bluuebunny/crossref_metadata_2025 huggingface dataset:
Interfacial energy constraints are sufficient to align cells over large distances
Authors: Tlili S. , Shagirov M. , Zhang S. , Saunders T. E.
Published: May 2019

During development and wound healing, cells need to form long-ranged ordered structures to ensure precise formation of organs and repair damage. This requires cells to locate specific partner cells to which to adhere. How such cell matching reliably happens is an open problem, particularly in the presence of biological variability. Here, we use an equilibrium energy model to simulate how cell matching can occur with subcellular precision. A single parameter – encapsulating the competition between selective cell adhesion and cell compressibility – can reproduce experimental observations of cell alignment in theDrosophilaembryonic heart. This demonstrates that adhesive differences between cells (in the case of the heart, mediated by filopodia interactions) are sufficient to drive cell matching without requiring cell rearrangements. The biophysical model can explain observed matching defects in mutant conditions and when there is significant biological variability. We also demonstrate that a dynamic vertex model gives results consistent with the equilibrium energy model. Overall, this work shows that equilibrium energy considerations are consistent with observed cell matching in cardioblasts, and has potential application to other systems, such as neuron connections and wound repair.

Statement of Significance

Cells often need to identify specific neighboring cells, such as during wound repair and forming neural connections. Here, we develop a biophysical model of such cell-cell interactions within the context of the developing heart. We demonstrate that precise cell matching can occur by minimizing the energy costs of interfacial interactions. This model can explain a breadth of experimental observations despite it being a steady-state approximation of a dynamic system. This opens the possibility that such approaches may be applicable to other systems, providing a powerful yet simple framework for understanding cell matching.
The genomic landscape of clonal hematopoiesis in Japan
Authors: Terao Chikashi , Suzuki Akari , Momozawa Yukihide , Akiyama Masato , Ishigaki Kazuyoshi , Yamamoto Kazuhiko , Matsuda Koichi , Murakami Yoshinori , McCarroll Steven A , Kubo Michiaki , Loh Po-Ru , Kamatani Yoichiro
Published: May 2019

Cancer and aging are widely assumed to involve similar biological trajectories in different populations, though such biology has not been systematically characterized on a population scale. Clonal hematopoiesis with acquired mutations is a pre-cancerous condition that becomes common with advancing age. Here we describe shared and population-specific patterns of genomic mutation revealed by 33,250 autosomal mosaic chromosomal alterations (mCAs) we ascertained from 179,417 Japanese participants in the BioBank Japan cohort and compared to analogous analyses of UK Biobank. In this long-lived Japanese population, mCAs were detected in more than 35.0% (s.e. 1.4%) of individuals older than 90 years, suggesting that such clones trend toward inevitability with aging. Japanese and Europeans exhibited key differences in the genomic locations of mutations in their respective hematopoietic clones, which anticipated the populations’ relative rates of CLL (more common among Europeans) and T-cell lymphoma (more common among Japanese). Multiple mutational precursors of CLL (including trisomy 12, 13q loss, and 13q CNN-LOH) were also 2-6x less common among the Japanese, suggesting that these populations differ in selective pressures on clones long before the development of clinically apparent CLL. Japanese and UK populations also exhibited very different rates of clones arising from B- and T-cell lineages, anticipating the relative rates of B- and T-cell cancers in these populations. We identified six new loci at which inherited variants predispose to mCAs that duplicate or remove inherited risk alleles, including large-effect rare variants at NBN, MRE11, and CTU2 (OR=28-91). Our results motivate further exploration of the global genomic landscape of clonal hematopoiesis and cancer, and point to population-specific selective pressures on hematopoietic clones.
Reading Increases the Compositionality of Visual Word Representations
Authors: Agrawal Aakash , Hari K.V.S. , Arun S. P.
Published: May 2019

Reading causes widespread changes in the brain but its effect on visual word representations is unknown. Reading may facilitate visual processing by forming specialized detectors for longer strings, or by making word responses more predictable from single letters, that is by increasing compositionality. We provide evidence for the latter hypothesis by comparing readers and nonreaders of two Indian languages, Telugu and Malayalam. Readers showed decreased interactions between letters during visual search, which predicted their overall reading fluency. Brain imaging revealed increased compositionality in readers, whereby responses to bigrams were more predictable from single letters. This effect was specific to the lateral occipital region, where activations best matched behavior. Thus, reading facilitates visual processing by increasing the compositionality of visual word representations.
Start codon context controls translation initiation in the fungal kingdom
Authors: Wallace Edward , Maufrais Corinne , Sales-Lee Jade , Tuck Laura , de Oliveira Luciana , Feuerbach Frank , Moyrand Frédérique , Natarajan Prashanthi , Madhani Hiten D. , Janbon Guilhem
Published: May 2019

Eukaryotic protein synthesis initiates at a start codon defined by an AUG and its surrounding Kozak sequence context, but studies of S.cerevisiaesuggest this context is of little importance in fungi. We tested this concept in two pathogenicCryptococcusspecies by genome-wide mapping of translation and of mRNA 5’ and 3’ ends. We observed that upstream open reading frames (uORFs) are a major contributor to translation repression, that uORF use depends on the Kozak sequence context of its start codon, and that uORFs with strong contexts promote nonsense-mediated mRNA decay. NumerousCryptococcusmRNAs encode predicted dual-localized proteins, including many aminoacyl-tRNA synthetases, in which a leaky AUG start codon is followed by a strong Kozak context in-frame AUG, separated by mitochondrial-targeting sequence. Further analysis shows that such dual-localization is also predicted to be common inNeurospora crassa. Kozak-controlled regulation is correlated with insertions in translational initiation factors in fidelity-determining regions that contact the initiator tRNA. Thus, start codon context is a signal that programs the expression and structures of proteins in fungi.
Collective forces of tumor spheroids in three-dimensional biopolymer networks
Authors: Mark Christoph , Grundy Thomas J. , Böhringer David , Steinwachs Julian , O’Neill Geraldine M. , Fabry Ben
Published: May 2019

We describe a method for quantifying the contractile forces that tumor spheroids collectively exert on highly nonlinear three-dimensional collagen networks. While three-dimensional traction force microscopy for single cells in a nonlinear matrix is computationally complex due to the variable cell shape, here we exploit the spherical symmetry of tumor spheroids to derive a scale-invariant relationship between spheroid contractility and the surrounding matrix deformations. This relationship allows us to directly translate the magnitude of matrix deformations to the total contractility of arbitrarily sized spheroids. We show that collective forces of tumor spheroids reflect the contractility of individual cells for up to 1h after seeding, while collective forces on longer time-scales are guided by mechanical feedback from the extracellular matrix.
Characterizing and comparing phylogenetic trait data from their normalized Laplacian spectrum
Authors: Lewitus Eric , Aristide Leandro , Morlon Helene
Published: May 2019

The dissection of the mode and tempo of phenotypic evolution is integral to our understanding of global biodiversity. Our ability to infer patterns of phenotypes across phylogenetic clades is essential to how we infer the macroevolutionary processes governing those patterns. Many methods are already available for fitting models of phenotypic evolution to data. However, there is currently no non-parametric comprehensive framework for characterising and comparing patterns of phenotypic evolution. Here we build on a recently introduced approach for using the phylogenetic spectral density profile to compare and characterize patterns of phylogenetic diversification, in order to provide a framework for non-parametric analysis of phylogenetic trait data. We show how to construct the spectral density profile of trait data on a phylogenetic tree from the normalized graph Laplacian. We demonstrate on simulated data the utility of the spectral density profile to successfully cluster phylogenetic trait data into meaningful groups and to characterise the phenotypic patterning within those groups. We furthermore demonstrate how the spectral density profile is a powerful tool for visualising phenotypic space across traits and for assessing whether distinct trait evolution models are distinguishable on a given empirical phylogeny. We illustrate the approach in two empirical datasets: a comprehensive dataset of traits involved in song, plumage and resource-use in tanagers, and a high-dimensional dataset of endocranial landmarks in New World monkeys. Considering the proliferation of morphometric and molecular data collected across the tree of life, we expect this approach will benefit big data analyses requiring a comprehensive and intuitive framework.
Overarching principles and dimensions of the functional organisation in the inferior parietal cortex
Authors: Humphreys Gina F. , Jackson Rebecca L. , Lambon Ralph Matthew A.
Published: May 2019

The parietal cortex (PC) is implicated in a confusing myriad of different cognitive processes/tasks. Consequently, understanding the nature and organisation of the core underlying neurocomputations is challenging. According to the Parietal Unified Connectivity-biased Computation (PUCC) model two properties underpin PC function and organisation. Firstly, PC is a multi-domain, context-dependent buffer of time-and space-varying input, the function of which, over time, becomes sensitive to the statistical temporal/spatial structure of events. Secondly, over and above this core buffering computation, differences in long-range connectivity will generate graded variations in task engagement across subregions. The current study tested these hypotheses using a group ICA technique with two independent fMRI datasets (task and resting state data). Three functional organisational principles were revealed. Factor 1: inferior PC was sensitive to the statistical structure of sequences for all stimulus types (pictures, sentences, numbers). Factor 2: a dorsal-ventral variation in generally task-positive vs. task-negative (variable) engagement. Factor 3: An anterior-posterior dimension in inferior PC reflecting different engagement in verbal vs. visual tasks, respectively. Together the data suggest that the core neurocomputation implemented by PC is common across domains, with graded task engagement across regions reflecting variations in the connectivity of task-specific networks that interact with parietal cortex.
Trapped ion mobility spectrometry (TIMS) and parallel accumulation - serial fragmentation (PASEF) enable in-depth lipidomics from minimal sample amounts
Authors: Vasilopoulou Catherine G. , Sulek Karolina , Brunner Andreas-David , Meitei Ningombam Sanjib , Schweiger-Hufnagel Ulrike , Meyer Sven , Barsch Aiko , Mann Matthias , Meier Florian
Published: May 2019

Lipids form a highly diverse group of biomolecules fulfilling central biological functions, ranging from structural components to intercellular signaling. Yet, a comprehensive characterization of the lipidome from limited starting material, for example in tissue biopsies, remains very challenging. Here, we develop a high-sensitivity lipidomics workflow based on nanoflow liquid chromatography and trapped ion mobility spectrometry. Taking advantage of the PASEF principle (Meier et al., PMID: 26538118), we fragmented on average nine precursors in each 100 ms TIMS scans, while maintaining the full mobility resolution of co-eluting isomers. The very high acquisition speed of about 100 Hz allowed us to obtain MS/MS spectra of the vast majority of detected isotope patterns for automated lipid identification. Analyzing 1 uL of human plasma, PASEF almost doubled the number of identified lipids over standard TIMS-MS/MS and allowed us to reduce the analysis time by a factor of three without loss of coverage. Our single-extraction workflow surpasses the plasma lipid coverage of extensive multi-step protocols in common lipid classes and achieves attomole sensitivity. Building on the high precision and accuracy of TIMS collisional cross section measurements (median CV 0.2%), we compiled 1,327 lipid CCS values from human plasma, mouse liver and human cancer cells. Our study establishes PASEF in lipid analysis and paves the way for sensitive, ion mobility-enhanced lipidomics in four dimensions.
Circadian time series proteomics reveals daily dynamics in cartilage physiology
Authors: Dudek Michal , Angelucci Constanza , Ruckshanthi Jayalath P.D. , Wang Ping , Mallikarjun Venkatesh , Lawless Craig , Swift Joe , Kadler Karl E. , Hoyland Judith A. , Lamande Shireen R. , Bateman John F. , Meng Qing-Jun
Published: May 2019

Objectives

Articular cartilage undergoes cyclical heavy loading and low load recovery during the 24-hour day/night cycle. We investigated the daily changes of protein abundance in mouse femoral head articular cartilage by performing 24-hour time-series proteomics study.

Methods

Tandem mass spectrometry analysis was used to quantify proteins extracted from mouse cartilage. Bioinformatics analysis was performed to quantify rhythmic changes in protein abundance. Primary chondrocytes were isolated and cultured for independent validation of selected rhythmic proteins.

Results

145 rhythmic proteins were detected. Among these were key cartilage molecules including CCN2, MATN1, PAI-1 and PLOD1 & 2. Pathway analysis revealed that proteins related to protein synthesis, cytoskeleton and glucose metabolism exhibited time-of-day dependent peaks in their abundance. Meta-analysis of published proteomics datasets from articular cartilage revealed that numerous rhythmic proteins were dysregulated in osteoarthritis and/or ageing.

Conclusions

Our circadian proteomics study revealed that articular cartilage is a much more dynamic tissue than previously thought. Chondrocytes exhibit circadian rhythms not only in gene expression but also in protein abundance. Our results clearly call for the consideration of circadian timing in understanding cartilage biology, osteoarthritis pathogenesis, treatment strategies and biomarker detection.
Relating anthropometric indicators to brain structure in 2-month-old Bangladeshi infants growing up in poverty: a pilot study
Authors: Turesky Ted , Xie Wanze , Kumar Swapna , Sliva Danielle D. , Gagoski Borjan , Vaughn Jennifer , Zöllei Lilla , Haque Rashidul , Kakon Shahria Hafiz , Islam Nazrul , Petri William A. , Nelson Charles A. , Gaab Nadine
Published: May 2019

Anthropometric indicators, including stunting, underweight, and wasting, have previously been associated with poor neurocognitive outcomes. This link may exist because malnutrition and infection, which are known to affect height and weight, also impact brain structure according to animal models. However, a relationship between anthropometric indicators and brain structural measures has not been tested yet, perhaps because stunting, underweight, and wasting are uncommon in higher-resource settings. Further, with diminished anthropomorphic growth prevalent in low-resource settings, where biological and psychosocial hazards are most severe, one might expect additional links between measures of poverty, anthropometry, and brain structure. To begin to examine these relationships, we conducted an MRI study in 2-3-month-old infants growing up in the extremely impoverished urban setting of Dhaka, Bangladesh. The sample size was relatively small because the challenges of investigating infant brain structure in a low-resource setting needed to be realized and resolved before introducing a larger cohort. Initially, fifty-four infants underwent T1 sequences using 3T MRI, and structural images were segmented into gray and white matter maps, which were carefully evaluated for accurate tissue labeling by a pediatric neuroradiologist. Gray and white matter volumes from 29 infants (79 ± 10 days-of-age; F/M = 12/17), whose segmentations were of relatively high quality, were submitted to semi-partial correlation analyses with stunting, underweight, and wasting, which were measured using height-for-age (HAZ), weight-for-age (WAZ), and weight-for-height (WHZ) scores. Positive semi-partial correlations (after adjusting for chronological age and sex and correcting for multiple comparisons) were observed between white matter volume and HAZ and WAZ; however, WHZ was not correlated with any measure of brain volume. In examining the role of poverty, no associations were observed between income-to-needs or maternal education and brain volumetric measures, suggesting that risk factors previously linked with poverty were not associated with total brain tissue volume pre- or peri-natally in this sample. Overall, these results provide the first link between diminished anthropomorphic growth and white matter volume in infancy. Challenges of conducting a developmental neuroimaging study in a low-resource country are described.
A unity of opposites in between Nrf1- and Nrf2-mediated responses to the endoplasmic reticulum stressor tunicamycin
Authors: Zhu Yu-ping , Hu Shaofan , Ru Xufang , Zheng Ze , Fan Zhuo , Qiu Lu , Zhang Yiguo
Published: May 2019

The water-soluble Nrf2 is accepted as a master regulator of antioxidant responses to cellular stress, it was also identified as a direct target of the endoplasmic reticulum (ER)-anchored PERK. However, the membrane-bound Nrf1 response to ER stress remains elusive. Herein, we report a unity of opposites in both Nrf1- and Nrf2-coordinated responses to the ER stressor tunicamycin (TU). The TU-inducible transcription of Nrf1 and Nrf2, as well as GCLM and HO-1, was accompanied by activation of ER stress signaling networks. The unfolded protein response (UPR) mediated by ATF6, IRE1 and PERK was significantly suppressed by Nrf1α-specific knockout, but hyper-expression of Nrf2, GCLM and HO-1 was retained in Nrf1α−/− cells. By contrast, Nrf2−/−ΔTA cells with a genomic deletion of its transactivation domain resulted in significant decreases of GCLM, HO-1 and Nrf1; this was accompanied by partial decreases of IRE1 and ATF6, but not PERK, along with an obvious increase of ATF4. Notably, Nrf1 glycosylation and its trans-activity to mediate transcriptional expression of 26S proteasomal subunits were repressed by TU. This inhibitory effect was enhanced by Nrf1α−/− and Nrf2−/−ΔTA, but not by a constitutive activator caNrf2ΔN (that increased abundances of non-glycosylated and processed Nrf1). Furthermore, caNrf2ΔN also enhanced induction of PERK and IRE1 by TU, but reduced expression of ATF4 and HO-1. Such distinct roles of Nrf1 and Nrf2 are unified to maintain cell homeostasis by a series of coordinated ER-to-nuclear signaling responses to TU. Overall, Nrf1α acts in a cell-autonomous manner to determine transcription of most of UPR-target genes, albeit Nrf2 is also partially involved in this process.
Universal latent axes capturing Parkinson’s patient deep phenotypic variation reveals patients with a high genetic risk for Alzheimer’s disease are more likely to develop a more aggressive form of Parkinson’s
Authors: Sandor Cynthia , Millin Stephanie , Dahl Andrew , Lawton Michael , Hubbard Leon , Bojovic Bobby , Peyret-Guzzon Marine , Matten Hannah , Blancher Christine , Williams Nigel , Ben-Shlomo Yoav , Hu Michele T. , Grosset Donald G. , Marchini Jonathan , Webber Caleb
Published: May 2019

The generation of deeply phenotyped patient cohorts offers an enormous potential to identify disease subtypes but are currently limited by the cohort size and the heterogeneity of the clinical assessments collected across different cohorts. Identifying the universal axes of clinal severity and progression is key to accelerating our understanding of how disease manifests and progresses. These universal axes would accelerate our understanding of how Parkinson’s disease (PD) manifests and progresses through which patients may be appropriately compared appropriately stratified, and personalised therapeutic strategies and treatments can be developed and targeted. We developed a Bayesian multiple phenotype mixed model incorporating the genetic relationships between individuals which is able to reduce a wide-array of different clinical measurements into a smaller number of continuous underlying factors named phenotypic axis. We identify three principal axes of PD patient phenotypic variation which are reproducibly found across three independent, deeply and diversely phenotyped cohorts. Together they explain over 75% of the observed clinical variation and remain robustly captured with a fraction of the clinically-recorded features. The most influential axis was associated with the genetic risk of Alzheimer’s disease (AD) and involves genetic pathways associated with neuroinflammation. Our results suggest PD patients with a high genetic risk for AD are more likely to develop a more aggressive form of PD including, but not limited to, dementia.
Mucin O-glycans facilitate symbiosynthesis to maintain gut immune homeostasis
Authors: Yamada Takahiro , Hino Shingo , Iijima Hideki , Genda Tomomi , Aoki Ryo , Nagata Ryuji , Han Ho , Hirota Masato , Kinashi Yusuke , Oguchi Hiroyuki , Suda Wataru , Furusawa Yukihiro , Fujimura Yumiko , Kunisawa Jun , Hattori Masahira , Fukushima Michihiro , Morita Tatsuya , Hase Koji
Published: May 2019

The dysbiosis of gut microbiota has been implicated in the pathogenesis of inflammatory bowel diseases (IBDs); however, the underlying mechanisms have not yet been elucidated. Heavily glycosylated mucin not only establishes a first-line barrier against pathogens, but also serves as a niche for microbial growth. We hypothesized that dysbiosis may cause abnormal mucin utilization and microbial metabolic dysfunction. To test this hypothesis, we analyzed short-chain fatty acids (SCFAs) and mucin components in the stool samples of 40 healthy subjects, 49 ulcerative colitis (UC) patients, and 44 Crohn’s disease (CD) patients from Japan. The levels of n-butyrate were significantly lower in the stools of both the CD and UC patients than in those of the healthy subjects. Correlation analysis identified 7 bacterial species positively correlated with n-butyrate levels, among which the major n-butyrate producer, Faecalibacterium prausnitzii, was particularly underrepresented in CD patients, but not in UC patients. In UC patients, there were inverse correlations between mucin O-glycan levels and the production of SCFAs, such as n-butyrate, suggesting that mucin O-glycans act as an endogenous fermentation substrate for n-butyrate production. Indeed, mucin-fed rodents exhibited enhanced n-butyrate production, leading to the expansion of RORgt+Treg cells and IgA-producing cells in the colonic lamina propria. Importantly, the availability of mucin-associated O-glycans to the microbiota was significantly reduced in n-butyrate-deficient UC patients. Taken together, our findings highlight the biological significance of the symbiosynthesis pathway in the production of n-butyrate, which maintains gut immune homeostasis.
AimB is a small protein regulator of cell size and MreB assembly
Authors: Werner John N. , Shi Handuo , Hsin Jen , Huang Kerwyn Casey , Gitai Zemer , Klein Eric A.
Published: May 2019

The MreB actin-like cytoskeleton assembles into dynamic polymers that coordinate cell shape in many bacteria. In contrast to most other cytoskeletons, few MreB interacting proteins have been well characterized. Here we identify a small protein fromCaulobacter crescentus, AimB, as anAssemblyInhibitor ofMreB. AimB overexpression mimics inhibition of MreB polymerization, leading to increased cell width and MreB delocalization. Molecular dynamics simulations suggest that AimB binds MreB at its monomer-monomer protofilament interaction cleft. We validate this model through functional analysis of point mutants in both AimB and MreB, photo-crosslinking studies with site-specific unnatural amino acids, and species-specific activity of AimB. Together, our findings indicate that AimB promotes MreB dynamics by inhibiting monomer-monomer assembly interactions, representing a new mechanism for regulating actin-like polymers and the first identification of a non-toxin MreB assembly inhibitor.
Dissecting the economic impact of soybean diseases in the United States over two decades
Authors: Bandara Ananda Y. , Weerasooriya Dilooshi K. , Bradley Carl A. , Allen Tom W. , Esker Paul D.
Published: May 2019

Soybean (Glycine maxL. Merrill) is a key commodity for United States agriculture. Here we analyze the economic impacts of 23 common soybean diseases in 28 soybean-producing states in the U.S., from 1996 to 2016. From 1996 to 2016, the total estimated economic loss due to soybean diseases in the U.S. was $81.39 billion, with $68.98 billion and $12.41 billion accounting for the northern and southern U.S. losses, respectively. Across states and years, soybean cyst nematode, charcoal rot, and seedling diseases were the most economically damaging pathogens/diseases while soybean rust, bacterial blight, and southern blight were the least economically damaging. Significantly positive linear correlation of mean soybean yield loss with the mean state-wide soybean production (MT) and mean soybean yield (kg ha−1) indicated that high production zones are more vulnerable to soybean diseases-associated yield losses. Our findings provide useful insights into how research, policy, and educational efforts should be prioritized in soybean disease management.
Sex chromosome evolution in muscid flies
Authors: Meisel Richard P. , Olafson Pia U. , Adhikari Kiran , Guerrero Felix D. , Konganti Kranti , Benoit Joshua B.
Published: May 2019

Sex chromosomes and sex determining genes can evolve fast, with the sex-linked chromosomes often differing between closely related species. A substantial body of population genetics theory has been developed and tested to explain the rapid evolution of sex chromosomes and sex determination. However, we do not know why the sex-linked chromosomes differ between some species pairs yet are relatively conserved in other taxa. Addressing this question will require comparing closely related taxa with conserved and divergent sex chromosomes and sex determination systems to identify biological features that could explain these rate differences. Cytological karyotypes suggest that muscid flies (e.g., house fly) and blow flies are such a taxonomic pair. The sex chromosomes appear to differ across muscid species, whereas they are highly conserved across blow flies. Despite the cytological evidence, we do not know the extent to which muscid sex chromosomes are independently derived along different evolutionary lineages. To address that question, we used genomic data to identify young sex chromosomes in two closely related muscid species, horn fly (Haematobia irritans) and stable fly (Stomoxys calcitrans). We provide evidence that the nascent sex chromosomes of horn fly and stable fly were derived independently from each other and from the young sex chromosomes of the closely related house fly (Musca domestica). We present three different scenarios that could have given rise to the sex chromosomes of horn fly and stable fly, and we describe how the scenarios could be distinguished. Distinguishing between these scenarios in future work could help to identify features of muscid genomes that promote sex chromosome divergence.
Bi-directional Mendelian randomization of epithelial ovarian cancer and schizophrenia and uni-directional Mendelian randomization of schizophrenia on circulating glycerophosphocholine metabolites
Authors: Adams Charleen D. , Neuhausen Susan L.
Published: May 2019

Most women with epithelial ovarian cancer (EOC) present with late-stage disease. As a result, globally, EOC is responsible for more than 150,000 deaths a year. Thus, a better understanding of risk factors for developing EOC is crucial for earlier screening and detection to improve survival. To that effort, there have been suggestions that there is an association of schizophrenia and cancer, possibly because metabolic changes are a hallmark of both cancer and schizophrenia (SZ). Perturbed choline metabolism has been documented in both diseases. Our objective was to use Mendelian randomization to evaluate whether SZ increased risk for developing EOC or the converse, and, whether SZ impacted glycerophosphocholine (GPC) metabolites. We found that SZ conferred a weak but increased risk for EOC, but not the reverse (no evidence that EOC caused SZ). SZ was also causally associated with lower levels of two GPC species and with suggestively lower levels in an additional three GPCs. We postulate that perturbed choline metabolism in SZ may mimic or contribute to a “cholinic” phenotype, as observed in EOC cells.
Assemblies of F-actin and myosin-II minifilaments: steric hindrance and stratification at the membrane cortex
Authors: Das Amit , Bhat Abrar , Sknepnek Rastko , Koster Darius , Mayor Satyajit , Rao Madan
Published: May 2019

Recentin-vivostudies have revealed that several membrane proteins are driven to form nanoclusters by active contractile flows arising from F-actin and myosin at the cortex. The mechanism of clustering was shown to be arising from the dynamic patterning of transient contractile platforms (asters) generated by actin and myosin. Myosin-II, which assemble as minifilaments consisting of tens of myosin heads, are rather bulky structures and hence a concern could be that steric considerations might obstruct the emergence of nanoclustering. Here, using coarse-grained, agent-based simulations that respect the size of constituents, we find that in the presence of steric hindrance, the patterns exhibited by actomyosin in two dimensions, do not resemble the steady state patterns observed in ourin-vitroreconstitution of actomyosin on a supported bilayer. We then perform simulations in a thin rectangular slab, allowing the separation of a layer of actin filaments from those of myosin-II minifilaments. This recapitulates the observed features ofin-vitropatterning. Using super resolution microscopy, we find direct evidence for stratification in ourin-vitrosystem. Our study suggests the possibility thatmolecular stratificationmay be an important organising feature of the cortical cytoskeletonin-vivo.
A nanometer difference in myofilament lattice spacing of two cockroach leg muscles explains their different functions
Authors: Tune Travis Carver , Ma Weikang , Irving Thomas C. , Sponberg Simon
Published: May 2019

Muscle is highly organized across scales. Consequently, small changes in arrangement of myofilaments can influence macroscopic function. Two leg muscles of a cockroach, have identical innervation, mass, twitch responses, length-tension curves, and force-velocity relationships. However, during running, one muscle is dissipative, while the other produces significant positive mechanical work. Using time resolved x-ray diffraction in intact, contracting muscle, we simultaneously measured the myofilament lattice spacing, packing structure, and macroscopic force production of these muscle to test if nanoscale differences could account for this conundrum. While the packing patterns are the same, one muscle has 1 nm smaller lattice spacing at rest. Under isometric activation, the difference in lattice spacing disappeared explaining the two muscles’ identical steady state behavior. During periodic contractions, one muscle undergoes a 1 nm greater change in lattice spacing, which correlates with force. This is the first identified feature that can account for the muscles’ different functions.
Aspirin compliance for cardiovascular disease and colorectal cancer prevention in the uninsured population
Authors: Liu Nina , Mathews Adithya , Swanson Justin , Mhaskar Rahul , Mathews Akshay , Ayoubi Noura , Mirza Abu-Sayeef
Published: May 2019

Aspirin is an effective anti-inflammatory and antiplatelet agent as an irreversible inhibitor of cyclooxygenase. In 2016, the U.S. Preventive Services Task Force recommended aspirin for primary prevention of cardiovascular disease (CVD) and colorectal cancer (CRC) in patients aged 50 to 69 with a 10% or greater 10-year CVD risk. Due to the lack of literature describing compliance with these recommendations in the uninsured patient population, we studied the aspirin adherence for CVD and CRC prevention in several free medical clinics. We investigated the records of 8857 uninsured patients who visited nine free medical clinics in the Tampa Bay Area in 2016-2017. Aspirin compliance was assessed for patients with prior myocardial infarction (MI) or coronary artery disease (CAD). 54% (n=1467) of patients met the criteria to take aspirin for primary prevention of CVD and CRC, but just 17% of these patients aged 50-59 were on the medication. 16% percent of patients aged 60-69 were taking aspirin and significantly more men than women were on aspirin (p=0.025). Of the 306 patients who had prior MI or CAD, 50% were on the medication for secondary prevention. Among the uninsured population, there is low compliance with recommendations for aspirin usage to reduce the risk of CVD and CRC. This study demonstrates that further improvements are needed to increase adherence to current guidelines and address barriers uninsured patients may face in maintaining their cardiovascular and colorectal health.
Lactic Acid Containing Polymers Produced in EngineeredSinorhizobium melilotiandPseudomonas putida
Authors: Tran Tam T. , Charles Trevor C.
Published: May 2019

This study demonstrates that novel polymer production can be achieved by introducing pTAM, a broad-host-range plasmid expressing codon-optimized genes encodingClostridium propionicumpropionate CoA transferase (PctCp) and a modifiedPseudomonassp. MBEL 6-19 polyhydroxyalkanoate (PHA) synthase 1 (PhaC1Ps6-19), intophaCmutant strains of the native polymer producersSinorhizobium melilotiandPseudomonas putida. Both phenotypic analysis and gas chromatography analysis indicated the synthesis and accumulation of biopolymers inS. melilotiandP. putidastrains. Expression inS. melilotiresulted in the production of PLA homopolymer up to 3.2% dried cell weight (DCW). The quaterpolymer P(3HB-co-LA-co-3HHx-co-3HO) was produced by expression inP. putida. TheP. putida phaCmutant strain produced this type of polymer the most efficiently with polymer content of 42% DCW when cultured in defined media with the addition of sodium octanoate, while the greatest LA fraction (4% mol) was achieved in the same strain cultured in LB with the addition of lactic acid. This is the first report, to our knowledge, of the production of a range of different biopolymers using the same plasmid-based system in different backgrounds. In addition, it is the first time that the novel polymer (P(3HB-co-LA-co-3HHx-co-3HO)), has been reported being produced in bacteria.
Turnover of ribosome-associated transcripts from de novo ORFs produces gene-like characteristics available for de novo gene emergence in wild yeast populations
Authors: Durand Éléonore , Gagnon-Arsenault Isabelle , Hallin Johan , Hatin Isabelle , Dubé Alexandre K. , Nielly-Thibault Lou , Namy Olivier , Landry Christian R.
Published: May 2019

Little is known about the rate of emergence of de novo genes, what their initial properties are, and how they spread in populations. We examined wild yeast populations (Saccharomyces paradoxus) to characterize the diversity and turnover of intergenic ORFs over short evolutionary timescales. We find that hundreds of intergenic ORFs show translation signatures similar to canonical genes, and we experimentally confirmed the translation of many of these ORFs in laboratory conditions using a reporter assay. Compared with canonical genes, intergenic ORFs have lower translation efficiency, which could imply a lack of optimization for translation or a mechanism to reduce their production cost. Translated intergenic ORFs also tend to have sequence properties that are generally close to those of random intergenic sequences. However, some of the very recent translated intergenic ORFs, which appeared <110 kya, already show gene-like characteristics, suggesting that the raw material for functional innovations could appear over short evolutionary timescales.
GIDVis: a comprehensive software tool for geometry-independent grazing-incidence X-ray diffraction data analysis and pole-figure calculations
Authors: Schrode Benedikt , Pachmajer Stefan , Dohr Michael , Röthel Christian , Domke Jari , Fritz Torsten , Resel Roland , Werzer Oliver
Published: May 2019

GIDVisis a software package based on MATLAB specialized for, but not limited to, the visualization and analysis of grazing-incidence thin-film X-ray diffraction data obtained during sample rotation around the surface normal.GIDVisallows the user to perform detector calibration, data stitching, intensity corrections, standard data evaluation (e.g.cuts and integrations along specific reciprocal-space directions), crystal phase analysisetc. To take full advantage of the measured data in the case of sample rotation, pole figures can easily be calculated from the experimental data for any value of the scattering angle covered. As an example,GIDVisis applied to phase analysis and the evaluation of the epitaxial alignment of pentacenequinone crystallites on a single-crystalline Au(111) surface.
Zn and Ni complexes of pyridine-2,6-dicarboxylates: crystal field stabilization matters!
Authors: Kremer Marius , Englert Ulli
Published: May 2019

Six reaction products of ZnII and NiII with pyridine-2,6-dicarboxylic acid (H2Lig1), 4-chloropyridine-2,6-dicarboxylic acid (H2Lig2) and 4-hydroxypyridine-2,6-dicarboxylic acid (H2Lig3) are used to pinpoint the structural consequences of crystal field stabilization by an incomplete d shell. The pseudo-octahedral ZnII coordination sphere in bis(6-carboxypicolinato)zinc(II) trihydrate, [Zn(C7H4NO4)2]·3H2O or [Zn(HLig1)2]·3H2O, (1), is significantly less regular than that about NiII in the isostructural compound bis(6-carboxypicolinato)nickel(II) trihydrate, [Ni(C7H4NO4)2]·3H2O or [Ni(HLig1)2]·3H2O, (2). The ZnII complexes poly[(4-chloropyridine-2,6-dicarboxylato)zinc(II)], [Zn(C7H2ClNO4)]
n
or [Zn(Lig2)]
n
, (3), and poly[[(4-hydroxypyridine-2,6-dicarboxylato)zinc(II)] monohydrate], {[Zn(C7H3NO5)]·H2O}
n
or {[Zn(Lig3)]·H2O}
n
, (4), represent two-dimensional coordination polymers with chelating and bridging pyridine-2,6-dicarboxylate ligands in which the coordination polyhedra about the central cations cannot be associated with any regular shape; their coordination environments range between trigonal–bipyramidal and square-pyramidal geometries. In contrast, the corresponding adducts of the diprotonated ligands to NiII, namely triaqua(4-chloropyridine-2,6-dicarboxylato)nickel(II), [Ni(C7H2ClNO4)(H2O)3] or [NiLig2(OH2)3)], (5), and triaqua(4-hydroxypyridine-2,6-dicarboxylato)nickel(II) 1.7-hydrate, [Ni(C7H3NO5)(H2O)3]·1.7H2O or [NiLig3(OH2)3)]·1.7H2O, (6), feature rather regular octahedral coordination spheres about the transition-metal cations, thus precluding the formation of analogous extended structures.
Crystal structure, DFT study and Hirshfeld surface analysis of ethyl 6-chloro-2-ethoxyquinoline-4-carboxylate
Authors: Bouzian Younos , Karrouchi Khalid , Anouar El Hassane , Bouhfid Rachid , Arshad Suhana , Essassi El Mokhtar
Published: May 2019

In the title quinoline derivative, C14H14ClNO3, there is an intramolecular C—H...O hydrogen bond forming an S(6) graph-set motif. The molecule is essentially planar with the mean plane of the ethyl acetate group making a dihedral angle of 5.02 (3)° with the ethyl 6-chloro-2-ethoxyquinoline mean plane. In the crystal, offset π–π interactions with a centroid-to-centroid distance of 3.4731 (14) Å link inversion-related molecules into columns along the c-axis direction. Hirshfeld surface analysis indicates that H...H contacts make the largest contribution (50.8%) to the Hirshfeld surface.
Crystal structure of 210,220-bis(2,6-dichlorophenyl)-4,7,12,15-tetraoxa-2(5,15)-nickel(II)porpyhrina-1,3(1,2)-dibenzena-cycloheptadecaphane-9-yne dichloromethane monosolvate
Authors: Peters Morten K. , Näther Christian , Herges Rainer
Published: May 2019

The asymmetric unit of the title compound, [Ni(C52H34Cl4N4O4)]·CH2Cl2, consists of two discrete complexes, which show significant differences in the conformation of the side chain. Each NiII cation is coordinated by four nitrogen atoms of a porphyrin molecule within a square-planar coordination environment. Weak intramolecular C—H...Cl and C—H...O interactions stabilize the molecular conformation. In the crystal structure, discrete complexes are linked by C—H...Cl hydrogen-bonding interactions. In addition, the two unique dichloromethane solvate molecules (one being disordered) are hydrogen-bonded to the Cl atoms of the chlorophenyl groups of the porphyrin molecules, thus stabilizing the three-dimensional arrangement. The crystal exhibits pseudo-orthorhombic metrics, but structure refinements clearly show that the crystal system is monoclinic and that the crystal is twinned by pseudo-merohedry.
Dichlorido{N,N,N′-trimethyl-N′-(1H-pyrazol-1-yl-κN
2)methyl]ethane-1,2-diamine-κ2
N,N′}copper(II) methanol monosolvate
Authors: Singh Ravindra , Ali Akram , Faizi Md. Serajul Haque , Singh Roona , Iskenderov Turganbay S. , Dege Necmi
Published: May 2019

In the title compound, [CuCl2(C9H18N4)]·CH3OH, the central CuII ion is coordinated by three N atoms from the pyrazole derivative ligand and two chloride co-ligands. The coordination geometry around the CuII ion is distorted trigonal–bipyramidal. In the crystal, the molecules are linked by C—H...O, C—H...Cl and O—H...Cl hydrogen bonds, forming a three-dimensional framework with the lattice solvent molecule.
Rhythmicity of health information behaviour
Authors: Tana Jonas , Eirola Emil , Eriksson-Backa Kristina
Published: May 2019

Purpose

This paper brings focus and attention to the aspect of time within health information behaviour. The purpose of this paper is to critically assess and present strengths and weaknesses of utilising the infodemiology approach and metrics as a novel way to examine temporal variations and patterns of online health information behaviour. The approach is shortly exemplified by presenting empirical evidence for temporal patterns of health information behaviour on different time-scales.

Design/methodology/approach

A short review of online health information behaviour is presented and methodological barriers to studying the temporal nature of this behaviour are emphasised. To exemplify how the infodemiology approach and metrics can be utilised to examine temporal patterns, and to test the hypothesis of existing rhythmicity of health information behaviour, a brief analysis of longitudinal data from a large discussion forum is analysed.

Findings

Clear evidence of robust temporal patterns and variations of online health information behaviour are shown. The paper highlights that focussing on time and the question of when people engage in health information behaviour can have significant consequences.

Practical implications

Studying temporal patterns and trends for health information behaviour can help in creating optimal interventions and health promotion campaigns at optimal times. This can be highly beneficial for positive health outcomes.

Originality/value

A new methodological approach to study online health information behaviour from a temporal perspective, a phenomenon that has previously been neglected, is presented. Providing evidence for rhythmicity can complement existing epidemiological data for a more holistic picture of health and diseases, and their behavioural aspects.
What does Google recommend when you want to compare insurance offerings?
Authors: Lewandowski Dirk , Sünkler Sebastian
Published: May 2019

Purpose

The purpose of this paper is to describe a new method to improve the analysis of search engine results by considering the provider level as well as the domain level. This approach is tested by conducting a study using queries on the topic of insurance comparisons.

Design/methodology/approach

The authors conducted an empirical study that analyses the results of search queries aimed at comparing insurance companies. The authors used a self-developed software system that automatically queries commercial search engines and automatically extracts the content of the returned result pages for further data analysis. The data analysis was carried out using the KNIME Analytics Platform.

Findings

Google’s top search results are served by only a few providers that frequently appear in these results. The authors show that some providers operate several domains on the same topic and that these domains appear for the same queries in the result lists.

Research limitations/implications

The authors demonstrate the feasibility of this approach and draw conclusions for further investigations from the empirical study. However, the study is a limited use case based on a limited number of search queries.

Originality/value

The proposed method allows large-scale analysis of the composition of the top results from commercial search engines. It allows using valid empirical data to determine what users actually see on the search engine result pages.
Towards task-sensitive assistance in public spaces
Authors: Kilian Melanie A. , Kattenbeck Markus , Ferstl Matthias , Ludwig Bernd , Alt Florian
Published: May 2019

Purpose

Performing tasks in public spaces can be demanding due to task complexity. Systems that can keep track of the current task state may help their users to successfully fulfill a task. These systems, however, require major implementation effort. The purpose of this paper is to investigate if and how a mobile information assistant which has only basic task-tracking capabilities can support users by employing a least effort approach. This means, we are interested in whether such a system is able to have an impact on the way a workflow in public space is perceived.

Design/methodology/approach

The authors implement and test AIRBOT, a mobile chatbot application that can assist air passengers in successfully boarding a plane. The authors apply a three-tier approach and, first, conduct expert and passenger interviews to understand the workflow and the information needs occurring therein; second, the authors implement a mobile chatbot application providing minimum task-tracking capabilities to support travelers by providing boarding-relevant information in a proactive manner. Finally, the authors evaluate this application by means of an in situ study (n = 101 passengers) at a major European airport.

Findings

The authors provide evidence that basic task-tracking capabilities are sufficient to affect the users’ task perception. AIRBOT is able to decrease the perceived workload airport services impose on users. It has a negative impact on satisfaction with non-personalized information offered by the airport, though.

Originality/value

The study shows that the number of features is not the most important means to successfully provide assistance in public space workflows. The study can, moreover, serve as a blueprint to design task-based assistants for other contexts.