bluuebunny/crossref_metadata_2025 huggingface dataset:
Community-identified recommendations to enhance cancer survivorship for Aboriginal and Torres Strait Islander people
Authors: Meiklejohn Judith A. , Arley Brian , Bailie Ross , Adams Jon , Garvey Gail , Martin Jennifer H. , Walpole Euan T. , Valery Patricia C.
Published: May 2018

Indigenous Australians diagnosed with cancer experience higher mortality and lower survival rates compared to non-Indigenous Australians. Reasons are multifaceted and complex. Knowledge about Indigenous cancer survivors’ perspectives of positive cancer survivorship is a gap in research evidence. The study explored cancer survivorship perspectives of Indigenous cancer survivors, their support people and healthcare workers with a view to developing recommendations for cancer survivorship. Indigenous Australians who completed cancer treatment in the previous 6 months to 5 years, their support people and primary healthcare workers were recruited from primary healthcare centres and a large tertiary Queensland hospital. Semi-structured interviews and focus groups were conducted with written and informed consent obtained prior. Participants emphasised key action areas and recommendations to enhance cancer survivorship, namely: establishing a community cancer advocate and peer support program, availability and use of a cancer-specific Indigenous primary healthcare worker and hospital-based Indigenous patient navigator, as well as adoption of question prompt lists and cancer survivorship care plans. Existing research suggests significant benefits from implementing the key recommendations identified in this study. Greater support and commitment across health sectors and funding bodies is needed to promote institutional change and health system development.
Nicolaus Clenardus’Institutiones grammaticae Latinae(1538)
Authors: Swiggers Pierre
Published: May 2018

In 1538 the Flemish humanist language scholar Nicolaus Clenardus (1493–1542) published a grammar of Latin in Braga (Portugal), theInstitutiones grammaticae Latinae. The grammar, the fruit of his public teaching in Braga, was the third in a series of grammars written by Clenardus: while active in Louvain (until 1531) he had published grammars of Hebrew (1529) and of Greek (1530). Clenardus’ Latin grammar is basically a didactic grammar, closely linked to his teaching in Portugal, for which he introduced an innovative methodology. It essentially consists of a morphological and syntactic part, followed by a series of mostly syntactic remarks and by a survey of principles of prosody and versification. Clenardus’ exposition is marked by a strong focus on formal markings (lists of nominal and verbal endings), and by the extensive integration of lexical information into the grammatical frame. Clenardus generally refrains from giving definitions of terms and concepts, and theoretical explanations are eschewed in favour of empirical exemplification. TheInstitutiones grammaticae Latinaeprovides its users with a large amount of examples, the majority of which stem from colloquial humanist Latin usage, but there are also various examples taken from classical Latin authors.
“Our Chief Political Editor reads between the lines of the Chancellor’s Budget speech”
Authors: Fetzer Anita
Published: May 2018

This paper examines the multilayeredness of computer-mediated political discourse, focussing on the interdependencies between the contextual constraints and requirements of the medium on the one hand, and contextualisation, indexicality of communicative action and conversational implicature on the other. Particular attention is given to implicit and entextualised references to differences between what is said and what is meant in the communicative act of follow-up, to the importation of context and provision of background information, to their function with respect to the interactional organisation of (non)credibility and argumentative (non)coherence, and to the co-construction of discourse common ground. Within the context of computer-mediated political discourse, these references are used strategically to accommodate the contextual constraints and requirements of a multilayered reception format and their multilayered felicity conditions, and to support speaker-intended interpretation of multilayered discourse on the production side.
Commenting on in-memoriam columns
Authors: Weizman Elda
Published: May 2018

The discussion in this paper proposes to shed light on a hitherto under-researched area: commenting on in-memoriam columns. Borrowing the basic notions of deliberative and epidictic genres from classical rhetoric and accommodating them to a pragmatic study of online interaction between commenters and columnists, readers’ comments are conceived as follow-ups, which necessarily re-contextualize the initiating column. The mixed character of the initiating columns, which combine deliberative and epidictic features, encourages the commenters to choose between different readings of the columns in context, and exercise their discursive power in re-contextualizing the commenting/column interaction. The analysis suggests that in the data discussed here, commenters manifest clear preference for the epidictic. By so doing, they depart from norms of deliberation manifest in habitual political commenting. On a more general level, the analysis supports the initial claim, namely that by choosing between different readings of the initiating columns and following-up on them, commenters have the discursive power to shape and re-shape the interaction through preferred commenting strategies.
A chimeric mutant analysis in yeast cells suggests BiP independent regulation of the mammalian endoplasmic reticulum-stress sensor IRE1α
Authors: Mai Thanh Chi , Munakata Takeo , Tran Duc Minh , Takagi Hiroshi , Kimata Yukio
Published: May 2018

An endoplasmic reticulum (ER)-located transmembrane protein, Ire1, triggers cytoprotective events upon ER stress. Chimeric yeast Ire1 carrying the luminal domain of the mammalian major Ire1 paralogue IRE1α is upregulated in ER-stressed yeast cells, but is poorly associated with the ER-located chaperone BiP even under non-stressed conditions. This observation contradicts the theory that BiP is the master regulator of IRE1α.
Body mass changes during training in elite rugby union: Is a single test of hydration indices reliable?
Authors: Black Katherine Elizabeth , Black Alistair David , Baker Dane , Fairbairn Kirsty
Published: May 2018

There is limited research studying fluid and electrolyte balance in rugby union players, and a paucity of information regarding the test–retest reliability. This study describes the fluid balance of elite rugby union players across multiple squads and the reliability of fluid balance measures between two equivalent training sessions. Sixty‐one elite rugby players completed a single fluid balance testing session during a game simulation training session. A subsample of 21 players completed a second fluid balance testing session during an equivalent training session. Players were weighed in minimal clothing before and after each training session. Each player was provided with their own drinks which were weighed before and after each training session. More players gained body weight (9 (14.8%)) during training than lost greater than 2% of their initial body mass (1 (1.6%)). Pre‐training body mass and rate of fluid loss were significantly associated (r = 0.318, p = .013). There was a significant correlation between rate of fluid loss in sessions 1 (1.74 ± 0.32 L h−1) and 2 (1.10 ± 0.31 L. h−1), (r = 0.470, p = .032). This could be useful for nutritionists working with rugby squads to identify players with high sweat losses.
Endothelial Differentiated Adipose-Derived Stem Cells Improvement of Survival and Neovascularization in Fat Transplantation
Authors: Harris William M , Plastini Michael , Kappy Nikolas , Ortiz Telisha , Chang Shaohua , Brown Spencer , Carpenter Jeffrey P , Zhang Ping
Published: May 2018

Background

Adipose-derived stem cells (ASCs) assisted lipotransfer have been considered to facilitate the survival of fat grafts. However, emerging evidence of insufficient vascularization is another obstacle for fat graft survival in cell-assisted lipotransfer.

Objectives

This study evaluated if endothelial phenotype ASCs with fat lipoaspirate improves survival and neovascularization in fat transplantation

Methods

ASCs were isolated from human periumbilical fat tissue and cultured in endothelial growth medium for 2 weeks. Fat lipoaspirate was mixed with fresh adipose stroma vascular fraction (SVF), endothelial differentiated ASCs (EC/ASCs), and fat lipoaspirate alone. Three fat mixtures were subcutaneously injected into the adult male Sprague–Dawley rat’s dorsum at 3 locations. At 8 weeks after transplantation, the grafted fat lipoaspirates were harvested, and the extracted fat was evaluated using photographic, survival weights measurements and histological examination. Neo-vascularization was quantified by immunofluorescence and real-time RT-PCR.

Results

Grafts from the EC/ASC assisted group had a higher survival rate, morphologic integrity, and most uniform lipid droplets. They also revealed less inflammation and fibrosis with increased number of vessels by histological and immunofluorescence analysis. Quantitative RT-PCR analysis indicated that the expression levels of EC-specific markers of CD31 and vWF were higher in the EC/ASC group compared with in the control and fat with SVF transplants.

Conclusions

These results indicated that co-implantation of fat lipoaspirate with ASCs differentiated toward an endothelial phenotype improves both survival and neovascularization of the transplanted fat lipoaspirate, which might provide benefits and represents a promising strategy for clinical application in autologous fat transplantation.
Enhancing Facelift With Simultaneous Submalar Implant Augmentation
Authors: Delaney Sean , Kridel Russell W H
Published: May 2018

Background

The midface is particularly prone to the senescent changes of soft tissue ptosis and volume loss, which in individuals with aging or low adiposity can manifest as submalar hollowing. Facelift alone in those with submalar hollowing inadequately addresses the volume loss and may result in a gaunt appearance postoperatively. Submalar implant augmentation is a powerful tool for permanent midface volume restoration for a more youthful and natural contour, as opposed to soft tissue fillers that diminish over time. When performed together, submalar augmentation and facelift synergistically enhance facial rejuvenation results.

Objectives

Determine the long-term safety and efficacy of submalar implant augmentation as an adjunct to facelift.

Methods

Retrospective review evaluating results and complications in all consecutive patients who had submalar implant augmentation with SMAS-plication facelift in a single surgeon private practice setting from January 1, 1991, to December 31, 2017.

Results

Forty-eight patients underwent submalar augmentation with simultaneous facelift with an overall satisfaction rate of 95.7%. Complications included 2.1%transient infraorbital hypoesthesia, 1.1% prolonged swelling, and 1.1% capsular contraction that required a minor adjustment under local anesthesia. No infection, implant migration, or extrusion or facial nerve injury occurred.

Conclusions

Submalar implant augmentation is a safe and effective means of enhancing facelift results through midface volume restoration, subperiosteal release, and improved soft tissue suspension in a more favorable vector. Submalar implant augmentation performed simultaneously with facelift may be an attractive alternative to repeated soft tissue filler or fat injections for patients with submalar hollowing who are interested in facial rejuvenation surgery.
DeepMirTar: a deep-learning approach for predicting human miRNA targets
Authors: Wen Ming , Cong Peisheng , Zhang Zhimin , Lu Hongmei , Li Tonghua
Published: May 2018

Motivation

MicroRNAs (miRNAs) are small non-coding RNAs that function in RNA silencing and post-transcriptional regulation of gene expression by targeting messenger RNAs (mRNAs). Because the underlying mechanisms associated with miRNA binding to mRNA are not fully understood, a major challenge of miRNA studies involves the identification of miRNA-target sites on mRNA. In silico prediction of miRNA-target sites can expedite costly and time-consuming experimental work by providing the most promising miRNA-target-site candidates.

Results

In this study, we reported the design and implementation of DeepMirTar, a deep-learning-based approach for accurately predicting human miRNA targets at the site level. The predicted miRNA-target sites are those having canonical or non-canonical seed, and features, including high-level expert-designed, low-level expert-designed and raw-data-level, were used to represent the miRNA-target site. Comparison with other state-of-the-art machine-learning methods and existing miRNA-target-prediction tools indicated that DeepMirTar improved overall predictive performance.

Availability and implementation

DeepMirTar is freely available at https://github.com/Bjoux2/DeepMirTar_SdA.

Supplementary information

Supplementary data are available at Bioinformatics online.
Bochner-type Formulas for the Weyl Tensor on Four-dimensional Einstein Manifolds
Authors: Catino Giovanni , Mastrolia Paolo
Published: May 2018

The very definition of an Einstein metric implies that all its geometry is encoded in the Weyl tensor. With this in mind, in this paper we derive higher-order Bochner-type formulas for the Weyl tensor on a four-dimensional Einstein manifold. In particular, we prove a 2nd Bochner-type formula that, formally, extends to the covariant derivative level the classical one for the Weyl tensor obtained by Derdziński in 1983. As a consequence, we deduce new integral identities involving the Weyl tensor and its derivatives on a compact four-dimensional Einstein manifold and we derive a new rigidity result.
Operational locality in global theories
Authors: Krämer Lea , del Rio Lídia
Published: May 2018

Within a global physical theory, a notion of locality allows us to find and justify information-processing primitives, like non-signalling between distant agents. Here, we propose exploring the opposite direction: to take agents as the basic building blocks through which we test a physical theory, and recover operational notions of locality from signalling conditions. First, we introduce an operational model for the effective state spaces of individual agents, as well as the range of their actions. We then formulate natural secrecy conditions between agents and identify the aspects of locality relevant for signalling. We discuss the possibility of taking commutation of transformations as a primitive of physical theories, as well as applications to quantum theory and generalized probability frameworks. This ‘it from bit’ approach establishes an operational connection between local actions and local observations, and gives a global interpretation to concepts like discarding a subsystem or composing local functions.

This article is part of a discussion meeting issue ‘Foundations of quantum mechanics and their impact on contemporary society’.
What is quantum in quantum randomness?
Authors: Grangier P. , Auffèves A.
Published: May 2018

It is often said that quantum and classical randomness are of different nature, the former being ontological and the latter epistemological. However, so far the question of ‘What is quantum in quantum randomness?’, i.e. what is the impact of quantization and discreteness on the nature of randomness, remains to be answered. In a first part, we make explicit the differences between quantum and classical randomness within a recently proposed ontology for quantum mechanics based on contextual objectivity. In this view, quantum randomness is the result of contextuality and quantization. We show that this approach strongly impacts the purposes of quantum theory as well as its areas of application. In particular, it challenges current programmes inspired by classical reductionism, aiming at the emergence of the classical world from a large number of quantum systems. In a second part, we analyse quantum physics and thermodynamics as theories of randomness, unveiling their mutual influences. We finally consider new technological applications of quantum randomness that have opened up in the emerging field of quantum thermodynamics.

This article is part of a discussion meeting issue ‘Foundations of quantum mechanics and their impact on contemporary society’.
The small stellated dodecahedron code and friends
Authors: Conrad J. , Chamberland C. , Breuckmann N. P. , Terhal B. M.
Published: May 2018

We explore a distance-3 homological CSS quantum code, namely the small stellated dodecahedron code, for dense storage of quantum information and we compare its performance with the distance-3 surface code. The data and ancilla qubits of the small stellated dodecahedron code can be located on the edges respectively vertices of a small stellated dodecahedron, making this code suitable for three-dimensional connectivity. This code encodes eight logical qubits into 30 physical qubits (plus 22 ancilla qubits for parity check measurements) in contrast with one logical qubit into nine physical qubits (plus eight ancilla qubits) for the surface code. We develop fault-tolerant parity check circuits and a decoder for this code, allowing us to numerically assess the circuit-based pseudo-threshold.

This article is part of a discussion meeting issue ‘Foundations of quantum mechanics and their impact on contemporary society’.
Quantum information versus black hole physics: deep firewalls from narrow assumptions
Authors: Braunstein Samuel L. , Pirandola Stefano
Published: May 2018

The prevalent view that evaporating black holes should simply be smaller black holes has been challenged by the firewall paradox. In particular, this paradox suggests that something different occurs once a black hole has evaporated to one-half its original surface area. Here, we derive variations of the firewall paradox by tracking the thermodynamic entropy within a black hole across its entire lifetime and extend it even to anti-de Sitter space–times. Our approach sweeps away many unnecessary assumptions, allowing us to demonstrate a paradox exists even
after
its initial onset (when conventional assumptions render earlier analyses invalid). The most natural resolution may be to accept firewalls as a real phenomenon. Further, the vast entropy accumulated implies a
deep firewall
that goes ‘all the way down’ in contrast with earlier work describing only a structure at the horizon.

This article is part of a discussion meeting issue ‘Foundations of quantum mechanics and their impact on contemporary society’.
Quantum reference frames and their applications to thermodynamics
Authors: Popescu Sandu , Sainz Ana Belén , Short Anthony J. , Winter Andreas
Published: May 2018

We construct a quantum reference frame, which can be used to approximately implement arbitrary unitary transformations on a system in the presence of any number of extensive conserved quantities, by absorbing any back action provided by the conservation laws. Thus, the reference frame at the same time acts as a battery for the conserved quantities. Our construction features a physically intuitive, clear and implementation-friendly realization. Indeed, the reference system is composed of the same types of subsystems as the original system and is finite for any desired accuracy. In addition, the interaction with the reference frame can be broken down into two-body terms coupling the system to one of the reference frame subsystems at a time. We apply this construction to quantum thermodynamic set-ups with multiple, possibly non-commuting conserved quantities, which allows for the definition of explicit batteries in such cases.

This article is part of a discussion meeting issue ‘Foundations of quantum mechanics and their impact on contemporary society’.
Machine characterization of rat toxin responses identifies disease states, tolerance mechanisms and organ to whole-body communication
Authors: Shimada Kenichi , Mitchison Timothy J.
Published: May 2018

Background

Living organisms are constantly exposed to toxic xenobiotics and have therefore evolved protective responses. In mammals, the liver and kidney play central roles in protecting the organism from xenobiotics, and are at high risk of xenobiotic-induced injury. Liver and kidney damage by drugs and industrial toxins have been extensively studied from both classical histopathologic and biochemical perspectives.

Methods and Findings

We introduce a machine learning approach for the analysis of toxicological response. Unsupervised characterization of physiological and histological changes in a large toxicogenomic dataset revealed nine discrete toxin-induced disease states. Transcriptome analysis showed that some of the machine-identified disease states correspond to known pathology, and to known effects of certain toxin classes, but others were novel. Analysis of dynamics revealed transitions between disease states at constant toxin exposure, mostly in the direction of decreased pathology, which implies induction of tolerance. Tolerance correlated with induction of known xenobiotic defense genes and novel decreased ferroptosis sensitivity biomarkers. These data reinforce emerging evidence that ferroptosis drives organ pathology, and suggest that its downreagulation may promote tolerance and recovery. Lastly, mechanism of body weight decrease, a known primary marker for toxicity, was investigated. Combined analysis of food consumption, body weight, and molecular biomarkers indicated that organ disease states promote cachexia by whole-body signaling through Gdf15 and Igf1, suggesting strategies for therapeutic intervention that may be broadly relevant to human disease.

Conclusions

Application of machine learning to systematic data collection of physiology, histopathology, transcriptome reveals multiple disease states, tolerance mechanisms and organ to whole-body communication.
Physiological predictors of reproductive performance in the European Starling (Sturnus vulgaris): II. Multivariate Analysis
Authors: Cohen Alan A. , Paquet Mélissa , Fowler Melinda A. , Legault Véronique , Williams Tony D.
Published: May 2018

Physiological variation is generally thought or supposed to underlie variation in fitness related traits in wild animals, including reproductive effort, reproductive success, and survival. However, physiological markers of individual quality have proven elusive. In this paper and its companion, we use data on 14 physiological parameters measured in 152 observations of 93 individual European starlings (Sturnus vulgaris) over 2 years in an attempt to understand how physiological variation relates to variation in current breeding productivity, future fecundity, and survival. The companion paper, focusing on univariate analysis, showed that individual physiological parameters have little relationship with these performance measures. Here, we used more sophisticated statistical approaches in an attempt to extract a multivariate signal from the biomarkers – physiological dysregulation as calculated via statistical distance, and a number of principal components analysis approaches. Broadly speaking, there was a surprising lack of association between physiology and performance: while some physiological summary measures were associated with some performance measures, the associations were not particularly strong or robust given the large number of statistical tests conducted. This implies either that there are relatively few links between physiology and performance, or, more likely, that the complexity of these relationships exceeds our ability to measure and model it, even using state-of-the-art statistical approaches. This is likely particularly true because our population was quite heterogeneous; we nonetheless urge caution regarding the over-interpretation of isolated significant findings in the literature.
EROS is required for phagocyte NADPH oxidase function in humans and its deficiency causes Chronic Granulomatous Disease
Authors: Thomas David C. , Charbonnier Louis-Marie , Schejtman Andrea , Aldhekri Hasan , Coomber Eve , Dufficy Elizabeth R. , Beenken Anne E. , Lee James C. , Clare Simon , Speak Annaliese O. , Thrasher Adrian J. , Santilli Giorgia , Al-Mousa Hamoud , Alkuraya Fowzan S. , Chatila Talal A. , Smith Kenneth G.C.
Published: May 2018

The phagocyte respiratory burst is mediated by the phagocyte NADPH oxidase, a multi-protein subunit complex that facilitates production of reactive oxygen species and which is essential for host defence. Monogenic deficiency of individual subunits leads to chronic granulomatous disease (CGD), which is characterized by an inability to make reactive oxygen species, leading to severe opportunistic infections and auto-inflammation. However, not all cases of CGD are due to mutations in previously identified subunits. We recently showed that Eros, a novel and highly conserved ER-resident transmembrane protein, is essential for the phagocyte respiratory burst in mice because it is required for expression of gp91phox-p22phox heterodimer, which are the membrane bound components of the phagocyte NADPH oxidase. We now show that the function of EROS is conserved in human cells and describe a case of CGD secondary to a homozygous EROS mutation that abolishes EROS protein expression. This work demonstrates the fundamental importance of EROS in human immunity and describes a novel cause of CGD.

Clinical Implications

Chronic granulomatous disease is caused by an inability to make reactive oxygen species via the phagocyte NADPH oxidase. Mutations in C17ORF62/EROS, which controls gp91phox- p22phox abundance, are a novel cause of chronic granulomatous disease.

Key Messages

The murine gene, Eros, is known to regulate abundance of gp91phox-p22phox heterodimer and Eros deficient mice are susceptible to infection

We show that the function of EROS is conserved in human cells and that a homozygous mutation in EROS causes chronic granulomatous disease
Identifying Plasmids in Bacterial Genome Assemblies
Authors: Hall Barry G.
Published: May 2018

Despite their importance to bacterial pathogenesis, plasmids are rarely identified in incomplete genome sequences. The free FindPlasmids (FP) package for Windows, Mac OS X, and Linux facilitates identification of plasmids in incomplete genome sequences. FP found plasmids in 98.8% of complete genomes in which they were present, correctly identifying plasmids ranging in number from 1 to 10 plasmids. In a sample of 50 E. coli genome assemblies it has identified from zero to three plasmids ranging in size from 1,549 to 133,843 bp and present in 42% of the assemblies examined.
Effective Variations of related Physicochemical Properties of Nucleotides Leading to Amino Acids for Characterizing Genes and Proteins
Authors: Sengupta Antara , Choudhury Pabitra Pal
Published: May 2018

The aim of this paper is to make quantitative analysis of the properties which is really being carried from DNA sequence and finally landing up to the properties of a protein structure through its primary protein sequence. Thus, the paper has a theory which is applicable for any arbitrary DNA sequence whether it is of various species or mutated data or a bunch of genes responsible for a function to be occurred. Irrespective to genes of any families, species, wild type or mutated, our paper here gives a standard model which defines a mapping between physicochemical properties of any arbitrary DNA sequence and physicochemical properties of its amino acid sequence. Experiments have been carried out with PPCA protein family and its four homologs PPC(B E) which establishes that DNA sequence keeps its signature even after its translation into the corresponding amino acid sequence.
Dynamic control of proinflammatory cytokines Il-1β and Tnf-α by macrophages is necessary for functional spinal cord regeneration in zebrafish
Authors: Tsarouchas Themistoklis M. , Wehner Daniel , Cavone Leonardo , Munir Tahimina , Keatinge Marcus , Lambertus Marvin , Underhill Anna , Barrett Thomas , Kassapis Elias , Ogryzko Nikolay , Feng Yi , van Ham Tjakko J. , Becker Thomas , Becker Catherina G.
Published: May 2018

Spinal cord injury leads to a massive response of innate immune cells (microglia, macrophages, neutrophils) both, in non-regenerating mammals and in successfully regenerating zebrafish, but the role of these immune cells in functional spinal cord regeneration in zebrafish has not been addressed. Here we show that inhibiting inflammation reduces and promoting it accelerates axonal regeneration in larval zebrafish. Mutant analyses show that peripheral macrophages, but not neutrophils or microglia, are necessary and sufficient for full regeneration. Macrophage-lessirf8mutants show prolonged inflammation with elevated levels of Il-1β and Tnf-α. Decreasing Il-1β levels or number of Il-1β+neutrophils rescues functional regeneration inirf8mutants. However, during early regeneration, interference with Il-1β function impairs regeneration inirf8and wildtype animals. Inhibiting Tnf-α does not rescue axonal growth inirf8mutants, but impairs it in wildtype animals, indicating a pro-regenerative role of Tnf-α. Hence, inflammation is tightly and dynamically controlled by macrophages to promote functional spinal cord regeneration in zebrafish.
Exploiting Index Cross-Talk to Modify Variant Calls
Authors: Ney Peter M. , Organick Lee , Koscher Karl , Kohno Tadayoshi , Ceze Luis
Published: May 2018

Modern next-generation DNA sequencers support multiplex sequencing to improve throughput and decrease costs. This is done by pooling and sequencing samples together in parallel, which are later demultiplexed according to their unique indexes1, 2. When reads are assigned to the wrong index, called index cross-talk, information is leaked between samples3–6. This creates a physical information side-channel, a well known class of vulnerabilities in information security7–10, that may be used to modify downstream results. Here we demonstrate the feasibility of such an attack through the use of a separately indexed library that causes a wild-type human exome to be misclassified as heterozygous at the sickle-cell locus. Simple methods can be used to minimize or detect attempts to modify genetic variants using this side-channel, such as filtering by read quality or finding outliers in read coverage. To further minimize this risk we recommend the use of new library preparation methods that reduce index cross-talk, like unique dual indexes11, 12, whenever samples are sequenced together in important applications. Biotechnology that interfaces molecular and digital information, like DNA sequencers, may have security risks typically associated with information systems, including the side-channel vulnerability described in this study. We encourage the community to consider the security of genomics-information pipelines before they reach mass adoption.
Myosin-driven fragmentation of actin filaments triggers contraction of a disordered actin network
Authors: Matsuda Kyohei , Kobayashi Takuya , Sugawa Mitsuhiro , Koiso Yurika , Toyoshima Yoko Y. , Yajima Junichiro
Published: May 2018

The dynamic cytoskeletal network is responsible for cell shape changes and cell division. The actin-based motor protein myosin II drives the remodeling of a highly disordered actin-based network and enables the network to perform mechanical work such as contraction, migration and adhesion. Myosin II forms bipolar filaments that self-associate via their tail domains. Such myosin minifilaments generate both extensile and compressive forces that pull and push actin filaments, depending on the relative position of myosin and actin filaments in the network. However, it remains unclear how the mechanical properties of myosin II that rely on the energy of ATP hydrolysis spontaneously contract the disordered actin network. Here, we used a minimal in vitro reconstituted experimental system consisting of actin, myosin, and a cross-linking protein, to gain insights into the molecular mechanism by which myosin minifilaments organize disordered actin networks into contractile states. We found that contracted cluster size and time required for the onset of network contraction decreased as ATP concentration decreased. Contraction velocity was negatively correlated with ATP concentrations. Reduction of ATP concentration caused fragmentation of actin filaments by myosin minifilament. We also found that gelsolin, a Ca2+-regulated actin filament-severing protein, induced contraction of a mechanically stable network, implying that fragmentations of actin filaments in the network weaken the intra-network connectivity and trigger contraction. Our findings reveal that the disordered actin network contraction can be controlled by fragmentation of actin filaments, highlighting the molecular mechanism underlying the myosin motor-severing activities, other than the sliding tensile and compressive stress in the disordered actin network.
Focusing quorum sensing signalling by nano‐magnetic assembly
Authors: Guan Yongguang , Tsao Chen‐Yu , Quan David N. , Li Ying , Mei Lei , Song Yingying , Zhang Boce , Liu Yi , Payne Gregory F. , Bentley William E. , Wang Qin
Published: May 2018

Quorum sensing (QS) exists widely among bacteria, enabling a transition to multicellular behaviour after bacterial populations reach a particular density. The coordination of multicellularity enables biotechnological application, dissolution of biofilms, coordination of virulence, and so forth. Here, a method to elicit and subsequently disperse multicellular behaviour among QS‐negative cells is developed using magnetic nanoparticle assembly. We fabricated magnetic nanoparticles (MNPs, ∼5 nm) that electrostatically collect wild‐type (WT) Escherichia coli BL21 cells and brings them into proximity of bioengineered E. coli [CT104 (W3110 lsrFG− luxS− pCT6 + pET‐DsRed)] reporter cells that exhibit a QS response after receiving autoinducer‐2 (AI‐2). By shortening the distance between WT and reporter cells (e.g., increasing local available AI‐2 concentrations), the QS response signalling was amplified four‐fold compared to that in native conditions without assembly. This study suggests potential applications in facilitating intercellular communication and modulating multicellular behaviours based on user‐specified designs.
Bloom of a denitrifying methanotroph, ‘Candidatus Methylomirabilis limnetica’, in a deep stratified lake
Authors: Graf Jon S. , Mayr Magdalena J. , Marchant Hannah K. , Tienken Daniela , Hach Philipp F. , Brand Andreas , Schubert Carsten J. , Kuypers Marcel M. M. , Milucka Jana
Published: May 2018

Methanotrophic bacteria represent an important biological filter regulating methane emissions into the atmosphere. Planktonic methanotrophic communities in freshwater lakes are typically dominated by aerobic gamma‐proteobacteria, with a contribution from alpha‐proteobacterial methanotrophs and the NC10 bacteria. The NC10 clade encompasses methanotrophs related to ‘Candidatus Methylomirabilis oxyfera’, which oxidize methane using a unique pathway of denitrification that tentatively produces N2 and O2 from nitric oxide (NO). Here, we describe a new species of the NC10 clade, ‘Ca. Methylomirabilis limnetica’, which dominated the planktonic microbial community in the anoxic depths of the deep stratified Lake Zug in two consecutive years, comprising up to 27% of the total bacterial population. Gene transcripts assigned to ‘Ca. M. limnetica’ constituted up to one third of all metatranscriptomic sequences in situ. The reconstructed genome encoded a complete pathway for methane oxidation, and an incomplete denitrification pathway, including two putative nitric oxide dismutase genes. The genome of ‘Ca. M. limnetica’ exhibited features possibly related to genome streamlining (i.e. less redundancy of key metabolic genes) and adaptation to its planktonic habitat (i.e. gas vesicle genes). We speculate that ‘Ca. M. limnetica’ temporarily bloomed in the lake during non‐steady‐state conditions suggesting a niche for NC10 bacteria in the lacustrine methane and nitrogen cycle.
Political support among winners and losers: Within‐ and between‐country effects of structure, process and performance in Europe
Authors: MARTINI SERGIO , QUARANTA MARIO
Published: May 2018

Why is the winner‐loser gap in political support wider in some countries and narrower in others? Previous studies have focused on how the input side of political systems (i.e., the institutional structure) affects the winner‐loser gap. This study suggests that one should also consider the output side (i.e., the quality of political process and economic performance) and posits that two mechanisms – rational and psychological – can explain how output factors affect the gap. Going beyond previous research, this article also considers whether contextual characteristics explain the variation in the gap not only between countries, but also within them. Applying mixed models to survey data from 30 European countries between 2002 and 2015, the study finds that the differences in support between winners and losers across countries are smaller in consensual systems, as in these contexts the support among losers is higher. However, changes in the institutional structure do not explain the over‐time variation in the winner‐loser gap. Moreover, increasing quality of process and economic performance do not attenuate the gap across countries and over time, as they affect positively the political support of both winners and losers. The study shows which contextual factors explain the winner‐loser gap and points to the conditions that increase losers’ consent, which is a crucial element of democratic legitimacy.
Social stress shortens lifespan in mice
Authors: Razzoli Maria , Nyuyki‐Dufe Kewir , Gurney Allison , Erickson Connor , McCallum Jacob , Spielman Nicholas , Marzullo Marta , Patricelli Jessica , Kurata Morito , Pope Emily A. , Touma Chadi , Palme Rupert , Largaespada David A. , Allison David B. , Bartolomucci Alessandro
Published: May 2018

Stress and low socioeconomic status in humans confer increased vulnerability to morbidity and mortality. However, this association is not mechanistically understood nor has its causation been explored in animal models thus far. Recently, cellular senescence has been suggested as a potential mechanism linking lifelong stress to age‐related diseases and shorter life expectancy in humans. Here, we established a causal role for lifelong social stress on shortening lifespan and increasing the risk of cardiovascular disease in mice. Specifically, we developed a lifelong chronic psychosocial stress model in which male mouse aggressive behavior is used to study the impact of negative social confrontations on healthspan and lifespan. C57BL/6J mice identified through unbiased cluster analysis for receiving high while exhibiting low aggression, or identified as subordinate based on an ethologic criterion, had lower median and maximal lifespan, and developed earlier onset of several organ pathologies in the presence of a cellular senescence signature. Critically, subordinate mice developed spontaneous early‐stage atherosclerotic lesions of the aortic sinuses characterized by significant immune cells infiltration and sporadic rupture and calcification, none of which was found in dominant subjects. In conclusion, we present here the first rodent model to study and mechanistically dissect the impact of chronic stress on lifespan and disease of aging. These data highlight a conserved role for social stress and low social status on shortening lifespan and increasing the risk of cardiovascular disease in mammals and identify a potential mechanistic link for this complex phenomenon.
Probiotic supplementation improves reproductive performance of unvaccinated farmed sows infected with porcine epidemic diarrhea virus
Authors: Tsukahara Takamitsu , Inatomi Takio , Otomaru Konosuke , Amatatsu Masaaki , Romero‐Pérez Gustavo A. , Inoue Ryo
Published: May 2018

We investigated if probiotic supplementation could improve the health and reproductive performance of unvaccinated lactating sows infected with porcine epidemic diarrhea (PED) virus. Twenty unvaccinated pregnant sows were equally allocated to probiotic‐supplemented (P) and control (C) groups. For the experiment, 15 g/day of probiotic compound BIO‐THREE PZ was given to P sows. Reproductive performance was checked daily. The number of neonates fostered by each sow was maintained at eight throughout the experiment. Individual milk production post‐parturition was measured twice. Milk protein and fat ratios were determined by a milk analyzer. Total immunoglobulin (Ig) A and G concentrations were measured by ELISA. At day 7 post‐parturition, the body weight of P sows was 10 kg higher than that of C sows, and at day 3 post‐parturition, P sows produced more milk (+2 kg) and had a higher IgA concentration in whey than did C sows (p < .05). Finally, unlike C sows, P sows tended to return to estrus faster, and had larger piglets at birth with a lower mortality percentage during early days of suckling. In conclusion, probiotic compound BIO‐THREE PZ helped strengthen the immune system of unvaccinated, PED‐infected sows and improved their reproductive performance.
Symbolic play promotes non‐verbal communicative exchange in infant–caregiver dyads
Authors: Quinn Sara , Kidd Evan
Published: May 2018

Symbolic play has long been considered a fertile context for communicative development (Bruner, 1983, Child's talk: Learning to use language, Oxford University Press, Oxford; Vygotsky, 1962, Thought and language, MIT Press, Cambridge, MA; Vygotsky, 1978, Mind in society: The development of higher psychological processes. Harvard University Press, Cambridge, MA). In the current study, we examined caregiver–infant interaction during symbolic play and compared it to interaction in a comparable but non‐symbolic context (i.e., ‘functional’ play). Fifty‐four (N = 54) caregivers and their 18‐month‐old infants were observed engaging in 20 min of play (symbolic, functional). Play interactions were coded and compared across play conditions for joint attention (JA) and gesture use. Compared with functional play, symbolic play was characterized by greater frequency and duration of JA and greater gesture use, particularly the use of iconic gestures with an object in hand. The results suggest that symbolic play provides a rich context for the exchange and negotiation of meaning, and thus may contribute to the development of important skills underlying communicative development.

Statement of contribution

Current knowledge

Symbolic play has long been linked to communicative development.

We do not know the extent to which the social context of symbolic play fosters communicative skills.

Present study

We test whether key communicative acts (joint attention, gesture) are more common in infant–caregiver dyads during symbolic versus functional play.

Joint attention was established more often and sustained for longer periods in symbolic play than in functional play.

Infants and caregivers produced more in‐hand representational gestures in symbolic compared to functional play.
A systematic review and meta‐analysis of the impact of lymphovascular invasion in bladder cancer transurethral resection specimens
Authors: Mari Andrea , Kimura Shoji , Foerster Beat , Abufaraj Mohammad , D'Andrea David , Hassler Melanie , Minervini Andrea , Rouprêt Morgan , Babjuk Marko , Shariat Shahrokh F.
Published: May 2018

The aim of the present review was to assess the prognostic impact of lymphovascular invasion (LVI) in transurethral resection (TUR) of bladder cancer (BCa) specimens on clinical outcomes. A systematic review and meta‐analysis of the available literature from the past 10 years was performed using MEDLINE, EMBASE and Cochrane library in August 2017. The protocol for this systematic review was registered on PROSPERO (Central Registration Depository: CRD42018084876) and is available in full on the University of York website. Overall, 33 studies (including 6194 patients) evaluating the presence of LVI at TUR were retrieved. LVI was detected in 17.3% of TUR specimens. In 19 studies, including 2941 patients with ≤cT1 stage only, LVI was detected in 15% of specimens. In patients with ≤cT1 stage, LVI at TUR of the bladder tumour (TURBT) was a significant prognostic factor for disease recurrence (pooled hazard ratio [HR] 1.97, 95% CI: 1.47–2.62) and progression (pooled HR 2.95, 95% CI: 2.11–4.13), without heterogeneity (I2 = 0.0%, P = 0.84 and I2 = 0.0%, P = 0.93, respectively). For patients with cT1–2 disease, LVI was significantly associated with upstaging at time of radical cystectomy (pooled odds ratio 2.39, 95% CI: 1.45–3.96), with heterogeneity among studies (I2 = 53.6%, P = 0.044). LVI at TURBT is a robust prognostic factor of disease recurrence and progression in non‐muscle invasive BCa. Furthermore, LVI has a strong impact on upstaging in patients with organ‐confined disease. The assessment of LVI should be standardized, reported, and considered for inclusion in the TNM classification system, helping clinicians in decision‐making and patient counselling.
Early to middle Holocene palaeoenvironmental reconstruction of the Beagle Channel (southernmost Argentina) based on terrestrial and marine palynomorphs
Authors: Candel María Soledad , Borromei Ana M. , Louwye Stephen
Published: May 2018

This paper presents the main palaeoenvironmental results obtained from a site located in the western sector of the Beagle Channel, Isla Grande de Tierra del Fuego, southernmost Argentina. The palynological analysis performed on marine sediments from Aserradero‐Lapataia 2 (latitude 54°51′22.7″S, longitude 68°34′22.8″W) allowed us to document the evolution of palaeoenvironmental conditions during the beginning of the Holocene marine transgression into the Beagle Channel. The results indicate that, prior to the marine incursion, the coastal areas were characterized by the presence of open‐grown shrubs and herbs along with woodland palaeocommunities. The aquatic environments were dominated exclusively by freshwater taxa. Around 8300 cal. a BP, seawater gradually flooded the channel while cold and high effective moisture conditions favoured the development of an arboreal vegetation with dominance of Nothofagus forest and scarcity of shrub and herbaceous communities. Gradually increasing salinities allowed the development of freshwater/marine transitional environments indicated by aquatic palynomorphs able to tolerate stressed conditions under fluctuating salinities. The increasing dinocyst diversification with dominance of heterotrophic taxa corroborates the establishment of a fully marine environment during the middle–late Holocene in the Beagle Channel.