bluuebunny/crossref_metadata_2025_split huggingface dataset:
Random mutagenesis of the nucleotide‐binding domain of NRC1 (NB‐LRR Required for Hypersensitive Response‐Associated Cell Death‐1), a downstream signalling nucleotide‐binding, leucine‐rich repeat (NB‐LRR) protein, identifies gain‐of‐function mutations in the nucleotide‐binding pocket
Authors: Sueldo Daniela J. , Shimels Mahdere , Spiridon Laurentiu N. , Caldararu Octav , Petrescu Andrei‐Jose , Joosten Matthieu H. A. J. , Tameling Wladimir I. L. 
Published: May 2015

Summary

Plant nucleotide‐binding, leucine‐rich repeat (NB‐LRR) proteins confer immunity to pathogens possessing the corresponding avirulence proteins. Activation of NB‐LRR proteins is often associated with induction of the hypersensitive response (HR), a form of programmed cell death.

NRC1 (NB‐LRR Required for HR‐Associated Cell Death‐1) is a tomato (Solanum lycopersicum) NB‐LRR protein that participates in the signalling cascade leading to resistance to the pathogens Cladosporium fulvum and Verticillium dahliae.

To identify mutations in NRC1 that cause increased signalling activity, we generated a random library of NRC1 variants mutated in their nucleotide‐binding domain and screened them for the ability to induce an elicitor‐independent HR in Nicotiana tabacum. Screening of 1920 clones retrieved 11 gain‐of‐function mutants, with 10 of them caused by a single amino acid substitution.

All substitutions are located in or very close to highly conserved motifs within the nucleotide‐binding domain, suggesting modulation of the signalling activity of NRC1. Three‐dimensional modelling of the nucleotide‐binding domain of NRC1 revealed that the targeted residues are centred around the bound nucleotide. Our mutational approach has generated a wide set of novel gain‐of‐function mutations in NRC1 and provides insight into how the activity of this NB‐LRR is regulated.
Self‐Legislation and Self‐Command in Kant's Ethics
Authors: Wilson Eric Entrican 
Published: May 2015

AbstractIn his later writings, Kant distinguishes between autonomy and self‐mastery or self‐command. My article explains the relation between these two ideas, both of which are integral to his understanding of moral agency and the pursuit of virtue. I point to problems with other interpretations of this relation and offer an alternative. On my view, self‐command is a condition or state achieved by those agents who become proficient at solving problems presented by the passions. Such agents are able to stick to the results of self‐legislation over time and thereby achieve a form of temporally extended freedom.
Surgical Site Infection 18 Months Following Intrathecal Pump Placement Secondary to an Asymptomatic Bowel Injury
Authors: Deibert Christopher P. , Gandhoke Gurpreet S. , Forsythe Raquel M. , Moossy John J. 
Published: May 2015

AbstractSurgical site infections following the implantation of intrathecal drug delivery systems typically present during the first 1 to 2 months following surgery. Surgical site infections occurring outside of this window are rare entities and require special attention to identify the source or underlying cause. In this report, we present a case of pump pocket infection 18 months following implantation due to an asymptomatic and unrecognized bowel injury associated with the catheter. This case highlights the need for a thorough evaluation in a patient with suspected infections more than 2 months after surgery to ensure adequate treatment.
Explaining and mapping total phosphorus content in French topsoils
Authors: Delmas M. , Saby N. , Arrouays D. , Dupas R. , Lemercier B. , Pellerin S. , Gascuel‐Odoux C. 
Published: May 2015

AbstractTotal phosphorus (TP) build‐up in agricultural soils represents both a threat to aquatic ecosystems and a valuable resource for future crop production, given the context of increasing food demand combined with the rapid depletion of the world's phosphate reserves. Therefore, it is crucially important (i) to identify the main factors controlling topsoil TP and (ii) to develop methods for mapping its spatial distribution. Multiple linear regression models were used with two distinct approaches to calculate TP and covariates linked to the P cycle. Firstly, covariates were selected from the Réseau de Mesures de la Qualité des Sols database, the French soil monitoring network, which consists of soil samples collected from 2158 sites on a 16‐km regular grid. Secondly, covariates were selected to map TP from spatially exhaustive datasets in France. The first approach explains 80% of variability in topsoil TP. The variables selected are linked to the autochthonous origin of P (parent material), to allochthonous origin (organic carbon and nitrogen contents) and to the retention capacity of soil (Al, Fe, Ca and clay contents). The predicted map obtained from the second approach provides a mean TP of 0.76 g/kg. This study demonstrates that creating national scale maps of TP, based on detailed soil sampling and many variables, is feasible and can be used to model the P cycle and P transfer processes. Such maps can be used in P erosion and transfer models over river basins, and therefore to predict P exports to surface waters.
Radiolabeled Antibodies for Therapy of Infectious Diseases
Authors: Dadachova Ekaterina , Casadevall Arturo 
Published: May 2015

ABSTRACT

Novel approaches to the treatment of infectious diseases are urgently needed. This need has resulted in renewing the interest in antibodies for therapy of infectious diseases. Radioimmunotherapy (RIT) is a cancer treatment modality that utilizes radiolabeled monoclonal antibodies. During the last decade we have translated RIT into the field of experimental fungal, bacterial, and HIV infections. In addition, successful proof of principle experiments with radiolabeled pan-antibodies that bind to antigens shared by major pathogenic fungi have been performed
in vitro
. The armamentarium of pan-antibodies would result in reducing our dependence on microorganism-specific antibodies and thus would speed up the development of RIT for infections. We believe that the time is ripe for deploying RIT in the clinic to combat infectious diseases.
Division of Labor in Biofilms: the Ecology of Cell Differentiation
Authors: van Gestel Jordi , Vlamakis Hera , Kolter Roberto 
Published: May 2015

ABSTRACT

The dense aggregation of cells on a surface, as seen in biofilms, inevitably results in both environmental and cellular heterogeneity. For example, nutrient gradients can trigger cells to differentiate into various phenotypic states. Not only do cells adapt physiologically to the local environmental conditions, but they also differentiate into cell types that interact with each other. This allows for task differentiation and, hence, the division of labor. In this article, we focus on cell differentiation and the division of labor in three bacterial species:
Myxococcus xanthus, Bacillus subtilis
, and
Pseudomonas aeruginosa
. During biofilm formation each of these species differentiates into distinct cell types, in some cases leading to cooperative interactions. The division of labor and the cooperative interactions between cell types are assumed to yield an emergent ecological benefit. Yet in most cases the ecological benefits have yet to be elucidated. A notable exception is
M. xanthus
, in which cell differentiation within fruiting bodies facilitates the dispersal of spores. We argue that the ecological benefits of the division of labor might best be understood when we consider the dynamic nature of both biofilm formation and degradation.
P Transposable Elements in
Drosophila
and other Eukaryotic Organisms
Authors: Majumdar* Sharmistha , Rio Donald C. 
Published: May 2015

ABSTRACT

P transposable elements were discovered in Drosophila as the causative agents of a syndrome of genetic traits called hybrid dysgenesis. Hybrid dysgenesis exhibits a unique pattern of maternal inheritance linked to the germline-specific small RNA piwi-interacting (piRNA) pathway. The use of P transposable elements as vectors for gene transfer and as genetic tools revolutionized the field of Drosophila molecular genetics. P element transposons have served as a useful model to investigate mechanisms of cut-and-paste transposition in eukaryotes. Biochemical studies have revealed new and unexpected insights into how eukaryotic DNA-based transposons are mobilized. For example, the P element transposase makes unusual 17nt-3′ extended double-strand DNA breaks at the transposon termini and uses guanosine triphosphate (GTP) as a cofactor to promote synapsis of the two transposon ends early in the transposition pathway. The N-terminal DNA binding domain of the P element transposase, called a THAP domain, contains a C
2
CH zinc-coordinating motif and is the founding member of a large family of animal-specific site-specific DNA binding proteins. Over the past decade genome sequencing efforts have revealed the presence of P element-like transposable elements or P element transposase-like genes (called THAP9) in many eukaryotic genomes, including vertebrates, such as primates including humans, zebrafish and Xenopus, as well as the human parasite
Trichomonas vaginalis
, the sea squirt
Ciona
, sea urchin and hydra. Surprisingly, the human and zebrafish P element transposase-related THAP9 genes promote transposition of the
Drosophila
P element transposon DNA in human and
Drosophila
cells, indicating that the THAP9 genes encode active P element “transposase” proteins.
Mating-type Gene Switching in
Saccharomyces cerevisiae
Authors: Lee Cheng-Sheng , Haber James E. 
Published: May 2015

ABSTRACT

The budding yeast
Saccharomyces cerevisiae
has two alternative mating types designated
MAT
a
and
MAT
α. These are distinguished by about 700 bp of unique sequences, Y
a
or Yα, including divergent promoter sequences and part of the open reading frames of genes that regulate mating phenotype. Homothallic budding yeast, carrying an active HO endonuclease gene,
HO
, can switch mating type through a recombination process known as gene conversion, in which a site-specific double-strand break (DSB) created immediately adjacent to the Y region results in replacement of the Y sequences with a copy of the opposite mating type information, which is harbored in one of two heterochromatic donor loci,
HML
α or
HMR
a
. HO gene expression is tightly regulated to ensure that only half of the cells in a lineage switch to the opposite
MAT
allele, thus promoting conjugation and diploid formation. Study of the silencing of these loci has provided a great deal of information about the role of the Sir2 histone deacetylase and its associated Sir3 and Sir4 proteins in creating heterochromatic regions.
MAT
switching has been examined in great detail to learn about the steps in homologous recombination.
MAT
switching is remarkably directional, with
MAT
a
recombining preferentially with
HML
α and
MAT
α using
HMR
a
. Donor preference is controlled by a
cis
-acting recombination enhancer located near
HML
. RE is turned off in
MAT
α cells but in
MAT
a
binds multiple copies of the Fkh1 transcription factor whose forkhead-associated phosphothreonine binding domain localizes at the DSB, bringing
HML
into conjunction with
MAT
a
.
piggyBacTransposon
Authors: Yusa Kosuke 
Published: May 2015

ABSTRACTThepiggyBactransposon was originally isolated from the cabbage looper moth,Trichoplusia ni, in the 1980s. Despite its early discovery and dissimilarity to the other DNA transposon families, thepiggyBactransposon was not recognized as a member of a large transposon superfamily for a long time. Initially, thepiggyBactransposon was thought to be a rare transposon. This view, however, has now been completely revised as a number of fully sequenced genomes have revealed the presence ofpiggyBac-like repetitive elements. The isolation of active copies of thepiggyBac-like elements from several distinct species further supported this revision. This includes the first isolation of an active mammalian DNA transposon identified in the bat genome. To date, thepiggyBactransposon has been deeply characterized and it represents a number of unique characteristics. In general, all members of thepiggyBacsuperfamily use TTAA as their integration target sites. In addition, thepiggyBactransposon shows precise excision, i.e., restoring the sequence to its preintegration state, and can transpose in a variety of organisms such as yeasts, malaria parasites, insects, mammals, and even in plants. Biochemical analysis of the chemical steps of transposition revealed thatpiggyBacdoes not require DNA synthesis during the actual transposition event. The broad host range has attracted researchers from many different fields, and thepiggyBactransposon is currently the most widely used transposon system for genetic manipulations.
Mechanisms of DNA Transposition
Authors: Hickman Alison B. , Dyda Fred 
Published: May 2015

ABSTRACT
DNA transposases use a limited repertoire of structurally and mechanistically distinct nuclease domains to catalyze the DNA strand breaking and rejoining reactions that comprise DNA transposition. Here, we review the mechanisms of the four known types of transposition reactions catalyzed by (1) RNase H-like transposases (also known as DD(E/D) enzymes); (2) HUH single-stranded DNA transposases; (3) serine transposases; and (4) tyrosine transposases. The large body of accumulated biochemical and structural data, particularly for the RNase H-like transposases, has revealed not only the distinguishing features of each transposon family, but also some emerging themes that appear conserved across all families. The more-recently characterized single-stranded DNA transposases provide insight into how an ancient HUH domain fold has been adapted for transposition to accomplish excision and then site-specific integration. The serine and tyrosine transposases are structurally and mechanistically related to their cousins, the serine and tyrosine site-specific recombinases, but have to date been less intensively studied. These types of enzymes are particularly intriguing as in the context of site-specific recombination they require strict homology between recombining sites, yet for transposition can catalyze the joining of transposon ends to form an excised circle and then integration into a genomic site with much relaxed sequence specificity.
Serine Resolvases
Authors: Rice Phoebe A. 
Published: May 2015

ABSTRACT
Serine resolvases are an interesting group of site-specific recombinases that, in their native contexts, resolve large fused replicons into smaller separated ones. Some resolvases are encoded by replicative transposons and resolve the transposition product, in which the donor and recipient molecules are fused, into separate replicons. Other resolvases are encoded by plasmids and function to resolve plasmid dimers into monomers. Both types are therefore involved in the spread and maintenance of antibiotic-resistance genes. Resolvases and the closely related invertases were the first serine recombinases to be studied in detail, and much of our understanding of the unusual strand exchange mechanism of serine recombinases is owed to those early studies. Resolvases and invertases have also served as paradigms for understanding how DNA topology can be harnessed to regulate enzyme activity. Finally, their relatively modular structure, combined with a wealth of structural and biochemical data, has made them good choices for engineering chimeric recombinases with designer specificity. This chapter focuses on the current understanding of serine resolvases, with a focus on the contributions of structural studies.
Mobile Bacterial Group II Introns at the Crux of Eukaryotic Evolution
Authors: Lambowitz Alan M. , Belfort Marlene 
Published: May 2015

ABSTRACTThis review focuses on recent developments in our understanding of group II intron function, the relationships of these introns to retrotransposons and spliceosomes, and how their common features have informed thinking about bacterial group II introns as key elements in eukaryotic evolution. Reverse transcriptase-mediated and host factor-aided intron retrohoming pathways are considered along with retrotransposition mechanisms to novel sites in bacteria, where group II introns are thought to have originated. DNA target recognition and movement by target-primed reverse transcription infer an evolutionary relationship among group II introns, non-LTR retrotransposons, such as LINE elements, and telomerase. Additionally, group II introns are almost certainly the progenitors of spliceosomal introns. Their profound similarities include splicing chemistry extending to RNA catalysis, reaction stereochemistry, and the position of two divalent metals that perform catalysis at the RNA active site. There are also sequence and structural similarities between group II introns and the spliceosome's small nuclear RNAs (snRNAs) and between a highly conserved core spliceosomal protein Prp8 and a group II intron-like reverse transcriptase. It has been proposed that group II introns entered eukaryotes during bacterial endosymbiosis or bacterial-archaeal fusion, proliferated within the nuclear genome, necessitating evolution of the nuclear envelope, and fragmented giving rise to spliceosomal introns. Thus, these bacterial self-splicing mobile elements have fundamentally impacted the composition of extant eukaryotic genomes, including the human genome, most of which is derived from close relatives of mobile group II introns.
The Ty1 LTR-Retrotransposon of Budding Yeast,Saccharomyces cerevisiae
Authors: Curcio M. Joan , Lutz Sheila , Lesage Pascale 
Published: May 2015

ABSTRACTLong-terminal repeat (LTR)-retrotransposons generate a copy of their DNA (cDNA) by reverse transcription of their RNA genome in cytoplasmic nucleocapsids. They are widespread in the eukaryotic kingdom and are the evolutionary progenitors of retroviruses. The Ty1 element of the budding yeastSaccharomyces cerevisiaewas the first LTR-retrotransposon demonstrated to mobilize through an RNA intermediate, and not surprisingly, is the best studied. The depth of our knowledge of Ty1 biology stems not only from the predominance of active Ty1 elements in theS. cerevisiaegenome but also the ease and breadth of genomic, biochemical, and cell biology approaches available to study cellular processes in yeast. This review describes the basic structure of Ty1 and its gene products, the replication cycle, the rapidly expanding compendium of host cofactors known to influence retrotransposition, and the nature of Ty1's elaborate symbiosis with its host. Our goal is to illuminate the value of Ty1 as a paradigm to explore the biology of LTR-retrotransposons in multicellular organisms, where the low frequency of retrotransposition events presents a formidable barrier to investigations of retrotransposon biology.
Mining Environmental Plasmids for Synthetic Biology Parts and Devices
Authors: Martínez-García Esteban , Benedetti Ilaria , Hueso Angeles , De Lorenzo Víctor 
Published: May 2015

ABSTRACT

The scientific and technical ambition of contemporary synthetic biology is the engineering of biological objects with a degree of predictability comparable to those made through electric and industrial manufacturing. To this end, biological parts with given specifications are sequence-edited, standardized, and combined into devices, which are assembled into complete systems. This goal, however, faces the customary context dependency of biological ingredients and their amenability to mutation. Biological orthogonality (i.e., the ability to run a function in a fashion minimally influenced by the host) is thus a desirable trait in any deeply engineered construct. Promiscuous conjugative plasmids found in environmental bacteria have evolved precisely to autonomously deploy their encoded activities in a variety of hosts, and thus they become excellent sources of basic building blocks for genetic and metabolic circuits. In this article we review a number of such reusable functions that originated in environmental plasmids and keep their properties and functional parameters in a variety of hosts. The properties encoded in the corresponding sequences include
inter alia
origins of replication, DNA transfer machineries, toxin-antitoxin systems, antibiotic selection markers, site-specific recombinases, effector-dependent transcriptional regulators (with their cognate promoters), and metabolic genes and operons. Several of these sequences have been standardized as BioBricks and/or as components of the SEVA (Standard European Vector Architecture) collection. Such formatting facilitates their physical composability, which is aimed at designing and deploying complex genetic constructs with new-to-nature properties.
Between compliance and resistance: exploring discourses on family planning in Community Health Committees in Mozambique
Authors: Capurchande Rehana Dauto , Coene Gily , Roelens Kristien , Meulemans Herman 
Published: May 2015

ObjectivesAlthough the Mozambican government has implemented a community-based approach to family planning (FP), little is known about the appropriateness of this process. We explore how members of Community Health Committees (CHCs) address and act regarding FP.Methods/settingsAn in-depth qualitative study of CHCs was conducted at two sites in Maputo province—Ndlavela and Boane—using focus group discussions (n=6), informal conversations (n=4) and observation. The analysis followed a phenomenological approach.ResultsCHCs in Ndlavela appeared to transfer more of the expected information than those in Boane. However, in the CHCs at both study sites, we found heterogeneity in CHCs’ perspectives leading to conflicting views among committee members (CMs). Arising issues included contraceptive type, target groups, the desirable number of children per family as well as the way FP was to be represented. Moreover, weak communication between CMs and health workers, and lack of payment for CMs’ activities influenced promotion of FP.ConclusionsThe two CHCs framed FP in different ways leading to inconsistent participation of CHC members in promoting FP. Policymakers should consider the diversity of discourses and aspirations of these committees when delivering information to them.
Defining a safe player run-off zone around rugby union playing areas
Authors: Fuller Colin W , Jones Rhys , Fuller Andrew D 
Published: May 2015

ObjectivesTo identify the circumstances in which international rugby players exit the playing area during match activities and to define a safe run-off distance around the playing area.MethodAn observational study using video recordings of 102 matches associated with the Rugby World Cup (2011), Rugby Championship (2013, 2014) and Six Nations Championship (2013, 2014) were used to analyse every event in which one or more players exited the playing area during normal match activities. The circumstances in which a player exited the playing area were categorised using a range of parameters: playing position, location, out-of-play region, match activity, distance travelled over the touchline, contacts made with pitchside fixtures and fittings.ResultsNinety-five per cent of player-excursions took place within 5.2 m of the touchline. Players exiting the playing area were nearly three times more likely to be a back than a forward (p<0.001) and the event was more likely to take place when a team was defending than attacking (p<0.001). Being forced out of play during a contact event (70%) was the major reason for players exiting the playing area. Most players (88%) exiting the playing area only made contact with the perimeter area surface; a small proportion of players contacted touchline flags (6.1%), advertising boards (2.3%) and TV cameras/equipment (1.0%).ConclusionsA minimum hazard-free distance of 5 m around a Rugby pitch is proposed based on the 95% percentile frequency distribution of player-excursion events into the areas contiguous with the playing area.