bluuebunny/crossref_metadata_2025_split huggingface dataset:
Elucidation of quantitative structural diversity of remarkable rearrangement regions, shufflons, in IncI2 plasmids
Authors: Sekizuka Tsuyoshi , Kawanishi Michiko , Ohnishi Mamoru , Shima Ayaka , Kato Kengo , Yamashita Akifumi , Matsui Mari , Suzuki Satowa , Kuroda Makoto 
Published: April 2017

AbstractA multiple DNA inversion system, the shufflon, exists in incompatibility (Inc) I1 and I2 plasmids. The shufflon generates variants of the PilV protein, a minor component of the thin pilus. The shufflon is one of the most difficult regions for de novo genome assembly because of its structural diversity even in an isolated bacterial clone. We determined complete genome sequences, including those of IncI2 plasmids carrying mcr-1, of three Escherichia coli strains using single-molecule, real-time (SMRT) sequencing and Illumina sequencing. The sequences assembled using only SMRT sequencing contained misassembled regions in the shufflon. A hybrid analysis using SMRT and Illumina sequencing resolved the misassembled region and revealed that the three IncI2 plasmids, excluding the shufflon region, were highly conserved. Moreover, the abundance ratio of whole-shufflon structures could be determined by quantitative structural variation analysis of the SMRT data, suggesting that a remarkable heterogeneity of whole-shufflon structural variations exists in IncI2 plasmids. These findings indicate that remarkable rearrangement regions should be validated using both long-read and short-read sequencing data and that the structural variation of PilV in the shufflon might be closely related to phenotypic heterogeneity of plasmid-mediated transconjugation involved in horizontal gene transfer even in bacterial clonal populations.
Unified Alignment of Protein-Protein Interaction Networks
Authors: Malod-Dognin Noël , Ban Kristina , Pržulj Nataša 
Published: April 2017

AbstractParalleling the increasing availability of protein-protein interaction (PPI) network data, several network alignment methods have been proposed. Network alignments have been used to uncover functionally conserved network parts and to transfer annotations. However, due to the computational intractability of the network alignment problem, aligners are heuristics providing divergent solutions and no consensus exists on a gold standard, or which scoring scheme should be used to evaluate them. We comprehensively evaluate the alignment scoring schemes and global network aligners on large scale PPI data and observe that three methods, HUBALIGN, L-GRAAL and NATALIE, regularly produce the most topologically and biologically coherent alignments. We study the collective behaviour of network aligners and observe that PPI networks are almost entirely aligned with a handful of aligners that we unify into a new tool, Ulign. Ulign enables complete alignment of two networks, which traditional global and local aligners fail to do. Also, multiple mappings of Ulign define biologically relevant soft clusterings of proteins in PPI networks, which may be used for refining the transfer of annotations across networks. Hence, PPI networks are already well investigated by current aligners, so to gain additional biological insights, a paradigm shift is needed. We propose such a shift come from aligning all available data types collectively rather than any particular data type in isolation from others.
Temperature-dependent folding allows stable dimerization of secretory and virus-associated E proteins of Dengue and Zika viruses in mammalian cells
Authors: Slon Campos J. L. , Marchese S. , Rana J. , Mossenta M. , Poggianella M. , Bestagno M. , Burrone O. R. 
Published: April 2017

AbstractDengue and Zika are two of the most important human viral pathogens worldwide. In both cases, the envelope glycoprotein E is the main target of the antibody response. Recently, new complex quaternary epitopes were identified which are the consequence of the arrangement of the antiparallel E dimers on the viral surface. Such epitopes can be exploited to develop more efficient cross-neutralizing vaccines. Here we describe a successful covalent stabilization of E dimers from Dengue and Zika viruses in mammalian cells. Folding and dimerization of secretory E was found to be strongly dependent on temperature but independent of PrM co-expression. In addition, we found that, due to the close relationship between flaviviruses, Dengue and Zika viruses E proteins can form heterodimers and assemble into mosaic viral particles. Finally, we present new virus-free analytical platforms to study and screen antibody responses against Dengue and Zika, which allow for differentiation of epitopes restricted to specific domains, dimers and higher order arrangements of E.
Neurons Export Extracellular Vesicles Enriched in Cysteine String Protein and Misfolded Protein Cargo
Authors: Deng Jingti , Koutras Carolina , Donnelier Julien , Alshehri Mana , Fotouhi Maryam , Girard Martine , Casha Steve , McPherson Peter S. , Robbins Stephen M. , Braun Janice E. A. 
Published: April 2017

AbstractThe fidelity of synaptic transmission depends on the integrity of the protein machinery at the synapse. Unfolded synaptic proteins undergo refolding or degradation in order to maintain synaptic proteostasis and preserve synaptic function, and buildup of unfolded/toxic proteins leads to neuronal dysfunction. Many molecular chaperones contribute to proteostasis, but one in particular, cysteine string protein (CSPα), is critical for proteostasis at the synapse. In this study we report that exported vesicles from neurons contain CSPα. Extracellular vesicles (EV’s) have been implicated in a wide range of functions. However, the functional significance of neural EV’s remains to be established. Here we demonstrate that co-expression of CSPα with the disease-associated proteins, polyglutamine expanded protein 72Q huntingtinex°n1 or superoxide dismutase-1 (SOD-1G93A) leads to the cellular export of both 72Q huntingtinex°n1 and SOD-1G93A via EV’s. In contrast, the inactive CSPαHPD-AAA mutant does not facilitate elimination of misfolded proteins. Furthermore, CSPα-mediated export of 72Q huntingtinex°n1 is reduced by the polyphenol, resveratrol. Our results indicate that by assisting local lysosome/proteasome processes, CSPα-mediated removal of toxic proteins via EVs plays a central role in synaptic proteostasis and CSPα thus represents a potential therapeutic target for neurodegenerative diseases.
Power Flow in a Large-Core Multimode Fiber under External Perturbation and its Applications
Authors: Qian Sen , Xu Yang , Zhong Lisheng , Su Lei 
Published: April 2017

AbstractLarge core optical multimode fiber provides benefits such as a large light-coupling tolerance, easy handling, and delivery of higher light power without undesirable nonlinear effects. In this research, we exploit the effects of external perturbation on the power flow within the large core fiber and present two relevant applications, namely a perturbation sensor and a doughnut beam tuner. Since conventional multimode fiber power flow model does not take into consideration the perturbation effect, we modify the power flow model so that the influence of time varying perturbation can be theoretically analyzed. Based on our theory, we further conduct the numerical simulation and experiments on these two applications. For the fiber vibration sensor, the proposed numerical model shows that the sensor sensitivity depends on the intensity profile of the launched beam and also the higher-order harmonics that were not reported previously can become interferences to affect the signal. For the beam tuner application, we prove both theoretically and experimentally that the doughnut intensity profile at the fiber output can be tuned in real-time by applying external perturbations to the fiber. We expect that the results can be useful to further exploit the external perturbation on large core fiber in various applications.
The tarantula toxin β/δ-TRTX-Pre1a highlights the importance of the S1-S2 voltage-sensor region for sodium channel subtype selectivity
Authors: Wingerd Joshua S. , Mozar Christine A. , Ussing Christine A. , Murali Swetha S. , Chin Yanni K.-Y. , Cristofori-Armstrong Ben , Durek Thomas , Gilchrist John , Vaughan Christopher W. , Bosmans Frank , Adams David J. , Lewis Richard J. , Alewood Paul F. , Mobli Mehdi , Christie Macdonald J. , Rash Lachlan D. 
Published: April 2017

AbstractVoltage-gated sodium (NaV) channels are essential for the transmission of pain signals in humans making them prime targets for the development of new analgesics. Spider venoms are a rich source of peptide modulators useful to study ion channel structure and function. Here we describe β/δ-TRTX-Pre1a, a 35-residue tarantula peptide that selectively interacts with neuronal NaV channels inhibiting peak current of hNaV1.1, rNaV1.2, hNaV1.6, and hNaV1.7 while concurrently inhibiting fast inactivation of hNaV1.1 and rNaV1.3. The DII and DIV S3-S4 loops of NaV channel voltage sensors are important for the interaction of Pre1a with NaV channels but cannot account for its unique subtype selectivity. Through analysis of the binding regions we ascertained that the variability of the S1-S2 loops between NaV channels contributes substantially to the selectivity profile observed for Pre1a, particularly with regards to fast inactivation. A serine residue on the DIV S2 helix was found to be sufficient to explain Pre1a’s potent and selective inhibitory effect on the fast inactivation process of NaV1.1 and 1.3. This work highlights that interactions with both S1-S2 and S3-S4 of NaV channels may be necessary for functional modulation, and that targeting the diverse S1-S2 region within voltage-sensing domains provides an avenue to develop subtype selective tools.
Paper strip-embedded graphene quantum dots: a screening device with a smartphone readout
Authors: Álvarez-Diduk Ruslan , Orozco Jahir , Merkoçi Arben 
Published: April 2017

AbstractSimple, inexpensive and rapid sensing systems are very demanded for a myriad of uses. Intrinsic properties of emerging paper-based analytical devices have demonstrated considerable potential to fulfill such demand. This work reports an easy-to-use, low cost, and disposable paper-based sensing device for rapid chemical screening with a smartphone readout. The device comprises luminescent graphene quantum dots (GQDs) sensing probes embedded into a nitrocellulose matrix where the resonance energy transfer phenomenon seems to be the sensing mechanism. The GQDs probes were synthesized from citric acid by a pyrolysis procedure, further physisorbed and confined into small wax-traced spots on the nitrocellulose substrate. The GQDs were excited by an UV LED, this, is powered by a smartphone used as both; energy source and imaging capture. The LED was contained within a 3D-printed dark chamber that isolates the paper platform from external light fluctuations leading to highly reproducible data. The cellulose-based device was proven as a promising screening tool for phenols and polyphenols in environmental and food samples, respectively. It opens up new opportunities for simple and fast screening of organic compounds and offers numerous possibilities for versatile applications. It can be especially useful in remote settings where sophisticated instrumentation is not always available.
Evolution of crystal structures in GeTe during phase transition
Authors: Jeong Kwangsik , Park Seungjong , Park Dambi , Ahn Min , Han Jeonghwa , Yang Wonjun , Jeong Hong-Sik , Cho Mann-Ho 
Published: April 2017

AbstractWe investigated changes in the crystal structure of GeTe during its phase transition. Using density functional theory (DFT) calculations, four possible crystal structures were identified: R3m, P1, Cm, and Fm3m. Among these, P1 and Cm were examined here for the first time. By calculating the internal energy of the crystal volume change, we verified that P1, R3m, and Cm can coexist in crystalline GeTe. The X-ray diffraction spectra of annealed and laser-irradiated GeTe films revealed coexisting P1 or R3m and Cm. In addition, we confirmed that Cm transforms into P1 or R3m after laser irradiation. The presence of these new structures was revealed in the crystal Raman spectra. Many of the Raman peaks in the crystalized GeTe could be explained by the coexistence of various structures. By calculating the band gaps of these structures, we also found that a structural transformation induces a change in the crystal resistance, owing to differences in the band gaps of individual structures. The generation of new crystal structures suggests a facile phase change and instability during the structural transformation.
A geographically-diverse collection of 418 human gut microbiome pathway genome databases
Authors: Hahn Aria S. , Altman Tomer , Konwar Kishori M. , Hanson Niels W. , Kim Dongjae , Relman David A. , Dill David L. , Hallam Steven J. 
Published: April 2017

AbstractAdvances in high-throughput sequencing are reshaping how we perceive microbial communities inhabiting the human body, with implications for therapeutic interventions. Several large-scale datasets derived from hundreds of human microbiome samples sourced from multiple studies are now publicly available. However, idiosyncratic data processing methods between studies introduce systematic differences that confound comparative analyses. To overcome these challenges, we developed GutCyc, a compendium of environmental pathway genome databases (ePGDBs) constructed from 418 assembled human microbiome datasets using MetaPathways, enabling reproducible functional metagenomic annotation. We also generated metabolic network reconstructions for each metagenome using the Pathway Tools software, empowering researchers and clinicians interested in visualizing and interpreting metabolic pathways encoded by the human gut microbiome. For the first time, GutCyc provides consistent annotations and metabolic pathway predictions, making possible comparative community analyses between health and disease states in inflammatory bowel disease, Crohn’s disease, and type 2 diabetes. GutCyc data products are searchable online, or may be downloaded and explored locally using MetaPathways and Pathway Tools.
A resource for assessing information processing in the developing brain using EEG and eye tracking
Authors: Langer Nicolas , Ho Erica J. , Alexander Lindsay M. , Xu Helen Y. , Jozanovic Renee K. , Henin Simon , Petroni Agustin , Cohen Samantha , Marcelle Enitan T. , Parra Lucas C. , Milham Michael P. , Kelly Simon P. 
Published: April 2017

AbstractWe present a dataset combining electrophysiology and eye tracking intended as a resource for the investigation of information processing in the developing brain. The dataset includes high-density task-based and task-free EEG, eye tracking, and cognitive and behavioral data collected from 126 individuals (ages: 6–44). The task battery spans both the simple/complex and passive/active dimensions to cover a range of approaches prevalent in modern cognitive neuroscience. The active task paradigms facilitate principled deconstruction of core components of task performance in the developing brain, whereas the passive paradigms permit the examination of intrinsic functional network activity during varying amounts of external stimulation. Alongside these neurophysiological data, we include an abbreviated cognitive test battery and questionnaire-based measures of psychiatric functioning. We hope that this dataset will lead to the development of novel assays of neural processes fundamental to information processing, which can be used to index healthy brain development as well as detect pathologic processes.
A high-throughput molecular data resource for cutaneous neurofibromas
Authors: Gosline Sara J.C. , Weinberg Hubert , Knight Pamela , Yu Thomas , Guo Xindi , Prasad Nripesh , Jones Angela , Shrestha Shristi , Boone Braden , Levy Shawn E. , La Rosa Salvatore , Guinney Justin , Bakker Annette 
Published: April 2017

AbstractNeurofibromatosis type 1 (NF1) is a genetic disorder with a range of clinical manifestations such as widespread growth of benign tumours called neurofibromas, pain, learning disorders, bone deformities, vascular abnormalities and even malignant tumours. With the establishment of the Children’s Tumour Foundation biobank, neurofibroma samples can now be collected directly from patients to be analysed by the larger scientific community. This work describes a pilot study to characterize one class of neurofibroma, cutaneous neurofibromas, by molecularly profiling of ~40 cutaneous neurofibromas collected from 11 individual patients. Data collected from each tumour includes (1) SNP Arrays, (2) Whole genome sequencing (WGS) and (3) RNA-Sequencing. These data are now freely available for further analysis at http://www.synapse.org/cutaneousNF.
X-ray computed tomography library of shark anatomy and lower jaw surface models
Authors: Kamminga Pepijn , De Bruin Paul W. , Geleijns Jacob , Brazeau Martin D. 
Published: April 2017

AbstractThe cranial diversity of sharks reflects disparate biomechanical adaptations to feeding. In order to be able to investigate and better understand the ecomorphology of extant shark feeding systems, we created a x-ray computed tomography (CT) library of shark cranial anatomy with three-dimensional (3D) lower jaw reconstructions. This is used to examine and quantify lower jaw disparity in extant shark species in a separate study. The library is divided in a dataset comprised of medical CT scans of 122 sharks (Selachimorpha, Chondrichthyes) representing 73 extant species, including digitized morphology of entire shark specimens. This CT dataset and additional data provided by other researchers was used to reconstruct a second dataset containing 3D models of the left lower jaw for 153 individuals representing 94 extant shark species. These datasets form an extensive anatomical record of shark skeletal anatomy, necessary for comparative morphological, biomechanical, ecological and phylogenetic studies.
The contemporary distribution of Trypanosoma cruzi infection in humans, alternative hosts and vectors
Authors: Browne Annie J. , Guerra Carlos A. , Alves Renato Vieira , da Costa Veruska Maia , Wilson Anne L. , Pigott David M. , Hay Simon I. , Lindsay Steve W. , Golding Nick , Moyes Catherine L. 
Published: April 2017

AbstractChagas is a potentially fatal chronic disease affecting large numbers of people across the Americas and exported throughout the world through human population movement. It is caused by the Trypanosoma cruzi parasite, which is transmitted by triatomine vectors to humans and a wide range of alternative host species. The database described here was compiled to allow the risk of vectorial transmission to humans to be mapped using geospatial models. The database collates all available records, published since 2003, for prevalence and occurrence of infection in humans, vectors and alternative hosts, and links each record to a defined time and location. A total of 16,802 records of infection have been extracted from the published literature and unpublished sources. The resulting database can be used to improve our understanding of the geographic variation in vector infection prevalence and to estimate the risk of vectorial transmission of T. cruzi to humans.
Geographic barriers and Pleistocene climate change shaped patterns of genetic variation in the Eastern Afromontane biodiversity hotspot
Authors: Mairal Mario , Sanmartín Isabel , Herrero Alberto , Pokorny Lisa , Vargas Pablo , Aldasoro Juan J. , Alarcón Marisa 
Published: April 2017

AbstractThe Eastern African Afromontane forest is getting increased attention in conservation studies because of its high endemicity levels and shrinking geographic distribution. Phylogeographic studies have found evidence of high levels of genetic variation structured across the Great Rift System. Here, we use the epiphytic plant species Canarina eminii to explore causal explanations for this pattern. Phylogeographic analyses were undertaken using plastid regions and AFLP fragments. Population genetic analyses, Statistical Parsimony, and Bayesian methods were used to infer genetic diversity, genealogical relationships, structure, gene flow barriers, and the spatiotemporal evolution of populations. A strong phylogeographic structure was found, with two reciprocally monophyletic lineages on each side of the Great Rift System, high genetic exclusivity, and restricted gene flow among mountain ranges. We explain this pattern by topographic and ecological changes driven by geological rifting in Eastern Africa. Subsequent genetic structure is attributed to Pleistocene climatic changes, in which sky-islands acted as long-term refuges and cradles of genetic diversity. Our study highlights the importance of climate change and geographic barriers associated with the African Rift System in shaping population genetic patterns, as well as the need to preserve the high levels of exclusive and critically endangered biodiversity harboured by current patches of the Afromontane forest.
An inter-residue network model to identify mutational-constrained regions on the Ebola coat glycoprotein
Authors: Quinlan Devin S. , Raman Rahul , Tharakaraman Kannan , Subramanian Vidya , del Hierro Gabriella , Sasisekharan Ram 
Published: April 2017

AbstractRecently, progress has been made in the development of vaccines and monoclonal antibody cocktails that target the Ebola coat glycoprotein (GP). Based on the mutation rates for Ebola virus given its natural sequence evolution, these treatment strategies are likely to impose additional selection pressure to drive acquisition of mutations in GP that escape neutralization. Given the high degree of sequence conservation among GP of Ebola viruses, it would be challenging to determine the propensity of acquiring mutations in response to vaccine or treatment with one or a cocktail of monoclonal antibodies. In this study, we analyzed the mutability of each residue using an approach that captures the structural constraints on mutability based on the extent of its inter-residue interaction network within the three-dimensional structure of the trimeric GP. This analysis showed two distinct clusters of highly networked residues along the GP1-GP2 interface, part of which overlapped with epitope surfaces of known neutralizing antibodies. This network approach also permitted us to identify additional residues in the network of the known hotspot residues of different anti-Ebola antibodies that would impact antibody-epitope interactions.
Correlated Mutation in the Evolution of Catalysis in Uracil DNA Glycosylase Superfamily
Authors: Xia Bo , Liu Yinling , Guevara Jose , Li Jing , Jilich Celeste , Yang Ye , Wang Liangjiang , Dominy Brian N. , Cao Weiguo 
Published: April 2017

AbstractEnzymes in Uracil DNA glycosylase (UDG) superfamily are essential for the removal of uracil. Family 4 UDGa is a robust uracil DNA glycosylase that only acts on double-stranded and single-stranded uracil-containing DNA. Based on mutational, kinetic and modeling analyses, a catalytic mechanism involving leaving group stabilization by H155 in motif 2 and water coordination by N89 in motif 3 is proposed. Mutual Information analysis identifies a complexed correlated mutation network including a strong correlation in the EG doublet in motif 1 of family 4 UDGa and in the QD doublet in motif 1 of family 1 UNG. Conversion of EG doublet in family 4 Thermus thermophilus UDGa to QD doublet increases the catalytic efficiency by over one hundred-fold and seventeen-fold over the E41Q and G42D single mutation, respectively, rectifying the strong correlation in the doublet. Molecular dynamics simulations suggest that the correlated mutations in the doublet in motif 1 position the catalytic H155 in motif 2 to stabilize the leaving uracilate anion. The integrated approach has important implications in studying enzyme evolution and protein structure and function.