bluuebunny/crossref_metadata_2025 huggingface dataset:
Empirical Analyses of Associations between State Political Attitudes and Gains in Health Insurance Coverage after the Affordable Care Act (ACA)
Authors: Sen Bisakha , Joseph Reena
Published: April 2019

Objectives

To explore whether state-level political-sentiment is associated with gains in insurance post Affordable Care Act (ACA). This is especially relevant given the lawsuit brought by several Republican-leaning states against the ACA, and the ruling of one Texas federal judge that the ACA is unconstitutional, which potentially jeopardizes ACA’s future.

Methods

Multivariate linear-probability models are estimated using data from the Behavioral Risk Factor Surveillance Systems for 2011-2017. The outcome is self-reported insurance status. States are placed in quartiles based on votes for President Obama in 2008 and 2012 elections. Starting 2014, ACA health exchanges became active and several states expanded Medicaid, so 2014 onwards is considered as the ‘post-ACA’ period. Models are estimated for all adults under 65-years and for young adults under 35-years. All models control extensively for respondent socio-economic-demographic characteristics and state characteristics.

Results

In the pre-ACA baseline period, respondents in states with higher Anti-Obama-voting (AOV) were less likely to have insurance. For example, residents in highest AOV-quartile states were 8.0-percentage-points less likely (p<0.001) to have insurance than those in the lowest AOV-quartile states. Post-ACA, fewer high AOV-quartile states expanded Medicaid, and overall insurance gains inclusive of Medicaid-expansion are similar across states. However, net of Medicaid-expansion, residents in higher AOV states saw higher insurance gains. For example, all adults had 2.8-percentage points higher likelihood (p<0.01) and young adults had 4.9-percentage point higher likelihood (p<0.01) of getting insurance in the highest AOV-quartile states compared to the lowest AOV quartile states. Minorities and those with chronic-conditions had larger insurance gains across the country post-ACA, but the extent of these gains did not differ by state AOV levels.

Conclusions

State AOV and insurance gains from ACA appear to be incongruent. Policymakers and stakeholders should be aware that non-Medicaid residents of higher-AOV states might potentially lose the most if ACA is revoked.
Structural instability and divergence from conserved residues underlie intracellular retention of mammalian odorant receptors
Authors: Ikegami Kentaro , de March Claire A. , Nagai Maira H. , Ghosh Soumadwip , Do Matthew , Sharma Ruchira , Bruguera Elise S. , Lu Yueyang Eric , Fukutani Yosuke , Vaidehi Nagarajan , Yohda Masafumi , Matsunami Hiroaki
Published: April 2019

Mammalian odorant receptors are a diverse and rapidly evolving set of G protein-coupled receptors expressed in olfactory cilia membranes. Most odorant receptors show little to no cell surface expression in non-olfactory cells due to endoplasmic reticulum retention, which has slowed down biochemical studies. Here, we provide evidence that structural instability and divergence from conserved residues of individual odorant receptors underlie intracellular retention using a combination of large-scale screening of odorant receptors cell surface expression in heterologous cells, point mutations, structural modeling, and machine learning techniques. We demonstrate the importance of conserved residues by synthesizing “consensus” odorant receptors that show high levels of cell surface expression similar to conventional G protein-coupled receptors. Furthermore, we associate in silico structural instability with poor cell surface expression using molecular dynamics simulations. We propose an enhanced evolutionary capacitance of olfactory sensory neurons that enable the functional expression of odorant receptors with cryptic mutations.

Significance Statement

Odor detection in mammals depends on the largest family of G protein-coupled receptors, the odorant receptors, which represent ∼2% of our protein-coding genes. The vast majority of odorant receptors are trapped within the cell when expressed in non-olfactory cells. The underlying causes of why odorant receptors cannot be functionally expressed in non-olfactory cells have remained enigmatic for over 20 years. Our study points to divergence from a consensus sequence as a key factor in a receptor’s inability to function in non-olfactory cells, which in turn, helps explain odorant receptors’ exceptional functional diversity and rapid evolution. We also show the success of protein engineering strategies for promoting odorant receptor cell surface expression.
CNTNAP2 ectodomain, detected in neuronal and CSF sheddomes, modulates Ca2+ dynamics and network synchrony
Authors: Martin-de-Saavedra M. Dolores , dos Santos Marc , Varea Olga , Spielman Benjamin P. , Gao Ruoqi , Forrest Marc , Myczek Kristoffer , Khalatyan Natalia , Hall Elizabeth A. , Sanz-Clemente Antonio , Comoletti Davide , Lichtenthaler Stefan F. , Savas Jeffrey N. , Penzes Peter
Published: April 2019

SUMMARY

While many neuronal membrane-anchored proteins undergo proteolytic cleavage, little is known about the biological significance of neuronal ectodomain shedding. Using mass spectrometry (MS)-based proteomics, we showed that the neuronal sheddome mirrors human cerebrospinal fluid (hCSF). Among shed synaptic proteins in hCSF was the ectodomain of CNTNAP2 (CNTNAP2-ecto), a risk factor for neurodevelopmental disorders (NDD). Using structured-illumination microscopy (SIM), we mapped the spatial organization of neuronal CNTNAP2-ecto shedding. Using affinity chromatography followed by MS, we identified the ATP2B/PMCA Ca2+ extrusion pumps as novel CNTNAP2-ecto binding partners. CNTNAP2-ecto coimmunoprecipitates with PMCA2, a known autism risk factor, and enhances its activity, thereby modulating neuronal Ca2+ levels. Finally, we showed that CNTNAP2-ecto regulates neuronal network synchrony in primary cultures and brain slices. These data provide new insights into the biology of synaptic ectodomain shedding and reveal a novel mechanism of regulation of Ca2+ homeostasis and neuronal network synchrony.
Horizontal acquisition followed by expansion and diversification of toxin-related genes in deep-sea bivalve symbionts
Authors: Sayavedra Lizbeth , Ansorge Rebecca , Rubin-Blum Maxim , Leisch Nikolaus , Dubilier Nicole , Petersen Jillian M.
Published: April 2019

Deep-sea bathymodioline mussels gain their nutrition from intracellular bacterial symbionts. Their sulfur-oxidizing (SOX) symbionts were recently shown to encode abundant toxin-related genes (TRGs) in their genomes, which may play a role in beneficial host-microbe interactions. Here, we compared TRGs in the genomes of SOX symbionts from 10 bathymodioline mussel and two sponge species to better understand their potential functions and evolutionary origins. Despite the close phylogenetic relatedness of these symbionts, the number and classes of encoded toxins varied greatly between host species. One of the TRG classes, YDs, has experienced gene expansions multiple times, suggesting that these genes are under adaptive selection. Some symbiont genomes contained secretion systems, which can play a role in host-microbe interactions. Both TRGs and secretion systems had a heterogeneous distribution, suggesting that these closely related bacteria have acquired different molecular mechanisms for interacting with the same family of animal hosts, possibly through convergent evolution.
Monitoring contractility in single cardiomyocytes and whole hearts with bio-integrated microlasers
Authors: Schubert Marcel , Woolfson Lewis , Barnard Isla RM , Morton Andrew , Casement Becky , Robertson Gavin B , Miles Gareth B , Pitt Samantha J , Tucker Carl S , Gather Malte C
Published: April 2019

Cardiac regeneration and stem cell therapies depend critically on the ability to locally resolve the contractile properties of heart tissue1,2. Current regeneration approaches explore the growth of cardiac tissue in vitro and the injection of stem cell-derived cardiomyocytes3–6 (CMs) but scientists struggle with low engraftment rates and marginal mechanical improvements, leaving the estimated 26 million patients suffering from heart failure worldwide without effective therapy7–9. One impediment to further progress is the limited ability to functionally monitor injected cells as currently available techniques and probes lack speed and sensitivity as well as single cell specificity. Here, we introduce microscopic whispering gallery mode (WGM) lasers into beating cardiomyocytes to realize all-optical recording of transient cardiac contraction profiles with cellular resolution. The brilliant emission and high spectral sensitivity of microlasers to local changes in refractive index enable long-term tracking of individual cardiac cells, monitoring of drug administration, and accurate measurements of organ scale contractility in live zebrafish. Our study reveals changes in sarcomeric protein density as underlying factor to cardiac contraction which is of fundamental importance for understanding the mechano-biology of cardiac muscle activation. The ability to non-invasively assess functional properties of transplanted cells and engineered cardiac tissue will stimulate the development of novel translational approaches and the in vivo monitoring of physiological parameters more broadly. Likewise, the use of implanted microlasers as cardiac sensors is poised to inspire the adaptation of the most advanced optical tools known to the microresonator community, like quantum-enhanced single-molecule biosensing or frequency comb spectroscopy10.
A reference map of the human protein interactome
Authors: Luck Katja , Kim Dae-Kyum , Lambourne Luke , Spirohn Kerstin , Begg Bridget E. , Bian Wenting , Brignall Ruth , Cafarelli Tiziana , Campos-Laborie Francisco J. , Charloteaux Benoit , Choi Dongsic , Cote Atina G. , Daley Meaghan , Deimling Steven , Desbuleux Alice , Dricot Amélie , Gebbia Marinella , Hardy Madeleine F. , Kishore Nishka , Knapp Jennifer J. , Kovács István A. , Lemmens Irma , Mee Miles W. , Mellor Joseph C. , Pollis Carl , Pons Carles , Richardson Aaron D. , Schlabach Sadie , Teeking Bridget , Yadav Anupama , Babor Mariana , Balcha Dawit , Basha Omer , Bowman-Colin Christian , Chin Suet-Feung , Choi Soon Gang , Colabella Claudia , Coppin Georges , D’Amata Cassandra , De Ridder David , De Rouck Steffi , Duran-Frigola Miquel , Ennajdaoui Hanane , Goebels Florian , Goehring Liana , Gopal Anjali , Haddad Ghazal , Hatchi Elodie , Helmy Mohamed , Jacob Yves , Kassa Yoseph , Landini Serena , Li Roujia , van Lieshout Natascha , MacWilliams Andrew , Markey Dylan , Paulson Joseph N. , Rangarajan Sudharshan , Rasla John , Rayhan Ashyad , Rolland Thomas , San-Miguel Adriana , Shen Yun , Sheykhkarimli Dayag , Sheynkman Gloria M. , Simonovsky Eyal , Taşan Murat , Tejeda Alexander , Twizere Jean-Claude , Wang Yang , Weatheritt Robert J. , Weile Jochen , Xia Yu , Yang Xinping , Yeger-Lotem Esti , Zhong Quan , Aloy Patrick , Bader Gary D. , De Las Rivas Javier , Gaudet Suzanne , Hao Tong , Rak Janusz , Tavernier Jan , Tropepe Vincent , Hill David E. , Vidal Marc , Roth Frederick P. , Calderwood Michael A.
Published: April 2019

Global insights into cellular organization and function require comprehensive understanding of interactome networks. Similar to how a reference genome sequence revolutionized human genetics, a reference map of the human interactome network is critical to fully understand genotype-phenotype relationships. Here we present the first human “all-by-all” binary reference interactome map, or “HuRI”. With ~53,000 high-quality protein-protein interactions (PPIs), HuRI is approximately four times larger than the information curated from small-scale studies available in the literature. Integrating HuRI with genome, transcriptome and proteome data enables the study of cellular function within essentially any physiological or pathological cellular context. We demonstrate the use of HuRI in identifying specific subcellular roles of PPIs and protein function modulation via splicing during brain development. Inferred tissue-specific networks reveal general principles for the formation of cellular context-specific functions and elucidate potential molecular mechanisms underlying tissue-specific phenotypes of Mendelian diseases. HuRI thus represents an unprecedented, systematic reference linking genomic variation to phenotypic outcomes.
Selective translation by alternative bacterial ribosomes
Authors: Chen Yu-Xiang , Xu Zhi-yu , Ge Xueliang , Sanyal Suparna , Lu Zhi John , Javid Babak
Published: April 2019

Alternative ribosome subunit proteins are prevalent in the genomes of diverse bacterial species but their functional significance is controversial. Attempts to study microbial ribosomal heterogeneity have mostly relied on comparing wild-type strains with mutants in which subunits have been deleted, but this approach does not allow direct comparison of alternate ribosome isoforms isolated from identical cellular contexts. Here, by simultaneously purifying canonical and alternative RpsR ribosomes from Mycobacterium smegmatis, we show that alternative ribosomes have distinct translational features compared with their canonical counterparts. Both alternative and canonical ribosomes actively take part in gene translation, although they translate a subset of genes with differential efficiency as measured by ribosome profiling. We also show that alternative ribosomes have a relative defect in initiation complex formation. Our work convincingly confirms the distinct and non-redundant contribution of alternative bacterial ribosomes for adaptation to hostile environments.

Significance Statement

Many organisms, including most bacteria code for multiple paralogues of some ribosomal protein subunits. The relative contribution of these alternative subunits to ribosome function and gene translation is unknown and controversial. Furthermore, many studies on alternative ribosomes have been confounded by isolation of alternative and canonical ribosomes from different strains and/ or different growth conditions, potentially confounding results. Here, we show unequivocally that one form of alternative ribosome from Mycobacterium smegmatis actively engages in gene translation, but its translational profile from an identical cellular context is subtly different from canonical ribosomes. Given the prevalence of alternative ribosomal genes in diverse organisms, our study suggests that alternative ribosomes may represent a further layer of regulation of gene translation.
An epigenome-wide association study of sex-specific chronological ageing
Authors: McCartney Daniel L. , Hillary Robert F. , Zhang Qian , Stevenson Anna J. , Walker Rosie M. , Bermingham Mairead L. , Morris Stewart W. , Campbell Archie , Murray Alison D. , Whalley Heather C. , Porteous David J. , Evans Kathryn L. , Chandra Tamir , Deary Ian J. , McIntosh Andrew M. , Visscher Peter M. , McRae Allan F. , Marioni Riccardo E.
Published: April 2019

Introduction

Advanced age is associated with cognitive and physical decline, and is a major risk factor for a multitude of disorders including neurodegenerative diseases such as Alzheimer’s disease. There is also a gap in life-expectancy between males and females. DNA methylation differences have been shown to be associated with both age and sex. Here, we investigate age-by-sex differences in DNA methylation in an unrelated cohort of 2,586 individuals between the ages of 18 and 87 years.

Methods

Genome-wide DNA methylation was measured on the Illumina HumanMethylationEPIC beadchip in a subset of unrelated individuals from the Generation Scotland cohort. Mixed linear model-based analyses were performed to investigate the relationship between DNA methylation and an interaction term between age and sex, as well as chronological age.

Results

At a genome-wide significance level of P < 3.6 × 10−8, 14 loci were associated with the age-by-sex interaction term, the majority of which were X-linked (n = 12). Seven of these loci were annotated to genes. The site with the greatest difference mapped to GAGE10, an X-linked gene. Here, DNA methylation levels remained stable across the male adult age range (DNA methylation x age r = 0.02), but decreased across female adult age range (DNA methylation x age r = −0.61). The seven age-by-sex-associated genes were enriched among differentially-expressed genes in lung, liver, testis and blood.

Conclusion

The majority of differences in age-associated DNA methylation trajectories between sexes are present on the X-chromosome. Several of these differences occur within genes which have implicated in multiple cancers, schizophrenia and systemic lupus erythematosus.
Proresolving mediators LXB4 and RvE1 regulate inflammation in stromal cells from patients with shoulder tendon tears
Authors: Dakin Stephanie G , Colas Romain A , Wheway Kim , Watkins Bridget , Appleton Louise , Rees Jonathan , Gwilym Stephen , Little Christopher , Dalli Jesmond , Carr Andrew J
Published: April 2019

Tendon stromal cells isolated from patients with chronic shoulder rotator-cuff tendon tears show dysregulated resolution responses. Current therapies do not address the biological processes concerned with persistent tendon inflammation, therefore new therapeutic approaches targeting tendon stromal cells are required. We determined if two specialised pro-resolving mediators (SPM) LXB4 and RvE1, modulated the bioactive lipid mediator (LM) profiles of IL-1β stimulated tendon cells derived from patients with shoulder tendon tears and healthy volunteers. We also determined if LXB4/RvE1 treatments moderated the pro-inflammatory phenotype of tendon tear stromal cells. Incubation of IL-1β treated patient derived tendon cells in LXB4/RvE1 upregulated concentrations of SPM. RvE1 treatment specifically increased 15-epi-LXB4 and regulated PGF2α. LXB4 or RvE1 also induced expression of the SPM biosynthetic enzymes 12-liopxygeanse (ALOX12), and ALOX15. RvE1 treatment upregulated proresolving receptor ERV1 compared to vehicle treated cells. Incubation in LXB4 or RvE1 moderated the proinflammatory phenotype of patient derived tendon tear cells, regulating markers of tendon inflammation, including Podoplanin, CD90, STAT-1 and IL-6. These treatments also suppressed JNK1/2/3, Lyn, STAT-3 and STAT-6 and induced p70s6kinase phospho-kinase signalling. LXB4 and RvE1 counter-regulate inflammatory processes in tendon stromal cells, supporting the role of these molecules as potential therapeutics to resolve tendon inflammation.
Performance assessment of age-adapted SOFA, qSOFA, and PELOD-2, PCIS, P-MODS for Hand, Foot and Mouth Disease
Authors: Yu Zhenjun , Li Ali , Huang Tingting , He Zebao , Chen Huazhong , Zhu Jiansheng
Published: April 2019

Objectives

Hand, foot and mouth disease (HFMD) is a common infectious disease in children caused by intestinal virus and an important cause of child death. Early identification of critical HFMD and timely intervention are the key to reduce mortality. However, there is no available unified critical HFMD screening standard. This study aimed to explore the predictive evaluation of HFMD with critical illness scoring systems.

Methods

A total of 31 patients with mild HFMD, 30 with severe HFMD, and 25 with critical HFMD were included. The platelet index in age-adapted sequential organ failure assessment score (SOFA) was re-assigned to constitute the SOFA for HFMD (H-SOFA). The results of age-adapted SOFA, quick SOFA (qSOFA), and pediatric logistic organ dysfunction score-2 (PELOD-2), pediatric multiple organ dysfunction score (P-MODS), pediatric critical illness score (PCIS), H-SOFA of the three groups were compared.

Results

Significant differences in the following parameters were found between severe group and critical group: enterovirus 71 positive, heart rate, respiration, vomiting, cold sweat, moist rales, disturbance in consciousness, platelet, and blood glucose (P<0.05), as well as all critical illness scoring data (P<0.001). age-adapted SOFA, qSOFA, and PELOD-2, P-MODS, H-SOFA were positively correlated with critical HFMD (odds ratio (OR): 3.213, 8.66, 2.64, 2.56, and 4.297 respectively; P<0.01), with area under the curve (AUC) values of 0.938, 0.823, 0.848, 0.910, and 0.956, respectively. PCIS was negatively correlated with critical HFMD (OR=0.76, P<0.001), with an AUC value of 0.865.

Conclusion

Increase in platelet count was related to the severity of HFMD. Age-adapted SOFA, qSOFA, and PELOD-2, P-MODS, PCIS, H-SOFA had high predictive value on critical HFMD, with H-SOFA being the highest.
Denoising High-field Multi-dimensional MRI with Local Complex PCA
Authors: Bazin Pierre-Louis , Alkemade Anneke , van der Zwaag Wietske , Caan Matthan , Mulder Martijn , Forstmann Birte U.
Published: April 2019

Modern high field and ultra high field magnetic resonance imaging (MRI) experiments routinely collect multi-dimensional data with high spatial resolution, whether multi-parametric structural, diffusion or functional MRI. While diffusion and functional imaging have benefited from recent advances in multi-dimensional signal analysis and denoising, structural MRI has remained untouched. In this work, we propose a denoising technique for multi-parametric quantitative MRI, combining a highly popular denoising method from diffusion imaging, over-complete local PCA, with a reconstruction of the complex-valued MR signal in order to define stable estimates of the noise in the decomposition. With this approach, we show signal to noise ratio (SNR) improvements in high resolution MRI without compromising the spatial accuracy or generating spurious perceptual boundaries.
Knockout of Babesia bovis rad51 ortholog and its complementation by expression from the BbACc3 artificial chromosome platform
Authors: Mack Erin A. , Xiao Yu-Ping , Allred David R.
Published: April 2019

Babesia bovis establishes persistent infections of long duration in cattle, despite the development of effective anti-disease immunity. One mechanism used by the parasite to achieve persistence is rapid antigenic variation of the VESA1 cytoadhesion ligand through segmental gene conversion (SGC), a phenomenon thought to be a form of homologous recombination (HR). To begin investigation of the enzymatic basis for SGC we initially identified and knocked out the Bbrad51 gene encoding the B. bovis Rad51 ortholog. BbRad51 was found to be non-essential for in vitro growth of asexual-stage parasites. However, its loss resulted in hypersensitivity to methylmethane sulfonate (MMS) and an apparent defect in HR. This defect rendered attempts to complement the knockout phenotype by reinsertion of the Bbrad51 gene into the genome unsuccessful. To circumvent this difficulty, we constructed an artificial chromosome, BbACc3, into which the complete Bbrad51 locus was inserted, for expression of BbRad51 under regulation by autologous elements. Maintenance of BbACc3 makes use of centromeric sequences from chromosome 3 and telomeric ends from chromosome 1 of the B. bovis C9.1 line. A selection cassette employing human dihydrofolate reductase enables recovery of transformants by selection with pyrimethamine. We demonstrate that the BbACc3 platform is stably maintained once established, assembles nucleosomes to form native chromatin, and expands in telomere length over time. Significantly, the MMS-sensitivity phenotype observed in the absence of Bbrad51 was successfully complemented at essentially normal levels. We provide cautionary evidence, however, that in HR-competent parasites BbACc3 can recombine with native chromosomes, potentially resulting in crossover. We propose that, under certain circumstances this platform can provide a useful alternative for the genetic manipulation of this group of parasites, particularly when regulated gene expression under the control of autologous elements may be important.
Innate CD8αα+cells and osteopontin promote ILC1-like intraepithelial lymphocyte homeostasis and intestinal inflammation
Authors: Nazmi Ali , Hoek Kristen , Greer Michael J. , Piazuelo M. Blanca , Minato Nagahiro , Olivares-Villagómez Danyvid
Published: April 2019

Innate CD8αα+cells, also referred to as iCD8α cells, are TCR-negative intraepithelial lymphocytes (IEL) possessing cytokine and chemokine profiles and functions related to innate immune cells. iCD8α cells constitute an important source of osteopontin in the intestinal epithelium. Osteopontin is a pleiotropic cytokine with diverse roles in bone and tissue remodeling, but also has relevant functions in the homeostasis of immune cells. In this report, we present evidence for the role of iCD8α cells and osteopontin in the homeostasis of TCR-negative NKp46+NK1.1+IEL (ILC1-like). We show that in the absence of iCD8α cells, the number of NKp46+NK1.1+IEL is significantly reduced. These ILC1-like cells are involved in intestinal pathogenesis in the anti-CD40 mouse model of intestinal inflammation. Reduced iCD8α cell numbers and/or osteopontin expression results in a milder form of intestinal inflammation in this disease model. Collectively, our results suggest that iCD8α cells and osteopontin promote survival of NKp46+NK1.1+IEL, which significantly impacts the development of intestinal inflammation.
A modified Rayleigh-Plesset equation for a liquid-crystalline shelled microbubble
Authors: Cowley James , Mulholland Anthony J. , Gachagan Anthony
Published: April 2019

Premanufactured shelled microbubbles composed of a protein shell are currently licensed as ultrasound imaging contrast agents. Current research is focussing on using the protein shelled microbubbles as transportation mechanisms for localised drug delivery particularly in the treatment of various types of cancer. For the very first time, a theoretical model is developed for an incompressible, gas loaded shelled microbubble with a thin shell composed of a liquid-crystalline material. We show that liquid-crystalline shelled microbubbles exhibit significantly different physical characteristics from commercial protein shelled microbubbles such as Sonovue and Optison. The authors propose that these significantly different physical characteristics may enhance localised drug delivery. We use the technique of linearisation to predict the shelled microbubble’s natural frequency and relaxation time. These physical parameters strongly influence sonoporation which is the mechanism that is used for localised drug delivery. The influence of the material properties of the shell on the natural frequency and relaxation time are discussed. We have discovered that liquid-crystalline shelled microbubbles have a relaxation time that is 10 times longer than Sonovue and Optison.
Measurement of ocular transmission in living human eyes with a double-pass system
Authors: Sánchez Roberto F. , de Paul Aníbal G. , Burgos-Fernández Francisco J. , Vilaseca Meritxell , Pujol Jaume , Issolio Luis A.
Published: April 2019

Purpose

To develop a methodology based on a double-pass system to obtain useful information about the transmission of ocular media, performing noninvasive measures in vivo.

Methods

This noninvasive procedure consists of recording double-pass images at different voltages of a laser diode of 780 nm and the determination of the scattering in an area between 25 and 35 arc minutes of each image.

Results

Ocular scattering showed a linear behavior respect to the voltage of the laser and the slope of the linear fit was proportional to the transmittance squared of the media evaluated. The relationship between the ocular light scattering of the images and the transmittance values of several filters located into an artificial eye was used as a calibration function. The measurements performed in a group of ten subjects with ages between 25 and 45 years old presented a mean direct transmittance of the whole eye including retina of 42.7 %, which agrees with the bibliography. No differences between dark eyes and light eyes were found.

Conclusion

We have developed a method to determine the transmittance of the human eye in vivo for a wavelength of 780 nm using the double-pass method, commonly used for the determination of the optical quality of an eye.
CD4 T-cell transcriptome expression reversal of the lncRNA-mRNA co-expression network in elite controllervs.normal-process HIV patients
Authors: Chen Chaoyu , Lu Xiangyun , Wu Nanping
Published: April 2019

Elite controller refers to a patient with human imunodeficienvcy virus infection with an undetected viral load without anti-viral treatment. Studies on gene expression and regulation in these individuals are limited but significant. We enrolled 196 patients and collected CD4 T-cell samples from two elite controllers, two normal-process infected patients, and two healthy controls to perform second-generation transcriptome sequencing. Using the Cuffdiff model, we identified differentially expressed mRNAs and long non-coding RNAs with corrected P value < 0.05, and constructed a protein-protein interaction network as well a long non-coding RNA-mRNA co-expression network based on the Pearson correlation coefficient. Interestingly, some interactions within the networks were identified as associated with viral infections and immune responses. This was the first study to examine gene transcription in elite controllers and to study their functional relationships. Our results provide a reference for subsequent functional verification at the molecular or cellular level.

Author Summary

Some individuals can spontaneously inhibit HIV replication after infection with HIV, and thus lack any symptoms. Studies on these patients, termed elite controllers (ECs) will help researchers and clinicians to understand the interrelationship between HIV and the host. In the present study, we focused on the interactions and functional relationships between significantly differentially expressed long non-coding RNAs (lncRNAs) and mRNAs in ECsvs. normal-process patients (NPs). RNA-sequencing was performed for six representative samples of CD4 T-cells. Using the Pearson correlation test, an lncRNA-mRNA co-expression network was constructed. Several new regulatory relationships between transcripts were revealed that might be closely related to the ability of ECs to maintain a low viral load for long periods without anti-viral treatment. For example, lncRNAC3orf35was upregulated in ECsvs. NPs and was positively related to downregulation ofGNG2mRNA (encoding G protein subunit gamma 2), which functions in chemokine signaling pathways and HIV-1 infection. Overall, we identified certain interesting genetic interactions that will provide information about the mechanism of host suppression of viral replication.
Helminth infection-induced carcinogenesis: spectrometric insights from the liver flukes, Opisthorchis and Fasciola
Authors: Gouveia Maria João , Pakharukova Maria Y. , Sripa Banchob , Rinaldi Gabriel , Brindley Paul J. , Mordvinov Viatcheslav A. , Gärtner Fátima , da Costa José M. C. , Vale Nuno
Published: April 2019

Chronic infections with the flatworm parasites Opisthorchis viverrini, Clonorchis sinensis and Schistosoma haematobium are classified as group 1 biological carcinogens, i.e. definitive causes of cancer. In addition, we reported findings that support the inclusion of Opisthorchis felineus in this list of biological carcinogens. By contrast, infections with close phylogenetic relatives including Fasciola hepatica have not been associated with carcinogenesis. Earlier reports revealed of oxysterol metabolites of Opisthorchis liver fluke origin conjugated with DNA bases, suggesting that the generation of these DNA-adducts may underlie the mutagenicity and carcinogenicity of the infection with these food-borne pathogens. Here we employed liquid chromatography-mass spectrometry (LC-MS/MS) to investigate, compare and contrast spectrograms of soluble extracts from F. hepatica adult worms from bile ducts of cattle with those from O. viverrini and O. felineus from experimentally-infected hamsters. F. hepatica displayed a complex spectrophotometric profile. F. hepatica and Opisthorchis spp. shared several common compounds including oxysterol-like metabolites, bile acids and DNA-adducts, but the spectrometric profiles of these Opisthorchis species included far fewer compounds than F. hepatica. These findings support the postulate that oxysterol-like metabolites of parasite origin can initiate carcinogenesis and they point to a molecular basis for the inconsistencies among major groups of liver flukes concerning infection-induced malignancy.

Author Summary

Several species of trematodes are parasites of the human hepatobiliary tract. Infection with two of these flukes, Clonorchis sinsensis and Opisthorchis viverrini, fresh water fish-borne parasites that occur in East Asia is classified as group 1 carcinogens by the International Agency for Research on Cancer (IARC), i.e. definitive causes of cancer in humans. By contrast, infection with a different liver fluke, Fasciola hepatica, does not lead to malignant transformation of the biliary tract. Given the close phylogeny of all three parasites, this difference in carcinogenicity is intriguing and, if explained, likely of value in novel therapeutic approaches. The importance of the current findings is informative because they present a mass spectrometric analysis and catalog of the similarities and differences between fluke of the genus Opisthorchis and F. hepatica, potentially identifying carcinogenic metabolites of liver fluke origin. These metabolites can be expected to provide deeper understanding of helminth infection induced malignancy.
Structural basis for inhibition of a response regulator of σS stability by a ClpXP antiadaptor
Authors: Dorich Victoria , Brugger Christiane , Tripathi Arti , Hoskins Joel R. , Tong Song , Suhanovsky Margaret M. , Sastry Amita , Wickner Sue , Gottesman Susan , Deaconescu Alexandra M.
Published: April 2019

The stationary phase promoter specificity subunit σS (RpoS) is delivered to the ClpXP machinery for degradation dependent on the adaptor RssB. This adaptor-specific degradation of σS provides a major point for regulation and transcriptional reprogramming during the general stress response. RssB is an atypical response regulator and the only known ClpXP adaptor that is inhibited by multiple but dissimilar antiadaptors (IraD, IraP, and IraM). These are induced by distinct stress signals and bind to RssB in poorly understood manners to achieve stress-specific inhibition of σS turnover. Here we present the first crystal structure of RssB bound to an antiadaptor, the DNA damage-inducible IraD. The structure reveals that RssB adopts a compact closed architecture with extensive interactions between its N-terminal and C-terminal domains. The structural data, together with mechanistic studies, suggest that RssB plasticity, conferred by an interdomain glutamate-rich flexible linker, is critical for regulation of σS degradation. Structural modulation of interdomain linkers may thus constitute a general strategy for tuning response regulators.
Native mass spectrometry provides sufficient ion flux for XFEL single-particle imaging
Authors: Uetrecht Charlotte , Lorenzen Kristina , Kitel Matthäus , Heidemann Johannes , Robinson Spencer Jesse Huron , Schlüter Hartmut , Schulz Joachim
Published: April 2019

The SPB/SFX instrument at the European XFEL provides unique conditions for single-particle imaging (SPI) experiments due to its high brilliance, nano-focus and unique pulse structure. Promising initial results provided by the international LCLS (Linac Coherent Light Source) SPI initiative highlight the potential of SPI. Current available injection methods generally have high sample consumption and do not provide any options for pulsing, selection or orientation of particles, which poses a problem for data evaluation. Aerosol-injector-based sample delivery is the current method of choice for SPI experiments, although, to a lesser extent, electrospray and electrospinning are used. Single particles scatter only a limited number of photons providing a single orientation for data evaluation, hence large datasets are required from particles in multiple orientations in order to reconstruct a structure. Here, a feasibility study demonstrates that nano-electrospray ionization, usually employed in biomolecular mass spectrometry, provides enough ion flux for SPI experiments. A novel instrument setup at the SPB/SFX instrument is proposed, which has the benefit of extremely low background while delivering mass over charge and conformation-selected ions for SPI.
Power and environmental reporting-practice in business networks
Authors: Bayne Lyndie , Purchase Sharon , Tarca Ann
Published: April 2019

Purpose

The purpose of this paper is twofold: first, the use of power in a business network context is investigated, in relation to companies’ environmental reporting and practice choices. Second, the environmental reporting-practice portrayal gap is examined, focussing on inter-organisational environmental practices (such as green supply chain management).

Design/methodology/approach

A network case study was undertaken in the Western Australian agrifood sector, with the two large, dominant supermarkets as focal actors. Data were drawn from 34 in-depth interviews from 2011 to 2013 and a document review including 15 years of supermarket reports.

Findings

The study showed the exercise of government power bases and its effect on supermarket and other supply chain actors’ reporting and practice choices. The data suggest a differential use of power by supermarkets with suppliers, depending on supplier type and environmental practice characteristics. The study revealed surprisingly transparent reporting of the lack of whole-of-supply-chain approach by the supermarkets and admission of shareholder power over reporting and practice choices. In addition, other reporting-practice portrayal gaps relating to inter-organisational environmental practices were found.

Originality/value

The study provides a unique network level analysis of how power relations interact and influence companies’ choices of environmental reporting and practice, thereby contributing to prior power and environmental reporting literature. Contributions are made to extant literature dealing with the reporting-practice portrayal gap by focussing on inter-organisational environmental reporting and practice.
The inclusion of competitor information in the three-factor theory of customer satisfaction
Authors: Albayrak Tahir
Published: April 2019

Purpose

The three-factor theory of customer satisfaction suggests that product attributes may have an asymmetric effect on customer satisfaction. Although this relationship has been demonstrated in many different settings, the main drawback of previous research is the lack of information about competitors. This study aims to propose asymmetric impact competitor analysis (AICA) for addressing this shortcoming.

Design/methodology/approach

The proposed method is conducted by using both impact asymmetry index and relative performance value of each product attribute. While the former is derived by penalty-reward contrast analysis, the latter is obtained by the comparison of the focal company’s performance with competitor’s performance.

Findings

The paper shows the application of AICA by using data belonging to two competing hotels. Results offered different strategies for each hotel attribute.

Originality/value

AICA considers both asymmetric effects of attributes on customer satisfaction and competitor information related to same attributes. The proposed method also suggests the strategies for each attribute depending on the quadrant it is located.
Value destruction in exaggerated online reviews
Authors: Baker Melissa A. , Kim Kawon
Published: April 2019

Purpose

This paper aims to examine the underlying motivations, attitudes and behaviors of exaggerated review posters and readers by examining the effect of review valence, emotional expression and language complexity on perceived poster, website and firm trustworthiness and subsequent behavioral intentions.

Design/methodology/approach

This research uses a mixed-method approach using the qualitative critical incident technique (CIT) and quantitative experimental design. Study 1 uses CIT to examine exaggerated online reviews from the poster perspective where Study 2 uses CIT to examine readers’ perceptions of exaggerated reviews. Study 3 conducts a between-subjects experimental design examining the impact of valence (positive vs negative) × emotion (low vs high) × language (vague vs detailed) on trustworthiness and behavior intention.

Findings

Results of the two qualitative studies (Study 1 and 2) find posters and readers use language complexity and emotions in exaggerated reviews. The results from the quantitative experimental design study (Study 3) find that language style and emotions influence customer perceptions of poster, website and firm trustworthiness, which also mediates the relationship between the qualitative aspects of review text on behavioral intentions.

Practical implications

The findings provide multiple practical implications on the prevalence of exaggerated online reviews and the importance of language and emotion in determining customer perceptions and behavioral intentions.

Originality/value

By focusing on both readers and posters in exaggerated eWOM, specific motivations, emotions and language, this research contributes to the literature of online reviews, customer misbehavior, trustworthiness, language use and value co-destruction in online environments.
Rheological characteristics of bovine colostrum and their correlation with immunoglobulin G
Authors: Ceniti Carlotta , Froiio Francesca , Britti Domenico , Paolino Donatella , Costanzo Nicola
Published: April 2019

Colostrum, the first mammary secretion after parturition, is an important source of nutrition and passive immunity. In this study, the rheological characteristics of bovine colostrum and their correlation with IgG concentration were investigated. Forty‐nine colostrum samples were collected from 21 Simmental dairy cows at different times after calving. Solid–liquid balance (SLB), macroscopic viscosity index (MVI), elasticity index (EI) and IgG were evaluated in each sample. A significant (P < 0.05) decrease in SLB and EI values as well as in the IgG concentration was observed. A suitable correlation (R2 = 0.737) between the EI values and the IgG concentration was evidenced.
Successful treatment with nivolumab for SMARCA4‐deficient non‐small cell lung carcinoma with a high tumor mutation burden: A case report
Authors: Naito Tomoyuki , Umemura Shigeki , Nakamura Hiroshi , Zenke Yoshitaka , Udagawa Hibiki , Kirita Keisuke , Matsumoto Shingo , Yoh Kiyotaka , Niho Seiji , Motoi Noriko , Aokage Keijyu , Tsuboi Masahiro , Ishii Genichiro , Goto Koichi
Published: April 2019

SMARCA4 is a subunit of the switch/sucrose non‐fermentable (SWI/SNF) chromatin‐remodeling complex. An effective treatment for SMARCA4‐deficient non‐small cell lung carcinoma (NSCLC) has not yet been established. Correlations between a response to immune checkpoint inhibitors and the SWI/SNF complex have been suggested, but little is known about the efficacy of immune checkpoint inhibitors against SMARCA4‐deficient NSCLC. A 43‐year‐old man underwent left upper lobe lung resection and was diagnosed with SMARCA4‐deficient lung adenocarcinoma. Two months after surgery, multiple lung metastases appeared. Immunohistochemical analysis showed no PD‐L1 expression. Whole‐exon sequencing revealed a relatively high tumor mutation burden at 396. After the failure of three standard chemotherapy regimens, the patient was treated with nivolumab as fourth‐line treatment. An obvious reduction in the lung metastases was obtained for more than 14 months. We report the first case of SMARCA4‐deficient NSCLC with a high tumor mutation burden successfully treated with nivolumab. Anti‐PD‐1 antibodies might be a promising treatment strategy for patients with SMARCA4‐deficient NSCLC.
Retrospective analysis of the efficacy and influencing factors of autologous hematopoietic stem cell transplantation for multiple myeloma
Authors: Zhang Bing‐Lei , Zhou Jian , Lin Quan‐De , Liu Yu‐Zhang , Zhang Yan‐Li , Gui Rui‐Rui , Song Yong‐Ping , Fang Bai‐Jun
Published: April 2019

This study aims to review the clinical efficacy and factors affecting the treatment of multiple myeloma (MM) by autologous hematopoietic stem cell transplantation (ASCT). The clinical data of 47 patients with MM from the Department of Hematology of Henan Cancer Hospital from September 2010 to July 2018 were retrospectively analyzed. At pre‐transplantation of autologous cells, 25.5% were in complete remission (CR), 14.9% were in very good partial remission (VGPR) and 59.6% were in partial remission (PR). Among these cases, one case had PR after three recurrences. At post‐transplantation, 51% were in CR, including two cases who received double transplantations, 27.7% were in VGPR, and 21.3% were in PR. The median follow‐up time was 27.6 months (4–96 months). The 3‐year progression free survival (PFS) and overall survival (OS) were 47.9% and 79.6%, respectively. The Analysis of variance (ANOVA) results revealed that factors that affected OS were international staging system (ISS) stage (P = 0.002), CR and VGPR post‐transplantation (P = 0.002), while factors that affected PFS were ISS stage (P = 0.005), pre‐transplant induction therapy (P = 0.032), and disease risk stratification (P = 0.017). The curative effects for PFS were CR and VGPR pre‐transplantation (P = 0.013) and post‐transplantation (P = 0.011). The Cox multivariate regression analysis revealed that ISS stage and CR and VGPR post‐transplantation were independent prognostic factors of OS. At post‐transplantation, CR and VGPR, ISS stage, and pre‐transplant induction therapy were independent prognostic factors for PFS. In conclusion, ASCT can improve the clinical efficacy and survival rate of MM patients. ISS stage, CR and VGPR post‐transplantation are independent prognostic factors of OS and PFS, while pre‐transplant induction therapy is an independent prognostic factor for PFS.
Out of the picture? How incompatible knowledge and distant visual stimuli may foster idea generation
Authors: Brun Juliette , Le Masson Pascal , Weil Benoit
Published: April 2019

Visual stimuli such as pictures, sketches or prototypes play a major role in idea generation. Companies today often promote the use of these non‐verbal tools during creativity sessions, at the early stages of design. However, recent studies tend to show that these tools do not systematically enhance idea generation. Our research project therefore aims to better understand the contribution of visual stimuli during creativity sessions, and especially the contribution of distant stimuli which present knowledge that appears to be incompatible with the design topic. This study is based on an exploration led at the automotive company Renault by a team working on new services for charging electric vehicles. During idea generation sessions, a set of pictures was used by a meeting facilitator to inspire the team with new ideas. We show that the effects produced by the different pictures are varied: they do not always promote radical expansion, and when they do, expansion is not always of the same nature. Moreover, represented knowledge appears to have a major influence on idea generation, as the most original ideas came from pictures that not only expanded initial knowledge, but also helped to reorder the team's knowledge base and introduce new design rules.