bluuebunny/crossref_metadata_2025_split 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

AbstractObjectivesTo 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.MethodsMultivariate 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.ResultsIn 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.ConclusionsState 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

AbstractMammalian 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 StatementOdor 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

SUMMARYWhile 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

AbstractDeep-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

AbstractCardiac 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

AbstractGlobal 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

AbstractAlternative 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 StatementMany 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

AbstractIntroductionAdvanced 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.MethodsGenome-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.ResultsAt 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.ConclusionThe 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

ABSTRACTTendon 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

AbstractObjectivesHand, 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.MethodsA 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.ResultsSignificant 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.ConclusionIncrease 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

AbstractModern 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

AbstractBabesia 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.