bluuebunny/crossref_metadata_2025 huggingface dataset:
Metformin induces CD11b+-cell-mediated growth inhibition of an osteosarcoma: implications for metabolic reprogramming of myeloid cells and anti-tumor effects
Authors: Uehara Takenori , Eikawa Shingo , Nishida Mikako , Kunisada Yuki , Yoshida Aki , Fujiwara Tomohiro , Kunisada Toshiyuki , Ozaki Toshifumi , Udono Heiichiro
Published: November 2018

CD11b+ myeloid subpopulations, including myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs), play crucial roles in the suppression of T-cell-mediated anti-tumor immunity. Regulation of these cell types is a primary goal for achieving efficient cancer immunotherapy. We found that metformin (Met) induces CD11b+-cell-mediated growth inhibition of a K7M2neo osteosarcoma independent of T cells, as growth inhibition of K7M2neo was still observed in wild-type (WT) mice depleted of T cells by antibodies and in SCID; this contrasted with the effect of Met on Meth A fibrosarcoma, which was entirely T-cell-dependent. Moreover, the inhibitory effect seen in SCID was abrogated by anti-CD11b antibody injection. PMN-MDSCs were significantly reduced in both spleens and tumors following Met treatment. In TAMs, production of IL-12 and TNF-α, but not IL-10, became apparent, and elevation of MHC class II with reduction of CD206 was observed, indicating a shift from an M2- to M1-like phenotype via Met administration. Metabolically, Met treatment decreased basal respiration and the oxygen consumption rate (OCR)/extracellular acidification rate (ECAR) ratio of CD11b+ cells in tumors, but not in the spleen. In addition, decreased reactive oxygen species (ROS) production and proton leakage in MDSCs and TAMs were consistently observed in tumors. Uptake of both 2-deoxy-2-d-glucose (2-NBDG) and BODIPY® decreased in MDSCs, but only BODIPY® incorporation was decreased in TAMs. Overall, our results suggest that Met redirects the metabolism of CD11b+ cells to lower oxidative phosphorylation (OXPHOS) while elevating glycolysis, thereby pushing the microenvironment to a state that inhibits the growth of certain tumors.
Competition and the Welfare Gains from Transportation Infrastructure: Evidence from the Golden Quadrilateral of India
Authors: Asturias Jose , García-Santana Manuel , Ramos Roberto
Published: November 2018

A significant amount of resources is spent every year on the improvement of transportation infrastructure in developing countries. In this paper, we investigate the effects of one such large project, the Golden Quadrilateral in India. We do so using a model of internal trade with variable markups. In contrast to the previous literature, our model incorporates several channels through which transportation infrastructure affects welfare. In particular, the model accounts for gains stemming from improvements in the allocative efficiency of the economy. We calibrate the model to the Indian manufacturing sector and find real income gains of 2.7%. We also find that allocative efficiency accounts for 7.4% of these gains. The importance of allocative efficiency varies greatly across states, and can account for up to 18% of the overall gains in some states. The remaining welfare gains are accounted for by changes in labor income, productive efficiency, and average markups that affect states’ terms of trade.
Effects of immune suppression in murine models of disseminated Candida glabrata and Candida tropicalis infection and utility of a synthetic peptide vaccine
Authors: Xin Hong
Published: November 2018

Candida species are the second most frequent cause of fungal infections worldwide. Current knowledge of immunity to Candida has been gleaned almost exclusively from studies on Candida albicans, the most common disease-causing species. Knowledge of immunity to non-albicans Candida (NAC) species is still at an early stage due to the lack of tractable animal models with which to study these important pathogens. This is partly because many NAC species are not usually pathogenic in mouse models of candidiasis. In this study, we established an immunosuppressed mouse model of disseminated candidiasis by the two clinically important NAC species, C. glabrata and C. tropicalis. The inbred mouse strains, A/J and BALB/c, show distinct susceptibilities to disseminated Candida infection. A/J mice, deficient for complement C5, are more susceptible to disseminated infection with both C. glabrata and C. tropicalis compared to BALB/c mice, the latter having functional C5. Here we show that peptide-pulsed dendritic cell (DC) vaccination with a peptide derived from a C. tropicalis cell surface protein, significantly improved survival and reduced the fungal burdens of disseminated candidiasis in these immunocompromised mice. Importantly, this study is the first report of protective efficacy conferred by a peptide vaccine against medically important NAC species in immunosuppressed hosts. Establishing this experimental mouse model provides an important tool to further understand pathogenesis and host resistance in Candida infection. Significantly, our findings also demonstrate how this model can be used to evaluate new control strategies against candidiasis, such as vaccines.
Quantitative non-vanishing results on L-functions
Authors: Jiang Yujiao , Lü Guangshi
Published: November 2018

In this paper, we establish a quantitative non-vanishing result on a class of twisted L-functions A(s,χ) of degree k, which satisfy some mild and standard assumptions. As a corollary, we show that for a positive proportion of characters in a specific set, the special values A(β,χ) are non-vanishing for ℜβ>1−1k. In particular, our argument holds for Rankin–Selberg L-functions and symmetric square L-functions on certain higher rank groups, and leads to some new non-trivial results for the first time.
Relationship Between Invasive Brown Marmorated Stink Bug (Halyomorpha halys) and Fumonisin Contamination of Field Corn in the Mid-Atlantic U.S.
Authors: Opoku Joseph , Kleczewski Nathan M. , Hamby Kelly A. , Herbert D. Ames , Malone Sean , Mehl Hillary L.
Published: November 2018

Brown marmorated stink bug (Halyomorpha halys Stål) is an invasive agricultural pest that causes severe damage to many crops. To determine potential associations between H. halys feeding damage, Fusarium infection, and mycotoxin contamination in field corn, a field survey was conducted in eight counties in Virginia. Results indicated an association between H. halys feeding damage and fumonisin contamination. Subsequent field experiments in Delaware, Maryland, and Virginia examined the ability of H. halys to increase Fusarium verticillioides (Sacc.) Nirenberg infection and fumonisin concentrations in corn. At the milk stage, H. halys (0 or 4 adults) and Fusarium (with or without F. verticillioides inoculum) treatments were applied to bagged ears in a two by two factorial randomized complete block design with 12 replicates. H. halys treatments increased levels of feeding damage (P < 0.0001) and Fusarium infection (P = 0.0380). Interaction between H. halys and Fusarium treatments influenced severity of infection (P = 0.0018) and fumonisin concentrations (P = 0.0360). Results suggest H. halys has the ability to increase both Fusarium infection and fumonisin concentrations in field corn. Further studies are needed to understand mechanisms by which H. halys increases fumonisin and to develop management strategies to mitigate impacts of H. halys on field corn in the region.
Identifying Lookouts for Epidemio-Surveillance: Application to the Emergence ofXylella fastidiosain France
Authors: Martinetti Davide , Soubeyrand Samuel
Published: November 2018

Recent detections of Xylella fastidiosa in Corsica Island, France, has raised concerns on its possible spread to mainland France and the rest of the Mediterranean Basin. Early detection of infected plants is paramount to prevent the spread of the bacteria, but little is known about this pathosystem in European environments, hence standard surveillance strategies may be ineffective. We present a new methodological approach for the design of risk-based surveillance strategies, adapted to the emerging risk caused by X. fastidiosa. Our proposal is based on a combination of machine learning techniques and network analysis that aims at understanding the main abiotic drivers of the infection, produce risk maps and identify lookouts for the design of future surveillance plans. The identified drivers coincide with known results in laboratory studies about the correlation between environmental variables, such as water stress and temperature, and the presence of the bacterium in plants. Furthermore, the produced risk maps overlap nicely with detected foci of infection, while they also highlight other susceptible regions where X. fastidiosa has not been found yet. We conclude the paper presenting a list of recommended regions for a risk-based surveillance campaign based on the predicted spread and probability of early detection of the disease.
Reclassification of Xanthomonas gardneri (ex Šutič 1957) Jones et al. 2006 as a later heterotypic synonym of Xanthomonas cynarae Trébaol et al. 2000 and description of X. cynarae pv. cynarae and X. cynarae pv. gardneri based on whole genome analyses
Authors: Timilsina S. , Kara S. , Jacques M. A. , Potnis N. , Minsavage G. V. , Vallad G. E. , Jones J. B. , Fischer-Le Saux M.
Published: November 2018

Multilocus sequence analysis of Xanthomonas species revealed a very close relationship between

Xanthomonas cynarae

, an artichoke pathogen and Xanthomonas gardneri, a tomato and pepper pathogen. Results of whole genome sequence comparisons using average nucleotide identity between representative strains of

X. gardneri

and X. cynarae were well above the threshold of 95–96 %. Inoculations of

X. gardneri

strains in artichoke leaves caused mild disease symptoms, but only weak symptoms were observed in the bracts. Both

X. cynarae

and X. gardneri grew equally and caused typical bacterial spot symptoms in pepper after artificial inoculation. However,

X. cynarae

induced a hypersensitive reaction in tomato, while

X. gardneri

strains were virulent. Pathogenicity-associated gene clusters, including the protein secretion systems, type III effector profiles, and lipopolysaccharide cluster were nearly identical between the two species. Based on our results from whole genome sequence comparison,

X. gardneri

and

X. cynarae

belong to the same species. The name

X. cynarae

has priority and

X. gardneri

should be considered as a later heterotypic synonym. An emended description of

X. cynarae

(type strain=CFBP 4188T, =DSM 16794T) is given. However, due to the host specificity in artichoke and tomato, two pathovars, X. cynarae pv. cynarae and X. cynarae pv. gardneri, are proposed.
Factors associated with sharing email information and mental health survey participation in large population cohorts
Authors: Adams Mark J. , Hill W. David , Howard David M. , Davis Katrina A. S. , Deary Ian J. , Hotopf Matthew , McIntosh Andrew M.
Published: November 2018

People who opt to participate in scientific studies tend to be healthier, wealthier, and more educated than the broader population. While selection bias does not always pose a problem for analysing the relationships between exposures and diseases or other outcomes, it can lead to biased effect size estimates. Biased estimates may weaken the utility of genetic findings because the goal is often to make inferences in a new sample (such as in polygenic risk score analysis). We used data from UK Biobank and Generation Scotland and conducted phenotypic and genome-wide association analyses on two phenotypes that reflected mental health data availability: (1) whether participants were contactable by email for follow-up) and (2) whether participants responded to a follow-up surveys of mental health. We identified nine genetic loci associated with email contact and 25 loci associated with mental health survey completion. Both phenotypes were positively genetically correlated with higher educational attainment and better health and negatively genetically correlated with psychological distress and schizophrenia. Recontact availability and follow-up participation can act as further genetic filters for data on mental health phenotypes.
Screening a Resource of Recombinant Protein Fragments for Targeted Proteomics
Authors: Edfors Fredrik , Forsström Björn , Vunk Helian , Kotol David , Fredolini Claudia , Maddalo Gianluca , Svensson Anne-Sophie , Boström Tove , Tegel Hanna , Nilsson Peter , Schwenk Jochen M. , Uhlen Mathias
Published: November 2018

The availability of proteomics resources hosting protein and peptide standards, as well as the data describing their analytical performances, will continue to enhance our current capabilities to develop targeted proteomics methods for quantitative biology. This study describes the analysis of a resource of 26,840 individually purified recombinant protein fragments corresponding to more than 16,000 human protein-coding genes. The resource was screened to identify proteotypic peptides suitable for targeted proteomics efforts and we report LC-MS/MS assay coordinates for more than 25,000 proteotypic peptides, corresponding to more than 10,000 unique proteins. Additionally, peptide formation and digestion kinetics were, for a subset of the standards, monitored using a time-course protocol involving parallel digestion of isotope-labelled recombinant protein standards and endogenous human plasma proteins. We show that the strategy by adding isotope-labelled recombinant proteins prior to trypsin digestion enables short digestion protocols (≤60 min) with robust quantitative precision. In a proof-of-concept study, we quantified 23 proteins in human plasma using assay parameters defined in our study and used the standards to describe distinct clusters of individuals linked to different levels of LPA, APOE, SERPINA5 and TFRC. In summary, we describe the use and utility of a resource of recombinant proteins to identify proteotypic peptides useful for targeted proteomics assay development.
Identifying sensor species to predict critical transitions in complex ecosystems
Authors: Aparicio Andrea , Velasco Jorge X. , Moog Claude H. , Liu Yang-Yu , Angulo Marco Tulio
Published: November 2018

Ecosystems provide key services needed for human well-being, such as purifying air and regulating our health, many of which are disrupted when these ecosystems undergo a critical transition to undesired states. Detecting early-warning signals of these critical transitions remains challenging for complex ecosystems with a large number of species. Here we built a mathematical formalism to identify minimal sets of “sensor species” from which we can determine the state of a whole ecosystem, allowing us to predict a critical transition in an ecosystem by monitoring a minimal subset of its species. We rigorously prove that minimal sets of sensor species can be generically identified knowing only the structure of the ecological network underlying the ecosystem, regardless of its population dynamics. We numerically validated our formalism to predict critical transitions in large complex ecosystems, and then we applied it to experimental data of a critical transition in a lake food-web. Our results contribute to better monitoring complex ecosystems, especially those with poorly known population dynamics such as host-associated microbial communities.
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

Gastrin-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.

Highlights

Validated expression of a Grp-Cre knock-in line in sensory neurons that innervate the skin

Opto-activation of Grp sensory neurons evokes itch behavior

Conditional deletion of Grp in sensory neurons reduces non-histaminergic itch behavior

Intersectional 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

The 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.

Synopsis

The 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

There 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

There 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

Aims

Bacterial 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 results

A 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 study

CRISPR 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

Glucocorticoid 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 statement

In 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

Pesticide 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

We 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

As 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

Dietary 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

One 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

Aims

To 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, Participants

Longitudinal 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).

Measurements

Self‐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.

Findings

Change 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.

Conclusions

Cannabis 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

The 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]
Neuroticism is associated with higher antenatal care utilization in obstetric low‐risk women
Authors: Axfors Cathrine , Hellgren Charlotte , Volgsten Helena , Skoog Svanberg Agneta , Ekselius Lisa , Wikström Anna‐Karin , Ramklint Mia , Skalkidou Alkistis , Sundström‐Poromaa Inger
Published: November 2018

Introduction

Elevated neuroticism is associated with higher health care utilization in the general population. This study aimed to investigate the association between neuroticism and the use of publicly financed antenatal care in obstetric low‐risk women, taking predisposing and need factors for health care utilization into consideration.

Material and methods

Participants comprised 1052 obstetric low‐risk women (no chronic diseases or adverse pregnancy conditions) included in several obstetrics/gynecology studies in Uppsala, Sweden. Neuroticism was self‐rated on the Swedish universities Scales of Personality. Medical records of their first subsequent pregnancy were scanned for antenatal care use. Associations between antenatal care use and neuroticism were analyzed with logistic regression (binary outcomes) or negative binomial regression (count outcomes) comparing the 75th and 25th neuroticism percentiles. Depending on the Akaike information criterion the exposure was modeled as either linear or with restricted cubic splines. Analyses were adjusted for predisposing (sociodemographic and parity) and need factors (body mass index and psychiatric morbidity).

Results

After adjustment, women with higher neuroticism had more fetal ultrasounds (incidence rate ratio = 1.09, 95% confidence interval (CI) 1.02‐1.16), more emergency visits to an obstetrician/gynecologist (incidence rate ratio = 1.22, 95% CI 1.03‐1.45) and were more likely to visit a fear‐of‐childbirth clinic (odds ratio = 2.71, 95% CI 1.71‐4.29). Moreover, they more often consulted midwives in specialized antenatal care facilities (significant J‐shaped association).

Conclusions

Neuroticism was associated with higher utilization of publicly financed antenatal care in obstetric low‐risk women, even after adjusting for predisposing and need factors. Future studies should address the benefits of interventions as a complement to routine antenatal care programs to reduce subclinical anxiety.
Voriconazole‐induced QTc prolongation in a paediatric population
Authors: Pasternak Y , Shechter N , Loebstein R , Markovits N , Gueta I , Halkin H , Yarden‐Bilavsky H
Published: November 2018

Aim

To evaluate Corrected QT (QTc) interval prolongation (QTcP) in paediatric patients treated with voriconazole (VRC) and identify its associated risk factors in this setting.

Methods

Clinical, VRC‐related and QTc interval data were collected retrospectively from the electronic medical records of VRC‐treated paediatric patients attending a large tertiary medical centre in 2011–2016 who underwent electrocardiography before and during therapy. Paired comparison of QTc intervals before and during VRC treatment was performed, adjusted for concurrent medications, electrolyte disturbances and co‐morbidities.

Results

Fifty‐five patients (mean age 10.1 ± 5.4 years) met the inclusion criteria; 34 had an oncologic or hemato‐oncologic diagnosis. Mean QTc interval was 402.8 ± 27.9 msec before VRC treatment and 440.0 ± 45.3 msec on treatment (p < 0.001). During treatment, 38 patients (61.8%) had QTcP ≥30 msec and 17 (30.9%), QTcP ≥60 msec; 10 patients (18.2%) had QTc ≥500 msec of whom one acquired torsades de pointes. On multivariate analysis, older age (p = 0.025), lower potassium level (p = 0.025) and longer baseline QTc (0.032) were associated QTcP ≥60 msec, but not daily or cumulative dose of VRC.

Conclusion

This study demonstrated a high rate of clinically significant QTcP in VRC‐treated children. Proper QTc monitoring, together with laboratory monitoring and electrolyte imbalance correction, is important to prevent cardiac arrhythmias in this patient population.
Immunomodulatory effect of γ‐irradiated Astragalus polysaccharides on immunosuppressed broilers
Authors: Li Shan , Ren Lina , Zhu Xudong , Li Jiaolong , Zhang Lin , Wang Xiaofei , Gao Feng , Zhou Guanghong
Published: November 2018

In this study, we irradiated Astragalus polysaccharides (APS) using 25 kGy 60Co γ ray to obtain γ‐irradiated Astragalus polysaccharides (IAPS) and then investigated the effects of IAPS on growth performance and immune function of cyclophosphamide (CPM)‐treated broilers. The physicochemical properties of APS and IAPS (molecular weight, water solubility, viscosity, morphological and structural properties) were evaluated. Then, 384 one‐day‐old Arbor Acres broiler chicks with similar initial weight were randomly assigned into 6 groups: the non‐treated group (control), and CPM‐treated groups were fed either a basal diet or the diets containing 900 mg/kg APS, or 900, 600, 300 mg/kg IAPS, respectively. On days 16, 18, and 20, all broilers except for the control group were intramuscularly injected with 0.5 ml CPM (40 mg/kg·BW). Broilers in the control group were intramuscularly injected with 0.5 ml sterilized saline (0.75%, wt/vol). This trial lasted for 21 days. The physicochemical treatment showed that γ irradiation could decrease the molecular weight and viscosity, and increase the water solubility of APS (p < 0.05), whereas the structural properties of APS was not affected. In the animal trial, 900 mg/kg APS or 900, 600 mg/kg IAPS relieved the decreased growth performance, thymus index, T lymphocytes proliferation, serum IgG concentration, NOS activity and the increased blood heterophil:lymphocyte ratio in CPM‐treated broilers (p < 0.05). CPM‐induced decreases in B lymphocytes proliferation and serum IgM concentration were only increased by IAPS at 900 mg/kg (p < 0.05). Overall, both APS and IAPS alleviated CPM‐induced immunosuppression. Especially, IAPS possessed better immunomodulatory effect than APS, indicating that γ irradiation could be used as an effective method to enhance the immunomodulatory activity of APS.
More present than absent: Men who use domestic violence and their fathering
Authors: Humphreys Cathy , Diemer Kristin , Bornemisza Anna , Spiteri‐Staines Anneliese , Kaspiew Rae , Horsfall Briony
Published: November 2018

An earlier article referred to the “absent presence” of the perpetrator in the lives of children and their mothers who have lived with domestic violence. It identified the ways in which the shadow of the perpetrator continued and was evidenced in the “symptoms of abuse” that both women and children experienced in spite of his absence. The current article argues that fathers who use violence are actually more present than absent in the lives of children (and women), even following separation. A mixed method approach surveyed men in Men's Behaviour Change Programs (N = 101), and interviewed women who had experienced violence (N = 50). The studies reported that the majority of men in both the quantitative men's study (80%) and the qualitative women's study (77%) had substantial contact with children. The women's interviews highlight the problematic fathering that many of their children experienced, both before and after separation. They reported very high levels of child abuse and poor attitudes to both women and children.

The article concludes that the family violence and child welfare systems are poorly configured to address fathers who use violence and continue to hold substantial parenting roles, including following separation.
Genetics meets DNA methylation in rare diseases
Authors: Velasco Guillaume , Francastel Claire
Published: November 2018

Alterations in epigenetic landscapes are hallmarks of many complex human diseases, yet, it is often challenging to assess the underlying mechanisms and causal link with clinical manifestations. In this regard, monogenic diseases that affect actors of the epigenetic machinery are of considerable interest to learn more about the etiology of complex traits. Spectacular breakthroughs in medical genetics are largely the result of advances in genome‐wide approaches to identify genomic and epigenomic alterations in patients. These approaches have enabled the identification of an ever‐increasing number of hereditary disorders caused by defects in the establishment of epigenetic marks early during development or in the perpetuation of such marks at later stages. We focus our review on particular cases where DNA methylation landscapes are altered at the genome scale, whether it is a direct consequence of mutations in DNA methyltransferases (DNMT) or that it reflects initial alterations of chromatin states or guiding factors caused by mutations in chromatin modifiers or transcription factors. Collectively, increased knowledge of these rare diseases will add to our understanding of the genetic determinants of DNA methylation in humans. Moreover, investigating how perturbations to these determinants affect genome function has far‐reaching potential to understand various complex human diseases.
EASING THE CONSTRAINTS OF MOTHERHOOD: THE EFFECTS OF ALL‐DAY SCHOOLS ON MOTHERS' LABOR SUPPLY
Authors: Padilla‐Romo María , Cabrera‐Hernández Francisco
Published: November 2018

Low rates of female labor force participation (LFP) have been linked to the absence of childcare policies. This article examines the degree to which extending the school day by 3.5 hours in elementary schools, a large implicit childcare subsidy, affects LFP, the number of weekly hours worked, and the monthly earnings of females with elementary‐school‐age children. To do so, we exploit within‐individual variation in access to full‐time schools and a rotating panel of households that contains 12 years of individual‐level data on labor outcomes and sociodemographic characteristics. Results from long‐difference models show that extending the school day increases mothers' labor supply, increasing LFP by 5.5 percentage points and the number of weekly hours worked by 1.8. Moreover, these increases are accompanied by a raise in monthly earnings. (JEL I25, J13, J22)