bluuebunny/crossref_metadata_2025_split huggingface dataset:
Aging-related mechanical degradation of cortical bone is driven by microstrucural changes in addition to porosity
Authors: Marty André Gutiérrez 
Published: March 2023

AbstractThis study aims to gain mechanistic understanding of how aging-related changes in the microstructure of cortical bone drive mechanical consequences at the macroscale. To that end, cortical bone was modeled as a bundle of elastic-plastic, parallel fibers loaded in uniaxial tension, which comprised osteons and interstitial tissue. Distinct material properties were assigned to each fiber in either the osteon or interstitial fiber “families.” Models representative of mature (20-60 yrs.) bone, and elderly (60+) bone were created. Aging-related changes were modeled along three independent dimensions: (i) increased porosity, (ii) increased ratio of osteon fibers relative to interstitial fibers, and (iii) a change in fiber material properties.The model captured decreases in modulus, yield stress, yield strain, ultimate stress, ultimate strain, and toughness with age of 14%, 11%, 8%, 6%, 20%, and 30%, respectively. In both mature and elderly bundles, rupture of the interstitial fibers drove the initial loss of strength following the ultimate point. Plasticity and more gradual rupture of the osteons drove the remainder of the response. Both the onset and completion of interstitial fiber rupture occurred at lower strains in the elderly vs. mature case.Changes along all three dimensions were required for the model to capture aging-related decline in the strength, ductility, and toughness of cortical bone. These findings point to the importance of studying microstructural changes beyond porosity, such as the area fraction of osteons and the microconstituent material properties of osteon and interstitial tissue, in order to further our understanding of aging-related changes in bone.
Screening tools used in primary health care settings to identify health behaviours in children (birth – 16 years); A systematic review of their effectiveness, feasibility and acceptability
Authors: Dutch Dimity , Bell Lucinda , Zarnowiecki Dorota , Johnson Brittany J , Denney-Wilson Elizabeth , Byrne Rebecca , Cheng Heilok , Rossiter Chris , Manson Alexandra , House Eve , Davidson Kamila , Golley Rebecca K 
Published: March 2023

ABSTRACTBackgroundChild health behaviour screening tools used in primary health care have potential as a transformative and effective strategy to support growth monitoring and the early identification of suboptimal behaviours to target strategies for intervention. This systematic review aimed to examine the effectiveness, acceptability and feasibility of child health behaviour screening tools used in primary health care settings.MethodsA systematic review of studies published in English in five databases (CINAHL, Medline, Scopus, PsycINFO and Web of Science) prior to July 2022 was undertaken using a PROSPERO protocol and PRISMA guidelines. Eligible studies: 1) described screening tools for health behaviours (dietary, physical activity, sedentary or sleep-related behaviours) used in primary health care settings in children birth to 16 years of age; 2) reported their acceptability, feasibility or effectiveness on child or practitioner behaviour or 3) reported implementation of the screening tool. Study selection and data extraction were conducted in duplicate. Results were narratively synthesised.ResultsOf the 7145 papers identified, 22 studies reporting on 14 unique screening tools were included. Four screening tools measured diet, physical activity, sedentary and sleep behaviours domains, with most screening tools only measuring two or three behaviour domains. Ten studies reported screening tools were effective in changing practitioner self-reported behaviour, knowledge, self-efficacy and provision of health behaviour education. Administration of screening tools varied across studies including mode, timing and caregiver or practitioner completion. Implementation strategies described included practitioner training and integration into electronic medical records. Practitioners and caregivers identified numerous benefits and challenges to screening; however, child views were not captured.ConclusionsFew screening tools exist to facilitate comprehensive screening of children’s health behaviours in primary health care. This review highlights the potential of health behaviour screening as an acceptable and feasible strategy to comprehensively assess and provide early intervention for children’s health behaviours in primary health care settings.Potential conflicts of interestAll authors have no conflicts of interest to declare.
A critical role of a eubiotic microbiota in gating proper immunocompetence inArabidopsis
Authors: Paasch Bradley C. , Sohrabi Reza , Kremer James M. , Nomura Kinya , Cheng Yu Ti , Martz Jennifer , Kvitko Brian , Tiedje James M. , He Sheng Yang 
Published: March 2023

AbstractAlthough many studies have shown that microbes can ectopically stimulate or suppress plant immune responses, the fundamental question of whether the entire preexisting microbiota is indeed required for proper development of plant immune response remains unanswered. Using a recently developed peat-based gnotobiotic plant growth system we found thatArabidopsisgrown in the absence of a natural microbiota lacked age-dependent maturation of plant immune response and were defective in several aspects of pattern-triggered immunity. Axenic plants exhibited hypersusceptibility to infection by the bacterial pathogenPseudomonas syringaepv.tomatoDC3000 and the fungal pathogenBotrytis cinerea. Microbiota-mediated immunocompetence was suppressed by rich nutrient conditions, indicating a tripartite interaction between the host, microbiota, and abiotic environment. A synthetic microbiota composed of 48 culturable bacterial strains from the leaf endosphere of healthyArabidopsisplants was able to substantially restore immunocompetence similar to plants inoculated with a soil-derived community. In contrast, a 52-member dysbiotic synthetic leaf microbiota overstimulated the immune transcriptome. Together, these results provide evidence for a causal role of a eubiotic microbiota in gating proper immunocompetence and age-dependent immunity in plants.
“Tumor Explants Elucidate a Cascade of Paracrine SHH, WNT, and VEGF Signals Driving Pancreatic Cancer Angiosuppression”
Authors: Hasselluhn Marie C. , Decker-Farrell Amanda R. , Vlahos Lukas , Thomas Dafydd H. , Curiel-Garcia Alvaro , Maurer H. Carlo , Wasko Urszula N. , Tomassoni Lorenzo , Sastra Stephen A. , Palermo Carmine F. , Dalton Tanner C. , Ma Alice , Li Fangda , Tolosa Ezequiel J. , Hibshoosh Hanina , Fernandez-Zapico Martin E. , Muir Alexander , Califano Andrea , Olive Kenneth P. 
Published: March 2023

AbstractThe sparse vascularity of Pancreatic Ductal Adenocarcinoma (PDAC) presents a mystery: what prevents this aggressive malignancy from undergoing neoangiogenesis to counteract hypoxia and better support growth? An incidental finding from prior work on paracrine communication between malignant PDAC cells and fibroblasts revealed that inhibition of the Hedgehog (HH) pathway partially relieved angiosuppression, increasing tumor vascularity through unknown mechanisms. Initial efforts to study this phenotype were hindered by difficulties replicating the complex interactions of multiple cell typesin vitro. Here we identify a cascade of paracrine signals between multiple cell types that act sequentially to suppress angiogenesis in PDAC. Malignant epithelial cells promote HH signaling in fibroblasts, leading to inhibition of WNT signaling in fibroblasts and epithelial cells, thereby limiting VEGFR2-dependent activation of endothelial hypersprouting. This cascade was elucidated using human and murine PDAC explant models, which effectively retain the complex cellular interactions of native tumor tissues.
A special envelope separates extra-chromosomal from mammalian chromosomal DNA in the cytoplasm
Authors: Schenkel Laura , Wang Xuan , Le Nhung , Burger Michael , Kroschewski Ruth 
Published: March 2023

AbstractExpression from transfected plasmid DNA is generally transient, but little do we know on what limits this. Live-cell imaging revealed that DNA transfected into mammalian cells was either captured directly in the cytoplasm, or was soon expelled from the nucleus, upon its entry. In the cytoplasm, plasmid DNA was rapidly surrounded by a double membrane and frequently colocalized with extra-chromosomal DNA of telomeric origin, also expelled from the nucleus. Therefore, we termed this long-term maintained structure exclusome. The exclusome envelope contains endoplasmic reticulum proteins, the inner-nuclear membrane proteins Lap2β and Emerin but differs from the nuclear envelope by the absence of the Lamin B Receptor, nuclear pore complexes and by the presence of fenestrations. Further, Emerin affects the frequency of cells with exclusomes. Thus, cells wrap chromosomes and extra-chromosomal DNA into similar yet distinct envelopes. Thereby, they distinguish, sort, cluster, package, and keep extra-chromosomal DNA in the exclusome but chromosomal DNA in the nucleus, where transcription occurs.
Marine predator spatial conservation priorities are taxon-specific
Authors: Boyse Elizabeth , Goodman Simon J. , Beger Maria 
Published: March 2023

AbstractMarine predators are globally threatened by anthropogenic stressors, but are key for ecosystem functioning. Their worsening conservation statuses indicate that current management is failing, requiring us to urgently reimagine their conservation needs to ensure their survival. Their life histories, threats, and resource needs are diverse. Consequently, spatial conservation areas targeting all species will overlook such heterogeneity, contributing to the problem. Here, we demonstrate that marine mammals, elasmobranchs and teleost fishes return drastically different spatial conservation priority areas, based on Marxan scenarios for 42 marine predator species in the Mediterranean Sea. None of the marine predators are sufficiently covered by the current marine protected area (MPA) system, with marine mammals being the least protected despite having the greatest designated MPA extent, highlighting disconnects between conservation goals and current management outcomes. To save marine predators, taxon specific ecological requirements and resulting spatial heterogeneity need to be accounted for in marine spatial planning.
Clustered synapses develop in distinct dendritic domains in visual cortex before eye opening
Authors: Leighton Alexandra H. , Cheyne Juliette E. , Lohmann Christian 
Published: March 2023

AbstractSynaptic inputs to cortical neurons are highly structured in adult sensory systems, such that neighboring synapses along dendrites are activated by similar stimuli. This organization of synaptic inputs, called synaptic clustering, is required for high-fidelity signal processing, and clustered synapses can already be observed before eye opening. However, how clustered inputs emerge during development is unknown. Here, we employed concurrentin vivowhole-cell patch clamp and dendritic calcium imaging to map spontaneous synaptic inputs to dendrites of layer 2/3 neurons in the mouse primary visual cortex during the second postnatal week until eye opening. We find that the number of functional synapses and the frequency of transmission events increase several fold during this developmental period. At the beginning of the second postnatal week, synapses assemble specifically in confined dendritic segments, whereas other segments are devoid of synapses. By the end of the second postnatal week, just before eye-opening, dendrites are almost entirely covered by domains of co-active synapses. Finally, co-activity with their neighbor synapses correlates with synaptic stabilization and potentiation. Thus, clustered synapses form in distinct functional domains presumably to equip dendrites with computational modules for high-capacity sensory processing when the eyes open.
Cell specialization and coordination inArabidopsisleaves upon pathogenic attack revealed by scRNA-seq
Authors: Delannoy Etienne , Batardiere Bastien , Pateyron Stéphanie , Soubigou-Taconnat Ludivine , Chiquet Julien , Colcombet Jean , Lang Julien 
Published: March 2023

SummaryPlant defense responses involve several biological processes that allow plants to fight against pathogenic attacks. How these different processes are orchestrated within organs and depend on specific cell types is poorly known. Here, using scRNA-seq technology on three independent biological replicates, we identified 10 distinct cell populations in wild-typeArabidopsisleaves inoculated with the bacterial pathogenPseudomonas syringaeDC3000. Among those, we retrieved major cell types of the leaves (mesophyll, guard, epidermal, companion and vascular S cells) to which we could associate characteristic transcriptional reprogramming and regulators, thereby specifying different cell-type responses to the pathogen. Further analyses of transcriptional dynamics, based on inference of cell trajectories, indicated that the different cell types, in addition to their characteristic defense responses, can also share similar modules of gene reprogramming, allowing for instance vascular S cells, epidermal cells and mesophyll cells to converge towards an identical cell fate, mostly characterized by lignification and detoxification functions. Moreover, it appeared that the defense responses of these three cell types can evolve along a second separate path. As this divergence does not correspond to the differentiation between immune and susceptible cells, we speculate that this might reflect the discrimination between cell-autonomous and non-cell-autonomous responses. Altogether our data provide an upgraded framework to describe, explore and explain the specialization and the coordination of plant cell responses upon pathogenic challenge.
An accessible and generalizable in vitro luminescence assay for detecting GPCR activation
Authors: Miller Ruby M. , Sescil Jennifer , Sarcinella Marina C. , Bailey Ryan C. , Wang Wenjing 
Published: March 2023

ABSTRACTG-protein coupled receptors (GPCRs) serve critical physiological roles as the most abundant family of receptors. Here we describe the design of a generalizable and accessibleIn vitroGPCR splitNanoLuc ligandTriggeredReporter (IGNiTR), having broad and diverse applications. IGNiTR leverages the interaction between a conformationspecific binder and agonist-activated GPCR to reconstitute a split nanoluciferase. We have demonstrated IGNiTR with three Gs-coupled GPCRs and a Gi-coupled GPCR with three classes of conformation-specific binders: nanobodies, miniG proteins, and G-protein peptidomimetics. IGNiTR demonstrated binding efficacy and potency values of various Dopamine Receptor D1 (DRD1) ligands that agree well with reported values. IGNiTR also allows the use of a synthetic G protein peptidomimetic, providing easily standardized reagents for characterizing GPCRs and ligands. We demonstrated three applications of IGNiTR: 1) characterizing GPCR functionality during Nanodisc-based reconstitution process; 2) highthroughput screening of ligands against DRD1; 3) detection of opioids for in the field applications. Due to its convenience, accessibility and consistency, IGNiTR will find extensive applications in GPCR ligand detection, screening and GPCR characterization.
FK506 binding protein 5 regulates cell quiescence-proliferation decision in zebrafish epithelium
Authors: Li Yingxiang , Liu Chengdong , Bai Xuanxuan , Li Mingyu , Duan Cunming 
Published: March 2023

AbstractThe cell proliferation-quiescence decision plays fundamental roles in tissue formation and regeneration, and its dysregulation can lead to human diseases. In this study, we performed transcriptomics and genetic analyses using a zebrafish model to identify pathways and genes involved in epithelial cell quiescence-proliferation regulation. In thisin vivomodel, a population of GFP-labeled epithelial cells known as ionocytes were induced to reenter the cell cycle by a physiological stress. Transcriptomics analysis identified 1168 genes up-regulated and 996 genes down-regulated in the reactivated cells. GO and KEGG pathway analyses revealed that genes involved in transcription regulation, cell cycle, Foxo signaling, and Wnt signaling pathway are enriched among the up-regulated genes, while those involved in ion transport, cell adhesion, and oxidation-reduction are enriched among the down-regulated genes. Among the top up-regulated genes is FK506 binding protein 5 (Fkbp5), a member of the conserved immunophilin family. CRISPR/Cas9-mediated Fkbp5 deletion abolished ionocyte reactivation and proliferation.Pharmacological inhibition of Fkbp5 had similar effects. Further analyses showed that genetic deletion and inhibition of Fkbp5 impaired Akt signaling. Forced expression of a constitutively active form of Akt rescued the defects caused by Fkbp5 inhibition. These results uncover a previously unrecognized role of Fbkp5 in regulating the quiescence-proliferation decision via Akt signaling.Impact StatementTranscriptomic and genetic deletion studies unravel a new role of Fkbp5 in promoting cell reactivation via Akt signaling.HighlightsTranscriptomic analysis reveals several molecular pathways altered during epithelial cell quiescence-proliferation transition.Fkbp5 is highly up-regulated in reactivated and dividing cells.Fkbp5 promotes epithelial cell reactivation and proliferation via Akt signaling.
The gut microbiome and resistome of conventionally- vs. pasture-raised pigs
Authors: Holman Devin B. , Gzyl Katherine E. , Kommadath Arun 
Published: March 2023

AbstractConventional swine production typically houses pigs indoors and in large groups, whereas pasture-raised pigs are reared outdoors in lower stocking densities. Pigs in both production systems are usually fed a grain-based diet but pasture-raised pigs may also consume plants and soil. Antimicrobial use also differs with conventionally-raised pigs often being exposed to antimicrobials directly or indirectly to control and prevent infectious disease. However, antimicrobial use can be associated with the development and persistence of antimicrobial resistance. In this study, we used shotgun metagenomic sequencing to compare the gut microbiomes and resistomes of pigs raised indoors on a conventional farm with those raised outdoors on pasture. The microbial compositions as well as the resistomes of both groups of pigs were significantly different from each other. Bacterial species such asIntestinibaculum porci, Pseudoscardovia radai, andSharpea azabuensiswere relatively more abundant in the gut microbiomes of pasture-raised pigs andHallella faecisandLimosilactobacillus reuteriin the conventionally-raised swine. The abundance of antimicrobial resistance genes (ARGs) was significantly higher in the conventionally-raised pigs for nearly all antimicrobial classes, including aminoglycosides, beta-lactams, macrolides-lincosamides-streptogramin B, and tetracyclines. Functionally, the gut microbiomes of the two group of pigs also differed significantly based on their CAZyme profiles, with certain CAZyme families associated with host mucin degradation enriched in the conventional pig microbiomes. We also recovered 1,043 dereplicated strain-level metagenome-assembled genomes (≥ 90% completeness and <5% contamination) to provide taxonomic context for specific ARGs and metabolic functions. Overall, the study provides insights into the differences between the gut microbiomes and resistomes of pigs raised under two very different production systems.
A global pause generates nonselective response inhibition during selective stopping
Authors: Wadsley Corey G. , Cirillo John , Nieuwenhuys Arne , Byblow Winston D. 
Published: March 2023

1AbstractResponse inhibition is essential for terminating inappropriate actions. Selective response inhibition may be required when stopping part of a multicomponent action. However, a persistent response delay (stopping-interference effect) indicates nonselective response inhibition during selective stopping. This study aimed to elucidate whether nonselective response inhibition is the consequence of a global pause process during attentional capture or specific to a nonselective cancel process during selective stopping. We hypothesised that the stopping-interference effect would be larger in response to stop than ignore signals, owing to stronger nonselective response inhibition for explicit selective stopping. Twenty healthy human participants of either sex performed a bimanual anticipatory response inhibition paradigm with selective stop and ignore signals. Frontocentral and sensorimotor beta (β)-bursts were recorded with electroencephalography. Corticomotor excitability (CME) and short-interval intracortical inhibition (SICI) in primary motor cortex were recorded with transcranial magnetic stimulation. Behaviourally, responses in the non-signalled hand were delayed during selective ignore and stop trials. The response delay was largest during selective stop trials and indicated that the stopping-interference effect could not be attributed entirely to attentional capture. A stimulus-nonselective increase in frontocentral β-bursts occurred during stop and ignore trials, whilst sensorimotor response inhibition was reflected in maintenance of β-bursts and SICI relative to disinhibition observed during go trials. Signatures of response inhibition in the sensorimotor cortex contralateral to the responding hand were not associated with the magnitude of stopping-interference. Therefore, nonselective response inhibition during selective stopping results primarily from a nonselective pause process but does not entirely account for the stopping-interference effect.2Significance statementSelective stopping is a complex form of response inhibition where a person must execute and cancel part of an action at the same time. A stopping-interference effect exemplifies the complexity of selective stopping. The present study examined whether nonselective response inhibition during selective stopping results from a global pause during attentional capture or is specific to a deliberate cancel process. Behaviourally, the interference effect was larger during selective stop stimuli than selective ignore stimuli. However, neurophysiological signatures of nonselective response inhibition were elicited in response to both stop and ignore stimuli. These findings indicate that nonselective response inhibition during selective stopping results primarily from a nonselective pause process but does not entirely account for the stopping-interference effect.