bluuebunny/crossref_metadata_2025_split huggingface dataset:
RNA-binding protein A1CF modulates plasma triglyceride levels through posttranscriptional regulation of stress-induced VLDL secretion
Authors: Lin Jennie , Conlon Donna M. , Wang Xiao , Van Nostrand Eric , Rabano Ines , Park YoSon , Strong Alanna , Radmanesh Behram , Barash Yoseph , Rader Daniel J. , Yeo Gene W. , Musunuru Kiran 
Published: August 2018

ABSTRACTBackgroundA recent human exome-chip study on plasma lipids identified a missense mutation in theA1CF(APOBEC1 complementation factor) gene that is associated with elevated triglyceride (TG) levels, but how A1CF, an RNA binding protein, influences plasma TG is unknown.MethodsWe generatedA1cfknockout (A1cf−/−) mice and knock-in mice homozygous for the TG-associated Gly398Ser mutation (A1cfGS/GS), determined lipid phenotypes, and assessed TG physiology through measurements of clearance and secretion. We further identified A1CF’s RNA binding targets using enhanced cross-linking and immunoprecipitation sequencing of cultured HepG2 cells and investigated pathways enriched for these targets. Transcriptomic effects of A1CF deficiency were evaluated through RNA sequencing and analyses for differential expression, alternative splicing, and RNA editing.ResultsBothA1cf−/−andA1cfGS/GSmice exhibited increased fasting plasma TG, establishing that the TG phenotype is due to A1CF loss of function.In vivoTG secretion and clearance studies revealed increased TG secretion without changes in clearance inA1cf−/−mice. Increased VLDL-apoB secretion was also seen inA1cf−/−rat hepatoma cells, but no increase in apoB synthesis was observed. This phenotype was seen without significant shifts in apoB-100/apoB-48 in A1CF deficiency. To discover novel pathways for A1CF’s role in TG metabolism, we identified A1CF’s RNA binding targets, which were enriched for pathways related to proteasomal catabolism and endoplasmic reticulum (ER) stress. Indeed, proteasomal inhibition led to increased cellular stress inA1cf−/−cells, and higher expression of ER-stress protein GRP78 was observed in restingA1cf−/−cells. RNA-seq of whole livers from wild-type andA1cf−/−mice revealed that pro-inflammatory, not lipogenesis, genes were upregulated as a secondary effect of A1CF deficiency. Differential alternative splicing (AS) analysis and RNA editing analysis revealed that genes involved in cellular stress and metabolism underwent differential changes in A1CF deficiency, and top A1CF binding target proteins with relevance to intracellular stress were differentially expressed on the protein but not mRNA level, implicating multiple mechanisms by which A1CF influences TG secretion.ConclusionsThese data suggest an important role for A1CF in mediating VLDL-TG secretion through regulating intracellular stress.
Molecular Mechanisms Governing Shade Responses in Maize
Authors: Shi Qingbiao , Kong Fanying , Zhang Haisen , Jiang Yu’e , Heng Siqi , Liang Ran , Liu Jisheng , Lu Xiaoduo , Li Pinghua , Li Gang 
Published: August 2018

AbstractLight is one of the most important environmental factors affecting plant growth and development. Plants use shade avoidance and shade tolerance strategies to adjust their growth and development thus increase their success in the competition for incoming light. To investigate the mechanism of shade responses in maize (Zea mays), we examined the anatomical and transcriptional dynamics of the early shade response in seedlings of the B73 inbred line. Transcriptome analysis identified 912 differentially expressed genes, including genes involved in light signaling, auxin responses, and cell elongation pathways. Grouping transcription factor family genes and performing enrichment analysis identified multiple types of transcription factors that are differentially regulated by shade and predicted putative core genes responsible for regulating shade avoidance syndrome. For functional tests, we ectopically over-expressedZmHB53, a type II HD-ZIP transcription factor gene significantly induced by shade, inArabidopsis thaliana. Transgenic Arabidopsis plants overexpressingZmHB53exhibited narrower leaves, earlier flowering, and enhanced expression of shade-responsive genes, suggesting that ZmHB53 participates in the regulation of shade responses in maize. This study increases our understanding of the regulatory network of the shade response in maize and provides a useful resource for maize genetics and breeding.HighlightOur findings not only increase the understanding of the regulatory network of the shade avoidance in maize, and also provide a useful resource for maize genetics and breeding.
Two Lytic Bacteriophages That Depend on theEscherichia coliMulti-Drug Efflux GenetolCand Differentially Affect Bacterial Growth and Selection
Authors: Burmeister Alita R. , Bender Rose G. , Fortier Abigail , Lessing Adam J. , Chan Benjamin K. , Turner Paul E. 
Published: August 2018

AbstractBacterial pathogens are increasingly evolving drug resistance under natural selection from antibiotics in medicine, agriculture, and nature. Meanwhile, bacteria ubiquitously encounter bacteriophages and can rapidly evolve phage resistance. However, the role of phages in interacting with drug-resistant and drug-sensitive bacteria remains unclear. To gain insight into such relationships, we screened for and characterized phages that rely on the multi-drug efflux pump genetolC. First, we screened a collection of 33 environmental and commercialEscherichia coliphages for their ability to infect cells that lackedtolC. Our screen revealed two phages that had reduced efficiency of plating (EOP) on thetolCknockout compared to wild type. We further characterized these phages with bacterial growth curves, transmission electron microscopy, and analysis of phage-resistant mutants. Phage U136B is a curly-tailed virus in familySiphoviridaewith no ability to infect atolCknockout, suggesting TolC is the U136B receptor. Phage 132 is a contractile-tailed virus in familyMyoviridaewith reduced EOP on cells lackingompFand its positive regulatorstolCandompR. U136B and 132 differentially effect bacterial growth and lysis, and U136B-resistant mutants contain mutations of thetolCgene. Together, these results show that thetolCgene involved in drug resistance can modify bacteria-phage interactions in multiple ways, altering bacterial lysis and selection. These new phages offer utility for studying evolution, tradeoffs, and infection mechanisms.ImportanceBacteria face strong selection by antibiotics in medicine and agriculture, resulting in increasing levels of drug resistance among bacterial pathogens. Slowing this process will require an understanding of the environmental contexts in which drug resistance evolutionarily increases or decreases. In this study, we investigate two newly-isolated bacteriophages that rely on a bacterial antibiotic resistance gene. These bacteriophages vary in their interactions with drug-resistant bacteria, with one of the phages selecting for phage-resistant mutants that have mutations in the antibiotic resistance gene. Further study of these new phages will be useful to understanding evolutionary tradeoffs and how phages might be applied in natural settings to reverse the problem of drug resistance.
OMA standalone: orthology inference among public and custom genomes and transcriptomes
Authors: Altenhoff Adrian M , Levy Jeremy , Zarowiecki Magdalena , Tomiczek Bartłomiej , Vesztrocy Alex Warwick , Dalquen Daniel A , Müller Steven , Telford Maximilian J , Glover Natasha M , Dessimoz Christophe 
Published: August 2018

AbstractGenomes and transcriptomes are now typically sequenced by individual labs, but analysing them often remains challenging. One essential step in many analyses lies in identifying orthologs—corresponding genes across multiple species—but this is far from trivial. The OMA (Orthologous MAtrix) database is a leading resource for identifying orthologs among publicly available, complete genomes. Here, we describe the OMA pipeline available as a standalone program for Linux and Mac. When run on a cluster, it has native support for the LSF, SGE, PBS Pro, and Slurm job schedulers and can scale up to thousands of parallel processes. Another key feature of OMA standalone is that users can combine their own data with existing public data by exporting genomes and pre-computed alignments from the OMA database, which currently contains over 2100 complete genomes. We compare OMA standalone to other methods in the context of phylogenetic tree inference, by inferring a phylogeny of the Lophotrochozoa, a challenging clade within the Protostomes. We also discuss other potential applications of OMA standalone, including identifying gene families having undergone duplications/losses in specific clades, and identifying potential drug targets in non-model organisms. OMA Standalone is available at http://omabrowser.org/standalone under the permissible open source Mozilla Public License Version 2.0.
Core architecture of a bacterial type II secretion system
Authors: Chernyatina Anastasia A , Low Harry H 
Published: August 2018

SummaryBacterial type II secretion systems (T2SS) translocate virulence factors, toxins and enzymes across the cell outer membrane (OM). An assembled T2SS has not yet been isolated in vitro. Here we use a fusion of negative stain and cryo-electron microscopy (EM) to reveal the core architecture of an assembled T2SS from the pathogen Klebsiella pneumoniae. We show that 7 proteins form a ∼2.5 MDa complex that spans the cell envelope. The outer membrane complex (OMC) includes the secretin PulD with all domains modelled and the pilotin PulS. The inner membrane assembly platform (AP) components PulC, PulE, PulL, PulM and PulN have a relative stoichiometric ratio of 2:1:1:1:1, respectively. The PulE ATPase, PulL and PulM combine to form a flexible hexameric hub. Symmetry mismatch between the OMC and AP is overcome by PulC linkers spanning the periplasm with PulC HR domains binding independently at the secretin base. Our results show the T2SS to have a highly dynamic modular architecture with implication for pseudo-pilus assembly and substrate loading.
Actomyosin-driven tension at compartmental boundaries orients cell division independently of cell geometryin vivo
Authors: Scarpa Elena , Finet Cédric , Blanchard Guy , Sanson Bénédicte 
Published: August 2018

AbstractDuring animal development, planar polarization of the actomyosin cytoskeleton underlies key morphogenetic events such as axis extension and boundary formation. Actomyosin is enriched along compartment boundaries during segmentation of theDrosophilaembryo, forming supracellular contractile cables that keep cells segregated at boundaries. Here, we show that these contractile actomyosin cables bias the orientation of division in cells in contact with compartment boundaries. By decreasing actomyosin cable tension locally using laser ablation or, conversely ectopically increasing tension using laser wounding, we demonstrate that localised subcellular force is necessary and sufficient to orient mitosesin vivo.Moreover this bias is independent of cell geometry and involves capture of the spindle pole by the actomyosin cortex.
Understanding the killing mechanism of action by virus-infected yeasts
Authors: Sheppard Sean , Dikicioglu Duygu 
Published: August 2018

AbstractKiller yeasts are microorganisms, which can produce and secrete proteinaceous toxins, a characteristic gainedviainfection by a virus. These toxins are able to kill sensitive cells of the same or a related species. From a biotechnological perspective, killer yeasts have been considered as beneficial due to their antifungal/antimicrobial activity, but also regarded as problematic for large-scale fermentation processes, whereby those yeasts would kill species off starter cultures and lead to stuck fermentations. Here, we propose a mechanistic model of the toxin-binding kinetics pertaining to the killer population coupled with the toxin-induced death kinetics of the sensitive population to study toxic actionin silico. Our deterministic model explains how killerSaccharomyces cerevisiaecells distress and consequently kill the sensitive members of the species, accounting for the K1, K2 and K28 toxin mode of action at high or low concentrations. The dynamic model captured the transient toxic activity starting from the introduction of killer cells into the culture at the time of inoculation through to induced cell death, and allowed us to gain novel insight on these mechanisms. The kinetics of K1/K2 activityviaits primary pathway of toxicity was 5.5 times faster than its activity at low concentration inducing the apoptotic pathway in sensitive cells. Conversely, we showed that the primary pathway for K28 was approximately 3 times slower than its equivalent apoptotic pathway, indicating the particular relevance of K28 in biotechnological applications where the toxin concentration is rarely above those limits to trigger the primary pathway of killer activity.
Assessment of abduction movement in older people with painful shoulder: an analysis based on inertial sensors
Authors: Roldán-Jiménez Cristina , Martín-Martín Jaime , Bennett Paul , McPhail Steven , Cuesta-Vargas Antonio I , Kerr Graham K. 
Published: August 2018

AbstractReduced range of motion in the shoulder can be a source of functional limitation. Current quantitative evaluation systems are limited to assessing the functionality or the maximum articular amplitudes in each of the planes of movement, both in isolation. These separate clinical evaluation systems may not allow the identification of the underlying impairments contributing to the functional limitation. The use of inertial sensors to quantify movement in addition to more common clinical assessments of the shoulder may allow clinicians to understand that are potentially unnoticed by the human eye. The main objective of this cross-sectional study was to generate an explanatory model for shoulder abduction based on data from inertial sensors. Shoulder abduction of thirteen older adults suffering from shoulder dysfunction was evaluated using two inertial sensors placed on the humerus and scapula. Movement variables (maximum angular mobility, angular peak of velocity, peak of acceleration) were used to explain the functionality of the upper limb (assessed using the Upper Limb Functional Index). Abduction movement of the shoulder was explained by six variables related to the mobility of the shoulder joint complex. A manova analysis was used to explain the results obtained on the functionality of the upper limb. The MANOVA model based on angular mobility explained 69% of the variance of the ULFI value (r-squared=0.69). The most relevant variables were the abduction-adduction of the humerus and the medial and lateral rotation of the scapula. However, given the limited sample size, none of these individual variables were statistically significant in the decomposition model on their own. The method used in the present study reveals the potential importance of the analysis of the scapular and humeral movements for comprehensive evaluation of the upper limb. Further research should include a wider sample and may seek to use this assessment technique in a range of potential clinical applications.
Impact of two neighbouring ribosomal protein clusters on biogenesis factor binding and assembly of yeast late small ribosomal subunit precursors
Authors: Linnemann Jan , Pöll Gisela , Jakob Steffen , Ferreira-Cerca Sébastien , Griesenbeck Joachim , Tschochner Herbert , Milkereit Philipp 
Published: August 2018

AbstractMany of the small ribosomal subunit proteins are required for the stabilisation of late small ribosomal subunit (SSU) precursors and for final SSU rRNA processing in S. cerevisiae. Among them are ribosomal proteins (r-proteins) which form a protein cluster around rpS0 (uS2) at the “neck” of the SSU (S0-cluster) and others forming a nearby protein cluster around rpS3 (uS3) at the SSU “beak”. Here we applied semi-quantitative proteomics together with complementary biochemical approaches to study how incomplete assembly of these two r-protein clusters affects binding and release of SSU maturation factors and assembly of other r-proteins in late SSU precursors in S. cerevisiae. For each of the two clusters specific impairment of the local r-protein assembly state was observed. Besides, cluster-specific effects on the association of biogenesis factors were detected.These suggested a role of S0-cluster formation for the efficient release of the two nuclear export factors Rrp12 and Slx9 from SSU precursors and for the correct incorporation of the late acting biogenesis factor Rio2. Based on our and on previous results we propose the existence of at least two different r-protein assembly checkpoints during late SSU maturation in S. cerevisiae. We discuss in the light of recent SSU precursor structure models how r-protein assembly states might be sensed by biogenesis factors at the S0-cluster checkpoint.
Reversible temporally-specific inhibition of muscle using a light-activated chloride channel
Authors: Gorini Christopher J. , Iyer Shrivats M. , Vyas Saurabh , Ramakrishnan Charu , Deisseroth Karl , Delp Scott L. 
Published: August 2018

AbstractAchieving reversible, temporally specific inhibition of motor neurons has the potential to revolutionize treatment of disorders marked by muscle hyperactivity. Current treatment strategies are inadequate – surgical interventions are irreversible and pharmaceutical interventions have off-target effects. Optogenetic strategies for inhibiting muscle activity have theoretical promise; however, trafficking and expression problems have prevented translatable optogenetic suppression of muscle activity. Here, we exploit recent innovations in opsin engineering to demonstrate virally mediated, temporally specific optogenetic inhibition of motor neurons and muscle activity in vivo. We show that intra-muscular injection of adeno-associated virus serotype 6 can drive expression of the inhibitory channelrhodopsin mutant iC++ in both immunodeficient and wild-type mice. Illumination of the sciatic nerve in wild-type mice resulted in 64.8% inhibition of evoked twitch force. Optical excitation during tetanic stimulation in wild-type mice resulted in 59.1% inhibition at 10 Hz and 55.4% at 25 Hz. The extent of optogenetic inhibition was titratable, and ranged from 0% to 78.4% as illumination intensity was changed from 1 mW to 20 mW/mm2. These results could have therapeutic applicability to disorders such as spasticity, hypertonia and urinary incontinence, and provide a new tool to neuroscientists and muscle physiologists wishing to reversibly inhibit motor neuron activity in vivo.
DrosophilaR8 photoreceptor cell subtype specification requiresNotchandhibris
Authors: Tan Hong , Fulton Ruth E. , Chou Wen-Hai , Birkholz Denise A. , Mannino Meridee P. , Yamaguchi David M. , Britt Steven G. 
Published: August 2018

AbstractCell differentiation and cell fate determination in sensory systems are essential for stimulus discrimination and coding of environmental stimuli. Color vision is based on the differential color sensitivity of retinal photoreceptors, however the developmental programs that control photoreceptor cell differentiation and specify color sensitivity are poorly understood. InDrosophila melanogaster,there is evidence that the color sensitivity of different photoreceptors in the compound eye is regulated by inductive signals between cells, but the exact nature of these signals and how they are propagated remains unknown. We conducted a genetic screen to identify additional regulators of this process and identified a novel mutation in thehibrisgene.hibrisencodes anirrecell recognition module protein (IRM). These immunoglobulin super family cell adhesion molecules include human neph and nephrin (NPHS1).hibrisis expressed dynamically in the developingDrosophila melanogastereye and loss-of-function mutations give rise to a diverse range of mutant phenotypes including disruption of the specification of R8 photoreceptors cell diversity. The specification of blue or green sensitivity in R8 cells is also dependent uponNotchsignaling. We demonstrate thathibrisis required within the retina, non-cell autonomously for these effects, suggesting an additional layer of complexity in the signaling process that produces paired expression of opsin genes in adjacent R7 and R8 photoreceptor cells.Author SummaryAs humans, our ability to distinguish different colors is dependent upon the presence of three different types of cone cell neurons in the retina of the eye. The cone cells express blue, green or red absorbing visual pigments that detect and discriminate between these colors. The principle of color discrimination by neurons “tuned” to different colors is an evolutionarily conserved specialization that occurs in many different animals. This specialization requires 1) visual pigments that detect different colors and 2) a developmental program that regulates the expression of these pigments in different types of cells. In this study we discovered that the fruit fly (Drosophila melanogaster) genehibrisis required for the developmental program that produces blue sensitive neurons in the fly retina. When we over-expressedhibristhroughout the developing retina, extra blue sensitive cells were produced. These results demonstrate that if there is not enoughhibris,too few blue sensitive cells form, but if there is too muchhibris, too many blue sensitive cells form. Finally, we discovered that thehibrisgene does not act in color sensitive neurons of the retina themselves. This surprising discovery suggests thathibrismay influence development of the retina in a completely new and different way.
Textual construction of comparative space
Authors: Tan Zhiyuan Simon 
Published: August 2018

PurposeThe purpose of this paper is to contribute to scholarly work on the role of sell-side financial analysts in corporate governance (CG). It examines the more recent work products pertaining specifically to CG that analysts based in the USA and UK have generated in the past two decades, namely, their CGCG reports. Specifically, this paper focusses on analysing how analyst CG reports constitute a comparative space in which the governance procedures of companies are evaluated and “best practices” are created.Design/methodology/approachThis study involves a social constructivist textual analysis of 48 CG reports produced by analysts based in the USA and UK between 1998 and 2009.FindingsAnalyst CG reports textually construct a comparative space comprising four dimensions. First, the space is constructed for some carefully edited users to evaluate the governance of companies. Second, the construction of this space requires the selection of “building materials”, i.e., governance issues included in the space that render companies amenable to evaluation and comparison. Third, by linking the range of governance issues chosen to formal regulations, firms are rendered governable and regulatory requirements reinterpreted. Lastly, by using different types of inscriptions, such as narratives and tables, the space highlights “winners”, i.e., those companies which do better than others, and constructs their governance procedures as “best practices”.Research limitations/implicationsThis research provides a first step towards an in-depth understanding of analyst CG reports. The insights from this paper generate a range of areas for future research, including how these reports are produced and used.Originality/valueThis paper adds to the existing literature focussing on the role of analysts in CG. It extends previous studies by examining the more recent and debatable work products generated by analysts, namely, their CG reports, and suggests an extended CG role for them. Theoretically, analyst CG reports are conceptualised as “inscriptions” that construct “documentary reality”. The notion of “editing” is also drawn upon, to analyse a particular way in which documentary reality is constructed. Accordingly, this paper broadens the theoretical perspectives used in CG research.