bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterizing and inferring quantitative cell cycle phase in single-cell RNA-seq data analysis
Authors: Hsiao Chiaowen Joyce , Tung PoYuan , Blischak John D. , Burnett Jonathan E. , Barr Kenneth A. , Dey Kushal K. , Stephens Matthew , Gilad Yoav
Published: February 2019

Cellular heterogeneity in gene expression is driven by cellular processes such as cell cycle and cell-type identity, and cellular environment such as spatial location. The cell cycle, in particular, is thought to be a key driver of cell-to-cell heterogeneity in gene expression, even in otherwise homogeneous cell populations. Recent advances in single-cell RNA-sequencing (scRNA-seq) facilitate detailed characterization of gene expression heterogeneity, and can thus shed new light on the processes driving heterogeneity. Here, we combined fluorescence imaging with scRNA-seq to measure cell cycle phase and gene expression levels in human induced pluripotent stem cells (iPSCs). Using these data, we developed a novel approach to characterize cell cycle progression. While standard methods assign cells to discrete cell cycle stages, our method goes beyond this, and quantifies cell cycle progression on a continuum. We found that, on average, scRNA-seq data from only five genes predicted a cell’s position on the cell cycle continuum to within 14% of the entire cycle, and that using more genes did not improve this accuracy. Our data and predictor of cell cycle phase can directly help future studies to account for cell-cycle-related heterogeneity in iPSCs. Our results and methods also provide a foundation for future work to characterize the effects of the cell cycle on expression heterogeneity in other cell types.
A new mechanism for tree mortality due to drought and heatwaves
Authors: Cochard Hervé
Published: February 2019

Abstract

Plants tend to die earlier in hot and drought conditions, but the underlying mechanisms are not yet understood. I propose here a new mechanism by which excessive residual water losses caused by high cuticular permeabilities and a high leaf-to-air vapor pressure deficits would trigger uncontrolled and sudden cavitation events. The combination of heat and drought stresses may therefore lead to an unsuspected risk of hydraulic failure. I explored this hypothesis with a new mechanistic model. The simulations support this hypothesis and highlight the critical role played by the cuticle phase transition temperature. Experiments are now awaited to confirm these predictions.
SUBSTRA: Supervised Bayesian Patient Stratification
Authors: Khakabimamaghani Sahand , Kelkar Yogeshwar , Grande Bruno , Morin Ryan , Ester Martin , Ziemek Daniel
Published: February 2019

Patient stratification methods are key to the vision of precision medicine. Here, we consider transcriptional data to segment the patient population into subsets relevant to a given phenotype. Whereas most existing patient stratification methods focus either on predictive performance or interpretable features, we developed a method striking a balance between these two important goals. We introduce a Bayesian method called SUBSTRA that uses regularized biclustering to identify patient subtypes and interpretable subtype-specific transcript clusters. The method iteratively re-weights feature importance to optimize phenotype prediction performance by producing more phenotype-relevant patient subtypes. We investigate the performance of SUBSTRA in finding relevant features using simulated data and successfully benchmark it against state-of-the-art unsupervised stratification methods and supervised alternatives. Moreover, SUBSTRA achieves predictive performance competitive with supervised benchmark methods and provides interpretable transcriptional features in diverse biological settings, such as drug response prediction, cancer diagnosis, or kidney transplant rejection.
Cerebral ischemia induces TRPC6 in the glomerular podocytes: A novel role for HIF1α/ZEB2 axis in the pathogenesis of stroke-induced proteinuria
Authors: Nakuluri Krishnamurthy , Nishad Rajkishor , Mukhi Dhanunjay , Kumar Sireesh , Nakka Venkata P , Kolligundla Lakshmi P , Narne Parimala , Natuva Sai Sampath K , Phanithi Prakash Babu , Pasupulati Anil K
Published: February 2019

Glomerular filtration apparatus (GFA) regulates the glomerular permselectivity and ultrafiltration of urine. Podocytes are specialized cells and a key component of the GFA. The mechanism by which the integrity of the GFA is compromised and manifest in proteinuria during ischemic stroke remains enigmatic. Hypoxia is a determining factor in the pathophysiology of ischemia. We investigated the mechanism of ischemic-hypoxia induced proteinuria in a middle cerebral artery occlusion (MCAO) model. Ischemic hypoxia resulted in the accumulation of HIF1α in the glomerular podocytes that resulted in the increased expression of ZEB2. ZEB2, in turn, induced TRPC6 (transient receptor potential cation channel, subfamily C, member 6), which has increased selectivity for calcium. Elevated expression of TRPC6 elicited increased calcium influx and aberrant activation of focal adhesion kinase (FAK) in podocytes. FAK activation resulted in the stress fibers reorganization and podocyte foot process effacement. Our study suggests overactive HIF1α/ZEB2 axis during ischemic-hypoxia induces intracellular calcium levels via TRPC6 and consequently altered podocyte integrity and permselectivity.
Cerebral Metabolic Changes during Visuomotor Adaptation Assessed using Quantitative FMRI
Authors: Foster Catherine , Steventon Jessica J , Helme Daniel , Tomassini Valentina , Wise Richard G.
Published: February 2019

The neural energetics underlying functional brain plasticity have not been thoroughly investigated in the healthy human brain. A better understanding of the blood flow and metabolism changes underlying plasticity will help us to address pathologies in which plasticity is compromised and, with interventions, could be enhanced for patient benefit.

Calibrated fMRI was conducted in 20 healthy participants during performance of a serial reaction time task which induces rapid motor adaptation. Regions of interest (ROIs) were defined from areas showing linearly decreasing task-induced BOLD and CBF responses. BOLD, CBF and relative CMRO2 responses were calculated for each block of the task. The flow-metabolism coupling ratio, n, was also calculated for each ROI. Increases from baseline in BOLD, CBF and CMRO2 were observed in multiple brain regions including the motor and sensorimotor cortices, cerebellum and hippocampus during SRT task performance, as well as changes in the response amplitude from early to late task blocks reflecting task adaptation. CMRO2 responses on average decreased faster than BOLD or CBF responses, potentially due to rapid neural adaptation. However, the mean flow-metabolism coupling ratio was not significantly different between ROIs or across blocks.

Calibrated fMRI can be used to study energetic changes during learning in the healthy brain and could be used to investigate the vascular and metabolic changes underlying reductions in plasticity in ageing and disease.
LXRβ controls glioblastoma cell growth, lipid balance, and immune modulation independently of ABCA1
Authors: Patel Deven , Ahmad Fahim , Kambach Diane M. , Sun Qian , Halim Alan S. , Stommel Jayne M.
Published: February 2019

Cholesterol is a critical component of membranes and a precursor for hormones and other signaling molecules. Previously, we showed that unlike astrocytes, glioblastoma cells do not downregulate cholesterol synthesis when plated at high density. In this report, we show that high cell density induces ABCA1 expression in glioblastoma cells, enabling them to get rid of excess cholesterol generated by an activated cholesterol biosynthesis pathway. Because oxysterols are agonists for Liver X Receptors (LXRs), we investigated whether increased cholesterol activates LXRs to maintain cholesterol homeostasis in highly-dense glioblastoma cells. We observed that dense cells had increased oxysterols, which activated LXRβ to upregulate ABCA1. Cells with CRISPR-mediated knockdown of LXRβ, but not ABCA1, had decreased cell cycle progression and cell survival, and decreased feedback repression of the mevalonate pathway in densely-plated glioma cells. LXRβ gene expression poorly correlates with ABCA1 in glioblastoma patients, and expression of each gene correlates with poor patient prognosis in different prognostic subtypes. Finally, gene expression and lipidomics analyses of crLXRβ cells revealed that LXRβ regulates the expression of immune response gene sets and lipids known to be involved in immune modulation. Thus, therapeutic targeting of LXRβ in glioblastoma might be effective through diverse mechanisms.
Mitochondrial-nuclear heme trafficking is regulated by GTPases that control mitochondrial dynamics
Authors: Martinez-Guzman Osiris , Dietz Jonathan V. , Bohovych Iryna , Medlock Amy E. , Khalimonchuk Oleh , Reddi Amit R.
Published: February 2019

Heme is an essential cofactor and signaling molecule. All heme-dependent processes require that heme is trafficked from its site of synthesis in the mitochondria to hemoproteins in virtually every subcellular compartment. However, the mechanisms governing the mobilization of heme out of the mitochondria, and the spatio-temporal dynamics of these processes, are poorly understood. To address this, we developed a pulse-chase assay in which, upon the initiation of heme synthesis, heme mobilization into the mitochondrial matrix, cytosol and nucleus is monitored using fluorescent heme sensors. Surprisingly, we found that heme trafficking to the nucleus occurs at a faster rate than to the matrix or cytosol. Further, we demonstrate that GTPases in control of mitochondrial fusion, Mgm1, and fission, Dnm1, are positive and negative regulators of mitochondrial-nuclear heme trafficking, respectively. We also find that heme controls mitochondrial network morphology. Altogether, our results indicate that mitochondrial dynamics and heme trafficking are integrally coupled.
Cohesin occupancy and composition at enhancers and promoters are linked to DNA replication origin proximity inDrosophila
Authors: Pherson, Michelle , Misulovin Ziva , Gause Maria , Dorsett Dale
Published: February 2019

Cohesin consists of the Smc1-Smc3-Rad21 tripartite ring and the SA protein that interacts with Rad21. The Nipped-B protein loads cohesin topologically around chromosomes to mediate sister chromatid cohesion and facilitate long-range control of gene transcription. It is largely unknown how Nipped-B and cohesin associate specifically with gene promoters and transcriptional enhancers, or how sister chromatid cohesion is established. Here we use genome-wide chromatin immunoprecipitation inDrosophilacells to show that SA and the Fs(1)h (BRD4) BET domain protein help recruit Nipped-B and cohesin to enhancers and DNA replication origins, while the MED30 subunit of the Mediator complex directs Nipped-B and Rad21 to promoters. All enhancers and their neighboring promoters are close to DNA replication origins and bind SA with proportional levels of cohesin subunits. Most promoters are far from origins and lack SA, but bind Nipped-B and Rad21 with sub-proportional amounts of Smc1, indicating that they bind SA-deficient cohesin part of the time. Genetic data confirm that Nipped-B and Rad21 function together with Fs(1)h in vivo to facilitateDrosophiladevelopment. These findings demonstrate that Nipped-B and cohesin are differentially targeted to enhancers and promoters and suggest models for how SA and DNA replication help establish sister chromatid cohesion and facilitate enhancer-promoter communication. They indicate that SA is not an obligatory cohesin subunit but a factor that controls cohesin location on chromosomes.
2’3’-cGAMP is an immunotransmitter produced by cancer cells and regulated by ENPP1
Authors: Carozza Jacqueline A. , Böhnert Volker , Shaw Kelsey E. , Nguyen Khanh C. , Skariah Gemini , Brown Jenifer A. , Rafat Marjan , von Eyben Rie , Graves Edward E. , Glenn Jeffrey S. , Smith Mark , Li Lingyin
Published: February 2019

2’3’-cyclic GMP-AMP (cGAMP) is characterized as an intracellular second messenger that is synthesized in response to cytosolic dsDNA and activates the innate immune STING pathway. Our previous discovery of its extracellular hydrolase ENPP1 hinted at the existence of extracellular cGAMP. Here, using mass spectrometry, we detected that cGAMP is continuously exported as a soluble factor by an engineered cell line but then efficiently cleared by ENPP1, explaining why it has escaped detection until now. By developing a potent, specific, and cell impermeable ENPP1 inhibitor, we detected cGAMP export in cancer cell lines commonly used for mouse tumor models. In tumors, depletion of extracellular cGAMP using neutralizing proteins decreased tumor-associated dendritic cells. Boosting extracellular cGAMP by genetic knockout and pharmacological inhibition of ENPP1 increased tumor-associated dendritic cells, shrunk tumors, and synergized with ionizing radiation and anti-CTLA-4 to cure tumors. In conclusion, cGAMP is an anti-cancer immunotransmitter released by tumors and detected by host innate immunity.
Deep motif deconvolution of HLA-II peptidomes for robust class II epitope predictions
Authors: Racle Julien , Michaux Justine , Rockinger Georg Alexander , Arnaud Marion , Bobisse Sara , Chong Chloe , Guillaume Philippe , Coukos George , Harari Alexandre , Jandus Camilla , Bassani-Sternberg Michal , Gfeller David
Published: February 2019

CD4 T cells are key for priming and regulating immune recognition of infected and cancer cells, but predictions of class II epitopes have limited accuracy. We combined unbiased Mass Spectrometry-based HLA-II peptidomics with a novel motif deconvolution algorithm to profile and analyze a total of 99’265 unique HLA-II ligands. Our work demonstrates substantial improvement in the definition of HLA-II binding motifs and enhanced accuracy in class II epitope predictions.
Locus-coeruleus norepinephrine activity gates sensory-evoked awakenings from sleep
Authors: Hayat Hanna , Regev Noa , Matosevich Noa , Sales Anna , Paredes-Rodriguez Elena , Krom Aaron J , Bergman Lottem , Li Yong , Lavigne Marina , Kremer Eric J. , Yizhar Ofer , Pickering Anthony E , Nir Yuval
Published: February 2019

A defining feature of sleep is reduced responsiveness to external stimuli, but the mechanisms gating sensory-evoked arousal remain unclear. We hypothesized that reduced locus-coeruleus norepinephrine (LC-NE) activity during sleep mediates unresponsiveness, and its action promotes sensory-evoked awakenings. We tested this using electrophysiological, behavioral, pharmacological, and optogenetic techniques alongside auditory stimulation in freely behaving rats. We found that systemic reduction of NE signaling lowered probability of sound-evoked awakenings (SEAs). The level of tonic LC activity during sleep anticipated SEAs. Optogenetic LC activation promoted arousal as evident in sleep-wake transitions, EEG desynchronization, and pupil dilation. Importantly, liminal LC excitation before sound presentation increased SEA probability. Optogenetic LC silencing using a soma-targeted anion-conducting channelrhodopsin (stGtACR2) suppressed LC spiking and constricted pupils. Brief periods of LC opto-silencing reduced the probability of SEAs. Thus, LC-NE activity determines the likelihood of sensory-evoked awakenings and its reduction during sleep constitutes a key factor mediating behavioral unresponsiveness.
Multiomic definition of generalizable endotypes in human acute pancreatitis
Authors: Neyton Lucile P. A. , Zheng Xiaozhong , Skouras Christos , Doeschl-Wilson Andrea , Gutmann Michael U. , Yau Christopher , Uings Iain , Rao Francesco V. , Nicolas Armel , Marshall Craig , Wilson Lisa-Marie , Baillie J. Kenneth , Mole Damian J.
Published: February 2019

Acute pancreatitis (AP) is sudden onset pancreas inflammation that causes multiple organ dysfunction syndrome (MODS) and death in certain individuals who develop AP yet minimal systemic inflammation in others. Here, we show that this observed diversity in systemic response and outcome is accompagnied by diversity in molecular subtypes that can be identified using computational analysis of clinical and multiomic data. We integrated co-incident whole blood transcriptomic, plasma proteomic, and serum metabolomic data at serial time points from a cohort of patients presenting with AP and systematically evaluated four different metrics for patient similarity, using unbiased mathematical, biological and clinical measures of internal and external validity. Our results identify four distinct and stable AP endotypes that are characterized by pathway and biomarker combination stereotypes into hypermetabolic, hepatopancreaticobiliary, catabolic and innate immune endotypes. The catabolic endotype in AP strikingly recapitulates a disease endotype previously reported in acute respiratory distress syndrome, a recognized complication of AP. Our findings demonstrate that clinically-relevant and generalizable endotypes exist in AP.
Investigating the Association Between Body Fat and Depression via Mendelian Randomization
Authors: Speed Maria S. , Jefsen Oskar H. , Børglum Anders D. , Speed Doug , Østergaard Søren D.
Published: February 2019

Obesity and depression are major public health concerns that are both associated with substantial morbidity and mortality. There is a considerable body of literature linking obesity to the development of depression. Recent studies using Mendelian Randomization indicate that this relationship is causal. Most studies of the obesity-depression association have used body mass index as a measure of obesity. Body mass index is defined as weight (measured in kilograms) divided by the square of height (meters) and therefore does not distinguish between the contributions of fat and non-fat to body weight. To better understand the obesity-depression association, we conduct a Mendelian Randomization study of the relationship between fat mass, non-fat mass, height, and depression, using genome-wide association study results from the UK Biobank (n=332,000) and the Psychiatric Genomics Consortium (n=480,000). Our findings suggest that both fat mass and height (short stature) are causal risk factors for depression, while non-fat mass is not. These results represent important new knowledge on the role of anthropometric measures in the etiology of depression. They also suggest that reducing fat mass will decrease the risk of depression, which lends further support to public health measures aimed at reducing the obesity epidemic.
Therapeutic Targeting of Casein Kinase 1δ/ε in an Alzheimer’s Disease Mouse Model
Authors: Adler Paula , Mayne Janice , Walker Krystal , Ning Zhibin , Figeys Daniel
Published: February 2019

Sleep disturbances and memory impairment are common symptoms of Alzheimer’s disease (AD). Given that the circadian clock regulates sleep, hippocampal function, and neurodegeneration, it represents a therapeutic target against AD. Casein kinase 1δ/ε (CK1δ/ε) are clock regulators and overexpressed in AD brains, making them viable targets to improve sleep and cognition. We assessed the effects of a small molecule CK1δ/ε inhibitor (PF-670462) in a cellular model of circadian clocks and in 3xTg-AD mice. Mass spectrometry–based proteomic analyses revealed that PF-670462 treatmentin vitroupregulated multiple proteins that are downregulated in AD, while administration in 3xTg-AD mice reversed hippocampal proteomic alterations in diverse AD-associated and clock-regulated pathways, including synaptic plasticity and amyloid precursor protein processing. Furthermore, PF-670462 rescued working memory and normalized behavioural circadian rhythms in 3xTg-AD mice. Our study provides proof of concept for CK1δ/ε inhibition and direct clock modulation against AD-related proteomic changes, memory impairment, and circadian disturbances.
KAI2 regulates root and root hair development by modulating auxin distribution
Authors: Villaecija-Aguilar José Antonio , Hamon-Josse Maxime , Carbonnel Samy , Kretschmar Annika , Ljung Karin , Bennett Tom , Gutjahr Caroline
Published: February 2019

Strigolactones (SLs) are endogenous signalling molecules that play important roles in controlling plant development. SL perception is closely related to that of karrikins, smoke-derived compounds presumed to mimic endogenous signalling molecules (KLs). SLs have been suggested to regulate root development. However, perception of both molecules requires the F-box protein MAX2 and the use ofmax2mutants has hampered defining the exact role of SLs in roots. Here we dissect the role of SL and KL signalling inArabidopsisroot development using mutants defective in the α/β hydrolase receptors D14 and KAI2, which specifically perceive SLs and KLs, respectively. Both pathways together regulate lateral root density (LRD), but contrary to previous reports, KL signalling alone controls root hair density, root hair length and additionally root skewing, straightness and diameter. Members of the SMXL protein family are downstream targets of SL (SMXL6, 7, 8) and KL (SMAX1, SMXL2) signalling. We identified distinct and overlapping roles of these proteins in the regulation of root development. Both SMAX1/SMXL2 and SMXL6/SMXL7/SMXL8 regulate LRD, confirming that SL and KL signalling act together to regulate this trait, while the KL-signalling specific SMAX1 and SMXL2 regulate all other investigated root traits. Finally, we show that KL signalling regulates root hair development by modulating auxin distribution within the root.
Bingeing in rats: Persistence of high intakes of palatable solutions induced by 1-in-4 days intermittent access
Authors: Rehn Simone , Boakes Robert A.
Published: February 2019

When animals are given access to a palatable food or drink on some days but not on others, the amount they consume can far exceed the daily amounts consumed by controls given daily access. In a previous study such bingeing was found when rats were given 4% sucrose solution; it also found that, following 1-in-4-days access for many weeks, intakes remained persistently higher than that of controls even when the conditions were changed to 1-in-2-days access for both groups. One aim of the three experiments reported here was to test whether such persistent bingeing could be found for other solutions. This was confirmed in rats for a saccharin solution and a highly palatable saccharin-plus-glucose solution. However, when a maltodextrin solution was used, initial increased intakes produced by the 1-in-4-days schedule were not maintained when this was changed to a 1-in-2-days schedule. These results suggested that the hedonic value of a solution is more important than its caloric content in determining whether it will support persistent bingeing. A second aim was to test for evidence that the 1-in-4-days procedure induced an addiction to the target solution. No such evidence was found using multiple measures including instrumental responding and anxiety-like behavior on the elevated plus-maze for craving and withdrawal respectively.
DETECTION OFFUSARIUM OXYSPORUMF. SP. ELAEIDIS CAUSING FUSARIUM WILT OF OIL PALM USING LOOP-MEDIATED ISOTHERMAL AMPLIFICATION (LAMP)
Authors: Adusei-Fosu Kwasi , Dickinson Matthew
Published: February 2019

Fusarium oxysporumf. sp.elaeidis(FOE) a pathogen that causes fusarium wilt disease in oil palm can be detected using polymerase chain reaction (PCR) but very time consuming. Loop-Mediated Isothermal Amplification (LAMP) was used to rapidly detectFusarium oxysporumf. sp.elaeidis(FOE) in oil palm seedlings. Eight additionalFusarium oxysporumisolates collected from symptomatic oil palm trees (i.e. presumed-FOE as their pathogenicity was not confirmed) and five other non-FOE isolates were sampled from symptomatic mature oil palm trees and tomato respectively to broaden the scope of the research. The identities of FOE, presumed-FOE and non-FOE were established via sequencing. LAMP primers designed for detecting FOE or presumed-FOE were based on partial sequences ofSecreted In Xylem(SIX8) andP-450cytochrome. The earliest detection time forSIX8andP-450cytochrome primers were 4:00 mins and 6:45 mins respectively with both recording late time for detection at 26:30 mins. Annealing derivative curves were used for assessing the level of specificity for bothSIX8andP-450cytochrome, but none of the LAMP primers could distinguish between FOE, presumed-FOE and non-FOE.
Streamlining and Cycle Time Reduction of the Start-up Phase of Clinical Trials
Authors: Abu-Shaheen Amani , Badr Ahmad Al , AlFayyad Isamme , Qutub Adel Al , Faqeih Eissa Ali , Altannir Mohamad
Published: February 2019

Objective

The start-up phase of a clinical trial (CT) plays a vital role in execution of novel drug development. Hence, this study aims to identify the factors responsible for delaying the CT start-up phase. Further, it focuses on streamlining and reducing the cycle time of the start-up phase of newly sponsored CTs.

Methodology

Thirteen sponsored CTs conducted (between 2016 and 2017) in clinical research department at King Fahad Medical City, Riyadh were analyzed to identify the data specific start-up metrics usingFind an improvement area-Organize a team-Clarify current practices-Understand source of variation/problem-Select a Strategy-Plan-Do-Check-Act (FOCUS-PDCA) cycle. Five measures incorporated in the metrics were: date of initial contact with site to the signing of confidentiality agreement; date of receiving questionnaire from sponsor to date of its completion; time taken to review protocol and approve investigational drug service (IDS) form; time taken to review protocol and approve pharmacy and pathology and clinical laboratory medicine (PCLM) form and date of receipt of institutional review board (IRB) submission package to final IRB approval.

Fishbone analysis was used to understand the potential causes of process variation. Mean time was calculated for each metrics prior to and post implementation of the intervention protocol to analyze and compare percentage reduction in the mean cycle time of CTs.

Results

Of the various potential factors of delay identified through Fishbone analysis, the two major ones were lack of well-defined timeline for approval and review of the study protocol; and inconsistent IRB meetings. Post introduction of the new intervention protocol, the entire CT lifecycle was reduced by 45.6% (24.8 weeks' vs 13 weeks, before and after intervention, respectively).

Conclusion

Varied factors are responsible for delay of the start-up phase of CTs and understanding the impact of each factor allows for optimization and faster execution of the start-up phase of CTs.
Optimal sample size calculation for null hypothesis significance tests
Authors: Mudge Joseph F. , Houlahan Jeffrey E.
Published: February 2019

Traditional study design tools for estimating appropriate sample sizes are not consistently used in ecology and can lead to low statistical power to detect biologically relevant effects. We have developed a new approach to estimating optimal sample sizes, requiring only three parameters; a maximum acceptable average of α and β, a critical effect size of minimum biological relevance, and an estimate of the relative costs of Type I vs. Type II errors.This approach can be used to show the general circumstances under which different combinations of critical effect sizes and maximum acceptable combinations of α and β are attainable for different statistical tests. The optimal α sample size estimation approach can require fewer samples than traditional sample size estimation methods when costs of Type I and II errors are assumed to be equal but recommends comparatively more samples for increasingly unequal Type I vs. Type II errors costs. When sampling costs and absolute costs of Type I and II errors are known, optimal sample size estimation can be used to determine the smallest sample size at which the cost of an additional sample outweighs its associated reduction in errors. Optimal sample size estimation constitutes a more flexible and intuitive tool than traditional sample size estimation approaches, given the constraints and unknowns commonly faced by ecologists during study.
Cyanobacteria is uniquely enriched in the roots of grain amaranths
Authors: Nambisan Suran , Sunil Meeta , Choudhary Bibha , Srinivasan Subhashini
Published: February 2019

Plants and microbes have coexisted for millions of years and some have evolved mechanisms to achieve symbiosis driving positive selection. The bartering of chemicals produced by soil microbes and plants favour enrichment of certain types of bacteria near the roots that offers selective advantage to the plant under a given environment. Grain amaranths display certain important agronomic characteristics like C4 dicot, high protein and high lysine grains, resistance to biotic and abiotic stress, which can be translated to other crops. Considering an unusual collection of desirable traits shown by grain amaranths, it is worth pondering if symbiosis with bacteria has played any role in these traits. The objective of this study is to identify bacterial root microflora unique to grain amaranths. Here, by comparing rhizospheric and endophytic composition of 16S rRNA from various sections of roots from selected species under major plant orders including the three varieties of grain amaranths, we report that Cyanobacteria are uniquely enriched by grain amaranths. The diversity in OTUs among the Cyanobacteria also significantly increased among samples from amaranth species compared to negative control. This finding is also validated using root transcriptome of Amaranthus hypochondriacus, where we observe relative increase in Cyanobacterial population between day 15 to day 30 compared to other abundant phylum during this period.
Imputation of canine genotype array data using 365 whole-genome sequences improves power of genome-wide association studies
Authors: Hayward Jessica J. , White Michelle E. , Boyle Michael , Shannon Laura M. , Casal Margret L. , Castelhano Marta G. , Center Sharon A. , Meyers-Wallen Vicki N. , Simpson Kenneth W. , Sutter Nathan B. , Todhunter Rory J. , Boyko Adam R.
Published: February 2019

Genomic resources for the domestic dog have improved with the widespread adoption of a 173k SNP array platform and updated reference genome. SNP arrays of this density are sufficient for detecting genetic associations within breeds but are underpowered for finding associations across multiple breeds or in mixed-breed dogs, where linkage disequilibrium rapidly decays between markers, even though such studies would hold particular promise for mapping complex diseases and traits. Here we introduce an imputation reference panel, consisting of 365 diverse, whole-genome sequenced dogs and wolves, which increases the number of markers that can be queried in genome-wide association studies approximately 130-fold. Using previously genotyped dogs, we show the utility of this reference panel in identifying novel associations and fine-mapping for canine body size and blood phenotypes, even when causal loci are not in strong linkage disequilibrium with any single array marker. This reference panel resource will improve future genome-wide association studies for canine complex diseases and other phenotypes.

Author Summary

Complex traits are controlled by more than one gene and as such are difficult to map. For complex trait mapping in the domestic dog, researchers use the current array of 173,000 variants, with only minimal success. Here, we use a method called imputation to increase the number of variants – from 173,000 to 24 million – that can be queried in canine association studies. We use sequence data from the whole genomes of 365 dogs and wolves to accurately predict variants, in a separate cohort of dogs, that are not present on the array. Using dog body size, we show that the increase in variants results in an increase in mapping power, through the identification of new associations and the narrowing of regions of interest. This imputation panel is particularly important because of its usefulness in improving complex trait mapping in the dog, which has significant implications for discovery of variants in humans with similar diseases.
Evaluation of DNA extracted from blood filter spots and eluates processed for enzyme linked immunosorbent assay (ELISA)
Authors: Xatse Mark Andy , Akorli Jewelna , Owusu Irene Offei , Gati Livingstone , Wilson Michael David
Published: February 2019

Dried filter blood spots have become a significant blood collection method for screening individuals for clinical purposes. When used for ELISAs, they are normally discarded after the blood has been eluted. However, they may still be useful for extraction of DNA for molecular-based assays. The aim of this work was to determine the integrity of DNA extracted from filter paper spots from which blood has initially been eluted for ELISA with sample dilution buffer (SDB) and phosphate buffered saline (PBS). DNA was extracted from the eluted filter spots, the eluate, and dried blood filter spots (controls) using spin column extraction. The quality and quantity of the extracted DNA was assessed and used for PCR to further evaluate their usefulness in molecular assays. Concentration of DNA obtained was dependent on the buffer used for processing the filter blood blots. Accounting for the DNA concentration obtained from dried blood spots, which were used as controls, DNA extracted from the already eluted blood spots were 32 times higher in PBS than SDB processed filter paper. The ratio was even higher for the eluates, which were 57 times higher in PBS than SDS eluates. SDB eluates had significantly higher average DNA concentration than their eluted filter paper, but their purity ratios were similar. 85% PCR success rate was achieved with the DNA samples. Useful DNA can be extracted from blood spots after it has been eluted with SDB. Although the DNA concentration and purity may be low, the DNA could be useful for rather simple PCR assays.

Author Summary

Collection of blood onto filter paper has become an accepted method for screening individuals for clinical and public health purposes since the 1960s. This method of blood collection has become increasingly popular due to its ease and convenience in collection and transportation. The use of dried blood spots for clinical evaluations and research has become very significant. For research purposes, DBS when used for ELISAs are discarded after single use. DNA may however be extracted from the used filter blots and used for molecular assays. The concentration of DNA obtained may be low but simple assays like PCR could be done using the DNA extracted from the eluted filter spot.
Mapping global and local coevolution across 600 species to identify novel homologous recombination repair genes
Authors: Sherill-Rofe Dana , Rahat Dolev , Findlay Steven , Mellul Anna , Guberman Irene , Braun Maya , Bloch Idit , Lalezari Alon , Samiei Arash , Sadreyev Ruslan , Goldberg Michal , Orthwein Alexandre , Zick Aviad , Tabach Yuval
Published: February 2019

The homologous recombination repair (HRR) pathway repairs DNA double-strand breaks in an error-free manner. Mutations in HRR genes can result in increased mutation rate and genomic rearrangements, and are associated with numerous genetic disorders and cancer. Despite intensive research, the HRR pathway is not yet fully mapped. Phylogenetic profiling analysis, which detects functional linkage between genes using coevolution, is a powerful approach to identify factors in many pathways. Nevertheless, phylogenetic profiling has limited predictive power when analyzing pathways with complex evolutionary dynamics such as the HRR. To map novel HRR genes systematically, we developed clade phylogenetic profiling (CladePP). CladePP detects local coevolution across hundreds of genomes and points to the evolutionary scale (e.g., mammals, vertebrates, animals, plants) at which coevolution occurred. We found that multiscale coevolution analysis is significantly more biologically relevant and sensitive to detect gene function. By using CladePP, we identified dozens of unrecognized genes that coevolved with the HRR pathway, either globally across all eukaryotes or locally in different clades. We validated eight genes in functional biological assays to have a role in DNA repair at both the cellular and organismal levels. These genes are expected to play a role in the HRR pathway and might lead to a better understanding of missing heredity in HRR-associated cancers (e.g., heredity breast and ovarian cancer). Our platform presents an innovative approach to predict gene function, identify novel factors related to different diseases and pathways, and characterize gene evolution.
Revisiting green packaging from a cost perspective
Authors: Singh Gaganpreet , Pandey Neeraj
Published: February 2019

Purpose

The purpose of this paper is to explore green packaging from the process dimension. Specifically, it focuses on understanding the behavior of costs associated with installing green packaging infrastructure.

Design/methodology/approach

The study used system dynamics to design the model. The model was tested on three industries employed in manufacturing glass bottles to generalize the result.

Findings

The study concludes that cost of remanufacturing which initially is higher because of recollection phases and reverse logistics costs eventually becomes lower than new manufacturing as soon as system achieves stability and continues to follow the same trend over the period of time.

Practical implications

The study put forwards an explanation to the concerns of manufacturers who were unwilling to install green packaging or remanufacturing infrastructure into their operations because of several cost- and risk-related dilemmas.

Originality/value

The study extends the academic literature by answering the queries raised by Kassaye and Holloway (2015).
Young people school-to-work transition in the aftermath of the Arab Spring
Authors: Selwaness Irene , Roushdy Rania
Published: February 2019

Purpose

The purpose of this paper is to examine the school-to-work transition of young people from subsequent school exit cohorts between 2001 and 2012 in Egypt, thus, presenting an early evidence on the adjustments of the labor market in terms of patterns of youth transition to a first job following the 2011 Egyptian uprising.

Design/methodology/approach

The analysis compares the early employment outcomes of those who left school after the January 25, 2011 uprising to that of those who left before 2011. The authors also separately control for the cohorts who left school in 2008 and 2009, in an attempt to disentangle any labor market adjustments that might have happened following the financial crisis, and before the revolution. Using novel and unexploited representative data from the 2014 Survey of Young People in Egypt (SYPE), the authors estimate the probability of transition to any first job within 18 months from leaving education and that of the transition to a good-quality job, controlling for the year of school exit. The authors also estimate the hazard of finding a first job and a good-quality job using survival analysis.

Findings

School exit cohorts of 2008–2009 (following the financial crisis) and those of 2011–2012 (in the aftermath of the 2011 uprisings) experienced a significantly higher likelihood of finding a first job within 18 months than that of the cohorts of 2001–2007. However, this came at the expense of the quality of job, conditional on having found a first job. The results of the hazard model show that school leavers after 2008 who were not able to transition to a job shortly after leaving school experienced longer unemployment spells than their peers who left school before 2007. The odds of finding a good-quality job appears to decline with time spent in non-employment or in a bad-quality first job.

Originality/value

This paper contributes to a limited, yet growing, literature on how school-to-work transition evolved during the global financial crisis and the Egyptian 2011 revolution. Using data from SYPE 2014, the most recent representative survey conducted in Egypt on youth and not previously exploited to study youth school-to-work transition, the paper investigates the short-term adjustments of the youth labor market opportunities during that critical period of Egypt and the region’s history.
Endorsement and visual complexity in food advertising on Instagram
Authors: Kusumasondjaja Sony , Tjiptono Fandy
Published: February 2019

Purpose

The purpose of this paper is to investigate the differences in consumer pleasure, arousal and purchase intention when consumers encounter food advertising on Instagram using different endorsers and visual complexity levels.

Design/methodology/approach

An experimental design was conducted involving 180 undergraduate students from several universities in Surabaya, Indonesia. The participants had actively used Instagram for at least one year.

Findings

Food ads endorsed by a celebrity generate more pleasure and arousal than those endorsed by food experts. Food advertising using high levels of visual complexity cues generates more pleasure and arousal than less complex advertising. However, less complex food ads using food experts create greater pleasure than those endorsed by celebrities. Consumer pleasure and arousal were significant mediators of the impact of endorser type and visual complexity on consumer purchase intentions.

Practical implications

As celebrities and higher levels of visual complexity result in more favorable responses to Instagram ads, food marketers need to consider increasing visual complexity when using celebrities in advertising by adding more objects, using more colors, objects, or textures and incorporating asymmetric elements in the advertisements.

Originality/value

This is one of the few studies comparing the effectiveness of celebrity and expert endorsers in Instagram advertising. Also, this research extends the existing knowledge about visual complexity in the context of social media advertising.
Multiple sequential mediation in an extended uses and gratifications model of augmented reality game Pokémon Go
Authors: Ghazali Ezlika M. , Mutum Dilip S. , Woon Mei Yuen
Published: February 2019

Purpose

The purpose of this paper is to investigate the mechanism by which uses and gratification (U&G) constructs predict continuance intention to play (ContInt) the augmented reality game Pokémon Go (PG), through multiple serial mediation technique, with enjoyment and flow as mediators. The model also integrates other motivational factors specific to PG, namely, network externality and nostalgia and investigates the process by which they influence ContInt through players’ inherent need-to-collect animated monsters and online community involvement, respectively.

Design/methodology/approach

The model was tested using 362 validated responses from an online survey of PG players in Malaysia. Partial least squares structural equation modeling was used to analyse the data. The predictive relevance of the model was tested via partial least squares-Predict.

Findings

ContInt is influenced through various mechanisms. Enjoyment is the most important mediator, mediating three U&G predictor constructs (achievement, escapism, challenge and social interaction) and the outcome ContInt. Flow did not have any influence on ContInt unless coupled with enjoyment as a serial mediator. Network externality and nostalgia were found to only influence ContInt through mediators, online community involvement and need-to-collect Pokémon Monsters, respectively. Overall, the results show evidence of four indirect-only mediation paths and one complementary partial mediation path.

Originality/value

Provides support for an integrated model incorporating psychological, social and gaming motivational factors. While most other studies focus on direct relationships, we focus on indirect relationships through multiple sequential mediation analysis, following the recent modern mediation analysis guidelines. Contrary to previous findings, flow was not an important factor in predicting ContInt for gaming and nostalgia does not link directly to ContInt.
Traceability for sustainability – literature review and conceptual framework
Authors: Garcia-Torres Sofia , Albareda Laura , Rey-Garcia Marta , Seuring Stefan
Published: February 2019

Purpose

This paper aims to examine how companies enact traceability in their global supply chains (SCs) to achieve sustainability goals and how this so-called traceability for sustainability (TfS) can contribute to (sustainable) supply chain management ([S]SCM). For this, the paper focuses on the paramount example of the apparel industry.

Design/methodology/approach

This study presents an integrative and systematic literature review of 89 peer-reviewed journal articles on the confluence of traceability and sustainability in global apparel SCs. It comprises content analysis and abductive category-building based on previous literature.

Findings

A conceptual framework emerges to describe TfS as an evolving cycle, comprising three dimensions: governance, collaboration and tracking and tracing. Resources and capabilities literature set the foundations for conceiving TfS as a distinctive meta-capability construct. Hence, besides being associated to increased performance, risk management and SC process transformation, TfS ultimately blurs boundaries and integrates non-traditional SC actors into the same ecosystem with important implications for sustainability and (S)SCM. This study refers to the industrial upgrading potential of global SCs to explain how leveraging enabling technologies for TfS may help to improve the triple-bottom-line (TBL) performance of the actors in the broad ecosystem while reducing the risks associated to those technologies. Thus, TfS can contribute to (S)SCM and to TBL sustainability within and beyond SC boundaries.

Originality/value

This study conceptually frames (S)SCM exploring TfS as a meta-capability and contributes to the underexplored question of how to achieve sustainability in global SCs.
Claudin reduction may relate to an impaired skin barrier in rosacea
Authors: Deng Zhili , Chen Mengting , Xie Hongfu , Jian Dan , Xu San , Peng Qinqin , Sha Ke , Liu Yingzi , Zhang Yiya , Shi Wei , Li Ji
Published: February 2019

Rosacea is a chronic inflammatory skin disorder whose pathophysiological mechanism remains largely unknown. Although recent studies have revealed the hypersensitivity of the skin towards chemical, thermal and biological stimuli, there is no direct molecular evidence suggesting the skin barrier is impaired in rosacea. In this study, we demonstrated that the mRNA levels of most claudins (CLDN), the main components of tight junctions determining the major barrier of the paracellular pathway between epithelial cells, were lowered in lesional skin of rosacea patients, especially with erythematotelangiectatic (ETR) and papulopustular (PPR) subtypes. Immunohistochemical analysis showed a significant decrease in the expression of CLDN1, CLDN3, CLDN4 and CLDN5 in the epidermis of ETR and PPR patients. However, the expression of other skin barrier genes, such as filaggrin, loricrin and keratin 10, was not altered. In vitro, various rosacea trigger factors reduced the protein levels of CLDN1, CLDN3 and CLDN5 in keratinocytes. Taken together, our results demonstrate a significant decrease in the expression of CLDN rather than other skin barrier genes, which may be associated with an impaired skin barrier responsible for the development of rosacea.