bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractOur 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

ABSTRACTMechanisms 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

AbstractGraphical 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

ABSTRACTAllelic 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.
A Comparison of Methods to Measure Fitness inEscherichia coli
Authors: Wiser Michael J , Lenski Richard E 
Published: March 2015

AbstractIn 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

AbstractThe 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.AbbreviationsAPC/CAnaphase Promoting Complex/CyclosomeDUBdeubiquitinaseSACspindle assembly checkpointUPSubiquitin-proteasome systemZMZM447439
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

AbstractStatistical 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.
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

Abstract
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

Abstract
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

Summary

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

Summary

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

Summary

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

Summary

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.