bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploring the Pharmacological Potential of Kaurenoic Acid Produced via Synthetic Biology
Authors: Pimentel Lígia L. , Teixeira Francisca S. , Soares Ana M. S. , Costa Paula T. , Fontes Ana Luiza , Vidigal Susana S. M. P. , Pintado Manuela E. , Rodríguez-Alcalá Luis M. 
Published: October 2024

AbstractBackgroundKaurenoic acid (KA) is a bioactive diterpenoid commonly found in traditional medicinal plants such as Copaifera species, widely used in Amazonian ethnomedicine for its anti-inflammatory and antimicrobial properties. However, the sustainable supply of KA is limited due to environmental pressures and its complex extraction process from natural sources. Synthetic biology presents an innovative solution for producing KA, potentially reducing environmental impact while maintaining its traditional medicinal value.Aim of the studyThis work discusses the potential bioactive properties of kaurenoic acid (KA) obtained through synthetic biology. While ethnopharmacological studies have highlighted the anti-inflammatory and antimicrobial effects of plant extracts containing KA, limited research has focused on the pure compound due to its cost and limited availability.Materials and methodsThe study employed quantitative structure-activity relationship (QSAR) modeling and in vitro assays to investigate the anti-inflammatory and antimicrobial activities of S-KA and KNa. Physicochemical characterization, including Fourier transform infrared spectroscopy (FTIR-ATR), differential scanning calorimetry (DSC), and X-ray diffraction (XRD), was conducted to compare structural properties and purity with G-KA. Additionally, solubility studies were performed across various solvents to assess the potential for different bioapplications.ResultsPurity assessments revealed 99.06% for S-KA versus 98.83% for a commercial standard. In silico calculations indicated that KA is hydrophobic. Solubility tests prompted the synthesis of a sodium salt derivative (KNa), increasing water solubility. Experimental evaluations demonstrated that S-KA and KNa exhibited similar (IL-6, IL-8) anti-inflammatory activity compared to betamethasone, and growth inhibition was observed against Staphylococcus aureus and Staphylococcus epidermidis.ConclusionThese findings highlight that kaurenoic acid from fermentation offers a sustainable alternative to naturally sourced KA with comparable bioactivity. The sodium salt derivative (KNa) enhances water solubility, expanding its potential for pharmacological applications. This study highlights the relevance of synthetic biology in preserving traditional medicinal knowledge while promoting environmental sustainability.
The evolution of root hydraulic traits in wheat over 100 years of breeding
Authors: Baca Cabrera Juan C. , Vanderborght Jan , Boursiac Yann , Behrend Dominik , Gaiser Thomas , Nguyen Thuy Huu , Lobet Guillaume 
Published: October 2024

AbstractWheat (Triticum aestivumL.) plays a vital role in global food security, and understanding its root traits is essential for improving water uptake under varying environmental conditions. This study investigates how breeding over a century has influenced root morphological and hydraulic properties in six German winter wheat cultivars released between 1895 and 2002. Field and hydroponic experiments were used to measure root diameter, root number, branching density, and whole root system hydraulic conductance (Krs). Results showed a significant decline in root axes number andKrsover time, while root diameter remained stable across cultivars. Additionally, dynamic functional-structural modeling using the whole-plant model CPlantBox was employed to simulate the development ofKrswith root system growth, revealing that older cultivars consistently had higher hydraulic conductance than modern ones. The combined approach of field phenotyping and modeling provided a comprehensive view of the changes in root traits with breeding. These findings suggest that breeding may have unintentionally favored cultivars with smaller root systems and more conservative water uptake strategies, under the high-input, high-density conditions of modern agriculture. The lessons from this study may inform future breeding efforts aimed at optimizing wheat root systems, helping to develop cultivars with water uptake better tailored to locally changing environmental conditions.
Latitudinal clines in climate and sleep patterns shape disease outcomes inDrosophila melanogasterinfected byMetarhizium anisopliae
Authors: Nan Mintong , Wang Jonathan B. , Siokis Michail , St. Leger Raymond J. 
Published: October 2024

AbstractMajor latitudinal clines have been observed inDrosophila melanogaster, a human commensal that originated in tropical Africa and has spread world-wide to colonize temperate habitats. However, despite the significant impact of pathogens on species distribution, the influence of geographical factors on disease susceptibility remains poorly understood. This study investigated the effects of latitudinal clines and biomes on disease resistance using the common fly pathogenMetarhizium anisopliaeand 43 globalDrosophila melanogasterpopulations. The results showed that disease resistance was correlated with latitudinal gradients of sleep duration, temperature and humidity. While fungal diversity at tropical latitudes may drive enhanced defenses, the most disease-resistant males were also the most susceptible to desiccation, indicating potential trade-offs between abiotic stress resistance, necessary for survival in temperate habitats, and disease resistance. The study also found that sex, mating status, and sleep interacted with abiotic stresses to impact disease resistance, with longer-sleeping males and virgin flies surviving infections longer, and extra daytime sleep post-infection being protective, especially in the most resistant fly lines. These findings promote the idea that sleep and defense against disease are intertwined traits related to organismal fitness and subject to joint clinal evolution.Abstract Figure
CLCFM3: An advanced photogrammetry algorithm for high-precision plant 3D modeling
Authors: Hayashi Atsushi , Kochi Nobuo , Kodama Kunihiro , Isobe Sachiko , Tanabata Takanari 
Published: October 2024

AbstractThis research aims to develop a novel technique to acquire a large amount of high-density, high-precision 3D point cloud data for plant phenotyping using photogrammetry technology. The complexity of plant structures, characterized by overlapping thin parts such as leaves and stems, makes it difficult to reconstruct accurate 3D point clouds. One challenge in this regard is occlusion, where points in the 3D point cloud cannot be obtained due to overlapping parts, preventing accurate point capture. Another is the generation of erroneous points in non-existent locations due to image-matching errors along object outlines. To overcome these challenges, we propose a 3D point cloud reconstruction method, CLCFM3 (Closed-Loop Coarse-to-Fine method with Multi-Masked Matching). This method repeatedly executes a process that generates point clouds locally to suppress occlusion (multi-matching) and a process that removes noise points using a mask image (masked matching). Furthermore, we propose the Closed-Loop Coarse-to-Fine Method (CLCFM) to improve the accuracy of structure from motion, which is essential for implementing the proposed point cloud reconstruction method. CLCFM solves loop-closure by performing coarse-to-fine camera position estimation. By facilitating the acquisition of high-density, high-precision 3D data on a large number of plant bodies, as is necessary for research activities, this approach is expected to enable comparative analysis of visible phenotypes in the growth process of a wide range of plant species based on 3D information.
Integrated Molecular Profiling of Rhabdomyosarcoma Subtypes by Targeted RNAseq
Authors: Avenarius Matthew R , Patton Ashley , Mohamed Nehad , Pan Xiaokang , Jones Dan 
Published: October 2024

AbstractAll subtypes of rhabdomyosarcoma (RMS) show skeletal muscle differentiation but each has different oncogenic mechanisms including recurrentPAX3andPAX7gene fusions (alveolar), a hotspot mutation inMYOD1(spindle/sclerosing) and mutations in other oncogenes and tumor suppressors (embryonal, pleomorphic). This range of genomic findings typically requires several different DNA and RNA-based diagnostic assays. Here, we utilize a clinically validated, targeted RNA next-generation sequencing (RNAseq) panel to simultaneously detectMYOD1transcript levels for lineage assignment,PAX3andPAX7translocations and mutations inMYOD1and other RMS-related genes for definitive subtyping in a single assay. RNA-based detection ofMYOD1p.L122R and other mutations were orthogonally validated with digital droplet (dd)PCR or DNA-based NGS. Expanding the utility of clinical-grade RNAseq data beyond the detection of gene fusions is a cost-effective and time-efficient approach for more comprehensive screening of RMS.Impact statementComprehensive and rapid molecular diagnostics is a key driver in the selection and initiation of targeted therapies.
The dinucleotide structure of NAD enables specific reduction on mineral surfaces
Authors: Henriques Pereira Delfina P. , Xie Xiulan , Beyazay Tuğçe , Paczia Nicole , Subrati Zainab , Belz Jürgen , Volz Kerstin , Tüysüz Harun , Preiner Martina 
Published: October 2024

AbstractNucleotide-derived cofactors could function as a missing link between the informational and the metabolic part at life’s emergence. One well-known example is nicotinamide dinucleotide (NAD), one of the evolutionarily most conserved redox cofactors found in metabolism. Here, we propose that the role of these cofactors could even extend to missing links between geo- and biochemistry. We show NAD+can be reduced under close-to nature conditions with nickel-iron-alloys found in water-rock-interaction settings rich in hydrogen (serpentinizing systems) and that nicotinamide mononucleotide (NMN), a precursor molecule to NAD, has different properties regarding reduction specificity and sensitivity than NAD. The additional adenosine monophosphate (AMP) “tail” of the dinucleotide, a shared trait between many organic cofactors, seems to play a crucial mechanistic role in preventing overreduction of the nicotinamide-bearing nucleotide. This specificity is also connected to the used transition metals. While the combination of nickel and iron promotes the reduction of NAD+to 1,4-NADH most efficiently, in the case of NMN, the presence of nickel leads to the accumulation of overreduction products. Testing the reducing abilities of both NADH and NMNH under abiotic conditions showed that both molecules act as equally effective, soluble hydride donors in non-enzymatic, proto-metabolic stages of life’s emergence.
Methylparaben dampens virulence and transmissibility of theDrosophilapathogenPseudomonas entomophila
Authors: Henry Youn , Canal-Domènech Berta , La Mendola Christine , Kawecki Tadeusz J. 
Published: October 2024

AbstractIn the last 20 years,Pseudomonas entomophila(Pe) has emerged as a model to explore insect immunity to bacterial intestinal pathogens. Laboratory studies evidenced multiple detrimental effects of Pe onDrosophila melanogaster. However, these effects require that the bacteria are ingested in extremely high concentrations of 1010– 1011CFU per mL (OD60020 – 200), questioning the relevance of this pathogen in nature. Here, we tested whether the need for such high doses may be due to protective effects of the food preservative methylparaben (Nipagin), a standard ingredient of artificialDrosophiladiets. While significant mortality in flies fed diet containing standard methylparaben concentration required doses of >1010CFU per mL, when methylparaben was absent we could observe mortality using 500,000× lower doses. Consistent with these results, we demonstrated strong bactericidal properties of methylparaben on Pein vitro. In the absence of methylparaben even the smallest inocula (105CFU per mL) led to high bacterial loads (106CFU per fly) after several days, indicating the ability of Pe to grow and overcome the flies’ defenses. We also demonstrate that in the absence of methylparaben, infected flies could easily transmit the pathogen to other adults and to offspring, resulting in high mortality and thus highlighting the potential of Pe as a pathogen ofDrosophilain nature. Our study also underscores that careful consideration should be given to food additives used in standard diets in laboratory research on host-pathogen interaction.ImportanceAccurate characterization of pathogen infections requires appropriate experimental methodologies. Infections of insects with Pe are frequently studied using fruit flies as a model organism, with laboratory cultures typically maintained on artificial media containing various food preservatives. In this study, we show that one commonly used preservative, methylparaben, significantly influences the outcome of oral infections with Pe. We found that minimal infection doses, far below the standards of the field, could be still lethal to flies raised on media without methylparaben. This increased virulence was also associated with increased transmission of the pathogen, both from infected adult flies to their offspring and to uninfected adults. Our findings show how subtle variations in experimental conditions can profoundly affect how we perceive pathogenic threats.
Comparative impact of porcine reproductive and respiratory virus and swine influenza A virus infections on respiratory lymph nodes B cells and macrophages
Authors: Hervet C. , Perrin A. , Renson P. , Deblanc C. , Muñoz M. , Meurens F. , Argilaguet J. , Simon G. , Bourry O. , Maisonnasse P. , Bertho N. 
Published: October 2024

AbstractPorcine Reproductive and Respiratory Syndrome Virus (PRRSV) strongly impacts the pig rearing sector due to its persistence in infected animals. Interestingly, although the PRRSV family exhibits considerable genome variability, with the PRRSV-1 and PRRSV-2 subtypes having been finally classified in two different species (Betaarterivirus suid 1 and 2). Both viruses, as well as their derived-attenuated vaccine strains, persist for months, due in part to their ability to delay the appearance of neutralizing antibodies. Thanks to extensive efforts over the past years, we have developed the capability to perform in-depth analysis of the previously poorly understood porcine inverted lymph node (LN). In this study, by comparing the early stages of LN B cell maturation upon PRRSV-1 infection to those induced upon the acute swine influenza A virus infection, we highlighted PRRSV-specific mechanisms, including the expression of PD-L1 in efferent macrophages, the induction of extrafollicular plasmocytes, and the influx of inflammatory monocytes/macrophages. Studies on PRRSV-2 infections report observations compatible with our results, that thus might be generalized to all PRRSV-strains. Moreover, these mechanisms can be compared with those used by the human immunodeficiency virus (HIV) and the murine chronic lymphocytic choriomeningitis virus (LCMV) to hijack the immune response. These similarities can be harnessed to develop new strategies to improve the development of more efficient anti-PRRSV vaccines.
Directional Immobilisation of SpyTag Bacteriophage on PDMS surfaces for Phage based Microfluidics
Authors: Liyanagedera Sahan B.W. , Williams Joshua , Wheatley Joseph P. , Biketova Alona Yu , Sagona Antonia P. , Feher Tamas , Kulkarn Vishwesh 
Published: October 2024

AbstractThe increasing incidence of bacterial infections caused by antibiotic-resistant pathogens worldwide underlines the need to develop novel diagnostic tools enabling the early initiation of targeted antimicrobial therapy. One promising possibility is to unite the high specificity and sensitivity of phage-based applications with the speed and sensitivity provided by microfluidic devices. As a prerequisite of developing such systems, we aimed at the directional immobilization of phages on the surface of Polydimethylsiloxane (PDMS), a material commonly used for building such devices. Our work utilised the covalent interaction between two proteins: SpyTag, genetically encoded on the capsid of the phage, and BslA-SpyCatcher fusion protein, purified and surface displayed on PDMS. We demonstrate a simple methodology for the directional tail up immobilisation of SpyTagged Phage on to user defined locations on the surface of a PDMS device and subsequent on chip capture and infection of a cognate host. Our technique serves to illustrate a generally applicable solution to develop the next generation of phage based bio-sensors.
Human brain changes after first psilocybin use
Authors: Lyons T , Spriggs M , Kerkelä L , Rosas FE , Roseman L , Mediano PAM , Timmermann C , Oestreich L , Pagni BA , Zeifman RJ , Hampshire A , Trender W , Douglass HM , Girn M , Godfrey K , Kettner H , Sharif F , Espasiano L , Gazzaley A , Wall MB , Erritzoe D , Nutt DJ , Carhart-Harris RL 
Published: October 2024

ABSTRACTPsychedelics have robust effects on acute brain function and long-term behavior but whether they also cause enduring functional and anatomical brain changes is unknown. In a placebo-controlled, within-subjects, electroencephalography, and magnetic resonance imaging study in 28 healthy, entirely psychedelic-naive participants, anatomical and functional brain changes were detected from one-hour to one-month after a single high-dose (25 mg) of psilocybin. Increases in cognitive flexibility, psychological insight, and well-being were seen at one-month. Diffusion imaging done before and one-month after 25mg psilocybin revealed decreased axial diffusivity bilaterally in prefrontal-subcortical tracts that correlated with decreased brain network modularity over the same time period. Decreased modularity also correlated with improved well-being. Increased cortical signal entropy at 1– and 2-hours post-dosing predicted improved psychological well-being at one-month. Next-day psychological insight mediated the entropy to well-being relationship. All effects were exclusive to 25mg psilocybin; no effects occurred with a 1mg psilocybin ‘placebo’ dose.
Accelerated Epigenetic Aging is Associated with Faster Glaucoma Progression: A DNA Methylation Study
Authors: Medeiros Felipe A. , Varma Achintya , Jammal Alessandro A. , Tseng Henry , Scott William K. 
Published: October 2024

ABSTRACTPurposeTo investigate the association between epigenetic age acceleration and glaucoma progression.DesignRetrospective cohort study.Participants100 primary open-angle glaucoma (POAG) patients with fast progression and 100 POAG patients with slow progression.MethodsSubjects were classified as fast or slow progressors based on rates of change in standard automated perimetry (SAP) mean deviation (MD) and retinal nerve fiber layer (RNFL) thickness. Epigenetic age was calculated using the Horvath, Hannum, PhenoAge, and GrimAge clocks from DNA methylation profiles obtained from blood samples. Age acceleration (AgeAccel) was defined as the residual from a linear regression of epigenetic age on chronologic age, with positive values suggesting faster biological aging. Multivariable logistic regression models estimated the association between AgeAccel and likelihood of fast progression, adjusting for confounders.Main Outcome MeasuresDifference in epigenetic age acceleration between fast and slow glaucoma progressors.ResultsThe mean rate of SAP MD change in the fastest progressing eye was −1.06 dB/year (95% CI: −1.28 to −0.85) for fast progressors compared to −0.10 dB/year (95% CI: −0.16 to −0.04) for slow progressors (P<0.001). For RNFL thickness, corresponding values were −1.60 μm/year (95% CI: −1.97 to −1.23) and −0.76 μm/year (95% CI: −1.04 to −0.48), respectively (P<0.001). Fast progressors demonstrated significantly greater age acceleration compared to slow progressors for the Horvath clock (mean difference = 2.93 years, 95% CI: 1.48 to 4.39, P<0.001) and Hannum clock (mean difference = 1.24 years, 95% CI: 0.03 to 2.46, P=0.045). In multivariable models, each year of Horvath AgeAccel was associated with 15% higher odds of fast progression (OR 1.15, 95% CI 1.07-1.23, P<0.001), after adjusting for sex, race, intraocular pressure, central corneal thickness, baseline disease severity, smoking status and follow-up time. Hannum and GrimAge clocks also showed significant associations with fast progression. The association between AgeAccel and fast progression was stronger in subjects with relatively low IOP during follow-up.ConclusionAccelerated epigenetic aging was associated with faster glaucoma progression. These findings suggest that faster biological age, as reflected in DNA methylation, may increase optic nerve susceptibility to damage, highlighting epigenetic age as a potential prognostic biomarker.
Lifetime Intimate Partner Violence (IPV) Against Mozambican Women: Individual and Contextual Level Factors Driving Its Prevalence
Authors: Muosieyiri Maud Z , Muhajarine Nazeem 
Published: October 2024

AbstractBackgroundIntimate partner violence (IPV) remains a significant public health issue in Mozambique. This study uses data from the 2022-2023 Mozambique Demographic and Health Survey (DHS) to examine the prevalence and sociodemographic determinants of Lifetime IPV among women.MethodsA nationally representative sample of 4,813 women aged 15-49 was analyzed to assess the prevalence of Lifetime IPV. Logistic regression models were used to identify individual- and contextual-level factors associated with Lifetime IPV.ResultsNearly 1 in 4 women (23.07%) reported experiencing physical abuse from a current or former partner in their lifetime. Marital status emerged as a key individual-level determinant, with married, cohabitating, and separated women being at significantly higher odds of experiencing IPV compared to women who had never been in a union. Educational attainment and current employment were also associated with increased odds of IPV. Similarly, women who justified physical abuse had higher odds of experiencing IPV. Additionally, husbands/partners’ alcohol consumption was one of the strongest predictors, nearly tripling the odds of Lifetime IPV. Finally, the effect modification between marital status and education showed that the intersection of these factors further shaped IPV risk. At the contextual level, provincial disparities were observed, with Cabo Delgado and Manica showing the highest IPV prevalence, while Inhambane and Gaza had the lowest.ConclusionThis study provides updated data on the prevalence of Lifetime IPV in Mozambique and highlights key individual and contextual factors contributing to IPV. The findings underscore the need for targeted interventions addressing socio-cultural norms, improving educational opportunities, mitigating alcohol consumption, and implementing province-specific strategies to reduce IPV and enhance women’s safety across Mozambique.