bluuebunny/crossref_metadata_2025_split huggingface dataset:
Simplifying the combined use of CRISPR-Cas9 and Cre-loxP technologies for the efficient generation of targeted conditional gene knockouts in mammalian cells
Authors: Noiman Tzahi , Kahana Chaim 
Published: December 2017

ABSTRACTGene knockout technologies have contributed fundamentally to our understanding of the cellular functions of various genes. Two prevalent systems used for the efficient elimination of the expression of specific genes are the Cre-LoxP system and the CRISPR-Cas9 system. Here we present a simple method that combines the use of CRISPR-Cas9 and Cre-loxP for the conditional deletion of essential genes in mammalian cells. First, an inducible Cre recombinase is stably expressed in the cells. Next CRISPR-Cas9 is used to knockout an essential gene, whose function is complemented by stable expression of a FLAG-tagged version of the same protein encoded from a floxed transcription unit containing silent mutations, making it refractory to the CRISPR-Cas9 guide. This FLAG-tagged protein can be deleted by activating the expressed Cre protein enabling evaluation of the cellular consequences of its deletion. We have further used this system to evaluate potential mutants of the tested gene.
The signaling lipid sphingosine 1-phosphate regulates mechanical pain
Authors: Hill Rose Z. , Hoffman Benjamin U. , Morita Takeshi , Campos Stephanie M. , Lumpkin Ellen A. , Brem Rachel B. , Bautista Diana M. 
Published: December 2017

AbstractSomatosensory neurons mediate responses to diverse mechanical stimuli, from innocuous touch to noxious pain. While recent studies have identified distinct populations of A mechanonociceptors (AMs) that are required for mechanical pain, the molecular underpinnings of mechanonociception remain unknown. Here, we show that the bioactive lipid sphingosine 1-phosphate (S1P) and S1P Receptor 3 (S1PR3) are critical regulators of acute mechanonociception. Genetic or pharmacological ablation of S1PR3, or blockade of S1P production, significantly impaired the behavioral response to noxious mechanical stimuli, with no effect on responses to innocuous touch or thermal stimuli. These effects are mediated by fast-conducting A mechanonociceptors, which displayed a significant decrease in mechanosensitivity in S1PR3 mutant mice. We show that S1PR3 signaling tunes mechanonociceptor excitability via modulation of KCNQ2/3 channels. Our findings define a new role for S1PR3 in regulating neuronal excitability and establish the importance of S1P/S1PR3 signaling in the setting of mechanical pain thresholds.
Spatial organization of single mRNPs at different stages of the gene expression pathway
Authors: Adivarahan Srivathsan , Livingston Nathan , Nicholson Beth , Rahman Samir , Wu Bin , Rissland Olivia , Zenklusen Daniel 
Published: December 2017

AbstractmRNAs form ribonucleoprotein complexes (mRNPs) by association with proteins that are crucial for mRNA metabolism. While the mRNP proteome has been well characterized, little is known about mRNP organization. Using a single molecule approach, we show that mRNA conformation changes depending on its cellular localization and translational state. Compared to nuclear mRNPs and lncRNPs, association with ribosomes decompacts individual mRNAs, while their sequestration into stress-granules leads to increased compaction. Moreover, translating mRNAs rarely show co-localizing 5’ and 3’ ends, indicating that mRNAs are either not translated in a closed-loop configuration, or that mRNA circularization is transient, suggesting that a stable closed-loop conformation is not a universal state for all translating mRNAs.One Sentence SummarySingle mRNA studies in cells show RNA compaction changes depending on translational state, but mRNAs are not translated in closed-loop conformation.
Directed evolution of CRISPR-Cas9 to increase its specificity
Authors: Lee Jungjoon K. , Jeong Euihwan , Lee Joonsun , Jung Minhee , Shin Eunji , Kim Young-hoon , Lee Kangin , Kim Daesik , Kim Seokjoong , Kim Jin-Soo 
Published: December 2017

AbstractThe use of CRISPR-Cas9 as a therapeutic reagent is hampered by its off-target effects. Although rationally designed S. pyogenes Cas9 (SpCas9) variants that display higher specificities than the wild-type SpCas9 protein are available, these attenuated Cas9 variants are often poorly efficient in human cells. Here, we have used a directed evolution approach in E. coli to obtain Sniper-Cas9, which shows high specificities without sacrificing on-target activities in human cells.
Identification and analysis of mobile genetic elements in Gibbon genome
Authors: Rawal Kamal , Jagannadham Jaisri , Kubba Chahat , Sharma Tanya 
Published: December 2017

AbstractRecent sequencing of genome of northern white-cheeked gibbon (Nomascus leucogenys) has provided important insight into fast evolution of gibbons and signatures relevant to gibbon biology. It was revealed that mobile genetic elements (MGE) seems to play major role in gibbon evolution. Here we report that most of the gibbon genome is occupied by the MGEs such as ALUs, MIRs, LINE1, LINE 2, LINE 3, ERVL, ERV-class1, ERV-class II and other DNA elements which include hAT Charlie and TcMar tigger. We provide detailed description and genome wide distribution of all the MGEs present in gibbon genome. Previously, it was reported that gibbon-specific retrotransposon (LAVA) tend to insert into chromosome segregation genes and alter transcription by providing a premature termination site, suggesting a possible molecular mechanism for the genome plasticity of the gibbon lineage. We show that insertion sites of LAVA elements present atypical signals/patterns which are different from typical signals present at insertion sites of Alu elements. This suggests possibility of distinct insertion mechanism used by LAVA elements for their insertions. We also find similarity in signals of LAVA elements insertion sites with atypical signals present at Alus /L1s insertion sites disrupting the genes leading to diseases such as cancer and Duchenne muscular dystrophy. This suggest role of LAVA in premature transcription termination.
Tri-methylation of Histone H3 Lysine 4 Facilitates Gene Expression in Ageing Cells
Authors: Cruz Cristina , Rosa Monica Della , Krueger Christel , Gao Qian , Field Lucy , Houseley Jonathan 
Published: December 2017

AbstractTranscription of protein coding genes is accompanied by recruitment of COMPASS to promoter-proximal chromatin, which deposits di- and tri-methylation on histone H3 lysine 4 (H3K4) to form H3K4me2 and H3K4me3. Here we determine the importance of COMPASS in maintaining gene expression across lifespan in budding yeast. We find that COMPASS mutations dramatically reduce replicative lifespan and cause widespread gene expression defects. Known repressive functions of H3K4me2 are progressively lost with age, while hundreds of genes become dependent on H3K4me3 for full expression. Induction of these H3K4me3 dependent genes is also impacted in young cells lacking COMPASS components including the H3K4me3-specific factor Spp1. Remarkably, the genome-wide occurrence of H3K4me3 is progressively reduced with age despite widespread transcriptional induction, minimising the normal positive correlation between promoter H3K4me3 and gene expression. Our results provide clear evidence that H3K4me3 is required to attain normal expression levels of many genes across organismal lifespan.
Tension-dependent regulation of mammalian Hippo signaling through LIMD1
Authors: Ibar Consuelo , Kirichenko Elmira , Keepers Benjamin , Enners Edward , Fleisch Katelyn , Irvine Kenneth D. 
Published: December 2017

ABSTRACTHippo signaling is regulated by biochemical and biomechanical cues that influence the cytoskeleton, but the mechanisms that mediate this have remained unclear. We show that all three mammalian Ajuba family proteins – AJUBA, LIMD1, and WTIP - exhibit tension-dependent localization to adherens junctions, and that both Lats family proteins, LATS1 and LATS2, exhibit an overlapping tension-dependent junctional localization. This localization of Ajuba and Lats family proteins is also influenced by cell density, and by Rho activation. We establish that junctional localization of Lats kinases requires LIMD1, and that LIMD1 is also specifically required for the regulation of Lats kinases and YAP by Rho. Our results identify a biomechanical pathway that contributes to regulation of mammalian Hippo signaling, establish that this occurs through tension-dependent LIMD1-mediated recruitment and inhibition of Lats kinases in junctional complexes, and identify roles for this pathway in both Rho-mediated and density-dependent regulation of Hippo signaling.
Breast cancer incidence as a function of the number of previous mammograms: analysis of the NHS screening programme
Authors: Corcos Daniel 
Published: December 2017

AbstractThe discrepancy between the protective effect of early surgery of breast cancer and the poor benefits of mammography screening programs in the long term can be explained if mammography induces breast cancer at a much higher rate than anticipated. Mammography screening is associated in most countries with a higher incidence of breast cancer, attributed to overdiagnosis. X-ray-induced cancers can be distinguished from overdiagnosed cancers by the fact that their incidence depends on the number of previous mammograms, whereas overdiagnosis solely depends on the last screening mammogram, leading to diagnosis. The unbiased relationship between the number of mammograms and breast cancer incidence was evaluated from the data of the NHS Breast Cancer screening programme in women aged from 50 to 64 years in the United Kingdom. The delay between mammography and increased breast cancer incidence was confirmed from the data of the “Age” trial, a randomized trial of annual screening starting at age 40 in the UK. In women aged 50-64 attending screening at the NHS Breast Cancer programme,in situbreast cancer incidence increased linearly from 1993 to 2005 as a function of the number of mammograms. Incidence did not increase anymore after 2005 when the number of mammograms and the delay after screening was stable. Invasive breast cancer incidence increased more specifically in the 60-69 age group. The risk of breast cancer almost doubled after 15 years of screening. Additional cancers began to occur less than 6 years after mammography. These results are evidence that X-ray-induced carcinogenesis, rather than overdiagnosis, is the cause of the increase in breast cancer incidence.
Phenotype loss is associated with widespread divergence of the gene regulatory landscape in evolution
Authors: Roscito Juliana G. , Sameith Katrin , Parra Genis , Langer Bjoern E. , Petzold Andreas , Rodrigues Miguel Trefaut , Hiller Michael 
Published: December 2017

AbstractDetecting the genomic changes underlying phenotypic changes between species is a main goal of evolutionary biology and genomics. Evolutionary theory predicts that changes incis-regulatory elements are important for morphological changes. Here, we combine genome sequencing and functional genomics with genome-wide comparative analyses to investigate the fate of regulatory elements in lineages that lost morphological traits. We first show that limb loss in snakes is associated with widespread divergence of limb regulatory elements. We next show that eye degeneration in subterranean mammals is associated with widespread divergence of eye regulatory elements. In both cases, sequence divergence results in an extensive loss of relevant transcription factor binding sites. Importantly, diverged regulatory elements are associated with key genes required for normal limb patterning or normal eye development and function, suggesting that regulatory divergence contributed to the loss of these phenotypes. Together, our results provide the first evidence that genome-wide decay of the phenotype-specificcis-regulatory landscape is a hallmark of lost morphological traits.
A united kinematic calibration method for a dual-machine system
Authors: Zhao Dan , Bi Yunbo , Ke Yinglin 
Published: December 2017

Purpose
This paper aims to propose a united kinematic calibration method for a dual-machine system in automatic drilling and riveting. The method takes both absolute and relative pose accuracy into account, which will largely influence the machining accuracy of the dual-machine system and assembly quality.

Design/methodology/approach
A comprehensive kinematic model of the dual-machine system is established by the superposition of sub-models with pose constraints, which involves base frame parameters, kinematic parameters and tool frame parameters. Based on the kinematic model and the actual pose error data measured by a laser tracker, the parameters of coordinated machines are identified by the Levenberg–Marquardt method as a multi-objective nonlinear optimization problem. The identified parameters of the coordinated machines will be used in the control system.

Findings
A new calibration method for the dual-machine system is developed, including a comprehensive kinematic model and an efficient parameter identification method. The experiment results show that with the proposed method, the pose accuracy of the dual-machine system was remarkably improved, especially the relative position and orientation errors.

Practical implications
This method has been used in an aircraft assembly project. The calibrated dual-machine system shows a good performance on system coordination and machining accuracy.

Originality/value
This paper proposes a new method with high accuracy and efficiency for the dual-machine system calibration. The research can be extended to multi-machine and multi-robot fields to improve the system precision.
Compliant assembly variation analysis of thin-walled structures based on the absolute nodal coordinate formulation
Authors: Yu Haidong , Zhao Chunzhang , Zheng Bin , Wang Hao 
Published: December 2017

Purpose
Thin-walled structures inevitably always have manufacturing deviations, which affects the assembly quality of mechanical products. The assembly quality directly determines the performances, reliability and service life of the products. To achieve the automatic assembly of large-scale thin-walled structures, the sizing force of the structures with deviations should be calculated, and its assembling ability should be studied before assembly process. The purpose of this study is to establish a precise model to describe the deviations of structures and to study the variation propagation during assembly process.

Design/methodology/approach
Curved thin-walled structures are modeled by using the shell element via the absolute nodal coordinate formulation. Two typical deviation modes of the structure are defined. The generalized elastic force of shell elements with anisotropic materials is deduced based on a continuum mechanics approach to account for the geometric non-linearity. The quasi-static method is introduced to describe the assembly process. The effects of the deviation forms, geometrical parameters of the thin-walled structures and material properties on assembly quality are investigated numerically.

Findings
The geometric non-linearity of structure and anisotropy of materials strongly affect the variation propagation and the assembly quality. The transformation and accumulation effects of the deviations are apparent in the multiple assembly process. The constraints on the structures during assembly can reduce assembly deviation.

Originality/value
The plate element via the absolute nodal coordinate formulation is first introduced to the variation propagation analysis. Two typical shape deviation modes are defined. The elastic force of structures with anisotropic materials is deduced. The variation propagation during the assembly of structures with various geometrical and material parameters is investigated.
Innovative management strategies for building and sustaining a digital initiatives department with limited resources
Authors: Miller A. 
Published: December 2017

Purpose
The purpose of this paper is to offer and explore innovative strategies for building and sustaining digital initiatives at information organizations. Although the examples provided are based on case studies at an academic library, the practices are rooted in project management principles and therefore applicable to all library types, museums, archives and other information organizations. The innovative strategies on staffing and funding will be particularly useful to organizations faced with monetary and staffing shortages and highlights collaborative management practices.

Design/methodology/approach
Concept of strategic and collaborative management practices led by an experienced project manager cross-trained in management, technical and soft skills enables the successful development and sustainability of digital initiatives. A cross-trained librarian’s management practices of leading the Digital Scholarship Initiatives at a particular university will be examined as a case study and aided with literature supporting the need for digital initiatives leaders to have training beyond the credentials of librarian, curator, archivist or historian in the technologically savvy twenty-first century ecology of information centers.

Findings
The innovative strategies implemented in the case study yielded increases in the number of hours of digital lab usage, digital projects developed, seminars or workshops presented, attendance of library hosted events, number of programs implemented and awareness on campus, all with limited staff and funding. The variety and level of production and marketing is instrumental to the growth and sustainability of digital initiatives.

Practical implications
The innovative strategies emphasized in this paper use the concept of borrowed or shared time to start staffing needs and is particularly helpful to organizations that do not have a strong line of dedicated staffing or funding to begin building digital initiatives. Offers small ways to start immediately while setting the stage to plan for big ideas for the future.

Originality/value
This paper suggests a credentialed information expert, such as a librarian, archivist or curator, that is, also cross-trained in project management and technology is the key to not only successfully leading digital initiatives but is instrumental for its sustainability and the marketing, growth and future of digital initiatives.
The humanitarian imperative for education in disaster response
Authors: Halman Paul Gerard , van de Fliert Elske , Khan M. Adil , Shevellar Lynda 
Published: December 2017

PurposeThe purpose of this paper is to present an argument showing the importance of education as a disaster response activity, and why it must figure more prominently in financial and material support for humanitarian disasters.Design/methodology/approachA critical review of the literature and case studies that have considered humanitarian response activities is carried out, drawing together conclusions on the varied impacts of Education in Emergencies (EiE) on affected populations and identifying the need for more research in this area.FindingsDespite rhetorical commitments to education as an emergency response activity, it is often dismissed as non-life saving, and receives the poorer share of funding and resources from humanitarian budgets. It places lower in the consciousness of states and donors than traditional response activities, yet rates highly by affected communities. However, education is both life-saving and life-sustaining when taking into account the impact of education beyond teaching and learning. The processes and effects of education as part of emergency response need to be better understood, and further research that links education and its life-saving capability will strengthen its case.Originality/valueThis paper argues how immediate response to restore education functions in affected communities after an emergency can significantly contribute to child protection and health. It provides compelling reasons for the status of EiE as a response activity, adding to the voice of more than 200 million people affected by disasters every year, many of whom continue to prioritise education.
Improving the visibility of library resources via mapping library subject headings to Wikipedia articles
Authors: Joorabchi Arash , Mahdi Abdulhussain E. 
Published: December 2017

PurposeLinking libraries and Wikipedia can significantly improve the quality of services provided by these two major silos of knowledge. Such linkage would enrich the quality of Wikipedia articles and at the same time increase the visibility of library resources. To this end, the purpose of this paper is to describe the design and development of a software system for automatic mapping of FAST subject headings, used to index library materials, to their corresponding articles in Wikipedia.Design/methodology/approachThe proposed system works by first detecting all the candidate Wikipedia concepts (articles) occurring in the titles of the books and other library materials which are indexed with a given FAST subject heading. This is then followed by training and deploying a machine learning (ML) algorithm designed to automatically identify those concepts that correspond to the FAST heading. In specific, the ML algorithm used is a binary classifier which classifies the candidate concepts into either “corresponding” or “non-corresponding” categories. The classifier is trained to learn the characteristics of those candidates which have the highest probability of belonging to the “corresponding” category based on a set of 14 positional, statistical, and semantic features.FindingsThe authors have assessed the performance of the developed system using standard information retrieval measures of precision, recall, andF-score on a data set containing 170 FAST subject headings manually mapped to their corresponding Wikipedia articles. The evaluation results show that the developed system is capable of achievingF-scores as high as 0.65 and 0.99 in the corresponding and non-corresponding categories, respectively.Research limitations/implicationsThe size of the data set used to evaluate the performance of the system is rather small. However, the authors believe that the developed data set is large enough to demonstrate the feasibility and scalability of the proposed approach.Practical implicationsThe sheer size of English Wikipedia makes the manual mapping of Wikipedia articles to library subject headings a very labor-intensive and time-consuming task. Therefore, the aim is to reduce the cost of such mapping and integration.Social implicationsThe proposed mapping paves the way for connecting libraries and Wikipedia as two major silos of knowledge, and enables the bi-directional movement of users between the two.Originality/valueTo the best of the authors’ knowledge, the current work is the first attempt at automatic mapping of Wikipedia to a library-controlled vocabulary.