bluuebunny/crossref_metadata_2025 huggingface dataset:
The Feminization of Forced Migration during Conflict: The Complex Experiences of Algerian Women Who Fled in the ‘Black Decade’
Authors: Narriman Guémar Latefa
Published: August 2018

The rise of fundamentalism and terrorism, and the violent acts committed against women, during the Algerian conflict of the 1990s (the ‘Black Decade’, also referred to as the Algerian ‘Dark Decade’) undoubtedly had a catalytic effect on the mass feminization of Algerian migration. However, they arguably served to amplify an existing migratory movement of women. This article argues that, during times of war or internal conflict, violence and a climate of fear may be the main reason why women flee, but it is not the only one. Women’s forced migration is complex and is often related to specific, gender-based oppression, which is exacerbated by conflict. This research, conducted amongst highly skilled women who left Algeria during and after the Black Decade, reveals that their decisions to leave were also greatly influenced by their position as women: the violence specifically targeted at educated or high-profile women, women’s legal situation and the oppression they experienced in family and society. Yet, despite the UNHCR’s gender guidelines, the complex experiences of women fleeing gender-based violence often remain unacknowledged by national asylum regimes.
Self-Locating Belief and Updating on Learning
Authors: Bradley Darren
Published: August 2018

Self-locating beliefs cause a problem for conditionalization. Miriam Schoenfield (2016) offers a solution: that on learning E, agents should update on the fact that they learned E. However, Schoenfield is not explicit about whether the fact that they learned E is self-locating. I will argue that if the fact that they learned E is self-locating then the original problem has not been addressed, and if the fact that they learned E is not self-locating then the theory generates implausible verdicts which Schoenfield explicitly rejects.
High Cervical Ependymoma Resection: 2-Dimensional Operative Video
Authors: Dekker Simone E , Glenn Chad A , Ostergard Thomas A , Rothstein Brian D , Bambakidis Nicholas C
Published: August 2018

This operative video illustrates resection of a cervical ependymoma in a 40-yr-old female with numbness of upper and lower extremities and ataxia. Magnetic resonance imaging (MRI) demonstrated an enhancing intramedullary intradural spinal mass at C2-3. The patient underwent a posterior cervical laminoplasty for tumor resection. This video highlights the natural history of this disease, treatment options, surgical procedure, potential risks and complications, and postoperative management of ependymomas. A posterior midline skin incision was made from the inion to the level of C4 which exposed the posterolateral elements of C1-3. C2 and C3 lamina were removed as a single piece using the high-speed drill. A C1 laminectomy was then also performed to provide adequate superior exposure. The dura was opened widely in the midline. Careful midline myelotomy was then performed overlying the tumor. The tumor is noted to be densely adherent to the surrounding spinal cord. Gross total resection was completed using ultrasonic aspiration and microdissection. The dura was closed in a watertight fashion followed by a synthetic dural sealant. The bony elements of C2, C3 were then reconstructed using osteoplastic laminoplasty, titanium miniplates, and screws at C2-3. The wound was closed in multiple layers using sutures. Specimens were sent for frozen and permanent pathological analysis, eventually demonstrating WHO grade II ependymoma. There were no complications. Postoperative MRI demonstrated gross total resection. The patient had an uneventful postoperative course. The strength was at baseline at long term follow-up, with small sensory deficit.
LAMP Detection of Four Plant-Pathogenic Oomycetes and Its Application in Lettuce Fields
Authors: Feng Wenzhuo , Hieno Ayaka , Kusunoki Mikio , Suga Haruhisa , Kageyama Koji
Published: August 2018

In Kagawa Prefecture, Japan, the pathogens Phytophthora pseudolactucae, Pythium irregulare, Pythium uncinulatum, and Pythium spinosum have caused huge losses in lettuce production. We used loop-mediated isothermal amplification (LAMP) to analyze soil and plants in lettuce fields for the presence of these four pathogens. To develop an effective on-site detection method, we contrasted the Plant-LAMP and Plant Culture-LAMP procedures for plant samples, and five soil DNA extraction methods for soil samples. Plant-LAMP and a Soil DNA Isolation kit were selected to analyze three fields for the pathogen species present, infected sites, and level of soil contamination. We found that the same wilting symptoms could be caused by Phytophthora or Pythium, or a mixture of species from both genera. Ph. pseudolactucae infects the pith of the lettuce in aboveground parts, whereas Pythium spp. mainly infect roots. Ph. pseudolactucae and Py. uncinulatum caused disease more frequently than the other two pathogens. Furthermore, not all of the pathogens existed in the soil near infected lettuce plants. Therefore, the LAMP method can be used to diagnose pathogenic oomycetes in the field, and will be useful in the development of control strategies in lettuce production.
Loss of HDAC6 alters gut microbiota and worsens obesity
Authors: Lieber Arnon D. , Beier Ulf H. , Xiao Haiyan , Wilkins Benjamin J. , Jiao Jing , Li Xinmin S. , Schugar Rebecca C. , Strauch Christopher M. , Wang Zeneng , Brown J. Mark , Hazen Stanley L. , Bokulich Nicholas A. , Ruggles Kelly V. , Akimova Tatiana , Hancock Wayne W. , Blaser Martin J.
Published: August 2018

Alterations in gut microbiota are known to affect intestinal inflammation and obesity. Antibiotic treatment can affect weight gain by elimination of histone deacetylase (HDAC) inhibitor‐producing microbes, which are anti‐inflammatory by augmenting regulatory T (Treg) cells. We asked whether mice that lack HDAC6 and have potent suppressive Treg cells are protected from microbiota‐induced accelerated weight gain. We crossed wild‐type and HDAC6‐deficient mice and subjected the offspring to perinatal penicillin, inducing weight gain via microbiota disturbance. We observed that male HDAC6‐deficient mice were not protected and developed profoundly accelerated weight gain. The antibiotic‐exposed HDAC6‐deficient mice showed a mixed immune phenotype with increased CD4+ and CD8+ T‐cell activation yet maintained the enhanced Treg cell–suppressive function phenotype characteristic of HDAC6‐deficient mice. 16S rRNA sequencing of mouse fecal samples reveals that their microbiota diverged with time, with HDAC6 deletion altering microbiome composition. On a high‐fat diet, HDAC6‐deficient mice were depleted in representatives of the S24‐7 family and Lactobacillus but enriched with Bacteroides and Parabacteroides; these changes are associated with obesity. Our findings further our understanding of the influence of HDACs on microbiome composition and are important for the development of HDAC6 inhibitors in the treatment of human diseases.—Lieber, A. D., Beier, U. H., Xiao, H., Wilkins, B. J., Jiao, J., Li, X. S., Schugar, R. C., Strauch, C. M., Wang, Z., Brown, J. M., Hazen, S. L., Bokulich, N. A., Ruggles, K. V., Akimova, T., Hancock, W. W., Blaser, M. J. Loss of HDAC6 alters gut microbiota and worsens obesity. FASEB J. 33, 1098–1109 (2019). www.fasebj.org
How does cognition shape social relationships?
Authors: Wascher Claudia A. F. , Kulahci Ipek G. , Langley Ellis J. G. , Shaw Rachael C.
Published: August 2018

The requirements of living in social groups, and forming and maintaining social relationships are hypothesized to be one of the major drivers behind the evolution of cognitive abilities. Most empirical studies investigating the relationships between sociality and cognition compare cognitive performance between species living in systems that differ in social complexity. In this review, we ask whether and how individuals benefit from cognitive skills in their social interactions. Cognitive abilities, such as perception, attention, learning, memory, and inhibitory control, aid in forming and maintaining social relationships. We investigate whether there is evidence that individual variation in these abilities influences individual variation in social relationships. We then consider the evolutionary consequences of the interaction between sociality and cognitive ability to address whether bi-directional relationships exist between the two, such that cognition can both shape and be shaped by social interactions and the social environment. In doing so, we suggest that social network analysis is emerging as a powerful tool that can be used to test for directional causal relationships between sociality and cognition. Overall, our review highlights the importance of investigating individual variation in cognition to understand how it shapes the patterns of social relationships.

This article is part of the theme issue ‘Causes and consequences of individual differences in cognitive abilities’.
The quick are the dead: pheasants that are slow to reverse a learned association survive for longer in the wild
Authors: Madden Joah R. , Langley Ellis J. G. , Whiteside Mark A. , Beardsworth Christine E. , van Horik Jayden O.
Published: August 2018

Cognitive abilities probably evolve through natural selection if they provide individuals with fitness benefits. A growing number of studies demonstrate a positive relationship between performance in psychometric tasks and (proxy) measures of fitness. We assayed the performance of 154 common pheasant (
Phasianus colchicus
) chicks on tests of acquisition and reversal learning, using a different set of chicks and different set of cue types (spatial location and colour) in each of two years and then followed their fates after release into the wild. Across all birds, individuals that were slow to reverse previously learned associations were more likely to survive to four months old. For heavy birds, individuals that rapidly acquired an association had improved survival to four months, whereas for light birds, slow acquirers were more likely to be alive. Slow reversers also exhibited less exploratory behaviour in assays when five weeks old. Fast acquirers visited more artificial feeders after release. In contrast to most other studies, we showed that apparently ‘poor’ cognitive performance (slow reversal speed suggesting low behavioural flexibility) correlates with fitness benefits in at least some circumstances. This correlation suggests a novel mechanism by which continued exaggeration of cognitive abilities may be constrained.

This article is part of the theme issue ‘Causes and consequences of individual differences in cognitive abilities’.
Cancer In The News: Bias And Quality In Media Reporting Of Cancer Research
Authors: Amberg Amanda , Saunders Darren N.
Published: August 2018

Cancer research in the news is often associated with sensationalising and inaccurate reporting, giving rise to false hopes and expectations. The role of study selection for cancer-related news stories is an important but less commonly acknowledged issue, as the outcomes of primary research are generally less reliable than those of meta-analyses and systematic reviews. Few studies have investigated the quality of research that makes the news and no previous analyses of the proportions of primary and secondary research in the news have been found in the literature. The main aim of this study was to investigate the nature and quality of cancer research covered in online news reports by four major news sources from USA, UK and Australia. We measured significant variation in reporting quality, and observed biases in many aspects of cancer research reporting, including the types of study selected for coverage, and in the spectrum of cancer types, gender of scientists, and geographical source of research represented. We discuss the implications of these finding for guiding accurate, contextual reporting of cancer research, which is critical in helping the public understand complex science and appreciate the outcomes of publicly funded research, avoid undermining trust in science, and assist informed decision-making.
Identification of deleterious and regulatory genomic variations in known asthma loci
Authors: Neville Matthew D. C. , Choi Jihoon , Lieberman Jonathan , Duan Qing Ling
Published: August 2018

Background

Candidate gene and genome-wide association studies have identified hundreds of asthma risk loci. The majority of associated variants, however, are not known to have any biological function and are believed to represent markers rather than true causative mutations. We hypothesized that many of these associated markers are in linkage disequilibrium (LD) with the elusive causative variants.

Methods

We compiled a comprehensive list of 447 asthma-associated variants previously reported in candidate gene and genome-wide association studies. Next, we identified all sequence variants located within the 304 unique genes using whole-genome sequencing data from the 1000 Genomes Project. Then, we calculated the LD between known asthma variants and the sequence variants within each gene. LD variants identified were then annotated to determine those that are potentially deleterious and/or functional (i.e. coding or regulatory effects on the encoded transcript or protein).

Results

We identified 10,048 variants in LD (r2 > 0.6) with known asthma variants. Annotations of these LD variants revealed that several have potentially deleterious effects including frameshift, alternate splice site, stop-lost, and missense. Moreover, 24 of the LD variants have been reported to regulate gene expression as expression quantitative trait loci (eQTLs).

Conclusions

This study is proof of concept that many of the genetic loci previously associated with complex diseases such as asthma are not causative but represent markers of disease, which are in LD with the elusive causative variants. We hereby report a number of potentially deleterious and regulatory variants that are in LD with the reported asthma loci. These reported LD variants could account for the original association signals with asthma and represent the true causative mutations at these loci.
Improvement in Patient-Reported Sleep in Type 2 Diabetes and Prediabetes Participants Receiving a Continuous Care Intervention with Nutritional Ketosis
Authors: Siegmann Morgan J. , Athinarayanan Shaminie J , Hallberg Sarah J , McKenzie Amy L. , Bhanpuri Nasir H. , Campbell Wayne W. , McCarter James P. , Phinney Stephen D. , Volek Jeff S. , Van Dort Christa J.
Published: August 2018

Objective

Sleep disruption is frequently associated with type 2 diabetes (T2D) and hyperglycemia. We recently reported the effectiveness of a continuous care intervention (CCI) emphasizing nutritional ketosis for improving HbA1c, body weight and cardiovascular risk factors in T2D patients. The present study assessed the effect of this CCI approach on sleep quality using a subjective patient-reported sleep questionnaire.

Methods

A non-randomized, controlled longitudinal study; 262 T2D and 116 prediabetes patientsenrolled in the CCI and 87 separately recruited T2D patients continued usual care (UC) treatment. Patients completed the Pittsburgh Sleep Quality Index (PSQI) questionnaire. A PSQI score of >5 (scale 0 to 21) was used to identify poor sleepers.

Results

Global sleep quality improved in the CCI T2D (p<0.001) and prediabetes (p<0.001) patients after one year of intervention. Subjective sleep quality (component 1), sleep disturbance (component 5) and daytime dysfunction (component 7), also showed improvements in the CCI T2D (p<0.01 for sleep quality and sleep disturbance; and p<0.001 for daytime dysfunction) and prediabetes patients (p<0.001 for all three components); compared to the UC T2D group after one year. The proportion of patients with poor sleep quality was significantly reduced after one year of CCI (T2D; from 68.3% at baseline to 56.5% at one year, p=0.001 and prediabetes; from 77.9% at baseline to 48.7% at one year, p<0.001).

Conclusion

This study demonstrates improved sleep quality as assessed by PSQI in patients with T2D and prediabetes undergoing CCI including nutritional ketosis but not in T2D patients receiving UC. The dietary intervention benefited both sleep quality and the severity of T2D symptoms suggesting that nutritional ketosis improves overall health via multiple mechanisms.
Nutritional and Meiotic Induction of Heritable Stress Resistant States in Budding Yeast
Authors: Gutierrez Heldder , Taghizada Bakhtiyar , Meneghini Marc D.
Published: August 2018

Transient exposures to environmental stresses induce altered physiological states in exposed cells that persist after the stresses have been removed. These states, referred to as cellular memory, can even be passed on to daughter cells and may thus be thought of as embodying a form of epigenetic inheritance. We find that meiotically produced spores in the budding yeastS. cerevisiaepossess a state of heightened stress resistance that, following their germination, persists for numerous mitotic generations. As yeast meiotic development is essentially a starvation response that a/alpha diploid cells engage, we sought to model this phenomenon by subjecting haploid cells to starvation conditions. We find also that haploid cells exposed to glucose withdrawal acquire a state of elevated stress resistance that persists after the reintroduction of these cells to glucose-replete media. Following release from lengthy durations of glucose starvation, we confirm that this physiological state of enhanced stress resistance is propagated in descendants of the exposed cells through two mitotic divisions before fading from the population. In both haploid starved cells and diploid produced meiotic spores we show that their cellular memories are not attributable to trehalose, a widely regarded stress protectant that accumulates in these cell types. Moreover, the heritable stress resistant state induced by glucose starvation in haploid cells is independent of the Msn2/4 transcription factors, which are known to program cellular memory induced by exposure of cells to NaCl. Our findings identify new developmentally and nutritionally induced states of cellular memory that exhibit striking degrees of perdurance and mitotic heritability.
γδ T cells do not contribute to peripheral inflammatory pain
Authors: Petrović Jelena , Silva Jaqueline Raymondi , Segal Julia P. , Marshall Abigail S. , Haird Cortney M. , Gilron Ian , Ghasemlou Nader
Published: August 2018

Circulating immune cells, which are recruited to the site of injury/disease, secrete various inflammatory mediators that are critical to nociception and pain. The role of tissue-resident immune cells, however, remains poorly characterized. One of the first cells to be activated in peripheral tissues following injury are γδ T cells, which serve important roles in infection and disease. Using a transgenic mouse line lacking these cells, we sought to identify their contribution to inflammatory pain. Three distinct models of inflammatory pain were used: intraplantar injection of formalin and incisional wound (as models of acute inflammatory pain) and intraplantar injection of complete Freund’s adjuvant (as a model of chronic inflammatory pain). Our results show that absence of these cells does not alter baseline sensitivity, nor does it result in changes to mechanical or thermal hypersensitivity after tissue injury. These results were consistent in both male and female mice, suggesting that there are no sex differences in these outcomes. This comprehensive characterization suggests that γδ T cells do not contribute to basal sensitivity or the development and maintenance of inflammatory pain.
Sodium chloride is an ionic checkpoint for human Th2 cell responses and shapes the atopic skin microenvironment
Authors: Matthias Julia , Maul Julia , Noster Rebecca , Meinl Hanna , Chao Ying-Yin , Gerstenberg Heiko , Jeschke Florian , Gasparoni Gilles , Welle Anna , Jörn Walter , Nordström Karl , Eberhardt Klaus , Renisch Dennis , Donakonda Sainitin , Knolle Percy , Soll Dominik , Grabbe Stephan , Garzorz-Stark Natalie , Eyerich Kilian , Biedermann Tilo , Baumjohann Dirk , Zielinski Christina E.
Published: August 2018

One sentence summary

Sodium is an ionic checkpoint for the induction and amplification of human Th2 cell responses and shapes the atopic skin microenvironment, where it could serve as a novel therapeutic target for Th2 mediated diseases.

There has been a strong increase in the incidence of allergic diseases over the last 50 years. Environmental factors most likely account for this phenomenon. However, the nature of these factors and the mode of action by which they induce the type 2 immune deviation, which is characteristic of atopic diseases, remains unclear. It has previously been reported that dietary sodium chloride promotes the polarization of Th17 cells with implications for autoimmune diseases such as multiple sclerosis. Here, we demonstrate that sodium chloride also potently promotes Th2 cell responses on multiple regulatory levels. Sodium chloride enhanced IL-4 and IL-13 production while suppressing IFN-γproduction in effector T cells. It diverted alternative T cell fates into the Th2 cell phenotype and also inducedde novoTh2 cell polarization from naïve T cell precursors. Mechanistically, it exerted its effects via the osmosensitive transcription factor NFAT-5 and the kinase SGK-1, which regulated Th2 signature cytokines and master transcription factors in hyperosmolar salt conditions. The skin of patients suffering from atopic dermatitis contained highly elevated amounts of sodium compared to non-lesional atopic and healthy skin. This demonstrates that sodium chloride represents a so far overlooked cutaneous microenvironmental factor in atopic dermatitis that can induce Th2 cell responses, the orchestrators of allergic diseases. Together, our data propose ionic signaling through sodium chloride as a novel checkpoint and potential therapeutic target for type 2 immunity and its associated allergic diseases.
Flux balance analysis predicts NADP phosphatase and NADH kinase are critical to balancing redox during xylose fermentation inScheffersomyces stipitis
Authors: Correia Kevin , Khusnutdinova Anna , Li Peter Yan , Joo Jeong Chan , Brown Greg , Yakunin Alexander F. , Mahadevan Radhakrishnan
Published: August 2018

Xylose is the second most abundant sugar in lignocellulose and can be used as a feedstock for next-generation biofuels by industry.Saccharomyces cerevisiae, one of the main workhorses in biotechnology, is unable to metabolize xylose natively but has been engineered to ferment xylose to ethanol with the xylose reductase (XR) and xylitol dehydrogenase (XDH) genes fromScheffersoymces stipitis. In the scientific literature, the yield and volumetric productivity of xylose fermentation to ethanol in engineeredS. cerevisiaestill lagsS. stipitis, despite expressing of the same XR-XDH genes. These contrasting phenotypes can be due to differences inS. cerevisiae’sredox metabolism that hinders xylose fermentation, differences inS. stipitis’redox metabolism that promotes xylose fermentation, or both. To help elucidate howS. stipitisferments xylose, we used flux balance analysis to test various redox balancing mechanisms, reviewed published omics datasets, and studied the phylogeny of key genes in xylose fermentation.In vivoandin silicoxylose fermentation cannot be reconciled without NADP phosphatase (NADPase) and NADH kinase. We identified eight candidate genes for NADPase.PHO3.2was the sole candidate showing evidence of expression during xylose fermentation. Pho3.2p and Pho3p, a recent paralog, were purified and characterized for their substrate preferences. Only Pho3.2p was found to have NADPase activity. Both NADPase and NAD(P)H-dependent XR emerged from recent duplications in a common ancestor ofScheffersoymcesandSpathasporato enable efficient xylose fermentation to ethanol. This study demonstrates the advantages of using metabolic simulations, omics data, bioinformatics, and enzymology to reverse engineer metabolism.
Cell-cell signaling elicits local Ca2+ transients in melanocyte dendrites and dendritic spine-like structures
Authors: Belote Rachel L. , Simon Sanford M.
Published: August 2018

Compartmentalized cytoplasmic fluctuations of Ca2+ within dendrites and dendritic spines regulate a variety of neuronal functions. Like some neurons and glia, melanocytes are neural crest derived and possess dendrites (Adameyko et al., 2009; Erickson et al., 1992; Fitzpatrick and Szabo, 1959). Here, we show that primary human melanocytes, when observed in situ have extensive dendritic branches with dendritic spines similar to neurons. When co-cultured with primary human keratinocytes, they have local Ca2+ transients within these spines and within the dendrites. These are elicited by secreted factors from adjacent keratinocytes. Thus other cell types with dendrites are capable of compartmentalized Ca2+ fluctuations in response to cell-cell communication. Furthermore, our observations within intact human skin suggest a more complex communication network between adjacent melanocytes and keratinocytes, and thus a more complex physiology to skin than previous appreciated.
Engineering a model cell for rational tuning of GPCR signaling
Authors: Shaw William M. , Yamauchi Hitoshi , Mead Jack , Gowers Glen-Oliver F. , Öling David , Larsson Niklas , Wigglesworth Mark , Ladds Graham , Ellis Tom
Published: August 2018

G protein-coupled receptor (GPCR) signaling is the primary method eukaryotes use to respond to specific cues in their environment. However, the relationship between stimulus and response for each GPCR is difficult to predict due to diversity in natural signal transduction architecture and expression. Using genome engineering in yeast, we here constructed an insulated, modular GPCR signal transduction system to study how the response to stimuli can be predictably tuned using synthetic tools. We delineated the contributions of a minimal set of key components via computational and experimental refactoring, identifying simple design principles for rationally tuning the dose-response. Using four different receptors, we demonstrate how this enables cells and consortia to be engineered to respond to desired concentrations of peptides, metabolites and hormones relevant to human health. This work enables rational tuning of cell sensing, while providing a framework to guide reprogramming of GPCR-based signaling in more complex systems.
Divergent methyl-coenzyme M reductase genes in a deep-subseafloor Archaeoglobi
Authors: Boyd Joel A. , Jungbluth Sean P. , Leu Andy O. , Evans Paul N. , Woodcroft Ben J. , Chadwick Grayson L. , Orphan Victoria J. , Amend Jan P. , Rappé Michael S. , Tyson Gene W.
Published: August 2018

The methyl-coenzyme M reductase (MCR) complex is a key enzyme in archaeal methane generation and has recently been proposed to also be involved in the oxidation of short-chain hydrocarbons including methane, butane and potentially propane. The number of archaeal clades encoding the MCR complex continues to grow, suggesting that this complex was inherited from an ancient ancestor, or has undergone extensive horizontal gene transfer. Expanding the representation of MCR-encoding lineages through metagenomic approaches will help resolve the evolutionary history of this complex. Here, a near-complete Archaeoglobi metagenome-assembled genome (MAG; rG16) was recovered from the deep subseafloor along the Juan de Fuca Ridge flank that encodes two divergent McrABG operons similar to those found inCandidatusBathyarchaeota andCandidatusSyntrophoarchaeum MAGs. rG16 is basal to members of the class Archaeoglobi, and encodes the genes for β-oxidation, potentially allowing an alkanotrophic metabolism similar to that proposed forCa.Syntrophoarchaeum. rG16 also encodes a respiratory electron transport chain that can potentially utilize nitrate, iron, and sulfur compounds as electron acceptors. As the first Archaeoglobi with the MCR complex, rG16 extends our understanding of the evolution and distribution of novel MCR encoding lineages among the Archaea.
Quality of eyeglass prescriptions from a low-cost wavefront autorefractor evaluated in rural India: results of a 708-participant field study
Authors: Durr Nicholas J. , Dave Shivang R. , Lim Daryl , Joseph Sanil , Ravilla Thulasiraj D , Lage Eduardo
Published: August 2018

ABSTACT

Aim

To assess the quality of eyeglass prescriptions provided by an affordable wavefront autorefractor operated by a minimally-trained technician in a low-resource setting.

Methods

708 participants were recruited from consecutive patients registered for routine eye examinations at Aravind Eye Hospital in Madurai, India, or an affiliated rural satellite vision centre. Visual acuity (VA) and patient preference were compared for eyeglasses prescribed from a novel wavefront autorefractor versus eyeglasses prescribed from subjective refraction by an experienced refractionist.

Results

Mean ± standard deviation VA was 0.30 ± 0.37, −0.02 ± 0.14, and −0.04 ± 0.11 LogMAR units before correction, with autorefractor correction, and with subjective refraction correction, respectively (all differences P < 0.01). Overall, 25% of participants had no preference, 33% preferred eyeglasses from autorefractor prescriptions, and 42% preferred eyeglasses from subjective refraction prescriptions (P < 0.01). Of the 438 patients 40 years old and younger, 96 had no preference and the remainder had no statistically-significant difference in preference for subjective refraction prescriptions (51%) versus autorefractor prescriptions (49%) (P = 0.52).

Conclusions

Average VAs from autorefractor-prescribed eyeglasses were one letter worse than those from subjective refraction. More than half of all participants either had no preference or preferred eyeglasses prescribed by the autorefractor. This marginal difference in quality may warrant autorefractor-based prescriptions, given the portable form-factor, short measurement time, low-cost, and minimal training required to use the autorefractor evaluated here.

SYNOPSIS

Eyeglass prescriptions can be accurately measured by a minimally-trained technician using a low-cost wavefront autorefractor in rural India. Objective refraction may be a feasible approach to increasing eyeglass accessibility in low-resource settings.
pWGBSSimla: a profile-based whole-genome bisulphite sequencing data simulator incorporating methylation QTLs, allele-specific methylations and differentially methylated regions
Authors: Chung Ren-Hua , Kang Chen-Yu
Published: August 2018

Motivation

DNA methylation plays an important role in regulating gene expression. There has been growing interest in investigating the roles that genetic variants play in changing the methylation levels (i.e., methylation quantitative trait loci or meQTLs), how methylation regulates the imprinting of gene expression (i.e., allele-specific methylation or ASM), and the differentially methylated regions (DMRs) among different cell types. However, none of the current simulation tools can generate whole-genome bisulphite sequencing (WGBS) data while modeling meQTLs, ASM, and DMRs.

Results

We developed pWGBSSimla, a profile-based WGBS data simulator, which simulates WGBS data for 29 cell types based on real data. meQTLs and ASM are modeled based on the block structures of methylation status at CpGs, and DMRs are simulated based on observations of methylation rates in real data.

Availability

pWGBSSimla is available at http://omicssimla.sourceforge.io.
A model of repetitive mild brain injury without symptoms – risk for Parkinson’s disease with aging?
Authors: Kulkarni Praveen , Morrison Thomas R , Cai Xuezhu , Iriah Sade , Lang Mary S. , Kennedy Laporsha , Sabrick Julia , Neuroth Lucas , Hoffman Gloria E , Ferris Craig F
Published: August 2018

Objectives

To test the hypothesis that repetitive mild traumatic brain injury in early life may be a potential risk factor for Parkinson’s disease.

Methods

A closed-head momentum exchange model was used to produce one or three mild concussions in young adult male rats as compare to non-injured, age and weight-matched controls. Six-seven weeks post-injury, rats were studied for deficits in cognitive and motor function Changes in brain anatomy and function were evaluated through analysis of resting state functional connectivity, diffusion weighted imaging with quantitative anisotropy and immunohistochemistry for neuroinflammation.

Results

Head injuries occurred without skull fracture or signs of intracranial bleeding or contusion. There were no significant differences in cognitive or motors behaviors between experimental groups. Rats concussed three times showed altered diffusivity in white matter tracts, basal ganglia, central amygdala, brainstem, and cerebellum. With a single concussion, the affected areas were limited to the caudate/putamen and central amygdala. Disruption of functional connectivity was most pronounced with three concussions as the midbrain dopamine system, hippocampus and brainstem/cerebellum showed hypoconnectivity. The suprachiasmatic nucleus was isolated from all functional connections. Interestingly, rats exposed to one concussion showedenhancedfunctional connectivity (or hyperconnectivity) across brain sites, particularly between the olfactory system and the cerebellum. Immunostaining for microglia activation showed inflammation in striatum and substantia nigra with three concussions but not with one.

Interpretation

Neuroradiological and immunohistochemical evidence of altered brain structure and function, particularly in striatal and midbrain dopaminergic areas, persists long after mild repetitive head injury. These changes may be long lasting and serve as early biomarkers of neurodegeneration and risk for Parkinson’s disease with aging.
droplet-Tn-Seq combines microfluidics with Tn-Seq identifying complex single-cell phenotypes
Authors: Thibault Derek , Wood Stephen , Jensen Paul , Opijnen Tim van
Published: August 2018

While Tn-Seq is a powerful tool to determine genome-wide bacterial fitness in high-throughput, culturing transposon-mutant libraries in pools can mask community or other complex single-cell phenotypes. droplet-Tn-seq solves that problem by microfluidics facilitated encapsulation of individual transposon mutants into liquid-in-oil droplets, thereby enabling isolated growth, free from the influence of the population. Importantly, all advantages of Tn-Seq are conserved, while reducing costs and greatly extending its applicability.
Fast, versatile, and quantitative annotation of complex images
Authors: Bates Kathleen , Jiang Shen , Bates Ruth , Chaudhary Shivesh , Jackson-Holmes Emily , Jue Melinda , McCaskey Erin , Goldman Daniel , Lu Hang
Published: August 2018

We report a generic smartphone app for quantitative annotation of complex images. The app is simple enough to be used by children, and annotation tasks are distributed across app users, contributing to efficient annotation. We demonstrate its flexibility and speed by annotating >30,000 images, including features of rice root growth and structure, stem cell aggregate morphology, and complex worm (C. elegans) postures, for which we show that the speed of annotation is >130-fold faster than state-of-the-art techniques with similar accuracy.
Conserved phosphorylation hotspots in eukaryotic protein domain families
Authors: Strumillo Marta J. , Oplová Michaela , Viéitez Cristina , Ochoa David , Shahraz Mohammed , Busby Bede P. , Sopko Richelle , Studer Romain A. , Perrimon Norbert , Panse Vikram G. , Beltrao Pedro
Published: August 2018

Protein phosphorylation is the best characterized post-translational modification that regulates almost all cellular processes through diverse mechanisms such as changing protein conformations, interactions, and localization. While the inventory for phosphorylation sites across different species has rapidly expanded, their functional role remains poorly investigated. Here, we have combined 537,321 phosphosites from 40 eukaryotic species to identify highly conserved phosphorylation “hotspot” regions within domain families. Mapping these regions onto structural data revealed that they are often found at interfaces, near catalytic residues and tend to harbor functionally important phosphosites. Notably, functional studies of a phospho-deficient mutant in the C-terminal hotspot region within the Ribosomal S11 domain in the yeast ribosomal protein uS11 showed cold-sensitive phenotype and impaired 20S pre-rRNA processing. Altogether, our study identified phosphorylation hotspots for 162 protein domains suggestive of an ancient role for the control of diverse eukaryotic domain families.
Reconciling fMRI and EEG indices of attentional modulations in human visual cortex
Authors: Itthipuripat Sirawaj , Sprague Thomas C , Serences John T
Published: August 2018

Functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) are the two most popular non-invasive methods used to study the neural mechanisms underlying human cognition. These approaches are considered complementary: fMRI has higher spatial resolution but sluggish temporal resolution, whereas EEG has millisecond temporal resolution, but only at a broad spatial scale. Beyond the obvious fact that fMRI measures properties of blood and EEG measures changes in electric fields, many foundational studies assume that, aside from differences in spatial and temporal precision, these two methods index the same underlying neural modulations. We tested this assumption by using EEG and fMRI to measure attentional modulations of neural responses to stimuli of different visual contrasts. We found that equivalent experiments performed using fMRI and EEG on the same participants revealed remarkably different patterns of attentional modulations: event-related fMRI responses provided evidence for an additive increase in responses across all contrasts equally, whereas early stimulus-evoked event-related potentials (ERPs) showed larger modulations with increasing stimulus contrast and only a later negative-going ERP and low-frequency oscillatory EEG signals showed effects similar to fMRI. These results demonstrate that there is not a one-to-one correspondence between the physiological mechanisms that give rise to modulations of fMRI responses and the most commonly used ERP markers, and that the typical approach of employing fMRI and EEG to gain complementary information about localization and temporal dynamics is over-simplified. Instead, fMRI and EEG index different physiological modulations and their joint application affords synergistic insights into the neural mechanisms supporting human cognition.
The genome of the soybean cyst nematode (Heterodera glycines) reveals complex patterns of duplications involved in the evolution of parasitism genes
Authors: Masonbrink Rick , Maier Tom R. , Muppiral Usha , Seetharam Arun S. , Lord Etienne , Juvale Parijat S. , Schmutz Jeremy , Johnson Nathan T. , Korkin Dmitry , Mitchum Melissa G. , Mimee Benjamin , Akker Sebastian Eves-van den , Hudson Matthew , Severin Andrew J. , Baum Thomas J.
Published: August 2018

Heterodera glycines, commonly referred to as the soybean cyst nematode (SCN), is an obligatory and sedentary plant parasite that causes over a billion-dollar yield loss to soybean production annually. Although there are genetic determinants that render soybean plants resistant to certain nematode genotypes, resistant soybean cultivars are increasingly ineffective because their multi-year usage has selected for virulentH. glycinespopulations. The parasitic success ofH. glycinesrelies on the comprehensive re-engineering of an infection site into a syncytium, as well as the long-term suppression of host defense to ensure syncytial viability. At the forefront of these complex molecular interactions are effectors, the proteins secreted byH. glycinesinto host root tissues. The mechanisms of effector acquisition, diversification, and selection need to be understood before effective control strategies can be developed, but the lack of an annotated genome has been a major roadblock. Here, we use PacBio long-read technology to assemble aH. glycinesgenome of 738 contigs into 123Mb with annotations for 29,769 genes. The genome contains significant numbers of repeats (34%), tandem duplicates (18.7Mb), and horizontal gene transfer events (151 genes). Using previously published effector sequences, the newly generatedH. glycinesgenome, and comparisons to other nematode genomes, we investigate the evolutionary mechanisms responsible for the emergence and diversification of effector genes.
Micro Computed Tomography as an Accessible Imaging Platform for Exploring Organism Development and Human Disease Modeling
Authors: Schoborg Todd A. , Smith Samantha L. , Smith Lauren N. , Morris H. Douglas , Rusan Nasser M.
Published: August 2018

Understanding how events at the molecular and cellular scales contribute to tissue form and function is key to uncovering mechanisms driving animal development, physiology and disease. Elucidating these mechanisms has been enhanced through the study of model organisms and the use of sophisticated genetic, biochemical and imaging tools. Here we present an optimized method for non-invasive imaging of Drosophila melanogaster at high resolution using micro computed tomography (μ-CT). Our method allows for rapid processing of intact animals at any developmental stage, provides precise quantitative assessment of tissue size and morphology, and permits analysis of inter-organ relationships. We then use the power of μ-CT imaging to model human diseases through the characterization of microcephaly in the fly. Our work demonstrates that μ-CT is a versatile and accessible tool that complements standard imaging techniques, capable of uncovering novel biological mechanisms that have remained undocumented due to limitations of current methods.
Multi-Scale Neural Sources of EEG: Genuine, Equivalent, and Representative. A Tutorial Review
Authors: Nunez Paul L. , Nunez Michael D. , Srinivasan Ramesh
Published: August 2018

A biophysical framework needed to interpret electrophysiological data recorded at multiple spatial scales of brain tissue is developed. Micro current sources at membrane surfaces produce local field potentials (LFP), electrocorticography (ECoG), and electroencephalography (EEG). We categorize multi-scale sources asgenuine,equivalent, orrepresentative.Genuine sourcesoccur at the micro scale of cell surfaces.Equivalent sourcesprovide identical experimental outcomes over a range of scales and applications. In contrast, eachrepresentative source distributionis just one of many possible source distributions that yield similar experimental outcomes. Macro sources (“dipoles”) may be defined at the macrocolumn (mm) scale and depend on several features of the micro sources—magnitudes, micro synchrony within columns, and distribution through the cortical depths. These micro source properties are determined by brain dynamics and the columnar structure of cortical tissue. The number ofrepresentative sourcesunderlying EEG data depends on the spatial scale of neural tissue under study. EEG inverse solutions (e.g. dipole localization) and high resolution estimates (e.g. Laplacian, dura imaging) have both strengths and limitations that depend on experimental conditions. The proposed theoretical framework informs studies of EEGsource localization,source characterization, andlow passes filtering. It also facilitates interpretations of brain dynamics and cognition, including measures ofsynchrony,functional connections between cortical locations, and other aspects ofbrain complexity.
Visuomotor Control of Ankle Joint using Position vs. Force
Authors: Farjadian Amir Bahador , Nabian Mohsen , Hartman Amber , Yen Sheng-Che , Nasseroleslami Bahman
Published: August 2018

Ankle joint plays a critical role in daily activities involving interactions with environment using force and position control. Neuromechanical dysfunctions (e.g. due to stroke or brain injury), therefore, have a major impact on individuals’ quality of life. The effective design of neurorehabilitation protocols for robotic rehabilitation platforms, relies on understanding the control characteristics of the ankle joint in interaction with external environment using force and position. This is particularly of interest since the findings in upper-limb may not be generalizable to the lower-limb. This study aimed to characterize the skilled performance of ankle joint in visuomotor position and force control. A 2-degree of freedom (DOF) robotic footplate was used to measure individuals’ force and position. Healthy individuals (n = 27) used ankle force or position for point-to-point and tracking control tasks in 1-DOF and 2-DOF virtual game environments. Subjects’ performance was quantified as a function of accuracy and completion time. While the performance measures in 1-DOF control tasks were comparable, the subjects’ performance in 2-DOF tasks was significantly better with position control. Subjective questionnaires on the perceived difficulty matched the objective experimental results; suggesting that the poor performance in force control was not due to experimental setup or fatigue but can be attributed to the different levels of challenge needed in neural control. It is inferred that in visuomotor coordination, the neuromuscular specialization of ankle provides better control over position rather than force. These findings can inform the design of neuro-rehabilitation platforms, selection of effective tasks, and therapeutic protocols.
Design of two series of 1:1 cocrystals involving 4-amino-5-chloro-2,6-dimethylpyrimidine and carboxylic acids
Authors: Rajam Ammaiyappan , Muthiah Packianathan Thomas , Butcher Raymond John , Jasinski Jerry P. , Wikaira Jan
Published: August 2018

Two series of a total of ten cocrystals involving 4-amino-5-chloro-2,6-dimethylpyrimidine with various carboxylic acids have been prepared and characterized by single-crystal X-ray diffraction. The pyrimidine unit used for the cocrystals offers two ring N atoms (positions N1 and N3) as proton-accepting sites. Depending upon the site of protonation, two types of cations are possible [Rajam et al. (2017). Acta Cryst. C73, 862–868]. In a parallel arrangement, two series of cocrystals are possible depending upon the hydrogen bonding of the carboxyl group with position N1 or N3. In one series of cocrystals, i.e. 4-amino-5-chloro-2,6-dimethylpyrimidine–3-bromothiophene-2-carboxylic acid (1/1), 1, 4-amino-5-chloro-2,6-dimethylpyrimidine–5-chlorothiophene-2-carboxylic acid (1/1), 2, 4-amino-5-chloro-2,6-dimethylpyrimidine–2,4-dichlorobenzoic acid (1/1), 3, and 4-amino-5-chloro-2,6-dimethylpyrimidine–2-aminobenzoic acid (1/1), 4, the carboxyl hydroxy group (–OH) is hydrogen bonded to position N1 (O—H...N1) of the corresponding pyrimidine unit (single point supramolecular synthon). The inversion-related stacked pyrimidines are doubly bridged by the carboxyl groups via N—H...O and O—H...N hydrogen bonds to form a large cage-like tetrameric unit with an R
4
2(20) graph-set ring motif. These tetrameric units are further connected via base pairing through a pair of N—H...N hydrogen bonds, generating R
2
2(8) motifs (supramolecular homosynthon). In the other series of cocrystals, i.e. 4-amino-5-chloro-2,6-dimethylpyrimidine–5-methylthiophene-2-carboxylic acid (1/1), 5, 4-amino-5-chloro-2,6-dimethylpyrimidine–benzoic acid (1/1), 6, 4-amino-5-chloro-2,6-dimethylpyrimidine–2-methylbenzoic acid (1/1), 7, 4-amino-5-chloro-2,6-dimethylpyrimidine–3-methylbenzoic acid (1/1), 8, 4-amino-5-chloro-2,6-dimethylpyrimidine–4-methylbenzoic acid (1/1), 9, and 4-amino-5-chloro-2,6-dimethylpyrimidine–4-aminobenzoic acid (1/1), 10, the carboxyl group interacts with position N3 and the adjacent 4-amino group of the corresponding pyrimidine ring via O—H...N and N—H...O hydrogen bonds to generate the robust R
2
2(8) supramolecular heterosynthon. These heterosynthons are further connected by N—H...N hydrogen-bond interactions in a linear fashion to form a chain-like arrangement. In cocrystal 1, a Br...Br halogen bond is present, in cocrystals 2 and 3, Cl...Cl halogen bonds are present, and in cocrystals 5, 6 and 7, Cl...O halogen bonds are present. In all of the ten cocrystals, π–π stacking interactions are observed.