bluuebunny/crossref_metadata_2025_split huggingface dataset:
Polyadenylation of Histone H3.1 mRNA Promotes Cell Transformation by Displacing H3.3 from Gene Regulatory Elements
Authors: Chen Danqi , Chen Qiao Yi , Wang Zhenjia , Zhu Yusha , Kluz Thomas , Tan Wuwei , Li Jinquan , Wu Feng , Fang Lei , Zhang Xiaoru , He Rongquan , Shen Steven , Sun Hong , Zang Chongzhi , Jin Chunyuan , Costa Max 
Published: October 2019

SummaryReplication-dependent canonical histone messenger RNAs (mRNAs) do not terminate with a poly(A) tail at the 3’ end. We previously demonstrated that exposure to arsenic, an environmental carcinogen, induces polyadenylation of canonical histone H3.1 mRNA. The addition of a poly(A) tail to the H3.1 mRNA caused transformation of human cells in vitro, but the underlying mechanisms are unknown. Here we report that polyadenylation of H3.1 mRNA increases H3.1 protein level, resulting in depletion of histone variant H3.3 at active promoters, enhancers, and insulator regions through its displacement. Cells underwent transcriptional deregulation, G2/M cell cycle arrest, chromosome aneuploidy and aberrations. Furthermore, knocking down the expression of H3.3 induced cell transformation, whereas ectopic expression of H3.3 attenuated arsenic-induced cell transformation, suggesting that H3.3 displacement might be central to tumorigenic effects of polyadenylated H3.1 mRNA. Our study provides novel insights into the importance of proper histone stoichiometry in maintaining genome integrity.HighlightsPolyadenylation of canonical histone H3.1 mRNA promotes tumor formation in nude miceHistone variant H3.3 is displaced from critical gene regulatory elements by overexpression of polyadenylated H3.1 mRNAIncreased polyadenylated H3.1 mRNA causes abnormal transcription, cell cycle arrest, and chromosomal instabilityArsenic induces polyadenylation of H3.1 mRNA in vivo
From stress to depression: Development of extracellular matrix-dependent cognitive impairment following social stress
Authors: Koskinen Maija-Kreetta , van Mourik Yvar , Smit August Benjamin , Riga Danai , Spijker Sabine 
Published: October 2019

AbstractStress can predispose to depressive episodes, yet the molecular mechanisms regulating the transition from the initial stress response to a persistent pathological depressive state remain poorly understood. To shed light on this stress-to-depression transition process, we profiled the development of an enduring depressive-like state in rat by assessing affective behavior and hippocampal function during the 2 months following social defeat stress. In addition, we measured remodeling of hippocampal extracellular matrix (ECM) during this period, as we recently identified ECM changes to mediate cognitive impairment during a sustained depressive-like state. We found affective disturbance and cognitive impairment to develop disparately after social stress. While affective deficits emerged gradually, spatial memory impairment was present both early after stress and during the late-emerging chronic depressive-like state. Surprisingly, these phases were separated by a period of normalized hippocampal function. Similarly, the SDPS paradigm induced a biphasic regulation of the hippocampal ECM coinciding with hippocampus-dependent memory deficits. Early after stress, synaptic ECM proteins and the number of perineuronal nets enwrapping parvalbumin-expressing interneurons were decreased. This was followed by a recovery period without ECM dysregulation, before subsequent decreased metalloproteinase activity and ECM build-up, previously shown to impair memory. This suggests that intact hippocampal function requires unaltered ECM levels. Together our data 1) reveal a dichotomy between affective and cognitive impairments similar to that observed in patients, 2) indicate different molecular processes taking place during early stress and the chronic depressive-like state, and 3) support a role of the ECM in mediating long-lasting memory-effects of social stress.
Extracellular ATP and CD39 activate cAMP-mediated mitochondrial stress response to promote cytarabine resistance in acute myeloid leukemia
Authors: Aroua Nesrine , Ghisi Margherita , Boet Emeline , Nicolau-Travers Marie-Laure , Saland Estelle , Gwilliam Ryan , de Toni Fabienne , Hosseini Mohsen , Mouchel Pierre-Luc , Farge Thomas , Bosc Claudie , Stuani Lucille , Sabatier Marie , Mazed Fetta , Larrue Clément , Jarrou Latifa , Gandarillas Sarah , Bardotti Massimiliano , Syrykh Charlotte , Laurent Camille , Gotanègre Mathilde , Bonnefoy Nathalie , Bellvert Floriant , Portais Jean-Charles , Nicot Nathalie , Azuale Francisco , Kaoma Tony , Tamburini Jérome , Vergez François , Récher Christian , Sarry Jean-Emmanuel 
Published: October 2019

ABSTRACTRelapses driven by chemoresistant leukemic cell populations are the main cause of mortality for patients with acute myeloid leukemia (AML). Here, we show that the ectonucleotidase CD39 (ENTPD1) is upregulated in cytarabine (AraC)-resistant leukemic cells from both AML cell lines and patient samplesin vivoandin vitro. CD39 cell surface expression and activity is increased in AML patients upon chemotherapy compared to diagnosis and enrichment in CD39-expressing blasts is a marker of adverse prognosis in the clinics. High CD39 activity promotes AraC resistance by enhancing mitochondrial activity and biogenesis through activation of a cAMP-mediated response. Finally, genetic and pharmacological inhibition of CD39 eATPase activity blocks the mitochondrial reprogramming triggered by AraC treatment and markedly enhances its cytotoxicity in AML cellsin vitroandin vivo. Together, these results reveal CD39 as a new prognostic marker and a promising therapeutic target to improve chemotherapy response in AML.SIGNIFICANCEExtracellular ATP and CD39-cAMP-OxPHOS axis are key regulators of cytarabine resistance, offering a new promising therapeutic strategy in AML.
The BSGatlas: An enhanced annotation of genes and transcripts for theBacillus subtilisgenome with improved information access
Authors: Geissler Adrian Sven , Anthon Christian , González-Tortuero Enrique , Poulsen Line Dahl , Kallehauge Thomas Beuchert , Seemann Stefan Ernst , Vinther Jeppe , Gorodkin Jan 
Published: October 2019

AbstractThe genome ofBacillus subtiliscontinues to provide exiting genomic insights. However, the growing collective genomic knowledge about this micro-organism is spread across multiple annotation resources. Thus, the full annotation is not directly accessible neither for specific genes nor for large-scale high-throughput analyses. Furthermore, access to annotation of non-coding RNA genes (ncRNAs) and polycistronic mRNAs is difficult. To address these challenges we introduce theBacillus subtilisgenome atlas, BSGatlas, in which we integrate and unify multiple existing annotation resources. Our integration provides twice as many ncRNAs than the individual resources, improves the positional annotation for 70% of the combined ncRNAs, and makes it possible to infer specific ncRNA types. Moreover, we unify known transcription start sites, termination, and transcriptional units (TUs) as a comprehensive transcript map. This transcript map implies 815 new TUs and 6, 164 untranslated regions (UTRs), which is a five-fold increase over existing resources. We furthermore, find 2, 309 operons covering the transcriptional annotation for 93% of all genes, corresponding to an improvement by 11%. The BSGatlas is available in multiple formats. A user can either download the entire annotation in the standardized GFF3 format, which is compatible with most bioinformatics tools for omics and high-throughput studies, or view the annotation in an online browser athttp://rth.dk/resources/bsgatlas.ImportanceTheBacillus subtilisgenome has been studied in numerous context and consequently multiple efforts have been made in providing a complete annotation. Unfortunately, a number of resources are no longer maintained, and (i) the collective annotation knowledge is dispersed over multiple resources, of which each has a different focus of what type of annotation information they provide. (ii) Thus, it is difficult to easily and at a large scale obtain information for a genomic region or genes of interest. (iii) Furthermore, all resources are essentially incomplete when it comes to annotating non-coding and structured RNA, and transcripts in general. Here, we address all three problems by first collecting existing annotations of genes and transcripts start and termination sites; afterwards resolving discrepancies in annotations and combining them, which doubled the number of ncRNAs; inferring full transcripts and 2,309 operons from the combined knowledge of known transcript boundaries and meta-information; and critically providing it all in a standardized UCSC browser. That interface and its powerful set of functionalities allow users to access all the information in a single resource as well as enables them to include own data on top the full annotation.
PATTIE: Publication access through tiered interaction & exploration
Authors: Ortiz Michael Segundo , Wang Mengqian , Seki Kazuhiro , Kim Heejun , Mostafa Javed 
Published: October 2019

AbstractIn this work we present Publication Access Through Tiered Interaction & Exploration (PATTIE) – an information foraging, sense-making, and exploratory spatial-semantic information retrieval (IR) system (http://pattie.unc.edu/plos). Non-spatial, spatial IR systems, and some recent studies focused on their principal functions are discussed and compared. To interactively work through a use-case from the biomedical domain, instructions are provided for readers to conduct exploratory searches directly on the PLOS archive based on the software embedded in the online version of this paper (http://vzlib.unc.edu/software/). To carefully evaluate some of the critical parameters of the PATTIE algorithm, and the core functions of the implemented system, a set of experiments were conducted. Along with details on the experimental methods and their rationale, key findings from the experiments are analyzed and presented. Finally, with an eye toward the future of software-embedded scientific papers, their potential benefits for supporting direct engagement with scientific content, replication, and validation are discussed.
Atypical Structural Tendencies Among Low-Complexity Domains in the Protein Data Bank Proteome
Authors: Cascarina Sean M. , Elder Mikaela R. , Ross Eric D. 
Published: October 2019

AbstractA variety of studies have suggested that low-complexity domains (LCDs) tend to be intrinsically disordered and are relatively rare within structured proteins in the protein data bank (PDB). Although LCDs are often treated as a single class, we previously found that LCDs enriched in different amino acids can exhibit substantial differences in protein metabolism and function. Therefore, we wondered whether the structural conformations of LCDs are likewise dependent on which specific amino acids are enriched within each LCD. Here, we directly examined relationships between enrichment of individual amino acids and secondary structure preferences across the entire PDB proteome. Secondary structure preferences varied as a function of the identity of the amino acid enriched and its degree of enrichment. Furthermore, divergence in secondary structure profiles often occurred for LCDs enriched in physicochemically similar amino acids (e.g. valine vs. leucine), indicating that LCDs composed of related amino acids can have distinct secondary structure preferences. Comparison of LCD secondary structure preferences with numerous pre-existing secondary structure propensity scales resulted in relatively poor correlations for certain types of LCDs, indicating that these scales may not capture secondary structure preferences as sequence complexity decreases. Collectively, these observations provide a highly resolved view of structural preferences among LCDs parsed by the nature and magnitude of single amino acid enrichment.Author SummaryThe structures that proteins adopt are directly related to their amino acid sequences. Low-complexity domains (LCDs) in protein sequences are unusual regions made up of only a few different types of amino acids. Although this is the key feature that classifies sequences as LCDs, the physical properties of LCDs will differ based on the types of amino acids that are found in each domain. For example, the sequences “AAAAAAAAAA”, “EEEEEEEEEE”, and “EEKRKEEEKE” will have very different properties, even though they would all be classified as LCDs by traditional methods. In a previous study, we developed a new method to further divide LCDs into categories that more closely reflect the differences in their physical properties. In this study, we apply that approach to examine the structures of LCDs when sorted into different categories based on their amino acids. This allowed us to define relationships between the types of amino acids in the LCDs and their corresponding structures. Since protein structure is closely related to protein function, this has important implications for understanding the basic functions and properties of LCDs in a variety of proteins.
Representation of Distance and Direction of Nearby Boundaries in Retrosplenial Cortex
Authors: Wijngaarden Joeri B.G. van , Babl Susanne S. , Ito Hiroshi T. 
Published: October 2019

AbstractBorders and edges are salient and behaviourally relevant features for navigating the environment. The brain forms dedicated neural representations of environmental boundaries, which are assumed to serve as a reference for spatial coding. Here we expand this border coding network to include the retrosplenial cortex (RSC) in which we identified neurons that increase their firing near all boundaries of an arena. RSC border cells specifically encode walls, but not objects, and maintain their tuning in the absence of direct sensory detection. Unlike border cells in the medial entorhinal cortex (MEC), RSC border cells are sensitive to the animal’s direction to nearby walls located contralateral to the recorded hemisphere. Pharmacogenetic inactivation of MEC led to a disruption of RSC border coding, but not vice versa, indicating network directionality. Together these data shed light on how information about distance and direction of boundaries is generated in the brain for guiding navigation behaviour.
Structural analysis of mycobacterial homoserine transacetylases central to methionine biosynthesis reveals druggable active site
Authors: Chaton Catherine T. , Rodriguez Emily S. , Reed Robert W. , Li Jian , Kenner Cameron W. , Korotkov Konstantin V. 
Published: October 2019

AbstractMycobacterium tuberculosis is the cause of the world’s most deadly infectious disease. Efforts are underway to target the methionine biosynthesis pathway, as it is not part of the host metabolism. The homoserine transacetylase MetX converts L-homoserine to O-acetyl-L-homoserine at the committed step of this pathway. In order to facilitate structure-based drug design, we determined the high-resolution crystal structures of three MetX proteins, including M. tuberculosis (MtMetX), Mycolicibacterium abscessus (MaMetX), and Mycolicibacterium hassiacum (MhMetX). A comparison of homoserine transacetylases from other bacterial and fungal species reveals a high degree of structural conservation amongst the enzymes. Utilizing homologous structures with bound cofactors, we analyzed the potential ligandability of MetX. The deep active-site tunnel surrounding the catalytic serine yielded many consensus clusters during mapping, suggesting that MtMetX is highly druggable.
An activity-guided map of electrophile-cysteine interactions in primary human immune cells
Authors: Vinogradova Ekaterina V. , Lazar Daniel C. , Suciu Radu M. , Wang Yujia , Bianco Giulia , Yamashita Yu , Crowley Vincent M. , Remillard Dave , Lum Kenneth M. , Simon Gabriel M. , Kemper Esther K. , Lazear Michael R. , Yin Sifei , Blewett Megan M. , Dix Melissa M. , Nguyen Nhan , Shokhirev Maxim N. , Chin Emily , Lairson Luke , Forli Stefano , Teijaro John R. , Cravatt Benjamin F. 
Published: October 2019

AbstractElectrophilic compounds originating from nature or chemical synthesis have profound effects on immune cells. These compounds are thought to act by cysteine modification to alter the functions of immune-relevant proteins; however, our understanding of electrophile-sensitive cysteines in the human immune proteome remains limited. Here, we present a global map of cysteines in primary human T cells that are susceptible to covalent modification by electrophilic small molecules. More than 3000 covalently liganded cysteines were found on functionally and structurally diverse proteins, including many that play fundamental roles in immunology. We further show that electrophilic compounds can impair T cell activation by distinct mechanisms involving direct functional perturbation and/or ligand-induced degradation of proteins. Our findings reveal a rich content of ligandable cysteines in human T cells, underscoring the potential of electrophilic small molecules as a fertile source for chemical probes and ultimately therapeutics that modulate immunological processes and their associated disorders.
The impact of national culture on the adoption of environmental management standards
Authors: Orcos Raquel , Palomas Sergio 
Published: October 2019

PurposeThe purpose of this paper is to explore how national cultures contribute to explain the uneven diffusion of ISO 14001 across countries. The paper focuses on two of the cultural dimensions developed by the global leadership and organizational behavior effectiveness (GLOBE) project, namely, performance orientation and institutional collectivism.Design/methodology/approachA database containing information about the diffusion of ISO 14001 in 52 countries during the period 1999–2016 was built to carry out this research. The countries considered in this study represent about 90 percent of worldwide ISO 14001 certifications. The information was gathered from publicly available data sources: the ISO Survey, published every year by the International Organization for Standardization, the world development indicators of the World Bank, the cultural dimensions of the GLOBE project and the Index of Economic Freedom provided by The Heritage Foundation.FindingsThis research finds that both performance orientation and institutional collectivism influence the diffusion of ISO 14001. Whereas performance orientation slows down the diffusion of ISO 14001, institutional collectivism speeds it up. Additionally, this research shows that the slowing effect of performance orientation decreases in strength over time, while the accelerating effect of institutional collectivism becomes stronger.Originality/valueThe study adds to the understanding of the influence of national culture on the diffusion of environmental management standards, with an emphasis on ISO 14001. A key contribution of this research is that it explores how the influence of cultural dimensions change over time as a result of the development and maturation of ISO 14001.
A technology management system for the development of single-task construction robots
Authors: Linner Thomas , Pan Wen , Hu Rongbo , Zhao Charlie , Iturralde Kepa , Taghavi Meysam , Trummer Julian , Schlandt Marcel , Bock Thomas 
Published: October 2019

Purpose
Because of the sharply growing interest worldwide of “hard” physical-mechanical robot systems for the execution of on-site construction tasks [i.e. single-task construction robots (STCRs)], the purpose of this study is to equip development projects with a systematic design-management system model that allows to integrate the different needs and aims of stakeholders.

Design/methodology/approach
This paper proposes a STCR-technology management system (STCR-TMS) for the complete development cycle of STCR designs. The STCR-TMS is based on established principles from systems engineering and management and STCR-specific activities developed and tested by the authors as standalone elements in previous research work.

Findings
The application of the STCR-TMS revealed the practicability of the method and the underlying concepts to provide practical guidance for the development process. Additional findings indicate that the method is sufficiently generic and flexible for application to different types of robots and indifferent world regions. This research has also shown that key activities need to be addressed to increase the practicability of the STCR-TMS.

Originality/value
A unique characteristic of this method is the evolution with each utilization cycle. In addition, individual elements are interchangeable and can be adapted based on external circumstances. These properties allow the TMS to be applied to other fields in construction robotics. With the progression of the verification and validation of the method, know-how and certain elements can be fed into standardization activities (e.g. establishing a management system standard).
Numerical simulation and experiments to improve throwing power for practical PCB through-holes plating
Authors: Xiang Jing , Wang Chong , Chen Yuanming , Xia Feng , He Wei , Miao Hua , Zhou Jinqun , Chen Qingguo , Jin Xiaofeng 
Published: October 2019

PurposeThe purpose of this study is to investigate the synergism of convection, current density distribution and additives by numerical simulation and electrochemical experiments for good throwing power (TP) of copper electro-deposition in printed circuit board (PCB) manufacture.Design/methodology/approachThe flow field of THs and current density distribution on various AR of THs are calculated and analyzed. Meanwhile, corresponding simulation is used to study the performance of plating electrolytes on TP. Two electrochemical parameters, overpotential (η) and potential difference (△η), are chosen to evaluate the electrochemical properties of different plating solutions by galvanostatic measurement and potentiodynamic cathode polarization at different rotating speeds.FindingsBy combining both the results of simulation and practical plating, these two electrochemical properties of electrolytes exhibit significant impact to the system at varied conditions. Especially, the electrolyte with higher polarizingηand △ηvalues lead to the elevated TP for AR of more than 2:1.Originality/valueThe harring cell model is built as a bridge between the theoretical and experimental study for control of uniformity of plating THs in PCB manufacturing. This dual-parameter evaluation is validated to be a promising decisive method to guide the THs plating with particular AR in industry.