bluuebunny/crossref_metadata_2025_split huggingface dataset:
Population genomics of the facultatively asexual duckweedSpirodela polyrhiza
Authors: Ho Eddie , Bartkowska Magdalena , Wright Stephen I. , Agrawal Aneil 
Published: March 2019

SummaryClonal propagation allows some plant species to achieve massive population sizes quickly but also reduces the evolutionary independence of different sites in the genome.We examine genome-wide genetic diversity inSpirodela polyrhiza, a duckweed that reproduces primarily asexually.We find that this geographically widespread and numerically abundant species has very low levels of genetic diversity. Diversity at nonsynonymous sites relative to synonymous sites is high, suggesting that purifying selection is weak. A potential explanation for this observation is that a very low frequency of sex renders selection in effective. However, there is a pronounced decay in linkage disequilibrium over 40 kb, suggesting that though sex may be rare at the individual level it is not too infrequent at the population level. In addition, neutral diversity is affected by the physical proximity of selected sites, which would be unexpected if sex was exceedingly rare at the population level.The amount of genetic mixing as assessed by the decay in linkage disequilibrium is not dissimilar from selfing species such asArabidopsis thaliana, yet selection appears to be much less effective in duckweed. We discuss alternative explanations for the signature of weak purifying selection.
Differential N-end rule degradation of RIN4/NOI fragments generated by the AvrRpt2 effector protease
Authors: Goslin Kevin , Eschen-Lippold Lennart , Naumann Christin , Linster Eric , Sorel Maud , Klecker Maria , Marchi Rémi de , Kind Anne , Wirtz Markus , Lee Justin , Dissmeyer Nico , Graciet Emmanuelle 
Published: March 2019

AbstractThe protein RPM1-INTERACTING PROTEIN4 (RIN4) is a central regulator of both layers of plant immunity systems, the so-called pattern-triggered immunity (PTI) and effector-triggered immunity (ETI). RIN4 is targeted by several effectors, including thePseudomonas syringaeprotease effector AvrRpt2. Cleavage of RIN4 by AvrRpt2 generates unstable RIN4 fragments, whose degradation leads to the activation of the resistance protein RPS2 (RESISTANT TO P. SYRINGAE2). Hence, identifying the determinants of RIN4 degradation is key to understanding RPS2-mediated ETI, as well as virulence functions of AvrRpt2. In addition to RIN4, AvrRpt2 cleaves host proteins from the nitrate-induced (NOI) domain family. Although cleavage of NOI-domain proteins by AvrRpt2 may contribute to PTI regulation, the (in)stability of these proteolytic fragments and the determinants that regulate their stability have not been examined. Notably, a common feature of RIN4 and of many NOI-domain protein fragments generated by AvrRpt2 cleavage is the exposure of a new N-terminal residue that is destabilizing according to the N-end rule. Using antibodies raised against endogenous RIN4, we show that the destabilization of AvrRpt2-cleaved RIN4 fragments is independent of the N-end rule pathway (recently renamed N-degron pathway). By contrast, several NOI-domain protein fragments arebona fidesubstrates of the N-degron pathway. The discovery of this novel set of substrates considerably expands the number of proteins targeted for degradation by this ubiquitin-dependent pathway, for which very few physiological substrates are known in plants. Our results also open new avenues of research to understand the role of AvrRpt2 in promoting bacterial virulence.One sentence summaryAnalysis of RIN4/NOI fragments released after cleavage by the bacterial effector protease AvrRpt2 reveals a novel role of the N-end rule in the degradation of NOI-domain proteins, but not of RIN4.
ITGA2is a target of miR-206 promoting cancer stemness and lung metastasis through enhancedACLYandCCND1expression in triple negative breast cancer
Authors: Adorno-Cruz Valery , Hoffmann Andrew D. , Liu Xia , Wray Brian , Keri Ruth A. , Liu Huiping 
Published: March 2019

AbstractAccumulating evidence demonstrates that cancer stemness is essential for both tumor development and progression, regulated by multi-layer factors at genetic, epigenetic and micro-environmental levels. However, how to target stemness-driven plasticity and eliminate metastasis remains one of the biggest challenges in the clinic. We aim to identify novel molecular mechanisms underlying stemness of triple negative breast cancer (TNBC) which frequently metastasizes to the visceral organs but lacks targeted therapies. Following our previous discovery of miR-206 as an epigenetic suppressor of tumorigenesis and metastasis, we now report that the integrin receptor CD49b-encodingITGA2is an oncogenic target of miR-206 in TNBC.ITGA2knockdown abolished cancer stemness (mammosphere formation, pluripotency marker expression, and FAK phosphorylation), inhibited cell cycling, compromised migration and invasion, and thereby decreasing lung metastasis of TNBC. RNA sequencing analyses of breast cancer cells revealed thatITGA2knockdown inhibits gene expression essential for both classical integrin-regulated pathways (cell cycle, wounding response, protein kinase, etc) and newly identified pathways such as lipid metabolism. Notably,ACLY-encoded ATP citrate lyase is one of the top targets in CD49b-regulated lipid metabolism andCCND1-encoded Cyclin D1 represents regulation of cell cycle and many other pathways. ACLY, known to catalyze the formation of cytosolic acetyl-CoA for fatty acid biosynthesis, is indispensable for cancer stemness. Overexpression ofCCND1rescues the phenotype ofITGA2knockdown-induced cell cycle arrest. High expression levels of theITGA2/ACLY/CCND1axis are correlated with an unfavorable relapse-free survival of patients with high grade breast cancer, in both basal-like and other subtypes. This study identifiesITGA2as a potential therapeutic target of TNBC stemness and metastasis.
Making plants into cost-effective bioreactors for highly active antimicrobial peptides
Authors: Ghidey Meron R , Islam S M Ashiqul , Pruett Grace , Kearney Christopher Michel 
Published: March 2019

AbstractAs antibiotic-resistant bacterial pathogens become an ever-increasing concern, antimicrobial peptides (AMPs) have grown increasingly attractive as alternatives. Potentially, plants could be used as cost-effective AMP bioreactors; however, reported heterologous AMP expression is much lower in plants compared toE. coliexpression systems and often results in plant cytotoxicity, even for AMPs fused to carrier proteins. We wondered if there were a physical factor that made heterologous AMPs difficult to express in plants. Using a meta-analysis of protein databases, we determined that native plant AMPs were significantly less cationic than AMPs native to other taxa. To apply this finding to plant expression, we tested the transient expression of 10 different heterologous AMPs, ranging in charge from +7 to −5, in the the tobacco,Nicotiana benthamiana. We first tested several carrier proteins and were able to express AMPs only with elastin-like polypeptide (ELP). Conveniently, ELP fusion allows for a simple, cost-effective temperature shift purification. Using the ELP system, all five anionic AMPs expressed well, with two at unusually high levels (375 and 563 µg/gfw). Furthermore, antimicrobial activity againstStaphylococcus epidermidiswas an order of magnitude stronger (average MIC = 0.26 µM) than that typically seen for AMPs expressed inE. coliexpression systems. Unexpectedly, this high level of antimicrobial activity was associated with the uncleaved fusion peptide. In contrast, all previous reports of AMPs expressed in both plant andE. coliexpression systems show cleavage from the fusion partner to be required before activity is seen. In summary, we describe a means of expressing AMP fusions in plants in high yield, purified with a simple temperature-shift protocol, resulting in a fusion peptide with high antimicrobial activity, without the need for a peptide cleavage step.
The Distributed Engram
Authors: Feldesh Ran 
Published: March 2019

AbstractNeural connectionism is a common theoretical abstraction of biological neural networks (1–3) and a basis for common artificial neural networks (4). Yet, it is clear that connectionism abstracts out much of the biological phenomena significant and necessary for many cognitive-driven behaviors, in particular intra-neuronal and inter-neuronal biochemical processes (5–8). This paper presents a model which adds an abstraction of these processes to a standard connectionism-based model. Specifically, a sub-system determines the synaptic weights. The resulting network has plastic synapses during non-learning-related behavior, in sharp contrast with most common models in which synapses are fixed outside of a learning-phase. Some synapses introduce plasticity that is causally related with behavior, while in others the plasticity randomly fluctuates, in correspondence with recent data (9,10). In this model the memory engram is distributed over the biochemical system, in addition to the synapses. The model yields better performance in memory-related tasks compared to a standard recurrent neural network trained with backpropagation.
Whole genome base-wise aggregation and functional prediction for human non-coding regulatory variants
Authors: Zhang Shijie , He Yukun , Liu Huanhuan , Zhai Haoyu , Huang Dandan , Yi Xianfu , Dong Xiaobao , Wang Zhao , Zhao Ke , Zhou Yao , Wang Jianhua , Yao Hongcheng , Xu Hang , Yang Zhenglu , Sham Pak Chung , Chen Kexin , Li Mulin Jun 
Published: March 2019

ABSTRACTPredicting the functional or pathogenic regulatory variants in the human non-coding genome facilitates the interpretation of disease causation. While numerous prediction methods are available, their performance is inconsistent or restricted to specific tasks, which raises the demand of developing comprehensive integration for those methods. Here, we compile whole genome base-wise aggregations, regBase, that incorporate largest prediction scores. Building on different assumptions of causality, we train three composite models to score functional, pathogenic and cancer driver non-coding regulatory variants respectively. We demonstrate the superior and stable performance of our models using independent benchmarks and show great success to fine-map causal regulatory variants. We believe that regBase database together with three composite models will be useful in different areas of human genetic studies, such as annotation-based casual variant fine-mapping, pathogenic variant discovery as well as cancer driver mutation identification. regBase is freely available athttps://github.com/mulinlab/regBase.
Reconstructing the evolutionary history of a functionally diverse gene family reveals complexity at the genetic origins of novelty
Authors: Koludarov Ivan , Jackson Timothy NW , Suranse Vivek , Pozzi Andrea , Sunagar Kartik , Mikheyev Alexander S 
Published: March 2019

AbstractGene duplication is associated with the evolution of many novel biological functions at the molecular level. The dominant view, often referred to as “neofunctionalization”, states that duplications precede many novel gene functions by creating functionally redundant copies which are less constrained than singletons. However, numerous alternative models have been formulated, including some in which novel functions emerge prior to duplication. Unfortunately, few studies have reconstructed the evolutionary history of a functionally diverse gene family sufficiently well to differentiate between these models. Here we examined the evolution of the g2 family of phospholipase A2 (EC 3.1.1.4) in the genomes of 93 species from all major lineages of Vertebrata. This family is evolutionarily important and has been co-opted for a diverse range of functions, including innate immunity and venom. The genomic region in which this family is located is remarkably syntenic. This allowed us to reconstruct all duplication events over hundreds of millions of years of evolutionary history using manual annotation of gene clusters, which enabled the discovery of a large number of previously un-annotated genes. Intriguingly, we found that the same ancestral gene in the phospholipase gene cluster independently acquired novel molecular functions in birds, mammals and snake, and all subsequent expansion of the cluster originates from this locus. This suggests that the locus has a deep ancestral propensity for multiplication, likely conferred by a structural arrangement of genomic material (i.e. the “genomic context” of the locus) that dates back at least the amniote MRCA. These results highlight the underlying complexity of gene family evolution, as well as the historical- and context-dependence of gene family evolution.Graphical abstract
Engineering strategy and vector library for the rapid generation of modular light-controlled protein-protein interactions
Authors: Tichy Alexandra-Madelaine , Gerrard Elliot J. , Legrand Julien M.D. , Hobbs Robin M. , Janovjak Harald 
Published: March 2019

ABSTRACTOptogenetics enables the spatio-temporally precise control of cell and animal behaviour. Many optogenetic tools are driven by light-controlled protein-protein-interactions (PPIs) that are repurposed from natural light-sensitive domains (LSDs). Applying light-controlled PPI to new target proteins is challenging because it is difficult to predict whether one the many available LSDs will yield robust light regulation. As a consequence, fusion protein libraries need to be prepared and tested, but methods and platforms to facilitate this process are currently not available. Here, we developed a genetic engineering strategy and vector library for the rapid generation of light-controlled PPIs. The strategy permits fusing a target protein to LSDs efficiently and in two orientations. The public and expandable library contains 29 vectors with blue, green or red light-responsive LSDs many of which have been previously appliedex vivoandin vivo.We demonstrate the versatility of the approach and the necessity for sampling LSDs by generating light-activated caspase-9 (casp9) enzymes. Collectively, this work provides a new resource for optical regulation of a broad range of target proteins in cell and developmental biology.
Efferocytosis perpetuates substance accumulation inside macrophage populations
Authors: Ford Hugh Z. , Zeboudj Lynda , Purvis Gareth S. D. , ten Bokum Annemieke , Zarebski Alexander E. , Bull Joshua A. , Byrne Helen M. , Myerscough Mary R. , Greaves David R. 
Published: March 2019

AbstractIn both cells and animals, cannibalism can transfer harmful substances from the consumed to the consumer. Macrophages are immune cells that consume their own dead via a process called cannibalistic efferocytosis. Macrophages that contain harmful substances are found at sites of chronic inflammation, yet the role of cannibalism in this context remains unexplored. Here we take mathematical and experimental approaches to study the relationship between cannibalistic efferocytosis and substance accumulation in macrophages. Through mathematical modelling, we deduce that substances which transfer between individuals through cannibalism will concentrate inside the population via a coalescence process. This prediction was confirmed for macrophage populations inside a closed system. We used image analysis of whole slide photomicrographs to measure both latex microbead and neutral lipid accumulation inside murine bone marrow-derived macrophages (104 – 105 cells) following their stimulation into an inflammatory state ex vivo. While the total number of phagocytosed beads remained constant, cell death reduced cell numbers and efferocytosis concentrated the beads among the surviving macrophages. Since lipids are also conserved during efferocytosis, these cells accumulated lipid derived from the membranes of dead and consumed macrophages (becoming macrophage foam cells). Consequently, enhanced macrophage cell death increased the rate and extent foam cell formation. Our results demonstrate that cannibalistic efferocytosis perpetuates exogenous (e.g. beads) and endogenous (e.g. lipids) substance accumulation inside macrophage populations. As such, cannibalism has similar detrimental consequences in both cells and animals.
Interleukin-17 and senescence regulate the foreign body response
Authors: Chung Liam , Maestas David , Lebid Andriana , Mageau Ashlie , Rosson Gedge D. , Wu Xinqun , Wolf Matthew T , Tam Ada , Vanderzee Isabel , Wang Xiaokun , Andorko James I , Narain Radhika , Sadtler Kaitlyn , Fan Hongni , Čiháková Daniela , Le Saux Claude Jourdan , Housseau Franck , Pardoll Drew M , Elisseeff Jennifer H. 
Published: March 2019

AbstractSynthetic biomaterials and medical devices suffer to varying levels from fibrosis via the foreign body response (FBR). To explore mechanistic connections between the immune response and fibrosis from the FBR, we first analyzed fibrotic capsule surrounding human breast implants and found increased numbers of interleukin (IL)17-producing γδ+T cells and CD4+TH17 cells as well as senescent cells. Further analysis in a murine model demonstrated an early innate IL17 response to synthetic implants, mediated by innate lymphoid cells and γδ+T cells, was followed by a chronic adaptive antigen dependent CD4+TH17 cell response. Mice deficient in IL17 signaling established that IL17 was required for the fibrotic response to materials and the development of p16INK4asenescent cells. Treatment with a senolytic agent reduced IL17 expression and fibrosis. Discovery of a feed-forward loop between the TH17 and senescence response to synthetic materials introduces new targets for therapeutic intervention in the foreign body response.
Disaster communication
Authors: Mason Alicia , Flores Lynzee , Liu Pan , Tims Kenzie , Spencer Elizabeth , Gire T. Gabby 
Published: March 2019

PurposeThe purpose of this paper is to understand the crisis communication strategies used by the Caribbean medical tourism industry in the 2017 hurricane season, and also evaluate the quality of the disaster communication messages delivered via digital mediums.Design/methodology/approachThis study includes a comprehensive, qualitative content analysis of 149 risk and crisis messages from 51 healthcare organizations distributed through digital media. The medical tourism providers (MTPs) include hospitals, medical tourism facilitators, practitioners/private physicians, specialty clinics, and dental and cosmetic providers.FindingsNearly half of the MTPs included in the data set delivered no post-disaster information to external audiences. The most prominent post-disaster message strategy utilized was conveying operational messages. Furthermore, an unexpected finding was the sheer magnitude of unrelated health-oriented and promotional destination marketing content disseminated before, during and after these events.Research limitations/implicationsThis analysis excludes internal organizational channels of communication which may have been used to communicate risk and crisis messages during these events (i.e. employee e-mails, announcements made through intercom systems, etc.). Our analysis does not include content disseminated through medical tourism forums (i.e. Realself.com, Health Traveler’s Forum, FlyerTalk Forum).Practical implicationsSmall-scale MTPs can improve on any weaknesses through proactive planning and preparation by creating organizational goals to complete basic crisis communication training courses and in doing so support the applied professional development of disaster and crisis responders in the Caribbean region. Second, MTPs exposed to similar risks of natural disasters may use these findings for comparative analysis purposes to support their own organizational planning. Finally, this study supports the continued utility of the National Center for Food Protection & Defense guidelines for analyzing and evaluating organizational performance.Originality/valueCurrently much of the academic scholarship of applied disaster communication narrowly focuses on the response strategies of one organization, or analyzes one social media platform at a time (i.e. Twitter). A strength of this analysis is the inclusion of an organizational sector (i.e. Caribbean medical tourism providers) and the range of platforms from which the content was captured (e.g. websites, org. blogs and social media networks).
MHD free convection flow of power-law nanofluid film along an inclined surface with viscous dissipation and joule heating
Authors: B. Vasu 
Published: March 2019

Purpose
The purpose of this study is to present the magnetohydrodynamic (MHD) flow and heat transfer in an accelerating film of a non-Newtonian pseudo-plastic nanofluid along an inclined surface with viscous dissipation and Joule heating.

Design/methodology/approach
An incompressible and inelastic fluid is assumed to obey the Ostwald-de-Waele power law model and the action of viscous stresses is conﬁned to the developing momentum boundary layer adjacent to the solid surface. Viscous dissipation and Joule heating on the flow of electrically conducting film in the presence of uniform transverse magnetic field is considered for the Carboxyl Methyl Cellulose (CMC) water-based nanofluid. The fluid is the CMC-water-based with concentration (0.1-0.4 per cent) containing three types of nano-solid particles Cu, Al2O3 and TiO2. The modeled boundary layer conservation equations are transformed to dimensionless, coupled and highly non-linear system of differential equations, and then solved numerically by means of a local non-similarity approach with shooting technique. To validate the numerical results, a comparison of the present results is made with the earlier published results and is found to be in good agreement.

Findings
The effects of magnetic parameter, Prandtl number, Eckert number and Biot numbers on the velocity and temperature fields are presented graphically and discussed for various values of thermo-physical parameters. It has been found that magnetic field decelerates the fluid velocity for both cases of Newtonian nanofluid and pseudo-plastic nanofluid because of the generated drag-like Lorentz force. This is of great benefit in magnetic materials processing operations, utilizing static transverse uniform magnetic field, as it allows a strong regulation of the flow field.

Research limitations/implications
The numerical study is valid for two-dimensional, steady, laminar film flow of Ostwald-de-Waele power law non-Newtonian nanofluid along an inclined plate. A uniform transverse magnetic field of strength B0 is applied perpendicular to the wall. Assume that the base fluid and the nano-solid particles are in thermal equilibrium with no slip effects. The interaction of magnetic field with nanofluid has several potential implications and may be used to deal with the problems such as cooling nuclear reactors by liquid sodium and inducting the flow meter which depends on the potential difference in the fluid along the direction perpendicular to the motion and to the magnetic field.

Practical implications
The study has significant applications in magnetic field control of materials processing systems.

Originality/value
The results of the present study may be attentiveness to the engineers and applied mathematicians who are interested in hydrodynamics and heat transfer enhancement associated with film flows.