bluuebunny/crossref_metadata_2025_split huggingface dataset:
A multi-host mechanistic model of African swine fever emergence and control in Romania
Authors: Hayes Brandon H. , Vergne Timothée , Rose Nicolas , Mortasivu Cristian , Andraud Mathieu 
Published: January 2024

AbstractAfrican swine fever (ASF) has devastating effects on swine production, farmer livelihood, animal welfare, and biodiversity. Extremely difficult to control, epidemic management is further complicated when spillover between domestic pig and wild boar populations is suspected. To quantify ASF viral transmission between domestic pigs and wild boar, a spatially-explicit stochastic mechanistic model was constructed using village centroids to represent aggregated backyard pig herds and a hexagonal raster of forest coverage to represent wild boar abundance. The model was parameterized to the initial six months of the ongoing Romanian epidemic through approximate Bayesian computation. It was estimated that a median of 69.4% (interquartile range: 53.0–80.0%) of domestic pig herd cases came from other infected domestic pig herds while 20.4% (11.2–33.8%) originated from infected wild boar sources, and 8.4% (4.7–14.2%) stemmed from external sources not explicitly represented. Also, 31.9% of infected wild boar habitat (16.7–56.2%) originated from domestic pig herds and 68.1% (43.8–83.3%) came from neighboring infected wild boar populations. Furthermore, it was found that habitats with a forest coverage greater than 15% were 2.6 times more infectious and 5.3 times more susceptible than other habitats. All alternative control scenarios, including culling domestic pig herds upon local domestic pig or wild boar case detection, improved epidemic outcomes, with the greatest decrease in final epidemic size being observed from the reactive culling of entire villages following case detection. These results can be used to further inform policy recommendations in ASF-epidemic regions.Significance StatementThe current African swine fever (ASF) pandemic is devastating to affected nations, and quantifying transmission parameters is critical to informing control strategies. Disease spillover between wild and domestic hosts further complicates control efforts, yet the influence of spillover events on epidemic propagation remains unknown. Using the context of Romania—one of the European nations with the most severe epidemic and where spillover transmission is strongly suspected—we show that targeting spillover mechanisms is critical for achieving holistic disease control, and then demonstrate the impact of alternative control scenarios had they been enacted. These results can inform control strategy policy decisions in the many nations at-risk for or actively experiencing ASF epidemics.
A conserved Pol II elongator SPT6L mediates Pol V transcription elongation to regulate RNA-directed DNA methylation inArabidopsis
Authors: Liu Yujuan , Shu Jie , Zhang Zhi , Ding Ning , Liu Jinyuan , Liu Jun , Cui Yuhai , Wang Changhu , Chen Chen 
Published: January 2024

AbstractIn plants, the plant-specific RNA polymerase V (Pol V) transcripts non-coding RNAs and provides a docking platform for the association of accessory proteins in the RNA-directed DNA methylation (RdDM) pathway. Various components have been uncovered that are involved in the process of DNA methylation, but it is still not clear how the transcription of Pol V is regulated. Here, we found that the conserved Pol II elongator, SPT6L, bound to thousands of intergenic regions in an RNA polymerase II (Pol II) independent manner. The intergenic enrichment of SPT6L, interestingly, co-occupied with the largest subunit of Pol V (NRPE1) and mutation of SPT6L led to the reduction of DNA methylation but not Pol V enrichment. Furthermore, the association of SPT6L at Pol V loci was dependent on the Pol V associated factor, SPT5L, rather than the presence of Pol V, and the interaction between SPT6L and NRPE1 was compromised inspt5l. Finally, Pol V RIP-seq revealed that SPT6L is required to maintain the amount and length of Pol V transcripts. Our findings thus uncovered the critical role of a Pol II conserved elongator in Pol V mediated DNA methylation and transcription, and shed light on the mutual regulation between Pol V and II in plants.
MprF-mediated immune evasion is necessary forLactiplantibacillus plantarumresilience inDrosophilagut during inflammation
Authors: Arias-Rojas Aranzazu , Arifah Adini , Angelidou Georgia , Alshaar Belal , Schombel Ursula , Forest Emma , Frahm Dagmar , Brinkmann Volker , Paczia Nicole , Beisel Chase , Gisch Nicolas , Iatsenko Igor 
Published: January 2024

AbstractBackgroundMultiple peptide resistance factor (MprF) confers resistance to cationic antimicrobial peptides (AMPs) in several pathogens, thereby enabling evasion of the host immune response. While MprF has been proven to be crucial for the virulence of various pathogens, its role in commensal gut bacteria remains uncharacterized. To close this knowledge gap, we used a common gut commensal of animals,Lactiplantibacillus plantarum, and its natural host, the fruit flyDrosophila melanogaster, as an experimental model to investigate the role of MprF in commensal-host interactions.ResultsTheL. plantarumΔmprFmutant that we generated exhibited deficiency in the synthesis of lysyl-phosphatidylglycerol (Lys-PG), resulting in increased negative cell surface charge and increased susceptibility to AMPs. Susceptibility to AMPs had no effect on ΔmprFmutant’s ability to colonize guts of uninfected flies. However, we observed significantly reduced abundance of the ΔmprFmutant after infection-induced inflammation in the guts of wild-type flies but not flies lacking AMPs. These results demonstrate that host AMPs reduce the abundance of the ΔmprFmutant during infection. We found in addition that the ΔmprFmutant compared to wild-typeL. plantaruminduces a stronger intestinal immune response in flies due to the increased release of immunostimulatory peptidoglycan fragments, indicating an important role of MprF in promoting host tolerance to commensals.ConclusionOverall, our results demonstrate that MprF, besides its well-characterized role in pathogen immune evasion and virulence, is also an important resilience factor in maintaining stable microbiota-host interactions during intestinal inflammation.
Mitochondrial respiration is essential for photosynthesis-dependent ATP supply of the plant cytosol
Authors: Vera-Vives Antoni M. , Novel Piero , Zheng Ke , Tan Shun-ling , Schwarzländer Markus , Alboresi Alessandro , Morosinotto Tomas 
Published: January 2024

AbstractPlants rely on solar energy to synthesize ATP and NADPH for photosynthetic carbon fixation. Since a substantial proportion of cellular ATP is consumed in the cytosol, photosynthesis-derived ATP needs to be supplied there. While the triose phosphate shuttle and mitochondrial respiration can both deliver ATP to the cytosol, the significance of the different mechanismsin vivohas been difficult to assess. Although mitochondrial respiration is essential in plants, whether this is due to heterotrophic bottlenecks during plant development or rather a need for respiration in photosynthetically active cells, has not been resolved. In this study, we examinedin vivochanges of cytosolic ATP concentration in response to light, employing a biosensing strategy in the mossPhyscomitrium patens. Our measurements revealed increased cytosolic ATP concentration caused by photosynthetic activity. Moss tissue depleted of respiratory complex I showed decreased cytosolic ATP accumulation, highlighting a critical role of mitochondrial respiration in light-dependent ATP supply of the cytosol. Consistently, targeting mitochondrial ATP production directly, through the construction of mutants deficient in mitochondrial ATPase (complex V), led to drastic growth reduction, despite only minor alterations in photosynthetic electron transport activity. SinceP. patensis photoautotrophic throughout its development, we conclude that heterotrophic bottlenecks cannot account for the indispensable role of mitochondrial respiration in plants. Instead, our results offer compelling evidence that mitochondrial respiration is essential for ATP provision to the cytosol in actively photosynthesizing cells. Mitochondrial respiration provides metabolic integration, ensuring a reliable supply of cytosolic ATP essential for supporting plant growth and development.
Identification of phospholipase Ds and phospholipid species involved in circadian clock alterations using CRISPR/Cas9-based multiplex editing of Arabidopsis
Authors: Kim Sang-Chul , Nusinow Dmitri A. , Wang Xuemin 
Published: January 2024

AbstractReciprocal regulation between the circadian clock and lipid metabolism is emerging, but its mechanisms remain elusive. We reported that a lipid metabolite phosphatidic acid (PA) bound to the core clock transcription factors LATE ELONGATED HYPOCOTYL (LHY) and CIRCADIAN CLOCK ASSOCIATED1 (CCA1) and chemical suppression of phospholipase D (PLD)-catalyzed PA formation perturbed the clock in Arabidopsis. Here, we identified, among 12 members, specific PLDs critical to regulating clock function. We approached this using a multiplex CRISPR/Cas9 system to generate a library of plants bearing randomly mutatedPLDs,then screening the mutants for altered rhythmic expression ofCCA1. AllPLDs, except forβ2, were effectively edited, and the mutations were heritable. Screening of T2 plants identified some with an altered rhythm ofCCA1expression, and this trait was observed in many of their progenies. Genotyping revealed that at least two of sixPLDs (α1, α3,γ1,δ,εandζ2) were mutated in the clock-altered plants. Those plants also had reduced levels of PA molecular species that bound LHY and CCA1. This study identifies combinations of two or more PLDs and changes in particular phospholipid species involved in clock outputs and also suggests a functional redundancy of the six PLDs for regulating the plant circadian clock.One sentence summaryThis study identifies combinations of two or more phospholipase Ds involved in altering clock outputs and the specific phosphatidic acid species impacting the clock rhythms.
Discovery and binding mode of small molecule inhibitors of the apo form of human TDO2
Authors: Lotz-Jenne Carina , Lange Roland , Cren Sylvaine , Bourquin Geoffroy , Goglia Laksmei , Kimmerlin Thierry , Wicki Micha , Müller Manon , Artico Nadia , Ackerknecht Sabine , Pfaff Philippe , Joesch Christoph , Mac Sweeney Aengus 
Published: January 2024

AbstractTryptophan-2,3-dioxygenase (TDO2) and indoleamine-2,3-dioxygenase (IDO1) catalyze the conversion of L-tryptophan to N-formyl-kynurenine and play important roles in metabolism, inflammation, and tumor immune surveillance. Their enzymatic activities depend on their heme contents, which vary dynamically according to biological conditions. Inhibitors binding to heme-containing holo-TDO2 are known, but to date no inhibitor that binds to the heme-free state (apo-TDO2) has been reported. We describe the discovery of the first apo-TDO2 targeting inhibitors, to our knowledge, together with their co-crystal structures and inhibition of cellular TDO2 activity at low nanomolar concentrations.
Continuous structural neuroplasticity during motor learning - a diffusion MRI study
Authors: Friedman Naama , Malovani Cfir , Perets Inbar , Kenin Etai , Bernstein-Eliav Michal , Tavor Ido 
Published: January 2024

AbstractHow does our brain transform when we encounter a new task? To fully answer this question, comparing brain states before and after learning may not be enough, but rather an on-going, continuous monitoring of brain changes during learning is required. While such continuous examinations of functional learning-induced changes are widely available using functional magnetic resonance imaging (fMRI), a continuous investigation of microstructural brain modifications during learning is yet to be reported.Here, we continuously acquire diffusion MRI images during task performance. We then compute the mean diffusivity (MD) using a sliding-window approach, resulting in a continuous measure of microstructural changes throughout learning. We demonstrate the utility of this method on a motor sequence learning (finger tapping) task (n=58). MD decrease was detected in task-related brain regions, including the parahippocampal gyrus, hippocampus, inferior temporal gyrus, and cerebellum. Analysis of the temporal patterns of decrease revealed a rapid MD reduction in the right temporal gyrus after 11 minutes of learning, with additional decrease in the right parahippocampal gyrus and left cerebellum after 22 minutes. We further computed “neuroplasticity networks” of brain areas showing similar change patterns and detected similarities between these networks and canonical functional connectivity networks.Our findings offer novel insights on the spatio-temporal dynamics of microstructural neuroplasticity by demonstrating continuous modifications during the encoding phase of learning itself, rather than comparing pre- and post-learning states.
Prevotella timonensisdegrades the vaginal epithelial glycocalyx through high fucosidase and sialidase activities
Authors: Segui-Perez Celia , de Jongh Rivka , Jonkergouw Robin , Pelayo Paula , Balskus Emily P. , Zomer Aldert , Strijbis Karin 
Published: January 2024

AbstractBacterial vaginosis (BV) is a polymicrobial infection of the female reproductive tract (FRT). BV is characterized by replacement of health-associatedLactobacillusspecies by diverse anaerobic bacteria, including the well-knownGardnerella vaginalis.Prevotella timonensisandPrevotella biviaare anaerobes that are found in a significant percentage of BV patients, but their pathogenic properties are yet to be determined. Defining characteristics of anaerobic overgrowth in BV are adherence to the mucosal surface and the increased activity of mucin-degrading enzymes such as sialidases in vaginal secretions. Here, we demonstrate thatP. timonensisbut notP. biviastrongly adhered to vaginal and endocervical cells to a similar level asG. vaginalisbut did not elicit a comparable pro-inflammatory response. TheP. timonensisgenome uniquely encodes a large set of mucus-degrading enzymes including 4 putative fucosidases and 2 putative sialidases, PtNanH1 and PtNanH2. Enzyme assays demonstrated that fucosidase and sialidase activity inP. timonensiscell-bound and secreted fractions was significantly higher than for other vaginal anaerobes. Infection assays revealed thatP. timonensisfucosidases and sialidases efficiently removed fucose and α2,3- and α2,6-linked sialic acid moieties from the epithelial glycocalyx. Recombinantly expressedP. timonensisNanH1 and NanH2 efficiently removed α2,3 and α2,6-linked sialic acids from the epithelial surface and sialic acid removal byP. timonensiscould be blocked using inhibitors. This study demonstrates thatP.timonensishas distinct virulence properties that include initial adhesion and a high capacity for mucin degradation at the vaginal epithelial mucosal surface. Our results underline the importance of understanding the role of different anaerobic bacteria in BV.Significance statement (Layman)Bacterial vaginosis (BV) is a common vaginal infection that affects a high percentage of women and is associated with reduced fertility and increased risk of secondary infections.Gardnerella vaginalisis the most well-known BV-associated bacterium, butPrevotellaspecies includingP. timonensisandP. biviamay also play an important role. We showed that, similar toG. vaginalis,P. timonensisadhered well to the vaginal epithelium, suggesting that both bacteria could be important in the first stage of infection. Compared to the other bacteria,P. timonensiswas unique in efficiently removing the protective mucin sugars that cover the vaginal epithelium. These results underscore that vaginal bacteria play different roles in the initiation and development of BV.
Exploratory and risk-taking behaviours in coexisting rodents
Authors: Hughes Bryan , Bowman Jeff , Schulte-Hostedde Albrecht 
Published: January 2024

AbstractThere has been an increasing interest in modelling the influence of animal personality on species interactions within ecosystems. Animal personality traits associated with dispersal, movement within a home range and risk-taking, including docility and exploration, have been shown to influence an array of environmental variables including seed dispersal and habitat availability. Despite growing interest however, little information is available to model the effects of differences in personality phenotypes among coexisting species. Since coexisting or sympatric species often compete for resources, differences in movement patterns can help mitigate the impact of intra- and interspecific competition. We used two standardized behavioural tests with three species of coexisting rodents in Algonquin Provincial Park, Ontario, Canada to measure exploration and docility personality phenotypes. To evaluate personalities, we modelled plastic changes in behaviours within species and phenotypic variation in behavioural strategies among species. We show empirical evidence to support differences in personality phenotypes in coexisting species and consider the importance of alternative personality strategies in shaping community dynamics.
Long-read sequencing reveals novel structural variation markers for key agronomic and quality traits of soybean
Authors: Wang Zhibo , Belay Kassaye , Paterson Joe , Bewick Patrick , Singer William , Song Qijian , Zhang Bo , Li Song 
Published: January 2024

AbstractIn plant genomic research, long read sequencing has been widely used to detect structure variations that are not captured by short read sequencing. In this letter, we described an analysis of whole genome re-sequencing of 29 soybean varieties using nanopore long-read sequencing. The compiled germplasm reflects diverse applications, including livestock feeding, soy milk and tofu production, as well as consumption of natto, sprouts, and vegetable soybeans (edamame). We have identified 365,497 structural variations in these newly re-sequenced genomes and found that the newly identified structural variations are associated with important agronomic traits. These traits include seed weight, flowering time, plant height, oleic acid content, methionine content, and trypsin inhibitor content, all of which significantly impact soybean production and quality. Experimental validation supports the roles of predicted candidate genes and structural variant in these biological processes. Our research provides a new source for rapid marker discovery in crop genomes using structural variation and whole genome sequencing.
Associations between common genetic variants and income provide insights about the socioeconomic health gradient
Authors: Kweon Hyeokmoon , Burik Casper A.P. , Ning Yuchen , Ahlskog Rafael , Xia Charley , Abner Erik , Bao Yanchun , Bhatta Laxmi , Faquih Tariq O. , de Feijter Maud , Fisher Paul , Gelemanović Andrea , Giannelis Alexandros , Hottenga Jouke-Jan , Khalili Bita , Lee Yunsung , Li-Gao Ruifang , Masso Jaan , Myhre Ronny , Palviainen Teemu , Rietveld Cornelius A. , Teumer Alexander , Verweij Renske M. , Willoughby Emily A. , Agerbo Esben , Bergmann Sven , Boomsma Dorret I. , Børglum Anders D. , Brumpton Ben M. , Davies Neil Martin , Esko Tõnu , Gordon Scott D. , Homuth Georg , Ikram M. Arfan , Johannesson Magnus , Kaprio Jaakko , Kidd Michael P. , Kutalik Zoltán , Kwong Alex S.F. , Lee James J. , Luik Annemarie I. , Magnus Per , Marques-Vidal Pedro , Martin Nicholas G. , Mook-Kanamori Dennis O. , Mortensen Preben Bo , Oskarsson Sven , Pedersen Emil M. , Polašek Ozren , Rosendaal Frits R. , Smart Melissa C. , Snieder Harold , van der Most Peter J. , Vollenweider Peter , Völzke Henry , Willemsen Gonneke , Beauchamp Jonathan P. , DiPrete Thomas A. , Linnér Richard Karlsson , Lu Qiongshi , Morris Tim T. , Okbay Aysu , Harden K. Paige , Abdellaoui Abdel , Hill W. David , de Vlaming Ronald , Benjamin Daniel J. , Koellinger Philipp D. 
Published: January 2024

AbstractWe conducted a genome-wide association study (GWAS) on income among individuals of European descent and leveraged the results to investigate the socio-economic health gradient (N=668,288). We found 162 genomic loci associated with a common genetic factor underlying various income measures, all with small effect sizes. Our GWAS-derived polygenic index captures 1 - 4% of income variance, with only one-fourth attributed to direct genetic effects. A phenome-wide association study using this polygenic index showed reduced risks for a broad spectrum of diseases, including hypertension, obesity, type 2 diabetes, coronary atherosclerosis, depression, asthma, and back pain. The income factor showed a substantial genetic correlation (0.92,s.e. = .006) with educational attainment (EA). Accounting for EA’s genetic overlap with income revealed that the remaining genetic signal for higher income related to better mental health but reduced physical health benefits and increased participation in risky behaviours such as drinking and smoking.
Transient frequency preference responses in cell signaling systems
Authors: Szischik Candela Lucia , Szemere Juliana Reves , Balderrama Rocío , de la Vega Constanza Sánchez , Ventura Alejandra C. 
Published: January 2024

AbstractLigand-receptor systems, covalent modification cycles, and transcriptional networks are the fundamental components of cell signaling and gene expression systems. While their behavior in reaching a steady state regime under step-like stimulation is well understood, their response under repetitive stimulation, particularly at early time stages is poorly characterized. This is despite the fact that early-stage responses to external inputs are arguably as informative as late-stage ones.In simple systems, a periodic stimulation elicits an initial transient response, followed by periodic behavior. Transient responses are relevant when the stimulation has a limited time span, or when the stimulated component’s timescale is slow as compared to the timescales of the downstream processes, in which case these fast processes may be capturing only those transients. In this study, we analyze the frequency response of simple motifs at different time stages. We use dose-conserved pulsatile input signals, meaning that the amplitude or the duration of the pulses varies along with frequency to conserve input dose, and consider different metrics versus frequency curves.We show that in ligand-receptor systems, there is a frequency preference response (band-pass filter) in some specific metrics during the transient stages, which is not present in the periodic regime. We suggest this is a general system-level mechanism that cells may use to filter input signals that have consequences for higher order circuits.Additionally, we evaluate how the described behavior in isolated motifs is reflected in similar types of responses in cascades and pathways of which they are a part. Our studies suggest that transient frequency preferences are important dynamic features of cell signaling and gene expression systems, which have been overlooked.