bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nitrogen regulator GlnR directly controls transcription ofprpDBCoperon involved in methylcitrate cycle inMycobacterium smegmatis
Authors: Liu Xin-Xin , Liu Wei-Bing , Shen Meng-Jia , Ye Bang-Ce 
Published: June 2018

AbstractMycobacterium tuberculosisutilizes the fatty acids of the host as the carbon source. While the metabolism of odd chain fatty acids produces propionyl-CoA. Methylcitrate cycle is essential for Mycobacteria to utilize the propionyl-CoA to persist and grow on these fatty acids. InM. smegmatis, methylcitrate synthase, methylcitrate dehydratase, and methylisocitrate lyase involved in methylcitrate cycle were respectively encoded byprpC,prpD,and prpBin operonprpDBC. In this study, we found that the nitrogen regulator GlnR directly binds to the promoter region ofprpDBCoperon and inhibits its transcription. The typical binding sequence of GlnR was identified by bioinformatics analysis and electrophoretic mobility shift assay. The GlnR-binding motif was seperated by 164 bp with the binding site of PrpR which was a pathway-specific transcriptional activator of methylcitrate cycle. Moreover, the affinity constant of GlnR was much stronger than that of PrpR toprpDBC. The deletion ofglnRresulted in poor growth in propionate or cholesterol medium comparing with wild-type strain. The ΔglnRmutant strain also showed a higher survival in macrophages. These results illustrated that the nitrogen regulator GlnR regulated methylcitrate cycle through directly repressing the transcription ofprpDBCoperon. The finding reveals an unprecedented link between nitrogen metabolism and methylcitrate pathway, and provides a potential application for controlling populations of pathogenic mycobacteria.Author SummaryNutrients are crucial for the survival and pathogenicity ofMycobacterium tuberculosis. The success of this pathogen survival in macrophage due to its ability to assimilate fatty acids and cholesterol from host. The cholesterol and fatty acids are catabolized via β-oxidation to generate propionyl-CoA, which is then mainly metabolized via the methylcitrate cycle. The assimilation of propionyl-CoA needs to be tightly regulated to prevent its accumulation and alleviate toxicity in cell. Here, we identified a new regulator GlnR (the nitrogen transcriptional regulator) that repressed the transcription ofprpoperon involved in methylcitrate cycle inM. smegmatis. In this study, we found a typical GlnR binding box inprpoperon, and the affinity is much stronger than that of PrpR which is known as a pathway-specific transcriptional activator of methylcitrate cycle. In addition, deletion ofglnRobviously affect the growth of mutant in propionate or cholesterol medium, and show a better viability in macrophage. The findings not only provide the insights into the regulatory mechanism underlying crosstalk of nitrogen metabolism and carbon metabolism, but also reveal a potential application for controlling populations of pathogenic mycobacteria.
β-lactam Antibiotics Stimulate the Pathogenicity of Methicillin-resistant Staphylococcus aureus Via SarA-controlled Tandem Lipoprotein Expression
Authors: Shang Weilong , Rao Yifan , Zheng Ying , Yang Yi , Hu Qiwen , Hu Zhen , Yuan Jizhen , Peng Huagang , Xiong Kun , Tan Li , Li Shu , Zhu Junmin , Li Ming , Hu Xiaomei , Mao Xuhu , Rao Xiancai 
Published: June 2018

AbstractMethicillin-resistant Staphylococcus aureus (MRSA) is a leading cause of nosocomial infections worldwide. MRSA resists nearly all β-lactam antibiotics that have a bactericidal activity and a signal inducer effect. However, studies have yet to clarify whether the inducer effect of empirically used β-lactams stimulates MRSA pathogenicity in vivo. Here, we showed that a new cluster of tandem lipoprotein genes (tlpps) was upregulated in MRSA in response to the subinhibitory concentrations of β-lactam induction. The increased Tlpps significantly altered immune responses by macrophages with high IL-6 and TNFα levels. The deletion of the tlpps mutant (N315Δtlpps) significantly decreased the proinflammatory cytokine levels in vitro and in vivo. The bacterial loads of N315Δtlpps in the mouse kidney were also reduced compared with those of the wild type N315. The β-lactam-treated MRSA exacerbated cutaneous infections with increased lesion size, extended illness, and flake-like abscess-formation compared with those of the nontreatment. The β-lactam antibiotics that promoted the MRSA pathogenicity were SarA dependent, and the increasing expression of tlpps after β-lactam treatment was directly controlled by the global regulator SarA. Overall, our findings suggested that β-lactams should be used carefully because it might lead to a worse outcome of MRSA infection than inaction in the treatment.Author summaryβ-lactams are widely used in practice to treat infectious diseases, however, β-lactams worsening the outcome of a certain disease is poorly understood. In this study, we have identified a new cluster of tandem lipoprotein genes (tlpps) that is upregulated in the major clinically prevalent MRSA clones in response to the subinhibitory concentrations of β-lactams induction. The major highlight in this work is that β-lactams induce SarA expression, and then SarA directly binds to the tlpp cluster promoter region and upregulates the tlpp expression in MRSA. Moreover, the β-lactam stimulated Tlpps are important virulence factors that enhance MRSA pathogenicity. The deletion of the tlpps mutant significantly decreases the proinflammatory cytokine levels in vitro and in vivo. The β-lactam induced Tlpps enhance the host inflammatory responses by triggering the expression of IL-6 and TNFα, thereby promoting bacterial colonization and abscess formation. These data elucidate that β-lactams can worsen the outcome of MRSA infection through the induction of tlpps that are controlled by the global regulator SarA.
Pan-cancer systematic identification of lncRNAs associated with cancer prognosis
Authors: Ung Matthew H. , Schaafsma Evelien , Mattox Daniel E. , Wang George L. , Cheng Chao 
Published: June 2018

AbstractThe “dark matter” of the genome harbors several non-coding RNA species including IncRNAs, which have been implicated in neoplasias but remain understudied. RNA-seq has provided deep insights into the nature of lncRNAs in cancer but current RNA-seq data are rarely accompanied by longitudinal patient survival information. In contrast, a plethora of microarray studies have collected these clinical metadata that can be leveraged to identify novel associations between gene expression and clinical phenotypes. In this study, we developed an analysis framework that computationally integrates RNA-seq and microarray data to systematically screen 9,463 lncRNAs for association with mortality risk across 20 cancer types. In total, we identified a comprehensive list of associations between lncRNAs and patient survival and demonstrate that these prognostic lncRNAs are under selective pressure and may be functional. Our results provide valuable insights that facilitate further exploration of lncRNAs and their potential as cancer biomarkers and drug targets.
Isolation and Purification of Active Antimicrobial Peptides from Hermetia illucens L., and Its Effects on CNE2 Cells
Authors: Tian Zhong , Feng Qun , Sun Hongxia , Liao Ye , Du Lianfeng , Yang Rui , Li Xiaofei , Yang Yufeng , Xia Qiang 
Published: June 2018

AbstractActive antimicrobial peptide HI-3 was isolated and purified from the 5th instar larvae of Hermetia illucens L., and its effects on proliferation, apoptosis and migration of nasopharyngeal carcinoma (CNE2) cells were investigated. The expressions of telomerase reverse transcriptase (hTERT) in CNE2 cells were also studied in vitro to elucidate the mechanism involved in the action of HI-3 on CNE2 cells. Results showed that three fractions (HI-1, HI-2, HI-3) were isolated from the hemolymph of H. illucens larvae. After purified by RP-HPLC, only HI-3 showed the inhibitory activities to four strains of bacteria. It was also showed that HI-3 could effectively inhibit the proliferation of CNE2 cells in a dose- and time-dependent manner. Apoptosis of CNE2 cells was observed in the treatment with 160 μg/ml HI-3, and the early apoptosis rate up to 27.59 ± 1.14%. However, no significantly inhibitory effects and apoptosis were found on human umbilical vein endothelial cells (HUV-C). Moreover, HI-3 could significantly reduce the migration ability of CNE2 cells when compared with that of the control. On the other hand, the levels of mRNA and protein of hTERT in the HI-3 treatment were all significantly lower than that of the control. Results indicated that HI-3 could inhibit the proliferation of CNE2 cells and induce the apoptosis of CNE2 cells by down-regulating the telomerase activity in CNE2 cells, while no obvious effect was occurred on HUV-C. It inferred that HI-3 is a potential anti-tumor drug with low toxicity to normal cells.Summary StatementAn active antimicrobial peptide HI-3 was isolated and purified.Inhibitory proliferation of CNE2 cells, but no effect on normal cells.A potential antitumoral drug.
CDeep3M - Plug-and-Play cloud based deep learning for image segmentation of light, electron and X-ray microscopy
Authors: Haberl Matthias G , Churas Christopher , Tindall Lucas , Boassa Daniela , Phan Sebastien , Bushong Eric A , Madany Matthew , Akay Raffi , Deerinck Thomas J , Peltier Steven T , Ellisman Mark H 
Published: June 2018

AbstractAs biological imaging datasets increase in size, deep neural networks are considered vital tools for efficient image segmentation. While a number of different network architectures have been developed for segmenting even the most challenging biological images, community access is still limited by the difficulty of setting up complex computational environments and processing pipelines, and the availability of compute resources. Here, we address these bottlenecks, providing a ready-to-use image segmentation solution for any lab, with a pre-configured, publicly available, cloud-based deep convolutional neural network on Amazon Web Services (AWS). We provide simple instructions for training and applying CDeep3M for segmentation of large and complex 2D and 3D microscopy datasets of diverse biomedical imaging modalities.
Hair Follicle Epidermal Stem Cells Define a Niche for Tactile Sensation
Authors: Cheng Chun-Chun , Tsutsui Ko , Taguchi Toru , Sanzen Noriko , Nakagawa Asako , Kakiguchi Kisa , Yonemura Shigenobu , Tanegashima Chiharu , Keeley Sean D. , Kiyonari Hiroshi , Furuta Yasuhide , Tomono Yasuko , Watt Fiona M. , Fujiwara Hironobu 
Published: June 2018

AbstractThe heterogeneity and compartmentalization of stem cells is a common principle in many epithelia, and is known to function in epithelial maintenance, but its other physiological roles remain elusive. Here we show transcriptional and anatomical contributions of compartmentalized epidermal stem cells (EpSCs) in tactile sensory unit formation in the hair follicle (HF). EpSCs in the follicle upper-bulge, where mechanosensory lanceolate complexes (LCs) innervate, express a unique set of extracellular matrix (ECM) and neurogenesis-related genes. These EpSCs deposit an ECM protein EGFL6 into the collar matrix, a novel ECM that tightly ensheathes LCs. EGFL6 is required for the proper patterning, touch responses, and αv integrin-enrichment of LCs. By maintaining a quiescent original EpSC niche, the old bulge, EpSCs provide anatomically stable HF-LC interfaces, irrespective of the stage of follicle regeneration cycle. Thus, compartmentalized EpSCs provide a niche linking the HF and the nervous system throughout the hair cycle.
Economic impact of data localization in five selected African countries
Authors: Badran Mona Farid 
Published: June 2018

Purpose
The purpose of this study is to quantify the impact of laws and regulations that govern the cross-border flow of data on the economies of five selected African countries, namely, Egypt, Morocco, South Africa, Kenya and Mauritius. Moreover, this study addresses the state of cloud computing in Africa. Finally, policy recommendations are provided in this respect.

Design/methodology/approach
To reach accurate finding the Global Trade Analysis Project (GTAP) data was used, and then the computable general equilibrium (CGE) was computed to estimate the total cost on the economy. Using the three data regulations linkages indexes (DRLs), the increased administrative cost effect was analyzed on five to six major economic sectors in the target countries. This was followed by estimating the loss in sector-wide total factor productivity (TFP) (for the five to six shortlisted sectors). Using this data, the computable general equilibrium model (CGE) was computed, in order to estimate the economy-wide impact. Based on these findings, a set of recommendations were offered to the policy maker, reflecting the obtained results and conclusions and their implications on drafting data-related policies.

Findings
The obtained data indexes reveal that Mauritius is the country with the most laws and regulations governing the cross border flow of data, followed by South Africa Egypt to a lesser extent and finally Morocco and Kenya both showing an obvious lack of data regulations. The small value of the estimated elasticity of the selected countries compared to the value of the estimated elasticity in the EU-0.347 shows that the impact of data localization is less in the selected African countries than in the other set of EU countries examined in the research paper. This is because the former has smaller economies with fewer linkages to the global economy and are less reliant on sectors that are heavy users of data. Thus, the overall impact of data localization was not as profound on TFP as is the case in advanced economies. This research paper arrives at the conclusion that fighting the trend of data localization is crucial. In fact, data localization hinders the necessary and essential role of global trade in realizing economic development. Specifically, this is evident in the increase in production costs as reflected in the increase of the prices of goods, which would lead to a decline in incomes.

Originality/value
Global studies looked at the impact of data localization on the EU, as well as China, India, Korea and Vietnam, providing some data on Asia Pacific. However, no study has ever been conducted on the Middle East and Africa. This study aims to fill this gap. The approach of this study is to capture the extent of data localization mandates encoded in the laws of each of the selected five African countries showing how these mandates govern their cross-border data flow and, in turn, affect their economies. Furthermore, the policy recommendations section of this research paper makes a contribution to the existing literature.
Breaking the triple lock: further education and transformative teaching and learning
Authors: Duckworth Vicky , Smith Rob 
Published: June 2018

Purpose
The purpose of this paper is to explore data from the University and College Union (UCU) Further Education in England: Transforming Lives and Communities research project and through this the paper develops a distinctive, theorised conceptualisation of transformative teaching and learning (TTL).

Design/methodology/approach
The research used an approach grounded in critical pedagogy utilising digital methods, including video interviews, to collect narratives from learners, teachers, family members and their communities from colleges across Britain.

Findings
Within a context in which there are structural pressures militating in favour of instrumentalising students in further education, TTL offers a way of theorising it as a transformative critical space that restores students’ hope and agency. The research provides evidence of how further education offers this “differential space” (Lefebvre, 1991) and subverts the prescriptive, linear spaces of compulsory education. While productivist approaches to vocational education and training support ideologies that legitimate prescribed knowledge, reproducing inequality and injustice through the practices employed (Ade-Ojo and Duckworth, 2017; Duckworth and Smith, 2017b), TTL shifts to a more holistic approach, achieving a different level of engagement with students.

Practical implications
The findings suggest that the TTL lens is a way of focusing on the dignity, needs and agency of further education students. The lens allows us also to identify how the existing structures associated with funding and marketisation can undermine the potential of TTL to activate students’ agency through education.

Originality/value
Extending on existing literature around transformative learning, and drawing on a range of theoretical frameworks, the paper formulates a new, contextually specific conceptualisation of TTL.
Inverted totalitarianism in (post) postnormal accelerated dystopia: the arrival of Brave New World and 1984 in the twenty-first century
Authors: Morgan Dennis Ray 
Published: June 2018

Purpose
This paper aims to depict how the state of inverted totalitarianism is emerging in post-postnormal times and illustrate how it shares many of the same features of the totalitarianism depicted in the novels Brave New World (A. Huxley) and 1984 (G. Orwell). It also shows how a “way forward” is possible through a paradigmatic reorientation of “well-being” and “happiness”.

Design/methodology/approach
The research is based on literature within the field of futures studies, as well as relevant sources outside the futures field. It applies R Slaughter’s critical futures and F Polak’s method of social critique and reconstruction in its analysis of the state of inverted totalitarianism in post postmodern times.

Findings
It finds that the technological society and the US empire (with its attendant corporatocracy, Panopticon and PAC man values) in post-postnormal times is drifting toward a state of inverted totalitarianism, which is remarkably beginning to resemble Aldous Huxley’s Brave New World and G. Orwell’s 1984.

Research limitations/implications
The research is an essay and conceptual paper, so it is limited by its conceptual, philosophical nature and the author’s interpretation of social phenomena. It could also include the latest research on the role that the manipulation of internet algorithms plays in the state of inverted totalitarianism. It could also include more reconstructive details.

Practical implications
Sheer consciousness of the state of inverted totalitarianism and the need for social reconstruction should lead to a reevaluation of the meaning of the good society and how to realize it.

Social implications
Social critique and reconstruction are essential to the survival of any given society or civilization, as the groundwork for the emergence of wise foresight. The creative minority of a civilization must understand its predicament, the nature of its civilizational crisis, before it can even begin to understand and meet the challenge of the future.

Originality/value
The paper presents post-postnormal times as the back drop through which a state of inverted totalitarianism is emerging – a social dystopia that resembles the dystopias depicted in the novels, Brave New World and 1984. Inverted totalitarianism is shown to be an outgrowth of the technological society and the American empire (a corporatocracy and Panopticon increasingly global in nature). Freedom from this emerging totalitarianism begins with the realization of its existence and its given assumptions about the meaning of life and the pursuit of happiness. The paper also posits social critique and reconstruction (as well as critical futures) as a fundamental method to deconstruct and reconstruct the paradigm that supports inverted totalitarianism.
Flexible education in Australia
Authors: Hardwick-Franco Kathryn Gay 
Published: June 2018

Purpose
The purpose of this paper is twofold: first, to explore the extent to which the South Australian flexible learning option (FLO) secondary school enrolment strategy supports some of the most vulnerable and disengaged students to simultaneously engage in secondary- and higher-education, skills and work-based learning; second, to explore the degree to which this FLO enrolment strategy addresses the United Nations (UN) principles of responsible management education and 17 sustainable development goals.

Design/methodology/approach
The approach includes a practice perspective, field-notes and documents analysis.

Findings
This paper finds the flexibility inherent in the FLO enrolment strategy goes some way to addressing inequity in education outcomes amongst those who traditionally disengage from education and work-based learning. Findings also highlight ways in which the FLO enrolment strategy addresses some of the UN principals and 17 goals.

Research limitations/implications
This paper supports the work of HESWBL by calling for future research into the long-term benefits of flexible education strategies that support HESWBL, through exploring the benefits to young people, from their perspective, with a view to providing accountability.

Social implications
The paper offers an example of a way a practice perspective can explore an education strategy that addresses “wicked problems” (Rittel and Webber, 1973). Currently, “wicked problems” that pervade member countries of the Organisation for Economic Co-operation and Development include intergenerational poverty, under-education and unemployment.

Originality/value
This paper is valuable because it explores from a practice perspective, how a secondary education enrolment strategy supports vulnerable students engage in their secondary schooling, while simultaneously supporting students achieve higher education, skills and work-based learning.
Generational differences in workplace attitudes and job satisfaction
Authors: Cucina Jeffrey M. , Byle Kevin A. , Martin Nicholas R. , Peyton Sharron T. , Gast Ilene F. 
Published: June 2018

PurposeThe purpose of this paper is to examine the presence of generational differences in items measuring workplace attitudes (e.g. job satisfaction, employee engagement).Design/methodology/approachData from two empirical studies were used; the first study examined generational differences in large sample, multi-organizational administrations of an employee survey at both the item and general-factor levels. The second study compared job satisfaction ratings between parents and their children from a large nationwide longitudinal survey.FindingsAlthough statistically significant, most generational differences in Study 1 did not meet established cutoffs for a medium effect size. Type II error was ruled out given the large power. In Study 2, generational differences again failed to reach Cohen’s cutoff for a medium effect size. Across both studies, over 98 percent of the variance in workplace attitudes lies within groups, as opposed to between groups, and the distributions of scores on these variables overlap by over 79 percent.Originality/valuePrior studies examining generational differences in workplace attitudes focused on scale-level constructs. The present paper focused on more specific item-level constructs and employed larger sample sizes, which reduced the effects of sampling error. In terms of workplace attitudes, it appears that generations are more similar than they are different.