bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential strengths of molecular determinants guide environment specific mutational fates
Authors: Dandage Rohan , Pandey Rajesh , Jayaraj Gopal , Chakraborty Kausik 
Published: May 2017

AbstractUnder the influence of selection pressures imposed by natural environments, organisms maintain competitive fitness through underlying molecular evolution of individual genes across the genome. For molecular evolution, how multiple interdependent molecular constraints play a role in determination of fitness under different environmental conditions is largely unknown. Here, using Deep Mutational Scanning (DMS), we quantitated empirical fitness of ∼2000 single site mutants of Gentamicin-resistant gene (GmR). This enabled a systematic investigation of effects of different physical and chemical environments on the fitness landscape of the gene. Molecular constraints of the fitness landscapes seem to bear differential strengths in an environment dependent manner. Among them, conformity of the identified directionalities of the environmental selection pressures with known effects of the environments on protein folding proves that along with substrate binding, protein stability is the common strong constraint of the fitness landscape. Our study thus provides mechanistic insights into the molecular constraints that allow accessibility of mutational fates in environment dependent manner.Author SummaryEnvironmental conditions play a central role in both organismal adaptations and underlying molecular evolution. Understanding of environmental effects on evolution of genotype is still lacking a depth of mechanistic insights needed to assist much needed ability to forecast mutational fates. Here, we address this issue by culminating high throughput mutational scanning using deep sequencing. This approach allowed comprehensive mechanistic investigation of environmental effects on molecular evolution. We monitored effects of various physical and chemical environments onto single site mutants of model antibiotic resistant gene. Alongside, to get mechanistic understanding, we identified multiple molecular constraints which contribute to various degrees in determining the resulting survivabilities of mutants. Across all tested environments, we find that along with substrate binding, protein stability stands out as the common strong constraints. Remarkable direct dependence of the environmental fitness effects on the type of environmental alteration of protein folding further proves that protein stability is the major constraint of the gene. So, our findings reveal that under the influence of environmental conditions, mutational fates are channeled by various degrees of strengths of underlying molecular constraints.
Extending causality tests with genetic instruments: an integration of Mendelian Randomization and the Classical Twin Design
Authors: Minică Camelia C. , Dolan Conor V. , Boomsma Dorret I. , Geus Eco de , Neale Michael C. 
Published: May 2017

ABSTRACTMendelian Randomization (MR) is an important approach to modelling causality in non-experimental settings. MR uses genetic instruments to test causal relationships between exposures and outcomes of interest. Individual genetic variants have small effects, and so, when used as instruments, render MR liable to weak instrument bias. Polygenic scores have the advantage of larger effects, but may be characterized by direct pleiotropy, which violates a central assumption of MR.We developedthe MR-DoC twin modelby integrating MR with the Direction of Causation twin model. This model allows us to test pleiotropy directly. We considered the issue of parameter identification, and given identification, we conducted extensive power calculations. MR-DoC allows one to test causal hypotheses and to obtain unbiased estimates of the causal effect given pleiotropic instruments (polygenic scores), while controlling for genetic and environmental influences common to the outcome and exposure. Furthermore, MR-DoC in twins has appreciably greater statistical power than a standard MR analysis applied to singletons, if the unshared environmental effects on the exposure and the outcome are uncorrelated. Generally, power increases with: 1) decreasing residual exposure-outcome correlation, and 2) decreasing heritability of the exposure variable.MR-DoC allows one to employ strong instrumental variables (polygenic scores, possibly pleiotropic), guarding against weak instrument bias and increasing the power to detect causal effects. Our approach will enhance and extend MR’s range of applications, and increase the value of the large cohorts collected at twin registries as they correctly detect causation and estimate effect sizes even in the presence of pleiotropy.
Cells with Treg-specificFOXP3demethylation but low CD25 are prevalent in autoimmunity
Authors: Ferreira Ricardo C. , Simons Henry Z. , Thompson Whitney S. , Rainbow Daniel B. , Yang Xin , Cutler Antony J. , Oliveira Joao , Dopico Xaquin Castro , Smyth Deborah J. , Savinykh Natalia , Mashar Meghavi , Vyse Tim , Dunger David B , Baxendale Helen , Chandra Anita , Wallace Chris , Todd John A , Wicker Linda S. , Pekalski Marcin L. 
Published: May 2017

AbstractIdentification of alterations in the cellular composition of the human immune system is key to understanding the autoimmune process. Recently, a subset of FOXP3+cells with low CD25 expression was found to be increased in peripheral blood from systemic lupus erythematosus (SLE) patients, although its functional significance remains controversial. Here we find in comparisons with healthy donors that the frequency of FOXP3+cells within CD127lowCD25lowCD4+T cells (here defined as CD25lowFOXP3+T cells) is increased in patients affected by autoimmune disease of varying severity, from combined immunodeficiency with active autoimmunity, SLE to type 1 diabetes. We show that CD25lowFOXP3+T cells share phenotypic features resembling conventional CD127lowCD25highFOXP3+Tregs, including demethylation of the Treg-specific epigenetic control region inFOXP3that is highly enriched in HELIOS+cells, and lack of IL-2 production. As compared to conventional Tregs, more CD25lowFOXP3+HELIOS+T cells are in cell cycle (33.0% vs 20.7% Ki-67+;P= 1.3 x 10-9) and express the late-stage inhibitory receptor PD-1 (67.2% vs 35.5%;P= 4.0 x 10-18), while having reduced expression of the early-stage inhibitory receptor CTLA-4, as well as other Treg markers, such as FOXP3 and CD15s. The number of CD25lowFOXP3+T cells are highly correlated (P= 1.2 x 10-19) with the proportion of CD25highFOXP3+T cells in cell cycle (Ki-67+). These findings suggest that CD25lowFOXP3+T cells represent a subset of Tregs that are derived from CD25highFOXP3+T cells, and are a peripheral marker of recent Treg expansion in response to an autoimmune reaction in tissues.Highlights- FOXP3+compartment within CD127lowCD25lowT cells is expanded in autoimmune patients.- Increased numbers of CD25lowFOXP3+T cells are a circulating marker of autoimmunity.- CD25lowFOXP3+HELIOS+T cells are fully demethylated at theFOXP3TSDR.- CD25lowFOXP3+T cells could represent a terminal stage of regulatory T cells.
Random Walk With Restart on Multiplex and Heterogeneous Biological Networks
Authors: Valdeolivas Alberto , Tichit Laurent , Navarro Claire , Perrin Sophie , Odelin Gaëlle , Levy Nicolas , Cau Pierre , Remy Elisabeth , Baudot Anaïs 
Published: May 2017

ABSTRACTRecent years have witnessed an exponential growth in the number of identified interactions between biological molecules. These interactions are usually represented as large and complex networks, calling for the development of appropriated tools to exploit the functional information they contain. Random walk with restart is the state-of-the-art guilt-by-association approach. It explores the network vicinity of gene/protein seeds to study their functions, based on the premise that nodes related to similar functions tend to lie close to each others in the networks.In the present study, we extended the random walk with restart algorithm to multiplex and heterogeneous networks. The walk can now explore different layers of physical and functional interactions between genes and proteins, such as protein-protein interactions and co-expression associations. In addition, the walk can also jump to a network containing different sets of edges and nodes, such as phenotype similarities between diseases.We devised a leave-one-out cross-validation strategy to evaluate the algorithms abilities to predict disease-associated genes. We demonstrate the increased performances of the multiplex-heterogeneous random walk with restart as compared to several random walks on monoplex or heterogeneous networks. Overall, our framework is able to leverage the different interaction sources to outperform current approaches.Finally, we applied the algorithm to predict genes candidate for being involved in the Wiedemann-Rautenstrauch syndrome, and to explore the network vicinity of the SHORT syndrome.The source code and the software are freely available at:https://github.com/alberto-valdeolivas/RWR-MH.
FCS in closed systems and application for membrane nanotubes
Authors: Jiang Yanfei , Melnykov Artem , Elson Elliot E. 
Published: May 2017

AbstractIn the present study, we developed the fluorescence correlation spectroscopy theory for closed systems with either periodic or reflective boundaries. The illumination could be any arbitrary function. We tested our theory with simulated data of both boundary conditions. We also tested the theory with experimental data of membrane nanotubes, whose circular direction is a closed system. The result shows that the correlation function for nanotubes falls between 1D and 2D diffusion model. The fitting with our model gives an accurate recovery of the diffusion time and nanotube radius. We also give some examples of single molecule experiments for which our theory can be potentially useful.
Ki-67 contributes to normal cell cycle progression and inactive X heterochromatin in p21 checkpoint-proficient human cells
Authors: Sun Xiaoming , Bizhanova Aizhan , Matheson Timothy D. , Yu Jun , Zhu Lihua Julie , Kaufman Paul D. 
Published: May 2017

AbstractKi-67 protein is widely used as a tumor proliferation marker. However, whether Ki-67 affects cell cycle progression has been controversial. Here, we demonstrate that depletion of Ki-67 in human hTERT-RPE1, WI-38, IMR90, hTERT-BJ cell lines and primary fibroblast cells slowed entry into S phase and coordinately downregulated genes related to DNA replication. Some gene expression changes were partially relieved in Ki-67-depleted hTERT-RPE1 cells by co-depletion of the Rb checkpoint protein, but more thorough suppression of the transcriptional and cell cycle defects was observed upon depletion of cell cycle inhibitor p21. Notably, induction of p21 upon depletion of Ki-67 was a consistent hallmark of cell types in which transcription and cell cycle distribution were sensitive to Ki-67; these responses were absent in cells that did not induce p21. Furthermore, upon Ki-67 depletion, a subset of inactive × (Xi) chromosomes in female hTERT-RPE1 cells displayed several features of compromised heterochromatin maintenance, including decreased H3K27me3 and H4K20me1 labeling. These chromatin alterations were limited to Xi chromosomes localized away from the nuclear lamina and were not observed in checkpoint-deficient 293T cells. Altogether, our results indicate that Ki-67 integrates normal S phase progression and Xi heterochromatin maintenance in p21 checkpoint-proficient human cells.
A multi-disciplinary approach to explaining workless-ness in Britain
Authors: Cagliesi Gabriella , Hawkes Denise Donna , Tookey Max 
Published: May 2017

PurposeThe purpose of this paper is to adopt the principles of labour economics, behavioural economics and social influence to identify constraints and enablers that influence people’s choices in relation to the labour market decisions.Design/methodology/approachA sequential empirical methodology has been adopted, where data from the British Household Panel Survey (2009) has been collected to explain various statuses of labour market activity, with a focus on workless-ness, across the categories of unemployment, being a student, disability, retirement and being a carer – differentiating for gender and age. The paper develops and substantiates the hypothesis theoretically and gives some indications using a multi-disciplinary approach.FindingsThe authors found that labour market opportunities, choices and achievements are affected by the interrelations and interactions of an individual’s demographic and psychological characteristics (such as age, gender, heuristics, perceptions, beliefs, attitude’s goals and ambitions) along with external factors (such as geographical, socio- cultural and economic conditions).Originality/valueThis study makes a unique contribution to labour economics as the authors abandon the traditional welfare approach and use a more general framework of capabilities and refined functioning to interpret how different types of constraints – ranging from socio-economic conditions and environmental background to specific features of individual processes of choices and decision making – affect preferences and functioning’s. The study also identifies how “under-employment” complements the use of BE/social influence in explaining labour market inactivity, and highlights how the findings of this study have important implications for policy.
Interaction and higher order effects of factors affecting the performance of microfinancing institutions
Authors: Nanayakkara Gemunu 
Published: May 2017

PurposeThe purpose of this paper is to find the factors that affect the “performance” of microfinancing institutions (MFIs) around the world and to further analyse the interaction and higher order effects of these factors on the performance. Although MFIs can have various objectives from a commercial focus to a social focus when performing their operations, this study analyses the factors that contribute to “performance” of MFIs in relation to their ability to “alleviate poverty in a sustainable manner”.Design/methodology/approachBased on the data relating to 234 MFIs across 63 countries, this study analyses eight factors that can affect performance of MFIs (as defined in this study) and their higher order and interaction effects using multiple regression models.FindingsThe results show that gender (female), literacy level of the borrowers, operational efficiency, offering only loans (not diversifying), age and emphasis on profitability have a significant effect on the performance. Analysis of higher order effects shows that the relationship of age with performance is a downward concave curve and that with operational efficiency is an upward concave curve. The interaction effects of gender and literacy, age and emphasis on female borrowers, and also age and emphasis on profitability were found to be significant.kOriginality/valueThe findings contribute to understanding the factors that affect the performance of MFIs to alleviate poverty in a sustainable manner and help the policy makers and managers of MFIs to improve their performance in this area. Considering the hundreds of millions of dollars injected into microfinancing, improvement in performance as a result of these findings can lead to savings in millions of dollars.
To immerse or not? Experimenting with two virtual retail environments
Authors: Papagiannidis Savvas , Pantano Eleonora , See-To Eric W.K. , Dennis Charles , Bourlakis Michael 
Published: May 2017

PurposeThe purpose of this paper is to examine the determinants of users’ simulated experience in a virtual store and to show the subsequent impact of that experience on engagement. The outcome of that engagement is examined in relation to enjoyment, satisfaction and purchase intentions.Design/methodology/approachThe method comprised an experiment comparing users’ perceptions of a standard 2D online clothing store with an enhanced, immersive one that aimed to provide shopping value approaching that of a traditional store by using a 3D experience where participants wore special glasses and a data glove.FindingsResults demonstrate the major role of telepresence components in simulated experience and the critical role of that experience, along with hedonic and utilitarian values, in engagement. Purchase intention is influenced by satisfaction, which is in turn influenced by enjoyment and engagement. Engagement in turn is influenced by utilitarian and hedonic value and the experience of product simulation or telepresence, which is composed of control, colour and graphics vividness, and 3D authenticity. In the immersive, 3D environment, experience is more associated with engagement and enjoyment, leading to greater purchase intention. The immersive, 3D environment, thus, has the potential to rival traditional shopping in terms of experience, resulting in higher sales for retailers and satisfaction for consumers.Originality/valueThis work has evaluated a robust model of purchase intention and demonstrated it to hold not only in a 3D environment on a conventional computer platform, but also in an immersive one, where participants wear special glasses and a data glove.
Multi-objective optimization of parametric combination of injected slub yarn for producing knitted and woven fabrics with least abrasive damage
Authors: Mukhopadhyay Arunangshu , Midha Vinay Kumar , Ray Nemai Chandra 
Published: May 2017

Purpose
This study aims to optimize the parametric combination of injected slub yarn to achieve least abrasive damage on fabrics produced from it.

Design/methodology/approach
Single base injected slub yarn structural parameters, vis-à-vis slub length, slub thickness and slub frequency, were varied during preparation of yarn samples under this research work. A total of 17 yarn samples were produced according to the Box and Bhenken design of the experiment. Subsequently knitted and woven (using injected slub yarns in the weft only) fabric samples were prepared from these yarns. Yarn and fabric samples were abraded with standard instruments to see the impact of yarn structural parameters on abrasive damage of fabric in terms of fabric mass loss and appearance deterioration. From the test results, empirical models relating to slub parameters and fabric abrasion behavior were developed through a backward elimination regression approach. Subsequently, a set of optimal parametric combinations was derived with multi-objective evolutionary algorithms by using MATLAB software. This was followed by ranking all optimal solutions through technique for order preference by similarity to idle solution (TOPSIS) score analysis.

Findings
The injected slub yarn’s structural parameters have a strong influence on the abrasive damage of knitted and woven fabric. It is seen that the best suitable parametric combination of slub parameters for achieving the least abrasive damage is not the same for knitted and woven fabric.

Practical implications
The spinner can explore this concept to find out the best suitable parametric combination during pattern making of injected slub yarn through MATLAB solution followed by TOPSIS score analysis based on their priority of criteria level to ensure better abrasion behavior of fabric produced.

Originality/value
Optimization of parametric combination of injected slub yarns will help to ensure production of fabric with most resistance to abrasion for specific applications. The studies showed that the optimal solution for woven and knitted fabrics is different. The result indicates that in the case of knitted fabric, comparatively lesser slub thickness is found to be suitable for getting better fabric abrasion resistance, whereas in the case of woven fabric, comparatively higher slub thickness is found suitable for the same.
Redesigning historic cities facing rapid tourism growth
Authors: Pinheiro Francisco Vizeu 
Published: May 2017

PurposeThe historical city of Macao has recently become one of the world’s centres for tourism and gaming. But growing traffic congestion in its narrow and old road network, especially in the city’s historic centre, raises concerns about the city’s traffic pollution, environmental impacts and negative effects on residents’ and visitors’ health. The purpose of this study is to address the possibility of mitigating emerging environmental problems with urban design solutions.Design/methodology/approachA review and background of the city’s evolution, from a Mediterranean-style town in the sixteenth century to its present status as one of the highest population density cities in the world, is first undertaken. The paper then critiques the urban layout that conditions current traffic and pollution trends.FindingsHigh levels of pollution of particulate matters are created by a mixture of circumstances related to tall buildings along narrow roads, especially in the historic centre’s San Ma Lou Avenue, that limit ventilation and trap pollution. Green solutions that are known to effectively mitigate this problem, as well as contribute to enhancing the area’s carrying capacity, are discussed.Originality/valueThe originality of this paper lies in its critique of the environmental impact of rapid and overwhelming tourism-oriented development on the quality of the urban environment. It advocates urban design solutions based on experiences from other global tourist cities that, if implemented, will not damage the historic centre’s built environment and will contribute to a more liveable city for residents and better experience for visitors.
Deciphering the effects of disperser assemblages and seed mass on patterns of seed dispersal in a rodent community
Authors: WRÓBEL Aleksandra , ZWOLAK Rafał 
Published: May 2017

AbstractThe sizes of both seed dispersers and seeds are traits that are likely to interact to influence seed fate in many synzoochoric plant species. Here, we examined whether members of a granivorous rodent community consisting of species of different body size vary in their effectiveness as seed dispersers, and how this relationship may be altered by seed size. We marked northern red oak (Quercus rubra) acorns with plastic tags and placed them in size‐selective rodent exclosures. The exclosures allowed differential access of rodent groups based on different body size: (i) small (e.g.Peromyscusspp.); (ii) small and medium (e.g.Tamias striatus); and (iii) small, medium and large (e.g.Sciurus carolinensis) species of rodents. Acorn removal did not differ among exclosure types, but more seeds were missing when removed by small rodents, probably because of larderhoarding. The treatments did not influence the relative frequency of acorn consumption. However, small rodents cached considerably fewer and partially ate more acorns than the other 2 groups. The mean dispersal distance was the longest for cages with medium openings, intermediate for cages with large openings and the shortest for cages with small openings. Acorn mass positively affected the probability of caching and this relationship was unaffected by exclosure type. In conclusion, granivorous rodents of different body sizes strongly differed in their interactions with acorns, with small rodents acting primarily as acorn predators and medium and large species contributing significantly more to dispersal of red oaks.