bluuebunny/crossref_metadata_2025 huggingface dataset:
A Systematic Evaluation of State Laws Governing Optometric Glaucoma Management in the United States Upto 2015
Authors: Chodnicki Kevin , Kalarn Sachin , Quinn Laura , Jampel Henry , Saeedi Osamah
Published: January 2018

Purpose:

To describe state laws that govern the optometric practice of glaucoma management in the United States and to correlate those laws with state demographics upto 2015.

Materials and Methods:

We performed a cross-sectional ecological study of the 50 United States and the District of Columbia. Regulations governing optometric scope of practice as written by each state Board of Optometry were reviewed. Specific optometric privileges assessed included: ability to manage glaucoma independently, use of diagnostic pharmaceutical agents, use of therapeutic pharmaceutical agents (including topical and oral steroids and other oral pharmaceutical agents), IV injections, intraocular injections, therapeutic lasers, presence of defined referral, and comanagement guidelines, and hours of yearly continuing education needed for glaucoma management. Optometric privilege was compared with demographic and employment information for each state.

Results:

Optometrists in all states, except for Massachusetts, and the District of Columbia are allowed to manage glaucoma; 16 states have defined comanagement guidelines. Therapeutic lasers are allowed in 3 states: Kentucky, Louisiana, and Oklahoma. States with defined comanagement guidelines had a mean of 6.9±1.9 ophthalmologists per 100,000 people, significantly more than the 5.3±1.1 in states without defined comanagement of glaucoma (P<0.01). Binary logistic regression showed that, accounting for population and area, the higher the number of optometrists in a state, the less likely there is to be defined comanagement [β (SE)=−0.008 (0.003), P=0.02] and the greater the number of ophthalmologists in a given state, the more likely a state has defined comanagement [β (SE)=−0.13 (0.006)].

Conclusions:

There is a diversity of regulations that govern optometric management of glaucoma in each of the 50 states and the District of Columbia. The number of optometrists and ophthalmologists in a state may influence state regulations governing optometric practice and referral guidelines.
Case Report: Xen Ab Interno Gel Stent Use in a Refractory Glaucoma Patient With Previous Filtration Surgeries
Authors: Sandhu Simrenjeet , Dorey Michael W.
Published: January 2018

This case study reports the successful implantation of the Xen ab interno gel stent in a 44-year-old man with refractory chronic open-angle glaucoma. The patient had multiple unsuccessful filtration surgeries including a trabeculectomy and 2 Ahmed glaucoma valves placed superotemporally and inferonasally oculus dexter. The patients intraocular pressure was reduced from 29 mm Hg preoperatively to 17 mm Hg 1 year after surgery, without any ocular complications. The Xen gel stent may be considered as a possible intervention to lower intraocular pressure in patients with refractory glaucoma, despite previous filtration surgeries if the superonasal conjunctiva is spared and healthy.
Factors Influencing Time‐to‐diagnosis of Biliary Atresia
Authors: Harpavat Sanjiv , Lupo Philip J. , Liwanag Loriel , Hollier John , Brandt Mary L. , Finegold Milton J. , Shneider Benjamin L.
Published: January 2018

Objectives:

Diagnosing biliary atresia (BA) quickly is critical, because earlier treatment correlates with delayed or reduced need for liver transplantation. However, diagnosing BA quickly is also difficult, with infants usually treated after 60 days of life. In this study, we aim to accelerate BA diagnosis and treatment, by better understanding factors influencing the diagnostic timeline.

Methods:

Infants born between 2007 and 2014 and diagnosed with BA at our institution were included (n = 65). Two periods were examined retrospectively: P1, the time from birth to specialist referral, and P2, the time from specialist referral to treatment. How sociodemographic factors associate with P1 and P2 were analyzed with Kaplan‐Meier curves and Cox proportional hazard models. In addition, to better characterize P2, laboratory results and early tissue histology were studied.

Results:

P1 associated with race/ethnicity, with shorter times in non‐Hispanic white infants compared to non‐Hispanic black and Hispanic infants (P = 0.007 and P = 0.004, respectively). P2 associated with referral age, with shorter times in infants referred after 30, 45, or 60 days of life (P < 0.001, P < 0.001, and P = 0.001, respectively). One potential reason for longer P2 in infants referred ⩽30 days is that aminotransferase levels were normal or near‐normal. However, despite reassuring laboratory values, tissue histology in early cases showed key features of BA.

Conclusions:

Our findings suggest 2 opportunities to accelerate BA diagnosis and treatment. First, to achieve prompt referrals for all races/ethnicities, universal screening strategies should be considered. Second, to ensure efficient evaluations independent of age, algorithms designed to detect early features of BA can be developed.
Symbiotic root infections inMedicago truncatularequire remorin-mediated receptor stabilization in membrane nanodomains
Authors: Liang Pengbo , Stratil Thomas F. , Popp Claudia , Marín Macarena , Folgmann Jessica , Mysore Kirankumar S. , Wen Jiangqi , Ott Thomas
Published: January 2018

Plant cell infection is tightly controlled by cell surface receptor-like kinases (RLKs) Alike other RLKs theMedicago truncatulaentry receptor LYK3 laterally segregates into membrane nanodomains in a stimulus-dependent manner. Although nanodomain localization arises as a generic feature of plant membrane proteins, molecular mechanisms underlying such dynamic transitions and their functional relevance remained poorly understood. Here, we demonstrate that actin and the flotillin protein FLOT4 form the primary and indispensable core of a specific nanodomain. Infection-dependent induction of the remorin protein and secondary molecular scaffold SYMREM1 results in subsequent recruitment of ligand-activated LYK3 and its stabilization within these membrane subcompartments. Reciprocally, the majority of this LYK3 receptor pool is destabilized at the plasma membrane and undergoes rapid endocytosis insymrem1mutants upon rhizobial inoculation resulting in premature abortion of host cell infections. These data reveal that receptor recruitment into nanodomains is indispensable for their function during host cell infection.

SIGNIFICANCE STATEMENT

Pattern recognition receptors control the cellular entry of pathogenic as well as symbiotic microbes. While ligand-induced changes in receptor mobility at the plasma membrane and their localization in membrane nanodomains appears as a general feature, the molecular mechanism and the biological relevance of this phenomenon remained unknown. Here, we show that immobilization of the symbiotic cell entry receptor LYK3 in nanodomains requires the presence of actin and the two molecular scaffold proteins FLOT4 and SYMREM1. While FLOT4 forms the initial core structure, infection-induced expression and subsequent physical interaction of SYMREM1 with LYK3 stabilizes the activated receptors in membrane nanodomains. This recruitment prevents its stimulus-dependent endocytosis and ensures progression of the primary infection thread into root cortical cells.
AFCMEasyModel: An Easy Interface for Modeling Competing Endogenous RNA Networks using ODEs
Authors: Tarek Mohammad M.
Published: January 2018

Competing endogenous RNA networks have been considered to be important regulators of genetic data expression. Circular RNAs and microRNAs interact to form a circular sponge that have been shown to regulate messenger RNAs and hence regulating gene expression. The kinetics by which these non-coding RNAs interact together affecting gene expression are crucial to understand the mechanism of their regulatory function. Herein, we developed AFCMEasyModel as a user-friendly shiny app that enables users to modify regulation parameters of a competing endogenous RNA network based on interaction between circular RNAs and microRNAs in the simulation environment to form a sponge complex. The App provides the source-code for more customized models and allow users to download simulation plots for supplementation of their publications.

The App was made available for public-access at: https://mohammadtarek.shinyapps.io/afcmeasymodel/
Comparison of computational methods for imputing single-cell RNA-sequencing data
Authors: Zhang Lihua , Zhang Shihua
Published: January 2018

Single-cell RNA-sequencing (scRNA-seq) is a recent breakthrough technology, which paves the way for measuring RNA levels at single cell resolution to study precise biological functions. One of the main challenges when analyzing scRNA-seq data is the presence of zeros or dropout events, which may mislead downstream analyses. To compensate the dropout effect, several methods have been developed to impute gene expression since the first Bayesian-based method being proposed in 2016. However, these methods have shown very diverse characteristics in terms of model hypothesis and imputation performance. Thus, large-scale comparison and evaluation of these methods is urgently needed now. To this end, we compared eight imputation methods, evaluated their power in recovering original real data, and performed broad analyses to explore their effects on clustering cell types, detecting differentially expressed genes, and reconstructing lineage trajectories in the context of both simulated and real data. Simulated datasets and case studies highlight that there are no one method performs the best in all the situations. Some defects of these methods such as scalability, robustness and unavailability in some situations need to be addressed in future studies.
A single spectrum of neuronal identities across thalamus
Authors: Phillips James W. , Schulmann Anton , Hara Erina , Liu Chenghao , Wang Lihua , Shields Brenda C. , Korff Wyatt , Lemire Andrew L. , Dudman Joshua , Nelson Sacha B. , Hantman Adam
Published: January 2018

Uncovering common principles by which diverse modalities of information are processed is a fundamental goal in neuroscience. In mammalian brain, thalamus is the central processing station for inputs from sensory systems, subcortical motor systems, and cortex; a function subserved by over 30 defined nuclei1,2. Multiple thalamic nuclei send convergent information to each region of the forebrain, but whether there is a conserved architecture across the set of thalamic pathways projecting to each forebrain area has remained unresolved3–5. To uncover organizational principles of thalamic pathways, we produced a near-comprehensive transcriptomic atlas of thalamus. This revealed a common logic for thalamic nuclei serving all major cortical modalities. We found that almost all nuclei belong to one of three major profiles, with a given cortical area getting input from each of these profiles. These profiles lie on a single axis of variance aligned with the mediolateral axis of thalamus, and this axis is strongly enriched in genes encoding receptors and ion channels. We further show that each projection profile exhibits different electrophysiological signatures. Single-cell profiling revealed that rather than forming discrete classes, thalamic neurons lie on a spectrum, with intermediate cells existing between profiles. Thus, in contrast to canonical models of thalamus that suggest it is a switchboard primarily concerned with routing distinct modalities of information to distinct cortical regions, we show that the thalamocortical system is more akin to a molecularly-defined ‘filter bank’ repeatedly applied across modality. Together, we reveal striking covariation in the organization of thalamic pathways serving all input modalities and output targets, establishing a simple and comprehensive thalamic functional architecture.
Binocular System with Asymmetric Eyes
Authors: Turski Jacek
Published: January 2018

I elaborate binocular geometry with a novel eye model that incorporates the fovea’s temporalward displacement and the cornea and the lens’ misalignment. The formulated binocular correspondence results in longitudinal horopters that are conic sections resembling empirical horopters. When the eye model’s asymmetry parameters’ range is that which is observed in healthy eyes, abathic distance also falls within its experimentally observed range. This range in abathic distance is similar to that of the vergence resting position distance. Further, the conic’s orientation is specified by the eyes’ version angle, integrating binocular geometry with eye movement. This integration presents the possibility for modeling 3D perceptual stability during physiological eye movements.

OCIS codes: (330.1400) Vision - binocular and stereopsis; (330.4060) Vision modeling
PRDM9 and an Epidemic of Gene Conversion and Non-Homologous Recombination among Alu Elements in Ancestral Gorillas
Authors: Wacholder Aaron C. , Pollock David D.
Published: January 2018

We performed a genome-wide scan for recombination-mediated interlocus gene conversion and deletion events among a set of orthologous Alu loci in the Great Apes, and were surprised to discover an extreme excess of such events in the gorilla lineage versus other lineages. Gorilla events, but not events in other Great Apes, are strongly associated with a 15 bp motif commonly found in Alu sequences. This result is consistent with evolutionarily transient targeting of the motif by PRDM9, which induces double strand breaks and crossovers during meiosis at specific but rapidly changing sequence motifs. The motif is preferentially found in conversion recipients but not donors, and is substantially depleted in gorillas, consistent with loss of PRDM9 targets by meiotic drive. Recombination probability falls of exponentially with distance between loci, is reduced slightly by sequence divergence, and drops substantially with recipient divergence from the target motif. We identified 16 other high-copy motifs in human, often associated with transposable elements, with lineage-specific depletion and nearby gene conversion signatures, consistent with transient roles as PRDM9 targets. This work strengthens our understanding of recombination-mediated events in evolution and highlights the potential for interactions between PRDM9 and repetitive sequences to cause rapid change in the genome.
Converting a broad matrix metalloproteinase family inhibitor into a specific inhibitor of MMP-9 and MMP-14
Authors: Shirian Jason , Arkadash Valeria , Cohen Itay , Sapir Tamila , Radisky Evette S. , Papo Niv , Shifman Julia M.
Published: January 2018

MMP-14 and MMP-9 are two well established cancer targets for which no specific clinically relevant inhibitor is available. Using a powerful combination of computational design and yeast surface display technology, we engineered such an inhibitor starting from a non-specific MMP inhibitor, N-TIMP2. The engineered purified N-TIMP2 variants showed enhanced specificity towards MMP-14 and MMP-9 relative to a panel of off-target MMPs. MMP-specific N-TIMP2 sequence signatures were obtained that could be understood from the structural perspective of MMP/N-TIMP2 interactions. Our MMP-9 inhibitor exhibited 1000-fold preference for MMP-9 vs. MMP-14, which is likely to translate into significant differences under physiological conditions. Our results provide new insights regarding evolution of promiscuous proteins and optimization strategies for design of inhibitors with single-target specificities.
Multivariate analysis reveals environmental and genetic determinants of element covariation in the maize grain ionome
Authors: Asaro Alexandra , Dilkes Brian P. , Baxter Ivan
Published: January 2018

Plants obtain elements from the soil through genetic and biochemical pathways responsive to physiological state and environment. Most perturbations affect multiple elements which leads the ionome, the full complement of mineral nutrients in an organism, to vary as an integrated network rather than a set of distinct single elements. To examine the genetic basis of covariation in the accumulation of multiple elements, we analyzed maize kernel ionomes from Intermated B73 × Mo17 (IBM) recombinant inbred populations grown in 10 environments. We compared quantitative trait loci (QTL) determining single-element variation to QTL that predict variation in principal components (PCs) of multiple-element covariance. Single-element and multivariate approaches detected partially overlapping sets of loci. In addition to loci co-localizing with single-element QTL, multivariate traits within environments were controlled by loci with significant multi-element effects not detectable using single-element traits. Gene-by-environment interactions underlying multiple-element covariance were identified through QTL analyses of principal component models of ionome variation. In addition to interactive effects, growth environment had a profound effect on the elemental profiles and multi-element phenotypes were significantly correlated with specific environmental variables.

Author Summary

A multivariate approach to the analysis of element accumulation in the maize kernel shows that elements are not regulated independently. By describing relationships between element accumulation we identified new genetic loci invisible to single-element approaches. The mathematical combinations of elements distinguish groups of plants based on environment, demonstrating that observed variation derives from interactions between genetically controlled factors and environmental variables. These results suggest that successful application of ionomics to improve human nutrition and plant productivity requires simultaneous consideration of multiple-element effects and variation of such effects in response to environment.
A Suv39H1-low chromatin state drives migratory cell populations in cervical cancers
Authors: Rodrigues Calvin , Pattabiraman Chitra , Narayana Suma Mysore , Kumar Rekha V. , Notani Dimple , Varga-Weisz Patrick , Krishna Sudhir
Published: January 2018

The emergence of migratory cell populations within tumours represents a critical early stage during cancer metastasis. We have previously reported one such population, marked by CD66, in cervical cancers. It is unclear what broad mechanisms regulate such migratory populations. Here, we describe the role of a Suv39H1-low heterochromatin state as a driver of cervical cancer migratory populations. Cervical cancer cells sorted based on migratory ability in vitro show low Suv39H1, and Suv39H1 knockdown enhances cell migration. Histopathology shows the emergence of migratory Suv39H1low populations in advanced carcinoma progression. Meta-analysis of data from The Cancer Genome Atlas (TCGA) reveals that Suv39H1-low tumours show migration and CD66 expression signatures, and correlate with lower patient survival. Lastly, genome-wide profiling of migrated populations using RNA-Seq and H3K9me3 ChIP-Seq reveals Suv39H1-linked transcriptome alterations and a broad loss of H3K9me3, suggesting an increase in chromatin plasticity in migrated populations. The understanding of such chromatin based regulation in migratory populations may prove valuable in efforts to develop anti-metastatic strategies.
DeepGS: Predicting phenotypes from genotypes using Deep Learning
Authors: Ma Wenlong , Qiu Zhixu , Song Jie , Cheng Qian , Ma Chuang
Published: January 2018

Motivation

Genomic selection (GS) is a new breeding strategy by which the phenotypes of quantitative traits are usually predicted based on genome-wide markers of genotypes using conventional statistical models. However, the GS prediction models typically make strong assumptions and perform linear regression analysis, limiting their accuracies since they do not capture the complex, non-linear relationships within genotypes, and between genotypes and phenotypes.

Results

We present a deep learning method, named DeepGS, to predict phenotypes from genotypes. Using a deep convolutional neural network, DeepGS uses hidden variables that jointly represent features in genotypic markers when making predictions; it also employs convolution, sampling and dropout strategies to reduce the complexity of high-dimensional marker data. We used a large GS dataset to train DeepGS and compare its performance with other methods. In terms of mean normalized discounted cumulative gain value, DeepGS achieves an increase of 27.70%~246.34% over a conventional neural network in selecting top-ranked 1% individuals with high phenotypic values for the eight tested traits. Additionally, compared with the widely used method RR-BLUP, DeepGS still yields a relative improvement ranging from 1.44% to 65.24%. Through extensive simulation experiments, we also demonstrated the effectiveness and robustness of DeepGS for the absent of outlier individuals and subsets of genotypic markers. Finally, we illustrated the complementarity of DeepGS and RR-BLUP with an ensemble learning approach for further improving prediction performance.

Availability

DeepGS is provided as an open source R package available at https://github.com/cma2015/DeepGS.
Transcranial alternating current stimulation modulates auditory temporal resolution in elderly people
Authors: Baltus Alina , Herrmann Christoph Siegfried
Published: January 2018

Recent research provides evidence for a functional role of brain oscillations for perception. For example, auditory temporal resolution seems to be linked to individual gamma frequency of auditory cortex. Individual gamma frequency not only correlates with performance in between-channel gap detection tasks but can be modulated via auditory transcranial alternating current stimulation. Modulation of individual gamma frequency is accompanied by an improvement in gap detection performance. Aging changes electrophysiological frequency components and sensory processing mechanisms. Therefore, we conducted a study to investigate the link between individual gamma frequency and gap detection performance in elderly people using auditory transcranial alternating current stimulation. In a within-subject design, nine participants were electrically stimulated with two individualized transcranial alternating current stimulation frequencies: 3 Hz above their individual gamma frequency (experimental condition) and 4 Hz below their individual gamma frequency (control condition) while they were performing a between-channel gap detection task. As expected, individual gamma frequencies correlated significantly with gap detection performance at baseline and in the experimental condition, transcranial alternating current stimulation modulated gap detection performance. In the control condition, stimulation did not modulate gap detection performance. In addition, in elderly, the effect of transcranial alternating current stimulation on auditory temporal resolution seems to be dependent on endogenous frequencies in auditory cortex: elderlies with slower individual gamma frequencies and lower auditory temporal resolution profit from auditory transcranial alternating current stimulation and show increased gap detection performance during stimulation. Our results strongly suggest individualized transcranial alternating current stimulation protocols for successful modulation of performance.
Polarization of Myosin II refines tissue material properties to buffer mechanical stress
Authors: Duda Maria , Khalilgharibi Nargess , Carpi Nicolas , Bove Anna , Piel Matthieu , Charras Guillaume , Baum Buzz , Mao Yanlan
Published: January 2018

As tissues develop, they are subjected to a variety of mechanical forces. Some of these forces, such as those required for morphogenetic movements, are instrumental to the development and sculpting of tissues. However, mechanical forces can also lead to accumulation of substantial tensile stress, which if maintained, can result in tissue damage and impair tissue function. Despite our extensive understanding of force-guided morphogenesis, we have only a limited understanding of how tissues prevent further morphogenesis, once shape is determined after development. Buffering forces to prevent cellular changes in response to fluctuations of mechanical stress is critical during the lifetime of an adult organism. Here, through the development of a novel tissue-stretching device, we uncover a mechanosensitive pathway that regulates tissue responses to mechanical stress through the polarization of Myosin II across the tissue. Mechanistically, this process is independent of conserved Rho-kinase signaling but is mediated by force-induced linear actin polymerization and depolymerization via the formin Diaphanous and actin severing protein Cofilin, respectively. Importantly, these stretch-induced actomyosin cables stiffen the tissue to limit changes in cell shape and to protect the tissue from further mechanical damage prior to stress dissipation. This tissue rigidification prevents fractures in the tissue from propagating by confining the damage locally to the injured cells. Overall this mechanism of force-induced changes in tissue mechanical properties provides a general model of force buffering that rapidly protects tissues from physical damage to preserve tissue shape.
A deep convolutional neural network approach for astrocyte detection
Authors: Suleymanova Ilida , Balassa Tamas , Tripathi Sushil , Molnar Csaba , Saarma Mart , Sidorova Yulia , Horvath Peter
Published: January 2018

Astrocytes are involved in brain pathologies such as trauma or stroke, neurodegenerative disorders like Alzheimer’s and Parkinson’s disease, chronic pain, and many others. Determining cell density and timing of morphological and biochemical changes is important for a proper understanding of the role of astrocytes in physiological and pathological conditions. One of the most important of such analyses is astrocytes count within a complex tissue environment in microscopy images. The most widely used approaches for the quantification of microscopy images data are either manual stereological cell counting or semi-automatic segmentation techniques. Detecting astrocytes automatically is a highly challenging computational task, for which we currently lack efficient image analysis tools. In this study, we developed a fast and fully automated software that assesses the number of astrocytes using Deep Convolutional Neural Networks (DCNN). The method highly outperforms state-of-the-art image analysis and machine learning methods and provides detection accuracy and precision comparable to that of human experts. Additionally, the runtime of cell detection is significantly less than other three analyzed computational methods, and it is faster than human observers by orders of magnitude. We applied DCNN-based method to examine the number of astrocytes in different brain regions of rats with opioid-induced hyperalgesia/tolerance (OIH/OIT) as morphine tolerance is believed to activate glial cells in the brain. We observed strong positive correlation between manual cell detection and DCNN-based analysis method for counting astrocytes in the brains of experimental animals.
Identification of an arabinopyranosyltransferase fromPhyscomitrella patensinvolved in the synthesis of the hemicellulose xyloglucan
Authors: Zhu Lei , Dama Murali , Pauly Markus
Published: January 2018

The hemicellulose xyloglucan consists of a backbone of a β-1,4 glucan substituted with xylosyl moieties and many other, diverse sidechains that are important for its proper function. Many, but not all glycosyltransferases involved in the biosynthesis of xyloglucan have been identified. Here, we report the identification of an hitherto elusive xyloglucan:arabinopyranosyltransferase. This glycosyltransferase was isolated from the mossPhyscomitrella patens, where it acts as aXyloglucan “D”-side-chainTransferase (XDT). Heterologous expression ofXDTin theArabidopsis thalianadouble mutantmur3.1 xlt2, where xyloglucan consists of a xylosylated glucan without further glycosyl substituents, results in the production of the arabinopyranose-containing “D” side chain as characterized by oligosaccharide mass profiling, glycosidic linkage analysis, and NMR analysis. In addition, expression of a relatedPhyscomitrellaglycosyltransferase hortholog ofXLT2leads to the production of the galactose-containing “L” side chain. The presence of the “D” and “L” xyloglucan side chains inPpXDT mur3.1 xlt2andPpXLT2 mur3.1 xlt2transgenic plants, respectively, rescue the dwarfed phenotype of untransformedmur3.1 xlt2mutants to nearly wild-type height. Expression ofPpXDTandPpXLT2in the Arabidopsismur3.1 xlt2mutant also enhanced root growth.
Caffeine downregulates inflammatory pathways involved in autoimmunity
Authors: Iris Merve , Tsou Pei-Suen , Sawalha Amr H.
Published: January 2018

Objectives

Caffeine is a widely consumed pharmacologically active product. In the present study, we focused on characterizing immunomodulatory effects of caffeine on peripheral blood mononuclear cells (PMBCs).

Methods

The effect of caffeine on gene expression profiles was initially evaluated using RNA sequencing data. Validation experiments were performed to confirm the results and examine dose-dependent effects of caffeine on PBMCs from healthy subjects. Gene expression levels were measured by real-time quantitative PCR, and cytokine production was determined using a multiplex cytokine assay.

Results

Caffeine at high doses showed a robust downregulatory effect of immune-related genes in PBMCs. Functional annotation analysis of downregulated genes revealed significant enrichment in cytokine activity and in genes related to several autoimmune diseases including lupus and rheumatoid arthritis. Dose-dependent validation experiments showed significant downregulation at the mRNA levels of key inflammatory genes including STAT1, TNF, and PPARG. TNF and PPARG were suppressed even with the lowest caffeine dose tested, which corresponds to the serum concentration of caffeine after administration of one cup of coffee. Cytokine levels of IL-8, MIP-1β, IL-6, IFN-γ, GM-CSF, TNF, IL-2, IL-4, MCP-1, and IL-10 were decreased significantly with caffeine treatment.

Conclusion

Our findings indicate potential downregulatory effects of caffeine on key inflammatory genes and cytokines, which play important role in autoimmunity. Further studies exploring therapeutic or disease-modulating potential of caffeine in autoimmune diseases and exploring the mechanisms involved are warranted.
Disequilibrium in Gender Ratios among Authors who Contributed Equally
Authors: Broderick Nichole A. , Casadevall Arturo
Published: January 2018

In recent decades, the biomedical literature has witnessed an increasing number of authors per article together with a concomitant increase of authors claiming to have contributed equally. In this study, we analyzed over 3000 publications from 1995–2017 claiming equal contributions for authors sharing the first author position for author number, gender, and gender position. The frequency of dual pairings contributing equally was male-male > mixed gender > female-female. For mixed gender pairs males were more often at the first position although the disparity has lessened in the past decade. Among author associations claiming equal contribution and containing three or more individuals, males predominated in both the first position and number of gender exclusive groupings. Our results show a disequilibrium in gender ratios among authors who contributed equally from expected ratios had the ordering been done randomly or alphabetical. Given the importance of the first author position in assigning credit for a publication, the finding of fewer than expected females in associations involving shared contributions raises concerns about women not receiving their fair share of expected credit. The results suggest a need for journals to request clarity on the method used to decide author order among individuals claiming to have made equal contributions to a scientific publication.
Mesophotic Coral Ecosystems Inside and Outside a Caribbean Marine Protected Area
Authors: Gress Erika , Arroyo-Gerez Maria J , Wright Georgina , Andradi-Brown Dominic A
Published: January 2018

Recent widespread shallow coral reef loss has led to calls for more holistic approaches to coral reef management, requiring inclusion of all ecosystems interacting with coral reefs in management plans. Yet almost all current reef management is biased towards shallow reefs, and overlooks that many reef species can also be found on mesophotic coral ecosystems (MCEs; reefs 30 −150 m). This study presents the first detailed quantitative characterisation of MCEs off Cozumel, in the Mexican Caribbean and provides insights into their general state. We investigate whether MCEs within the marine park have similar ecological communities to mesophotic reefs outside protection, despite widely recognised shallow reef impacts outside the protected area. Results show some taxon specific differences in MCE benthic communities between sites within the protected area and areas outside; although overall communities are similar. Regardless of protection and location, and in contrast to shallow reefs, all observed Cozumel MCEs were continuous reefs dominated by calcareous macroalgae, sponges, octocorals, and black corals. Hard corals were present on MCEs, but at low abundance. We found that 42.5 % of fish species recorded on Cozumel could be found on both shallow reefs and MCEs, including many commercially-important fish species. This suggest that MCEs may play a role in supporting fish populations. However, regardless of protection status and depth we found that large-body fishes (>500 mm) were nearly absent at all studied sites. MCEs should be incorporated into the existing shallow-reef focused management plan in Cozumel, with well informed and implemented fisheries and harvesting regulations.
PlasmoTron: an open-source platform for automated culture of malaria parasites
Authors: Sanderson Theo , Rayner Julian C.
Published: January 2018

We have created a system which allows an inexpensive opensource liquid-handling robot to automate most aspects of bloodstage malaria parasite culture. Parasites are cultured in multiwell microplates, with their details recorded in a database. Information in the database is used to generate commands for the robot to feed, monitor and passage parasite cultures. We show that the system is capable of raising cultures after transfection and then maintaining them at desired parasitaemias, facilitiating significant scale up of both routine culture and experimental genetic modification. The PlasmoTron software is available at plasmotron.org.
Adoption of digital payment systems in the era of demonetization in India
Authors: Sivathanu Brijesh
Published: January 2018

Purpose

This study aims to investigate the actual usage (AU) of digital payment systems by the consumers during the period of demonetization (from November 9, 2016 to December 30, 2016) in India.

Design/methodology/approach

The conceptual frame work for this study is based on the unified theory of acceptance and use of technology (UTAUT 2) and innovation resistance theory. A total of 766 sample respondents were surveyed using a pre-tested questionnaire. The empirical validation of the framework and analysis was done using partial least squares (PLS)-structural equation modeling (SEM) technique.

Findings

The results suggest that the behavioral intention (BI) to use and innovation resistance (IR) affect the usage of digital payment systems. The relation between BI to use digital payment systems and the AU of digital payment systems is moderated by the stickiness to cash payments.

Research limitations/implications

This cross-sectional study is limited by geographic constraints and highlights the AU of digital payment systems by using the UTAUT 2 and IR theory only during the demonetization period.

Practical implications

This study offers valuable insights to the economists, policymakers and digital payment service providers regarding the usage of digital payment systems by consumers during demonetization.

Originality/value

This study assumes importance as it empirically examines the influence of BI and IR on the AU of digital payment systems during the demonetization period in India. This study empirically validates the moderating influence of stickiness to cash payments on the AU of digital payment systems.
Framebuilder entrepreneurship
Authors: Shuart Joshua
Published: January 2018

The handmade bicycle industry has grown exponentially over the past decade. Although existing for decades in much smaller numbers, the popularity and credibility of framebuilder entrepreneurship–custom, handmade bike frames–has increased significantly in the past 10 years. The companies that specialize in custom-producing bicycle frames vary in size, scope, reputation, profitability, and even building materials.
The missing link in information and records management: personal knowledge registration
Authors: Haraldsdottir Ragna Kemp , Gunnlaugsdottir Johanna
Published: January 2018

Purpose

The purpose of this paper is to present the findings of a research on collaborative personal knowledge registration (PKR). It seeks to explain the interrelationship between records professionals and human resource (HR) and training professionals, as well as the views of management and quality managers on collaborative PKR. It aims to raise awareness of records professionals as specialists in information management, including personal knowledge.

Design/methodology/approach

Qualitative methodology was used to conduct the research. It was a multiple-case study, covering 12 organizations in Iceland. In these organizations, 32 professionals were interviewed. The research sought to understand how PKR was being facilitated, as well as how personal knowledge was made accessible and usable for employees.

Findings

The organizations had not been as successful as anticipated in PKR. The role and responsibility of records professionals was limited in the PKR process. Different professionals seemed unaware of the possible synergy effect of collaborative PKR.

Originality/value

There is a lack of studies that explore the juxtaposition and collaboration of records professionals and HR and training professionals in organizations. The aim of this research was to bridge this gap. Its originality lies in how it approaches diverse professions and their collaborative PKR effort. This research provides a valuable practical and theoretical contribution to a rapidly growing interdisciplinary field of information and records management. It can lay the foundation for further research into the field.
Judicial Diversity in France: The Unspoken and the Unspeakable
Authors: Cohen Mathilde
Published: January 2018

Despite the importance of judicial diversity for litigants and the broader public, no previous study has examined this issue within the French judiciary. This article begins to fill this gap by using original, qualitative data that shed light on judges’, prosecutors', and other legal actors' discourses on racial, ethnic, and sexual diversity. Its main contribution is to show that these legal professionals deploy three strategies—linguistic, institutional, and geographic—to dodge or downplay the relevance of race, ethnicity, and sexual orientation. The first, linguistic, form of avoidance lies in refusing to name and discuss race and ethnicity explicitly; the second, institutional, in denying that the judiciary has a diversity problem or that the problem lies within its power; and the third, geographic, consists in relegating the issue of diversity to distant places—the United States and overseas France. The article concludes by discussing key directions for future research.
Age‐related changes in the structure and function of mammalian neuromuscular junctions
Authors: Willadt Silvia , Nash Mark , Slater Clarke
Published: January 2018

As mammals age, their neuromuscular junctions (NMJs) change their form, with an increasingly complex system of axonal branches innervating increasingly fragmented regions of postsynaptic differentiation. It has been suggested that this remodeling is associated with impairment of neuromuscular transmission and that this contributes to age‐related muscle weakness in mammals, including humans. Here, we review previous work on NMJ aging, most of which has focused on either structure or function, as well as a new study aimed at seeking correlation between the structure and function of individual NMJs. While it is clear that extensive structural changes occur as part of the aging process, it is much less certain how, if at all, these are correlated with an impairment of function. This leaves open the question of whether loss of NMJ function is a significant cause of age‐related muscle weakness.
AIRE: a missing link to explain female susceptibility to autoimmune diseases
Authors: Berrih‐Aknin Sonia , Panse Rozen Le , Dragin Nadine
Published: January 2018

Women are more susceptible to autoimmune diseases than men. Autoimmunity results from tolerance breakdown toward self‐components. Recently, three transcription modulators were identified in medullary thymic epithelial cells that orchestrate immune central tolerance processes: the autoimmune regulator (AIRE), FEZ family zinc finger 2 (FEZF2 or FEZ1), and PR domain zinc finger protein 1 (PRDM1). Interestingly, these three transcription modulators regulate nonredundant tissue‐specific antigen subsets and thus cover broad antigen diversity. Recent data from different groups demonstrated that sex hormones (estrogen and testosterone) are involved in the regulation of thymic AIRE expression in humans and mice through direct transcriptional modulation and epigenetic changes. As a consequence, AIRE displays gender‐biased thymic expression, with females showing a lower expression compared with males, a finding that could explain the female susceptibility to autoimmune diseases. So far, FEZF2 has not been related to an increased gender bias in autoimmune disease. PRDM1 expression has not been shown to display gender‐differential thymic expression, but its expression level and its gene polymorphisms are associated with female‐dependent autoimmune disease risk. Altogether, various studies have demonstrated that increased female susceptibility to autoimmune diseases is in part a consequence of hormone‐driven reduced thymic AIRE expression.
Efficient long‐term depletion of CD20+ B cells by rituximab does not affect gut‐resident plasma cells
Authors: Uzzan Mathieu , Ko Huaibin M. , Rosenstein Adam K. , Pourmand Kamron , Colombel Jean‐Frederic , Mehandru Saurabh
Published: January 2018

The vast majority of antibody‐producing B cells are located within the gastrointestinal tract and are key players in maintaining homeostasis. The failure of rituximab, a potent B cell–depleting agent, to ameliorate ulcerative colitis in a single clinical trial has dampened enthusiasm to study B cells in patients with inflammatory bowel disease (IBD). However, several lines of evidence suggest that intestinal B cells may be affected in IBD. Additionally, the pathophysiological mechanisms underlying rituximab's lack of efficacy in IBD remain unclear. Here, on the basis of detailed immunophenotyping of a patient who underwent a colonoscopy 6 months after the end of rituximab‐based therapy, we observed that rituximab did not deplete colon‐resident plasma cells (PCs) while ablating all CD20+ B cells in tissues and in the circulation. On the basis of these observations, we propose that one factor underlying the lack of efficacy of rituximab relates to the fact that it does not affect the entire B cell compartment in tissues, sparing the intestinal‐resident PCs while effectively depleting CD20+ B cell populations. Thus, we contend that, despite the results of the Rituximab study, there is a need for more intensive B cell–oriented research in inflammatory disorders, including IBD.
Speculative Bubbles in the Near Future? Not Unlikely Indeed
Authors: COSSIGA Dott. Giovanni Antonio
Published: January 2018

In the near future, the world economy would be crossed by a new wave of speculative crisis? To answer this question, we can have a look at the economy performance during the speculative bubble formation and the 2008-2009 financial crisis. Our intention is to verify whether the troubles of the last decade speculative crisis may recur again in the coming years. Particularly, we want to look at the price trend, which may be the forerunner of new speculative waves, if and when prices would show a prolonged deflation trend. At the same time, we’ll look at the growth profile in the economy which, during the speculative phase, is showing an ambiguous measured trend. This behaviour of the main variables, low inflation and almost regular growth, is for operators and families a sort of mirage about the economy outlook. A deceptive mirage, however, that gives the feeling that the speculative wave is a sort of catalyst for a long growth phase. Actually, the economic system seems to follow the physical laws of the material world, according to a growth trend compatible with environmental resources. A system derailing from this path becomes unstable and sooner or later must return to the equilibrium natural state. The speculative wave can be defined as an extreme natural mechanism, put in place by the system to get out of the accumulated errors. If this correction is done, the wave of speculative tensions ends with the return of the economy within the compatible growth virtuous course. Well, there are symptoms that the natural correction of economic systems is not complete, despite the strength and intensity of the 2008-2009 crisis. Therefore, we can expect that a new speculation wave could be hidden in our next future.
Context-Dependent Requirements for FimH and Other Canonical Virulence Factors in Gut Colonization by Extraintestinal Pathogenic Escherichia coli
Authors: Russell Colin W. , Fleming Brittany A. , Jost Courtney A. , Tran Alexander , Stenquist Alan T. , Wambaugh Morgan A. , Bronner Mary P. , Mulvey Matthew A.
Published: January 2018

Extraintestinal pathogenic
Escherichia coli
(ExPEC) acts as a commensal within the mammalian gut but can induce pathology upon dissemination to other host environments such as the urinary tract and bloodstream. ExPEC genomes are likely shaped by evolutionary forces encountered within the gut, where the bacteria spend much of their time, provoking the question of how their extraintestinal virulence traits arose. The principle of coincidental evolution, in which a gene that evolved in one niche happens to be advantageous in another, has been used to argue that ExPEC virulence factors originated in response to selective pressures within the gut ecosystem. As a test of this hypothesis, the fitness of ExPEC mutants lacking canonical virulence factors was assessed within the intact murine gut in the absence of antibiotic treatment. We found that most of the tested factors, including cytotoxic necrotizing factor type 1 (CNF1), Usp, colibactin, flagella, and plasmid pUTI89, were dispensable for gut colonization. The deletion of genes encoding the adhesin PapG or the toxin HlyA had transient effects but did not interfere with longer-term persistence. In contrast, a mutant missing the type 1 pilus-associated adhesin FimH displayed somewhat reduced persistence within the gut. However, this phenotype varied dependent on the presence of specific competing strains and was partially attributable to aberrant flagellin expression in the absence of
fimH
. These data indicate that FimH and other key ExPEC-associated factors are not strictly required for gut colonization, suggesting that the development of extraintestinal virulence traits is not driven solely by selective pressures within the gut.
On the system of p-Laplacian equations with critical growth
Authors: Liu Xiangqing , Zhao Junfang , Liu Jiaquan
Published: January 2018

In this paper, we consider the system of [Formula: see text]-Laplacian equations with critical growth [Formula: see text] where [Formula: see text] is a bounded smooth domain in [Formula: see text] the first eigenvalue of the [Formula: see text]-Laplacian operator [Formula: see text] with the Dirichlet boundary condition, [Formula: see text] for [Formula: see text]. The existence of infinitely many sign-changing solutions is proved by the truncation method and by the concentration analysis on the approximating solutions, provided [Formula: see text].