bluuebunny/crossref_metadata_2025_split huggingface dataset:
Computational identification of cell-specific variable regions in ChIP-seq data
Authors: Andreani Tommaso , Albrecht Steffen , Fontaine Jean-Fred , Andrade-Navarro Miguel A. 
Published: October 2019

ABSTRACTChromatin immunoprecipitation followed by sequencing (ChIP-seq) is used to identify genome-wide DNA regions bound by proteins. Given one ChIP-seq experiment with replicates, binding sites not observed in all the replicates will usually be interpreted as noise and discarded. However, the recent discovery of high-occupancy target (HOT) regions suggests that there are regions where binding of multiple transcription factors can be identified. To investigate ChIP-seq variability, we developed a reproducibility score and a method that identifies cell-specific variable regions in ChIP-seq data by integrating replicated ChIP-seq experiments for multiple protein targets on a particular cell type. Using our method, we found variable regions in human cell lines K562, GM12878, HepG2, MCF-7, and in mouse embryonic stem cells (mESCs). These variable-occupancy target regions (VOTs) are CG dinucleotide rich, and show enrichment at promoters and R-loops. They overlap significantly with HOT regions, but are not blacklisted regions producing non-specific binding ChIP-seq peaks. Furthermore, in mESCs, VOTs are conserved among placental species suggesting that they could have a function important for this taxon. Our method can be useful to point to such regions along the genome in a given cell type of interest, to improve the downstream interpretative analysis before follow up experiments.
Maternal immune activation in rats is associated with a lower number of dopamine receptor 3-expressing granulocytes in the male offspring with no alterations in cocaine reward, resistance to extinction or cue-induced reinstatement
Authors: Santos-Toscano Raquel , Ucha Marcos , Borcel Érika , Ambrosio Emilio , Higuera-Matas Alejandro 
Published: October 2019

ABSTRACTThere is evidence for increased rates of drug use among schizophrenic patients. However, the causality in this relationship remains unclear. In addition, biomarkers of schizophrenia are vital, given the heterogeneous nature of the disorder that can lead to difficulties in the early diagnosis. In the present work, we use a maternal immune activation model to experimentally test whether animals at high risk of developing a schizophrenia-like condition are more prone to acquire cocaine self-administration, show enhanced sensitivity to the reinforcing actions of cocaine or if they are resistant to extinction or vulnerable to relapse. Pregnant rats were injected with lipopolysaccharide (LPS) (2 mg/kg s.c.) or saline every other day during pregnancy, and the offspring was tested for sensorimotor gating (prepulse inhibition –PPI-). After this test, one group of rats was submitted to cocaine self-administration (0.5 mg/kg) under fixed and progressive ratio schedules, dose-response testing, extinction and cue-induced drug-seeking. Another group was sacrificed to study potential biomarkers in the immune blood cells by flow cytometry. While rats born to LPS-treated mothers showed impaired PPI, there were no differences in cocaine self-administration acquisition, responsiveness to dose shifts, extinction or cue-induced reinstatement. Finally, there were fewer DRD3+ granulocytes in the LPS-offspring and an exciting trend for CNR2+ lymphocytes to be more abundant in LPS-exposed rats. Our results indicate that the higher prevalence of cocaine abuse among people with schizophrenia is not due to a pre-existing pathology and suggest that DRD3+ granulocytes and possibly CNR2+ lymphocytes could be potential biomarkers of schizophrenia.
Amino Acid Requirements of the Chinese Hamster Ovary Cell Metabolism during Recombinant Protein Production
Authors: Traustason Bergthor 
Published: October 2019

SummaryMajority of biopharmaceutical drugs today are produced by Chinese hamster ovary (CHO) cells, which have been the standard industry host for the past decades. To produce and secrete a substantial amount of the target recombinant proteins the CHO cells must be provided with suitable growth conditions and provided with the necessary nutrients. Amino acids play a key role in this as the building blocks of proteins, playing important roles in a large number of metabolic pathways and being important sources of nitrogen as well as carbon under certain conditions. In this study exploratory analysis of the amino acid requirements of CHO cells was carried out using metabolic modelling approaches. Flux balance analysis was employed to evaluate the optimal distribution of fluxes in a genome-scale model of CHO cells to gain information on the cells’ metabolic response in silico.The results showed that providing non-essential amino acids (NEAAs) has a positive effect on CHO cell biomass production and that cysteine as well as tyrosine play a fundamental role in this. This implies that extracellular provision of NEAAs limits the extent of energy loss in amino acid biosynthetic pathways and renders additional reducing power available for other biological processes. Detailed analysis of the possible secretion and uptake of D-serine in the CHO model was also performed and its influence on the rest of the metabolism mapped out, which revealed results matching various existing literature. This is interesting since no mention of D-serine in regard to CHO cells was found in current literature, as well as the fact that this opens up the possibility of using the model for better understanding of certain disorders in higher up organisms that have been implicated with D-serine, such as motor neuron and cognitive degeneration. Finally, outcome from the model optimisation of different recombinant proteins demonstrated clearly how the difference in protein structure and size can influence the production outcome. These results show that systematic and model-based approaches have great potential for broad de novo exploration as well as being able to handle the cellular burden associated with the production of different types of recombinant protein.
Immuno-moodulin: a new anxiogenic factor produced by autoimmune-prone T cells
Authors: Piras Giuseppa , Rattazzi Lorenza , Paschalidis Nikolaos , Oggero Silvia , Berti Giulio , Ono Masahiro , Bellia Fabio , D’Addario Claudio , Dell’Osso Bernardo , Pariante Carmine Maria , Perretti Mauro , D’Acquisto Fulvio 
Published: October 2019

AbstractPatients suffering from autoimmune diseases are more susceptible to mental disorders yet, the existence of specific cellular and molecular mechanisms behind the co-morbidity of these pathologies is far from being fully elucidated. By generating transgenic mice overexpressing Annexin-A1 exclusively in T cells to study its impact in models of autoimmune diseases, we made the unpredicted observation of an increased level of anxiety. Gene microarray of Annexin-A1 CD4+T cells identified a novel anxiogenic factor, a small protein of approximately 21kDa encoded by the gene 2610019F03Rik which we named Immuno-moodulin. Neutralizing antibodies against Immuno-moodulin reverted the behavioral phenotype of Annexin-A1 transgenic mice and lowered the basal levels of anxiety in wild type mice; moreover, we also found that patients suffering from obsessive compulsive disorders show high levels of Imoodin their peripheral mononuclear cells. We thus identify this protein as a novel peripheral determinant that modulates anxiety behavior. Therapies targeting Immuno-moodulin may lead to a new type of treatment for mental disorders through regulation of the functions of the immune system, rather than directly acting on the nervous system.
Enzyme-constrained models and omics analysis of Streptomyces coelicolor reveal metabolic changes that enhance heterologous production
Authors: Sulheim Snorre , Kumelj Tjaša , van Dissel Dino , Salehzadeh-Yazdi Ali , Du Chao , van Wezel Gilles P. , Nieselt Kay , Almaas Eivind , Wentzel Alexander , Kerkhoven Eduard J 
Published: October 2019

AbstractMany biosynthetic gene clusters (BGCs) require heterologous expression to realize their genetic potential, including silent and metagenomic BGCs. Although the engineeredStreptomyces coelicolorM1152 is a widely used host for heterologous expression of BGCs, a systemic understanding of how its genetic modifications affect the metabolism is lacking and limiting further development. We performed a comparative analysis of M1152 and its ancestor M145, connecting information from proteomics, transcriptomics, and cultivation data into a comprehensive picture of the metabolic differences between these strains. Instrumental to this comparison was the application of an improved consensus genome-scale metabolic model (GEM) ofS. coelicolor. Although many metabolic patterns are retained in M1152, we find that this strain suffers from oxidative stress, possibly caused by increased oxidative metabolism. Furthermore, precursor availability is likely not limiting polyketide production, implying that other strategies could be beneficial for further development ofS. coelicolorfor heterologous production of novel compounds.
Plexin-Bs enhance their GAP activity with a novel activation switch loop generating a cooperative enzyme
Authors: Li Zhen-lu , Müller-Greven Jeannine , Kim SoonJeung , Tamagnone Luca , Buck Matthias 
Published: October 2019

AbstractPlexins receive guidance cues from semaphorin ligands and transmit their signal through the plasma membrane. This family of proteins is unique amongst single-pass transmembrane receptors as their intracellular regions interact directly with several small GTPases, which regulate cytoskeletal dynamics and cell adhesion. Here, we characterize the GTPase Activating Protein (GAP) function of Plexin-B1 and find that a cooperative GAP activity towards the substrate GTPase, Rap1b, is associated with the N-terminal Juxtamembrane region of Plexin-B1. Importantly, we unveil an activation mechanism of Plexin-B1 by identifying a novel functional loop which partially blocks Rap1b entry to the plexin GAP domain. Consistent with the concept of allokairy developed for other systems, Plexin-B activity is increased by an apparent substrate mediated cooperative effect. Simulations and mutagenesis suggest the repositioned JM conformation is stabilized by the new activation switch loop when the active site is occupied, giving rise to faster enzymatic turnover and cooperative behavior. The biological implications, essentially of a threshold behavior for cell migration are discussed.
Vaping nicotine-containing electronic cigarettes produces addiction-like behaviors and cardiopulmonary abnormalities in rats
Authors: Smith Lauren C. , Kallupi Marsida , Tieu Lani , Jaquish Abigail , Barr Jamie , Su Yujuan , Velarde Nathan , Sedighim Sharona , Klodnicki Mike , Carrette Lieselot L. G. , Sun Xin , de Guglielmo Giordano , George Olivier 
Published: October 2019

AbstractThe debate about electronic cigarettes has divided healthcare professionals, policymakers, and communities. Central points of disagreement are whether vaping electronic cigarettes are addictive and whether they produce major pulmonary complications. We developed a novel model of nicotine vapor self-administration in rats and found that rats voluntarily exposed themselves to nicotine vapor to the point of reaching blood nicotine levels that are similar to humans, exhibiting both addiction-like behaviors and cardiopulmonary abnormalities. The smoking cessation drug varenicline decreased electronic cigarette self-administration. These findings confirm the addictive properties and harmful effects of nicotine vapor and identify a potential medication for the treatment of electronic cigarette addiction.One Sentence SummaryVaping nicotine-containing electronic cigarettes produces cardiopulmonary abnormalities, nicotine dependence and addiction-like behaviors, which are reduced by the smoking cessation drug varenicline.
Differential sorting behavior for soluble and transmembrane cargoes at the trans-Golgi network in endocrine cells
Authors: Hummer Blake H. , Maslar Drew , Soltero Gutierrez Margarita , de Leeuw Noah F. , Asensio Cedric S. 
Published: October 2019

AbstractRegulated secretion of neuropeptides and peptide hormones by secretory granules (SGs) is central to physiology. Formation of SGs occurs at the trans-Golgi network (TGN) where their soluble cargo aggregates to form a dense core, but the mechanisms controlling the sorting of regulated secretory cargoes (soluble and transmembrane) away from constitutively secreted proteins remain unclear. Optimizing the use of the retention using selective hooks (RUSH) method in (neuro-)endocrine cells, we now quantify TGN budding kinetics of constitutive and regulated secretory cargoes. We further show that, by monitoring two cargoes simultaneously, it becomes possible to visualize sorting to the constitutive and regulated secretory pathways in real-time. Further analysis of the localization of SG cargoes immediately after budding from the TGN revealed that, surprisingly, the bulk of two studied transmembrane SG cargoes (phogrin and VMAT2) does not sort directly onto SGs during budding, but rather exit the TGN into non-regulated vesicles to get incorporated to SGs at a later step. This differential behavior of soluble and transmembrane cargoes suggests a more complex model of SG biogenesis than anticipated.
Conformational dynamics at microsecond timescale in the RNA-binding regions of dsRNA-binding domains
Authors: Paithankar H , Chugh J 
Published: October 2019

AbstractDouble-stranded RNA-binding domains (dsRBDs) are involved in a variety of biological functions via recognition and processing of dsRNAs. Though the primary substrate of the dsRBDs are dsRNAs with A-form helical geometry; they are known to interact with structurally diverse dsRNAs. Here, we have employed two model dsRBDs – TAR-RNA binding protein and Adenosine deaminase that acts on RNA – to understand the role of intrinsic protein dynamics in RNA binding. We have performed a detailed characterization of the residue-level dynamics by NMR spectroscopy for the two dsRBDs. While the dynamics profiles at the ps-ns timescale of the two dsRBDs were found to be different, a striking similarity was observed in the μs-ms timescale dynamics for both the dsRBDs. Motions at fast μs timescale (kex > 50000 s−1) were found to be present not only in the RNA-binding residues but also in some allosteric residues of the dsRBDs. We propose that this intrinsic μs timescale dynamics observed independently in two distinct dsRBDs allows them to undergo conformational rearrangement that may aid dsRBDs to target substrate dsRNA from the pool of structurally different RNAs in cellular environment.Statement of SignificanceThis study reports for the first time the detailed characterization of microsecond timescale dynamics observed in RNA-binding regions of two distinct double-stranded RNA-binding domains (dsRBDs) using NMR relaxation dispersion experiments. dsRBDs have been known to target topologically distinct dsRNAs. However, the mechanistic details of the structural adaptation of proteins is not fully understood. We propose that the presence of such dynamics may have large-scale implications in understanding the RNA recognition mechanisms by the dsRBDs.
DMD-based super-resolution structured illumination microscopy visualizes live cell dynamics at high speed and low cost
Authors: Sandmeyer Alice , Lachetta Mario , Sandmeyer Hauke , Hübner Wolfgang , Huser Thomas , Müller Marcel 
Published: October 2019

Structured illumination microscopy (SIM) is among the most widely used super-resolution fluorescence microscopy techniques for visualizing the dynamics of cellular organelles, such as mitochondria, the endoplasmic reticulum, or the cytoskeleton. In its most wide-spread implementation, SIM relies on the creation of an interference pattern at the diffraction limit using the coherent addition of laser beams created by a diffraction pattern.Spatial light modulators based on liquid crystal displays allow SIM micro-scopes to run at image rates of up to hundreds of super-resolved images per second. Digital micromirror devices are another natural choice for creating interference-based SIM patterns, but are not used to their fullest potential because of the blazed grating effect. This effect arises due to the fixed angles between which the mirrors can be switched, creating a sawtooth arrangement of mirrors and thus leading to a change in the intensity distribution of the diffracted beams. This results in SIM patterns with varying modulation contrast which are prone to reconstruction artifacts.We have carefully studied the blazed grating effect of DMDs by simulations, varying a range of parameters and compared the simulation results with experiments. This allowed us to identify settings which result in very high modulation contrast across all angles and phases required to generate 2-beam SIM pattern. The use of inexpensive industry-grade CMOS cameras as well as low-cost lasers enabled us to construct a cost-effective, high-speed SIM system. Reconstruction of the super-resolved SIM images is achieved on a recently demonstrated parallel-computing platform, which allowed us to visualize living cells with super-resolution at multiple reconstructed frames per second in real time. We demonstrate the versatility of this new platform by imaging cellular organelle dynamics based on live-cell fluorescent stains as well as with fluorescent protein stained samples.
The maize heterotrimeric G-protein β subunit controls shoot meristem development and immune responses
Authors: Wu Qingyu , Xu Fang , Liu Lei , Char Si Nian , Ding Yezhang , Schmelz Eric , Yang Bing , Jackson David 
Published: October 2019

AbstractHeterotrimeric G-proteins are important transducers of receptor signaling, functioning in plants with CLAVATA receptors in control of shoot meristem size, and with pathogen associated molecular pattern (PAMP) receptors in basal immunity. However, whether specific members of the heterotrimeric complex potentiate crosstalk between development and defense, and the extent to which these functions are conserved across species, has not been addressed. Here we used CRISPR/Cas9 to knockout the maize Gβ subunit gene, and found that the mutants were lethal, differing from Arabidopsis, where homologous mutants have normal growth and fertility. We show that lethality is not caused by a specific developmental arrest, but by autoimmunity. We used a genetic diversity screen to suppress the lethal gβ phenotype, and also identified a new maize Gβ allele with weak autoimmune responses but strong development phenotypes. Using these tools, we show that Gβ controls meristem size in maize, acting epistatically with Gα, suggesting that Gβ and Gα function in a common signaling complex. Furthermore, we used an association study to show that natural variation in Gβ influences maize kernel row number, an important agronomic trait. Our results demonstrate the dual role of Gβ in immunity and development in a cereal crop, and suggest that it functions in crosstalk between these competing signaling networks. Therefore, modification of Gβ has the potential to optimize the tradeoff between growth and defense signaling to improve agronomic production.SignificanceCereal crops, such as maize provide our major food and feed. Crop productivity has been significantly improved by selection of favorable architecture and development alleles, however crops are constantly under attack from pathogens, which severely limits yield due to a defense-growth tradeoff. Therefore, it is critical to identify key signaling regulators that control both developmental and immune signaling, to provide basic knowledge to maximize productivity. This work shows that the maize G protein β subunit regulates both meristem development and immune signaling, and suggests that manipulation of this gene has the potential to optimize the tradeoff between yield and disease resistance to improve crop yields.
Textual analysis for China’s financial markets: a review and discussion
Authors: Huang Alan , Wu Wenfeng , Yu Tong 
Published: October 2019

Purpose
This is a literature survey paper. The purpose of this paper is to focus on the latest developments in textual analysis on China’s financial markets, highlighting its differences from existing works in the US markets.

Design/methodology/approach
The authors review the literature and carry out an experiment of sentiment analysis based on a small sample of Chinese news articles.

Findings
Based on the experiment of sentiment analysis, there is limited evidence on the association between sentiment and other contemporaneous or future returns.

Originality/value
The supply of financial textual information has grown exponentially in the past decades. Technological advancements in recent years make the programming-based analysis an effective tool to digest such information. The authors highlight the use of credible textual information and discuss directions of research in this important field.
Unleashing the power of salespersons’ implementation intentions through coaching
Authors: Pousa Claudio 
Published: October 2019

Purpose
The purpose of the paper is to validate if managers (through the use of managerial coaching) can help subordinates develop implementation intentions to address difficult problems and situations with customers. These implementation intentions take the form of new task strategies and go beyond the automated mechanisms of providing more effort, persisting longer in the pursuit of goals or adapting old strategies to solve new problems.

Design/methodology
We designed a cross-sectional field study with a convenience sample of 184 salespeople from different companies. Respondents provided information concerning the coaching received from their supervisors, the degree to which they were able to develop implementation intentions in future encounters with customers, and sales performance. Data was analyzed using structural equation modeling in AMOS.

Findings
We found that coaching can help salespeople develop better implementation intentions and, thus, be more effective in their interactions with customers, ultimately increasing their sales performance.

Originality
The paper explores the use of coaching to help subordinates develop new task-oriented strategies, using two theoretical frameworks: implementation intentions and goal-setting.
Cultivating voice through hands, heart, and spirit: motivating language’s role in gaining feedback
Authors: Mayfield Milton , Mayfield Jacqueline 
Published: October 2019

Purpose
This manuscript presents guidelines for how managers can use communication (motivating language) to increase the feedback they receive from their followers.

Design/methodology/approach
These guidelines were developed from careful analysis of leader motivating language and follower voice literature.

Findings
Analysis results lead research based suggestions for how leaders can increase feedback from followers.

Originality/value
This manuscript will help leaders to increase needed feedback from followers on how to improve and develop organizations.