixture, as commonly thought, but also from a mixed ancestry of the First Americans.

Journal ArticleDOI
TL;DR: Individual benefit-risk might be improved by tailoring dabigatran dose after considering selected patient characteristics, and the risk of ischemic stroke and bleeding outcomes were correlated with dabig atran plasma concentrations.

Journal ArticleDOI
TL;DR: This paper proposes a smart combination of small cells, joint transmission coordinated multipoint (JT CoMP), and massive MIMO to enhance the spectral efficiency with affordable complexity and shows in measurements with macro-plus-smallcell scenarios that spectral efficiency can be improved by flexible clustering and efficient user selection.
Abstract: 5G will have to support a multitude of new applications with a wide variety of requirements, including higher peak and user data rates, reduced latency, enhanced indoor coverage, increased number of devices, and so on. The expected traffic growth in 10 or more years from now can be satisfied by the combined use of more spectrum, higher spectral efficiency, and densification of cells. The focus of the present article is on advanced techniques for higher spectral efficiency and improved coverage for cell edge users. We propose a smart combination of small cells, joint transmission coordinated multipoint (JT CoMP), and massive MIMO to enhance the spectral efficiency with affordable complexity. We review recent achievements in the transition from theoretical to practical concepts and note future research directions. We show in measurements with macro-plus-smallcell scenarios that spectral efficiency can be improved by flexible clustering and efficient user selection, and that adaptive feedback compression is beneficial to reduce the overhead significantly. Moreover, we show in measurements that fast feedback reporting combined with advanced channel prediction are able to mitigate the impairment effects of JT CoMP.

Journal ArticleDOI
Haidong Wang1, Chelsea A. Liddell1, Matthew M Coates1, Meghan D. Mooney1  +228 moreInstitutions (123)
TL;DR: Decreases since 2000 in under-5 mortality rates are accelerating in many developing countries, especially in sub-Saharan Africa, and rising income per person and maternal education and changes in secular trends led to 4·2 million fewer deaths.

Journal ArticleDOI
Hans Ellegren1
TL;DR: High-throughput sequencing technologies are revolutionizing the life sciences, and the past 12 months have seen a burst of genome sequences from non-model organisms, in each case representing a fundamental source of data of significant importance to biological research.
Abstract: High-throughput sequencing technologies are revolutionizing the life sciences. The past 12 months have seen a burst of genome sequences from non-model organisms, in each case representing a fundamental source of data of significant importance to biological research. This has bearing on several aspects of evolutionary biology, and we are now beginning to see patterns emerging from these studies. These include significant heterogeneity in the rate of recombination that affects adaptive evolution and base composition, the role of population size in adaptive evolution, and the importance of expansion of gene families in lineage-specific adaptation. Moreover, resequencing of population samples (population genomics) has enabled the identification of the genetic basis of critical phenotypes and cast light on the landscape of genomic divergence during speciation.


Journal ArticleDOI
TL;DR: It is argued that although recent progress has been impressive, the next decade will yield even more substantial insights not only into how domestication took place, but also when and where it did, and where and why it did not.
Abstract: It is difficult to overstate the cultural and biological impacts that the domestication of plants and animals has had on our species. Fundamental questions regarding where, when, and how many times domestication took place have been of primary interest within a wide range of academic disciplines. Within the last two decades, the advent of new archaeological and genetic techniques has revolutionized our understanding of the pattern and process of domestication and agricultural origins that led to our modern way of life. In the spring of 2011, 25 scholars with a central interest in domestication representing the fields of genetics, archaeobotany, zooarchaeology, geoarchaeology, and archaeology met at the National Evolutionary Synthesis Center to discuss recent domestication research progress and identify challenges for the future. In this introduction to the resulting Special Feature, we present the state of the art in the field by discussing what is known about the spatial and temporal patterns of domestication, and controversies surrounding the speed, intentionality, and evolutionary aspects of the domestication process. We then highlight three key challenges for future research. We conclude by arguing that although recent progress has been impressive, the next decade will yield even more substantial insights not only into how domestication took place, but also when and where it did, and where and why it did not.

Journal ArticleDOI
TL;DR: This work presents a technique for extruding gel-like LCP with embedded membrane protein microcrystals, providing a continuously renewed source of material for serial femtosecond crystallography.
Abstract: Lipidic cubic phase (LCP) crystallization has proven successful for high-resolution structure determination of challenging membrane proteins. Here we present a technique for extruding gel-like LCP ...

Journal ArticleDOI
TL;DR: This Progress Report focuses on the design of novel Pt-free CE catalytic materials, including design ideas, fabrication approaches, characterization techniques, first-principle density functional theory (DFT) calculations, ab-initio Car-Parrinello molecular dynamics (CPMD) simulations, and stability evaluations, that serve as practical alternatives to conventional noble metal Pt electrodes.
Abstract: Dye-sensitized solar cells (DSSCs) have attracted widespread attention in recent years as potential cost-effective alternatives to silicon-based and thin-film solar cells. Within typical DSSCs, the counter electrode (CE) is vital to collect electrons from the external circuit and catalyze the I3- reduction in the electrolyte. Careful design of the CEs can improve the catalytic activity and chemical stability associated with the liquid redox electrolyte used in most cells. In this Progress Report, advances made by our groups in the development of CEs for DSSCs are reviewed, highlighting important contributions that promise low-cost, efficient, and robust DSSC systems. Specifically, we focus on the design of novel Pt-free CE catalytic materials, including design ideas, fabrication approaches, characterization techniques, first-principle density functional theory (DFT) calculations, ab-initio Car-Parrinello molecular dynamics (CPMD) simulations, and stability evaluations, that serve as practical alternatives to conventional noble metal Pt electrodes. We stress the merits and demerits of well-designed Pt-free CEs, such as carbon materials, conductive polymers, transition metal compounds (TMCs) and their corresponding hybrids. Also, the prospects and challenges of alternative Pt catalysts for their applications in new-type DSSCs and other catalytic fields are discussed. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Journal ArticleDOI
TL;DR: Lowering blood pressure provides similar relative protection at all levels of baseline cardiovascular risk, but progressively greater absolute risk reductions as baseline risk increases.

Journal ArticleDOI
John R. B. Perry, Felix R. Day1, Cathy E. Elks1, Patrick Sulem2  +217 moreInstitutions (64)
02 Oct 2014-Nature
TL;DR: In this article, the authors used genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies and found robust evidence for 123 signals at 106 genomic loci associated with age at menarche.
Abstract: Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition.