bluuebunny/crossref_metadata_2025 huggingface dataset:
Genome improvement and genetic map construction for Aethionema arabicum, the first divergent branch in the Brassicaceae family
Authors: Nguyen Thu-Phuong , Mühlich Cornelia , Mohammadin Setareh , van den Bergh Erik , Platts Adrian E. , Haas Fabian B. , Rensing Stefan A. , Schranz M. Eric
Published: June 2019

Background

The genus Aethionema is a sister-group to the core-group of the Brassicaceae family that includes Arabidopsis thaliana and the Brassica crops. Thus, Aethionema is phylogenetically well-placed for the investigation and understanding of genome and trait evolution across the family. We aimed to improve the quality of the reference genome draft version of the annual species Aethionema arabicum. Secondly, we constructed the first Ae. arabicum genetic map. The improved reference genome and genetic map enabled the development of each other.

Results

We started with the initially published genome (version 2.5). PacBio and MinION sequencing together with genetic map v2.5 were incorporated to produce the new reference genome v3.0. The improved genome contains 203 MB of sequence, with approximately 94% of the assembly made up of called bases, assembled into 2,883 scaffolds. The N50 (10.3 MB) represents an 80-fold over the initial genome release. We generated a Recombinant Inbred Line (RIL) population that was derived from two ecotypes: Cyprus and Turkey (the reference genotype. Using a Genotyping by Sequencing (GBS) approach, we generated a high-density genetic map with 749 (v2.5) and then 632 SNPs (v3.0) was generated. The genetic map and reference genome were integrated, thus greatly improving the scaffolding of the reference genome into 11 linkage groups.

Conclusions

We show that long-read sequencing data and genetics are complementary, resulting in an improved genome assembly in Ae. arabicum. They will facilitate comparative genetic mapping work for the Brassicaceae family and are also valuable resources to investigate wide range of life history traits in Aethionema.
Predicting the Evolution of White Matter Hyperintensities in Brain MRI using Generative Adversarial Networks and Irregularity Map
Authors: Rachmadi Muhammad Febrian , Valdés-Hernández Maria del C. , Makin Stephen , Wardlaw Joanna M. , Komura Taku
Published: June 2019

We propose a Generative Adversarial Network (GAN) model named Disease Evolution Predictor GAN (DEP-GAN) to predict the evolution (i.e., progression and regression) of White Matter Hyperintensities (WMH) in small vessel disease. In this study, the evolution of WMH is represented by the “Disease Evolution Map” (DEM) produced by subtracting irregularity map (IM) images from two time points: baseline and follow-up. DEP-GAN uses two discriminators (critics) to enforce anatomically realistic follow-up image and DEM. To simulate the non-deterministic and unknown parameters involved in WMH evolution, we propose modulating an array of random noises to the DEP-GAN’s generator which forces the model to imitate a wider spectrum of alternatives in the results. Our study shows that the use of two critics and random noises modulation in the proposed DEP-GAN improves its performance predicting the evolution of WMH in small vessel disease. DEP-GAN is able to estimate WMH volume in the follow-up year with mean (std) estimation error of −1.91 (12.12)mland predict WMH evolution with mean rate of 72.01% accuracy (i.e., 88.69% and 23.92% better than Wasserstein GAN).
Serial position effects reflect the integrity of distinct brain regions in Major and Minor Neurocognitive Disorder
Authors: Foldi Nancy S. , Taylor Kirsten I. , Monsch Andreas U. , Sollberger Marc , Kivisaari Sasa L.
Published: June 2019

Serial Position Effects (SPE) in wordlist learning provide a rich set of metrics of cognitive functioning. In this study, we systematically mapped the neuroanatomical correlates of SPEs across delays in Major and Minor Neurocognitive disorders. Primacy, middle, and recency SPE scores of the California Verbal Learning Test at Learning, Short delay, and Long delay in healthy controls and patients with neurodegenerative disease were correlated with MRI gray matter signal intensities (voxel-based morphometry, VBM). The VBM analyses revealed distinct patterns of brain-behavioral correlations depending on both the SPE and the time-point. Unlike patients, the healthy controls’ performance incrementally improved recall of primacy items from Learning to Short and to Long delay, i.e., primacy progression. Moreover, the proportion of correct primacy items recalled at long delay compared to Learning correlated with bilateral medial temporal lobe regions, which commonly bear the brunt of pathology of Alzheimer’s disease. The results implicate the primacy progression score as an accessible and sensitive measure for disease detection, progression, and therapeutic response in Major and Minor Neurocognitive disorders.
Aimed Limb Movements in a Hemimetabolous Insect are Intrinsically Compensated for Allometric Wing Growth by Developmental Mechanisms
Authors: Patel Alexandra J. , Matheson Thomas
Published: June 2019

For aimed limb movements to remain functional they must be adapted to developmental changes in body morphology and sensory-motor systems. Insects use their limbs to groom the body surface or to dislodge external stimuli, but they face the particular problem of adapting these movements to step-like changes in body morphology during metamorphosis or moulting. Locusts are hemimetabolous insects in which the imaginal moult to adulthood results in a sudden and dramatic allometric growth of the wings relative to the body and the legs. We show that, despite this, hind limb scratches aimed at mechanosensory stimuli on the wings remain targeted to appropriate locations after moulting. In juveniles, the tips of the wings extend less than half way along the abdomen, but in adults they extend well beyond the posterior end. Kinematic analyses were used to examine the scratching responses of juveniles (5thinstars) and adults to touch of anterior (wing base) and posterior (distal abdomen) targets that develop isometrically, and to wing tip targets that are anterior in juveniles but posterior in adults. Juveniles reach the (anterior) wing tip with the distal tibia of the hind leg using anterior rotation of the thoraco-coxal and coxo-trochanteral (‘hip’) joints and flexion of the femoro-tibial (‘knee’) joint. Adults, however, reach the corresponding (but now posterior) wing tip using posterior rotation of the hip and extension of the knee, reflecting a different underlying motor pattern. This change in kinematics occurs immediately after the adult moult without learning, indicating that the switch is developmentally programmed.

SUMMARY STATEMENT

A developmentally programmed change in the scratching movements of locusts permits adult animals to aim their movements at new wing tip targets, without learning.
Homogenization of Rhizosphere Bacterial Communities by Pea (Pisum sativum L.) Cultivated under Different Conservation Agricultural Practices in the Eastern Himalayas
Authors: Chaudhari Diptaraj , Rangappa Krishnappa , Das Anup , Layek Jayanta , Basavaraju Savita , Shouche Yogesh , Rahi Praveen
Published: June 2019

Conservation agriculture offers a suitable system to harmonize agriculture with the environment, especially in fragile ecosystems of North-East India. Soil microbes play pivotal roles in ecosystem functioning and act as indispensable indicators of overall fitness of crop plant and soil health. Here we demonstrated that altercations in residue management and tillage practices lead to the development of differential bacterial communities forcing the pea plants to recruit special groups of bacteria leading to highly homogenous rhizosphere communities. Pea rhizosphere and bulk soil samples were collected, and bacterial community structure was estimated by 16S rRNA gene amplicon sequencing and predictive functional analysis was performed using Tax4Fun. The effect on pea plants was evident in the bacterial communities as the overall diversity of rhizosphere samples was significantly higher to that of bulk soil samples. Bacillus, Staphylococcus, Planomicrobium, Enterobacter, Arthrobacter, Nitrobacter, Geobacter, and Sphingomonas were noticed as the most abundant genera in the rhizosphere and bulk soil samples. The abundance of Firmicutes and Proteobacteria altered significantly in the rhizosphere and bulk samples, which was further validated by qPCR. Selection of specific taxa by pea plant was indicated by the higher values of mean proportion of Rhizobium, Pseudomonas, Pantoea, Nitrobacter, Enterobacter and Sphingomonas in rhizosphere samples, and Massilia, Paenibacillus and Planomicrobium in bulk soil samples. Tillage and residue management treatments did not significantly alter the bacterial diversity, while their influence was observed on the abundance of few genera. Recorded results revealed that pea plant selects specific taxa into its rhizosphere plausibly to meet its requirements for nutrient uptake and stress amelioration under the different tillage and residue management practices.
Myelin development in visual scene-network tracts beyond late childhood: A multimethod neuroimaging study
Authors: Meissner Tobias W , Genç Erhan , Mädler Burkhard , Weigelt Sarah
Published: June 2019

The visual scene-network - comprising the parahippocampal place area (PPA), retrosplenial cortex (RSC), and occipital place area (OPA) - shows a prolonged functional development. Structural development of white matter that underlies the scene-network has not been investigated despite its potential influence on scene-network function. The key factor for white matter maturation is myelination. However, research on myelination using the gold standard method of post-mortem histology is scarce. In vivo alternatives diffusion-weighed imaging (DWI) and myelin water imaging (MWI) so far report broad-scale findings that prohibit inferences concerning the scene-network. Here, we combine MWI, DWI tractography, and fMRI to investigate myelination in scene-network tracts in middle childhood, late childhood, and adulthood. We report increasing myelin from middle childhood to adulthood in right PPA-OPA, and trends towards increases in the left and right RSC-OPA tracts. Investigating tracts to regions highly connected with the scene-network, such as early visual cortex and the hippocampus did not yield any significant age group differences. Our findings indicate that structural development coincides with functional development in the scene-network, possibly enabling structure-function interactions.
Ginsenoside Rg1 defenses PC-12 cells against hydrogen peroxide-caused damage via up-regulation of miR-216a-5p
Authors: Yi Guangkun , Liu Li , Lv Chaoliang , Wei Yanchun , Yan Tingzhen
Published: June 2019

Background

Spinal cord injury (SCI) is a destructive trauma accompanying with local injury, half of which cause chronic paralysis. Ginsenoside Rg1 exerts anti-apoptosis and anti-autophagy properties. Therefore, our goal was to study the protective mechanism of Rg1 in attenuating cell injury.

Methods

MiR-216a-5p inhibitor was transfected into PC-12 cells, then cells were pre-treated by Rg1 and treated with 300 μM hydrogen peroxide (H2O2) for 24 h. CCK-8 and apoptosis experiments were done to test cell activity and apoptosis respectively. Expression of miR-216a-5p and cell damage relative factors was tested via qRT-PCR and western blot experiments, respectively.

Results

H2O2induced cell activity suppression, apoptosis and autophagy well at the concentration of 300 μM, leading cell injury. Rg1 could attenuate cell injury induced by H2O2at the working concentration of 200 μM that it elevated cell activity, attenuated apoptosis and autophagy and activated PI3K/AKT and AMPK signal pathways. Further, miR-216a-5p was up-regulated by Rg1. Rg1 played its role in relieving cell injury by positively regulating miR-216a-5p.

Conclusion

Our study demonstrated that Rg1 attenuated H2O2-caused cell injury through positively regulated miR-216a-5p.
Protein Acetylation Induced by Dichloroacetate (DCA) Treatment is Associated with Decreased Respiration in Cultured Hepatocytes: Preliminary Results
Authors: Meyer Jesse G.
Published: June 2019

Protein post-translational modification (PTM) by acetylation at the ε-amine on lysine residues in proteins regulates various cellular processes including transcription and metabolism. Several metabolic and genetic perturbations are known to increase acetylation of various proteins. Hyper-acetylation can also be induced using deacetylase inhibitors. While there is much interest in discovering drugs that can reverse protein acetylation, pharmacological tools that increase non-enzymatic protein acetylation are needed in order to understand the physiological role of excess protein acetylation. In this study, I assessed whether inhibition of pyruvate dehydrogenase kinase (PDHK) could cause protein hyper-acetylation due to excess production of acetyl-CoA by pyruvate dehydrogenase (PDH). Western blot of total protein from dichloroacetate (DCA) treated hepatocytes with anti-acetyl-lysine antibody showed increased protein acetylation, and seahorse respirometry of DCA pretreated hepatocytes indicated a subtle decrease in basal and maximal respiratory capacity.
Multi-omic analyses reveal antibody-dependent natural killer cell-mediated cytotoxicity in autoimmune thyroid diseases
Authors: Martin Tiphaine C. , Illieva Kristina M. , Visconti Alessia , Beaumont Michelle , Kiddle Steven J. , Dobson Richard J.B. , Mangino Massimo , Lim Ee Mun , Pezer Marija , Steves Claire J. , Bell Jordana T. , Wilson Scott G. , Lauc Gordan , Roederer Mario , Walsh John P. , Spector Tim D. , Karagiannis Sophia N.
Published: June 2019

The pathogenesis of autoimmune thyroid diseases (AITD) is poorly understood. We previously observed systemic depletion of IgG core fucosylation and antennary α1,2 fucosylation of peripheral blood mononuclear cells in AITD, correlated with thyroid peroxidase antibody (TPOAb) levels. We hypothesized that deficiency in IgG core fucose enhances antibody-dependent cell-mediated cytotoxicity of thyrocytes by TPOAb, contributing to thyroid autoimmunity. Multi-omic evaluations in 622 individuals (172 with AITD) from the TwinsUK cohort showed decreased IgG core fucosylation levels associated with a subpopulation of natural killer (NK) cells featuring CD335, CD314, and CD158b immunoreceptors, and increased levels of apoptosis-associated Caspase-2 and Interleukin-1α, positively associated with AITD. AITD-associated genetic variants rs1521 and rs3094228 alter expression of thyrocyte ligands of the CD314 and CD158b immunoreceptors on NK cells. The combination of low-core fucose IgG associated with an NK cell subpopulation and genetic variant-promoted ligand activation in thyrocytes may promote antibody-dependent NK cell-mediated cytotoxicity of thyrocytes in AITD.
The emergent Yo-yo movement of nuclei driven by collective cytoskeletal remodeling in pseudo-synchronous mitotic cycles
Authors: Lv Zhiyi , Rosenbaum Jan , Mohr Stephan , Zhang Xiaozhu , Kong Deqing , Preiß Helen , Kruss Sebastian , Alim Karen , Aspelmeier Timo , Großhans Jörg
Published: June 2019

Many aspects in tissue morphogenesis are attributed to the collective behavior of the participating cells. Yet, the mechanism for emergence of dynamic tissue behavior is not understood completely. Here we report the “yo-yo”-like nuclear drift movement in Drosophila syncytial embryo displays typical emergent feature of collective behavior, which is associated with pseudo-synchronous nuclear division cycle. We uncover the direct correlation between the degree of asynchrony of mitosis and the nuclear collective movement. Based on experimental manipulations and numerical simulations, we find the ensemble of spindle elongation, rather than a nucleus’ own spindle, is the main driving force for its drift movement. The cortical F-actin acts as viscoelastic medium to dampen the movements and plays a critical role in restoring the nuclear positions after a mitosis cycle. Our study provides insights into how the interactions between cytoskeleton as individual elements leads to collective movement of the nuclear array on a macroscopic scale.
Antigen-Specific Immune Decoys Intercept and Exhaust Autoimmunity to Prevent Disease
Authors: Griffin J. Daniel , Song Jimmy Y. , Huang Aric , Sedlacek Alexander R. , Flannagan Kaitlin L. , Berkland Cory J.
Published: June 2019

Relapsing-remitting patterns of many autoimmune diseases such as multiple sclerosis (MS) are perpetuated by a recurring circuit of adaptive immune cells that amplify in secondary lymphoid organs (SLOs) and traffic to compartments where antigen is abundant to elicit damage. Some of the most effective immunotherapies impede the migration of immune cells through this circuit, however, broadly suppressing immune cell migration can introduce life-threatening risks for patients. We developed antigen-specific immune decoys (ASIDs) to mimic tissues targeted in autoimmunity and selectively intercept autoimmune cells to preserve host tissue. Using Experimental Autoimmune Encephalomyelitis (EAE) as a model, we conjugated autoantigen PLP139-151 to a microporous collagen scaffold. By subcutaneously implanting ASIDs after induction but prior to the onset of symptoms, mice were protected from paralysis. ASID implants were rich with autoimmune cells, however, reactivity to cognate antigen was substantially diminished and apoptosis was prevalent. ASID-implanted mice consistently exhibited engorged spleens when disease normally peaked. In addition, splenocyte antigen-presenting cells were highly activated in response to PLP rechallenge, but CD3+ and CD19+ effector subsets were significantly decreased, suggesting exhaustion. ASID-implanted mice never developed EAE relapse symptoms even though the ASID material had long since degraded, suggesting exhausted autoimmune cells did not recover functionality. Together, data suggested ASIDs were able to sequester and exhaust immune cells in an antigen-specific fashion, thus offering a compelling approach to inhibit the migration circuit underlying autoimmunity.
A versatile method for circulating cell-free DNA methylome profiling by reduced representation bisulfite sequencing
Authors: De Koker A. , Van Paemel R. , De Wilde B. , De Preter K. , Callewaert N.
Published: June 2019

The methylation profile of circulating cell-free DNA (cfDNA) in blood can be exploited to detect and diagnose cancer and other tissue pathologies and is therefore of great diagnostic interest. There is an urgent need for a cost-effective genome-wide methylation profiling method that is simple, robust and automatable and that works on highly fragmented cfDNA. We report on a novel sample preparation method for reduced representation bisulfite sequencing (RRBS), rigorously designed and customized for minute amounts of highly fragmented DNA. Our method works in particular on cfDNA from blood plasma. It is a performant and cost-effective methodology (termed cf-RRBS) which enables clinical cfDNA epigenomics studies.
Nucleus Basalis links sensory stimuli with delayed reinforcement to support learning
Authors: Guo W. , Polley D.B.
Published: June 2019

Linking stimuli with delayed reinforcement requires neural circuits that can bridge extended temporal gaps. Auditory cortex (ACx) circuits reorganize to support auditory fear learning, but only when afferent sensory inputs temporally overlap with cholinergic reinforcement signals. Here we show that mouse ACx neurons rapidly reorganize to support learning, even when sensory and reinforcement cues are separated by a long gap. We found that cholinergic basal forebrain neurons bypass the temporal delay through multiplexed, short-latency encoding of sensory and reinforcement cues. At the initiation of learning, cholinergic neurons in Nucleus Basalis increase responses to conditioned sound frequencies and increase functional connectivity with ACx. By rapidly scaling up responses to sounds that predict reinforcement, cholinergic inputs jump the gap to align with bottom-up sensory traces and support associative cortical plasticity.
Purinergic signaling is enhanced in the absence of UT-A1 and UT-A3
Authors: Himmel Nathaniel J. , Rogers Richard T. , Redd Sara K. , Wang Yirong , Blount Mitsi A.
Published: June 2019

ATP is an important paracrine regulator of renal tubular water and urea transport. The activity of P2Y2, the predominant P2Y receptor of the medullary collecting duct, is mediated by ATP, and modulates urinary concentration. To investigate the role of purinergic signaling in the absence of urea transport in the collecting duct, we housed wild-type (WT) and UT-A1/A3 null (UT-A1/A3 KO) mice in metabolic cages to monitor urine output, and collected tissue samples for analysis. We confirmed that UT-A1/A3 KO mice are polyuric, and concurrently observed lower levels of urinary cAMP as compared to WT, despite elevated serum vasopressin (AVP) levels. Because P2Y2inhibits AVP-stimulated transport by dampening cAMP synthesis, we suspected that, similar to other models of AVP-resistant polyuria, purinergic signaling is increased in UT-A1/A3 KO mice. In fact, we observed that both urinary ATP and purinergic-mediated prostanoid (PGE2) levels were elevated. Tissue analysis shows that P2Y2mRNA levels remain unchanged, while P2Y2protein levels are elevated in KO mice. Collectively, our data suggest that the reduction of medullary osmolality due to the lack of UT-A1 and UT-A3 induces an AVP-resistant polyuria that is possibly exacerbated by, or at least correlated with, enhanced purinergic signaling.

Summary statement

Physiological analyses suggest that mice lacking urea transporters have increased renal purinergic signaling, perhaps contributing to previously observed vasopressin-resistant polyurias.
Effectiveness of treatments for firework fears in dogs
Authors: Riemer Stefanie
Published: June 2019

An online questionnaire survey investigated (1) management and (2) treatment methods for firework fears in dogs employed by dog owners and their (perceived) effectiveness. A PCA on data from 1225 respondents revealed four management strategies (i.e. interventions during firework exposure): the principal components “Environmental modification” (e.g. providing a hiding place, keeping windows and blinds closed, and playing music), “Feed/Play” (providing the dog with chews, play and food during fireworks in general, as well as contingent on loud bangs), “Alternative” (use of calming nutraceuticals, pheromones, herbal products, homeopathic products, Bach flowers, and essential oils) and “Interaction” (allowing body contact, petting and talking to the dog when loud bangs occurred). To explore possible effects of these management methods on fear development, the components were correlated with a score for fear progression. Of the four components, only “Feed/Play” was statistically associated with an improvement in fear responses to fireworks. To evaluate the effectiveness of various treatment strategies, owners were asked to select from a range of options which interventions they had used and whether they considered them as effective. With prescription medication (N=202), improvements were noted by 69% of owners, with high success rates reported for the most frequently prescribed drugs, alprazolam (91%) and Sileo® (74%). While individual products were not evaluated, the reported success rates for the categories “pheromones” (N=316), “herbal products” (N=282), “nutraceuticals” (N=211), “essential oils” (N=183), “homeopathic remedies” (N=250) and “Bach flowers” (N=281) were all in the range of 27-35%, which is not higher than would be expected based on a placebo effect. Pressure vests were deemed as effective by 44% of respondents (N=300). Counterconditioning (providing desirable stimuli after the occurrence of noises) was the most successful training technique according to the owners (N=694), with a reported effectiveness of over 70%. Relaxation training (N=433) was reported to be almost as successful at 69%, while noise CDs (N=377) were effective in 55% of cases. Thus, counterconditioning, relaxation training and anxiolytic medication appear to be the most effective strategies in the treatment of firework fears in dogs. On this basis it is recommended that ad-hoc counterconditioning and relaxation training should complement the standard behavioral technique of desensitization/ counterconditioning with noise recordings.

Highlights

An online survey on treatment options for firework fears in dogs was performed

Feeding or playing with dogs during fireworks was associated with fear improvement

Success was highest for ad-hoc counterconditioning, relaxation training and medication

Success was similar for pheromones, nutraceuticals and other alternative products

Success rates for these alternative products are consistent with a placebo effect
RHOA mediated mechanical force generation through Dectin-1
Authors: Choraghe Rohan P. , Kołodziej Tomasz , Buser Alan , Rajfur Zenon , Neumann Aaron K.
Published: June 2019

Dectin-1 is an innate immune pattern recognition receptor which recognizes β-glucan on theCandida albicans(C. albicans) cell wall. Recognition of β-glucan by immune cells leads to phagocytosis, oxidative burst, cytokine and chemokine production. We looked for specific mechanisms that coordinate phagocytosis downstream of Dectin-1 leading to actin reorganization and internalization of fungus. We found that stimulation of Dectin-1 by soluble β-glucan leads to mechanical force generation and areal contraction in Dectin-1 transfected HEK-293 cells and M1 macrophages. With inhibitor studies, we found this force generation is a SYK-independent, SFK (SRC Family Kinase)-dependent process mediated through the RHOA-ROCK-MLC pathway. We confirmed activation of RHOA downstream of Dectin-1 using G-LISA and stress fiber formation. Through phagocytosis assays, we found direct evidence for importance of RHOA-ROCK-MLC pathway in process of phagocytosis ofC. albicans. In conclusion, we found evidence for RHOA-ROCK-MLC mediated mechanical force generation downstream of Dectin-1 forC. albicansphagocytosis.
Molecularly distinct cores coexist inside stress granules
Authors: Cirillo Luca , Cieren Adeline , Gotta Monica
Published: June 2019

Stress granules are membraneless organelles that form in eukaryotic cells after stress exposure. Stress granules are constituted by a stable core and a dynamic shell that establishes a liquid-liquid phase separation with the surrounding cytosol. The structure and assembly of stress granules and how different components contribute to their formation are not fully understood. Here, using super resolution and expansion microscopy, we find that the stress granule component UBAP2L and the core protein G3BP1 occupy different domains inside stress granules. Since UBAP2L displays typical properties of a core protein, our results indicate that different cores coexist inside the same granule. Consistent with a role as a core protein, UBAP2L is required for stress granule assembly in several stress conditions and reverse genetics show that it acts upstream of G3BP1. We propose a model in which UBAP2L is an essential stress granule nucleator that facilitates G3BP1 core formation and stress granule assembly and growth.
Long acyl chain ceramides govern cholesterol and cytoskeleton dependence of membrane outer leaflet dynamics
Authors: Gupta Anjali , Muralidharan Sneha , Torta Federico , Wenk Markus R. , Wohland Thorsten
Published: June 2019

The cellular plasma membrane composition and organization is crucial for the regulation of biological processes. Based on our earlier work showing that the same lipid probe, DiI, exhibits different dynamics in CHO-K1 and RBL-2H3 cells, we investigate the molecular factors that govern these differences. First, we determined that the cytoskeleton-interacting Immunoglobulin E receptor (FcεRI), which is abundant in RBL-2H3 but not in CHO-K1 cells, is not responsible for the DiI confinement found in RBL-2H3 cells. Second, lipid mass spectrometry of the plasma membrane of the two cells indicated differences in ceramide content, especially with long and very long acyl chains (C16 to C24). We, therefore, measure membrane dynamics by imaging total internal reflection fluorescence correlation spectroscopy in dependence on these ceramides. Our results show that C24 and C16 saturated ceramides uniquely alter the membrane dynamics by promoting the formation of cholesterol-independent domains and by elevating inter-leaflet coupling.
A key interfacial residue identified with in-cell structure characterization of a class A GPCR dimer
Authors: Yang Ju , Gong Zhou , Lu Yun-Bi , Xu Chan-Juan , Wei Tao-Feng , Yang Men-Shi , Zhan Tian-Wei , Yang Yu-Hong , Lin Li , Liu Jian-Feng , Tang Chun , Zhang Wei-Ping
Published: June 2019

G protein coupled receptors (GPCRs) have been shown homo-dimeric. Despite extensive studies, no single residue has been found essential for dimerization. Lacking an efficient method to shift the monomer-dimer equilibrium also makes functional relevance of GPCR dimer elusive. Here, using fluorescence lifetime-based imaging for distance measurements, we characterize the dimeric structure of GPR17, a class A GPCR, in cells. The structure reveals transmembrane helices 5 and 6 the dimer interface, and pinpoints F229 a key residue, mutations of which can render GPR17 monomeric or dimeric. Using the resulting mutants, we show that GPR17 dimer is coupled to both Gαi and Gαq signaling and is internalized, whereas GPR17 monomer is coupled to Gαi signaling only and is not internalized. We further show that residues equivalent to F229 of GPR17 in several other class A GPCRs are also important for dimerization. Our findings thus provide fresh insights into GPCR structure and function.
Use of solvent extraction–indigenous microbial degradation technology to repair soils contaminated by high concentrations of mechanical oil
Authors: Chen Guo , Yin Zhongyi , Liu Anping , Zheng Xuxu
Published: June 2019

Remediation of soils contaminated by mechanical oil has become a difficult problem worldwide. In this study, soil contaminated by mechanical oil was repaired by domestication and inoculation of microorganisms collected from the contaminated site, and soil quality and plant growth indexes were evaluated to verify the efficacy of our solvent extraction–indigenous microbial degradation technology. Solvent extraction of the contaminated soil removed 97.03% mechanical oil, increased soil water-holding capacity by 68.20%, and improved root activity and soluble sugar content of alfalfa plants. However, solvent extraction depleted 82.98% of the soil organic matter. Screening and domestication of strain TB-6 from the contaminated site revealed that it is anEnterobacterwith obvious degradation effects on petroleum hydrocarbons (C15–C28). After the solvent-extracted soil was inoculated with TB-6 for 30 days, the soil structure became loose; degradation rate of residual mechanical oil was 19.45%; and soil organic matter content, water-holding capacity, alfalfa root activity, and soluble sugar content increased by 35.00%, 9.01%, 44.60%, and 7.03%, respectively. These results indicate that TB-6 has a good repairing effect on the soil after solvent extraction, and the combined technology efficiently removed mechanical oil from the soil and reduced the damage caused by the solvent.
A machine learning algorithm predicts molecular subtypes in pancreatic ductal adenocarcinoma with differential response to gemcitabine-based versus FOLFIRINOX chemotherapy
Authors: Kaissis Georgios , Ziegelmayer Sebastian , Lohöfer Fabian , Steiger Katja , Algül Hana , Muckenhuber Alexander , Yen Hsi-Yu , Rummeny Ernst , Friess Helmut , Schmid Roland , Weichert Wilko , Siveke Jens T. , Braren Rickmer
Published: June 2019

Purpose

Development of a supervised machine-learning model capable of predicting clinically relevant molecular subtypes of pancreatic ductal adenocarcinoma (PDAC) from diffusion-weighted-imaging-derived radiomic features.

Methods

The retrospective observational study assessed 55 surgical PDAC patients. Molecular subtypes were defined by immunohistochemical staining of KRT81. Tumors were manually segmented and 1606 radiomic features were extracted withPyRadiomics. A gradient-boosted-tree algorithm (XGBoost) was trained on 70% of the patients (N=28) and tested on 30% (N=17) to predict KRT81+ vs. KRT81-tumor subtypes. The average sensitivity, specificity and ROC-AUC value were calculated. Chemotherapy response was assessed stratified by subtype. Radiomic feature importance was ranked.

Results

The mean±STDEV sensitivity, specificity and ROC-AUC were 0.90±0.07, 0.92±0.11, and 0.93±0.07, respectively. Patients with a KRT81+ subtype experienced significantly diminished median overall survival compared to KRT81-patients (7.0 vs. 22.6 months, HR 1.44, log-rank-test P=<0.001) and a significantly improved response to gemcitabine-based chemotherapy over FOLFIRINOX (10.14 vs. 3.8 months median overall survival, HR 0.85, P=0.037) compared to KRT81-patients, who responded significantly better to FOLFIRINOX over gemcitabine-based treatment (30.8 vs. 13.4 months median overall survival, HR 0.88, P=0.027).

Conclusions

The machine-learning based analysis of radiomic features enables the prediction of subtypes of PDAC, which are highly relevant for overall patient survival and response to chemotherapy.
Focused attention meditation changes the boundary and configuration of functional networks in the brain
Authors: Kajimura Shogo , Masuda Naoki , Lau Johnny King , Murayama Kou
Published: June 2019

Research has shown that meditation not only improves our cognitive and motivational functioning (e.g., attention, mental health), it influences the way how our brain networks [e.g., default mode network (DMN), fronto-parietal network (FPN), and sensory-motor network (SMN)] function and operate. However, surprisingly little attention has been paid to the possibility that meditation alters the structure (composition) of these functional brain networks. Here, using a single-case experimental design with longitudinal intensive data, we examined the effect of mediation practice on intra-individual changes in the composition of whole-brain networks. The results showed that meditation (1) changed the community size (with a number of regions in the FPN being merged into the DMN after meditation), (2) changed the brain regions composing the SMN community without changing its size, and (3) led to instability in the community allegiance of the regions in the FPN. These results suggest that, in addition to altering specific functional connectivity, meditation leads to reconfiguration of whole-brain network structure. The reconfiguration of community structure in the brain provides fruitful information about the neural mechanisms of meditation.
Differential base-sharing between humans and Neanderthals: inter-breeding or greater mutability in heterozygotes?
Authors: Amos William
Published: June 2019

The idea that humans interbred with other Hominins, most notably Neanderthals, is now accepted as fact. The finding of hybrid skeletons shows that fertile matings did occur. However, inferences about the size of the resulting legacy assume that back-mutations are rare enough to be ignored and that mutation rate does not vary. In reality, back-mutations are common, mutation rate does vary between populations and there is mounting evidence that heterozygosity and mutation rate covary. If so, the large loss of heterozygosity that occurred when humans migrated out of Africa would have reduced the mutation rate, leaving Africans to diverge faster from our common ancestor and from related lineages like Neanderthals. To test whether this idea impacts estimates of introgressed fraction, I calculated D, a measure of relative base-sharing with Neanderthals, and heterozygosity difference between all pairwise combinations of populations in the 1000 genomes Phase 3 data. D and heterozygosity difference are ubiquitously negatively correlated across all comparisons, between all regions and even between populations within each major region including Africa. In addition, the larger sample of populations in the Simons Genome Diversity project reveals a pan-Eurasian correlation between Neanderthal and Denisovan fraction. These correlations challenge a simple hybridisation model but do seem consistent with a model where more heterozygous human populations tend to diverge faster from Neanderthals than populations with lower heterozygosity. Indeed, the strongest correlation between Neanderthal content and geography indicates and origin where humans likely left Africa, exactly mimicking the pattern seen for loss of heterozygosity. Such a model explains why evidence for inter-breeding is found more or less wherever archaic and human populations are compared. How much of variation in D is due to introgression and how much is due to heterozygosity-mediated variation in mutation rate remains to be determined.

Author summary

The idea that humans inter-bred with related lineages such as Neanderthals, leaving an appreciable legacy in modern genomes, has rapidly progressed from shocking revelation to accepted dogma. My analysis explores an alternative model in which mutation rate slowed when diversity was lost in a population bottleneck as humans moved out of Africa to colonise the world. I find that, across Eurasia, the size of inferred legacy closely matches the pattern of diversity loss but shows no relationship to where human and Neanderthal populations likely overlapped. My results do not challenge the idea that some inter-breeding occurred, but they do indicate that some, much or even most of the signal that has be attributed entirely to archaic legacies, arises from unexpected variation in mutation rate. More generally, my analysis helps explain why inter-breeding is inferred almost wherever tests are conducted even though most species avoid hybridisation.
Electrical and rheological percolation threshold of graphene pastes for screen-printing
Authors: Dybowska-Sarapuk Lucja , Janczak Daniel , Podsiadly Bartlomiej , Jakubowska Malgorzata , Sloma Marcin
Published: June 2019

Purpose

A comparison of electric and viscosity percolation threshold is crucial from the scientific and technical points of view to understand the features and capabilities of heterogeneous graphene composite materials and properly select the functional phase volume. Therefore, the purpose of this paper is to present the analysis of the electrical and rheological percolation thresholds in the polymer–graphene screen printing pastes and the analysis of the relation between these two parameters.

Design/methodology/approach

In the paper, the properties of polymer-based pastes with graphene nanoplatelets were tested: paste viscosity and printed layers conductivity. The tests of pastes with different filler content allowed to determine both the electrical and rheological percolation thresholds using power law, according to Kirkpatrick’s percolation model.

Findings

The electrical percolation threshold for graphene nanoplatelets (GNPs) in the composite was 0.74 Vol.% when the rheological percolation threshold is observed to be at 1.00 Vol.% of nanoplatelets. The percolation threshold values calculated using the Kirkpatrick’s percolation model were 0.87 and 0.5 Vol.% of GNPs in the paste for electrical and rheological percolation thresholds, respectively.

Originality/value

Recently, GNPs are becoming more popular as the material of the functional phase in screen printing heterophase materials, because of their unique mechanical and electrical properties. However, till date no research presented in the literature is related to the direct comparison of both the electrical and rheological percolation thresholds. Such analysis is important for the optimization of the printing process toward the highest quality of printed conductive paths, and finally the best electrical properties.
Is it disqualifying? Practitioner responses to criminal offenses in hiring decisions
Authors: Kuhn Kristine M.
Published: June 2019

Purpose

The purpose of this paper is to explore variation in the responses of human resource practitioners and managers to criminal offenses.

Design/methodology/approach

This paper considers background checks as a personnel selection test. In the first study, 280 professionals with hiring experience indicate how various criminal offenses, described as having occurred either within the past year or several years ago, would affect their evaluation of an applicant for a call center position. In the second study, a separate sample of 109 practitioners evaluates criminal as well as non-criminal transgressions that might appear on a background report.

Findings

In Study 1, both the apparent seriousness of an offense and its recency influence modal responses. Even non-violent misdemeanors from several years ago, however, are judged as automatically disqualifying by some participants. Study 2 shows that a practitioner’s attitude toward criminal offenses is distinct from their attitude to related forms of stigma. Results from both studies find associations between demographic variables and general willingness to accept applicants with criminal records.

Originality/value

This work provides quantitative data on practitioner reactions to several specific criminal offenses for a specific job context. By considering differences among offenses and among gatekeepers, rather than among applicants, it identifies challenges to fair implementation of background checks during the hiring process.
Human resource management (HRM) practices and organizational performance
Authors: Otoo Frank Nana Kweku
Published: June 2019

Purpose

The purpose of this paper is to examine the mediating role of employee competencies in the relationship between human resource management (HRM) practices and organizational performance.

Design/methodology/approach

An integrated research model was developed by combining principal factors from existing literature. Data were collected through questionnaire from 600 employees of the selected hotels. The validity of the model and hypotheses was tested using structural equation modeling. The reliability and validity of the dimensions are established through confirmatory factor analysis.

Findings

The results indicate that some HRM practices impact organizational performance through their influence on employee competencies. The study further revealed that employee competencies mediate the relationship between HRM practices and organizational performance.

Research limitations/implications

The research was undertaken in the hotel industry and the analysis based on cross-sectional data which cannot be generalized across a broader range of sectors and international environment.

Practical implications

The findings of the study have the potential to help policy makers, stakeholders and management of hotels in adopting proper and well-articulated HRM practices in building human capital and stimulating the necessary behaviors that create advantage for the organization.

Originality/value

This study extends the literature by empirically adducing evidence that employee competencies mediated the relationship between HRM practices and organizational performance of the hotel industry in Ghana.
How servant leadership creates and accumulates social capital personally owned in hotel firms
Authors: Zoghbi-Manrique-de-Lara Pablo , Ruiz-Palomino Pablo
Published: June 2019

Purpose

This paper aims to test whether servant leaders lead followers to socially interact more frequently, closely and personally with peers, and if this social interaction links servant leaders with employees’ personal social capital, both in terms of bonding (networks linking employees of a similar kind) and bridging (networks linking agents of different kinds).

Design/methodology/approach

Data were collected from 403 employees from 59 large Spanish hotels. Structural equation modeling was used to test the hypotheses.

Findings

The results reveal that servant leadership has a positive effect on bonding and bridging, which is mediated by employees’ social interactions with peers inside and outside their groups, respectively.

Research limitations/implications

The findings suggest that hotel managers should adopt servant leadership to facilitate social interactions at work, thus allowing employees to individually gain personal assets that improve the hotel’s social capital resources.

Originality/value

This is the first study to analyze whether servant leadership shapes personal social capital in business settings. Moreover, it is the first to show the mechanisms (social interactions with peers inside and outside their groups) through which managerial servant leadership encourages this valuable personal asset in hotels.
Inexorable transformation in healthcare-seeking behaviour: a paradigm of choice
Authors: Pillai K.R. , Nallavalli Soundarya , Immaculate Christina
Published: June 2019

Purpose

Healthcare is traditionally considered an indispensable service in both personal and social points of views. In this regard, healthcare-seeking behaviour is driven by utilitarian orientation, given its existential value. But this trend is changing, as the propensity to avail (un)necessary healthcare services is burgeoning with changing lifestyle and practices. From the supply point of view, the market appears to be relentless in enforcing propensity to seek healthcare. The service providers, generally, create unnecessary needs and aspirations, taking undue advantage of the prospects’ over-conscious health concerns and overzealous longing for wellness. This study aims to find whether utilitarianism or hedonism is the prominent paradigm of healthcare-seeking behaviour in the onset of changing preferences and lifestyles and supply-driven market forces.

Design/methodology/approach

The study followed an empirical approach to accomplish the aim of research. Subjects for the study constitute sample respondents in the age of 18-60 years, who were identified on inspection. A structured questionnaire, drawn upon literature, was used to elicit information.

Findings

The study offered new insight into the basic psychological motive for healthcare-seeking. The results have empirically validated the pre-eminence of a hedonic attribute of consumer behaviour in healthcare-seeking.

Practical implications

The outcome of the study has implications for healthcare providers to tailor-make their future products and services and for governing bodies to design suitable policy guidelines.

Originality/value

The study explores the emerging trends in health-seeking behaviour.