bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of Phosphorylation on the Collision Cross Sections of Peptide Ions in Ion Mobility Spectrometry
Authors: Ogata Kosuke , Chang Chih-Hsiang , Ishihama Yasushi 
Published: June 2020

AbstractThe insertion of ion mobility spectrometry (IMS) between LC and MS can improve peptide identification in both proteomics and phosphoproteomics by providing structural information that is complementary to LC and MS, because IMS separates ions on the basis of differences in their shapes and charge states. However, it is necessary to know how phosphate groups affect the peptide collision cross sections (CCS) in order to accurately predict phosphopeptide CCS values and to maximize the usefulness of IMS. In this work, we systematically characterized the CCS values of 4,433 pairs of mono-phosphopeptide and corresponding unphosphorylated peptide ions using trapped ion mobility spectrometry (TIMS). Nearly one-third of the mono-phosphopeptide ions evaluated here showed smaller CCS values than their unphosphorylated counterparts, even though phosphorylation results in a mass increase of 80 Da. Significant changes of CCS upon phosphorylation occurred mainly in structurally extended peptides with large numbers of basic groups, possibly reflecting intramolecular interactions between phosphate and basic groups.
Genome-wide mapping of therapeutically-relevant SARS-CoV-2 RNA structures
Authors: Manfredonia Ilaria , Nithin Chandran , Ponce-Salvatierra Almudena , Ghosh Pritha , Wirecki Tomasz K. , Marinus Tycho , Ogando Natacha S. , Snider Eric J. , van Hemert Martijn J. , Bujnicki Janusz M. , Incarnato Danny 
Published: June 2020

SummarySARS-CoV-2 is a betacoronavirus with a linear single-stranded, positive-sense RNA genome of ∼30 kb, whose outbreak caused the still ongoing COVID-19 pandemic. The ability of coronaviruses to rapidly evolve, adapt, and cross species barriers makes the development of effective and durable therapeutic strategies a challenging and urgent need. As for other RNA viruses, genomic RNA structures are expected to play crucial roles in several steps of the coronavirus replication cycle. Despite this, only a handful of functionally conserved structural elements within coronavirus RNA genomes have been identified to date.Here, we performed RNA structure probing by SHAPE-MaP to obtain a single-base resolution secondary structure map of the full SARS-CoV-2 coronavirus genome. The SHAPE-MaP probing data recapitulate the previously described coronavirus RNA elements (5′ UTR, ribosomal frameshifting element, and 3′ UTR), and reveal new structures. Secondary structure-restrained 3D modeling of highly-structured regions across the SARS-CoV-2 genome allowed for the identification of several putative druggable pockets. Furthermore, ∼8% of the identified structure elements show significant covariation among SARS-CoV-2 and other coronaviruses, hinting at their functionally-conserved role. In addition, we identify a set of persistently single-stranded regions having high sequence conservation, suitable for the development of antisense oligonucleotide therapeutics.Collectively, our work lays the foundation for the development of innovative RNA-targeted therapeutic strategies to fight SARS-related infections.
Oriented Soft DNA Curtains for Single Molecule Imaging
Authors: Kopūstas Aurimas , Ivanovaitė Šarūnė , Rakickas Tomas , Pocevičiūtė Ernesta , Paksaitė Justė , Karvelis Tautvydas , Zaremba Mindaugas , Manakova Elena , Tutkus Marijonas 
Published: June 2020

AbstractOver the past twenty years, single-molecule methods have become extremely important for biophysical studies. These methods, in combination with new nanotechnological platforms, can significantly facilitate experimental design and enable faster data acquisition. A nanotechnological platform, which utilizes flow-stretch of immobilized DNA molecules, called DNA Curtains, is one of the best examples of such combinations. Here, we employed new strategies to fabricate a flow-stretch assay of stably immobilized and oriented DNA molecules using protein template-directed assembly. In our assay a protein template patterned on a glass coverslip served for directional assembly of biotinylated DNA molecules. In these arrays, DNA molecules were oriented to one another and maintained extended either by single- or both-ends immobilization to the protein templates. For oriented both-end DNA immobilization we employed heterologous DNA labeling and protein template coverage with the anti-digoxigenin antibody. In contrast to the single-end, both-ends immobilization does not require constant buffer flow for keeping DNAs in an extended configuration, allowing us to study protein-DNA interactions at more controllable reaction conditions. Additionally, we increased immobilization stability of the biotinylated DNA molecules using protein templates fabricated from traptavidin. Finally, we demonstrated that double-tethered Soft DNA Curtains can be used in nucleic acid-interacting protein (e.g. CRISPR-Cas9) binding assay that monitors binding location and position of individual fluorescently labeled proteins on DNA.
FEM-Based Mechanics Modeling of Bio-Inspired Compliant Mechanisms for Medical Applications
Authors: Sun Yilun , Zhang Dingzhi , Liu Yuqing , Lueth Tim C. 
Published: June 2020

AbstractCompliant mechanisms are widely used in the design of medical robotics and devices because of their monolithic structure and high flexibility. Many compliant mechanisms derive their design ideas from nature, since the structure of biological organisms sometimes offers a better solution than the conventional mechanisms. However, the bio-inspired structures usually have very complex geometries which cannot be easily modeled and analyzed using traditional methods. In this paper, we present a novel finite element method (FEM) based modeling framework in Matlab to analyze the mechanics of different bio-inspired compliant mechanisms. Since the basic linear FEM formulation can only be employed to model small displacements of compliant mechanisms, a non-linear FEM formulation that integrates the modeling of large displacements, tendon-driven mechanisms and contact problems was implemented in the proposed framework to overcome the limitations. Simulations and experiments were also conducted to evaluate the performance of the modeling framework. Results have demonstrated the accuracy and plausibility of the proposed non-linear FEM formulation. Furthermore, the proposed framework can also be used to achieve structural optimization of bio-inspired compliant mechanisms.
Principal curve approaches for inferring 3D chromatin architecture
Authors: Tuzhilina Elena , Hastie Trevor J. , Segal Mark R. 
Published: June 2020

AbstractThree dimensional (3D) genome spatial organization is critical for numerous cellular processes, including transcription, while certain conformation-driven structural alterations are frequently oncogenic. Genome architecture had been notoriously difficult to elucidate, but the advent of the suite of chromatin conformation capture assays, notably Hi-C, has transformed understanding of chromatin structure and provided downstream biological insights. Although many findings have flowed from direct analysis of the pairwise proximity data produced by these assays, there is added value in generating corresponding 3D reconstructions deriving from superposing genomic features on the reconstruction. Accordingly, many methods for inferring 3D architecture from proximity d hyperrefata have been advanced. However, none of these approaches exploit the fact that single chromosome solutions constitute a one dimensional (1D) curve in 3D. Rather, this aspect has either been addressed by imposition of constraints, which is both computationally burdensome and cell type specific, or ignored with contiguity imposed after the fact. Here we target finding a 1D curve by extending principal curve methodology to the metric scaling problem. We illustrate how this approach yields a sequence of candidate solutions, indexed by an underlying smoothness or degrees-of-freedom parameter, and propose methods for selection from this sequence. We apply the methodology to Hi-C data obtained on IMR90 cells and so are positioned to evaluate reconstruction accuracy by referencing orthogonal imaging data. The results indicate the utility and reproducibility of our principal curve approach in the face of underlying structural variation.
Chip-seq and gene expression data for the identification of functional sub-pathways: a proof of concept in lung cancer
Authors: Atsalaki Xanthoula , Koumakis Lefteris , Potamias George , Tsiknakis Manolis 
Published: June 2020

AbstractHigh-throughput technologies, such as chromatin immunoprecipitation (ChIP) with massively parallel sequencing (ChIP-seq) have enabled cost and time efficient generation of immense amount of genome data. The advent of advanced sequencing techniques allowed biologists and bioinformaticians to investigate biological aspects of cell function and understand or reveal unexplored disease etiologies. Systems biology attempts to formulate the molecular mechanisms in mathematical models and one of the most important areas is the gene regulatory networks (GRNs), a collection of DNA segments that somehow interact with each other. GRNs incorporate valuable information about molecular targets that can be corellated to specific phenotype.In our study we highlight the need to develop new explorative tools and approaches for the integration of different types of -omics data such as ChIP-seq and GRNs using pathway analysis methodologies. We present an integrative approach for ChIP-seq and gene expression data on GRNs. Using public microarray expression samples for lung cancer and healthy subjects along with the KEGG human gene regulatory networks, we identified ways to disrupt functional sub-pathways on lung cancer with the aid of CTCF ChIP-seq data, as a proof of concept.We expect that such a systems biology pipeline could assist researchers to identify corellations and causality of transcription factors over functional or disrupted biological sub-pathways.
Cannabidiol Interactions with Voltage-Gated Sodium Channels
Authors: Sait Lily Goodyer , Sula Altin , Hollingworth David , Whalley Benjamin J. , Rana Rohini R. , Wallace B.A. 
Published: June 2020

AbstractVoltage-gated sodium channels are targets for a range of pharmaceutical drugs developed for treatment of neurological diseases. Cannabidiol (CBD), the non-psychoactive compound isolated from cannabis plants, was recently approved for treatment of two types of epilepsy associated with sodium channel mutations. This study used high resolution X-ray crystallography to demonstrate the detailed nature of the interactions between CBD and the NavMs voltage-gated sodium channel, showing CBD binds at a novel site at the interface of the fenestrations and the central hydrophobic cavity of the channel. Binding at this site blocks the transmembrane-spanning sodium ion translocation pathway, providing a molecular mechanism for channel inhibition. Modelling studies illuminate why the closely-related psychoactive compound THC may not bind to these channels. Finally, comparisons are made with the TRPV2 channel, also recently proposed as a target site for CBD. In summary, this study provides novel insight into a possible mechanism for CBD with sodium channels.
Efficient population coding depends on stimulus convergence and source of noise
Authors: Röth Kai , Shao Shuai , Gjorgjieva Julijana 
Published: June 2020

AbstractSensory organs transmit information to downstream brain circuits using a neural code comprised of spikes from multiple neurons. According to the prominent efficient coding framework, the properties of sensory populations have evolved to encode maximum information about stimuli given biophysical constraints. How information coding depends on the way sensory signals from multiple channels converge downstream is still unknown, especially in the presence of noise which corrupts the signal at different points along the pathway. Here, we calculated the optimal information transfer of a population of nonlinear neurons under two scenarios. First, a lumped-coding channel where the information from different inputs converges to a single channel, thus reducing the number of neurons. Second, an independent-coding channel when different inputs contribute independent information without convergence. In each case, we investigated information loss when the sensory signal was corrupted by two sources of noise. We determined critical noise levels at which the optimal number of distinct thresholds of individual neurons in the population changes. Comparing our system to classical physical systems, these changes correspond to first- or second-order phase transitions for the lumped- or the independent-coding channel, respectively. We relate our theoretical predictions to coding in a population of auditory nerve fibers recorded experimentally, and find signatures of efficient coding. Our results yield important insights into the diverse coding strategies used by neural populations to optimally integrate sensory stimuli in the presence of distinct sources of noise.
Dietary and pharmacological induction of serine synthesis genes
Authors: Vazquez Alexei 
Published: June 2020

AbstractThere is an increasing interest in the pathway of L-serine synthesis and its. Although L-serine and downstream products can be obtained from the diet, serine deficiency has been documented in neurological disorders, macular degeneration and aging. This evidence calls for strategies to induce serine synthesis. Here I address this problem taking advantage of the wealth of data deposited in the gene expression omnibus database. I uncover that low protein and ketogenic diets increase the expression of serine synthesis genes in the liver and the brain relative to control diets. I discover oestrogen medications, the antifolate methotrexate and serine synthesis inhibitors as classes of compounds inducing the expression of serine synthesis genes in the liver. Future work is required to investigate the use of these interventions for the management of serine deficiency disorders.
Uncovering candidate genes involved in photosynthetic capacity using unexplored genetic variation in Spring Wheat
Authors: Joynson Ryan , Molero Gemma , Coombes Benedict , Gardiner Laura-Jayne , Rivera-Amado Carolina , Piñera-Chávez Francisco J , Evans John R , Furbank Robert T , Reynolds Matthew P , Hall Anthony 
Published: June 2020

AbstractTo feed an ever-increasing population we must leverage advances in genomics and phenotyping to harness the variation in wheat breeding populations for traits like photosynthetic capacity which remains unoptimized. Here we survey a diverse set of wheat germplasm containing elite, introgression and synthetic derivative lines uncovering previously uncharacterised variation. We demonstrate how strategic integration of exotic material alleviates the D genome genetic bottleneck in wheat, increasing SNP rate by 62% largely due to Ae. tauschii synthetic wheat donors. Across the panel, 67% of the Ae. tauschii donor genome is represented as introgressions in elite backgrounds. We show how observed genetic variation together with hyperspectral reflectance data can be used to identify candidate genes for traits relating to photosynthetic capacity using association analysis. This demonstrates the value of genomic methods in uncovering hidden variation in wheat and how that variation can assist breeding efforts and increase our understanding of complex traits.
Sex-specific variation in the use of vertical habitat by a resident Antarctic top predator
Authors: Photopoulou Theoni , Heerah Karine , Pohle Jennifer , Boehme Lars 
Published: June 2020

1AbstractPatterns of habitat use are commonly studied in horizontal space, but this does not capture the four-dimensional nature of ocean habitats. There is strong seasonal variation in vertical ocean structuring, particularly at the poles, and deep-diving marine animals encounter a range of oceanographic conditions. We use hidden Markov models fitted to telemetry data from an air-breathing top predator to identify different diving behaviours and understand usage patterns of vertically distributed habitat. We show that preference for oceanographic conditions in the Weddell Sea, Antarctica, varies by sex in Weddell seals, and present the first evidence that both sexes use high-density, continental shelf water masses. Males spend more time in the colder, unique high-salinity shelf water masses found at depth, while females also venture off the continental shelf and visit warmer, shallower pelagic water masses. Both sexes exhibit a diurnal pattern in diving behaviour that persists from austral autumn into winter. These findings provide insights into the Weddell Sea shelf and open ocean ecosystem from a top predator perspective. The differences in habitat use in a resident, sexually monomorphic Antarctic top predator suggest a different set of needs and constraints operating at the intraspecific level, which are not driven by body size.
Genomic selection strategies for clonally propagated crops
Authors: Werner Christian R. , Gaynor R. Chris , Sargent Daniel J. , Lillo Alessandra , Gorjanc Gregor , Hickey John M. 
Published: June 2020

AbstractFor genomic selection in clonal breeding programs to be effective, crossing parents should be selected based on genomic predicted cross performance unless dominance is negligible. Genomic prediction of cross performance enables a balanced exploitation of the additive and dominance value simultaneously. Here, we compared different strategies for the implementation of genomic selection in clonal plant breeding programs. We used stochastic simulations to evaluate six combinations of three breeding programs and two parent selection methods. The three breeding programs included i) a breeding program that introduced genomic selection in the first clonal testing stage, and ii) two variations of a two-part breeding program with one and three crossing cycles per year, respectively. The two parent selection methods were i) selection of parents based on genomic estimated breeding values, and ii) selection of parents based on genomic predicted cross performance. Selection of parents based on genomic predicted cross performance produced faster genetic gain than selection of parents based on genomic estimated breeding values because it substantially reduced inbreeding when the dominance degree increased. The two-part breeding programs with one and three crossing cycles per year using genomic prediction of cross performance always produced the most genetic gain unless dominance was negligible. We conclude that i) in clonal breeding programs with genomic selection, parents should be selected based on genomic predicted cross performance, and ii) a two-part breeding program with parent selection based on genomic predicted cross performance to rapidly drive population improvement has great potential to improve breeding clonally propagated crops.
Mainly on the Plane: Deep Subsurface Bacterial Proteins Bind and Alter Clathrate Structure
Authors: Johnson Abigail M. , Huard Dustin J.E. , Kim Jongchan , Raut Priyam , Dai Sheng , Lieberman Raquel L. , Glass Jennifer B. 
Published: June 2020

ABSTRACTGas clathrates are both a resource and a hindrance. They store massive quantities of natural gas but also can clog natural gas pipelines, with disastrous consequences. Eco-friendly technologies for controlling and modulating gas clathrate growth are needed. Type I Antifreeze Proteins (AFPs) from cold-water fish have been shown to bind to gas clathrates via repeating motifs of threonine and alanine. We tested whether proteins encoded in the genomes of bacteria native to natural gas clathrates bind to and alter clathrate morphology. We identified putative clathrate-binding proteins (CBPs) with multiple threonine/alanine motifs in a putative operon (cbp) in metagenomes from natural clathrate deposits. We recombinantly expressed and purified five CbpA proteins, four of which were stable, and experimentally confirmed that CbpAs bound to tetrahydrofuran (THF) clathrate, a low-pressure analog for structure II gas clathrate. When grown in the presence of CbpAs, THF clathrate was polycrystalline and plate-like instead of forming single, octahedral crystals. Two CbpAs yielded branching clathrate crystals, similar to the effect of Type I AFP, while the other two produced hexagonal crystals parallel to the [1 1 1] plane, suggesting two distinct binding modes. Bacterial CBPs may find future utility in industry, such as maintaining a plate-like structure during gas clathrate transportation.Table of Contents Graphic
Ancient evolutionary origin of intrinsically disordered cancer risk regions
Authors: Pajkos Mátyás , Zeke András , Dosztányi Zsuzsanna 
Published: June 2020

AbstractCancer is a heterogeneous genetic disease that alters the proper functioning of proteins involved in key regulatory processes such as cell cycle, DNA repair, survival or apoptosis. Mutations often accumulate in hot-spots regions, highlighting critical functional modules within these proteins that need to be altered, amplified or abolished for tumor formation. Recent evidence suggests that these mutational hotspots can not only correspond to globular domains but also to intrinsically disordered regions (IDRs), which play a significant role in a subset of cancer types. IDRs have distinct functional properties that originate from their inherent flexibility. Generally, they correspond to more recent evolutionary inventions and show larger sequence variations across species. In this work we analyzed the evolutionary origin of disordered regions that are specifically targeted in cancer. Surprisingly, the majority of these disordered cancer risk regions showed remarkable conservation with ancient evolutionary origin, stemming from the earliest multicellular animals or even beyond. Nevertheless, we encountered several examples, where the mutated region emerged at a later stage compared to the origin of the gene family. We also showed the cancer risk regions become quickly fixated after their emergence, but evolution continues to tinker with their genes with novel regulatory elements introduced even at the level of humans. Our concise analysis provides a much clearer picture of the emergence of key regulatory elements in proteins and highlights the importance of taking into account the modular organisation of proteins for the analyses of evolutionary origin.
Prediction of amphipathic helix – membrane interactions with Rosetta
Authors: Gulsevin Alican , Meiler Jens 
Published: June 2020

AbstractAmphipathic helices have hydrophobic and hydrophilic/charged residues situated on opposite faces of the helix. They can anchor peripheral membrane proteins to the membrane, be attached to integral membrane proteins, or exist as independent peptides. Despite the widespread presence of membrane-interacting amphipathic helices, there is no computational tool within Rosetta to model their interactions with membranes. In order to address this need, we developed the AmphiScan protocol with PyRosetta, which runs a grid search to find the most favorable position of an amphipathic helix with respect to the membrane. The performance of the algorithm was tested in benchmarks with theRosettaMembrane, ref2015_memb, andfranklin2019score functions on six engineered and 44 naturally-occurring amphipathic helices using membrane coordinates from the OPM and PDBTM databases, OREMPRO server, and MD simulations for comparison. The AmphiScan protocol predicted the coordinates of amphipathic helices within less than 3Å of the reference structures and identified membrane-embedded residues with a Matthews Correlation Constant (MCC) of up to 0.57. Overall, AmphiScan stands as fast, accurate, and highly-customizable protocol that can be pipelined with other Rosetta and Python applications.