bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fate of telomere entanglements is dictated by the timing of anaphase midregion nuclear envelope breakdown
Authors: Nageshan Rishi Kumar , Ortega Raquel , Krogan Nevan , Cooper Julia Promisel 
Published: February 2023

AbstractPersisting replication intermediates can confer mitotic catastrophe if left unresolved. Loss of the fission yeast telomere protein Taz1 (ortholog of mammalian TRF1/TRF2) causes telomeric replication fork stalling and in turn, telomere entanglements that stretch between the segregating chromosomes at anaphase. At ≤20°C, these entanglements fail to resolve, resulting in lethality. Rif1, a conserved DNA replication/repair protein, localizes between the segregating chromosomes and specifically hinders the resolution of telomere entanglements without affecting their formation. During anaphase, the spindle and the last segments of segregating chromatin are encased by the nuclear envelope (NE), creating a microdomain termed the anaphase midregion. In the final stages of fission yeast mitosis, this midregion undergoes local NE breakdown. Here we demonstrate that in response totaz1Δtelomeric entanglements, Rif1 delays midregion NE breakdown, and this delay disfavors entanglement resolution. Accordingly, gene deletions that hasten midregion NE breakdown phenocopy, and are epistatic with,rif1+deletion. Conversely, gene deletions that delay midregion NE breakdown block thetaz1Δtelomere detanglement afforded by loss of Rif1. Overexpression of Rif1 in a wild type background causes cold-specific NE defects and lethality, which are rescued by treatment with a membrane fluidizing agent. We propose that delayed NE breakdown normally favors the resolution of simple entanglements, arising from incomplete replication, by delaying exposure to the cytoplasm. In contrast, resolution of more complex entanglements involving strand invasion, like entanglements between nonsistertaz1Δtelomeres, requires more rapid exposure to the cytoplasm. These observations uncover an unexpected coordination between NE remodeling and DNA processing events that can prevent or promote aneuploidy.
Phylogenomic analysis of the Lake Kronotskoe species flock of Dolly Varden charr reveals genetic and developmental signatures of sympatric radiation
Authors: Woronowicz Katherine C. , Esin Evgeny V. , Markevich Grigorii N. , Martinez Crisvely Soto , McMenamin Sarah K. , Daane Jacob M. , Harris Matthew P. , Shkil Fedor N. 
Published: February 2023

AbstractRecent adaptive radiations provide evolutionary case studies, which provide the context to parse the relationship between genomic variation and the origins of distinct phenotypes. Sympatric radiations of the charr complex (genusSalvelinus) present a trove for phylogenetics as charrs have repeatedly diversified into multiple morphs with distinct feeding specializations. However, species flocks normally comprise only two to three lineages. Dolly Varden charr inhabiting Lake Kronotske represent the most extensive radiation described for the charr genus, containing at least seven lineages, each with defining morphological and ecological traits. Here, we perform the first genome-wide analysis of this species flock to parse the foundations of adaptive change. Our data support distinct, reproductively isolated lineages with little evidence of hybridization. We also find that specific selection on thyroid signaling and craniofacial genes forms a genomic basis for the radiation. Thyroid hormone is further implicated in subsequent lineage partitioning events. These results delineate a clear genetic basis for the diversification of specialized lineages, and highlight the role of developmental mechanisms in shaping the forms generated during adaptive radiation.Significance StatementDolly Varden Charr (Salvelinus malma) radiation in Lake Kronotskoe provides a unique case study of the genetics of adaptation and morphological evolution. We provide first genomic and experimental analyses of this radiation and show that major axes of change may be shaped by developmental constraints.
Can deep learning predict human intelligence from structural brain MRI?
Authors: Hussain Mohammad Arafat , LaMay Danielle , Grant Ellen , Ou Yangming 
Published: February 2023

ABSTRACTCan brain structure predict human intelligence? T1-weighted structural brain magnetic resonance images (sMRI) have been correlated with intelligence. Nevertheless, population-level association does not fully account for individual variability in intelligence. To address this, individual prediction studies emerge recently. However, they are mostly on predicting fluid intelligence (the ability to solve new problems). Studies are lacking to predict crystallized intelligence (the ability to accumulate knowledge) or general intelligence (fluid and crystallized intelligence combined). This study tests whether deep learning of sMRI can predict an individual subject’s verbal, comprehensive, and full-scale intelligence quotients (VIQ, PIQ, FSIQ), which reflect both fluid and crystallized intelligence. We performed a comprehensive set of 432 experiments, using different input images, six deep learning models, and two outcome settings, on 850 autistic and healthy subjects 6-64 years of age. Results show promise with statistical significance, and also open up questions inviting further future studies.
How Healthy Older Adults Enact Lateral Maneuvers While Walking
Authors: Desmet David M. , Kazanski Meghan E. , Cusumano Joseph P. , Dingwell Jonathan B. 
Published: February 2023

AbstractBackgroundWalking requires frequent maneuvers to navigate changing environments with shifting goals. Humans accomplish maneuvers and simultaneously maintain balance primarily by modulating their foot placement, but a direct trade-off between these two objectives has been proposed. As older adults rely more on foot placement to maintain lateral balance, they may be less able to adequately adapt stepping to perform lateral maneuvers.Research QuestionHow do older adults adapt stepping to enact lateral lane-change maneuvers, and how do physical and perceived ability influence their task performance?MethodsTwenty young (21.7 ± 2.6 yrs) and 18 older (71.6 ± 6.0 yrs) adults walked on a motorized treadmill in a virtual environment. Following an audible and visual cue, participants switched between two parallel paths, centered 0.6m apart, to continue walking on their new path. We quantified when participants initiated the maneuver following the cue, as well as their step width, lateral position, and stepping variability ellipses at each maneuver step.ResultsYoung and older adults did not differ in when they initiated the maneuver, but participants with lower perceived ability took longer to do so. Young and older adults also did not exhibit differences in step width or lateral positions at any maneuver step, but participants with greater physical ability reached their new path faster. While only older adults exhibited stepping adaptations prior to initiating the maneuver, both groups traded-off stability for maneuverability to enact the lateral maneuver.SignificancePhysical and perceived balance ability, rather than ageper se, differentially influenced maneuver task performance. Humans must make decisions related to the task of walking itself and do so based on both physical and perceived factors. Understanding and targeting these interactions may help improve walking performance among older adults.
Patient-specific simulation of Retinal Hemangioblastoma provides new perspectives on the role of antiangiogenic therapy
Authors: Pradelli Franco , Minervini Giovanni , Tosatto Silvio C.E. 
Published: February 2023

ABSTRACTRetinal Hemangioblastoma (RH) is the most frequent manifestation of the von Hippel-Lindau syndrome (VHL), a rare disease associated with the germline mutation of the von Hippel-Lindau protein (pVHL). An emblematic feature of RH is the high vascularity, which is easily explained by the overexpression of angiogenic factors (AFs) arising from the pVHL impairment. The introduction of Optical Coherence Tomography Angiography (OCTA) allowed observing this feature with exceptional detail. However, our understanding of RH is limited by the absence of an animal model fully recapitulating the tumor. Here, we exploit a cancer mathematical model as an alternative way to explore RH development and angiogenesis. We derived our model from the agreed pathology for this tumor and compared our results with patient-specific OCTA images. Our simulations closely resemble the medical images, proving the capability of our model to recapitulate RH pathology. Our results also suggest that angiogenesis in RH occurs suddenly when the tumor reaches a critical mass, with full capillary invasion in the order of days. These findings open a new perspective on the critical role of time in antiangiogenic therapy in RH, which has resulted ineffective. Indeed, it might be that when RH is diagnosed, angiogenesis is already too advanced to be effectively targeted with this mean.
A portable regulatory RNA array design enables tunable and complex regulation across diverse bacteria
Authors: Liu Baiyang , Cuba Samaniego Christian , Bennett Matthew R. , Franco Elisa , Chappell James 
Published: February 2023

ABSTRACTA lack of composable and tunable gene regulators has hindered efforts to engineer non-model bacteria and consortia. To address this, we explore the broad-host potential of small transcription activating RNA (STAR) and propose a novel design strategy to achieve tunable gene control. First, we demonstrate that STARs optimized forE. colifunction across different Gram-negative species and can actuate using phage RNA polymerase, suggesting that RNA systems acting at the level of transcription are portable. Second, we explore a novel RNA design strategy that uses arrays of tandem and transcriptionally fused RNA regulators to precisely alter regulator concentration from 1 to 8 copies. This provides a simple means to predictably tune output gain across species and does not require access to large regulatory part libraries. Finally, we show RNA arrays can be used to achieve tunable cascading and multiplexing circuits across species, analogous to the motifs used in artificial neural networks.
Identification of anti-fungal bioactive terpenoids from the bioenergy crop switchgrass (Panicum virgatum)
Authors: Li Xingxing , Chou Ming-Yi , Bonito Gregory M. , Last Robert L. 
Published: February 2023

AbstractPlant derived bioactive small molecules have attracted attention of scientists across fundamental and applied scientific disciplines. We seek to understand the influence of these phytochemicals on functional phytobiomes. Increased knowledge of specialized metabolite bioactivities could inform strategies for sustainable crop production. Our recent investigations of metabolomes of the upland and lowland ecotypes of the bioenergy crop switchgrass (Panicum virgatum) revealed large differences in types and abundances of terpenoid specialized metabolites. We hypothesized that – consistent with accumulating evidence that switchgrass genotype impacts microbiome assembly – differential terpenoid accumulation contributes to switchgrass ecotype-specific microbiome composition. An initialin vitroplate-based disc diffusion screen of 18 switchgrass root derived fungal isolates revealed differential responses to upland- and lowland-isolated metabolites. To identify specific fungal growth-modulating metabolites, we tested fractions from root extracts on three ecologically important fungal isolates –Linnemania elongata, Trichodermasp. andFusariumsp. Saponins and diterpenoids were identified as the most prominent antifungal metabolites. Finally, analysis of liquid chromatography-purified terpenoids revealed fungal inhibition structure – activity relationships (SAR). Saponin antifungal activity was primarily determined by the number of sugar moieties – saponins glycosylated at a single core position were inhibitory whereas saponins glycosylated at two core positions were inactive. Saponin core hydroxylation and acetylation were also associated with reduced activity. Diterpenoid activity required the presence of an intact furan ring for strong fungal growth inhibition. This study demonstrates that switchgrass genotype-specific metabolites differentially inhibit fungal isolates from the root and rhizosphere, supporting the hypothesis that these small molecules contribute to microbiome assembly and function.
BERBERINE BRIDGE ENZYME-LIKE OXIDASES OF CELLODEXTRINS AND MIXED-LINKED β-GLUCANS CONTROL SEED COAT FORMATION
Authors: Costantini Sara , Benedetti Manuel , Pontiggia Daniela , Giovannoni Moira , Cervone Felice , Mattei Benedetta , De Lorenzo Giulia 
Published: February 2023

ABSTRACTA member of the Arabidopsis Berberine Bridge Enzyme-like (BBE-l) protein family named CELLODEXTRIN OXIDASE 2 (CELLOX2) has been characterized in this paper and shown to display structural and enzymatic features similar to the previously characterized CELLOX1. These include the capability to oxidize the mixed-linked β-1→3/β-1→4-glucans (MLGs), recently described as cell wall-derived damage-associated molecular patterns (DAMPs) that activate plant immunity. The two paralogous genes show a different expression profile. UnlikeCELLOX1, CELLOX2is not expressed in seedlings or in adult plants and is not involved in immunity againstBotrytis cinerea.Both genes are expressed in a concerted manner in the seed coat during development: whereasCELLOX2transcripts are detected mainly during the heart stage,CELLOX1transcripts are detected later, when the expression ofCELLOX2decreases. Analysis of seeds ofcellox1andcellox2knock-out mutants show alterations in the structure of the coat and mucilage, but not in their monosaccharide composition. We propose that the cell wall structure of specific organs is not only the result of a coordinated synthesis/degradation of polysaccharides but also of their exposure to enzymatic oxidation. Our results also reinforce the view that the family of BBE-l proteins is at least in part devoted to the control of the activity of cell wall-derived oligosaccharides acting as DAMPs.SENTENCETwo Arabidopsis BBE–like oxidases of the cell wall DAMPs cellodextrins and mixed-linked β-glucans inactivate their elicitor activity. Seed coat and mucilage are altered in null mutants of two enzymes.
Differentially deregulated microRNAs contribute to ultraviolet radiation-induced photocarcinogenesis through immunomodulation: An-analysis of microRNAs expression profiling
Authors: Agarwal Anshu , Kansal Vikash , Farooqi Humaira , Singh Vijay Kumar , Prasad Ram 
Published: February 2023

AbstractMicroRNAs (miRNAs) are short non-coding RNA molecules (18-25 nucleotides) that regulate several fundamental biological processes. Emerging evidence has shown more than 1500 miRNAs functions in the cell cycle, proliferation, apoptosis, oxidative stress, immune response, DNA damage, and epigenetics alterations. miRNAs are bidirectionally in nature and act as a tumor suppressor and as an oncogene through crosstalk between tumor cells and immune cells. Although the roles of miRNAs in several cancers are well studied, little is known about ultraviolet B (UVB) radiation-induced skin cancer. Here, we performed a comprehensive screening of 1281 miRNAs in tumor tissues and compared their expression with normal skin. Our results demonstrate that the expression levels of 587 miRNAs were altered in tumor tissues compared to their expression in normal skin. The expression of 337 miRNAs was upregulated from 1.5-12 folds, while the expression of 250 miRNAs was downregulated up to 1.5-10 folds in tumors. Further, intraperitoneal injection of a mimic of down-regulated miR-15b (30nM) and an inhibitor of upregulated miR-133a (20nM) protect UVB-induced suppression of contact hypersensitivity (CHS) response. In conclusion, we identified a network of altered miRNAs in tumors that can serve as prognostic biomarkers and therapeutic targets to manage photocarcinogenesis effectively.
Norwegian general population normative data for the EORTC questionnaires; the core QLQ-C30, the sexual health questionnaire QLQ-SHQ22, and sexual domains of the QLQ-BR23/BR45
Authors: Åsberg R.E , Nilsen M , Hjermstad M.J , Reinertsen K.V , Karlsen J , Giskeødegård G.F , Reidunsdatter R.J. 
Published: February 2023

AbstractObjectiveThe aim of this study was to provide gender-, age-, and morbidity-specific Norwegian general population normative values for the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaires QLQ-C30, the sexual health questionnaire QLQ-SHQ22, and the sexual domains of the breast modules QLQ-BR23 and QLQ-BR45.MethodsA random nation-wide sample stratified by gender and age groups (18–29, 30-39, 40–49, 50–59, 60–69 and ≥70 years) was drawn from the Norwegian National Population Register. Participants were notified through National online health services (HelseNorge) and by postal mail. The survey included sociodemographic background information, HRQoL assessed by the EORTC questionnaires, and morbidity by The Self-Administered Comorbidity Questionnaire. Multivariable linear regression was carried out to estimate the associations of age, sex, and morbidity with the EORTC scale and item scores.ResultsOf the 15,627 eligible individuals, 5.135 (33%) responded. Women and persons with morbidities reported lower functioning and higher symptom burden than men and persons without morbidities, respectively, on nearly all EORTC scales. Sex differences were most prominent forEmotional Functioning, Pain, Fatigue, andInsomnia(QLQ-C30),Body Image, Sexual Functioning(QLQ-BR23/45),Importance of Sexual Activity, Libido, andFatigue(QLQ-SHQ22). The score differences between persons with and without morbidity were highly significant and largest among the youngest and middle-aged groups.ConclusionThe present study is the first to provide normative values for the EORTC sexual health questionnaire QLQ-SHQ22 and the sexual subscales of the QLQ-BR23 and QLQ-BR45, for all separately in age groups by sex and morbidity.
MDTOMO: Continuous conformational variability analysis in cryo electron subtomogram data using flexible fitting based on Molecular Dynamics simulations
Authors: Vuillemot Rémi , Rouiller Isabelle , Jonić Slavica 
Published: February 2023

AbstractCryo electron tomography (cryo-ET) allows observing macromolecular complexes in their native environment. The common routine of subtomogram averaging (STA) allows obtaining the three-dimensional (3D) structure of abundant macromolecular complexes, and can be coupled with discrete classification to reveal conformational heterogeneity of the sample. However, the number of complexes extracted from cryo-ET data is usually small, which restricts the discrete-classification results to a small number of enough populated states and, thus, results in a largely incomplete conformational landscape. Alternative approaches are currently being investigated to explore the continuity of the conformational landscapes thatin situcryo-ET studies could provide. In this article, we present MDTOMO, a method for analyzing continuous conformational variability in cryo-ET subtomograms based on Molecular Dynamics (MD) simulations. MDTOMO allows obtaining an atomic-scale model of conformational variability and the corresponding free-energy landscape, from a given set of cryo-ET subtomograms. The article presents the performance of MDTOMO on a synthetic ABC exporter dataset and anin situSARS-CoV-2 spike dataset. MDTOMO allows analyzing dynamic properties of molecular complexes to understand their biological functions, which could also be useful for structure-based drug discovery.
Boosting the toolbox for live imaging of translation
Authors: Bellec Maelle , Chen Ruoyu , Dhayni Jana , Trullo Antonello , Avinens Damien , Karaki Hussein , Mazzarda Flavia , Lenden-Hasse Helene , Favard Cyril , Lehmann Ruth , Bertrand Edouard , Lagha Mounia , Dufourt Jeremy 
Published: February 2023

AbstractLive imaging of translation based on tag recognition by a single chain antibody is a powerful technique to assess translation regulation in living cells. However, especially in a multicellular organism, this approach is challenging and requires optimization in terms of expression level and detection sensitivity of the system. Here, we improved existing fluorescent tools and developed new ones to image and quantify nascent translation in the livingDrosophilaembryo and in mammalian cells. We tested and characterized five different Green Fluorescent Protein variants fused to the single chain fragment variable (scFv) and uncover photobleaching, aggregation and intensity disparities. Using different strengths of germline and somatic drivers, we determined that the availability of the scFv is critical in order to detect translation throughout development. We introduced a new translation imaging method based on a nanobody/tag system named ALFA-array, allowing the sensitive and simultaneous detection of the translation of several distinct mRNA species. Finally, we developed a largely improved RNA imaging system based on an MCP-tdStaygold fusion.
Evaluation of non-modified wireframe DNA origami for acute toxicity and biodistribution in mice
Authors: Wamhoff Eike-Christian , Knappe Grant A. , Burds Aurora A. , Du Rebecca R. , Neun Barry W. , Difilippantonio Simone , Sanders Chelsea , Edmondson Elijah F. , Matta Jennifer L. , Dobrovolskaia Marina A. , Bathe Mark 
Published: February 2023

AbstractWireframe DNA origami can be used to fabricate virus-like particles for a range of biomedical applications, including the delivery of nucleic acid therapeutics. However, the acute toxicity and biodistribution of these wireframe nucleic acid nanoparticles (NANPs) have not previously been characterized in animal models. In the present study, we observed no indications of toxicity in BALB/c mice following therapeutically relevant dosage of unmodified DNA-based NANPs via intravenous administration, based on liver and kidney histology, liver biochemistry, and body weight. Further, the immunotoxicity of these NANPs was minimal, as indicated by blood cell counts and type-I interferon and pro-inflammatory cytokines. In an SJL/J model of autoimmunity, we observed no indications of NANP-mediated DNA-specific antibody response or immune-mediated kidney pathology following the intraperitoneal administration of NANPs. Finally, biodistribution studies revealed that these NANPs accumulate in the liver within one hour, concomitant with substantial renal clearance. Our observations support the continued development of wireframe DNA-based NANPs as next-generation nucleic acid therapeutic delivery platforms.