bluuebunny/crossref_metadata_2025 huggingface dataset:
Competing with barnacle cement: wetting resistance of a re-entrant surface reduces underwater adhesion of barnacles
Authors: Petersen Dennis S. , Kleinteich Thomas , Gorb Stanislav N. , Heepe Lars
Published: August 2018

Surfaces with re-entrant topographies can repel liquids even of extremely low surface tension, almost independently of the material's inherent wettability. We show that this topography-based wetting resistance can also be applied to underwater applications, reducing the permanent adhesion of marine hardfouling organisms. Having combined a biofouling assay in the marine environment with microscopic analyses, we demonstrate how a synergistic effect of a soft silicone-based material with a re-entrant mushroom-shaped surface topography strongly increases the fouling release ability of such coatings compared with a smooth control made from the same material. Our coating inhibited the complete wetting of the solidifying glues produced by marine organisms, which resulted in a decreased contact area and, consequently, low adhesion. Our work suggests that topography-induced wetting resistance of surfaces may become a viable approach in preventing permanent adhesion of marine hardfouling organisms.
Cross-sectional pinching in human femoropopliteal arteries due to limb flexion, and stent design optimization for maximum cross-sectional opening and minimum intramural stresses
Authors: Desyatova Anastasia , Poulson William , MacTaggart Jason , Maleckis Kaspars , Kamenskiy Alexey
Published: August 2018

High failure rates of femoropopliteal artery (FPA) interventions are often attributed to severe mechanical deformations that occur with limb flexion. One of these deformations, cross-sectional pinching, has a direct effect on blood flow, but is poorly characterized. Intra-arterial markers were deployed into
n
= 50
in situ
cadaveric FPAs (80 ± 12 years old, 14F/11M), and limbs were imaged in standing, walking, sitting and gardening postures. Image analysis was used to measure marker openings and calculate FPA pinching. Parametric finite element analysis on a stent section was used to determine the optimal combination of stent strut amplitude, thickness and the number of struts per section to maximize cross-sectional opening and minimize intramural mechanical stress and low wall shear stress. Pinching was higher distally and increased with increasing limb flexion. In the walking, sitting and gardening postures, it was 1.16–1.24, 1.17–1.26 and 1.19–1.35, respectively. Stent strut amplitude and thickness had strong effects on both intramural stresses and pinching. Stents with a strut amplitude of 3 mm, thickness of 175 µm and 20 struts per section produced pinching and intramural stresses typical for a non-stented FPA, while also minimizing low wall shear stress areas, and ensuring a stent lifespan of at least 10
7
cycles. These results can help guide the development of improved devices and materials to treat peripheral arterial disease.
Natural history values and meanings in nineteenth-century Chile
Authors: Schell Patience A.
Published: August 2018

In nineteenth-century Chile, naturalists and their supporters argued that scientific work and study, including natural history, were good for individuals and society because they developed and tempered the character of their practitioners. These practitioners and boosters, Chileans, European visitors and European immigrants, made this argument in a context in which Chilean state support for natural history institutions, publications and education helped disseminate scientific training, perspectives and practices. Examining this nineteenth-century discourse of beneficial science is important for three reasons: first, the discourse of value-laden sciences offered this field a powerful justification for its development, especially in the face of criticism; second, because naturalists believed in this discourse, it helps explain what their work meant to them, and, finally, these values highlight the disjuncture between discourses about natural history and its links to military conquests, as well as the ways in which natural history was an exclusionary practice.
John Wallis and the Catholics: confessional and theological antagonism in Wallis's mathematics and philosophy
Authors: Richter Adam D.
Published: August 2018

Like many of his contemporaries, the mathematician and Anglican minister John Wallis (1616–1703) repeatedly made disparaging remarks about Roman Catholics, particularly the pope and the Jesuits. This paper considers how Wallis's anti-Catholic attitude affected his reception of ideas about nature and mathematics. A well-known example is his resistance to the adoption of the Gregorian calendar in England, which he claimed would be an implicit acknowledgement of the pope's authority. This was not an isolated case in Wallis's career. For instance, the same attitude is evident in his earliest publication,
Truth Tried
(1643), wherein he adopts a position on the metaphysics of time and place that explicitly opposes the doctrine of transubstantiation. In addition, anti-Catholicism made Wallis more receptive to subjects that otherwise did not interest him, namely numerology and biblical prophecy. This helps to explain his decision to publish a Latin translation of Francis Potter's
Interpretation of the Number 666
(1642), which Wallis seems to have appreciated mainly because of its argument that the pope is the Antichrist. These cases offer insights about Wallis's motivations as a natural philosopher and mathematician, and how they relate to anti-Catholicism in early modern English science more generally.
A unified view of spatio-temporal control of mitotic entry: Polo kinase as the key
Authors: Pintard Lionel , Archambault Vincent
Published: August 2018

The Polo kinase is an essential regulator of cell division. Its ability to regulate multiple events at distinct subcellular locations and times during mitosis is remarkable. In the last few years, a much clearer mechanistic understanding of the functions and regulation of Polo in cell division has emerged. In this regard, the importance of coupling changes in activity with changes in localization is striking, both for Polo itself and for its upstream regulators. This review brings together several new pieces of the puzzle that are gradually revealing how Polo is regulated, in space and time, to enable its functions in the early stages of mitosis in animal cells. As a result, a unified view of how mitotic entry is spatio-temporally regulated is emerging.
Implicit and explicit influences of religious cognition on Dictator Game transfers
Authors: Billingsley Joseph , Gomes Cristina M. , McCullough Michael E.
Published: August 2018

Does religion promote prosocial behaviour? Despite numerous publications that seem to answer this question affirmatively, divergent results from recent meta-analyses and pre-registered replication efforts suggest that the issue is not yet settled. Uncertainty lingers around (i) whether the effects of religious cognition on prosocial behaviour were obtained through implicit cognitive processes, explicit cognitive processes or both and (ii) whether religious cognition increases generosity only among people disinclined to share with anonymous strangers. Here, we report two experiments designed to address these concerns. In Experiment 1, we sought to replicate Shariff and Norenzayan's demonstration of the effects of implicit religious priming on Dictator Game transfers to anonymous strangers; unlike Shariff and Norenzayan, however, we used an online environment where anonymity was virtually assured. In Experiment 2, we introduced a ‘taking’ option to allow greater expression of baseline selfishness. In both experiments, we sought to activate religious cognition implicitly and explicitly, and we investigated the possibility that religious priming depends on the extent to which subjects view God as a punishing, authoritarian figure. Results indicated that in both experiments, religious subjects transferred more money on average than did non-religious subjects. Bayesian analyses supported the null hypothesis that
implicit
religious priming did not increase Dictator Game transfers in either experiment, even among religious subjects. Collectively, the two experiments furnished support for a small but reliable effect of
explicit
priming, though among religious subjects only. Neither experiment supported the hypothesis that the effect of religious priming depends on viewing God as a punishing figure. Finally, in a meta-analysis of relevant studies, we found that the overall effect of implicit religious priming on Dictator Game transfers was small and did not statistically differ from zero.
Behaviourally mediated predation avoidance in penguin prey:in situevidence from animal-borne camera loggers
Authors: Handley Jonathan M. , Thiebault Andréa , Stanworth Andrew , Schutt David , Pistorius Pierre
Published: August 2018

Predator dietary studies often assume that diet is reflective of the diversity and relative abundance of their prey. This interpretation ignores species-specific behavioural adaptations in prey that could influence prey capture. Here, we develop and describe a scalable biologging protocol, using animal-borne camera loggers, to elucidate the factors influencing prey capture by a seabird, the gentoo penguin (Pygoscelis papua). From the video evidence, we show, to our knowledge for the first time, that aggressive behavioural defence mechanisms by prey can deter prey capture by a seabird. Furthermore, we provide evidence demonstrating that these birds, which were observed hunting solitarily, target prey when they are most discernible. Specifically, birds targeted prey primarily while ascending and when prey were not tightly clustered. In conclusion, we show that prey behaviour can significantly influence trophic coupling in marine systems because despite prey being present, it is not always targeted. Thus, these predator–prey relationships should be accounted for in studies using marine top predators as samplers of mid- to lower trophic-level species.
Characterization of biocarbon generated by high- and low-temperature pyrolysis of soy hulls and coffee chaff: for polymer composite applications
Authors: Quosai Peter , Anstey Andrew , Mohanty Amar K. , Misra Manjusri
Published: August 2018

The physical properties of biocarbon vary widely with the biomass used, and the temperature and duration of pyrolysis. This study identifies the effects of feedstock characteristics and pyrolysis conditions on the production of biocarbon and the corresponding properties for industrial applications. For coffee chaff and soy hulls, ash content and carbon content increased with pyrolysis temperature and duration. Ash content increased thermal conductivity and specific heat, and decreased electrical conductivity. Change in surface area with pyrolysis conditions was dependent on type of feedstock. Increased surface area corresponded with increased thermal and electrical conductivity. Increased carbon content corresponded with increased graphitization and thermal stability and decreased surface functionality. Properties of soy hull biocarbons were found to be similar to the properties of other biocarbons with industrial applications such as incorporation into polymer composites.
An experimental study on coflow diffusion combustion in a pellet-packed bed with different bed lengths
Authors: Shi Junrui , Liu Yang , Liu Yongqi , Mao Mingming , Xia Yongfang , Ma Rui , Xu Youning
Published: August 2018

In experimental investigations on axial symmetry, over-ventilated CH
4
/air diffusion combustion in a packed bed is executed to study the height, shape and stability of the flame. The combustor is a quartz tube packed with alumina pellets in which a cylindrical fuel stream is surrounded by a coflow air nozzle. The results show that the bed length and pellet diameter have a significant influence on the flame properties. In general, the flame above the pellet surface has axial symmetry, and its shape and colour are similar to those of a conventional diffusion flame when the bed length is smaller. The colour of the flame front varies with the bed length. The changed colour indicates an increased flame front temperature and that the combustion regime above the bed surface may change from non-premixed combustion to partially premixed combustion or even premixed combustion owing to the mix and dispersion effect in the packed bed. In addition, multiple flame behaviours, such as an inclined flame front, isolated reaction zone and oscillatory motion followed by a pulsating sound with a few hertz in a packed bed, are observed experimentally. The possible reasons for these phenomena are discussed.
Geomorphological evidence of large vertebrates interacting with the seafloor at abyssal depths in a region designated for deep-sea mining
Authors: Marsh Leigh , Huvenne Veerle A. I. , Jones Daniel O. B.
Published: August 2018

Exploration licences for seafloor mineral deposits have been granted across large areas of the world's oceans, with the abyssal Pacific Ocean being the primary target for polymetallic nodules—a potentially valuable source of minerals. These nodule-bearing areas support a large diversity of deep-sea life and although studies have begun to characterize the benthic fauna within the region, the ecological interactions between large bathypelagic vertebrates of the open ocean and the abyssal seafloor remain largely unknown. Here we report seafloor geomorphological alterations observed by an autonomous underwater vehicle that suggest large vertebrates could have interacted with the seafloor to a maximum depth of 4258 m in the recent geological past. Patterns of disturbance on the seafloor are broadly comparable to those recorded in other regions of the world's oceans attributed to beaked whales. These observations have important implications for baseline ecological assessments and the environmental management of potential future mining activities within this region of the Pacific.
Waterborne polyurethane as a carbon coating for micrometre-sized silicon-based lithium-ion battery anode material
Authors: Yan Chunfeng , Huang Tao , Zheng Xiangzhen , Gong Cuiran , Wu Maoxiang
Published: August 2018

Waterborne polyurethane (WPU) is first used as a carbon-coating source for micrometre-sized silicon. The remaining nitrogen (N) and oxygen (O) heteroatoms during pyrolysis of the WPU interact with the surface oxide on the silicon (Si) particles via hydrogen bonding (Si–OH⋯N and Si–OH⋯O). The N and O atoms involved in the carbon network can interact with the lithium ions, which is conducive to lithium-ion insertion. A satisfactory performance of the Si@N, O-doped carbon (Si@CNO) anode is gained at 25 and 55°C. The Si@CNO anode shows stable cycling performance (capacity retention of 70.0% over 100 cycles at 25°C and 60.3% over 90 cycles at 55°C with a current density of 500 mA g−1) and a superior rate capacity of 864.1 mA h g−1at 1000 mA g−1(25°C). The improved electrochemical performance of the Si@CNO electrode is attributed to the enhanced electrical conductivity and structural stability.
Global demographic history of human populations inferred from whole mitochondrial genomes
Authors: Miller Eleanor F. , Manica Andrea , Amos William
Published: August 2018

The Neolithic transition has led to marked increases in census population sizes across the world, as recorded by a rich archaeological record. However, previous attempts to detect such changes using genetic markers, especially mitochondrial DNA (mtDNA), have mostly been unsuccessful. We use complete mtDNA genomes from over 1700 individuals, from the 1000 Genomes Project Phase 3, to explore changes in populations sizes in five populations for each of four major geographical regions, using a sophisticated coalescent-based Bayesian method (extended Bayesian skyline plots) and mutation rates calibrated with ancient DNA. Despite the power and sophistication of our analysis, we fail to find size changes that correspond to the Neolithic transitions of the study populations. However, we do detect a number of size changes, which tend to be replicated in most populations within each region. These changes are mostly much older than the Neolithic transition and could reflect either population expansion or changes in population structure. Given the amount of migration and population mixing that occurred after these ancient signals were generated, we caution that modern populations will often carry ghost signals of demographic events that occurred far away from their current location.
Structural and temporal patterns of the first global trading market
Authors: Ribeiro Ana Sofia , Pinheiro Flávio L. , Santos Francisco C. , Polónia Amélia , Pacheco Jorge M.
Published: August 2018

Little is known about the structural patterns and dynamics of the first global trading market (FGTM), which emerged during the sixteenth century as a result of the Iberian expansion, let alone how it compares to today's global financial markets. Here we build a representative network of the FGTM using information contained in 8725 (handwritten) Bills of Exchange from that time—which were (human) interpreted and digitalized into an online database. We show that the resulting temporal network exhibits a hierarchical, highly clustered and disassortative structure, with a power-law dependence on the connectivity that remains remarkably robust throughout the entire period investigated. Temporal analysis shows that, despite major turnovers in the number and nature of the links—suggesting fast adaptation in response to the geopolitical and financial turmoil experienced at the time—the overall characteristics of the FGTM remain robust and virtually unchanged. The methodology developed here demonstrates the possibility of building and analysing complex trading and finance networks originating from pre-statistical eras, enabling us to highlight the striking similarities between the structural patterns of financial networks separated by centuries in time.
Assessing the accumulated stickiness magnitude from fabric–skin friction: effect of wetness level of various fabrics
Authors: Tang Ka-Po Maggie , Chau Kam-Hong , Kan Chi-Wai , Fan Jin-tu
Published: August 2018

Increasing skin wetness tends to increase fabric–skin adhesion and friction, resulting in wear discomfort or skin injuries. Here, the magnitude estimation approach was used to assess the stickiness sensation perceived in fabrics. Seven fabric types were wetted by putting onto wet ‘skin’ surface and dried for different durations to achieve different wetness levels, simulating wearing conditions during the recovery period after sweating. Results showed that the relationship between magnitude estimates of stickiness and amount of water present in fabric demonstrated a power function. The exponents and constant from power regression show the growth rate of stickiness sensation with moisture intensity and the perceived stickiness under fixed stimulus intensity, respectively. A novel parameter, accumulated stickiness magnitude (ASM), describing how much discomfort a wetted fabric offered throughout the drying period, was developed. Thin cotton fabrics (fabric W01 and W03), having higher saturation level after contacting with wetted skin surface, arouse stronger stickiness feeling and their ASM is remarkably higher. The difference in stickiness estimates is due to the difference in chemical composition and surface geometry. This study suggests us the way to predict perceived stickiness in fabrics with different wetness levels which is useful for applications like sportswear, intimate apparel or healthcare products.
Convenient fabrication of conjugated polymer semiconductor nanotubes and their application in organic electronics
Authors: Ma Lanchao , Dai Shuixing , Zhan Xiaowei , Liu Xinyang , Li Yu
Published: August 2018

Organic heterojunction is indispensable in organic electronic devices, such as organic solar cells, organic light-emitting diodes and so on. Fabrication of core–shell nanostructure provides a feasible and novel way to prepare organic heterojunction, which is beneficial for miniaturization and integration of organic electronic devices. Fabrication of nanotubes which constitute the core–shell structure in large quantity is the key for the realization of application. In this work, a simple and convenient method to prepare nanotubes using conjugated copolymer of perylene diimide and dithienothiophene (P(PDI-DTT)) was demonstrated. The relationship between preparation conditions (solvent atmosphere, solution concentration and pore diameter of templates) and morphology of nanostructure was studied systematically. P(PDI-DTT) nanotubes could be fabricated in regular shape and large quantity by preparing the solution with appropriate concentration and placing anodic aluminium oxide template with nanopore diameter of 200 nm in the solvent atmosphere. The tubular structure was confirmed by scanning electron microscopy. P(PDI-DTT) nanotubes exhibited electron mobility of 0.02 cm
2
V
–1
s
–1
in field-effect transistors under ambient condition. Light-emitting nanostructures were successfully fabricated by incorporating tetraphenylethylene into polymer nanotubes.
Host–pathogen coevolution in the presence of predators: fluctuating selection and ecological feedbacks
Authors: Best Alex
Published: August 2018

Host–pathogen coevolution is central to shaping natural communities and is the focus of much experimental and theoretical study. For tractability, the vast majority of studies assume the host and pathogen interact in isolation, yet in reality, they will form one part of complex communities, with predation likely to be a particularly key interaction. Here, I present, to my knowledge, the first theoretical study to assess the impact of predation on the coevolution of costly host resistance and pathogen transmission. I show that fluctuating selection is most likely when predators selectively prey upon infected hosts, but that saturating predation, owing to large handling times, dramatically restricts the potential for fluctuations. I also show how host evolution may drive either enemy to extinction, and demonstrate that while predation selects for low host resistance and high pathogen infectivity, ecological feedbacks mean this results in lower infection rates when predators are present. I emphasize the importance of accounting for varying population sizes, and place the models in the context of recent experimental studies.
White matter aberrations and age-related trajectories in patients with schizophrenia and bipolar disorder revealed by diffusion tensor imaging
Authors: Tønnesen Siren , Kaufmann Tobias , Doan Nhat Trung , Alnæs Dag , Córdova-Palomera Aldo , der Meer Dennis van , Rokicki Jaroslav , Moberget Torgeir , Gurholt Tiril P. , Haukvik Unn K. , Ueland Torill , Lagerberg Trine Vik , Agartz Ingrid , Andreassen Ole A. , Westlye Lars T.
Published: August 2018

Supported by histological and genetic evidence implicating myelin, neuroinflammation and oligodendrocyte dysfunction in schizophrenia spectrum disorders (SZ), diffusion tensor imaging (DTI) studies have consistently shown white matter (WM) abnormalities when compared to healthy controls (HC). The diagnostic specificity remains unclear, with bipolar disorders (BD) frequently conceptualized as a less severe clinical manifestation along a psychotic spectrum. Further, the age-related dynamics and possible sex differences of WM abnormalities in SZ and BD are currently understudied.

Using tract-based spatial statistics (TBSS) we compared DTI-based microstructural indices between SZ (n=128), BD (n=61), and HC (n=293). We tested for age-by-group and sex-by-group interactions, computed effect sizes within different age-bins and within genders.

TBSS revealed global reductions in fractional anisotropy (FA) and increases in radial (RD) diffusivity in SZ compared to HC, with strongest effects in the body and splenium of the corpus callosum, and lower FA in SZ compared to BD in right inferior longitudinal fasciculus and right inferior fronto-occipital fasciculus, and no significant differences between BD and HC. The results were not strongly dependent on age or sex. Despite lack of significant group-by-age interactions, a sliding-window approach supported widespread WM involvement in SZ with most profound differences in FA from the late 20s.
Large-scale chemical-genetics yields new Mycobacterium tuberculosis inhibitor classes
Authors: Johnson Eachan O. , LaVerriere Emily , Stanley Mary , Office Emma , Meyer Elisabeth , Kawate Tomohiko , Gomez James , Audette Rebecca E. , Bandyopadhyay Nirmalya , Betancourt Natalia , Delano Kayla , Silva Israel Da , Davis Joshua , Gallo Christina , Gardner Michelle , Golas Aaron , Guinn Kristine M. , Korn Rebecca , McConnell Jennifer A. , Moss Caitlin E. , Murphy Kenan C. , Nietupski Ray , Papavinasasundaram Kadamba G. , Pinkham Jessica T. , Pino Paula A. , Proulx Megan K. , Ruecker Nadine , Song Naomi , Thompson Matthew , Trujillo Carolina , Wakabayashi Shoko , Wallach Joshua B. , Watson Christopher , Ioerger Thomas R. , Lander Eric S. , Hubbard Brian K. , Serrano-Wu Michael H. , Ehrt Sabine , Fitzgerald Michael , Rubin Eric J. , Sassetti Christopher M. , Schnappinger Dirk , Hung Deborah T.
Published: August 2018

New antibiotics are needed to combat rising resistance, with new Mycobacterium tuberculosis (Mtb) drugs of highest priority. Conventional whole-cell and biochemical antibiotic screens have failed. We developed a novel strategy termed PROSPECT (PRimary screening Of Strains to Prioritize Expanded Chemistry and Targets) in which we screen compounds against pools of strains depleted for essential bacterial targets. We engineered strains targeting 474 Mtb essential genes and screened pools of 100-150 strains against activity-enriched and unbiased compounds libraries, measuring > 8.5-million chemical-genetic interactions. Primary screens identified >10-fold more hits than screening wild-type Mtb alone, with chemical-genetic interactions providing immediate, direct target insight. We identified > 40 novel compounds targeting DNA gyrase, cell wall, tryptophan, folate biosynthesis, and RNA polymerase, as well as inhibitors of a novel target EfpA. Chemical optimization yielded EfpA inhibitors with potent wild-type activity, thus demonstrating PROSPECT’s ability to yield inhibitors against novel targets which would have eluded conventional drug discovery.
Centrosome Aurora A gradient ensures a single PAR-2 polarity axis by regulating RhoGEF ECT-2 localization inC. elegansembryos
Authors: Kapoor Sukriti , Kotak Sachin
Published: August 2018

The proper establishment of the cell polarity is essential for development and morphogenesis. In theCaenorhabditis elegansone-cell embryo, a centrosome localized signal provides spatial information that is responsible for generating a single polarity axis. It is hypothesized that such a signal causes local inhibition of cortical actomyosin network in the vicinity of the centrosome. This pivotal event initiates symmetry breaking to direct partitioning of the partition defective proteins (PARs) in the one-cell embryo. However, the molecular nature of the centrosome regulated signal that impinges on the posterior cortex to bring upon cortical anisotropy in the actomyosin network and to promote polarity establishment remains elusive. Here, we discover that Aurora A kinase (AIR-1 inC. elegans) is essential for proper cortical contractility in the one-cell embryo. Loss of AIR-1 causes pronounced cortical contractions on the entire embryo surface during polarity establishment phase, and this creates more than one PAR-2 polarity axis. Moreover, we show that in the absence of AIR-1, centrosome positioning becomes dispensable in dictating the PAR-2 polarity axis. Interestingly, we identify that Rho Guanine Exchange Factor (GEF) ECT-2 acts downstream to AIR-1 to control excess contractility and notably AIR-1 loss affects ECT-2 cortical localization and thereby polarity establishment. Overall, our study unravels a novel insight whereby an evolutionarily conserved kinase Aurora A inhibits promiscuous PAR-2 domain formation and ensures singularity in the polarity establishment axis.
Staufen2 mediated RNA recognition and localization requires combinatorial action of multiple domains
Authors: Heber Simone , Gáspár Imre , Tants Jan-Niklas , Günther Johannes , Fernandez Moya Sandra M. , Janowski Robert , Ephrussi Anne , Sattler Michael , Niessing Dierk
Published: August 2018

Throughout metazoans, Staufen (Stau) proteins are core factors of mRNA localization particles. They consist of three to four double-stranded RNA binding domains (dsRBDs) and a C-terminal dsRBD-like domain. Mouse Staufen2 (mStau2) likeDrosophilaStau (dmStau) contains four dsRBDs. Existing data suggest that only dsRBDs 3-4 are necessary and sufficient for mRNA binding. Here, we show that dsRBDs 1 and 2 of mStau2 bind RNA with similar affinities and kinetics as dsRBDs 3 and 4. While RNA binding by these tandem domains is transient, all four dsRBDs recognize their target RNAs with high stability. Rescue experiments inDrosophilaoocytes demonstrate that mStau2 partially rescues dmStau-dependent mRNA localization. In contrast, a rescue with mStau2 bearing RNA-binding mutations in dsRBD1-2 fails, confirming the physiological relevance of our findings. In summary, our data show that the dsRBDs 1-2 play essential roles in the mRNA recognition and function of Stau- family proteins of different species.
MSCypher: an integrated database searching and machine learning workflow for multiplexed proteomics
Authors: Kapp Eugene A. , Infusini Giuseppe , Zhong Yunshan , Dagley Laura F. , Speed Terence P. , Webb Andrew I.
Published: August 2018

Improvements in shotgun proteomics approaches are hampered by increases in multiplexed (chimeric) spectra, as improvements in peak capacity, sensitivity or dynamic range all increase the number of co-eluting peptides. This results in diminishing returns using traditional search algorithms, as co-fragmented spectra are known to decrease identification rates. Here we describe MSCypher, a freely available software suite that enables an extensible workflow including a hybrid supervised machine learned strategy that dynamically adjusts to individual datasets. This results in improved identification rates and quantification of low-abundant peptides and proteins. In addition, the integration of peptide de novo sequencing and database searching enables an unbiased view of variants and high-intensity unassigned peptide spectral matches.

Highlights

Open-source end-to-end label-free proteomics workflow

Integrated database searching and machine learning

Customisable and extensible workflow including de novo sequencing

Optimised for multiplexed spectra, challenging proteomics datasets and peptidomics applications
Cyclin D-Cdk4,6 drives cell cycle progression via the retinoblastoma protein’s C-terminal helix
Authors: Topacio Benjamin R. , Zatulovskiy Evgeny , Cristea Sandra , Xie Shicong , Tambo Carrie S. , Rubin Seth M. , Sage Julien , Kõivomägi Mardo , Skotheim Jan M.
Published: August 2018

The cyclin-dependent kinases Cdk4 and Cdk6 form complexes with D-type cyclins to drive cell proliferation. A well-known target of cyclin D-Cdk4,6 is the retinoblastoma protein, Rb, which inhibits cell cycle progression until its inactivation by phosphorylation. However, the role of cyclin D-Cdk4,6 phosphorylation of Rb in cell cycle progression is unclear because Rb can be phosphorylated by other cyclin-Cdk complexes and cyclin D-Cdk4,6 complexes have other targets that may drive cell division. Here, we show that cyclin D-Cdk4,6 docks one side of an alpha-helix in the C-terminus of Rb, which is not recognized by cyclins E, A, and B. This helix-based docking mechanism is shared by the p107 and p130 Rb-family members across metazoans. Mutation of the Rb C-terminal helix prevents phosphorylation, promotes G1 arrest, and enhances Rb’s tumor suppressive function. Our work conclusively demonstrates that the cyclin D-Rb interaction drives cell division and defines a new class of cyclin-based docking mechanisms.
RNA-binding protein A1CF modulates plasma triglyceride levels through posttranscriptional regulation of stress-induced VLDL secretion
Authors: Lin Jennie , Conlon Donna M. , Wang Xiao , Van Nostrand Eric , Rabano Ines , Park YoSon , Strong Alanna , Radmanesh Behram , Barash Yoseph , Rader Daniel J. , Yeo Gene W. , Musunuru Kiran
Published: August 2018

Background

A recent human exome-chip study on plasma lipids identified a missense mutation in theA1CF(APOBEC1 complementation factor) gene that is associated with elevated triglyceride (TG) levels, but how A1CF, an RNA binding protein, influences plasma TG is unknown.

Methods

We generatedA1cfknockout (A1cf−/−) mice and knock-in mice homozygous for the TG-associated Gly398Ser mutation (A1cfGS/GS), determined lipid phenotypes, and assessed TG physiology through measurements of clearance and secretion. We further identified A1CF’s RNA binding targets using enhanced cross-linking and immunoprecipitation sequencing of cultured HepG2 cells and investigated pathways enriched for these targets. Transcriptomic effects of A1CF deficiency were evaluated through RNA sequencing and analyses for differential expression, alternative splicing, and RNA editing.

Results

BothA1cf−/−andA1cfGS/GSmice exhibited increased fasting plasma TG, establishing that the TG phenotype is due to A1CF loss of function.In vivoTG secretion and clearance studies revealed increased TG secretion without changes in clearance inA1cf−/−mice. Increased VLDL-apoB secretion was also seen inA1cf−/−rat hepatoma cells, but no increase in apoB synthesis was observed. This phenotype was seen without significant shifts in apoB-100/apoB-48 in A1CF deficiency. To discover novel pathways for A1CF’s role in TG metabolism, we identified A1CF’s RNA binding targets, which were enriched for pathways related to proteasomal catabolism and endoplasmic reticulum (ER) stress. Indeed, proteasomal inhibition led to increased cellular stress inA1cf−/−cells, and higher expression of ER-stress protein GRP78 was observed in restingA1cf−/−cells. RNA-seq of whole livers from wild-type andA1cf−/−mice revealed that pro-inflammatory, not lipogenesis, genes were upregulated as a secondary effect of A1CF deficiency. Differential alternative splicing (AS) analysis and RNA editing analysis revealed that genes involved in cellular stress and metabolism underwent differential changes in A1CF deficiency, and top A1CF binding target proteins with relevance to intracellular stress were differentially expressed on the protein but not mRNA level, implicating multiple mechanisms by which A1CF influences TG secretion.

Conclusions

These data suggest an important role for A1CF in mediating VLDL-TG secretion through regulating intracellular stress.
Molecular Mechanisms Governing Shade Responses in Maize
Authors: Shi Qingbiao , Kong Fanying , Zhang Haisen , Jiang Yu’e , Heng Siqi , Liang Ran , Liu Jisheng , Lu Xiaoduo , Li Pinghua , Li Gang
Published: August 2018

Light is one of the most important environmental factors affecting plant growth and development. Plants use shade avoidance and shade tolerance strategies to adjust their growth and development thus increase their success in the competition for incoming light. To investigate the mechanism of shade responses in maize (Zea mays), we examined the anatomical and transcriptional dynamics of the early shade response in seedlings of the B73 inbred line. Transcriptome analysis identified 912 differentially expressed genes, including genes involved in light signaling, auxin responses, and cell elongation pathways. Grouping transcription factor family genes and performing enrichment analysis identified multiple types of transcription factors that are differentially regulated by shade and predicted putative core genes responsible for regulating shade avoidance syndrome. For functional tests, we ectopically over-expressedZmHB53, a type II HD-ZIP transcription factor gene significantly induced by shade, inArabidopsis thaliana. Transgenic Arabidopsis plants overexpressingZmHB53exhibited narrower leaves, earlier flowering, and enhanced expression of shade-responsive genes, suggesting that ZmHB53 participates in the regulation of shade responses in maize. This study increases our understanding of the regulatory network of the shade response in maize and provides a useful resource for maize genetics and breeding.

Highlight

Our findings not only increase the understanding of the regulatory network of the shade avoidance in maize, and also provide a useful resource for maize genetics and breeding.
Two Lytic Bacteriophages That Depend on theEscherichia coliMulti-Drug Efflux GenetolCand Differentially Affect Bacterial Growth and Selection
Authors: Burmeister Alita R. , Bender Rose G. , Fortier Abigail , Lessing Adam J. , Chan Benjamin K. , Turner Paul E.
Published: August 2018

Bacterial pathogens are increasingly evolving drug resistance under natural selection from antibiotics in medicine, agriculture, and nature. Meanwhile, bacteria ubiquitously encounter bacteriophages and can rapidly evolve phage resistance. However, the role of phages in interacting with drug-resistant and drug-sensitive bacteria remains unclear. To gain insight into such relationships, we screened for and characterized phages that rely on the multi-drug efflux pump genetolC. First, we screened a collection of 33 environmental and commercialEscherichia coliphages for their ability to infect cells that lackedtolC. Our screen revealed two phages that had reduced efficiency of plating (EOP) on thetolCknockout compared to wild type. We further characterized these phages with bacterial growth curves, transmission electron microscopy, and analysis of phage-resistant mutants. Phage U136B is a curly-tailed virus in familySiphoviridaewith no ability to infect atolCknockout, suggesting TolC is the U136B receptor. Phage 132 is a contractile-tailed virus in familyMyoviridaewith reduced EOP on cells lackingompFand its positive regulatorstolCandompR. U136B and 132 differentially effect bacterial growth and lysis, and U136B-resistant mutants contain mutations of thetolCgene. Together, these results show that thetolCgene involved in drug resistance can modify bacteria-phage interactions in multiple ways, altering bacterial lysis and selection. These new phages offer utility for studying evolution, tradeoffs, and infection mechanisms.

Importance

Bacteria face strong selection by antibiotics in medicine and agriculture, resulting in increasing levels of drug resistance among bacterial pathogens. Slowing this process will require an understanding of the environmental contexts in which drug resistance evolutionarily increases or decreases. In this study, we investigate two newly-isolated bacteriophages that rely on a bacterial antibiotic resistance gene. These bacteriophages vary in their interactions with drug-resistant bacteria, with one of the phages selecting for phage-resistant mutants that have mutations in the antibiotic resistance gene. Further study of these new phages will be useful to understanding evolutionary tradeoffs and how phages might be applied in natural settings to reverse the problem of drug resistance.
OMA standalone: orthology inference among public and custom genomes and transcriptomes
Authors: Altenhoff Adrian M , Levy Jeremy , Zarowiecki Magdalena , Tomiczek Bartłomiej , Vesztrocy Alex Warwick , Dalquen Daniel A , Müller Steven , Telford Maximilian J , Glover Natasha M , Dessimoz Christophe
Published: August 2018

Genomes and transcriptomes are now typically sequenced by individual labs, but analysing them often remains challenging. One essential step in many analyses lies in identifying orthologs—corresponding genes across multiple species—but this is far from trivial. The OMA (Orthologous MAtrix) database is a leading resource for identifying orthologs among publicly available, complete genomes. Here, we describe the OMA pipeline available as a standalone program for Linux and Mac. When run on a cluster, it has native support for the LSF, SGE, PBS Pro, and Slurm job schedulers and can scale up to thousands of parallel processes. Another key feature of OMA standalone is that users can combine their own data with existing public data by exporting genomes and pre-computed alignments from the OMA database, which currently contains over 2100 complete genomes. We compare OMA standalone to other methods in the context of phylogenetic tree inference, by inferring a phylogeny of the Lophotrochozoa, a challenging clade within the Protostomes. We also discuss other potential applications of OMA standalone, including identifying gene families having undergone duplications/losses in specific clades, and identifying potential drug targets in non-model organisms. OMA Standalone is available at http://omabrowser.org/standalone under the permissible open source Mozilla Public License Version 2.0.
Core architecture of a bacterial type II secretion system
Authors: Chernyatina Anastasia A , Low Harry H
Published: August 2018

Bacterial type II secretion systems (T2SS) translocate virulence factors, toxins and enzymes across the cell outer membrane (OM). An assembled T2SS has not yet been isolated in vitro. Here we use a fusion of negative stain and cryo-electron microscopy (EM) to reveal the core architecture of an assembled T2SS from the pathogen Klebsiella pneumoniae. We show that 7 proteins form a ∼2.5 MDa complex that spans the cell envelope. The outer membrane complex (OMC) includes the secretin PulD with all domains modelled and the pilotin PulS. The inner membrane assembly platform (AP) components PulC, PulE, PulL, PulM and PulN have a relative stoichiometric ratio of 2:1:1:1:1, respectively. The PulE ATPase, PulL and PulM combine to form a flexible hexameric hub. Symmetry mismatch between the OMC and AP is overcome by PulC linkers spanning the periplasm with PulC HR domains binding independently at the secretin base. Our results show the T2SS to have a highly dynamic modular architecture with implication for pseudo-pilus assembly and substrate loading.
Actomyosin-driven tension at compartmental boundaries orients cell division independently of cell geometryin vivo
Authors: Scarpa Elena , Finet Cédric , Blanchard Guy , Sanson Bénédicte
Published: August 2018

During animal development, planar polarization of the actomyosin cytoskeleton underlies key morphogenetic events such as axis extension and boundary formation. Actomyosin is enriched along compartment boundaries during segmentation of theDrosophilaembryo, forming supracellular contractile cables that keep cells segregated at boundaries. Here, we show that these contractile actomyosin cables bias the orientation of division in cells in contact with compartment boundaries. By decreasing actomyosin cable tension locally using laser ablation or, conversely ectopically increasing tension using laser wounding, we demonstrate that localised subcellular force is necessary and sufficient to orient mitosesin vivo.Moreover this bias is independent of cell geometry and involves capture of the spindle pole by the actomyosin cortex.
Understanding the killing mechanism of action by virus-infected yeasts
Authors: Sheppard Sean , Dikicioglu Duygu
Published: August 2018

Killer yeasts are microorganisms, which can produce and secrete proteinaceous toxins, a characteristic gainedviainfection by a virus. These toxins are able to kill sensitive cells of the same or a related species. From a biotechnological perspective, killer yeasts have been considered as beneficial due to their antifungal/antimicrobial activity, but also regarded as problematic for large-scale fermentation processes, whereby those yeasts would kill species off starter cultures and lead to stuck fermentations. Here, we propose a mechanistic model of the toxin-binding kinetics pertaining to the killer population coupled with the toxin-induced death kinetics of the sensitive population to study toxic actionin silico. Our deterministic model explains how killerSaccharomyces cerevisiaecells distress and consequently kill the sensitive members of the species, accounting for the K1, K2 and K28 toxin mode of action at high or low concentrations. The dynamic model captured the transient toxic activity starting from the introduction of killer cells into the culture at the time of inoculation through to induced cell death, and allowed us to gain novel insight on these mechanisms. The kinetics of K1/K2 activityviaits primary pathway of toxicity was 5.5 times faster than its activity at low concentration inducing the apoptotic pathway in sensitive cells. Conversely, we showed that the primary pathway for K28 was approximately 3 times slower than its equivalent apoptotic pathway, indicating the particular relevance of K28 in biotechnological applications where the toxin concentration is rarely above those limits to trigger the primary pathway of killer activity.
Assessment of abduction movement in older people with painful shoulder: an analysis based on inertial sensors
Authors: Roldán-Jiménez Cristina , Martín-Martín Jaime , Bennett Paul , McPhail Steven , Cuesta-Vargas Antonio I , Kerr Graham K.
Published: August 2018

Reduced range of motion in the shoulder can be a source of functional limitation. Current quantitative evaluation systems are limited to assessing the functionality or the maximum articular amplitudes in each of the planes of movement, both in isolation. These separate clinical evaluation systems may not allow the identification of the underlying impairments contributing to the functional limitation. The use of inertial sensors to quantify movement in addition to more common clinical assessments of the shoulder may allow clinicians to understand that are potentially unnoticed by the human eye. The main objective of this cross-sectional study was to generate an explanatory model for shoulder abduction based on data from inertial sensors. Shoulder abduction of thirteen older adults suffering from shoulder dysfunction was evaluated using two inertial sensors placed on the humerus and scapula. Movement variables (maximum angular mobility, angular peak of velocity, peak of acceleration) were used to explain the functionality of the upper limb (assessed using the Upper Limb Functional Index). Abduction movement of the shoulder was explained by six variables related to the mobility of the shoulder joint complex. A manova analysis was used to explain the results obtained on the functionality of the upper limb. The MANOVA model based on angular mobility explained 69% of the variance of the ULFI value (r-squared=0.69). The most relevant variables were the abduction-adduction of the humerus and the medial and lateral rotation of the scapula. However, given the limited sample size, none of these individual variables were statistically significant in the decomposition model on their own. The method used in the present study reveals the potential importance of the analysis of the scapular and humeral movements for comprehensive evaluation of the upper limb. Further research should include a wider sample and may seek to use this assessment technique in a range of potential clinical applications.