bluuebunny/crossref_metadata_2025_split huggingface dataset:
Extended insight into the preponderance of LRRs - a docking & simulation study with members of the TLR1 subfamily
Authors: Dey Debayan , Dhar Dipanjana , Das Sucharita , Maulik Aditi , Basu Soumalee 
Published: March 2019

AbstractThe widespread structural motif of Leucine-rich repeats (LRR) constitute the extracellular part of the Toll-like receptor (TLR) family preceded by an intracellular Toll/interleukin-1 receptor (TIR) domain at the C-terminus. The benefit of using LRRs in these pattern recognition receptors (PRR) that are responsible for early detection of pathogens to elicit inflammatory/innate immune response still remains elusive. Phylogenetic analyses (Maximum Likelihood and Bayesian Inference) of nine TLR (TLR 1-9) genes from 36 mammals reconfirmed the existence of two distinct clades, one (TLR1/2/6) for recognizing bacterial cell wall derivatives and another (TLR7/8/9) for various nucleic acids. TLR3, TLR4 and TLR5 showed independent line of evolution. The distinction of the TLR1 subfamily to form heterodimers within its members and the existence of the paralogs TLR1 and TLR6 therein, was appealing enough to carry out further studies with the extracellular recognition domain. Dimerizing and ligand binding residues from the crystal structures of TLR1 and TLR6 were interchanged to generate chimeric proteins. The dimer forming ability of these variants with their common partner, TLR2, were checked before running MD simulations. The chimeras were compared with wild type dimers to find no significant alterations in the overall structure. Finally, interchanged ligands were docked to the variants to ratify reversal of the binding function. Intriguingly, sequence change in substantial numbers, 16 in TLR1 and 18 in TLR6, preserves the native scaffold offered by LRRs. This exercise thus depicts how the LRR motif has been advantageous to be selected as an evolutionarily conserved motif for essential cellular processes.
A Mechanism for Epithelial-Mesenchymal Heterogeneity in a Population of Cancer Cells
Authors: Tripathi Shubham , Levine Herbert , Kumar Jolly Mohit 
Published: March 2019

SummaryEpithelial-mesenchymal heterogeneity, wherein cells within the same tumor can exhibit an epithelial, a mesenchymal, or one or more hybrid epithelial-mesenchymal phenotype(s), has been observed across cancer types and implicated in metastatic aggressiveness. Here, we have used computational modeling to show that this heterogeneity can emerge from the noise in the partitioning of RNAs and proteins among the daughter cells during cancer cell division. Our model captures the population-level behavior of murine prostate cancer cells, the hysteresis in the dynamics of epithelial-mesenchymal plasticity, and how hybrid phenotype-promoting factors alter the phenotypic composition of a population. We further used the model to describe the implications of heterogeneity for therapeutics. By linking the dynamics of an intracellular regulatory circuit to the phenotypic composition of a population, the study contributes towards understanding how non-genetic heterogeneity can be generated and propagated from a small, homogeneous population, and towards therapeutic targeting of cancer cell heterogeneity.
Induction of p73, Δ133p53, Δ160p53, pAKT leads to neuroprotection via DNA repair by 5-LOX inhibition
Authors: Shekhar Shashank , Dey Sharmistha 
Published: March 2019

AbstractLipooxygenase-5 (5-LOX), protein is involved in the pathologic phenotype of AD which includes amyloid-plague and tau hyperphosphorylation. This study aims to identify the mechanistic role in neuroprotection by peptide YWCS, the 5-LOX inhibitor in neurotoxic SH-SY5Y cell line developed by the treatment of Aβ25-35. The cells were treated with Aβ25-35 and with different doses of YWCS. The effect on cell survival pathways were determined by western blot using polyclonal anti body of p53, anti-Akt and anti-phosphorylated-Akt. Immunoprecipitation and mass spectroscopic studies were done to identify the altered proteins. Over expression of phosphorylated-Akt and 3 bands of p53 isoforms were observed which correspond to p73, Δ133p53 and Δ160p53 in the cells treated only with 80µM of YWCS compare to untreated cells. However, no alteration of total p53 and Akt were observed. The results exposed the novel mechanistic pathway of neuroprotection by 5-LOX inhibition, which is likely to be mediated by DNA DSB repair through p53 isoforms and PI3K/Akt pathway. Our finding has opened a new window in the therapeutic approach for the prevention of AD.
Control of human testis-specific gene expression
Authors: Brown Jay C. 
Published: March 2019

AbstractBackgroundAs a result of decades of effort by many investigators we now have an advanced level of understanding about several molecular systems involved in the control of gene expression. Examples include CpG islands, promoters, mRNA splicing and epigenetic signals. It is less clear, however, how such systems work together to integrate the functions of a living organism. Here I describe the results of a study to test the idea that a contribution might be made by focusing on genes specifically expressed in a particular tissue, the human testis.Experimental DesignA database of 239 testis-specific genes was accumulated and each was examined for the presence of features relevant to control of gene expression. These include: (1) the presence of a promoter, (2) the presence of a CpG island (CGI) within the promoter, (3) the presence in the promoter of a transcription factor binding site near the transcription start site, (4) the level of gene expression, and (5) the above features in genes of cell types such as spermatocyte and spermatid that differ in their extent of differentiation.ResultsOf the 107 database genes with an annotated promoter, 56 were found to have one or more transcription factor binding sites near the transcription start site. Three of the binding sites observed, Pax-5, AP-2αA and GRα, stand out in abundance suggesting they may be involved in testis-specific gene expression. Compared to less differentiated testis-specific cells, genes of more differentiated cells were found to be (1) more likely to lack a CGI, (2) more likely to lack introns and (3) higher in expression level. The results suggest genes of more differentiated cells have a reduced need for CGI-based regulatory repression, reduced usage of gene splicing and a smaller set of expressed proteins
Gene Cascade Finder: A tool for identification of gene cascades and its application inCaenorhabditis elegans
Authors: Nomoto Yusuke , Kubota Yukihiro , Kasahara Kota , Tomita Aimi , Oshime Takehiro , Yamashita Hiroki , Fahmi Muhamad , Ito Masahiro 
Published: March 2019

AbstractObtaining a comprehensive understanding of the gene regulatory networks, or gene cascades, involved in cell fate determination and cell lineage segregation inCaenorhabditis elegansis a long-standing challenge. Although RNA-sequencing (RNA-Seq) is a promising technique to resolve these questions, the bioinformatics tools to identify associated gene cascades from RNA-Seq data remain inadequate. To overcome these limitations, we developed Gene Cascade Finder (GCF) as a novel tool for building gene cascades by comparison of mutant and wild-type RNA-Seq data along with integrated information of protein-protein interactions, expression timing, and domains. Application of GCF to RNA-Seq data confirmed that SPN-4 and MEX-3 regulate the canonical Wnt pathway during embryonic development. Moreover,lin-35, hsp-3, andgpa-12were found to be involved in MEX-1-dependent neurogenesis, and MEX-3 was found to control the gene cascade promoting neurogenesis throughlin-35andapl-1. Thus, GCF could be a useful tool for building gene cascades from RNA-Seq data.
Assessing the multiple dimensions of poverty. Data mining approaches to the 2004-14 Health and Demographic Surveillance System in Cuatro Santos, Nicaragua
Authors: Källestål Carina , Blandón Elmer Zelaya , Peña Rodolfo , Peréz Wilton , Contreras Mariella , Persson Lars-Åke , Sysoev Oleg , Selling Katarina Ekholm 
Published: March 2019

AbstractWe aimed to describe multiple dimensions of poverty according to the capability approach theory by applying data mining approaches to the Cuatro Santos Health and Demographic Surveillance databases, Nicaragua. Four municipalities in northern Nicaragua constitute the Cuatro Santos area, with 25,893 inhabitants in 5,966 households (2014). A local process analyzing poverty-related problems and prioritizing suggested actions, was initiated 1997 based on a community action plan 2002-2015. Priority interventions were school breakfasts, environmental protection, water and sanitation, preventive healthcare, home gardening, micro credits, technical training, stipends for university education, and the use of Internet. In 2004, a survey of basic health and demographic information was performed in the whole population followed by surveillance updates in 2007, 2009, and 2014 linking households and individuals by unique identifiers. Information included the house (floor, walls) and services (water, sanitation, electricity) as well as demographic data (birth, deaths, migration). Data on participation in interventions, on food security, household assets, and women’s self-rated health were collected in 2014. A K-means algorithm were used to cluster the household data (54 variables). The poverty ranking of household clusters using the unsatisfied basic needs index (UBN) variables changed when including variables describing basic capabilities. The households in the fairly rich cluster, having assets as motorbikes and computers were described as modern. Those in the fairly poor cluster, having different degrees of food insecurity were labeled vulnerable. Poor and poorest clusters of households were traditional e.g. in using horses for transport. Results displayed a society transforming from traditional to a modern, where the forerunners were not the richest but educated, had more working members of household, fewer children and were food secure. Those lagging were the poor, traditional and food insecure. The approach and results may be useful for an improved understanding of poverty and to direct local interventions.
Highly reproducible murine model of oralSalmonellainfection via inoculated food
Authors: Nilsson Olof R. , Kari Laszlo , Steele-Mortimer Olivia 
Published: March 2019

AbstractOral infection of mice withSalmonellaTyphimurium is an important model system. In particular C57Bl/6 mice, which are susceptible toSalmonella, are used to study both systemic and gastrointestinal pathogenesis. Pretreatment with streptomycin disrupts the intestinal microbiota and results in colitis resembling human intestinalSalmonellosis. Oral gavage is typically used for delivery of both antibiotic and bacteria. Although convenient, this method requires a moderate level of expertise, can be stressful for experimental animals, and may lead to unwanted tracheal or systemic introduction of bacteria. Here, we demonstrate a simple method for oral infection of mice using small pieces of regular mouse chow inoculated with a known number of bacteria. Mice readily ate chow pieces containing up to 108CFUSalmonella, allowing for a wide range of infectious doses. In mice pretreated with streptomycin, infection with inoculated chow resulted in less variability in numbers of bacteria recovered from tissues compared to oral gavage, and highly consistent infections even at doses as low as 103Salmonella. Mice not treated with streptomycin, as well as resistant Nramp1 reconstituted C57Bl/6J mice, were also readily infected using this method. In summary, we show that foodborne infection of mice by feeding with pieces of chow inoculated withSalmonellaresults in infection comparable to oral gavage but represents a natural route of infection with fewer side effects and less variability among mice.
Circulating Th17.1 cells as candidate for prediction of therapeutic response to abatacept in patients with rheumatoid arthritis: exploratory research
Authors: Maeda Shinji , Osaga Satoshi , Maeda Tomoyo , Takeda Norihisa , Tamechika Shin-ya , Naniwa Taio , Niimi Akio 
Published: March 2019

AbstractT helper 17.1 cells (Th17.1) are highly pathogenic T cells in inflammatory diseases. This study aimed to identify Th cell biomarkers, including the analysis of Th17.1, that predict therapeutic response to abatacept in patients with rheumatoid arthritis. The circulating Th subsets among CD4+ T lymphocytes in 40 patients with rheumatoid arthritis before abatacept treatment were determined using multicolor flow cytometry. All patients received abatacept treatment for 24 weeks, and the change in disease activity score, including 28-joint count C-reactive protein, and the responsiveness of other indices to abatacept treatment were evaluated according the European League Against Rheumatism criteria [good responders, moderate responders, and non-responders]. The correlation between the abatacept responses and the Th subsets (baseline) was analyzed. Logistic regression analysis with inverse probability weighting method was conducted to calculate odds ratio adjusted for patient characteristics. The proportion of baseline Th17.1 cells was significantly lower in patients categorized as good responders than in those categorized as non-good responders (moderate responders and non-responders; p = 0.0064). The decrease in 28-joint count C-reactive protein after 24 weeks of abatacept therapy also showed a significant negative correlation with the proportion of Th17.1 cells. The adjusted odds ratio for achieving good response in patients with baseline Th17.1 level below the median value was 14.6 (95% confidence interval, 2.9–72.3; p = 0.0021) relative to that in the remaining patients. The proportion of Th17.1 cells at baseline is a good candidate for the prediction of response to abatacept treatment. These novel findings may represent an important step in the pursuit of precision medicine.
Characterisation ofStaphylococcus aureuslipids by nanoelectrospray ionisation tandem mass spectrometry (nESI-MS/MS)
Authors: Young Simon A. , Desbois Andrew P. , Coote Peter J. , Smith Terry K. 
Published: March 2019

AbstractStaphylococcus aureusis a major opportunistic pathogen that is exposed to antimicrobial innate immune effectors and antibiotics that can disrupt its cell membrane. An understanding ofS. aureuslipid composition and its role in defending the cell against membrane-disrupting agents is of fundamental importance. Common methods for characterising lipid profiles suffer shortcomings such as low sensitivity of detection and inferior resolution of the positional assignments of fatty acid chains in lipids. This present study developed a rapid and sensitive nano-electrospray ionisation tandem mass spectrometry (nESI-MS/MS) method to characterise the lipid composition of three commonly studiedS. aureusisolates: Newman, Mu50 and BB270. Confirming previous studies, nESI-MS/MS revealed that phosphatidylglycerols were most abundant inS. aureusmembranes, while diglucosyldiacylglycerols and lysyl-phosphatidylglycerols were also detected. Positional assignments for individual fatty acid chains within these lipids were also determined. Concomitantly, gas chromatography mass spectrometry of the fatty acids validated the molecular characterization and showed the principal species present in each strain were predominately anteiso- and iso-branched chain fatty acids. Though the fatty acid and lipid profiles were similar between theS. aureusstrains, this method was sufficiently sensitive to distinguish minor differences in lipid composition. In conclusion, this nESI-MS/MS methodology can characterise the role of lipids in antimicrobial resistance, and may even be applied to the rapid diagnosis of drug-resistant strains in the clinic.
Vibrational behavior of psyllids (Hemiptera: Psylloidea): functional morphology and mechanisms
Authors: Liao Yi-Chang , Wu Zong-Ze , Yang Man-Miao 
Published: March 2019

AbstractVibrational behavior of psyllids was first documented more than six decades ago. Over the years, workers have postulated as to what the exact signal-producing mechanisms of psyllids might be but the exact mechanism has remained elusive. The aim of this study is to determine the specific signal-producing structures and mechanisms of the psyllids. Here we examine six hypotheses of signal-producing mechanisms from both previous and current studies that include: wing vibration, wing-wing friction, wing-thorax friction, wing-leg friction, leg-abdomen friction, and axillary sclerite-thorax friction. Through selective removal of possible signal producing structures and observing wing-beat frequency with a high-speed video recorder, six hypotheses were tested. Extensive experiments were implemented on the speciesMacrohomotoma gladiataKuwayama, while other species belonging to different families, i.e.,Trioza sozanica(Boselli),Mesohomotoma camphoraeKuwayama,Cacopsylla oluanpiensis(Yang), andCacopsylla tobirae(Miyatake) were also examined to determine the potential prevalence of each signal-producing mechanism within the Psylloidea. Further, scanning electron microscopy (SEM) was used to examine possible rubbing structures. The result of high speed photography showed that wing-beating frequency did not match the dominant frequency of vibrational signals, resulting in the rejection of wing vibration hypothesis. As for the selective removal experiments, the axillary sclerite-thorax friction hypothesis is accepted and wing-thorax friction hypothesis is supported partially, while others are rejected. The SEM showed that the secondary axillary sclerite of forewing bears many protuberances that would be suitable for stridulation. In conclusion, the signal-producing mechanism of psyllids involves two sets of morphological structures. The first is stridulation between the axillary cord and anal area of the forewing. The second is stridulation between the axillary sclerite of the forewing and the mesothorax.
Religion, science and secularization: a consumer-centric analysis of religion’s functional obsolescence
Authors: Pinelli Michele , Einstein Mara 
Published: March 2019

Purpose
This paper aims to offer a marketing perspective to the multidisciplinary debate on whether religion is expanding, declining or resurging in contemporary and allegedly secular society. Specifically, it examines the “secularization hypothesis”, which predicts that religion tends to lose its central role in people’s lives as secular reasoning spreads and scientific knowledge accumulates.

Design/methodology/approach
Borrowing from psychology literature, the authors identify the psychological and social needs satisfied by religion and in doing so uncover its functions. They then discussed whether religion can be claimed to be functionally obsolete.

Findings
The authors identified four functions of religion: explanatory, relieving, membership and moral. The content of religious doctrines offers consumers of religion unambiguous knowledge, absolute morality and promises of immortality, immanent justice and centrality in the universe. Religion also provides a social identity, through which people can build meaningful connections with others in the community and with their own history.

Originality/value
A change in the role of religion would be highly relevant for consumer research because religious ideologies shape consumption practices, social relations, products and brands. The authors observe that the content of religious answers is so well-crafted around human psychology that the explaining, relieving and moral functions of religion have not lost reliability. However, cultural change has weakened religion’s ability to gratify human psychology through social identity and meaningful socialization, which led to the marketization of religion, the rise of spirituality and the intensification of socialization around consumption.
The performance of equity unit investment trusts
Authors: Comer George , Rodriguez Javier 
Published: March 2019

Purpose
The purpose of this paper is to examine the risk adjusted performance of unit investment trusts (UITs). These UITs are a unique investment vehicle in that the trusts invest in a fixed portfolio of stocks for a predetermined period of time and hold limited cash positions.

Design/methodology/approach
Using a sample of 1,487 UITs from January 2004 to December 2013, the authors estimate the risk adjusted performance of the UITs. The authors use daily return data and four different returns based models to measure the alphas of the UITs.

Findings
The authors find that before fees and expenses the UITs generate significant negative alphas. The authors also find that observable trust characteristics are unable to explain the poor risk adjusted performance of the trusts.

Originality/value
Despite $85bn being invested in these unique buy and hold vehicles, the academic literature has not examined the risk adjusted performance of the trusts. The poor performance of these trusts indicates that restricting flexibility and maintaining full investment for a fixed period of time may not be beneficial to investors.
Adaptive theory: an underutilised approach to sexual offender research
Authors: Youssef Carollyne 
Published: March 2019

Purpose
While most studies utilise quantitative methodologies to examine issues relevant to sexual offending behaviour, such as treatment programmes and risk assessments; substantially fewer studies have utilised qualitative methods, and specifically Layder’s Adaptive Theory (AT) as a methodology; and there is a paucity of research examining community maintenance programmes altogether. The purpose of this paper is to report on the use of AT to the understanding of the significance of community maintenance programmes for high-risk sexual offenders.

Design/methodology/approach
Using AT as a unique framework, this study examined an Australian sample of services providers and high-risk sexual offenders participating in a community maintenance programme. In particular, the current research aimed to develop an understanding of community maintenance programmes for released sexual offenders, in a bid to develop a theoretical framework for these programmes. The research had three subject groups, service providers, programme participants who had not reoffended and programme participants who had sexually reoffended.

Findings
It appears that this methodology is a useful approach to studies within forensic rehabilitation and offender research. Common, reoccurring themes have been gathered through this approach, which would not have been possible with a quantitative methodology.

Research limitations/implications
While this research methodology was applied to a small sample size, its use suggested that AT was an informative and useful research approach to utilise in offender research more broadly, yielding rich in-depth information.

Practical implications
Utilising AT provided an in-depth understanding and exploration of experiences for offender populations as well as staff delivering programmes, which enhances the efficacy of programmes delivered by incorporating “user feedback” and allows programme developers to utilise such feedback to improve programmes. An AT approach to offender rehabilitation has been useful in providing exploratory information in the absence of any conceptual or theoretical frameworks and with a very little extant information. Given maintenance programmes are quite understudied, this approach allowed for common themes to emerge in order to guide future research as well as the development of a paradigm. It is worth considering the utility of this methodology for a variety of forensic research, particularly areas which remain understudied.

Social implications
Sexual offending behaviour is a significant societal concern. A better understanding of what makes programmes more effective for those who use them and run them, will assist in reducing recidivism, which will benefit the community at large.

Originality/value
Layder’s AT has not been used with an offender population in the past, and specifically within the sexual offending realm, thus this paper offers a unique and effective approach to offender research.