bluuebunny/crossref_metadata_2025 huggingface dataset:
A study of circulating microRNAs identifies a new potential biomarker panel to distinguish aggressive prostate cancer
Authors: Farran Batoul , Dyson Gregory , Craig Douglas , Dombkowski Alan , Beebe-Dimmer Jennifer L , Powell Isaac J , Podgorski Izabela , Heilbrun Lance , Bolton Susan , Bock Cathryn H
Published: February 2018

Prostate cancer is one of the most common cancers in men worldwide. Currently available diagnostic and prognostic tools for this disease, such as prostate specific antigen, suffer from lack of specificity and sensitivity, resulting in over- and misdiagnosis. Hence, there is an urgent need for clinically relevant biomarkers capable of distinguishing between aggressive and nonaggressive forms of prostate cancer to aid in stratification, management and therapeutic decisions. To address this unmet need, we investigated the patterns of expression of a panel of 68 plasma-derived microRNAs (miRNAs) in a cohort of African American (AA) and European American (EA) prostate cancer patients (n = 114). miRNA qPCR results were analyzed using in-depth statistical methods, and a bioinformatics analysis was conducted to identify potential targets of the differentially expressed miRNAs. Our data demonstrate that a new previously unreported circulating miRNA signature consisting of a combination of interacting miRNAs (miR-17/miR-192) and an independent miRNA (miR-181a) are capable of segregating aggressive and nonaggressive prostate cancer in both AA and EA patients. The interacting miRNAs outperformed independent miRNAs in identifying aggressiveness. Our results suggest that these circulating miRNAs may constitute novel biomarkers of prostate cancer aggressiveness in both races and warrant further investigation.
Gapless Genome Assembly of the Potato and Tomato Early Blight Pathogen Alternaria solani
Authors: Wolters Pieter J. , Faino Luigi , van den Bosch Trudy B. M. , Evenhuis Bert , Visser Richard G. F. , Seidl Michael F. , Vleeshouwers Vivianne G. A. A.
Published: February 2018

The Alternaria genus consists of saprophytic fungi as well as plant-pathogenic species that have significant economic impact. To date, the genomes of multiple Alternaria species have been sequenced. These studies have yielded valuable data for molecular studies on Alternaria fungi. However, most of the current Alternaria genome assemblies are highly fragmented, thereby hampering the identification of genes that are involved in causing disease. Here, we report a gapless genome assembly of A. solani, the causal agent of early blight in tomato and potato. The genome assembly is a significant step toward a better understanding of pathogenicity of A. solani.
Impact of Summer Flooding on Viability of Sclerotinia minor and S. sclerotiorum Sclerotia in Soil
Authors: Matheron Michael E. , Porchas Martin
Published: February 2018

Lettuce drop, caused by the soilborne fungi Sclerotinia minor and S. sclerotiorum, is an important and destructive disease of lettuce. Research trials in Arizona have shown that some fungicides, such as boscalid and iprodione, can reduce disease incidence up to 50 to 60%. Prior research also demonstrated that viability of S. minor and S. sclerotiorum sclerotia was completely arrested after subjection to a respective 2- and 3-week period of continuous flooding in soil during the summer. Widespread adoption of this cultural disease management tool led to concerns in southwestern Arizona about misuse of a precious resource in an arid environment, damage to drainage canals from excessive ground water, and rising water tables adversely affecting lettuce growth. Overall data from current studies, which compared reduction of sclerotia viability after continuous flooding to less intensive flooding of one 8-h period for 1 to 3 weeks or two 8-h periods for 3 weeks, revealed that continuous flooding was not better than 8-h flooding periods for sclerotia of S. minor but was superior for sclerotia of S. sclerotiorum. Because Arizona lettuce growers have to contend with both species of Sclerotinia, continuous flooding is still the best flooding alternative to achieve virtual elimination of viable sclerotia of both pathogens.
Relative Effects of Demethylation-Inhibiting Fungicides on Late Leaf Spot of Peanut
Authors: Culbreath A. K. , Gevens A. J. , Stevenson K. L.
Published: February 2018

Field experiments were conducted in Tifton, GA, in 2007, 2008, and 2016, and in Plains, GA, in 2016 to examine the effects of various demethylation-inhibiting (DMI) fungicides on late leaf spot (Nothopassalora personata) of peanut (Arachis hypogaea) and to determine the relative efficacy of the DMI fungicides compared with tebuconazole and the protectant fungicide chlorothalonil. In all trials, leaf spot control provided by tebuconazole, metconazole, tetraconazole, propiconazole, and flutriafol was inferior to that provided by chlorothalonil. However, prothioconazole was superior to chlorothalonil for control of leaf spot in all trials. These results indicated that reduced efficacy of tebuconazole for control of late leaf spot coincides with similar reductions in control with most other available DMI fungicides. However, superior leaf spot control obtained with prothioconazole relative to the other DMI fungicides and chlorothalonil implies that efficacy of tebuconazole is not indicative of the performance of all other DMI fungicides on this disease.
First Report of Peanut mottle virus in Forage Peanut (Arachis pintoi) in the United States
Authors: Dey K. K. , Hassell L. , Li C. , Elliott M. , Sun X.
Published: February 2018

Arachis pintoi is one of the many perennial peanuts grown in many tropical and subtropical countries around the world. Although Peanut mottle virus (PeMoV) was reported in Arachis glabrata from Georgia in 2007, there are no reports of PeMoV infecting A. pintoi in the United States. In June 2017, samples of A. pintoi that originated from Hardee County, FL, plants showed a variety of symptoms ranging from yellowing to dark islands, green vein banding, and mild mottling. They tested positive initially with broad-spectrum lateral flow antibody immunoassay and later were confirmed by sequencing the reverse-transcription PCR products. Detection of PeMoV in A. pintoi is significant because it is transmitted by aphids in a nonpersistent manner and is seed-borne in A. hypogea. It is not known if PeMoV is seed-borne in A. pintoi. However, A. pintoi is commonly vegetatively propagated using stolon cuttings. It is possible that PeMoV can spread to A. pintoi in Florida by all these means, making maintenance of virus-free propagation stock plants important. To our knowledge, this is the first report of PeMoV in A. pintoi the United States.
Fungicide Resistance Management Guidelines for Cucurbit Downy and Powdery Mildew Control in the Mid-Atlantic and Northeast Regions of the United States in 2018
Authors: Wyenandt Christian A. , McGrath Margaret T. , Everts Kathryne L. , Rideout Steven L. , Gugino Beth K. , Kleczewski Nathan
Published: February 2018

In the mid-Atlantic and Northeast regions of the United States, more than 163,000 acres of fresh-market vegetable crops are grown annually. Two important diseases of cucurbit crops across the Unites States and world are powdery mildew caused by Podosphaera xanthii (formerly Sphaerotheca fuliginea [Schlecht ex Fr.] Poll.) and downy mildew caused by Pseudoperonospora cubensis. Resistance to a number of high-risk fungicides has been detected in both pathogens. To help cucurbit growers in the mid-Atlantic and Northeast regions properly manage both diseases, an updated fungicide resistance management table has been developed to promote the importance of understanding Fungicide Resistance Action Committee (FRAC) codes. This table provides a tool to allow cucurbit growers to develop season-long cucurbit downy and powdery mildew control programs.
Neutralizing Gatad2a-Chd4-Mbd3 Axis within the NuRD Complex Facilitates Deterministic Induction of Naïve Pluripotency
Authors: Mor Nofar , Rais Yoach , Peles Shani , Sheban Daoud , Aguilera-Castrejon Alejandro , Zviran Asaf , Elinger Dalia , Viukov Sergey , Geula Shay , Krupalnik Vladislav , Zerbib Mirie , Chomsky Elad , Lasman Lior , Shani Tom , Bayerl Jonathan , Gafni Ohad , Hanna Suhair , Buenrostro Jason D. , Hagai Tzachi , Masika Hagit , Bergman Yehudit , Greenleaf William J. , Esteban Miguel A. , Levin Yishai , Massarwa Rada , Merbl Yifat , Novershtern Noa , Hanna Jacob H.
Published: February 2018

The Nucleosome Remodeling and Deacytelase (NuRD) complex is a co-repressive complex involved in many pathological and physiological processes in the cell. Previous studies have identified one of its components, Mbd3, as a potent inhibitor for reprogramming of somatic cells to pluripotency. Following OSKM induction, early and partial depletion of Mbd3 protein followed by applying naïve ground-state pluripotency conditions, results in a highly efficient and near-deterministic generation of mouse iPS cells. Increasing evidence indicates that the NuRD complex assumes multiple mutually exclusive protein complexes, and it remains unclear whether the deterministic iPSC phenotype is the result of a specific NuRD sub complex. Since complete ablation of Mbd3 blocks somatic cell proliferation, here we aimed to identify alternative ways to block Mbd3-dependent NuRD activity by identifying additional functionally relevant components of the Mbd3/NuRD complex during early stages of reprogramming. We identified Gatad2a (also known as P66α), a relatively uncharacterized NuRD-specific subunit, whose complete deletion does not impact somatic cell proliferation, yet specifically disrupts Mbd3/NuRD repressive activity on the pluripotency circuit during both stem cell differentiation and reprogramming to pluripotency. Complete ablation of Gatad2a in somatic cells, but not Gatad2b, results in a deterministic naïve iPSC reprogramming where up to 100% of donor somatic cells successfully complete the process within 8 days. Genetic and biochemical analysis established a distinct sub-complex within the NuRD complex (Gatad2a-Chd4-Mbd3) as the functional and biochemical axis blocking reestablishment of murine naïve pluripotency. Disassembly of this axis by depletion of Gatad2a, results in resistance to conditions promoting exit of naïve pluripotency and delays differentiation. We further highlight context- and posttranslational dependent modifications of the NuRD complex affecting its interactions and assembly in different cell states. Collectively, our work unveils the distinct functionality, composition and interactions of Gatad2a-Chd4-Mbd3/NuRD subcomplex during the resolution and establishment of mouse naïve pluripotency.
Reconstructing complex lineage trees from scRNA-seq data using MERLoT
Authors: Parra R. Gonzalo , Papadopoulos Nikolaos , Ahumada-Arranz Laura , Kholtei Jakob El , Mottelson Noah , Horokhovsky Yehor , Treutlein Barbara , Soeding Johannes
Published: February 2018

Advances in single-cell transcriptomics techniques are revolutionizing studies of cellular differentiation and heterogeneity. Consequently, it becomes possible to track the trajectory of thousands of genes across the cellular lineage trees that represent the temporal emergence of cell types during dynamic processes. However, reconstruction of cellular lineage trees with more than a few cell fates has proved challenging. We present MERLoT (https://github.com/soedinglab/merlot), a flexible and user-friendly tool to reconstruct complex lineage trees from single-cell transcriptomics data and further impute temporal gene expression profiles along the reconstructed tree structures. We demonstrate MERLoT’s capabilities on various real cases and hundreds of simulated datasets.
IFIT3 and IFIT2/3 promote IFIT1-mediated translation inhibition by enhancing binding to non-self RNA
Authors: Fleith Renata C , Mears Harriet V , Emmott Edward , Graham Stephen C , Mansur Daniel S , Sweeney Trevor R
Published: February 2018

Interferon-induced proteins with tetratricopeptide repeats (IFITs) are highly expressed during the cell-intrinsic immune response to viral infection. IFIT1 inhibits translation by binding directly to the 5′ end of foreign RNAs, particularly those with non-self cap structures, precluding the recruitment of the cap-binding eukaryotic translation initiation factor 4F and subsequent 40S recruitment. Interaction of different IFIT family members is well described, but little is known of the molecular basis of IFIT association or its impact on function. Here, we reconstituted different complexes of IFIT1, IFIT2 and IFIT3 in vitro, which enabled us to reveal critical aspects of IFIT complex assembly. IFIT1 interacts rapidly and strongly with IFIT3 forming a stable heterotetramer. IFIT2 and IFIT3 homodimers dissociate to form a more stable heterodimer that associates with IFIT1, forming an IFIT1:IFIT2:IFIT3 trimer. Site-directed mutagenesis revealed a C-terminal ‘YxxxL’ motif in IFIT1 that mediates its association with IFIT3. Using various reporter mRNAs, we demonstrate for the first time that IFIT3 stabilises IFIT1 binding to cap0-mRNA and enhances its translation inhibition activity. Disrupting the binding interface between IFIT1 and IFIT3 abrogated this enhancement. This work reveals molecular aspects of IFIT assembly and provides an important ‘missing link’ between IFIT interaction and function.
Cell-matrix adhesion controls Golgi organization and function by regulating Arf1 activation in anchorage dependent cells
Authors: Singh Vibha , Erady Chaitanya , Balasubramanian Nagaraj
Published: February 2018

Cell-matrix adhesion regulates membrane trafficking to control anchorage-dependent signaling. While a dynamic Golgi complex can contribute to this pathway, its control by adhesion remains untested. We find the loss of adhesion rapidly disorganizes the Golgi in mouse and human fibroblast cells, its integrity restored rapidly on re-adhesion to fibronectin (but not poly-l-lysine coated beads) along the microtubule network. Adhesion regulates the trans-Golgi more prominently than the cis /cis-medial Golgi, though they show no fallback into the ER making this reorganization distinct from known Golgi fragmentation. This is controlled by an adhesion-dependent drop and recovery of Arf1 activation, mediated through the Arf1 GEF BIG1/2 over GBF1. Constitutively active Arf1 disrupts this regulation and prevents Golgi disorganization in non-adherent cells. Adhesion regulates active Arf1 binding to the microtubule minus-end motor protein dynein to control Golgi reorganization, which ciliobrevin blocks. This regulation by adhesion controls Golgi function, promoting cell surface glycosylation on the loss of adhesion that constitutively active Arf1 blocks. This study hence identifies cell-matrix adhesion to be a novel regulator of Arf1 activation, controlling Golgi organization and function in anchorage-dependent cells.

Summary Statement

This study identifies a role for cell-matrix adhesion in regulating organelle (Golgi) architecture and function which could have implications for multiple cellular pathways and function.
Context-specific regulation of monocyte surface IL7R expression and soluble receptor secretion by a common autoimmune risk allele
Authors: Al-Mossawi Hussein , Yager Nicole , Taylor Chelsea , Lau Evelyn , Danielli Sara , de Wit Jelle , Gilchrist James , Nassiri Isar , Mahe Elise A , Lee Wanseon , Rizvi Laila , Makino Seiko , Cheeseman Jane , Neville Matt , Knight Julian C , Bowness Paul , Fairfax Benjamin P
Published: February 2018

IL-7 is a key factor in T-cell immunity and IL7R polymorphisms are implicated in autoimmune pathogenesis. IL7R mRNA is induced in stimulated monocytes in a genetically determined manner, yet a role for IL7R in monocyte biology remains unexplored. Here we characterize genetic regulation of IL7R at the protein level across multiple cell subsets and conditions in healthy individuals. We find monocyte surface and soluble IL7R (sIL7R) protein are markedly expressed in response to lipopolysaccharide (LPS). We further demonstrate alleles of rs6897932, a non-synonymous IL7R polymorphism associated with susceptibility to Multiple Sclerosis, Ankylosing Spondylitis and Primary Biliary Cirrhosis, form the key determinant of both surface IL7R and sIL7R in the context of inflammation. No effect of this allele was observed in unstimulated monocytes or across lymphoid subsets. Production of sIL7R by monocytes greatly exceeded that of CD4+ T-cells, and was strongly associated with both rs6897932 genotype and expression of the splicing factor gene DDX39A. Stimulated monocytes were sensitive to exogenous IL-7, which elicits a defined transcriptional signature. Flow cytometry and single-cell sequencing of synovial fluid derived monocytes from patients with spondyloarthritis showed an enlarged subset of IL7R+ monocytes with a unique transcriptional profile that markedly overlaps that induced by IL-7 in-vitro and shows similarity to the previously described ‘Mono4’ subset. These data demonstrate disease-associated genetic variants at IL7R specifically impact monocyte surface IL7R and sIL7R following innate immune stimulation, suggesting a previously unappreciated key role for monocytes in IL-7 pathway biology and IL7R-associated diseases.
Functional Improbable Antibody Mutations Critical for HIV Broadly Neutralizing Antibody Development
Authors: Wiehe Kevin , Bradley Todd , Meyerhoff R. Ryan , Hart Connor , Williams Wilton , Easterhoff David , Faison William J. , Kepler Thomas B. , Saunders Kevin , Alam S. Munir , Bonsignori Mattia , Haynes Barton F.
Published: February 2018

HIV-1 broadly neutralizing antibodies (bnAbs) require high levels of activation-induced cytidine deaminase (AID) catalyzed somatic mutations for optimal neutralization potency. Probable mutations occur at sites of frequent AID activity, while improbable mutations occur where AID activity is infrequent. One bottleneck for induction of bnAbs is the evolution of viral envelopes (Envs) that can select bnAb B cell receptors (BCR) with improbable mutations. Here we define the probability of bnAb mutations and demonstrate the functional significance of key improbable mutations in three bnAb B cell lineages. We show that bnAbs are enriched for improbable mutations, implying their elicitation will be critical for successful vaccine induction of potent bnAb B cell lineages. We outline a mutation-guided vaccine strategy for identification of Envs that can select B cells with BCRs with key improbable mutations required for bnAb development. Our analysis suggests that through generations of viral escape, Env trimers evolved to hide in low probability regions of antibody sequence space.
Properties of Gene Expression and Chromatin Structure with Mechanically Regulated Transcription
Authors: Sevier Stuart A. , Levine Herbert
Published: February 2018

The mechanical properties of transcription have emerged as central elements in our understanding of gene expression. Recent work has been done introducing a simple description of the basic physical elements of transcription where RNA elongation, RNA polymerase (RNAP) rotation and DNA supercoiling are coupled [1]. Here we generalize this framework to accommodate the behavior of many RNAPs operating on multiple genes on a shared piece of DNA. The resulting framework is combined with well-established stochastic processes of transcription resulting in a model which characterizes the impact of the mechanical properties of transcription on gene expression and DNA structure. Transcriptional bursting readily emerges as a common phenomenon with origins in the geometric nature of the genetic system and results in the bounding of gene expression statistics. Properties of a multiple gene system are examined with special attention paid to role that genome composition (gene orientation, size, and intergenic distance) plays in the ability of genes to transcribe. The role of transcription in shaping DNA structure is examined and the possibility of transcription driven domain formation is discussed.

PACS numbers:
Substrate conformational dynamics drive structure-specific recognition of gapped DNA by DNA polymerase
Authors: Craggs Timothy D. , Sustarsic Marko , Plochowietz Anne , Mosayebi Majid , Kaju Hendrik , Cuthbert Andrew , Hohlbein Johannes , Domicevica Laura , Biggin Philip C. , Doye Jonathan P. K. , Kapanidis Achillefs N.
Published: February 2018

DNA-binding proteins utilise different recognition mechanisms to locate their DNA targets. Some proteins recognise specific nucleotide sequences, while many DNA repair proteins interact with specific (often bent) DNA structures. While sequence-specific DNA binding mechanisms have been studied extensively, structure-specific mechanisms remain unclear. Here, we study structure-specific DNA recognition by examining the structure and dynamics of DNA polymerase I (Pol) substrates both alone and in Pol-DNA complexes. Using a rigid-body docking approach based on a network of 73 distance restraints collected using single-molecule FRET, we determined a novel solution structure of the singlenucleotide-gapped DNA-Pol binary complex. The structure was highly consistent with previous crystal structures with regards to the downstream primer-template DNA substrate; further, our structure showed a previously unobserved sharp bend (~120°) in the DNA substrate; we also showed that this pronounced bending of the substrate is present in living bacteria. All-atom molecular dynamics simulations and single-molecule quenching assays revealed that 4-5 nt of downstream gap-proximal DNA are unwound in the binary complex. Coarsegrained simulations on free gapped substrates reproduced our experimental FRET values with remarkable accuracy (<ΔFRET> = -0.0025 across 34 independent distances) and revealed that the one-nucleotide-gapped DNA frequently adopted highly bent conformations similar to those in the Pol-bound state (ΔG < 4 kT); such conformations were much less accessible to nicked (> 7 kT) or duplex (>> 10 kT) DNA. Our results suggest a mechanism by which Pol and other structure-specific DNA-binding proteins locate their DNA targets through sensing of the conformational dynamics of DNA substrates.

Significance Statement

Most genetic processes, including DNA replication, repair and transcription, rely on DNA-binding proteins locating specific sites on DNA; some sites contain a specific sequence, whereas others present a specific structure. While sequence-specific recognition has a clear physical basis, structure-specific recognition mechanisms remain obscure. Here, we use single-molecule FRET and computer simulations to show that the conformational dynamics of an important repair intermediate (1nt-gapped DNA) act as central recognition signals for structure-specific binding by DNA polymerase I (Pol). Our conclusion is strongly supported by a novel solution structure of the Pol-DNA complex wherein the gapped-DNA is significantly bent. Our iterative approach combining precise single-molecule measurements with molecular modelling is general and can elucidate the structure and dynamics for many large biomachines.
A plug-and-play system for enzyme production at commercially viable levels in fed-batch cultures of Escherichia coli BL21 (DE3)
Authors: Sohoni Sujata Vijay , Kundalia Paras Harendra , Shetty Adarsh G. , Sunder Avinash Vellore , Gaikaiwari Raghavendra P. , Wangikar Pramod P.
Published: February 2018

Commercial exploitation of enzymes in biotransformation necessitates a robust method for enzyme production that yields high enzyme titer. Nitrilases are a family of hydrolases that can transform nitriles to enantiopure carboxylic acids, which are important pharmaceutical intermediates. Here, we report a fed-batch method that uses a defined medium and involves growth under carbon limiting conditions using DO-stat feeding approach combined with an optimized post-induction strategy, yielding high cell densities and maximum levels of active and soluble enzyme. This strategy affords strict control of nutrient feeding and growth rates, and ensures sustained protein synthesis over a longer period. The method was optimized for highest titer of nitrilase reported so far (247 kU/l) using recombinant E. coli expressing the Alcaligenes sp. ECU0401 nitrilase. The fed-batch protocol presented here can also be employed as template to produce a wide variety of enzymes with minimal modification, as demonstrated for alcohol dehydrogenase and formate dehydrogenase.
Efficient Zygotic Genome Editing via RAD51-Enhanced Interhomolog Repair
Authors: Wilde Jonathan J. , Aida Tomomi , Wienisch Martin , Zhang Qiangge , Qi Peimin , Feng Guoping
Published: February 2018

Recent advances in genome editing have greatly improved knock-in (KI) efficiency1–9. Searching for factors to further improve KI efficiency for therapeutic use and generation of non-human primate (NHP) models, we found that the strand exchange protein RAD51 can significantly increase homozygous KI using CRISPR/Cas9 in mouse embryos through an interhomolog repair (IHR) mechanism. IHR is well-described in the context of meiosis10, but only occurs at low frequencies in mitotic cells11,12 and its existence in zygotes is controversial. Using a variety of approaches, we provide evidence for an endogenous IHR mechanism in zygotes that can be enhanced by RAD51. We show that this process can be harnessed for generating homozygous KI animals from wildtype zygotes based on exogenous donors and for converting heterozygous alleles into homozygous alleles without exogenous templates. Furthermore, we elucidate additional factors that contribute to zygotic IHR and identify a RAD51 mutant capable of insertion-deletion (indel)-free stimulation of IHR. Thus, our study provides conclusive evidence for the existence of zygotic IHR and demonstrates methods to enhance IHR for potential use in gene drives, gene therapy, and biotechnology.
Conserved Roles of C. elegans and Human MANFs in Sulfatide Binding and Cytoprotection
Authors: Bai Meirong , Vozdek Roman , Hnízda Aleš , Jiang Chenxiao , Wang Bingying , Kuchar Ladislav , Li Tiejun , Zhang Yuefan , Wood Chase , Feng Liang , Dang Yongjun , Ma Dengke K.
Published: February 2018

Mesencephalic Astrocyte-Derived Neurotrophic Factor (MANF) is an endoplasmic reticulum (ER) protein that can be secreted and protect dopamine neurons and cardiomyocytes from ER stress and apoptosis. The mechanism of action of extracellular MANF has long been elusive. From a genetic screen for mutants with abnormal ER stress response, we identified the gene Y54G2A.23 as the evolutionarily conserved C. elegans MANF orthologue. We find that MANF binds to the lipid sulfatide, also known as 3-O-sulfogalactosylceramide present in serum and outer-cell membrane leaflets, directly in isolated forms and in reconstituted lipid micelles. Sulfatide binding promotes cellular MANF uptake and cytoprotection from hypoxia-induced cell death. Heightened ER stress responses of MANF-null C. elegans mutants and mammalian cells are alleviated by human MANF in a sulfatide-dependent manner. Our results demonstrate conserved roles of MANF in sulfatide binding and ER stress response, supporting sulfatide as a long-sought lipid mediator of MANF’s cytoprotection.
Epigenomic plasticity of Arabidopsismsh1mutants under prolonged cold stress
Authors: Kenchanmane Raju Sunil Kumar , Shao Mon-Ray , Wamboldt Yashitola , Mackenzie Sally
Published: February 2018

Dynamic transcriptional and epigenetic changes enable rapid adaptive benefit to environmental fluctuations. However, the underlying mechanisms and the extent to which this occurs are not well known.MutS Homolog 1(MSH1) mutants cause heritable developmental phenotypes accompanied by modulation of defense, phytohormone, stress-response and circadian rhythm genes, as well as heritable changes in DNA methylation patterns. Consistent with gene expression changes,msh1mutants display enhanced tolerance for abiotic stress including drought and salt stress, while showing increased susceptibility to freezing temperatures and bacterial pathogenP syringae. Our results suggest that chronic cold and low light stress (10 °C, 150 μE) influences non-CG methylation to a greater degree inmsh1mutants compared to wild type Col-0. Furthermore, CHG changes are more closely pericentromeric, whereas CHH changes are generally more dispersed. This increased variation in non-CG methylation pattern does not significantly affect themsh1-derived enhanced growth behavior after mutants are crossed with isogenic wild type, reiterating the importance of CG methylation changes inmsh1-derived enhanced vigor. These results indicate thatmsh1methylome is hyper-responsive to environmental stress in a manner distinct from the wild type response, but CG methylation changes are potentially responsible for growth vigor changes in the crossed progeny.
Ancestry and Genetic Associations with Bronchopulmonary Dysplasia in Preterm Infants
Authors: Torgerson Dara G. , Ballard Philip L. , Keller Roberta L. , Oh Sam S. , Huntsman Scott , Hu Donglei , Eng Celeste , Burchard Esteban G. , Ballard Roberta A.
Published: February 2018

Bronchopulmonary dysplasia in premature infants is a common and often severe lung disease with long term sequelae. A genetic component is suspected but not fully defined. We performed an ancestry and genome-wide association study to identify variants, genes and pathways associated with survival without bronchopulmonary dysplasia in 387 high-risk infants treated with inhaled nitric oxide in the Trial of Late Surfactant study. Global African genetic ancestry was associated with increased survival without bronchopulmonary dysplasia among infants of maternal self-reported Hispanic White race/ethnicity (OR=4.5, p=0.01). Admixture mapping found suggestive outcome associations with local African ancestry at 18q21 and 10q22 among infants of maternal self-reported African American race/ethnicity. For all infants, the top individual variant identified was within the intron ofNBL1, which is expressed in mid-trimester lung and is an antagonist of bone morphogenetic proteins (rs372271081, OR=0.17, p=7.4 × 10−7). The protective allele of this variant was significantly associated with lower nitric oxide metabolites in the urine of non-Hispanic white infants (p= 0.006), supporting a role in the racial differential response to nitric oxide. Interrogating genes upregulated in bronchopulmonary dysplasia lungs indicated association with variants inCCL18, a cytokine associated with fibrosis and interstitial lung disease, and pathway analyses implicated variation in genes involved in immune/inflammatory processes in response to infection and mechanical ventilation. Our results suggest that genetic variation related to lung development, drug metabolism, and immune response contribute to individual and racial/ethnic differences in respiratory outcomes following inhaled nitric oxide treatment of high-risk premature infants.
The variability of song variability in wild and domesticated zebra finchesTaeniopygia guttata
Authors: Lansverk Allison L. , London Sarah E. , Griffith Simon C. , Clayton David F. , Balakrishnan Christopher N.
Published: February 2018

Birdsong is a classic example of a learned social behavior. Like many traits of interest, however, song production is also influenced by genetic factors and understanding the relative contributions of genetic and environmental influences remains a major research goal. In this study we take advantage of genetic variation among captive zebra finch populations to examine variation in a population-level song trait: song variability. We find that zebra finch populations differ in levels of song variability. DomesticatedT. g. castanotispopulations displayed higher song diversity than more recently wild-derived populations of both zebra finch subspeciesT. g. castanotisandT. g. guttata, the Timor zebra finch. To determine whether these differences could have a genetic basis, we cross-fostered domesticatedT. g. castanotisand Timor zebra finches to Bengalese finchesLonchura striata domestica. Following cross-fostering, domesticatedT. g. castanotismaintained a higher level of song diversity thanT. g. guttata. We suggest that the high song variability of domesticated zebra finches may be a consequence of reduced purifying selection acting on song traits. Intraspecific differences in the mechanisms underlying song variability therefore represent an untapped opportunity for probing the mechanisms of song learning and production.
miRNA profiling of primate cervicovaginal lavage and extracellular vesicles reveals miR-186-5p as a potential retroviral restriction factor in macrophages
Authors: Zhao Zezhou , Muth Dillon C. , Mulka Kathleen , Liao Zhaohao , Powell Bonita H. , Hancock Grace V. , Metcalf Pate Kelly A. , Witwer Kenneth W.
Published: February 2018

The goal of this study was to characterize extracellular vesicles (EVs) and miRNAs of primate cervicovaginal lavage (CVL) during the menstrual cycle and simian immunodeficiency virus (SIV) infection, and to determine if differentially regulated CVL miRNAs might influence retrovirus replication. CVL and peripheral blood were collected from SIV-infected and uninfected macaques. EVs were enriched by stepped ultracentrifugation and characterized thoroughly. miRNA profiles were assessed with a medium-throughput stem-loop/hydrolysis probe qPCR platform and validated by single qPCR assays. Hormone cycling was abnormal in infected subjects, but EV concentration correlated with progesterone concentration in uninfected subjects. miRNAs were present predominantly in the EV-depleted CVL supernatant. Only a small number of CVL miRNAs were found to vary during the menstrual cycle or SIV infection. Among them was miR-186-5p, which was depleted in retroviral infection. In experiments with infected macrophages in vitro, this miRNA inhibited HIV replication. These results provide further evidence for the potential of EVs and small RNAs as biomarkers or effectors of disease processes in the reproductive tract.
A model for assessment of uncertainty in tacit knowledge acquisition
Authors: Akhavan Peyman , Shahabipour Ali , Hosnavi Reza
Published: February 2018

Purpose

Expert systems have come to the forefront in the modeling of problems. One of the major problems facing the expert system designers is to develop an accurate knowledge base and a meaningful model of uncertainty associated with complex models. Decision-making is based on knowledge, and decision system support needs a knowledge base as well. An adequate knowledge acquisition (KA) process leads to accurate knowledge and improves the decision-making process. To manage the risk of a medical service (twin pregnancy in this case) a knowledge management system was created. The captured knowledge may be associated with an uncertainty. This study aims to introduce a method for evaluating the reliability of a tacit KA model. It assisted engineering managers in assessing and prioritizing risks. The study tried to use this method in risk management and new case in the health domain.

Design/methodology/approach

In this study, relevant variables were identified in the knowledge management literature reviews and the domain of expertise management. They are validated by a group of domain experts. Kendall’s W indicator was used to assess the degree of consensus. On the basis of combined cognitive maps, a cognitive network was constructed. Using Bayesian belief networks and fuzzy cognitive maps, an uncertainty assessment method of tacit KA was introduced. To help managers focus on major variables, a sensitivity analysis was conducted. Reliability of model was calculated for optimistic and pessimistic values. The applicability and efficacy of the proposed method were verified and validated with data from a medical university.

Findings

Results show that tacit KA uncertainty can be defined by independent variables, including environmental factors, personality and acquisition process factors. The reliability value shows the accuracy of the captured knowledge and the effectiveness of the acquisition process. The proposed uncertainty assessment method provides the reliability value of the acquisition model for knowledge engineers, so it can be used to implement the project and prevent failures in vital factors through necessary actions. If there is not a satisficed level of reliability, the KA project reliability can be improved by risk factors. The sensitivity analysis can help to select proper factors based on the resources. This approach mitigated some of the disadvantages of other risk evaluation methods.

Originality/value

The contribution of this study is to combine the uncertainty assessment with tacit KA based on fuzzy cognitive maps and the Bayesian belief networks approach. This approach used the capabilities of both narrative and computational approaches.
Key drivers of SMEs export performance: the mediating effect of competitive advantage
Authors: Rua Orlando , França Alexandra , Fernández Ortiz Rubén
Published: February 2018

Purpose

With its focus on the context of small firm internationalization, this paper aims to assess the important contribution of strategic determinants that influence export performance (EP), considering the mediating effect of competitive strategy.

Design/methodology/approach

Based on survey data from 247 Portuguese small and medium-sized enterprises (SMEs) exporting textiles, members of the Portugal’s Textile Association (ATP), this research adopted a quantitative methodological approach, conducting an exploratory and transversal empirical study.

Findings

The paper finds suggest that entrepreneurial orientation (EO) has a positive and significant influence on differentiation and EP. Moreover, the results also highlight the role of intangible resources (IR) in the design of both differentiation and cost leadership strategies, which drives EP. Finally, absorptive capabilities (ACAPs) are highly related with EP.

Practical implications

The paper provides empirical evidence that EO, IR and ACAPs are predictors of competitive strategies and EP. Moreover, and alongside with firm’s resources, this study validates that competitive strategy does matters for small firm managers and the development of one type of competitive advantage is also a major performance enhancer.

Originality/value

This study provides fresh insights into entrepreneurship and strategic management literature, as it considers the importance of multiple factors to SMEs business growth. Moreover, this paper presents empirical evidences of the strategies that small firm managers should pursue and policy makers should support. Finally, this is an original study applied to the Portuguese textile industry.
Transforming school culture through inquiry-driven learning and iPads
Authors: Thumlert Kurt , Owston Ron , Malhotra Taru
Published: February 2018

Purpose

The purpose of this paper is to provide an overview of a commissioned research study that analyzed a schooling initiative with the ambitious goal of transforming learning environments across the district by advancing innovative, inquiry-driven pedagogical practices combined with 1:1 iPad distribution. The paper explores impacts of the initiative on pedagogical innovation, twenty-first century learning, and related impacts on professional learning, collaboration, and culture change in the pilot schools analyzed in the study.

Design/methodology/approach

A multi-dimensional case study approach was used to analyze how the initiative was implemented, and to what extent teaching, learning, and professional cultures were transformed, based on action plan inputs and “change drivers”. Research methods included structured, open-ended interviews conducted with randomly selected teachers and key informants in leadership roles, focus groups held with students, as well as analysis of policy documents, student work samples, and other data sources.

Findings

The authors found evidence of a synergistic relationship between innovations in inquiry-driven pedagogy and professional learning cultures, with evidence of increased collaboration, deepened engagement and persistence, and a climate of collegiality and risk-taking at both classroom and organizational levels. Based on initiative inputs, the authors found that innovations in collaborative technology/pedagogy practices in classrooms paralleled similar innovations and transformations in professional learning cultures and capacity-building networks.

Practical implications

This initiative analyzed in this paper provides a case study in large-scale system change, offering a compelling model for transformative policies and initiatives where interwoven innovations in pedagogy and technology mobilization are supported by multiple drivers for formal and informal professional learning/development and networked collaboration. Challenges and recommendations are highlighted in the concluding discussion.

Originality/value

The transformative initiative analyzed in this paper provides a very timely case-model for innovations in twenty-first century learning and, specifically, for enacting and sustaining large-scale system change where inquiry-driven learning and technology tools are being mobilized to support “deep learning”, “new learning partnerships”, and multilevel transformations in professional learning (Fullan and Donnelly, 2013). This research advances scholarly work in the areas of twenty-first century learning, identifying relationships between technology/pedagogy innovation and professional capital building (Hargreaves and Fullan, 2012).
Will China’s entrepreneurial migrant managers awaken Africa’s dream of becoming the next factory of the world?
Authors: Leavy Brian
Published: February 2018

Purpose

China’s biggest contribution to Africa’s modernization is more likely to come from the rapidly expanding number of Chinese migrants determined to seek their fortunes by setting up manufacturing businesses across the continent, according to Irene Yuan Sun in her new book The Next Factory of the World: How Chinese Investment is Reshaping Africa. She is interviewed by S&L contributing editor Brian Leavy.

Design/methodology/approach

Irene Sun, a senior McKinsey consultant has spent years researching infrastructure modernization and manufacturing expansion in Africa for her new book.

Findings

China is the fastest-growing source of foreign investment in Africa, and this has enormous consequences for Africa and for the global economy.

Practical implications

Nowadays, a lot of the managers with the needed skills and resilience are Chinese people who worked their way up in factories in China in conditions that not so long ago were very similar to what’s in Africa today.

Originality/value

Sun’s big insight: “I’d like Westerners to understand that China’s activities in Africa don’t represent a threat, either to Africa or to the West.” For Western observers who are alarmed by China’s strategy of investing in African infrastructure to gain favorable access to its natural resources she offers a new context: China’s experience at industrialization under primitive conditions can transform Africa into the next Factory of the World.
Fertilising semi‐natural grasslands may cause long‐term negative effects on both biodiversity and ecosystem stability
Authors: Melts Indrek , Lanno Kaire , Sammul Marek , Uchida Kei , Heinsoo Katrin , Kull Tiiu , Laanisto Lauri
Published: February 2018

Some short‐term experiments in applied ecology and agricultural research have demonstrated that nutrient applications in semi‐natural grasslands can maintain productivity and will not result in the decrease of plant species richness. Such findings may have an impact on management choices and quality of valuable plant communities, and therefore, further discussion of this topic is necessary.

We highlight three aspects regarding the management suggestions in grassland communities with high biodiversity: (1) short‐term study results may not reflect potential long‐term changes; (2) broad range of grasslands may respond to disturbance in site specific ways; and (3) practical advices should contain careful consideration of existing ecological literature regarding grassland management and sustainable biodiversity.

Synthesis and applications. Considering effects of fertilisation on biodiversity, we argue against nutrient application to semi‐natural grasslands. Biodiversity supports the resilience of grassland ecosystems and maintains a stable biomass yield. Current short‐term experiments are good indicators about the need for a long‐term experiments and meta‐analysis for detailed understanding of ecosystem functions in different types and areas during global change.
rs294775 is a cis‐regulatory SNP for human UGT2B10
Authors: Ruan Ji , Yang Yu‐Chen , Long Fu‐Quan , Sun Chang
Published: February 2018

UGT2B10 is an important metabolism enzyme in human body and its substrates include multiple amine‐containing compounds, especially nicotine, tamoxifen and multiple antidepressants. Multiple common SNPs have been observed in its promoter region, but their role in expression regulation has never been investigated. In this preliminary study, we identified a novel cis‐regulatory SNP, rs294775, for UGT2B10 by plasmid construction, mutagenesis, and luciferase assay, whose mechanism was also investigated. Our work provides a basis for further pharmacogenetics study.
Equilibrium Analysis of A Dual‐CHannel Supply Chain Under Different Market Powers
Authors: Tang Chunhua , Zhu Shujin , Cao Erbao
Published: February 2018

We examine the effect of firms’ market powers on the optimal strategies and profits of partners and make comparisons under different structures in a dual‐channel supply chain, where the manufacturer provide a value‐added service to differentiate the product for the customer to some extent. We consider centralised decision and decentralised decision cases where supply chain partners have different market power structures, including the Manufacturer‐Stackelberg, Retailer‐Stackelberg and Nash Game. We find that the direct sale price and added value are unchanged under different power structures. However, dominating power structures always lead to inefficiency for the whole dual‐channel supply chain. The more power one of the channel partners has, the larger profit loss the whole supply chain will suffer.
Seeking certainty through narrative closure: men's stories of prostate cancer treatments in a state of liminality
Authors: Pietilä Ilkka , Jurva Raisa , Ojala Hanna , Tammela Teuvo
Published: February 2018

Radical treatments of prostate cancer often lead to a pervasive liminal state that is characterised by multiple uncertainties that relate both to a possible recurrence of cancer and recovery from side effects, such as erectile and urinary dysfunctions. Liminality can make it difficult for cancer patients to narrate their experiences, as their stories lack a definite ending. After interviews with 22 Finnish men who had undergone radical prostatectomy, we analysed how men produce closure in their illness narratives. Focusing on the timelines of control visits or their anticipated recovery from side effects, these interviewees sought provisional certainty within a seemingly chaotic future. By locating erectile dysfunction in the wider context of a life‐course and interpreting their fading sexuality as a ‘natural’ consequence of ageing, these men were adjusting to their post‐operative lives. Our study further shows that the inability to adjust personal experiences to positive culturally available storylines that provide a chance for the narrative reconstruction of life, can cause materialised negative consequences, such as relationship breakdowns.
The Silent Minority: Supporting students with Selective Mutism using systemic perspectives
Authors: Lawrence Zena
Published: February 2018

Selective Mutism (SM) is an under‐researched area of child development. While the incidence rate is low, the impact of this difficulty can be pervasive and can present as a significant risk for student mental health and wellbeing. The following article presents a case study focusing on parent‐student intervention for a preadolescent male, using an eclectic programme which blended psycho‐education, aspects of a manualised Cognitive Behavioural Therapy (CBT) programme, and specific selective mutism strategies. This article does not seek to evaluate the effectiveness of the programme but instead highlights practice considerations derived from systemic theoretical perspectives and present considerations for school staff.