bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring the moral compass
Authors: Márquez Reiter Rosina , Orthaber Sara
Published: January 2019

With the advent of the internet and social media, car and vanpooling have become easily available alternatives to public transport in many parts of the world. This paper draws on publicly available data from a Facebook car and vanpooling group used by Slovenian cross-border commuters to make their journeys to and from Austria more economically sustainable. It examines public displays of moral indignation following allegations of malpractice by relatively new members whose whole purpose in joining the group was to earn a living from driving vans across borders. Vanpool users collaboratively denounce van service providers for transgressing some of the social responsibilities that ought to bind members of the group together and for their lack of accountability. The accusations which entail exaggerations, complaints, insults and threats, among other hostile verbal attacks, convey moral indignation and are similarly resisted and challenged by the drivers. They offer a window into conflicting behavioural expectations at a time of socioeconomic change and transition. The alleged lack of van providers’ accountability which, in turn, informs the van users’ displays of moral indignation is indicative of the moral relativism that emerges as a result of the relocalisation and, the nature of a contemporary global practice at a time when changes in social life are underway. The primacy of the economic return that car and vanpooling offers service providers and cross-commuters with is oriented to by the former as outstripping the social responsibilities typically related to the provision of the regulated services, and by the latter, as morally unjustifiable despite acknowledging its economic value.
La vida tiene muchas curvas [Life has many curves]
Authors: Link Holly , Arango Obed
Published: January 2019

In this article, a conceptual discussion grounded in our practice as educators and scholars we use a bilingual
poem, collaboratively written by young people from Latinx immigrant backgrounds, as an entry point to engage with existing
discussions among practitioners and scholars on connections between translanguaging and Freirean praxis, and more broadly, on
translanguaging and its potential for social transformation. Grounding our discussion in our work at a bilingual community
education non-profit organization that seeks to empower Latinx immigrants, we explore how we are developing translanguaging spaces
for immigrant students and families, spaces guided by a collective vision of social transformation, through what we call
translanguaging praxis. Through articulating this translanguaging praxis, we foreground the transformative
potential of translanguaging. We argue that translanguaging is not only a political act but that it can also be a critical,
rebellious and creative one through which educators, students and families can respond to dominant narratives on Latinx immigrants
in the US, co-constructing counter-stories through which they express who they are from their own perspectives and in dialogue
with each other.
To language differently
Authors: Robinson Elizabeth
Published: January 2019

This article explores the synergies between translanguaging and feminist poststructuralism to deepen understandings of how educators can teach for justice. I highlight how both theories challenge dominant structures and boundaries; how they privilege process over product; and how they both illuminate non-dominant voices and experiences. I explore how both translanguaging and feminist poststructuralism have helped me challenge foundational epistemologies, ontologies, and methodologies as a teacher educator in the field of teaching English. Throughout this article I examine what taking up these theories to challenge and question the status quo means for how we might better engage language as a tool for justice.
Soy sauce increased the oxidative stress tolerance of nematode via p38 MAPK pathway
Authors: Sugawara Takaya , Saraprug Danaporn , Sakamoto Kazuichi
Published: January 2019

Soy sauce – a fermented food made from soybeans and wheat – is considered a healthy seasoning, but little scientific evidence is available to support this. In this study, physiological effects of soy sauce were analyzed using Caenorhabditis elegans. When soy sauce was fed to C. elegans together with Escherichia coli OP50, fat accumulation decreased, and resistance to oxidative stress by H2O2 was greatly increased in the nematodes. qRT-PCR revealed that mRNA expression of oxidative stress tolerance genes, including sod, ctl, and gpx, was markedly increased in soy sauce-fed nematodes. Worms ingesting soy sauce showed high mitochondrial membrane potential and reactive oxygen species (ROS) and low intracellular ROS, suggesting that soy sauce induced mitohormesis and decreased cytoplasmic ROS. Therefore, soy sauce ingestion affects the mitochondria and may alter the fat metabolism in C. elegans. Furthermore, the increase in oxidative stress tolerance is mediated through p38 MAPK pathway.
Cryo-EM of retinoschisin branched networks suggests an intercellular adhesive scaffold in the retina
Authors: Heymann J. Bernard , Vijayasarathy Camasamudram , Huang Rick K. , Dearborn Altaira D. , Sieving Paul A. , Steven Alasdair C.
Published: January 2019

Mutations in the retinal protein retinoschisin (RS1) cause progressive loss of vision in young males, a form of macular degeneration called X-linked retinoschisis (XLRS). We previously solved the structure of RS1, a 16-mer composed of paired back-to-back octameric rings. Here, we show by cryo–electron microscopy that RS1 16-mers can assemble into extensive branched networks. We classified the different configurations, finding four types of interaction between the RS1 molecules. The predominant configuration is a linear strand with a wavy appearance. Three less frequent types constitute the branch points of the network. In all cases, the “spikes” around the periphery of the double rings are involved in these interactions. In the linear strand, a loop (usually referred to as spike 1) occurs on both sides of the interface between neighboring molecules. Mutations in this loop suppress secretion, indicating the possibility of intracellular higher-order assembly. These observations suggest that branched networks of RS1 may play a stabilizing role in maintaining the integrity of the retina.
Models to determine the kinetic mechanisms of ion-coupled transporters
Authors: Lolkema Juke S. , Slotboom Dirk J.
Published: January 2019

With high-resolution structures available for many ion-coupled (secondary active) transporters, a major challenge for the field is to determine how coupling is accomplished. Knowledge of the kinetic mechanism of the transport reaction, which defines the binding order of substrate and co-ions, together with the sequence with which all relevant states are visited by the transporter, will help to reveal this coupling mechanism. Here, we derived general mathematical models that can be used to analyze data from steady-state transport measurements and show how kinetic mechanisms can be derived. The models describe how the apparent maximal rate of substrate transport depends on the co-ion concentration, and vice versa, in different mechanisms. Similarly, they describe how the apparent affinity for the transported substrate is affected by the co-ion concentration and vice versa. Analyses of maximal rates and affinities permit deduction of the number of co-ions that bind before, together with, and after the substrate. Hill analysis is less informative, but in some mechanisms, it can reveal the total number of co-ions transported with the substrate. However, prior knowledge of the number of co-ions from other experimental approaches is preferred when deriving kinetic mechanisms, because the models are generally overparameterized. The models we present have wide applicability for the study of ion-coupled transporters.
Labour challenges in Ethiopia’s textile and leather industries: no voice, no loyalty, no exit?
Authors: Hardy Vincent , Hauge Jostein
Published: January 2019

A state-led industrialization push inspired by the East Asian ‘developmental state’ model is at the centre of Ethiopia’s recent economic success. This model has historically proved potent for achieving rapid industrialization, but the business-state alliance at the heart of the model generally aimed to curb the power of labour. Focusing on textile and leather manufacturing in Ethiopia, this article addresses two questions: are workers capable of extracting gains from the process of industrialization, and have the actions of workers affected global value chain integration in the two industries? Our data show that opportunities for collective voice among workers are limited. However, workers have expressed their discontent by leaving employers when working conditions fail to meet their expectations. The resulting turnover has generated significant obstacles for local and foreign firms attempting to participate in global value chains. In response, the Ethiopian state and employers implemented a number of measures, including restrictions on emigration and more generous non-wage benefits. Recent research on global value chains and labour highlights how workers are able to influence work practices through individual action. The present article builds on these ideas, but shows that firms and governments have the ability to respond and limit this power.
Improved indel detection in DNA and RNA via realignment with ABRA2
Authors: Mose Lisle E , Perou Charles M , Parker Joel S
Published: January 2019

Motivation

Genomic variant detection from next-generation sequencing has become established as an extremely important component of research and clinical diagnoses in both cancer and Mendelian disorders. Insertions and deletions (indels) are a common source of variation and can frequently impact functionality, thus making their detection vitally important. While substantial effort has gone into detecting indels from DNA, there is still opportunity for improvement. Further, detection of indels from RNA-Seq data has largely been an afterthought and offers another critical area for variant detection.

Results

We present here ABRA2, a redesign of the original ABRA implementation that offers support for realignment of both RNA and DNA short reads. The process results in improved accuracy and scalability including support for human whole genomes. Results demonstrate substantial improvement in indel detection for a variety of data types, including those that were not previously supported by ABRA. Further, ABRA2 results in broad improvements to variant calling accuracy across a wide range of post-processing workflows including whole genomes, targeted exomes and transcriptome sequencing.

Availability and implementation

ABRA2 is implemented in a combination of Java and C/C++ and is freely available to all from: https://github.com/mozack/abra2.

Supplementary information

Supplementary data are available at Bioinformatics online.
Cbs overdosage is necessary and sufficient to induce cognitive phenotypes in mouse models of Down syndrome and interacts genetically with Dyrk1a
Authors: Marechal Damien , Brault Véronique , Leon Alice , Martin Dehren , Lopes Pereira Patricia , Loaëc Nadege , Birling Marie-Christine , Friocourt Gaelle , Blondel Marc , Herault Yann
Published: January 2019

Identifying dosage-sensitive genes is a key to understand the mechanisms underlying intellectual disability in Down syndrome (DS). The Dp(17Abcg1-Cbs)1Yah DS mouse model (Dp1Yah) shows cognitive phenotypes that need to be investigated to identify the main genetic driver. Here, we report that three copies of the cystathionine-beta-synthase gene (Cbs) in the Dp1Yah mice are necessary to observe a deficit in the novel object recognition (NOR) paradigm. Moreover, the overexpression of Cbs alone is sufficient to induce deficits in the NOR test. Accordingly, overexpressing human CBS specifically in Camk2a-expressing neurons leads to impaired objects discrimination. Altogether, this shows that Cbs overdosage is involved in DS learning and memory phenotypes. To go further, we identified compounds that interfere with the phenotypical consequence of CBS overdosage in yeast. Pharmacological intervention in Tg(CBS) mice with one selected compound restored memory in the NOR test. In addition, using a genetic approach, we demonstrated an epistatic interaction between Cbs and Dyrk1a, another human chromosome 21-located gene (which encodes the dual-specificity tyrosine phosphorylation-regulated kinase 1a) and an already known target for DS therapeutic intervention. Further analysis using proteomic approaches highlighted several molecular pathways, including synaptic transmission, cell projection morphogenesis and actin cytoskeleton, that are affected by DYRK1A and CBS overexpression. Overall, we demonstrated that CBS overdosage underpins the DS-related recognition memory deficit and that both CBS and DYRK1A interact to control accurate memory processes in DS. In addition, our study establishes CBS as an intervention point for treating intellectual deficiencies linked to DS.
Early extubation improves outcome following extracardiac total cavopulmonary connection
Authors: Ono Masamichi , Georgiev Stanimir , Burri Melchior , Mayr Benedikt , Cleuziou Julie , Strbad Martina , Balling Gunter , Hager Alfred , Hörer Jürgen , Lange Rüdiger
Published: January 2019

OBJECTIVES

The aim of this study was to investigate the impact of an early extubation strategy on the outcome following extracardiac total cavopulmonary connection.

METHODS

From 1999 through 2017, 458 patients underwent extracardiac total cavopulmonary connection; 257 (56%) patients were managed with an early extubation strategy adopted in 2009 (group A). Their outcome was compared with those of 201 (44%) patients treated before 2009 (group B). In group A, the outcome of unstable patients, defined as >75th percentile for volume administered and inotrope scores, was compared with those of stable patients.

RESULTS

Ventilation time (median: 4 h vs 16 h, P < 0.001), fluid volume administered during the first 24 h (mean: 110 ml/kg vs 164 ml/kg, P = 0.003), chest tube duration (median: 3 days vs 4 days, P = 0.028) and length of intensive care unit stay (median: 6 days vs 7 days, P = 0.001) were less in group A than in group B. The reintubation rate (7% vs 6%, P = 0.547) and early mortality (0.8% vs 1.5%, P = 0.465) were similar between groups. The 80 unstable group A patients received more inotropic support (P < 0.001) and fluid volume (P < 0.001) than stable patients, but the ventilation time (6 h vs 5 h, P = 0.220), the reintubation rate (10% vs 6%, P = 0.283) and the length of intensive care unit stay (7 days vs 6 days, P = 0.590) were similar. In unstable patients, mean arterial pressure before extubation was significantly lower than stable patients (P = 0.001). However, mean arterial pressure in unstable patients increased significantly (P < 0.001) soon after extubation, and became similar to the value in stable patients.

CONCLUSIONS

Early extubation following extracardiac total cavopulmonary connection improves postoperative haemodynamics and recovery regardless of the initial haemodynamic status.
Rat Hepatitis E Virus Linked to Severe Acute Hepatitis in an Immunocompetent Patient
Authors: Andonov Anton , Robbins Mark , Borlang Jamie , Cao Jingxin , Hatchette Todd , Stueck Ashley , Deschambault Yvon , Murnaghan Kyle , Varga Jessy , Johnston Lynn
Published: January 2019

Hepatitis E virus (HEV) is a major public health concern in developing countries where the primary transmission is via contaminated water. Zoonotic HEV cases have been increasingly described in Europe, Japan, and the United States, with pigs representing the main animal reservoir of infection. We report an unusual acute hepatitis infection in a previously healthy man caused by a rat HEV with a considerably divergent genomic sequence compared with other rat HEV strains. It is possible that rat HEV is an underrecognized cause of hepatitis infection, and further studies are necessary to elucidate its potential risk and mode of transmission.
The Devil You Know: Self-Esteem and Switching Responses to Poor Service
Authors: Consiglio Irene , van Osselaer Stijn M J
Published: January 2019

We investigate a psychological factor regulating consumers’ switching in response to poor service quality: chronic global self-esteem. Whereas high-self-esteem consumers tend to switch to other providers in response to poor service quality, low-self-esteem consumers often do not. This happens because low-self-esteem consumers who experience poor service become risk-averse, and therefore reluctant to engage in new committed service relationships. Indeed, low-self-esteem consumers’ likelihood to switch to an alternative provider in response to poor service quality increases when this provider offers a less risky, low commitment (vs. more risky, high commitment) contract. Moreover, experimentally reducing low-self-esteem consumers’ risk aversion increases their likelihood to switch to alternative providers in response to poor service quality. Finally, low-self-esteem consumers’ risk aversion mediates their reluctance to switch in response to poor service. We rule out failure severity perceptions, power, autonomy, affect, and action orientation as alternative explanations. The implication of this research for public policy makers is that promoting competition (by offering consumers options and by reducing switching costs) may not be enough to protect the welfare of low-self-esteem consumers. We also suggest ways in which firms can untie vulnerable consumers from negative service relationships.
The Poetics of Narrativity: Understanding Trauma, Temporality, and Spatiality Forty Years after the Birmingham Pub Bombings
Authors: Nasar Saima , Schaffer Gavin
Published: January 2019

This article explores the social history of the Birmingham Pub Bombings (UK). In addition to individual losses and injuries, the bombings triggered widespread anti-Irish prejudice and violence, wrongful convictions and community tensions. The resultant disharmony within the city of Birmingham lasted for generations, while the voices of communities not directly involved in the events of November 21, 1974, have mostly remained silent. This article offers new lessons in the historical construction of trauma and how we make sense of traumatic events. Using original oral history interviews and witness seminars, it explores the layers of trauma that have been transmitted socially, politically, spatially, and intergenerationally. It begins by first focusing on the temporal and spatial dimensions of this local history, which reveal how the reconfiguring of temporalities can be used to locate an inner voice for British postwar, urban, social history. Then, it contextualizes individual and collective experiences of the Birmingham Pub Bombings in order to reveal the ways in which traumatic experiences are placed within a narrative form that orders and facilitates the integration of past trauma within the present. As such, we argue that the poetics of narrativity—or the narrative framing of how and when trauma memories are told, heard, and negotiated—has the potential to pull together a richer, more inclusive, community history.
Prospective multicenter surveillance of clinically isolated Aspergillus species revealed azole-resistant Aspergillus fumigatus isolates with TR34/L98H mutation in the Kyoto and Shiga regions of Japan
Authors: Tsuchido Yasuhiro , Tanaka Michio , Nakano Satoshi , Yamamoto Masaki , Matsumura Yasufumi , Nagao Miki
Published: January 2019

The prevalence of azole-resistant Aspergillus fumigatus (ARAF) in Japan is unclear. We aimed to investigate the epidemiology of clinically isolated Aspergillus species and the frequency of azole resistance in Aspergillus species, particularly Aspergillus fumigatus, in the Kyoto and Shiga regions of Japan. Strains of clinically isolated Aspergillus species were prospectively collected from nine acute care hospitals. Species identification was performed by DNA sequence analysis, and all strains were subjected to antifungal susceptibility testing. Sequencing of the Aspergillus cyp51A gene and promoter region and genotyping by short tandem repeats were performed for ARAF isolates. A total of 149 strains were collected, and 130 strains were included for the subsequent analysis after the exclusion of duplicate isolates. The most commonly isolated species was Aspergillus fumigatus, accounting for 43.1% (56 isolates) overall, and seven (12.7%) of 55 strains of A. fumigatus were azole-resistant. Azole-resistance of other Aspergillus species were also found that two (22.2%) of nine strains of A. tubingensis and two (28.6%) of seven strains of A. flavus were azole-resistant. DNA sequence analysis of the ARAF strains revealed that two carried the cyp51A TR34/L98H mutation, one carried G448S, one carried M220I, and three had no relevant mutations (wild type). Genotyping and phylogenetic analyses showed that the TR34/L98H strains were clustered with the strains from the Netherlands and France. These data suggest the emergence of ARAF with TR34/L98H in Japan, and continuous surveillance will be important to identify trends in resistance.
The Use of Anterior Lumbosacral Interbody Fusion in Spinopelvic Stabilization After High Partial Sacrectomy
Authors: Kashlan Osama N , Monson David K , Refai Daniel
Published: January 2019

BACKGROUND AND IMPORTANCE

Traditionally, when a patient presents with a midline chordoma with extension to the mid-S1 body where neither S1 nerve roots can be spared, the recommendation would be to perform a total sacrectomy for en bloc resection. This procedure, however, results in a large bony defect that makes it difficult to achieve fusion across the lumbosacral and sacroiliac junction (SIJ). To help prevent this challenge in the situation described above, we propose performing a high sacrectomy for en bloc resection with placement of an anterior L5-S1 graft instead in specific situations where the tumor extends to the mid-S1 body leaving the superior aspect of S1 unaffected.

CLINICAL PRESENTATION

A 56-yr-old female presented to our clinic with back pain, leg pain, urinary incontinence, and perineal numbness. She was found to have a chordoma that extended to the mid-S1 body superiorly. Her S1 nerve roots were involved extraforaminally. We performed the operation described above with no signs of hardware malfunction or tumor recurrence at 5 mo.

CONCLUSION

In patients where the sacral tumor that involves the S1 nerve roots but does not involve the superior portion of the S1 body, there continues to be unaffected SIJ to allow for arthrodesis, and an anterior approach is necessary for other indications, we recommend performing a high partial sacrectomy with placement of an anterior L5-S1 graft rather than a total sacrectomy as long as the bony resection offers ability to obtain tumor margins.
Can Medium-Resolution Satellite Imagery Measure Economic Activity at Small Geographies? Evidence from Landsat in Vietnam
Authors: Goldblatt Ran , Heilmann Kilian , Vaizman Yonatan
Published: January 2019

This study explores the potential and the limits of medium-resolution satellite data as a proxy for economic activity at small geographic units. Using a commune-level dataset from Vietnam, it compares the performance of commonly used nightlight data and higher resolution Landsat imagery, which measures daytime light reflection. The analysis suggests that Landsat outperforms nighttime lights at predicting enterprise counts, employment, and expenditure in simple regression models. A parsimonious combination of the first two moments of the Landsat spectral bands can explain a reasonable share of the variation in economic activity in the cross-section. There is, however, poor prediction power of either satellite measure for changes over time.
Antifungal Activity and Action Mechanism of the Natural Product Cinnamic Acid Against Sclerotinia sclerotiorum
Authors: Wang Yong , Sun Yang , Wang Jiali , Zhou Mingxia , Wang Miaomaio , Feng Juntao
Published: January 2019

Sclerotinia stem rot caused by Sclerotinia sclerotiorum (Lib.) de Bary spreads worldwide and causes serious economic losses. Considering the development of fungicide resistance and chemical residues, it is urgently necessary to explore alternative fungicides. In this study, the activity of the natural product cinnamic acid was assessed. The EC50 values for cinnamic acid inhibition of mycelial growth of 103 S. sclerotiorum strains ranged from 9.37 to 42.54 µg/ml with an average EC50 value of 18.77 (±3.39) µg/ml. No cross-resistance was detected between cinnamic acid and the commonly used fungicides carbendazim or dimethachlon. After treatment with cinnamic acid, mycelia distorted with more branches, no sclerotia developed, and the oxalic acid content decreased, whereas cell membrane permeability increased significantly. In pot experiments, cinnamic acid at 2,000 µg/ml provided over 95% efficacy against both carbendazim-sensitive and carbendazim-resistant strains of S. sclerotiorum. The expression of the sclerotia development-correlated genes Sac1, Pac1, Smk1, and Pka1 decreased, whereas the Cna1 gene expression increased. Altogether, cinnamic acid shows potential to be a natural alternative to commercial fungicides or a lead compound to develop new fungicides for the control of Sclerotinia stem rot. The biological characteristics contribute to the understanding of the action mechanism of cinnamic acid against S. sclerotiorum.
Thalassococcus profundi sp. nov., a marine bacterium isolated from deep seawater of the Okinawa Trough
Authors: Yu Min , Ren Qiaomeng , Wu Yanhong , Tian Xiaorong , Zhang Xiao-Hua
Published: January 2019

A novel Gram-stain-negative, strictly aerobic, rod-shaped motile bacterium with a single flagellum, designated strain WRAS1T, was isolated from deep seawater of the Okinawa Trough. Growth occurred in the presence of 0.0–9.0 % NaCl (w/v; optimum, 3.0–4.0 %), at 4–45 °C (optimum, 28–37 °C) and pH 7.0–10.0 (optimum, pH 7.0–8.0). The major fatty acid (>10 % of total fatty acids) was summed feature 8, comprising C18:1
ω6c and/or C18:1
ω7c. The major polar lipids were phosphatidylcholine, phosphatidylglycerol, phosphatidylethanolamine and three unidentified lipids. The major respiratory quinone was ubiquinone-10. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain WRAS1T was in the genus

Thalassococcus

and showed the highest 16S rRNA gene sequence similarity of 97.5 % to

Thalassococcus halodurans

JCM13833T. Genome relatedness between strain WRAS1T and

T. halodurans

JCM13833T was computed using both average nucleotide identity and DNA–DNA hybridization with values of 74.11 % and 22.70±2.3 %, respectively. The genomic DNA G+C content calculated from the genome sequence of strain WRAS1T was 65.6 %. On the basis of polyphasic analyses, strain WRAS1T is considered to represent a novel species in the genus

Thalassococcus

, for which the name

Thalassococcus
profundi sp. nov. is proposed. The type strain is WRAS1T (=CGMCC 1.16123T=MCCC 1K03253T =KCTC 52696T).
Multi-step genomic dissection of a suspected intra-hospital Helicobacter cinaedi outbreak
Authors: Gotoh Yasuhiro , Taniguchi Takako , Yoshimura Dai , Katsura Keisuke , Saeki Yuji , Hirabara Yasutoshi , Fukuda Mayumi , Takajo Ichiro , Tomida Junko , Kawamura Yoshiaki , Ogura Yoshitoshi , Itoh Takehiko , Misawa Naoaki , Okayama Akihiko , Hayashi Tetsuya
Published: January 2019

Helicobacter cinaedi

is an emerging pathogen causing bacteraemia and cellulitis. Nosocomial transmission of this microbe has been described, but detailed molecular-epidemiological analyses have not been performed. Here, we describe the results of a multi-step genome-wide phylogenetic analysis of a suspected intra-hospital outbreak of

H. cinaedi

that occurred in a hospital in Japan. The outbreak was recognized by the infectious control team (ICT) of the hospital as a sudden increase in

H. cinaedi

bacteraemia. ICT defined this outbreak case based on 16S rRNA sequence data and epidemiological information, but were unable to determine the source and route of the infections. We therefore re-investigated this case using whole-genome sequencing (WGS). We first performed a species-wide analysis using publicly available genome sequences to understand the level of genomic diversity of this under-studied species. The clusters identified were then separately analysed using the genome sequence of a representative strain in each cluster as a reference. These analyses provided a high-level phylogenetic resolution of each cluster, identified a confident set of outbreak isolates, and discriminated them from other closely related but distinct clones, which were locally circulating and invaded the hospital during the same period. By considering the epidemiological data, possible strain transmission chains were inferred, which highlighted the role of asymptomatic carriers or environmental contamination. The emergence of a subclone with increased resistance to fluoroquinolones in the outbreak was also recognized. Our results demonstrate the impact of the use of a closely related genome as a reference to maximize the power of WGS.
The time-course of component processes of selective attention
Authors: Wen Tanya , Duncan John , Mitchell Daniel J
Published: January 2019

Attentional selection shapes human perception, enhancing relevant information, according to behavioral goals. While many studies have investigated individual neural signatures of attention, here we used multivariate decoding of electrophysiological brain responses (MEG/EEG) to track and compare multiple component processes of selective attention. Auditory cues instructed participants to select a particular visual target, embedded within a subsequent stream of displays. Combining single and multi-item displays with different types of distractors allowed multiple aspects of information content to be decoded, distinguishing distinct components of attention, as the selection process evolved. Although the task required comparison of items to an attentional “template” held in memory, signals consistent with such a template were largely undetectable throughout the preparatory period but re-emerged after presentation of a non-target choice display. Choice displays evoked strong neural representation of multiple target features, evolving over different timescales. We quantified five distinct processing operations with different time-courses. First, visual properties of the stimulus were strongly represented. Second, the candidate target was rapidly identified and localized in multi-item displays, providing the earliest evidence of modulation by behavioral relevance. Third, the identity of the target continued to be enhanced, relative to distractors. Fourth, only later was the behavioral significance of the target explicitly represented in single-item displays. Finally, if the target was not identified and search was to be resumed, then an attentional template was weakly reactivated. The observation that an item’s behavioral relevance directs attention in multi-item displays prior to explicit representation of target/non-target status in single-item displays is consistent with two-stage models of attention.
A Unified Theory Of Early Visual Representations From Retina To Cortex Through Anatomically Constrained Deep CNNs
Authors: Lindsey Jack , Ocko Samuel A. , Ganguli Surya , Deny Stephane
Published: January 2019

Abstract

The vertebrate visual system is hierarchically organized to process visual information in successive stages. Neural representations vary drastically across the first stages of visual processing: at the output of the retina, ganglion cell receptive fields (RFs) exhibit a clear antagonistic center-surround structure, whereas in the primary visual cortex (V1), typical RFs are sharply tuned to a precise orientation. There is currently no unified theory explaining these differences in representations across layers. Here, using a deep convolutional neural network trained on image recognition as a model of the visual system, we show that such differences in representation can emerge as a direct consequence of different neural resource constraints on the retinal and cortical networks, and for the first time we find a single model from which both geometries spontaneously emerge at the appropriate stages of visual processing. The key constraint is a reduced number of neurons at the retinal output, consistent with the anatomy of the optic nerve as a stringent bottleneck. Second, we find that, for simple downstream cortical networks, visual representations at the retinal output emerge as nonlinear and lossy feature detectors, whereas they emerge as linear and faithful encoders of the visual scene for more complex cortical networks. This result predicts that the retinas of small vertebrates (e.g. salamander, frog) should perform sophisticated nonlinear computations, extracting features directly relevant to behavior, whereas retinas of large animals such as primates should mostly encode the visual scene linearly and respond to a much broader range of stimuli. These predictions could reconcile the two seemingly incompatible views of the retina as either performing feature extraction or efficient coding of natural scenes, by suggesting that all vertebrates lie on a spectrum between these two objectives, depending on the degree of neural resources allocated to their visual system.
No trace of phase: Corticomotor excitability is not tuned by phase of pericentral mu-rhythm
Authors: Madsen Kristoffer Hougaard , Karabanov Anke Ninija , Krohne Lærke Gebser , Safeldt Mads Gylling , Tomasevic Leo , Siebner Hartwig Roman
Published: January 2019

Background

The motor potentials evoked by transcranial magnetic stimulation (TMS) over the motor hand area (M1-HAND) show substantial inter-trial variability. Pericentral mu-rhythm oscillations, might contribute to inter-trial variability. Recent studies targeting mu-activity based on real-time electroencephalography (EEG) reported an influence of mu-power and mu-phase on the amplitude of motor evoked potentials (MEPs) in a preselected group with strong pericentral mu-activity. Other studies that determined mu-power or mu-phase based on post-hoc trial sorting according in non-preselected individuals were largely negative.

Objectives

To reassess if cortico-spinal activity is modulated by the mu-rhythm, we applied single-pulse TMS to the M1-HAND conditional on the phase of the intrinsically expressed pericentral mu-rhythm in 14 non-preselected healthy young participants.

Methods

TMS was given at 0, 90, 180, and 270 degrees of the mu-phase. Based on the absence of effects of mu-phase or mu-power when analyzing the mean MEP amplitudes, we also computed a linear mixed effects model, which included mu-phase, mu-power, inter-stimulus interval (ISIs) as fixed effects, treating the subject factor as a random effect.

Results

Mixed model analysis revealed a significant effect of mu-power and ISI, but no effect of mu-phase and no interactions. MEP amplitude scaled linearly with lower mu-power or longer ISIs, but these modulatory effects were very small relative to inter-trial MEP variability.

Conclusion

Our largely negative results are in agreement with previous offline TMS-EEG studies and point to a possible influence of ISI. Future research needs to clarify under which circumstances the responsiveness of human the M1-HAND to TMS depends on the synchronicity with mu-power and mu-phase.

Highlights

Phase-triggered TMS at four distinct phases of the ongoing mu-oscillations is technically feasible in non-preselected young volunteers

Targeting the ongoing mu-activity did not reveal consistent modulatory effect of mu-phase on corticospinal excitability in a non-preselected group

Mixed-effects analysis revealed a weak but significant effect of pre-stimulus mu-power and ISI on corticospinal excitability
A stress response that allows highly mutated eukaryotic cells to survive and proliferate
Authors: Zabinsky Rebecca A. , Mares Jonathan , She Richard , Zeman Michelle K. , Silvers Thomas R. , Jarosz Daniel F.
Published: January 2019

Rapid mutation fuels the evolution of many cancers and pathogens. Much of the ensuing genetic variation is detrimental, but cells can survive by limiting the cost of accumulating mutation burden. We investigated this behavior by propagating hypermutating yeast lineages to create independent populations harboring thousands of distinct genetic variants. Mutation rate and spectrum remained unchanged throughout the experiment, yet lesions that arose early were more deleterious than those that arose later. Although the lineages shared no mutations in common, each mounted a similar transcriptional response to mutation burden. The proteins involved in this response formed a highly connected network that has not previously been identified. Inhibiting this response increased the cost of accumulated mutations, selectively killing highly mutated cells. A similar gene expression program exists in hypermutating human cancers and is linked to survival. Our data thus define a conserved stress response that buffers the cost of accumulating genetic lesions and further suggest that this network could be targeted therapeutically.
Association of variants within the GST and other genes with anti-tubercular agents related toxicity: a systematic review and meta-analysis
Authors: Richardson Marty , Kirkham Jamie , Dwan Kerry , Sloan Derek J , Davies Geraint , Jorgensen Andrea L
Published: January 2019

Background

Individuals receiving treatment with anti-tuberculosis (TB) drugs may experience serious side-effects, such as anti-TB drug-induced hepatotoxicity (ATDH). Genetic variants, such as polymorphisms of the GST gene and other genes, may increase the risk of experiencing such toxicity events. This systematic review and meta-analysis provides a comprehensive evaluation of the evidence base for associations between variants of the GST gene and other genes and toxicity outcomes related to anti-TB drugs.

Methods

We searched for relevant studies in MEDLINE, PubMed, EMBASE, BIOSIS and Web of Science. We pooled effect estimates for each genotype on each outcome, and stratified all analyses by country. We qualitatively assessed the methodological quality of the included studies.

Results

We included data from 28 distinct cohorts of patients in the review. The methodological quality of included studies was variable, with several important areas of concern. For GSTM1, patients with the homozygous null genotype were significantly more likely to experience hepatotoxicity than patients with heterozygous or homozygous present genotype (odds ratio [OR]=1.44, 95% confidence interval [CI] 1.15, 1.82). Moderate heterogeneity was observed in this analysis (I2=51.2%). No significant difference was observed for the GSTT1 null polymorphism. For the rs3814057 polymorphism of the PXR gene, both heterozygous genotype and homozygous mutant-type significantly increased hepatotoxicity risk compared with homozygous wild-type (heterozygous versus homozygous wild-type: OR=1.98, 95% CI 1.06, 3.69; I2=0%; homozygous mutant-type versus homozygous wild-type: OR=2.18, 95% CI 1.07, 4.44; I2=0%).

Conclusions

We found that it is challenging to perform robust synthesis of the evidence base for associations between GST and other genetic variants and toxicity related to anti-TB drugs. We identified significant associations between the GSTM1 null and PXR rs3814057 polymorphisms and ATDH. To the best of our knowledge, no meta-analyses on genetic variants other than variants of the NAT2, CYP2E1, GSTM1 and GSTT1 genes have been published. Our results therefore add to the existing understanding of the association between genetic variants and hepatotoxicity.
Character displacement within the breeding area questions reinforcement inFicedulaflycatchers
Authors: Grinkov Vladimir G. , Palko Igor V. , Sternberg Helmut
Published: January 2019

At present, studies of reinforcement should be focused on demonstrating how often this process occurs in nature and how important it is for speciation. Here we study the character displacement within the breeding area in the Pied Flycatcher to check the validity of the reinforcement inFicedulaflycatchers. We used point-referenced spatial data and a random forest to find the most important explanatory factors of the character displacement, and to reconstruct the phenotypic structure of the populations. The environmental temperature, and not the distance to sympatry, were proven to better describe the geographic pattern of the mean breeding plumage colour of the Pied Flycatcher populations. We conclude that ecologically distinct adaptations drive the morphological differentiation of the Old World flycatchers, and not reinforcement.
Plasmids for independently tunable, low-noise expression of two genes
Authors: Silva João P. N. , Vidigal Lopes Soraia , Grilo Diogo J. , Hensel Zach
Published: January 2019

Some microbiology experiments and biotechnology applications can be improved if it is possible to tune the expression of two different genes at the same time with cell-to-cell variation at or below the level of genes constitutively expressed from the chromosome (the “extrinsic noise limit”). This was recently achieved for a single gene by exploiting negative autoregulation by the tetracycline repressor (TetR) and bicistronic gene expression to reduce gene expression noise. We report new plasmids that use the same principles to achieve simultaneous, low-noise expression for two genes. The TetR system was moved to a compatible plasmid backbone, and a system based on the lac repressor (LacI) was found to also exhibit gene expression noise below the extrinsic noise limit. We characterize gene expression mean and noise across the range of induction levels for these plasmids, apply the LacI system to tune expression for single-molecule mRNA detection in two different growth conditions, and show that two plasmids can be co-transformed to independently tune expression of two different genes.
Multivoxel Pattern Analysis Reveals Dissociations Between Subjective Fear and Its Physiological Correlates
Authors: Taschereau-Dumouchel Vincent , Kawato Mitsuo , Lau Hakwan
Published: January 2019

In studies of anxiety and other affective disorders, objectively measured physiological responses have commonly been used as a proxy for measuring subjective experiences associated with pathology. However, this commonly adopted ‘biosignal’ approach has recently been called into question on the grounds that subjective experiences and objective physiological responses may dissociate. We performed machine-learning based analysis on functional magnetic resonance imaging (fMRI) data to assess this issue in the case of fear. Participants were presented with pictures of commonly feared animals in an fMRI experiment. Multivoxel brain activity decoders were trained to predict participants’ subjective fear ratings and their skin conductance reactivity, respectively. While subjective fear and objective physiological responses were correlated in general, the respective whole-brain multivoxel decoders for the two measures were not identical. Some key brain regions such as the amygdala and insula appear to be primarily involved in the prediction of physiological reactivity, while some regions previously associated with metacognition and conscious perception, including some areas in the prefrontal cortex, appear to be primarily predictive of the subjective experience of fear. The present findings are in support of the recent call for caution in assuming a one-to-one mapping between subjective sufferings and their putative biosignals, despite the clear advantages in the latter’s being objectively and continuously measurable in physiological terms.
Standardised imaging pipeline for phenotyping mouse laterality defects and associated heart malformations, at multiple scales and multiple stages
Authors: Desgrange Audrey , Lokmer Johanna , Marchiol Carmen , Houyel Lucile , Meilhac Sigolène M.
Published: January 2019

Laterality defects are developmental disorders resulting from aberrant left/right patterning. In the most severe cases, such as in heterotaxy, they are associated with complex malformations of the heart. Advances in understanding the underlying physiopathological mechanisms have been hindered by the lack of a standardised and exhaustive procedure in mouse models, for phenotyping left/right asymmetries of all visceral organs. Here, we have developed a multimodality imaging pipeline, which combines non-invasive micro-ultrasound imaging, micro-CT and HREM, to acquire 3D images at multiple stages of development and at multiple scales. Based on the position in the uterine horns, we track, in a single individual, the progression of organ asymmetry, thesitusof all visceral organs in their thoracic or abdominal environment, together with fine anatomical left/right asymmetries of cardiac segments. We provide reference anatomical images and organ reconstructions in the mouse, and discuss differences with humans. This standardised pipeline, which we validated in a mouse model of heterotaxy, offers a fast and easy-to-implement framework. The extensive 3D phenotyping of organ asymmetry in the mouse uses the clinical nomenclature for direct comparison with patient phenotypes. It is compatible with automated and quantitative image analyses, which is essential to compare mutant phenotypes with incomplete penetrance and gain mechanistic insight into laterality defects.

Summary statement

Laterality defects, which combine anomalies in several visceral organs, are challenging to phenotype. We have now developed a standardised approach for multimodality 3D imaging in mice, generating quantifiable phenotypes.
The persistent influence of caste on under-five mortality: Factors that explain the caste-based gap in high focus Indian states
Authors: Bora Jayanta Kumar , Raushan Rajesh , Lutz Wolfgang
Published: January 2019

Objective

Although under-five mortality (U5M) is declining in India, it is still high in a few selected states and among the scheduled caste (SC) and scheduled tribe (ST) population of the country. This study re-examines the association between castes and U5M in high focus Indian states following the implementation of the country’s National Rural Health Mission (NRHM) program. In addition, we aim to quantify the contribution of socioeconomic determinants in explaining the gap in U5M between the SC/ST population and non-SC/ST population in high focus states in India.

Data and method

Using data from the National Family Health Survey (NFHS), we calculated the under-five mortality rate (U5MR) by applying a synthetic cohort probability approach. We applied a binary logistic regression model to examine the association of U5M with the selected covariates. Further, we used Fairlie’s decomposition technique to understand the relative contribution of socioeconomic variables on U5M risk between the caste groups.

Findings

In high focus Indian states, the parallel gap in U5M between well-off and deprived caste children has disappeared in the post-NRHM period, indicating a positive impact in terms of reducing caste-based inequalities in the high focus states. Despite the reduction in U5M, particularly among children belonging to STs, children belonging to the SC and ST population still experience higher mortality rates than children belonging to the non-SC/ST population from 1992 to 2016. Both macro level (district level mortality rates) and individual (regression analysis) analyses showed that children belonging to SCs experience the highest likelihood of dying before their fifth birthday. A decomposition analysis revealed that 78% of the caste-based gap in U5M is due to the effect of women’s level of educational attainment and household wealth between the SC/ST and non-SC/ST population. Program indicators such as place of delivery and number of antenatal care (ANC) visits also contributed significantly to widening caste-based gaps in U5M.

Conclusion

The study indicates that there is still scope to improve access to health facilities for mothers and children belonging to deprived caste groups in India. Continuous efforts to raise the level of maternal education and the economic status of people belonging to deprived caste groups should be pursued simultaneously.