bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative Effectiveness of Retromuscular and Intraperitoneal Repair: What Is the Value of Posterior Sheath Reconstruction?
Authors: Carney Martin J. , Messa Charles A. , Weissler Jason M. , Shakir Sameer , Wes Ari M. , Enriquez Fabiola A. , Hsu Jesse Y. , Roth J. Scott , Kovach Stephen J. , Fischer John P.
Published: April 2018

Background:

The authors hypothesize that posterior sheath reconstruction to achieve retromuscular mesh placement provides outcomes comparable to traditional retromuscular mesh placement and superior to intraperitoneal repair.

Methods:

Patients were divided into three groups: (1) retromuscular mesh placement with repaired posterior sheath defects, (2) retromuscular repair with an intact posterior sheath, and (3) intraperitoneal repair. Primary outcomes included recurrence, surgical-site occurrences, and cost.

Results:

Overall, 179 patients were included. Posterior sheath defects were repaired primarily with absorbable suture or biological mesh. Recurrence rates differed significantly between standard retromuscular repair and intraperitoneal repair groups (p < 0.009), trended toward significance between repaired posterior sheath and intraperitoneal repair groups (p < 0.058), and showed no difference between repaired posterior sheath and standard retromuscular repair (p < 0.608). Retromuscular repair was clinically protective and cost-effective.

Conclusions:

This analysis of posterior sheath reconstruction suggests outcomes comparable to traditional retromuscular repair and a trend toward superiority compared with intraperitoneal repair. Achieving retromuscular closure appears to demonstrate clinical and cost efficacy.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, III.
Carpal Tunnel Syndrome Management in Breast Cancer Survivors at Risk for Lymphedema: A Markov Model
Authors: Retrouvey Helene , Krahn Murray , Baltzer Heather L.
Published: April 2018

Background:

Breast cancer survivors that have undergone axillary lymph node dissection have an increased risk of developing same-side upper extremity lymphedema. Patients with carpal tunnel syndrome in the ipsilateral limb may not receive appropriate surgical therapy (carpal tunnel release) because of concerns that it may trigger or worsen lymphedema.

Methods:

A state transition cohort model was used to evaluate the treatment options for breast cancer survivors at risk of upper extremity lymphedema presenting with carpal tunnel syndrome. The model reflected three treatment strategies: (1) early surgical intervention, (2) delayed surgical intervention, or (3) nonsurgical management. Both life-years and quality-adjusted life-years were modeled over a 30-year time horizon.

Results:

Over a 30-year time horizon, the preferred strategy was delayed surgery, which resulted in 21.41 quality-adjusted life-years. Early surgery and nonsurgical management yielded 20.42 and 21.06 quality-adjusted life-years, respectively. The model was robust and was not sensitive to variation in any of the parameters within the clinically plausible ranges.

Conclusions:

Based on this decision analytic model, the optimal choice for breast cancer survivors with mild carpal tunnel syndrome who are at risk for lymphedema would be delaying surgery until severe symptoms develop. This strategy balances the potential increased risk of lymphedema following carpal tunnel release with the decreased long-term risk of severe carpal tunnel syndrome. The model comprehensively assesses a controversial area in the breast cancer and hand surgery literature to inform decision-making for patients and clinicians.
Self-awareness of Driving Ability in the Healthy Elderly and Patients With Mild Cognitive Impairment (MCI)
Authors: Fragkiadaki Stella , Beratis Ion N. , Kontaxopoulou Dionysia , Pavlou Dimosthenis , Andronas Nikolaos , Papanicolaou Andrew , Economou Alexandra , Yannis George , Papageorgiou Sokratis G.
Published: April 2018

Introduction:

According to latest research, a percentage of cognitively impaired drivers fail to recognize their areas of weakness and overestimate their driving abilities.

Methods:

Twenty-seven individuals with amnestic mild cognitive impairment (MCI) and 26 healthy elderly drivers participated in a driving simulator study. After the driving assessment, participants were asked to self-evaluate their performance in comparison with what they considered as average for people of similar age and educational level.

Results:

According to the applied mixed analysis of variance model, the MCI patients presented increased difficulties in estimating their driving performance to a greater extent in the rural environment in comparison with the urban condition.

Discussion:

Our findings suggest that the ability of MCI patients to evaluate their driving performance accurately seems to be enhanced or compromised, depending on the number of cues available in their environment, suggesting that providing feedback may improve their metacognitive abilities.
Improved Analysis of Phage ImmunoPrecipitation Sequencing (PhIP-Seq) Data Using a Z-score Algorithm
Authors: Yuan Tiezheng , Mohan Divya , Laserson Uri , Ruczinski Ingo , Baer Alan N. , Larman H. Benjamin
Published: April 2018

Phage ImmunoPrecipitation Sequencing (PhIP-Seq) is a massively multiplexed, phage-display based methodology for analyzing antibody binding specificities, with several advantages over existing techniques, including the uniformity and completeness of proteomic libraries, as well as high sample throughput and low cost. Data generated by the PhIP-Seq assay are unique in many ways. The only published analytical approach for these data suffers from important limitations. Here, we propose a new statistical framework with several improvements. Using a set of replicate mock immunoprecipitations (negative controls lacking antibody input) to generate background binding distributions, we establish a statistical model to quantify antibody-dependent changes in phage clone abundance. Our approach incorporates robust regression of experimental samples against the mock IPs as a means to calculate the expected phage clone abundance, and provides a generalized model for calculating each clone’s expected abundance-associated standard deviation. In terms of bias removal and detection sensitivity, we demonstrate that this z-score algorithm outperforms the previous approach. Further, in a large cohort of autoantibody-defined Sjögren’s Syndrome (SS) patient sera, PhIP-Seq robustly identified Ro52, Ro60, and SSB/La as known autoantigens associated with SS. In an effort to identify novel SS-specific binding specificities, SS z-scores were compared with z-scores obtained by screening Ropositive sera from patients with systemic lupus erythematosus (SLE). This analysis did not yield any commonly targeted SS-specific autoantigens, suggesting that if they exist at all, their epitopes are likely to be discontinuous or post-translationally modified. In summary, we have developed an improved algorithm for PhIP-Seq data analysis, which was validated using a large set of sera with clinically characterized autoantibodies. This z-score approach will substantially improve the ability of PhIP-Seq to detect and interpret antibody binding specificities. The associated Python code is freely available for download here: https://github.com/LarmanLab/PhIP-Seq-Analyzer.
Interaction paths promote module integration and network-level robustness of spliceosome to cascading effects
Authors: Guimarães Paulo R. , Pires Mathias M. , Cantor Maurício , Coltri Patricia P.
Published: April 2018

The functionality of distinct types of protein networks depends on the patterns of protein-protein interactions. A problem to solve is understanding the fragility of protein networks to predict system malfunctioning due to mutations and other errors. Spectral graph theory provides tools to understand the structural and dynamical properties of a system based on the mathematical properties of matrices associated with the networks. We combined two of such tools to explore the fragility to cascading effects of the network describing protein interactions within a key macromolecular complex, the spliceosome. UsingS. cerevisiaeas a model system we show that the spliceosome network has more indirect paths connecting proteins than random networks. Such multiplicity of paths may promote routes to cascading effects to propagate across the network. However, the modular network structure concentrates paths within modules, thus constraining the propagation of such cascading effects, as indicated by analytical results from the spectral graph theory and by numerical simulations of a minimal mathematical model parameterized with the spliceosome network. We hypothesize that the concentration of paths within modules favors robustness of the spliceosome against failure, but may lead to a higher vulnerability of functional subunits which may affect the temporal assembly of the spliceosome. Our results illustrate the utility of spectral graph theory for identifying fragile spots in biological systems and predicting their implications.
Three new genome assemblies support a rapid radiation in Musa acuminata (wild banana)
Authors: Rouard M , Droc G , Martin G , Sardos J , Hueber Y , Guignon V , Cenci A , Geigle B , Hibbins M S , Yahiaoui N , Baurens F-C , Berry V , Hahn M W , D’Hont A , Roux N
Published: April 2018

Edible bananas result from interspecific hybridization between Musa acuminata and Musa balbisiana, as well as among subspecies in M. acuminata. Four particular M. acuminata subspecies have been proposed as the main contributors of edible bananas, all of which radiated in a short period of time in southeastern Asia. Clarifying the evolution of these lineages at a whole-genome scale is therefore an important step toward understanding the domestication and diversification of this crop. This study reports the de novo genome assembly and gene annotation of a representative genotype from three different subspecies of M. acuminata. These data are combined with the previously published genome of the fourth subspecies to investigate phylogenetic relationships and genome evolution. Analyses of shared and unique gene families reveal that the four subspecies are quite homogenous, with a core genome representing at least 50% of all genes and very few M. acuminata species-specific gene families. Multiple alignments indicate high sequence identity between homologous single copy-genes, supporting the close relationships of these lineages. Interestingly, phylogenomic analyses demonstrate high levels of gene tree discordance, due to both incomplete lineage sorting and introgression. This pattern suggests rapid radiation within Musa acuminata subspecies that occurred after the divergence with M. balbisiana. Introgression between M. a. ssp. malaccensis and M. a. ssp. burmannica was detected across a substantial portion of the genome, though multiple approaches to resolve the subspecies tree converged on the same topology. To support future evolutionary and functional analyses, we introduce the PanMusa database, which enables researchers to exploration of individual gene families and trees.
Genetic diversity of CHC22 clathrin impacts its function in glucose metabolism
Authors: Fumagalli Matteo , Camus Stephane M. , Diekmann Yoan , Burke Alice , Camus Marine D. , Norman Paul J. , Joseph Agnel Praveen , Abi-Rached Laurent , Benazzo Andrea , Rasteiro Rita , Mathieson Iain , Topf Maya , Parham Peter , Thomas Mark G. , Brodsky Frances M.
Published: April 2018

CHC22 clathrin plays a key role in intracellular membrane traffic of the insulin-responsive glucose transporter GLUT4 in humans. We performed population genetic and phylogenetic analyses of the CHC22-encodingCLTCL1gene, revealing independent gene loss in at least two vertebrate lineages, after arising from gene duplication. All vertebrates retained the paralogousCLTCgene encoding CHC17 clathrin, which mediates endocytosis. For vertebrates retainingCLTCL1, strong evidence for purifying selection supports CHC22 functionality. All human populations maintained two high frequencyCLTCL1allelic variants, encoding either methionine or valine at position 1316. Functional studies indicated that CHC22-V1316, which is more frequent in farming populations than in hunter-gatherers, has different cellular dynamics than M1316-CHC22 and is less effective at controlling GLUT4 membrane traffic, attenuating its insulin-regulated response. These analyses suggest that ancestral human dietary change influenced selection of allotypes that affect CHC22’s role in metabolism and have potential to differentially influence the human insulin response.
Alopecia areata susceptibility variant identified by MHC risk haplotype sequencing reproduces symptomatic patched hair loss in mice
Authors: Oka Akira , Takagi Atsushi , Komiyama Etsuko , Mano Shuhei , Hosomichi Kazuyoshi , Suzuki Shingo , Motosugi Nami , Hatanaka Tomomi , Kimura Minoru , Takahashi Ueda Mahoko , Nakagawa So , Miura Hiromi , Ohtsuka Masato , Haida Yuko , Tanaka Masayuki , Komiyama Tomoyoshi , Otomo Asako , Hadano Shinji , Mabuchi Tomotaka , Beck Stephan , Inoko Hidetoshi , Ikeda Shigaku
Published: April 2018

Background

Alopecia areata (AA) is a highly heritable multifactorial and complex disease. However, no convincing susceptibility gene has yet been pinpointed in the major histocompatibility complex (MHC), a region in the human genome known to be associated with AA as compared to other regions.

Results

By sequencing MHC risk haplotypes, we identified a variant (rs142986308, p.Arg587Trp) in the coiled-coil alpha-helical rod protein 1 (CCHCR1) gene as the only non-synonymous variant in the AA risk haplotype. Using CRISPR/Cas9 for allele-specific genome editing, we then phenocopied AA symptomatic patched hair loss in mice engineered to carry theCchcr1risk allele. Skin biopsies of these alopecic mice showed strong up-regulation of hair-related genes, including hair keratin and keratin-associated proteins (KRTAPs). Using transcriptomics findings, we further identified CCHCR1 as a novel component of hair shafts and cuticles in areas where the engineered alopecic mice displayed fragile and impaired hair.

Conclusions

These results suggest an alternative mechanism for the aetiology of AA based on aberrant keratinization, in addition to generally well-known autoimmune events.
Strength in numbers: collaborative science for new experimental model systems
Authors: Waller Ross F. , Cleves Phillip A. , Rubio-Brotons Maria , Woods April , Bender Sara J. , Edgcomb Virginia , Gann Eric R. , Jones Adam C. , Teytelman Leonid , von Dassow Peter , Wilhelm Steven W. , Collier Jackie L.
Published: April 2018

Our current understanding of biology is heavily based on the contributions from a small number of genetically tractable model organisms. Most eukaryotic phyla lack such experimental models, and this limits our ability to explore the molecular mechanisms that ultimately define their biology, ecology, and diversity. In particular, marine protists suffer from a paucity of model organisms despite playing critical roles in global nutrient cycles, food webs, and climate. To address this deficit, an initiative was launched in 2015 to foster development of ecologically and taxonomically diverse marine protist genetic models. This multifaceted, complex but important challenge required a highly collaborative community-based approach. Herein we describe this approach, the advances achieved, and the lessons learned by participants in this novel community-based model for research.
Probing the chemical-biological relationship space with the Drug Target Explorer
Authors: Allaway Robert , Rosa Salvatore La , Guinney Justin , Gosline Sara
Published: April 2018

Modern phenotypic high-throughput screens (HTS) present several challenges including identifying the target(s) that mediate the effect seen in the screen, characterizing ‘hits’ with a polypharmacologic target profile, and contextualizing screen data within the large potential space of drugs and biological screening model combinations. To address these challenges, we developed an interactive web application that enables exploration of the chemical-biological interaction space. Compound-target interaction data from public resources were quantified for over 280,000 molecules. Each molecule was annotated with a name and chemical structure, and every target was annotated with gene identifiers. The Drug-Target Explorer allows users to query molecules within this database of experimentally-derived and curated compound-target interactions and identify structurally similar molecules. It also enables network-based visualizations of the compound-target interaction space, and incorporates comparisons to publicly-availablein vitroHTS datasets. Users can also identify compounds given one or more targets of interest. The Drug Target Explorer is a multifunctional platform for exploring chemical space as it relates to biological targets, and may be useful at several steps along the drug development pipeline including target discovery, structure-activity relationship, and lead compound identification studies.
Force-based three-dimensional model predicts mechanical drivers of cell sorting
Authors: Revell Christopher , Blumenfeld Raphael , Chalut Kevin
Published: April 2018

Many biological processes, including tissue morphogenesis, are driven by mechanical sorting. However, the primary mechanical drivers of cell sorting remain controversial, in part because there remains a lack of appropriate threedimensional computational methods to probe the mechanical interactions that drive sorting. To address this important issue, we developed a three-dimensional, local force-based simulation method to enable such investigation into the sorting mechanisms of multicellular aggregates. Our method utilises the subcellular element method, in which cells are modeled as collections of locally-interacting force-bearing elements, accommodating cell growth and cell division. We define two different types of intracellular elements, assigning different attributes to boundary elements to model a cell cortex, which mediates the interfacial interaction between different cells. By tuning interfacial adhesion and tension in each cell cortex, we can control and predict the degree of sorting in cellular aggregates. The method is validated by comparing the interface areas of simulated cell doublets to experimental data and to previous theoretical work. We then define numerical measures of sorting and investigate the effects of mechanical parameters on the extent of sorting in multicellular aggregates. Using this method, we find that a minimum adhesion is required for differential interfacial tension to produce inside-out sorting of two cell types with different mechanical phenotypes. We predict the value of the minimum adhesion, which is in excellent agreement with observations in several developmental systems. We also predict the level of tension asymmetry needed for robust sorting. The generality and flexibility of the method make it applicable to tissue self-organization in a myriad of biological processes, such as tumorigenesis and embryogenesis.
Influence of different modes of morphological character correlation on phylogenetic tree inference
Authors: Guillerme Thomas , Brazeau Martin D.
Published: April 2018

Phylogenetic analysis algorithms require the assumption of character independence - a condition generally acknowledged to be violated by morphological data. Correlation between characters can originate from intra-organismal features, shared phylogenetic history or forced by particular character-state coding schemes. Although the two first sources can be investigated by biologists a posteriori and the third one can be avoided a priori with good practices, phylogenetic software do not distinguish between any of them.

In this study, we propose a new metric of raw character difference as a proxy for character correlation. Using thorough simulations, we test the effect of increasing or decreasing character differences on tree topology. Overall, we found an expected positive effect of reducing character correlations on recovering the correct topology. However, this effect is less important for matrices with a small number of taxa (25 in our simulations) where reducing character correlation is not more effective than randomly drawing characters. Furthermore, in bigger matrices (350 characters), there is a strong effect of the inference method with Bayesian trees being consistently less affected by character correlation than maximum parsimony trees.

These results suggest that ignoring the problem of character correlation or independence can often impact topology in phylogenetic analysis. However, encouragingly, they also suggest that, unless correlation is actively maximised or minimised, probabilistic methods can easily accommodate for a random correlation between characters.
Edge orientation perception during active touch
Authors: Olczak Derek , Sukumar Vaishnavi , Andrew Pruszynski J.
Published: April 2018

Previous studies investigating the perceptual attributes of tactile edge-orientation processing have applied their stimuli to an immobilized fingertip. Here we tested the perceptual attributes of edge orientation processing when participants actively touched the stimulus. Our participants moved their finger over two pairs of edges–one pair parallel and the other nonparallel to varying degrees–and were asked to identify which of the two pairs was nonparallel. In addition to the psychophysical estimates of edge orientation acuity, we measured the speed at which participants moved their finger and the forces they exerted when moving their finger over the stimulus. We report four main findings. First, edge orientation acuity during active touch averaged 12.4°, similar to that previously reported during passive touch. Second, on average, participants moved their finger over the stimuli at 23.9 mm/s and exerted contact forces of 0.47 N. Third, across participants, there was no clear relationship between how people moved their finger or how they pressed on the stimulus and their edge orientation acuity. However, within participants, there appeared to be a weak effect of speed on performance whereby error trials included slightly faster finger movements; no equivalent effect was found for contact force. Fourth, consistent with previous work testing spatial acuity, we found significant correlation between fingertip size and orientation acuity such that people with smaller fingertips tended to have better orientation acuity.
Interspecies DNA acquisition by a naturally competentAcinetobacter baumanniistrain
Authors: Traglia German M. , Place Kori , Dotto Cristian , Fernandez Jennifer S. , Bahiense Camila dos Santos , Soler-Bistue Alfonso , Iriarte Andres , Tolmasky Marcelo E. , Bonomo Robert A , Melano Roberto G. , Ramírez María Soledad
Published: April 2018

Acinetobacter baumanniiis a human pathogen that frequently acquires antibiotic resistance genes leading to the emergence of multi-drug-resistant (MDR) strains. To investigate the role of transformation in the acquisition of resistance determinants by this species, the susceptible strain A118 was exposed to genomic DNA of carbapenem-resistantKlebsiella pneumoniae(CRKp). Resistant transformants were obtained and an increase in the resistance level to all β-lactam antibiotics was observed. Whole genome analysis of transformant clones demonstrated the acquisition of CRKp DNA. The most frequently acquired genes correspond to mobile elements, antibiotic resistance genes, and operons involved in metabolism. Bioinformatic analyses andin silicogene flow prediction strengthen our findings, showing that a continuing exchange of genetic material betweenA. baumanniiandK. pneumoniaeoccurs when they share the same niche. Our results reinforce the idea that natural transformation may play a key role in the increasing emergence ofA. baumanniiMDR.

IMPORTANCE

Since the characterization of antibiotic resistance in the late ‘50s, antibiotic resistance propagation was classically associated with horizontal gene transfer (HGT) mediated by plasmids bearing multiple resistance genes. Here we show that, at least in the human pathogenA. baumannii, transformation also plays a major role in the acquisition of antibiotic resistance determinants. This study unravels that at least for certain pathogens the propagation of resistance genes occurs by alternative HGT mechanisms which in the past have been unappreciated.
The lipid droplet protein Pgc1 controls the subcellular distribution of phosphatidylglycerol
Authors: Kubalová Dominika , Veselá Petra , Awadová Thuraya , Daum Günther , Malínský Jan , Balážová Mária
Published: April 2018

The biosynthesis of yeast phosphatidylglycerol (PG) takes place in the inner mitochondrial membrane. Outside mitochondria, the abundance of PG is low. Here we present evidence that the subcellular distribution of PG is maintained by locally controlled enzymatic activity of the PG-specific phospholipase, Pgc1. We document that the Pgc1 absence leads to spreading of PG over various cellular membranes. Fluorescently labeled Pgc1 protein strongly accumulates at the surface of lipid droplets (LD). We show, however, that LD are not only dispensable for Pgc1-mediated PG degradation, but even host no phospholipase activity of Pgc1. Ourin vitroassays document the capability of LD-accumulated Pgc1 to degrade PG upon entry to membranes of the endoplasmic reticulum, mitochondria, and even of artificial phospholipid vesicles. FRAP analysis confirms continuous exchange of GFP-Pgc1 within individual LDin situ, suggesting that a steady-state equilibrium exists between LD and membranes to regulate immediate phospholipase activity of Pgc1. In this model, LD serve as storage place and shelter Pgc1 preventing untimely degradation, while both phospholipase activity and degradation of the enzyme occur in membranes.
Structural, functional and molecular dynamics analysis of cathepsin B gene SNPs associated with tropical calcific pancreatitis, a rare disease of tropics
Authors: Singh Garima , Jayadev MSK , Sharma Rinku , Bhat Basharat , Madhusudhan CH , Singh Ashutosh
Published: April 2018

Tropical Calcific Pancreatitis (TCP) is a neglected juvenile form of chronic non-alcoholic pancreatitis. Cathepsin B (CTSB), a lysososmal protease involved in cellular degradation process, is recently been studied as a potential candidate gene in the pathogenesis of TCP. According to cathepsin B hypothesis, mutated CTSB can lead to premature intracellular activation of trypsinogen, which is a key regulatory mechanism in pancreatitis. So far, CTSB mutations have been studied in pancreatitis and neurodegenerative disorders but little is known about the structural and functional effect of variants in CTSB. In this study, we investigated the effect of single nucleotide variants (SNVs) associated with TCP, using molecular dynamics and simulation algorithms. There were two non-synonymous variants in the coding region (L26V and S53G) of CTSB, located in the propeptide region. We tried to predict the effect of these variants on structure and function using multiple algorithms: SIFT, Polyphen2, Panther, SDM sever, i-Mutant2.0 suite, mCSM algorithm and Vadar. Further, using databases like miRdbSNP, PolymiRTS and miRNASNP, two SNPs in 3’UTR region were predicted to affect the miRNA binding sites. Structural mutated models of nsSNP mutants (L26V and S53G) were prepared by MODELLER v9.15 and evaluated using TM-Align, Verify 3D, ProSA and Ramachandran plot. The results showed that the models (L26V and S53G) were of high accuracy. The 3D mutated structures were simulated using GROMACS 5.0 to predict the impact of these SNPs on protein stability. The results from in silico analysis and molecular dynamics simulations suggested that these variants in the propeptide region of cathepsin B could lead to structural and functional changes in the protein. Hence, the structural and functional analysis results have given interim conclusions that these variants can have deleterious effect in TCP and thus should be screen in samples from all TCP patients to decipher its distribution in patient population.
Homeostatic plasticity scales dendritic spine volumes and changes the threshold and specificity of Hebbian plasticity
Authors: Hobbiss Anna F. , Cortés Yazmin Ramiro , Israely Inbal
Published: April 2018

Information is encoded within neural networks through synaptic weight changes. Synaptic learning rules involve a combination of rapid Hebbian plasticity with slower homeostatic synaptic plasticity (HSP) that regulates neuronal activity through global synaptic scaling. While Hebbian plasticity has been extensively investigated, much less is known about HSP. Here we investigate the structural and functional consequences of HSP at dendritic spines of mouse hippocampal neurons. We find that prolonged activity blockade induces spine growth, paralleling synaptic strength increases. Following activity blockade, glutamate uncaging-mediated long-term potentiation at single spines leads to size-dependent structural plasticity: smaller spines undergo robust growth, while larger spines remain unchanged. Moreover, we find that neighboring spines in the vicinity of the stimulated spine exhibit volume changes following HSP, indicating that plasticity has spread across a group of synapses. Overall, these findings demonstrate that Hebbian and homeostatic plasticity shape neural connectivity through coordinated structural plasticity of clustered inputs.
Distinctive types of postzygotic single-nucleotide mosaicisms in healthy individuals revealed by genome-wide profiling of multiple organs
Authors: Yue Huang August , Yang Xiaoxu , Wang Sheng , Zheng Xianing , Wu Qixi , Yongxin Ye Adam , Wei Liping
Published: April 2018

Postzygotic single-nucleotide mosaicisms (pSNMs) have been extensively studied in tumors and are known to play critical roles in tumorigenesis. However, the patterns and origin of pSNMs in normal organs of healthy humans remain largely unknown. Using whole-genome sequencing and ultra-deep amplicon re-sequencing, we identified and validated 164 pSNMs from 27 postmortem organ samples obtained from five healthy donors. The mutant allele fractions ranged from 1.0% to 29.7%. Inter- and intra-organ comparison revealed two distinctive types of pSNMs, with about half originating during early embryogenesis (embryonic pSNMs) and the remaining more likely to result from clonal expansion events that had occurred more recently (clonal expansion pSNMs). Compared to clonal expansion pSNMs, embryonic pSNMs had higher proportion of C>T mutations with elevated mutation rate at CpG sites. We observed differences in replication timing between these two types of pSNMs, with embryonic and clonal expansion pSNMs enriched in early- and late-replicating regions, respectively. An increased number of embryonic pSNMs were located in open chromatin states and topologically associating domains that transcribed embryonically. Our findings provide new insights into the origin and spatial distribution of postzygotic mosaicism during normal human development.

Author Summary

Genomic mosaicism led by postzygotic mutation is the major cause of cancers and many non-cancer developmental disorders. Theoretically, postzygotic mutations should be accumulated during the developmental process of healthy individuals, but the genome-wide characterization of postzygotic mosaicisms across many organ types of the same individual remained limited. In this study, we identified and validated two types of postzygotic mosaicism from the whole-genomes of 27 organs obtained from five healthy donors. We further found that the postzygotic mosaicisms arising during early embryogenesis and later clonal expansion events show distinct genomic patterns in mutation spectrum, replication timing, and chromatin status.
Elevated alpha-1 antitrypsin is a major component of GlycA-associated risk for future morbidity and mortality
Authors: Ritchie Scott C. , Kettunen Johannes , Brozynska Marta , Nath Artika P. , Havulinna Aki S. , Männistö Satu , Perola Markus , Salomaa Veikko , Ala-Korpela Mika , Abraham Gad , Würtz Peter , Inouye Michael
Published: April 2018

Integration of electronic health records with systems-level biomolecular data has led to the discovery that GlycA, a complex nuclear magnetic resonance (NMR) spectroscopy biomarker, predicts long-term risk of disease onset and death from myriad causes. To determine the molecular underpinnings of the disease risk of the heterogeneous GlycA signal, we used machine learning to build imputation models for GlycA’s constituent glycoproteins, then estimated glycoprotein levels in 11,861 adults across two population-based cohorts with long-term follow-up. While alpha-1-acid glycoprotein had the strongest correlation with GlycA, our analysis revealed that alpha-1 antitrypsin (AAT) was the most predictive of morbidity and mortality for the widest range of diseases, including heart failure (HR=1.60 per s.d., P=1×10−10), influenza and pneumonia (HR=1.37, P=6×10−10), and liver diseases (HR=1.81, P=1×10−6). Despite emerging evidence of AAT's role in suppressing inflammation, transcriptional analyses revealed elevated expression of diverse inflammatory immune pathways with elevated AAT levels, suggesting AAT is elevating to compensate for low-grade chronic inflammation. This study clarifies the molecular underpinnings of the GlycA biomarker and its associated disease risk, and indicates a previously unrecognised association between elevated AAT and severe disease onset and mortality.
Domain swap in the C-terminal ubiquitin-like domain of human doublecortin
Authors: Rufer Arne C. , Kusznir Eric , Burger Dominique , Stihle Martine , Ruf Armin , Rudolph Markus G.
Published: April 2018

Doublecortin, a microtubule-associated protein that is only produced during neurogenesis, cooperatively binds to microtubules and stimulates microtubule polymerization and cross-linking by unknown mechanisms. A domain swap is observed in the crystal structure of the C-terminal domain of doublecortin. As determined by analytical ultracentrifugation, an open conformation is also present in solution. At higher concentrations, higher-order oligomers of the domain are formed. The domain swap and additional interfaces observed in the crystal lattice can explain the formation of doublecortin tetramers or multimers, in line with the analytical ultracentrifugation data. Taken together, the domain swap offers a mechanism for the observed cooperative binding of doublecortin to microtubules. Doublecortin-induced cross-linking of microtubules can be explained by the same mechanism. The effect of several mutations leading to lissencephaly and double-cortex syndrome can be traced to the domain swap and the proposed self-association of doublecortin.
Why people use social networking sites passively
Authors: Zhu Xinhua , Bao Zheshi
Published: April 2018

Purpose

The purpose of this paper is to explore the underlying mechanism of how passive social networking site (SNS) use happens from aspects of impression management concern, privacy concern, and SNS fatigue, and then examine whether sense of membership can work as a moderator in this process.

Design/methodology/approach

The authors proposed a research model by integrating impression management concern, privacy concern, and SNS fatigue. A total of 301 valid online questionnaires were collected, and these data were assessed by PLS-SEM.

Findings

The results show that both impression management concern and privacy concern have direct and positive effects on passive SNS use, and meanwhile they can also indirectly and positively affect passive SNS use through SNS fatigue. Besides, the relationships between impression management concern and its outcomes (SNS fatigue and passive SNS use) can be moderated by sense of membership.

Originality/value

This research is novel in focusing on the formation of passive SNS use and providing new insight into some factors which can trigger users’ passive behaviors in SNS usage. The findings will contribute to SNS literature by offering a well proven conceptual model that facilitates the understanding of passive SNS use.
Intra-national diversity
Authors: Stamenkovic Srecko , Ratkovic Njegovan Biljana , Vukadinovic Maja S.
Published: April 2018

Purpose

The purpose of this paper is to investigate the impact of organizational justice on the ethical climate in organizations in Serbia.

Design/methodology/approach

In the study, 3,413 employees participated whose task was to assess the dimensions of organizational justice (procedural, distributive and interactional) as well as the dimensions of ethical climate (egoism, benevolence and principle).

Findings

The obtained results show that the dimensions of organizational justice are significant predictors of dimensions of ethical climate. The dimension of distributive justice significantly predicts the dimensions of egoism and principle, while the dimensions of procedural and interactional justice significantly predict the dimensions of benevolence and principle. Concerning the structure of the relationship between dimensions of organizational justice and ethical climate, the results also showed that there is intra-national diversity depending on the region of the Republic of Serbia where the organization operates. Ethical climate based on maximization of personal interest is more connected to economically more developed regions with a larger population, while ethical climate based on duties related to norms, laws, rules and policies characterizes less developed regions with a smaller population.

Originality/value

In the context of contemporary Serbian business surrounding, the obtained results are discussed regarding the possibilities for improvement of ethical climate, which should be accompanied and supported by the positive impact of organizational justice.
Rural residents’ understanding and willingness to pay higher prices for mitigation against global warming in China
Authors: Chang Genying
Published: April 2018

Purpose

Studies addressing rural residents’ understanding of global warming and their willingness to pay higher prices to mitigate it are very limited. The purpose of this study is to examine the general understanding and attitudes of rural residents in China regarding global warming and their willingness to pay higher prices to mitigate it.

Design/methodology/approach

This study surveyed 1,185 rural residents in three counties of coastal, middle and western China. Multivariate regression analysis was conducted to reveal the relationships between the willingness to pay higher prices to mitigate global warming and influencing factors.

Findings

The majority of respondents had heard of global warming; however, their knowledge of the phenomenon and its causes was very limited. Most respondents admitted the likelihood of risks from global warming. Although most respondents thought they had an obligation to mitigate global warming, only a small percentage of them were willing to pay higher prices to address the problem; the unwillingness of respondents to pay higher prices to mitigate global warming may have been associated with their low income and perceived inability to handle the cost, externalisation of responsibility and causes and lack of knowledge of how to affect it.

Originality/value

This study examines the general understanding and attitudes of rural residents in China regarding global warming and their willingness to pay higher prices to mitigate it. The research is conducive to climate change communications and the implementation of climate policies in China’s rural areas.
Customer online shopping experience data analytics
Authors: Wong Eugene , Wei Yan
Published: April 2018

Purpose

The purpose of this paper is to develop a customer online behaviour analysis tool, segment high-value customers, analyse their online purchasing behaviour and predict their next purchases from an online air travel corporation.

Design/methodology/approach

An operations review of the customer online shopping process of an online travel agency (OTA) is conducted. A customer online shopping behaviour analysis tool is developed. The tool integrates competitors’ pricing data mining, customer segmentation and predictive analysis. The impacts of competitors’ price changes on customer purchasing decisions regarding the OTA’s products are evaluated. The integrated model for mining pricing data, identifying potential customers and predicting their next purchases helps the OTA recommend tailored product packages to its individual customers with reference to their travel patterns.

Findings

In the customer segmentation analysis, 110,840 customers are identified and segmented based on their purchasing behaviour. The relationship between the purchasing behaviour in an OTA and the price changes of different OTAs are analysed. There is a significant relationship between the flight duration time and the purchase lead time. The next travel destinations of segmented high-value customers are predicted with reference to their travel patterns and the significance of the relationships between destination pairs.

Practical implications

The developed model contributes to pricing evaluation, customer segmentation and package customization for online customers.

Originality/value

This study provides novel method and insights into customer behaviour towards OTAs through an integrated model of customer segmentation, customer behaviour and prediction analysis.
Something old, something new: the role of partitioned pricing in consumers’ preference for new versus used products
Authors: Crosno Jody L. , Cui Annie Peng
Published: April 2018

Purpose

This research aims to represent an initial exploration of how partitioned pricing influences consumers’ purchase decisions of new versus used products from the theoretical perspectives of prospect theory and gain/loss decision frames.

Design/methodology/approach

Four experiments to test the hypotheses with multiple product categories have been conducted.

Findings

Results from a series of experimental studies find that consumers prefer partitioned pricing over all-inclusive pricing for new products, whereas all-inclusive pricing is more preferred for used products. In addition, the authors demonstrate that a high-quality brand can reverse this effect for used products; specifically, consumers prefer partitioned pricing over all-inclusive pricing for a used product with a high-quality brand.

Originality/value

This research contributes to the literature on second-hand consumption by examining the impact of pricing strategies on consumer purchase decisions of new versus used products. This study deepens our understanding of consumer decision-making for new versus used products and it provides implications for bolstering sustainable consumption.
Price promotions: examining the buyer mix and subsequent changes in purchase loyalty
Authors: Dawes John G.
Published: April 2018

Purpose

This paper aims to investigate the extent to which temporary price promotions attract people who do not normally buy a brand, and whether buyers change their propensity to buy the promoted brand afterwards.

Design/methodology/approach

The study analyses promotions in 18 consumer goods categories in the UK and USA. It calculates the proportion of promotion purchasers that have bought a brand at least once in their last five purchases and the Share of Category Requirements of those purchasers. These figures are then compared to normal-price purchasers.

Findings

The study finds the majority of price-promotion buyers already bought the brand at least once in their last five category purchases (average = 77 per cent). This figure is similar to that for normal-price purchases (average = 81 per cent). Average Household SCR to the brand is also very similar for price-promotion purchases compared to normal price purchases. Therefore, promotions do not attract a markedly different mix of buyers. Furthermore, buyer propensity to buy the brand is the same after a promotion purchase as it was before.

Research limitations/implications

A contribution of the paper is that it supports a theory of consumers as cognitive misers, who screen out promotion information about unfamiliar brands. The paper also highlights that in packaged-goods markets, consumers can be generally seen as experienced buyers, who do not learn new information from buying brands they have previously purchased.

Practical implications

The managerial implication is that price promotions must be judged on their immediate profitability. There seems little recourse to the idea they can result in “try it, like it, buy it again later” effects.

Originality/value

While many studies have examined the effects of price promotions, this is the first to explicitly compare the mix of buyers attracted from a price promotion to that which occurs when a brand is sold at normal price.
Antecedents to consumers’ showrooming behaviour: an integrated TAM-TPB framework
Authors: Arora Sourabh , Sahney Sangeeta
Published: April 2018

Purpose

The purpose of this study is to propose an integrated framework utilizing the theory of planned behaviour (TPB) and technology acceptance model (TAM) to augment the understanding on consumers’ showrooming behaviour.

Design/methodology/approach

Selective sampling was used for data collection. The integrated TAM-TPB framework led to 12 propositions, which were tested using partial least squares-structural equation modelling.

Findings

Both perceived relative search benefits offline and relative purchase benefits online significantly determined the consumers’ showrooming behaviour along with perceived ease purchasing online and the overall usefulness of the showrooming sequence. Results of the study revealed that the showrooming sequence helped consumers avoid the regret of making suboptimal product choices and paying a higher price for the same product. Online trust was found to partially mediate the relationship between consumers’ intention to showrooming and the actual showrooming behaviour.

Research limitations/implications

Notwithstanding the fact that further research is required to arrive at definitive conclusions, this study is an initial move towards understanding the consumers’ showrooming behaviour, and the research provides meaningful insights.

Practical implications

As showrooming substantially erodes profits, devising strategies to defend showrooming customers becomes crucial. The findings of the study provide the basis for formulating strategies to counter showrooming customers.

Originality/value

The paper is amongst the first studies which helps enhance the understanding of consumers’ showrooming behaviour, which is an emerging area in the present multi-channel retailing environment.