bluuebunny/crossref_metadata_2025_split huggingface dataset:
Motor unit discharge properties of the vastii muscles and their modulation with contraction level depend on the knee-joint angle
Authors: Valenčič Tamara , Maeo Sumiaki , Kluzek Stefan , Holobar Aleš , Škarabot Jakob , Folland Jonathan P 
Published: December 2024

ABSTRACTThis study examined the effect of the knee-joint angle on motor unit (MU) discharge properties of the vastii muscles and their modulation with contraction level. Twelve young adults performed unilateral isometric knee-extension contractions during three experimental sessions at either 25, 55, and 85° of knee flexion (full extension: 0°) in a randomised order. Each session involved maximal voluntary contractions (MVCs) followed by submaximal trapezoidal and triangular contractions at different levels relative to maximal voluntary torque (MVT). High-density surface electromyograms were recorded from vastus lateralis and medialis muscles and, subsequently, decomposed to obtain discharge timings of individual MUs. MVT was the greatest, whereas MU discharge rate (DR) during MVCs and submaximal contraction levels (≥30% MVT) was the lowest at the intermediate joint angle (55°). The highest DR during MVCs and high-level contractions (70% MVT), however, was at the most flexed knee position (85°), which was due to a greater DR increase 50-70% MVT compared to 25° and 55°. The onset-offset DR hysteresis (ΔF), an estimate of persistent inward current contribution to motoneuron discharge, decreased with knee flexion and increased with contraction level, whereas the degree of motoneuron input-output nonlinearity (brace height) did not vary with joint angle but decreased with contraction level. At 85°, ΔF increased more and brace height decreased less with contraction level compared to 25° and 55°. These findings indicate that vastii MU DR and its modulation with contraction level vary with knee-joint angle, which could be partly explained by the modulation of motoneuron intrinsic electrical properties.NEW & NOTEWORTHYThis study explored the relationship between motoneuron output to the vastii muscles at different knee-joint angles (quadriceps lengths) and isometric contraction levels. We showed that the motor unit discharge rate was lowest at the angle of the greatest absolute torque capacity, whereas the contraction-level-induced increases in discharge rate and motoneuron excitability were the greatest in the flexed position. These findings suggest that joint-angle-dependent adjustments in sensory feedback modulate motor control of the knee-extensor muscles.
Using animal tracking for early detection of mass poisoning events
Authors: Curk T. , Santangeli A. , Rast W. , Portas R. , Shatumbu G. , Cloete C. , Beytell P. , Aschenborn O. , Melzheimer J. 
Published: December 2024

Abstract1 Amidst the sixth mass extinction, some groups, such as vultures, the only obligate scavengers among vertebrates, are disappearing at an unprecedented rate. Vulture populations worldwide are largely threatened by poisoning. As many vulture species are social foragers, they can congregate in large numbers to scavenge at a carcass, potentially increasing their exposure to poisoning risk. Current anti-poisoning prevention and mitigation measures are insufficient to tackle this threat. There is an urgent need for new effective strategies to prevent mass vulture mortality.2 In this study, we used agent-based modeling to: (1) quantify the impact of different foraging strategies on vulture poisoning risk, and (2) evaluate the cost-effectiveness of using vultures as sentinels for poisoning detection. This approach involves GPS tracking of various numbers of vultures and using the data to quickly detect poisoning incidents and decontaminate carcasses. These actions help mitigate further vulture mortality and prevent mass poisoning.3 Our results indicate that social foraging significantly elevates the risk of vultures being poisoned. Vulture tracking contributes substantially to the early detection of poisoning events, which results in reduced mortality. Poisoning can be mitigated by tracking more vultures and responding faster, with an optimal cost-effectiveness achieved by tracking 5% of the vulture population (25 individuals in our system) and a budget of 58,728 USD. This approach could potentially prevent 45% of poisoning-related mortalities if interventions occur within 2 hours.4Synthesis and applications: Our results suggest that, in order to reduce mortality incidences from poisoning, it is sufficient to track a small proportion of the vulture population, which would act as sentinels for the rest. By evaluating the costs and ecological benefits of these mitigation strategies, we provide evidence-based solutions that practitioners can use to design conservation plans. These findings are therefore instrumental in supporting vulture and scavenger conservation policy and practice.
PlantRing: A high-throughput wearable sensor system for decoding plant growth, water relations and innovating irrigation
Authors: Sun Ting , Lu Chenze , Shi Zheng , Zou Mei , Bi Peng , Xu Xiaodong , Xie Qiguang , Jiang Rujia , Liu Yunxiu , Cheng Rui , Xu Wenzhao , Zhang Yingying , Xu Pei 
Published: December 2024

AbstractThe combination of flexible electronics and plant science has generated various plant-wearable sensors, yet challenges persist in their applications in real-world agriculture, particularly in high-throughput settings. Overcoming the trade-off between sensing sensitivity and range, adapting them to a wide range of crop types, and bridging the gap between sensor measurements and biological understandings remain the primary obstacles. Here we introduce PlantRing, an innovative, nano-flexible sensing system designed to address the aforementioned challenges. PlantRing employs bio-sourced carbonized silk georgette as the strain sensing material, offering exceptional resolution (tensile deformation: < 100 μm), stretchability (tensile strain up to 100 %), and remarkable durability (season long), exceeding existing plant strain sensors. PlantRing effectively monitors plant growth and water status, by measuring organ circumference dynamics, performing reliably under harsh conditions and being adaptable to a wide range of plants. Applying PlantRing to study fruit cracking in tomato and watermelon reveals novel hydraulic mechanism, characterized by genotype-specific excess sap flow within the plant to fruiting branches. Its high-throughput application enabled large-scale quantification of stomatal sensitivity to soil drought, a traditionally difficult-to-phenotype trait, facilitating drought tolerant germplasm selection. Combing PlantRing with soybean mutant led to the discovery of a potential novel function of theGmLNK2circadian clock gene in stomatal regulation. More practically, integrating PlantRing into feedback irrigation achieves simultaneous water conservation and quality improvement, signifying a paradigm shift from experience- or environment-based to plant-based feedback control. Collectively, PlantRing represents a groundbreaking tool ready to revolutionize botanical studies, agriculture, and forestry.
Functional insights intoPlasmodiumactin depolymerizing factor interactions with phosphoinositides
Authors: Lasiwa Devaki , Kursula Inari 
Published: December 2024

AbstractMalaria is caused by protozoan parasites,Plasmodiumspp., that belong to the phylum Apicomplexa. The life cycle of these parasites depends on two different hosts; the definitive host, or vector, is a mosquito, and the intermediate host is a vertebrate, such as human. Malaria parasites use a unique form of substrate-dependent motility for host cell invasion and egress, which is dependent on an actomyosin motor complex called the glideosome. Apicomplexa have a small set of actin regulators, which are poorly conserved compared to their equivalents in higher eukaryotes. Actin depolymerizing factors (ADFs) are key regulators responsible for accelerating actin turnover in eukaryotic cells. The activity of ADFs is regulated by membrane phosphoinositides. Malaria parasites express two ADF isoforms at different life stages. ADF1 differs substantially from canonical ADF/cofilins and fromPlasmodiumADF2 in terms of both structure and function. Here, we studied the interaction of bothPlasmodiumADFs with phosphoinositides using biochemical and biophysical methods and mapped their binding sites on ADF1. BothPlasmodiumADFs bind to different phosphoinositides, and bindingin vitrorequires the formation of vesicles or micelles. Interaction with phosphoinositides increases the α-helical content of the parasite ADFs, and the affinities are in the micromolar range. The binding site for PI(4,5)P2 inPfADF1 involves a small, positively charged surface patch.
Industrialization of three-dimensional hiPSC-cardiac microtissues for high-throughput cardiac safety and drug discovery screening
Authors: de Korte Tessa , Johnson Benjamin B. , Kosmidis Georgios , Samson-Couterie Benoit , Mol Mervyn P. H. , van Helden Ruben W. J. , François Louise , Meraviglia Viviana , Yiangou Loukia , Kuipers Tom , Mei Hailiang , Bellin Milena , Braam Stefan R. , Jain Shushant , Mummery Christine L. , Davis Richard P. 
Published: December 2024

SummaryCurrent cardiac cell models for drug screening often face a trade-off between cellular maturity and achieving high throughput. While three-dimensional human induced pluripotent stem cell-based heart models typically exhibit more adult-like features, their application is hindered by the need for large cell numbers or complex equipment. Here, we developed cost-effective methods to scale up production of three-dimensional cardiac microtissues (cMTs) containing three cardiac cell types, and assess calcium transients and action potential metrics for high-throughput screening (HTS). Automating the procedure revealed reproducible drug responsiveness and predictive accuracy in a reference compound screen. Furthermore, an arrhythmic phenotype was reliably triggered in cMTs containing cardiomyocytes with a RYR2 mutation. A screen of FDA-approved drugs identified 17 drugs that rescued the arrhythmic phenotype. Our findings underscore the scalability of cMTs and their utility in disease modelling and HTS. The advanced “technology-readiness-level” of cMTs supports their regulatory uptake and acceptance within the pharmaceutical industry.
Adaptation of the tetracycline-repressible system for modulating the expression of essential genes inCryptococcus neoformans
Authors: Fu Ci , Robbins Nicole , Cowen Leah E. 
Published: December 2024

AbstractThe opportunistic human fungal pathogenCryptococcus neoformanshas an enormous impact on human health as the causative agent of cryptococcal meningitis, an AIDS-defining illness that results in significant human mortality. To combatC. neoformansinfections, there is a dire need to expand our current antifungal arsenal. Essential gene products often serve as ideal targets for antimicrobials, and thus identifying and characterizing essential genes in a pathogen of interest is critical for drug development. Unfortunately, characterization of essential genes inC. neoformansis limited due to its haploid nature and lack of genetic tools for generating effective conditional-expression mutants. To date, the copper-repressible promoterpCTR4is the mostly widely used system to regulate essential gene expression, however, its expression is leaky and copper has pleiotropic effects. In diverse fungal species, includingSaccharomyces cerevisiae, Candida albicans, andCandida auris, the tetracycline-repressible promoter system is a powerful tool to regulate gene expression, however, it has yet to be adapted forC. neoformans. In this study, we successfully implemented the tetracycline-repressible system inC. neoformansto regulate the expression of the essential geneHSP90. Supplementation of cultures with the tetracycline analog doxycycline efficiently depletedHSP90at both transcript and protein levels and inhibitedC. neoformansgrowth and viability. Thus, this work unveils a novel approach to generate conditional-expression mutants inC. neoformans, providing unprecedented potential to systematically study essential gene function in this important human fungal pathogen.
Concordance between upper and lower airway microbiota in children with Cystic Fibrosis
Authors: Nassirnia Sedreh , Scherz Valentin , Greub Gilbert , Caruana Giorgia , Taffé Patrick , Jaton Katia , Papis Sebastien , Posfay-Barbe Klara M. , Mornand Anne , Rochat-Guignard Isabelle , Bertelli Claire , Asner Sandra A. 
Published: December 2024

AbstractBackgroundSputum is the sample to monitor the lower respiratory tract microbiota in cystic fibrosis (CF), but young patients often cannot expectorate. We hypothesized that throat swabs could reflect lower airway colonization and assessed the concordance of bacterial community composition between paired sputum and throat swab samples from children with CF.MethodsThe prospective longitudinal multicenter MUCOVIB cohort included 379 samples from 61 CF children. Using V3-V4 16S rRNA amplicon metagenomics, we compared bacterial community diversity and composition between sputum and throat swabs in the full cohort and in 11 patients with paired samples from the same visit.ResultsSputum and Throat swabs exhibited similar bacterial diversity, regardless of the exacerbation status, and presented a substantial agreement for detecting pathogens (Cohen’s Kappa: 0.6). Differences in bacterial abundance were observed (p=0.001), but not presence/absence (p=0.098). Community typing revealed three distinct community types, with 86% of paired samples falling into the same cluster, highlighting the homogeneity between sputum and throat swabs microbiota. Network analysis demonstrated slight, non-random similarities in microbial interactions between sample types (ARI = 0.08 and 0.10). The average distance between samples collected from the same visit was shorter (0.505, ± 0.056 95%CI), compared to sputum (0.695, ± 0.017) or throat swab (0.704, ± 0.045) from the same patient collected during different visits.ConclusionsThroat swabs can provide representative information on lower respiratory microbiota. Clinicians should collect throat swabs rather than relying on sputum samples from previous visits to guide antibiotic prescriptions in CF children unable to expectorate.
Genome-wide mapping of EBV-induced genomic variations identifies the role of MUC19 in EBV latency
Authors: Yu Jingwen , Wang Yaohao , Liu Qirong , Zhou Xiaohui , Robertson Erle S , Pei Yonggang 
Published: December 2024

AbstractEpstein-Barr virus (EBV) infects over 95% of the world’s population and is tightly associated with multiple human malignant diseases. As the first discovered human oncovirus, EBV is known to induce genomic instability by promoting various types of genomic modifications in host chromosomes. However, the mechanisms through which EBV interacts with the host genome and regulates cellular gene expression in genomic modifications are not yet fully elucidated. In this study, we conducted primary EBV infection in B cells and performed the analyses of copy number variants using whole genome sequencing. After comparing to other distinct B cells with varying EBV infection backgrounds, we identified susceptible regions and unveiled critical host factors induced by EBV infection on chromosomes. Combined with the genome-wide transcriptomic analyses, we found that the mucin geneMUC19is distinctively activated by EBV infection and MUC19 promotes oncogenesis through the activation of mTOR signaling in lymphoblastoid cell lines (LCLs). Further results indicate that EBV nuclear antigen 1 (EBNA1) binds to multiple regions withinMUC19and enhances the expression ofMUC19. Moreover, sequence alignment has shown intriguing motif homology between the basic repeat unit ofMUC19and EBV genome, suggesting the potential of EBV-specific integration. To conclude, our study maps the genomic perturbations induced by EBV primary infection and offers new insights into the oncogenic roles of MUC19 during EBV latency.
Rhizobium rhizogenesA4-derived strains mediate hyper-efficient transient gene expression inNicotiana benthamianaand other solanaceous plants
Authors: Lopez-Agudelo Juan Carlos , Goh Foong-Jing , Tchabashvili Sopio , Huang Yu-Seng , Huang Ching-Yi , Lee Kim-Teng , Wang Yi-Chieh , Wu Yu , Chang Hao-Xun , Kuo Chih-Horng , Lai Erh-Min , Wu Chih-Hang 
Published: December 2024

AbstractAgroinfiltration, a method utilizing agrobacteria to transfer DNA into plant cells, is widely used for transient gene expression in plants. Besides the commonly usedAgrobacteriumstrains,Rhizobium rhizogenescan also introduce foreign DNA into host plants for gene expression. While manyR. rhizogenesstrains have been known for inducing hairy root symptoms, their use for transient expression has not been fully explored. Here, we showed thatR. rhizogenesA4 outperformed all other tested agrobacterial strains in agroinfiltration experiments on leaves ofNicotiana benthamianaand other solanaceous plants. By conducting an agroinfiltration screening inN. benthamianaleaves using various agrobacterial strains carrying the RUBY reporter gene cassette, we discovered that A4 mediates the strongest and fastest transient expression. Utilizing the genomic information, we developed a collection of disarmed and modified strains derived from A4. By performing vacuum infiltration assays, we demonstrated that these A4-derived strains efficiently transiently transform 6-week-oldN. benthamianaleaves, showing less sensitivity to the age of plants compared to the laboratory strain GV3101. Furthermore, we performed agroinfiltration using AS109, an A4-derived disarmed strain, on the leaves of tomato, pepper, and eggplant. Remarkably, AS109 mediated transient gene expression on tested solanaceous plants more effectively than all the tested commonly used agrobacterial strains. This discovery paves the way for establishingR. rhizogenesA4-derived strains as a new option for enhancing transient expression inN. benthamianaand facilitating the functional study of plant genes in other solanaceous species.
Functional, Biotinylproteomic and Bioinformatic Analysis of Both Cytoskeletal and Plastoskeletal Proteins in Plant Mechanoresponse
Authors: Wu Kebin , Yang Nan , Ren Jia , Liu Shichang , Wang Kai , Dai Shuaijian , Lu Yinglin , An Yuxing , Tian Fuyun , Gao Zhaobing , Yang Zhu , Zhang Yage , Yu Weichuan , Li Ning 
Published: December 2024

AbstractTo investigate the early signaling components of skeletal proteins in mediating Arabidopsis thigmomorphogenesis, both microscopic and proximity labeling (PL)-based quantitative biotinylproteomics were applied to investigate the subcellular location and putative interactors of a touch-responsive WPRa4 protein. These experiments have demonstrated that the cytoskeletal protein WPRa4 is localized nearby the plastid. Several cytosolic Plastid Movement-Impaired (PMI) proteins and a member of the plastidic translocon were identified as putative interactors of WPRa4, suggesting an integrated network of skeletal proteins linking the cytoskeleton with the plastid membrane. Further bioinformatic analysis of both Proximity Labeling- and XL-MS-based proteomic results suggested that Plastid Movement-Impaired 4 (PMI4) protein may serve as a candidate in mediating the plant touch response. The loss-of-functionpmi4mutant showed neither the touch-induced bolting delay nor the rosette size reduction upon repetitive touches, suggesting thatpmi4is a unique type of mutant of Arabidopsis thigmomorphogenesis. Moreover, the null mutantpmi4displayed a severe defect in the touch-induced Ca2+oscillation. Further transcriptomic analysis performed on both the wild-type Arabidopsis andpmi4mutant indicated that the mutatedpmi4gene suppressed the expression of a number of touch rapidly induced transcripts and a JA-responsive gene,LOX2. These findings led us to propose a revised touch force-sensing theory, in which the interconnected cytosolic and plastidic skeletal proteins serve as the early mechano-sensing components mediating Arabidopsis thigmomorphogenesis and the retrograde calcium signaling in response to touch.
Defining and Controlling Axial Nephron Patterning in Human Kidney Organoids with Synthetic Wnt-Secreting Organizers
Authors: Fausto Connor C. , Glykofrydis Fokion , Kumar Navneet , Schnell Jack , Csipan Reka L. , De Kuyper Faith , Grubbs Brendan , Thornton Matthew , Achieng MaryAnne , Morsut Leonardo , Lindström Nils O. 
Published: December 2024

AbstractCurrent human pluripotent stem cell-derived kidney organoids contain nephron-like structures that lack organotypic patterning. It is thought that during human development, nephrons form their proximal-distal axial polarity in response to collecting duct-derived signals that are absent in kidney organoids. To delineate how nephron polarities establish, we profiled human kidney development by spatial transcriptomic approaches. Our analyses describe a new axial polarity in the nephron and demonstrate that the nephron proximal-distal polarity develops adjacent to a transcriptional boundary in the collecting duct where non-canonicalWNT11is downregulated and canonicalWNT9Bligand is upregulated. The nephron region closest to this boundary in turn activates a series of canonical WNT target genes inferring positional nephron identities. To establish whether a canonical WNT source can improve organoid patterning to anin vivo-like state, we bioengineered self-organizing WNT-secreting synthetic organizers. Organizer-coupled kidney organoids respond to WNT ligands by forming expression gradients and developing distal cell identities. Tuning the WNT dose produced nephrons with continuous patterning along the proximal-distal axis. Strikingly, polarized iPSC-derived nephrons directed their distal tubules towards the WNT-source, indicating axial patterning and morphogenetic programs are tuned by WNTs from the synthetic organizers. Our data present a strategy to control organ patterning, build an artificial kidney, and highlights the power of synthetic organizer systems for advancing organoid models.
Impact of Temporal Uncertainty on Sign-tracking Behavior
Authors: Kaneko Rie , Simpson Eleanor H , Balsam Peter D 
Published: December 2024

AbstractSign-tracking behavior, also known as “autoshaping”, is defined as approach and interaction with reward-predictive cues. It is associated with addiction-related phenotypes and compulsive behavior. Several previous studies have demonstrated that when there is uncertainty about reward properties (e.g. probability, size), sign-tracking is increased. However, the effect of cue-uncertainty on sign-tracking behavior is not known. Here, using a Pavlovian conditioning paradigm, we manipulated the temporal uncertainty about the appearance of cues by implementing either fixed or variable inter-trial intervals (ITIs) of different durations across groups of mice. We found that temporal uncertainty during acquisition significantly enhances sign-tracking, which persists during extinction, even when ITI variability was different in the extinction session than in the acquisition session. This suggests that the effects of temporal uncertainty are learned and retained, rather than performance-based. Our results demonstrate that sign-tracking behavior is not only modified by the characteristic of the reward, but it can also be modified by the uncertainty regarding cues. These findings highlight how temporal predictability shapes cue-directed behaviors and has implications for understanding reward-related behavioral responses including sign-tracking behaviors.