bluuebunny/crossref_metadata_2025 huggingface dataset:
Transcriptome Analysis Identifies Accumulation of Natural Killer Cells with Enhanced Lymphotoxin-β Expression during Glioblastoma Progression
Authors: Monaco Gianni , Khavaran Ashkan , Gasull Adrià Dalmau , Cahueau Jonathan , Diebold Martin , Chhatbar Chintan , Friedrich Mirco , Heiland Dieter Henrik , Sankowski Roman
Published: October 2022

Glioblastomas are the most common primary brain tumors. Despite extensive clinical and molecular insights into these tumors, the prognosis remains dismal. While targeted immunotherapies have shown remarkable success across different non-brain tumor entities, they failed to show efficacy in glioblastomas. These failures prompted the field to reassess the idiosyncrasies of the glioblastoma microenvironment. Several high-dimensional single-cell RNA sequencing studies generated remarkable findings about glioblastoma-associated immune cells. To build on the collective strength of these studies, we integrated several murine and human datasets that profiled glioblastoma-associated immune cells at different time points. We integrated these datasets and utilized state-of-the-art algorithms to investigate them in a hypothesis-free, purely exploratory approach. We identified a robust accumulation of a natural killer cell subset that was characterized by a downregulation of activation-associated genes with a concomitant upregulation of apoptosis genes. In both species, we found a robust upregulation of the Lymphotoxin-β gene, a cytokine from the TNF superfamily and a key factor for the development of adaptive immunity. Further validation analyses uncovered a correlation of lymphotoxin signaling with mesenchymal-like glioblastoma regions in situ and in TCGA and CGGA glioblastoma cohorts. In summary, we identify lymphotoxin signaling as a potential therapeutic target in glioblastoma-associated natural killer cells.
Production of Trans-Cinnamic and p-Coumaric Acids in Engineered E. coli
Authors: Liu Yuqi , Xu Weizhuo , Xu Wei
Published: October 2022

Trans-cinnamic acid and p-coumaric acid are valuable intermediates in the synthesis of flavonoids and are widely employed in food, flavor and pharmaceutical industries. These products can be produced by the deamination of L-phenylalanine and L-tyrosine catalyzed by phenylalanine ammonia lyase or tyrosine ammonia lyase. Phenylalanine ammonia-lyase (PAL, EC 4.3.1.5) from Rhodotorula glutinis do not exhibit strong substrate specificity and can convert both L-phenylalanine and L-tyrosine. In this study, the PAL was utilized as the whole-cell biocatalyst, and the reaction conditions were optimized, and the production of trans-cinnamic acid and p-coumaric acid of 597 mg/L and 525 mg/L were achieved with high purity (>98%).
Ceramic Papers as Structured Catalysts: Preparation and Application for Particulate Removal
Authors: Leonardi Sabrina A. , Miró Eduardo E. , Milt Viviana G.
Published: October 2022

Fibers represent a type of structure of great interest in catalysis since they combine high area to volume ratio and can be fabricated from many types of materials, such as ceramic oxides, polymers, and alloys. They can be used in isolated form or structured, as in the case of the ceramic papers synthesized in this work, following a modified papermaking technique. The addition of cationic and anionic polyelectrolytes improved the retention of ceramic fibers during the ceramic paper formation stage by adsorption processes, through the formation of floccules. In the complex aqueous system containing charged macromolecules, the amounts of polyelectrolytes to be added were determined by titrations. To enhance mechanical properties of ceramic papers, different classes of nanoparticle suspensions can be used as binders. As a novel alternative, we have used different borate-type compounds. Among them, we selected natural ulexite, which was purified and used as a binder of ceramic fibers. In order to improve mechanical resistance and flexibility, measured from tensile indexes and elastic module, the amounts of NaCaB5O6(OH)6.5H2O and the calcination temperature were varied. In this contribution, to take advantage of the unique characteristics of the ulexite-containing ceramic papers, they were impregnated with Co,Ce and Co,Ba,K and tested for diesel soot combustion.
A New Series of Tungstophosphoric Acid-Polymeric Matrix Catalysts: Application in the Green Synthesis of 2-Benzazepines and Analogous Rings
Authors: Aguilera Palacios Edna , Palermo Valeria , Sathicq Angel , Pizzio Luis , Romanelli Gustavo
Published: October 2022

A new series of composite materials (PLMTPA) based on tungstophosphoric acid (TPA) included in a polymeric matrix of polyacrylamide (PLM), with a TPA:PLM ratio of 20/80, 40/60, and 60/40, were synthesized and well characterized by FT-IR, XRD, 31P MAS-NMR, TGA-DSC, and SEM-EDAX. Their acidic and textural properties were determined by potentiometric titration and nitrogen adsorption–desorption isotherms, respectively. Considering 31P MAS-NMR and FT-IR analyses, the main species present in the samples is the [PW12O40]3− anion that, according to XRD results, is highly dispersed in the polymeric matrix or appears as a noncrystalline phase. The thermogravimetric analysis revealed that PLMTPA materials did not undergo any remarkable chemical changes up to 200 °C. Additionally, the PLMTPA materials showed strong acid sites whose number increased with the increment of their TPA content. Finally, PLMTPA materials were used as efficient and recyclable noncorrosive catalysts for the synthesis of 2-benzazepines and related compounds. Good yields (55–88%) and high purity were achieved by a Pictet-Spengler variant reaction between N-aralkylsulfonamides and s-trioxane in soft reaction conditions: low toluene volume, at 70 °C, for 3 h. The described protocol results in a useful and environmentally friendly alternative with operative simplicity. The best catalyst in the optimized reaction conditions, PLMTPA60/40100, was reused six times without appreciable loss of activity.
Photocatalytic Degradation of Methylene Blue under Visible Light Using TiO2 Thin Films Impregnated with Porphyrin and Anderson-Type Polyoxometalates (Cu and Zn)
Authors: Sanguino Alexander , Diaz-Uribe Carlos , Duran Freider , Vallejo William , Guzman Leidy , Ruiz Daniela , Puello Esneyder , Quiñones Cesar , Schott Eduardo , Zarate Ximena
Published: October 2022

In this work, tetra(4-carboxyphenyl)porphyrin (TCPP) and two Anderson-type polyoxomolybdates (containing Cu and Zn, respectively; CuPOM, ZnPOM) were synthesized and deposited on TiO2 thin films. The properties of the obtained materials were characterized through UV–vis spectroscopy, Fourier transform infrared spectroscopy (FT-IR), diffuse reflection spectroscopy, scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDX). The adsorption and photodegradation under the visible light irradiation of methylene blue (MB) were studied for TiO2, TCPP/TiO2, TCPP/CuPOM/TiO2 and TCPP/ZnPOM/TiO2 thin films in aqueous solution. The results of the diffuse reflectance showed two bands in the visible light spectrum for the TCPP/POM/TiO2 systems compared to unmodified TiO2 that does not show any bands in the same region of the spectrum. The TCPP/POM/TiO2 systems showed a higher removal of MB, with an adsorption rate near to 31% for the TCPP/CuPOM/TiO2 film compared to 9% adsorption on the TiO2 film. The kinetic results show that the pseudo-second order model was the best fitting model for the MB adsorption process onto fabricated materials. The photodegradation studies under visible light showed a better performance on TCPP/POM/TiO2 thin films, with an efficiency in the MB photodegradation of near 49% and 44% in aqueous solution for TCPP/CuPOM/TiO2 and TCPP/ZnPOM/TiO2, respectively. The reusability test indicated that the porphyrin films are moderately stable after the performed cycles.
Copper Supported on MgAlOx and ZnAlOx Porous Mixed-Oxides for Conversion of Bioethanol via Guerbet Coupling Reaction
Authors: Liu Zongyang , Li Jie , Tan Yuan , Guo Luyao , Ding Yunjie
Published: October 2022

The direct conversion of biomass-derived ethanol to high-valued-added chemicals has attracted widespread attention recently due to the great economic and environmental advantages. In the present study, the conversion of bioethanol through the Guerbet coupling process was studied in a fixed-bed reactor for MgAlOx and ZnAlOx mixed-oxides supported Cu catalysts. From the results, Cu adding into the system greatly enhance the dehydrogenation of ethanol and increase the H-transfer in the course of Guerbet coupling process. Simultaneously, the porous mixed-oxides provide the acid-base property of the catalysts for intermediate transformation. Notably, for Cu/MgAlOx, the main product of ethanol conversion is butanol, but for Cu/ZnAlOx, the primary product is ethyl acetate. Characterizations such as X-ray diffraction (XRD), high-resolution transmission electron microscopy (HRTEM), X-ray photoelectron spectroscopy (XPS), in situ diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) and CO2 temperature programmed desorption (TPD) were carried out to evaluate the structure and property of the catalysts. In combination with the catalytic performances with the characterization results, the synergistic catalytic effect between metal sites and acid-base sites were elaborated.
Enhanced Electrocatalytic Properties of Co3O4 Nanocrystals Derived from Hydrolyzed Polyethyleneimines in Water/Ethanol Solvents for Electrochemical Detection of Cholesterol
Authors: Alshgari Razan A. , Nafady Ayman , Shah Aqeel Ahmed , Aboelmaaref Amal , Aftab Umair , Ibupoto Mazhar Hussain , Vigolo Brigitte , Tahira Aneela , Ibupoto Zafar Hussain
Published: October 2022

The present study describes the effect of hydrolysis of polyethyleneimines in water/ethanol mixture on the morphology of the cobalt oxide (Co3O4), used as the main sensor component. The structure of the generated Co3O4 nanocrystals is consistent with a well-defined cubic phase crystallography, having only cobalt and oxygen elements. Developing simple, low-cost, sensitive, and selective cholesterol biosensors is essential for accurate monitoring of cholesterol to avoid cardiovascular diseases. These nanocrystals exhibit large surfaces suitable for facile and high loading of cholesterol oxidase enzyme through the physical adsorption method. Then, the fabricated cholesterol oxidase/ Co3O4 nanocrystals composite was implemented for potentiometric detection of cholesterol in 10 mM phosphate buffer of pH 7.3. Importantly, the presented cholesterol biosensor revealed a wide linear range of 0.005 mM to 3.0 mM with a limit of detection (LOD) of 0.001 mM. Additionally, the sensitivity of biosensor was estimated around 60 mVdec−1. The selectivity, stability, reproducibility, and repeatability were also observed as satisfactory. The dynamic response of the proposed method demonstrated a fast response time of less than 1 s. Furthermore, the successive addition method confirmed a remarkably stable response towards various cholesterol concentrations. Thus, the developed cholesterol oxidase/ Co3O4 nanocomposite may be used as an efficient alternative method to monitor low cholesterol concentrations form real samples.
Hydrogenation of Flax Shives in Ethanol over a Ni/C Catalyst
Authors: Miroshnikova Angelina V. , Kazachenko Aleksandr S. , Tarabanko Valery E. , Sychev Valentin V. , Skripnikov Andrey M. , Mikhlin Yuri L. , Kosivtsov Yuriy , Chudina Anna I. , Taran Oxana P.
Published: October 2022

Hydrogenation of flax shives in ethanol over bifunctional Ni/C catalysts at 225 °C has been studied. It has been shown that the 10% Ni/C catalyst enhances the yield of monomeric products from 1.1 to 9.7 wt %, decreases the solid product content from 45 to 35 wt %, and increases the degree of delignification to 91%. The main monomeric compounds obtained during hydrogenation are propyl guaiacol and propenyl guaiacol. It has been established that an increase in the mass transfer intensity via increasing the stirring rate or decreasing the catalyst grain size leads to an increase in the total yield of monomeric compounds and the propanol guaiacol yield. Alkaline and acid pretreatment increases the cellulose content in the solid product from 42 to 73 wt %. The proposed sequential scheme of the transformation and formation of monomeric products over the bifunctional nickel catalyst is lignin—coniferyl alcohol—4-propanol guaiacol—4-propenyl guaiacol—4-propyl guaiacol.
Insights of Selective Catalytic Reduction Technology for Nitrogen Oxides Control in Marine Engine Applications
Authors: Napolitano Pierpaolo , Liotta Leonarda Francesca , Guido Chiara , Tornatore Cinzia , Pantaleo Giuseppe , La Parola Valeria , Beatrice Carlo
Published: October 2022

The international shipping industry is facing increasingly stringent limitations on nitrogen oxide (NOx) emissions. New solutions for reducing NOx emitted by marine engines need to be investigated to find the best technology. Selective Catalytic Reduction (SCR) is an advanced active emissions control technology successfully used in automotive diesel engines; it could be applied to marine engines with ad-hoc solutions to integrate it in the exhaust of large engines. In this study, a commercial SCR was tested at the exhaust of a diesel engine in inlet gas conditions typical of a marine engine. The SCR system consisted of a custom monolith (provided by Hug-Engineering AG) that enabled seamless integration for a broad range of engine sizes; the active phases were V2O5 (3 wt%)-WO3 (7 wt%)-TiO2 (75 wt%). The monolith was studied at the laboratory scale for its in-depth chemical/physical characterization and by means of an intermediate-scale engine, reproducing the exhaust gas conditions of a full-scale marine engine. The system’s effectiveness in terms of NOx removal for the selected engine operating conditions was evaluated in a wide range of temperature and NOx emissions values and for different quantities of the reduction agent (AdBlue or ammonia) added to exhaust gases. The investigated technological solution resulted in efficient NOx emission control from a marine engine.
A Ca2+-Mediated Switch of Epiplakin from a Diffuse to Keratin-Bound State Affects Keratin Dynamics
Authors: Ratajczyk Sonia , Drexler Corinne , Windoffer Reinhard , Leube Rudolf E. , Fuchs Peter
Published: October 2022

Keratins exert important structural but also cytoprotective functions. They have to be adaptable to support cellular homeostasis. Epiplakin (EPPK1) has been shown to decorate keratin filaments in epithelial cells and to play a protective role under stress, but the mechanism is still unclear. Using live-cell imaging of epithelial cells expressing fluorescently tagged EPPK1 and keratin, we report here an unexpected dynamic behavior of EPPK1 upon stress. EPPK1 was diffusely distributed throughout the cytoplasm and not associated with keratin filaments in living cells under standard culture conditions. However, ER-, oxidative and UV-stress, as well as cell fixation, induced a rapid association of EPPK1 with keratin filaments. This re-localization of EPPK1 was reversible and dependent on the elevation of cytoplasmic Ca2+ levels. Moreover, keratin filament association of EPPK1 led to significantly reduced keratin dynamics. Thus, we propose that EPPK1 stabilizes the keratin network in stress conditions, which involve increased cytoplasmic Ca2+.
Clinical and Prognostic Value of PPIA, SQSTM1, and CCL20 in Hepatocellular Carcinoma Patients by Single-Cell Transcriptome Analysis
Authors: Mou Lisha , Jia Chenyang , Wu Zijing , Xin Boyang , Liang Zhen Carmen Alicia , Wang Bailiang , Ni Yong , Pu Zuhui
Published: October 2022

Hepatocellular carcinoma (HCC) is the most malignant and poor-prognosis subtype of primary liver cancer. The scRNA-seq approach provides unique insight into tumor cell behavior at the single-cell level. Cytokine signaling in the immune system plays an important role in tumorigenesis and has both pro-tumorigenic and anti-tumorigenic functions. A biomarker of cytokine signaling in immune-related genes (CSIRG) is urgently required to assess HCC patient diagnosis and treatment. By analyzing the expression profiles of HCC single cells, TCGA, and ICGC data, we discovered that three important CSIRG (PPIA, SQSTM1, and CCL20) were linked to the overall survival of HCC patients. Cancer status and three hub CSIRG were taken into account while creating a risk nomogram. The nomogram had a high level of predictability and accuracy. Based on the CSIRG risk score, a distinct pattern of somatic tumor mutational burden (TMB) was detected between the two groups. The enrichment of the pyrimidine metabolism pathway, purine metabolism pathway, and lysosome pathway in HCC was linked to the CSIRG high-risk scores. Overall, scRNA-seq and bulk RNA-seq were used to create a strong CSIRG signature for HCC diagnosis.
Endothelial Nogo-B Suppresses Cancer Cell Proliferation via a Paracrine TGF-β/Smad Signaling
Authors: Li Hengyu , Cheng Zhuo , Yang Pinghua , Huang Wei , Li Xizhou , Xiang Daimin , Wu Xiaojun
Published: October 2022

Nogo-B has been reported to play a critical role in angiogenesis and the repair of damaged blood vessels; however, its role in the tumor microenvironment remains unclear. Here, we observed the differential expression of Nogo-B in endothelial cells from hepatocellular carcinoma (HCC) and glioma samples. Downregulation of Nogo-B expression correlated with the malignant phenotype of cancer and a poor prognosis for patients. In subsequent studies, endothelial Nogo-B inhibition robustly promoted the growth of HCC or glioma xenografts in nude mice. Intriguingly, endothelial Nogo-B silencing dramatically suppressed endothelial cell expansion and tumor angiogenesis, but potently enhanced the proliferation of neighboring HCC and glioma cells. Based on the results of the ELISA assay, Nogo-B silencing reduced TGF-β production in endothelial cells, which attenuated the phosphorylation and nuclear translocation of Smad in neighboring cancer cells. The endothelial Nogo-B silencing-mediated increase in cancer cell proliferation was abolished by either a TGF-β neutralizing antibody or TGF-β receptor inhibitor, indicating the essential role for TGF-β in endothelial Nogo-B-mediated suppression of cancer growth. These findings not only broaden our understanding of the crosstalk between cancer cells and endothelial cells but also provide a novel prognostic biomarker and a therapeutic target for cancer treatments.
Functional Diversity of Neuronal Cell Adhesion and Recognition Molecule L1CAM through Proteolytic Cleavage
Authors: Stoyanova Irina I. , Lutz David
Published: October 2022

The neuronal cell adhesion and recognition molecule L1 does not only ‘keep cells together’ by way of homophilic and heterophilic interactions, but can also promote cell motility when cleaved into fragments by several proteases. It has largely been thought that such fragments are signs of degradation. Now, it is clear that proteolysis contributes to the pronounced functional diversity of L1, which we have reviewed in this work. L1 fragments generated at the plasma membrane are released into the extracellular space, whereas other membrane-bound fragments are internalised and enter the nucleus, thus conveying extracellular signals to the cell interior. Post-translational modifications on L1 determine the sequence of cleavage by proteases and the subcellular localisation of the generated fragments. Inside the neuronal cells, L1 fragments interact with various binding partners to facilitate morphogenic events, as well as regenerative processes. The stimulation of L1 proteolysis via injection of L1 peptides or proteases active on L1 or L1 mimetics is a promising tool for therapy of injured nervous systems. The collective findings gathered over the years not only shed light on the great functional diversity of L1 and its fragments, but also provide novel mechanistic insights into the adhesion molecule proteolysis that is active in the developing and diseased nervous system.
Biochemical Pathways of Cellular Mechanosensing/Mechanotransduction and Their Role in Neurodegenerative Diseases Pathogenesis
Authors: Tortorella Ilaria , Argentati Chiara , Emiliani Carla , Morena Francesco , Martino Sabata
Published: October 2022

In this review, we shed light on recent advances regarding the characterization of biochemical pathways of cellular mechanosensing and mechanotransduction with particular attention to their role in neurodegenerative disease pathogenesis. While the mechanistic components of these pathways are mostly uncovered today, the crosstalk between mechanical forces and soluble intracellular signaling is still not fully elucidated. Here, we recapitulate the general concepts of mechanobiology and the mechanisms that govern the mechanosensing and mechanotransduction processes, and we examine the crosstalk between mechanical stimuli and intracellular biochemical response, highlighting their effect on cellular organelles’ homeostasis and dysfunction. In particular, we discuss the current knowledge about the translation of mechanosignaling into biochemical signaling, focusing on those diseases that encompass metabolic accumulation of mutant proteins and have as primary characteristics the formation of pathological intracellular aggregates, such as Alzheimer’s Disease, Huntington’s Disease, Amyotrophic Lateral Sclerosis and Parkinson’s Disease. Overall, recent findings elucidate how mechanosensing and mechanotransduction pathways may be crucial to understand the pathogenic mechanisms underlying neurodegenerative diseases and emphasize the importance of these pathways for identifying potential therapeutic targets.
RUNX Family in Hypoxic Microenvironment and Angiogenesis in Cancers
Authors: Lee You Mie
Published: October 2022

The tumor microenvironment (TME) is broadly implicated in tumorigenesis, as tumor cells interact with surrounding cells to influence the development and progression of the tumor. Blood vessels are a major component of the TME and are attributed to the creation of a hypoxic microenvironment, which is a common feature of advanced cancers and inflamed premalignant tissues. Runt-related transcription factor (RUNX) proteins, a transcription factor family of developmental master regulators, are involved in vital cellular processes such as differentiation, proliferation, cell lineage specification, and apoptosis. Furthermore, the RUNX family is involved in the regulation of various oncogenic processes and signaling pathways as well as tumor suppressive functions, suggesting that the RUNX family plays a strategic role in tumorigenesis. In this review, we have discussed the relevant findings that describe the crosstalk of the RUNX family with the hypoxic TME and tumor angiogenesis or with their signaling molecules in cancer development and progression.
Anti-Inflammatory Properties of the SGLT2 Inhibitor Empagliflozin in Activated Primary Microglia
Authors: Heimke Marvin , Lenz Florian , Rickert Uta , Lucius Ralph , Cossais François
Published: October 2022

Sodium-glucose cotransporter 2 (SGLT2) inhibitors, including empagliflozin, are routinely used as antidiabetic drugs. Recent studies indicate that beside its beneficial effects on blood glucose level, empagliflozin may also exert vascular anti-inflammatory and neuroprotective properties. In the brain, microglia are crucial mediators of inflammation, and neuroinflammation plays a key role in neurodegenerative disorders. Dampening microglia-mediated inflammation may slow down disease progression. In this context, we investigated the immunomodulatory effect of empagliflozin on activated primary microglia. As a validated experimental model, rat primary microglial cells were activated into a pro-inflammatory state by stimulation with LPS. The influence of empagliflozin on the expression of pro-inflammatory mediators (NO, Nos2, IL6, TNF, IL1B) and on the anti-inflammatory mediator IL10 was assessed using quantitative PCR and ELISA. Further, we investigated changes in the activation of the ERK1/2 cascade by Western blot and NFkB translocation by immunostaining. We observed that empagliflozin reduces the expression of pro- and anti-inflammatory mediators in LPS-activated primary microglia. These effects might be mediated by NHE-1, rather than by SGLT2, and by the further inhibition of the ERK1/2 and NFkB pathways. Our results support putative anti-inflammatory effects of empagliflozin on microglia and suggest that SGLT2 inhibitors may exert beneficial effects in neurodegenerative disorders.
Genotype-by-Environment Interaction Analysis of Metabolites in Pearl Millet Genotypes with High Concentrations of Slowly Digestible and Resistant Starch in Their Grains
Authors: Yadav Chandra Bhan , Gangashetty Prakash I. , Beckmann Manfred , Mur Luis A. J. , Yadav Rattan S.
Published: October 2022

Genotype × environment interactions (GEIs) should play an important role in the selection of suitable germplasm in breeding programmes. We here assessed GEI effects on pearl millet (Pennisetum glaucum L.) genotypes, selected to possess a high concentration of slowly digestible starch (SDS) and resistant starch (RS) in their grains. Entries were grown in a randomized complete block design with three replications at locations in Bawku-Ghana, Sadore-Niger, Bamako-Mali, Konni-Nigeria, and Gampella-Burkina Faso across West Africa. Harvested grains from these locations were metabolomically profiled using flow injection ionization-high-resolution mass spectrometry (FIE-HRMS). A total of 3144 mass features (m/z) (1560 negative ion mode and 1584 positive ion mode) were detected, of which, 475 m/z were linked to metabolites be involved in starch, antioxidant and lipid biosynthesis, and vitamin metabolism. Combined ANOVA revealed that the GEI was significantly evident for 54 health-benefiting metabolites, many associated with sugar, especially galactose, metabolism. Additive main effects and multiplicative interaction (AMMI) analysis examined genotype variation and GEI effects, which, when combined with principal component analysis (PCA), found that m/z 171.14864 (positive ionisation, propenyl heptanoate) accounted for 89% of the GEI variation along PC1. The AMMI-based stability parameter (ASTAB), modified AMMI stability value (MASV), and modified AMMI stability index (MASI) were then applied to identify stable and high-performing genotypes for all the health-benefiting metabolites. Similarly, the best-linear-unbiased-prediction (BLUP)-based stability estimation was also performed using the harmonic mean of genotypic values (HMGV), relative performance of genotypic values (RPGV), and harmonic mean of relative performance of genotypic values (HMRPGV), to identify genotype rankings across multiple environments. The multi-trait stability index (MTSI) was calculated and found that the genotypes G1 (ICMH-177111) and G24 (ICMX-207137) were the most stable and were the best mean performers across 52 health-benefiting metabolic traits. These findings demonstrate the potential of G × E assessments on the delivery of health-benefiting metabolite-rich grains in future varieties and hybrids of pearl millet.
The Tryptophan Catabolite or Kynurenine Pathway in a Major Depressive Episode with Melancholia, Psychotic Features and Suicidal Behaviors: A Systematic Review and Meta-Analysis
Authors: Almulla Abbas F. , Thipakorn Yanin , Vasupanrajit Asara , Tunvirachaisakul Chavit , Oxenkrug Gregory , Al-Hakeim Hussein K. , Maes Michael
Published: October 2022

Major depressive disorder (MDD) and bipolar disorder (BD) with melancholia and psychotic features and suicidal behaviors are accompanied by activated immune-inflammatory and oxidative pathways, which may stimulate indoleamine 2,3-dioxygenase (IDO), the first and rate-limiting enzyme of the tryptophan catabolite (TRYCAT) pathway resulting in increased tryptophan degradation and elevated tryptophan catabolites (TRYCTAs). The purpose of the current study is to systematically review and meta-analyze levels of TRP, its competing amino acids (CAAs) and TRYCATs in patients with severe affective disorders. Methods: PubMed, Google Scholar and SciFinder were searched in the present study and we recruited 35 studies to examine 4647 participants including 2332 unipolar (MDD) and bipolar (BD) depressed patients and 2315 healthy controls. Severe patients showed significant lower (p < 0.0001) TRP (standardized mean difference, SMD = −0.517, 95% confidence interval, CI: −0.735; −0.299) and TRP/CAAs (SMD = −0.617, CI: −0.957; −0.277) levels with moderate effect sizes, while no significant difference in CAAs were found. Kynurenine (KYN) levels were unaltered in severe MDD/BD phenotypes, while the KYN/TRP ratio showed a significant increase only in patients with psychotic features (SMD = 0.224, CI: 0.012; 0.436). Quinolinic acid (QA) was significantly increased (SMD = 0.358, CI: 0.015; 0.701) and kynurenic acid (KA) significantly decreased (SMD = −0.260, CI: −0.487; −0.034) in severe MDD/BD. Patients with affective disorders with melancholic and psychotic features and suicidal behaviors showed normal IDO enzyme activity but a lowered availability of plasma/serum TRP to the brain, which is probably due to other processes such as low albumin levels.
The Roles of RUNX Proteins in Lymphocyte Function and Anti-Tumor Immunity
Authors: Seo Wooseok , Nomura Aneela , Taniuchi Ichiro
Published: October 2022

The Runt-related transcription factor (RUNX) family of proteins are crucial for many developmental and immuno-physiological processes. Their importance in cellular and tissue development has been repeatedly demonstrated as they are often found mutated and implicated in tumorigenesis. Most importantly, RUNX have now emerged as critical regulators of lymphocyte function against pathogenic infections and tumorigenic cells, the latter has now revolutionized our current understandings as to how RUNX proteins contribute to control tumor pathogenicity. These multifunctional roles of RUNX in mammalian immune responses and tissue homeostasis have led us to appreciate their value in controlling anti-tumor immune responses. Here, we summarize and discuss the role of RUNX in regulating the development and function of lymphocytes responding to foreign and tumorigenic threats and highlight their key roles in anti-tumor immunity.
In Vivo Inhibition of miR-34a Modestly Limits Cardiac Enlargement and Fibrosis in a Mouse Model with Established Type 1 Diabetes-Induced Cardiomyopathy, but Does Not Improve Diastolic Function
Authors: Bernardo Bianca C. , Yildiz Gunes S. , Kiriazis Helen , Harmawan Claudia A. , Tai Celeste M. K. , Ritchie Rebecca H. , McMullen Julie R.
Published: October 2022

MicroRNA 34a (miR-34a) is elevated in the heart in a setting of cardiac stress or pathology, and we previously reported that inhibition of miR-34a in vivo provided protection in a setting of pressure overload-induced pathological cardiac hypertrophy and dilated cardiomyopathy. Prior work had also shown that circulating or cardiac miR-34a was elevated in a setting of diabetes. However, the therapeutic potential of inhibiting miR-34a in vivo in the diabetic heart had not been assessed. In the current study, type 1 diabetes was induced in adult male mice with 5 daily injections of streptozotocin (STZ). At 8 weeks post-STZ, when mice had established type 1 diabetes and diastolic dysfunction, mice were administered locked nucleic acid (LNA)-antimiR-34a or saline-control with an eight-week follow-up. Cardiac function, cardiac morphology, cardiac fibrosis, capillary density and gene expression were assessed. Diabetic mice presented with high blood glucose, elevated liver and kidney weights, diastolic dysfunction, mild cardiac enlargement, cardiac fibrosis and reduced myocardial capillary density. miR-34a was elevated in the heart of diabetic mice in comparison to non-diabetic mice. Inhibition of miR-34a had no significant effect on diastolic function or atrial enlargement, but had a mild effect on preventing an elevation in cardiac enlargement, fibrosis and ventricular gene expression of B-type natriuretic peptide (BNP) and the anti-angiogenic miRNA (miR-92a). A miR-34a target, vinculin, was inversely correlated with miR-34a expression, but other miR-34a targets were unchanged. In summary, inhibition of miR-34a provided limited protection in a mouse model with established type 1 diabetes-induced cardiomyopathy and failed to improve diastolic function. Given diabetes represents a systemic disorder with numerous miRNAs dysregulated in the diabetic heart, as well as other organs, strategies targeting multiple miRNAs and/or earlier intervention is likely to be required.
Concise Review: Stem Cell Models of SCN1A-Related Encephalopathies—Current Perspective and Future Therapies
Authors: Zayat Valery , Szlendak Roza , Hoffman-Zacharska Dorota
Published: October 2022

Mutations in the SCN1A gene can cause a variety of phenotypes, ranging from mild forms, such as febrile seizures and generalized epilepsy with febrile seizures plus, to severe, such as Dravet and non-Dravet developmental epileptic encephalopathies. Until now, more than two thousand pathogenic variants of the SCN1A gene have been identified and different pathogenic mechanisms (loss vs. gain of function) described, but the precise molecular mechanisms responsible for the deficits exhibited by patients are not fully elucidated. Additionally, the phenotypic variability proves the involvement of other genetic factors in its final expression. This is the reason why animal models and cell line models used to explore the molecular pathology of SCN1A-related disorders are only of limited use. The results of studies based on such models cannot be directly translated to affected individuals because they do not address each patient’s unique genetic background. The generation of functional neurons and glia for patient-derived iPSCs, together with the generation of isogenic controls using CRISPR/Cas technology, and finally, the 3D brain organoid models, seem to be a good way to solve this problem. Here, we review SCN1A-related encephalopathies, as well as the stem cell models used to explore their molecular basis.
Supraphysiological Oxygen Levels in Mammalian Cell Culture: Current State and Future Perspectives
Authors: Alva Ricardo , Gardner Georgina L. , Liang Ping , Stuart Jeffrey A.
Published: October 2022

Most conventional incubators used in cell culture do not regulate O2 levels, making the headspace O2 concentration ~18%. In contrast, most human tissues are exposed to 2–6% O2 (physioxia) in vivo. Accumulating evidence has shown that such hyperoxic conditions in standard cell culture practices affect a variety of biological processes. In this review, we discuss how supraphysiological O2 levels affect reactive oxygen species (ROS) metabolism and redox homeostasis, gene expression, replicative lifespan, cellular respiration, and mitochondrial dynamics. Furthermore, we present evidence demonstrating how hyperoxic cell culture conditions fail to recapitulate the physiological and pathological behavior of tissues in vivo, including cases of how O2 alters the cellular response to drugs, hormones, and toxicants. We conclude that maintaining physioxia in cell culture is imperative in order to better replicate in vivo-like tissue physiology and pathology, and to avoid artifacts in research involving cell culture.
Willin/FRMD6 Mediates Mitochondrial Dysfunction Relevant to Neuronal Aβ Toxicity
Authors: Chen Doris , Yu Wanjia , Aitken Laura , Gunn-Moore Frank
Published: October 2022

Willin/FRMD6 has been reported as a potential Alzheimer’s disease (AD) risk gene in a series of genome-wide association and neuroimaging studies; however, the mechanisms underlying its potential role in AD pathogenesis remain unknown. Here, we demonstrate the direct effects of Aβ on Willin/FRMD6 expression and position mitochondrial oxidative stress as a novel potential mechanism underlying the role of Willin/FRMD6 in AD pathogenesis. Specifically, using mouse hippocampal HT-22 cells and primary mouse neurons, we show that Aβ induces downregulation of Willin/FRMD6 protein expression. Furthermore, we demonstrate that Willin/FRMD6 knockdown leads to mitochondrial dysfunction and fragmentation, as well as upregulation of ERK1/2 signaling, both of which are reported to be key early features of AD pathogenesis. Importantly, increasing Willin/FRMD6 expression was able to rescue Aβ-induced abnormalities in mitochondrial morphology, function, and energetics. Thus, enhancing Willin/FRMD6 expression holds potential as a therapeutic strategy for protecting against Aβ-induced mitochondrial and neuronal dysfunction.
Bta-miR-223 Targeting the RHOB Gene in Dairy Cows Attenuates LPS-Induced Inflammatory Responses in Mammary Epithelial Cells
Authors: Jiao Peng , Wang Jinpeng , Yang Jian , Wang Xingping , Luoreng Zhuoma
Published: October 2022

Bovine mammary epithelial cells (bMECs) are part of the first line of defense against pathogens. In recent studies, bta-miR-223 has been reported to activate congenital and innate immunity against inflammatory damage during the pathogenesis of mastitis in dairy cows. The purpose of this study was to identify the regulatory mechanism of bta-miR-223 and its downstream target genes in inflammatory bMECs. A double luciferase reporter gene assay demonstrated that ras homolog family member B (RHOB) was the target gene of bta-miR-223. To further elucidate the role of bta-miR-223 in congenital immune responses, bta-miR-223 mimics (mimic/inhibitor) were transfected into bMECs stimulated with lipopolysaccharide (LPS), which activates the Toll-like receptor 4/nuclear factor-κB (TLR4/NF-κB) signaling pathway. Real-time quantitative PCR (qPCR) and Western blot were used to detect the expression of related genes and proteins, and enzyme-linked immunosorbent assay (ELISA) was used to detect secreted inflammatory factors. Results showed that bta-miR-223 expression during inflammation in bMECs reduced the secretion of inflammatory factors by targeting RHOB and deactivation of NF-κB gene activity. Silencing RHOB inhibited LPS-induced inflammatory response in bMECs. Overall, bta-miR-223 attenuated LPS-induced inflammatory response, and acted as a negative feedback regulator via targeting RHOB, providing a novel avenue for mastitis treatment.
Chromatin Liquid–Liquid Phase Separation (LLPS) Is Regulated by Ionic Conditions and Fiber Length
Authors: Chen Qinming , Zhao Lei , Soman Aghil , Arkhipova Anastasia Yu , Li Jindi , Li Hao , Chen Yinglu , Shi Xiangyan , Nordenskiöld Lars
Published: October 2022

The dynamic regulation of the physical states of chromatin in the cell nucleus is crucial for maintaining cellular homeostasis. Chromatin can exist in solid- or liquid-like forms depending on the surrounding ions, binding proteins, post-translational modifications and many other factors. Several recent studies suggested that chromatin undergoes liquid–liquid phase separation (LLPS) in vitro and also in vivo; yet, controversial conclusions about the nature of chromatin LLPS were also observed from the in vitro studies. These inconsistencies are partially due to deviations in the in vitro buffer conditions that induce the condensation/aggregation of chromatin as well as to differences in chromatin (nucleosome array) constructs used in the studies. In this work, we present a detailed characterization of the effects of K+, Mg2+ and nucleosome fiber length on the physical state and property of reconstituted nucleosome arrays. LLPS was generally observed for shorter nucleosome arrays (15-197-601, reconstituted from 15 repeats of the Widom 601 DNA with 197 bp nucleosome repeat length) at physiological ion concentrations. In contrast, gel- or solid-like condensates were detected for the considerably longer 62-202-601 and lambda DNA (~48.5 kbp) nucleosome arrays under the same conditions. In addition, we demonstrated that the presence of reduced BSA and acetate buffer is not essential for the chromatin LLPS process. Overall, this study provides a comprehensive understanding of several factors regarding chromatin physical states and sheds light on the mechanism and biological relevance of chromatin phase separation in vivo.
The Railmap of Type I Interferon Induction: Subcellular Network Plan and How Viruses Can Change Tracks
Authors: Weber Laura , Vieyres Gabrielle
Published: October 2022

The innate immune response constitutes the cell’s first line of defense against viruses and culminates in the expression of type I interferon (IFN) and IFN-stimulated genes, inducing an antiviral state in infected and neighboring cells. Efficient signal transduction is a key factor for strong but controlled type I IFN expression and depends on the compartmentalization of different steps of the signaling cascade and dynamic events between the involved compartments or organelles. This compartmentalization of the innate immune players not only relies on their association with membranous organelles but also includes the formation of supramolecular organizing centers (SMOCs) and effector concentration by liquid–liquid phase separation. For their successful replication, viruses need to evade innate defenses and evolve a multitude of strategies to impair type I IFN induction, one of which is the disruption of spatial immune signaling dynamics. This review focuses on the role of compartmentalization in ensuring an adequate innate immune response to viral pathogens, drawing attention to crucial translocation events occurring downstream of pattern recognition and leading to the expression of type I IFN. Furthermore, it intends to highlight concise examples of viral countermeasures interfering with this spatial organization to alleviate the innate immune response.
TFEB; Beyond Its Role as an Autophagy and Lysosomes Regulator
Authors: Franco-Juárez Berenice , Coronel-Cruz Cristina , Hernández-Ochoa Beatriz , Gómez-Manzo Saúl , Cárdenas-Rodríguez Noemi , Arreguin-Espinosa Roberto , Bandala Cindy , Canseco-Ávila Luis Miguel , Ortega-Cuellar Daniel
Published: October 2022

Transcription factor EB (TFEB) is considered the master transcriptional regulator of autophagy and lysosomal biogenesis, which regulates target gene expression through binding to CLEAR motifs. TFEB dysregulation has been linked to the development of numerous pathological conditions; however, several other lines of evidence show that TFEB might be a point of convergence of diverse signaling pathways and might therefore modulate other important biological processes such as cellular senescence, DNA repair, ER stress, carbohydrates, and lipid metabolism and WNT signaling-related processes. The regulation of TFEB occurs predominantly at the post-translational level, including phosphorylation, acetylation, SUMOylating, PARsylation, and glycosylation. It is noteworthy that TFEB activation is context-dependent; therefore, its regulation is subjected to coordinated mechanisms that respond not only to nutrient fluctuations but also to stress cell programs to ensure proper cell homeostasis and organismal health. In this review, we provide updated insights into novel post-translational modifications that regulate TFEB activity and give an overview of TFEB beyond its widely known role in autophagy and the lysosomal pathway, thus opening the possibility of considering TFEB as a potential therapeutic target.
Nasal Microbiome and Its Interaction with the Host in Childhood Asthma
Authors: Zeng Yao , Liang Jessie Qiaoyi
Published: October 2022

Childhood asthma is a major chronic non-communicable disease in infants and children, often triggered by respiratory tract infections. The nasal cavity is a reservoir for a broad variety of commensal microbes and potential pathogens associated with respiratory illnesses including asthma. A healthy nasal microenvironment has protective effects against respiratory tract infections. The first microbial colonisation in the nasal region is initiated immediately after birth. Subsequently, colonisation by nasal microbiota during infancy plays important roles in rapidly establishing immune homeostasis and the development and maturation of the immune system. Dysbiosis of microbiota residing in the mucosal surfaces, such as the nasopharynx and guts, triggers immune modulation, severe infection, and exacerbation events. Nasal microbiome dysbiosis is related to the onset of symptomatic infections. Dynamic interactions between viral infections and the nasal microbiota in early life affect the later development of respiratory infections. In this review, we summarise the existing findings related to nasal microbiota colonisation, dynamic variations, and host–microbiome interactions in childhood health and respiratory illness with a particular examination of asthma. We also discuss our current understanding of biases produced by environmental factors and technical concerns, the importance of standardised research methods, and microbiome modification for the prevention or treatment of childhood asthma. This review lays the groundwork for paying attention to an essential but less emphasized topic and improves the understanding of the overall composition, dynamic changes, and influence of the nasal microbiome associated with childhood asthma.
Childcare Center Evacuation to Vertical Shelters in a Nankai Trough Tsunami: Models to Predict and Mitigate Risk
Authors: Nakai Hisao , Horiike Ryo , Itatani Tomoya , Matsumoto Yukari
Published: October 2022

Following the Great East Japan Earthquake, vertical evacuation shelters (VES) were constructed to reduce tsunami risk. Childcare centers (CCs) in the inundation area are required to evacuate to the nearest VES in the event of a tsunami. The study aim was to identify CCs and VES predicted to be inundated by a Nankai Trough earthquake-generated tsunami, and to clarify CC inundation risk. We identified 52 (45.6%) CCs in the tsunami inundation area and found that 14 (25.9%) would evacuate toward the tsunami. If the walking speed was 2.24 km/h and a 0.3 m tsunami arrived in 10 min, nine (17.3%) CCs would be late to safe evacuation. If the tsunami arrival time was 20 min, four (7.7%) CCs would have late evacuation. At a walking speed of 1.00 km/h, 38 (73.1%) and 20 (38.5%) CCs would have late evacuation, with tsunami arrival times of 10 min and 20 min, respectively. Evacuation direction is important in avoiding tsunami damage. An evacuation strategy is needed that evacuates people away from the tsunami, and takes into account children’s age, walking speed, and evacuation method. The evaluation of tsunami risk in this study may support the development of tsunami countermeasures in other coastal areas with latent tsunami risks.