bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hepatic Nrf1 (Nfe2l1) promotes VLDL dependent liver defense against sepsis
Authors: Trites Michael J. , Li Lei , Akl May G. , Hydomako Aidan , Widenmaier Scott B. 
Published: July 2024

AbstractSepsis causes mortality by triggering organ damage. Interest has emerged in stimulating disease tolerance to reduce organ damage. Liver plays a role in disease tolerance by mediating defensive adaptations, but sepsis-induced liver damage limit these effects. Here, we investigated whether stress defending transcription factors nuclear factor erythroid 2 related factor-1 (Nrf1) and -2 (Nrf2) in hepatocytes protect against sepsis. Using mice, we evaluated responses by hepatic Nrf1 and Nrf2 during sepsis triggered by lipopolysaccharide orEscherichia coli. We also genetically altered hepatic Nrf1 and Nrf2 activity to determine the protective role of these factors in sepsis. Our results show hepatic Nrf1 and Nrf2 activity is reduced in severe sepsis and hepatic Nrf1, but not Nrf2, deficiency predisposes for hypothermia and mortality. In contrast, enhancing hepatic Nrf1 activity protects against hypothermia and improves survival. Moreover, in sepsis hepatic Nrf1 deficiency reduces VLDL secretion whereas enhancing hepatic Nrf1 increases VLDL secretion, and inhibiting VLDL secretion with lomitapide obstructs protective actions of hepatic Nrf1. Gene expression profiles suggest Nrf1 promotes this effect by inducing stress defenses. Hence, we show mortality in sepsis may result from impaired stress defense and that hepatic Nrf1 improves disease tolerance during sepsis by promoting VLDL dependent liver defense.
Characterization of theCannabis sativaglandular trichome epigenome
Authors: Conneely Lee J. , Hurgobin Bhavna , Ng Sophia , Tamiru-Oli Muluneh , Lewsey Mathew G. 
Published: July 2024

AbstractBackgroundThe relationship between epigenomics and plant specialised metabolism remains largely unexplored despite the fundamental importance of epigenomics in gene regulation and, potentially, yield of products of plant specialised metabolic pathways. The glandular trichomes ofCannabis sativaare an emerging model system that produce large quantities of cannabinoid and terpenoid specialised metabolites with known medicinal and commercial value. To address the lack of epigenomic data in plant specialised metabolism, glandular trichomes, andC. sativa, we mapped H3K4 trimethylation, H3K56 acetylation, H3K27 trimethylation post-translational modifications and the histone variant H2A.Z, using chromatin immunoprecipitation, in glandular trichomes, leaf, and stem tissues. Corresponding transcriptomic (RNA-seq) datasets were integrated, and tissue-specific analyses conducted to relate chromatin states to glandular trichome specific gene expression.ResultsCannabinoid and terpenoid biosynthetic genes, specialised metabolite transporters, and defence related genes, were co-located with distal H3K56ac chromatin, a histone mark that flanks active distal enhancersin planta, exclusively in glandular trichomes. Glandular trichome specific H3K4 trimethylated chromatin was associated with genes involved in specialised metabolism and sucrose and starch metabolism. Bi-valent chromatin loci specific to glandular trichomes, marked with H3K4 trimethylation and H3K27 trimethylation, was associated with genes of MAPK signalling pathways and plant specialised metabolism pathways, supporting recent hypotheses that implicate bi-valent chromatin in plant defence. The histone variant H2A.Z was largely found in intergenic regions and enriched in chromatin that contained genes involved in DNA homeostasis.ConclusionWe report the first genome-wide histone post-translational modification maps forC. sativaglandular trichomes, and more broadly for glandular trichomes in plants. Our findings have implications in plant adaptation and stress response and provide a basis for enhancer-mediated, targeted, gene transformation studies in plant glandular trichomes.
Effector T cells in poorly perfused tumor regions exhibit a distinct signature of augmented IFN response and reduced PD-1 expression
Authors: Riera-Borrull Marta , Vaquero Sonia Tejedor , Porqueras Víctor Cerdán , Aramburu Jose , López-Rodríguez Cristina 
Published: July 2024

ABSTRACTEffector T lymphocytes are avid glucose consumers, but can function in the nutrient-poor environments of tumors. However, availability of blood-delivered nutrients throughout the tumor is not homogeneous, and how this affects effector T cells is not well known. Here we have isolated tumor-infiltrating T lymphocytes (TILs) from mouse solid tumors by their capacity to capture blood-transported probes, and compared them with glucose-restricted T cells. Glucose restrictionin vitroarrested cell proliferation but reduced only moderately the induction of hallmark glucose-dependent cytokines interferon gamma (IFNγ) and IL-17.In vivo, effector TILs with reduced access to blood had characteristics of glucose-restricted cells, such as reduced expression of IFNγ and genes associated with cell proliferation. However, they expressed more CXCR3, which identifies effective antitumor T lymphocytes, showed an enhanced IFN response signature, and had reduced expression of surface PD-1. We also identified genes regulated by the enzyme ACSS2, which allows TILs to sustain gene expression in glucose-poor environments. Thus, effector T lymphocytes infiltrating tumors express different gene signatures in regions with different accessibility to blood, and can maintain specific glucose-dependent responses even in poorly perfused tumor regions. Our results can help better understand nutrient-dependent TIL heterogeneity in changing tumor microenvironments.Abstract Figure
DNA walk of specific fused oncogenes exhibit distinct fractal geometric characteristics in nucleotide patterns
Authors: Das Abhijeet , Sehgal Manas , Singh Ashwini , Goyal Rishabh , Prabhakar Mallika , Fricke Jeremy , Mambetsariev Isa , Kulkarni Prakash , Jolly Mohit Kumar , Salgia Ravi 
Published: July 2024

AbstractBackground/ObjectivesThe complex system of cancer has led to an emphasis on understanding the more general causal relationship within the disease. In this context, concepts of symmetry and symmetry-breaking in distinct biological cell features or components have been examined as an approach to cancer investigation. However, there can be possible limitations in directly interpreting the symmetry-based approach from a physical viewpoint due to the lack of understanding of physical laws governing symmetry in complex systems like cancer.MethodsFractal geometry and DNA walk representation were employed to investigate the geometric features i.e., self-similarity and heterogeneity in DNA nucleotide coding sequences of wild-type and mutated oncogenes, tumour-suppressor, and other unclassified genes. The mutation-facilitated self-similar and heterogenous features were quantified by the fractal dimension and lacunarity coefficient measures, respectively. Additionally, the geometrical orderedness and disorderedness in the analyzed sequences were interpreted from the combination of the fractal measures.ResultsThe findings showed distinct fractal geometric features in the case of fusion mutations. It also highlights the possible interpretation of the observed fractal features as geometric analogues concerning explicit observations corresponding to specific cancer types. In addition, the two-dimensional multi-fractal analysis highlighted the presence of a single exponent in the scaling of mutation-mediated gene sequence self-similarity/complexity and heterogeneity.ConclusionsThe approach identified mutation-induced geometric features in gene sequences, demonstrating the potential of DNA walks and fractal analysis in translational research regarding cancer. The findings suggest that investigating fractal parameters can capture unique geometric features in nucleotide sequences, contributing to the understanding of cancer’s molecular complexity.
Landscape conservation and orchard management influence carob tree yield through changes in pollinator communities
Authors: Gómez-Martínez Carmelo , González-Estévez Miguel A. , deCastro-Arrazola Indradatta , Unglaub Peter , Lázaro Amparo 
Published: July 2024

AbstractWorldwide pollinator declines are a major problem for agricultural production. However, understanding how landscape characteristics and local management influence crop production through its pollinators is still a challenge. By sampling 20 orchards in Mallorca island (Spain), we evaluated how the landscape (habitat loss) and orchard local management (farming system: conventional vs. ecological; male-to-female ratio) influenced pollinator communities and production in carob trees (Ceratonia siliqua), a crop of high economic importance in Mediterranean areas. We found that orchards surrounded by larger natural areas received more visits by wild bees and butterflies and fewer by honeybees. Ecological farming tended to increase overall pollinator abundance in the orchards. High male-to-female ratio enhanced overall pollinator abundance and shaped pollinator composition, by increasing hoverfly abundance and decreasing wasps and flies. Male-to-female ratio showed hump-shaped relationships with fruit and seed production per female tree (peak at 0.7 males/female), whereas total orchard production maximized with 20-30% of males. Seed weight (farmer’s highest economic value) increased in conserved landscapes where wild pollinators prevailed, and with overall pollinator abundance; however, it decreased with male-to-female ratio, likely due to seed number-size trade-offs. Management strategies to enhance carob production may optimize sex ratios and favor wild pollinators by reducing pesticide use and preserving natural landscapes.
TSS-Captur: A User-Friendly Characterization Pipeline for Transcribed but Unclassified RNA transcripts
Authors: Paz Mathias Witte , Vogel Thomas , Nieselt Kay 
Published: July 2024

AbstractRNA-seq and its 5’-enrichment-based methods for prokaryotes have enabled the base-exact identification of transcription starting sites (TSSs) and have improved gene expression analysis. Computational methods analyze this experimental data to identify TSSs and classify them based on proximal annotated genes. While some TSSs cannot be classified at all (orphan TSSs), other TSSs are found on the reverse strand of known genes (antisense TSSs), but are not associated with the direct transcription of any known gene. Here, we introduceTSS-Captur, a novel pipeline, that uses computational approaches to characterize genomic regions starting from experimentally confirmed, but unclassified TSSs. By analyzing experimental TSS data,TSS-Capturcharacterizes unclassified signals, hence complementing prokaryotic genome annotation tools and enhancing the bacterial transcriptome understanding.TSS-Capturclassifies extracted transcripts into coding or non-coding genes and predicts for each putative transcript its transcription termination site. For non-coding genes, the secondary structure is computed. Furthermore, putative promoter regions are analyzed to identify enriched motifs. An interactive report allows a seamless data exploration. We validatedTSS-Capturwith aCampylobacter jejunidataset and characterized unlabeled non-coding RNAs inStreptomyces coelicolor. Besides its usage over the command-line,TSS-Capturis available as a web-application to enhance its user accessibility and explorative capabilities.
Decision-making shapes dynamic inter-areal communication within macaque ventral frontal cortex
Authors: Stoll Frederic M. , Rudebeck Peter H. 
Published: July 2024

SUMMARYMacaque ventral frontal cortex is comprised of a set of anatomically heterogeneous and highly interconnected areas. Collectively these areas have been implicated in many higher-level affective and cognitive processes, most notably the adaptive control of decision-making. Despite this appreciation, little is known about how subdivisions of ventral frontal cortex dynamically interact with each other during decision-making. Here we assessed functional interactions between areas by analyzing the activity of thousands of single neurons recorded from eight anatomically defined subdivisions of ventral frontal cortex in macaques performing a visually guided two-choice probabilistic task for different fruit juices. We found that the onset of stimuli and reward delivery globally increased communication between all parts of ventral frontal cortex. Inter-areal communication was, however, temporally specific, occurred through unique activity subspaces between areas, and depended on the encoding of decision variables. In particular, areas 12l and 12o showed the highest connectivity with other areas while being more likely to receive information from other parts of ventral frontal cortex than to send it. This pattern of functional connectivity suggests a role for these two areas in integrating diverse sources of information during decision processes. Taken together, our work reveals the specific patterns of inter-areal communication between anatomically connected subdivisions of ventral frontal cortex that are dynamically engaged during decision-making.
Stat3 mediates Fyn kinase driven dopaminergic neurodegeneration and microglia activation
Authors: Siddiqui Sahiba , Liu Fang , Kanthasamy Anumantha G. , McGrail Maura 
Published: July 2024

AbstractThe Alzheimer’s Disease and Parkinson’s Disease risk locus Fyn kinase is implicated in neurodegeneration and inflammatory signaling. To investigatein vivomechanisms of Fyn driven neurodegeneration, we built a zebrafish neural specific Gal4:UAS model of constitutively active FynY531F signaling. Usingin vivolive imaging we demonstrate neural FynY531F expression lead to dopaminergic neuron loss and mitochondrial aggregation in 5 day larval brain. Dopaminergic loss coincided with microglia activation and induction oftnfa,il1b, andil12ainflammatory cytokine expression. Transcriptome analysis revealed Stat3 signaling as a potential Fyn target. Chemical inhibition experiments confirmed Fyn driven dopaminergic neuron loss and the inflammatory response were dependent upon activation of Stat3 and NF-κB pathways. Dual chemical inhibition demonstrated Stat3 acts synergistically with NF-κB in dopaminergic neuron degeneration. These results identify Stat3 as a novel downstream effector of Fyn signaling in neurodegeneration and inflammation.Summary StatementThis study describes a novelin vivomodel of neural Fyn Kinase activation and identifies Stat3 signaling as a downstream Fyn effector in dopaminergic neuron degeneration and neuroinflammation.Abstract FigureGraphical abstract- Neural Fyn signaling drives dopaminergic neurodegeneration, mitochondria accumulation, and microglia activation- Fyn driven neurodegeneration and cytokine expression are dependent on Stat3- Stat3 and NF-kB pathways synergize in dopaminergic neuron degeneration
Regulation of cell–nanoparticle interactions through mechanobiology
Authors: Cassani Marco , Niro Francesco , Durikova Helena , Morazzo Sofia , Pereira-Sousa Daniel , Fernandes Soraia , Vrbsky Jan , Oliver-De La Cruz Jorge , Klimovic Simon , Pribyl Jan , Loja Tomas , Skladal Petr , Caruso Frank , Forte Giancarlo 
Published: July 2024

AbstractBio–nano interactions have been extensively explored in nanomedicine to develop selective delivery strategies, reduce systemic toxicity, and minimize therapeutic dosing requirements. To enhance the delivery of nanocarriers to cancer cells and improve the therapeutic efficiency and clinical translation of nanomedicines, numerous nanomaterials with diverse and tunable properties have been developed. However, the limited clinical translation of nanoparticle-based therapies, largely due to issues associated with poor targeting and therapeutic delivery, requires a deeper understanding of the biological phenomena underlying cell–nanoparticle interactions. In this context, herein we investigate the molecular and cellular mechanobiology parameters that control such interactions. We demonstrate that the pharmacological inhibition or the genetic ablation of the key mechanosensitive component of the Hippo pathway, i.e., yes-associated protein, enhances nanoparticle internalization by 1.5-fold. Importantly, this phenomenon occurs independently of nanoparticle properties, such as size, or cell properties such as surface area, substrate adhesion, and stiffness. Our study reveals that the internalization of nanoparticles in target cells can be controlled by modulating cell mechanosensing pathways, potentially ultimately enhancing nanoparticle delivery and nanotherapy specificity.
Investigating the Efficacy of Ergothioneine to Delay Cognitive Decline in Mild Cognitively Impaired Subjects: A Pilot Study
Authors: Yau Yu Fung , Cheah Irwin K. , Mahendran Rathi , Tang Richard M.Y. , Chua Ru Yuan , Goh Rachel E.S. , Feng Lei , Li Jialiang , Kua Ee Heok , Chen Christopher , Halliwell Barry 
Published: July 2024

AbstractBackground and objectiveDementia, particularly Alzheimer’s disease, is a major healthcare challenge in ageing societies. Therefore, this study aimed to investigate the efficacy and safety of a dietary compound, ergothioneine, in delaying cognitive decline in elderly individuals.Design, intervention and measurementsNineteen subjects aged 60 or above with mild cognitive impairment were recruited for this double-blinded, randomized, and placebo- controlled study. Subjects received either ergothioneine (25mg per capsule) or a placebo, taken 3 times a week for one year. The whole blood profile, markers of renal and liver functions, neurocognitive performance, plasma levels of ergothioneine and its metabolites, and plasma biomarkers related to neurodegeneration were measured across the study.ResultErgothioneine intake did not alter clinical safety markers (blood counts, kidney and liver function) throughout the study, further validating its safety for human consumption. Subjects receiving ergothioneine demonstrated improved performance in assessment of learning ability and stabilized plasma levels of neurofilament light chain, compared with placebo group which saw no improvement in cognitive assessments and a significant increase in neurofilament light chain.ConclusionProlonged intake of ergothioneine showed no toxicity in elderly individuals. Enhanced Rey Auditory Verbal Learning Test performance and stabilized neurofilament light chain levels suggest improvements in memory and learning abilities, alongside a deceleration of neuronal damage. Our results add to existing data that ergothioneine is safe for extended consumption and may hold the potential to delay cognitive decline in the elderly.
Non-contact and non-constraining monitoring of the respiratory rate including sleep disordered breathing using ultra-wideband radar
Authors: Kazuo Chin , Shigeaki Okumura , Daisuke Endo , Kazuma Nagata , Tatsuya Ito , Kimihiko Murase , Hironobu Sunadome , Mamiko Hoshi , Hisato Hiranuma , Yutaka Kozu , Susumu Sato , Toyohiro Hirai , Yasuhiro Gon , Takuya Sakamoto , Hirofumi Taki , Toshiki Akahoshi 
Published: July 2024

AbstractBackgroundThe respiratory rate (RR) is a critical vital sign controlled by not only metabolic factors but behavior while awake. The prevalence of obstructive sleep apnea (OSA) is remarkably high. Therefore, a non-constraining and non-contact respiratory monitor to measure the RR both while awake and asleep is preferable.MethodsA millimeter wave radar (MWR) device was used for RR monitoring of participants suspected of OSA while awake (supine before and after polysomnography [PSG], sitting, and positioned on both sides) and asleep. Apnea and hypopnea during 1 hour of sleep (AHI) by PSG was compared with 1 hour of respiratory events (REI) judged by MWR. Portable monitoring (PM) and percutaneous arterial O2(SpO2) monitoring were done simultaneously.ResultsCorrelations between the RR by MWR and respiratory inductance plethysmography at PSG while awake in every measured position including the supine position before and after PSG were very high (r=0.92∼0.99) (n=60). The REI by MWR were significantly correlated with AHI determined by PSG, PM, or SpO2monitoring (p<0.001). Brand-Altman plot showed that the MWR for AHI monitoring was acceptable. Predicted AHI by MWR relative to PSG was almost the same as with PM or SpO2monitoring.ConclusionsThe developed MWR respiratory monitor was useful during wakefulness and sleep, including detection of apnea and hypopnea. This system can be useful in multiple medical settings such as critical care with and without sleep apnea, pandemic infection, elder care at home, etc. Trial registration number: UMIN000045833 (http://www.umin/ac.jp)
Typing of feces-derivedCandida albicansstrains using a novel seven-locus microsatellite panel reveals associations with yeast phenotype in individuals with inflammatory bowel disease
Authors: van Thiel Isabelle A.M. , Kreulen Irini A.M. , Bénard Mèlanie V. , de Goffau Marcus C. , Theelen Bart , Heinsbroek Sigrid E.M. , Zylka Patrycja K. , Ponsioen Cyriel Y. , Boekhout Teun , de Jonge Wouter J. , Rosendahl Søren , van den Wijngaard René M. , Hagen Ferry 
Published: July 2024

AbstractInflammatory diseases of the human gastrointestinal tract are affected by the microbes that reside in the mucosal surfaces along this tract. Patients with inflammatory bowel diseases (IBD) have altered bacterial and fungal intestinal compositions, including higher levels of fecalCandidayeasts. Ongoing research indicates that genetic and phenotypic diversity ofCandida albicansmay be linked with disease severity. In this study, we set out to investigate feces-derivedC. albicansstrains from individuals with Crohn’s disease, ulcerative colitis, and healthy volunteers through microsatellite-based genotyping and phenotypic assays. A seven-locus microsatellite panel was applied, of which six loci were newly developed. Combined interpretation of minimum spanning networks and principal component analysis (PCA) led to indications that there is no specific lineage ofC. albicansthat is associated with IBD, but rather that the three study populations do have distinguishable distributions of genotypes. In addition, phenotypic characterization by means of enzyme release assays revealed trends between genotypes and virulence-related enzyme activity. Furthermore, correlations were observed between the clinical inflammation biomarker fecal calprotectin and serum anti-Saccharomyces cerevisiaeantibodies, as well as between lipase activity of feces-derivedC. albicansstrains and serum 1,3-β-glucan levels. We thus show that microsatellite typing can describe genetic diversity of feces-derivedC. albicansstrains, and that phenotypic diversity of these strains may indeed correlate with fungal genotype or disease. This study opens further possibilities to investigate fecal fungi in relation to severity of inflammation in IBD or in other (intestinal) diseases.