bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stochastic Yield Catastrophes and Robustness in Self-Assembly
Authors: Gartner Florian M. , Graf Isabella R. , Wilke Patrick , Geiger Philipp M. , Frey Erwin 
Published: June 2019

ABSTRACTA guiding principle in self-assembly is that, for high production yield, nucleation of structures must be significantly slower than their growth. However, details of the mechanism that impedes nucleation are broadly considered irrelevant. Here, we analyze self-assembly into finite-sized target structures employing mathematical modeling. We investigate two key scenarios to delay nucleation: (i) by introducing a slow activation step for the assembling constituents and, (ii) by decreasing the dimerization rate. These scenarios have widely different characteristics. While the dimerization scenario exhibits robust behavior, the activation scenario is highly sensitive to demographic fluctuations. These demographic fluctuations ultimately disfavor growth compared to nucleation and can suppress yield completely. The occurrence of this stochastic yield catastrophe does not depend on model details but is generic as soon as number fluctuations between constituents are taken into account. On a broader perspective, our results reveal that stochasticity is an important limiting factor for self-assembly and that the specific implementation of the nucleation process plays a significant role in determining the yield.
Adaptive and maladaptive genetic diversity in small populations; insights from the Brook Charr (Salvelinus fontinalis)case study
Authors: Ferchaud Anne-Laure , Leitwein Maeva , Laporte Martin , Boivin-Delisle Damien , Bougas Bérénice , Hernandez Cécilia , Normandeau Éric , Thibault Isabel , Bernatchez Louis 
Published: June 2019

AbstractInvestigating the relative importance of neutralversusselective processes governing the accumulation of genetic variants is a key goal in evolutionary biology. This is particularly true in the context of small populations, where genetic drift can counteract the effect of selection. In this study, we investigated the accumulation of putatively beneficial and harmful variations using 7,950 high-quality filtered SNPs among 36 lacustrine, seven riverine and seven anadromous Brook Charr (Salvelinus fontinalis) populations (n = 1,193) from Québec, Canada. Using the Provean algorithm, we observed an accumulation of deleterious mutations that tend to be more prevalent in isolated lacustrine and riverine populations than the more connected anadromous populations. In addition, the absence of correlation between the occurrence of putative beneficial nor deleterious mutations and local recombination rate supports the hypothesis that genetic drift might be the main driver of the accumulation of such variants. Despite the effect of pronounced genetic drift and limited gene flow in non-anadromous populations, several loci representing biological functions of potential adaptive significance were associated with environmental variables, and particularly with temperature. We also identified genomic regions associated with anadromy. We also observed an overrepresentation of transposable elements associated with variation in environmental variables, thus supporting the importance of transposable elements in adaptation.
The drug-induced phenotypic landscape of colorectal cancer organoids
Authors: Betge Johannes , Rindtorff Niklas , Sauer Jan , Rauscher Benedikt , Dingert Clara , Gaitantzi Haristi , Herweck Frank , Srour-Mhanna Kauthar , Miersch Thilo , Valentini Erica , Hauber Veronika , Gutting Tobias , Frank Larissa , Belle Sebastian , Gaiser Timo , Buchholz Inga , Jesenofsky Ralf , Härtel Nicolai , Zhan Tianzuo , Fischer Bernd , Breitkopf-Heinlein Katja , Burgermeister Elke , Ebert Matthias P. , Boutros Michael 
Published: June 2019

AbstractPatient derived organoids resemble the biology of tissues and tumors, enablingex vivomodeling of human diseases from primary patient samples. Organoids can be used as models for drug discovery and are being explored to guide clinical decision making. Patient derived organoids can have heterogeneous morphologies with unclear biological causes and relationship to treatment response. Here, we used high-throughput, image-based profiling to quantify phenotypes of over 5 million individual colorectal cancer organoids after treatment with more than 500 small molecules. Integration of data using a joint multi-omics modelling framework identified organoid size and cystic vs. solid organoid architecture as axes of morphological variation across organoids. Mechanistically, we found that organoid size was linked to IGF1 receptor signaling, while a cystic organoid architecture was associated with an LGR5+ stemness program. Treatment-induced organoid morphology reflected organoid viability, drug mechanism of action, and was biologically interpretable using joint modelling. Inhibition of MEK led to cystic reorganization of organoids and increased expression of LGR5, while inhibition of mTOR induced IGF1 receptor signaling. In conclusion, we identified shared axes of variation for colorectal cancer organoid morphology, their underlying biological mechanisms, and pharmacological interventions with the ability to move organoids along them. Image-based profiling of patient derived organoids coupled with multi-omics integration facilitates drug discovery by linking drug responses with underlying biological mechanisms.
Seizure pathways change on circadian and slower timescales in individual patients with focal epilepsy
Authors: Schroeder Gabrielle M , Diehl Beate , Chowdhury Fahmida A , Duncan John S , de Tisi Jane , Trevelyan Andrew J , Forsyth Rob , Jackson Andrew , Taylor Peter N , Wang Yujiang 
Published: June 2019

AbstractPersonalised medicine requires that treatments adapt to not only the patient, but changing factors within each individual. Although epilepsy is a dynamic disorder that is characterised by pathological fluctuations in brain state, surprisingly little is known about whether and how seizures vary in the same patient. We quantitatively compared within-patient seizure network dynamics using intracranial recordings of over 500 seizures from 31 patients with focal epilepsy (mean 16.5 seizures/patient). In all patients, we found variability in seizure paths through the space of possible network dynamics, producing either a spectrum or clusters of different dynamics. Seizures with similar pathways tended to occur closer together in time, and a simple model suggested that seizure pathways change on circadian and/or slower timescales in the majority of patients. These temporal relationships occurred independent of whether the patient underwent antiepileptic medication reduction. Our results suggest that various modulatory processes, operating at different timescales, shape within-patient seizure dynamics, leading to variable seizure pathways that may require tailored treatment approaches.
Sensor localization using magnetic dipole-like coils: A method for highly accurate co-registration in on-scalp MEG
Authors: Pfeiffer Christoph , Ruffieux Silvia , Andersen Lau M. , Kalabukhov Alexei , Winkler Dag , Oostenveld Robert , Lundqvist Daniel , Schneiderman Justin F. 
Published: June 2019

AbstractSource modelling in magnetoencephalography (MEG) requires precise co-registration of the sensor array and the anatomical structure of the measured individual’s head. In conventional MEG, positions and orientations of the sensors relative to each other are fixed and known beforehand, requiring only localization of the head relative to the sensor array. Since the sensors in on-scalp MEG are positioned on the scalp, locations of the individual sensors depend on the subject’s head shape and size. The positions and orientations of on-scalp sensors must therefore be measured at every recording. This can be achieved by inverting conventional head localization, localizing the sensors relative to the head - rather than the other way around.In this study we present a practical method for localizing sensors using magnetic dipole-like coils attached to the subject’s head. We implement and evaluate the method in a set of on-scalp MEG recordings using a 7-channel on-scalp MEG system based on high critical temperature superconducting quantum interference devices (high-Tc SQUIDs). The method provides accurate estimates of individual sensor positions and orientations with short averaging time (≤ 2 mm and < 3 degrees, respectively, with 1-second averaging), enabling continuous sensor localization. Calibrating and jointly localizing the sensor array can further improve the localization accuracy (< 1 mm and < 2.5 degrees, respectively, with 1-second coil recordings).We demonstrate source localization of on-scalp recorded somatosensory evoked activity based on co-registration with our method. Equivalent current dipole fits of the evoked responses corresponded well (within 5.3 mm) with those based on a commercial, whole-head MEG system.
Functional and comparative genomic analysis of integrated prophage-like sequences inCandidatus Liberibacter asiaticus
Authors: Dominguez-Mirazo Marian , Jin Rong , Weitz Joshua S. 
Published: June 2019

AbstractHuanglongbing (HLB; yellow shoot disease) is a severe worldwide infectious disease for citrus family plants. The pathogenCandidatus Liberibacter asiaticus(CLas) is an alphapro-teobacterium of theRhizobiaceaefamily that has been identified as the cause. The virulence of CLas has been attributed, in part, to prophage encoded genes. Prophage and prophage like elements have been identified in 12 of the 15 CLas available genomes, and are classified into three prophage types. Here, we re-examined all 15 CLas genomes using ade novoprediction approach and expanded the number of prophage like elements from 16 to 33. Further, we find that all CLas contain at least one prophage-like sequence. Comparative analysis reveals a prevalent, albeit previously unknown, prophage-like sequence type that is a remnant of an integrated prophage. Notably, this remnant prophage is found in the Ishi-1 CLas strain that had previously been reported as lacking prophages. Our findings provide both a resource and new insights into the evolutionary relationship between phage and CLas pathogenicity.
Effect of accelerated ageing on seed membrane integrity and chemical composition of Tetrapleura tetraptera (schum. & thonn.)
Authors: Sossou H. S. , Asomaning J. M. , Gaveh E. A. , Sodedji A. F. K. , Agoyi E. E. , Sarkodie-Addo J. , Assogbadjo A. E. 
Published: June 2019

ABSTRACTSeed ageing is one of the major issues in the storage of seeds. Accelerated ageing test has shown great potential for studying the mechanism of ageing and associated deterioration processes of seeds. This study was conducted to evaluate the effects of accelerated ageing process on seed membrane integrity and chemical composition of Tetrapleura tetraptera (schum. & thonn.). Seeds were subjected to traditional accelerated ageing (100% RH at 38 and 41°C for 48, 72 and 96 h) and salt-saturated accelerated ageing (76% RH at 38 and 41°C for 48, 72 and 96 h) tests and the aged seeds were tested for moisture content, leachate conductivity and chemical composition. Results showed that the accelerated ageing process led to an increase in seed moisture content, carbohydrate, fat, ash and crude fibre content and a reduction in crude protein content in the aged seeds. Also, the leachate conductivity test revealed a loss in membrane integrity of T. tetraptera seed indicating that the accelerated ageing process triggered the seed coat dormancy release in T. tetraptera seed and led to the leaching of the mineral constituent of the seed. The accelerated ageing test combined with a storage experiment could therefore be a promising technique for estimating the storage potential of T tetraptera seed but further investigations including the enzyme activity, are required to standardize the appropriate testing conditions for the species.
Elucidating the molecular determinants of Aβ aggregation with deep mutational scanning
Authors: Gray Vanessa E. , Sitko Katherine , Kameni Floriane Z. Ngako , Williamson Miriam , Stephany Jason J. , Hasle Nicholas , Fowler Douglas M. 
Published: June 2019

AbstractDespite the importance of Aβ aggregation in Alzheimer’s disease etiology, our understanding of the sequence determinants of aggregation is sparse and largely derived from in vitro studies. For example, in vitro proline and alanine scanning mutagenesis of Aβ40 proposed core regions important for aggregation. However, we lack even this limited mutagenesis data for the more disease-relevant Aβ42. Thus, to better understand the molecular determinants of Aβ42 aggregation in a cell-based system, we combined a yeast DHFR aggregation assay with deep mutational scanning. We measured the effect of 791 of the 798 possible single amino acid substitutions on the aggregation propensity of Aβ42. We found that ~75% of substitutions, largely to hydrophobic residues, maintained or increased aggregation. We identified 11 positions at which substitutions, particularly to hydrophilic and charged amino acids, disrupted Aβ aggregation. These critical positions were similar but not identical to critical positions identified in previous Aβ mutagenesis studies. Finally, we analyzed our large-scale mutagenesis data in the context of different Aβ aggregate structural models, finding that the mutagenesis data agreed best with models derived from fibrils seeded using brain-derived Aβ aggregates.
Bacterial survival in microscopic droplets
Authors: Grinberg Maor , Orevi Tomer , Steinberg Shifra , Kashtan Nadav 
Published: June 2019

AbstractPlant leaves constitute a huge microbial habitat of global importance. How microorganisms survive the dry daytime on leaves and avoid desiccation is not well-understood. There is evidence that microscopic wetness in the form of thin films and micrometer-sized droplets, invisible to the naked eye, persists on leaves during daytime due to deliquescence – the absorption of water until dissolution – of hygroscopic aerosols. Here we study how such microscopic wetness affects cell survival. We show that, on surfaces drying under moderate humidity, stable microdroplets form around bacterial aggregates due to deliquescence and capillary pinning. Notably, droplet-size increases with aggregate-size and the survival of cells is higher the larger the droplet. This phenomenon was observed for 13 different bacterial species, two of which –Pseudomonas fluorescensandP. putida– were studied in depth. Microdroplet formation around aggregates are likely key to bacterial survival in a variety of unsaturated microbial habitats, including leaf surfaces.
Analyzing effect of altitudinal variation in Enzymatic antioxidants ofColeus forskohliifrom Uttarakhand, India
Authors: Rana Pawan Singh , Saklani Pooja 
Published: June 2019

AbstractEnzymatic antioxidant activity of the five populations of the medicinal plantColeus forskohliifrom five locations of varied altitudes was assayed to analyze the effect of altitude on the enzymatic antioxidant potential. The various enzymes assayed were SOD, CAT, POD, PPO, APX and GR. Highest activity for all the enzymes was observed at higher altitudes. Strong positive correlation was observed between the protein content, enzyme activities and altitude. CAT, POD and GR activity increases significantly with the altitude while SOD was least affected. APX and PPO shows positive correlation. High activity of all these enzymes seems to be to combat the high oxidative stress at higher altitudes. Results of the present study suggest thatColeus forskohliipopulation growing at a higher altitude has higher antioxidant potential than those at lower altitude. Thus, the population ofColeus forskohliifrom a higher altitude can be used as a source of antioxidants and for commercial propagation.
Evolution at two time-frames: ancient and common origin of two structural variants involved in local adaptation of the European plaice (Pleuronectes platessa)
Authors: Le Moan Alan , Bekkevold Dorte , Hemmer-Hansen Jakob 
Published: June 2019

AbstractChanging environmental conditions can lead to population diversification through differential selection on standing genetic variation. Structural variant (SV) polymorphisms provide examples of ancient alleles that in time become associated with novel environmental gradients. The European plaice (Pleuronectes platessa) is a marine flatfish showing large allele frequency differences at two putative SVs associated with environmental variation. In this study, we explored the contribution of these SVs to population structure across the North East Atlantic. We compared genome wide population structure using sets of RAD sequencing SNPs with the spatial structure of the SVs. We found that in contrast to the rest of the genome, the SVs were only weakly associated with an isolation-by-distance pattern. Indeed, both SVs showed important allele frequency differences associated with two different environmental gradients, with the same allele increasing both along the salinity gradient of the Baltic Sea, and the latitudinal gradient along the Norwegian coast. Nevertheless, both SVs were found to be polymorphic across most sampling sites, even in the Icelandic population inferred to originate from a different glacial refuge than the remaining populations from the European continental shelf. Phylogenetic analyses suggested that the SV alleles are much older than the age of the Baltic Sea itself. These results suggest that the SVs are older than the age of the environmental gradients with which they currently co-vary. Interestingly, both SVs shared similar phylogenetic and genetic diversity, suggesting that they have a common origin. Altogether, our results suggest that the plaice SVs were shaped by evolutionary processes occurring at two time-frames, firstly following their common origin and secondly related to their current association with more recent environmental gradients such as those found in the North Sea − Baltic Sea transition zone.
Improvement of baculovirus as protein expression vector and as biopesticide by CRISPR/Cas9 editing
Authors: Pazmiño-Ibarra Verónica , Mengual Adriá , Targovnik Alexandra , Herrero Salvador 
Published: June 2019

AbstractThe CRISPR (Clustered Regularly Interspaced Short Palindromic repeats) system associated Cas9 endonuclease is a molecular tool that enables specific sequence edition with high efficiency. The edition using CRISPR/Cas9 system has been successfully reported in small and large viral genomes. In this study, we have explored the use of CRISPR/Cas9 system for the edition of the baculovirus genome. We have shown that the delivering of Cas9-sgRNA ribonucleoprotein (RNP) complex with or without DNA repair template into Sf21 insect cells through lipofection might be efficient to produce knocks-out as well as knocks-in into the baculovirus. To evaluate potential application of our CRISPR/Cas9 method to improve baculovirus as protein expression vector and as biopesticide, we attempted to knock-out several genes from a recombinant AcMNPV form used in the baculovirus expression system as well as in a natural occurring viral isolate from the same virus. We have additionally confirmed the adaptation of this methodology for the generation of viral knocks-in specific regions of the viral genome. Analysis of the generated mutants revealed that the edition efficiency and the type of changes was variable but relatively high. Depending on the targeted gene, the rate of edition ranged from 10% to 40%. This study established the first report revealing the potential of CRISPR/Cas9 for the edition of baculovirus contributing to the engineering of baculovirus as protein expression vector as well as a biological control agent.
Introducing Rhythmic Sinusoidal Amplitude-Modulated Auditory Stimuli with Multiple Message Frequency Coding for Fatigue Reduction in Normal Subjects: An EEG Study
Authors: Shamsi Elham , Shirzhiyan Zahra , Keihani Ahmadreza , Farahi Morteza , Mahnam Amin , Haidari Mohsen Reza , Jafari Amir Homayoun 
Published: June 2019

AbstractMany of the brain-computer interface (BCI) systems depend on the user’s voluntary eye movements. However, voluntary eye movement is impaired in people with some neurological disorders. Since their auditory system is intact, auditory paradigms are getting more patronage from researchers. However, lack of appropriate signal-to-noise ratio in auditory BCI necessitates using long signal processing windows to achieve acceptable classification accuracy at the expense of losing information transfer rate. Because users eagerly listen to their interesting stimuli, the corresponding classification accuracy can be enhanced without lengthening of the signal processing windows. In this study, six sinusoidal amplitude-modulated auditory stimuli with multiple message frequency coding have been proposed to evaluate two hypotheses: 1) these novel stimuli provide high classification accuracies (greater than 70%), 2) the novel rhythmic stimuli set reduces the subjects’ fatigue compared to its simple counterpart. We recorded EEG from nineteen normal subjects (twelve female). Five-fold cross-validated naïve Bayes classifier classified EEG signals with respect to power spectral density at message frequencies, Pearson’s correlation coefficient between the responses and stimuli envelopes, canonical correlation coefficient between the responses and stimuli envelopes. Our results show that each stimuli set elicited highly discriminative responses according to all the features. Moreover, compared to the simple stimuli set, listening to the rhythmic stimuli set caused significantly lower subjects’ fatigue. Thus, it is worthwhile to test these novel stimuli in a BCI experiment to enhance the number of commands and reduce the subjects’ fatigue.Significance StatementAuditory BCI users eagerly listen to the stimuli they are interested in. Thus, response classification accuracy may be enhanced without the need for trial lengthening. Since humans enjoy listening to rhythmic sounds, this study was carried out for introducing novel rhythmic sinusoidal amplitude-modulated auditory stimuli with multiple message frequency coding. Our results show that each stimuli set evoked reliably discriminative responses according to all the features, and rhythmic stimuli set caused significantly lower fatigue in subjects. Thus, it is worthwhile to test these novel stimuli in a BCI study to increase the number of commands (by NN permutations of just N message frequencies) and reduce the subjects’ fatigue.
Alvis: a tool for contig and read ALignment VISualisation and chimera detection
Authors: Martin Samuel , Leggett Richard M. 
Published: June 2019

AbstractBackgroundThe analysis of long reads or the assessment of assembly or target capture data often necessitates running alignments against reference genomes or gene sets. Aligner outputs are often parsed automatically by scripts, but many kinds of analysis can benefit from the understanding that can follow human inspection of individual alignments.FindingsWe developed Alvis, a simple command line tool that can generate visualisations for a number of common alignment analysis tasks. Alvis is a fast and portable tool that accepts input in the most common alignment formats and will output production ready vector images. Additionally, Alvis will highlight potentially chimeric reads or contigs, a common source of misassemblies. We found that splitting chimeric reads using the output provided by Alvis can improve the contiguity of assemblies, while maintaining correctness.