bluuebunny/crossref_metadata_2025_split huggingface dataset:
The MYC antagonist MNT autoregulates its expression and supports proliferation in MAX deficient cells
Authors: Lafita-Navarro M Carmen , Liaño-Pons Judit , Quintanilla Andrea , Varela Ignacio , Ourique Fabiana , Bretones Gabriel , Blanco Rosa , Aresti Julia , Carroll Patrick , Hurlin Peter , Eisenman Robert N. , Delgado M. Dolores , León Javier 
Published: November 2017

ABSTRACTMNT is a transcription factor of the MXD family. MNT-MAX dimers down-regulate genes by binding to E-box sequences, which can also be bound by MYC-MAX to activate transcription. MNT has been described as a modulator of MYC activity but little is known about MNT regulation and whether MNT has MAX-independent functions. Using a MAX deficient cell line and siRNA-mediated silencing of MAX, we show that in the absence of MAX, the total MNT levels are elevated and that MNT localizes both in the cytoplasm and the nucleus. In contrast, MNT is predominantly nuclear when MAX is expressed. MNT is required for optimal cell proliferation even in the absence of MAX, being the first report of a MAX-independent function of MNT. Interestingly, MNT forms homodimers and autoregulates its expression by repressing its own promoter. The tight MNT regulation and its activity in absence of MAX suggest its importance on cell homeostasis.
An efficient gene regulatory network inference algorithm for early Drosophila melanogaster embryogenesis
Authors: Matsumoto Hirotaka , Kiryu Hisanori , Kojima Yasuhiro , Yaginuma Suguru , Nikaido Itoshi 
Published: November 2017

AbstractThe spatial patterns of gene expression in early Drosophila melanogaster embryogenesis have been studied experimentally and theoretically to reveal the molecular basis of morphogenesis. In particular, the gene regulatory network (GRN) of gap genes has been investigated through mathematical modeling and simulation. Although these simulation-based approaches are useful for describing complex dynamics and have revealed several important regulations in spatial patterning, they are computationally intensive because they optimize GRN with iterative simulation. Recently, the advance of experimental technologies is enabling the acquisition of comprehensive spatial expression data, and an efficient algorithm will be necessary to analyze such large-scale data. In this research, we developed an efficient algorithm to infer the GRN based on a linear reaction-diffusion model. First, we qualitatively analyzed the GRNs of gap genes and pair-rule genes based on our algorithm and showed that two mutual repressions are fundamental regulations. Then, we inferred the GRN from gap gene data, and identified asymmetric regulations in addition to the two mutual repressions. We analyzed the effect of these asymmetric regulations on spatial patterns, and showed that they have the potential to adjust peak position. Our algorithm runs in sub-second time, which is significantly smaller than the runtime of simulation-based approaches (between 8 and 160 h, for exmaple). Neverthe-less, our inferred GRN was highly correlated with the simulation-based GRNs. We also analyzed the gap gene network of Clogmia albipunctata and showed that different mutual repression regulations might be important in comparison with those of Drosophila melanogaster. As our algorithm can infer GRNs efficiently and can be applied to several different network analysis, it will be a valuable approach for analyzing large-scale data.
A genetically encoded Ca2+ indicator based on circularly permutated sea anemone red fluorescent protein
Authors: Shen Yi , Dana Hod , Abdelfattah Ahmed S. , Patel Ronak , Shea Jamien , Molina Rosana S. , Rawal Bijal , Rancic Vladimir , Chang Yu-Fen , Wu Lanshi , Chen Yingche , Qian Yong , Wiens Matthew D. , Hambleton Nathan , Ballanyi Klaus , Hughes Thomas E. , Drobizhev Mikhail , Kim Douglas S. , Koyama Minoru , Schreiter Eric R. , Campbell Robert E. 
Published: November 2017

AbstractGenetically-encoded calcium ion (Ca2+) indicators (GECIs) are indispensable tools for measuring Ca2+ dynamics and neuronal activities in vitro and in vivo. Red fluorescent protein (RFP)-based GECIs enable multicolor visualization with blue or cyan-excitable fluorophores and combined use with blue or cyan-excitable optogenetic actuators. Here we report the development, structure, and validation of a new red fluorescent Ca2+ indicator, K-GECO1, based on a circularly permutated RFP derived from the sea anemone Entacmaea quadricolor. We characterized the performance of K-GECO1 in cultured HeLa cells, dissociated neurons, stem cell derived cardiomyocytes, organotypic brain slices, zebrafish spinal cord in vivo, and mouse brain in vivo.
Tracing the genetic etiology of cardiovascular disease using a hierarchy of common genetic variants derived from patient subgroups stratified by differential levels in severity
Authors: Fatakia Sarosh N. 
Published: November 2017

AbstractA pedagogical review in informatics based on computational molecular evolution is synopsized to illustrate the role of common genetic variants during adaptation to diverse habitat and physiological functions across disparate species. With that background, an evolutionary perspective is motivated to trace lifestyle-related disease progression in humans. Cardiovascular disease (CVD) is a multi-factorial disease, where maladaptation due to a sedentary lifestyle and faulty diet may influence its prognosis, but a healthy diet and lifestyle may as well restrict it. However, a comprehensive genetic basis for the differential severity in CVD remains unreported. Here, we have computed that CVD severity may be associated with the hierarchical plasticity of genes whose common genetic variants are exclusive among those patients having disparate levels of disease severity. Most importantly, we have used a small and outbred subpopulation to demonstrate that constellation of common variants can be exploited to trace the disease etiology. Taken together, we report a novel perspective to identify a hierarchy of common variants associated with differential CVD severity and subsequently hypothesize how the constellations of common variants may collectively modulate disease severity, which in turn may result in a relatively broad and complex spectrum of severity at the population-level. To corroborate our findings, we report a hierarchical plasticity of LDLR gene, which has been previously implicated in the differential response to lipid metabolism, is associated with differential CVD severity in the subpopulation under consideration.
Comparison of feature representations in MRI-based MCI-to-AD conversion prediction
Authors: Gómez-Sancho Marta , Tohka Jussi , Gómez-Verdejo Vanessa ,   for the Alzheimer’s Disease Neuroimaging Initiative
Published: November 2017

AbstractAlzheimer’s Disease (AD) is a progressive neurological disorder in which the death of brain cells causes memory loss and cognitive decline. The identifica-tion of at-risk subjects yet showing no dementia symptoms but who will later convert to AD can be crucial for the effective treatment of AD. For this, Magnetic Resonance Imaging (MRI) is expected to play a crucial role. During recent years, several Machine Learning (ML) approaches to AD-conversion prediction have been proposed using different types of MRI features. However, few studies comparing these different feature representations exist, and the existing ones do not allow to make definite conclusions. We evaluated the performance of various types of MRI features for the conversion prediction: voxel-based features extracted based on voxel-based morphometry, hippocampus volumes, volumes of the entorhinal cortex, and a set of regional volumetric, surface area, and cortical thickness measures across the brain. Regional features consistently yielded the best performance over two classifiers (Support Vector Machines and Regularized Logistic Regression), and two datasets studied. However, the performance difference to other features was not statistically significant. There was a consis-tent trend of age correction improving the classification performance, but the improvement reached statistical significance only rarely.
Application of the immunoregulatory receptor LILRB1 as a novel crystallisation chaperone for class I peptide-MHC complexes
Authors: Mohammed Fiyaz , Stones Daniel H. , Willcox Benjamin E. 
Published: November 2017

AbstractX-ray crystallographic studies of class I peptide-MHC molecules (pMHC) continue to provide important insights into immune recognition, however their success depends on generation of diffraction-quality crystals, which remains a significant challenge. While protein engineering techniques such as surface-entropy reduction and lysine methylation have proven utility in facilitating and/or improving protein crystallisation, they risk affecting the conformation and biochemistry of the class I MHC antigen binding groove. An attractive alternative is the use of noncovalent crystallisation chaperones, however these have not been developed for pMHC. Here we describe a method for promoting class I pMHC crystallisation, by exploiting its natural ligand interaction with the immunoregulatory receptor LILRB1 as a novel crystallisation chaperone. First, focussing on a model HIV-1-derived HLA-A2-restricted peptide, we determined a 2.4Å HLA-A2/LILRB1 structure, which validated that co-crystallisation with LILRB1 does not alter conformation of the antigenic peptide. We then demonstrated that addition of LILRB1 enhanced the crystallisation of multiple pMHC complexes, and identified a generic condition for initial co-crystallisation. LILRB1 chaperone-based pMHC crystallisation enabled structure determination for class I pMHC previously intransigent to crystallisation, including both conventional and post-translationally-modified peptides, of diverse lengths. LILRB1 chaperone-mediated crystallisation should expedite molecular insights into the immunobiology of diverse immune-related diseases and immunotherapeutic strategies, particularly involving class I pMHC complexes that are challenging to crystallise. Moreover, since the LILRB1 recognition interface involves predominantly non-polymorphic regions of the MHC molecule, the approach we outline could prove applicable to a diverse range of class I pMHC.
Evidence that loss of consciousness under anesthesia is not associated with impaired stimulus representation in auditory cortex
Authors: Banks Matthew I. , Krause Bryan M. , Moran Nicholas S. , Grady Sean M. , Kakes Jeremiah , Uhlrich Daniel J. , Manning Karen 
Published: November 2017

AbstractThe mechanism whereby anesthetics cause loss of consciousness (LOC) is poorly understood. Current theories suggest that impaired representation of information in cortico-thalamic networks contributes to LOC under anesthesia. We sought to determine whether such changes are present in auditory cortex using information theoretic analysis of multiunit responses in rats. We tested the effects of three agents with different molecular targets: isoflurane, which acts at multiple pre- and postsynaptic loci, propofol, which acts primarily on GABAA receptors, and dexmedetomidine, an α2 adrenergic agonist. We reasoned that changes in the representation of sensory stimuli causative for LOC would be present regardless of the molecular target of the anesthetic. All three agents caused LOC, as assayed by the loss of righting reflex (LORR). We presented acoustic stimuli that varied across a wide range of temporal and spectral dynamics under control, sub-hypnotic (i.e. dose too low to cause LORR), just-hypnotic (a dose just sufficient to cause LORR) and recovery conditions. Changes in mutual information (MI) between the stimulus and spike responses under anesthesia diverged in two ways from predictions of a model in which stimulus representation is impaired upon LOC. First, the sign of changes in MI was agent-specific: MI increased under dexmedetomidine, while it decreased under isoflurane and propofol. Second, there was no consistent change in MI when transitioning from sub-hyptnotic to just-hypnotic doses: for none of the agents did MI decrease at the higher dose, and in some cases MI actually increased relative to the sub-hypnotic dose. Changes in MI under anesthesia were strongly correlated with changes in precision and reliability of spike timing, consistent with the importance of temporal stimulus features in driving auditory cortical activity. These data indicate that primary sensory cortex is not the locus for changes in information representation causative for LOC under anesthesia.
Single-cell sequencing reveals αβ chain pairing shapes the T cell repertoire
Authors: Grigaityte Kristina , Carter Jason A. , Goldfless Stephen J. , Jeffery Eric W. , Hause Ronald J. , Jiang Yue , Koppstein David , Briggs Adrian W. , Church George M. , Vigneault Francois , Atwal Gurinder S. 
Published: November 2017

ABSTRACTA diverse T cell repertoire is a critical component of the adaptive immune system, providing protection against invading pathogens and neoplastic changes, relying on the recognition of foreign antigens and neoantigen peptides by T cell receptors (TCRs). However, the statistical properties and function of the T cell pool in an individual, under normal physiological conditions, are poorly understood. In this study, we report a comprehensive, quantitative characterization of the T cell repertoire from over 1.9 million cells, yielding over 200,000 high quality paired αβ sequences in 5 healthy human subjects. The dataset was obtained by leveraging recent biotechnology developments in deep RNA sequencing of lymphocytes via single-cell barcoding in emulsion. We report non-random associations and non-monogamous pairing between the α and β chains, lowering the theoretical diversity of the T cell repertoire, and increasing the frequency of public clones shared among individuals. T cell clone size distributions closely followed a power law, with markedly longer tails for CD8+ cytotoxic T cells than CD4+ helper T cells. Furthermore, clonality estimates based on paired chains from single T cells were lower than that from single chain data. Taken together, these results highlight the importance of sequencing αβ pairs to accurately quantify lymphocyte receptor diversity.
Welfare governmentalities: pastoralism and parties’ youth wings in Mexico
Authors: Zavala Pelayo Edgar 
Published: November 2017

Purpose
From a micro-macro perspective, the purpose of this paper is to analyze the welfare-related criteria reported by the heads of political parties’ youth wings in Mexico, the implicit and explicit religious beliefs that inform some of those criteria and the (Foucauldian) pastoral genealogy of both the criteria and beliefs.

Design/methodology/approach
The paper draws on qualitative data from semi-structured interviews with a group of 32 heads of three political parties’ youth wings in Mexico. The interpretation of the data builds on a previous genealogical analysis of Foucauldian pastoralism in colonial Mexico.

Findings
The respondents’ criteria on a state that should aim at procuring “material-spiritual” and “material-transcendental” types of well-being and politics as “help,” are partly informed by religious values. Such criteria and religious values have been partly constructed out of a pastoralism which was deployed during the Spanish colonial regime and included “temporal” and “spiritual” teleologies of government and the practice of charity as (self-)governmental technique.

Originality/value
The literature on welfare/social policies of Latin American countries like Mexico tends not to problematize issues of secularity other than the religions’ undesirable intrusions in the political field. Governmentality studies also tend to bypass Foucault’s discussion of pastoralism. An empirical study of the pastoral genealogy of contemporary political rationalities in a constitutionally secular country such as Mexico can prompt further research on the gaps above and comparative analyses of pastoral and welfare governmentalities across Latin American and other world regions.
If you always do what you have always done, you will always get what you have always got: commissioning and regulating care homes to prevent abuse
Authors: Moore Steve 
Published: November 2017

Purpose
The purpose of this paper is to present a review of some of the fundamental theoretical and contextual components of commissioning and regulatory processes as applied to care home services, revisiting and examining how they impact on the potential prevention of abuse.

Design/methodology/approach
By revisiting a number of the theoretical bases of commissioning activity, some of which may also be applied to regulatory functions, the reasons for the apparent limited impact on the prevention of the abuse that occurs in care homes by these agencies are analysed.

Findings
The paper demonstrates how the application of commissioning and regulatory theory may be applied to the oversight of care homes to inform proposed preventative strategies.

Practical implications
The paper offers strategies to improve the prevention of abuse in care homes for older people.

Originality/value
A factual and “back to basics” approach is taken to demonstrate why current strategies that should contribute to tackling abuse in care homes are of limited efficacy.
Participation in developing youth mental health services: “Cinderella service” to service re-design
Authors: Collins Rebecca , Notley Caitlin , Clarke Tim , Wilson Jon , Fowler David 
Published: November 2017

PurposeWhilst there are pockets of excellence in the provision of Child and Adolescent Mental Health Services (CAMHS), many services fail to meet young people’s needs. Considering this, the purpose of this paper is to ascertain perceptions of CAMHS provision in a rural county of the UK to inform re-design of youth mental health services.Design/methodology/approachThe study comprised of two phases: phase one involved analysis of questionnaire data of youth views of CAMHS. Phase two involved analysis of the “Have Your Say” event data which explored perceptions of CAMHS and future service re-design. Data were thematically analysed.FindingsKnowledge of the existence and purpose of CAMHS was variable. Participants wanted accessible information about services, rights, confidentiality and for this to be provided in multiple media. Young people wanted staff who were easy to talk to, genuine, understanding and who valued their insights. Participants wanted to be offered choice about appointments, location and timing. An ideal mental health service was described as a “one-stop-shop” of co-locality and multi-agency collaboration. Young people clearly expressed a desire to influence the design and delivery of the radical service re-design and to be embedded in its development.Practical implicationsThe results highlighted multiple problems with CAMHS provision and provided a clear justification for the re-design of services.Originality/valueThis was a novel approach demonstrating the importance, utility and power of effective participatory practices for informing the re-design of services.
A superpower? An educational initiative? Or something else …
Authors: Kessel Anthony , Neill Michael , Marmur Elizabeth , Malik Rifat 
Published: November 2017

Purpose
The purpose of this paper is to raise awareness of an understanding of “how the mind works” that has been gaining considerable traction in the coaching world and, increasingly, in the health education sphere.

Design/methodology/approach
A brief review of the “Three Principles” understanding of how the mind works (including definitions of the principles of thought, consciousness and mind), and an assessment of the strengths and challenges of this understanding.

Findings
Examples are provided of how this approach (labelled an educational initiative rather than a therapy) is being used professionally and how this understanding of how the mind works can make stress, anxiety and work-related problems appear different; recommendations include the establishment of a professional body, and the need for more research around the effectiveness of the approach.

Originality/value
Despite the need for greater professionalisation and more research evidence, the “Three Principles” understanding has huge potential to transform people’s lives – whether at work or home, for individuals with (or without) common mental health problems, and for those with chronic long-term conditions.
Factors affecting outcomes of EU-supported investments in innovation among SMEs in the Greater Poland (Wielkopolska) region, Poland
Authors: Mikołajczak Paweł , Pawlak Jacek 
Published: November 2017

Purpose
The European Union offers support mechanisms to help small and medium sized enterprises (SMEs) to innovate and grow. Given the substantial contribution of SMEs to national economies, the present paper explores what factors tend to be associated with the success of EU-supported innovation by SMEs in Poland during its early post-accession period.

Design/methodology/approach
A conceptual model relating the type of innovation, investment purpose, funding type and financial readiness, location and collaboration possibilities, company size and sector of operation to changes in the capital base, employment, unit price and revenue is proposed. This model is operationalised and estimated as a structural equations model and estimated using a sample of 110 SMEs surveyed in 2008 in the Greater Poland (Wielkopolska) region in Poland.

Findings
Two approaches to the successful use of innovation support have been observed among the studied companies. The first approach implements market innovations to establish a presence in foreign markets and to move the product or service up the value chain. The second approach uses the funding to de-risk workforce expansion and increase production capacity.

Originality/value
The paper provides the first systematic disaggregate level analysis of an early post-accession context where impacts of EU support for SME innovation are decomposed into effects of specific investment conditions and innovation type on changes in capital base, employment, unit price and ultimately revenue. The insights provided here are valuable for managers developing business and innovation strategies on the one hand, but also for policymakers responsible for creating an entrepreneurship friendly environment in emerging economies.
Use of information and communication technologies for administration and management of schools in Nigeria
Authors: Omotayo Funmilola Olubunmi , Chigbundu Michael Chinweike 
Published: November 2017

Purpose
The purpose of this paper is to investigate the adoption and use of information and communication technologies (ICTs) by school administrators in the management of schools, as well as factors that influence use of ICTs by the administrators.

Design/methodology/approach
Survey research design was adopted. A two-stage sampling procedure (random and purposive) was used to select the respondents, while quantitative and qualitative methods were used for data collection.

Findings
Findings reveal that the school administrators use various ICTs to carry out administrative and management duties. Task characteristics, task-technology fit, attitude and perceived ease of use have significant relationships with use of ICTs by the administrators.

Research limitations/implications
The findings and conclusion from this paper cannot be generalised to all schools in Nigeria because the population was limited to only private secondary schools.

Practical implications
The study contributes to an existing knowledge on adoption and use of ICTs in schools, and provides information to policymakers on factors that should be given consideration when there is a need to implement ICTs in schools.

Social implications
This paper could assist school administrators that are yet to adopt and implement ICTs in their schools of the need to do so in order to enjoy the benefits associated with ICTs use in the workplace.

Originality/value
This paper is one of the first pieces of empirical research that has adopted the integrated technology acceptance and task-technology fit models to investigate use of ICTs by administrators of schools in Nigeria.