bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multi-model functionalization of disease-associated PTEN missense mutations identifies multiple molecular mechanisms underlying protein dysfunction
Authors: Post Kathryn L. , Belmadani Manuel , Ganguly Payel , Meili Fabian , Dingwall Riki , McDiarmid Troy A. , Meyers Warren M. , Herrington Caitlin , Young Barry P. , Callaghan Daniel B. , Rogic Sanja , Edwards Matthew , Niciforovic Ana , Cau Alessandro , Rankin Catharine H. , O’Connor Timothy P. , Bamji Shernaz X. , Loewen Christopher J. , Allan Douglas W. , Pavlidis Paul , Haas Kurt 
Published: October 2019

ABSTRACTFunctional variomics provides the foundation for personalized medicine by linking genetic variation to disease expression, outcome and treatment, yet its utility is dependent on appropriate assays to evaluate mutation impact on protein function. To fully assess the effects of 106 missense and nonsense variants of PTEN associated with autism spectrum disorder, somatic cancer and PHTS, we take a deep phenotypic profiling approach using 18 assays in 5 model systems spanning diverse cellular environments ranging from molecular function to neuronal morphogenesis and behavior. Variants inducing instability occurred across the protein, resulting in partial to complete loss of function (LoF), which was well correlated across models. However, assays were selectively sensitive to variants located in substrate binding and catalytic domains, which exhibited complete LoF or dominant negativity independent of effects on stability. Our results indicate that full characterization of variant impact requires assays sensitive to instability and a range of protein functions.
Genetic signatures of evolutionary rescue by a selective sweep
Authors: Osmond Matthew M. , Coop Graham 
Published: October 2019

AbstractOne of the most useful models in population genetics is that of a selective sweep and the consequent hitch-hiking of linked neutral alleles. While variations on this model typically assume constant population size, many instances of strong selection and rapid adaptation in nature may co-occur with complex demography. Here we extend the hitch-hiking model to evolutionary rescue, where adaptation and demography not only co-occur but are intimately entwined. Our results show how this feedback between demography and evolution determines – and restricts – the genetic signatures of evolutionary rescue, and how these differ from the signatures of sweeps in populations of constant size. In particular, we find rescue to harden sweeps from standing variance or new mutation (but not from migration), reduce genetic diversity both at the selected site and genome-wide, and increase the range of observed Tajima’sDvalues. For a given initial rate of population decline, the feedback between demography and evolution makes all of these differences more dramatic under weaker selection, where bottlenecks are prolonged. Nevertheless, it is likely difficult to infer the co-incident timing of the sweep and bottleneck from these simple signatures, never-mind a feedback between them. Temporal samples spanning contemporary rescue events may offer one way forward.
Drosophila suzukii wing spot size is robust to developmental temperature
Authors: Varón-González Ceferino , Fraimout Antoine , Debat Vincent 
Published: October 2019

ABSTRACTPhenotypic plasticity is an important mechanism allowing adaptation to new environments and as such it has been suggested to facilitate biological invasions. Under this assumption, invasive populations are predicted to exhibit stronger plastic responses than native populations. Drosophila suzukii is an invasive species whose males harbor a spot on the wing tip. In this study, by manipulating developmental temperature, we compare the phenotypic plasticity of wing spot size of two invasive populations with that of a native population. We then compare the results with data obtained from wild-caught flies from different natural populations. While both wing size and spot size are plastic to temperature, no difference in plasticity was detected between native and invasive populations, rejecting the hypothesis of a role of the wing-spot plasticity in the invasion success. In contrast we observed a remarkable stability in the spot-to-wing ratio across temperatures, as well as among geographic populations. This stability suggests either that the spot relative size is under stabilizing selection, or that its variation might be constrained by a tight developmental correlation between spot size and wing size. Our data show that this correlation was lost at high temperature, leading to an increased variation in the relative spot size, particularly marked in the two invasive populations. This suggests (i) that D. suzukii’s development is impaired by hot temperatures, in agreement with the cold-adapted status of this species; (ii) that the spot size can be decoupled from wing size, rejecting the hypothesis of an absolute constraint and suggesting that the wing color pattern might be under stabilizing (sexual) selection; (iii) that such sexual selection might be relaxed in the invasive populations. Finally, a subtle but consistent directional asymmetry in spot size was detected in favor of the right side in all populations and temperatures, possibly indicative of a lateralized sexual behavior.
Primary myeloid cell proteomics and transcriptomics: importance of ß tubulin isotypes for osteoclast function
Authors: Guérit David , Marie Pauline , Morel Anne , Maurin Justine , Verollet Christel , Raynaud-Messina Brigitte , Urbach Serge , Blangy Anne 
Published: October 2019

AbstractAmong hematopoietic cells. osteoclasts (Oc) and immature dendritic cells (Dc) are closely related myeloid cells with distinct functions; Oc participate skeleton maintenance while Dc sample the environment for foreign antigens. Such specificities rely on profound modifications of gene and protein expression during Oc and Dc differentiation. We provide global proteomic and transcriptomic analyses of primary mouse Oc and Dc. based on original SILAC and RNAseq data. We established specific signatures for Oc and Dc including genes and proteins of unknown functions. In particular. we showed that Oc and Dc have the same α and β tubulin isotypes repertoire but that Oc express much more β tubulin isotype Tubb6. In both mouse and human Oc. we demonstrate that elevated expression of Tubb6 in Oc is necessary for correct podosomes organization and thus for the structure of the sealing zone. which sustains the bone resorption apparatus. Hence. lowering Tubb6 expression hindered Oc resorption activity. Overall. we highlight here potential new regulators of Oc and Dc biology and illustrate the functional importance of the tubulin isotype repertoire in the biology of differentiated cells.Summary statementThis study provides original proteomic and transcriptomic data of primary myeloid cells. The analysis led to signatures for osteoclasts and for immature dendritic cells including potential new regulators of their specific biology. RNA interference showed in particular that ß tubulin isotype Tubb6 participates in osteoclast podosome patterning. sealing zone structure and in the resorption activity.
Resolving cellular systems by ultra-sensitive and economical single-cell transcriptome filtering
Authors: Vallejo Andres F. , Davies James , Grover Amit , Tsai Ching-Hsuan , Jepras Robert , Polak Marta E. , West Jonathan 
Published: October 2019

AbstractSingle-cell transcriptomics has sensitivity limits that restrict low abundance transcript identification, affects clustering and introduce artefact. Here, we describe Constellation DropSeq (C-DropSeq), a molecular transcriptome filter that delivers two orders of magnitude sensitivity gains by maximising read utility while reducing sequencing depth and costs. The simple and powerful method is broadly compatible with library preparation routines and was demonstrated by identifying and characterizing the activation of rare dendritic cell sub-populations.
Decorin inhibits glucose-induced lens epithelial cell apoptosis via suppressing p22phox-p38 MAPK signaling pathway
Authors: Du Shanshan , Shao Jingzhi , Xie Dandan , Zhang Fengyan 
Published: October 2019

AbstractPurposeTo determine the effect of decorin on oxidative stress and apoptosis of human lens epithelial (HLE) cells under high glucose condition.MethodsHLE cell line (HLEB3) was incubated in normal glucose (5.5 mM) or high glucose (60 mM) medium. Decorin (50 nM) was applied 2 hours before high glucose medium was added. Apoptosis detection was executed by flow cytometry and western blotting (analysis of bcl-2 and bax). Oxidative stress level was measured by the generation of reactive oxygen species (ROS), glutathione peroxidase (GSH) and superoxide dismutase (SOD). P38 mitogen-activated protein kinase (MAPK) phosphorylation, the expression of p22phox of HLE cells and human lens anterior capsules were detected by western blotting. Small interfering RNA transfection to p22phox and p38 MAPK was also carried out on HLEB3.ResultsHigh glucose caused HLE cells oxidative stress and apoptosis exhibiting the increase of apoptotic cells and ROS production and decrease of bcl-2/bax ratio, GSH/GSSG ration and SOD activity. P22phox and phospho-p38 MAPK were upregulated in high glucose treated HLEB3 cells. Knocking down p22phox or p38 by siRNAs can reduce high glucose induced cell apoptosis and oxidative stress level. Silencing p22phox by siRNA can downregulate p38 MAPK activation. Decorin can inhibit the apoptosis, oxidative stress level and the induction of p22phox and p-p38 of HLEB3 induced by high glucose. Furthermore, the expression of p22phox and p38 were found significantly increased in lens anterior capsules of diabetic cataract patients compared to that of normal age-related cataract patients.ConclusionsResults showed that p22phox-p38 pathway may be particepated in high glucose induced lens epithelial cell injury, decorin may inhibit the high glucose induced apoptosis and oxidative stress injury by suppressing this pathway in part.
Thyroid hormone receptor beta mutations alter photoreceptor development and function inDanio rerio(zebrafish)
Authors: Deveau Ciana , Jiao Xiaodong , Suzuki Sachihiro , Krishnakumar Asha , Yoshimatsu Takeshi , Hejtmancik J Fielding , Nelson Ralph F. 
Published: October 2019

AbstractWe investigate a splice variant ofthrbisolated in the retina,trβ2, identifying functional changes in larval and adult mutant zebrafish lacking trβ2. We constructed two CRISPR mutant zebrafish with mutations located in the N-terminus region. The first is a6BP+1insertion deletion frameshift resulting in a truncated protein. The second is a3BPin frame deletion with intact binding domains. ERG recordings showed that the6BP+1mutants did not respond to red wavelengths of light while the3BPmutants did respond.6BP+1mutants lacked optomotor and optokinetic responses to red/black and green/black contrasts. Adult6BP+1mutants exhibit a loss of red-cone contribution to the ERG, and an increase in green and UV contributions. Anatomical markers show loss of red-cones in the6BP+1mutant but increase in blue, green, and UV cone density. Our results confirmtrβ2’s role in retinal cone development.Author SummaryThere are four cone photoreceptors responsible for color vision in zebrafish: red, green, blue, and UV. The thyroid hormone receptortrβ2is localized in the vertebrate retina. We know that it is necessary for the development of long-wavelength-sensitive cones (red), but here we investigate the functional alterations that accompany a loss oftrβ2. Our work contributes to the ongoing investigations of retinal development and the involvement of thyroid hormone receptors. Confirming previous morphological findings, we see that the fish become red colorblind whentrβ2is knocked out, but the contributions of the other three cone types shift in response. Our work highlights the plasticity of the retinal circuit as we see changes in opsin peaks and cone sensitivity, increases in contributions of UV cones, and an attempt at a mosaic pattern in the adult retina all in the absence oftrβ2and red cones. We now have an increased understanding of mechanisms underlying retinal development
Visual discrimination of optical material properties: a large-scale study
Authors: Sawayama Masataka , Dobashi Yoshinori , Okabe Makoto , Hosokawa Kenchi , Koumura Takuya , Saarela Toni , Olkkonen Maria , Nishida Shin’ya 
Published: October 2019

AbstractComplex visual processing involved in perceiving the object materials can be better elucidated by taking a variety of research approaches. Sharing stimulus and response data is an effective strategy to make the results of different studies directly comparable and can assist researchers with different backgrounds to jump into the field. Here, we constructed a database containing several sets of material images annotated with visual discrimination performance. We created the material images using physically-based computer graphics techniques and conducted psychophysical experiments with them in both laboratory and crowdsourcing settings. The observer’s task was to discriminate materials on one of six dimensions (gloss contrast, gloss distinctness-of-image, translucent vs. opaque, metal vs. plastic, metal vs. glass, and glossy vs. painted). The illumination consistency and object geometry were also varied. We used a non-verbal procedure (an oddity task) applicable for diverse use-cases such as cross-cultural, cross-species, clinical, or developmental studies. Results showed that the material discrimination depended on the illuminations and geometries and that the ability to discriminate the spatial consistency of specular highlights in glossiness perception showed larger individual differences than in other tasks. In addition, analysis of visual features showed that the parameters of higher-order color texture statistics can partially, but not completely, explain task performance. The results obtained through crowdsourcing were highly correlated with those obtained in the laboratory, suggesting that our database can be used even when the experimental conditions are not strictly controlled in the laboratory. Several projects using our dataset are underway.
BiomeSeq: A Tool for the Characterization of Animal Microbiomes from Metagenomic Data
Authors: Mulholland Kelly A. , Keeler Calvin L. 
Published: October 2019

AbstractThe complete characterization of a microbiome is critical in elucidating the complex ecology of the microbial composition within healthy and diseased animals. Many microbiome studies characterize only the bacterial component, for which there are several well-developed sequencing methods, bioinformatics tools and databases available. The lack of comprehensive bioinformatics workflows and databases have limited efforts to characterize the other components existing in a microbiome. BiomeSeq is a tool for the analysis of the complete animal microbiome using metagenomic sequencing data. With its comprehensive workflow, customizable parameters and microbial databases, BiomeSeq can rapidly quantify the viral, fungal, bacteriophage and bacterial components of a sample and produce informative tables for analysis. BiomeSeq was employed in detecting and quantifying the respiratory microbiome of a commercial poultry broiler flock throughout its grow-out cycle from hatching to processing. It successfully processed 780 million reads, of which 5,163 aligned to avian DNA viral genomes, 71,936 aligned to avian RNA viral genomes, 469,937 aligned to bacterial genomes, 504,682 aligned to bacteriophage genomes and 1,964 aligned to fungal genomes. For each microbial species detected, BiomeSeq calculated the normalized abundance, percent relative abundance, and coverage as well as the diversity for each sample. BiomeSeq provides for the detection and quantification of the microbiome from next-generation metagenomic sequencing data. This tool is implemented into a user-friendly container that requires one command and generates a table consisting of taxonomical information for each microbe detected as well as normalized abundance, percent relative abundance, coverage and diversity calculations.
Transposable elements contribute to regulatory hub stress-related long noncoding RNAs in Maize
Authors: Lv Yuanda , Hu Fengqin , Zhou Yongfeng , Wu Feilong , Zhou Ling , Gaut Brandon S. 
Published: October 2019

AbstractSeveral studies have mined short-read RNA sequencing datasets to identify lncRNAs, and others have focused on the function of individual lncRNA in abiotic stress response. However, our understanding of the complement, function and origin of long-non-coding RNA (lncRNAs) response to abiotic stress, especially transposon derived lncRNA (TE-lncRNA), is still in its infancy. To discover and study lncRNAs in maize (Zea mays ssp. mays), we utilized a dataset of 127 RNA sequencing samples that included PacBio fl-cDNA and total RNA-Seq datasets. Overall, we identified 23,309 candidate lncRNAs, 60% of which were identified in polyadenylated (polyA+) samples. The majority (65%) of the 23,309 lncRNAs had sequence similarity to transposable elements (TEs). Most had similarity to long-terminal-repeat retrotransposons from the Copia and Gypsy superfamilies, representing the high proportion of these elements in the genome, but class II, DNA transposons were enriched for lncRNAs relative to their genomic representation by 2-fold. By assessing the fraction of lncRNAs that respond to abiotic stresses like heat, cold, salt and drought, we identified 1,077 differentially expressed lncRNA transcripts. Their expression was correlated (r2=0.48) with their nearest gene, suggesting that lncRNAs are subject to some of the cis regulatory features as neighboring genes. By inferring co-expression networks across our large dataset, we found that 39 lncRNAs act as major hubs in co-expression networks, of which 18 appeared to be derived from TEs. These results suggest that lncRNAs, especially TE-lncRNAs, may play key regulatory roles in moderating abiotic responses.
Urbanism under dictatorship
Authors: Javanmardi Leila 
Published: October 2019

Purpose
By analyzing urbanism products, development plans and the process of modernization in Iran, the purpose of this paper is to critically trace the effect of dictatorial control on urbanism and the emergence of government-imposed urban segregation.

Design/methodology/approach
The main body of this work is concentrated on studying the history of urbanism in Iran, of which collecting data and descriptions played a crucial role. To prevent the limitations associated with singular methods, the methodology of this research is based on methodological triangulation (Denzin, 2017). With the triangulation scheme, the data are gathered by combining different qualitative and quantitative methods such as library, archival and media research, online resources, non-participatory observation and photography. For the empirical part, the city of Tehran is selected as the case study. Moreover, individual non-structured interviews with the locals were conducted to gain more insights regarding the housing projects.

Findings
The results reveal that despite the intense propaganda, the regime policies barely mentioned the urban poor. With the rise of new principles of architecture and urban planning, the regime tried to promote the image of an updated society; restructuring of the urban space was part of this process. However, the majority of the urban projects disregarded the financial ability of low-income groups and eventually benefited only the middle and upper classes. Also, by imposing a physical distance, low-income neighborhoods were located in the south in order to marginalize the urban poor who were in contrast with the idea of a modern city. Under these circumstances, severe economic inequality was provoked, which to this day has transformed into a complex socio-spatial segregation.

Originality/value
The works of general historical studies are not concentrated on urbanism and urban researchers have mostly focused on urbanism products during different periods, regardless, of the importance of urbanism as a tool in the service of hegemony. In other words, the majority of existing research investigates the evolution of urbanism and architecture in modern Iran, by questioning “what has been built?” and has ignored to trace the beneficiaries of the urban projects and to question “built for whom?”. Moreover, urbanism under the government of Mossadegh (1951–1953) has been largely overlooked, which could be due to his short time as Prime Minister of Iran. Mossadegh’s government was the first democratic government in Iran; hence investigating the policies used in this period has a great importance.
A fuzzy-based vulnerability assessment model for infrastructure networks incorporating reliability and centrality
Authors: Zarghami Seyed Ashkan , Gunawan Indra 
Published: October 2019

Purpose
The purpose of this paper is to attempt to shift away from an exclusive probabilistic viewpoint or a pure network theory-based perspective for vulnerability assessment of infrastructure networks (INs), toward an integrated framework that accounts for joint considerations of the consequences of component failure as well as the component reliability.

Design/methodology/approach
This work introduces a fuzzy inference system (FIS) model that deals with the problem of vulnerability analysis by mapping reliability and centrality to vulnerability. In the presented model, reliability and centrality are first fuzzified, then 16 different rules are defined and finally, a defuzzification process is conducted to obtain the model output, termed the vulnerability score. The FIS model developed herein attempts to explain the linkage between reliability and centrality so as to evaluate the degree of vulnerability for INs elements.

Findings
This paper compared the effectiveness of the vulnerability score in criticality ranking of the components against the conventional vulnerability analysis methods. Comparison of the output of the proposed FIS model with the conventional vulnerability indices reveals the effectiveness of the vulnerability score in identifying the criticality of components. The model result showed the vulnerability score decreases by increasing reliability and decreasing centrality.

Practical implications
Two key practical implications for vulnerability analysis of INs can be drawn from the suggested FIS model in this research. First, the maintenance strategy based on the vulnerability analysis proposed herein will provide an expert facilitator that helps infrastructure utilities to identify and prioritize the vulnerabilities. The second practical implication is especially valuable for designing an effective risk management framework, which allows for least cost decisions to be made for the protection of INs.

Originality/value
As part of the first contribution, we propose a novel fuzzy-based vulnerability assessment model in building a qualitative and quantitative picture of the vulnerability of INs. The second contribution is especially valuable for vulnerability analysis of INs by virtue of offering a key to understanding the component vulnerability principle as being constituted by the component likely behavior as well as the component importance in the network.