bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Updated Properties Model (UPM): A topology optimization algorithm for the creation of macro-micro optimized structures with variable stiffness
Authors: Saucedo-Mora Luis , Ben-Yelun Ismael , García-Modet Hugo , Sanz-Gómez Miguel Ángel , Montáns Francisco Javier 
Published: October 2022

AbstractThe design and manufacturing of high value industrial components is suffering a change of paradigm with 3D printing. In this change of paradigm, metamaterials have an important role because when a component is 3D-printed, it is performed from the micro level, where custom structures may be designed to endow the material and the component of special of customized mechanical properties. Topology optimization techniques facilitate the design of both the microstructures and the overall component topology, and today the component topology may be designed assuming a continuous spectrum of mechanical properties facilitated by different locally designed microstructures. However, current topology optimization techniques do not operate directly with the mechanical properties of the material, but through density intermediates, using density-based limits like a minimum or maximum density, assuming an homogeneous base material. We propose here a novel topology optimization algorithm which operates directly on the mechanical properties and energies, without employing density intermediates. The proposed approach reduces the algorithmic complexity since the optimization is performed by the direct iterative update of the mechanical properties, through information taken from its finite element analysis. We show that the proposed methodology can reach similar results as the current techniques based on a gradient descent optimization, eliminating the need for external parameters and, hence, increasing the easy of use and its robustness. The proposed technique is specially suitable for two-level concurrent material-component design using functionally graded metamaterials.
PiDeeL: Pathway-Informed Deep Learning Model for Survival Analysis and Pathological Classification of Gliomas
Authors: Kaynar Gun , Cakmakci Doruk , Bund Caroline , Todeschi Julien , Namer Izzie Jacques , Cicek A. Ercument 
Published: October 2022

AbstractOnline assessment of tumor characteristics during surgery is important and has the potential to establish an intraoperative surgeon feedback mechanism. With the availability of such feedback, surgeons could decide to be more liberal or conservative regarding the resection of the tumor. While there are methods to perform metabolomics-based online tumor pathology prediction, their model complexity and, in turn, the predictive performance is limited by the small dataset sizes. Furthermore, the information conveyed by the feedback provided on the tumor tissue could be improved both in terms of content and accuracy. In this study, we propose a metabolic pathway-informed deep learning model, PiDeeL, to perform survival analysis and pathology assessment based on metabolite concentrations. We show that incorporating pathway information into the model architecture substantially reduces parameter complexity and achieves better survival analysis and pathological classification performance. With these design decisions, we show that PiDeeL improves tumor pathology prediction performance of the state-of-the-art in terms of the Area Under the ROC Curve (AUC-ROC) by 3.38% and the Area Under the Precision-Recall Curve (AUC-PR) by 4.06%. Similarly, with respect to the time-dependent concordance index (c-index), we observe that PiDeeL achieves better survival analysis performance (improvement up to 4.3%) when compared to the state-of-the-art. Moreover, we show that importance analyses performed on input metabolite features as well as pathway-specific hidden-layer neurons of PiDeeL provide insights into tumor metabolism. We foresee that the use of this model in the surgery room will help surgeons adjust the surgery plan on the fly and will result in better prognosis estimates tailored to surgical procedures.AvailabilityThe code is released athttps://github.com/ciceklab/PiDeeL. The data used in this study is released athttps://zenodo.org/record/7228791.Contactcicek@cs.bilkent.edu.trSupplementary informationSupplementary data are available atBriefings in Bioinformaticsonline.
Engineering a minimal SilkCatcher/Tag pair compatible with SpyCatcher/Tag pair for the production of native-sized spider silk
Authors: Fan Ruxia , Hakanpää Johanna , Elfving Karoliina , Taberman Helena , Linder Markus B. , Aranko A. Sesilja 
Published: October 2022

AbstractProtein/peptide pairs, called Catcher/Tag pairs, are applied for biological isopeptide-bond mediated Click-reactions. Covalent protein ligation using Catcher/Tag pairs has turned out to be a valuable tool in biotechnology and biomedicines. It is essential to increase the current toolbox of Catcher/Tag pairs to expand the range of applications further, e.g., for multiple-fragment ligation that requires several orthogonal ligases. We report here engineering of novel Catcher/Tag pairs for protein ligation, aided by a new crystal structure of a minimal CnaB domain fromLactobacillus plantarum. We engineer several split variants, characterize in detail one of them, named SilkCatcher/Tag pair, and show that the newly engineered SilkCatcher/Tag pair is orthogonal and compatible with the widely used SpyCatcher/Tag pair. Finally, we demonstrate the use of the new SilkCatcher/Tag pair in the production of native-sized highly repetitive spider-silk-like proteins with >90% purity, which is not possible with the traditional recombinant production.
KIN: A method to infer relatedness from low-coverage ancient DNA
Authors: Popli Divyaratan , Peyrégne Stéphane , Peter Benjamin M. 
Published: October 2022

AbstractGenetic kinship of ancient individuals can provide insights into their culture and social hierarchy, and is relevant for downstream genetic analyses. However, estimating relatedness from ancient DNA is difficult due to low-coverage, ascertainment bias, or contamination from various sources. Here, we present KIN, a method to estimate the relatedness of a pair of individuals from the identical-by-descent segments they share. KIN accurately classifies up to 3rd-degree relatives using ≥ 0.05xsequence coverage and differentiates siblings from parent-child. It incorporates additional models to adjust for contamination and detect inbreeding, which improves classification accuracy.
The Western Lake Erie Culture Collection: A promising resource for evaluating the physiological and genetic diversity ofMicrocystisand its associated microbiome
Authors: Yancey Colleen E. , Kiledal E. Anders , Denef Vincent J. , Errera Reagan M. , Evans Jacob T. , Hart Lauren , Isailovic Dragan , James William , Kharbush Jenan K. , Kimbrel Jeffrey A , Li Wei , Mayali Xavier , Nitschky Helena , Polik Catherine , Powers McKenzie A , Premathilaka Sanduni H. , Rappuhn Nicole , Reitz Laura A. , Rivera Sara R. , Zwiers Claire C. , Dick Gregory J. 
Published: October 2022

AbstractCyanobacteria harmful algal blooms (cyanoHABs) dominated byMicrocystisspp. have significant public health and economic implications in freshwater bodies around the world. These blooms are capable of producing a variety of cyanotoxins, including microcystins, that affect fishing and tourism industries, human and environmental health, and access to drinking water. In this study, we isolated and sequenced the genomes of 21 unialgalMicrocystiscultures collected from western Lake Erie between 2017-2019. While some cultures isolated in different years have a high degree of genetic similarity (Average Nucleotide Identity >99%), genomic data shows that these cultures also represent much of the breadth of knownMicrocystisdiversity in natural populations. Only 5 isolates contained all the genes required for microcystin synthesis while 2 isolates contained a previously described partialmcyoperon. Microcystin production within cultures was also assessed using Enzyme-Linked Immunosorbent Assay (ELISA) and supported genomic results with high concentrations (up to 900 μg L-1) in cultures with completemcyoperons and no or low toxin detected otherwise. These xenic cultures also contained a substantial diversity of bacteria associated withMicrocystis, which has become increasingly recognized as an essential component of cyanoHAB community dynamics. These results highlight the genomic diversity amongMicrocystisstrains and associated bacteria in Lake Erie, and their potential impacts on bloom development, toxin production, and toxin degradation. This collection significantly increases the availability of environmentally relevantMicrocystisstrains from temperate North America, which is changing rapidly due to climate change.HighlightsTwenty one xenicMicrocystiscultures were isolated from western Lake Erie and capture the diversity ofMicrocystisstrains observed in natural populations as well as their associated bacteriaMicrocystisstrains show variability in core and accessory gene content, and genetically similar strains produce varying concentrations and congeners of microcystinsThis collection is a valuable resource for studying strain diversity and interactions betweenMicrocystisand associated bacteriaOur collection increases the availability of environmentally relevant strains from temperate North America, which is historically underrepresented in culture collections.
Structure of the Wnt-Frizzled-LRP6 initiation complex reveals the basis for co-receptor discrimination
Authors: Tsutsumi Naotaka , Hwang Sunhee , Hansen Simon , Waghray Deepa , Wang Nan , Miao Yi , Glassman Caleb R. , Caveney Nathanael A. , Jude Kevin M. , Janda Claudia Y. , Hannoush Rami N. , Garcia K. Christopher 
Published: October 2022

AbstractWnt morphogens are critical for embryonic development and tissue regeneration. Canonical Wnts form ternary receptor complexes composed of tissue-specific Frizzled receptors together with the shared LRP5/6 co-receptors to initiate β-catenin signaling. The structure of a ternary complex of an affinity-matured XWnt8-Frizzled8-LRP6 complex elucidates the basis of co-receptor discrimination by canonical Wnts by means of their N-termini and linker domains that engage the LRP6 E1E2 domain funnels. Chimeric Wnts bearing modular linker ‘grafts’ were able to transfer LRP6 domain specificity between different Wnts and enable non-canonical Wnt5a to signal through the canonical pathway. Synthetic peptides comprising the linker domain serve as Wnt-specific antagonists. The structure of the ternary complex provides a topological blueprint for the orientation and proximity of Frizzled and LRP6 within the Wnt cell surface signalosome.
Facilitatory stimulation of the pre-SMA enhances semantic cognition via remote network effects on task-based activity and connectivity
Authors: Martin Sandra , Frieling Regine , Saur Dorothee , Hartwigsen Gesa 
Published: October 2022

AbstractBackgroundThe continuous decline of executive abilities with age is mirrored by increased neural activity of domain-general networks during task processing. So far, it remains unclear how much domain-general networks contribute to domain-specific processes such as language when cognitive demands increase. The current neuroimaging study explored the potential of intermittent theta-burst stimulation (iTBS) over a domain-general hub to enhance executive and semantic processing in healthy middle-aged to older adults.MethodsWe implemented a cross-over within-subject study design with three task-based neuroimaging sessions per participant. Using an individualized stimulation approach, we stimulated each participant once with effective and once with sham iTBS over the pre-supplementary motor area (pre-SMA), a region of domain-general control. Subsequently, task-specific stimulation effects were assessed in functional MRI using a semantic and a non-verbal executive task with varying cognitive demand.ResultsEffective stimulation increased activation relative to sham stimulation only during semantic processing in visual and dorsal attention networks. Further, iTBS induced increased functional connectivity in task-specific networks for semantic and executive conditions with high cognitive load. Notably, stimulation-induced changes in activation and connectivity related differently to behavior: While increased activation of the parietal dorsal attention network was linked to poorer semantic performance, its enhanced coupling with the pre-SMA was associated with more efficient semantic processing.ConclusionsiTBS modulates networks in a task-dependent manner and generates effects at regions remote to the stimulation site. These neural changes are linked to more efficient semantic processing, which underlines the general potential of network stimulation approaches in cognitive aging.
The ancestral chromatin landscape of land plants
Authors: Hisanaga Tetsuya , Wu Shuangyang , Schafran Peter , Axelsson Elin , Akimcheva Svetlana , Dolan Liam , Li Fay-Wei , Berger Frédéric 
Published: October 2022

AbstractBackgroundIn animals and flowering plants specific chromatin modifications define three chromosomal domains: euchromatin comprising transcribed genes, facultative heterochromatin comprising repressed genes, and constitutive heterochromatin comprising transposons. However, recent studies have shown that the correlation between chromatin modifications and transcription vary among different eukaryotic organisms including mosses and liverworts that differ from one another. Mosses and liverworts diverged from hornworts, altogether forming the lineage of bryophytes that shared a common ancestor with all land plants. We aimed to obtain chromatin landscapes in hornworts to establish synapomorphies across bryophytes.ResultsWe mapped the chromatin landscape of the model hornwortAnthoceros agrestis.By comparing chromatin landscapes across bryophytes we defined the common chromatin landscape of the ancestor of extant bryophytes. In this group, constitutive heterochromatin was characterized by a scattered distribution across autosomes, which contrasted with the dense compartments of heterochromatin surrounding the centromeres in flowering plants. Topologically associated domains were primarily occupied by transposons with genes at their boundaries and nearly half of the hornwort transposons were associated with facultative heterochromatin and euchromatin.ConclusionsMost of the features observed in hornworts are also present in liverworts but are distinct from flowering plants. Hence, the ancestral genome of bryophytes was likely a patchwork of units of euchromatin interspersed within facultative and constitutive heterochromatin and each unit contained both transposons and genes sharing the same chromatin state. We propose this genome organization was ancestral to land plants and prevented transposons from being segregated as constitutive heterochromatin around point centromeres as in flowering plants.
Accounting for central place foraging constraints in habitat selection studies
Authors: Benhamou Simon , Courbin Nicolas 
Published: October 2022

AbstractHabitat selection studies contrast the actual space use with the expected use under the null hypothesis of no preference (hereafter neutral use). Neutral use is most often assimilated to the relative abundance of the different habitat types. This generates a considerable bias when studying habitat selection by foragers that perform numerous back and forth to a central place (CP). Indeed, the increased space use close to the CP with respect to distant places reflects a mechanical effect rather than a true preference for the closest habitats. Yet, correctly estimating habitat selection by CP foragers is of paramount importance for a better understanding of their ecology and efficiency of conservation actions. We show that (1) including the distance to the CP as a covariate in unconditional Resource Selection Functions (RSFs), as did in several studies, is quite inefficient to correct for the bias. Bias can be eliminated only by contrasting the actual use distribution to an appropriate neutral distribution that takes the CP forager behavior into account. (2) The need to specify such an appropriate neutral use distribution can be bypassed by relying on a conditional RSF, where the neutral use is assessed locally without reference to the CP.
R-loop editing by DNA cytosine deaminase APOBEC3B determines the activity of estrogen receptor enhancers
Authors: Zhang Chi , Lu Yu-jing , Chen Bingjie , Bai Zhiyan , Hervieu Alexia , Licciardello Marco P. , Wang Mei , Mitsopoulos Costas , Al-Lazikani Bissan , Totorici Marcello , Rossanese Olivia W. , Workman Paul , Clarke Paul A. 
Published: October 2022

SummaryEstrogen receptor (ER) activation results in the formation of DNA double strand breaks (DSB), which promote genomic instability and tumour heterogeneity in ER-positive breast cancers. The single-stranded DNA (ssDNA) cytosine deaminase APOBEC3B (A3B) regulates ER activity by inducing DSB at ER enhancers. To delineate how A3B recognises its substrates and unveil the underlying mechanism leading to the formation of ER-induced DSB, we sampled A3B-mediated deamination sites using whole genome sequencing in a human breast cancer cell model lacking base excision repair function. Our genome-wide analysis revealed that C>U conversions carried out by A3B in R-loop structures are processed into DSB in the vicinity of ER promoters or enhancers. A mechanism which required both the processing of A3B-editing sites and R-loops by distinct DNA damage repair mechanisms. In addition, using BioID-enabled mass-spectroscopy proteomics, we identified TDRD3 as a key A3B-binding partner directing the activity of A3B to ER-induced R-loops. This study suggests a function for A3B in sustaining tumour evolution as an adaptive response at the transcriptional and epigenetic level and supports A3B as a promising target to control ER activity in cancer.
A cost-free CURE: Using bioinformatics to identify DNA-binding factors at a specific genomic locus
Authors: Schmidt Casey A. , Hodkinson Lauren J. , Comstra H. Skye , Rieder Leila E. 
Published: October 2022

ABSTRACTResearch experiences provide diverse benefits for undergraduates. Many academic institutions have adopted course-based undergraduate research experiences (CUREs) to improve student access to research opportunities. However, potential instructors of a CURE might still face financial or practical hurdles that prevent implementation. Bioinformatics research offers an alternative that is free, safe, compatible with remote learning, and may be more accessible for students with disabilities. Here, we describe a bioinformatics CURE that leverages publicly available datasets to discover novel proteins that target an instructor-determined genomic locus of interest. We use the free, user-friendly bioinformatics platform Galaxy to map ChIP-seq datasets to a genome, which removes the computing burden from students. Both faculty and students directly benefit from this CURE, as faculty can perform candidate screens and publish CURE results. Students gain not only basic bioinformatics knowledge, but also transferable skills, including scientific communication, database navigation, and primary literature experience. The CURE is flexible and can be expanded to analyze different types of high-throughput data or to investigate different genomic loci in any species.
Clustering of CaV1.3 L-type calcium channels by Shank3
Authors: Yang Qian , Perfitt Tyler L. , Quay Juliana , Hu Lan , Colbran Roger J. 
Published: October 2022

AbstractClustering of neuronal L-type voltage-gated Ca2+channels (LTCC) in the plasma membrane is increasingly implicated in creating highly localized Ca2+signaling nanodomains. For example, LTCC activation can increase phosphorylation of the nuclear CREB transcription factor by increasing Ca2+concentrations within a nanodomain close to the channel, without requiring bulk Ca2+increases in the cytosol or nucleus. However, the molecular basis for LTCC clustering is poorly understood. The postsynaptic scaffolding protein Shank3 specifically associates with one of the major neuronal LTCCs, the CaV1.3 calcium channel, and is required for optimal LTCC-dependent excitation-transcription coupling. Here, we co-expressed CaV1.3 α1 subunits with two distinct epitope-tags with or without Shank3 in HEK cells. Co-immunoprecipitation studies using the cell lysates revealed that Shank3 can assemble multiple CaV1.3 α1 subunits in a complex under basal conditions. Moreover, CaV1.3 LTCC complex formation was facilitated by CaVβ subunits (β3 and β2a), which also interact with Shank3. Shank3 interactions with CaV1.3 LTCCs and multimeric CaV1.3 LTCC complex assembly were disrupted following addition of Ca2+and calmodulin (Ca2+/CaM) to cell lysates, perhaps simulating conditions within an activated CaV1.3 LTCC nanodomain. In intact HEK293T cells, co-expression of Shank3 enhanced the intensity of membrane-localized CaV1.3 LTCC clusters under basal conditions, but not after Ca2+channel activation. Live cell imaging studies also revealed that Ca2+influx through LTCCs disassociated Shank3 from CaV1.3 LTCCs clusters and reduced the CaV1.3 cluster intensity. Deletion of the PDZ domain from Shank3 prevented both binding to CaV1.3 and the changes in multimeric CaV1.3 LTCC complex assembly in vitro and in HEK293 cells. Finally, we found that shRNA knock-down of Shank3 expression in cultured rat primary hippocampal neurons reduced the intensity of surface-localized CaV1.3 LTCC clusters in dendrites. Taken together, our findings reveal a novel molecular mechanism contributing to neuronal LTCC clustering under basal conditions.
O2photoreduction at acceptor side of Photosystem I provide photoprotection to conifer thylakoids in early spring
Authors: Bag Pushan , Shutova Tatyana , Shevela Dmitry , Lihavainen Jenna , Nanda Sanchali , Ivanov Alexander G. , Messinger Johannes , Jansson Stefan 
Published: October 2022

AbstractGreen organisms evolve O2via photosynthesis and consume by respiration. Net O2consumption only becomes dominant when photosynthesis is suppressed at night. Here, we show that green thylakoid membranes of Scots pine (Pinus sylvestris L) and Norway spruce (Picea abies) needles demonstrate strong O2consumption even in the presence of light when extremely low temperatures coincide with high solar irradiation during early spring. This phenomenon deviates from the general finding that photosynthetic organisms evolve O2upon illumination. By using different electron transport chain inhibitors, we showed that O2consumption occurred around photosystem (PS) I and correlated with higher abundance of flavodiiron (Flv) A protein in ES thylakoid membranes. Furthermore, by measuring P700 absorption changes, we separated different alternative electron flow pathways and demonstrated that electron scavenging from the acceptor-side of PSI via O2photoreduction is a major alternative pathway in ES. This photoprotection mechanism in vascular plants indicates that conifers have developed an adaptative evolution trajectory for growing in harsh environments.