bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single-cell RNA-seq reveals dynamic transcriptome profiling in human early neural differentiation
Authors: Shang Zhouchun , Chen Dongsheng , Wang Quanlei , Wang Shengpeng , Deng Qiuting , Wu Liang , Liu Chuanyu , Ding Xiangning , Wang Shiyou , Zhong Jixing , Zhang Doudou , Cai Xiaodong , Zhu Shida , Yang Huanming , Liu Longqi , Fink J. Lynn , Chen Fang , Liu Xiaoqing , Gao Zhengliang , Xu Xun 
Published: August 2018

AbstractBackgroundInvestigating cell fate decision and subpopulation specification in the context of the neural lineage is fundamental to understanding neurogenesis and neurodegenerative diseases. The differentiation process of neural-tube-like rosettesin vitrois representative of neural tube structures, which are composed of radially organized, columnar epithelial cells and give rise to functional neural cells. However, the underlying regulatory network of cell fate commitment during early neural differentiation remains elusive.ResultsIn this study, we investigated the genome-wide transcriptome profile of single cells from six consecutive reprogramming and neural differentiation time points and identified cellular subpopulations present at each differentiation stage. Based on the inferred reconstructed trajectory and the characteristics of subpopulations contributing the most towards commitment to the central nervous system (CNS) lineage at each stage during differentiation, we identified putative novel transcription factors in regulating neural differentiation. In addition, we dissected the dynamics of chromatin accessibility at the neural differentiation stages and revealed active c/s-regulatory elements for transcription factors known to have a key role in neural differentiation as well as for those that we suggest are also involved. Further, communication network analysis demonstrated that cellular interactions most frequently occurred among embryoid body (EB) stage and each cell subpopulation possessed a distinctive spectrum of ligands and receptors associated with neural differentiation which could reflect the identity of each subpopulation.ConclusionsOur study provides a comprehensive and integrative study of the transcriptomics and epigenetics of human early neural differentiation, which paves the way for a deeper understanding of the regulatory mechanisms driving the differentiation of the neural lineage.
Potential Application of Bacteriophages in Enrichment Culture for Improved PrenatalStreptococcus agalactiaeScreening
Authors: Uchiyama Jumpei , Matsui Hidehito , Murakami Hironobu , Kato Shini-chiro , Watanabe Naoki , Nasukawa Tadahiro , Mizukami Keijiro , Ogata Masaya , Sakaguchi Masahiro , Matsuzaki Shigenobu , Hanaki Hideaki 
Published: August 2018

ABSTRACTVertical transmission ofStreptococcus agalactiaecan cause neonatal infections. A culture test in the late stage of pregnancy is used to screen for the presence of maternalS. agalactiaefor intrapartum antibiotic prophylaxis. For the test, vaginal-rectal swab sampling is immediately followed by enrichment culture and bacterial identification. In some cases,Enterococcus faecaliscompetes with and overgrowthsS. agalactiaein the enrichment culture. Consequently, the identification test occasionally yields false-negative results. Bacterial viruses, bacteriophages (phages), infect and kill specific host bacteria. In the current study, we explored the feasibility of using phages to minimize the undesirableE. faecalisoutgrowth and facilitateS. agalactiaedetection in an experimental setting. Phage mixture was prepared using three phages that specifically infectE. faecalis:phiEF24C, phiEF17H, and phiM1EF22. The mixture inhibited the growth of 86.7% (26/30) ofE. faecalisstrains tested in the enrichment broth. When single strains ofE. faecalisandS. agalactiaewere inoculated in the enrichment broth containing the phage mixture, bacterial growth was inhibited or facilitated, respectively. Further, several sets ofS. agalactiaeandE. faecalisstrains were co-cultured, and bacteria were detected on chromogenic agar after the enrichment culture.S. agalactiaewas dominant after plating a phage mixture-treated co-culture, while it was barely detected after plating the untreated co-culture. Considering these observations, the phage mixture can be employed in theS. agalactiaeculture test to increase test accuracy.
Novel allosteric mechanism of p53 activation by small molecules for targeted anticancer therapy
Authors: Zawacka-Pankau Joanna , Grinkevich Vera V. , Burmakin Mikhail , Vema Aparna , Fawkner Karin , Issaeva Natalia , Andreotti Virginia , Dickinson Eleanor R. , Hedström Elisabeth , Spinnler Clemens , Inga Alberto , Larsson Lars-Gunnar , Karlén Anders , Tarasova Olga , Poroikov Vladimir , Lavrenov Sergey , Preobrazhenskaya Maria , Barran Perdita E. , Okorokov Andrei L. , Selivanova Galina 
Published: August 2018

AbstractGiven the immense significance of p53 restoration for anti-cancer therapy, elucidation of the mechanisms of action of p53-activating molecules is of the utmost importance. Here we report a discovery of novel allosteric modulation of p53 by small molecules, which is an unexpected turn in the p53 story. We identified a structural element involved in p53 regulation, whose targeting by RITA, PpIX and licofelone block the binding of p53 inhibitors, MDM2 and MDMX. Deletion and mutation analysis followed by molecular modeling, identified the key p53 residues S33 and S37 targeted by RITA and PpIX. We propose that the binding of small molecules to the identified site induces a conformational trap preventing p53 from the interaction with MDM2 and MDMX. These results point to a high potential of allosteric activators. Our study provides the basis for the development of therapeutics with a novel mechanism of action, thus extending the p53 pharmacological potential.
Spermatoproteasome-deficient mice are proficient in meiotic DNA repair but defective in meiotic exit
Authors: Gómez-H Laura , Felipe-Medina Natalia , Condezo Yazmine B. , Garcia-Valiente Rodrigo , Ramos Isabel , Roig Ignasi , Sánchez-Martin Manuel , de Rooij Dirk , Llano Elena , Pendas Alberto M. 
Published: August 2018

AbstractMeiotic recombination generates crossovers which are essential to ensure genome haploidization. The ubiquitin proteasome system regulates meiotic recombination through its association to the synaptonemal complex, a ‘zipper’-like structure that holds homologs and provides the structural framework for meiotic recombination. Here we show that the testis-specific α4s subunit (PSMA8) of the spermatoproteasome is located at the synaptonemal complex and is essential for the assembly of its activator PA200. Accordingly, synapsis-deficient mice show delocalization of PSMA8 from the synaptonemal complex. Genetic analysis of Psma8-deficient mice shows normal meiotic DNA repair, crossing over formation and an increase of spermatocytes at metaphase I and metaphase II which either enter into apoptosis or slip to give rise to an early spermatid arrest and infertility. Thus, spermatoproteasome-dependent histone degradation is dispensable for meiotic recombination. We show that PSMA8 deficiency alters the proteostasis of several key meiotic players such as acetylated histones, SYCP3, SYCP1, CDK1 and TRIP13 which in turn leads to an aberrant meiotic exit and early spermatid arrest prior to the histone displacement process that take place subsequently.
An efficient timer and sizer of biomacromolecular motions
Authors: Chan Justin , Lin Hong-Rui , Takemura Kazuhiro , Chang Kai-Chun , Chang Yuan-Yu , Joti Yasumasa , Kitao Akio , Yang Lee-Wei 
Published: August 2018

SUMMARYLife ticks as fast as how efficiently proteins perform their functional dynamics. Well-folded/structured biomacromolecules perform functions via large-scale intrinsic motions across multiple conformational states, which occur at timescales of nano-to milliseconds. Computationally expensive molecular dynamics (MD) simulation has been the only theoretical tool to gauge the time and sizes of these motions, though barely to their slowest ends. Here, we convert a computationally cheap elastic network model (ENM) into a molecular timer and sizer to gauge the slowest functional motions of proteins and ribosome. Quasi-harmonic analysis, fluctuation-profile matching (FPM) and the Wiener–Khintchine theorem (WKT) are used to define the “time-periods”,t, for anharmonic principal components (PCs) which are validated by NMR order parameters. The PCs with their respective “time-periods” are mapped to the eigenvalues (λENM) of the corresponding ENM modes. Thus, the power lawst(ns) = 86.9λENM−1.9and σ2(Å2) = 46.1λENM−2.5are established allowing the characterization of the time scales of NMR-resolved conformers, crystallographic anisotropic displacement parameters, and important ribosomal motions, as well as motional sizes of the latter.GRAPHICAL ABSTRACT
A revisit to a low-cost method for the isolation of microsatellite markers: the case of the endangered Malayan tapir (Tapirus indicus)
Authors: Lim Qi Luan , Ismail Nurul Adilah , Arumugam Ramitha , Ng Wei Lun , Yien Yong Christina Seok , Ismail Ahmad , Rovie-Ryan Jeffrine J. , Rosli Norsyamimi , Annavi Geetha 
Published: August 2018

AbstractThere are many approaches to develop microsatellite markers. We revisited an easy and rapid Polymerase Chain Reaction (PCR)-cloning-sequencing method to design microsatellite markers for Tapirus indicus. Using six random amplified microsatellite (RAM) markers, this study had rapidly generated 45 unique genomic sequences containing microsatellites. After screening 15 terminal and seven intermediate microsatellite loci, we shortlisted five and seven which were amplified either by single- or multiplex PCR using the economical three-primer PCR method. Genotyping attempts were made with ten Tapirus indicus individuals using three of the terminal microsatellite loci and all seven intermediate loci. However, none of the terminal microsatellite loci were considered useful for population genotyping studies, while the seven intermediate loci showed good amplification but were monomorphic in the ten samples. Despite successful detection of amplified loci, we would like to highlight that, researchers who are interested in this alternative method for isolation of microsatellite loci to be cautious and be aware of the limitations and downfalls reported herein that could render these loci unsuitable for population genotyping.
Deep learning image recognition enables efficient genome editing in zebrafish by automated injections
Authors: Cordero-Maldonado Maria Lorena , Perathoner Simon , Kolk Kees-Jan van der , Boland Ralf , Heins-Marroquin Ursula , Spaink Herman P. , Meijer Annemarie H. , Crawford Alexander D. , Sonneville Jan de 
Published: August 2018

AbstractOne of the most popular techniques in zebrafish research is microinjection, as it is a rapid and efficient way to genetically manipulate early developing embryos, and to introduce microbes or tracers at larval stages.Here we demonstrate the development of a machine learning software that allows for microinjection at a trained target site in zebrafish eggs at unprecedented speed. The software is based on the open-source deep-learning library Inception v3.In a first step, the software distinguishes wells containing embryos at one-cell stage from wells to be skipped with an accuracy of 93%. A second step was developed to pinpoint the injection site. Deep learning allows to predict this location on average within 42 µm to manually annotated sites. Using a Graphics Processing Unit (GPU), both steps together take less than 100 milliseconds. We first tested our system by injecting a morpholino into the middle of the yolk and found that the automated injection efficiency is as efficient as manual injection (~ 80%). Next, we tested both CRISPR/Cas9 and DNA construct injections into the zygote and obtained a comparable efficiency to that of an experienced experimentalist. Combined with a higher throughput, this results in a higher yield. Hence, the automated injection of CRISPR/Cas9 will allow high-throughput applications to knock out and knock in relevant genes to study their mechanisms or pathways of interest in diverse areas of biomedical research.
Multilayer network analysis of miRNA and protein expression profiles in breast cancer patients
Authors: Zhang Yang , Chen Jiannan , Wang Dehua , Cong Weihui , Lai Bo Shiun , Zhao Yi 
Published: August 2018

AbstractMiRNAs and proteins play important roles in different stages of tumor development and serve as biomarkers for the early diagnosis of cancer. A new algorithm that combines machine learning algorithms and multilayer complex network analysis is hereby proposed to explore the potential diagnostic values of miRNAs and proteins. XGBoost and random forest algorithms were employed to exclude unrelated miRNAs and proteins, and the most significant candidates were retained for the further analysis. Given these candidates’ possible functional relationships to one other, a multilayer complex network was constructed to identify miRNAs and proteins that could serve as biomarkers for breast cancer. Proteins and miRNAs that are nodes in the network were subsequently categorized into two network layers considering their distinct functions. Maximal information coefficient (MIC) was applied to assess intralayer and interlayer connection. The betweenness centrality was used as the first measurement of the importance of the nodes within each single layer. To further characterize the interlayer interaction between miRNAs and proteins, the degree of the nodes was chosen as the second measurement to map their signalling pathways. By combining these two measurements into one score and comparing the difference of the same candidate between normal tissue and cancer tissue, this novel multilayer network analysis could be applied to successfully identify molecules associated with breast cancer.
HERI-1 is a Chromodomain Protein that Negatively Regulates Transgenerational Epigenetic Inheritance
Authors: Perales Roberto , Pagano Daniel , Wan Gang , Fields Brandon , Saltzman Arneet L. , Kennedy Scott G. 
Published: August 2018

AbstractTransgenerational epigenetic inheritance (TEI) is the inheritance of epigenetic information for two or more generations. In most cases, TEI is limited to 2-3 generations. This short-term nature of TEI could be set by innate biochemical limitations to TEI or by genetically encoded systems that actively limit TEI. dsRNA-mediated gene silencing (RNAi) can be inherited inC. elegans(termed RNAi inheritance or RNA-directed TEI). To identify systems that might actively limit RNA-directed TEI, we conducted a forward genetic screen for factors whose mutation enhanced RNAi inheritance. This screen identified the geneheritableenhancer ofRNAi(heri-1), whose mutation causes RNAi inheritance to last longer (>20 generations) than normal.heri-1encodes a protein with a chromodomain and a kinase-homology domain that is expressed in germ cells and localizes to nuclei. InC. elegans, a nuclear branch of the RNAi pathway (nuclear RNAi or NRDE pathway) is required for RNAi inheritance. We find that this NRDE pathway is hyper-responsive to RNAi inheri-1mutant animals, suggesting that a normal function of HERI-1 is to limit nuclear RNAi and that limiting nuclear RNAi may be the mechanism by which HERI-1 limits RNAi inheritance. Interestingly, we find that HERI-1 binds to genes targeted by RNAi, suggesting that HERI-1 may have a direct role in limiting nuclear RNAi and, therefore, RNAi inheritance. Surprisingly, recruitment of the negative regulator HERI-1 to genes depends upon that same NRDE factors that drive co-transcriptional gene silencing during RNAi inheritance. We therefore speculate that the generational perdurance of RNAi inheritance is set by competing pro- and anti-silencing outputs of the NRDE nuclear RNAi machinery.
Logistics practices in healthcare organizations in Bogota
Authors: Velasco Nubia , Moreno Juan-Pablo , Rebolledo Claudia 
Published: August 2018

PurposeThe purpose of this paper is to explore the current state of logistics practices in healthcare organizations in Bogota, Colombia.Design/methodology/approachThe assessment is based on case study research using open interviews, focused interviews, a questionnaire and direct observations as sources of evidence. Seven Colombian health care settings are analyzed: four public hospitals and three private clinics. Cross-case analysis allows the identification of patterns regarding supply management, inventory management, replenishment and use of information and communication technologies.FindingsManual procedures, poor planning, little recognition from top management and a lack of specialized personnel characterize the current situation. Innovative practices with a potential to improve the efficacy of logistics activities are rare, particularly in public hospitals.Research avenuesFuture research could replicate this study in other Colombian cities, in order to generalize the results to the whole country. It could also be interesting to document successful and less successful implementations of innovative logistics practices in Colombian hospitals to guide and promote their adoption.Research limitations/implicationsThe small number of cases considered, and the fact that the research is concentrated in one city, limits the generalizability of the results.Originality/valueTo the best of the authors’ knowledge, this research is the first to explore the state of healthcare logistics practices in Colombia.
Explanatory factors and limitations of Spanish local debt
Authors: Vera Jorge Olmo 
Published: August 2018

Purpose
The purpose of this paper is to evaluate the impact of the Law on Budgetary Stability of 2012 over the level of accumulated debt in Spanish municipalities. The paper also analyses the influence of the socioeconomic environment, political factors and budgetary indicators on the level of accumulated debt for the 2008–2014 period, which coincides with the economic crisis.

Design/methodology/approach
The paper uses panel data methodology. First, the t-test of difference of means is used to analyse which political variables are significant. Then, the analysis is carried out using the generalised method of moments in order to obtain the explanatory variables of the level of debt.

Findings
The results show that in 2013–2014, the Law on Budgetary Stability did not have a significant effect on reducing the accumulated debt. However, the law has led to a change of the trend in debt levels, as the debt decreased from 2013 to 2014. Moreover, population, unemployment, immigration, personnel expenditure, direct fiscal pressure and level of investment have an influence over the level of accumulated debt.

Originality/value
This paper contributes to analyse to what extent the Law on Budgetary Stability has affected accumulated debt. The study reveals a slight impact on reducing debt, although it is not significant. An original aspect of this paper is that it uses dynamic models to study the accumulated debt of Spanish municipalities. The study shows the impact of socioeconomic, environmental and political factors as well as of budgetary indicators on the level of debt in the context of economic crisis.
A real option approach for the valuation of switching output flexibility in residential property investment
Authors: Mintah Kwabena , Higgins David , Callanan Judith 
Published: August 2018

Purpose
Uncertainties in residential property investment performance require that real estate assets are designed in a flexible manner to respond to impacts of market dynamics. Though estimating the cost of flexibility is straightforward, assessing the economic value of flexibility is not. The purpose of this study is to explore the potential practical application of real option analysis to determine the economic value of a switching output flexibility embedded in a residential property investment in Australia. The study involves the exploration of an optimal strategy for investment in a residential development through real option analysis and valuation of a mixed use investment.

Design/methodology/approach
The real option valuation model developed by McDonald and Siegel (1986) is adopted for the evaluation because the switching output flexibility is likened to a perpetual American call option with dividend payout.

Findings
Through real option analysis, the economic value of switching output flexibility of the mixed use building was determined to be higher than the initial upfront costs. Moreover, a payoff of about $4million was determined to be the value of the switching output flexibility, therefore justifying upfront investments in flexibility as an uncertainty and risk management tool.

Practical implications
This application is an important demonstration of the practical use of options pricing techniques (real options analysis) and delivers further evidence needed to support the adoption of real option valuation in practice. Flexibility can also enhance risks and uncertainty management in residential property investment better than the adjustment of discount rates.

Originality/value
There is limited evidence on the use of real options techniques for the valuation of switching output flexibility in practice, and this comes as an original application; both the case study and data are all initial applications of switching flexibility in the Australian property market.
High-skilled female immigrants: career strategies and experiences
Authors: Colakoglu Saba , Yunlu Dilek G. , Arman Gamze 
Published: August 2018

Purpose
The purpose of this paper is to uncover career-related issues that high-skilled female immigrants face and their strategies for rebuilding their careers upon migration for a diverse range of reasons including following a spouse, furthering education and self-initiated expatriation.

Design/methodology/approach
Using grounded theory to explore this topic, the authors performed 14 in-depth interviews with female immigrants that fit pre-determined inclusion criteria for high-skilled (e.g. educated, gainfully and professionally employed). The study context of immigration is the USA, and the authors performed interviews with high-skilled immigrants from Turkey – an underrepresented nation in the US migrant population.

Findings
Content analysis of in-depth interviews revealed five primary theoretical themes that captured the career experiences of these individuals: non-linear career entry, career orientation, strong commitment and will to succeed, socialization patterns at work and support network. Integrating these findings with theories on adult learning, the authors developed an experiential learning model of career reconstruction among high-skilled immigrants.

Originality/value
This study contributes to the global mobility literature by developing an experiential learning theory of careers and taking a gendered perspective to the career experiences of high-skilled female immigrants. It answers the questions: what are the individual and situation factors associated with career success among high-skilled female immigrants? and what is the process that high-skilled immigrants go through to rebuild their careers?