bluuebunny/crossref_metadata_2025 huggingface dataset:
Treatment of cardiac transthyretin amyloidosis: an update
Authors: Emdin Michele , Aimo Alberto , Rapezzi Claudio , Fontana Marianna , Perfetto Federico , Seferović Petar M , Barison Andrea , Castiglione Vincenzo , Vergaro Giuseppe , Giannoni Alberto , Passino Claudio , Merlini Giampaolo
Published: April 2019

Transthyretin (TTR) is a tetrameric protein synthesized mostly by the liver. As a result of gene mutations or as an ageing-related phenomenon, TTR molecules may misfold and deposit in the heart and in other organs as amyloid fibrils. Cardiac involvement in TTR-related amyloidosis (ATTR) manifests typically as left ventricular pseudohypertrophy and/or heart failure with preserved ejection fraction. ATTR is an underdiagnosed disorder as well as a crucial determinant of morbidity and mortality, thus justifying the current quest for a safe and effective treatment. Therapies targeting cardiac damage and its direct consequences may yield limited benefit, mostly related to dyspnoea relief through diuretics. For many years, liver or combined heart and liver transplantation have been the only available treatments for patients with mutations causing ATTR, including those with cardiac involvement. The therapeutic options now include several pharmacological agents that inhibit hepatic synthesis of TTR, stabilize the tetramer, or disrupt fibrils. Following the positive results of a phase 3 trial on tafamidis, and preliminary findings on patisiran and inotersen in patients with ATTR-related neuropathy and cardiac involvement, we provide an update on this rapidly evolving field, together with practical recommendations on the management of cardiac involvement.
IncI1 ST3 and IncI1 ST7 plasmids from CTX-M-1-producing Escherichia coli obtained from patients with bloodstream infections are closely related to plasmids from E. coli of animal origin
Authors: Valcek Adam , Roer Louise , Overballe-Petersen Søren , Hansen Frank , Bortolaia Valeria , Leekitcharoenphon Pimlapas , Korsgaard Helle B , Seyfarth Anne Mette , Hendriksen Rene S , Hasman Henrik , Hammerum Anette M
Published: April 2019

Objectives

Fully sequenced IncI1 plasmids obtained from CTX-M-1-producing Escherichia coli of human and animal origin were compared.

Methods

Twelve E. coli isolates sharing identical ESBL genes and plasmid multilocus STs sequenced on Illumina and MinION platforms were obtained from the Danish antimicrobial resistance surveillance programme, DANMAP. After de novo assembly, the sequences of plasmids harbouring blaCTX-M-1 were manually curated and ORFs annotated. Within-group comparisons were performed separately for the IncI1 ST3 plasmid type and the IncI1 ST7 plasmid type. The IncI1 ST3 plasmid group was obtained from 10 E. coli isolates (2 from patients with bloodstream infections, 6 from food and 2 from animals). The IncI1 ST7 plasmids originated from E. coli isolates obtained from a patient with bloodstream infection and from a pig. Sequences of IncI1 ST3 and IncI1 ST7 plasmids harbouring blaCTX-M-1 with determined origin were retrieved from GenBank and used for comparison within the respective group.

Results

The 10 IncI1 ST3 blaCTX-M-1 plasmids were highly similar in structure and organization with only minor plasmid rearrangements and differences in the variable region. The IncI1 ST7 blaCTX-M-1 plasmids also showed high similarity in structure and organization. The high level of similarity was also observed when including plasmids from E. coli of animal origin from Australia, Switzerland, the Netherlands and France.

Conclusions

This study shows broad spread of a very successful CTX-M-1-producing IncI1 type plasmid among E. coli of both human and animal origin.
Irregular hatching patterns of Branchinecta orientalis G.O. Sars, 1901 (Branchiopoda: Anostraca) in response to parental food, brood order, and pre-inundation conditions
Authors: Pormehr Navid , Van Stappen Gilbert , Agh Naser , Atashbar Behrooz , Beladjal Lynda
Published: April 2019

Highly variable environmental conditions can put the survival of inhabitants of temporary pools at high risk, as they may not complete their life cycle. Different evolutionary responses can prevent the extinction of the inhabitants of ephemeral wetland habitats. One specific mode of response to environmental changes is bet-hedging as risk-spreading strategy and long-term fluctuating selection. The fairy shrimp Branchinecta orientalis G.O. Sars, 1901 is a broadly distributed species in Europe and Asia. We investigated the hatching pattern of B. orientalis resting eggs as a result of various factors, alone or interacting: 1) brood order, 2) food supplied to the parental generation, and 3) various pre-inundation conditions. Results were recorded for cumulative hatching over 10 d, hatching at the first day, and the first day of hatching. The factors with significant effects on hatching percentage were 1) brood order, 2) type of food, 3) pre-inundation conditions, 4) interaction between brood order and type of food, and 5) interaction between type of food and pre-inundation conditions (P < 0.05). Within the first 24 h, 44% of total hatching occurred. Resting eggs from the first brood showed the highest cumulative hatching. The lowest mean resting egg size was found when parents were fed fish pond effluents supplemented with Haematococcus sp. (Chlorophyta); this group of resting eggs also had the highest cumulative hatching percentage. Eggs that had stayed for one week in the parental medium showed significantly higher cumulative hatching percentage, than eggs that had stayed in the medium for two weeks, or that had not stayed in the medium at all (P < 0.05). Overall, hatching showed an irregular pattern, affected by the mode of response of the resting eggs to our experimental factors. The irregular hatching pattern may result in fairy shrimps better adapted to environmental instability.
Where Does ’Ayyē Come From? Proclisis and Affix Pleonasm in the Biblical Hebrew Interrogatives ’Ē and ’Ayyē
Authors: Kantor Benjamin
Published: April 2019

Interrogatives from the base *’ayy- are common throughout Semitic. Two of the reflexes of this base in Biblical Hebrew, ’ē ‘where?’ and ’ayyē ‘where?’, exhibit atypical phonological features. In the case of ’ē (< *’ayy-v), the diphthong *ay ought to have been preserved due to the following gemination (cf. day [< *dayy-v] ‘sufficiency’). In the case of ’ayyē, the final ṣere is unusual. In this paper, I argue that contraction has occurred in ’ē because it is proclitic and that the ṣere (-ē) ending in ’ayyē is from the Semitic adverbial ending *-ay, which also contracted to -ē due to proclisis. The morphosyntactic developments of these forms, taken within their wider Semitic context, shed light on the linguistic phenomenon of ‘affix pleonasm‘ in both Hebrew and Semitic.
Mass functions, luminosity functions, and completeness measurements from clustering redshifts
Authors: Bates Dominic J , Tojeiro Rita , Newman Jeffrey A , Gonzalez-Perez Violeta , Comparat Johan , Schneider Donald P , Lima Marcos , Streblyanska Alina
Published: April 2019

This paper presents stellar mass functions and i-band luminosity functions for Sloan Digital Sky Survey (SDSS) galaxies with i < 21 using clustering redshifts. From these measurements, we also compute targeting completeness measurements for the Baryon Oscillation Spectroscopic Survey (BOSS). Clustering redshifts is a method of obtaining the redshift distribution of a sample of galaxies with only photometric information by measuring the angular cross-correlation with a spectroscopic sample in different redshift bins. We construct a spectroscopic sample containing data from the BOSS + eBOSS surveys, allowing us to recover redshift distributions from photometric data out to z ≃ 2.5. We produce k-corrected i-band luminosity functions and stellar mass functions by applying clustering redshifts to SDSS DR8 galaxies in small bins of colour and magnitude. There is little evolution in the mass function between 0.2 < z < 0.8, implying that the most massive galaxies form most of their mass before z = 0.8. These mass functions are used to produce stellar mass completeness estimates for the BOSS, giving a stellar mass completeness of $80{{\ \rm per\ cent}}$ above M⋆ > 1011.4 between 0.2 < z < 0.7, with completeness falling significantly at redshifts higher than 0.7, and at lower masses. Large photometric data sets will be available in the near future (DECaLS, DES, Euclid), so this and similar techniques will become increasingly useful in order to fully utilize these data.
Altered Localization of Hybrid Incompatibility Proteins in Drosophila
Authors: Cooper Jacob Carter , Lukacs Andrea , Reich Shelley , Schauer Tamas , Imhof Axel , Phadnis Nitin
Published: April 2019

Understanding the molecular basis of hybrid incompatibilities is a fundamental pursuit in evolutionary genetics. In crosses between Drosophila melanogaster females and Drosophila simulans males, an interaction between at least three genes is necessary for hybrid male lethality: Hmr mel, Lhr sim, and gfzf sim. Although HMR and LHR physically bind each other and function together in a single complex, the connection between gfzf and either of these proteins remains mysterious. Here, we show that GFZF localizes to many regions of the genome in both D. melanogaster and D. simulans, including at telomeric retrotransposon repeats. We find that GFZF localization at telomeres is significantly different between these two species, reflecting the rapid evolution of telomeric retrotransposon copy number composition between the two species. Next, we show that GFZF and HMR normally do not colocalize in D. melanogaster. In interspecies hybrids, however, HMR shows extensive mis-localization to GFZF sites, thus uncovering a new molecular interaction between these hybrid incompatibility factors. We find that spreading of HMR to GFZF sites requires gfzf sim but not Lhr sim, suggesting distinct roles for these factors in the hybrid incompatibility. Finally, we find that overexpression of HMR and LHR within species is sufficient to mis-localize HMR to GFZF binding sites, indicating that HMR has a natural low affinity for GFZF sites. Together, these studies provide the first insights into the different properties of gfzf between D. melanogaster and D. simulans, and uncover a molecular interaction between gfzf and Hmr in the form of altered protein localization.
Depression and change in occupational functioning in type 2 diabetes
Authors: Moulton C D , Murray L , Winkley K , Amiel S A , Ismail K , Patel A
Published: April 2019

Background

The effect of depression on both employment and productivity in type 2 diabetes (T2D) is poorly understood.

Aims

We tested whether depressive symptoms at diagnosis of T2D are associated with change in employment status and productivity over 2-year follow-up.

Methods

In a prospective analysis of working-age (18–63 years) people with newly diagnosed T2D recruited from primary care, we tested the association between depressive symptoms at diagnosis of T2D (baseline) and employment rates over 2 years. Using the Patient Health Questionnaire-9, depressive symptoms were measured categorically (depression caseness score ≥10) and continuously. In those employed, we measured changes in presenteeism and absenteeism using the World Health Organization (WHO) Health and Work Performance Questionnaire in univariate and multivariate models, respectively, including and excluding part-time workers.

Results

Of 1202 people aged 18–63 at baseline, 982 (82%) provided employment information; the mean age was 50.3 (SD 8.1) years, 44% were female, 59% of non-white ethnicity and 16% had depression. After adjustment for age, sex, ethnicity, socio-economic status, diabetes control and depression treatment, depression caseness was associated with worsening unemployment over 2 years only in full-time workers (odds ratio 0.43 (95% CI 0.20, 0.96), P < 0.05). In those employed full-time or part-time, total depressive symptoms were associated with worsening presenteeism over 2 years after full adjustment (β = −2.63 (95% CI −4.81, −0.45), P < 0.05), despite no association with worsening absenteeism.

Conclusions

In newly diagnosed T2D, depressive symptoms demonstrate an association with worsening employment rate and decline in work productivity over 2-year follow-up.
Spectral properties of gamma-ray bursts observed by the Suzaku wide-band all-sky monitor
Authors: Ohmori Norisuke , Yamaoka Kazutaka , Yamauchi Makoto , Urata Yuji , Ohno Masanori , Sugita Satoshi , Hurley Kevin , Tashiro Makoto S , Fukazawa Yasushi , Iwakiri Wataru , Katsukura Daisuke , Kokubun Motohide , Makishima Kazuo , Murakami Souta , Nakagawa Yujin E , Nakazawa Kazuhiro , Odaka Katsuya , Takahashi Kaito , Takahashi Tadayuki , Terada Yukikatsu
Published: April 2019

We have systematically studied the spectral properties of 302 localized gamma-ray bursts (GRBs) observed by the Suzaku wide-band all-sky monitor (WAM) from 2005 August to 2010 December. The energy spectra in the 100–5000 keV range integrated over the entire emission and the 1 s peak were fitted by three models: a single power law, a power law with an exponential cutoff (CPL), and the GRB Band function (GRB). Most of the burst spectra were well fitted by a single power law. The average photon index α was −2.11 and −1.73 for long and short bursts, respectively. For the CPL and GRB models, the low-energy and high-energy photon indices (α and β) for the entire emission spectra were consistent with previous measurements. The averages of the α and β were −0.90 and −2.65 for long-duration GRBs, while the average α was −0.55 and the β was not well constrained for short-duration GRBs. However, the average peak energy Epeak was 645 and 1286 keV for long- and short-duration GRBs respectively, which are higher than previous Fermi/GBM measurements (285 keV and 736 keV). The α and Epeak of the 1 s peak spectra were larger, i.e., the spectra were harder, than the total fluence spectra. Spectral simulations based on Fermi-GBM results suggest that the higher Epeaks measured by the Suzaku WAM could be due to detector selection bias, mainly caused by the limited energy range above 100 keV.
Self-Disorders in Asperger Syndrome Compared to Schizotypal Disorder: A Clinical Study
Authors: Nilsson Maria , Arnfred Sidse , Carlsson Jessica , Nylander Lena , Pedersen Lennart , Mortensen Erik Lykke , Handest Peter
Published: April 2019

Objective

There are historical and theoretical indications of a difference in subjective experience between autism spectrum disorder (ASD) and the schizophrenia spectrum. However, this difference has not been empirically explored. Therefore, to explore potential differences in subjective experience between the 2 spectra, we examined the presence/absence of self-disorders in Asperger syndrome/autism spectrum disorder (As/ASD) compared to schizotypal disorder (Sd). Self-disorders represent changes in basic self-awareness which have been found to accumulate within the schizophrenia spectrum.

Methods

All participants were recruited from clinical units and interviewed with a focus on the exploration of presence/absence of self-disorders, with the Examination of Anomalous Self-Experience (EASE) scale, and a general assessment of present psychopathology, with Schedules for Clinical Assessment in Neuropsychiatry (SCAN).

Results

A total of 51 participants (As/ASD, n = 22; Sd, n = 29) were included in the statistical analyses. When controlling for age, gender, years of education, mental problems before the age of 16, and special needs school attendance, there was a clear difference in presence/absence of self-disorders between the 2 groups, with significantly higher levels in the Sd group. Further, there was an overlap in SCAN-rated symptoms between the 2 groups.

Conclusion

Our results indicate a significant difference between As/ASD and Sd at the level of the basic self, which, in turn, indicates that an exploration of anomalous self-experience is a valuable supplement in the clinical differentiation between As/ASD and Sd.
Neighborhood Characteristics at Birth and Positive and Negative Psychotic Symptoms in Adolescence: Findings From the ALSPAC Birth Cohort
Authors: Solmi Francesca , Lewis Glyn , Zammit Stanley , Kirkbride James B
Published: April 2019

Background

Urban birth is associated with risk of non-affective psychoses, but the association with subclinical positive and negative symptoms is less clear, despite emerging evidence. Further the extent to which these findings are confounded by polygenic risk scores (PRS) for schizophrenia is also unknown.

Methods

Using data from the Avon Longitudinal Study of Parents and Children, linked to census geographical indicators, we examined whether various indices of urbanicity at birth were associated with negative and positive psychotic symptoms at age 16 and 18 years, respectively. We used logistic regression models, controlling for child’s ethnicity, maternal age, education, marital status, social class, depressive symptoms, other neighborhood exposures, and, in a subsample of children of white ethnicity (N = 10 283), PRS for schizophrenia.

Results

Amongst 11 879 adolescents, those born in the most densely populated tertile had greater odds of reporting positive psychotic experiences, after multivariable adjustment (odds ratio [OR]: 1.57, 95% confidence intervals (CIs): 1.14–2.17). Adolescents born in the most socially fragmented neighborhoods had greater odds of negative symptoms, after multivariable adjustment (OR: 1.43, 95% CI: 1.06–1.85). Although we found that greater schizophrenia PRS were associated with an increased risk of being born in more deprived and fragmented (bot not more densely populated areas), these associations were not confounded by PRS.

Interpretation

Birth into more densely populated and socially fragmented environments increased risk of positive and negative psychotic phenomena in adolescence, respectively, suggesting that different forms of neighborhood social adversity may impinge on different psychopathophysiologies associated with the clinical expression of psychosis.
Co-producing European knowledge and publics amidst controversy: The EU expert network on unconventional hydrocarbons
Authors: Lis Aleksandra , Kama Kärg , Reins Leonie
Published: April 2019

To date, social sciences have devoted little attention to the processes of expert knowledge production related to the exploitation of unconventional hydrocarbon resources. In this article, we examine an epistemic experiment led by the European Commission, the European Science and Technology Network on Unconventional Hydrocarbon Extraction, which was aimed at producing authoritative knowledge claims on shale energy development. By developing the idiom of ‘co-production’, the article provides a more fine-grained understanding of the processes through which competing knowledge claims, forms of epistemic authority, and new energy publics co-evolve in a situation of highly-politicized controversy. Drawing on our first-hand observations as participants representing the social sciences in the expert network, this article provides an in-depth ethnographic account of the struggles of the European Union authorities to manage and delimit the controversy. In this way, the analysis develops our understanding of the challenges in improving the deliberation of shale gas as a transnational energy policy issue.
Visual experience drives sleep need in Drosophila
Authors: Kirszenblat Leonie , Yaun Rebecca , van Swinderen Bruno
Published: April 2019

Sleep optimizes waking behavior, however, waking experience may also influence sleep. We used the fruit fly Drosophila melanogaster to investigate the relationship between visual experience and sleep in wild-type and mutant flies. We found that the classical visual mutant, optomotor-blind (omb), which has undeveloped horizontal system/vertical system (HS/VS) motion-processing cells and are defective in motion and visual salience perception, showed dramatically reduced and less consolidated sleep compared to wild-type flies. In contrast, optogenetic activation of the HS/VS motion-processing neurons in wild-type flies led to an increase in sleep following the activation, suggesting an increase in sleep pressure. Surprisingly, exposing wild-type flies to repetitive motion stimuli for extended periods did not increase sleep pressure. However, we observed that exposing flies to more complex image sequences from a movie led to more consolidated sleep, particularly when images were randomly shuffled through time. Our results suggest that specific forms of visual experience that involve motion circuits and complex, nonrepetitive imagery, drive sleep need in Drosophila.
Assessment of cognitive profile as a prodromal marker of the evolution of rapid eye movement sleep behavior disorder
Authors: Terzaghi Michele , Toscano Gianpaolo , Casoni Francesca , Picascia Marta , Arnaldi Dario , Rustioni Valter , Versino Maurizio , Sinforiani Elena , Manni Raffaele
Published: April 2019

Study Objectives

To search for a specific neuropsychological profile in idiopathic REM sleep behavior disorder (iRBD), able to predict the onset of neurodegenerative disorders.

Methods

In a longitudinal follow-up study of 63 consecutive iRBD patients (follow-up duration 6.7 ± 3.8 years), the baseline cognitive profile of converters to neurodegenerative disease was compared with that of the nonconverters. Five cognitive domains were assessed: memory, attention-working memory, executive functions, visuospatial abilities, language. Mild cognitive impairment (MCI) was diagnosed according to the Movement Disorder Society’s diagnostic criteria for Parkinson’s disease.

Results

30 subjects (47.6%) developed a neurodegenerative disease (latency to conversion 60.33 ± 44.81 months). MCI was found in 50% of the converters and 12% of the nonconverters (p = .001), and its presence conferred a neurodegenerative disease risk of 10% at 3 years, 36% at 5 years, and 73% at 10 years (p = .002). Pathological equivalent scores on at least one neuropsychological test were detected in 46.7% of the converters versus 21.2% of the nonconverters in the memory domain (p = .032), in 40.0% versus 6.1% in that of executive functions (p = .002), and in 20.0% versus 3% in the visuospatial abilities domain (p = .047). On multivariate analysis, impaired executive functions significantly correlated with phenoconversion (p = .018). Lower Mini Mental State Examination (MMSE) scores (p = .004) and memory deficits (p = .031) were found in patients who developed dementia first.

Conclusions

Cognitive profile is useful for stratifying risk of phenoconversion in patients with iRBD. The presence of MCI and impaired executive functions, memory, and visuospatial abilities discriminated the converters. Lower MMSE scores and memory deficits may characterize those subjects who first develop dementia.
A Taxonomy of Child Policies: Conceptualizing the Missing Step in Defamilization of Social Policy
Authors: Palme Joakim , Heimer Maria
Published: April 2019

The UN Convention on the Rights of the Child has created momentum for the notion of child policy to be advanced. The article elaborates a taxonomy of child policies for analyzing policy instruments aimed at promoting various aspects of children’s welfare, and four different types of child policies are identified. The article explores the feasibility of this conceptual framework with a case study of Sweden. We frame the move toward child-centered policies in terms of defamilization: such policies may enhance “freedom as non-domination” and could be seen as the second round of the defamilization of social policy.
Practical open science: tools and techniques for improving the reproducibility and transparency of your research
Authors: DeHaven Alexander , Mellor David
Published: April 2019

Science progresses through critical evaluation of underlying evidence and independent replication of results. However, most research findings are disseminated without access to supporting raw data, and findings are not routinely replicated. Furthermore, undisclosed flexibility in data analysis, such as incomplete reporting, unclear exclusion criteria, and optional stopping rules allow for presenting exploratory research findings using the tools of confirmatory hypothesis testing. These questionable research practices make results more publishable, though it comes at the expense of their credibility and future replicability. The Center for Open Science builds tools and encourages practices that incentivizes work that is not only good for the scientist, but also good for science. These include open source platforms to organize research, archive results, preregister analyses, and disseminate findings. This poster presents an overview of those practices and gives practical advice for researchers who want to increase the rigor of their practices.
ModelTest-NG: a new and scalable tool for the selection of DNA and protein evolutionary models
Authors: Darriba Diego , Posada David. , Kozlov Alexey M. , Stamatakis Alexandros , Morel Benoit , Flouri Tomas
Published: April 2019

ModelTest-NG is a re-implementation from scratch of jModelTest and ProtTest, two popular tools for selecting the best-fit nucleotide and amino acid substitution models, respectively. ModelTest-NG is one to two orders of magnitude faster than jModelTest and ProtTest but equally accurate, and introduces several new features, such as ascertainment bias correction, mixture and FreeRate models, or the automatic processing of partitioned datasets. ModelTest-NG is available under a GNU GPL3 license at https://github.com/ddarriba/modeltest.
Toward A Reproducible, Scalable Framework for Processing Large Neuroimaging Datasets
Authors: Johnson Erik C. , Wilt Miller , Rodriguez Luis M. , Norman-Tenazas Raphael , Rivera Corban , Drenkow Nathan , Kleissas Dean , LaGrow Theodore J. , Cowley Hannah , Downs Joseph , Matelsky Jordan , Hughes Marisa , Reilly Elizabeth , Wester Brock , Dyer Eva , Kording Konrad , Gray-Roncal William
Published: April 2019

Emerging neuroimaging datasets (collected through modalities such as Electron Microscopy, Calcium Imaging, or X-ray Microtomography) describe the location and properties of neurons and their connections at unprecedented scale, promising new ways of understanding the brain. These modern imaging techniques used to interrogate the brain can quickly accumulate gigabytes to petabytes of structural brain imaging data. Unfortunately, many neuroscience laboratories lack the computational expertise or resources to work with datasets of this size: computer vision tools are often not portable or scalable, and there is considerable difficulty in reproducing results or extending methods. We developed an ecosystem of neuroimaging data analysis pipelines that utilize open source algorithms to create standardized modules and end-to-end optimized approaches. As exemplars we apply our tools to estimate synapse-level connectomes from electron microscopy data and cell distributions from X-ray microtomography data. To facilitate scientific discovery, we propose a generalized processing framework, that connects and extends existing open-source projects to provide large-scale data storage, reproducible algorithms, and workflow execution engines. Our accessible methods and pipelines demonstrate that approaches across multiple neuroimaging experiments can be standardized and applied to diverse datasets. The techniques developed are demonstrated on neuroimaging datasets, but may be applied to similar problems in other domains.
Resistance to aztreonam in combination with non-β-lactam β-lactamase inhibitors due to the layering of mechanisms in Escherichia coli identified following mixed culture selection
Authors: Cheung Ching Hei Phoebe , Dulyayangkul Punyawee , Heesom Kate J. , Avison Matthew B.
Published: April 2019

Using mixed culture selection, we show how reduced envelope permeability, reduced target-site affinity, and increased β-lactamase production layer to confer aztreonam/β-lactamase inhibitor resistance in Escherichia coli. We report a clinical isolate producing CTX-M-15 and CMY-4, lacking OmpF, and carrying a PBP3 mutation. It is resistant to aztreonam plus the inhibitors avibactam, relebactam and vaborbactam. Mobilisation of blaSHV-12 into this isolate generated a derivative additionally resistant to aztreonam plus the bicyclic boronate inhibitors 2 and taniborbactam.
Stable maintenance of a hidden switch as a way to increase the gene expression stability
Authors: Kuwahara Hiroyuki , Gao Xin
Published: April 2019

In response to severe stress, wild-type organisms can release alternative phenotypes that are hidden under normal conditions and are associated with underlying genetic variations. A number of such stress-induced phenotypic switchings have been reported to be based on reactivation of hidden thresholds; under the normal condition, a high barrier separating alternative phenotypes ensures the expression of single discrete phenotype, but a severe perturbation can lower the barrier to a level at which to expose cryptic alternatives. While the importance of such threshold-based switches as the mechanism to generate adaptive novelties under variable environments has been appreciated, it still remains elusive how naturally selected organisms can maintain the phenotypic switching capability when such switching has been disused for a long period of time. Here, through the use of computer simulation, we analyzed adaptive evolution of gene circuits under stabilizing selection. We found that different strategies evolved to acquire reduced levels of gene expression noise around the optimum expression level. To incrementally improve the gene expression stability from a founding population with bistable individuals, the evolution consistently took the direction to raise the height of the potential barrier of bistable systems. Our results demonstrate that hidden phenotypic switches can be stably maintained during environmental stasis, facilitating the release of potentially adaptive phenotypic alternatives in the event of substantial perturbations.
The evolutionary advantage of toxin production among cyanobacteria, the oldest known organisms on Earth
Authors: Tristão Ramos Ravi José , Ionescu Crina-Maria , Koča Jaroslav
Published: April 2019

Cyanobacteria produce toxic secondary metabolites for reasons hitherto unclear. Using a phylogenetic approach that accounts for the high complexity of biosynthetic gene clusters (full or partial inversions, variable length, different number of genes, non-orthologues), we analyzed the sequences of 76 biosynthetic gene clusters covering 19 cyanotoxins. The phylogenetic tree of biosynthetic gene clusters branches first according to the bioactivity of the toxic metabolite (molecular target in another organism), then according to the chemical class and chemical structure of the secondary metabolite, and finally according to the organism and area of origin. The bioactivity of a toxic metabolite can be deduced directly from the nucleotide sequence of the biosynthetic gene cluster, without needing to examine the enzymes themselves or to measure expression levels. Bioactivity may have been the primary driving force behind the diversity of secondary metabolism in cyanobacteria. This genetic machinery evolved to facilitate three specific survival strategies acting separately or in tandem, with dominant cyanobacteria possessing the genetic machinery to support all three strategies. Transmembrane (direct) toxicity targeting ion channels, intracellular (indirect) toxicity targeting cell-cycle regulation, and digestion inhibition targeting proteases may have provided the survival advantage underpinning the evolutionary success of both cyanobacteria and their early symbiotic hosts.
Identification of Host Biomarkers of EBV Latency IIb and Latency III
Authors: Messinger Joshua E. , Dai Joanne , Stanland Lyla J. , Price Alexander M. , Luftig Micah A.
Published: April 2019

Deciphering the molecular pathogenesis of virally induced cancers is challenging due, in part, to the heterogeneity of both viral and host gene expression. Epstein-Barr Virus (EBV) is a ubiquitous herpesvirus prevalent in B-cell lymphomas of the immune suppressed. EBV infection of primary human B cells leads to their immortalization into lymphoblastoid cell lines (LCLs) serving as a model of these lymphomas. In previous studies, our lab has described a temporal model for immortalization with an initial phase characterized by expression of the Epstein-Barr Nuclear Antigens (EBNAs), high c-Myc activity, and hyper-proliferation in the absence of the Latent Membrane Proteins (LMPs), called latency IIb. This is followed by the long-term outgrowth of LCLs expressing the EBNAs along with the LMPs, particularly the NFκB-activating LMP1, defining latency III. LCLs, however, express a broad distribution of LMP1 such that a subset of these cells expresses LMP1 at levels seen in latency IIb, making it difficult to distinguish these two latency states. In this study, we performed mRNA-Seq on early EBV-infected latency IIb cells and latency III LCLs sorted by NFκB activity. We found that latency IIb transcriptomes clustered independently from latency III independent of NFκB. We identified and validated mRNAs defining these latency states. Indeed, we were able to distinguish latency IIb cells from LCLs expressing low levels of LMP1 using multiplex RNA-FISH targeting EBV EBNA2, LMP1, and human CCR7. This study defines latency IIb as abona fidelatency state independent from latency III and identifies biomarkers for understanding EBV-associated tumor heterogeneity.

IMPORTANCE

EBV is a ubiquitous pathogen with >95% of adults harboring a life-long latent infection in memory B cells. In immunocompromised individuals, latent EBV infection can result in lymphoma. The established expression profile of these lymphomas is latency III, which includes expression of all latency genes. However, single cell analysis of EBV latent gene expression in these lymphomas suggests heterogeneity where most cells express the transcription factor, EBNA2, and only a fraction express the membrane protein LMP1. Our work describes an early phase after infection where the EBNAs are expressed without LMP1, called latency IIb. However, LMP1 levels within latency III vary widely making these states hard to discriminate. This may have important implications for therapeutic responses. It is crucial to distinguish these states to understand the molecular pathogenesis of these lymphomas. Ultimately, better tools to understand the heterogeneity of these cancers will support more efficacious therapies in the future.
Animal, fungi, and plant genome sequences harbour different non-canonical splice sites
Authors: Frey Katharina , Pucker Boas
Published: April 2019

Most protein encoding genes in eukaryotes contain introns which are interwoven with exons. After transcription, introns need to be removed in order to generate the final mRNA which can be translated into an amino acid sequence. Precise excision of introns by the spliceosome requires conserved dinucleotides which mark the splice sites. However, there are variations of the highly conserved combination of GT at the 5’ end and AG at the 3’ end of an intron in the genome. GC-AG and AT-AC are two major non-canonical splice site combinations which have been known for years. During the last years, various minor non-canonical splice site combinations were detected with numerous dinucleotide permutations. Here we expand systematic investigations of non-canonical splice site combinations in plants to all eukaryotes by analysing fungal and animal genome sequences. Comparisons of splice site combinations between these three kingdoms revealed several differences such as a substantially increased CT-AC frequency in fungal genome sequences. Canonical GT-AG splice site combinations in antisense transcripts could be one explanation for this observation. In addition, high numbers of GA-AG splice site combinations were observed in Eurytemora affinis and Oikopleura dioica. A variant in one U1 snRNA isoform might allow the recognition of GA as 5’ splice site. In depth investigation of splice site usage based on RNA-Seq read mappings indicates a generally higher flexibility of the 3’ splice site compared to the 5’ splice site across animals, fungi, and plants.
Invasive species-driven trophic cascades: Are cane toads indirectly contributing to small mammal collapses across tropical Australia?
Authors: Radford Ian James , Woolley Leigh-Ann , Dickman Chris R. , Corey Ben , Trembath Dane , Fairman Richard
Published: April 2019

Apex predators are fundamentally important in regulating many ecosystems, and perturbations of their populations are frequently implicated in ecosystem declines or collapses. In considering small mammal declines in northern Australia, most attention has focused on interactions between a mammalian apex predator—the dingoCanis dingo—and a meso-predator, the feral cat—Felis catus. Little consideration has been given to the possible implications of changed reptilian predator assemblages resulting from invasion by a toxic anuran invader, the cane toad (Rhinella marina), on small mammals. We used reptile removal records from licenced reptile catchers in three widely spaced towns in the savannas of northern Australia to explore potential impacts of toads on apex and meso-predatory snakes and large lizards. In addition, simultaneous fauna survey data from one town with reptile removal records, coinciding with toad invasion, were used to identify cascading impacts through the savanna ecosystem. Intervention analyses revealed empirical linkages between toad invasion, apex predator declines, meso-predator increases and declines of small mammals and other prey groups. Based on the timing and strength of intervention we postulate a novel conceptual model linking recent mammal declines with trophic cascades following toad invasion, where the loss of large, anurophagous (toad-eating) reptilian apex predators allowed increases in mammal-eating meso-predatory snakes. The conceptual model is discussed in relation to prevailing hypotheses regarding northern Australia’s dramatic small mammal declines. Future studies will need to quantify these putative interactions and test their comparative importance so that appropriate management can be implemented to stem the ongoing losses of mammal fauna.
Rapid and highly sensitive detection of pyocyanin biomarker in differentPseudomonas aeruginosainfections using gold nanoparticles modified sensor
Authors: Elkhawaga Amal A. , Khalifa Marwa M. , El-badawy Omnia H.B. , Hassan Mona A. , El-Said Waleed A.
Published: April 2019

Successful antibiotic treatment of infections relies on accurate and rapid identification of the infectious agents.Pseudomonas aeruginosais implicated in a wide range of human infections that almost complicated and become life threating especially in immunocompromised and critically ill patients. Conventional microbiological methods take more than 3 days to obtain accurate results. Pyocyanin is a distinctive electroactive biomarker forPseudomonas aeruginosa. Here, we have developed a rapid diagnostic (polyaniline) PANI gold nanoparticles (Au NPs) modified indium tin oxide (ITO) electrode that showed 100% sensitivity for pyocyanin in culture ofPseudomonas aeruginosaclinical isolates and high selectivity for pyocyanin at low concentration when measured in the presence of other substances like ascorbic acid, uric acid, and glucose as interferences. The constructed electrode was characterized using scanning electron microscopy and cyclic voltammetry. The determined linear range for pyocyanin detection was from 238 µM to 1.9 µM with a detection limit of 500 nM. Compared to the screen-printed electrode used before, the constructed electrode showed a 4-fold enhanced performance.
Monitoring soil microorganisms with community-level physiological profiles using Biolog EcoPlates™ in Chaohu lakeside wetland, east China
Authors: Teng Zhen , Fan Wei , Wang Huiling , Cao Xiaoqing , Xu Xiaoniu
Published: April 2019

Under the circumstance of wetland degradation, we used Biolog EcoPlates™ method to investigate the impact of ecological restoration on the function of topsoil microbial communities by monitoring their metabolic diversity around Chaohu lakeside wetland. Four restoration patterns including reed shoaly land (RL), poplar plantation land (PL), abandoned shoaly grassland (GL) and cultivated flower land (FL) were selected. The result showed a rapid growth trend at the initial stage of incubation, following the fastest change rate at 72 h in both dormant and growing seasons, and the AWCD values of RL pattern was the highest at the detection points of each culture time, while the GL were the lowest. The calculation of diversity indicators also displayed significant lower McIntosh index in dormant season and Shannon-Wiener index in growing season in GL than in the others (P < 0.05). Carbohydrates and carboxylic acids were found to be the dominant substrates used in dormant season, whereas amino acids, polymers and phenolic acids were increasingly utilized by the microbial communities in growing season. We observed soil total potassium as the key factor that significantly affected the utilization efficiency of different carbon sources in both seasons (P < 0.05).
Beta-binomial modeling of CRISPR pooled screen data identifies target genes with greater sensitivity and fewer false negatives
Authors: Jeong Hyun-Hwan , Kim Seon Young , Rousseaux Maxime W.C. , Zoghbi Huda Y. , Liu Zhandong
Published: April 2019

The simplicity and cost-effectiveness of CRISPR technology have made high-throughput pooled screening approaches accessible to virtually any laboratory. Analyzing the large sequencing data derived from these studies, however, still demands considerable bioinformatics expertise. Various methods have been developed to lessen this requirement, but there are still three tasks for accurate CRISPR screen analysis that involve bioinformatic know-how, if not prowess: designing a proper statistical hypothesis test for robust target identification, developing an accurate mapping algorithm to quantify sgRNA levels, and minimizing the parameters that need to be fine-tuned. To make CRISPR screen analysis more reliable as well as more readily accessible, we have developed a new algorithm, called CRISPRBetaBinomial or CB2. Based on the beta-binomial distribution, which is better suited to sgRNA data, CB2 outperforms the eight most commonly used methods (HiTSelect, MAGeCK, PBNPA, PinAPL-Py, RIGER, RSA, ScreenBEAM, and sgRSEA) in both accurately quantifying sgRNAs and identifying target genes, with greater sensitivity and a much lower false discovery rate. It also accommodates staggered sgRNA sequences. In conjunction with CRISPRcloud, CB2 brings CRISPR screen analysis within reach for a wider community of researchers.
Probing the spatial coherence of wide X-ray beams with Fresnel mirrors at BL25SU of SPring-8
Authors: Takeo Yoko , Motoyama Hiroto , Senba Yasunori , Kishimoto Hikaru , Ohashi Haruhiko , Mimura Hidekazu
Published: April 2019

Probing the spatial coherence of X-rays has become increasingly important when designing advanced optical systems for beamlines at synchrotron radiation sources and free-electron lasers. Double-slit experiments at various slit widths are a typical method of quantitatively measuring the spatial coherence over a wide wavelength range including the X-ray region. However, this method cannot be used for the analysis of spatial coherence when the two evaluation points are separated by a large distance of the order of millimetres owing to the extremely narrow spacing between the interference fringes. A Fresnel-mirror-based optical system can produce interference patterns by crossing two beams from two small mirrors separated in the transverse direction to the X-ray beam. The fringe spacing can be controlled via the incidence angles on the mirrors. In this study, a Fresnel-mirror-based optical system was constructed at the soft X-ray beamline (BL25SU) of SPring-8. The relationship between the coherence and size of the virtual source was quantitatively measured at 300 eV in both the vertical and horizontal directions using the beam. The results obtained indicate that this is a valuable method for the optimization of optical systems along beamlines.
Crystal structure and Hirshfeld surface analysis of (E)-3-[(4-fluorobenzylidene)amino]-5-phenylthiazolidin-2-iminium bromide
Authors: Khalilov Ali N. , Atioğlu Zeliha , Akkurt Mehmet , Duruskari Gulnara Sh. , Toze Flavien A. A. , Huseynova Afet T.
Published: April 2019

In the cation of the title salt, C16H15FN3S+·Br−, the phenyl ring is disordered over two sets of sites with a refined occupancy ratio of 0.503 (4):0.497 (4). The mean plane of the thiazolidine ring makes dihedral angles of 13.51 (14), 48.6 (3) and 76.5 (3)° with the fluorophenyl ring and the major- and minor-disorder components of the phenyl ring, respectively. The central thiazolidine ring adopts an envelope conformation. In the crystal, centrosymmetrically related cations and anions are linked into dimeric units via N—H...Br hydrogen bonds, which are further connected by weak C—H...Br hydrogen bonds into chains parallel to [110]. Hirshfeld surface analysis and two-dimensional fingerprint plots indicate that the most important contributions to the crystal packing are from H...H (44.3%), Br...H/H...Br (16.8%), C...H/H...C (13.9%), F...H/H...F (10.3%) and S...H/H...S (3.8%) interactions.
Economic and technical feasibility studies: technologies for second generation biofuels
Authors: Mungodla Sarah Gabashwediwe , Linganiso Linda Zikhona , Mlambo Sukoluhle , Motaung Tshwafo
Published: April 2019

Purpose

In 2008, a number of Southern African countries cultivated about 900,000 ha of Jatropha, with a number of biodiesel plants ready for production; however, none of the projects succeeded. In 2014, KiOR advanced biofuel Energy Company in the USA announced bankruptcy due to incompetent technology. Studies disclose that the reasons for biofuel plants failure are not only due to lack of incentives and unclear policies but also due to lack of economic feasibility and low production yields. This paper aims to review the techno-economy assessment of second-generation biofuel technologies. The purpose of this paper is to summarize specific techno-economic indicators such as production cost, technology efficiency and process life cycle analysis for advanced biofuel technology and to narrate and illustrate a clear view of what requires assessment to deploy a feasible advanced biofuel technology. This study also reviews assessment of biomass supply chain, feedstock availability and site selection criteria. The review also elaborates on the use of different processes, forecasting and simulation-modeling tools used in different techno-economic analysis studies. The review provides guidance for conducting a technical and economic feasibility study for the advanced biofuels energy business.

Design/methodology/approach

The aim of this review is, therefore, to evaluate the techno-economic feasibility studies for the establishment of viable industrial scale production of second-generation biofuels. It does so by grouping studies based on technology selection, feedstock availability and suitability, process simulation and economies as well as technology environmental impact assessment.

Findings

In conclusion, techno-economic analysis tools offer researchers insight in terms of where their research and development should focus, to attain the most significant enhancement for the economics of a technology. The study patterns within the scope of techno-economics of advanced biofuel reveal that there is no generic answer as to which technology would be feasible at a commercial scale. It is therefore important to keep in mind that models can only simplify and give a simulation of reality to a certain extent. Nevertheless, reviewed studies do not reach the same results, but some results are logically similar.

Originality/value

The originality of this article specifically illustrates important technical and economic indicators that should be considered when conducting feasibility studies for advance biofuels.