bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploration of Sensory and Spinal Neurons Expressing GRP in Itch and Pain
Authors: Barry Devin M. , Liu Xue-Ting , Yang Qianyi , Liu Xian-Yu , Zeng Xiansi , Liu Ben-Long , Chen Zhou-Feng 
Published: November 2018

AbstractGastrin-releasing peptide (GRP) is a putative itch-specific neurotransmitter, but definite evidence in the dorsal root ganglion (DRG) and spinal cord is lacking. We generated and validated a Grp-Cre knock-in (GrpCre-KI) mouse line whereby Grp neurons are genetically labeled. Cre-dependent marking analysis revealed exclusive innervation of the upper epidermis of the skin by GRP fibers. Importantly, optical stimulation of Grp fibers expressing channel rhodopsin (ChR2) in the skin evoked itch but not pain-related scratching behaviors, while conditional deletion of Grp in sensory neurons attenuated non-histaminergic itch. In contrast, intersectional genetic ablation of spinal Grp neurons did not affect itch nor pain transmission. Our study demonstrates a role of GRP in sensory neurons in itch and suggests that GRP sensory neurons are dedicated to itch transmission. GrpCre-KI mice provide a long-sought avenue for investigating peripheral coding mechanism of itch and further interrogation of itch-nerve fibers in the skin under chronic pruritus.HighlightsValidated expression of a Grp-Cre knock-in line in sensory neurons that innervate the skinOpto-activation of Grp sensory neurons evokes itch behaviorConditional deletion of Grp in sensory neurons reduces non-histaminergic itch behaviorIntersectional ablation of Grp spinal neurons does not affect itch or pain behaviors
Homochiral and racemic MicroED structures of a peptide from the ice nucleation protein InaZ
Authors: Zee Chih-Te , Glynn Calina , Gallagher-Jones Marcus , Miao Jennifer , Santiago Carlos G. , Cascio Duilio , Gonen Tamir , Sawaya Michael R. , Rodriguez Jose A. 
Published: November 2018

AbstractThe ice nucleation protein InaZ of Pseudomonas syringae contains a large number of degenerate repeats that span more than a quarter of its sequence and include the segment GSTSTA. We determine ab initio structures of this repeat segment, resolved to 1.1Å by microfocus x-ray crystallography and 0.9Å by the cryoEM method MicroED, from both racemic and homochiral crystals. We evaluate the benefits of racemic protein crystals for structure determination by MicroED and confirm that phase restriction introduced by crystal centrosymmetry increases the number of successful trials during ab initio phasing of electron diffraction data. Both homochiral and racemic GSTSTA form amyloid-like protofibrils with labile, corrugated antiparallel beta sheets that mate face to back. The racemic GSTSTA protofibril represents a new class of amyloid assembly in which all left-handed sheets mate with their all right-handed counterparts. Our determination of racemic amyloid assemblies by MicroED reveals complex amyloid architectures and illustrates the racemic advantage in macromolecular crystallography, now with sub-micron sized crystals.SynopsisThe atomic asymmetry, left or right handedness, present in macromolecules and first described by Pasteur in his experiments with tartaric acid, is evident even in complex molecular assemblies like amyloid fibrils. Here, using the cryoEM method MicroED, we show that a segment from the ice nucleation protein InaZ assembles into homochiral and racemic water-binding amyloid protofibrils.
Clinical Benefit Index
Authors: Basu Amrita , Esserman Laura 
Published: November 2018

AbstractThere are limited methods to analyze both efficacy of a drug and toxicity to a patient in response to treatment. We have developed a metric, the clinical benefit index (CBI) which is quantitative, and a scalable way to integrate patient-reported side effects and efficacy for adaptive randomization. Instead of using efficacy as a singular attribute in decision making for agent selection, we will consider the impact on QoL since many of the newer agents will be less toxic. This will be developed in effort to standardize PRO analysis methods. The clinical benefit index provides an alternative framework for evaluation and would help us to develop a regulatory model for approval of those drugs that have less toxicity by providing a replicable model for measuring toxicity and integrating it with efficacy. Reporting of clinical data can inform the management of toxicity and the integration into a clinical benefit index will help promote regulatory evaluation and preference for less toxic drug/combinations.
Deep Neural Networks and Kernel Regression Achieve Comparable Accuracies for Functional Connectivity Prediction of Behavior and Demographics
Authors: He Tong , Kong Ru , Holmes Avram J. , Nguyen Minh , Sabuncu Mert R. , Eickhoff Simon B. , Bzdok Danilo , Feng Jiashi , Yeo B.T. Thomas 
Published: November 2018

AbstractThere is significant interest in the development and application of deep neural networks (DNNs) to neuroimaging data. A growing literature suggests that DNNs outperform their classical counterparts in a variety of neuroimaging applications, yet there are few direct comparisons of relative utility. Here, we compared the performance of three DNN architectures and a classical machine learning algorithm (kernel regression) in predicting individual phenotypes from whole-brain resting-state functional connectivity (RSFC) patterns. One of the DNNs was a generic fully-connected feedforward neural network, while the other two DNNs were recently published approaches specifically designed to exploit the structure of connectome data. By using a combined sample of almost 10,000 participants from the Human Connectome Project (HCP) and UK Biobank, we showed that the three DNNs and kernel regression achieved similar performance across a wide range of behavioral and demographic measures. Furthermore, the generic feedforward neural network exhibited similar performance to the two state-of-the-art connectome-specific DNNs. When predicting fluid intelligence in the UK Biobank, performance of all algorithms dramatically improved when sample size increased from 100 to 1000 subjects. Improvement was smaller, but still significant, when sample size increased from 1000 to 5000 subjects. Importantly, kernel regression was competitive across all sample sizes. Overall, our study suggests that kernel regression is as effective as DNNs for RSFC-based behavioral prediction, while incurring significantly lower computational costs. Therefore, kernel regression might serve as a useful baseline algorithm for future studies.
Genotyping ofSalmonellaspp. on the basis of CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)
Authors: Jiksing Calvin , Yusop Normah , Nasib Farhan Nazaie , Rodrigues Kenneth Francis 
Published: November 2018

ABSTRACTAimsBacterial genotyping on the basis of the CRISPR array has been established inMycobacterium tuberculosiswith a method called spacer oligonucleotide typing (spoligotyping). The spoligotyping method had been widely used for both detection and typing ofM. tuberculosiscomplex bacteria. This present study aimed at determining if the CRISPR array inSalmonellaspp. could be applied to establish a correlationship between serogroup and the fingerprint generated by CRISPR typing.Methodology and resultsA total of 30 samples were obtained from Diagnostic Veterinary Laboratory, Kota Kinabalu, Sabah. Serogroup was determined on the basis of ELISA (enzyme-linked immunosorbent assay). Four different serogroups were identified which were serogroup B, C, D, and E. DNA (deoxyribonucleic acid) was extracted and PCR (polymerase chain reaction) was performed using primers which were designed to amplify the CRISPR array inSalmonellagenome. Our results indicate that there is a correlationship between serogroup obtained using ELISA and the profile generated by CRISPR typing.Conclusion, significance and impact of studyCRISPR typing has the potential to be applied for the genotyping ofSalmonella.
Glucocorticoids inhibit macrophage differentiation towards a pro-inflammatory phenotype upon wounding without affecting their migration
Authors: Xie Yufei , Tolmeijer Sofie , Oskam Jelle , Tonkens Tijs , Meijer Annemarie H. , Schaaf Marcel J.M 
Published: November 2018

AbstractGlucocorticoid drugs are widely used to treat immune-related diseases, but their use is limited by side effects and by resistance, which especially occurs in macrophage-dominated diseases. In order to improve glucocorticoid therapies, more research is required into the mechanisms of glucocorticoid action. In the present study, we have used a zebrafish model for inflammation to study glucocorticoid effects on the innate immune response. In zebrafish larvae, the migration of neutrophils towards a site of injury is inhibited by the synthetic glucocorticoid beclomethasone, while migration of macrophages is glucocorticoid resistant. We show that wounding-induced increases in expression of genes encoding neutrophil-specific chemoattractants (Il8 and Cxcl18b) are attenuated by beclomethasone, but that beclomethasone does not attenuate the induction of the genes encoding Ccl2 and Cxcl11aa, which we show to be required for macrophage recruitment. RNA sequencing on Fluorescence-Activated Cell Sorting (FACS)-sorted macrophages showed that the vast majority of the wounding-induced transcriptional changes in these cells are inhibited by beclomethasone, whereas a small subset is glucocorticoid-insensitive. As a result, beclomethasone decreases the number of macrophages that differentiate towards a pro-inflammatory (M1) phenotype, which we demonstrated using atnfa:eGFP-Freporter line and analysis of macrophage morphology. We conclude that the glucocorticoid resistance of the wounding-induced macrophage migration is due to the insensitivity of the induction of macrophage-specific chemoattractants to glucocorticoid inhibition, which may explain the relative resistance of macrophage-dominated diseases to glucocorticoid therapy. However, the induction of pro-inflammatory genes in macrophages is strongly attenuated, which inhibits their differentiation to an M1 phenotype.Summary statementIn a zebrafish model for inflammation, glucocorticoids do not affect the migration of macrophages, but inhibit differentiation towards an M1 phenotype, by strongly attenuating transcriptional responses in these cells.
Long-term population studies uncover the genome structure and genetic basis of xenobiotic and host plant adaptation in the herbivoreTetranychus urticae
Authors: Wybouw Nicky , Kosterlitz Olivia , Kurlovs Andre H. , Bajda Sabina , Greenhalgh Robert , Snoeck Simon , Bui Huyen , Bryon Astrid , Dermauw Wannes , Van Leeuwen Thomas , Clark Richard M. 
Published: November 2018

ABSTRACTPesticide resistance arises rapidly in arthropod herbivores, as can host plant adaptation, and both are significant problems in agriculture. These traits have been challenging to study as both are often polygenic and many arthropods are genetically intractable. Here, we examined the genetic architecture of pesticide resistance and host plant adaptation in the two-spotted spider mite,Tetranychus urticae,a global agricultural pest. We show that the short generation time and high fecundity ofT. urticaecan be readily exploited in experimental evolution designs for high-resolution mapping of quantitative traits. As revealed by selection with spirodiclofen, an acetyl-CoA decarboxylase inhibitor, in populations from a cross between a spirodiclofen resistant and a susceptible strain, and which also differed in performance on tomato, we found that a limited number of loci could explain quantitative resistance to this compound. These were resolved to narrow genomic intervals, suggesting specific candidate genes, includingacetyl-CoA decarboxylaseitself, clustered and copy variable cytochrome P450 genes, andNADPH cytochrome P450 reductase, which encodes a redox partner for cytochrome P450s. For performance on tomato, candidate genomic regions for response to selection were distinct from those responding to the synthetic compound and were consistent with a more polygenic architecture. In accomplishing this work, we exploited the continuous nature of allele frequency changes across experimental populations to resolve the existing fragmentedT.urticaedraft genome to pseudochromosomes. This improved assembly was indispensable for our analyses, as it will be for future research with this model herbivore that is exceptionally amenable to genetic studies.
Optic disc centered imaging versus quadrant imaging in retinal oximetry
Authors: Mohan Ashwin , Shetty Rohit , Mahendradas Padmamalini , Webers Carroll AB , Berendschot Tos TJM 
Published: November 2018

AbstractWe aimed to compare intra eye quadrant variation in retinal vessel oxygen saturation in optic disc centered versus quadrant imaging. Forty two consecutive healthy subjects were included in the study. Fifty degree optic disc centered images and images of 4 quadrants (supero-temporal - ST, supero-nasal - SN, infero-nasal - IN and infero-temporal - IT) were taken. The thickest arteriole and venule were chosen in each quadrant in the optic disc centered images. For quadrant images averaged values of 3 segments of thickest arterioles and venules, each above 100µm were chosen. The intra-eye variation between quadrants for arteriolar and venous saturation (%) was compared between optic disc centered and quadrant images. Smaller vessels (70 – 100 µm) in the quadrant images were selected to study the effect of vessel calibre on oxygen saturation. Optic disc centered images gave average arteriolar saturation (%) of 90, 94, 93 and 89 and venous saturation of 58, 60, 60 and 52 in the ST, SN, IN and IT respectively. For quadrant images the average arteriolar saturation was 94, 95, 94 and 91 and the venous saturation was 62, 60, 61 and 60 in the ST, SN, IN and IT respectively. Temporally, the saturation values were significantly different (p<0.001) between optic disc centered and quadrant images. We found no differences nasally. The average intra eye range for arterioles was 11.9 in optic disc centered versus 7.1 in quadrant images (p<0.001) and for venules was 11.6 in optic disc centered versus 7.5 in quadrant images (p<0.001). We found a positive correlation of r=0.18 between saturation and vessel calibre for arteries (p=0.001) and a negative correlation of r=-0.52 for venes (p<0.001). Quadrant imaging significantly reduced intra eye variation between quadrant measurements indicating that maybe the larger variation observed in optic disc centered images are artefactual. Differences in saturation between optic disc centered and quadrant imaging were only seen temporally. We also see physiologically reducing saturation from large arterioles to small arterioles to small venules to large venules.
Measuring popularity of ecological topics in a temporal dynamical knowledge network
Authors: Huang Tian-Yuan , Zhao Bin 
Published: November 2018

AbstractAs interdisciplinary branches of ecology are developing rapidly in the 21st century, contents of ecological researches have become more abundant than ever before. Along with the exponential growth of number of published literature, it is more and more difficult for ecologists to get a clear picture of their discipline. Nevertheless, the era of big data has brought us massive information of well documented historical literature and various techniques of data processing, which greatly facilitates the implementation of bibliometric analysis on ecology. Frequency has long been used as the primary metric in keyword analysis to detect ecological hotspots, however, this method could be somewhat biased. In our study, we have suggested a method called PAFit to measure keyword popularity, which considered ecology-related topics in a large temporal dynamical knowledge network, and found out the popularity of ecological topics follows the “rich get richer” and “fit get richer” mechanism. Feasibility of network analysis and its superiority over simply using frequency had been explored and justified, and PAFit was testified by its outstanding performance of prediction on the growth of frequency and degree. In addition, our research also encourages ecologists to consider their domain knowledge in a large dynamical network, and be ready to participate in interdisciplinary collaborations when necessary.
Reconciling nutritional geometry with classical dietary restriction: Effects of nutrient intake, not calories, on survival and reproduction
Authors: Moatt Joshua P. , Fyfe Murray A. , Heap Elizabeth , Mitchell Luke J. M. , Moon Fiona , Walling Craig A. 
Published: November 2018

AbstractDietary restriction (DR) is one of the main experimental paradigms to investigate the mechanisms that determine lifespan and aging. Yet, the exact nutritional parameters responsible for DR remain unclear. Recently, the advent of the geometric framework of nutrition (GF) has refocussed interest from calories to dietary macronutrients. However, GF experiments focus on invertebrates, with the importance of macronutrients in vertebrates still widely debated. This has led to the suggestion of a fundamental difference in the mode of action of DR between vertebrates and invertebrates, questioning the suggestion of an evolutionarily conserved mechanism. The use of dietary dilution rather than restriction in GF studies makes comparison with traditional DR studies difficult. Here, using a novel nonmodel vertebrate system (the stickleback fish, Gasterosteus aculeatus), we test the effect of macronutrient versus calorie intake on key fitness‐related traits, both using the GF and avoiding dietary dilution. We find that the intake of macronutrients rather than calories determines both mortality risk and reproduction. Male mortality risk was lowest on intermediate lipid intakes, and female risk was generally reduced by low protein intakes. The effect of macronutrient intake on reproduction was similar between the sexes, with high protein intakes maximizing reproduction. Our results provide, to our knowledge, the first evidence that macronutrient, not caloric, intake predicts changes in mortality and reproduction in the absence of dietary dilution. This supports the suggestion of evolutionary conservation in the effect of diet on lifespan, but via variation in macronutrient intake rather than calories.
LncRNAs regulating stemness in aging
Authors: Sousa‐Franco António , Rebelo Kenny , da Rocha Simão Teixeira , Bernardes de Jesus Bruno 
Published: November 2018

AbstractOne of the most outstanding observations from next‐generation sequencing approaches was that only 1.5% of our genes code for proteins. The biggest part is transcribed but give rise to different families of RNAs without coding potential. The functional relevance of these abundant transcripts remains far from elucidated. Among them are the long non‐coding RNAs (lncRNAs), a relatively large and heterogeneous group of RNAs shown to be highly tissue‐specific, indicating a prominent role in processes controlling cellular identity. In particular, lncRNAs have been linked to both stemness properties and detrimental pathways regulating the aging process, being novel players in the intricate network guiding tissue homeostasis. Here, we summarize the up‐to‐date information on the role of lncRNAs that affect stemness and hence impact upon aging, highlighting the likelihood that lncRNAs may represent an unexploited reservoir of potential therapeutic targets for reprogramming applications and aging‐related diseases.
Disentangling longitudinal relations between youth cannabis use, peer cannabis use, and conduct problems: developmental cascading links to cannabis use disorder
Authors: Defoe Ivy N. , Khurana Atika , Betancourt Laura M. , Hurt Hallam , Romer Daniel 
Published: November 2018

AbstractAimsTo determine whether cannabis use during adolescence can increase risk not only for cannabis use disorder (CUD) but also for conduct problems, potentially mediated by exposure to peers who use cannabis.Design, Setting, ParticipantsLongitudinal study analyzing four waves of longitudinal data from 364 racially and socio‐economically diverse, urban, US community youth (at baseline: Mage = 13.51 (0.95); 49.1% female).MeasurementsSelf‐reports of cannabis use, conduct problems, proportion of peers using cannabis and CUD criteria at the final wave were analyzed using a method sensitive to changes over development, the random‐intercept cross‐lagged panel model.FindingsChange in cannabis use did not predict changes in conduct problems or peer cannabis use over time, controlling for gender, race–ethnicity and socio‐economic status. Instead, increases in conduct problems predicted increases in cannabis use and ultimately CUD, with some of the effect mediated by increases in the prevalence of peer cannabis use [β = 0.12, 95% confidence interval (CI) = 0.07, 0.20]. Additionally, affiliation with peers who used cannabis predicted subsequent CUD via increased personal cannabis use (β = 0.08, 95% CI = 0.04, 0.14). Significant within‐person betas for the cross‐lagged effects ranged between 0.20 and 0.27.ConclusionsCannabis use in adolescence does not appear to lead to greater conduct problems or association with cannabis‐using peers apart from pre‐existing conduct problems. Instead, adolescents who (1) increasingly affiliate with cannabis‐using peers or (2) have increasing levels of conduct problems are more likely to use cannabis, and this cascading chain of events appears to predict cannabis use disorder in emerging adulthood.
Citizens United, citizens divided:
Authors: GREENHOUSE CAROL J. 
Published: November 2018

ABSTRACTThe US Supreme Court's decision in Citizens United largely deregulated corporations’ contributions to political campaigns. Immediately and persistently controversial, the case is significant for its reasoning with respect to interests, influence, identity, and equality as registers of the public interest—conceptually fusing democracy and economy through corporations. Citizens operates on many scales, though, and its domains are not limited to election law—notably including two abortion law cases among its cited precedents. Following that arrow leads to landmark abortion opinions—particularly to their dissents, key elements of which are echoed in the Citizens opinion. The discursive connections across these bodies of law suggest Citizens’ implications for personal liberty as contingent on an individual's corporate identity. [law, courts, corporations, elections, abortion, discourse, Citizens United, United States]