bluuebunny/crossref_metadata_2025_split huggingface dataset:
Major QTLs for resistance to early and late leaf spot diseases are identified on chromosomes 3 and 5 in peanut (Arachis hypogaea)
Authors: Chu Ye , Chee Peng , Culbreath Albert , Isleib Tom G. , Holbrook Corley C. , Ozias-Akins Peggy 
Published: March 2019

AbstractEarly and late leaf spots are the major foliar diseases of peanut responsible for severely decreased yield in the absence of intensive fungicide spray programs. Pyramiding host resistance to leaf spots in elite cultivars is a sustainable solution to mitigate the diseases. In order to determine the genetic control of leaf spot disease resistance in peanut, a recombinant inbred line population (Florida-07 x GP-NC WS16) segregating for resistance to both diseases was used to construct a SNP-based linkage map consisting of 855 loci. QTL mapping revealed three resistance QTLs for late leaf spot qLLSA05 (phenotypic variation explained, PVE=7-10%), qLLSB03 (PVE=5-7%), and qLLSB05 (PVE=15-41%) that were consistently expressed over multi-year analysis. Two QTL, qLLSA05 and qLLSB05, confirmed our previously published QTL-seq results. For early leaf spot, three resistance QTLs were identified in multiple years, two on chromosome A03 (PVE=8-12%) and one on chromosome B03 (PVE=13-20%), with the locus qELSA03_1.1 coinciding with the previously published genomic region for LLS resistance in GPBD4. Comparative analysis of the genomic regions spanning the QTLs suggests that resistance to early and late leaf spots are largely genetically independent. In addition, QTL analysis on yield showed that the presence of resistance allele in qLLSB03 and qLLSB05 loci might result in protection from yield loss caused by LLS disease damage. Finally, post hoc analysis of the RIL subpopulation that was not utilized in the QTL mapping revealed that the flanking markers for these QTLs can successfully select for resistant and susceptible lines, confirming the effectiveness of pyramiding these resistance loci to improve host-plant resistance in peanut breeding programs using marker-assisted selection.
The reactivity of an unusual amidase may explain colibactin’s DNA cross-linking activity
Authors: Jiang Yindi , Stornetta Alessia , Villalta Peter W. , Wilson Matthew R. , Boudreau Paul D. , Zha Li , Balbo Silvia , Balskus Emily P. 
Published: March 2019

ABSTRACTCertain commensal and pathogenic bacteria produce colibactin, a small molecule genotoxin that causes interstrand cross-links in host cell DNA. Though colibactin has been found to alkylate DNA, the molecular basis for cross-link formation is unclear. Here, we report that the colibactin biosynthetic enzyme ClbL is an amide bond-forming enzyme that links aminoketone and β-keto thioester substrates in vitro and in vivo. The substrate specificity of ClbL strongly supports a role for this enzyme in terminating the colibactin NRPS-PKS assembly line. This transformation would incorporate two electrophilic cyclopropane warheads into the final natural product scaffold. Overall, this work provides a biosynthetic explanation for colibactin’s DNA crosslinking activity and paves the way for further study of its chemical structure.
Induction of the nicotinamide riboside kinase NAD+ salvage pathway in skeletal myopathy of H6PDH KO mice
Authors: Doig Craig L. , Zielinska Agnieszka E. , Fletcher Rachel S. , Oakey Lucy A. , Elhassan Yasir S. , Garten Antje , Cartwright David , Heising Silke , Alsheri Ahmed , Watson David G. , Adamski Jerzy , Tennant Daniel A. , Lavery Gareth G. 
Published: March 2019

AbstractBackgroundHexose-6-Phosphate Dehydrogenase (H6PDH) is a generator of NADPH in the Endoplasmic/Sarcoplasmic Reticulum (ER/SR). Interaction of H6PDH with 11β-hydroxysteroid dehydrogenase type 1 provides NADPH to support oxo-reduction of inactive to active glucocorticoids, but the wider understanding of H6PDH in ER/SR NAD(P)(H) homeostasis is incomplete. Muscle specific lack of H6PDH results in a deteriorating skeletal myopathy, altered glucose homeostasis, ER stress and activation of the unfolded protein response. Here we further assess muscle responses to H6PDH deficiency to delineate pathways that may underpin myopathy and link SR redox status to muscle wide metabolic adaptation.MethodsWe analysed skeletal muscle from H6PDH knockout (H6PDKO), H6PDH and NRK2 double knockout (DKO) and wild-type (WT) mice. H6PDKO mice were supplemented with the NAD+ precursor nicotinamide riboside. Skeletal muscle samples were subject to biochemical analysis including NAD(H) measurement, LC/MS based metabolomics, Western immunoblotting, and high resolution mitochondrial respirometry. Genetic and supplement models were assessed for degree of myopathy compared to H6PDKO.ResultsH6PDKO skeletal muscle showed adaptations in the routes regulating nicotinamide and NAD+ biosynthesis, with significant activation of the Nicotinamide Riboside Kinase 2 (NRK2) pathway. Associated with changes in NAD+ biosynthesis H6PDKO muscle had impaired mitochondrial respiratory capacity with altered mitochondrial acylcarnitine and acetyl CoA metabolism. Boosting NAD+ levels through the NRK2 pathway using the precursor nicotinamide riboside had no effect to mitigate ER stress and dysfunctional mitochondrial respiratory capacity or Acetyl-CoA metabolism. Similarly, H6PDKO/NRK2 double KO mice did not display an exaggerated timing or severity of myopathy or overt change in mitochondrial metabolism despite depression of NAD+ availability.ConclusionsThese findings suggest a complex metabolic response to changes to muscle SR NADP(H) redox status that result in impaired mitochondrial energy metabolism and activation of cellular NAD+ salvage pathways. It is possible that SR can sense and signal perturbation in NAD(P)(H) that cannot be rectified in the absence of H6PDH. Whether NRK2 pathway activation is a direct response to changes in SR NAD(P)(H) availability or adaptation to deficits in metabolic energy availability remains to be resolved.
Rapid, precise, and reliable measurement of delay discounting using a Bayesian learning algorithm
Authors: Ahn Woo-Young , Gu Hairong , Shen Yitong , Haines Nathaniel , Hahn Hunter A. , Teater Julie E. , Myung Jay I. , Pitt Mark A. 
Published: March 2019

AbstractMachine learning has the potential to facilitate the development of computational methods that improve the measurement of cognitive and mental functioning. In three populations (college students, patients with a substance use disorder, and Amazon Mechanical Turk workers), we evaluated one such method, Bayesian adaptive design optimization (ADO), in the area of delay discounting by comparing its test-retest reliability, precision, and efficiency with that of a conventional staircase method. In all three populations tested, the results showed that ADO led to 0.95 or higher test-retest reliability of the discounting rate within 10-20 trials (under 1-2 minutes of testing), captured approximately 10% more variance in test-retest reliability, was 3-5 times more precise, and was 3-8 times more efficient than the staircase method. The ADO methodology provides efficient and precise protocols for measuring individual differences in delay discounting.
Modulation of Flagellar Rotation in Surface-Attached Bacteria: A Circuit for Rapid Surface-Sensing
Authors: Schniederberend Maren , Johnston Jessica F. , Shine Emilee , Shen Cong , Jain Ruchi , Emonet Thierry , Kazmierczak Barbara I. 
Published: March 2019

AbstractAttachment is a necessary first step in bacterial commitment to surface-associated behaviors that include colonization, biofilm formation, and host-directed virulence. The Gram-negative opportunistic pathogenPseudomonas aeruginosacan initially attach to surfaces via its single polar flagellum. Although many bacteria quickly detach, some become irreversibly attached and express surface-associated structures, such as Type IV pili, and behaviors, including twitching motility and biofilm initiation.P. aeruginosathat lack the GTPase FlhF assemble a randomly placed flagellum that is motile; however, we observed that these mutant bacteria show defects in biofilm formation comparable to those seen for non-motile, aflagellate bacteria. This phenotype was associated with altered behavior of ΔflhFbacteria immediately following surface-attachment. Forward and reverse genetic screens led to the discovery that FlhF interacts with FimV to control flagellar rotation at a surface, and implicated cAMP signaling in this pathway. Although cAMP controls many transcriptional programs inP. aeruginosa, the known targets of this second messenger were not required to modulate flagellar rotation in surface-attached bacteria. Instead, alterations in switching behavior of the motor appear to result from previously undescribed effects of cAMP on switch complex proteins and/or the motor-stators associated with them.Author SummaryAttachment to a surface often triggers programs of gene expression that alter the behavior, virulence and fitness of bacteria. Initial contact is usually mediated by surface exposed adhesins, such as flagella or pili/fimbriae, and there is much interest in how these structures might sense and respond to surface attachment. The human bacterial pathogenPseudomonas aeruginosausually contacts surfaces via its polar flagellum, the rotary motor that also powers bacterial swimming. We observed that wild-type bacteria quickly stopped rotating their flagellum after surface attachment, but that a mutant lacking the flagellar-associated protein FlhF did not. Using a combination of genetic approaches, we demonstrated that FlhF interacts with a component of the flagellar rotor (FliG) and with a polar scaffolding protein that positively regulates cAMP production (FimV) to stop flagellar rotation and thereby favor bacterial persistence at a surface. We provide evidence that the second messenger cAMP is the likely signal generated by flagellar-mediated surface attachment and show that cAMP is sufficient to alter the behavior of the flagellar motor.
Bioisosterism reveals new structure-odor relationships
Authors: Tahirova Narmin , Poivet Erwan , Xu Lu , Peterlin Zita , Zou Dong-Jing , Firestein Stuart 
Published: March 2019

ABSTRACTThe question of structure-odor relationship (SOR) has inspired numerous studies into chemical odorants via their perceptual similarities. Much of this data comes from psychophysical studies on humans, precluding the possibility of direct measurements of receptor or receptor neuron activation. Remarkably, we find that many of the perceptual classifications used by human subjects translate well enough to mouse that we can apply cellular methods to better understand the molecular mechanism, that leads to odor discrimination and perception. Using a well studied and well recognizable odor percept of bitter almond, we have tested an odorant panel of aldehydes and ketones that were reported to share such perceptual qualities. These odorants include aromatic and aliphatic, as well as cyclic and allylic features. When parsing these odorants using chemical descriptors, we have a clear separation of molecules possessing these various features. However, here we show that OSN responses better recapitulate the physiological percept. Using these odorants, we also provide a proof-of-concept for non-classical bioisosterism at work in the olfactory system.
Clustering co-abundant genes identifies components of the gut microbiome that are reproducibly associated with colorectal cancer and inflammatory bowel disease
Authors: Minot Samuel S. , Willis Amy D. 
Published: March 2019

AbstractBackgroundWhole-genome “shotgun” (WGS) metagenomic sequencing is an increasingly widely used tool for analyzing the metagenomic content of microbiome samples. While WGS data contains gene-level information, it can be challenging to analyze the millions of microbial genes which are typically found in microbiome experiments. To mitigate the ultrahigh dimensionality challenge of gene-level metagenomics, it has been proposed to cluster genes by co-abundance to form Co-Abundant Gene groups (CAGs). However, exhaustive co-abundance clustering of millions of microbial genes across thousands of biological samples has previously been intractable purely due to the computational challenge of performing trillions of pairwise comparisons.ResultsHere we present a novel computational approach to the analysis of WGS datasets in which microbial gene groups are the fundamental unit of analysis. We use the Approximate Nearest Neighbor heuristic for near-exhaustive average linkage clustering to group millions of genes by co-abundance. This results in thousands of high-quality CAGs representing complete and partial microbial genomes. We applied this method to publicly available WGS microbiome surveys and found that the resulting microbial CAGs associated with inflammatory bowel disease (IBD) and colorectal cancer (CRC) were highly reproducible and could be validated independently using multiple independent cohorts.ConclusionsThis powerful approach to gene-level metagenomics provides a powerful path forward for identifying the biological links between the microbiome and human health. By proposing a new computational approach for handling high dimensional metagenomics data, we identified specific microbial gene groups that are associated with disease that can be used to identify strains of interest for further preclinical and mechanistic experimentation.
Characterizing the nuclear and cytoplasmic transcriptomes in developing and mature human cortex uncovers new insight into psychiatric disease gene regulation
Authors: Price Amanda J. , Hwang Taeyoung , Tao Ran , Burke Emily E. , Rajpurohi Anandita , Shin Joo Heon , Hyde Thomas M. , Kleinman Joel E. , Jaffe Andrew E. , Weinberger Daniel R. 
Published: March 2019

AbstractTranscriptome compartmentalization by the nuclear membrane provides both stochastic and functional buffering of transcript activity in the cytoplasm and has recently been implicated in neurodegenerative disease processes. Although many mechanisms regulating transcript compartmentalization are also prevalent in brain development, the extent to which subcellular localization differs as the brain matures has yet to be addressed. To characterize the nuclear and cytoplasmic transcriptomes during brain development, we sequenced both RNA fractions from homogenate prenatal and adult human postmortem cortex using PolyA+ and RiboZero library preparation methods. We find that while many genes are differentially expressed by fraction and developmental expression changes are similarly detectable in nuclear and cytoplasmic RNA, the compartmented transcriptomes become more distinct as the brain matures, perhaps reflecting increased utilization of nuclear retention as a regulatory strategy in adult brain. We examined potential mechanisms of this developmental divergence including alternative splicing, RNA editing, nuclear pore composition, RNA binding protein motif enrichment, and RNA secondary structure. Intron retention is associated with greater nuclear abundance in a subset of transcripts, as is enrichment for several splicing factor binding motifs. Finally, we examined disease association with fraction-regulated gene sets and found nuclear-enriched genes were also preferentially enriched in gene sets associated with neurodevelopmental psychiatric diseases. These results suggest that although gene-level expression is globally comparable between fractions, nuclear retention of transcripts may play an underappreciated role in developmental regulation of gene expression in brain, particularly in genes whose dysregulation is related to neuropsychiatric disorders.
Plant-soil feedback contributes to predicting plant invasiveness of 68 alien plant species differing in invasive status
Authors: Aldorfová Anna , Knobová Pavlína , Münzbergová Zuzana 
Published: March 2019

Abstract1. Understanding what species characteristics allow some alien plants to become invasive while others fail to is critical to our understanding of community assembly processes. While many characteristics have been shown to predict plant invasiveness, the importance of plant-soil feedbacks (PSFs) in invasions has been difficult to assess since individual studies include only a few species and use disparate methodology.2. We studied PSFs of 68 invasive and non-invasive alien species in a single two-phase garden experiment, and compared the relative importance of PSF, residence time, phylogenetic novelty and plant traits for plant invasiveness. Additionally, we tested for relationships between PSF, residence time and phylogenetic novelty.3. PSF for seedling establishment belonged to five best predictors of plant invasiveness, along with specific leaf area, height, seedling growth rate, and residence time. Invasive species had more positive PSF for seedling establishment, but not for biomass, than non-invasive species. Phylogenetically novel species experienced less negative PSF than species with native congeners, suggesting they benefit more from enemy release. PSF of non-invasive species, contrary to that of invasive species, was becoming more negative with increasing residence time.4.Synthesis. We demonstrated that PSF plays a role in predicting invasiveness that is comparable with other species characteristics that are more commonly studied. PSF should thus receive more attention in studies predicting community structure and in programs assessing the likely invasions of aliens.
Production of nonnatural straight-chain amino acid 6-aminocaproate via an artificial iterative carbon-chain-extension cycle
Authors: Cheng Jie , Song Tingting , Wang Huayu , Zhou Xiaohua , Torrens-Spence Michael P. , Wang Dan , Weng Jing-Ke , Wang Qinhong 
Published: March 2019

AbstractBioplastics produced from microbial source are promising green alternatives to traditional petrochemical-derived plastics. Nonnatural straight-chain amino acids, especially 5-aminovalerate, 6-aminocaproate and 7-aminoheptanoate are potential monomers for the synthesis of polymeric bioplastics as their primary amine and carboxylic acid are ideal functional groups for polymerization. Previous pathways for 5-aminovalerate and 6-aminocaproate biosynthesis in microorganisms are derived from L-lysine catabolism and citric acid cycle, respectively. Here, we show the construction of an artificial iterative carbon-chain-extension cycle inEscherichia colifor simultaneous production of a series of nonnatural amino acids with varying chain length. Overexpression of L-lysine α-oxidase inE. coliyields 2-keto-6-aminocaproate as a non-native substrate for the artificial iterative carbon-chain-extension cycle. The chain-extended α-ketoacid is subsequently decarboxylated and oxidized by an α-ketoacid decarboxylase and an aldehyde dehydrogenase, respectively, to yield the nonnatural straight-chain amino acid products. The engineered system demonstrated simultaneousin vitroproduction of 99.16 mg/L of 5-aminovalerate, 46.96 mg/L of 6-aminocaproate and 4.78 mg/L of 7-aminoheptanoate after 8 hours of enzyme catalysis starting from 2-keto-6-aminocaproate as the substrate. Furthermore, simultaneous production of 2.15 g/L of 5-aminovalerate, 24.12 mg/L of 6-aminocaproate and 4.74 mg/L of 7-aminoheptanoate was achieved in engineeredE. coli. This work illustrates a promising metabolic-engineering strategy to access other medium-chain organic acids with -NH2,-SCH3, -SOCH3, -SH, -COOH, -COH, or -OH functional groups through carbon-chain-elongation chemistry.
Towards a further understanding of measles vaccine hesitancy in Khartoum state, Sudan: A qualitative study
Authors: Sabahelzain Majdi M. , Moukhyer Mohamed , Dubé Eve , Hardan Ahmed , Bosma Hans , van den Borne Bart 
Published: March 2019

AbstractBackgroundVaccine hesitancy is one of the contributors to low vaccination coverage in both developed and developing countries. Sudan is one of the countries that suffers from low measles vaccine coverage and from measles outbreaks. For a further understanding of measles vaccine hesitancy in Sudan, this study aimed at exploring the opinions of Expanded Program on Immunization officers at ministries of health, WHO, UNICEF and vaccine care providers at Khartoum-based primary healthcare centers.MethodsQualitative data were collected using semi-structured interviews during the period January-March 2018. The topic list for the interviews was developed and analyzed using the framework “Determinants of Vaccine Hesitancy Matrix” that developed by the WHO-SAGE Working Group.FindingsThe interviews were conducted with 14 participants. The majority of participants confirmed the existence of measles vaccine hesitancy in Khartoum state. They further identified various determinants that grouped into three domains including contextual, groups and vaccination influences. The main contextual determinant as reported is the presence of “anti-vaccination”; who mostly belong to some religious and ethnic groups. Parents’ beliefs about prevention and treatment from measles are the main determinants of the group influences. Attitude of the vaccine providers, measles vaccine schedule and its mode of delivery were the main vaccine related determinants.ConclusionMeasles vaccine hesitancy in Sudan appears complex and highly specific to local circumstances. To better understand the magnitude and the context-specific causes of measles vaccine hesitancy and to develop adapted strategies to address them, there is a need to investigate measles vaccine hesitancy among parents.
Managing formal institutional challenges when entering Cuba
Authors: Rottig Daniel , Muscarella Sebastian , Torres de Oliveira Rui 
Published: March 2019

PurposeThe purpose of this paper is to analyze the formal political, legal and economic institutional legitimacy challenges for (US-based) multinational corporations (MNCs) attempting to enter the Cuban market, discuss the key local constituencies in Cuba that are able to grant legitimacy and sketch out respective strategies to deal with each of these formal institutional challenges.Design/methodology/approachA qualitative research approach comprising semi-structured executive interviews was used, combined with the analysis of media accounts and recent governmental policies and developments. The authors interpreted the gathered data and information based on institutional theory.FindingsThis paper sketches out specific legitimacy challenges for (US-based) MNCs when entering Cuba and discusses strategies to manage these challenges.Research limitations/implicationsThe authors provide an application of institutional theory in the specific context of Cuba and so demonstrate the value of applying this theoretical lens to better understand the local legitimacy processes in this particular emerging market environment.Practical implicationsThis study presents a framework of strategies (US-based) MNCs may use to inform their entry strategies into the Cuban market, based on an analysis of the local institutional environment, legitimacy pressures and constituencies able to grant or withdraw the approval and support of foreign MNCs.Originality/valueThis paper is an original application of institutional theory to the emerging market of Cuba using a qualitative research approach, and so contributes to an emerging stream of research studying this market context from an academic and practical perspective.