bluuebunny/crossref_metadata_2025 huggingface dataset:
Specific Gene Expression in Pseudomonas Putida U Shows New Alternatives for Cadaverine and Putrescine Catabolism
Authors: Getino Luis , Chamizo-Ampudia Alejandro , Martín José Luis , Luengo José María , Barreiro Carlos , Olivera Elías R.
Published: October 2023

Pseudomonas putida strain U can be grown using, as sole carbon sources, the biogenic amines putrescine or cadaverine, as well as their catabolic intermediates, ɣ-aminobutyrate or δ-aminovalerate, respectively. Several paralogs for the genes that encode some of the activities involved in the catabolism of these compounds, such as a putrescine-pyruvate aminotransferase (spuC1 and spuC2 genes) and a ɣ-aminobutyrate aminotransferase (gabT1 and gabT2 genes) have been identified in this bacterium. When the expression pattern of these genes is analyzed by qPCR, it is drastically conditioned by supplying the carbon sources. Thus, spuC1 is upregulated by putrescine, whereas spuC2 seems to be exclusively induced by cadaverine. However, gabT1 increases its expression in response to different polyamines or aminated catabolic derivatives from them (i.e., ɣ-aminobutyrate or δ-aminovalerate), although gabT2 does not change its expression level concerning no-amine unrelated carbon sources (citrate). These results reveal differences between the mechanisms proposed for polyamine catabolism in P. aeruginosa and Escherichia coli concerning P. putida strain U, as well as allow a deeper understanding of the enzymatic systems used by this last strain during polyamine metabolism.
Survival and Enrichment Analysis of Epithelial–Mesenchymal Transition Genes in Bladder Urothelial Carcinoma
Authors: Ali Waleed , Xiao Weirui , Jacobs Daniel , Kajdacsy-Balla Andre
Published: October 2023

The escalating prevalence of bladder cancer, particularly urothelial carcinoma, necessitates innovative approaches for prognosis and therapy. This study delves into the significance of genes related to epithelial–mesenchymal transition (EMT), a process inherently linked to carcinogenesis and comparatively better studied in other cancers. We examined 1184 EMT-related gene expression levels in bladder urothelial cancer cases through the TCGA dataset. Genes shown to be differentially expressed in relation to survival underwent further network and enrichment analysis to uncover how they might shape disease outcomes. Our in silico analysis revealed a subset of 32 genes, including those significantly represented in biological pathways such as VEGF signaling and bacterium response. In addition, these genes interact with genes involved in the JAK-STAT signaling pathway. Additionally, some of those 32 genes have been linked to immunomodulators such as chemokines CCL15 and CCL18, as well as to various immune cell infiltrates. Our findings highlight the prognostic utility of various EMT-related genes and identify possible modulators of their effect on survival, allowing for further targeted wet lab research and possible therapeutic intervention.
Altered Transcript Levels of MMP13 and VIT Genes in the Muscle and Connective Tissue of Pigs with Umbilical Hernia
Authors: Wozniak Jakub , Loba Weronika , Wysocka Alicja , Dzimira Stanislaw , Przadka Przemyslaw , Switonski Marek , Nowacka-Woszuk Joanna
Published: October 2023

Umbilical hernia (UH) and inguinal hernia (IH) are among the most common defects in pigs, affecting their welfare and resulting in economic losses. In this study, we aimed to verify the association of previously reported differences in transcript levels of the ACAN, COL6A5, MMP13, and VIT genes with the occurrence of UH and IH. We examined mRNA levels in muscle and connective tissue from 68 animals—34 affected by UH and 34 controls. In a second cohort, we examined inguinal channel samples from 46 pigs (in four groups). We determined DNA methylation levels in muscle tissue for the UH and control animals. The transcript level of MMP13 changed in the UH cases, being upregulated and downregulated in muscle and connective tissue, respectively, and the VIT gene also showed an increased muscular mRNA level. The transcript of the ACAN gene significantly decreased in old pigs with IH. We further observed an increased DNA methylation level for one CpG site within the MMP13 gene in UH individuals. We conclude that these alterations in gene mRNA levels in the UH animals depend on the tissue and can sometimes be a consequence of, not a cause of, the affected phenotype.
The Submerged, Post-Truth “Island of Happiness” in Michel Houellebecq’s Extension du domaine de la lutte
Authors: Moser Keith
Published: October 2023

This article proposes a Debordian reading of Michel Houellebecq’s first work Extension du domaine de la lutte that would thrust him into the spotlight as France’s most popular and controversial writer. Specifically, this investigation demonstrates that Debord’s theories are a useful lens from which to analyze Houellebecq’s harsh critique of late capitalism. Owing to a radical paradigm shift in the capitalist paradigm, Debord and Houellebecq posit that we live in a brave new world in which millions of individuals no longer have a frame of reference for distinguishing between commonplace reality and its simulation on a screen. On the informational battlefield where simulations of the good(s) life have proliferated themselves to the brink of replacing the real in the collective imagination of consumer citizens, they illustrate that the timeless search for happiness also seems to be even more fraught with peril in the 21st century.
So-Called Sovereign Settlers: Settler Conspirituality and Nativism in the Australian Anti-Vax Movement
Authors: Day Madi , Carlson Bronwyn
Published: October 2023

The COVID-19 pandemic, and the social and economic instability that followed, has given new life to conspirituality and far-right ideology in so-called Australia. This article discusses how politico-spiritual communities invested in both conspiracy theories and New Age spirituality have pieced together settler narratives about a New World Order and external threats to Western society from far-right and white supremacist Christian ideology circulated via new media. Using anti-colonial discourse analysis, we elucidate the undercurrent of white supremacist ideology in the Australian anti-vax movement, and highlight the misuse of Indigeneity in far-right and anti-vax narratives. We discuss how these narratives are settler-colonial and how conspiritualists co-opt and perform Indigeneity as a form of settler nativism. As a case study, we analyse the use of the term sovereignty by settlers attached to Muckadda Camp—a camp of ‘Original Sovereigns’ occupying the lawn outside Old Parliament house from December 2021 to February 2022. Using Indigenous critique from both new media and academia, we argue that although settlers may perform Indigeneity, they are exercising white supremacist settler narratives, and not Indigenous sovereignty.
Influence of Ripening Process on Pecan Nut (Carya illinoinensis) Kernel Quality: Phenolic Profile, Antioxidant Activity, and Carbohydrate Composition
Authors: Bouali Intidhar , Tsafouros Athanassios , Ntanos Efstathios , Albouchi Ali , Boukhchina Sadok , Roussos Peter A.
Published: October 2023

Pecan nuts (Carya illinoinensis) provide a wide range of bioactive compounds (particularly polyphenols) that improve the nutritional quality of diets. This study aimed to monitor the evolution of polyphenolic compounds (total phenols, total flavonoids, total flavanols, total condensed tannins, and total o-diphenols), the phenolic profile, the antioxidant activity, and the sugar concentration during pecan nut development in three Tunisian cultivars. Condensed tannins (41.98–221.13 mg catechin assay equivalents g−1 FW) were the dominant class of phenolics at all maturity stages, followed by total phenols (12.25–57.92 mg gallic acid equivalents g−1 FW). Ellagic acid and catechin were the most abundant phenolics at all maturity stages. The highest phenolic content and antioxidant activity were found at an early stage of ripening but as maturity progressed, a decreasing trend was observed. Sucrose (6.09–30.79 mg g−1 FW) was the predominant sugar followed by fructose and then glucose. A decreasing and later increasing trend of total carbohydrate concentration was detected during nut development. A Canonical Discriminant Analysis of the data succeeded in separating the three pecan cultivars due to their unique characteristics. Overall, the cultivar and the degree of maturity are the major factors controlling the chemical composition and antioxidant capacity of pecan nuts. This study provides more information on the optimal period when the maximum concentration of these health-enhancing compounds is found for use in food, nutraceutical, cosmetic, and pharmaceutical applications.
Far-Red Light Affects Stomatal Opening and Evapotranspiration of Sweet Basil
Authors: Park Ji Up , An Seong Kwang , Kim Jongyun
Published: October 2023

Far-red light (FR; wavelength: 700–800 nm) is known for its effects on plant morphology and photosynthesis. However, its effects on stomatal responses and transpiration are not well understood. This study investigated the effects of FR on stomatal development and evapotranspiration in sweet basil grown under red, blue, and green (RGB) light-emitting diodes (LED). FR was provided for 10 days at 0, 30, 100, and 130 μmol·m−2·s−1 with the same base light (RGB ratio of 6:2:2; a photosynthetic photon flux density of 200 μmol·m−2·s−1). Evapotranspiration was measured using a load cell, and stomatal development was monitored microscopically. FR increased the height of sweet basil mostly due to the shade avoidance syndrome. The photosynthetic rate was not improved with FR, probably due to insufficient base light intensity. Despite similar leaf area and root growth, daily evapotranspiration increased with FR, resulting in higher water use. Although the stomatal density and guard cell area were similar across treatments, the stomatal aperture area was larger in plants with FR, thus increasing evapotranspiration. In conclusion, FR with the base RGB light intensity of 200 μmol·m−2·s−1 enhanced the evapotranspiration of sweet basil by regulating stomatal opening, but it did not enhance photosynthesis.
Changes in Physicochemical Characteristics, Peel Color, and Juice Attributes of ‘Moro’ Blood Orange Fruit Treated with Glycine Betaine and Methyl Salicylate during Cold Quarantine Storage
Authors: Habibi Fariborz , Sarkhosh Ali , Guillén Fabián , Serrano María , Valero Daniel
Published: October 2023

Cold quarantine storage is the practice of subjecting citrus fruit to low temperatures after harvesting to comply with stringent international phytosanitary standards for export, but fruit quality can be affected during storage. Therefore, this study investigated the effects of glycine betaine (GB) and/or methyl salicylate (MeSA) on physicochemical changes, chemical attributes of juice, and peel color of ‘Moro’ blood orange at cold quarantine storage (2 °C) for 60 days. Fruit were treated with GB (15 and 30 mM) by vacuum infiltration at 30 kPa for 8 min and vapor treatment of MeSA (100 µM) for 18 h as well as the combination of both GB concentrations with MeSA. The key findings of this research revealed that the combined treatment of 30 mM GB and 100 µM MeSA significantly mitigated weight and firmness losses in ‘Moro’ blood orange fruit during the cold quarantine period. Furthermore, there was a decrease in titratable acidity (TA) across all treatments, with the highest TA recorded for the 30 mM GB + 100 µM MeSA combination. Conversely, total soluble solids (TSS), TSS/TA ratio, and juice pH increased in all treatments, with the control treatment displaying the highest values. Regarding peel color parameters, which encompass L* (lightness), b*, hue angle (h°), chroma (C*), and a*, as well as the citrus color index (CCI), these exhibited characteristic changes during cold quarantine storage. However, the application of GB and MeSA, especially at the 30 mM GB + 100 µM MeSA level, noticeably delayed these peel color variations. Overall, GB and MeSA treatments offer significant advantages in preserving the physicochemical characteristics and chemical attributes of ‘Moro’ blood oranges during cold quarantine storage. These findings underscore the potential of GB and MeSA treatments for maintaining the quality of ‘Moro’ blood oranges during cold quarantine storage, with a noteworthy synergistic effect between MeSA and GB in preserving fruit quality.
Overexpression of Cytosolic Glyceraldehyde-3-Phosphate Dehydrogenase 1 Gene Improves Nitrogen Absorption and Utilization in Potato
Authors: Liu Jingrui , Song Jun , Zhuang Xiaoyu , Lu Yifei , Wang Qiang , Yang Shimin , Lu Liming , Wang Xiyao , Li Liqin
Published: October 2023

Nitrogen is one of the most important elements for improving potato yield. However, excessive application of nitrogenous fertilizer not only produces river and other environmental pollution but also increases agricultural production costs. In recent years, to explain the molecular mechanisms of nitrogen metabolites, some vital genes involved have been reported; however, only limited success has been achieved in potato. Here, we report that the expression of cytosolic glyceraldehyde-3-phosphate dehydrogenase 1 (StGAPC1) is increased under low-nitrogen stress. StGAPC1-overexpressing potato seedlings had more biomass and a significant increase in total nitrogen content and root nitrate influx rate compared to the wild type. The overexpression of StGAPC1 also increased the expression of nitrate transporters and increased ROS system activity to reduce hydrogen peroxide content under low-nitrogen stress. Our results provide a foundation for further research on StGAPC1 function in nitrogen absorption and utilization mechanisms in potato.
Enrichment and Temporal Trends of Groundwater Salinity in Central Mexico
Authors: Colmenero-Chacón Claudia Patricia , Morales-deAvila Heriberto , Gutiérrez Mélida , Esteller-Alberich Maria Vicenta , Alarcón-Herrera Maria Teresa
Published: October 2023

Groundwater salinization is a major threat to the water supply in coastal and arid areas, a threat that is expected to worsen by increased groundwater withdrawals and by global warming. Groundwater quality in Central Mexico may be at risk of salinization due to its arid climate and since groundwater is the primary source for drinking and agriculture water. Only a handful of studies on groundwater salinization have been reported for this region, most constrained to a small area and without trend analyses. To determine the extent of salinization, total dissolved solids (TDS), sodium (Na+), nitrate as nitrogen (NO3-N) and sodium adsorption ratio (SAR) are commonly used. Available water quality data for about 200 wells, sampled annually between 2012 and 2021, were used to map the spatial distribution of NO3-N, TDS, Na+, and SAR. Upward trends and Spearman correlation were also determined. The study area was subdivided into three sections to estimate the impact of climate and lithologies on groundwater salinity. The results showed that human activities (agriculture) and dissolution of carbonate and evaporite rocks were major sources of salinity, and evaporation an enriching factor. Temporal trends occurred in only a few (about 7%) wells, primarily in NO3-N. The water quality for irrigation was generally good, (SAR < 10 in 95% of samples); however, eight wells contained water hazardous to soil (TDS > 1750 mg L−1 and SAR > 9). The results detected one aquifer with consistently high concentrations and upward trends and eight lesser impacted aquifers. Identifying the wells with upward trends is important in narrowing down the possible causes of their concentration increase with time and to develop strategies that will infuse sustainability to groundwater management.
Economic Disruptions in Repayment of Peer Loans
Authors: Maloney David , Hong Sung-Chul , Nag Barin
Published: October 2023

Economic disruptions can alter the likelihood of defaults on peer-to-peer loans, causing those impacted to adjust. The option to declare economic hardship and temporarily reduce the payment burden can provide some relief. When this occurs, the borrower’s financial qualifications have changed. The qualities instrumental in successfully securing the original loan terms must be reanalyzed to manage risk. This is a critical point in the life of the loan because the declaration of financial hardship can signal that the borrower’s ability to repay has diminished. We present a novel default detection scheme for borrowers experiencing an economic disruption based on the Two-Class Support Vector Machine, a data classification algorithm for supervised learning problems. The method utilizes data from actual loan records (15,355 loans from 2016 through 2020), specifically from borrowers who declared economic hardship. We provide a detailed description of the default detection process and present results that show defaults among borrowers experiencing financial hardship can be predicted accurately.
Enhanced Photovoltaic Properties of Y6 Derivatives with Asymmetric Terminal Groups: A Theoretical Insight
Authors: Xiang Yunjie , Cao Zhijun , Zhang Xiaolu , Zou Zhuo , Zheng Shaohui
Published: October 2023

Y6 derivatives with asymmetric terminal groups have attracted considerable attention in recent years. However, the effects of the asymmetric modification of terminal groups on the photovoltaic performance of Y6 derivatives are not well understood yet. Therefore, we designed a series of Y6-based acceptors with asymmetric terminal groups by endowing them with various electron-withdrawing abilities and different conjugated rings to conduct systematic research. The electron-withdrawing ability of the Y6-D1 terminal group (substituted by IC-2F and IC-2NO2 terminals) is strongest, followed by Y6 (substituted by two same IC-2F terminals), Y6-D2 (substituted by IC-2F and 2-(4-oxo-4,5-dihydro-6H-cyclopenta[b]thiophen-6-ylidene)malononitrile terminals), Y6-D4 (substituted by IC-2F and indene ring), and Y6-D3 (substituted by IC-2F and thiazole ring). Computed results show that A–A stacking is the main molecular packing mode of Y6 and four other asymmetric Y6 derivatives. The ratios of A–A stacking face-on configuration of Y6-D1, Y6-D2, Y6-D3, Y6-D4, and Y6 are 51.6%, 55.0%, 43.5%, 59.3%, and 62.4%, respectively. Except for Y6-D1 substituted by the IC-2F and IC-2NO2 (the strongest electron-withdrawing capacity) terminal groups, the other three asymmetric molecules are mainly electron-transporting and can therefore act as acceptors. The open-circuit voltages of organic solar cells (OSCs) based on Y6-D2, Y6-D3, and Y6-D4, except for Y6-D1, may be higher than those of OSCs based on the Y6 acceptor because of their higher energy levels of lowest unoccupied molecular orbital (LUMO). PM6/Y6-D3 and PM6/Y6-D4 have better light absorption properties than PM6/Y6 due to their higher total oscillator strength. These results indicate that Y6-D3 and Y6-D4 can be employed as good acceptors.
Advances in Biomedical Applications of Solution Blow Spinning
Authors: Carriles Javier , Nguewa Paul , González-Gaitano Gustavo
Published: October 2023

In recent years, Solution Blow Spinning (SBS) has emerged as a new technology for the production of polymeric, nanocomposite, and ceramic materials in the form of nano and microfibers, with similar features to those achieved by other procedures. The advantages of SBS over other spinning methods are the fast generation of fibers and the simplicity of the experimental setup that opens up the possibility of their on-site production. While producing a large number of nanofibers in a short time is a crucial factor in large-scale manufacturing, in situ generation, for example, in the form of sprayable, multifunctional dressings, capable of releasing embedded active agents on wounded tissue, or their use in operating rooms to prevent hemostasis during surgical interventions, open a wide range of possibilities. The interest in this spinning technology is evident from the growing number of patents issued and articles published over the last few years. Our focus in this review is on the biomedicine-oriented applications of SBS for the production of nanofibers based on the collection of the most relevant scientific papers published to date. Drug delivery, 3D culturing, regenerative medicine, and fabrication of biosensors are some of the areas in which SBS has been explored, most frequently at the proof-of-concept level. The promising results obtained demonstrate the potential of this technology in the biomedical and pharmaceutical fields.
Mitochondrial Metabolism in the Spotlight: Maintaining Balanced RNAP III Activity Ensures Cellular Homeostasis
Authors: Szatkowska Roza , Furmanek Emil , Kierzek Andrzej M. , Ludwig Christian , Adamczyk Malgorzata
Published: October 2023

RNA polymerase III (RNAP III) holoenzyme activity and the processing of its products have been linked to several metabolic dysfunctions in lower and higher eukaryotes. Alterations in the activity of RNAP III-driven synthesis of non-coding RNA cause extensive changes in glucose metabolism. Increased RNAP III activity in the S. cerevisiae maf1Δ strain is lethal when grown on a non-fermentable carbon source. This lethal phenotype is suppressed by reducing tRNA synthesis. Neither the cause of the lack of growth nor the underlying molecular mechanism have been deciphered, and this area has been awaiting scientific explanation for a decade. Our previous proteomics data suggested mitochondrial dysfunction in the strain. Using model mutant strains maf1Δ (with increased tRNA abundance) and rpc128-1007 (with reduced tRNA abundance), we collected data showing major changes in the TCA cycle metabolism of the mutants that explain the phenotypic observations. Based on 13C flux data and analysis of TCA enzyme activities, the present study identifies the flux constraints in the mitochondrial metabolic network. The lack of growth is associated with a decrease in TCA cycle activity and downregulation of the flux towards glutamate, aspartate and phosphoenolpyruvate (PEP), the metabolic intermediate feeding the gluconeogenic pathway. rpc128-1007, the strain that is unable to increase tRNA synthesis due to a mutation in the C128 subunit, has increased TCA cycle activity under non-fermentable conditions. To summarize, cells with non-optimal activity of RNAP III undergo substantial adaptation to a new metabolic state, which makes them vulnerable under specific growth conditions. Our results strongly suggest that balanced, non-coding RNA synthesis that is coupled to glucose signaling is a fundamental requirement to sustain a cell’s intracellular homeostasis and flexibility under changing growth conditions. The presented results provide insight into the possible role of RNAP III in the mitochondrial metabolism of other cell types.
Evaluation of the Polygenic Risk Score for Alzheimer’s Disease in Russian Patients with Dementia Using a Low-Density Hydrogel Oligonucleotide Microarray
Authors: Ikonnikova Anna , Morozova Anna , Antonova Olga , Ochneva Alexandra , Fedoseeva Elena , Abramova Olga , Emelyanova Marina , Filippova Marina , Morozova Irina , Zorkina Yana , Syunyakov Timur , Andryushchenko Alisa , Andreuyk Denis , Kostyuk Georgy , Gryadunov Dmitry
Published: October 2023

The polygenic risk score (PRS), together with the ɛ4 allele of the APOE gene (APOE-ɛ4), has shown high potential for Alzheimer’s disease (AD) risk prediction. The aim of this study was to validate the model of polygenic risk in Russian patients with dementia. A microarray-based assay was developed to identify 21 markers of polygenic risk and ɛ alleles of the APOE gene. This case–control study included 348 dementia patients and 519 cognitively normal volunteers. Cerebrospinal fluid (CSF) amyloid-β (Aβ) and tau protein levels were assessed in 57 dementia patients. PRS and APOE-ɛ4 were significant genetic risk factors for dementia. Adjusted for APOE-ɛ4, individuals with PRS corresponding to the fourth quartile had an increased risk of dementia compared to the first quartile (OR 1.85; p-value 0.002). The area under the curve (AUC) was 0.559 for the PRS model only, and the inclusion of APOE-ɛ4 improved the AUC to 0.604. PRS was positively correlated with tTau and pTau181 and inversely correlated with Aβ42/Aβ40 ratio. Carriers of APOE-ɛ4 had higher levels of tTau and pTau181 and lower levels of Aβ42 and Aβ42/Aβ40. The developed assay can be part of a strategy for assessing individuals for AD risk, with the purpose of assisting primary preventive interventions.
Deciphering the Mysterious Relationship between the Cross-Pathogenetic Mechanisms of Neurodegenerative and Oncological Diseases
Authors: Aleksandrova Yulia , Neganova Margarita
Published: October 2023

The relationship between oncological pathologies and neurodegenerative disorders is extremely complex and is a topic of concern among a growing number of researchers around the world. In recent years, convincing scientific evidence has accumulated that indicates the contribution of a number of etiological factors and pathophysiological processes to the pathogenesis of these two fundamentally different diseases, thus demonstrating an intriguing relationship between oncology and neurodegeneration. In this review, we establish the general links between three intersecting aspects of oncological pathologies and neurodegenerative disorders, i.e., oxidative stress, epigenetic dysregulation, and metabolic dysfunction, examining each process in detail to establish an unusual epidemiological relationship. We also focus on reviewing the current trends in the research and the clinical application of the most promising chemical structures and therapeutic platforms that have a modulating effect on the above processes. Thus, our comprehensive analysis of the set of molecular determinants that have obvious cross-functional pathways in the pathogenesis of oncological and neurodegenerative diseases can help in the creation of advanced diagnostic tools and in the development of innovative pharmacological strategies.
QTL Mapping of Soybean (Glycine max) Vine Growth Habit Trait
Authors: Song Jian , Liu Kanglin , Yang Xuezhen , Chen Yijie , Xiong Yajun , Yang Qichao , Wang Jing , Zhang Zhihao , Wu Caiyu , Wang Jun , Qiu Lijuan
Published: October 2023

The vine growth habit (VGH) is a notable property of wild soybean plants that also holds a high degree of importance in domestication as it can preclude using these wild cultivars for breeding and improving domesticated soybeans. Here, a bulked segregant analysis (BSA) approach was employed to study the genetic etiology of the VGH in soybean plants by integrating linkage mapping and population sequencing approaches. To develop a recombinant inbred line (RIL) population, the cultivated Zhongdou41 (ZD41) soybean cultivar was bred with ZYD02787, a wild soybean accession. The VGH status of each line in the resultant population was assessed, ultimately leading to the identification of six and nine QTLs from the BSA sequencing of the F4 population and F6-F8 population sequence mapping, respectively. One QTL shared across these analyzed generations was detected on chromosome 19. Three other QTLs detected by BSA-seq were validated and localized to the 90.93 kb, 2.9 Mb, and 602.08 kb regions of chromosomes 6 and 13, harboring 14, 53, and 4 genes, respectively. Three consistent VGH-related QTLs located on chromosomes 2 and 19 were detected in a minimum of three environments, while an additional six loci on chromosomes 2, 10, 13, and 18 were detected in at least two environments via ICIM mapping. Of all the detected loci, five had been reported previously whereas seven represent novel QTLs. Together, these data offer new insights into the genetic basis of the VGH in soybean plants, providing a rational basis to inform the use of wild accessions in future breeding efforts.
Ursolic Acid Alleviates Neuroinflammation after Intracerebral Hemorrhage by Mediating Microglial Pyroptosis via the NF-κB/NLRP3/GSDMD Pathway
Authors: Lei Pan , Li Zhiyang , Hua Qiuwei , Song Ping , Gao Lun , Zhou Long , Cai Qiang
Published: October 2023

The neuroinflammatory response after intracerebral hemorrhage (ICH) causes a large amount of neuronal loss, and inhibiting the inflammatory response can improve the prognosis. In previous laboratory studies and clinical trials, ursolic acid (UA) inhibited the inflammatory response, but whether it can be administered to inhibit the neuroinflammatory response after cerebral hemorrhage is unknown. The aim of this study was to investigate the effects of ursolic acid after cerebral hemorrhage. Online databases were used to obtain potential therapeutic targets of ursolic acid for the treatment of cerebral hemorrhage, and possible mechanisms were analyzed by KEGG, GO, and molecular docking. A rat model of cerebral hemorrhage was established using collagenase, and an in vitro cerebral hemorrhage model was constructed by adding hemin to BV2 cell culture medium. Enzyme-linked immunosorbent assay (ELISA), Western blotting (WB), immunofluorescence, TUNEL staining, and calcein/PI staining were used to investigate the degree of microglial M1 polarization, changes in the levels of inflammatory factors, activation of the NF-κB pathway, and changes in the indicators of cellular death after ursolic acid treatment. In addition, phorbol 12-myristate 13-acetate (PMA) was used to activate the NF-κB pathway to verify that ursolic acid exerts its anti-neuroinflammatory effects by regulating the NF-κB/NLRP3/GSDMD pathway. Network pharmacology and bioinformatics analyses revealed that ursolic acid may exert its therapeutic effects on cerebral hemorrhage through multiple pathways. Together, in vivo and in vitro experiments showed that ursolic acid inhibited microglial M1 polarization and significantly reduced the levels of p-NF-κB, GSDMD-N, cleaved caspase-1, TNF-α, IL-6, and IL-1β, which were significantly inhibited by the use of PMA. Ursolic acid inhibits microglial pyroptosis via the NF-κB/NLRP3/GSDMD pathway to alleviate neuroinflammatory responses after cerebral hemorrhage.
Mitoquinone Alleviates Donation after Cardiac Death Kidney Injury during Hypothermic Machine Perfusion in Rat Model
Authors: Radajewska Anna , Szyller Jakub , Krzywonos-Zawadzka Anna , Olejnik Agnieszka , Sawicki Grzegorz , Bil-Lula Iwona
Published: October 2023

Transplanted organs are subjected to harmful conditions through stopping blood flow, hypothermic storage of the graft, and subsequent reperfusion. In particular, kidneys donated from patients after cardiac arrest (DCD) are classified as more vulnerable to ischemia–reperfusion injury (IRI). Hypothermic machine perfusion is proposed as a solution for better kidney storage before transplantation, and it is a good platform for additional graft treatment. Antioxidants have gained interest in regenerative medicine due to their ability to scavenge reactive oxygen species (ROS), which play a key role in IRI. We evaluated the effect of Mitoquinone (MitoQ), a strong mitochondria-targeted antioxidant, administered directly to the perfusing buffer. Rat kidneys were isolated, randomly classified into one of the following groups, donation after brainstem death (DBD), DCD, and DCD with MitoQ, and perfused for 22 hours with a hypothermic machine perfusion system. Subsequently, we detected levels of kidney injury (KIM-1) and oxidative stress (ROS/RNS, cytochrome C oxidase, and mitochondrial integrity) markers. We compared the activation of the apoptosis pathway (caspase 3 and 9), the concentration of phosphorylated Akt (pAkt), and the pAkt/total Akt ratio. MitoQ reduces KIM-1 concentration, total ROS/RNS, and the level of caspases. We observed a decrease in pAkt and the pAkt/total Akt ratio after drug administration. The length of warm ischemia time negatively impacts the graft condition. However, MitoQ added to the perfusing system as an ‘on pump’ therapy mitigates injury to the kidney before transplantation by inhibiting apoptosis and reducing ROS/RNS levels. We propose MitoQ as a potential drug for DCD graft preconditioning.
The Cytoprotective Role of Autophagy in Response to BRAF-Targeted Therapies
Authors: Elshazly Ahmed M. , Gewirtz David A.
Published: October 2023

BRAF-targeted therapies are widely used for the treatment of melanoma patients with BRAF V600 mutations. Vemurafenib, dabrafenib as well as encorafenib have demonstrated substantial therapeutic activity; however, as is the case with other chemotherapeutic agents, the frequent development of resistance limits their efficacy. Autophagy is one tumor survival mechanism that could contribute to BRAF inhibitor resistance, and multiple studies support an association between vemurafenib-induced and dabrafenib-induced autophagy and tumor cell survival. Clinical trials have also demonstrated a potential benefit from the inclusion of autophagy inhibition as an adjuvant therapy. This review of the scientific literature relating to the role of autophagy that is induced in response to BRAF-inhibitors supports the premise that autophagy targeting or modulation could be an effective adjuvant therapy.
Genetic Channelization Mechanism of Four Chalcone Isomerase Homologous Genes for Synergistic Resistance to Fusarium wilt in Gossypium barbadense L.
Authors: Zu Qianli , Deng Xiaojuan , Qu Yanying , Chen Xunji , Cai Yongsheng , Wang Caoyue , Li Ying , Chen Qin , Zheng Kai , Liu Xiaodong , Chen Quanjia
Published: October 2023

Duplication events occur very frequently during plant evolution. The genes in the duplicated pathway or network can evolve new functions through neofunctionalization and subfunctionalization. Flavonoids are secondary metabolites involved in plant development and defense. Our previous transcriptomic analysis of F6 recombinant inbred lines (RILs) and the parent lines after Fusarium oxysporum f. sp. vasinfectum (Fov) infection showed that CHI genes have important functions in cotton. However, there are few reports on the possible neofunctionalization differences of CHI family paralogous genes involved in Fusarium wilt resistance in cotton. In this study, the resistance to Fusarium wilt, expression of metabolic pathway-related genes, metabolite content, endogenous hormone content, reactive oxygen species (ROS) content and subcellular localization of four paralogous CHI family genes in cotton were investigated. The results show that the four paralogous CHI family genes may play a synergistic role in Fusarium wilt resistance. These results revealed a genetic channelization mechanism that can regulate the metabolic flux homeostasis of flavonoids under the mediation of endogenous salicylic acid (SA) and methyl jasmonate (MeJA) via the four paralogous CHI genes, thereby achieving disease resistance. Our study provides a theoretical basis for studying the evolutionary patterns of homologous plant genes and using homologous genes for molecular breeding.
Annexin A2 Stabilizes Oncogenic JAG1 Intracellular Domain by Inhibiting Proteasomal Degradation in Glioblastoma Cells
Authors: Ham Seok Won , Kim Jung Yun , Seo Sunyoung , Hong Nayoung , Park Min Ji , Kim Yoonji , Jang Junseok , Park Sehyeon , Lee Silvee Jisoo , Kim Jun-Kyum , Kim Eun-Jung , Kim Sung-Ok , Kim Sung-Chan , Park Jong-Whi , Kim Hyunggee
Published: October 2023

Glioblastoma (GBM) is the most lethal brain cancer, causing inevitable deaths of patients owing to frequent relapses of cancer stem cells (CSCs). The significance of the NOTCH signaling pathway in CSCs has been well recognized; however, there is no NOTCH-selective treatment applicable to patients with GBM. We recently reported that Jagged1 (JAG1), a NOTCH ligand, drives a NOTCH receptor-independent signaling pathway via JAG1 intracellular domain (JICD1) as a crucial signal that renders CSC properties. Therefore, mechanisms regulating the JICD1 signaling pathway should be elucidated to further develop a selective therapeutic regimen. Here, we identified annexin A2 (ANXA2) as an essential modulator to stabilize intrinsically disordered JICD1. The binding of ANXA2 to JICD1 prevents the proteasomal degradation of JICD1 by heat shock protein-70/90 and carboxy-terminus of Hsc70 interacting protein E3 ligase. Furthermore, JICD1-driven propagation and tumor aggressiveness were inhibited by ANXA2 knockdown. Taken together, our findings show that ANXA2 maintains the function of the NOTCH receptor-independent JICD1 signaling pathway by stabilizing JICD1, and the targeted suppression of JICD1-driven CSC properties can be achieved by blocking its interaction with ANXA2.
Epigenetic Marks as Predictors of Metabolic Response to Bariatric Surgery: Validation from an Epigenome Wide Association Study
Authors: Gutiérrez-Repiso Carolina , Cantarero-Cuenca Antonio , González-Jiménez Andrés , Linares-Pineda Teresa , Peña-Montero Nerea , Ocaña-Wilhelmi Luis , Tinahones Francisco J. , Morcillo Sonsoles
Published: October 2023

Little is known about the potential role of epigenetic marks as predictors of the resolution of obesity-related comorbidities after bariatric surgery. In this study, 20 patients were classified according to the metabolic improvement observed 6 months after sleeve gastrectomy, based on the diagnosis of metabolic syndrome, into responders if metabolic syndrome reversed after bariatric surgery (n = 10) and non-responders if they had metabolic syndrome bariatric surgery (n = 10). Blood DNA methylation was analyzed at both study points using the Infinium Methylation EPIC Bead Chip array-based platform. Twenty-six CpG sites and their annotated genes, which were previously described to be associated with metabolic status, were evaluated. Cg11445109 and cg19469447 (annotated to Cytochrome P450 2E1 (CYP2E1) gene) were significantly more hypomethylated in the responder group than in the non-responder group at both study points, whilst cg25828445 (annotated to Nucleolar Protein Interacting With The FHA Domain Of MKI67 Pseudogene 3 (NIFKP3) gene) showed to be significantly more hypermethylated in the non-responder group compared to the responder group at both study points. The analysis of the methylation sites annotated to the associated genes showed that CYP2E1 had 40% of the differentially methylated CpG sites, followed by Major Histocompatibility Complex, Class II, DR Beta 1 (HLA-DRB1) (33.33%) and Zinc Finger Protein, FOG Family Member 2 (ZFPM2) (26.83%). Cg11445109, cg19469447 and cg25828445 could have a role in the prediction of metabolic status and potential value as biomarkers of response to bariatric surgery.
Systemic Effects of Homoarginine Supplementation on Arginine Metabolizing Enzymes in Rats with Heart Failure with Preserved Ejection Fraction
Authors: Büttner Petra , Werner Sarah , Böttner Julia , Ossmann Susann , Schwedhelm Edzard , Thiele Holger
Published: October 2023

A restoration of low homoarginine (hArg) levels in obese ZSF1 rats (O-ZSF1) before (S1-ZSF1) and after (S2-ZSF1) the manifestation of heart failure with preserved ejection fraction (HFpEF) did not affect the worsening of cardiac HFpEF characteristics. Here, potential regulation of key enzymes of arginine metabolism in other organs was analyzed. Arginase 2 (ARG2) was reduced >35% in the kidney and small intestine of hArg-supplemented rats compared to O-ZSF1. Glycine amidinotransferase (GATM) was 29% upregulated in the kidneys of S1-ZSF1. Dimethylarginine dimethylaminohydrolase 1 (DDAH1) levels were reduced >50% in the livers of O-ZSF1 but restored in S2-ZSF1 compared to healthy rats (L-ZSF1). In the skeletal muscle, iNOS was lower in O-ZSF1 and further decreased in S1-ZSF1 and S2-ZSF1 compared to L-ZSF1. iNOS levels were lower in the liver of the S2-ZSF1 group but higher in the kidneys of S1-ZSF1 compared to L-ZSF1. Supplementation with hArg in an in vivo HFpEF model resulted in the inhibition of renal ARG2 and an increase in GATM expression. This supplementation might contribute to the stabilization of intestinal iNOS and ARG2 imbalances, thereby enhancing barrier function. Additionally, it may offer protective effects in skeletal muscle by downregulating iNOS. In the conceptualization of hArg supplementation studies, the current disease progression stage as well as organ-specific enzyme regulation should be considered.
Integrated Bioinformatics Analysis Confirms the Diagnostic Value of Nourin-Dependent miR-137 and miR-106b in Unstable Angina Patients
Authors: Elgebaly Salwa A. , Peacock W. Frank , Christenson Robert H. , Kreutzer Donald L. , Faraag Ahmed Hassan Ibrahim , Sarguos Amir Mahfouz Mokhtar , El-Khazragy Nashwa
Published: October 2023

The challenge of rapidly diagnosing myocardial ischemia in unstable angina (UA) patients presenting to the Emergency Department (ED) is due to a lack of sensitive blood biomarkers. This has prompted an investigation into microRNAs (miRNAs) related to cardiac-derived Nourin for potential diagnostic application. The Nourin protein is rapidly expressed in patients with acute coronary syndrome (ACS) (UA and acute myocardial infarction (AMI)). MicroRNAs regulate gene expression through mRNA binding and, thus, may represent potential biomarkers. We initially identified miR-137 and miR-106b and conducted a clinical validation, which demonstrated that they were highly upregulated in ACS patients, but not in healthy subjects and non-ACS controls. Using integrated comprehensive bioinformatics analysis, the present study confirms that the Nourin protein targets miR-137 and miR-106b, which are linked to myocardial ischemia and inflammation associated with ACS. Molecular docking demonstrated robust interactions between the Nourin protein and miR137/hsa-miR-106b, involving hydrogen bonds and hydrophobic interactions, with −10 kcal/mol binding energy. I-TASSER generated Nourin analogs, with the top 10 chosen for structural insights. Antigenic regions and MHCII epitopes within the Nourin SPGADGNGGEAMPGG sequence showed strong binding to HLA-DR/DQ alleles. The Cytoscape network revealed interactions of -miR137/hsa-miR--106b and Phosphatase and tensin homolog (PTEN) in myocardial ischemia. RNA Composer predicted the secondary structure of miR-106b. Schrödinger software identified key Nourin-RNA interactions critical for complex stability. The study identifies miR-137 and miR-106b as potential ACS diagnostic and therapeutic targets. This research underscores the potential of miRNAs targeting Nourin for precision ACS intervention. The analysis leverages RNA Composer, Schrödinger, and I-TASSER tools to explore interactions and structural insights. Robust Nourin-miRNA interactions are established, bolstering the case for miRNA-based interventions in ischemic injury. In conclusion, the study contributes to UA and AMI diagnosis strategies through bioinformatics-guided exploration of Nourin-targeting miRNAs. Supported by comprehensive molecular analysis, the hypoxia-induced miR-137 for cell apoptosis (a marker of cell damage) and the inflammation-induced miR-106b (a marker of inflammation) confirmed their potential clinical use as diagnostic biomarkers. This research reinforces the growing role of miR-137/hsa-miR-106b in the early diagnosis of myocardial ischemia in unstable angina patients.
Overview of Membrane Protein Sample Preparation for Single-Particle Cryo-Electron Microscopy Analysis
Authors: Vénien-Bryan Catherine , Fernandes Carlos A. H.
Published: October 2023

Single-particle cryo-electron microscopy (cryo-EM SPA) has recently emerged as an exceptionally well-suited technique for determining the structure of membrane proteins (MPs). Indeed, in recent years, huge increase in the number of MPs solved via cryo-EM SPA at a resolution better than 3.0 Å in the Protein Data Bank (PDB) has been observed. However, sample preparation remains a significant challenge in the field. Here, we evaluated the MPs solved using cryo-EM SPA deposited in the PDB in the last two years at a resolution below 3.0 Å. The most critical parameters for sample preparation are as follows: (i) the surfactant used for protein extraction from the membrane, (ii) the surfactant, amphiphiles, nanodiscs or other molecules present in the vitrification step, (iii) the vitrification method employed, and (iv) the type of grids used. The aim is not to provide a definitive answer on the optimal sample conditions for cryo-EM SPA of MPs but rather assess the current trends in the MP structural biology community towards obtaining high-resolution cryo-EM structures.
Transcriptional Regulation of Airway Epithelial Cell Differentiation: Insights into the Notch Pathway and Beyond
Authors: Cumplido-Laso Guadalupe , Benitez Dixan A. , Mulero-Navarro Sonia , Carvajal-Gonzalez Jose Maria
Published: October 2023

The airway epithelium is a critical component of the respiratory system, serving as a barrier against inhaled pathogens and toxins. It is composed of various cell types, each with specific functions essential to proper airway function. Chronic respiratory diseases can disrupt the cellular composition of the airway epithelium, leading to a decrease in multiciliated cells (MCCs) and an increase in secretory cells (SCs). Basal cells (BCs) have been identified as the primary stem cells in the airway epithelium, capable of self-renewal and differentiation into MCCs and SCs. This review emphasizes the role of transcription factors in the differentiation process from BCs to MCCs and SCs. Recent advancements in single-cell RNA sequencing (scRNAseq) techniques have provided insights into the cellular composition of the airway epithelium, revealing specialized and rare cell types, including neuroendocrine cells, tuft cells, and ionocytes. Understanding the cellular composition and differentiation processes within the airway epithelium is crucial for developing targeted therapies for respiratory diseases. Additionally, the maintenance of BC populations and the involvement of Notch signaling in BC self-renewal and differentiation are discussed. Further research in these areas could provide valuable insights into the mechanisms underlying airway epithelial homeostasis and disease pathogenesis.
Broadband EPR Spectroscopy of the Triplet State: Multi-Frequency Analysis of Copper Acetate Monohydrate
Authors: Hagen Wilfred R.
Published: October 2023

Electron paramagnetic resonance spectroscopy is a long-standing method for the exploration of electronic structures of transition ion complexes. The difficulty of its analysis varies considerably, not only with the nature of the spin system, but more so with the relative magnitudes of the magnetic interactions to which the spin is subject, where particularly challenging cases ensue when two interactions are of comparable magnitude. A case in point is the triplet system S = 1 of coordination complexes with two unpaired electrons when the electronic Zeeman interaction and the electronic zero-field interaction are similar in strength. This situation occurs in the X-band spectra of the thermally excited triplet state of dinuclear copper(II) complexes, exemplified by copper acetate monohydrate. In this study, applicability of the recently developed low-frequency broadband EPR spectrometer to S = 1 systems is investigated on the analysis of multi-frequency, 0.5–16 GHz, data from [Cu(CH3COO)2H2O]2. Global fitting affords the spin Hamiltonian parameters gz = 2.365 ± 0.008; gy = 2.055 ± 0.010; gx = 2.077 ± 0.005; Az = 64 gauss; D = 0.335 ± 0.002 cm−1; E = 0.0105 ± 0.0003 cm−1. The latter two define zero-field absorptions at ca. 630, 7730, and 10,360 MHz, which show up in the spectra as one half of a sharpened symmetrical line. Overall, the EPR line shape is Lorentzian, reflecting spin-lattice relaxation, which is a combination of an unusual, essentially temperature-independent, inverted Orbach process via the S = 0 ground state, and a Raman process proportional to T2. Other broadening mechanisms are limited to at best minor contributions from a distribution in E values, and from dipolar interaction with neighboring copper pairs. Monitoring of a first-order double-quantum transition between 8 and 35 GHz shows a previously unnoticed very complex line shape behavior, which should be the subject of future research.