bluuebunny/crossref_metadata_2025_split huggingface dataset:
Two distinct non-ribosomal peptide synthetase-independent siderophore synthetase gene clusters identified in Armillaria and other species in the Physalacriaceae
Authors: Narh Mensah Deborah L , Wingfield Brenda D , Coetzee Martin P A 
Published: October 2023

Abstract
Siderophores are important for ferric iron solubilization, sequestration, transportation, and storage, especially under iron-limiting conditions such as aerobic conditions at high pH. Siderophores are mainly produced by non-ribosomal peptide synthetase-dependent siderophore pathway, non-ribosomal peptide synthetase-independent siderophore synthetase pathway, or the hybrid non-ribosomal peptide synthetases/non-ribosomal peptide synthetases-independent siderophore pathway. Outcompeting or inhibition of plant pathogens, alteration of host defense mechanisms, and alteration of plant-fungal interactions have been associated with fungal siderophores. To understand these mechanisms in fungi, studies have been conducted on siderophore biosynthesis by ascomycetes with limited focus on the basidiomycetes. Armillaria includes several species that are pathogens of woody plants and trees important to agriculture, horticulture, and forestry. The aim of this study was to investigate the presence of non-ribosomal peptide synthetases-independent siderophore synthetase gene cluster(s) in genomes of Armillaria species using a comparative genomics approach. Iron-dependent growth and siderophore biosynthesis in strains of selected Armillaria spp. were also evaluated in vitro. Two distinct non-ribosomal peptide synthetases-independent siderophore synthetase gene clusters were identified in all the genomes. All non-ribosomal peptide synthetases-independent siderophore synthetase genes identified putatively encode Type A′ non-ribosomal peptide synthetases-independent siderophore synthetases, most of which have IucA_IucC and FhuF-like transporter domains at their N- and C-terminals, respectively. The effect of iron on culture growth varied among the strains studied. Bioassays using the CAS assay on selected Armillaria spp. revealed in vitro siderophore biosynthesis by all strains irrespective of added FeCl3 concentration. This study highlights some of the tools that Armillaria species allocate to iron homeostasis. The information generated from this study may in future aid in developing molecular based methods to control these phytopathogens.
Near-infrared photoimmunotherapy and anti-cancer immunity
Authors: Nakajima Kohei , Ogawa Mikako 
Published: October 2023

Abstract
The activation of the anti-cancer immune system is an important strategy to control cancer. A new form of cancer phototherapy, near-infrared photoimmunotherapy (NIR-PIT), was approved for clinical use in 2020 and uses IRDye® 700DX (IR700)-conjugated antibodies and NIR light. After irradiation with NIR light, the antibody–IR700 conjugate forms water-insoluble aggregations on the plasma membrane of target cells. This aggregation causes lethal damage to the plasma membrane, and effectively leads to immunogenic cell death (ICD). Subsequently, ICD activates anti-cancer immune cells such as dendritic cells and cytotoxic T cells. Combination therapy with immune-checkpoint blockade has synergistically improved the anti-cancer effects of NIR-PIT. Additionally, NIR-PIT can eliminate immunosuppressive immune cells in light-irradiated tumors by using specific antibodies against regulatory T cells and myeloid-derived suppressor cells. In addition to cancer-cell-targeted NIR-PIT, such immune-cell-targeted NIR-PIT has shown promising results by activating the anti-cancer immune system. Furthermore, NIR-PIT can be used to manipulate the tumor microenvironment by eliminating only targeted cells in the tumor, and thus it also can be used to gain insight into immunity in basic research.
In vitro synergy of the combination of sulbactam-durlobactam and cefepime at clinically relevant concentrations against A. baumannii, P. aeruginosa and Enterobacterales
Authors: Fouad Aliaa , Nicolau David P , Gill Christian M 
Published: October 2023

Abstract

Background
Sulbactam-durlobactam is a potent combination active against Acinetobacter baumannii; however, it lacks activity against other nosocomial pathogens. Cefepime is a common first-line therapy for hospital/ventilator-associated pneumonia caused by Gram-negative pathogens including Pseudomonas aeruginosa and Enterobacterales. With increasing resistance to cefepime, and the significant proportion of polymicrobial nosocomial infections, effective therapy for infections caused by Acinetobacter baumannii, P. aeruginosa and Enterobacterales is needed. This study investigated the in vitro synergy of sulbactam-durlobactam plus cefepime against relevant pathogens.

Methods
Static time–kills assays were performed in duplicate against 14 cefepime-resistant isolates (A. baumannii, n = 4; P. aeruginosa, n = 4; Escherichia coli, n = 3; Klebsiella pneumoniae, n = 3). One WT K. pneumoniae isolate was included. Antibiotic concentrations simulated the free-steady state average concentration of clinically administered doses in patients.

Results
Sulbactam-durlobactam alone showed significant activity against A. baumannii consistent with the MIC values. Sulbactam-durlobactam plus cefepime showed synergy against one A. baumannii isolate with an elevated MIC to sulbactam-durlobactam (32 mg/L). Against all P. aeruginosa isolates, synergy was observed with sulbactam-durlobactam plus cefepime. For the Enterobacterales, one E. coli isolate demonstrated synergy while the others were indifferent due to significant kill from sulbactam-durlobactam alone. The combination of sulbactam-durlobactam plus cefepime showed synergy against one of the K. pneumoniae and additive effects against the other two K. pneumoniae tested. No antagonism was observed in any isolates including the WT strain.

Conclusions
Synergy and no antagonism was observed with a combination of sulbactam-durlobactam and cefepime; further in vivo pharmacokinetic/pharmacodynamics data and clinical correlation are necessary to support our findings.
Predictive factors and oncological outcomes of pathological T3a upstaging in patients with clinical T1 renal cell carcinoma undergoing partial nephrectomy
Authors: Ishiyama Ryo , Omae Kenji , Kondo Tsunenori , Iizuka Junpei , Yoshida Kazuhiko , Fukuda Hironori , Tachibana Hidekazu , Ishihara Hiroki , Kobayashi Hirohito , Takagi Toshio 
Published: October 2023

Abstract

Objectives
To investigate predictive factors and oncological outcomes of pathological T3a upstaging in renal cell carcinoma patients who were initially diagnosed as clinical T1 and treated with partial nephrectomy.

Methods and materials
The clinical records and survival data of 1617 patients, who had undergone partial nephrectomy for clinical T1 renal cell carcinoma at Tokyo Women’s Medical University, Tokyo, Japan between January 2011 and December 2020, were analyzed retrospectively.

Results
Of 1617 clinical T1 renal cell carcinoma patients who underwent partial nephrectomy, 28 (1.73%) had pathological T3a upstaging. In the multivariable analysis for pathological T3a upstaging using logistic regression models, male sex and clinical T1b were significant factors associated with pathological T3a upstaging (male sex: odds ratio = 5.07, 95% confidence interval: 1.18–21.8, clinical T1b: odds ratio = 8.36, 95% confidence interval: 3.56–19.6). The Kaplan–Meier method of the recurrence-free survival showed shorter recurrence-free survival in patients with pathological T3a upstaging than in those with pathological T1 (P &lt; 0.0001). In the multivariable analysis using Cox proportional hazards regression models, pathological T3a upstaging was no longer significantly associated with recurrence-free survival after adjustment for other pathological factors (hazard ratio = 1.59, 95% confidence interval: 0.58–4.36). In a sensitivity analysis that analyzed its components individually instead of whole pathological T3a, neither perinephric fat invasion, sinus fat invasion, nor renal vein invasion was associated with recurrence-free survival.

Conclusions
Male sex and clinical T1b were significant predictors for pathological T3a upstaging after partial nephrectomy in clinical T1 renal cell carcinoma patients. Although patients with pathological T3a upstaging had worse recurrence-free survival compared with those without upstaging, multivariable analyses revealed that pathological T3a upstaging was not an independent predictor for poor recurrence-free survival.
Metaphilosophical myopia and the ideal of expansive pluralism
Authors: Kidd Ian James 
Published: October 2023

AbstractThis paper argues for the diversification of university-level philosophy curricula. I defend the ideal of expansionist pluralism and connect it to metaphilosophical myopia—problematically limited or constrained visions of the range of forms taken by philosophy. Expansively pluralist curricula work to challenge metaphilosophical myopia and one of its costs, namely, a specific kind of hermeneutical injustice, perpetrated against the communities and traditions shaped by the occluded forms of philosophy.
Pyrroline-5-carboxylate metabolism protein complex detected in Arabidopsis thaliana leaf mitochondria
Authors: Zheng Yao , Cabassa-Hourton Cécile , Eubel Holger , Chevreux Guillaume , Lignieres Laurent , Crilat Emilie , Braun Hans-Peter , Lebreton Sandrine , Savouré Arnould 
Published: October 2023

Abstract
Proline dehydrogenase (ProDH) and pyrroline-5-carboxylate (P5C) dehydrogenase (P5CDH) catalyse the oxidation of proline into glutamate via the intermediates P5C and glutamate-semialdehyde (GSA), which spontaneously interconvert. P5C and GSA are also intermediates in the production of glutamate from ornithine and α-ketoglutarate catalysed by ornithine δ-aminotransferase (OAT). ProDH and P5CDH form a fused bifunctional PutA enzyme in Gram-negative bacteria and are associated in a bifunctional substrate-channelling complex in Thermus thermophilus; however, the physical proximity of ProDH and P5CDH in eukaryotes has not been described. Here, we report evidence of physical proximity and interactions between Arabidopsis ProDH, P5CDH, and OAT in the mitochondria of plants during dark-induced leaf senescence when all three enzymes are expressed. Pairwise interactions and localization of the three enzymes were investigated using bimolecular fluorescence complementation with confocal microscopy in tobacco and sub-mitochondrial fractionation in Arabidopsis. Evidence for a complex composed of ProDH, P5CDH, and OAT was revealed by co-migration of the proteins in native conditions upon gel electrophoresis. Co-immunoprecipitation coupled with mass spectrometry analysis confirmed the presence of the P5C metabolism complex in Arabidopsis. Pull-down assays further demonstrated a direct interaction between ProDH1 and P5CDH. P5C metabolism complexes might channel P5C among the constituent enzymes and directly provide electrons to the respiratory electron chain via ProDH.
Discovery adductomics provides a comprehensive portrait of tissue-, age- and sex-specific DNA modifications in rodents and humans
Authors: Guilbaud Axel , Ghanegolmohammadi Farzan , Wang Yijun , Leng Jiapeng , Kreymerman Alexander , Gamboa Varela Jacqueline , Garbern Jessica , Elwell Hannah , Cao Fang , Ricci-Blair Elisabeth M , Liang Cui , Balamkundu Seetharamsing , Vidoudez Charles , DeMott Michael S , Bedi Kenneth , Margulies Kenneth B , Bennett David A , Palmer Abraham A , Barkley-Levenson Amanda , Lee Richard T , Dedon Peter C 
Published: October 2023

Abstract
DNA damage causes genomic instability underlying many diseases, with traditional analytical approaches providing minimal insight into the spectrum of DNA lesions in vivo. Here we used untargeted chromatography-coupled tandem mass spectrometry-based adductomics (LC–MS/MS) to begin to define the landscape of DNA modifications in rat and human tissues. A basis set of 114 putative DNA adducts was identified in heart, liver, brain, and kidney in 1–26-month-old rats and 111 in human heart and brain by ‘stepped MRM’ LC–MS/MS. Subsequent targeted analysis of these species revealed species-, tissue-, age- and sex-biases. Structural characterization of 10 selected adductomic signals as known DNA modifications validated the method and established confidence in the DNA origins of the signals. Along with strong tissue biases, we observed significant age-dependence for 36 adducts, including N2-CMdG, 5-HMdC and 8-Oxo-dG in rats and 1,N6-ϵdA in human heart, as well as sex biases for 67 adducts in rat tissues. These results demonstrate the potential of adductomics for discovering the true spectrum of disease-driving DNA adducts. Our dataset of 114 putative adducts serves as a resource for characterizing dozens of new forms of DNA damage, defining mechanisms of their formation and repair, and developing them as biomarkers of aging and disease.
Expanding the coverage of regulons from high-confidence prior knowledge for accurate estimation of transcription factor activities
Authors: Müller-Dott Sophia , Tsirvouli Eirini , Vazquez Miguel , Ramirez Flores Ricardo O , Badia-i-Mompel Pau , Fallegger Robin , Türei Dénes , Lægreid Astrid , Saez-Rodriguez Julio 
Published: October 2023

Abstract
Gene regulation plays a critical role in the cellular processes that underlie human health and disease. The regulatory relationship between transcription factors (TFs), key regulators of gene expression, and their target genes, the so called TF regulons, can be coupled with computational algorithms to estimate the activity of TFs. However, to interpret these findings accurately, regulons of high reliability and coverage are needed. In this study, we present and evaluate a collection of regulons created using the CollecTRI meta-resource containing signed TF–gene interactions for 1186 TFs. In this context, we introduce a workflow to integrate information from multiple resources and assign the sign of regulation to TF–gene interactions that could be applied to other comprehensive knowledge bases. We find that the signed CollecTRI-derived regulons outperform other public collections of regulatory interactions in accurately inferring changes in TF activities in perturbation experiments. Furthermore, we showcase the value of the regulons by examining TF activity profiles in three different cancer types and exploring TF activities at the level of single-cells. Overall, the CollecTRI-derived TF regulons enable the accurate and comprehensive estimation of TF activities and thereby help to interpret transcriptomics data.
TCOD: an integrated resource for tropical crops
Authors: Kang Hailong , Huang Tianhao , Duan Guangya , Meng Yuyan , Chen Xiaoning , He Shuang , Xia Zhiqiang , Zhou Xincheng , Chao Jinquan , Tang Bixia , Wang Zhonghuang , Zhu Junwei , Du Zhenglin , Sun Yanlin , Zhang Sisi , Xiao Jingfa , Tian Weimin , Wang Wenquan , Zhao Wenming 
Published: October 2023

Abstract
Tropical crops are vital for tropical agriculture, with resource scarcity, functional diversity and extensive market demand, providing considerable economic benefits for the world's tropical agriculture-producing countries. The rapid development of sequencing technology has promoted a milestone in tropical crop research, resulting in the generation of massive amount of data, which urgently needs an effective platform for data integration and sharing. However, the existing databases cannot fully satisfy researchers’ requirements due to the relatively limited integration level and untimely update. Here, we present the Tropical Crop Omics Database (TCOD, https://ngdc.cncb.ac.cn/tcod), a comprehensive multi-omics data platform for tropical crops. TCOD integrates diverse omics data from 15 species, encompassing 34 chromosome-level de novo assemblies, 1 255 004 genes with functional annotations, 282 436 992 unique variants from 2048 WGS samples, 88 transcriptomic profiles from 1997 RNA-Seq samples and 13 381 germplasm items. Additionally, TCOD not only employs genes as a bridge to interconnect multi-omics data, enabling cross-species comparisons based on homology relationships, but also offers user-friendly online tools for efficient data mining and visualization. In short, TCOD integrates multi-species, multi-omics data and online tools, which will facilitate the research on genomic selective breeding and trait biology of tropical crops.
BioKA: a curated and integrated biomarker knowledgebase for animals
Authors: Wang Yibo , Lin Yihao , Wu Sicheng , Sun Jiani , Meng Yuyan , Jin Enhui , Kong Demian , Duan Guangya , Bei Shaoqi , Fan Zhuojing , Wu Gangao , Hao Lili , Song Shuhui , Tang Bixia , Zhao Wenming 
Published: October 2023

AbstractBiomarkers play an important role in various area such as personalized medicine, drug development, clinical care, and molecule breeding. However, existing animals’ biomarker resources predominantly focus on human diseases, leaving a significant gap in non-human animal disease understanding and breeding research. To address this limitation, we present BioKA (Biomarker Knowledgebase for Animals, https://ngdc.cncb.ac.cn/bioka), a curated and integrated knowledgebase encompassing multiple animal species, diseases/traits, and annotated resources. Currently, BioKA houses 16 296 biomarkers associated with 951 mapped diseases/traits across 31 species from 4747 references, including 11 925 gene/protein biomarkers, 1784 miRNA biomarkers, 1043 mutation biomarkers, 773 metabolic biomarkers, 357 circRNA biomarkers and 127 lncRNA biomarkers. Furthermore, BioKA integrates various annotations such as GOs, protein structures, protein–protein interaction networks, miRNA targets and so on, and constructs an interactive knowledge network of biomarkers including circRNA–miRNA–mRNA associations, lncRNA–miRNA associations and protein–protein associations, which is convenient for efficient data exploration. Moreover, BioKA provides detailed information on 308 breeds/strains of 13 species, and homologous annotations for 8784 biomarkers across 16 species, and offers three online application tools. The comprehensive knowledge provided by BioKA not only advances human disease research but also contributes to a deeper understanding of animal diseases and supports livestock breeding.
No adults allowed: Adolescents and Medical Decision Making
Authors: Nemetz Elisheva T A , Huang Ryan S , Das Sunit 
Published: October 2023

Abstract
The majority of the literature focused on whether consent should be extended to the adolescent population arises from themes adapted from American tort law. In contrast to the USA, Ontario does not delineate an age of consent for medical treatment and relying on American guidelines to guide practice in Ontario is problematic. While the literature is saturated with discussions for and against seeking adolescent consent, there are currently no bioethical guidelines on adolescent consent in the province of Ontario. This paper explores adolescent refusal of care and adolescent request for care in opposition to parental wishes. The paper seeks to answer the following questions: What is the difference between an adolescent and an adult in medical decision-making? What are the barriers to seeking adolescent consent? And, can the neurobiological argument be an accurate guide for obtaining adolescent consent?
Silicate Microfiber Scaffolds Support the Formation and Expansion of the Cortical Neuronal Layer of Cerebral Organoids With a Sheet-Like Configuration
Authors: Terada Eisaku , Bamba Yohei , Takagaki Masatoshi , Kawabata Shuhei , Tachi Tetsuro , Nakamura Hajime , Nishida Takeo , Kishima Haruhiko 
Published: October 2023

Abstract
Cerebral organoids (COs) are derived from human-induced pluripotent stem cells in vitro and mimic the features of the human fetal brain. The development of COs is largely dependent on “self-organization” mechanisms, in which differentiating cells committed to cortical cells autonomously organize into the cerebral cortex-like tissue. However, extrinsic manipulation of their morphology, including size and thickness, remains challenging. In this study, we discovered that silicate microfiber scaffolds could support the formation of cortical neuronal layers and successfully generated cortical neuronal layers, which are 9 times thicker than conventional COs, in 70 days. These cortical neurons in the silicate microfiber layer were differentiated in a fetal brain-like lamination pattern. While these cellular characteristics such as cortical neurons and neural stem/progenitor cells were like those of conventional COs, the cortical neuronal layers were greatly thickened in sheet-like configuration. Moreover, the cortical neurons in the scaffolds showed spontaneous electrical activity. We concluded that silicate microfiber scaffolds support the formation of the cortical neuronal layers of COs without disturbing self-organization-driven corticogenesis. The extrinsic manipulation of the formation of the cortical neuronal layers of COs may be useful for the research of developmental mechanisms or pathogenesis of the human cerebral cortex, particularly for the development of regenerative therapy and bioengineering.
Is Over-parameterization a Problem for Profile Mixture Models?
Authors: Baños Hector , Susko Edward , Roger Andrew J 
Published: October 2023

Abstract
Biochemical constraints on the admissible amino acids at specific sites in proteins lead to heterogeneity of the amino acid substitution process over sites in alignments. It is well known that phylogenetic models of protein sequence evolution that do not account for site heterogeneity are prone to long-branch attraction (LBA) artifacts. Profile mixture models were developed to model heterogeneity of preferred amino acids at sites via a finite distribution of site classes each with a distinct set of equilibrium amino acid frequencies. However, it is unknown whether the large number of parameters in such models associated with the many amino acid frequency vectors can adversely affect tree topology estimates because of over-parameterization. Here, we demonstrate theoretically that for long sequences, over-parameterization does not create problems for estimation with profile mixture models. Under mild conditions, tree, amino acid frequencies, and other model parameters converge to true values as sequence length increases, even when there are large numbers of components in the frequency profile distributions. Because large sample theory does not necessarily imply good behavior for shorter alignments we explore the performance of these models with short alignments simulated with tree topologies that are prone to LBA artifacts. We find that over-parameterization is not a problem for complex profile mixture models even when there are many amino acid frequency vectors. In fact, simple models with few site classes behave poorly. Interestingly, we also found that misspecification of the amino acid frequency vectors does not lead to increased LBA artifacts as long as the estimated cumulative distribution function of the amino acid frequencies at sites adequately approximates the true one. In contrast, misspecification of the amino acid exchangeability rates can severely negatively affect parameter estimation. Finally, we explore the effects of including in the profile mixture model an additional “F-class” representing the overall frequencies of amino acids in the data set. Surprisingly, the F-class does not help parameter estimation significantly and can decrease the probability of correct tree estimation, depending on the scenario, even though it tends to improve likelihood scores.