bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protein fold prediction using simulated DEER distance distributions and decay traces
Authors: Alamo Diego del , Tessmer Maxx , Stein Richard , Feix Jimmy B. , Mchaourab Hassane S. , Meiler Jens 
Published: March 2019

AbstractDespite advances in sampling and scoring strategies, Monte Carlo modeling methods still struggle to accurately predict de novo the structures of large proteins, membrane proteins, or proteins of complex topologies. Previous approaches have addressed these shortcomings by leveraging sparse distance data gathered using site-directed spin labeling and electron paramagnetic resonance spectroscopy (SDSL-EPR) to improve protein structure prediction and refinement outcomes. However, existing computational implementations must choose between coarse-grained models of the spin label that lower the resolution and explicit models that lead to resource-intense simulations. Existing methods are further limited by their reliance on distance distributions, which are calculated from a primary refocused echo decay signal and may contain artifacts introduced during this processing step. Here, we addressed these challenges by developing RosettaDEER, a scoring method within the Rosetta software suite capable of simulating distance distributions and echo decay traces between spin labels fast enough to fold proteins de novo. We demonstrate that the accuracy of resulting distance distributions match or exceed those generated by more computationally intensive methods. Moreover, decay traces generated from these distributions recapitulate intermolecular background coupling parameters, allowing RosettaDEER to discriminate between poorly-folded and native-like models even when the time window of EPR data collection is truncated, rendering them unsuitable for accurate transformation into distance distributions. Finally, we demonstrate that one decay trace per nine residues is sufficient to predict the folds of Bax and the C-terminus of ExoU, two soluble proteins with surface-exposed amphipathic structural features that prevent the Rosetta energy function from correctly identifying native-like models in the absence of experimental data. These benchmarking results confirm that RosettaDEER can effectively leverage sparse experimental data for a wide array of modeling applications built into the Rosetta software suite.
Allelopathic effect of Anogeissus pendula Edgew. and Grewia flavescens A.Juss on Desmodium species in Alwar district of Rajasthan
Authors: Prasad Rajendra , Yadav A S 
Published: March 2019

AbstractThe effect of leaf leachates of Anogeissus pendula Edgew. and Grewia flavescens A.Juss was evaluated on growth of the three species of Desmodium in Alwar district of Rajasthan (27°4’ to 28°4’ N and 76°7’ to 77°13’ E). Anogeissus pendula reduced the seed germination of Desmodium repandum from 85% in control to 43% at 2% concentration, Desmodium gangeticum from 80% in control to 50% at 6% concentration and Desmodium triflorum from 78% in control to 28% at 0.1% concentration of leaf leachates. Similarly, the leaf leachates of Grewia flavescens reduced the seed germination of Desmodium repandum from 85% in control to 40% at 2% concentration, Desmodium gangeticum from 80% in control to 50% even at 0.1% concentration and Desmodium triflorum from 78% in control to 21% at 0.5% concentration. The leaf leachates of both the species also reduced the elongation of radicle and plumule of three Desmodium species; however, the adverse effect of leaf leachate of Grewia flavescens was more severe than that of the other species. Among the three Desmodium species, the allelopathic effect of Grewia flavescens and Anogeissus pendula was more severe on Desmodium triflorum as compared to the other two species. It may be suggested that the population of three species of Desmodium is partly regualated by the allelopathic effect of Anogeissus pendula and Grewia flavescens in this tropical dry deciduous forest.
A type III CRISPR ancillary ribonuclease degrades its cyclic oligoadenylate activator
Authors: Athukoralage Januka S. , Graham Shirley , Grüschow Sabine , Rouillon Christophe , White Malcolm F. 
Published: March 2019

Cyclic oligoadenylate (cOA) secondary messengers are generated by type III CRISPR systems in response to viral infection. cOA allosterically activates the CRISPR ancillary ribonucleases Csx1/Csm6, which degrade RNA non-specifically using a HEPN (Higher Eukaryotes and Prokaryotes, Nucleotide binding) active site. This provides effective immunity, but can also lead to growth arrest in infected cells, necessitating a means to deactivate the ribonuclease once viral infection has been cleared. In the crenarchaea, dedicated ring nucleases degrade cA4(cOA consisting of 4 AMP units), but the equivalent enzyme has not been identified in bacteria. We demonstrate that, inThermus thermophilusHB8, the uncharacterised protein TTHB144 is a cA4-activated HEPN ribonuclease that also degrades its activator. TTHB144 binds and degrades cA4at an N-terminal CARF (CRISPR Associated Rossman Fold) domain. The two activities can be separated by site-directed mutagenesis. TTHB144 is thus the first example of a self-limiting CRISPR ribonuclease.Graphical abstract
Effect of partial selfing and polygenic selection on establishment in a new habitat
Authors: Sachdeva Himani 
Published: March 2019

AbstractThis paper analyzes how partial selfing in a large source population influences its ability to colonize a new habitat via the introduction of a few founder individuals. Founders experience inbreeding depression due to partially recessive deleterious alleles as well as maladaptation to the new environment due to selection on a large number of additive loci. I first introduce a simplified version of the Inbreeding History Model (Kelly, 2007) in order to characterize mutation-selection balance in a large, partially selfing source population under selection involving multiple non-identical loci. I then use individual-based simulations to study the eco-evolutionary dynamics of founders establishing in the new habitat under a model of hard selection. The study explores how selfing rate shapes establishment probabilities of founders via effects on both inbreeding depression and adaptability to the new environment, and also distinguishes the effects of selfing on the initial fitness of founders from its effects on the long-term adaptive response of the populations they found. A high rate of (but not complete) selfing is found to aid establishment over a wide range of parameters, even in the absence of mate limitation. The sensitivity of the results to assumptions about the nature of polygenic selection are discussed.
Dynamic ubiquitination determines transcriptional activity of the plant immune coactivator NPR1
Authors: Skelly Michael J. , Furniss James J. , Grey Heather L. , Wong Ka-Wing , Spoel Steven H. 
Published: March 2019

ABSTRACTActivation of systemic acquired resistance in plants is associated with transcriptome reprogramming induced by the unstable coactivator NPR1. Immune-induced ubiquitination and proteasomal degradation of NPR1 are thought to facilitate continuous delivery of active NPR1 to target promoters, thereby maximising gene expression. Because of this potentially costly sacrificial process, we investigated if ubiquitination of NPR1 plays transcriptional roles prior to its proteasomal turnover. Here we show ubiquitination of NPR1 is a processive event in which initial modification by a Cullin-RING E3 ligase promotes its chromatin association and expression of target genes. Only when polyubiquitination of NPR1 is enhanced by the E4 ligase, UBE4, it is targeted for proteasomal degradation. Conversely, ubiquitin ligase activities are opposed by UBP6/7, two proteasome-associated deubiquitinases that enhance NPR1 longevity. Thus, immune-induced transcriptome reprogramming requires sequential actions of E3 and E4 ligases balanced by opposing deubiquitinases that fine-tune activity of NPR1 without strict requirement for its sacrificial turnover.
The dynamics of centromere motion through the metaphase-to-anaphase transition reveal a centromere separation order
Authors: Armond Jonathan W. , Dale Katie L. , Burroughs Nigel J. , McAinsh Andrew D. , Vladimirou Elina 
Published: March 2019

AbstractDuring cell division, chromosomes align at the equator of the cell before sister chromatids separate to move to each daughter cell during anaphase. We use high-speed imaging, Bayesian modelling and quantitative analysis to examine the regulation of centromere dynamics through the metaphase-to-anaphase transition. We find that, contrary to the apparent instantaneous separation seen in low-frequency imaging, centromeres separate asynchronously over 1-2 minutes. The timing of separations negatively correlates with the centromere intersister distance during metaphase, which could potentially be explained by variable amounts of cohesion at centromeres. Depletion of condensin I increases this asynchrony. Depletion of condensin II, on the other hand, abolishes centromere metaphase oscillations and impairs centromere speed in anaphase. These results suggest that condensin complexes have broader direct roles in mitotic chromosome dynamics than previously believed and may be crucial for the regulation of chromosome segregation.
Sex Solves Haldane’s Dilemma
Authors: Hickey Donal A. , Golding G. Brian 
Published: March 2019

AbstractThe cumulative reproductive cost of multi-locus selection has been seen as a potentially limiting factor on the rate of adaptive evolution. In this paper, we show that Haldane’s arguments for the accumulation of reproductive costs over multiple loci are valid only for a clonally reproducing population of asexual genotypes. We show that a sexually reproducing population avoids this accumulation of costs. Thus, sex removes a perceived reproductive constraint on the rate of adaptive evolution. The significance of our results is twofold. First, the results demonstrate that adaptation based on multiple genes – such as selection acting on the standing genetic variation - does not entail a huge reproductive cost as suggested by Haldane, provided of course that the population is reproducing sexually. Secondly, this reduction in the cost of natural selection provides a simple biological explanation for the advantage of sex. Specifically, Haldane’s calculations illustrate the evolutionary disadvantage of asexuality; sexual reproduction frees the population from this disadvantage.
Identifying the neural representation of fast and slow states in force field adaptation via fMRI
Authors: Farrens Andria J. , Sergi Fabrizio 
Published: March 2019

AbstractNeurorehabilitation is centered on motor learning and control processes, however our understanding of how the brain learns to control movements is still limited. Motor adaptation is a rapid form of motor learning that is amenable to study in the laboratory setting. Behavioral studies of motor adaptation have coupled clever task design with computational modeling to study the control processes that underlie motor adaptation. These studies provide evidence of fast and slow learning states in the brain that combine to control neuromotor adaptation.Currently, the neural representation of these states remains unclear, especially for adaptation to changes in task dynamics, commonly studied using force fields imposed by a robotic device. Our group has developed the MR-Softwrist, a robot capable of executing dynamic adaptation tasks during functional magnetic resonance imaging (fMRI) that can be used to localize these networks in the brain.We simulated an fMRI experiment to determine if signal arising from a switching force field adaptation task can localize the neural representations of fast and slow learning states in the brain. Our results show that our task produces reliable behavioral estimates of fast and slow learning states, and distinctly measurable fMRI activations associated with each state under realistic levels of behavioral and measurement noise. Execution of this protocol with the MR-Softwrist will extend our knowledge of how the brain learns to control movement.
Cardiac remodeling after six weeks of high-intensity interval training to exhaustion in endurance-trained males
Authors: Mahjoub Haïfa , Le Blanc Olivier , Paquette Myriam , Imhoff Sarah , Labrecque Lawrence , Drapeau Audrey , Poirier Paul , Bédard Élisabeth , Pibarot Philippe , Brassard Patrice 
Published: March 2019

ABSTRACTHigh-intensity interval training (HIIT) improves physical performance of endurance athletes, although studies examining its cardiovascular effects are sparse. We evaluated the impact of HIIT on blood pressure, heart rate and cardiac cavities size and function in endurance-trained adults. Seventeen endurance-trained males underwent 24-hour ambulatory blood pressure monitoring (ABPM) and Doppler echocardiography at baseline and after 6 weeks of HIIT. Participants were divided in 2 groups (85% maximal aerobic power (MP); HIIT85, n=8 and 115% MP; HIIT115, n = 9) in order to compare the impact of different HIIT intensities. ABPM and cardiac chambers size and function were similar between groups at baseline. HIIT reduced heart rate (55 ± 8 vs. 51 ± 7 bpm; p= 0.003), systolic blood pressure (SBP; 121 ± 11 vs 118 ± 9 mmHg; p = 0.01), mean arterial pressure (MAP; 90 ± 8 vs 89 ± 6 mmHg; p = 0.03) and pulse pressure (52 ± 6 vs 49 ± 5 mmHg; p = 0.01), irrespective of training intensity. Left atrium (LA) volumes increased after HIIT (maximal: 50 ± 14 vs 54 ±14 ml; p= 0.02; minimal: 15 ± 5 vs 20 ± 8 ml; p = 0.01) in both groups. Right ventricle (RV) global longitudinal strain lowered after training in the HIIT85 group only (20 ± 4 vs. 17 ± 3%, p = 0.04). In endurance-trained males, six weeks of HIIT reduce SBP and MAP and increase LA volumes irrespective of training intensity, whereas submaximal HIIT deteriorates RV systolic function.Key pointsHigh-intensity interval training improves physical performance of endurance athletes, although studies examining its cardiovascular effects are sparse.We evaluated the impact of submaximal (85% maximal aerobic power) and supramaximal (115% maximal aerobic power) high-intensity interval training on ambulatory blood pressure, heart rate and cardiac cavities size and function in endurance-trained adults.Irrespective of training intensity, six weeks of high-intensity interval training increase left atrial volumes in endurance-trained adults, whereas the submaximal training decreases right ventricular systolic function.These results may help identify the exercise threshold for potential toxicity of intense exercise training for at-risk individuals and ideal exercise training regimens conferring optimal cardiovascular protection and adapted endurance training for athletes.
A stochastic hybrid model of DNA replication incorporating 3D protein mobility dynamics
Authors: Windhager Jonas , Paine Amelia , Nathanailidou Patroula , Tasiudi Eve , Rodríguez Martínez María , Lygeros John , Lygerou Zoi , Rapsomaniki Maria Anna 
Published: March 2019

SummaryDNA replication, the basis of genetic information maintenance, is a remarkably robust yet highly stochastic process. We present a computational model that incorporates experimental genome structures and protein mobility dynamics to mechanistically describe the stochastic foundations of DNA replication. Analysis of about 300,000in silicoprofiles for fission yeast indicates that the number of firing factors is rate-limiting and dominates completion time. Incorporating probabilistic activation and binding, a full-genome duplication was achieved with at least 300 firing factors, with the only assumption that factors get recycled upon replication fork collision. Spatial patterns of replication timing were reproduced only when firing factors were explicitly activated proximally to the spindle pole body. Independentin vivoexperiments corroborate that the spindle pole body acts as a replication activator, driving origin firing. Our model provides a framework to realistically simulate full-genome DNA replication and investigate the effects of nuclear architecture.
Air mass source determines airborne microbial diversity at the ocean-atmosphere interface of the Great Barrier Reef marine ecosystem
Authors: Archer Stephen D.J. , Lee Kevin C , Caruso Tancredi , King-Miaow Katie , Harvey Mike , Huang Danwei , Wainwright Benjamin J , Pointing Stephen B 
Published: March 2019

AbstractThe atmosphere is the least understood biome on Earth despite its critical role as a microbial transport medium. The influence of surface cover on composition of airborne microbial communities above marine systems is unclear. Here we report evidence for a dynamic microbial presence at the ocean-atmosphere interface of a major marine ecosystem, the Great Barrier Reef, and identify that recent air mass trajectory over an oceanic or continental surface associated with observed shifts in airborne bacterial and fungal diversity. Relative abundance of shared taxa between air and coral microbiomes varied between 2.2-8.8% and included those identified as part of the core coral microbiome. We propose that this variable source of atmospheric inputs may in part contribute to the diverse and transient nature of the coral microbiome.
The signaling mechanism of Hcy-induced atrial fibrosis mediated by TRPC3
Authors: Han Lu , Tang Yanhua , Wu Yanqing , Chen Xiaoshu , Hong Kui , Li Juxiang 
Published: March 2019

AbstractBackgroundHigh plasma levels of homocysteine (Hcy) are regarded as a risk factor for atrial fibrillation (AF), which is closely associated with the pathological consequence of atrial fibrosis and can lead to heart failure with a high mortality rate; Currently, there is no effective therapy for preventing atrial fibrosis, owing to a lack in fundamental understanding of the underlying mechanism. Here, we show that atrial fibrosis is mediated by the relationship between canonical transient receptor potential 3 (TRPC3) channels and sirtuin type 1 (SIRT1) under the stimulation of Hcy.MethodsThe left atrial appendage was obtained from patients with either sinus rhythm (SR) or AF, who underwent cardiothoracic surgery, and used to evaluate the relationship between the concentration of Hcy and a potential mechanism of cardiac fibrosis mediated by TRPC3 and SIRT1. We next performed transverse aortic constriction (TAC) in mouse to investigate the relationship. The mechanisms underlying atrial fibrosis involving TRPC3 and SIRT1 proteins were explored by co-immunoprecipitation (co-IP), bio-layer interferometry (BLI) and lentivirus transfection experiments. Quantitative polymerase chain reaction (qPCR) and western blotting (WB) were performed to analyse gene and protein expression, respectively.ResultsThe majority of AF patients displayed atrial fibrosis, as demonstrated by Masson staining and immunohistochemistry. In the mouse model of TAC, more severe fibrosis was detected in the high-Hcy diet (HH) group, compared to NH mice; and the duration of induced AF was longer in the HH groups than in the normal diet (NH) group. Moreover, the HH group exhibited higher expression levels of TRPC3 and related fibrosis proteins, such as TGF-ß and Col-I, than the NH group, despite also showing a higher level of SIRT1 was observed. The activator of SIRT1 (Resveratrol, Res) attenuated the enhancement of TRPC3 and decrease in SIRT1 observed in the HH group. Further cell culture experiments confirmed that Hcy could promote the proliferation and differentiation of fibroblasts, the up-regulation of TRPC3, and the decrease in the protein level of SIRT1. Ultimately, the results of Co-IP and BLI indicated a direct interaction between TRPC3-C terminal domain (569-863) and SIRT1 proteins, in which the two proteins are antagonistic and in combination regulate the pathogenesis of atrial fibrosis.ConclusionsThe higher level of atrial fibrosis were observed in the HH mouse group, compared with the NH mice group, Such results suggest that AF patients may be more susceptible to atrial fibrosis and possess a high probability of progressing to hyperhomocysteinemia. Moreover, our findings are consistent with the hypothesis that TRPC3 channel up-regulation leads to abnormal accumulation of collagen, with the down-regulation of SIRT1 as an aetiological factor of high Hcy, which in turn predisposes to atrial fibrosis and strongly enhances the possibility of AF.
Evaluation of PicoGreen variants for use in microscopy and flow cytometry
Authors: Khatoo Muznah , Yang Jongtae , Gee Kyle R. , Gasser Stephan 
Published: March 2019

AbstractPicoGreen is a fluorescent probe that binds dsDNA and forms a highly luminescent complex when compared to the free dye in solution. This unique probe is widely used in DNA quantitation assays but has limited application in flow cytometry and microscopy. Here we have investigated various PicoGreen variants for the ability to stain low amounts of cytosolic DNA present in many tumor cells. Analysis of stained cells by flow cytometry and fluorescent microscopy showed that certain variants improved the ability to stain low levels of cytosolic DNA when compared to the commercially available PicoGreen molecule.
Understanding credibility judgements for web search snippets
Authors: Kattenbeck Markus , Elsweiler David 
Published: March 2019

Purpose
It is well known that information behaviour can be biased in countless ways and that users of web search engines have difficulty in assessing the credibility of results. Yet, little is known about how search engine result page (SERP) listings are used to judge credibility and in which if any way such judgements are biased. The paper aims to discuss these issues.

Design/methodology/approach
Two studies are presented. The first collects data by means of a controlled, web-based user study (N=105). Studying judgements for three controversial topics, the paper examines the extent to which users agree on credibility, the extent to which judgements relate to those applied by objective assessors and to what extent judgements can be predicted by the users’ position on and prior knowledge of the topic. A second, qualitative study (N=9) utilises the same setup; however, transcribed think-aloud protocols provide an understanding of the cues participants use to estimate credibility.

Findings
The first study reveals that users are very uncertain when assessing credibility and their impressions often diverge from objective judges who have fact checked the sources. Little evidence is found indicating that judgements are biased by prior beliefs or knowledge, but differences are observed in the accuracy of judgements across topics. Qualitatively analysing think-aloud transcripts from participants think-aloud reveals ten categories of cues, which participants used to determine the credibility of results. Despite short listings, participants utilised diverse cues for the same listings. Even when the same cues were identified and utilised, different participants often interpreted these differently. Example transcripts show how participants reach varying conclusions, illustrate common mistakes made and highlight problems with existing SERP listings.

Originality/value
This study offers a novel perspective on how the credibility of SERP listings is interpreted when assessing search results. Especially striking is how the same short snippets provide diverse informational cues and how these cues can be interpreted differently depending on the user and his or her background. This finding is significant in terms of how search engine results should be presented and opens up the new challenge of discovering technological solutions, which allow users to better judge the credibility of information sources on the web.