bluuebunny/crossref_metadata_2025_split huggingface dataset:
Complexity-Aware Simple Modeling
Authors: Gómez-Schiavon Mariana , El-Samad Hana 
Published: January 2018

AbstractMathematical models continue to be essential for deepening our understanding of biology. On one extreme, simple or small-scale models help delineate general biological principles. However, the parsimony of detail in these models as well as their assumption of modularity and insulation make them inaccurate for describing quantitative features. On the other extreme, large-scale and detailed models can quantitatively recapitulate a phenotype of interest, but have to rely on many unknown parameters, making them often difficult to parse mechanistically and to use for extracting general principles. We discuss some examples of a new approach — complexity-aware simple modeling — that can bridge the gap between the small‐ and large-scale approaches.HighlightsSimple or small-scale models allow deduction of fundamental principles of biological systemsDetailed or large-scale models can be quantitatively accurate but difficult to analyzeComplexity-aware simple models can extract principles that are robust to the presence of unknown complex interactionsGraphical abstract
USP7 cooperates with NOTCH1 to drive the oncogenic transcriptional program in T cell leukemia
Authors: Arcipowski Kelly M. , Martinez Carlos A. , Jin Qi , Zhu Yixing , Diaz Blanca Teresa Gutierrez , Wang Kenneth K. , Johnson Megan R. , Volk Andrew G. , Wang Feng , Wu Jian , Wang Hui , Sokirniy Ivan , Thomas Paul M. , Goo Young Ah , Abshiru Nebiyu A. , Hijiya Nobuko , Peirs Sofie , Vandamme Niels , Berx Geert , Goosens Steven , Marshall Stacy A. , Randleman Emily J. , Takahashi Yoh-hei , Wang Lu , Bartom Elizabeth T. , Collings Clayton K. , Vlierberghe Pieter Van , Strikoudis Alexandros , Kelly Stephen , Ueberheide Beatrix , Mantis Christine , Kandela Irawati , Bourquin Jean-Pierre , Bornhauser Beat , Serafin Valentina , Bresolin Silvia , Paganin Maddalena , Accordi Benedetta , Basso Giuseppe , Kelleher Neil L. , Weinstock Joseph , Kumar Suresh , Crispino John D. , Shilatifard Ali , Ntziachristos Panagiotis 
Published: January 2018

AbstractT-cell acute lymphoblastic leukemia (T-ALL) is an aggressive disease, affecting children and adults. Treatments1-6 show high response rates but have debilitating effects and carry risk of relapse5,7,8. Previous work implicated NOTCH1 and other oncogenes1,2,9-20. However, direct inhibition of these pathways affects healthy tissues and cancer alike. Here, we demonstrate that ubiquitin-specific protease 7 (USP7)21-32 controls leukemia growth by stabilizing the levels of the NOTCH1 and JMJD3 demethylase. USP7 is overexpressed T-ALL and is transcriptionally regulated by NOTCH1. In turn, USP7 controls NOTCH1 through deubiquitination. USP7 is bound to oncogenic targets and controls gene expression through H2B ubiquitination and H3K27me3 changes via stabilization of NOTCH1 and JMJD3. We also show that USP7 and NOTCH1 bind T-ALL superenhancers, and USP7 inhibition alters associated gene activity. These results provide a new model for deubiquitinase activity through recruitment to oncogenic chromatin loci and regulation of both oncogenic transcription factors and chromatin marks to promote leukemia. USP7 inhibition33 significantly blocked T-ALL cell growth in vitro and in vivo. Our studies also show that USP7 is upregulated in the aggressive high-risk cases of T-ALL and suggest that USP7 expression might be a prognostic marker in ALL and its inhibition could be a therapeutic tool against aggressive leukemia.
Impact of Human Behavioral Papers at Journal of Neuroscience
Authors: Herzfeld David , Shadmehr Reza 
Published: January 2018

AbstractA recent policy change at Journal of Neuroscience (JN) has significantly increased editorial “desk rejections”, reducing the number of papers that are considered for publication. Survey results from 130 scientists suggested that the new policy may have had a particularly large impact on studies that focused on human behavioral techniques. To quantify the effects of the new policy, we gathered data on all papers ever published in JN (~35,000), as well as all papers that had cited the JN papers (~2.7 million papers). We found that the recent change in editorial policy had disproportionately affected rejection rates of human behavioral papers: since 2015, the number of human behavioral papers as a proportion of all papers published in JN has seen a 30% decline. While there has been a long-term declining trend in the journal’s impact factor, we found that this declining impact factor was shared by both human behavioral papers as well as other papers in the journal. This suggested that whatever may have been the source of the declining impact factor at JN, this source was affecting the various areas of research equally. That is, it was unlikely that papers in any one field were responsible for the declining impact factor number at JN. Indeed, when impact was measured over the long-term, we found that the average human behavioral paper at JN consistently outperformed other papers, generating a significantly higher number of citations per year at 5 and 10 years post publication.
Recapitulation of human germline coding variation in an ultra-mutated infant leukemia
Authors: Gout Alexander M , Kotecha Rishi S , Kaur Parwinder , Abad Ana , Foley Bree , Carter Kim W , Cole Catherine H , Bond Charles S , Kees Ursula R , Waithman Jason , Cruickshank Mark N 
Published: January 2018

AbstractBackgroundMixed lineage leukemia/Histone-lysine N-methyltransferase 2Agene rearrangements occur in 80% of infant acute lymphoblastic leukemia, but the role of cooperating events is unknown. While infant leukemias typically carry few somatic lesions, we identified a case with over 100 somatic point mutations per megabase and here report unique genomic-features of this case.ResultsThe patient presented at 82 days of age, one of the earliest manifestations of cancer hypermutation recorded. The transcriptional profile showed global similarities to canonical cases. Coding lesions were predominantly clonal and almost entirely targeting alleles reported in human genetic variation databases with a notable exception in the mismatch repair gene,MSH2. There were no rare germline alleles or somatic mutations affecting proof-reading polymerase genesPOLEorPOLD1, however there was a predicted damaging mutation in the error prone replicative polymerase,POLK. The patient’s diagnostic leukemia transcriptome was depleted of rare and low-frequency germline alleles due to loss-of-heterozygosity, while somatic point mutations targeted low-frequency and common human alleles in proportions that offset this discrepancy. Somatic signatures of ultra-mutations were highly correlated with germline single nucleotide polymorphic sites indicating a common role for 5-methylcytosine deamination, DNA mismatch repair and DNA adducts.ConclusionsThese data suggest similar molecular processes shaping population-scale human genome variation also underlies the rapid evolution of an infant ultra-mutated leukemia.
MaREA: Metabolic feature extraction, enrichment and visualization of RNAseq data
Authors: Graudenzi Alex , Maspero Davide , Isella Claudio , Filippo Marzia Di , Mauri Giancarlo , Medico Enzo , Antoniotti Marco , Damiani Chiara 
Published: January 2018

AbstractThe characterization of the metabolic deregulations that distinguish cancer phenotypes, and which might be effectively targeted by ad-hoc strategies, is a key open challenge. To this end, we here introduce MaREA (Metabolic Reaction Enrichment Analysis), a computational pipeline that processes cross-sectional RNAseq data to identify the metabolic reactions that are significantly up-/ down-regulated in different sample subgroups. MaREA relies on the definition of a Reaction Activity Score, computed as a function of the expression level of genes encoding for reaction enzymes, which can also be used as an effective metrics to cluster samples into distinct metabolic subgroups. MaREA finally allows to visualize the results in a graphical form directly on metabolic maps. We apply MaREA to distinct cancer datasets and we show that it can produce useful information and new experimental hypotheses on metabolic deregulation of cancer cells, also allowing to stratify patients in metabolic clusters with significantly different survival expectancy.
Luminal MCF-12A and myoepithelial-like Hs 578Bst cells form bilayered acini similar to human breast
Authors: Weber-Ouellette Anne , Busby Mélanie , Plante Isabelle 
Published: January 2018

2.3.1AbstractThe mammary gland is a complex organ, structured in a ramified epithelium supported by the stroma. The epithelium’s functional unit is the bilayered acinus, made of a layer of luminal cells surrounded by a layer of basal cells mainly composed of myoepithelial cells. The aim of this study was to develop a reproducible and manipulable three-dimensional co-culture model of the bilayered acinusin vitroto study the interactions between the two layers. Two different combinations of cell lines were co-cultured in Matrigel: SCp2 and SCg6 mice cells, or MCF-12A and Hs 578Bst human cell lines. Cell ratios and Matrigel concentration were optimized. The resulting acini were analysed by confocal microscopy using epithelial (E-cadherin) and myoepithelial (α-smooth muscle actin) markers. SCp2 and SCg6 cells formed distinct three-dimensional structures, whereas MCF-12A and Hs 578Bst cells formed some bilayered acini. Thisin vitrobilayered acini model will allow us to understand the role of interactions between luminal and myoepithelial cells in the normal breast development.
Interfering with MIF-CD74 signalling on macrophages and dendritic cells with a peptide-based approach restores the immune response against metastatic melanoma
Authors: Figueiredo Carlos R. , Azevedo Ricardo A. , Mousdell Sasha , Resende-Lara Pedro T. , Ireland Lucy , Santos Almudena , Girola Natalia , Cunha Rodrigo L.O.R. , Schmid Michael C. , Polonelli Luciano , Travassos Luiz R. , Mielgo Ainhoa 
Published: January 2018

ABSTRACTMounting an effective immune response against cancer requires the activation of innate and adaptive immune cells. Metastatic melanoma is the most aggressive form of skin cancer. Immunotherapies that boost the activity of effector T cells have shown a remarkable success in melanoma treatment. Patients, however, can develop resistance to such therapies by mechanisms that include the establishment of an immune suppressive tumour microenvironment. Understanding how metastatic melanoma cells suppress the immune system is vital to develop effective immunotherapies against this disease. In this study, we find that the innate immune cells, macrophages and dendritic cells are suppressed in metastatic melanoma. The Ig-CDR-based peptide C36L1 is able to restore macrophages and dendritic cells’ immunogenic functions and to inhibit metastatic growth in vivo. Mechanistically, we found that C36L1 interferes with the MIF-CD74 tumour-innate immune cells immunosuppressive signalling pathway and thereby restores an effective anti-tumour immune response. C36L1 directly binds to CD74 on macrophages and dendritic cells, disturbing CD74 structural dynamics and inhibiting MIF signalling through CD74. Our findings suggest that interfering with MIF-CD74 immunosuppressive signalling in macrophages and dendritic cells using peptide-based immunotherapy can restore the anti-tumour immune response in metastatic melanoma. Our study provides the rationale for further development of peptide-based therapies to restore the anti-tumour immune response.
Proteasome Substrate Capture and Gate Activation by Mycobacterium tuberculosis PafE
Authors: Hu Kuan , Jastrab Jordan B. , Zhang Susan , Kovach Amanda , Zhao Gongpu , Darwin K. Heran , Li Huilin 
Published: January 2018

ABSTRACTIn all domains of life, proteasomes are gated chambered proteases that require opening by activators in order to facilitate protein degradation. Twelve proteasome accessory factor E (PafE) monomers assemble into a single, dodecameric ring to promote proteolysis that is required for the full virulence of the human bacterial pathogen Mycobacterium tuberculosis. While the best characterized proteasome activators use ATP to deliver proteins into a proteasome, PafE does not require ATP. In order to understand the mechanism of PafE-mediated protein targeting and proteasome activation, we studied the interactions of PafE with native substrates, including a newly identified proteasome substrate, Rv3213c, and with proteasome core particles. We characterized the function of a highly conserved feature conserved in bacterial proteasome activator proteins: a glycine-glutamine-tyrosine-leucine or "GQYL" motif at their carboxyl-termini that is essential to stimulate proteolysis. Using cryo-electron microscopy, we found that the GQYL motif of PafE interacts with specific residues in the α-subunits of the proteasome core particle to trigger gate opening and degradation. Finally, we found that PafE rings have 40-Å openings lined with hydrophobic residues that form a chamber for capturing substrates prior to the onset of degradation. This result suggests PafE has a previously unrecognized chaperone activity. Collectively, our data provide new insights on the mechanistic understanding of ATP-independent proteasome degradation in bacteria.
TMEM16F activation by Ca2+triggers plasmalemma expansion and directs PD-1 trafficking
Authors: Bricogne Christopher , Fine Michael , Pereira Pedro M. , Sung Julia , Tijani Maha , Henriques Ricardo , Collins Mary K , Hilgemann Donald W. 
Published: January 2018

AbstractTMEM16F, an ion channel gated by high cytoplasmic Ca2+, is required for cell surface phosphatidylserine exposure during platelet aggregation and T cell activation. Here we demonstrate in Jurkat T cells and HEK293 cells that TMEM16F activation triggers large-scale surface membrane expansion in parallel with lipid scrambling. Following TMEM16F mediated scrambling and surface expansion, cells undergo extensive membrane shedding. The membrane compartment that expands the cell surface does not involve endoplasmic reticulum or acidified lysosomes. Surprisingly, T cells lacking TMEM16F expression not only fail to expand surface membrane, but instead rapidly internalize membrane via massive endocytosis (MEND). The T cell co-receptor PD-1 is selectively shed when TMEM16F triggers membrane expansion, while it is selectively internalized in the absence of TMEM16F. Its participation in this trafficking is determined by its single transmembrane domain. Thus, we establish a fundamental role for TMEM16F as a regulator of Ca2+-activated membrane trafficking.
Improvement the structural behavior of recycled RC elements using CdO nanoparticles
Authors: Atta Ahmed , Ali Nehal , Taman Mohamed , Etman Emad 
Published: January 2018

Purpose
This study aims to investigate the use of CdO nanoparticles with recycled aggregates (RAs) and its effect on the structural behavior of reinforced concrete (RC) slab elements.

Design/methodology/approach
The study has been conducted through three phases: in the first phase, the structure of lab-synthesized CdO nanoparticles was investigated and then cement was partially replaced by CdO nanoparticles to estimate the optimum dose. The second phase focused on the properties of the RA collected from demolition wastes. In the third phase, RC slabs with different concrete mixes using RA and CdO nanoparticles were experimentally tested.

Findings
The results indicated good effect of using CdO nanoparticles with RA to improve the RC slab specimens’ behavior compared with the control specimen.

Originality/value
In present times, nanoparticles have a promising importance in the construction field. The influence of nanoparticles on the compressive strength of the concrete has been investigated by many researchers, but using it with RA is considered a new topic.
Engaging with arranged marriages: a lesson for transnational higher education
Authors: Annabi Carrie Amani , McStay Amanda L. , Noble Allyson Fiona , Sidahmed Maha 
Published: January 2018

Purpose
High levels of absenteeism have been observed amongst male students attending two transnational higher education (TNHE) institutions in the United Arab Emirates (UAE). One reason offered is an obligation to attend engagement ceremonies. Many ceremonies are linked to arranged marriages. The purpose of this paper is to contradict assumptions that suggest that higher education reduces arranged marriages, and to highlight that university policies overlook cultural nuances.

Design/methodology/approach
Semi-structured interviews were conducted with 25 male postgraduate students aged between 22 and 45. Content analysis was used to analyse and interpret the data.

Findings
Several interviewees chose to have an arranged marriage and some saw their postgraduate studies as an opportunity to have a better chance of securing a wife. Equally, several students felt that university policies were unsympathetic to cultural obligations.

Research limitations/implications
This research was restricted to male students from two TNHE institutes in the UAE.

Practical implications
This research provides insight for TNHE managers by providing student-centric research into cultural reasons that prevent student attendance.

Social implications
TNHE is not fully responsive to familial obligations within collective societies. In consequence, there has been a lack of sympathy within policies regarding students’ requirement to fulfil cultural commitments.

Originality/value
The paper explores the challenges of creating culturally sensitive educational policy and practices.
Managing international branch campuses
Authors: Hill Christopher , Thabet Rawy Abdelrahman 
Published: January 2018

PurposeInternational branch campuses (IBCs) are complex entities and while much has been written about their expansion and development, the literature is largely from an external perspective. There have been few longitudinal studies examining the development of an IBC over time. The purpose of this paper is to review the development of one IBC over an eight-year time period, to identify the key learning points for institutional managers of other IBCs or for institutions intending to establish an IBC.Design/methodology/approachThis paper is a culmination of research, conducted during the eight years when the lead author worked at the University of Nottingham Malaysia Campus (UNMC). The author was involved in practical management aspects as well as the research and analysis of IBC development. This paper represents a form of ethnographic research where the author conducted interviews, meetings and discussion groups, observed institutional policies, strategies and operations in action and was in an ideal position to identify and discuss their impacts on institutional performance.FindingsThis paper examines key management issues during the early, developing and evolving stages of an IBC and discusses key issues including communication, curriculum, identity and management. Key challenges, procedural issues, managerial responses and strategy will be presented to highlight foundational concerns for IBC development and areas and topics that must be given priority and support.Originality/valueThis paper considers the management of an IBC from the reflective standpoint of an author employed in a senior management position, during a period of significant growth of UNMC. The author provides insights and discussion involving practical experience.
The differential effect of cognitive and emotional elements of experience quality on the customer-service provider’s relationship
Authors: Alnawas Ibrahim , Hemsley-Brown Jane 
Published: January 2018

Purpose
The purpose of this paper is twofold: first, to examine the differential effect of two cognitive (i.e. product experience, outcome focussed) and two emotional experiences (i.e. surprise and immersion) on customers’ cognitive outcomes (i.e. satisfaction, trust and value), and customers’ emotional outcomes (i.e. passion, connection and affection); and second, to test the differential effect of customers’ cognitive and emotional outcomes on switching resistance loyalty (SRL).

Design/methodology/approach
Survey data were collected from 843 respondents using an online panel in the UK. Structural equation modelling was employed to analyse the data (AMOS 18.0).

Findings
First, cognitive experiences had a more significant effect on customers’ cognitive outcomes compared to their effect on customers’ emotional outcomes. Second, emotional experiences had a more significant effect on customers’ emotional outcomes compared to their effect on customers’ cognitive outcomes. Third, the impact of customers’ emotional outcomes on SRL was not significantly higher compared to that of customers’ cognitive outcomes. Fourth, the indirect effect of cognitive experiences on SRL was significantly higher, compared to that of emotional experiences.

Originality/value
The key contribution of this research stems from examining the differential effect of cognitive and emotional experiences on different consumers’ cognitive and emotional outcomes, thus providing deeper insights into the nature of the relationship between such variables.
Mental capacity legislation and its impact on parents with learning difficulties involved in childcare and family law proceedings assessments in England and Wales
Authors: Wilcox Daniel T. , Craig Leam A. , Donathy Marguerite L. , MacDonald Peter 
Published: January 2018

Purpose
The purpose of this paper is to consider the impact of mental capacity legislation when applied to parents with learning difficulties who lack capacity within childcare and family law proceedings in England and Wales.

Design/methodology/approach
The paper relies on a range of material including reports published by independent mental health foundations, official inquiries and other public bodies. It also refers to academic and practitioner material in journals and government guidance.

Findings
The paper critically reviews the application of the guidance when assessing mental capacity legislation as applied in England and Wales and offers by way of illustration several case examples where psychological assessments, and the enhancement of capacity, have assisted parents who were involved in childcare and family law proceedings.

Research limitations/implications
There has been little published research or governmental reports on the number of cases when parents involved in childcare and family law proceedings have been found to lack capacity. No published prevalence data are available on the times when enhancing capacity has resulted in a change of outcome in childcare and family law proceedings.

Practical implications
The duty is on the mental health practitioners assessing mental capacity that they do so in a structured and supportive role adhering to good practice guidance and follow the guiding principles of mental capacity legislation assuming that the individual has capacity unless it is established that they lack capacity. Guidance and training is needed to ensure that the interpretation of the Mental Capacity Act (MCA) and its application is applied consistently.

Social implications
For those who are considered to lack mental capacity to make specific decisions, particularly within childcare and family law proceedings, safeguards are in place to better support such individuals and enhance their capacity in order that they can participate more fully in proceedings.

Originality/value
While the MCA legislation has now been enacted for over ten years, there is very little analysis of the implications of capacity assessments on parents involved in childcare and family law proceedings. This paper presents an overview and, in places, a critical analysis of the new safeguarding duties of mental health practitioners when assessing for, and enhancing capacity in parents.