bluuebunny/crossref_metadata_2025_split huggingface dataset:
UV irradiation remodels the specificity landscape of transcription factors
Authors: Mielko Zachery , Zhang Yuning , Liu Yiling , Schaich Matthew A , Schnable Brittani , Burdinski Debbie , Adar Sheera , Pufall Miles , Van Houten Bennett , Gordan Raluca , Afek Ariel 
Published: October 2022

ABSTRACTSomatic mutations are highly enriched at transcription factor (TF) binding sites, with the strongest trend being observed for ultraviolet light (UV)-induced mutations in melanomas. One of the main mechanisms proposed for this hyper-mutation pattern is the inefficient repair of UV lesions within TF-binding sites, caused by competition between TFs bound to these lesions and the DNA repair proteins that must recognize the lesions to initiate repair. However, TF binding to UV-irradiated DNA is poorly characterized, and it is unclear whether TFs maintain specificity for their DNA sites after UV exposure. We developed UV-Bind, a high-throughput approach to investigate the impact of UV irradiation on protein-DNA binding specificity. We applied UV-Bind to ten TFs from eight structural families, and found that UV lesions significantly altered the DNA-binding preferences of all TFs tested. The main effect was a decrease in binding specificity, but the precise effects and their magnitude differ across factors. Importantly, we found that despite the overall reduction in DNA-binding specificity in the presence of UV lesions, TFs can still compete with repair proteins for lesion recognition, in a manner consistent with their specificity for UV-irradiated DNA. In addition, for a subset of TFs we identified a surprising but reproducible effect at certain non-consensus DNA sequences, where UV irradiation leads to a high increase in the level of TF binding. These changes in DNA-binding specificity after UV irradiation, at both consensus and non-consensus sites, have important implications for the regulatory and mutagenic roles of TFs in the cell.
KNOWLEDGE GRAPH AIDS COMPREHENSIVE EXPLANATION OF DRUG TOXICITY
Authors: Hao Yun , Romano Joseph D. , Moore Jason H. 
Published: October 2022

ABSTRACTIn computational toxicology, prediction of complex endpoints has always been challenging, as they often involve multiple distinct mechanisms. State-of-the-art models are either limited by low accuracy, or lack of interpretability due to their black-box nature. Here we introduce AIDTox, an interpretable deep learning model which incorporates curated knowledge of chemical-gene connections, gene-pathway annotations, and pathway hierarchy. AIDTox accurately predicts cytotoxicity outcomes in HepG2 and HEK293 cells. It also provides comprehensive explanations of cytotoxicity covering multiple aspects of drug activity including target interaction, metabolism, and elimination. In summary, AIDTox provides a computational framework for unveiling cellular mechanisms for complex toxicity endpoints.
Primitive purine biosynthesis connects ancient geochemistry to modern metabolism
Authors: Goldford Joshua E. , Smith Harrison B. , Longo Liam M. , Wing Boswell A. , McGlynn Shawn E. 
Published: October 2022

AbstractA major unresolved question in the origin and evolution of life is whether a continuous path from geochemical precursors to the majority of molecules in the biosphere can be reconstructed from modern day biochemistry. Here we simulated the emergence of ancient metabolic networks and identified a feasible path from simple geochemically plausible precursors (e.g., phosphate, sulfide, ammonia, simple carboxylic acids, and metals) using only known biochemical reactions and models of primitive coenzymes. We find that purine synthesis constitutes a bottleneck for metabolic expansion, and that non-autocatalytic phosphoryl coupling agents are necessary to enable expansion from geochemistry to modern metabolic networks. Our model predicts punctuated phases of metabolic evolution characterized by the emergence of small molecule coenzymes (e.g., ATP, NAD+, FAD). Early phases in the resulting expansion are associated with enzymes that are metal dependent and structurally symmetric, supporting models of early biochemical evolution. This expansion trajectory produces distinct hypotheses regarding the timing and mode of metabolic pathway evolution, including a late appearance of methane metabolisms and oxygenic photosynthesis consistent with the geochemical record. The concordance between biological and geological analysis suggests that this trajectory provides a plausible evolutionary history for the vast majority of core biochemistry.
A novel porcine model of CLN3 Batten disease recapitulates clinical phenotypes
Authors: Swier Vicki J. , White Katherine A. , Johnson Tyler B. , Wang Xiaojun , Han Jimin , Pearce David A. , Singh Ruchira , Rogers Christopher S. , Brudvig Jon J. , Weimer Jill M. 
Published: October 2022

AbstractMouse models of CLN3 Batten disease, a rare lysosomal storage disorder with no cure, have improved our understanding of CLN3 biology and therapeutics through their ease of use and a consistent display of cellular pathology. However, the translatability of murine models is limited by disparities in anatomy, body size, life span, and inconsistent, subtle behavior deficits that can be difficult to detect in CLN3 mutant mouse models, limiting their utility in preclinical studies. Here we present a longitudinal characterization of a novel miniswine model of CLN3 disease that recapitulates the most common human pathogenic variant, an exon 7-8 deletion (CLN3Δex7/8). Progressive pathology and neuron loss is observed in various regions of theCLN3Δex7/8miniswine brain and retina. Additionally, mutant miniswine present with vision impairment and motor abnormalities, similar to deficits seen in human patients. Taken together, theCLN3Δex7/8miniswine model shows consistent and progressive Batten disease pathology and behavioral impairment mirroring clinical presentation, demonstrating its value in studying the role of CLN3 and safety/efficacy of novel disease modifying therapeutics.
Discovery of deep-sea coral symbionts from a novel family of marine bacteria, Oceanoplasmataceae, with severely reduced genomes
Authors: Vohsen Samuel A. , Gruber-Vodicka Harald R. , Dubilier Nicole , Fisher Charles R. , Baums Iliana B. 
Published: October 2022

AbstractMicrobes perform critical functions in corals yet most knowledge is derived from the photic zone. Here, we discovered two mollicutes that dominate the microbiome of the deep-sea octocoral,Callogorgia delta,and reside in the mesoglea. These symbionts were abundant across the host’s range, absent in the water, and rare in sediments. The symbionts lack all known fermentative capabilities including glycolysis and can only generate energy from arginine provided by the coral host. Their genomes feature extensive mechanisms to interact with foreign DNA which may be indicative of their role in symbiosis. We erect the novel family Oceanoplasmataceae which includes these symbionts and others associated with four marine invertebrate phyla. Its exceptionally broad host range suggests that the diversity of this enigmatic family remains largely undiscovered. Oceanoplasmataceae genomes are the most highly reduced among mollicutes providing new insight into their reductive evolution and the roles of coral symbionts.
Too Much Information Is No Information: How Machine Learning and Feature Selection Could Help in Understanding the Motor Control of Pointing
Authors: Thomas Elizabeth , Ben Ali Ferid , Tolambiya Arvind , Chambellent Florian , Gaveau Jérémie 
Published: October 2022

AbstractThe aim of this study was to develop the use of Machine Learning techniques as a means of multivariate analysis in studies of motor control. These studies generate a huge amount of data, the analysis of which continues to be largely univariate. We propose the use of machine learning classification and feature selection as a means of uncovering feature combinations that are altered between conditions. High dimensional electromyograms (EMG) vectors were generated as several arm and trunk muscles were recorded while subjects pointed at various angles above and below the gravity neutral horizontal plane. We used Linear Discriminant Analysis (LDA) to carry out binary classifications between the EMG vectors for pointing at a particular angle, versus pointing at the gravity neutral direction. Classification success provided a composite index of muscular adjustments for various task constraints – in this case, pointing angles. In order to find the combination of features that were significantly altered between task conditions, we conducted a post classification feature selection i.e. investigated which combination of features had allowed for the classification. Feature selection was done by comparing the representations of each category created by LDA for the classification. In other words computing the difference between the representations of each class. We propose that this approach will help with comparing high dimensional EMG patterns in two ways; i) quantifying the effects of the entire pattern rather than using single arbitrarily defined variables and ii) identifying the parts of the patterns that convey the most information regarding the investigated effects.
Identification of Novel Transcripts and Exons by RNA-Seq of Transcriptome in Durio zibethinus Murr
Authors: Husin Nurul Arneida 
Published: October 2022

AbstractDurio zibethinus is a popular seasonal fruit among the Asian population and is frequently associated with economic losses due to a rapid post-harvest process. To identify novel transcripts and characterize D. zibethinus transcriptome, we employed high throughput RNA-Seq analysis. In this study, we characterized the growth and development of D. zibethinus at different growth stages, including the young, mature, and ripening stages of growth. After mapping, 110 million high-quality reads were analysed for each of the nine samples, revealing that each contains in range of 76,700 to 89,117 transcripts and 561,211 to 646,291 exons. With Cuffcompare to obtain the unannotated transcript, the novel exons, introns and loci were identified in the developmental stage with value of 3,438/313,476 (1.1%), 1,657/245,129 (0.7%) and 1,197/44,509 (2.7%), respectively. The differential expression genes (DEGs) in up-regulation were compared under the three growth stages: 1,496 (YS/MS), 2,154 (YS/RS), and 2,153 (MS/RS). These genes were then subjected to clustering analysis. A comprehensive study from the heatmap indicates that response to stress, hormone signalling, cuticle formation, general transporter, receptor and protein kinase and transcription factors are highly regulated gene functions for all growth stages. In the present analysis, we emphasized identifying and classifying unknown important transcripts, disregarding transcripts with accurate annotations. Differential expression analysis identified 280 unknown significant transcripts, presumably involved in various biological functions in durian growth. Top blastn results for 183 unknown transcripts revealed homology (80%–100%) to Bombax ceiba, Gossypium hirsutum, Gossypium raimondii, Herrania umbratica, Juglans regia, and Theobroma cacao. Under the category of unknown transcripts without a Blastn match, two unknown transcripts match GO terms. TCONS 00034019 and TCONS 00058246 match the InterPro GO Names for Biological Process (P) P:GO:0046622; P: positive regulation of organ growth. In the category of sequences with no BLASTx hit and no IPS match, three ORF sequences longer than 300 nt were identified. Our results significantly improved D. zibethinus transcript annotation and provide valuable resources for functional genomics and studies in durian.
Transcriptome analysis during fruit developmental stages in durian (Durio zibethinus Murr.) var. D24
Authors: Husin Nurul Arneida 
Published: October 2022

AbstractDurian (Durio zibethinus Murr.) fruits are famous for their unique aroma. This study analysed the Durian fruit transcriptome to discover the expression patterns of genes and to understand their regulation. Three developmental stages of Durian fruit, namely, early [90 days post-anthesis (DPA)], mature (120 DPA), and ripen (127 DPA), were studied. The Illumina HiSeq platform was used for sequencing. The sequence data were analysed using four different mapping aligners and statistical methods: CLC Genomic Workbench, HISAT2+DESeq2, Tophat+Cufflinks, and HISAT2+edgeR. The analyses showed that over 110 million clean reads were mapped to the Durian genome, yielding 19,976, 11,394, 17,833, and 24,351 differentially expressed genes during 90-127 days post-anthesis. Many identified differentially expressed genes were linked to the fruit ripening processes. The data analysis suggests that most genes with increased expression at the ripening stage were primarily involved in the metabolism of cofactors and vitamins, nucleotide metabolism, and carbohydrate metabolism. Significantly expressed genes from the young to mature stage were mainly associated with carbohydrate metabolism, amino acid metabolism, and cofactor and vitamin metabolism. The transcriptome data will serve as a foundation for understanding Durian fruit development-specific genes and could be helpful in fruit’s trait improvement.
How do individual factors affect career sustainability? An investigation of cascading effects through the career construction model of adaptation
Authors: Talluri Surendra Babu , Schreurs Bert , Uppal Nishant 
Published: October 2022

PurposeThough the recent conceptualization of career sustainability, defining its indicators and dimensions prompted an important field of careers research, empirical research is still in its infancy. The current study empirically investigates how proactive personality, career adaptability and proactive career behaviors promote career sustainability based on the career construction model of adaptation.Design/methodology/approachThe authors used a two-wave survey design to collect data from 414 full-time working professionals representing different organizations located in India. The authors tested the proposed hypotheses using structural equation modeling in IBM SPSS AMOS.FindingsResults supported a serial indirect effect model with career adaptability and proactive career behaviors carrying the effect of proactive personality on career sustainability.Originality/valueThe study contributes to the emerging sustainable careers literature by unveiling the role of individual factors in career sustainability. Furthermore, the authors investigated these relationships through the complete career construction model of adaptation. By doing so, the current study contributes to careers literature by revealing the linkage between the career construction model of adaptation and career sustainability.
Content, tools, and surrogates: assessing K-12 teachers’ criteria for interactively searching for digital video
Authors: Albertson Dan , Johnston Melissa P. 
Published: October 2022

Purpose
Digital video is regularly used to supplement instruction in K-12 education. However, more research is needed on how teachers interactively search for video to support their instructional tasks and activities. The purpose of the study is to better understand teachers’ perceptions of their video searches which can help facilitate video needs and interactions with digital tools.

Design/methodology/approach
Based on an existing image search model, variables were constructed and adapted to reflect the experiences of an interactive video search in an educational context or setting. A survey was then implemented and presented to K-12 teachers to gather perceptions about video searches. Statistical tests were used to examine certain variables that were categorized according to video needs, search tools and video surrogates or representations. The tests included descriptive tests and mean comparisons of variables within the categories to better understand priority among the criteria of teachers when interactively searching for video.

Findings
Results produced various statistical differences between variables within each of the categories of video needs, search tools and video surrogates or representations; as a result, certain priorities among the criteria of a video search emerged.

Originality/value
Online resources, particularly digital video, are likely to keep growing in importance for instruction and learning in K-12 settings. This study provides an important step to understanding different aspects of teachers’ criteria and perspectives of the video search process which will help better facilitate fulfillment of information needs.
Smallholder farmers' perception of climate change and choice of adaptation strategies in East Hararghe Zone, Eastern Ethiopia
Authors: Zeleke Titay , Beyene Fekadu , Deressa Temesgen , Yousuf Jemal , Kebede Temesgen 
Published: October 2022

Purpose
Change of climate is attributed to human activity that alters the composition of the global atmosphere observed over comparable periods. The purpose of this paper is to explore smallholder farmers' perceptions of climate change and compare it with meteorological data, as well as to identify perceived adaptation barriers and examine the factors that influence the choice of adaptation options in eastern Ethiopia.

Design/methodology/approach
In total, 384 sample households were chosen from four districts of the zone. A cross-sectional survey was used to conduct the study. Primary data was acquired through key informant interviews, focus group discussions and semistructured interviews, whereas meteorological data was collected from the National Meteorological Service Agency of Ethiopia. A Mann–Kendall statistical test was used to analyze temperature and rainfall trends over 33 years. A multivariate probit (MVP) model was used to identify the determinants of farmers' choice of climate change adaptation strategies.

Findings
The result indicated that temperature was significantly increased, whereas rainfall was significantly reduced over the time span of 33 years. This change in climate over time was consistently perceived by farmers. Smallholder farmers use improved varieties of crops, crop diversification, adjusting planting dates, soil and water conservation practices, reducing livestock holdings, planting trees and small-scale irrigation adaptation strategies. Moreover, this study indicated that sex of the household head, landholding size, livestock ownership, access to extension, access to credit, social capital, market distance, access to climate change-related training, nonfarm income, agroecological setting and poverty status of the households significantly influence farmers’ choice of adaptation strategies.

Research limitations/implications
Further research is required to evaluate the economic impact of each adaptation options on the livelihood of smallholder farmers.

Practical implications
Institutional variables significantly influenced how farmers adapted to climate change, and all of these issues might potentially be addressed by improving institutional service delivery. To improve farm-level adaptation, local authorities are recommended to investigate the institutional service provision system while also taking demographic and agroecological factors in to account.

Originality/value
This study compared farmers' perceptions with temperature and rainfall trend analysis, which has been rarely addressed by other studies. This study adopts an MVP model and indicated the adaptation strategies that complement/substitute strategies each other. Furthermore, this study discovered that the choice of adaptation options differed between poor and nonpoor households, which has been overlooked in previous climate change adaptation research.
Evaluation of the influence of preliminary low-velocity impacts on the residual fatigue life of CFRP composites
Authors: Staroverov Oleg , Lobanov Dmitriy , Strungar Elena , Lunegova Ekaterina 
Published: October 2022

PurposeThe main purpose of this study was to evaluate the mechanical behaviour of layered fibrous carbon-fibre reinforced plastic (CFRP) under complex low-speed bending and impact loads and subsequent cyclic tensile loads.Design/methodology/approachA comprehensive approach was adopted to study the damage accumulation processes using state-of-the-art testing and diagnostic equipment. In the course of the study, a microstructure analysis of damages caused by a transverse impact and cyclic tension was performed.FindingsA dependence of residual fatigue life of the studied composite material on the intensity of the preliminary impact bending was established. Temperature field distribution fields on the surface of the sample during tests were shown. Data on damage accumulation processes were presented, which were obtained during the registration of acoustic emission signals.Originality/valueA connection was established between changes of registered acoustic response signals and thermal imaging camera data, which was supported by the results of an experimental study. The results of the comprehensive approach showed a qualitative correlation.
Substance use and sentiment and topical tendencies: a study using social media conversations of youth experiencing homelessness
Authors: Deng Tianjie , Barman-Adhikari Anamika , Lee Young Jin , Dewri Rinku , Bender Kimberly 
Published: October 2022

PurposeThis study investigates associations between Facebook (FB) conversations and self-reports of substance use among youth experiencing homelessness (YEH). YEH engage in high rates of substance use and are often difficult to reach, for both research and interventions. Social media sites provide rich digital trace data for observing the social context of YEH's health behaviors. The authors aim to investigate the feasibility of using these big data and text mining techniques as a supplement to self-report surveys in detecting and understanding YEH attitudes and engagement in substance use.Design/methodology/approachParticipants took a self-report survey in addition to providing consent for researchers to download their Facebook feed data retrospectively. The authors collected survey responses from 92 participants and retrieved 33,204 textual Facebook conversations. The authors performed text mining analysis and statistical analysis including ANOVA and logistic regression to examine the relationship between YEH's Facebook conversations and their substance use.FindingsFacebook posts of YEH have a moderately positive sentiment. YEH substance users and non-users differed in their Facebook posts regarding: (1) overall sentiment and (2) topics discussed. Logistic regressions show that more positive sentiment in a respondent's FB conversation suggests a lower likelihood of marijuana usage. On the other hand, discussing money-related topics in the conversation increases YEH's likelihood of marijuana use.Originality/valueDigital trace data on social media sites represent a vast source of ecological data. This study demonstrates the feasibility of using such data from a hard-to-reach population to gain unique insights into YEH's health behaviors. The authors provide a text-mining-based toolkit for analyzing social media data for interpretation by experts from a variety of domains.