bluuebunny/crossref_metadata_2025_split huggingface dataset:
The histone demethylase KDM5 controls developmental timing inDrosophilaby promoting prothoracic gland endocycles
Authors: Drelon Coralie , Belalcazar Helen M. , Secombe Julie 
Published: April 2019

AbstractInDrosophila, the larval prothoracic gland integrates nutritional status with developmental signals to regulate growth and maturation through the secretion of the steroid hormone ecdysone. While the nutritional signals and cellular pathways that regulate prothoracic gland function are relatively well studied, the transcriptional regulators that orchestrate the activity of this tissue remain largely unknown. Here we show thatlysine demethylase 5 (KDM5) is essential for prothoracic gland function. Indeed, restoringkdm5expression only in the prothoracic gland in an otherwisekdm5mutant animal is sufficient to rescue both the larval developmental delay and the pupal lethality caused by loss of KDM5. Molecularly, our studies show that KDM5 functions by promoting the endoreplication of prothoracic gland cells, a process that increases ploidy and is rate-limiting for the expression of ecdysone biosynthetic genes. This occurs through KDM5-mediated regulation of the receptor tyrosine kinasetorso, which in in turn promotes polyploidization and growth through activation of the MAPK signaling pathway. Taken together, our studies provide key insights into the biological processes regulated by KDM5 and the molecular mechanisms that govern the transcriptional regulation of animal development.
Neighbor predation linked to natural competence fosters the transfer of large genomic regions inVibrio cholerae
Authors: Matthey Noémie , Stutzmann Sandrine , Stoudmann Candice , Guex Nicolas , Iseli Christian , Blokesch Melanie 
Published: April 2019

AbstractNatural competence for transformation is a primary mode of horizontal gene transfer (HGT). Competent bacteria are able to absorb free DNA from their surroundings and exchange this DNA against pieces of their own genome when sufficiently homologous. And while it is known that transformation contributes to evolution and pathogen emergence in bacteria, there are still questions regarding the general prevalence of non-degraded DNA with sufficient coding capacity. In this context, we previously showed that the naturally competent bacteriumVibrio choleraeuses its type VI secretion system (T6SS) to actively acquire DNA from non-kin neighbors under chitin-colonizing conditions. We therefore sought to further explore the role of the T6SS in acquiring DNA, the condition of the DNA released through T6SS-mediated killing versus passive cell lysis, and the extent of the transfers that occur due to these conditions. To do this, we herein measured the frequency and the extent of genetic exchanges in bacterial co-cultures on competence-inducing chitin under various DNA-acquisition conditions. We show that competentV. choleraestrains acquire DNA fragments with an average and maximum length exceeding 50 kbp and 150 kbp, respectively, and that the T6SS is of prime importance for such HGT events. Collectively, our data support the notion that the environmental lifestyle ofV. choleraefosters HGT and that the coding capacity of the exchanged genetic material is sufficient to significantly accelerate bacterial evolution.Significance StatementDNA shuffled from one organism to another in an inheritable manner is a common feature of prokaryotes. It is a significant mechanism by which bacteria acquire new phenotypes, for example by first absorbing foreign DNA and then recombining it into their genome. In this study, we show the remarkable extent of the exchanged genetic material, frequently exceeding 150 genes in a seemingly single transfer event, inVibrio cholerae. We also show that to best preserve its length and quality, bacteria mainly acquire this DNA by killing adjacent, healthy neighbors then immediately absorbing the released DNA before it can be degraded. These new insights into this prey-killing DNA acquisition process shed light on how bacterial species evolve in the wild.
Gene-Specific Methylation Profiles for Integrative Methylation-Expression Analysis in Cancer Research
Authors: Liu Yusha , Baggerly Keith A. , Orouji Elias , Manyam Ganiraju , Chen Huiqin , Lam Michael , Davis Jennifer S. , Lee Michael S. , Broom Bradley M. , Menter David G. , Rai Kunal , Kopetz Scott , Morris Jeffrey S. 
Published: April 2019

AbstractDNA methylation is a key epigenetic factor regulating gene expression. While promoter-associated methylation has been extensively studied, recent publications have revealed that functionally important methylation also occurs in intergenic and distal regions, and varies across genes and tissue types. Given the growing importance of inter-platform integrative genomic analyses, there is an urgent need to develop methods to construct gene-level methylation summaries that account for the potentially complex relationships between methylation and expression. We introduce a novel sequential penalized regression approach to construct gene-specific methylation profiles (GSMPs) which find for each gene and tissue type a sparse set of CpGs best explaining gene expression and weights indicating direction and strength of association. Using TCGA and MD Anderson colorectal cohorts to build and validate our models, we demonstrate our strategy better explains expression variability than standard approaches and produces gene-level scores showing key methylation differences across recently discovered colorectal cancer subtypes. We share an R Shiny app that presents GSMP results for colorectal, breast, and pancreatic cancer with plans to extend it to all TCGA cancer types. Our approach yields tissue-specific, gene-specific sparse lists of functionally important CpGs that can be used to construct gene-level methylation scores that are maximally correlated with gene expression for use in integrative models, and produce a tissue-specific summary of which genes appear to be strongly regulated by methylation. Our results introduce an important resource to the biomedical community for integrative genomics analyses involving DNA methylation.
Disrupted basal ganglia—thalamocortical loops in focal to bilateral tonic-clonic seizures
Authors: He Xiaosong , Chaitanya Ganne , Asma Burcu , Caciagli Lorenzo , Bassett Danielle S. , Tracy Joseph I. , Sperling Michael R. 
Published: April 2019

AbstractFocal to bilateral tonic-clonic seizures are associated with lower quality of life, higher risk of seizure-related injuries, increased chance of sudden unexpected death, as well as unfavorable treatment outcomes. Achieving greater understanding of its underlying circuitry offers better opportunity to control these particularly serious seizures. Towards this goal, we provide a network science perspective of the interactive pathways among basal ganglia, thalamus and the cortex, to explore the imprinting of secondary seizure generalization on the mesoscale brain network in temporal lobe epilepsy. Specifically, we parameterized the functional organization of both the thalamocortical network and the basal ganglia—thalamus network with resting-state functional magnetic resonance imaging in three groups of patients with different focal to bilateral tonic-clonic seizure histories. Using the participation coefficient to describe the pattern of thalamocortical connections among different cortical networks, we showed that, compared to patients with no previous history, those with positive histories of focal to bilateral tonic-clonic seizures, including both remote (none for over one year) and current (within the past year) histories, presented more uniform distribution patterns of thalamocortical connections in the ipsilateral medial-dorsal thalamic nuclei. As a sign of greater thalamus mediated cortico-cortical communication, this result comports with greater susceptibility to secondary seizure generalization from the epileptogenic temporal lobe to broader brain networks in these patients. Using interregional integration to characterize the functional interaction between basal ganglia and thalamus, we demonstrated that patients with current history presented increased interaction between putamen and globus pallidus internus, and decreased interaction between the latter and the thalamus, compared to the other two patient groups. Importantly, through a series of “disconnection” simulations, we showed that these changes in interactive profiles of the basal ganglia—thalamus network in the current history group mainly depended upon the direct but not the indirect basal ganglia pathway. It is intuitively plausible that such disruption in the striatum modulated tonic inhibition of the thalamus from the globus pallidus internus could lead to an under-suppressed thalamus, which in turn may account for their greater vulnerability to secondary seizure generalization. Collectively, these findings suggest that the broken balance between the basal ganglia inhibition and thalamus synchronization can inform the presence and effective control of focal to bilateral tonic-clonic seizures. The mechanistic underpinnings we uncover may shed light on the development of new treatment strategies for patients with temporal lobe epilepsy.
Identification of neuronal lineages in theDrosophilaperipheral nervous system with a novel multi-spectral lineage tracing system
Authors: Veling Macy W. , Li Ye , Veling Mike T. , Litts Christopher , Michki Nigel , Liu Hao , Cai Dawen , Ye Bing 
Published: April 2019

SUMMARYElucidating cell lineages provides crucial understanding of development. Recently developed sequencing-based techniques enhance the scale of lineage tracing but eliminate the spatial information offered by conventional approaches. Multispectral labeling techniques, such asBrainbow, have the potential to identify lineage-related cellsin situ. Here, we reportLineage Tracker Bitbow, a “digital” version ofBrainbowthat greatly expands the color diversity, and a suite of statistical methods for quantifying the lineage relationship of any two cells. Applying these tools toDrosophilaperipheral nervous system, we determined lineage relationship between all neuronal pairs. Based on the refined lineage map, we explored whether distinctcis-regulatory elements are used in controlling the expression of a terminal selector gene in distinct lineage patterns. This study demonstratesLT-Bitbowas an efficient tool forin-situlineage mapping and its potential in studying molecular mechanisms in the lineage context.
Differential Expression Gene Explorer (DrEdGE): A tool for generating interactive online data visualizations for exploration of quantitative transcript abundance datasets
Authors: Tintori Sophia C. , Golden Patrick , Goldstein Bob 
Published: April 2019

AbstractAs the scientific community becomes increasingly interested in data sharing, there is a growing need for tools that facilitate the querying of public data. Mining of RNA-seq datasets, for example, has value to many biomedical researchers, yet is often effectively inaccessible to non-genomicist experts, even when the raw data are available. Here we present DrEdGE (dredge.bio.unc.edu), a free Web-based tool that facilitates data sharing between genomicists and their colleagues. The DrEdGE software guides genomicists through easily creating interactive online data visualizations, which colleagues can then explore and query according to their own conditions to discover genes, samples, or patterns of interest. We demonstrate DrEdGE’s features with three example websites we generated from publicly available datasets—human neuronal tissue, mouse embryonic tissue, and a C. elegans embryonic series. DrEdGE increases the utility of large genomics datasets by removing the technical obstacles that prevent interested parties from exploring the data independently.
The structural basis for RNA selectivity by the IMP family of RNA binding proteins
Authors: Biswas Jeetayu , Patel Vivek L. , Bhaskar Varun , Chao Jeffrey A. , Singer Robert H. , Eliscovich Carolina 
Published: April 2019

AbstractThe Igf2 mRNA binding proteins (ZBP1/IMP1, IMP2, IMP3) are highly conserved post-transcriptional regulators of RNA stability, localization and translation. They play important roles in cell migration, neural development, metabolism and cancer cell survival. The knockout phenotypes of individual IMP proteins suggest that each family member regulates a unique pool of RNAs, yet evidence and an underlying mechanism for this is lacking. Here, we combine SELEX and NMR spectroscopy to demonstrate that the major RNA binding domains of the two most distantly related IMPs (ZBP1 and IMP2) bind to different consensus sequences and regulate targets consistent with their knockout phenotypes and roles in disease. We find that the targeting specificity of each IMP is determined by few amino acids in their variable loops. As variable loops often differ amongst KH domain paralogs, we hypothesize that this is a general mechanism for evolving specificity and regulation of the transcriptome.
Thermophilic PHB depolymerase ofStenotrophomonassp., an isolate from the plastic contaminated site is best purified on Octyl-Sepharose CL-4B
Authors: Sayyed R Z , Wani S J , Shaikh S S , Al-Harthi Helal F. , Syed Asad , El-Enshasy Hesham Ali 
Published: April 2019

AbstractThere are numerous reports on PHB depolymerases produced by a wide variety of microorganisms isolated from various habitats, however, reports on PHB depolymerase isolated from plastic contaminated sites are scares. Thermophilic PHB polymerase produced by isolates obtained from plastic contaminated sites is expected to have better relevance for its application in plastic/ bioplastic degradation. Although PHB has attracted commercial significance, the inefficient production and recovery methods, inefficient purification of PHB depolymerase and lack of ample knowledge on PHB degradation by PHB depolymerase have hampered its large scale commercialization. Therefore, to ensure the biodegradability of biopolymers, it becomes imperative to study the purification of the biodegrading enzyme system. We report the production, purification, and characterization of extracellular PHB depolymerase fromStenotrophomonassp. RZS 7 isolated from a plastic contaminated site. The isolate produced extracellular poly-β-hydroxybutyrate (PHB) depolymerase in the mineral salt medium at 30oC during 4 days of incubation under shake flask condition. Purification of the enzyme was carried out by three different methods using PHB as a substrate. Purification of PHB depolymerase by ammonium salt precipitation, column chromatography, and solvent purification method was successfully carried out. Among the purification method tested, the enzyme was best purified by column chromatography on Octyl-Sepharose CL-4B column with maximum (0.7993 U/mg/ml) purification yield. The molecular weight of purified PHB depolymerase (40 kDa) closely resembled with PHB depolymerase ofAureobacterium saperdae.
Force-dependent facilitated dissociation can generate protein-DNA catch bonds
Authors: Dahlke K. , Zhao J. , Sing C.E. , Banigan E. J. 
Published: April 2019

AbstractCellular structures are continually subjected to forces, which may serve as mechanical signals for cells through their effects on biomolecule interaction kinetics. Typically, molecular complexes interact via “slip bonds,” so applied forces accelerate off rates by reducing transition energy barriers. However, biomolecules with multiple dissociation pathways may have considerably more complicated force dependencies. This is the case for DNA-binding proteins that undergo “facilitated dissociation,” in which competitor biomolecules from solution enhance molecular dissociation in a concentration-dependent manner. Using simulations and theory, we develop a generic model that shows that proteins undergoing facilitated dissociation can form an alternative type of molecular bond, known as a “catch bond,” for which applied forces suppress protein dissociation. This occurs because the binding by protein competitors responsible for the facilitated dissociation pathway can be inhibited by applied forces. Within the model, we explore how the force dependence of dissociation is regulated by intrinsic factors, including molecular sensitivity to force and binding geometry, and the extrinsic factor of competitor protein concentration. We find that catch bonds generically emerge when the force dependence of the facilitated unbinding pathway is stronger than that of the spontaneous unbinding pathway. The sharpness of the transition between slip- and catch-bond kinetics depends on the degree to which the protein bends its DNA substrate. These force-dependent kinetics are broadly regulated by the concentration of competitor biomolecules in solution. Thus, the observed catch bond is mechanistically distinct from other known physiological catch bonds because it requires an extrinsic factor – competitor proteins – rather than a specific intrinsic molecular structure. We hypothesize that this mechanism for regulating force-dependent protein dissociation may be used by cells to modulate protein exchange, regulate transcription, and facilitate diffusive search processes.Statement of significanceMechanotransduction regulates chromatin structure and gene transcription. Forces may be transduced via biomolecular interaction kinetics, particularly, how molecular complexes dissociate under stress. Typically, molecules form “slip bonds” that dissociate more rapidly under tension, but some form “catch bonds” that dissociate more slowly under tension due to their internal structure. We develop a model for a distinct type of catch bond that emerges via an extrinsic factor: protein concentration in solution. Underlying this extrinsic catch bond is “facilitated dissociation,” whereby competing proteins from solution accelerate protein-DNA unbinding by invading the DNA binding site. Forces may suppress invasion, inhibiting dissociation, as for catch bonds. Force-dependent facilitated dissociation can thus govern the kinetics of proteins sensitive to local DNA conformation and mechanical state.
The e-government paradox in post-Soviet countries
Authors: Knox Colin , Janenova Saltanat 
Published: April 2019

Purpose
The purpose of this paper is to investigate the emergence of e-government in post-Soviet countries using Kazakhstan as a case study. Extant research on e-government in developing countries highlights significant benefits including improved public services, reduced corruption, and more open and inclusive government. The paper asserts the presence of an e-government paradox which limits its potential to improve public services.

Design/methodology/approach
Primary data were collected from a number of sources: 6 focus groups with central government agencies, local authorities and civil society organisations; 25 structured and semi-structured interviews; and participant observation.

Findings
The research finds evidence of an e-government paradox in five forms: an emphasis on technological development; transactional services are faster but have displaced attention from core public services; petty corruption has been reduced but grand corruption remains; isomorphic mimicry; and greater participation by citizens has been limited.

Research limitations/implications
The focus of the research is Kazakhstan. Applying the lessons learned to other post-Soviet countries has limitations given their different stages of development since independence.

Practical implications
The key practical implication of this research is that countries can become absorbed by e-government technology without questioning the fundamental business model which underpins how public services are delivered. Ultimately, this impacts on the social value of e-government.

Originality/value
While existing research has examined how e-government has been implemented in developing countries, this paper focusses on Kazakhstan as an authoritarian state with wider implications for post-Soviet countries.
Interorganizational knowledge sharing in a science and technology park: the use of knowledge sharing mechanisms
Authors: Balle Andrea Raymundo , Steffen Mário Oscar , Curado Carla , Oliveira Mírian 
Published: April 2019

Purpose
This paper aims to uncover the combinations of knowledge sharing mechanisms that organizations in a science and technology park in Brazil use to share managerial and technical knowledge.

Design/methodology/approach
This research adopts a qualitative approach that uses a fuzzy set qualitative comparative analysis to analyze data that are gathered from 51 managers of organizations in a science and technology park.

Findings
The results show that knowledge sharing happens regardless of the type of knowledge. There are more alternative paths that lead to knowledge sharing than to its absence. Regarding the type of knowledge shared, there are more alternative configurations that lead to managerial knowledge sharing than to technical knowledge sharing. Only the older organizations in the science and technology park abstain from knowledge sharing.

Research limitations/implications
Due to the qualitative nature of the study, no generalization is possible. Additionally, the study’s limitation is that it involves organizations from a single science and technology park.

Practical implications
The results offer managers of organizations in science and technology parks to choose from alternative combinations of mechanisms to either boost their knowledge sharing or to promote knowledge protection.

Originality/value
The paper provides an original contribution by identifying the combinations of mechanisms that organizations in a science and technology park use that leads to the sharing of specific knowledge types. The findings also identify the combination of mechanisms that older organizations use that prevents them from sharing knowledge.
Politically exposed entities: how to tailor PEP requirements to PEP owned legal entities
Authors: Canestri Daniele 
Published: April 2019

Purpose
This paper aims to address the money laundering risk posed by politically exposed person’s (PEP’s) controlled legal entities. International standards and national legislation require enhanced due diligence of political office holders but no specific requirements exist on entities controlled by PEPs. While regulators expect the stringent AML risk mitigation regarding this type of entities, financial institutions have no guidelines to follow. This gap produces inconsistent due diligence measures applied to entities with significant PEPs’ connection.

Design/methodology/approach
The paper uses comparative analysis to identify discrepancies between legal requirements and their interpretation. Moreover, an empirical approach results in a standardised solution to address these discrepancies.

Findings
The paper defines the concept of politically exposed entities and the applicable due diligence framework. Anticipating legislative measures, it proposes to introduce this concept via best practices of financial institutions and private banking initiatives such as the Wolfsberg Group.

Research limitations/implications
The research addresses the topic from a legal point of view. However, the implementation of proposed ideas depends on decisions which are political by nature and are not within the scope of this paper.

Practical implications
The paper aims at stimulating a debate in both the private and public sector to form a consistent approach to AML due diligence of legal entities associated to PEPs.

Originality/value
This paper responds to an identified need to study how legal entities connected to PEPs should be defined and monitored.