bluuebunny/crossref_metadata_2025_split huggingface dataset:
Signaling from the plasma-membrane localized plant immune receptor RPM1 requires self-association of the full-length protein
Authors: El Kasmi Farid , Chung Eui-Hwan , Anderson Ryan G. , Li Jinyue , Wan Li , Eitas Timothy K. , Gao Zhiyong , Dangl Jeffery L. 
Published: August 2017

Significance
Pathogen recognition first occurs at the plasma membrane, where receptor-like kinases perceive pathogen-derived molecules and initiate immune responses. To abrogate this immune response, pathogens evolved effector proteins that act as virulence factors, often following delivery to the host cell. Plants evolved intracellular receptors, known as NOD-like receptors (NLRs), to detect effectors, thereby ensuring activation of effector-triggered immunity. However, despite their importance in immunity, the molecular mechanisms underlying effector recognition and subsequent immune activation by membrane-localized NLRs remain to be fully elucidated. Our analyses reveal the importance of and need for self-association and the coordinated interplay of specific domains and conserved residues for NLR activity. This could provide strategies for crop improvement, contributing to effective, environmentally friendly, and sustainable solutions for future agriculture.
De novo mutations in inhibitors of Wnt, BMP, and Ras/ERK signaling pathways in non-syndromic midline craniosynostosis
Authors: Timberlake Andrew T. , Furey Charuta G. , Choi Jungmin , Nelson-Williams Carol ,   Yale Center for Genome Analysis, Loring Erin , Galm Amy , Kahle Kristopher T. , Steinbacher Derek M. , Larysz Dawid , Persing John A. , Lifton Richard P. , Bilguvar Kaya , Mane Shrikant , Tikhonova Irina , Castaldi Christopher , Knight James 
Published: August 2017

SignificanceCraniosynostosis is a common congenital malformation resulting from premature fusion of the bones that comprise the cranial vault, requiring surgery in infancy to prevent adverse neurologic outcomes. Eighty-five percent of cases are non-syndromic and of unknown cause. By exome sequencing of families with non-syndromic midline craniosynostosis, we show that 5% of cases have de novo damaging mutations in negative regulators of the Wnt, bone morphogenetic protein (BMP), and Ras/ERK signaling pathways, developmental cascades that converge on common nuclear targets to promote bone formation. Another 5% have transmitted mutations in these pathways. Common variants nearBMP2show genetic interaction with these rare mutations. The results provide insight into pathophysiology and have immediate implications for the diagnosis and genetic counseling of families with craniosynostosis.
Vertical distribution of snow crab (Chionoecetes opilio) pelagic stages in the Gulf of St. Lawrence (Canada) and effect of temperature on development and survival
Authors: Ouellet Patrick , Sainte-Marie Bernard 
Published: August 2017

AbstractKnowledge of the vertical distribution, thermal habitat, and growth of the larvae of the cold stenothermic snow crab (Chionoecetes opilio) is incomplete and inconsistent. This study explored aspects of the vertical distribution and development rate of larvae from eastern Canada. In the Gulf of St. Lawrence (GSL), during 2002, the mean vertical positions of the snow crab zoeae I and II larvae were recorded within and above the permanent thermocline and in close association with the depth of strong density discontinuities in the stratified water column. No statistically significant differences were detected between nighttime and daytime vertical positions. The water temperatures at the centre of the larvae distributions were 2–3 °C in late May in the colder northern GSL and 7–8 °C in June in the warmer southern GSL. Data from the literature and from a rearing experiment in 2014 were used to develop functions linking development and survival to water temperature. Assuming the snow crab larvae remain in the upper mixed layer until final metamorphosis, development may last 2.2–4 months depending on hatch time and location. Development would be prolonged by several weeks if premolt megalopae move into and reside in the deeper, colder waters as appears to be the case. A relative survival index suggests that optimum temperature for development is around 10.8 °C, 9.5 °C, and 8.7 °C for snow crab zoea I, zoea II, and megalopa, respectively. These results should contribute to modelling efforts that aim to evaluate the extent of larval drift and location of potential settlement areas, as well as the potential impact of climate change on snow crab in the North Atlantic.
Minimally Clinically Important Change in the Activity Measure for Post-Acute Care (AM-PAC), a Generic Patient-Reported Outcome Tool, in People With Low Back Pain
Authors: Lee Natalie , Thompson Nicolas R. , Passek Sandra , Stilphen Mary , Katzan Irene L. 
Published: August 2017

Abstract

Background
The Activity Measure for Post-Acute Care (AM-PAC) is a generic metric of patient-reported functional status. The minimal clinically important difference (MCID) in the AM-PAC score has not been determined.

Objective
The study objective was to determine the MCID for AM-PAC in people with low back pain.

Design
This was a retrospective cohort study.

Methods
Anchor-based and distribution-based methods were used to estimate the MCID. The Modified Low Back Pain Disability Questionnaire was used as the anchor. Adults who had a primary ICD-9 code for low back pain in at least 1 outpatient physical therapist visit during an episode of care and who completed both the AM-PAC and the Modified Low Back Pain Disability Questionnaire in at least 2 visits during the care episode were included. The MCID was calculated for the AM-PAC basic mobility version as well its adapted version, which the Cleveland Clinic uses for patients 65 years old or older.

Results
A total of 1,271 participants were eligible for study. For the AM-PAC basic mobility version, anchor-based methods yielded MCID estimates of between 3.4 and 5.1, whereas distribution-based methods yielded estimates of 1.7 to 4.2. The minimal detectable change (MDC) for the AM-PAC basic mobility version was 3.3. For the adapted AM-PAC basic mobility version, the MCID was estimated to be between 2.9 and 4.0 via anchor-based methods and between 1.2 to 3.5 via distribution-based methods. The MDC for the adapted AM-PAC basic mobility version was 3.5.

Limitations
The estimated MCID was designed for people with low back pain only.

Conclusions
The MCID ranged from 3.3 to 5.1 for the AM-PAC basic mobility version and 3.5 to 4 for the adapted version, with the MDC as the lower limit. Changes in the AM-PAC for people with low back pain may be interpreted using the estimated MCID. Future studies are needed to determine the AM-PAC MCID for populations other than those with low back pain.
Increased SBPase activity improves photosynthesis and grain yield in wheat grown in greenhouse conditions
Authors: Driever Steven M. , Simkin Andrew J. , Alotaibi Saqer , Fisk Stuart J. , Madgwick Pippa J. , Sparks Caroline A. , Jones Huw D. , Lawson Tracy , Parry Martin A. J. , Raines Christine A. 
Published: August 2017

To meet the growing demand for food, substantial improvements in yields are needed. This is particularly the case for wheat, where global yield has stagnated in recent years. Increasing photosynthesis has been identified as a primary target to achieve yield improvements. To increase leaf photosynthesis in wheat, the level of the Calvin–Benson cycle enzyme sedoheptulose-1,7-biphosphatase (SBPase) has been increased through transformation and expression of aBrachypodium distachyonSBPase gene construct. Transgenic lines with increased SBPase protein levels and activity were grown under greenhouse conditions and showed enhanced leaf photosynthesis and increased total biomass and dry seed yield. This showed the potential of improving yield potential by increasing leaf photosynthesis in a crop species such as wheat. The results are discussed with regard to future strategies for further improvement of photosynthesis in wheat.This article is part of the themed issue ‘Enhancing photosynthesis in crop plants: targets for improvement’.
A bioarchitectonic approach to the modular engineering of metabolism
Authors: Kerfeld Cheryl A. 
Published: August 2017

Dissociating the complexity of metabolic processes into modules is a shift in focus from the single gene/gene product to functional and evolutionary units spanning the scale of biological organization. When viewing the levels of biological organization through this conceptual lens, modules are found across the continuum: domains within proteins, co-regulated groups of functionally associated genes, operons, metabolic pathways and (sub)cellular compartments. Combining modules as components or subsystems of a larger system typically leads to increased complexity and the emergence of new functions. By virtue of their potential for ‘plug and play’ into new contexts, modules can be viewed as units of both evolution and engineering. Through consideration of lessons learned from recent efforts to install new metabolic modules into cells and the emerging understanding of the structure, function and assembly of protein-based organelles, bacterial microcompartments, a structural bioengineering approach is described: one that builds from an architectural vocabulary of protein domains. This bioarchitectonic approach to engineering cellular metabolism can be applied to microbial cell factories, used in the programming of members of synthetic microbial communities or used to attain additional levels of metabolic organization in eukaryotic cells for increasing primary productivity and as the foundation of a green economy.
This article is part of the themed issue ‘Enhancing photosynthesis in crop plants: targets for improvement’.
Somatic genome editing with the RCAS/TVA-CRISPR/Cas9 system for precision tumor modeling
Authors: Oldrini Barbara , Curiel-García Álvaro , Marques Carolina , Matia Veronica , Uluçkan Özge , Torres-Ruiz Raul , Rodriguez-Perales Sandra , Huse Jason T. , Squatrito Massimo 
Published: August 2017

AbstractIt has been gradually established that the vast majority of human tumors are extraordinarily heterogeneous at a genetic level. To accurately recapitulate this complexity, it is now evident that in vivo animal models of cancers will require to recreate not just a handful of simple genetic alterations, but possibly dozens and increasingly intricate. Here, we have combined the RCAS/TVA system with the CRISPR/Cas9 genome editing tools for precise modeling of human tumors. We show that somatic deletion in neural stem cells (NSCs) of a variety of known tumor suppressor genes (Trp53, Cdkn2a and Pten), in combination with the expression of an oncogene driver, leads to high-grade glioma formation. Moreover, by simultaneous delivery of pairs of guide RNAs (gRNAs) we generated different gene fusions, either by chromosomal deletion (Bcan-Ntrk1) or by chromosomal translocation (Myb-Qk), and we show that they have transforming potential in vitro and in vivo. Lastly, using homology-directed-repair (HDR), we also produced tumors carrying the Braf V600E mutation, frequently identified in a variety of subtypes of gliomas. In summary, we have developed an extremely powerful and versatile mouse model for in vivo somatic genome editing, that will elicit the generation of more accurate cancer models particularly appropriate for pre-clinical testing.
Global accumulation of circRNAs during aging inCaenorhabditis elegans
Authors: Cortés-López Mariela , Gruner Matthew , Cooper Daphne A. , Gruner Hannah N. , Voda Alexandru-Ioan , der Linden Alexander van , Miura Pedro 
Published: August 2017

SummaryCircular RNAs (CircRNAs) are a newly appreciated class of RNAs that lack free 5´ and 3´ ends, are expressed by the thousands in diverse forms of life, and are mostly of enigmatic function. Ostensibly due to their resistance to exonucleases, circRNAs are known to be exceptionally stable. Here, we examined the global profile of circRNAs inC. elegansduring aging by performing ribo-depleted total RNA-seq from the fourth larval stage (L4) through 10-day old adults. Using stringent bioinformatic criteria and experimental validation, we annotated 1,166 circRNAs, including 575 newly discovered circRNAs. These circRNAs were derived from 797 genes with diverse functions, including genes involved in the determination of lifespan. A massive accumulation of circRNAs during aging was uncovered. Many hundreds of circRNAs were significantly increased among the aging time-points and increases of select circRNAs by over 40-fold during aging were quantified by qRT-PCR. The age-accumulation of circRNAs was not accompanied by increased expression of linear RNAs from the same host genes. We attribute the global scale of circRNA age-accumulation to the high composition of postmitotic cells in adultC. elegans, coupled with the high resistance of circRNAs to decay. These findings suggest that the exceptional stability of circRNAs might explain age-accumulation trends observed from neural tissues of other organisms, which also have a high composition of post-mitotic cells. Given the suitability ofC. elegansfor aging research, it is now poised as an excellent model system to determine if there are functional consequences of circRNA accumulation during aging.
A stable beneficial symbiotic relationship between endophytic fungusSchizophyllum communeand host plantPanax ginseng
Authors: Zhai Xin , Chen Ling , Jia Min , Li Changhui , Shen Hui , Ye Bingzhu , Qin Luping , Han Ting 
Published: August 2017

AbstractEndophytes and plants can establish specific long-term symbiosis through the accumulation of secondary metabolites. Interactions between microbial inhabitants represent a novel area of study for natural products research. In this study, a strain of endophyte 3R-2 that can enhance the biomass and contents of ginsenoside Rc, ginsenoside Rg2 and ginsenoside Rg3 ofPanax ginsenghairy roots was screened out via HPLC, which was identified asSchizophyllum communethrough the morphological and molecular identification. On the base, we found the infection of the endophyte were obviously observed widely in theP. ginsengand the strain formed a stable relationship withP. ginsenghairy roots in parenchyma cells around through tissues embedding slicing, HE ammonium silver staining and immunofluorescence staining. On the other hand, elicitors of fungus 3R-2 can also significantly promote hairy root growth and contents of several ginsenosides, even several times higher than 3R-2 mycelium did. Moreover,S. commune3R-2 mycelium and its elicitor could enhance the transcriptional activity of key genes during the ginsenosides biosynthetic pathway dramatically. Thus, endophyteS. commune3R-2 and its elicitor change the chemical substance content by regulating the expression of genes involved in the secondary metabolite biosynthetic pathway.
HNRNPA1 promotes recognition of splice site decoys by U2AF2in vivo
Authors: Howard Jonathan M. , Lin Hai , Kim Garam , Draper Jolene M , Haeussler Maximilian , Katzman Sol , Toloue Masoud , Liu Yunlong , Sanford Jeremy R. 
Published: August 2017

AbstractAlternative pre-mRNA splicing plays a major role in expanding the transcript output of human genes. This process is regulated, in part, by the interplay oftrans-acting RNA binding proteins (RBPs) with myriadcis-regulatory elements scattered throughout pre-mRNAs. These molecular recognition events are critical for defining the protein coding sequences (exons) within pre-mRNAs and directing spliceosome assembly on non-coding regions (introns). One of the earliest events in this process is recognition of the 3’ splice site by U2 small nuclear RNA auxiliary factor 2 (U2AF2). Splicing regulators, such as the heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1), influence spliceosome assembly bothin vitroandin vivo, but their mechanisms of action remain poorly described on a global scale. HNRNPA1 also promotes proof reading of 3’ss sequences though a direct interaction with the U2AF heterodimer. To determine how HNRNPA1 regulates U2AF-RNA interactions in vivo, we analyzed U2AF2 RNA binding specificity using individual-nucleotide resolution crosslinking immunoprecipitation (iCLIP) in control- and HNRNPA1 over-expression cells. We observed changes in the distribution of U2AF2 crosslinking sites relative to the 3’ splice sites of alternative cassette exons but not constitutive exons upon HNRNPA1 over-expression. A subset of these events shows a concomitant increase of U2AF2 crosslinking at distal intronic regions, suggesting a shift of U2AF2 to “decoy” binding sites. Of the many non-canonical U2AF2 binding sites, Alu-derived RNA sequences represented one of the most abundant classes of HNRNPA1-dependent decoys. Splicing reporter assays demonstrated that mutation of U2AF2 decoy sites inhibited HNRNPA1-dependent exon skippingin vivo. We propose that HNRNPA1 regulates exon definition by modulating the interaction of U2AF2 with decoy orbona fide3’ splice sites.
A bestiary of localized sequence rearrangements in human DNA
Authors: Frith Martin C. , Khan Sofia 
Published: August 2017

AbstractGenomes mutate and evolve in ways simple (substitution or deletion of bases) and complex (e.g. chromosome shattering). We do not fully understand what types of complex mutation occur, and we cannot routinely characterize arbitrarily-complex mutations in a high-throughput, genome-wide manner. Long-read DNA sequencing methods (e.g. PacBio, nanopore) are promising for this task, because one read may encompass a whole complex mutation. We describe an analysis pipeline to characterize arbitrarily-complex “local” mutations, i.e. intrachromosomal mutations encompassed by one DNA read. We apply it to nanopore and PacBio reads from one human cell line (NA12878), and survey sequence rearrangements, both real and artifactual. Almost all the real rearrangements belong to recurring patterns or motifs: the most common is tandem multiplication (e.g. heptuplication), but there are also complex patterns such as localized shattering, which resembles DNA damage by radiation. Gene conversions are identified, including one between hemoglobin gamma genes. This study demonstrates a way to find intricate rearrangements with any number of duplications, deletions, and repositionings. It demonstrates a probability-based method to resolve ambiguous rearrangements involving highly similar sequences, as occurs in gene conversion. We present a catalog of local rearrangements in one human cell line, and show which rearrangement patterns occur.
Nanopore sequencing enables near-completede novoassembly ofSaccharomyces cerevisiaereference strain CEN.PK113-7D
Authors: Salazar Alex N. , Gorter de Vries Arthur R. , van den Broek Marcel , Wijsman Melanie , de la Torre Cortés Pilar , Brickwedde Anja , Brouwers Nick , Daran Jean-Marc G. , Abeel Thomas 
Published: August 2017

AbstractThe haploidSaccharomyces cerevisiaestrain CEN.PK113-7D is a popular model system for metabolic engineering and systems biology research. Current genome assemblies are based on short-read sequencing data scaffolded based on homology to strain S288C. However, these assemblies contain large sequence gaps, particularly in subtelomeric regions, and the assumption of perfect homology to S288C for scaffolding introduces bias.In this study, we obtained a near-complete genome assembly of CEN.PK113-7D using only Oxford Nanopore Technology’s MinION sequencing platform. 15 of the 16 chromosomes, the mitochondrial genome, and the 2-micron plasmid are assembled in single contigs and all but one chromosome starts or ends in a telomere cap. This improved genome assembly contains 770 Kbp of added sequence containing 248 gene annotations in comparison to the previous assembly of CEN.PK113-7D. Many of these genes encode functions determining fitness in specific growth conditions and are therefore highly relevant for various industrial applications. Furthermore, we discovered a translocation between chromosomes III and VIII which caused misidentification of aMALlocus in the previous CEN.PK113-7D assembly. This study demonstrates the power of long-read sequencing by providing a high-quality reference assembly and annotation of CEN.PK113-7D and places a caveat on assumed genome stability of microorganisms.
A genomics approach reveals the global genetic polymorphism, structure and functional diversity of ten accessions of the marine model diatomPhaeodactylum tricornutum
Authors: Rastogi Achal , Vieira FRJ , Deton-Cabanillas Anne-Flore , Veluchamy Alaguraj , Cantrel Catherine , Wang Gaohong , Vanormelingen Pieter , Bowler Chris , Piganeau Gwenael , Hu Hanhua , Tirichine Leila 
Published: August 2017

AbstractDiatoms emerged in the Mesozoic period and presently constitute one of the main primary producers in the world’s ocean and are of a major economic importance. In the current study, using whole genome sequencing of ten accessions of the model diatomPhaeodactylum tricornutum, sampled at broad geospatial and temporal scales, we draw a comprehensive landscape of the genomic diversity within the species. We describe strong genetic subdivisions of the accessions into four genetic clades (A-D) with constituent populations of each clade possessing a conserved genetic and functional makeup, likely a consequence of the limited dispersal ofP. tricornutumin the open ocean. We further suggest dominance of asexual reproduction across all the populations, as implied by high linkage disequilibrium. Finally, we show limited yet compelling signatures of genetic and functional convergence inducing changes in the selection pressure on many genes and metabolic pathways. We propose these findings to have significant implications for understanding the genetic structure of diatom populations in nature and provide a framework to assess the genomic underpinnings of their ecological success and impact on aquatic ecosystems where they play a major role. Our work provides valuable resources for functional genomics and for exploiting the biotechnological potential of this model diatom species.
Beer produced via hydrodynamic cavitation retains higher amounts of xanthohumol and other hops prenylflavonoids
Authors: Ciriminna Rosaria , Albanese Lorenzo , Stefano Vita Di , Delisi Riccardo , Avellone Giuseppe , Meneguzzo Francesco , Pagliaro Mario 
Published: August 2017

AbstractA fraction of the most valuable bioactive compounds in beer comes from hop’s polyphenols, mainly flavonoids, some of which are unique to inflorescences of that flowering plant. Although far from pharmacologically relevant concentrations, the intake of low doses of xanthohumol and related prenylflavonoids found in beer contributes to significant preventive actions with regards to certain diseases, such as cardiovascular and neurodegenerative, as well as to distinct chemopreventive effects on certain cancer types. Hence the efforts to explore both ingredients and methods able to enhance the concentration of such bioactive compounds in the final beers. A novel brewing method assisted by hydrodynamic cavitation was proved able, under suitable process conditions, to retain or generate higher amounts of xanthohumol, desmethylxanthohumol and 6-geranylnaringenin, extending recent evidence about different food and respective bioproducts, as well as adding to its distinct benefits to the brewing process.