bluuebunny/crossref_metadata_2025_split huggingface dataset:
HaHB11 transformed maize has improved yield under waterlogging and defoliation in control and field conditions
Authors: Raineri Jesica , Caraballo Luciano , Rigalli Nicolás , Portapila Margarita , Otegui María Elena , Chan Raquel Lía 
Published: October 2021

AbstractHaHB11 is a sunflower transcription factor previously described as conferring improved yield to maize hybrids and lines. Here we report that transgenic HaHB11 maize lines exhibited a better performance funder waterlogging, both in greenhouse and field trials carried out during three growth cycles. One of these trials was particularly affected by a strong storm during flowering, causing severe defoliation. Controlled defoliation assays indicated that the transgenic genotypes were able to set more grains than controls. Hybrids were generated by crossing B73 HaHB11 lines with the contrasting Mo17 lines and tested in the field. These hybrids exhibited the same beneficial traits as the parental lines when compared with their respective controls. Waterlogging tolerance coursed via the root architecture improvement, including more xylem vessels, reduced tissue damage, less superoxide accumulation, and altered carbohydrate metabolism compared to controls. Multivariate analyses corroborated the robustness of the differential traits observed. Furthermore, canopy spectral reflectance data, computing 29 vegetation indices associated with biomass, chlorophyll, and abiotic stress, helped to identify genotypes as well as their growing conditions. Altogether the results reported here indicate that this sunflower gene constitutes a suitable tool to improve maize plants for environments prone to waterlogging and/or wind defoliation.One sentence summaryPhenotyping and big data analyses indicate that the transcription factor HaHB11 confers waterlogging and defoliation tolerance, and increased yield to maize lines and hybrids in all tested conditions.
The anterior insular cortex associates temporally discontiguous stimuli during threat learning
Authors: Namkung Ho , Lockhart Sedona , de Chabot Josephine , Guttman Lauren , Isehak Imad , Kwon Hyung-Bae , Sawa Akira 
Published: October 2021

AbstractLearning about potential threats in the environment is indispensable for survival. Deficits in threat learning constitute a key dimension of multiple brain disorders, which include posttraumatic stress disorder and anxiety disorder. While human brain imaging studies have highlighted a reliable engagement of the anterior insular cortex (AIC) in threat learning, its precise role remains elusive partly due to the lack of animal studies that can address causality and mechanistic questions. Filling in this gap, the present mouse study proposes a novel AIC-mediated mechanism underlying the association of temporally discontiguous stimuli during threat learning. We identified that activity of AIC layer 5 (L5) pyramidal neurons is required for associating temporally discontiguous stimuli, specifically during a time interval between them. Notably, the AIC is not required for associating temporally contiguous stimuli during threat learning. The AIC not only sends the essential information, via its L5 pyramidal neurons, to the basolateral amygdala (BLA) during the time interval, but also receives from the BLA. We also identified a modulatory role of AIC dopamine D1 receptor (D1R)-mediated dopamine signaling in associating temporally discontiguous stimuli during the time interval.
Cellular adhesion is a controlling factor in neutrophil extracellular trap formation induced by antineutrophil cytoplasmic antibodies
Authors: Lelliott Patrick M. , Nishide Masayuki , Pavillon Nicolas , Okita Yasutaka , Shibahara Takayuki , Mizuno Yumiko , Yoshimura Hanako , Obata Sho , Kumanogoh Atsushi , Smith Nicholas I. 
Published: October 2021

AbstractAnti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV) is a life-threatening condition characterized by improper activation of neutrophils and release of neutrophil extracellular traps (NETs) in small vessels. This study aimed to explain the role of NETs in AAV pathogenesis by investigating a link between neutrophil adhesion and NET release. We leveraged an imaging flow cytometry-based assay and three-dimensional culture to demonstrate that neutrophil adhesion is essential for ANCA induced NET formation. We confirmed this requirement for cell adhesion using standard microscopy on ultra-low attachment hydrogel surfaces and demonstrate that this depends on the focal adhesion kinase pathway as determined using inhibitors for multiple targets in this process. ANCA increased expression of β2 integrins on neutrophils, and we confirmed that these integrins were required for NET formation using blocking antibodies. Finally, inhibitors for oxidative burst prevented NET formation, and this oxidative burst was mediated by the focal adhesion pathway. Overall, our findings reveal a central role for neutrophil attachment in NET formation in response to ANCA, helping to explain the restricted localization pattern of vessel damage, and suggesting that targeting neutrophil adhesion factors may be beneficial in preventing pathological damage from NETs during AAV.
Identification of novel therapeutic targets for polyglutamine toxicity disorders that target mitochondrial fragmentation
Authors: Traa Annika , Machiela Emily , Rudich Paige D. , Soo Sonja K. , Senchuk Megan M. , Van Raamsdonk Jeremy M. 
Published: October 2021

AbstractHuntington’s disease (HD) is one of at least nine polyglutamine toxicity disorders caused by a trinucleotide CAG repeat expansion, all of which lead to age-onset neurodegeneration. Mitochondrial dynamics and function are disrupted in HD and other polyglutamine toxicity disorders. While multiple studies have found beneficial effects from decreasing mitochondrial fragmentation in HD models by disrupting the mitochondrial fission protein DRP1, disrupting DRP1 can also have detrimental consequences in wild-type animals and HD models. In this work, we examine the effect of decreasing mitochondrial fragmentation in a neuronal C. elegans model of polyglutamine toxicity called Neur-67Q. We find that Neur-67Q worms have deficits in mitochondrial morphology in GABAergic neurons and decreased mitochondrial function. Disruption of drp-1 eliminates differences in mitochondrial morphology and rescues deficits in both movement and longevity in Neur-67Q worms. In testing twenty-four RNA interference (RNAi) clones that decrease mitochondrial fragmentation, we identified eleven clones that increase movement and extend lifespan in Neur-67Q worms. Overall, we show that decreasing mitochondrial fragmentation may be an effective approach to treat polyglutamine toxicity disorders and identify multiple novel genetic targets that circumvent the potential negative side effects of disrupting the primary mitochondrial fission gene drp-1.Significance StatementPolyglutamine toxicity disorders are caused by a trinucleotide CAG repeat expansion that leads to neurodegeneration. Both mitochondrial dynamics and function are disrupted in these disorders. In this work we use a simple genetic model organism, the worm C. elegans, to define the role of mitochondrial morphology in polyglutamine toxicity disorders. We show that CAG repeat expansion is sufficient to disrupt mitochondrial morphology and that genetic strategies that decrease mitochondrial fragmentation are beneficial in a neuronal model of polyglutamine toxicity. This work identifies multiple novel genes that are protective in worm models of polyglutamine toxicity, which may serve as potential therapeutic targets for Huntington’s disease and other polyglutamine toxicity disorders.
Ligand geometry dictates cellular and in vivo uptake of 3D DNA nanostructures
Authors: Gada Anjali Rajwar , RS Shravani , Vaswani Payal , Morya Vinod , Barai Amlan , Sen Shamik , Gupta Sharad , Sonawane Mahendra , Bhatia Dhiraj 
Published: October 2021

AbstractFabrication of nanoscale DNA devices to generate 3D nano-objects with precise control of shape, size, and presentation of ligands has shown tremendous potential for therapeutic applications. The interactions between different topologies of 3D DNA nanostructures and the cell membranes are crucial for designing efficient tools for interfacing DNA devices with biological systems. The practical applications of these DNA nanocages are still limited in cellular and biological systems owing to the limited understanding of interactions of different surface topologies of DNA nanodevices with cell membranes. The correlation between the geometry of DNA nanostructures and their internalization efficiency remains elusive. We investigated the influence of the shape and size of 3D DNA nanostructure on their cellular internalization efficiency. We found that of different geometries designed, one particular geometry, i.e., the tetrahedral shape, is more favoured over other geometries for their cellular uptake in 2D and 3D cell models. This is also replicable for cellular processes like 3D cell invasion assays in 3D spheroid models and passing the epithelial barriers in in-vivo zebrafish model systems. Our work establishes ground rules for the rational designing of DNA nanodevices for their upcoming biological and biomedical applications.
A Single-Cell Approach Reveals Variation in Cellular Phage-Producing Capacities
Authors: Kannoly Sherin , Oken Gabriella , Shadan Jon , Musheyev David , Singh Kevin , Singh Abhyudai , Dennehy John J. 
Published: October 2021

ABSTRACTVirus burst size, a component of viral fitness, is the average number of viral particles released from a single infected cell. In this study, we estimated bacteriophage lambda (λ) burst size mean and distribution at different lysis times. To estimate phage λ burst sizes at single-cell level, we employed a lysis-deficient E. coli lysogen, which allowed chemical lysis at desired times after the induction of lytic cycle. Induced cultures of E. coli lysogen were diluted and aliquoted into the wells of 96-well plates. A high dilution rate results in mostly empty wells and minimizes the probability of having multiple cells in wells that do receive cells. Burst size was estimated by titering single-cell lysates obtained after chemical lysis at desired times. Our data shows that the viral burst size initially increases exponentially with the lysis time, and then saturates at longer lysis times. We also demonstrate that cell-to-cell variation or “noise” in lysis timing does not significantly contribute to the burst size noise. The burst size noise remains constant with increasing mean burst size. The most likely explanation for the experimentally observed constant burst size noise is that cell-to-cell differences in burst size originate from differences in cellular capacity to produce phages. The mean burst size measured at different lysis times is positively correlated to cell volume, which may determine the cellular phage production capacity. However, experiments controlling for cell size indicates that there are other factors in addition to cell size that determine this cellular capacity.ARTICLE IMPORTANCEPhages produce offspring by hijacking a cell’s replicative machinery. Previously, it was noted that the variation in the number of phages produced by single infected cells far exceeded cell size variation. It has been hypothesized that this variation is a consequence of variation in the timing of host cell lysis. Here we show that cell-to-cell variation in lysis timing does not significantly contribute to the burst size variation. We suggest that the constant burst size variation across different host lysis times results from cell-to-cell differences in capacity to produce phages. We find that the mean burst size measured at different lysis times is positively correlated to cell volume, which may determine the cellular phage production capacity. However, experiments controlling for cell size indicates that there are other factors in addition to cell size that determine this cellular capacity.
Response to Tozinameran (BNT162b2) booster in twice-vaccinated kidney transplant and maintenance dialysis patients
Authors: Ben-Dov Iddo Z. , Tzukert Keren , Aharon Michal , Pri-Chen Hadas , Oster Yonatan , Oiknine-Djian Esther , Wolf Dana G. , Elhalel Michal Dranitzki 
Published: October 2021

AbstractBackgroundPatients needing chronic RRT are at risk for severe COVID-19 and mount a lesser response to mRNA vaccination. We describe the impact of booster administration in these patients, amidst a third wave of infections and deaths.MethodsIn the setting of a prospective COVID-19-centred cohort study in dialysis and kidney transplant patients we examined humoral responses to booster vaccination, and subsequent infection risk.ResultsWe quantified antibodies (DiaSorin) in 198 maintenance dialysis patients, 314 kidney transplant patients and 82 controls, without prior COVID-19 infection. Prior to boosting, 79% of controls, 35% of dialysis and 11% of transplant patients had levels ≥59 AU/ml (putatively protective), while 8-54 days after a third injection, respective rates were 100%, 93% and 58%. Risk factors for antibodies <60 AU/ml despite booster injection were transplant vs dialysis, OR=18.4 (p<0.0001), transitioning from dialysis to transplantation or vice versa, OR=15.7 (p<0.01) and days post injection, OR=0.953 (p<0.05). Antibody step-up after the booster inversely correlated with the second dose step-up (r=-0.33, p<0.01). In this surge, 2 controls, 2 dialysis and 9 transplant patients had COVID-19. Antibody level ≥59 AU/ml at any time point independently associated with reduced risk of infection during this surge, OR=0.264 (p=0.048).ConclusionsWe show that a third dose of tozinameran boosts antibody levels in patients receiving RRT, as it did in controls. Most patients have now reached antibody levels likely to protect from infection. Antibodies were higher after the third dose compared to previous peaks, which may hint that the latest immune response may be more robust and sustainable, even in immune-compromised patients. Kidney transplant recipients showed the most striking enhancement, exhibiting >5.5-fold increase in the percentage of patients with protective antibody levels. However, many transplant patients remain below threshold even after boost injection, necessitating further boosting strategies.
Evolutionary trade-offs between heat and cold tolerance limit responses to fluctuating climates
Authors: Schou Mads F. , Engelbrecht Anel , Brand Zanell , Svensson Erik I. , Cloete Schalk , Cornwallis Charlie K. 
Published: October 2021

AbstractThe evolutionary potential of species to cope with short-term temperature fluctuations during reproduction is critical to predicting responses to future climate change. Despite this, vertebrate research has focused on reproduction under high or low temperatures in relatively stable temperate climates. Here, we characterize the genetic basis of reproductive thermal tolerance to temperature fluctuations in the ostrich that lives in tropical and sub-tropical Africa. Both heat and cold tolerance are under selection and heritable, indicating that evolutionary responses to mean temperature change are possible. However, a negative, genetic correlation between heat and cold tolerance limits the potential for adaptation to fluctuating temperatures. Genetic constraints between heat and cold tolerance appears a crucial, yet underappreciated, factor influencing responses to climate change.One-sentence summaryReproductive success in fluctuating climates is constrained by a negative genetic correlation between heat and cold tolerance
OsMADS58 stabilizes gene regulatory circuits during rice stamen development
Authors: Shen Liping , Tian Feng , Cheng Zhukuan , Zhao Qiang , Feng Qi , Zhao Yan , Han Bin , Fang Yuhan , Lin Yanan , Chen Rui , Wang Donghui , Sun Wenfeng , Sun Jiaqi , Zeng Hongyun , Yao Nan , Gao Ge , Luo Jingchu , Xu Zhihong , Bai Shunong 
Published: October 2021

ABSTRACTRice (Oryza sativa) OsMADS58 is a C-class MADS box protein, and characterization of a transposon insertion mutant osmads58 suggested that OsMADS58 plays a role in stamen development. However, as no null mutation has been obtained, its role has remained unclear. Here, we report that the CRISPR knockout mutant osmads58 exhibits complex altered phenotypes, including anomalous diploid germ cell differentiation, aberrant meiosis, and delayed tapetum degeneration. This CRISPR mutant line exhibited stronger changes in expression of OsMADS58 target genes compared with the osmads58 dSpm (transposon insertion) line, along with changes in multiple pathways related to early stamen development. Notably, transcriptional regulatory circuits in young panicles covering the stamen at stages 4–6 were substantially altered in the CRISPR line compared to the dSpm line. These findings strongly suggest that the pleiotropic effects of OsMADS58 on stamen development derive from a potential role in stabilizing gene regulatory circuits during early stamen development. Thus, this work opens new avenues for viewing and deciphering the regulatory mechanisms of early stamen development from a network perspective.
Parameter Sensitivity and Experimental Validation for Fractional-Order Dynamical Modeling of Neurovascular Coupling
Authors: Alhazmi Fahd , Belkhatir Zehor , Bahloul Mohamed A. , Laleg-Kirati Taous-Meriem 
Published: October 2021

AbstractGoalNeurovascular coupling is a fundamental mechanism linking neural activity to cerebral blood flow (CBF) response. Modeling this coupling is very important to understand brain functions, yet challenging due to the complexity of the involved phenomena. One key feature that different studies have reported is the time delay that is inherently present between the neural activity and cerebral blood flow, which has been described by adding a delay parameter in standard models. An alternative approach was recently proposed where the framework of fractional-order modeling is employed to characterize the complex phenomena underlying the neurovascular. Thanks to its nonlocal property, a fractional derivative is suitable for modeling delayed and power-law phenomena.MethodsIn this study, we analyzed and validated an effective fractional-order for the effective modeling and characterization of the neurovascular coupling mechanism. To show the added value of the fractional order parameters of the proposed model, we perform a parameter sensitivity analysis of the fractional model compared to its integer counterpart. Moreover, the model was validated using neural activity-CBF data related to both event and block design experiments that were acquired using electrophysiology and laser Doppler flowmetry recordings, respectively.ResultsThe validation results show the aptitude and flexibility of the fractional-order paradigm in fitting a more comprehensive range of well-shaped CBF response behaviors while maintaining a low model complexity. Comparison with the standard integer-order models shows the added value of the fractional-order parameters in capturing various key determinants of the cerebral hemodynamic response, e.g., post-stimulus undershoot.ConclusionsThis investigation authenticates the ability and adaptability of the fractional-order framework to characterize a wider range of well-shaped cerebral blood flow responses while preserving low model complexity through a series of unconstrained and constrained optimizations.Impact StatementThe present study proposes a novel fractional-order framework for modeling neurovascular coupling. A parameter sensitivity analysis demonstrates the potential flexibility, and effectiveness of the fractional-order paradigm in reconstructing the cerebral hemodynamics with manageable complexity; and a real experimental validation analysis demonstrates the ability of the model in modeling a wider range of well-shaped CBF responses.
Modelling altered signalling of G-protein coupled receptors in inflamed environment to advance drug design
Authors: Ray Sourav , Thies Arne , Sunkara Vikram , Wulkow Hanna , Celik M. Özgür , Yergöz Fatih , Schütte Christof , Stein Christoph , Weber Marcus , Winkelmann Stefanie 
Published: October 2021

AbstractWe previously reported the successful design, synthesis and testing of the prototype opioid painkiller NFEPP that does not elicit adverse side effects. Uniquely, this design was based on mathematical modelling of extracellular interactions between G-protein coupled receptors (GPCRs) and ligands, recognizing that GPCRs function differently under pathological versus healthy conditions. We now present a novel stochastic model of GPCR function that includes intracellular dissociation of G-protein subunits and modulation of plasma membrane calcium channels associated with parameters of inflamed and healthy tissue (pH, radicals). The model is validated against in vitro experimental data for NFEPP and fentanyl ligands at different pH values. We found markedly reduced calcium channel inhibition induced by NFEPP at normal pH compared to lower pH, in contrast to the effect of fentanyl, and enhanced constitutive G-protein activation but lower probability of ligand binding with increasing radical concentrations. By means of molecular dynamics simulations, we also assessed qualitative changes of reaction rates due to additional disulfide bridges inside the GPCR binding pocket. The results suggest that, compared to radicals, low pH is a more important determinant of overall GPCR function in an inflamed environment. Future drug design efforts should take this into account.