bluuebunny/crossref_metadata_2025_split huggingface dataset:
Automatic recognition of complementary strands: Lessons regarding machine learning abilities in RNA folding
Authors: Chasles Simon , Major François 
Published: April 2023

AbstractPrediction of RNA secondary structure from single sequences still needs substantial improvements. The application of machine learning (ML) to this problem has become increasingly popular. However, ML algorithms are prone to overfitting, limiting the ability to learn more about the inherent mechanisms governing RNA folding. It is natural to use high-capacity models when solving such a difficult task, but poor generalization is expected when too few examples are available. Here, we report the relation between capacity and performance on a fundamental related problem: determining whether two sequences are fully complementary. Our analysis focused on the impact of model architecture and capacity as well as dataset size and nature on classification accuracy. We observed that low-capacity models are better suited for learning with mislabelled training examples, while large capacities improve the ability to generalize to structurally dissimilar data. It turns out that neural networks struggle to grasp the fundamental concept of base complementarity, especially in lengthwise extrapolation context. Given a more complex task like RNA folding, it comes as no surprise that the scarcity of usable examples hurdles the applicability of machine learning techniques to this field.
Convergence of multiple RNA-silencing pathways on GW182/TNRC6
Authors: Welte Thomas , Goulois Alison , Stadler Michael B. , Hess Daniel , Soneson Charlotte , Neagu Anca , Azzi Chiara , Lübke Marlena J. , Seebacher Jan , Schmidt Isabel , Estoppey David , Nigsch Florian , Reece-Hoyes John , Hoepfner Dominic , Großhans Helge 
Published: April 2023

AbstractThe RNA-binding protein TRIM71/LIN-41 is a phylogenetically conserved developmental regulator that functions in mammalian stem cell reprogramming, brain development and cancer. TRIM71 recognizes target mRNAs through hairpin motifs and silences them through molecular mechanisms that await identification. Here, we uncover that TRIM71 silences its targets by recruiting TNRC6/GW182, a core component of the miRNA-induced silencing complex (miRISC). Co-immunoprecipitation reveals interaction of TNRC6A with additional RNA-binding proteins and we demonstrate that AGO2, TRIM71, and UPF1 each recruit TNRC6 to specific, largely distinct sets of transcripts to silence them. As cellular TNRC6 levels are limiting, competition occurs among the silencing pathways, such that loss of AGO2 protein, or of AGO2 binding to TNRC6, enhances the activities of the other pathways. We conclude that a miRNA-like silencing activity is shared among different mRNA silencing pathways and that use of TNRC6 as a central hub provides a means to integrate their activities.
p73 activates transcriptional signatures of basal lineage identity and ciliogenesis in pancreatic ductal adenocarcinoma
Authors: Hur Stella K. , Somerville Tim D.D. , Wu Xiaoli S. , Maia-Silva Diogo , Demerdash Osama E. , Tuveson David A. , Notta Faiyaz , Vakoc Christopher R. 
Published: April 2023

AbstractDuring the progression of pancreatic ductal adenocarcinoma (PDAC), tumor cells are known to acquire transcriptional and morphological properties of the basal (also known as squamous) epithelial lineage, which leads to more aggressive disease characteristics. Here, we show that a subset of basal-like PDAC tumors aberrantly express p73 (TA isoform), which is a known transcriptional activator of basal lineage identity, ciliogenesis, and tumor suppression in normal tissue development. Using gain- and loss- of function experiments, we show that p73 is necessary and sufficient to activate genes related to basal identity (e.g.KRT5), ciliogenesis (e.g.FOXJ1), and p53-like tumor suppression (e.g.CDKN1A) in human PDAC models. Owing to the paradoxical combination of oncogenic and tumor suppressive outputs of this transcription factor, we propose that PDAC cells express a low level of p73 that is optimal for promoting lineage plasticity without severe impairment of cell proliferation. Collectively, our study reinforces how PDAC cells exploit master regulators of the basal epithelial lineage during disease progression.
Association of Oxytetracycline and Florfenicol affects zebrafish larvae behavioral repertoire
Authors: Gusso Darlan , Gobbo Marilia Oberto da Silva , Rübensam Gabriel , Bonan Carla Denise 
Published: April 2023

AbstractThe fish farms are increasingly growing and, consequently, the use of antibiotics in aquaculture. Oxytetracycline (OTC) and Florfenicol (FF) are the most common antibiotics applied in the fish production sector and livestock farming. The elucidation of the effects of the antibiotics is essential to control their use and their physiological and pharmacological implications. Here we studied the behavioral effects of the 96 h-exposure to OTC (2, 10, 20, and 100 mg/L), FF (0.01, 0.05, 2 and 10 mg/L) or OTC (10 mg/L) + FF (10 mg/L) in zebrafish larvae. We observed that the covered distance and the movement increased in animals exposed to OTC + FF when compared to control. In addition, fish entered the center of the plate test more often and stayed there longer. The turn angle was reduced at OTC + FF. We also observed that the optomotor response was compromised by 10 and 20 mg/L OTC and to OTC + FF. Our data demonstrated that there is an increase in the number of entries in the center area and time spent in center area for FF- and OTC + FF-treated groups. These data showed that the antibiotics promoted a reduction of anxiety-like behavior allowing larvae to explore more the novel environment as well as a detrimental performance for the optomotor response.HighlightsFlorfenicol (FF) did not alter exploratory and anxiety-like behavior in zebrafish larvae.Oxytetracycline (OTC) did not alter exploratory behavior, but there was an increase in the time spent in the center areaOTC plus FF increased distance and movement in zebrafish larvae.OTC plus FF reduced the anxiety-like behavior in zebrafish larvae.Optomotor behavior was compromised by treatments with OTC or OTC + FF.
Shedding light (… electrons) on human bone ultrastructure with correlative on-axis electron tomography and energy dispersive X-ray spectroscopy tomography
Authors: Micheletti Chiara , Shah Furqan A. , Palmquist Anders , Grandfield Kathryn 
Published: April 2023

ABSTRACTMineralized collagen fibrils are the building block units of bone at the nanoscale. While it is known that collagen fibrils are mineralized both inside their gap zones (intra-fibrillar mineralization) and on their outer surfaces (extra-fibrillar mineralization), a clear visualization of this architecture in three dimensions (3D), combining structural and compositional information over large volumes, but without compromising the resolution, remains challenging. In this study, we demonstrate the use of on-axis Z-contrast electron tomography (ET) with correlative energy-dispersive X-ray spectroscopy (EDX) tomography to examine rod-shaped samples with a diameter up to 700 nm prepared from individual osteonal lamellae in the human femur. Our work mainly focuses on two aspects: i) low-contrast nanosized circular spaces (“holes”) observed in sections of bone oriented perpendicular to the long axis of a long bone; and ii) extra-fibrillar mineral, especially in terms of morphology and spatial relationship with respect to intra-fibrillar mineral and collagen fibrils. From our analyses, it emerges quite clearly that most “holes” are cross-sectional views of collagen fibrils. While this had been postulated before, our 3D reconstructions and reslicing along meaningful two-dimensional (2D) cross-sections provide a direct visual confirmation. Extra-fibrillar mineral appears composed of thin plates that are interconnected and span over several collagen fibrils, confirming that mineralization is cross-fibrillar, at least for the extra-fibrillar phase. EDX tomography shows mineral signature (Ca and P) within the gap zones, but the signal appears weaker than that associated to the extra-fibrillar mineral, pointing towards the existence of dissimilarities between the two types of mineralization.
A discrete model for the growth and spread of the Scottish populations of red squirrels (Sciurus vulgaris) and grey squirrels (Sciurus carolinensis)
Authors: Gramain Jean-Baptiste 
Published: April 2023

AbstractIn this article, a model, discrete in space and time, is developed to describe the growth and spread of the Scottish populations of red squirrels (Sciurus vulgaris) and grey squirrel (Sciurus carolinensis). The initial state for the model is designed using a large dataset of records of sightings of individuals of both species reported by members of the public. Choices of parameters involved in the model and their values are informed by the analysis of this dataset for the period 2011-2016, and model predictions are compared to records for the years 2006-2019.
Pyroptosis inhibiting nanobodies block Gasdermin D pore formation
Authors: Kopp Anja , Hagelueken Gregor , Jamitzky Isabell , Moecking Jonas , Schiffelers Lisa D. J. , Schmidt Florian I. , Geyer Matthias 
Published: April 2023

AbstractGasdermin D (GSDMD) is a key mediator of pyroptosis, a pro-inflammatory form of cell death occurring downstream of inflammasome activation as part of the innate immune defence. Upon cleavage by inflammatory caspases, the N-terminal domain of GSDMD forms pores in the plasma membrane resulting in cytokine release and eventually cell death. Targeting GSDMD is an attractive way to dampen inflammation. In this study, six GSDMD targeting nanobodies were characterized in terms of their binding affinity, stability, and effect on GSDMD pore formation. Three of the nanobodies inhibited GSDMD pore formation in a liposome leakage assay, although caspase cleavage was not perturbed. We determined the crystal structure of human GSDMD in complex with two nanobodies at 1.9 Å resolution, providing detailed insights into the GSDMD–nanobody interactions and epitope binding. The pore formation is sterically blocked by one of the nanobodies that binds to the oligomerization interface of the N-terminal domain in the multi-subunit assembly. Our biochemical and structural findings provide new tools for studying inflammasome biology and build a framework for the design of novel GSDMD targeting drugs.
The Role of MAP3K1 in the Development of the Female Reproductive Tract
Authors: Kimura Eiki , Mongan Maureen , Xiao Bo , Wang Jingjing , Carreira Vinicius S , Bolon Brad , Zhang Xiang , Burns Katherine A. , Biesiada Jacek , Medvedovic Mario , Puga Alvaro , Xia Ying 
Published: April 2023

AbstractMitogen-Activated Protein 3 Kinase 1 (MAP3K1) is a dynamic signaling molecule with a plethora of cell-type specific functions, most of which are yet to be understood. Here we describe a role for MAP3K1 in the development of female reproductive tract (FRT). MAP3K1 kinase domain-deficient (Map3k1ΔKD) females exhibit imperforate vagina, labor failure, and infertility. These defects correspond to a shunted Müllerian duct (MD), the principle precursor of the FRT, in embryos, while they manifest as a contorted caudal vagina with abrogated vaginal-urogenital sinus fusion in neonates. In epithelial cells, MAP3K1 acts through JNK and ERK to activate WNT, yetin vivoMAP3K1 is crucial for WNT activity in mesenchyme associated with the caudal MD. Expression ofWnt7bis high in wild type, but low inMap3k1knockout MD epithelium and MAP3K1-deficient keratinocytes. Correspondingly, conditioned media derived from MAP3K1-competent epithelial cells activate TCF/Lef-luciferase reporter in fibroblasts, suggesting that MAP3K1-induced factors released from epithelial cells trans-activate WNT signaling in fibroblasts. Our results reveal a temporal-spatial and paracrine MAP3K1-WNT crosstalk contributing to MD caudal elongation and FRT development.HighlightsMAP3K1 deficient female mice exhibit imperforate vagina and infertilityLoss of MAP3K1 kinase activity impedes Müllerian duct (MD) caudal elongation and fusion with urogenital sinus (UGS) in embryogenesisThe MAP3K1-MAPK pathway up-regulates WNT signaling in epithelial cellsMAP3K1 deficiency down-regulates Wnt7b expression in the MD epithelium and prevents WNT activity in mesenchyme of the caudal MD
The Promise and Pitfalls of Prophages
Authors: McKerral Jody C. , Papudeshi Bhavya , Inglis Laura K. , Roach Michael J. , Decewicz Przemyslaw , McNair Katelyn , Luque Antoni , Dinsdale Elizabeth A. , Edwards Robert A. 
Published: April 2023

AbstractPhages dominate every ecosystem on the planet. While virulent phages sculpt the microbiome by killing their bacterial hosts, temperate phages provide unique growth advantages to their hosts through lysogenic conversion. Many prophages benefit their host, and prophages are responsible for genotypic and phenotypic differences that separate individual microbial strains. However, the microbes also endure a cost to maintain those phages: additional DNA to replicate and proteins to transcribe and translate. We have never quantified those benefits and costs. Here, we analysed over two and a half million prophages from over half a million bacterial genome assemblies. Analysis of the whole dataset and a representative subset of taxonomically diverse bacterial genomes demonstrated that the normalised prophage density was uniform across all bacterial genomes above 2 Mbp. We identified a constant carrying capacity of phage DNA per bacterial DNA. We estimated that each prophage provides cellular services equivalent to approximately 2.4 % of the cell’s energy or 0.9 ATP per bp per hour. We demonstrate analytical, taxonomic, geographic, and temporal disparities in identifying prophages in bacterial genomes that provide novel targets for identifying new phages. We anticipate that the benefits bacteria accrue from the presence of prophages balance the energetics involved in supporting prophages. Furthermore, our data will provide a new framework for identifying phages in environmental datasets, diverse bacterial phyla, and from different locations.
Protein multiple conformations prediction using multi-objective evolution algorithm
Authors: Hou Ming-Hua , Jin Si-Rong , Cui Xin-Yue , Peng Chun-Xiang , Zhao Kai-Long , Song Le , Zhang Gui-Jun 
Published: April 2023

AbstractMotivationWith the breakthrough of AlphaFold2 and the publication of AlphaFold DB, the protein structure prediction has made remarkable progress, which may further promote many potential applications of proteomics in all areas of life. However, it should be noted that AlphaFold2 models tend to represent only a single static structure, and accurately predicting multiple conformations remains a challenge. Therefore, it is essential to develop methods for predicting multiple conformations, which enable us to gain knowledge of multiple conformational states and the broader conformational landscape to better understand the mechanism of action.ResultsIn this work, we proposed a multiple conformational states folding method using the distance-based multi-objective evolutionary algorithm framework, named MultiSFold. First, a multi-objective energy landscape with multiple competing constraints generated by deep learning is constructed. Then, an iterative modal exploration and exploitation strategy based on multi-objective optimization, geometric optimization and structural similarity clustering is designed to perform conformational sampling. Finally, the final population is generated using a loop-specific perturbation strategy to adjust the spatial orientations. MultiSFold was compared with state-of-the-art methods on a developed benchmark testset containing 81 proteins with two representative conformational states. Based on the proposed metric, the success ratio of MultiSFold predicting multiple conformations was 70.4% while that of AlphaFold2 was 9.88%, which may indicate that conformational sampling combined with knowledge gained through deep learning has the potential to produce conformations spanned the range between two experimental structures. In addition, MultiSFold was tested on 244 human proteins with low structural accuracy in AlphaFold DB to test whether it could further improve the accuracy of static structures. The experimental results demonstrate that the TM-score of MultiSFold is 2.97% and 7.72% higher than that of AlphaFold2 and RoseTTAFold, respectively, supporting our hypothesis that multiple competing optimization objectives can further assist conformational search to improve prediction accuracy.
Environmental impacts of cultured meat: A cradle-to-gate life cycle assessment
Authors: Risner Derrick , Kim Yoonbin , Nguyen Cuong , Siegel Justin B. , Spang Edward S. 
Published: April 2023

AbstractInterest in animal cell-based meat (ACBM) or cultured meat as a viable environmentally conscious replacement for livestock production has been increasing, however a life cycle assessment for the current production methods of ACBM has not been conducted. Currently, ACBM products are being produced at a small scale and at an economic loss, however ACBM companies are intending to industrialize and scale-up production. This study assesses the potential environmental impact of near term ACBM production. Updated findings from recent technoeconomic assessments (TEAs) of ACBM and a life cycle assessment of Essential 8™ were utilized to perform a life cycle assessment of near-term ACBM production. A scenario analysis was conducted utilizing the metabolic requirements examined in the TEAs of ACBM and a purification factor from the Essential 8™ life cycle assessment was utilized to account for growth medium component processing. The results indicate that the environmental impact of near-term ACBM production is likely to be orders of magnitude higher than median beef production if a highly refined growth medium is utilized for ACBM production.
Identification of FAM53C as a cytosolic-anchoring inhibitory binding protein of the kinase DYRK1A
Authors: Miyata Yoshihiko , Nishida Eisuke 
Published: April 2023

AbstractThe protein kinase DYRK1A encoded in human chromosome 21 is the major contributor to the multiple symptoms observed in Down syndrome patients. In addition, DYRK1A malfunction is associated with various other neurodevelopmental disorders such as autism spectrum disorder. Here we identified FAM53C with no hitherto known biological function as a novel suppressive binding partner of DYRK1A. FAM53C bound to the catalytic protein kinase domain of DYRK1A, whereas DCAF7/WDR68, the major DYRK1A-binding protein, binds to the N-terminal domain of DYRK1A. The binding of FAM53C inhibited autophosphorylation activity of DYRK1A and its kinase activity to an exogenous substrate MAPT/Tau. FAM53C did not bind directly to DCAF7/WDR68, whereas DYRK1A tethered FAM53C and DCAF7/WDR68 by binding concurrently to both of them, forming a tri-protein complex. DYRK1A possesses a nuclear localization signal and accumulates in the nucleus when overexpressed in cells. Co-expression of FAM53C induced cytoplasmic re-localization of DYRK1A, revealing the cytoplasmic anchoring function of FAM53C to DYRK1A. Moreover, the binding of FAM53C to DYRK1A suppressed the DYRK1A-dependent nuclear localization of DCAF7/WDR68. All the results show that FAM53C binds to DYRK1A, suppresses its kinase activity, and anchors it in the cytoplasm. In addition, FAM53C bound to the DYRK1A-related kinase DYRK1B with an Hsp90/Cdc37-independent manner. The results explain for the first time why endogenous DYRK1A is distributed in the cytoplasm in normal brain tissue. FAM53C-dependent regulation of the kinase activity and intracellular localization of DYRK1A may play a significant role in gene expression regulation caused by normal and aberrant levels of DYRK1A.
AI and supportive technology experiences of customers with visual impairments in hotel, restaurant, and travel contexts
Authors: Liu Aijing , Ma Emily , Wang Yao-Chin , Xu Shi (Tracy) , Grillo Tyran 
Published: April 2023

Purpose
The purpose of this study is to critically reflect on visually impaired customers’ technology assistance needs and the perceptions of existing technologies’ performance in the contexts of hospitality and tourism.

Design/methodology/approach
Following a qualitative approach, this study used in-depth semistructured interviews with 19 participants with visual impairments.

Findings
Positive and negative sides of technology-assisted experiences in the hotel, restaurant, and travel domains were summarized, and room for improvement was discussed to enhance the quality of life and travel experience of visually impaired customers.

Practical implications
Findings from this study offer actionable implications and future directions to technicians and managers to make hospitality and travel experiences more inclusive.

Originality/value
This timely reflection addresses a critical situation by offering original ideas and calling for more discussion of under-represented groups with visual impairments.
Do human capital and relational capital influence knowledge-intensive firm competitiveness? The roles of export orientation and marketing knowledge capability
Authors: Mohammad Shafiee Majid , Warkentin Merrill , Motamed Setare 
Published: April 2023

Purpose
This study aims to investigate the key roles of human and relational capital in the export orientation and competitiveness of knowledge-intensive cooperative companies. It is also aimed to examine the moderating role of marketing knowledge capabilities.

Design/methodology/approach
Data from 552 managers at 86 companies, selected from knowledge-intensive export cooperatives, were analyzed with structural equation modeling with the partial least squares approach.

Findings
Results indicate that both human and relational capital exert considerable effects on competitiveness. Export orientation was a driving factor for cooperatives’ competitiveness. Human and relational capital fostered the effects of export orientation on competitiveness. Moreover, marketing knowledge capabilities were found to moderate the relationships between human and relational capital and export orientation, as well as between export orientation and competitiveness.

Originality/value
By highlighting the role of human capital and relational capital in export orientation and competitiveness, this study offers an analysis of important managerial processes within cooperative companies, which have not been sufficiently addressed in previous research. This research also demonstrated the moderating role of marketing knowledge capabilities in strengthening relationships between human and relational capital and export orientation, as well as between export orientation and competitiveness, which has been neglected in previous studies. These findings provide academics and practitioners with a new framework for examining the relationships between these constructs, which will enable them to establish strategies for achieving a competitive advantage.