bluuebunny/crossref_metadata_2025_split huggingface dataset:
Apomixis-related genes identified from a coexpression network inPaspalum notatum, a Neotropical grass
Authors: de Oliveira Fernanda A. , Vigna Bianca B. Z. , da Silva Carla C. , Fávero Alessandra P. , Matta Frederico de P. , Azevedo Ana L. S. , de Souza Anete P. 
Published: July 2018

AbstractApomixis is a highly desirable trait in modern agriculture, due to the maintenance of characteristics of the mother plant in the progeny. However, incorporating it into breeding programs requires a deeper knowledge of its regulatory mechanisms.Paspalum notatumis considered a good model for such studies because it exhibits both sexual and apomictic cytotypes, facilitating the performance of comparative approaches. Therefore, we used comparative transcriptomics between contrastingP. notatumcytotypes to identify novel candidate genes involved in the regulation of the expression of this phenotype. We assembled and characterized a transcriptome from leaf and inflorescence from apomictic tetraploids and sexual diploids/tetraploids ofP. notatumaccessions, and then assembled a coexpression network based on pairwise correlation between transcripts expression profiles. We identified genes exclusively expressed in each cytotype and differentially expressed genes between pairs of cytotypes. Gene ontology enrichment analyses were performed for the interpretation of data. Wede novoassembled 114,306 of reference transcripts. 536 novel candidate genes for the control of apomixis were detected through statistical analyses of expression data, contains in this set, the interactions among genes potentially linked to the apomixis-controlling region, differentially expressed, several genes also already reported in the literature and their neighbors transcriptionally related in the coexpression network. The reference transcriptome obtained in this study represents a robust set of expression data forP. notatum. Additionally, novel candidate genes identified in this work represent a valuable resource for future grass breeding programs.Author SummaryClonal mode of reproduction by seeds is termed apomixis, which results from the failure of gamete formation (meiosis) and fertilization in the sexual female reproductive pathway. The manipulation of seeds production genetically identical to the mother plant bears great promise for agricultural applications, however clarification regarding gene interactions involved in reproductive process is needed.Paspalumis considered a model genus for the analysis of apomixis mechanisms. Here, we describe an overall analysis of the expression profiles ofPaspalum notatumtranscripts in response to changes in reproductive mode (sexual to apomictic), which allowed us to identify several candidate apomixis genes. Among these, we found genes potentially associated with the apomixis control region, in addition to genes already described in the literature forPaspalum, which highlights the representativeness of assembled transcriptome. For the first time in the literature, we explored the main biological processes involved in controlling the expression of apomictic reproduction based on co-regulatory networks of candidate apomixis genes.
Genetic and environmental perturbations lead to regulatory decoherence
Authors: Lea Amanda , Subramaniam Meena , Ko Arthur , Lehtimäki Terho , Raitoharju Emma , Kähönen Mika , Seppälä Ilkka , Mononen Nina , Raitakari Olli T. , Ala-Korpela Mika , Pajukanta Päivi , Zaitlen Noah A. , Ayroles Julien F. 
Published: July 2018

AbstractCorrelation among traits is a fundamental feature of biological systems. From morphological characters, to transcriptional or metabolic networks, the correlations we routinely observe between traits reflect a shared regulation that remains poorly understood and difficult to study. To address this problem, we developed a new and flexible approach that allows us to identify factors associated with variation in correlation between individuals. Here, we use data from three large human cohorts to study the effects of genetic variation and environmental perturbation on correlations among mRNA transcripts and among NMR metabolites. We first show that environmental exposures (namely, infection and disease) lead to a systematic loss of correlation, which we define as ‘decoherence’. Using longitudinal data, we show that decoherent metabolites are better predictors of whether someone will develop metabolic syndrome than metabolites commonly used as biomarkers of this disease. Finally, we show that correlation itself is a trait under genetic control: specifically, we mapped and replicated hundreds of ‘correlation QTLs’, which often involve transcription factors or their known target genes. Together, this work furthers our understanding of how and why coordinated biological processes break down, and highlights the role of decoherence in disease emergence.
Multi-omics analysis of AML cells treated with azacitidine reveals highly variable cell surface proteome remodeling
Authors: Leung Kevin K , Nguyen Aaron , Shi Tao , Tang Lin , Ni Xiaochun , Escoubet Laure , MacBeth Kyle J , DiMartino Jorge , Wells James A 
Published: July 2018

AbstractMyelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are diseases of abnormal hematopoietic differentiation with aberrant epigenetic alterations. Azacitidine (AZA) is a DNA methyltransferase inhibitor (DNMTi) widely used to treat MDS and AML, yet the impact of AZA on the cell surface proteome has not been defined. To identify potential therapeutic targets for use in combination with AZA in AML patients, we investigated the effects of AZA treatment on four AML cell lines (KG1a, HL60, HNT34, and AML193), representing different stages of differentiation. The effect of AZA treatment on these cell lines was characterized at three levels: the DNA methylome (methylation array), the transcriptome (gene expression array), and the cell surface proteome (glycoprotein capture with SILAC labeling). Untreated AML cell lines showed substantial overlap in their methylomes, transcriptomes, and cell surface proteomes. AZA treatment globally reduced DNA methylation in all cell lines, but changes in the transcriptome and surface proteome were subtle and differed among the cell lines. Transcriptome analysis identified five commonly up-regulated coding genes upon AZA treatment in all four cell lines, TRPM4 being the only gene encoding a surface protein, and surface proteomics analysis found no commonly regulated proteins. Gene Set Enrichment Analysis (GSEA) of differentially-regulated RNA and surface proteins showed a decrease in metabolism pathways and an increase in immune defense response pathways. As such, AZA treatment in four AML cell lines had diverse effects at the individual gene and protein level, but converged to regulation of metabolism and immune response at the pathway level. Given the heterogeneous response of AZA in the four cell lines at the gene and protein level, we discuss potential therapeutic strategies for combinations with AZA.
The impact of cigarette smoke exposure, and COPD or asthma status on ABC transporter gene expression in human airway epithelial cells
Authors: Aguiar Jennifer A. , Tamminga Andrea , Lobb Briallen , Huff Ryan D. , Nguyen Jenny , Kim Yechan , Dvorkin-Gheva Anna , Stampfli Martin R. , Doxey Andrew C. , Hirota Jeremy A. 
Published: July 2018

AbstractRationaleThe respiratory mucosa coordinates responses to infections, allergens, and exposures to air pollution. A relatively unexplored aspect of the respiratory mucosa are the expression and function of ATP Binding Cassette (ABC) transporters. ABC transporters are conserved in prokaryotes and eukaryotes, with humans expressing 48 transporters divided into 7 classes (ABCA, ABCB, ABCC, ABCD, ABDE, ABCF, and ABCG). Throughout the human body, ABC transporters regulate cAMP levels, chloride secretion, lipid transport, and anti-oxidant responses. A deeper exploration of the expression patterns of ABC transporters in the respiratory mucosa is warranted to determine their relevance in lung health and disease.MethodsWe used a bioinformatic approach complemented with in vitro experimental methods for validation of candidate ABC transporters. We analyzed the expression profiles of all 48 human ABC transporters in the respiratory mucosa using bronchial epithelial cell gene expression datasets available in NCBI GEO from well-characterized patient populations of healthy subjects and individuals that smoke cigarettes, or have been diagnosed with COPD or asthma. The Calu-3 airway epithelial cell line was used to interrogate selected results using a cigarette smoke extract exposure model.ResultsUsing 9 distinct gene-expression datasets of primary human airway epithelial cells, we completed a focused analysis on 48 ABC transporters in samples from healthy subjects and individuals that smoke cigarettes, or have been diagnosed with COPD or asthma. In situ gene expression data demonstrate that ABC transporters are i) variably expressed in epithelial cells from different airway generations (top three expression levels - ABCA5, ABCA13, and ABCC5), ii) regulated by cigarette smoke exposure (ABCA13, ABCB6, ABCC1, and ABCC3), and iii) differentially expressed in individuals with COPD and asthma (ABCA13, ABCC1, ABCC2, ABCC9). An in vitro cell culture model of cigarette smoke exposure was able to recapitulate the in situ changes observed in cigarette smokers for ABCA13 and ABCC1.ConclusionsOur in situ human gene expression data analysis reveals that ABC transporters are expressed throughout the airway generations in airway epithelial cells and can be modulated by environmental exposures important in chronic respiratory disease (e.g. cigarette smoking) and in individuals with chronic lung diseases (e.g. COPD or asthma). Our work highlights select ABC transporter candidates of interest and a relevant in vitro model that will enable a deeper understanding of the contribution of ABC transporters in the respiratory mucosa in lung health and disease.
Stable sub-complexes observedin situsuggest a modular assembly pathway of the bacterial flagellar motor
Authors: Kaplan Mohammed , Subramanian Poorna , Ghosal Debnath , Oikonomou Catherine M. , Pirbadian Sahand , Starwalt-Lee Ruth , Gralnick Jeffrey A. , El-Naggar Mohamed Y. , Jensen Grant J. 
Published: July 2018

AbstractThe self-assembly of cellular macromolecular machines such as the bacterial flagellar motor requires the spatio-temporal synchronization of gene expression, protein localization and association of a dozen or more unique components. InSalmonellaandEscherichia coli, a sequential, outward assembly mechanism has been proposed for the flagellar motor starting from the inner membrane, with each subsequent component stabilizing the last. Here, using electron cryo-tomography of intactLegionella pneumophila,Pseudomonas aeruginosaandShewanella oneidensiscells, we observe stable outer-membrane-embedded sub-complexes of the flagellar motor. These sub-complexes consist of the periplasmic embellished P- and L-rings, in the absence of other flagellar components, and bend the membrane inward dramatically. Additionally, we also observe independent inner-membrane sub-complexes consisting of the C- and MS-rings and export apparatus. These results suggest an alternate model for flagellar motor assembly in which outer- and inner-membrane-associated sub-complexes form independently and subsequently join, enabling later steps of flagellar production to proceed.
Genetic Diversity Patterns and Domestication Origin of Soybean
Authors: Jeong Soon-Chun , Moon Jung-Kyung , Park Soo-Kwon , Kim Myung-Shin , Lee Kwanghee , Lee Soo Rang , Jeong Namhee , Choi Man Soo , Kim Namshin , Kang Sung-Taeg , Park Euiho 
Published: July 2018

AbstractUnderstanding diversity and evolution of a crop is an essential step to implement a strategy to expand its germplasm base for crop improvement research. Samples intensively collected from Korea, which is a small but central region in the distribution geography of soybean, were genotyped to provide sufficient data to underpin genome-wide population genetic questions. After removing natural hybrids and duplicated or redundant accessions, we obtained a non-redundant set comprising 1,957 domesticated and 1,079 wild accessions to perform population structure analyses. Our analysis demonstrates that while wild soybean germplasm will require additional sampling from diverse indigenous areas to expand the germplasm base, the current domesticated soybean germplasm is saturated in terms of genetic diversity. We then showed that our genome-wide polymorphism map enabled us to detect genetic loci underling flower color, seed-coat color, and domestication syndrome. A representative soybean set consisting of 194 accessions were divided into one domesticated subpopulation and four wild subpopulations that could be traced back to their geographic collection areas. Population genomics analyses suggested that the monophyletic group of domesticated soybeans was originated in eastern Japan. The results were further substantiated by a phylogenetic tree constructed from domestication-associated single nucleotide polymorphisms identified in this study.
High-risk human papillomaviruses down-regulate expression of the Ste20 family kinase MST1 to inhibit the Hippo pathway and promote transformation
Authors: Morgan Ethan L. , Patterson Molly R. , Lee Siu Yi , Wasson Christopher W. , Macdonald Andrew 
Published: July 2018

AbstractHuman papillomaviruses (HPV) are a major cause of malignancy worldwide They are the aetiological agent of almost all cervical cancers and an increasing number of head and neck carcinomas. Deregulation of the Hippo pathway component YAP1 has recently been demonstrated to play a role in HPV-mediated cervical cancer, but whether other components of this pathway are implicated in the pathogenesis of this disease remains poorly understood.The expression level and activation status of critical Hippo pathway components were analysed across multiple cytology samples from patients with cervical disease, as well as HPV positive (HPV+) and HPV negative (HPV-) cervical cancer cell lines using real time qPCR, western blot and immunohistochemistry. In parallel, we assessed the effects of MST1 and MST2 overexpression upon cervical cancer cell proliferation, migration and invasion. Finally, we interrogated the consequences of interrupted MST1 and MST2 function using a targeted small molecule inhibitor in tandem with kinase inactive MST mutants. Our analysis found that expression of the Ste20 kinase MST1 was decreased within both HPV+ primary patient samples and cervical cancer cell lines. This effect was mediated by the virus-coded oncoproteins E6 and E7, which impair MST1 transcription. Reintroduction of MST1, or its paralogue MST2, into HPV positive cervical cancer cells re-activated the Hippo pathway, leading to a reduction in cell proliferation, migration and invasion. Finally, using a small molecule inhibitor of MST1/2 or kinase inactive mutants of either protein, we demonstrated that this effect required the kinase function of MST1/2. Our results reveal that HPV down regulates MST1 expression to inactivate the Hippo pathway and so drive cells towards transformation.
It takes a dimer to tango: Oligomeric small heat-shock proteins dissociate to capture substrate
Authors: Santhanagopalan Indu , Degiacomi Matteo T. , Shepherd Dale A. , Hochberg Georg K.A. , Benesch Justin L.P. , Vierling Elizabeth 
Published: July 2018

AbstractSmall heat-shock proteins (sHsps) are ubiquitous molecular chaperones, and their mutations or altered expression are linked to multiple human disease states. sHsp monomers assemble into large oligomers with dimeric substructure, and the dynamics of sHsp oligomers has led to major questions about the form that captures substrate, a critical aspect of their mechanism of action. We show that substructural dimers of plant dodecameric sHsps, Ta16.9 and homologous Ps18.1, are functional units in the initial encounter with unfolding substrate. We introduced inter-polypeptide disulfide bonds at the two dodecameric interfaces, dimeric and non-dimeric, to restrict how their assemblies can dissociate. When disulfide bonded at the non-dimeric interface, mutants of Ta16.9 and Ps18.1 (TaCT-ACD and PsCT-ACD) were inactive, but when reduced had wild-type-like chaperone activity, demonstrating that dissociation at non-dimeric interfaces is essential for activity. In addition, the size of the TaCT-ACD and PsCT-ACD covalent unit defined a new tetrahedral geometry for these sHsps, different than the Ta16.9 x-ray structure. Importantly, oxidized Tadimer (disulfide bonded at the dimeric interface) showed greatly enhanced ability to protect substrate, indicating that strengthening the dimeric interface increases chaperone efficiency. Size and secondary structure changes with temperature revealed that folded sHsp dimers interact with substrate, and support dimer stability as a determinant of chaperone efficiency. These data yield a model in which sHsp dimers capture substrate prior to assembly into larger, heterogeneous sHSP-substrate complexes for subsequent substrate refolding or degradation, and suggest that tuning the strength of the dimer interface can be used to engineer sHsp chaperone efficiency.
Double Dissociation of Nicotinic α7 and α4/β2 Sub-receptor Agonists for Enhancing Learning and Attentional Filtering of Distraction
Authors: Azimi Maryzeh , Oemisch Mariann , Womelsdorf Thilo 
Published: July 2018

AbstractNicotinic acetylcholine receptors (nAChR) modulate attention, memory, and higher executive functioning, but it has remained unclear whether nAChR sub-receptors tap into different neural mechanisms of these functions. We therefore set out to contrast the contributions of selective alpha-7 nAChR and alpha-4/beta-2 nAChR agonists in mediating value learning and attentional filtering of distractors in the nonhuman primate. We found that the alpha-7 nAChR agonist PHA-543613 selectively enhanced the learning speed of feature values but did not modulate how salient distracting information was filtered from ongoing choice processes. In contrast, the selective alpha-4/beta-2 nAChR agonist ABT-089 did not affect learning speed but reduced distractibility. This double dissociation was dose-dependent and evident in the absence of systematic changes in overall performance, reward intake, motivation to perform the task, perseveration tendencies, or reaction times. These results suggest nicotinic sub-receptor-specific mechanisms consistent with (1) alpha-4/beta-2 nAChR specific amplification of cholinergic transients in prefrontal cortex linked to enhanced cue detection in light of interferences, and (2) alpha-7 nAChR specific activation prolonging cholinergic transients, which could facilitate subjects to follow-through with newly established attentional strategies when outcome contingencies change. These insights will be critical for developing function-specific drugs alleviating attention and learning deficits in neuro-psychiatric diseases.
Gender-related differences in the use of technology in mathematics classrooms
Authors: Abidin Zaenal , Mathrani Anuradha , Hunter Roberta 
Published: July 2018

Purpose
The use of technology in education is still seen as a symbol of modernity in Indonesia. Without adequate technological infrastructural support from institutions, teachers develop ways to incorporate technology into their classrooms. The purpose of this paper is to investigate the affective domain in learning mathematics with technology across genders and across two student groups, where in one group the students shared learning devices, while the other group of students used individual devices.

Design/methodology/approach
The study adopts both quantitative and qualitative methods and is based on data collected from five secondary schools in Indonesia.

Findings
The findings reveal attitudinal differences are associated with technology usage in mathematics classrooms. Quantitative measurements across four attitudinal subscales—mathematics motivation, attitudes to the use of technology in mathematics, technological confidence and mathematics confidence—indicate that affordances in technologies influence boys and girls attitudes; while qualitative data share further insights on gender perspectives related to attitudinal differences.

Research limitations/implications
Appropriate pedagogical approaches with equitable access to technologies are important for engaging students in learning mathematics with technology.

Social implications
This empirical study reveals aspects related to student participation with technologies in classrooms, which has important implications for student development.

Originality/value
The study contributes to literature on mathematics education related to the use of learning technologies in secondary schools of a developing country.
Urinary stress incontinence and other maternal outcomes 2 years after caesarean or vaginal birth for twin pregnancy: a multicentre randomised trial
Authors: Hutton EK , Hannah ME , Willan AR , Ross S , Allen AC , Armson BA , Gafni A , Joseph KS , Mangoff K , Ohlsson A , Sanchez JJ , Asztalos EV , Barrett JFR ,   the Twin Birth Study Collaborative Group
Published: July 2018

ObjectiveDoes planned caesarean compared with planned vaginal birth lower the risk of problematic urinary stress, faecal, or flatal incontinence?DesignWomen between 320/7 and 386/7 weeks of gestation with a twin pregnancy were randomised to planned caesarean or planned vaginal birth.SettingThe trial took place at 106 centres in 25 countries.PopulationA total of 2305 of the 2804 women enrolled in the study completed questionnaires at 2 years (82.2% follow‐up): 1155 in the planned caesarean group and 1150 in the planned vaginal birth group.MethodsA structured self‐administered questionnaire completed at 2 years postpartum.Main outcome measuresThe primary maternal outcome of the Twin Birth Study was problematic urinary stress, or fecal, or flatal incontinence at 2 yearsResultsWomen in the planned caesarean group had lower problematic urinary stress incontinence rates compared with women in the planned vaginal birth group [93/1147 (8.11%) versus 140/1143 (12.25%); odds ratio, 0.63; 95% confidence interval, 0.47–0.83; P = 0.001]. Among those with problematic urinary stress incontinence, quality of life (measured using the Incontinence Impact Questionnaire, IIQ‐7) was not different for planned caesarean versus planned vaginal birth groups [mean (SD): 18.4 (21.0) versus 19.1 (21.5); P = 0.82]. There were no differences in problematic faecal or flatal incontinence, or in other maternal outcomes.ConclusionsAmong women with a twin pregnancy and no prior history of urinary stress incontinence, a management strategy of planned caesarean compared with planned vaginal birth reduces the risk of problematic urinary stress incontinence at 2 years postpartum. Our findings show that the prevalence but not the severity of urinary stress incontinence was associated with mode of birth.FundingCanadian Institutes of Health Research (CIHR) (grant no. MCT‐63164).Tweetable abstractFor women with twins, planned caesarean compared with planned vaginal birth is associated with decreased prevalence but not severity of urinary stress incontinence at 2 years.