bluuebunny/crossref_metadata_2025 huggingface dataset:
Gas valves, forests and global change: a commentary on Jarvis (1976) ‘The interpretation of the variations in leaf water potential and stomatal conductance found in canopies in the field’
Authors: Beerling David J.
Published: March 2015

Microscopic turgor-operated gas valves on leaf surfaces—stomata—facilitate gas exchange between the plant and the atmosphere, and respond to multiple environmental and endogenous cues. Collectively, stomatal activities affect everything from the productivity of forests, grasslands and crops to biophysical feedbacks between land surface vegetation and climate. In 1976, plant physiologist Paul Jarvis reported an empirical model describing stomatal responses to key environmental and plant conditions that predicted the flux of water vapour from leaves into the surrounding atmosphere. Subsequent theoretical advances, building on this earlier approach, established the current paradigm for capturing the physiological behaviour of stomata that became incorporated into sophisticated models of land carbon cycling. However, these models struggle to accurately predict observed trends in the physiological responses of Northern Hemisphere forests to recent atmospheric CO
2
increases, highlighting the need for improved representation of the role of stomata in regulating forest–climate interactions. Bridging this gap between observations and theory as atmospheric CO
2
rises and climate change accelerates creates challenging opportunities for the next generation of physiologists to advance planetary ecology and climate science. This commentary was written to celebrate the 350th anniversary of the journal
Philosophical Transactions of the Royal Society
.
Extraordinary fossils reveal the nature of Cambrian life: a commentary on Whittington (1975) ‘The enigmatic animalOpabinia regalis, Middle Cambrian, Burgess Shale, British Columbia’
Authors: Briggs Derek E. G.
Published: March 2015

Harry Whittington's 1975 monograph onOpabiniawas the first to highlight how some of the Burgess Shale animals differ markedly from those that populate today's oceans. Categorized by Stephen J. Gould as a ‘weird wonder’ (Wonderful life, 1989)Opabinia, together with other unusual Burgess Shale fossils, stimulated ongoing debates about the early evolution of the major animal groups and the nature of the Cambrian explosion. The subsequent discovery of a number of other exceptionally preserved fossil faunas of Cambrian and early Ordovician age has significantly augmented the information available on this critical interval in the history of life. AlthoughOpabiniainitially defied assignment to any group of modern animals, it is now interpreted as lying below anomalocaridids on the stem leading to the living arthropods. This commentary was written to celebrate the 350th anniversary of the journalPhilosophical Transactions of the Royal Society.
A model model: a commentary on DiFrancesco and Noble (1985) ‘A model of cardiac electrical activity incorporating ionic pumps and concentration changes’
Authors: Dibb Katharine , Trafford Andrew , Zhang Henggui , Eisner David
Published: March 2015

This paper summarizes the advances made by the DiFrancesco and Noble (DFN) model of cardiac cellular electrophysiology, which was published in
Philosophical Transactions B
in 1985. This model was developed at a time when the introduction of new techniques and provision of experimental data had resulted in an explosion of knowledge about the cellular and biophysical properties of the heart. It advanced the cardiac modelling field from a period when computer models considered only the voltage-dependent channels in the surface membrane. In particular, it included a consideration of changes of both intra- and extracellular ionic concentrations. In this paper, we summarize the most important contributions of the DiFrancesco and Noble paper. We also describe how computer modelling has developed subsequently with the extension from the single cell to the whole heart as well as its use in understanding disease and predicting the effects of pharmaceutical interventions. This commentary was written to celebrate the 350th anniversary of the journal
Philosophical Transactions of the Royal Society
.
From plant extract to molecular panacea: a commentary on Stone (1763) ‘An account of the success of the bark of the willow in the cure of the agues’
Authors: Wood John N.
Published: March 2015

The application of aspirin-like drugs in modern medicine is very broad, encompassing the treatment of inflammation, pain and a variety of cardiovascular conditions. Although anecdotal accounts of willow bark extract as an anti-inflammatory drug have occurred since written records began (for example by Hippocrates), the first convincing demonstration of a potent anti-pyretic effect of willow bark containing salicylates was made by the English cleric Edward Stone in the late eighteenth century. Here, we discuss the route to optimizing and understanding the mechanism of action of anti-inflammatory drugs that have their origins in Stone's seminal study, ‘An account of the success of the bark of the willow in the cure of agues’. This commentary was written to celebrate the 350th anniversary of the journal
Philosophical Transactions of the Royal Society
.
The early evolution of land plants, from fossils to genomics: a commentary on Lang (1937) ‘On the plant-remains from the Downtonian of England and Wales'
Authors: Edwards Dianne , Kenrick Paul
Published: March 2015

During the 1920s, the botanist W. H. Lang set out to collect and investigate some very unpromising fossils of uncertain affinity, which predated the known geological record of life on land. His discoveries led to a landmark publication in 1937, ‘On the plant-remains from the Downtonian of England and Wales’, in which he revealed a diversity of small fossil organisms of great simplicity that shed light on the nature of the earliest known land plants. These and subsequent discoveries have taken on new relevance as botanists seek to understand the plant genome and the early evolution of fundamental organ systems. Also, our developing knowledge of the composition of early land-based ecosystems and the interactions among their various components is contributing to our understanding of how life on land affects key Earth Systems (e.g. carbon cycle). The emerging paradigm is one of early life on land dominated by microbes, small bryophyte-like organisms and lichens. Collectively called cryptogamic covers, these are comparable with those that dominate certain ecosystems today. This commentary was written to celebrate the 350th anniversary of the journalPhilosophical Transactions of the Royal Society.
The unseen world: reflections on Leeuwenhoek (1677) ‘Concerning little animals’
Authors: Lane Nick
Published: March 2015

Leeuwenhoek's 1677 paper, the famous ‘letter on the protozoa’, gives the first detailed description of protists and bacteria living in a range of environments. The colloquial, diaristic style conceals the workings of a startlingly original experimental mind. Later scientists could not match the resolution and clarity of Leeuwenhoek's microscopes, so his discoveries were doubted or even dismissed over the following centuries, limiting their direct influence on the history of biology; but work in the twentieth century confirmed Leeuwenhoek's discovery of bacterial cells, with a resolution of less than 1 µm. Leeuwenhoek delighted most in the forms, interactions and behaviour of his little ‘animalcules', which inhabited a previously unimagined microcosmos. In these reflections on the scientific reach of Leeuwenhoek's ideas and observations, I equate his questions with the preoccupations of our genomic era: what is the nature of Leeuwenhoek's animalcules, where do they come from, how do they relate to each other? Even with the powerful tools of modern biology, the answers are far from resolved—these questions still challenge our understanding of microbial evolution. This commentary was written to celebrate the 350th anniversary of the journalPhilosophical Transactionsof the Royal Society.
From high symmetry to high resolution in biological electron microscopy: a commentary on Crowther (1971) ‘Procedures for three-dimensional reconstruction of spherical viruses by Fourier synthesis from electron micrographs’
Authors: Rosenthal Peter B.
Published: March 2015

Elucidation of the structure of biological macromolecules and larger assemblies has been essential to understanding the roles they play in living processes. Methods for three-dimensional structure determination of biological assemblies from images recorded in the electron microscope were therefore a key development. In his paper published in
Philosophical Transactions B
in 1971, Crowther described new computational procedures applied to the first three-dimensional reconstruction of an icosahedral virus from images of virus particles preserved in negative stain. The method for determining the relative orientation of randomly oriented particles and combining their images for reconstruction exploited the high symmetry of the virus particle. Computational methods for image analysis have since been extended to include biological assemblies without symmetry. Further experimental advances, combined with image analysis, have led to the method of cryomicroscopy, which is now used by structural biologists to study the structure and dynamics of biological machines and assemblies in atomic detail. This commentary was written to celebrate the 350th anniversary of the journal
Philosophical Transactions of the Royal Society
.
Deciphering death: a commentary on Gompertz (1825) ‘On the nature of the function expressive of the law of human mortality, and on a new mode of determining the value of life contingencies’
Authors: Kirkwood Thomas B. L.
Published: March 2015

In 1825, the actuary Benjamin Gompertz read a paper, ‘On the nature of the function expressive of the law of human mortality, and on a new mode of determining the value of life contingencies’, to the Royal Society in which he showed that over much of the adult human lifespan, age-specific mortality rates increased in an exponential manner. Gompertz's work played an important role in shaping the emerging statistical science that underpins the pricing of life insurance and annuities. Latterly, as the subject of ageing itself became the focus of scientific study, the Gompertz model provided a powerful stimulus to examine the patterns of death across the life course not only in humans but also in a wide range of other organisms. The idea that the Gompertz model might constitute a fundamental ‘law of mortality’ has given way to the recognition that other patterns exist, not only across the species range but also in advanced old age. Nevertheless, Gompertz's way of representing the function expressive of the pattern of much of adult mortality retains considerable relevance for studying the factors that influence the intrinsic biology of ageing. This commentary was written to celebrate the 350th anniversary of the journalPhilosophical Transactions of the Royal Society.
Medawar's legacy to cellular immunology and clinical transplantation: a commentary on Billingham, Brent and Medawar (1956) ‘Quantitative studies on tissue transplantation immunity. III. Actively acquired tolerance’
Authors: Simpson Elizabeth
Published: March 2015

‘Quantitative studies on tissue transplantation immunity. III. Actively acquired tolerance’, published inPhilosophical Transactions Bin 1956 by Peter Medawar and his colleagues, PhD graduate Leslie Brent and postdoctoral fellow Rupert Billingham, is a full description of the concept of acquired transplantation tolerance. Their 1953Naturepaper (Billingham REet al. 1953Nature172, 603–606. (doi:10.1038/172603a0)) had provided initial evidence with experimental results from a small number of neonatal mice, with mention of similar findings in chicks. ThePhilosophical Transactions B1956 paper is clothed with an astonishing amount of further experimental detail. It is written in Peter Medawar's landmark style: witty, perceptive and full of images that can be recalled even when details of the supporting information have faded. Those images are provided not just by a series of 20 colour plates showing skin graft recipient mice, rats, rabbits, chickens and duck, bearing fur or plumage of donor origin, but by his choice of metaphor, simile and analogy to express the questions being addressed and the interpretation of their results, along with those of relevant published data and his prescient ideas of what the results might portend. This work influenced both immunology researchers and clinicians and helped to lay the foundations for successful transplantation programmes. It led to the award of a Nobel prize in 1960 to Medawar, and subsequently to several scientists who advanced these areas. This commentary was written to celebrate the 350th anniversary of the journalPhilosophical Transactions of the Royal Society.
Memory, modelling and Marr: a commentary on Marr (1971) ‘Simple memory: a theory of archicortex’
Authors: Willshaw D. J. , Dayan P. , Morris R. G. M.
Published: March 2015

David Marr's theory of the archicortex, a brain structure now more commonly known as the hippocampus and hippocampal formation, is an epochal contribution to theoretical neuroscience. Addressing the problem of how information about 10 000 events could be stored in the archicortex during the day so that they can be retrieved using partial information and then transferred to the neocortex overnight, the paper presages a whole wealth of later empirical and theoretical work, proving impressively prescient. Despite this impending success, Marr later apparently grew dissatisfied with this style of modelling, but he went on to make seminal suggestions that continue to resonate loudly throughout the field of theoretical neuroscience. We describe Marr's theory of the archicortex and his theory of theories, setting them into their original and a contemporary context, and assessing their impact. This commentary was written to celebrate the 350th anniversary of the journal
Philosophical Transactions of the Royal Society
.
Rouxiella chamberiensis gen. nov., sp. nov., a member of the family Enterobacteriaceae isolated from parenteral nutrition bags
Authors: Le Flèche-Matéos Anne , Levast Marion , Lomprez Fabienne , Arnoux Yolande , Andonian Clément , Perraud Michel , Vincent Véronique , Ar Gouilh Meriadeg , Thiberge Jean-Michel , Vandenbogaert Mathias , Diancourt Laure , Caro Valérie , Burguière Ana Maria , Manuguerra Jean-Claude
Published: March 2015

Parenteral nutrition bags for newborns were found contaminated by a previously undescribed member of the family

Enterobacteriaceae

. The six isolates studied by rrs gene (encoding 16S rRNA) sequence analysis and multi-locus sequence analysis (MLSA) formed a discrete branch close to the genera

Ewingella

,

Rahnella

,

Yersinia

,

Hafnia

and

Serratia

. Phenotypically, the new taxon was distinct from these five genera. The new taxon gave positive results in Voges–Proskauer, Simmons citrate and o-nitrophenyl-β-galactoside hydrolysis tests; fermented d-glucose, d-mannitol, l-rhamnose, melibiose, l-arabinose and d-xylose; hydrolysed aesculin; and did not ferment maltose, trehalose, raffinose, d-sorbitol, sucrose or cellobiose. Tests for motility, gas production, urease, gelatinase and nitrate reduction were also negative. All isolates failed to grow at 37 °C. The DNA G+C content of strain 130333T was 53 mol%. On the basis of data obtained in this study, the six isolates represent a novel species of a new genus in the family

Enterobacteriaceae

, named Rouxiella chamberiensis gen. nov., sp. nov. The type strain of the type species is 130333T ( = CIP 110714T = DSM 28324T).
Plantactinospora veratri sp. nov., an actinomycete isolated from black false hellebore root (Veratrum nigrum L.)
Authors: Xing He , Liu Chongxi , Zhang Yuejing , Zhao Junwei , Li Chuang , Liu Hui , Li Lianjie , Wang Xiangjing , Xiang Wensheng
Published: March 2015

A novel actinomycete, designated strain NEAU-FHS4T, was isolated from the root of black false hellebore (Veratrum nigrum L.). Strain NEAU-FHS4T formed single spores with smooth surfaces on substrate mycelium. The novel strain contained meso-diaminopimelic as amino acid of the peptidoglycan and xylose and glucose as whole-cell sugars. The predominant menaquinones were MK-10(H6) and MK-10(H8). Mycolic acids were not detected. The diagnostic phospholipids were phosphatidylethanolamine, diphosphatidylglycerol and phosphatidylinositol. The predominant cellular fatty acids were iso-C16 : 0, C16 : 0, C18 : 0 and anteiso-C17 : 0. Phenotypic and chemotaxonomic analysis showed that the novel isolate had characteristics typical of members of the genus

Plantactinospora

. 16S rRNA gene sequence analysis also indicated that strain NEAU-FHS4T belonged to the genus

Plantactinospora

, with highest sequence similarities to

Plantactinospora mayteni

YIM 61359T (98.88 %) and

Plantactinospora endophytica

YIM 68255T (98.85 %). The results of DNA–DNA hybridization and physiological and biochemical tests allowed genotypic and phenotypic differentiation of the novel strain from the most closely related strains. Based on morphological, chemotaxonomic and phylogenetic data, strain NEAU-FHS4T is considered to represent a novel species of the genus

Plantactinospora

, for which the name Plantactinospora veratri sp. nov. is proposed. The type strain is NEAU-FHS4T ( = CGMCC 4.7143T = DSM 46718T).
Defluviimonas alba sp. nov., isolated from an oilfield
Authors: Pan Xin-Chi , Geng Shuang , Lv Xiang-Lin , Mei Ran , Jiangyang Jing-Hong , Wang Ya-Nan , Xu Lian , Liu Xue-Ying , Tang Yue-Qin , Wang Ge-Jiao , Wu Xiao-Lei
Published: March 2015

Two Gram-stain-negative, rod-shaped bacterial strains, cai42T and b45, were isolated from oil-production water taken from Xinjiang Oilfield, China. Optimum growth was observed at 30 °C, at pH 8 and with 1–3 % (w/v) NaCl. According to phylogenetic analyses, the two strains were members of the genus

Defluviimonas

, with 16S rRNA gene sequence similarities of 95.5−96.3 % with the type strains of species of the genus. The major cellular fatty acids of strains cai42T and b45 were C10 : 0 3-OH, C16 : 0 and summed feature 8 (C18 : 1ω7c/C18 : 1ω6c), and the predominant ubiquinone was Q-10, all of these data being typical for the genus

Defluviimonas

. The polar lipids were phosphatidylethanolamine, phosphatidylglycerol, glycolipid, phosphatidylcholine, two unidentified aminolipids, an unidentified phospholipid and two unidentified lipids. The mean genomic DNA G+C contents of strains cai42T and b45 were 60.8±1.1 and 60.4±1.0 mol%, respectively. On the basis of phylogenetic, physiological and chemotaxonomic analyses, strains cai42T and b45 represent a novel species of the genus

Defluviimonas

, for which the name Defluviimonas alba sp. nov. is proposed. The type strain is cai42T ( = CGMCC 1.12518T = LMG 27406T).
Mbd3/NuRD is a Key Inhibitory Module During the Induction and Maintenance of Naïve Pluripotency
Authors: Zviran Asaf , Rais Yoach , Mor Nofar , Novershtern Noa , Hanna Jacob H.
Published: March 2015

Our group has published a study on induced pluripotent stem cell (iPSC) reprogramming (Rais et al. Nature 20131) that reached the following conclusions: a) Mbd3/NuRD is a repressor of inducing naïve pluripotency from mouse Epiblast stem cells (EpiSCs), primordial germ cells (PGCs), murine somatic cells and human secondary fibroblasts; b) Up to 100% iPSC formation efficiency can be achieved via optimized Mbd3/NuRD depletion, in concert with optimized OKSM delivery and naïve pluripotency conditions (2i supplement applied only after 48 hours, human LIF, hypoxia and Vitamin C containing Knockout serum replacement)1. This represented the first proof for deterministic/near-deterministic iPSC reprogramming, and highlighted a previously unappreciated role for Mbd3/NuRD in hampering the re-establishment of pluripotency. Recent reports have seemingly provided contradictory results and attempted to dispute our iPSC efficiency quantifications and/or the role of Mbd3/NuRD in blocking reprogramming2,3. Here we provide a detailed response to these reports based on extended discussions and providing new data. The synthesis presented herein disagrees with claims made by Silva, Hendrich, Bertone and colleagues2,3, and reconfirms that Mbd3/NuRD is a major pathway that inhibits the maintenance and induction of pluripotency1. Further, we foresee that its controlled manipulation is likely to become an integral pathway for inducing and maintaining naïve pluripotency in a variety of species.
Nitric oxide regulates growth coordination during regeneration
Authors: Jaszczak Jacob S. , Wolpe Jacob B. , Dao Anh Q. , Halme Adrian
Published: March 2015

Mechanisms that coordinate the growth of different tissues during development are essential for producing adult animals with proper organ proportion. Here we describe a pathway through which tissues communicate with each other to coordinate growth. DuringDrosophila melanogasterlarval development, damage to imaginal discs activates a regeneration checkpoint that produces both a delay in developmental timing and slows the growth of undamaged tissues, coordinating regeneration of the damaged tissue with developmental progression and overall growth. Both developmental delay and growth control are mediated by secretion of the insulin/relaxin family peptide Dilp8 from regenerating tissues. Here we demonstrate that Dilp8-dependent growth coordination between regenerating and undamaged tissues, but not developmental delay, requires the activity of nitric oxide synthase (NOS) in the prothoracic gland. NOS limits the growth of undamaged tissues by reducing ecdysone biosynthesis, a requirement for imaginal disc growth during both the regenerative checkpoint and normal development. Therefore, NOS activity in the prothoracic gland translates information about the growth status of individual tissues into coordinated tissue growth through the regulation of endocrine signals.
Similarity Estimation Between DNA Sequences Based on Local Pattern Histograms of Binary Images
Authors: Kobori Yusei , Mizuta Satoshi
Published: March 2015

Graphical representation of DNA sequences is one of the most popular techniques of alignment-free sequence comparison. In this article, we propose a new method for extracting features of DNA sequences represented by binary images, in which we estimate the similarity between DNA sequences by the frequency histograms of local bitmap patterns on the images. Our method has linear time complexity for the length of DNA sequences, which is practical even for comparison of long sequences. We tested five distance measures to estimate sequence similarities and found thathistogram intersectionandManhattan distanceare most appropriate for our method among them.
Tools and best practices for allelic expression analysis
Authors: Castel Stephane E. , Moonshine Ami Levy , Mohammadi Pejman , Banks Eric , Lappalainen Tuuli
Published: March 2015

Allelic expression (AE) analysis has become an important tool for integrating genome and transcriptome data to characterize various biological phenomena such ascis-regulatory variation and nonsense-mediated decay. In this paper, we systematically analyze the properties of AE read count data and technical sources of error, such as low-quality or double-counted RNA-seq reads, genotyping errors, allelic mapping bias, and technical covariates due to sample preparation and sequencing, and variation in total read depth. We provide guidelines for correcting and filtering for such errors, and show that the resulting AE data has extremely low technical noise. Finally, we introduce novel software for high-throughput production of AE data from RNA-sequencing data, implemented in the GATK framework. These improved tools and best practices for AE analysis yield higher quality AE data by reducing technical bias. This provides a practical framework for wider adoption of AE analysis by the genomics community.
Detecting Signals of Seasonal Influenza Severity through Age Dynamics
Authors: Lee Elizabeth C , Viboud Cécile , Simonsen Lone , Khan Farid , Bansal Shweta
Published: March 2015

Background: Measures of population-level influenza severity are important for public health planning, but estimates are often based on case-fatality and case-hospitalization risks, which require multiple data sources, are prone to surveillance biases, and are typically unavailable in the early stages of an outbreak. In this study, we develop a severity index based on influenza age dynamics estimated from routine surveillance data that can be used in retrospective and early warning contexts. Methods and Findings: Our method relies on the observation that age-specific attack rates vary between seasons, so that key features of the age distribution of cases may be used as a marker of severity early in an epidemic. We illustrate our method using weekly outpatient medical claims of influenza-like illness (ILI) in the United States from the 2001 to 2009 and develop a novel population-level influenza severity index based on the relative risk of ILI among working-age adults to that among school-aged children. We validate our ILI index against a benchmark that comprises traditional influenza severity indicators such as viral activity, hospitalizations and deaths using publicly available surveillance data. We find that severe influenza seasons have higher relative rates of ILI among adults than mild seasons. In reference to the benchmark, the ILI index is a robust indicator of severity during the period of peak epidemic growth (87.5% accuracy in retrospective classification), and may have predictive power during the period between Thanksgiving and the winter holidays (57.1% accuracy in early warning). We further apply our approach at the state-level to characterize regional severity patterns across seasons. We hypothesize that our index is a proxy for severity because working-age adults have both pre-existing immunity to influenza and a high number of contacts, infecting them preferentially in severe seasons associated with antigenic changes in circulating influenza viruses. Our analysis is limited by its application to seasonal influenza epidemics and a relatively short study period. Conclusions: Our severity index and research on the link between age dynamics and seasonal influenza severity will enable decision makers to better target public health strategies in severe seasons and improve our knowledge of influenza epidemiology and population impact. These findings demonstrate that routine surveillance data can be translated into operational information for policymakers. Our study also highlights the need for further research on the putative age-related mechanisms of severity in seasonal and pandemic influenza seasons.
A Comparison of Methods to Measure Fitness inEscherichia coli
Authors: Wiser Michael J , Lenski Richard E
Published: March 2015

In order to characterize the dynamics of adaptation, it is important to be able to quantify how a population’s mean fitness changes over time. Such measurements are especially important in experimental studies of evolution using microbes. The Long-Term Evolution Experiment (LTEE) withEscherichia coliprovides one such system in which mean fitness has been measured by competing derived and ancestral populations. The traditional method used to measure fitness in the LTEE and many similar experiments, though, is subject to a potential limitation. As the relative fitness of the two competitors diverges, the measurement error increases because the less-fit population becomes increasingly small and cannot be enumerated as precisely. Here, we present and employ two alternatives to the traditional method. One is based on reducing the fitness differential between the competitors by using a common reference competitor from an intermediate generation that has intermediate fitness; the other alternative increases the initial population size of the less-fit, ancestral competitor. We performed a total of 480 competitions to compare the statistical properties of estimates obtained using these alternative methods with those obtained using the traditional method for samples taken over 50,000 generations from one of the LTEE populations. On balance, neither alternative method yielded measurements that were more precise than the traditional method.
Efficient APC/C substrate degradation in cells undergoing mitotic exit depends on K11 ubiquitin linkages
Authors: Min Mingwei , Mevissen Tycho , De Luca Maria , Komander David , Lindon Catherine
Published: March 2015

The ubiquitin proteasome system (UPS) directs programmed destruction of key cellular regulators via post-translational modification of its targets with polyubiquitin chains. These commonly contain Lysine 48 (K48)-directed ubiquitin linkages, but chains containing atypical Lysine 11 (K11) linkages also target substrates to the proteasome, for example to regulate cell cycle progression. A single ubiquitin ligase, the Anaphase Promoting Complex/Cyclosome (APC/C), controls mitotic exit. In higher eukaryotes, the APC/C works with the E2 enzyme UBE2S to assemble K11 linkages in cells released from mitotic arrest, and these are proposed to constitute an improved proteolytic signal during exit from mitosis. We have tested this idea by correlating quantitative measures ofin vivoK11-specific ubiquitination of individual substrates, including Aurora kinases, with their degradation kinetics tracked at the single cell level. We report that all anaphase substrates tested by this methodology are stabilized by depletion of K11 linkages via UBE2S knockdown, even if the same substrates are significantly modified with K48-linked polyubiquitin. Specific examination of substrates depending on the APC/C coactivator Cdh1 for their degradation revealed Cdh1-dependent enrichment of K11 chains on these substrates, while other ubiquitin linkages on the same substrates added during mitotic exit were Cdh1-independent. Therefore we show that K11 linkages provide the APC/C with a means to regulate the rate of substrate degradation in a co-activator-specified manner.

Abbreviations

APC/C

Anaphase Promoting Complex/Cyclosome

DUB

deubiquitinase

SAC

spindle assembly checkpoint

UPS

ubiquitin-proteasome system

ZM

ZM447439
Pathway based factor analysis of gene expression data produces highly heritable phenotypes that associate with age
Authors: Brown Andrew , Ding Zhihao , Viñuela Ana , Glass Dan , Parts Leopold , Spector Tim , Winn John , Durbin Richard
Published: March 2015

Statistical factor analysis methods have previously been used to remove noise components from high dimensional data prior to genetic association mapping, and in a guided fashion to summarise biologically relevant sources of variation. Here we show how the derived factors summarising pathway expression can be used to analyse the relationships between expression, heritability and ageing. We used skin gene expression data from 647 twins from the MuTHER Consortium and applied factor analysis to concisely summarise patterns of gene expression, both to remove broad confounding influences and to produce concise pathway-level phenotypes. We derived 930 “pathway phe-notypes” which summarised patterns of variation across 186 KEGG pathways (five phenotypes per pathway). We identified 69 significant associations of age with phenotype from 57 distinct KEGG pathways at a stringent Bon-ferroni threshold (P< 5.38 × 10−5). These phenotypes are more heritable (h2= 0.32) than gene expression levels. On average, expression levels of 16% of genes within these pathways are associated with age. Several significant pathways relate to metabolising sugars and fatty acids, others with insulin signalling. We have demonstrated that factor analysis methods combined with biological knowledge can produce more reliable phenotypes with less stochastic noise than the individual gene expression levels, which increases our power to discover biologically relevant associations. These phenotypes could also be applied to discover associations with other environmental factors.
The role of DNA methylation in directing the functional organization of the cancer epigenome
Authors: Lay Fides D. , Liu Yaping , Kelly Theresa K. , Witt Heather , Farnham Peggy J. , Jones Peter A. , Berman Benjamin P.
Published: March 2015

The holistic role of DNA methylation in the organization of the cancer epigenome is not well understood. Here we perform a comprehensive, high-resolution analysis of chromatin structure to compare the landscapes of HCT116 colon cancer cells and a DNA methylation-deficient derivative. The NOMe-seq accessibility assay unexpectedly revealed symmetrical and transcription-independent nucleosomal phasing across active, poised, and inactive genomic elements. DNA methylation abolished this phasing primarily at enhancers and CpG island (CGI) promoters, with little effect on insulators and non-CGI promoters. Abolishment of DNA methylation led to the context-specific reestablishment of the poised and active states of normal colon cells, which were marked in methylation-deficient cells by distinct H3K27 modifications and the presence of either well-phased nucleosomes or nucleosome-depleted regions, respectively. At higher-order genomic scales, we found that long, H3K9me3-marked domains had lower accessibility, consistent with a more compact chromatin structure. Taken together, our results demonstrate the nuanced and context-dependent role of DNA methylation in the functional, multiscale organization of cancer epigenomes.
Binding of SEC11 Indicates Its Role in SNARE Recycling after Vesicle Fusion and Identifies Two Pathways for Vesicular Traffic to the Plasma Membrane
Authors: Karnik Rucha , Zhang Ben , Waghmare Sakharam , Aderhold Christin , Grefen Christopher , Blatt Michael R.
Published: March 2015

SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) proteins drive vesicle fusion in all eukaryotes and contribute to homeostasis, pathogen defense, cell expansion, and growth in plants. Two homologous SNAREs, SYP121 (=SYR1/PEN1) and SYP122, dominate secretory traffic to the Arabidopsis thaliana plasma membrane. Although these proteins overlap functionally, differences between SYP121 and SYP122 have surfaced, suggesting that they mark two discrete pathways for vesicular traffic. The SNAREs share primary cognate partners, which has made separating their respective control mechanisms difficult. Here, we show that the regulatory protein SEC11 (=KEULE) binds selectively with SYP121 to affect secretory traffic mediated by this SNARE. SEC11 rescued traffic block by dominant-negative (inhibitory) fragments of both SNAREs, but only in plants expressing the native SYP121. Traffic and its rescue were sensitive to mutations affecting SEC11 interaction with the N terminus of SYP121. Furthermore, the domain of SEC11 that bound the SYP121 N terminus was itself able to block secretory traffic in the wild type and syp122 but not in syp121 mutant Arabidopsis. Thus, SEC11 binds and selectively regulates secretory traffic mediated by SYP121 and is important for recycling of the SNARE and its cognate partners.
ENHANCED DISEASE RESISTANCE4 Associates with CLATHRIN HEAVY CHAIN2 and Modulates Plant Immunity by Regulating Relocation of EDR1 in Arabidopsis
Authors: Wu Guangheng , Liu Simu , Zhao Yaofei , Wang Wei , Kong Zhaosheng , Tang Dingzhong
Published: March 2015

Obligate biotrophs, such as the powdery mildew pathogens, deliver effectors to the host cell and obtain nutrients from the infection site. The interface between the plant host and the biotrophic pathogen thus represents a major battleground for plant-pathogen interactions. Increasing evidence shows that cellular trafficking plays an important role in plant immunity. Here, we report that Arabidopsis thaliana ENHANCED DISEASE RESISTANCE4 (EDR4) plays a negative role in resistance to powdery mildew and that the enhanced disease resistance in edr4 mutants requires salicylic acid signaling. EDR4 mainly localizes to the plasma membrane and endosomal compartments. Genetic analyses show that EDR4 and EDR1 function in the same genetic pathway. EDR1 and EDR4 accumulate at the penetration site of powdery mildew infection, and EDR4 physically interacts with EDR1, recruiting EDR1 to the fungal penetration site. In addition, EDR4 interacts with CLATHRIN HEAVY CHAIN2 (CHC2), and edr4 mutants show reduced endocytosis rates. Taken together, our data indicate that EDR4 associates with CHC2 and modulates plant immunity by regulating the relocation of EDR1 in Arabidopsis.
The genetics of intra‐ and interspecific competitive response and effect in a local population of an annual plant species
Authors: Baron Etienne , Richirt Julien , Villoutreix Romain , Amsellem Laurent , Roux Fabrice
Published: March 2015

While competition is recognized as a major factor responsible for plant community dynamics, the genetics of intra‐ and interspecific competitive ability of a target species (i.e. level of intra‐population genetic variation, identity of phenotypic traits under selection and genetic bases) still deserves a deeper investigation at the local spatial scale by considering both numerous genotypes and several interacting species.

In this study, we tested whether the genetics of competitive response and effect in Arabidopsis thaliana was dependent on the competitive environment at both the intraspecific and interspecific levels. We used a mapping population of 48 accessions (i) that maximize the genetic diversity of a local population of A. thaliana and (ii) that have been genotyped for 168 503 single nucleotide polymorphisms.

In a common garden experiment, those 48 accessions were grown in six competitive environments: the absence of competition, intraspecific competition and interspecific competition with four species frequently associated with A. thaliana in natural plant communities (i.e. Poa annua, Stellaria media, Trifolium repens and Veronica arvensis). A suite of nine phenotypic traits, including a proxy of fitness, were scored on each target A. thaliana plant and the above‐ground dry biomass of its corresponding competitor was estimated.

We first showed that crossing reaction norms of competitive response (A. thaliana performance) and effect (competitor biomass) might promote maintenance of genetic variation in a local population of A. thaliana and species coexistence at a fine spatial scale. By estimating genotypic gradients of selection, we then demonstrated that the optimal phenotypic strategies in response to competition depend on the identity of the competitor species. Finally, a genomewide association mapping approach highlighted that genomic regions associated with direct genetic effects were (i) dependent on the competitor species and (ii) different from genomic regions associated with interspecific indirect genetic effects.

While a first step, this study highlighted the power of adding ecology to genomics in A. thaliana to identify genetic bases underlying micro‐geographic adaptation to competition. Next‐generation sequencing technologies will undoubtedly facilitate the discovery of molecular and genetic mechanisms underlying competitive ability in other plant species, and thereby the prediction of evolutionary trajectories of plant communities.
Microbial communities and nutrient dynamics in experimental microcosms are altered after the application of a high dose of Bti
Authors: Duguma Dagne , Hall Michael W. , Rugman‐Jones Paul , Stouthamer Richard , Neufeld Josh D. , Walton William E.
Published: March 2015

Bacillus thuringiensis subsp. israelensis (Bti) is the most widely used biopesticide against mosquitoes and blackflies, with a history of high specificity and efficacy. High doses of Bti have been suggested for extended vector control in some environments; however, the effects of Bti application on the native microfauna in the environment are poorly understood.

Two Bti (VectoBac G) treatments (high = 48·1 kg ha−1; low = 0·6 kg ha−1), in addition to an untreated control, were assigned to replicate 300 L microcosms.

Culex abundance, phytoplankton biomass, sestonic particulates and nutrients were reduced significantly in the high Bti treatment. These changes affected other physicochemical variables in the water column during the 44‐day field study.

Bacterial communities present in the water column were assessed by Illumina sequencing of 16S rRNA genes. The most abundant aquatic bacteria in microcosms subject to a low dose of Bti and untreated control, Cyanobacteria, Cytophagales, Cyclobacteriaceae (phylum Bacteroidetes) and Sphingomonas (class Alphaproteobacteria), were suppressed in microcosms subject to a high dose of Bti. Bacteria in the high Bti treatment were dominated by Mucilaginibacter, Sediminibacterium (phylum Sphingobacteria) and Polaromonas (class Betaproteobacteria) and were more diverse than in the other treatments.

Synthesis and applications. The biotic and abiotic changes resulting from a biopesticide application that significantly reduced mosquito abundance by more than 50% persisted longer than the period during which larval mosquito numbers were reduced. This warranted further investigation into the ecosystem‐level effects of Bti application rates used routinely for mosquito control. Application rates greater than the label rate for a Bti biopesticide can reduce mosquito abundance for an extended period of time and therefore lessen the operational cost of repeated application, but they could exceed manufacturer's recommendations and might violate country‐specific regulations governing biopesticide applications in natural habitats. Results of our study suggest that the widespread adoption of Bti application above the recommended label rate should be discouraged in habitats where algal abundance and its effect on primary production, microbial communities and nutrient cycling could affect the functioning of aquatic food webs.
Developing and enhancing biodiversity monitoring programmes: a collaborative assessment of priorities
Authors: Pocock Michael J. O. , Newson Stuart E. , Henderson Ian G. , Peyton Jodey , Sutherland William J. , Noble David G. , Ball Stuart G. , Beckmann Björn C. , Biggs Jeremy , Brereton Tom , Bullock David J. , Buckland Stephen T. , Edwards Mike , Eaton Mark A. , Harvey Martin C. , Hill Mark O. , Horlock Martin , Hubble David S. , Julian Angela M. , Mackey Edward C. , Mann Darren J. , Marshall Matthew J. , Medlock Jolyon M. , O'Mahony Elaine M. , Pacheco Marina , Porter Keith , Prentice Steve , Procter Deborah A. , Roy Helen E. , Southway Sue E. , Shortall Chris R. , Stewart Alan J. A. , Wembridge David E. , Wright Mark A. , Roy David B.
Published: March 2015

Biodiversity is changing at unprecedented rates, and it is increasingly important that these changes are quantified through monitoring programmes. Previous recommendations for developing or enhancing these programmes focus either on the end goals, that is the intended use of the data, or on how these goals are achieved, for example through volunteer involvement in citizen science, but not both. These recommendations are rarely prioritized.

We used a collaborative approach, involving 52 experts in biodiversity monitoring in the UK, to develop a list of attributes of relevance to any biodiversity monitoring programme and to order these attributes by their priority. We also ranked the attributes according to their importance in monitoring biodiversity in the UK. Experts involved included data users, funders, programme organizers and participants in data collection. They covered expertise in a wide range of taxa.

We developed a final list of 25 attributes of biodiversity monitoring schemes, ordered from the most elemental (those essential for monitoring schemes; e.g. articulate the objectives and gain sufficient participants) to the most aspirational (e.g. electronic data capture in the field, reporting change annually). This ordered list is a practical framework which can be used to support the development of monitoring programmes.

People's ranking of attributes revealed a difference between those who considered attributes with benefits to end users to be most important (e.g. people from governmental organizations) and those who considered attributes with greatest benefit to participants to be most important (e.g. people involved with volunteer biological recording schemes). This reveals a distinction between focussing on aims and the pragmatism in achieving those aims.

Synthesis and applications. The ordered list of attributes developed in this study will assist in prioritizing resources to develop biodiversity monitoring programmes (including citizen science). The potential conflict between end users of data and participants in data collection that we discovered should be addressed by involving the diversity of stakeholders at all stages of programme development. This will maximize the chance of successfully achieving the goals of biodiversity monitoring programmes.
Extinction debt of a common shrub in a fragmented landscape
Authors: González‐Varo Juan P. , Albaladejo Rafael G. , Aizen Marcelo A. , Arroyo Juan , Aparicio Abelardo
Published: March 2015

Environmental stochasticity and low demographic rates may cause delayed extinctions of habitat‐specialist species that were initially retained within remnant patches after habitat loss and fragmentation. Detecting such extinction debts opens opportunities to counteract future biodiversity loss, yet knowing the underlying causes of population declines is a basic need for targeting specific guidelines for conservation and restoration (e.g. habitat quantity, quality or connectivity).

Here, we examine the extinction debt in the common Mediterranean shrub Myrtus communis (myrtle) occurring in woodland patches of a highly fragmented region that has lost nearly half of the remnant woodland cover during the last 50 years (1956–2002).

We sampled myrtle occurrence in 304 woodland patches and modelled its probability of occurrence in relation to patch size, patch disturbance and woodland cover in the surrounding landscape. In order to test for extinction debt evidence, we tested whether myrtle occurrence is better predicted by past (1956) than by present (2002) woodland cover.

We found that the probability of myrtle occurrence is associated with present patch features (size and disturbance) that are linked to causes of individual mortality and/or recruitment collapse. However, it was associated with past – rather than present – woodland cover in the surrounding landscape, proving a still unpaid extinction debt. Specifically, myrtle occurrence is very unlikely in small and highly disturbed patches located in long‐term deforested landscapes.

Synthesis and applications. Individual longevity of the Mediterranean shrub Myrtus communis (myrtle) can delay local extinctions, but paying the debt is a matter of time, especially considering the elevated susceptibility of small and disturbed populations to environmental stochasticity. However, these populations still offer management opportunities, and reducing disturbances and improving habitat quality, especially within small woodland patches, should be a top priority for conservation and restoration.